Search

BackgroundVaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.MethodsIn this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5–7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4–8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.FindingsChronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5–7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03).InterpretationOverall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.

BackgroundSince Aedes aegypti mosquitoes preferentially breed in domestic containers, control efforts focus on larval source reduction. Our objectives were to design and test the effectiveness of a source reduction intervention to improve caregiver knowledge and behaviors in coastal Kenya.Methodology/principal findingsWe conducted a cluster-randomized controlled trial with 261 households from 5 control villages and 259 households from 5 intervention villages. From each household, one child (10-16 years old) and his or her primary caregiver participated in the intervention. We assessed caregiver knowledge and behavior at baseline, as well as 3 and 12 months after the intervention. We assessed household entomological indices at baseline and 12 months after the intervention to avoid seasonal interference. We conducted qualitative interviews with 34 caregivers to understand barriers and facilitators to change. We counted and weighed containers collected by children and parents during a community container clean-up and recycling event. After 12 months, caregiver knowledge about and self-reported behavior related to at least one source reduction technique was more than 50 percentage points higher in the intervention compared to control arm (adjusted risk differences for knowledge: 0.69, 95% CI [0.56 to 0.82], and behavior: 0.58 [0.43 to 0.73]). Respondents stated that other family members' actions were the primary barriers to proper container management. The number of containers at households did not differ significantly across arms even though children and parents collected 17,200 containers (1 ton of plastics) which were used to planted 4,000 native trees as part of the community event.Conclusions/significanceOur study demonstrates that source reduction interventions can be effective if designed with an understanding of the social and entomological context. Further, source reduction is not an individual issue, but rather a social/communal issue, requiring the participation of other household and community members to be sustained.

The effects of climate on vector-borne disease systems are highly context-dependent. Here, the authors incorporate laboratory-measured physiological traits of the mosquito Aedes aegypti into climate-driven mechanistic models to predict number, timing, and duration of outbreaks in Ecuador and Kenya.

Anecdotal evidence has long suggested that patients with lower urinary tract symptoms (LUTS) develop mood disorders, such as depression and anxiety, at a higher rate than the general population and recent prospective studies have confirmed this link. Breakthroughs in our understanding of the diseases underlying LUTS have shown that many have a substantial inflammatory component and great strides have been made recently in our understanding of how this inflammation is triggered. Meanwhile, studies on mood disorders have found that many are associated with central neuroinflammation, most notably in the hippocampus. Excitingly, work on other diseases characterized by peripheral inflammation has shown that they can trigger central neuroinflammation and mood disorders. In this review, we discuss the current evidence tying LUTS to mood disorders, its possible bidirectionally, and inflammation as a common mechanism. We also review modern theories of inflammation and depression. Finally, we discuss exciting new animal studies that directly tie two bladder conditions characterized by extensive bladder inflammation (cyclophosphamide-induced hemorrhagic cystitis and bladder outlet obstruction) to neuroinflammation and depression. We conclude with a discussion of possible mechanisms by which peripheral inflammation is translated into central neuroinflammation with the resulting psychiatric concerns.

The BlueFlux field campaign, supported by NASA’s Carbon Monitoring System, will develop prototype blue carbon products to inform coastal carbon management. While blue carbon has been suggested as a nature-based climate solution (NBS) to remove carbon dioxide (CO _2 ) from the atmosphere, these ecosystems also release additional greenhouse gases (GHGs) such as methane (CH _4 ) and are sensitive to disturbances including hurricanes and sea-level rise. To understand blue carbon as an NBS, BlueFlux is conducting multi-scale measurements of CO _2 and CH _4 fluxes across coastal landscapes, combined with long-term carbon burial, in Southern Florida using chambers, flux towers, and aircraft combined with remote-sensing observations for regional upscaling. During the first deployment in April 2022, CO _2 uptake and CH _4 emissions across the Everglades National Park averaged −4.9 ± 4.7 μ mol CO _2 m ^−2 s ^−1 and 19.8 ± 41.1 nmol CH _4 m ^−2 s ^−1 , respectively. When scaled to the region, mangrove CH _4 emissions offset the mangrove CO _2 uptake by about 5% (assuming a 100 year CH _4 global warming potential of 28), leading to total net uptake of 31.8 Tg CO _2 -eq y ^−1 . Subsequent field campaigns will measure diurnal and seasonal changes in emissions and integrate measurements of long-term carbon burial to develop comprehensive annual and long-term GHG budgets to inform blue carbon as a climate solution.

