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Chromolaena odorata is a noxious alien invasive weed species with an enormous impact on the terrestrial ecosystem. The allelopathic potentials of this weed have had little attention, leading to changes in soil properties and microbial communities. This study investigates the impacts of Chromolaena odorata invasion gradients on rhizospheric soil chemical properties and microbial response in the Mount Cameroon Region. Forty-eight soil samples at four different degrees of invasion (uninvaded, low degree invasion, moderate degree invasion and high degree invasion) based on species coverage within subplots in four study areas were collected and rhizospheric soil chemical properties, microbial load, phosphatases activities and secondary metabolites were evaluated. At medium-degree invasion, rhizospheric soil concentrations of P, K and Fe increased with arbuscular mycorrhizal fungi (AMF) colonization and phosphatases enzyme activities. Soil C, N and organic matter were significantly increased at high-degree invasion, supporting the use of the plant as a fallow crop. Acid phosphatase activity ranged from 0.69 to 0.90 mmol h-1 kg-1 and was significantly different at different degrees of invasion. AMF colonization ranged from 23.33 to 50.00%, with a strong positive correlation between AMF colonization and phosphatase activity. Soil bacterial load was high (46 × 105 CFU/g- 67 × 105 CFU/g), with mostly Staphylococcus having health concerns about its spread. The invasion situation had no significant effect on soil bacterial load, but high-degree invasion significantly increased fungal load. Low-degree invaded soils had high saponin (24.55±0.00 mg/g), flavonoid (47.7 mg/g) and tannin (28.68 mg/g) concentrations. The investigation reveals that Chromolaena odorata invasion altered rhizospheric soil properties and microbial communities significantly, thereby influencing ecosystem dynamics and soil nutrient availability. However, further studies elucidating kinds of secondary metabolites, identifying microbial communities, and monitoring soil changes influenced by C. odorata are essential for effective ecosystem management.

BackgroundHealth personnel (HP) are on the frontlines during response to public health emergencies like COVID-19. This risk of exposure suggests the need for safety in responding to any pandemic. Therefore, to ascertain the rate of SARS-CoV-2 infection and immunity, and their determinants amongst HP become relevant.MethodsA cross sectional health facility-based study was carried-out amongst HP in the Centre Region of Cameroon from 1st February to 30th June 2021. Characteristics and access to preventive tools were collected using face-to-face administered questionnaire. Nasopharyngeal swabs and whole blood were collected for PCR, IgG and IgM testing respectively. STATA version 17 software was used for data analysis. Determinants of COVID-19 infection were explored by estimating crude and adjusted Odd Ratio.ResultsOut of 510 HP reached, 458 were enrolled with mean age of 35 (±10) years. Thirty-four (7.4%) were PCR-positive to SARS-CoV-2 with 73.5% being clinicians versus 9 (26.4%) non-clinicians (p = 0.05). Sero-positivity to SARS-CoV-2 IgG/IgM was 40.2% (184/458), with 84.2% being clinicians versus 29 (15.8%) non-clinicians (p = 0.733). Amongst the 34 HP with PCR-positivity, 16 (47%) had no antibodies, while, 15 (44%) were IgG only. An estimate of HP (43.7%) had at least an evidence of PCR, IgG or IgM contact to COVID-19. Determinants of PCR-positivity was being clinical staff (AOR = 0.29, P = 0.039); and that of IgG/IgM were being non clinical staff (AOR = 0.41, p = 0.018) and regular use of face masks (AOR = 0.44, p = 0.001). HP trained on IPC (24%) were mainly from peripheral level (74.7%, p = 0.002).ConclusionActive infections were within the range of pandemic control (

BackgroundPatients can experience persistent cognitive complaints and deficits in long-COVID. Inflammation and capillary damage may contribute to symptoms by interfering with tissue oxygenation.MethodsThis was an exploratory pilot crossover study designed to describe the effects of supplemental oxygen (portable oxygen concentrator, POC) on cognitive performance and peripheral and cerebral oxygen saturation at rest and exercise. Participants with long-COVID (n = 21) were randomized 1:1 to: 1) POC (3h/day) for 2 weeks followed by standard of care (Control) for 2 weeks or 2) Control for 2 weeks then POC (3h/day) for 2 weeks, with a 1-week washout. Cognitive assessment (global cognition [Montreal Cognitive Assessment, MoCA], episodic memory [Hopkins], working memory [Digit Span], executive function [Verbal fluency]) was performed at baseline and after each treatment period. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 were completed. Peripheral and cerebral oxygen saturation were measured at rest and exercise (treadmill) at baseline and after each treatment period. Statistical analyses were descriptive without formal testing.ResultsMoCA scores were similar under POC (26.45±2.31) and Control (26.37±2.85); overall POC-Control difference was -0.090 (95% CI [-1.031, 0.850]). Because of a learning effect, post-hoc analyses were performed for Period 1, where the MoCA score difference was 1.705 [0.140, 3.271]. MoCA subscores suggested better performance with POC for Visuospatial/executive (0.618 [-0.106, 1.342]) and Attention (0.975 [0.207, 1.743]). POC trended to have better scores on Digit Span backward (difference: 0.822 [-0.067, 1.711]) and self-reported depressive symptoms (difference: -1.335 [-3.166, 0.495]). For specific PHQ-9 items, POC tended to have lower (better) scores for Q1 (Little interest/pleasure) and Q7 (Trouble concentrating). Cerebral oxygen saturations at end of exercise showed no difference between POC and Control. Peripheral saturations during exercise were similar under POC and Control (difference: 0.519% [-1.675, 2.714]).ConclusionAn advantage of POC over Control was observed for global cognition, attention, visuospatial/executive performance and depressive symptoms. Results need to be validated in a larger study.

Grape sour rot (GSR) is a disease complex involving fungi and bacteria that can cause significant yield losses of susceptible varieties. It is widely spread in the eastern U.S. and other grape-growing regions globally. Previous studies suggest that damaged fruit skin and feeding insects like Drosophila spp. are required for the disease to occur. Current control strategies for the management of sour rot are not sustainable, and research on the implications of chemical management of the disease on microbiome diversity is scarce. Our aim was to: i) investigate the effect of insecticide application and netting treatment on the microbiota of GSR-susceptible and tolerant grape varieties; and ii) identify the core microbial assemblages potentially associated with grape sour rot development in Maryland. Using a combined analysis of culture-dependent and independent data, we found that microbiota diversity of healthy grape berries did not change with netting, insecticide application, and between varieties. There was a significant difference in bacterial diversity between healthy and sour rot-affected berries. Komagataeibacter was consistently associated with infected berries followed by Acetobacter and Gluconobacter. This is the first study to report the association of Komagataeibacter with GSR-infected berries. It is thus imperative to investigate its role alongside that of other identified core microbiomes in sour rot development. Candida and Pichia were also consistent genera in infected berries. Several unidentified Candida, Pichia, and other fungal species from infected berries formed the core mycobiomes and it would be worth investigating their involvement in GSR development in Mid-Atlantic vineyards. [ABSTRACT FROM AUTHOR]

