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Background: Swift identification and diagnosis of gastrointestinal infections are crucial for prompt treatment, prevention of complications, and reduction of the risk of hospital transmission. The radiological appearance on computed tomography could potentially provide important clues to the etiology of gastrointestinal infections. We aimed to describe features based on computed tomography of patients diagnosed with Campylobacter, Salmonella or Shigella infections in South Sweden. Methods: This was a retrospective observational population-based cohort study conducted between 2019 and 2022 in Skane, southern Sweden, a region populated by 1.4 million people. Using data from the Department of Clinical Microbiology combined with data from the Department of Radiology, we identified all patients who underwent computed tomography of the abdomen CTA two days before and up to seven days after sampling due to the suspicion of Campylobacter, Salmonella or Shigella during the study period. Results: A total of 215 CTA s scans performed on 213 patients during the study period were included in the study. The median age of included patients was 45 years (range 11-86 years), and 54% (114/213) of the patients were women. Of the 215 CTA s, 80% (n = 172) had been performed due to Campylobacter and 20% (n = 43) due to Salmonella enteritis. CTA was not performed for any individual diagnosed with Shigella during the study period. There were no statistically significant differences in the radiological presentation of Campylobacter and Salmonella infections. Conclusion: The most common location of Campylobacter and Salmonella infections was the cecum, followed by the ascending colon. Enteric wall edema, contrast loading of the affected mucosa, and enteric fat stranding are typical features of both infections. The CTA characteristics of Campylobacter and Salmonella are similar, and cannot be used to reliably differentiate between different infectious etiologies. [ABSTRACT FROM AUTHOR]

AbstractBackground Swift identification and diagnosis of gastrointestinal infections are crucial for prompt treatment, prevention of complications, and reduction of the risk of hospital transmission. The radiological appearance on computed tomography could potentially provide important clues to the etiology of gastrointestinal infections. We aimed to describe features based on computed tomography of patients diagnosed with Campylobacter, Salmonella or Shigella infections in South Sweden.Methods This was a retrospective observational population-based cohort study conducted between 2019 and 2022 in Skåne, southern Sweden, a region populated by 1.4 million people. Using data from the Department of Clinical Microbiology combined with data from the Department of Radiology, we identified all patients who underwent computed tomography of the abdomen CTA two days before and up to seven days after sampling due to the suspicion of Campylobacter, Salmonella or Shigella during the study period.Results A total of 215 CTAs scans performed on 213 patients during the study period were included in the study. The median age of included patients was 45 years (range 11–86 years), and 54% (114/213) of the patients were women. Of the 215 CTAs, 80% (n = 172) had been performed due to Campylobacter and 20% (n = 43) due to Salmonella enteritis. CTA was not performed for any individual diagnosed with Shigella during the study period. There were no statistically significant differences in the radiological presentation of Campylobacter and Salmonella infections.Conclusion The most common location of Campylobacter and Salmonella infections was the cecum, followed by the ascending colon. Enteric wall edema, contrast loading of the affected mucosa, and enteric fat stranding are typical features of both infections. The CTA characteristics of Campylobacter and Salmonella are similar, and cannot be used to reliably differentiate between different infectious etiologies.

Background: The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation. Methods: A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature. Results: The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals' autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation. Conclusion: The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine. [ABSTRACT FROM AUTHOR]

(1) Background: Menopause is an important event in women's lives, possibly contributing to the development of CVD, which is associated with changes in the cardiovascular risk profile, markers of metabolic health, and subclinical atherosclerosis. The aim of this study was to assess the association of menopause with CVD risk factors and subclinical markers of cardiometabolic disease. (2) Methods: The study involved 235 women from the general population at different stages of menopause. The methods used in this study were: diagnostic survey, anthropometric measurement (WC, height, BMI, WHtR), blood pressure measurement, biochemical analysis of venous blood (lipid profile, glucose, insulin, HbA1c), and CVD risk assessment (ASCVD Risk Calculator, POL-SCORE, SCORE-2). (3) Results: The vast majority of respondents had low cardiovascular risk, irrespective of the scale used for measuring the risk of CVD. The age at menopause was not an independent risk factor for CVD. In Model 1, the age at menopause and the time since menopause were found to be factors that increased CVD risk (OR = 1.186 and 1.267, respectively). In Models 2 and 3, the severity of menopausal symptoms was not a risk factor for CVD. Models 3 and 4 demonstrated that women with metabolic syndrome (MetS) were at a significantly higher risk of CVD. In model 5, the odds ratio of CVD with MetS as a standalone factor was 13.812. (4) Conclusions: Menopause predisposes women to an increased risk and MetS to a significantly higher risk of CVD. [ABSTRACT FROM AUTHOR]

The Fluorescent Carbon Quantum Dots (FCQDs) have been extensively explored for medical applications. Primarily, the research concentrated on diagnosis, imaging, and alternative therapeutics for various diseases. The FCQDs, a class of new-generation carbon nanoparticles with a size of less than 10 nm, demonstrate a quantum confinement effect. They have an atomic nature and inherent features like high photostability, variable photoluminescence (PL), high biocompatibility, and good water solubility. All these properties with minimum invasiveness have made quantum dots grab the spotlight in cancer diagnosis. The review introduces tunable fluorescence properties of quantum dots and provides a brief classification of FCQDs. Furthermore, the recent advances of FCQDs for tumor imaging and their refinements for futuristic applications are highlighted.

A 38-year-old woman presented to the emergency department with recurrent severe headaches. Although initial computer tomography (CT) brain imaging was unremarkable, a later CT venogram demonstrated a small subarachnoid haemorrhage. Magnetic resonance angiogram (MRA) brain imaging subsequently confirmed reversible cerebral vasoconstriction syndrome (RCVS). In the acute setting, RCVS rarely falls into a differential diagnosis for headache presentations, as in this case. The radiological variability can make diagnosis of RCVS challenging. However, there are clinical consistencies that can aid physicians into accurately diagnosing RCVS. A thorough history, including a medication history, can help identify potential triggers of RCVS. As in this case, the combination of commonly used drugs, including antihistamines, provides a plausible trigger for RCVS. The direct vasoactive role of antihistamines is unclear, yet there is suggestion for its ability to potentiate the vasoactive action of other drugs. In this case we propose a causal relationship between the use of antihistamine and the development of RCVS.

Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an 'RR signature' of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-β downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria. [ABSTRACT FROM AUTHOR]

Background: The presence of infections is one of the main factors that leads to delays in healing or non-closure of cutaneous wounds. Although the goal of antibiotic use is to treat or prevent infection, there is currently no agreement on the effectiveness of these products. Aim: The aim of this study was to evaluate the efficacy of antibiotic use during the healing process of skin wounds in animal models not intentionally infected, as well as to analyze the advances and limitations of the studies carried out in this field. Main methods: This systematic review was performed according to the PRISMA guidelines, using a structured search on the MedLine (PubMed) and Scopus platforms to retrieve studies published until August 29, 2018, 13:35p.m. The studies included were limited to those that used excision or incision wound models and that were not intentionally infected. The data for the animal models, antibiotic used, and the main results of the studies were extracted, and compared where possible. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Key findings: Twenty-seven studies were selected. Overall, the effects of the antibiotic on the wound decreased inflammatory cell infiltration and promoted an increased number of fibroblasts, extracellular matrix constituents, re-epithelialization and tissue strength. A great deal of important information about the methodology was not presented, such as: the statistical analysis used, the animal model (sex and age), antibiotic dosage, blinding and randomization of the animals chosen. Significance: Based on the results found, we believe that antibiotic therapy can be considered a viable alternative for the treatment of cutaneous wounds. However, current evidence obtained from the methodological quality analysis points towards a high risk of bias. This is due to the incomplete characterization of the experimental design and treatment protocol, which compromises the reproducibility of the studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies have assessed the incremental economic burden of treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder (i.e., non-TRD MDD) in commercially-insured and Medicaid-insured patients, but none have focused on Medicare-insured patients. Objective: To assess healthcare resource utilization (HRU) and costs of patients with TRD versus non-TRD MDD or without major depressive disorder (MDD; i.e., non-MDD) in a Medicare-insured population. Methods: Adult patients were retrospectively identified from the Chronic Condition Warehouse de-identified 100% Medicare database (01/2010-12/2016). MDD was defined as ≥1 MDD diagnosis and ≥1 claim for an antidepressant. Patients initiated on a third antidepressant following two antidepressant treatment regimens of adequate dose and duration were considered to have TRD. The index date was defined as the date of the first antidepressant claim for the TRD and non-TRD MDD cohorts, and as a randomly imputed date for the non-MDD cohort. Patients with TRD were matched 1:1 to non-TRD MDD patients and randomly selected non-MDD patients based on propensity scores. Analyses were also performed for a subset of patients aged ≥65. Results: Of 29,543 patients with MDD, 3,225 (10.9%) met the study definition of TRD; 157,611 were included in the non-MDD cohort. Matched patients with TRD and non-TRD MDD were, on average, 58.9 and 59.0 years old, respectively. The TRD cohort had higher per-patient-per-year (PPPY) HRU than the non-TRD MDD (e.g., inpatient visits: incidence rate ratio [IRR] = 1.36) and non-MDD cohorts (e.g., inpatient visits: IRR = 1.84, all P<0.001). The TRD cohort had significantly higher total PPPY healthcare costs than the non-TRD MDD cohort ($25,517 vs. $20,425, adjusted cost difference = $3,385) and non-MDD cohort ($25,517 vs. $14,542, adjusted cost difference = $4,015, all P<0.001). Similar results were found for the subset of patients ≥65. Conclusion: Among Medicare-insured patients, those with TRD had higher HRU and costs compared to those with non-TRD MDD and non-MDD. [ABSTRACT FROM AUTHOR]

Purpose: MitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD). Methods: Simulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated. Results: MitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101). Conclusions: MitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the dependability and accuracy of midkine (MK) in the diagnosis of hepatocellular carcinoma (HCC). Methods: PubMed, EMBASE, Web of Science, China Biology Medicine disc and grey literature sources were searched from the date of database inception to January 2019. Two authors (B-H.Z. and B.L.) independently extracted the data and evaluated the study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR−) were estimated using a bivariate model. Moreover, hierarchical summary receiver operating characteristic curves were generated. The diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled using a univariate model. Results: Nine articles (11 studies) were included (1941 participants). The bivariate analysis revealed that the sensitivity and specificity of MK for HCC diagnosis were 0.85 (95% CI 0.78–0.91) and 0.83 (95% CI 0.76–0.88), respectively. We also found a LR+ of 5.05 (95% CI 3.33–7.40), a LR− of 0.18 (95% CI 0.11–0.28), a DOR of 31.74 (95% CI 13.98–72.09) and an AUC of 0.91 (95% CI 0.84–0.99). Subgroup analyses showed that MK provided the best efficiency for HCC diagnosis when the cutoff value was greater than 0.5 ng/mL. Conclusions: MK has an excellent diagnostic value for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Biological, ecological, social, and technological systems are complex structures with multiple interacting parts, often represented by networks. Correlation matrices describing interdependency of the variables in such structures provide key information for comparison and classification of such systems. Classification based on correlation matrices could supplement or improve classification based on variable values, since the former reveals similarities in system structures, while the latter relies on the similarities in system states. Importantly, this approach of clustering correlation matrices is different from clustering elements of the correlation matrices, because our goal is to compare and cluster multiple networks–not the nodes within the networks. A novel approach for clustering correlation matrices, named "snakes-&-dragons," is introduced and illustrated by examples from neuroscience, human microbiome, and macroeconomics. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to examine the effects of physical exercise cum cognitive-behavioural therapy (CBT) on alleviating pain intensity, functional disabilities, and mood/mental symptoms in those suffering with chronic musculoskeletal pain. MEDLINE, EMBASE, PubMEd, PsycINFO and CINAHL were searched to identify relevant randomised controlled trials from inception to 31 December 2018. The inclusion criteria were: (a) adults ≥18 years old with chronic musculoskeletal pain ≥3 months, (b) randomised controlled design, (c) a treatment arm consisting of physical intervention and CBT combined, (d) the comparison arm being waitlist, usual care or other non-pharmacological interventions such as physical exercise or CBT alone, and (e) outcomes including pain intensity, pain-related functional disabilities (primary outcomes), or mood/mental symptoms (secondary outcome). The exclusion criteria were: (a) the presence of comorbid mental illnesses other than depression and anxiety and (b) non-English publication. The search resulted in 1696 records and 18 articles were selected for review. Results varied greatly across studies, with most studies reporting null or small effects but a few studies reporting very large effects up to 2-year follow-up. Pooled effect sizes (Hedges' g) were ~1.00 for pain intensity and functional disability, but no effect was found for mood/mental symptoms. The effects were mainly driven by several studies reporting unusually large differences between the exercise cum CBT intervention and exercise alone. When these outliers were removed, the effect on pain intensity disappeared at post-intervention while a weak effect (g = 0.21) favouring the combined intervention remained at follow-up assessment. More consistent effects were observed for functional disability, though the effects were small (g = 0.26 and 0.37 at post-intervention and follow-up respectively). More importantly, the value of adding CBT to exercise interventions is questionable, as consistent benefits were not seen. The clinical implications and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Objectives: An extended-wavelength diffuse reflectance spectroscopy (EWDRS) technique was evaluated for its ability to differentiate between and classify different skin and tissue types in an in vivo pig model. Materials and methods: EWDRS recordings (450–1550 nm) were made on skin with different degrees of pigmentation as well as on the pig snout and tongue. The recordings were used to train a support vector machine to identify and classify the different skin and tissue types. Results: The resulting EWDRS curves for each skin and tissue type had a unique profile. The support vector machine was able to classify each skin and tissue type with an overall accuracy of 98.2%. The sensitivity and specificity were between 96.4 and 100.0% for all skin and tissue types. Conclusion: EWDRS can be used in vivo to differentiate between different skin and tissue types with good accuracy. Further development of the technique may potentially lead to a novel diagnostic tool for e.g. non-invasive tumor margin delineation. [ABSTRACT FROM AUTHOR]