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014–2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014–2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

Financial statements are a form of a report presented by a company that shows the financial performance of the company. In many cases of financial report fraud committed by Public Accounting Firm, they beautify the financial statements so that many investors are interested in the company. Therefore, this study aims to examine the influence of the Fraud Triangle factor in detecting fraudulent financial statements. The object of this study uses the financial statements of the Cigarettes and Cosmetics subsectors that are listed on the Indonesia Stock Exchange in the period 2016-2018. This study uses thirty sample data using purposive methods based on criteria. Data analysis using logistic linear regression analysis. The results showed that Rationalization had a significant effect on financial statement fraud. Meanwhile, Financial Stability, External Pressure, Personal Financial Need, Financial Targets, Ineffective Monitoring, Nature of Industry have no significant effect on financial statement fraud. Keywords: Fraud, Pressure, Opportunity, Rationalization, Financial Statement Fraud

Mycorrhizal symbioses have evolved repeatedly in diverse fungal lineages. A large phylogenomic analysis sheds light on genomic changes associated with transitions from saprotrophy to symbiosis, including divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild.

AbstractMembers of the fungal genus PhyllostictaCitrusCitrus sinensisCitrus limonCitrus maximaPhyllostictaPhyllostictaPhyllosticta citrichinaensisPhyllostictaCitrusPhyllosticta citrichinaensisPhyllosticta citrichinaensisPhyllosticta

Identifying the mechanism of naturally acquired immunity against Plasmodium falciparum malaria could contribute to the design of effective malaria vaccines. Using a recently developed multiplexed FluoroSpot assay, we assessed cross-sectional pre-existing memory B-cells (MBCs) and antibody responses against six well known P. falciparum antigens (MSP-119, MSP-2 (3D7), MSP-2 (FC27), MSP-3, AMA-1 and CSP) and measured their associations with previous infections and time to clinical malaria in the ensuing malaria season in Kenyan children. These children were under active weekly surveillance for malaria as part of a long-term longitudinal malaria immunology cohort study, where they are recruited from birth. After performing Cox regression analysis, we found that children with a breadth of three or more antigen-specific MBC or antibody responses at the baseline had a reduced risk for malaria in the ensuing P. falciparum transmission season. Specifically, MBC responses against AMA-1, MSP-2 (3D7) and MSP-3, as well as antibody responses to MSP-2 (3D7) and MSP-3 were prospectively associated with a reduced risk for malaria. The magnitude or breadth of MBC responses were however not correlated with the cumulative number of malaria episodes since birth. We conclude that increased breadth for merozoite antigen-specific MBC and antibody responses is associated with protection against malaria.

Background: Snakebites affect over 5 million people each year, and over 100,000 per year die as a result. The only available treatment is antivenom, which has many shortcomings including high cost, intravenous administration, and high risk of adverse events. One of the most abundant and harmful components of viper venoms are the zinc-dependent snake venom metalloproteinases (SVMPs). Unithiol is a chelating agent which is routinely used to treat heavy metal poisoning. In vivo experiments in small animal models have demonstrated that unithiol can prevent local tissue damage and death caused by a certain viper species. This phase I clinical trial will assess the safety of ascending doses of unithiol with a view for repurposing for snakebite indication. Methods: This open label, single agent, phase I clinical trial of a repurposed drug has a primary objective to evaluate the safety of escalating doses of unithiol, and a secondary objective to describe its pharmacokinetics. In total, 64 healthy Kenyan volunteers from Kilifi County will be dosed in consecutive groups of eight, with dose escalation decisions dependent on review of safety data by an independent data safety monitoring board. Four groups will receive ascending single oral doses, two will receive multiple oral doses, and two will receive single intravenous doses. Follow-up will be for 6-months and includes full adverse event reporting. Pharmacokinetic analysis will define the Cmax, Tmax, half-life and renal elimination. Conclusions: This clinical trial will assess the safety and tolerability of a promising oral therapeutic in a relevant setting where snakebites are prevalent. Unithiol is likely to be safer than antivenom, is easier to manufacture, has activity against diverse snake species, and can be administered orally, and thus shows promise for repurposing for tropical snakebite. Pan African Clinical Trials Registry: PACTR202103718625048 (3/3/2021)