Background Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)—and thus transmissibility. Methods In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. Results Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2–38.4%) by RDT, 39.8% (36.6–43.0%) by saliva PCR, 40.1% (36.9–43.3%) by NP PCR, and 41.5% (38.3–44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3–33.3), 31.4% (28.4–34.5), 31.5% (28.5–34.6), and 31.6% (28.6–34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6–90.6%) for all positive patients, 94.5% (91.5–96.7%) for those with VL≥105 and 96.5% (93.6–98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4–96.9%), 86.1% (78.6–91.7%) and 84.1% (76.9–89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5–99.3%), 97.8% (92.1–99.7%) and 95.3% (89.4–98.5%) respectively. No patient with VLConclusions RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. Trial registration ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

In the sea of data generated daily, unlabeled samples greatly outnumber labeled ones. This is due to the fact that, in many application areas, labels are scarce or hard to obtain. In addition, unlabeled samples might belong to new classes that are not available in the label set associated with data. In this context, we propose A3SOM, an abstained explainable semi-supervised neural network that associates a self-organizing map to dense layers in order to classify samples. Abstained classification enables the detection of new classes and class overlaps. The use of a self-organizing map in A3SOM allows integrated visualization and makes the model explainable. Along with describing our approach, this paper shows that the method is competitive with other classifiers and demonstrates the benefits of including abstention rules. A use case is presented on breast cancer subtype classification and discovery to show the relevance of our method in real-world medical problems.

BackgroundSepsis is a leading cause of morbidity and mortality. Prompt recognition and management are critical to improve outcomes.MethodsWe conducted a survey among nurses and physicians of all adult departments of the Lausanne University Hospital (LUH) and paramedics transporting patients to our hospital. Measured outcomes included professionals' demographics (age, profession, seniority, unit of activity), quantification of prior sepsis education, self-evaluation, and knowledge of sepsis epidemiology, definition, recognition, and management. Correlation between surveyed personnel and sepsis perceptions and knowledge were assessed with univariable and multivariable logistic regression models.ResultsBetween January and October 2020, we contacted 1'216 of the 4'417 professionals (27.5%) of the LUH, of whom 1'116 (91.8%) completed the survey, including 619 of 2'463 (25.1%) nurses, 348 of 1'664 (20.9%) physicians and 149 of 290 (51.4%) paramedics. While 98.5% of the participants were familiar with the word "sepsis" (97.4% of nurses, 100% of physicians and 99.3% of paramedics), only 13% of them (physicians: 28.4%, nurses: 5.9%, paramedics: 6.8%) correctly identified the Sepsis-3 consensus definition. Similarly, only 48% and 49.3% of the physicians and 10.1% an 11.9% of the nurses knew that SOFA was a sepsis defining score and that the qSOFA score was a predictor of increased mortality, respectively. Furthermore, 15.8% of the physicians and 1.0% of the nurses knew the three components of the qSOFA score. For patients with suspected sepsis, 96.1%, 91.6% and 75.8% of physicians respectively chose blood cultures, broad-spectrum antibiotics and fluid resuscitation as therapeutic interventions to be initiated within 1 (76.4%) to 3 (18.2%) hours. For nurses and physicians, recent training correlated with knowledge of SOFA score (ORs [95%CI]: 3.956 [2.018-7.752] and 2.617 [1.527-4.485]) and qSOFA (ORs [95%CI]: 5.804 [2.653-9.742] and 2.291 [1.342-3.910]) scores purposes. Furthermore, recent training also correlated with adequate sepsis definition (ORs [95%CI]: 1.839 [1.026-3.295]) and the components of qSOFA (ORs [95%CI]: 2.388 [1.110-5.136]) in physicians.ConclusionsThis sepsis survey conducted among physicians, nurses and paramedics of a tertiary Swiss medical center identified a deficit of sepsis awareness and knowledge reflecting a lack of sepsis-specific continuing education requiring immediate corrective measures.

Chromolaena odorata is a noxious alien invasive weed species with an enormous impact on the terrestrial ecosystem. The allelopathic potentials of this weed have had little attention, leading to changes in soil properties and microbial communities. This study investigates the impacts of Chromolaena odorata invasion gradients on rhizospheric soil chemical properties and microbial response in the Mount Cameroon Region. Forty-eight soil samples at four different degrees of invasion (uninvaded, low degree invasion, moderate degree invasion and high degree invasion) based on species coverage within subplots in four study areas were collected and rhizospheric soil chemical properties, microbial load, phosphatases activities and secondary metabolites were evaluated. At medium-degree invasion, rhizospheric soil concentrations of P, K and Fe increased with arbuscular mycorrhizal fungi (AMF) colonization and phosphatases enzyme activities. Soil C, N and organic matter were significantly increased at high-degree invasion, supporting the use of the plant as a fallow crop. Acid phosphatase activity ranged from 0.69 to 0.90 mmol h-1 kg-1 and was significantly different at different degrees of invasion. AMF colonization ranged from 23.33 to 50.00%, with a strong positive correlation between AMF colonization and phosphatase activity. Soil bacterial load was high (46 × 105 CFU/g– 67 × 105 CFU/g), with mostly Staphylococcus having health concerns about its spread. The invasion situation had no significant effect on soil bacterial load, but high-degree invasion significantly increased fungal load. Low-degree invaded soils had high saponin (24.55±0.00 mg/g), flavonoid (47.7 mg/g) and tannin (28.68 mg/g) concentrations. The investigation reveals that Chromolaena odorata invasion altered rhizospheric soil properties and microbial communities significantly, thereby influencing ecosystem dynamics and soil nutrient availability. However, further studies elucidating kinds of secondary metabolites, identifying microbial communities, and monitoring soil changes influenced by C. odorata are essential for effective ecosystem management. [ABSTRACT FROM AUTHOR]

Background: Patients can experience persistent cognitive complaints and deficits in long-COVID. Inflammation and capillary damage may contribute to symptoms by interfering with tissue oxygenation. Methods: This was an exploratory pilot crossover study designed to describe the effects of supplemental oxygen (portable oxygen concentrator, POC) on cognitive performance and peripheral and cerebral oxygen saturation at rest and exercise. Participants with long-COVID (n = 21) were randomized 1:1 to: 1) POC (3h/day) for 2 weeks followed by standard of care (Control) for 2 weeks or 2) Control for 2 weeks then POC (3h/day) for 2 weeks, with a 1-week washout. Cognitive assessment (global cognition [Montreal Cognitive Assessment, MoCA], episodic memory [Hopkins], working memory [Digit Span], executive function [Verbal fluency]) was performed at baseline and after each treatment period. Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder-7 were completed. Peripheral and cerebral oxygen saturation were measured at rest and exercise (treadmill) at baseline and after each treatment period. Statistical analyses were descriptive without formal testing. Results: MoCA scores were similar under POC (26.45±2.31) and Control (26.37±2.85); overall POC-Control difference was -0.090 (95% CI [-1.031, 0.850]). Because of a learning effect, post-hoc analyses were performed for Period 1, where the MoCA score difference was 1.705 [0.140, 3.271]. MoCA subscores suggested better performance with POC for Visuospatial/executive (0.618 [-0.106, 1.342]) and Attention (0.975 [0.207, 1.743]). POC trended to have better scores on Digit Span backward (difference: 0.822 [-0.067, 1.711]) and self-reported depressive symptoms (difference: -1.335 [-3.166, 0.495]). For specific PHQ-9 items, POC tended to have lower (better) scores for Q1 (Little interest/pleasure) and Q7 (Trouble concentrating). Cerebral oxygen saturations at end of exercise showed no difference between POC and Control. Peripheral saturations during exercise were similar under POC and Control (difference: 0.519% [-1.675, 2.714]). Conclusion: An advantage of POC over Control was observed for global cognition, attention, visuospatial/executive performance and depressive symptoms. Results need to be validated in a larger study. [ABSTRACT FROM AUTHOR]