Introduction: While extracorporeal membrane oxygenation (ECMO) is effective in preventing further hypoxemia and maintains blood flow in endotoxin-induced shock, ECMO alone does not reverse the hypotension. In this study, we tested whether concurrent vasopressor use with ECMO would provide increased circulatory support and blood flow, and characterized regional blood flow distribution to vital organs. Methods: Endotoxic shock was induced in piglets to achieve a 30% decrease in mean arterial pressure (MAP). Measurements of untreated pigs were compared to pigs treated with ECMO alone or ECMO and vasopressors. Results: ECMO provided cardiac support during vasodilatory endotoxic shock and improved oxygen delivery, but vasopressor therapy was required to return MAP to normotensive levels. Increased blood pressure with vasopressors did not alter oxygen consumption or extraction compared to ECMO alone. Regional microcirculatory blood flow (RBF) to the brain, kidney, and liver were maintained or increased during ECMO with and without vasopressors. Conclusion: ECMO support and concurrent vasopressor use improve regional blood flow and oxygen delivery even in the absence of full blood pressure restoration. Vasopressor-induced selective distribution of blood flow to vital organs is retained when vasopressors are administered with ECMO. [ABSTRACT FROM AUTHOR]

Background: There has been an increase in the number of individuals aged ≥60 years in Tanzania and in sub Saharan Africa in general due to improved survival. However, data is scarce on the disease burden and outcomes following admission in this population. We herein describe the pattern of diagnoses, outcomes and factors associated with the outcomes among elderly patients admitted at Muhimbili National Hospital (MNH) and Jakaya Kikwete Cardiac Institute (JKCI) medical wards. Methodology: From October to December 2017, we consecutively enrolled patients aged ≥60 years (elderly) admitted to the MNH and JKCI medical wards. The ICD 10 was used to code for disease diagnosis at discharge or death. The Modified Barthel index was used to assess for functional activity on admission and at discharge. Results: We enrolled 336 (30.1%) elderly participants out of 1301 medical admissions. The mean age ± SD was 70.6 ± 8.9 years; 169 (50%) were female and the average number of diagnoses was 2 per participant. The most common diagnoses were: hypertension 151 (44.9%), stroke 106 (31.5%), heart failure 62 (18.5%), pneumonia 60 (17.9%), diabetes mellitus 58 (17.3%) and chronic kidney disease 55 (16.4%). The median duration of hospital stay was 5 (IQR 3–10) days and in-hospital mortality was 86 (25.6%), 56 (65%) deaths were due to non-communicable diseases and 48 (55.8%) deaths occurred within 72 hours of hospitalization. A modified Barthel score ≤20 on admission was associated with an OR 15.43 (95% CI: 7.5–31.7, p<0.001) for death. Conclusion: Elderly patients constituted a significant proportion of medical admissions at MNH and JKCI with high in-hospital mortality. A modified Barthel index score ≤20 during admission is associated with mortality and can be used to identify patients requiring special attention. [ABSTRACT FROM AUTHOR]

Background: Worldwide, the number of emerging and re-emerging infectious diseases is increasing, highlighting the importance of global disease pathogen surveillance. Traditional population-based methods may fail to capture important events, particularly in settings with limited access to health care, such as urban informal settlements. In such environments, a mixture of surface water runoff and human feces containing pathogenic microorganisms could be used as a surveillance surrogate. Method: We conducted a temporal metagenomic analysis of urban sewage from Kibera, an urban informal settlement in Nairobi, Kenya, to detect and quantify bacterial and associated antimicrobial resistance (AMR) determinants, viral and parasitic pathogens. Data were examined in conjunction with data from ongoing clinical infectious disease surveillance. Results: A large variation of read abundances related to bacteria, viruses, and parasites of medical importance, as well as bacterial associated antimicrobial resistance genes over time were detected. Significant increased abundances were observed for a number of bacterial pathogens coinciding with higher abundances of AMR genes. Vibrio cholerae as well as rotavirus A, among other virus peaked in several weeks during the study period whereas Cryptosporidium spp. and Giardia spp, varied more over time. Conclusion: The metagenomic surveillance approach for monitoring circulating pathogens in sewage was able to detect putative pathogen and resistance loads in an urban informal settlement. Thus, valuable if generated in real time to serve as a comprehensive infectious disease agent surveillance system with the potential to guide disease prevention and treatment. The approach may lead to a paradigm shift in conducting real-time global genomics-based surveillance in settings with limited access to health care. [ABSTRACT FROM AUTHOR]

For early breast cancer detection, mammography is nowadays the commonly used standard imaging approach, offering a valuable clinical tool for visualization of suspicious findings like microcalcifications and tumors within the breast. However, due to the superposition of anatomical structures, the sensitivity of mammography screening is limited. Within the last couple of years, the implementation of contrast-enhanced spectral mammography (CESM) based on K-edge subtraction (KES) imaging helped to improve the identification and classification of uncertain findings. In this study, we introduce another approach for CESM based on a two-material decomposition, with which we expect fundamental improvements compared to the clinical procedure. We demonstrate the potential of our proposed method using the quasi-monochromatic radiation of a compact synchrotron source—the Munich Compact Light Source (MuCLS)—and a modified mammographic accreditation phantom. For direct comparison with the clinical CESM approach, we also performed a standard dual-energy KES at the MuCLS, which outperformed the clinical CESM images in terms of contrast-to-noise ratio (CNR) and spatial resolution. However, the dual-energy-based two-material decomposition approach achieved even higher CNR values. Our experimental results with quasi-monochromatic radiation show a significant improvement of the image quality at lower mean glandular dose (MGD) than the clinical CESM. At the same time, our study indicates the great potential for the material-decomposition instead of clinically used KES to improve the quantitative outcome of CESM. [ABSTRACT FROM AUTHOR]

Context: Whether all degrees of periventricular leukomalacia (PVL) and peri-intraventricular haemorrhage (PIVH) have a negative impact on neurodevelopment. Objective: To determine the impact of PVL and PIVH in the incidence of cerebral palsy, sensorineural impairment and development scores in preterm neonates. Registered in PROSPERO (CRD42017073113). Data sources: PubMed, Embase, SciELO, LILACS, and Cochrane databases. Study selection: Prospective cohort studies evaluating neurodevelopment in children born preterm which performed brain imaging in the neonatal period. Data extraction: Two independent researchers extracted data using a predesigned data extraction sheet. Statistical methods: A random-effects model was used, with Mantel-Haenszel approach and a Sidik-Jonkman method for the estimation of variances, combined with Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed through the I2 statistic and sensitivity analysis were performed when possible. No funnel plots were generated but publication bias was discussed as a possible limitation. Results: Our analysis concluded premature children with any degree of PIVH are at increased risk for cerebral palsy (CP) when compared to children with no PIVH (3.4, 95% CI 1.60–7.22; 9 studies), a finding that persisted on subgroup analysis for studies with mean birth weight of less than 1000 grams. Similarly, PVL was associated with CP, both in its cystic (19.12, 95% CI 4.57–79.90; 2 studies) and non-cystic form (9.27, 95% CI 5.93–14.50; 2 studies). We also found children with cystic PVL may be at risk for visual and hearing impairment compared to normal children, but evidence is weak. Limitations: Major limitations were the lack of data for PVL in general, especially for the outcome of neurodevelopment, the high heterogeneity among methods used to assess neurodevelopment and the small number of studies, which led to meta-analysis with high heterogeneity and wide confidence intervals. Conclusions: There was no evidence supporting the hypothesis that PIVH causes impairment in neuropsychomotor development in our meta-analysis, but review of newer studies show an increased risk for lower intelligence scores in children with severe lesions, both PIVH and PVL. There is evidence to support the hypothesis that children with any degree of PIVH, especially those born below 1000 grams and those with severe haemorrhage, are at increased risk of developing CP, as well as children with PVL, both cystic and non-cystic. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer. Methods: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging. Results: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031). Conclusion: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence. [ABSTRACT FROM AUTHOR]