After decades of research, our understanding of when and why individuals infected with Plasmodium falciparum develop clinical malaria is still limited. Correlates of immune protection are often sought through prospective cohort studies, where measured host factors are correlated against the incidence of clinical disease over a set period of time. However, robustly inferring individual-level protection from these population-level findings has proved difficult due to small effect sizes and high levels of variance underlying such data. In order to better understand the nature of these inter-individual variations, we analysed the long-term malaria epidemiology of children ≤12 years old growing up under seasonal exposure to the parasite in the sub-location of Junju, Kenya. Despite the cohort’s limited geographic expanse (ca. 3km x 10km), our data reveal a high degree of spatial and temporal variability in malaria prevalence and incidence rates, causing individuals to experience varying levels of exposure to the parasite at different times during their life. Analysing individual-level infection histories further reveal an unexpectedly high variability in the rate at which children experience clinical malaria episodes. Besides exposure to the parasite, measured as disease prevalence in the surrounding area, we find that the birth time of year has an independent effect on the individual’s risk of experiencing a clinical episode. Furthermore, our analyses reveal that those children with a history of an above average number of episodes are more likely to experience further episodes during the upcoming transmission season. These findings are indicative of phenotypic differences in the rates by which children acquire clinical protection to malaria and offer important insights into the natural variability underlying malaria epidemiology.

Background: Studies of long-term malaria cohorts have provided essential insights into how Plasmodium falciparum interacts with humans, and influences the development of antimalarial immunity. Immunity to malaria is acquired gradually after multiple infections, some of which present with clinical symptoms. However, there is considerable variation in the number of clinical episodes experienced by children of the same age within the same cohort. Understanding this variation in clinical symptoms and how it relates to the development of naturally acquired immunity is crucial in identifying how and when some children stop experiencing further malaria episodes. Where variability in clinical episodes may result from different rates of acquisition of immunity, or from variable exposure to the parasite. Methods: Using data from a longitudinal cohort of children residing in an area of moderate P. falciparum transmission in Kilifi district, Kenya, we fitted cumulative episode curves as monotonic-increasing splines, to 56 children under surveillance for malaria from the age of 5 to 15. Results: There was large variability in the accumulation of numbers of clinical malaria episodes experienced by the children, despite being of similar age and living in the same general location. One group of children from a particular sub-region of the cohort stopped accumulating clinical malaria episodes earlier than other children in the study. Despite lack of further clinical episodes of malaria, these children had higher asymptomatic parasite densities and higher antibody titres to a panel of P. falciparum blood-stage antigens. Conclusions: This suggests development of clinical immunity rather than lack of exposure to the parasite, and supports the view that this immunity to malaria disease is maintained by a greater exposure to P. falciparum, and thus higher parasite burdens. Our study illustrates the complexity of anti-malaria immunity and underscores the need for analyses which can sufficiently reflect the heterogeneity within endemic populations.

Studies focused on jumping performance in humans have so far investigated either its biological or sociocultural significance, with very little attentions paid to the inseparable relations of these two aspects in daily life of people. Integrating both ethnographic and biomechanical methods, this research investigated the biosocial features of the jump performance of Maasai youth in its most well observed context, the wedding ceremony. Ethnographic data were used to explain the social status of participants, the physical movements and singing tempo of performers, and their interactions. Biomechanical methods were applied to assess the heights and frequencies of identified repetitive double-legged vertical jumps (n = 160, from 15 male youths). All youth performers followed a certain posture pattern, paying specific attention to their final landing. Large variations exist in their jumping heights [coefficient of variation (CV) = 0.237]; however, the frequency in jump repetitions were maintained with the least variations (CV = 0.084). Cheering interactions were confirmed, but with no significant difference in height between the cheered and non-cheered groups. These results indicate that the Maasai youths did not compete for jump height during local ceremonies. Rather, they emphasized the rhythmical retention of jumps, corresponding to other youth mates who were singing alongside. In the broader context of human behaviors, the analysis addresses the diverse meanings of motor performances in different daily contexts that reject the generalized sports regime of "higher/faster-the-better".