Tree improvement programs often focus on improving productivity-related traits; however, under present climate change scenarios, climate change-related (adaptive) traits should also be incorporated into such programs. Therefore, quantifying the genetic variation and correlations among productivity and adaptability traits, and the importance of genotype by environment interactions, including defense compounds involved in biotic and abiotic resistance, is essential for selecting parents for the production of resilient and sustainable forests. Here, we estimated quantitative genetic parameters for 15 growth, wood quality, drought resilience, and monoterpene traits for Picea glauca (Moench) Voss (white spruce). We sampled 1,540 trees from three open-pollinated progeny trials, genotyped with 467,224 SNP markers using genotyping-by-sequencing (GBS). We used the pedigree and SNP information to calculate, respectively, the average numerator and genomic relationship matrices, and univariate and multivariate individual-tree models to obtain estimates of (co)variance components. With few site-specific exceptions, all traits examined were under genetic control. Overall, higher heritability estimates were derived from the genomic- than their counterpart pedigree-based relationship matrix. Selection for height, generally, improved diameter and water use efficiency, but decreased wood density, microfibril angle, and drought resistance. Genome-based correlations between traits reaffirmed the pedigree-based correlations for most trait pairs. High and positive genetic correlations between sites were observed (average 0.68), except for those pairs involving the highest elevation, warmer, and moister site, specifically for growth and microfibril angle. These results illustrate the advantage of using genomic information jointly with productivity and adaptability traits, and defense compounds to enhance tree breeding selection for changing climate.

IntroductionMorphometric assessment of Chiari malformation type I (CMI) is typically performed on a midsagittal MRI. However, errors arising from an imprecise selection of the midsagittal plane are unknown. We define absolute parasagittal error as the absolute difference between morphometric measurements at the midsagittal and parasagittal planes. Our objective was to determine the absolute parasagittal error at various lateral distances for morphometric parameters commonly used in CMI research.MethodsSagittal T1-weighted MRI scans of 30 CMI adult female subjects were included. Image sets were evaluated to assess 14 CMI morphometric parameters in the midsagittal plane and four parasagittal planes located 1 and 2 mm lateral (left and right). Comparisons between measurements at the midsagittal and parasagittal planes were conducted to determine the mean individual absolute and mean group parasagittal errors for all 14 parameters.ResultsThe mean individual absolute parasagittal error was > 1 unit (1 mm for lengths and 1 degree for angles) for 9/14 parameters within a lateral distance of 2 mm. No significant group parasagittal errors were seen in 14/14 parameters, including tonsillar position within a lateral distance of 2 mm.ConclusionOur results show that the absolute errors for imprecise midsagittal plane selection may impact the clinical assessment of an individual patient. However, the impact on group measurements, such as in a research setting, will be minimal.

IntroductionTo sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving.MethodsThe VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences.Expected outcomesEvidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving.Trial registrationThe study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020).

Cervical cancer remains the third most frequently diagnosed and fourth leading cause of cancer death in women worldwide. We sought to develop a micro-RNA signature that was prognostic for disease-free survival, which could potentially allow tailoring of treatment for cervical cancer patients. A candidate prognostic 9-micro-RNA signature set was identified in the training set of 79 frozen specimens. However, three different approaches to validate this signature in an independent cohort of 87 patients with formalin-fixed paraffin-embedded (FFPE) specimens, were unsuccessful. There are several challenges and considerations associated with developing a prognostic micro-RNA signature for cervical cancer, namely: tumour heterogeneity, lack of concordance between frozen and FFPE specimens, and platform selection for global micro-RNA expression profiling in this disease. Our observations provide an important cautionary tale for future miRNA signature studies for cervical cancer, which can also be potentially applicable to miRNA profiling studies involving other types of human malignancies.

The down-regulation of microRNA-196b (miR-196b) has been reported, but its contribution to cervical cancer progression remains to be investigated. In this study, we first demonstrated that miR-196b down-regulation was significantly associated with worse disease-free survival (DFS) for cervical cancer patients treated with combined chemo-radiation. Secondly, using a tri-modal approach for target identification, we determined that homeobox-B7 (HOXB7) was a bona fide target for miR-196b, and in turn, vascular endothelial growth factor (VEGF) was a downstream transcript regulated by HOXB7. Reconstitution of miR-196b expression by transient transfection resulted in reduced cell growth, clonogenicity, migration and invasion in vitro, as well as reduced tumor angiogenesis and tumor cell proliferation in vivo. Concordantly, siRNA knockdown of HOXB7 or VEGF phenocopied the biological effects of miR-196b over-expression. Our findings have demonstrated that the miR-196b/HOXB7/VEGF pathway plays an important role in cervical cancer progression; hence targeting this pathway could be a promising therapeutic strategy for the future management of this disease.

BackgroundMalnutrition and low birth weight (LBW) are two common causes of morbidity and mortality among children in sub-Saharan Africa. Both malnutrition and LBW affect early childhood development with long term consequences that may vary in their degree depending on the geographical setting. This study evaluates growth, nutritional status and mortality of infants from Lambaréné and Fougamou in Gabon from a birth cohort of a malaria in pregnancy clinical trial (NCT00811421).MethodA prospective longitudinal birth cohort conducted between 2009 and 2012, included infants that were followed up from birth until their first-year anniversary. The exposure of interest was low birth weight and the outcomes explored were growth represented by weight gain, the nutritional status including stunting, wasting and underweight, and the mortality. Scheduled follow-up visits were at one, nine and 12 months of age. Logistic regression was used to assess the association between low birth weight and growth and nutritional outcomes, and cox regression was used for mortality.ResultA total of 907 live-born infants were included in the analysis. The prevalence of LBW was 13% (115). At one month of life, out of 743 infants 10% and 4% presented with stunting and underweight, respectively, while these proportions increased at 12 months of life to 17% and 21%, respectively, out of 530 infants. The proportion of infants with wasting remained constant at 7% throughout the follow-up period. Stunting and underweight were associated with LBW, adjusted odds ratio (aOR): 2.6, 95% confidence interval (95%CI): 1.4-4.9 and aOR: 4.5, 95%CI: 2.5-8.1, respectively. Preterm birth was associated with stunting, aOR: 2.7, 95%CI: 1.2-6.3 and underweight, aOR: 5.4, 95%CI: 1.7-16.1 at one month of life. Infants with LBW were at higher hazard of death during the first year of life, adjusted hazard ratio 4.6, 95%CI: 1.2-17.0.ConclusionLow birthweight infants in Gabon are at higher risks of growth and nutritional deficits and mortality during the first year of life. Tailored interventions aiming at preventing adverse pregnancy outcomes including LBW, early detection and appropriate management of growth, and nutritional deficits in infants are necessary in Gabon.