Background: In many low- and middle-income countries, data on the prevalence of surgical diseases have been derived primarily from hospital-based studies, which may lead to an underestimation of disease burden within the community. Community-based prevalence studies may provide better estimates of surgical need to enable proper resource allocation and prioritization of needs. This study aims to assess the prevalence of common surgical conditions among children in a diverse rural and urban population in Nigeria. Methods: Descriptive cross-sectional, community-based study to determine the prevalence of congenital and acquired surgical conditions among children in a diverse rural-urban area of Nigeria was conducted. Households, defined as one or more persons 'who eat from the same pot' or slept under the same roof the night before the interview, were randomized for inclusion in the study. Data was collected using an adapted and modified version of the interviewer-administered questionnaire—Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool and analysed using the REDCap web-based analytic application. Main results: Eight-hundred-and-fifty-six households were surveyed, comprising 1,883 children. Eighty-one conditions were identified, the most common being umbilical hernias (20), inguinal hernias (13), and wound injuries to the extremities (9). The prevalence per 10,000 children was 85 for umbilical hernias (95% CI: 47, 123), and 61 for inguinal hernias (95% CI: 34, 88). The prevalence of hydroceles and undescended testes was comparable at 22 and 26 per 10,000 children, respectively. Children with surgical conditions had similar sociodemographic characteristics to healthy children in the study population. Conclusion: The most common congenital surgical conditions in our setting were umbilical hernias, while injuries were the most common acquired conditions. From our study, it is estimated that there will be about 2.9 million children with surgically correctable conditions in the nation. This suggests an acute need for training more paediatric surgeons. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present work is to analyze the modulation of the brain activity within the areas involved in lipreading when an additional visual stimulus is included. Methods: The experiment consisted of two fMRI runs (lipreading_only and lipreading+picture) where two conditions were considered in each one (oral speech sentences condition [OSS] and oral speech syllables condition [OSSY]). Results: During lipreading-only, higher activity in the left middle temporal gyrus (MTG) was identified for OSS than OSSY; during lipreading+picture, apart from the left MTG, higher activity was also present in the supplementary motor area (SMA), the left precentral gyrus (PreCG) and the left inferior frontal gyrus (IFG). The comparison between these two runs revealed higher activity for lipreading-only in the SMA and the left IFG. Conclusion: The presence of a visual reference during a lipreading task leads to a decrease in activity in frontal areas. [ABSTRACT FROM AUTHOR]

Artemisinin resistance is threatening global efforts for malaria control and elimination. Primaquine (PQ) and methylene blue (MB) are gametocytocidal drugs that can be combined with artemisinin-based combination therapy (ACT) to reduce malaria transmission, including resistant strains. Children (6–59 months) with uncomplicated falciparum malaria in Burkina Faso were treated with artesunate-amodiaquine (AS-AQ) and randomized to MB (15 mg/kg/day for 3 days) or PQ (0.25 mg/kg at day 2) with the aim to show non-inferiority of the MB regimen with regard to haematological recovery at day 7 (primary endpoint). MB-AS-AQ could not be shown to be non-inferior to PQ-AS-AQ (mean Hb difference between treatment groups on day 7 was -0.352, 95% CI -0.832–0.128, p = 0.0767), however, haemoglobin recovery following treatment was alike in the two study arms (day 7: mean 0.2±1.4 g/dl vs. 0.5±0.9 g/dl, p = 0.446). Occurrence of adverse events was similar in both groups, except for vomiting, which was more frequent in the MB than in the PQ arm (20/50 vs 7/50, p = 0.003). Adequate clinical and parasitological response was above 95% in both groups, but significantly more asexual parasites were cleared in the MB arm compared to the PQ arm already on day 1 (48/50, 96%, vs 40/50, 80%, p = 0.014). Moreover, P. falciparum gametocyte prevalence and density were lower in the MB arm than in the PQ arm, which reached statistical significance on day 2 (prevalence: 2/50, 4%, vs 15/49, 31%, p<0.001; density: 9.6 vs 41.1/μl, p = 0.024). However, it should be considered that PQ was given only on day 2. MB-ACT appears to be an interesting alternative to PQ-ACT for the treatment of falciparum malaria. While there is a need to further improve MB formulations, MB-ACT may already be considered useful to reduce falciparum malaria transmission intensity, to increase treatment efficacy, and to reduce the risk for resistance development and spread. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Background: The function of the pelvic bones is to transfer load generated by body weight. Proper function of the pelvic bones can be disturbed by alignment changes that occur during pregnancy. Further, misalignment of the pelvic bones can lead to pain, urinary incontinence, and other complications. An understanding of the timing and nature of pelvic alignment changes during pregnancy may aid in preventing and treating these complications. Objective: To investigate the changes in pelvic alignment during pregnancy and one month after childbirth. Methods: This is a prospective, longitudinal cohort study. Pelvic measurements were obtained for 201 women at 12, 24, 30, and 36 weeks of pregnancy, and 1 month after childbirth. The anterior and posterior width of the pelvis (the distance between the bilateral anterior superior iliac spines and the bilateral posterior superior iliac spines), the anterior pelvic tilt, and pelvic asymmetry (the mean left and right pelvic tilt degrees and the bilateral difference of the anterior pelvic tilt) were measured. For the change in pelvic alignment, a Friedman test was conducted to determine any significant difference in the measurements over time. Results: The anterior and posterior width of the pelvis became significantly wider with pregnancy progress and the anterior width of the pelvis at 1 month after childbirth remained wider than that at 12 weeks of pregnancy (p < 0.001). The anterior pelvic tilt increased during pregnancy and decreased after childbirth (p < 0.05). Conclusion: Some changes in pelvic alignment occur continuously during the perinatal period. Changes in the anterior width of the pelvis are not recovered at one month post-childbirth. Understanding these perinatal changes may help clinicians avert complications due to pelvic misalignment. [ABSTRACT FROM AUTHOR]

Cells damaged by mechanical or infectious injury release proinflammatory mitochondrial DNA (mtDNA) fragments into the circulation. We evaluated the relation between plasma levels of mtDNA fragments in obese type 2 diabetes mellitus (T2DM) patients and measures of chronic inflammation and insulin resistance. In 10 obese T2DM patients and 12 healthy control (HC) subjects, we measured levels of plasma cell-free mtDNA with quantitative real-time polymerase chain reaction, and mtDNA damage in skeletal muscle with quantitative alkaline Southern blot. Also, markers of systemic inflammation and oxidative stress in skeletal muscle were measured. Plasma levels of mtDNA fragments, mtDNA damage in skeletal muscle and plasma tumor necrosis factor α levels were greater in obese T2DM patients than HC subjects. Also, the abundance of plasma mtDNA fragments in obese T2DM patients levels positively correlated with insulin resistance. To the best of our knowledge, this is the first published evidence that elevated level of plasma mtDNA fragments is associated with mtDNA damage and oxidative stress in skeletal muscle and correlates with insulin resistance in obese T2DM patients. Plasma mtDNA may be a useful biomarker for predicting and monitoring insulin resistance in obese patients. [ABSTRACT FROM AUTHOR]