Alesha Wale,1 Mark Ireland,2 Rowan Yemm,1 Sarah Hiom,3 Alison Jones,3 John Paul Spark,3 Mark Francis,4 Karen May,5 Louise Allen,5 Steve Ridd,6 Efi Mantzourani1,7 1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, Wales, UK; 2Community Pharmacy Wales, Cardiff, Wales, UK; 3St. Mary’s Pharmaceutical Unit, Cardiff, Wales, UK; 4Swansea Bay University Health Board, Swansea, Wales, UK; 5Cardiff and Vale University Health Board, Swansea, Wales, UK; 6Mayberry Pharmacy, Cardiff, Wales, UK; 7NHS Wales Informatics Service, Cardiff, Wales, UKCorrespondence: Efi Mantzourani Email MantzouraniE1@cardiff.ac.ukObjective: Community pharmacy staff are responsible for obtaining and supplying unlicensed “special” medicines to patients in primary care. Less well-defined parameters for safe and effective use of unlicensed compared to licensed medicines, along with issues around maintaining consistency between care settings or among manufacturers, have been associated with increased risks. This study aimed to explore the views and experiences of community pharmacy staff on accessing and supplying unlicensed “special” medicines to patients in Wales and the perceived impact of challenges faced on patient care.Methods: A qualitative, phenomenological approach was employed, involving semi-structured interviews with pharmacists and pharmacy technicians working at one small chain of community pharmacies in Wales. The interview schedule focused on the personal experiences and perceptions of the participants on the processes involved in accessing and supplying unlicensed “special” medicines from a community pharmacy. Interviews were audio-recorded and transcribed verbatim.Results: A total of six participants completed the interview. Three main themes were constructed from inductive thematic analysis of the transcribed interviews: requirement for additional patient responsibilities; influences on the confidence felt by pharmacy staff when accessing and supplying unlicensed “special” medicines; and continuity of supply.Conclusion: This study gives a preliminary insight into the views and experiences of community pharmacy staff in Wales when accessing and supplying unlicensed “special” medicines. Further research is required to see if these views and experiences are representative of community pharmacy staff across the country.Keywords: unlicensed medicines, “special” medicines, specials, community pharmacy, transfer of care, medicines supply, transmural care, off-label, compounding

Excited charge carriers, such as photoelectrons, play an important role in fundamental and technological fields. Here the authors employ an ultrafast electron microscope to directly visualize the cyclotron oscillations and oblate-to-prolate shape change of a photoemitted electron gas from a laser-excited copper surface.

Abstract Background Most of our understanding on the social behavior and genomics of bees and other social insects is centered on the Western honey bee, Apis mellifera. The genus Apis, however, is a highly derived branch comprising less than a dozen species, four of which genomically characterized. In contrast, for the equally highly eusocial, yet taxonomically and biologically more diverse Meliponini, a full genome sequence was so far available for a single Melipona species only. We present here the genome sequence of Frieseomelitta varia, a stingless bee that has, as a peculiarity, a completely sterile worker caste. Results The assembly of 243,974,526 high quality Illumina reads resulted in a predicted assembled genome size of 275 Mb composed of 2173 scaffolds. A BUSCO analysis for the 10,526 predicted genes showed that these represent 96.6% of the expected hymenopteran orthologs. We also predicted 169,371 repetitive genomic components, 2083 putative transposable elements, and 1946 genes for non-coding RNAs, largely long non-coding RNAs. The mitochondrial genome comprises 15,144 bp, encoding 13 proteins, 22 tRNAs and 2 rRNAs. We observed considerable rearrangement in the mitochondrial gene order compared to other bees. For an in-depth analysis of genes related to social biology, we manually checked the annotations for 533 automatically predicted gene models, including 127 genes related to reproductive processes, 104 to development, and 174 immunity-related genes. We also performed specific searches for genes containing transcription factor domains and genes related to neurogenesis and chemosensory communication. Conclusions The total genome size for F. varia is similar to the sequenced genomes of other bees. Using specific prediction methods, we identified a large number of repetitive genome components and long non-coding RNAs, which could provide the molecular basis for gene regulatory plasticity, including worker reproduction. The remarkable reshuffling in gene order in the mitochondrial genome suggests that stingless bees may be a hotspot for mtDNA evolution. Hence, while being just the second stingless bee genome sequenced, we expect that subsequent targeting of a selected set of species from this diverse clade of highly eusocial bees will reveal relevant evolutionary signals and trends related to eusociality in these important pollinators.