At least 2.1 billion people around the world use contaminated drinking water, causing 485,000 diarrheal deaths each year, mostly among children under 5 years old. A study conducted 10 years ago in Bafoussam (West Cameroon) recorded concentrations of bacteria among surface and groundwater. High levels of bicarbonates, phosphates, chlorides and suspended matters were also found. The aim of this study was to assess the microbiological and chemical qualities of domestic water sources in 5 localities of the West region of Cameroon. Water samples from 22 water sources (wells, springs, water drilling and river) were aseptically collected in plastic bottles and transferred in 50 ml sterile tubes. For chlorinated water sources, 1 ml of Thiosulfate was added to the water sample; immediately placed in an ice box and transported to the laboratory for analysis. Water temperature and pH were measured on site. The microbiological quality of water was determined by testing Total Coliforms (TC) using the Micro Biological Survey method. 1 ml of each water sample was inoculated in the MBS vial initially rehydrated with 10 ml of sterile distilled water. The initial color of the vials is red. Color changes were monitored at three different time intervals (12h, 19h and 24h), corresponding to three levels of contamination. The chemical quality of water was assessed using micronucleus (MN) test in selected Vicia faba seeds secondary root tips permanently mounted in Dibutylphthalate Polystyrene Xylene mountant for histology after 72 hours of direct exposition in water samples and in dark. The mitotic indices and MN frequencies were evaluated in 10 root tips per site analysing 5000 cells per tip. Statistical analyses were done using Stata IC/15.0 software. The Student t-test was used for mean comparison and the significance level was set at 1%. The majority of samples were collected from wells (63.6%). The mean water pH ranged from 5.5 to 8.3 and the temperature varied from 23 to 26°C. A very high concentration of TC [>103 CFU/ml] was found in 8 (36.4%) samples. 10 (45.5%) and 2 (9.1%) samples turned yellow at 19 and 24 hours respectively after incubation corresponding to TC concentration of [10

BackgroundAntiretroviral therapy (ART) success has led people to live longer with HIV/AIDS (PLWH) and thus be exposed to increasing risk of cardiovascular diseases (CVD). Hypertension (HTN), the biggest contributor to CVD burden, is a growing concern among PLWH. The current report describes the prevalence and predictors of HTN among PLWH in care in Cameroon.MethodsThis cross-sectional study included all PLWH aged 20 years and above who received care between 2016 and 2019 at one of the three Central Africa International Epidemiology Databases to Evaluate AIDS (CA-IeDEA) sites in Cameroon (Bamenda, Limbe, and Yaoundé). HTN was defined as blood pressure (BP) ≥140/90 mm Hg or self-reported use of antihypertensive medication. Logistic regressions models examined the relationship between HTN and clinical characteristics, and HIV-related factors.ResultsAmong 9,839 eligible PLWH, 66.2% were women and 25.0% had prevalent HTN [age-standardized prevalence 23.9% (95% CI: 22.2-25.6)], among whom 28 (1.1%) were on BP lowering treatment, and 6 of those (21.4%) were at target BP levels. Median age (47.4 vs. 40.5 years), self-reported duration of HIV infection (5.1 vs 2.8 years years), duration of ART exposure (4.7 vs 2.3 years), and CD4 count (408 vs 359 cell/mm3) were higher in hypertensives than non-hypertensives (all pConclusionAbout a quarter of these Cameroonian PLWH had HTN, driven among others by age and adiposity. Appropriate integration of HIV and NCDs services is needed to improve early detection, treatment and control of common comorbid NCD risk factors like hypertension and safeguard cardiovascular health in PLWH.

Background: Health personnel (HP) are on the frontlines during response to public health emergencies like COVID-19. This risk of exposure suggests the need for safety in responding to any pandemic. Therefore, to ascertain the rate of SARS-CoV-2 infection and immunity, and their determinants amongst HP become relevant. Methods: A cross sectional health facility-based study was carried-out amongst HP in the Centre Region of Cameroon from 1st February to 30th June 2021. Characteristics and access to preventive tools were collected using face-to-face administered questionnaire. Nasopharyngeal swabs and whole blood were collected for PCR, IgG and IgM testing respectively. STATA version 17 software was used for data analysis. Determinants of COVID-19 infection were explored by estimating crude and adjusted Odd Ratio. Results: Out of 510 HP reached, 458 were enrolled with mean age of 35 (±10) years. Thirty-four (7.4%) were PCR-positive to SARS-CoV-2 with 73.5% being clinicians versus 9 (26.4%) non-clinicians (p = 0.05). Sero-positivity to SARS-CoV-2 IgG/IgM was 40.2% (184/458), with 84.2% being clinicians versus 29 (15.8%) non-clinicians (p = 0.733). Amongst the 34 HP with PCR-positivity, 16 (47%) had no antibodies, while, 15 (44%) were IgG only. An estimate of HP (43.7%) had at least an evidence of PCR, IgG or IgM contact to COVID-19. Determinants of PCR-positivity was being clinical staff (AOR = 0.29, P = 0.039); and that of IgG/IgM were being non clinical staff (AOR = 0.41, p = 0.018) and regular use of face masks (AOR = 0.44, p = 0.001). HP trained on IPC (24%) were mainly from peripheral level (74.7%, p = 0.002). Conclusion: Active infections were within the range of pandemic control (<10%). However, around two-fifths of participants have had contact with the virus, indicating that HP remains a population at risk of COVID-19 and other similarly-transmitted epidemic prone diseases, and also an important source of transmission. There is need of vaccine to achieve protectiveness, and optimal response also requires capacity building to improve the health system when challenged by a future pandemic. [ABSTRACT FROM AUTHOR]