Breaks filled with different break activities often interrupt cognitive performance in everyday life. Previous studies have reported that both enhancing and deteriorating effects on challenging ongoing tasks such as working memory updating, depend on the type of break activity. However, neural mechanisms of these break-related alterations in working memory performance have not been studied, to date. Therefore, we conducted a brain imaging study to identify the neurobiological correlates of effects on the n-back working memory task related to different break activities. Before performing the n-back task in the magnetic resonance imaging (MRI) scanner, young adults were exposed to break activities in the MRI scanner involving (i) eyes-open resting, (ii) listening to music, and (iii) playing the video game "Angry Birds". Heart rate was measured by a pulse oximeter during the experiment. We found that increased heart rate during gaming as well as decreased relaxation levels after a video gaming break was related to poorer n-back task performance, as compared to listening to music. On the neural level, video gaming reduced supplementary motor area activation during working memory performance. These results may indicate that video gaming during a break may affect working memory performance by interfering with arousal state and frontal cognitive control functions. [ABSTRACT FROM AUTHOR]

Hindsight bias (HB) is the tendency to retrospectively exaggerate one's foresight knowledge about the outcome of an event. Cognitive processes influenced by newly obtained outcome information are used to explain the HB phenomenon, but the neural correlates remain unknown. This study investigated HB in the context of election results using a memory design and functional magnetic resonance imaging for the first time. Participants were asked to predict and recall the percentage of votes obtained by (pairs of) candidates before and after an election. The results revealed that 88% of participants showed HB by recalling that their predictions were closer to the actual outcomes than they really were; and participants had HB for 38% of the events. The HB effect was associated with activation in the medial superior frontal gyrus and bilateral inferior frontal gyrus (IFG), which have been implicated in updating an old belief due to new information and is similar to the process of reconstruction bias. Furthermore, participants with a greater HB effect showed greater activation of the left IFG. In conclusion, we successfully observed the HB phenomenon in election results, and our imaging results suggested that the HB phenomenon might involve reconstruction bias. [ABSTRACT FROM AUTHOR]

Background: Rare diseases (RD) result in a wide variety of clinical presentations, and this creates a significant diagnostic challenge for health care professionals. We hypothesized that there exist a set of consistent and shared phenomena among all individuals affected by (different) RD during the time before diagnosis is established. Objective: We aimed to identify commonalities between different RD and developed a machine learning diagnostic support tool for RD. Methods: 20 interviews with affected individuals with different RD, focusing on the time period before their diagnosis, were performed and qualitatively analyzed. Out of these pre-diagnostic experiences, we distilled key phenomena and created a questionnaire which was then distributed among individuals with the established diagnosis of i.) RD, ii.) other common non-rare diseases (NRO) iii.) common chronic diseases (CD), iv.), or psychosomatic/somatoform disorders (PSY). Finally, four combined single machine learning methods and a fusion algorithm were used to distinguish the different answer patterns of the questionnaires. Results: The questionnaire contained 53 questions. A total sum of 1763 questionnaires (758 RD, 149 CD, 48 PSY, 200 NRO, 34 healthy individuals and 574 not evaluable questionnaires) were collected. Based on 3 independent data sets the 10-fold stratified cross-validation method for the answer-pattern recognition resulted in sensitivity values of 88.9% to detect the answer pattern of a RD, 86.6% for NRO, 87.7% for CD and 84.2% for PSY. Conclusion: Despite the great diversity in presentation and pathogenesis of each RD, patients with RD share surprisingly similar pre-diagnosis experiences. Our questionnaire and data-mining based approach successfully detected unique patterns in groups of individuals affected by a broad range of different rare diseases. Therefore, these results indicate distinct patterns that may be used for diagnostic support in RD. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the diagnostic accuracy of breast MRI for detecting residual tumor and the tumor size whether it would be affected after neoadjuvant chemotherapy. Methods: Total 109 patients with NAC and 682 patients without NAC were included in this retrospective study. Measurement of the largest diameter of tumors at pathology was chosen as gold standard and compared with preoperative breast MRI. A concordance threshold of ±25% of maximal tumor size was used. The accuracy of MRI was graded as concordant, underestimation, or overestimation rate. Further subgroup analysis with tumor stages, histologic subgroups and intrinsic subtypes was performed. Results: The post-NAC MRI was associated with 92.5% sensitivity, 55.2% specificity, 85.1% positive predictive value, 72.7% negative predictive value, and overall 82.6% accuracy for detecting residual tumor. In determining tumor size, the overall concordance rates of the non-NAC group and the NAC group were 43.5% and 41.3%, respectively (p = 0.678). But the overestimation rate and underestimation rate were 26.6% and 32.1% for NAC group, and 52.9% and 3.5% for the non-NAC group (p<0.001). While in the subgroups analysis, the concordance rate of the NAC group (26.7%) was lower than that of the non-NAC group (82.1%) at T3 stage (p<0.001). There were no statistically significant differences between different tumor histologic subgroups and intrinsic subtypes. Conclusions: The overall accuracy of MRI in predicting tumor size was not affected by NAC; however, it tends to underestimate tumor size after NAC, especially in patients with T3 lesions and above. [ABSTRACT FROM AUTHOR]

The development of automatic methods for segmenting anatomy from medical images is an important goal for many medical and healthcare research areas. Datasets that can be used to train and test computer algorithms, however, are often small due to the difficulties in obtaining experts to segment enough examples. Citizen science provides a potential solution to this problem but the feasibility of using the public to identify and segment anatomy in a medical image has not been investigated. Our study therefore aimed to explore the feasibility, in terms of performance and motivation, of using citizens for such purposes. Public involvement was woven into the study design and evaluation. Twenty-nine citizens were recruited and, after brief training, asked to segment the spine from a dataset of 150 magnetic resonance images. Participants segmented as many images as they could within three one-hour sessions. Their accuracy was evaluated by comparing them, as individuals and as a combined consensus, to the segmentations of three experts. Questionnaires and a focus group were used to determine the citizens' motivation for taking part and their experience of the study. Citizen segmentation accuracy, in terms of agreement with the expert consensus segmentation, varied considerably between individual citizens. The citizen consensus, however, was close to the expert consensus, indicating that when pooled, citizens may be able to replace or supplement experts for generating large image datasets. Personal interest and a desire to help were the two most common reasons for taking part in the study. [ABSTRACT FROM AUTHOR]

