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Aging profoundly affects the immune system leading to an increased propensity for inflammation. Age-related dysregulation of immune cells is implicated in the development and progression of numerous age-related diseases such as: cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Monocytes and monocyte-derived macrophages, being important players in the inflammatory response, significantly influence the aging process and the associated increase in inflammatory disease risk. Ischemic stroke is among age-related diseases where inflammation, particularly monocyte-derived macrophages, plays an important deteriorating role but could also strongly promote post-stroke recovery. Also, biological sex influences the incidence, presentation, and outcomes of ischemic stroke, reflecting both biological differences between men and women. Here, we studied whether human peripheral blood monocyte subtype (classical, intermediate, and non-classical) expression of genes implicated in stroke-related inflammation and post-stroke tissue regeneration depends on age and sex. A flow cytometry analysis of blood samples from 44 healthy volunteers (male and female, aged 28 to 98) showed that in contrast to other immune cells, the proportion of NK-cells increased in females. The proportion of B-cells decreased in both sexes with age. Gene expression analysis by qPCR identified several genes differentially correlating with age and sex within different monocyte subtypes. Interestingly, ANXA1 and CD36 showed a consistent increase with aging in all monocytes, specifically in intermediate (CD36) and intermediate and non-classical (ANXA1) subtypes. Other genes (IL-1β, S100A8, TNFα, CD64, CD33, TGFβ1, TLR8, CD91) were differentially changed in monocyte subtypes with increasing age. Most age-dependent gene changes were differentially expressed in female monocytes. Our data shed light on the nuanced interplay of age and sex in shaping the expression of inflammation- and regeneration-related genes within distinct monocyte subtypes. Understanding these dynamics could pave the way for targeted interventions and personalized approaches in post-stroke care, particularly for the aging population and individuals of different sexes. [ABSTRACT FROM AUTHOR]

Background: We developed the HIV Triplex multiplex bead assay to identify and serotype HIV infection with high sensitivity and specificity; and distinguish recent from long-term HIV-1 infections. It can facilitate accurate incidence estimation, while reducing the number of tests and blood collected, which is highly desirable for use in future studies and surveys. Using previously collected, treatment-naive longitudinal seroconversion HIV-1 positive panels and specimens from individuals infected for >12 months, we determined the assay's mean duration of recent infection (MDRI) and false-recency rate (FRR) respectively, at various mean fluorescent intensity (MFI) cutoffs. Methods: We tested seroconversion specimens (N = 814) from 142 individuals infected with HIV-1 subtypes B, C, or AE, and 1341 cross-sectional specimens from individuals infected >12 months. The MFI cutoffs of 1000 to 2000 were evaluated for recency classification, including an MFI of 1250 corresponding to the limiting antigen avidity enzyme immunoassay (LAg-EIA) cutoff of 1.5 normalized optical density for MDRI and FRR. We used four statistical methods: Methods 1 and 2 used the empirically balanced observation time approach. Method 2 MFI values were raised to power = 1.33, based on a repeated measures model to linearize the relationship between MFI and time points, whereas Method 1 was not linearized. Methods 3 and 4 employed quadratic and linear interpolations for each seroconversion panel. FRR was calculated by dividing the number of specimens misclassified as recent by the total number of specimens tested. Results: MDRI values ranged from 135–146 days at MFI = 1000 to 229–279 days at MFI = 2000 by the 4 methods. FRR varied from 0.15%-1.27% with increasing MFI cutoff. At MFI = 1250, the average MDRI of 4 methods was 169 days and ranged from 159–183 with overlapping 95% CIs and FRR = 0.52%. Conclusion: The HIV Triplex assay demonstrates a longer dynamic range compared to current HIV recency assays with a low FRR for cutoffs examined. With a longer dynamic range and low FRR, the MDRI for recent infection can be extended as appropriate to detect more recent infections, increasing the value of incidence assays benefiting public health surveillance and future surveys. [ABSTRACT FROM AUTHOR]

Background: Analysis of existing mutations of Angiotensin-I-Converting Enzyme (ACE) led us to hypothesize that the carriers of damaging ACE mutations (accompanied by low ACE levels) could be at risk for the development of late-onset Alzheimer's disease (AD). Methodology/Principal findings: We quantified blood ACE levels in EDTA-containing plasma from 15 patients with 11 different heterozygous ACE mutations and estimated the effects of these mutations on ACE phenotypes, using a set of mAbs to ACE and two ACE substrates. We confirmed prior observations that the relatively frequent Y215C mutation in the N domain of ACE (present in ~1% of the population) is associated with both Alzheimer's disease (AD) and reduced plasma levels of ACE (~50% of controls), indicating that it likely results in a transport-deficient protein. In addition, we identified another 4 mutations in both ACE domains (M118T, C734Y, V992M and V997M) which are also associated with decreased ACE levels in the blood, and, thus, could be putative risk factors for late-onset AD. One of these mutations, C734Y, is likely transport-deficient, while the other mutations appear to influence ACE catalytic properties. The precipitation of mutant M118T by mAb 2D1 and ACE mutant C734Y by mAb 3F10 increased 2-3-fold compared to native ACE, and therefore, these mAbs could be markers of these mutations. Also, we identified a mutation I989T, which is associated with increased ACE levels in the blood. Conclusions/Significance: Conducting a systematic analysis of blood ACE levels in patients with ACE mutations holds promise for identifying individuals with low blood ACE levels. Such individuals may be at increased risk for late-onset AD. The patients with transport-deficient ACE mutations may benefit from therapeutic treatment with a combination of chemical and pharmacological chaperones and proteasome inhibitors, as was demonstrated previously using a cell model of the transport-deficient ACE mutation, Q1069R [Danilov et al, PLoS One, 2010]. [ABSTRACT FROM AUTHOR]

Background: Following reduction of public health and social measures concurrent with SARS-CoV-2 Omicron emergence in late 2021 in Australia, COVID-19 case notification rates rose rapidly. As rates of direct viral testing and reporting dropped, true infection rates were most likely to be underestimated. Objective: To better understand infection rates and immunity in this population, we aimed to estimate SARS-CoV-2 seroprevalence in Australians aged 0–19 years. Methods: We conducted a national cross sectional serosurvey from June 1, 2022, to August 31, 2022, in children aged 0–19 years undergoing an anesthetic procedure at eight tertiary pediatric hospitals. Participant questionnaires were administered, and blood samples tested using the Roche Elecsys Anti-SARS-CoV-2 total spike and nucleocapsid antibody assays. Spike and nucleocapsid seroprevalence adjusted for geographic and socioeconomic imbalances in the participant sample compared to the Australian population was estimated using multilevel regression and poststratification within a Bayesian framework. Results: Blood was collected from 2,046 participants (median age: 6.6 years). The overall adjusted seroprevalence of spike-antibody was 92.1% (95% credible interval (CrI) 91.0–93.3%) and nucleocapsid-antibody was 67.0% (95% CrI 64.6–69.3). In unvaccinated children spike and nucleocapsid antibody seroprevalences were 84.2% (95% CrI 81.9–86.5) and 67.1% (95%CrI 64.0–69.8), respectively. Seroprevalence was similar across geographic remoteness index and socioeconomic quintiles. Nucleocapsid antibody seroprevalence increased with age while the point seroprevalence of the spike antibody seroprevalence decreased in the first year of life and then increased to 97.8 (95% Crl 96.1–99.2) by 12–15 years of age. Conclusion: Most Australian children and adolescents aged 0–19 years, across all jurisdictions were infected with SARS-CoV-2 by August 2022, suggesting rapid and uniform spread across the population in a very short time period. High seropositivity in unvaccinated children informed COVID-19 vaccine recommendations in Australia. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after radical resection because of subclinical tumors. To manage them, a reliable biomarker that can indicate the presence of subclinical tumors and predict their chemosensitivity is required. This study aimed to identify a miRNA as a biomarker that can be used to individualize postoperative adjuvant chemotherapy using postoperative peripheral blood samples. Integrating miRNA microarray data from the blood of 18 patients with PDAC and the in vitro results regarding the phenotypes of chemoresistant PDAC cells, a candidate miRNA was identified. The relationships between candidate miRNA expression and chemosensitivity were examined in vitro and in clinical samples from other cohorts of 33 patients with recurrence. Comprehensive analyses of blood samples detected 5 candidate miRNAs. Of these, miR-26a-5p was considered a candidate biomarker of chemosensitive phenotypes. In validation experiments, chemosensitivity was inversely correlated with miR-26a-5p expression in vitro. Moreover, the ability of miR-26a-5p to predict chemosensitivity was clinically evaluated using blood samples. Patients with high miR-26a-5p expression in the blood after radical resection exhibited a significantly longer survival time after recurrence. Thus, we concluded that miR-26a-5p is a potentially useful biomarker for managing patients with PDAC, especially those undergoing adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2–6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment. [ABSTRACT FROM AUTHOR]