BackgroundThe presupposition of genomic selection (GS) is that predictive accuracies should be based on population-wide linkage disequilibrium (LD). However, in species with large, highly complex genomes the limitation of marker density may preclude the ability to resolve LD accurately enough for GS. Here we investigate such an effect in two conifer species with ~ 20 Gbp genomes, Douglas-fir (Pseudotsuga menziesii Mirb. (Franco)) and Interior spruce (Picea glauca (Moench) Voss x Picea engelmannii Parry ex Engelm.). Random sampling of markers was performed to obtain SNP sets with totals in the range of 200-50,000, this was replicated 10 times. Ridge Regression Best Linear Unbiased Predictor (RR-BLUP) was deployed as the GS method to test these SNP sets, and 10-fold cross-validation was performed on 1,321 Douglas-fir trees, representing 37 full-sib F1 families and on 1,126 Interior spruce trees, representing 25 open-pollinated (half-sib) families. Both trials are located on 3 sites in British Columbia, Canada.ResultsAs marker number increased, so did GS predictive accuracy for both conifer species. However, a plateau in the gain of accuracy became apparent around 10,000-15,000 markers for both Douglas-fir and Interior spruce. Despite random marker selection, little variation in predictive accuracy was observed across replications. On average, Douglas-fir prediction accuracies were higher than those of Interior spruce, reflecting the difference between full- and half-sib families for Douglas-fir and Interior spruce populations, respectively, as well as their respective effective population size.ConclusionsAlthough possibly advantageous within an advanced breeding population, reducing marker density cannot be recommended for carrying out GS in conifers. Significant LD between markers and putative causal variants was not detected using 50,000 SNPS, and GS was enabled only through the tracking of relatedness in the populations studied. Dramatically increasing marker density would enable said markers to better track LD with causal variants in these large, genetically diverse genomes; as well as providing a model that could be used across populations, breeding programs, and traits.

We studied a cohort of 367 healthy related donors who volunteered to donate their hematopoietic stem cells for allogeneic transplantation. All donors were homogeneously cared for at a single institution, and received rhG-CSF as a mobilization treatment prior to undergoing apheresis. Peripheral blood CD34+ cell counts were used as the main surrogate marker for rhG-CSF induced mobilization. We searched whether inter-individual variations in known genetic polymorphisms located in genes whose products are functionally important for mobilization, could affect the extent of CD34+ mobilization, either individually or in combination. We found little or no influence of individual SNPs or haplotypes for the SDF1, CXCR4, VCAM and VLA4 genes, whether using CD34+ cell counts as a continuous or a categorical variable. Simple clinical characteristics describing donors such as body mass index, age and possibly sex are more potent predictors of stem cell mobilization. The size of our cohort remains relatively small for genetic analyses, however compares favorably with cohorts analyzed in previously published reports suggesting associations of genetic traits to response to rhG-CSF; notwithstanding this limitation, our data do not support the use of genetic analyses when the choice exists of several potential donors for a given patient.

BACKGROUND:High-throughput sequencing technology has revolutionized both medical and biological research by generating exceedingly large numbers of genetic variants. The resulting datasets share a number of common characteristics that might lead to poor generalization capacity. Concerns include noise accumulated due to the large number of predictors, sparse information regarding the p≫n problem, and overfitting and model mis-identification resulting from spurious collinearity. Additionally, complex correlation patterns are present among variables. As a consequence, reliable variable selection techniques play a pivotal role in predictive analysis, generalization capability, and robustness in clustering, as well as interpretability of the derived models. METHODS AND FINDINGS:K-dominating set, a parameterized graph-theoretic generalization model, was used to model SNP (single nucleotide polymorphism) data as a similarity network and searched for representative SNP variables. In particular, each SNP was represented as a vertex in the graph, (dis)similarity measures such as correlation coefficients or pairwise linkage disequilibrium were estimated to describe the relationship between each pair of SNPs; a pair of vertices are adjacent, i.e. joined by an edge, if the pairwise similarity measure exceeds a user-specified threshold. A minimum k-dominating set in the SNP graph was then made as the smallest subset such that every SNP that is excluded from the subset has at least k neighbors in the selected ones. The strength of k-dominating set selection in identifying independent variables, and in culling representative variables that are highly correlated with others, was demonstrated by a simulated dataset. The advantages of k-dominating set variable selection were also illustrated in two applications: pedigree reconstruction using SNP profiles of 1,372 Douglas-fir trees, and species delineation for 226 grasshopper mouse samples. A C++ source code that implements SNP-SELECT and uses Gurobi optimization solver for the k-dominating set variable selection is available (https://github.com/transgenomicsosu/SNP-SELECT).

BackgroundThe intermittent preventive treatment in infants (IPTi) trial that took place in Papua New Guinea showed an overall reduction of 29% of the risk of malaria when delivering single-dose sulfadoxine-pyrimethamine (SP) associated to 3 days of amodiaquine (AQ) every three months to children during the first year of life. The aim of the present study was to assess if the last two doses of AQ were truly administered as prescribed by the parents at home based on drug level measurement and PK modelling, which is a good proxy of medication adherence. It provides also important information to discuss the efficacy of the intervention and on feasibility of self-administered preventive malaria treatment.Methods and findingsDuring the three-arm randomized double-blinded IPTi trial, each child was prescribed one dose of SP (day 0) and 3 doses of either AQ or artesunate (AS) at day 0, 1 & 2 adjusted to weight or placebo. Treatments were given at 3, 6, 9 and 12 months of age. The first day of treatment was delivered by nursing staff (initiation under directly observed treatment (DOT)) and the two last doses of AQ or AS by parents at home without supervision. For this cross-sectional study, 206 consecutive children already involved in the IPTi trial were enrolled over a 2-month period. At the time of the survey, allocation of the children to one of the three arms was not known. Blood samples for drug level measurement were collected from finger pricks one day after the planned last third dose intake. Only children allocated to the SP-AQ arm were included in the present analysis. Indeed, the half-life of AS is too short to assess if drugs were given on not. Because of the short half-life of AQ, desethyl-AQ (metabolite of AQ (DAQ)) measurements were used to investigate AQ medication adherence. Two PK (PK) models from previously published studies in paediatric populations were applied to the dataset using non-linear mixed effect modelling (NONMEM) to estimate the number of doses really given by the parents. The study nurse reported the administration time for the first AQ dose while it was estimated by the parents for the remaining two doses. Out of 206 children, 64 were in the SP-AQ arm. The adjusted dosing history for each individual was identified as the one with the lowest difference between observed and individual predicted concentrations estimated by the two PK models for all the possible adherence schemes. The median (range) blood concentration AQ in AQ arm was 9.3 ng/mL (0-1427.8 ng/mL), (Quartiles 1-3: 2.4 ng/mL -22.2 ng/mL). The median (range) for DAQ was 162.0 ng/mL (0-712 ng/mL), (Quartiles 1-3: 80.4 ng/mL-267.7 ng/mL). Under the assumption of full adherence for all participants, a marked underprediction of concentrations was observed using both PK models. Our results suggest that only 39-50% of children received the three scheduled doses of AQ as prescribed, 33-37% two doses and 17-24% received only the first dose administered by the study nurse. Both models were highly congruent to classify adherence patterns.ConclusionsConsidering the IPTi intervention, our results seem to indicate that medication adherence is low in the ideal trial research setting and is likely to be even lower if given in day-to-day practice, questioning the real impact that this intervention might have. More generally, the estimation of the number of doses truly administered, a proxy measure of adherence and an assessment of the feasibility of the mode of administration, should be more thoroughly studied when discussing the efficacy of the interventions in trials investigating self-administered malaria preventive treatments.