Abstract Wolbachia, intracellular endosymbionts, are estimated to infect about half of all arthropod species. These bacteria manipulate their hosts in various ways for their maximum benefits. The rising global temperature may accelerate species migration, and thus, horizontal transfer of Wolbachia may occur across species previously not in contact. We transinfected and then cured the alpine fly Drosophila nigrosparsa with Wolbachia strain wMel to study its effects on this species. We found low Wolbachia titer, possibly cytoplasmic incompatibility, and an increase in locomotion of both infected larvae and adults compared with cured ones. However, no change in fecundity, no impact on heat and cold tolerance, and no change in wing morphology were observed. Although Wolbachia increased locomotor activities in this species, we conclude that D. nigrosparsa may not benefit from the infection. Still, D. nigrosparsa can serve as a host for Wolbachia because vertical transmission is possible but may not be as high as in the native host of wMel, Drosophila melanogaster.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a novel coronavirus. The outbreak started in Wuhan, China, in December 2019 and began to spread rapidly to more than 100 countries and territories. By March 11, the World Health Organization (WHO) officially declared COVID-19 a pandemic. Objective: To review the effectiveness of American and South Koren testing approaches of the COVID-19 plan. Method: Daily reports of the USA and South Korea COVID-19 cases from February 15 to April 15, 2020 were examined. The outcome of interest was total number of cases and tests per 1 million population, daily cases reported, and percent of recovered cases and case fatality rate (CFR). Data were analysed using Microsoft excel 2010 excel sheet and tables and figures generated. Result: As of April 15 2020, USA’s and South Korea's number of cases per million population are 1,946 and 207 cases, respectively. The daily USA’s confirmed cases of COVID-19 had been increasing steadily from February 15 to April 15, 2020. Our study shows that South Korea and the USA recovered cases were 97% and 63%, respectively, while the case fatality rate in the USA was 37 % and 3% in South Korea. Conclusion: Despite its advanced health care systems, the USA is currently experiencing a devastating virus that has claimed many lives. This is because the USA has approached the outbreak differently. The evidence suggests that South Korea's aggressive testing has effectively managed to control the spread of COVID-19, it increased the recovered rate and reduced the CFR more than the USA conservative testing approach. Although the South Korea health care system is not comparable to those in the developing countries, it worth mentioning that its plan would suit well these countries and should be adopted.

The purpose of this study aimed to look at the effect of the Investment Opportunity Set and Capital Structure on Stock Return with Profitability as the control variable at bank companies that are listed in INFOBANK15. The sampling is used is purposive sampling. The sample that are collected is from 8 out of 15 bank companies listed in INFOBANK15 from year 2014-2018. Analysis data is done using the descriptive statistic, correlation, significant test, and linier regression analysis. Investment Opportunity Set using the CAPBVA proxy and Capital Structure using the Debt to Equity Ratio with Profitability as the variable control using the Return on Asset ratio. The result shows that Investment Opportunity Set, Capital Structure and Return on Asset have a significant effect on Stock Return. This shows that the performance of the company can have an effect on investment decisions on investors in the banks studied.