The skin is an anatomical reservoir for African trypanosomes, yet the prevalence of extravascular parasite carriage in the population at risk of gambiense Human African Trypanosomiasis (gHAT) remains unclear. Here, we conducted a prospective observational cohort study in the HAT foci of Forecariah and Boffa, Republic of Guinea. Of the 18,916 subjects serologically screened for gHAT, 96 were enrolled into our study. At enrolment and follow-up visits, participants underwent a dermatological examination and had blood samples and superficial skin snip biopsies taken for examination by molecular and immuno-histological methods. In seropositive individuals, dermatological symptoms were significantly more frequent as compared to seronegative controls. Trypanosoma brucei DNA was detected in the blood of 67% of confirmed cases (22/33) and 9% of unconfirmed seropositive individuals (3/32). However, parasites were detected in the extravascular dermis of up to 71% of confirmed cases (25/35) and 41% of unconfirmed seropositive individuals (13/32) by PCR and/or immuno-histochemistry. Six to twelve months after treatment, trypanosome detection in the skin dropped to 17% of confirmed cases (5/30), whereas up to 25% of unconfirmed, hence untreated, seropositive individuals (4/16) were still found positive. Dermal trypanosomes were observed in subjects from both transmission foci, however, the occurrence of pruritus and the PCR positivity rates were significantly higher in unconfirmed seropositive individuals in Forecariah. The lower sensitivity of superficial skin snip biopsies appeared critical for detecting trypanosomes in the basal dermis. These results are discussed in the context of the planned elimination of gHAT. Author summary: The skin is a reservoir for African trypanosomes. Here, we conducted a prospective study in Forecariah and Boffa, Guinea, to estimate the proportion of skin-dwelling parasites in the population. Of the 18,916 subjects screened for HAT, 96 were enrolled into our study. Participants underwent a dermatological examination and had blood samples and superficial skin biopsies taken for examination by molecular and immuno-histological methods. In individuals seropositive for HAT, dermatological symptoms were significantly more frequent. Trypanosome DNA was detected in the blood of 67% of confirmed cases and 9% of unconfirmed seropositive individuals. However, parasites were detected in the skin of up to 71% of confirmed cases and 41% of unconfirmed seropositive individuals. After treatment, trypanosome detection in the skin dropped to 17% of confirmed cases, whereas up to 25% of unconfirmed, hence untreated, seropositive individuals were still found positive. Dermal trypanosomes were observed in subjects from both regions; however, the occurrence of itching and the PCR positivity were significantly higher in unconfirmed seropositive individuals in Forecariah. The lower sensitivity of superficial skin biopsies appeared critical for detecting trypanosomes. These results are discussed in the context of the planned elimination of HAT. [ABSTRACT FROM AUTHOR]

Objective: To compare preferences, uptake, and cofactors for unassisted home-based oral self-testing (HB-HIVST) versus clinic-based rapid diagnostic blood tests (CB-RDT) for maternal HIV retesting. Design: Prospective cohort. Methods: Between November 2017 and June 2019, HIV-negative pregnant Kenyan women receiving antenatal care were enrolled and given a choice to retest with HB-HIVST or CB-RDT. Women were asked to retest between 36 weeks gestation and 1-week post-delivery if the last HIV test was <24 weeks gestation or at 6 weeks postpartum if ≥24 weeks gestation, and self-report on retesting at a 14-week postpartum. Results: Overall, 994 women enrolled and 33% (n = 330) selected HB-HIVST. HB-HIVST was selected because it was private (n = 224, 68%), convenient (n = 211, 63%), and offered flexibility in the timing of retesting (n = 207, 63%), whereas CB-RDT was selected due to the trust of providers to administer the test (n = 510, 77%) and convenience of clinic testing (n = 423, 64%). Among 905 women who reported retesting at follow-up, 135 (15%) used HB-HIVST. Most (n = 595, 94%) who selected CB-RDT retested with this strategy, compared to 39% (n = 120) who selected HB-HIVST retesting with HB-HIVST. HB-HIVST retesting was more common among women with higher household income and those who may have been unable to test during pregnancy (both retested postpartum and delivered <37 weeks gestation) and less common among women who were depressed. Most women said they would retest in the future using the test selected at enrollment (99% [n = 133] HB-HIVST; 93% [n = 715] CB-RDT-RDT). Conclusions: While most women preferred CB-RDT for maternal retesting, HB-HIVST was acceptable and feasible and could be used to expand HIV retesting options. [ABSTRACT FROM AUTHOR]

Background: Identifying patients presenting with nonspecific abdominal symptoms who have underlying cancer is a challenge. Common blood tests are widely used to investigate these symptoms in primary care, but their predictive value for detecting cancer in this context is unknown. We quantify the predictive value of 19 abnormal blood test results for detecting underlying cancer in patients presenting with 2 nonspecific abdominal symptoms. Methods and findings: Using data from the UK Clinical Practice Research Datalink (CPRD) linked to the National Cancer Registry, Hospital Episode Statistics and Index of Multiple Deprivation, we conducted a population-based cohort study of patients aged ≥30 presenting to English general practice with abdominal pain or bloating between January 2007 and October 2016. Positive and negative predictive values (PPV and NPV), sensitivity, and specificity for cancer diagnosis (overall and by cancer site) were calculated for 19 abnormal blood test results co-occurring in primary care within 3 months of abdominal pain or bloating presentations. A total of 9,427/425,549 (2.2%) patients with abdominal pain and 1,148/52,321 (2.2%) with abdominal bloating were diagnosed with cancer within 12 months post-presentation. For both symptoms, in both males and females aged ≥60, the PPV for cancer exceeded the 3% risk threshold used by the UK National Institute for Health and Care Excellence for recommending urgent specialist cancer referral. Concurrent blood tests were performed in two thirds of all patients (64% with abdominal pain and 70% with bloating). In patients aged 30 to 59, several blood abnormalities updated a patient's cancer risk to above the 3% threshold: For example, in females aged 50 to 59 with abdominal bloating, pre-blood test cancer risk of 1.6% increased to: 10% with raised ferritin, 9% with low albumin, 8% with raised platelets, 6% with raised inflammatory markers, and 4% with anaemia. Compared to risk assessment solely based on presenting symptom, age and sex, for every 1,000 patients with abdominal bloating, assessment incorporating information from blood test results would result in 63 additional urgent suspected cancer referrals and would identify 3 extra cancer patients through this route (a 16% relative increase in cancer diagnosis yield). Study limitations include reliance on completeness of coding of symptoms in primary care records and possible variation in PPVs if extrapolated to healthcare settings with higher or lower rates of blood test use. Conclusions: In patients consulting with nonspecific abdominal symptoms, the assessment of cancer risk based on symptoms, age and sex alone can be substantially enhanced by considering additional information from common blood test results. Male and female patients aged ≥60 presenting to primary care with abdominal pain or bloating warrant consideration for urgent cancer referral or investigation. Further cancer assessment should also be considered in patients aged 30 to 59 with concurrent blood test abnormalities. This approach can detect additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites. Meena Rafiq and co-workers explore the predictive value of abnormal blood tests for detecting cancer in patients presenting to primary care with non-specific abdominal symptoms. Author summary: Why was this study done?: Half of all patients with as-yet-undetected cancer will first present with nonspecific symptoms that can be challenging to diagnose. Many of these patients are investigated in primary care with commonly used blood tests that could help to identify which patients are most likely to have underlying cancer (to prioritise them for referral) and which patients can be safely monitored in primary care. This study aimed to assess the predictive value of abnormal blood tests for detecting cancer in patients presenting to primary care with 2 nonspecific abdominal symptoms. What did the researchers do and find?: Using linked UK primary care data (CPRD), we conducted a cohort study of 477,870 patients aged ≥30 years presenting with new abdominal pain or bloating and calculated the predictive value of 19 abnormal blood test results for detecting cancer by age and sex. Males and females aged ≥60 presenting with either symptom had a risk of underlying cancer exceeding the 3% threshold used by the UK National Institute for Health and Care Excellence for recommending urgent cancer referral. In patients aged 30 to 59 with abdominal pain or bloating, several blood abnormalities updated a patient's cancer risk to above the 3% threshold and they should be considered for urgent cancer referral. What do these findings mean?: Commonly used primary care blood test results can improve the detection of underlying cancer in patients consulting with nonspecific abdominal symptoms. These findings can inform updates to clinical guidelines to allow detection of additional patients with underlying cancer through expedited referral routes and can guide decisions on specialist referrals and investigation strategies for different cancer sites. Limitations include the results applying to patients who had been recorded as having abdominal pain and bloating by their clinician and who had been selected by the clinician for blood testing (and therefore have a higher cancer risk that all patients with abdominal pain and bloating). [ABSTRACT FROM AUTHOR]

Le Dantec virus (LDV), assigned to the species Ledantevirus ledantec, genus Ledantevirus, family Rhabdoviridae has been associated with human disease but has gone undetected since the 1970s. We describe the detection of LDV in a human case of undifferentiated fever in Uganda by metagenomic sequencing and demonstrate a serological response using ELISA and pseudotype neutralisation. By screening 997 individuals sampled in 2016, we show frequent exposure to ledanteviruses with 76% of individuals seropositive in Western Uganda, but lower seroprevalence in other areas. Serological cross-reactivity as measured by pseudotype-based neutralisation was confined to ledanteviruses, indicating population seropositivity may represent either exposure to LDV or related ledanteviruses. We also describe the discovery of a closely related ledantevirus in blood from the synanthropic rodent Mastomys erythroleucus. Ledantevirus infection is common in Uganda but is geographically heterogenous. Further surveys of patients presenting with acute fever are required to determine the contribution of these emerging viruses to febrile illness in Uganda. Author summary: Understanding the viruses capable of human infection is important for outbreak prevention and early intervention in viral epidemics. Le Dantec virus (LDV) is a member of the viral genus Ledantevirus (Rhabodoviridae) and has previously been isolated only once previously in a child with febrile illness in Senegal in 1965. We detected the genome of LDV in blood sampled from a patient presenting with febrile illness in Western Uganda in 2012. To estimate the extent to which LDV may be causing human infection in the region, we tested stored blood samples collected in 2016 for evidence of antibodies to LDV, revealing that up to 76% of Ugandans in some areas had previously been exposed to either to LDV or a closely related virus. Seroprevalence was highest in Western Uganda, an area of high biodiversity where several other ledanteviruses have been isolated in association with ectoparasites of bats. To investigate potential ecological reservoirs of zoonotic viruses we tested blood from wild rodents inhabiting areas close to human settlements. We detected a new ledantevirus, closely related to LDV, in blood from a wild rodent Mastomys erythroleucus. Our work shows that ledanteviruses are a common cause of human infection in Uganda. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen's Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration, this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR-182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary. [ABSTRACT FROM AUTHOR]