Background: Chiropractic maintenance care is effective as secondary/tertiary prevention of non-specific low back pain (LBP), but the potential effect moderation by psychological characteristics is unknown. The objective was to investigate whether patients in specific psychological sub-groups had different responses to MC with regard to the total number of days with bothersome pain and the number of treatments. Method: Data from a two-arm randomized pragmatic multicenter trial with a 12-month follow up, designed to investigate the effectiveness of maintenance care, was used. Consecutive patients, 18–65 years of age, with recurrent and persistent LBP seeking chiropractic care with a good effect of the initial treatment were included. Eligible subjects were randomized to either maintenance care (prescheduled care) or to the control intervention, symptom-guided care. The primary outcome of the trial was the total number of days with bothersome LBP collected weekly for 12 months using an automated SMS system. Data used to classify patients according to psychological subgroups defined by the West Haven-Yale Multidimensional Pain Inventory (adaptive copers, interpersonally distressed and dysfunctional) were collected at the screening visit. Results: A total of 252 subjects were analyzed using a generalized estimating equations linear regression framework. Patients in the dysfunctional subgroup who received maintenance care reported fewer days with pain (-30.0; 95% CI: -36.6, -23.4) and equal number of treatments compared to the control intervention. In the adaptive coper subgroup, patients who received maintenance care reported more days with pain (10.7; 95% CI: 4.0, 17.5) and more treatments (3.9; 95% CI: 3.5, 4.2). Patients in the interpersonally distressed subgroup reported equal number of days with pain (-0.3; 95% CI: -8.7, 8.1) and more treatments (1.5; 95% CI: 0.9, 2.1) on maintenance care. Conclusions: Psychological and behavioral characteristics modify the effect of MC and should be considered when recommending long-term preventive management of patients with recurrent and persistent LBP. [ABSTRACT FROM AUTHOR]

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality in Nigeria and in most low- and middle-income countries. The World Health Organization (WHO) strongly recommends oxytocin as effective, affordable, and the safest drug of first choice in the prevention and treatment of PPH in the third stage of labor. However, there are concerns about its quality. Very high prevalence of poor-quality oxytocin, especially in Africa and Asia, has been reported in literature. Excessive and inappropriate use of oxytocin is also common in low-resource settings. Objective: To assess clinical experiences with quality of oxytocin used by healthcare providers in Lagos State, Nigeria. Methods: This was a descriptive cross-sectional study conducted in 2017, with 705 respondents (doctors and nurses) who use oxytocin for obstetrics and gynecological services recruited from 195 health facilities (public and registered private) across Lagos State. Data collection was quantitative, using a pretested self-administered questionnaire. Data analysis was performed with IBM SPSS version 21. Statistical significance was set at 5 percent (p<0.05). Ethical approval was obtained from Lagos University Teaching Hospital Health Research Ethics Committee. Results: Only 52 percent of the respondents knew oxytocin should be stored at 2°C to 8°C. About 80 percent of respondents used oxytocin for augmentation of labor, 68 percent for induction of labor, 51 percent for stimulation of labor, and 78 percent for management of PPH. Forty-one percent used 20IU and as much as 10% used 30IU to 60IU for management of PPH. About 13 percent of respondents reported believing they had used an ineffective brand of oxytocin in their practice. Just over a third (36%) had an available means of documenting or reporting perceived ineffectiveness of drugs in their facility; of these, only about 12 percent had pharmacovigilance forms in their facilities to report the ineffectiveness. Conclusion: The inappropriate and inconsistent use of oxytocin, especially overdosing, likely led to the high perception of medicine effectiveness among respondents. This is coupled with lack of suspicion of medicine ineffectiveness by clinicians as a possible root cause of poor treatment response or disease progression. Poor knowledge of oxytocin storage and consequent poor storage practices could have contributed to the ineffectiveness reported by some respondents. It is necessary to establish a unified protocol for oxytocin use that is strictly complied with. Continuous training of healthcare providers in medicine safety monitoring is advocated. [ABSTRACT FROM AUTHOR]

The problem of handling non-ignorable non-response has been typically addressed under the design-based approach using the well-known sub-sampling technique introduced by Hansen and Hurwitz [1946, Journal of the American Statistical Association, Vol 41(236), Page 517- 529]. Alternatively, the model-based paradigm emphasizes on utilizing the underlying model relationship between the outcome variable and one or more covariate(s) whose population values are known prior to the survey. This article utilizes the model relationship between the study variable and covariate(s) for handling non-ignorable non-response and obtaining an unbiased estimator for the population total under the sub-sampling technique. The main idea is to combine the estimates obtained from the sample on first call and the sub-sample from second call using separate model relationships. The contribution of this paper helps us in providing unbiased estimates with an improved efficiency under model-based paradigm in presence of non-ignorable non-response. The provided method is more economical than the available estimators under callback methods as we are working sub-sampling and also increase response rate as a stronger mode of interview is employed for data collection. A numerical study using Monte Carlo is presented to illustrate the behavior of the proposed and the efficiency comparison. [ABSTRACT FROM AUTHOR]

The developmental speed of new antimicrobials does not meet the emergence of multidrug-resistant bacteria sufficiently. A potential shortcut is assessing the antimicrobial activity of already approved drugs. Intrudingly, the antibacterial action of glatiramer acetate (GA) has recently been discovered. GA is a well-known and safe immunomodulatory drug particular effective against Gram-negative bacteria, which disrupts biological membranes by resembling the activity of antimicrobial peptides. Thus, GA can potentially be included in treatment strategies used to combat infections caused by multidrug-resistant Gram-negatives. One potential application is chronic respiratory infections caused by Pseudomonas aeruginosa, however the safety of GA inhalation has never been assessed. Here, the safety of inhaling nebulized GA is evaluated in a preclinical pig model. The potential side effects, i.e., bronchoconstriction, respiratory tract symptoms and systemic- and local inflammation were assessed by ventilator monitoring, clinical observation, biochemistry, flowcytometry, and histopathology. No signs of bronchoconstriction assessed by increased airway peak pressure, Ppeak, or decreased oxygen pressure were observed. Also, there were no signs of local inflammation in the final histopathology examination of the pulmonary tissue. As we did not observe any potential pulmonary side effects of inhaled GA, our preliminary results suggest that GA inhalation is safe and potentially can be a part of the treatment strategy targeting chronic lung infections caused by multidrug-resistant Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Malignant gliomas remain incurable with a poor prognosis despite of aggressive treatment. We have been studying the development of brain tumors in a glioma rat model, where rats develop brain tumors after prenatal exposure to ethylnitrosourea (ENU), and there is a sizable interval between when the first pathological changes are noted and tumors become detectable with MRI. Our aim to define a molecular timeline through proteomic profiling of the cerebrospinal fluid (CSF) such that brain tumor commitment can be revealed earlier than at the presymptomatic stage. A comparative proteomic approach was applied to profile CSF collected serially either before, at and after the time MRI becomes positive. Elastic net (EN) based models were developed to infer the timeline of normal or tumor development respectively, mirroring a chronology of precisely timed, "clocked", adaptations. These CSF changes were later quantified by longitudinal entropy analyses of the EN predictive metric. False discovery rates (FDR) were computed to control the expected proportion of the EN models that are due to multiple hypothesis testing. Our ENU rat brain tumor dating EN model indicated that protein content in CSF is programmed even before tumor MRI detection. The findings of the precisely timed CSF tumor microenvironment changes at presymptomatic stages, deviation from the normal development timeline, may provide the groundwork for the understanding of adaptation of the brain environment in tumorigenesis to devise effective brain tumor management strategies. [ABSTRACT FROM AUTHOR]