ObjectiveThis secondary analysis of data of a randomized controlled trial (RCT) retrospectively investigated the performance of pulse oximetry in identifying children with severe illnesses, with and without respiratory signs/symptoms, in a cohort of children followed for morbid episodes in an intervention trial assessing the efficacy of Intermittent Preventive Treatment for malaria in infants (IPTi) in Papua New Guinea (PNG) from June 2006 to May 2010.SettingThe IPTi study was conducted in a paediatric population visiting two health centres on the north coast of PNG in the Mugil area of the Sumkar District.ParticipantsA total of 669 children visited the clinic and a total of 1921 illness episodes were recorded. Inclusion criteria were: age between 3 and 27 months, full clinical record (signs/symptoms) and pulse oximetry used systematically to assess sick children at all visits. Children were excluded if they visited the clinic in the previous 14 days.OutcomesThe outcome measures were severe illness, severe pneumonia, pneumonia, defined by the Integrated Management of Childhood Illness (IMCI) definitions, and hospitalization.ResultsOut of 1921 illness episodes, 1663 fulfilled the inclusion criteria. A total of 139 severe illnesses were identified, of which 93 were severe pneumonia. The ROC curves of pulse oximetry (continuous variable) showed an AUC of 0.63, 0.68 and 0.65 for prediction of severe illness, severe pneumonia and hospitalization, respectively. Pulse oximetry allowed better discrimination between severe and non-severe illness, severe and non-severe pneumonia, admitted and non-admitted patients, in children ≤12-months of age relative to older patients. For the threshold of peripheral arterial oxygen saturation ≤ 94% measured by pulse oximetry (SpO2), unadjusted odds ratios for severe illness, severe pneumonia and hospitalization were 6.1 (95% Confidence Interval (CI) 3.9-9.8), 8.5 (4.9-14.6) and 5.9 (3.4-10.3), respectively.ConclusionPulse oximetry was helpful in identifying children with severe illness in outpatient facilities in PNG. A SpO2 of 94% seems the most discriminative threshold. Considering its affordability and ease of use, pulse oximetry could be a valuable additional tool assisting the decision to admit for treatment.

IntroductionArtemisinin-based combination therapy is currently the best option for the treatment of uncomplicated malaria. Quinine is recommended as a rescue treatment. Safety information during repeated treatment with the same drug is scarce. We report safety data from the Quinact randomized clinical trial (RCT) that was designed to assess efficacy and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and quinine+clindamycin (QnC).MethodologyMales and females aged 12 to 59 months with uncomplicated malaria were treated with ASAQ and followed up during 42 days (preRCT). Clinical failures were randomized to one of the 3 treatments and followed up for 28 days (RCT). Subsequent failures were repeatedly treated with ASAQ several times as needed (postRCT1, postRCT2 and so on) until a 28-days follow up period without parasitaemia.ResultsEight hundred and sixty-five, 242 and 64 patients were recruited respectively in preRCT, RCT and postRCTs. In preRCT, 433 (50.0%) patients experienced at least one drug-related adverse event (AE). The most reported AEs were anorexia (22.9%), asthenia (19.4%), and abnormal behavior (14.6%). Twenty-nine AEs (3.5%) were reported to be severe. In RCT, at least one drug-related AE was reported in 54.7%, 21.5% and 40.0% of patient randomized respectively to ASAQ, AL and QnC (pConclusionThe proportion of AEs did not increase over the treatment courses with ASAQ. However, continuous monitoring is important.

BACKGROUND:Understanding pattern of antimalarials use at large scale helps ensuring appropriate use of treatments and preventing the spread of resistant parasites. We estimated the proportion of individuals in community surveys with residual antimalarials in their blood and identified the factors associated with the presence of the most commonly detected drugs, lumefantrine and/or desbutyl-lumefantrine (LF/DLF) or sulfadoxine-pyrimethamine (SP). METHODS:A cross-sectional survey was conducted in 2015 in three regions of Tanzania with different levels of malaria endemicity. Interviews were conducted and blood samples collected through household surveys for further antimalarial measurements using liquid chromatography coupled to tandem mass spectrometry. In addition, diagnosis and treatment availability was investigated through outlet surveys. Multilevel mixed effects logistic regression models were used to estimate odds ratios for having LF/DLF or SP in the blood. RESULTS:Amongst 6391 participants, 12.4% (792/6391) had LF/DLF and 8.0% (510/6391) SP in the blood. Factors associated with higher odds of detecting LF/DLF in the blood included fever in the previous two weeks (OR = 2.6, p

BACKGROUND:Quick Sequential Organ Failure Assessment (qSOFA) is a three-item clinical instrument for bedside identification of sepsis patients at risk of poor outcome. qSOFA could be a valuable triage tool in emergency departments of low-income countries, yet its performance in resource-limited settings remains unknown. The prognostic accuracy of qSOFA for 28-day all-cause mortality in febrile adults treated at the EDs in a low-income country was evaluated. METHODS:Retrospective analysis of a prospective cohort study of consecutive patients (≥18 years) with fever (tympanic temperature ≥38°C and fever ≤7 days) who presented between July 2013 and May 2014 at four emergency departments in Dar es Salaam, Tanzania. Medical history, clinical examination, laboratory and microbiological data were collected to document the cause of fever. Variables for the previous and new sepsis criteria were collected at inclusion and qSOFA, SOFA and SIRS were measured at inclusion. Patients were followed up by phone at day 28. The performance (sensitivity, specificity and area under the receiver operating curve [AUROC]) of qSOFA (score ≥2), SOFA (increase of ≥2 points) and SIRS (≥2 criteria) as predictors of 28-day all-cause mortality was evaluated. RESULTS:Among the 519 patients (median age: 30 years) included in the analysis, 47% were female and 25% were HIV positive. Overall, 85% had a microbiologically and/or clinically documented infection and 15% a fever of unknown origin. The most common site and causes of infections were the respiratory tract (43%), dengue (26%), malaria (6%) and typhoid fever (5%). Twenty-eight-day all-cause mortality was 6%: 3% for patients with a qSOFA

Melilotus is an important genus of legume plants and an herbage with excellent nitrogen fixation; it can tolerate extreme environmental conditions and possesses important medicinal value. However, there is limited genetic information about the genus; thus, we analysed four chloroplast loci (rbcL, matK, psbA-trnH and trnL-F) and one nuclear region (ITS) to determine the genetic diversity of 199 accessions from 18 Melilotus species. The rbcL and matK sequences were highly conserved, whereas the trnL-F and ITS sequences contained variable and parsimony-informative sites. In our analyses of the single and combined regions, we calculated the pairwise distance, haplotype and nucleotide diversity and gaps and then constructed phylogenetic trees to assess the genetic diversity, and our results revealed significant variations among the different accessions. The genetic distance values were between zero and nine, and based on the combined regions, the highest frequency value was approximately four. Melilotus showed high haplotype and nucleotide diversity, particularly in the ITS sequences, with values of 0.86 and 0.0087, respectively. The single ITS sequence, psbA-trnH, and the combined matK+rbcL+trnL-F (MRT) and matK+rbcL+psbA-trnH+trnL-F+ITS (MRPTI) regions showed interspecific variation in the gap analysis. Phylogenetic trees calculated using ITS, psbA-trnH and MRPTI sequences indicated distinct genetic relationship in 18 species, and these species could be divided into two groups. By determining the genetic diversity of plants, we can evaluate the genetic relationships among species and accessions, providing a basis for preserving and utilizing the genetic resources of Melilotus.