Introduction: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. Methods: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. Results: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5–10 years old (26.6%), adolescents aged 10–19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06–3.20). Participants aged 5–9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02–1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). Conclusion: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this study was to examine the feasibility of recruitment, retention, and delivery of biomarker feedback among men partaking in Shape Up, a physical activity for health programme. Secondarily, it explored the potential effects of biomarker feedback on participants' adherence and motivation levels. Methods: In this two-arm non-randomised pilot study, 46 men (mean±SD age 46.0±8.6 years) participating in the 12-week Shape Up programme were assigned to a control group or biomarker feedback group. Biomarker feedback consisted of 3 blood test panels: at baseline, 12 weeks, and 24 weeks (follow-up), each with a doctor's report. Both groups completed questionnaires (Short Active Lives Survey [SALS], Treatment Self-Regulation Questionnaire [TSRQ], and EQ-5D-5L) to gauge levels of motivation and engagement. The mean difference was calculated between baseline and programme end. Recruitment, retention, and attendance rates were determined. Results: Mean recruitment (approach-to-consent), retention, and attendance rates were 96.3%, 92.3%, and 83.7% in the control group, and 85.2%, 86.2%, and 81.5% in the biomarker feedback group, respectively. Of biomarker feedback group participants, 86.4% attended their 12-week blood test and 45.5% attended their follow-up blood test. The mean 12-week differences (95% CI) for the control group and biomarker feedback group were 138.1 (2.7, 273.5) and 467.3 (249.4, 685.2) for active minutes per week, 0.2 (-0.8, 1.2) and 0.4 (0.0, 0.8) for autonomous TSRQ domains, 0.2 (-0.3, 0.8) and 0.8 (0.1, 1.4) for controlled TSRQ domains, and 19 (12.7, 26.5) and 27.2 (19.8, 34.6) for EQ-5D-5L scores, respectively. Conclusion: Biomarker feedback was well-received by participants and deemed feasible, with high recruitment and retention rates for the duration of the 12-week programme. Biomarker feedback may affect aspects of motivation but did not appear to influence adherence to the programme. Biomarker data may provide additional evidence of programme efficacy. Important design considerations are provided for definitive larger-scale trials. [ABSTRACT FROM AUTHOR]

Blood gas analysis reflects the exchange of oxygen and carbon dioxide in the lungs. This test provides important information, since the relationship between these gases has a direct impact on the acid-basic balance in the body. Given the significance of blood gas analysis in Brazilian reptiles, this study set out to establish temperature-corrected and uncorrected reference intervals for venous blood gas measurements in Chelonoidis carbonarius, and to compare values between females and males. In this study, 19 animals were used, 8 males and 11 females. Blood samples were collected from the dorsal coccygeal vein, and the analyses were performed immediately after blood sample collection. The following parameters were measured: pH, PO2, HCO3-, TCO2, BEecf, Na, K, ICa, and Glu, and were compared between females and males. Additionally, pH, pCO2, and pO2 values were compared with and without temperature correction. Oxygen saturation and Na levels were significantly higher (p<0.05) in males. Furthermore, it was possible to infer that the lower the body temperature relative to the environmental temperature, the larger the difference in pH following temperature correction. [ABSTRACT FROM AUTHOR]

The extent to which dengue virus has been circulating globally and especially in Africa is largely unknown. Testing available blood samples from previous cross-sectional serological surveys offers a convenient strategy to investigate past dengue infections, as such serosurveys provide the ideal data to reconstruct the age-dependent immunity profile of the population and to estimate the average per-capita annual risk of infection: the force of infection (FOI), which is a fundamental measure of transmission intensity. In this study, we present a novel methodological approach to inform the size and age distribution of blood samples to test when samples are acquired from previous surveys. The method was used to inform SERODEN, a dengue seroprevalence survey which is currently being conducted in Ghana among other countries utilizing samples previously collected for a SARS-CoV-2 serosurvey. The method described in this paper can be employed to determine sample sizes and testing strategies for different diseases and transmission settings. Author summary: The historical circulation of dengue virus is still poorly understood in many parts of the world, and age-stratified seroprevalence surveys can provide the data to quantify population exposure to dengue and its transmission intensity. In this work, we developed a simulation-based method that can be used to identify the sample sizes and age-distribution of the samples needed to obtain informative estimates of dengue force of infection from existing blood samples. We apply this method to data obtained from a SARS-CoV-2 serological survey, previously conducted in three cities in Ghana. The methods and code developed in this paper can be used to design serological surveys for dengue and other pathogens when using existing blood samples with accompanying information on age and location. [ABSTRACT FROM AUTHOR]

Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all Schistosoma species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10–15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response. Author summary: Schistosomiasis is a neglected tropical disease transmitted via an intermediate snail host through contact with contaminated fresh water. Even with routine Mass Drug Administration for treatment of the infection, re-infections are still common and variations in infection intensity and pathology are still observed in individuals in the same location. These may be due to differences in individuals' response to S. mansoni infection. In this study, we used RNAseq to identify differentially expressed genes associated with S. mansoni infection in children between 10–15 years. We conducted comparisons between phenotypes including infection intensities measured by circulating anodic antigen, wasting by body mass index and stunting by height-for-age Z-score. Our data showed very low numbers of significantly differentially expressed genes in all comparisons. Some of the few differentially expressed genes that were observed were associated with fibrosis which is the cause of pathology in humans and has been observed in late stages of S. mansoni infection in murine studies. [ABSTRACT FROM AUTHOR]

Background: Serum or whole blood collection, processing, transport and storage still present significant challenges in low resource settings where mass surveillance is required to sustain disease elimination. Therefore, in this study, we explored the diagnostic efficacy of dried blood spots (DBS) as a minimally invasive and potentially cost-effective alternative sampling technique to whole blood sampling procedures for subsequent detection of Leishmania donovani antibodies or DNA. Methodology and principal findings: Archived serum, DNA samples from whole blood of visceral leishmaniasis (VL) cases and healthy controls, and DBS from corresponding cases and controls, were used. Both molecular and serological assays were optimized to detect L. donovani antibodies or DNA in DBS elute and results were compared against those obtained with whole blood. Serological assays (both rK28 ELISA and rK39 ELISA) of DBS samples showed sensitivity and specificity of 100% and had excellent agreement with results from whole blood samples (kappa value ranged from 0.98–1). Bland-Altman analysis of OD values from rK28-ELISA with DBS elute and patients' serum showed an excellent agreement (ICC = 0.9) whereas a good agreement (ICC = 0.8) was observed in the case of rK39-ELISA. However, qPCR and RPA of DBS samples had a diminished sensitivity of 76% and 68%, respectively, and poor agreement was observed with the whole blood samples. Conclusion: Our results demonstrate that DBS offer excellent diagnostic efficiency for serological assays and represent a viable alternative to whole blood sampling procedures. Author summary: Since the inception of the National Kala-azar Elimination Program (NKEP) in 2005, visceral leishmaniasis (VL) cases have declined significantly in Bangladesh. Bangladesh has achieved the elimination targets set by the WHO and continuous strides have been enforced by the government and non-government organizations in the present maintenance phase. To sustain the outcomes of the NKEP, move towards a zero-transmission goal and subvert the endgame challenges, an effective surveillance strategy is a primary focus. As part of this strategy, we examined whether using dried blood spots (DBS), rather than whole blood samples as currently recommended, could serve as a minimally invasive sampling technique prior to subsequent diagnostic tests. We determined the accuracy of molecular and serological assays using DBS samples compared with whole blood samples. While using DBS, excellent diagnostic accuracy was observed for serological assays (rK28 ELISA and rK39 ELISA), whereas sensitivity and specificity using molecular assays for DNA detection (qPCR and RPA) declined in comparison to whole blood. Given the low cost and field feasibility of DBS, we believe this simple sample collection technique coupled with serology-based detection of L. donovani meets the requirements for mass surveillance towards detecting residual VL transmission. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis (PBC) is an autoimmune disorder characterized by intrahepatic bile duct destruction and cholestatic liver injury. Diagnosis of PBC is generally based on the existence of anti-mitochondrial antibody (AMA) in blood samples; however, some PBC patients are negative for serum AMA tests, and invasive liver histological testing is required in rare PBC cases. The current study seeks novel candidate genes that are associated with PBC status and have potentials for blood diagnostic testing. Human transcriptomic profiling data of liver and blood samples were obtained from Gene Expression Omnibus (GEO). Three GEO data series (GSE79850, GSE159676, and GSE119600) were downloaded, and bioinformatic analyses were performed. Various differentially expressed genes were identified in three data series by comparing PBC patients and control individuals. Twelve candidate genes were identified, which were upregulated in both liver tissues and blood samples of PBC patients in all three data series. The enrichment analysis demonstrated that 8 out of 12 candidate genes were associated with biological functions, which were closely related to autoimmune diseases including PBC. Candidate genes, especially ITGAL showed good potentials to distinguish PBC with other diseases. These candidate genes could be useful for diagnostic blood testing of PBC, although further clinical studies are required to evaluate their potentials as diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

A complete blood count (CBC) is a routinely performed blood examination. Only a few studies assess the relationship between CBC and oxidative stress (OS) in schizophrenia (SZ). The aim of the study was to assess the utility of CBC in the prediction of SZ diagnosis, and the relationship between CBC and OS. The study included: 47 individuals with the first episode of psychosis (26 drug-naive: FEP-nt; 21 patients under antipsychotic treatment: FEP-t) and 30 healthy persons (control group, HC). CBC and oxidative stress-related parameters were assessed in blood samples. The FEP group had higher levels of WBC, MCHC, NEU, MONO, EOZ, BASO, and %EOZ compared to HC (p<0.05). Various relationships between OS and CBC were found, and this connection was significantly different between healthy individuals and patients. The most promising C&RT model for discriminating FEP from HC was combining monocytes, eosinophils, and neutrophils (accuracy: 77%, 95%CI = 0.67–0.87). The analysis singled out WBC and HT (accuracy: 74%, 95%CI = 0.64–0.90) as the most promising to distinguish FEP-nt from HC; WBC and %Neu to allocate to FEP-t or HC group (accuracy: 87%, 95%CI = 0.64–0.90); RDW-SD and LYMPH (accuracy: 86%, 95% CI = 0.75–97) for distinguishing FEP-nt from FEP-t. CBC could be a promising, cheap tool to determine abnormalities related to schizophrenia. However, more studies with larger sample sizes are required. [ABSTRACT FROM AUTHOR]