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects in Lima, Peru that conducted under an approved study protocol in Peru. The sera were made anonymous under a protocol approved by the CDC Institutional Review Board. Definitive diagnosis of the specimen was established by computed-tomography and/or magnetic resonance imaging. To test the specificity of the assay, we evaluated a panel of serum samples obtained from patients with other infections (n = 24), and serum samples from persons in the United States and Egypt who had not traveled outside their country, and therefore are presumed negative for cysticercosis (n = 128). The assay specificity in the negative panel was 99% (95–100%) while assay sensitivity was 89% (79–95%) in NCC patients with two or more viable cysts. Our assay has performance characteristics similar to those of traditional platforms for the detection of NCC and shows promise as a mobile phone reader-based point-of-care test for antibody detection. [ABSTRACT FROM AUTHOR]

Defining cases of Zika virus (ZIKV) infection is a critical challenge for epidemiological research. Due to ZIKV’s overlapping clinical features and potential immunologic cross-reactivity with other flaviviruses and the current lack of an optimal ZIKV-specific diagnostic assay, varying approaches for identifying ZIKV infections have been employed to date. This paper presents the laboratory results and diagnostic criteria developed by the Microcephaly Epidemic Research Group for defining cases of maternal ZIKV infection in a cohort of pregnant women with rash (N = 694) recruited during the declining 2015–2017 epidemic in northeast Brazil. For this investigation, we tested maternal sera for ZIKV by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Immunoglobulin (Ig) M and IgG3 enzyme-linked immunosorbent assays (ELISAs), and Plaque Reduction Neutralization Test (PRNT50). Overall, 23.8% of participants tested positive by qRT-PCR during pregnancy (range of detection: 0–72 days after rash onset). However, the inter-assay concordance was lower than expected. Among women with qRT-PCR-confirmed ZIKV and further testing, only 10.1% had positive IgM tests within 90 days of rash, and only 48.5% had ZIKV-specific PRNT50 titers ≥20 within 1 year of rash. Given the complexity of these data, we convened a panel of experts to propose an algorithm for identifying ZIKV infections in pregnancy based on all available lines of evidence. When the diagnostic algorithm was applied to the cohort, 26.9% of participants were classified as having robust evidence of a ZIKV infection during pregnancy, 4.0% as having moderate evidence, 13.3% as having limited evidence of a ZIKV infection but with uncertain timing, and 19.5% as having evidence of an unspecified flavivirus infection before or during pregnancy. Our findings suggest that integrating longitudinal data from nucleic acid and serologic testing may enhance diagnostic sensitivity and underscore the need for an on-going dialogue regarding the optimization of strategies for defining cases of ZIKV in research. [ABSTRACT FROM AUTHOR]

Background: Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D.Methods and Findings: A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation.Conclusions: Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups. [ABSTRACT FROM AUTHOR]

Background: Neonatal mortality is a significant contributor to infant mortality. Causes and predictors of neonatal death are known to vary in different settings and across different contexts. This study aimed to assess predictors, causes, and trends of neonatal mortality amongst neonates admitted to Nekemte Referral Hospital neonatal unit between 2010–2014. Methods: Retrospective data was collected for 2090 live born neonates admitted to the neonatal intensive care unit of Nekemte Referral Hospital by reviewing records between 2010 to 2014. Variables were collected from the neonatal registration book and patient card on the predictors, causes, and trends of neonatal death using a standard checklist developed by the World Health Organization (WHO). Data was analyzed using Epi info version 3.5.1, and SPSS version 25 for windows. The level of significance was set at P<0.05 with the corresponding confidence intervals at 95%. A logistic regression model was used for analysis and to control for confounders. Microsoft Excel 2007 was used to construct the trend analysis. Results: There were 183 deaths in the cohort equivalent to 8.8% of deaths among total admitted neonates during the study period. Early neonatal deaths accounted for 8% and late neonatal deaths accounted for 0.71% of deaths among total admitted neonates. Main predictors identified for an increased risk of neonatal mortality were; neonates from rural residents [AOR 1.35, (95% CI, 1.35–1.87)], birth order of greater than five [AOR 5.10, (95% CI, 1.15–22.63)], home delivery [AOR 3.41, (95% CI, 2.24–5.19)], very low birth weight [AOR 6.75, (95% CI, 3.63–12.54)] and low birth weight [AOR 2.81, (95% CI, 1.95–4.05)] and inability to cry at birth [AOR 2.21, (95% CI, 1.51–3.22)]. The trend analysis showed a sharp fall for the neonatal mortality over the last five years with a mean reduction of 16%. Conclusions: Data from the Nekemte Referral Hospital Neonatal Intensive Care Unit analysis revealed majority of the deaths were occurred during early neonatal period. The main predictors of neonatal mortality identified from this study needs strengthening an appropriate public health intervention through addressing antenatal care, curbing home delivery. [ABSTRACT FROM AUTHOR]

Hypoxia and angiogenesis are critical components in the progression of solid cancer, including gastric cancers (GCs). miR-382 has been identified as a hypoxia-induced miR (hypoxamiR), but the clinical significance in GCs has not been identified yet. To explore the clinical and prognostic importance of miR-382 in GCs, the surgical specimens of 398 patients with GCs in KNU hospital in Korea, the total of 183 patients was randomly selected using simple sampling methods and big data with 446 GCs and 45 normal tissues from the data portal () were analysed. Expression of miR-382 as well as miR-210, as a positive control hypoxamiR by qRT-PCR in histologically malignant region of GCs showed significantly positive correlation (R = 0.516, p<0.001). High miR-210 and miR-382 expression was significantly correlated with unfavorable prognosis including advanced GCs (AGC), higher T category, N category, pathologic TNM stage, lymphovascular invasion, venous invasion, and perinueral invasion, respectively (all p<0.05). In univariate analysis, high miR-210 expression was significantly associated with worse overall survival (OS) (p = 0.036) but not high miR-382. In paired 60 gastric normal and cancer tissues, miR-382 expression in cancer tissues was significantly higher than normal counterpart (p = 0.003), but not miR-210 expression. However, by increasing the patient number from the big data analysis, miR-210 as well as miR-382 expression in tumor tissues was significantly higher than the normal tissues. Our results suggest that miR-382, as novel hypoxamiR, can be a prognostic marker for advanced GCs and might be correlated with metastatic potential. miR-382 might play important roles in the aggressiveness, progression and prognosis of GCs. In addition, miR-382 give a predictive marker for progression of GCs compared to the normal or preneoplastic lesion. [ABSTRACT FROM AUTHOR]

Network coupled cells, such as astrocytes, regulate their cellular homeostasis via Ca2+ signals spread between the cells through gap junctions. Intracellular Ca2+ release is controlled by different signaling pathways that can be stimulated by ATP, glutamate and serotonin (5-HT). Based on our findings, all these pathways are influenced by inflammatory agents and must be restored to fully recover the Ca2+ signaling network. An ultralow concentration of the local anesthetic agent bupivacaine reduced 5-HT-evoked intracellular Ca2+ release, and an ultralow concentration of the phosphodiesterase-5 inhibitor sildenafil in combination with vitamin D3 reduced ATP-evoked intracellular Ca2+ release. Combinations of these three substances downregulated 5-HT-, glutamate- and ATP-evoked intracellular Ca2+ release to a more normal Ca2+ signaling state. Furthermore, inflammatory Toll-like receptor 4 expression decreased with a combination of these three substances. Substance P receptor neurokinin (NK)-1 expression was reduced by ultralow concentrations of bupivacaine. Here, bupivacaine and sildenafil (at extremely low concentrations) combined with vitamin D3 have potential anti-inflammatory properties. According to the present study, drug combinations at the right concentrations, especially extremely low concentrations of bupivacaine and sildenafil, affect different cellular biochemical mechanisms and represent a potential solution for downregulating inflammatory parameters, thereby restoring cells or networks to normal physiological homeostasis. [ABSTRACT FROM AUTHOR]