BACKGROUND:In most emergency departments (EDs), few patients account for a relatively high number of ED visits. To improve the management of these patients, the university hospital of Lausanne, Switzerland, implemented an interdisciplinary case management (CM) intervention. This study examined whether the CM intervention-compared with standard care (SC) in the ED-reduced costs generated by frequent ED users, not only from the hospital perspective, but also from the third-party payer perspective, that is, from a broader perspective that takes into account the costs of health care services used outside the hospital offering the intervention. METHODS:In this randomized controlled trial, 250 frequent ED users (>5 visits during the previous 12 months) were allocated to either the CM or the SC group and followed up for 12 months. Cost data were obtained from the hospital's analytical accounting system for the entire sample and from health insurance companies for a subgroup (n = 140). Descriptive statistics and multivariate regressions were used to make comparisons between groups and assess the contribution of patient characteristics to the main cost components. RESULTS:At the end of the 12-month follow-up, 115 patients were in the CM group and 115 in the SC group (20 had died). Despite differences in economic costs between patients in the CM intervention and the SC groups, our results do not show any statistically significant reduction in costs associated with the intervention, either for the hospital that housed the intervention or for the third-party payer. Frequent ED users were big users of health services provided by both the hospital and community-based services, with 40% of costs generated outside the hospital that housed the intervention. Higher age, Swiss citizenship, and having social difficulty increased costs significantly. CONCLUSIONS:As the role of the CM team is to guide patients through the entire care process, the intervention location is not limited to the hospital but often extends into the community.

Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers. The most abundant rings were composed of 16 monomers and had an outer and inner ring diameter of ~30 nm and ~20 nm, respectively. Three-dimensional analysis was performed with rings containing 16 monomers. The single-particle cryo-electron microscopy map of the 16 monomer DRP1 rings suggests a side-by-side assembly of the monomer with the membrane in a parallel fashion. The inner ring diameter of 20 nm is insufficient to allow four membranes to exist as separate entities. Furthermore, we observed that mitochondria were tubulated upon incubation with DRP1 protein in vitro. The tubes had a diameter of ~ 30nm and were decorated with protein densities. These findings suggest DRP1 tubulates mitochondria, and that additional steps may be required for final mitochondrial fission.

Melilotus, an annual or biennial herb, belongs to the tribe Trifolieae (Leguminosae) and consists of 19 species. As an important green manure crop, diverse Melilotus species have different values as feed and medicine. To identify different Melilotus species, we examined the efficiency of five candidate regions as barcodes, including the internal transcribed spacer (ITS) and two chloroplast loci, rbcL and matK, and two non-coding loci, trnH-psbA and trnL-F. In total, 198 individuals from 98 accessions representing 18 Melilotus species were sequenced for these five potential barcodes. Based on inter-specific divergence, we analysed sequences and confirmed that each candidate barcode was able to identify some of the 18 species. The resolution of a single barcode and its combinations ranged from 33.33% to 88.89%. Analysis of pairwise distances showed that matK+rbcL+trnL-F+trnH-psbA+ITS (MRTPI) had the greatest value and rbcL the least. Barcode gap values and similarity value analyses confirmed these trends. The results indicated that an ITS region, successfully identifying 13 of 18 species, was the most appropriate single barcode and that the combination of all five potential barcodes identified 16 of the 18 species. We conclude that MRTPI is the most effective tool for Melilotus species identification. Taking full advantage of the barcode system, a clear taxonomic relationship can be applied to identify Melilotus species and enhance their practical production.

Prison healthcare is an important public health concern given the increasing healthcare needs of a growing and aging prison population, which accumulates vulnerability factors and suffers from higher disease prevalence than the general population. This study identifies the key factors associated with outpatient general practitioner (GP), nursing or psychiatric healthcare utilization (HCU) within prisons. Cross-sectional data systematically collected by the prison medical staff were obtained for a sample of 1664 adult prisoners of the Canton of Vaud, Switzerland, for the year 2011. They contain detailed information on demographics (predisposing factors), diagnosed chronic somatic and psychiatric disorders (needs factors), as well as prison stay characteristics (contextual factors). For GP, nurse and psychiatric care, two-part regressions are used to model separately the probability and the volume of HCU. Predisposing factors are generally not associated with the probability to use healthcare services after controlling for needs factors. However, female inmates use higher volumes of care, and the volume of GP consultations increases with age. Chronic somatic and psychiatric conditions are the most important predictors of the probability of HCU, but associations with volumes differ in their magnitude and significance across disease groups. Infectious, musculoskeletal, nervous and circulatory diseases actively mobilize GP and nursing staff. Schizophrenia, illicit drug and pharmaceuticals abuse are strongly positively associated with psychiatric and nurse HCU. The occupancy rate displays positive associations among contextual factors. Prison healthcare systems face increasingly complex organizational, budgetary and ethical challenges. This study provides relevant insights into the HCU patterns of a marginalized and understudied population.

To construct evidence-based guidelines for management of febrile illness, it is essential to identify clinical predictors for the main causes of fever, either to diagnose the disease when no laboratory test is available or to better target testing when a test is available. The objective was to investigate clinical predictors of several diseases in a cohort of febrile children attending outpatient clinics in Tanzania, whose diagnoses have been established after extensive clinical and laboratory workup.From April to December 2008, 1005 consecutive children aged 2 months to 10 years with temperature ≥38°C attending two outpatient clinics in Dar es Salaam were included. Demographic characteristics, symptoms and signs, comorbidities, full blood count and liver enzyme level were investigated by bi- and multi-variate analyses (Chan, et al., 2008). To evaluate accuracy of combined predictors to construct algorithms, classification and regression tree (CART) analyses were also performed.62 variables were studied. Between 4 and 15 significant predictors to rule in (aLR+>1) or rule out (aLR+3 days (45%,83%); viral disease: runny nose, cough and age