Photoacoustic and absorption spectroscopy imaging are safe and non-invasive molecular quantification techniques, which do not utilize ionizing radiation and allow for repeated probing of samples without them being contaminated or damaged. Here we assessed the potential of these techniques for measuring biochemical parameters. We investigated the statistical association between 31 time and frequency domain features derived from photoacoustic and absorption spectroscopy signals and 19 biochemical blood parameters. We found that photoacoustic and absorption spectroscopy imaging features are significantly correlated with 14 and 17 individual biochemical parameters, respectively. Moreover, some of the biochemical blood parameters can be accurately predicted based on photoacoustic and absorption spectroscopy imaging features by polynomial regression. In particular, the levels of uric acid and albumin can be accurately explained by a combination of photoacoustic and absorption spectroscopy imaging features (adjusted R-squared > 0.75), while creatinine levels can be accurately explained by the features of the photoacoustic system (adjusted R-squared > 0.80). We identified a number of imaging features that inform on the biochemical blood parameters and can be potentially useful in clinical diagnosis. We also demonstrated that linear and non-linear combinations of photoacoustic and absorption spectroscopy imaging features can accurately predict some of the biochemical blood parameters. These results demonstrate that photoacoustic and absorption spectroscopy imaging systems show promise for future applications in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Envenoming by Echis spp. (carpet or saw-scaled vipers) causes haemorrhage and coagulopathy and represents a significant proportion of snakebites in the savannah regions of West Africa. Early diagnosis of envenoming is crucial in the management of these patients and there is limited evidence on the utility of the 20-minute whole blood clotting test (20WBCT) in diagnosing venom-induced consumptive coagulopathy (VICC) following envenoming by Echis ocellatus. Methods: A prospective observational cohort study was conducted at the Kaltungo General Hospital in North-eastern Nigeria from September 2019 to September 2021. Standardised 20WBCTs were conducted by trained hospital staff and citrated plasma samples were collected at numerous timepoints. Prothrombin time (PT) and international normalised ratio (INR) were determined using a semi-automated analyser and INR values were calculated using international sensitivity indices (ISI). The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and likelihood ratios of the 20WBCT compared to an INR ≥ 1.4 were calculated, alongside 95% confidence intervals. Results: We enrolled 121 patients into our study, with a median age of 26 (18.0–35.0) years and a male predominance (75.2%). The 20WBCT was positive (abnormal) in 101 out of 121 patients at timepoint 0h, of which 95 had an INR ≥ 1.4, giving a sensitivity of 87.2% (95%CI 79.4–92.8). Among patients with a negative 20WBCT (normal), six had an INR < 1.4 giving a specificity of 50% (95%CI 21.1–78.9%). The positive and negative likelihood ratios were 1.7 (95%CI 1.6–1.9) and 0.3 (95%CI 0.1–0.4) respectively. Conclusion: The 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with venom induced consumptive coagulopathy (VICC) following envenoming by E. ocellatus, although false positives do occur. Repeated 20WBCTs can identify patients with new, persistent, and rebound coagulopathy. Author summary: Bites by the West African carpet viper (Echis ocellatus) are very common in the savannah regions of west Africa and envenomed victims usually develop a bleeding syndrome. Routine laboratory coagulation tests are unavailable in health facilities where most snakebite victims are treated. We conducted analysis of 20-minute whole blood clotting tests (20WBCT) performed on snakebite patients in Kaltungo General Hospital, Nigeria who presented within 24 hours of the bite and who brought a dead snake along for snake identification, and we assessed its ability to detect venom induced consumptive coagulopathy (defined as an INR ≥1.4). In our cohort of 121 patients, the 20WBCT had a sensitivity of 87% and a specificity of 50% in detecting VICC. Performing the 20WBCT increased the probability of detecting VICC among our study participants, and it was useful in identifying patients with persistent and rebound coagulopathies who may require extra doses of antivenom. Our findings show that the 20WBCT is a simple, cheap, and easily accessible bedside test with a high sensitivity for the detection of patients with VICC following carpet viper envenoming in North-eastern Nigeria. [ABSTRACT FROM AUTHOR]

This study aimed at exploring the proteomic profile of PBMCs to predict treatment response in pulmonary tuberculosis (PTB). This was a pilot study conducted among 8 adult patients from Zanzibar, Tanzania with confirmed PTB. Blood samples were collected at baseline, at 2 months of treatment, and at the end of treatment at 6 months. Proteins were extracted from PBMCs and analyzed using LC-MS/MS based label free quantitative proteomics. Overall, 3,530 proteins were quantified across the samples, and 12 differentially expressed proteins were identified at both 2 months of treatment and at treatment completion, which were involved in cellular and metabolic processes, as well as binding and catalytic activity. Seven were downregulated proteins (HSPA1B/HSPA1A, HSPH1, HSP90AA1, lipopolysaccharide-binding protein, complement component 9, calcyclin-binding protein, and protein transport protein Sec31A), and 5 proteins were upregulated (SEC14 domain and spectrin repeat-containing protein 1, leucine-rich repeat-containing 8 VRAC subunit D, homogentisate 1,2-dioxygenase, NEDD8-activating enzyme E1 regulatory subunit, and N-acetylserotonin O-methyltransferase-like protein). The results showed that proteome analysis of PBMCs can be used as a novel technique to identify protein abundance change with anti-tuberculosis treatment. The novel proteins elucidated in this work may provide new insights for understanding PTB pathogenesis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) incidence in Malaysia is increasing, and most CRC patients are diagnosed at a late stage. This study investigated participant awareness of CRC and their perceptions and views about CRC screening, barriers, benefits, and facilitators towards CRC screening participation as well as health-seeking behaviour and the use of preventative health services. Method: Eleven focus group discussions (FGDs) were conducted with a purposive sample of 89 participants aged > 50 from the major ethnic groups in the Segamat District, Johor State. FGDs were audiotaped, transcribed verbatim, and translated into English. Data were analysed using thematic analysis. Results: We identified trust in doctors as a key reason for whether or not to seek health care. Generally, the participants had low awareness of CRC sign/symptoms and screening. Emotional and logistic concerns about sending a stool sample to a clinic emerged as the main barriers to screening. Simplified illustrated instructions about stool collection in Malay, Chinese and Tamil, free screening at health clinics and reminders to complete the iFOBT test were perceived to facilitate engagement in screening, and posited as strategies that were likely to increase iFOBT uptake. Conclusion: Primary care physicians play a crucial role in terms of reducing patient's misperceptions, recommending screening to patients, enhancing attendance, and improving uptake of CRC screening. There is a need for further research to investigate ways in which to reduce identified barriers and implement and test potential facilitative strategies as well as examine adherence by doctors to clinical guidelines about CRC screening. [ABSTRACT FROM AUTHOR]

Expert consensus on the potential benefits of early cancer detection does not exist for most cancer types. We convened 10 practicing oncologists using a RAND/UCLA modified Delphi panel to evaluate which of 20 solid tumors, representing >40 American Joint Committee on Cancer (AJCC)-identified cancer types and 80% of total cancer incidence, would receive potential clinical benefits from early detection. Pre-meeting, experts estimated how long cancers take to progress and rated the current curability and benefit (improvement in curability) of an annual hypothetical multi-cancer screening blood test. Post-meeting, experts rerated all questions. Cancers had varying estimates of the potential benefit of early cancer detection depending on estimates of their curability and progression by stage. Cancers rated as progressing quickly and being curable in earlier stages (stomach, esophagus, lung, urothelial tract, melanoma, ovary, sarcoma, bladder, cervix, breast, colon/rectum, kidney, uterus, anus, head and neck) were estimated to be most likely to benefit from a hypothetical screening blood test. Cancer types rated as progressing quickly but having comparatively lower cure rates in earlier stages (liver/intrahepatic bile duct, gallbladder, pancreas) were estimated to have medium likelihood of benefit from a hypothetical screening blood test. Cancer types rated as progressing more slowly and having higher curability regardless of stage (prostate, thyroid) were estimated to have limited likelihood of benefit from a hypothetical screening blood test. The panel concluded most solid tumors have a likelihood of benefit from early detection. Even among difficult-to-treat cancers (e.g., pancreas, liver/intrahepatic bile duct, gallbladder), early-stage detection was believed to be beneficial. Based on the panel consensus, broad coverage of cancers by screening blood tests would deliver the greatest potential benefits to patients. [ABSTRACT FROM AUTHOR]

Introduction: The goal in appendicitis is early diagnosis and early treatment. Complications develop as treatment is delayed. Therefore, there is a need for fast, low-cost markers that can be diagnosed earlier. The aim of this study is to show the effectiveness of immature granulocyte (IG) level in determining the complication of acute appendicitis. Method: In this retrospective cross-sectional study, 99 patients with acute appendicitis and 41 control groups were included in the study. Acute appendicitis patients were divided into two groups as acute simple appendicitis(n = 65) and acute complicated appendicitis(n = 34). In all groups, demographic data, immature granulocyte (IG) count(x103/μL), IG ratio (IG%), white blood cell (WBC), polymorphonuclear leukocytes (PNL), lymphocyte, monocyte, platelet, mean platelet volume (MPV), ferritin levels were recorded. The blood analyses were performed the Mindray BC6800 automated hematology analyzer using standard laboratory protocols. All statistical testing was undertaken using IBM SPSS Statistics for Mac. Results: Compared to the acute simple appendicitis, acute complicated appendicitis patients had significantly higher levels WBC, PNL, monocyte, IG count, and IG% (p = 0.009, p = 0047, p = 0.001, p = 0.018; respectively) while there was no significant difference in ferritin between groups (p = 0.49). In the ROC analysis, AUC value was found for IG count and IG% (0.893 and 0.725, cut-off 0.005 and 0.05; respectively) for acute appendicitis. The negative predictive value of IG for Acute Appendicitis was 85% and was the same as that of WBC. In acute complicated appendicitis, the AUC for IG and IG% was 0.796 (cut-off 0.02) and 0.693 (cut-off 0.2), respectively. Positive Likelihood Ratio (+LR; 2.1) value of IG was found higher than other complete blood count (CBC) tests. Conclusion: The IG count is test with fast, more predictive value than another CBC tests, and without cost in the early diagnosis of acute complicated appendicitis. It is strong negative predictive test for Acute Appendicitis disease. [ABSTRACT FROM AUTHOR]