Background: Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Methods: Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Results: Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. Conclusion: This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes. [ABSTRACT FROM AUTHOR]

Objectives: Aging is associated with low muscle mass and has been linked to adverse health outcomes. The objectives of this cross-sectional study were: (1) to describe anthropometry, body composition, appendicular skeletal muscle mass index (ASMI; appendicular skeletal muscle mass/height2), and prevalence of low ASMI in older people with normal nutritional status (Malnutrition Universal Screening Tool score = 0); (2) to determine factors associated with ASMI, and odds ratios of having low ASMI. Methods: SHIELD is a study of community-dwelling older people aged 65 years and above in Singapore. ASMI was determined using bioelectrical impedance analysis and low ASMI was defined as <7.0 kg/m2 for males and <5.7 kg/m2 for females (Asian Working Group for Sarcopenia, 2014). Results: A total of 400 older people (183 males and 217 females) took part in this study. The overall prevalence of low ASMI was 20.6% (15.5% in males and 24.9% in females). Females had significantly lower ASMI than males (P < 0.0001), age was inversely associated with ASMI (P = 0.0024) while BMI and calf circumference were positively associated with ASMI (both P < 0.0001) in the total cohort. In addition, ASMI was positively associated with bone mass in both genders (both P < 0.0001). After adjusting for covariates, the odds ratios of having low ASMI with every 1 year and 10 years increase in age were 1.13 (95% CI: 1.06, 1.20) and 3.36 (95% CI: 1.82, 6.21) respectively. Conclusions: The high prevalence of low ASMI in community-dwelling older people with normal nutritional status highlights the need for early screening. There was a strong inverse association between age and ASMI while BMI, calf circumference and bone mass were positively associated with ASMI. These findings will give further weight to the importance and development of public health strategies in maintaining and improving muscle health in this population group. [ABSTRACT FROM AUTHOR]

Background: The association between sugar-sweetened beverage (SSB) consumption and colorectal cancer (CRC) risk remains unclear and published data are limited. Methods: The analytic cohort included 99,798 women, free of cancer at baseline, from the California Teachers Study, a longitudinal cohort comprised of 133,477 female teachers and administrators who were active or recently retired members of the California State Teachers Retirement System in 1995. SSB consumption constituted caloric soft drinks, sweetened bottled waters and teas, and fruit drinks, derived from a self-administered food frequency questionnaire. Consumption was divided into four categories: Rare or never, >rare/never to <1 serving/week, ≥1 serving/week to <1 serving/day, and ≥1 serving/day. CRC endpoints were based on annual linkage with California Cancer Registry, defined as first diagnosis of CRC, and classified following the Surveillance, Epidemiology, and End Results Program coding system. Multivariable-adjusted Cox proportional hazards models were used to generate hazard ratios (HR) and 95% confidence intervals (CI) for assessing the association between SSB consumption and incident CRC. Results: A total of 1,318 incident CRC cases were identified over 20 years of follow-up (54.5% proximal colon and 45.5% distal colorectum). Compared with rare/never consumers, the multivariable-adjusted HRs (95% CI) were 1.14 (0.86, 1.53) for total CRC; 1.11 (0.73, 1.68) for proximal colon; and 1.22 (0.80, 1.86) for distal colorectum cancers among women consuming ≥ 1 serving/day of SSBs. Conclusion: SSBs were not significantly associated with CRC risk. The biological effects of high SSB consumption make it important to continue to evaluate whether SSBs are associated with CRC. Additionally, future studies should further assess SSBs in large, racial/ethnically diverse cohorts of males and females, and, if feasible, address changes in SSB consumption over time. [ABSTRACT FROM AUTHOR]

Background and aims: Many countries lack resources to identify patients at risk of developing Type 2 diabetes mellitus (diabetes). We aimed to develop and validate a diabetes risk score based on easily accessible clinical data. Methods: Prospective study including 5277 participants (55.0% women, 51.8±10.5 years) free of diabetes at baseline. Comparison with two other published diabetes risk scores (Balkau and Kahn clinical, respectively 5 and 8 variables) and validation on three cohorts (Europe, Iran and Mexico) was performed. Results: After a mean follow-up of 10.9 years, 405 participants (7.7%) developed diabetes. Our score was based on age, gender, waist circumference, diabetes family history, hypertension and physical activity. The area under the curve (AUC) was 0.772 for our score, vs. 0.748 (p<0.001) and 0.774 (p = 0.668) for the other two. Using a 13-point threshold, sensitivity, specificity, positive and negative predictive values (95% CI) of our score were 60.5 (55.5–65.3), 77.1 (75.8–78.2), 18.0 (16.0–20.1) and 95.9 (95.2–96.5) percent, respectively. Our score performed equally well or better than the other two in the Iranian [AUC 0.542 vs. 0.564 (p = 0.476) and 0.513 (p = 0.300)] and Mexican [AUC 0.791 vs. 0.672 (p<0.001) and 0.778 (p = 0.575)] cohorts. In the European cohort, it performed similarly to the Balkau score but worse than the Kahn clinical [AUC 0.788 vs. 0.793 (p = 0.091) and 0.816 (p<0.001)]. Diagnostic capacity of our score was better than the Balkau score and comparable to the Kahn clinical one. Conclusion: Our clinically-based score shows encouraging results compared to other scores and can be used in populations with differing diabetes prevalence. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Non-AIDS-related mortality rates among HIV-infected patients still exceed those of their uninfected peers. A major driver of this excess mortality is a higher risk of non-infectious comorbidities, including cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, osteoporosis and cancer. The prevalence of mental illness and other chronic non-infectious comorbidities is identified as a primary concern of antiretroviral prescribers in Australia. Methods: We conducted a cross-sectional, observational study using data from MedicineInsight, a large-scale Australian primary care database comprising longitudinal data from electronic clinical information systems. The HIV-infected cohort included all men with a recorded diagnosis of HIV. The non-HIV-infected cohort comprised all other men from the same practices. The prevalence and risk of cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, osteoporosis, cancer, anxiety and depression were compared between the groups. Results: We included 2,406 HIV-infected males and 648,205 males with no record of HIV diagnosis attending primary care in this study. HIV-infected men were less socioeconomically disadvantaged and more urban-dwelling than men in the primary care cohort. We found that HIV-infected men attending primary care in Australia are at increased risk of chronic kidney disease, cancer, osteoporosis, anxiety and depression. There appears to be a risk of premature onset of cardiovascular disease, osteoporosis and cancer among younger HIV-infected patients. There is a high prevalence of anxiety and depression among HIV-infected men. Conclusions: Increased prevalence of non-infectious comorbidities among HIV-infected men has broad implications for the effective management of those with these chronic conditions. Education to raise awareness among both HIV-infected men and their care providers, together with a greater focus on risk reduction, monitoring and preventive care, may be effective strategies in primary healthcare settings to further narrow the gap in health outcomes between people living with HIV and their uninfected counterparts. [ABSTRACT FROM AUTHOR]