The period from conception to 24 months of age is a crucial window for nutrition interventions. Personalized maternal counseling may improve childbirth outcomes, growth, and health. We assessed the effectiveness of facility-based personalized maternal nutrition counseling (from pregnancy to 18 months after birth) in improving child growth and health in rural Burkina Faso. We conducted a paired cluster randomized controlled trial in a rural district of Burkina Faso with 12 primary health centers (clusters). Healthcare providers in the intervention centers received patient-centered communication and nutrition counseling training. Pregnant women in the third trimester living in the center catchment areas and intending to stay for the next 2 years were prospectively included. We followed 2253 mother-child pairs quarterly until the child was aged 18 months. Women were interviewed about counseling experiences, dietary practices during pregnancy, and their child's feeding practices and morbidity history. Anthropometric measurements were taken at each visit using standardized methods. The primary outcomes were the cumulative incidence of wasting, and changes in child weight-for-height z-score (WHZ). Secondary outcomes were the women's prenatal dietary practices, early breastfeeding practices, exclusive breastfeeding, timely introduction of complementary food, child's feeding frequency and dietary diversity, children's mean birth weight, endpoint prevalence of stunting, and cumulative incidence of diarrhea, fever, and acute respiratory infection. All analyses were by intention-to-treat using mixed effects models. The intervention and control arms each included six health centers. Mothers in the intervention arm had a significantly higher exposure to counseling with 11.2% for breastfeeding techniques to 75.7% for counseling on exclusive breastfeeding. Mothers of infants below 6 months of age in the intervention arm were more likely to exclusively breastfeed (54.3% vs 42.3%; Difference of Proportion (DP) 12.8%; 95% CI: 2.1, 23.6; p = 0.020) as compared to the control arm. Between 6 and 18 months of age, more children in the intervention arm benefited from the required feeding frequency (68.8% vs 53.4%; DP 14.1%; 95% CI: 9.0, 19.2; p

In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the multiplicity of infection in children with uncomplicated malaria.Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and multiplicity of infection (MOI).In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8-58.8) and 92.8% (95%CI: 91.0-94.6) respectively, as 83.6% (95%CI: 79.1-87.2) of the recurrences were new infections. Compared to monoclonal infections, polyclonal infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20-2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7-6.7) decreased to 3 (IQR: 1-5) in the recurrent samples (p

BACKGROUND:We assessed nasopharyngeal (NP) carriage of five pathogens in febrile children with and without acute respiratory infection (ARI) of the upper (URTI) or lower tract, attending health facilities in Tanzania. METHODS:NP swabs collected from children (N = 960) aged 2 months to 10 years, and with a temperature ≥38°C, were utilized to quantify bacterial density of S. pneumoniae (Sp), H. influenzae (Hi), M. catarrhalis (Mc), S. aureus (Sa), and N. meningitidis (Nm). We determined associations between presence of individual species, densities, or concurrent carriage of all species combination with respiratory diseases including clinical pneumonia, pneumonia with normal chest radiography (CXR) and endpoint pneumonia. RESULTS:Individual carriage, and NP density, of Sp, Hi, or Mc, but not Sa, or Nm, was significantly associated with febrile ARI and clinical pneumonia when compared to febrile non-ARI episodes. Density was also significantly increased in severe pneumonia when compared to mild URTI (Sp, p

SCN5A is a susceptibility gene for type 3 long QT syndrome, Brugada syndrome, and sudden infant death syndrome. INa dysfunction from mutated SCN5A can depend upon the splice variant background in which it is expressed and also upon environmental factors such as acidosis. S1787N was reported previously as a LQT3-associated mutation and has also been observed in 1 of 295 healthy white controls. Here, we determined the in vitro biophysical phenotype of SCN5A-S1787N in an effort to further assess its possible pathogenicity.We engineered S1787N in the two most common alternatively spliced SCN5A isoforms, the major isoform lacking a glutamine at position 1077 (Q1077del) and the minor isoform containing Q1077, and expressed these two engineered constructs in HEK293 cells for electrophysiological study. Macroscopic voltage-gated INa was measured 24 hours after transfection with standard whole-cell patch clamp techniques. We applied intracellular solutions with pH7.4 or pH6.7. S1787N in the Q1077 background had WT-like INa including peak INa density, activation and inactivation parameters, and late INa amplitude in both pH 7.4 and pH 6.7. However, with S1787N in the Q1077del background, the percentages of INa late/peak were increased by 2.1 fold in pH 7.4 and by 2.9 fold in pH 6.7 when compared to WT.The LQT3-like biophysical phenotype for S1787N depends on both the SCN5A splice variant and on the intracellular pH. These findings provide further evidence that the splice variant and environmental factors affect the molecular phenotype of cardiac SCN5A-encoded sodium channel (Nav1.5), has implications for the clinical phenotype, and may provide insight into acidosis-induced arrhythmia mechanisms.

Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including neurodegenerative disorders. In the present study, we report that chronic PMB treatment mitigates dopaminergic loss induced by unilateral overexpression of human α-synuclein (α-syn) in the substantia nigra of an AAV-based rat genetic model of Parkinson's disease (PD). In this model, daily exposure of both sides of the rat's head to 808-nm near-infrared light for 28 consecutive days alleviated α-syn-induced motor impairment, as assessed using the cylinder test. This treatment also significantly reduced dopaminergic neuronal loss in the injected substantia nigra and preserved dopaminergic fibers in the ipsilateral striatum. These beneficial effects were sustained for at least 6 weeks after discontinuing the treatment. Together, our data point to PBM as a possible therapeutic strategy for the treatment of PD and other related synucleinopathies.

Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance.We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis.Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038).In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

Cervical cancer remains the third most frequently diagnosed and fourth leading cause of cancer death in women worldwide. We sought to develop a micro-RNA signature that was prognostic for disease-free survival, which could potentially allow tailoring of treatment for cervical cancer patients. A candidate prognostic 9-micro-RNA signature set was identified in the training set of 79 frozen specimens. However, three different approaches to validate this signature in an independent cohort of 87 patients with formalin-fixed paraffin-embedded (FFPE) specimens, were unsuccessful. There are several challenges and considerations associated with developing a prognostic micro-RNA signature for cervical cancer, namely: tumour heterogeneity, lack of concordance between frozen and FFPE specimens, and platform selection for global micro-RNA expression profiling in this disease. Our observations provide an important cautionary tale for future miRNA signature studies for cervical cancer, which can also be potentially applicable to miRNA profiling studies involving other types of human malignancies.

The decline of malaria and scale-up of rapid diagnostic tests calls for a revision of IMCI. A new algorithm (ALMANACH) running on mobile technology was developed based on the latest evidence. The objective was to ensure that ALMANACH was safe, while keeping a low rate of antibiotic prescription.Consecutive children aged 2-59 months with acute illness were managed using ALMANACH (2 intervention facilities), or standard practice (2 control facilities) in Tanzania. Primary outcomes were proportion of children cured at day 7 and who received antibiotics on day 0.130/842 (15∙4%) in ALMANACH and 241/623 (38∙7%) in control arm were diagnosed with an infection in need for antibiotic, while 3∙8% and 9∙6% had malaria. 815/838 (97∙3%;96∙1-98.4%) were cured at D7 using ALMANACH versus 573/623 (92∙0%;89∙8-94∙1%) using standard practice (p