Seroprevalence studies can contribute to a better assessment of the actual incidence of infection. Since long-term data for Germany are lacking, we determined the seroprevalence of immunoglobulin G (IgG) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in residual plasma samples of 3,759 German regular blood donors between July 2020 and June 2021. Over almost the entire study period, the incidences determined based on our data were higher than those officially reported by the Robert Koch Institute, the public health institute in Germany. Using our serological testing strategy, we retrospectively detected natural infection in 206/3,759 (5.48%; 95% confidence interval (CI): 4.77–6.25) individuals. The IgG seroprevalence ranked from 5.15% (95% CI: 3.73–6.89) in Lower Saxony to 5.62% (95% CI: 4.57–6.84) in North Rhine Westphalia. The analyses of follow-up samples of 88 seropositive blood donors revealed a comparable fast decay of binding and neutralizing anti-SARS-CoV-2 IgG antibodies. The antibody avidity remained at a low level throughout the whole follow-up period of up to 181 days. Interestingly, female donors seem to express a stronger and longer lasting humoral immunity against the new coronavirus when compared to males. Conclusion: Overall, our data emphasizes that seroprevalence measurements can and should be used to understand the true incidence of infection better. Further characterization of follow-up samples from seropositive donors indicated rapid antibody waning with sex-specific differences concerning the strength and persistence of humoral immune response. [ABSTRACT FROM AUTHOR]

Background: Flow cytometric analysis of peripheral blood neutrophil myeloperoxidase expression is accurate in ruling out myelodyplastic syndromes (MDS) but might not be suitable for implementation in busy clinical laboratories. We aimed to simplify the original gating strategy and examine its accuracy. Methods: Using the individual data from 62 consecutive participants enrolled in a prospective validation study, we assessed the agreement in intra-individual robust coefficient of variation (RCV) of peripheral blood neutrophil myeloperoxidase expression and compared diagnostic accuracy between the simplified and original gating strategies. Results: Cytomorphological evaluation of bone marrow aspirate confirmed MDS in 23 patients (prevalence, 37%), unconfirmed MDS in 32 patients (52%), and was uninterpretable in 7 patients (11%). Median intra-individual RCV for simplified and original gating strategies were 30.7% (range, 24.7–54.4) and 30.6% (range, 24.7–54.1), with intra-class correlation coefficient quantifying absolute agreement equal to 1.00 (95% confidence interval [CI], 0.99 to 1.00). The areas under the receiver operating characteristic (ROC) curves were 0.93 (95% CI, 0.82–0.98) and 0.92 (95% CI, 0.82–0.98), respectively (P =.32). Using simplified or original gating strategy, intra-individual RCV values lower than a pre-specified threshold of 30.0% ruled out MDS for 35% (19 of 55) patients, with both sensitivity and negative predictive value estimates of 100%. Conclusions: The simplified gating strategy performs as well as the original one for ruling out MDS and has the potential to save time and reduce resource utilization. Yet, prospective validation of the simplified gating strategy is warranted before its adoption in routine. Trial registration: ClinicalTrials.gov Identifier: NCT03363399 (First posted on December 6, 2017). [ABSTRACT FROM AUTHOR]

Objective: To determine the expression profile of microRNAs in the peripheral blood of pregnant women with preterm premature rupture of membranes (PPROM) compared to that of healthy pregnant women. Study design: This was a pilot study with case-control design in pregnant patients enrolled between January 2017 and June 2019. Patients with healthy pregnancies and those affected by PPROM between 20- and 33+6 weeks of gestation were matched by gestational age and selected for inclusion to the study. Patients were excluded for multiple gestation and presence of a major obstetrical complication such as preeclampsia, diabetes, fetal growth restriction and stillbirth. A total of ten (n = 10) controls and ten (n = 10) patients with PPROM were enrolled in the study. Specimens were obtained before administration of betamethasone or intravenous antibiotics. MicroRNA expression was analyzed for 800 microRNAs in each sample using the NanoString nCounter Expression Assay. Differential expression was calculated after normalization and log2- transformation using the false discovery rate (FDR) method at an alpha level of 5%. Results: Demographic characteristics were similar between the two groups. Of the 800 miRNAs analyzed, 116 were differentially expressed after normalization. However, only four reached FDR-adjusted statistical significance. Pregnancies affected by PPROM were characterized by upregulation of miR-199a-5p, miR-130a-3p and miR-26a-5p and downregulation of miR-513b-5p (FDR adjusted p-values <0.05). The differentially expressed microRNAs participate in pathways associated with altered collagen and matrix metalloprotease expression in the extracellular matrix. Conclusion: Patients with PPROM have a distinct peripheral blood microRNA profile compared to healthy pregnancies as measured by the NanoString Expression Assay. [ABSTRACT FROM AUTHOR]

Despite the world-wide prevalence of hypertension, there is a lack in open-source software for analyzing blood pressure data. The R package bp fills this gap by providing functionality for blood pressure data processing, visualization, and feature extraction. In addition to the comprehensive functionality, the package includes six sample data sets covering continuous arterial pressure data (AP), home blood pressure monitoring data (HBPM) and ambulatory blood pressure monitoring data (ABPM), making it easier for researchers to get started. The R package bp is publicly available on CRAN and at https://github.com/johnschwenck/bp. [ABSTRACT FROM AUTHOR]

The disruptive potentials of drones are rapidly growing including for the delivery of blood samples in healthcare. Maintenance of the quality of blood samples is important to ascertain that the drone is a safe mode of transportation, particularly during emergencies and in critical cases. The influence of the drone carriage material on blood samples transportation was investigated in this study. Two phases of drone simulation flights were conducted in Cyberjaya, Malaysia. In Phase 1, the effect of drone carriage material on the internal storage temperature during blood samples transportation was determined. Three types of carriage materials were compared: aluminium, expanded polystyrene (EPS) foam, and polypropylene (PP) plastic. In Phase 2, the quality of drone-transported blood samples was assessed, using the best material from Phase 1 as the drone carriage material. Biochemical and hematological analyses of 60 blood samples were conducted using five parameters. In Phase 1, EPS foam was found to be the best material to maintain a stable and favorable internal storage temperature at mean kinetic temperature ±SD of 4.70 ±1.14°C. Much higher and unfavorable mean kinetic temperatures were recorded for aluminium (11.46 ±0.35°C) and plastic (14.17 ±0.05°C). In Phase 2, laboratory tests show that the quality of blood samples was well maintained, and the mean biochemical and hematological parameters of drone-transported blood samples showed no significant alteration compared to ground controls. Drone carriage material is an important determinant of the quality of blood samples transported by drone, particularly in hot equatorial climates as in Malaysia. The blood storage temperature was best maintained using EPS foam, as evidenced by the favorable average temperature and preservation of hematological and biochemical parameters of the blood samples. [ABSTRACT FROM AUTHOR]

Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June and September 2020. The aim was to determine the extent of infection spread and whether seroprevalence varied demographically in proportion to reported cases of infection. The design involved stratified sampling of residual specimens from blood donors (aged 20–69 years) in three postcode groups defined by low (<3 cases/1,000 population), medium (3–7 cases/1,000 population) and high (>7 cases/1,000 population) COVID-19 incidence based on case notification data. All specimens were tested using the Wantai SARS-CoV-2 total antibody assay. Seroprevalence was estimated with adjustment for test sensitivity and specificity for the Melbourne metropolitan blood donor and residential populations, using multilevel regression and poststratification. Overall, 4,799 specimens were collected between 23 November and 17 December 2020. Seroprevalence for blood donors was 0.87% (90% credible interval: 0.25–1.49%). The highest estimates, of 1.13% (0.25–2.15%) and 1.11% (0.28–1.95%), respectively, were observed among donors living in the lowest socioeconomic areas (Quintiles 1 and 2) and lowest at 0.69% (0.14–1.39%) among donors living in the highest socioeconomic areas (Quintile 5). When extrapolated to the Melbourne residential population, overall seroprevalence was 0.90% (0.26–1.51%), with estimates by demography groups similar to those for the blood donors. The results suggest a lack of extensive community transmission and good COVID-19 case ascertainment based on routine testing during Victoria's second epidemic wave. Residual blood donor samples provide a practical epidemiological tool for estimating seroprevalence and information on population patterns of infection, against which the effectiveness of ongoing responses to the pandemic can be assessed. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is an ongoing pandemic leading to exhaustion of the hospital care system. Our health care system has to deal with a high level of sick leave of health care workers (HCWs) with COVID-19 related complaints, in whom an infection with SARS-CoV-2 has to be ruled out before they can return back to work. The aim of the present study is to investigate if the recently described CoLab-algorithm can be used to exclude COVID-19 in a screening setting of HCWs. Methods: In the period from January 2021 till March 2021, HCWs with COVID-19-related complaints were prospectively collected and included in this study. Next to the routinely performed SARS-CoV-2 RT-PCR, using a set of naso- and oropharyngeal swab samples, two blood tubes (one EDTA- and one heparin-tube) were drawn for analysing the 10 laboratory parameters required for running the CoLab-algorithm. Results: In total, 726 HCWs with a complete CoLab-laboratory panel were included in this study. In this group, 684 HCWs were tested SARS-CoV-2 RT-PCR negative and 42 cases RT-PCR positive. ROC curve analysis showed an area under the curve (AUC) of 0.853 (95% CI: 0.801–0.904). At a safe cut-off value for excluding COVID-19 of -6.525, the sensitivity was 100% with a specificity of 34% (95% CI: 21 to 49%). No SARS-CoV-2 RT-PCR cases were missed with this cut-off and COVID-19 could be safely ruled out in more than one third of HCWs. Conclusion: The CoLab-score is an easy and reliable algorithm that can be used for screening HCWs with COVID-19 related complaints. A major advantage of this approach is that the results of the score are available within 1 hour after collecting the samples. This results in a faster return to labour process of a large part of the COVID-19 negative HCWs (34%), next to a reduction in RT-PCR tests (reagents and labour costs) that can be saved. [ABSTRACT FROM AUTHOR]

Aims: This study established blood group analysis methods using whole-genome sequencing (WGS) data and conducted blood group analyses to determine the domestic allele frequency using public data from the Korean whole sequence analysis of the Korean Reference Genome Project conducted by the Korea Disease Control and Prevention Agency (KDCA). Materials and methods: We analyzed the differences between the human reference sequences (hg19) and the conventional reference cDNA sequences of blood group genes using the Clustal Omega website, and established blood group analysis methods using WGS data for 41 genes, including 39 blood group genes involved in 36 blood group antigens, as well as the GATA1 and KLF1 genes, which are erythrocyte-specific transcription factor genes. Using CLC genomics Workbench 11.0 (Qiagen, Aarhus, Denmark), variant analysis was performed on these 41 genes in 250 Korean WGS data sets, and each blood group's genotype was predicted. The frequencies for major alleles were also investigated and compared with data from the Korean rare blood program (KRBP) and the Erythrogene database (East Asian and all races). Results: Among the 41 blood group-related genes, hg19 showed variants in the following genes compared to the conventional reference cDNA: GYPA, RHD, RHCE, FUT3, ACKR1, SLC14A1, ART4, CR1, and GCNT2. Among 250 WGS data sets from the Korean Reference Genome Project, 70.6 variants were analyzed in 205 samples; 45 data samples were excluded due to having no variants. In particular, the FUT3, GNCT2, B3GALNT1, CR1, and ACHE genes contained numerous variants, with averages of 21.1, 13.9, 13.4, 9.6, and 7.0, respectively. Except for some blood groups, such as ABO and Lewis, for which it was difficult to predict the alleles using only WGS data, most alleles were successfully predicted in most blood groups. A comparison of allele frequencies showed no significant differences compared to the KRBP data, but there were differences compared to the Erythrogene data for the Lutheran, Kell, Duffy, Yt, Scianna, Landsteiner-Wiener, and Cromer blood group systems. Numerous minor blood group systems that were not available in the KRBP data were also included in this study. Conclusions: We successfully established and performed blood group analysis using Korean public WGS data. It is expected that blood group analysis using WGS data will be performed more frequently in the future and will contribute to domestic data on blood group allele frequency and eventually the supply of safe blood products. [ABSTRACT FROM AUTHOR]

Background: In a previous study, we had investigated the intensive care course of patients with coronavirus disease 2019 (COVID-19) in the first wave in Germany by calculating models for prognosticating in-hospital death with univariable and multivariable regression analysis. This study analyzed if these models were also applicable to patients with COVID-19 in the second wave. Methods: This retrospective cohort study included 98 critical care patients with COVID-19, who had been treated at the University Medical Center Regensburg, Germany, between October 2020 and February 2021. Data collected for each patient included vital signs, dosage of catecholamines, analgosedation, anticoagulation, and antithrombotic medication, diagnostic blood tests, treatment with extracorporeal membrane oxygenation (ECMO), intensive care scores, ventilator therapy, and pulmonary gas exchange. Using these data, expected mortality was calculated by means of the originally developed mathematical models, thereby testing the models for their applicability to patients in the second wave. Results: Mortality in the second-wave cohort did not significantly differ from that in the first-wave cohort (41.8% vs. 32.2%, p = 0.151). As in our previous study, individual parameters such as pH of blood or mean arterial pressure (MAP) differed significantly between survivors and non-survivors. In contrast to our previous study, however, survivors and non-survivors in this study showed significant or even highly significant differences in pulmonary gas exchange and ventilator therapy (e.g. mean and minimum values for oxygen saturation and partial pressure of oxygen, mean values for the fraction of inspired oxygen, positive expiratory pressure, tidal volume, and oxygenation ratio). ECMO therapy was more frequently administered than in the first-wave cohort. Calculations of expected mortality by means of the originally developed univariable and multivariable models showed that the use of simple cut-off values for pH, MAP, troponin, or combinations of these parameters resulted in correctly estimated outcome in approximately 75% of patients without ECMO therapy. [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3–60.0%) sensitivity and a 98.5% (95% CI: 97.0–99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4–90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3–68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs. [ABSTRACT FROM AUTHOR]

Background: The Comprehensive Case Management Project (CCMP), was a collaborative implementation research initiative to strengthen malaria early detection and complete treatment in Odisha State, India. Methods: A two-arm quasi-experimental design was deployed across four districts in Odisha, representing a range of malaria endemicity: Bolangir (low), Dhenkanal (moderate), Angul (high), and Kandhamal (hyper). In each district, a control block received routine malaria control measures, whereas a CCMP block received a range of interventions to intensify surveillance, diagnosis, and case management. Impact was evaluated by difference-in-difference (DID) analysis and interrupted time-series (ITS) analysis of monthly blood examination rate (MBER) and monthly parasite index (MPI) over three phases: phase 1 pre-CCMP (2009–2012) phase 2 CCMP intervention (2013–2015), and phase 3 post-CCMP (2016–2017). Results: During CCMP implementation, adjusting for control blocks, DID and ITS analysis indicated a 25% increase in MBER and a 96% increase in MPI, followed by a –47% decline in MPI post-CCMP, though MBER was maintained. Level changes in MPI between phases 1 and 2 were most marked in Dhenkanal and Angul with increases of 976% and 287%, respectively, but declines in Bolangir (−57%) and Kandhamal (−22%). Between phase 2 and phase 3, despite the MBER remaining relatively constant, substantial decreases in MPI were observed in Dhenkanal (−78%), and Angul (−59%), with a more modest decline in Bolangir (−13%), and an increase in Kandhamal (14%). Conclusions: Overall, CCMP improved malaria early detection and treatment through the enhancement of the existing network of malaria services which positively impacted case incidence in three districts. In Kandhamal, which is hyperendemic, the impact was not evident. However, in Dhenkanal and Angul, areas of moderate-to-high malaria endemicity, CCMP interventions precipitated a dramatic increase in case detection and a subsequent decline in malaria incidence, particularly in previously difficult-to-reach communities. [ABSTRACT FROM AUTHOR]

Background: Chinese herbs for supplementing qi and activating blood circulation (CH) combined with N-acetylcysteine (NAC) is widely used for idiopathic pulmonary fibrosis (IPF) in China, but there is a lack of literature to evaluate its efficacy and clinical value. Purpose: This study compared CH + NAC with other treatments by network meta-analysis to clarify its clinical value. Methods: Cochrane Library, PubMed, Embase, Web of Science, China National Knowledge Infrastructure, WanFang Data, VIP Database, and China Biology Medicine were searched. Outcomes included lung function (DLCO (%), VC (%), FVC (%), FVC (L)), 6-min walking distance (6MWD), score of St George's respiratory questionnaire (SGRQ), blood gas analysis (PaO2, PaCO2). The data were analyzed by Review Manager 5.4, Stata 12.0 and ADDIS 1.16.5. Results: 23 studies including 1390 patients (702 in intervention group and 688 in control group) were collected to compare 8 outcome indicators among different treatments involving CH, CH+NAC, CH+PFD, NAC, PFD and PFD+NAC on IPF. Network meta-analysis showed that CH was better than NAC in terms of DLCO (%) (MD = 5.14, 95%CI: 1.01 to 8.68) and 6MWD (MD = 49.17, 95%CI: 25.97 to 71.36) as well as PFD + NAC was better than NAC in terms of FVC (L) (MD = -0.56, 95%CI: -0.83 to -0.31). In rankings results, CH + NAC is the best in terms of FVC (%), SGRQ, PaO2 and PaCO2; CH is the best in terms of DLCO (%), VC (%) and 6MWD; CH + PFD is the best in terms of FVC (L). Conclusion: CH related treatments may have advantages in the treatment of IPF and CH + NAC may have clinical application value. However, limited by the quality and quantity of researches included, more rational and scientific randomized controlled trials containing large sample sizes need to be conducted to further verify our conclusions. [ABSTRACT FROM AUTHOR]

Fig 8 is in the position Fig 5 should be in and Fig 5 is in the position Fig 8 should be in. Correction: The 20-minute whole blood clotting test (20WBCT) for snakebite coagulopathy - A systematic review and meta-analysis of diagnostic test accuracy There are errors in Fig 5 and Fig 8. [Extracted from the article]

Chagas disease is mainly transmitted by triatomine insect vectors that feed on vertebrate blood. The disease has complex domiciliary infestation patterns and parasite transmission dynamics, influenced by biological, ecological, and socioeconomic factors. In this context, feeding patterns have been used to understand vector movement and transmission risk. Recently, a new technique using Liquid chromatography tandem mass spectrometry (LC-MS/MS) targeting hemoglobin peptides has showed excellent results for understanding triatomines' feeding patterns. The aim of this study was to further develop the automated computational analysis pipeline for peptide sequence taxonomic identification, enhancing the ability to analyze large datasets data. We then used the enhanced pipeline to evaluate the feeding patterns of Triatoma dimidiata, along with domiciliary infestation risk variables, such as unkempt piles of firewood or construction material, cracks in bajareque and adobe walls and intradomiciliary animals. Our new python scripts were able to detect blood meal sources in 100% of the bugs analyzed and identified nine different species of blood meal sources. Human, chicken, and dog were the main blood sources found in 78.7%, 50.4% and 44.8% of the bugs, respectively. In addition, 14% of the bugs feeding on chicken and 15% of those feeding on dogs were captured in houses with no evidence of those animals being present. This suggests a high mobility among ecotopes and houses. Two of the three main blood sources, dog and chicken, were significantly (p < 0.05) affected by domiciliary infestation risk variables, including cracks in walls, construction material and birds sleeping in the intradomicile. This suggests that these variables are important for maintaining reproducing Triatoma dimidiata populations and that it is critical to mitigate these variables in all the houses of a village for effective control of these mobile vectors. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B is endemic in Lao PDR and about 9% of the adult population is chronically infected. In this study, we investigated regional, occupational, age and sex-related differences in hepatitis B epidemiology in Lao blood donors. Methods: 5017 voluntary blood donors from 8 different provinces were tested for hepatitis B markers by ELISA. Predictors for the prevalence of hepatitis B surface antigen (HBsAg) and antibodies against the core antigen (anti-HBc) were assessed by bivariate and multivariable analyses. Results: In total, 41% of the participants were positive for anti-HBc; the HBsAg prevalence was estimated at 6.9% among all participants (9.2% among first-time donors and 3.9% among repeat donors). Among first-time donors, HBsAg positivity was associated independently with being male (p<0.001), being from the North (p<0.001) and being soldier (p<0.001). Participants were more likely to be anti-HBc positive when they were male (p<0.001), from the Northern provinces (p<0.001) and older than 20 years (p<0.01). Conclusion: In conclusion, our study confirmed an overall high HBsAg and anti-HBc prevalence in Lao PDR, albeit with considerable regional variation. The identification of a sizeable number of HBsAg positives among repeat donors warrants a thorough investigation of current blood screening, record keeping, donor identification and counselling practises. [ABSTRACT FROM AUTHOR]

Several studies of patients with COVID-19 have evaluated biological markers for predicting outcomes, most of them retrospectively and with a wide scope of clinical severity. We followed a prospective cohort of patients admitted in hospital wards with moderate COVID-19 disease, including those with a history of kidney transplantation, and examined the ability of changes in routine hematologic laboratory parameters to predict and mirror the patients' clinical course regarding the severity of their condition (classified as critical vs. non-critical) and in-hospital mortality or hospital discharge. Among the 68 patients, 20 (29%) were kidney transplanted patients (KT), and they had much higher mortality than non-kidney transplanted patients in this cohort (40% X 8.3%). Lymphocytes, neutrophils and neutrophils/lymphocytes ratio (NLR) at admission and platelets as well as the red blood cells parameters hemoglobin, hematocrit, and RDW by the time of hospital discharge or death clearly differentiated patients progressing to critical disease and those with clinical recovery. Patients with deteriorating clinical courses presented elevated and similar NLRs during the first week of hospitalization. However, they were dramatically different at hospital discharge, with a decrease in the survivors (NLR around 5.5) and sustained elevation in non-survivors (NLR around 21). Platelets also could distinguish survivors from non-survivors among the critical patients. In conclusion, routine hematologic tests are useful to monitor the clinical course of COVID-19 patients admitted with moderate disease. Unexpectedly, changes in hematologic tests, including lymphopenia, were not predictive of complicated outcomes among KT recipients. [ABSTRACT FROM AUTHOR]

The uptake of the immunochemical faecal occult blood test (iFOBT) in many countries with an opportunistic colorectal cancer (CRC) screening programme remains suboptimal. This study aimed to determine the rate, associated factors and reasons of refusal to perform the iFOBT test offered under an opportunistic CRC screening programme in semi-urban communities. This cross-sectional study was conducted among the average-risk individuals living in semi-urban areas, who sought care from public primary care centres across Kedah state, Malaysia. The information regarding the sociodemographic and clinical characteristics of individuals who were offered the iFOBT between January and April 2019, along with their willingness to perform the test, was gathered. The factors associated with the refusal were further explored using the logistic regression analysis. The individuals offered the iFOBT (n = 920) were mainly female (52.4%) and had a mean age of 58.7±10.6 years. The refusal rate of the iFOBT was 32.2%. Patients who did not have hypertension (adjusted OR: 3.33; 95% CI: 2.44, 4.54), did not have CRC symptoms (adjusted OR: 3.15; 95% CI:1.26, 7.89), had the test offered by either medical assistants (adjusted OR: 2.44; 95% CI: 1.71, 3.49) or nurses (adjusted OR: 2.41; 95% CI 1.65, 3.51), did not have diabetes (adjusted OR: 1.99; 95% CI: 1.42, 2.77),and were not active smokers (adjusted OR: 1.74; 95% CI: 1.22, 2.47), were more likely to refuse the iFOBT. The common reasons of refusing the test included "feeling not ready for the test" (21.6%) and "feeling healthy" (14.9%). The iFOBT was refused by one-third of the average-risk individuals from semi-urban communities. The associated factors and reasons of refusal found in this study could guide policymakers in developing targeted interventions to boost the uptake of CRC screening in Malaysia. [ABSTRACT FROM AUTHOR]

Background: Numerous studies on involuntary weight loss (IWL) have been published since the 1980s, although most of them have included small samples of patients with specific symptoms. The aim of the present study was to determine the causes, demographic and clinical characteristics and mortality at 12 months in patients attended at a rapid diagnostic unit (RDU) for isolated IWL. Methods: A single-center retrospective observational study including all patients presenting to the RDU for isolated IWL between 2005 and 2013. The following data were recorded: demographic and clinical variables, results of complementary tests (blood tests, x-rays, computed tomography scan and digestive endoscopy), main diagnosis and vital status at 12 months. Results: Seven hundred and ninety-one patients met the criteria for IWL. Mean age was 67.9 years (SD 4.7), 50.4% were male and mean weight loss was 8.3 kg (SD 4.7). The cause for IWL was malignant disease in 23.6% of patients, non-malignant organic disease in 44.5%, psychiatric disorder in 29.0% and unknown in 3.2%. Overall mortality at 12 months was 18.6% (95%CI: 16.1–21.6). The mortality rate was highest in the group with malignancy (61.1%; 95%CI: 54.2–68.2). Conclusions: Almost a quarter of all patients attended at the RDU for IWL were diagnosed with cancer. Mortality at 12 months was higher in this group than in the other three. Malignancy should therefore be ruled out during the first visit for patients attended for IWL. [ABSTRACT FROM AUTHOR]

Background: Virological failure is under-recognized issue among children living with human immunodeficiency virus in developing countries. This partly may lead to failure to achieve the global goal of 90-90-90 targets in most developing countries including Ethiopia. Objectives: This study aimed to assess the virological failure and its predictors among children receiving antiretroviral therapy at the University of Gondar comprehensive specialized hospital, Northwest Ethiopia. Methods: An institutional based cross-sectional study was conducted among 253 study cohorts from January 2020-April 2021. Socio-demographic characteristics were collected using a structured questionnaire via a face-to-face interview, while detailed clinical data of the children were collected by reviewing the medical record. About 5 ml of blood were collected for the analysis of complete blood count and viral load quantification. Data were analyzed using SPSS version 20 and variables at p-value < 0.05 in the multivariable analysis were considered as statistically significant. Results: In this study, the viral load suppression rate among antiretroviral therapy experienced children was 68.8%. Meanwhile, the overall virological failure among study participants was 19.4%. Children living without family (AOR = 3.63; 95%CI: 1.27–10.24), children with unemployed family (AOR = 4.95; 95%CI: 1.74–14.12), being wasted (AOR = 3.02; 95%CI: 1.19–7.67) being stunted (AOR = 2.38;95%CI:1.03–5.46), anemia (AOR = 5.50:95%CI;1.37–22.04) and being lymphopenic (AOR = 2.69:95%CI;1.04–7.75) were significantly associated with virological failure among children under treatment. Conclusion: Higher virological failure among children was noteworthy in the present study. Caretakers other than immediate family, unemployed family, wasted, stunted, anemia, and lymphopenia were significant independent predictors of virological failure. Hence, standard, and optimal management of children under treatment should be warranted. [ABSTRACT FROM AUTHOR]

Background: Efforts to minimize COVID-19 exposure during the current SARS-CoV-2 pandemic have led to limitations in access to medical care and testing. The Tasso-SST kit includes all of the components necessary for remote, capillary blood self-collection. In this study, we sought to investigate the accuracy and reliability of the Tasso-SST device as a self-collection device for measurement of SARS-CoV-2 IgG antibodies. Methods: Capillary blood was obtained via unsupervised and supervised application of the Tasso-SST device, and venous blood was collected by standard venipuncture. Unsupervised self-collected blood samples underwent either extreme summer or winter-simulated shipping conditions prior to testing. Sera obtained by all three methods were tested concurrently using the EuroImmun anti-SARS-CoV-2 S1 IgG assay in a CLIA-certified clinical laboratory. Results: Successful Tasso-SST capillary blood collection by unsupervised and supervised administration was completed by 93.4% and 94.5% of participants, respectively. Sera from 56 participants, 55 with documented (PCR+) COVID-19, and 33 healthy controls were then tested for anti-SARS-CoV-2 IgG antibodies. Compared to venous blood results, Tasso-SST-collected (unstressed) and the summer- and winter-stressed blood samples demonstrated Deming regression slopes of 1.00 (95% CI: 0.99–1.02), 1.00 (95% CI: 0.98–1.01), and 0.99 (95% CI: 0.97–1.01), respectively, with an overall accuracy of 98.9%. Conclusions: Capillary blood self-collection using the Tasso-SST device had a high success rate. Moreover, excellent concordance was found for anti-SARS-CoV-2 IgG results between Tasso-SST capillary and standard venous blood-derived sera. The Tasso-SST device should enable widespread collection of capillary blood for testing without medical supervision, facilitating epidemiologic studies. [ABSTRACT FROM AUTHOR]

Background: Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer.Methods and Findings: We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors.Conclusions: Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral. [ABSTRACT FROM AUTHOR]

Background: Loa loa and Mansonella perstans–the causative agents of loiasis and mansonellosis—are vector-borne filarial parasites co-endemic in sub-Saharan Africa. Diagnosis of both infections is usually established by microscopic analysis of blood samples. It was recently established that the odds for detecting Plasmodium spp. is higher in capillary (CAP) blood than in venous (VEN) blood. In analogy to this finding this analysis evaluates potential differences in microfilaraemia of L. loa and M. perstans in samples of CAP and VEN blood. Methods: Recruitment took place between 2015 and 2019 at the CERMEL in Lambaréné, Gabon and its surrounding villages. Persons of all ages presenting to diagnostic services of the research center around noon were invited to participate in the study. A thick smear of each 10 microliters of CAP and VEN blood was prepared and analysed by a minimum of two independent microscopists. Differences of log2-transformed CAP and VEN microfilaraemia were computed and expressed as percentages. Furthermore, odds ratios for paired data were computed to quantify the odds to detect microfilariae in CAP blood versus in VEN blood. Results: A total of 713 participants were recruited among whom 52% were below 30 years of age, 27% between 30–59 years of age and 21% above 60 years of age. Male-female ratio was 0.84. Among 152 participants with microscopically-confirmed L. loa infection median (IQR) microfilaraemia was 3,650 (275–11,100) per milliliter blood in CAP blood and 2,775 (200–8,875) in VEN blood (p<0.0001), while among 102 participants with M. perstans this was 100 (0–200) and 100 (0–200), respectively (p = 0.44). Differences in linear models amount up to an average of +34.5% (95% CI: +11.0 to +63.0) higher L. loa microfilaria quantity in CAP blood versus VEN blood and for M. perstans it was on average higher by +24.8% (95% CI: +0.0 to +60.5). Concordantly, the odds for detection of microfilaraemia in CAP samples versus VEN samples was 1.24 (95% CI: 0.65–2.34) and 1.65 (95% CI: 1.0–2.68) for infections with L. loa and M. perstans, respectively. Conclusion: This analysis indicates that average levels of microfilaraemia of L. loa are higher in CAP blood samples than in VEN blood samples. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was higher in CAP than in VEN blood which may pre-dispose CAP blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in CAP blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in CAP and VEN blood above the limit of detection of 100 microfilariae/ml. Yet, it cannot be excluded that the study was underpowered to detect a moderate difference. Author summary: Microfilaraemia of Loa loa and Mansonella perstans was investigated by light microscopy in paired thick smears of capillary and venous blood; each sample was prepared using a standardised quantity of 10 microliters of blood and analysed by a minimum of two independent microscopists. Microfilaraemia was on average +34.5% (95% CI: +11.0 to +63.0) higher in capillary than in venous blood samples for L. loa and +24.8% (95% CI: +0.0 to +60.5) for M. perstans. This might have implications for treatment algorithms of onchocerciasis and loiasis, in which exact quantification of L. loa microfilaraemia is of importance. Furthermore, the odds for detection of M. perstans microfilariae was 65% higher in capillary than in venous blood which may pre-dispose capillary blood for detection of M. perstans infection in large epidemiological studies when sampling of large blood quantities is not feasible. No solid evidence for a higher odds of L. loa microfilariae detection in capillary blood was revealed, which might be explained by generally high levels of L. loa microfilaraemia in capillary and venous blood. [ABSTRACT FROM AUTHOR]

Background: The 20-minute whole blood clotting test (20WBCT) has been used to detect coagulopathy following snakebite for almost 50 years. A systematic review and meta-analysis of the 20WBCT was conducted to evaluate the accuracy of the 20WBCT to detect coagulopathy, indicative of systemic envenoming. Methods and findings: Databases were searched from inception up to 09/12/2020 to identify studies that compared the 20WBCT and INR/fibrinogen on five or more subjects. Data was extracted from full-text articles by two reviewers using a predetermined form. Authors of 29 studies that lacked sufficient details in the manuscript were contacted and included if data meeting the inclusion criteria were provided. Included studies were evaluated for bias using a tailored QUADAS-2 checklist. The study protocol was prospectively registered on PROSPERO database (CRD42020168953). The searches identified 3,599 studies, 15 met the inclusion criteria and 12 were included in the meta-analysis. Data was reported from 6 countries and included a total of 2,270 patients. The aggregate weighted sensitivity of the 20WBCT at detecting INR >1.4 was 0.84 (CI 0.61 to 0.94), the specificity was 0.91 (0.76 to 0.97) and the SROC AUC was 0.94 (CI 0.91 to 0.96). The aggregate weighted sensitivity of the 20WBCT at detecting fibrinogen <100 mg/dL was 0.72 (CI 0.58 to 0.83), the specificity was 0.94 (CI 0.88 to 0.98) and the SROC AUC was 0.93 (0.91 to 0.95). Both analyses that used INR and fibrinogen as the reference test displayed considerable heterogeneity. Conclusions: In the absence of laboratory clotting assays, the 20WBCT remains a highly specific and fairly sensitive bedside test at detecting coagulopathy following snakebite. However, clinicians should be aware of the importance of operator training, standardized equipment and the lower sensitivity of the 20WBCT at detecting mild coagulopathy and resolution of coagulopathy following antivenom. Author summary: Snakebite is a neglected tropical disease and responsible for an estimated 130,000 deaths per year. Coagulopathy is the commonest clinical manifestation of systemic snakebite envenoming and is indicative of a need for antivenom. The 20WBCT is a simple, cheap and quick bedside clotting test devised to detect coagulopathy after snakebite. The test is used widely and is incorporated in multiple national and WHO guidelines. However, following a publication questioning its diagnostic accuracy, there is a lack of consensus regarding its diagnostic accuracy and utility. In this review, we conclude that the 20WBCT is capable of detecting coagulopathy following snakebite with high specificity and acceptable sensitivity. Diagnostic test accuracy of the 20WBCT is improved when assessing for the presence of severe coagulopathy. Inclusion of data in this analysis from a variety of countries, make the findings widely applicable. However, the heterogeneity in study findings indicates the need for local assessment of external validity. The results of this study support the WHO guidelines that recommend its continued use in the absence of conventional laboratory clotting assays. Urgent efforts are required to identify an optimal method of detecting systemic snakebite envenoming and the response to treatment through pharmacokinetic and pharmacodynamic studies of venom and antivenom. [ABSTRACT FROM AUTHOR]

This study assessed the postoperative severity after three different visceral surgical interventions in rats by using objective parameters pertaining to various disciplines. The objective was to evaluate whether the degree of severity increases with the invasiveness of the intervention and whether this is in accordance with the EU Directive 2010/63. 136 adult male WistarHan rats were assigned to three groups: Sham-laparotomy (Sham) [7 days post-surgical survival time]; 50% partial hepatectomy (PH); 70% PH [PH groups with 1, 3, or 7 days post-surgical survival times]. Post-surgical severity assessment was performed via several multimodal assessment tools: I) model-specific score sheet focusing on body weight, general condition, spontaneous behavior, and the animals' willingness to move as well as on wound healing; II) Open Field tests evaluating the total distance and velocity an animal moved within 10 minutes and its rearing behavior during the test; III) telemetric data analyzing heart rate and blood pressure; and IV) analysis of blood (AST, ALT, and hemogram) and fecal samples (fecal corticosterone metabolites). Significant differences among the experimental groups and models were observed. We demonstrated that the Open Field test can detect significant changes in severity levels. Sham-laparotomy and removal of 50% of the liver mass were associated with comparable severity (mild–moderate); the severity parameters returned to baseline levels within seven days. Removal of 70% of the liver tissue seemed to be associated with a moderate severity grade and entailed a longer recovery period (>7 days) for complete regeneration. We recommend the use of Open Field tests as part of multimodal objective severity assessment. [ABSTRACT FROM AUTHOR]

A second wave of COVID-19 has demonstrated how challenging it will be to achieve sustained control of the disease, even with vaccination underway in many countries. Therefore, it remains relevant to keep improving our understanding of the distribution of COVID-19, especially of asymptomatic individuals, among different populations, and particularly in vulnerable regions. Hence, this population-based serosurvey had the objective of estimating the prevalence of individuals 18 years of age or older infected by SARS-CoV-2, and the proportion of asymptomatic individuals, among a vulnerable population living in an urban setting. This was a cross-sectional single-stage cluster sampling serosurvey conducted between September and December of 2019, in a vulnerable region of the city of São Paulo, Brazil. Families covered by three public primary healthcare units represented the selected clusters. After study inclusion, participants were asked about signs and symptoms related to COVID-19, and had collected 10 mL of blood for serology testing. A total of 272 individuals from 185 families were included in the study, out of the 400 eligible individuals for inclusion, resulting in a non-response rate of 32%. The post stratified prevalence of individuals infected by SARS-CoV-2 was 45.2% (95% CI: 39.4–51.0%), with a proportion of asymptomatic cases of 30.2% (95% CI: 23.3–38.0%). This population-based serosurvey identified a greater prevalence of infected individuals by SARS-CoV-2 compared to data from the beginning of the pandemic, and from a recent citywide serosurvey, with a similar proportion of asymptomatic individuals. It demonstrated the value of primary healthcare services for disease surveillance activities, and the importance of more focused serosurveys, especially in vulnerable locations, and the need to evaluate new surveillance strategies to take into account asymptomatic cases. [ABSTRACT FROM AUTHOR]