Abstract Objective Skin tags are associated with an insulin resistant phenotype but studies in White Europeans with morbid obesity are lacking. We sought to determine whether the presence of cervical or axillary skin tags was associated with increased cardiovascular risk in Irish adults with morbid obesity. We conducted a cross-sectional study of patients attending our Irish regional bariatric centre with a BMI ≥ 40 kg m−2 (or ≥ 35 kg m−2 with co-morbidities). We compared anthropometric and metabolic characteristics in those with versus without skin tags. Results Of 164 patients, 100 (31 male, 37 with type 2 diabetes, 36 on lipid lowering therapy, 41 on antihypertensive therapy) participated. Mean age was 53.7 ± 11.3 (range 31.1–80) years. Cervical or axillary tags were present in 85 patients. Those with tags had higher systolic blood pressure 138.0 ± 16.0 versus 125.1 ± 8.3 mmHg, p = 0.003) and HbA1c (46.5 ± 13.2 versus 36.8 ± 3.5 mmol/mol, p = 0.017). Tags were present in 94.6% of patients with diabetes, compared to 79.4% of those without diabetes (p = 0.039). Antihypertensive therapy was used by 45.8% of patients with skin tags compared to 13.3% without tags (p = 0.018). In bariatric clinic attenders skin tags were associated with higher SBP and HbA1c and a higher prevalence of diabetes and hypertension, consistent with increased vascular risk, but lipid profiles were similar.

Abstract Background Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. Methods We assayed iron and inflammatory biomarkers in 4853 children aged 0–8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin

Abstract Background Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls. Methods Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 ± 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 ± 13.8 years) were evaluated. Results FAP-cases had significantly lower IQ (p = 0.005). Across all tasks of the Batería III Woodcock-Muñoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls (p

Abstract Background To decentralize point-of-care early infant diagnosis (POC EID), task shifting to cadres such as nurses is important. However, this should not compromise quality of testing through generating high rates of internal quality control (IQC) failures and long result turnaround times. We used data from a POC EID project in Zimbabwe to compare IQC rates and result return to caregivers for samples run on a POC EID technology (Alere q HIV 1/2 Detect) between nurses and laboratory-trained personnel to assess effects of task shifting on quality of testing. Methods This cross-sectional retrospective study used data from all 46 sites (10 hub and 36 spoke sites in Zimbabwe that piloted POC EID for routine clinical use from December 2016 to June 2017). IQC failure rates were downloaded from each POC EID platform and exported to excel to analyze IQC failure rates by type of operator. Turnaround time (TAT) from sample collection to issuing of results to caregiver was extracted from the EID test request form and uploaded into a project specific Excel-based database for analysis. Results A total of 1847 tests were conducted by 45 testers (12 laboratory-trained and 33 non-laboratory-trained personnel), including 165 errors. There were no significant differences in IQC failure rates between non-laboratory testers (137 [9.2%] of 14830 tests) and specialized laboratory-trained (28 [7.7%] of 364 tests; p = 0.354). Over time, IQC failure rates for both non-laboratory (χ 2 = 18.5, p < 0.000) and specialized laboratory-trained testers (χ 2 = 8.7, p < 0.003) decreased significantly. There were similar proportions of clients who were issued with results between samples processed by non-laboratory testers (1283 [98.9%] of 1297 tests) and samples processed by specialized laboratory-trained testers (315 [98.7%] of 319 tests; p = 0.790). The overall median turnaround time from sample collection to receipt of results by caregiver for samples run by laboratory-specialized testers was not statistically different from samples run by non-laboratory-specialized testers (1 day [IQR 0–3] versus 0 days [IQR 0–2]; p = 0.583). Conclusions Similar IQC failure rates and TATs between non-laboratory and specialized laboratory-trained operators suggest that non-specialized laboratory-trained personnel can perform POC EID equally well as specialized laboratory personnel.

Abstract Background Previous research suggests that the 17-item Hamilton Depression Rating Scale (HAM-D17) is less sensitive in detecting differences between active treatment and placebo for major depressive disorder (MDD) than is the HAM-D6 scale, which focuses on six core depression symptoms. Whether HAM-D6 shows greater sensitivity when comparing two active MDD treatment arms is unknown. Methods This post hoc analysis used data from the intent-to-treat (ITT) cohort (N = 1541) of the Genomics Used to Improve DEpression Decisions (GUIDED) trial, a rater- and patient-blinded randomized controlled trial. GUIDED compared combinatorial pharmacogenomics-guided care with treatment as usual (TAU) in patients with MDD. Percent of symptom improvement, response rate and remission rate from baseline to week 8 were evaluated using both scales. Analyses were performed for the full cohort and for the subset of patients who at baseline were taking medications predicted by the test to have moderate or significant gene-drug interactions. A Mokken scale analysis was conducted to compare the homogeneity of HAM-D17 with that of HAM-D6. Results At week 8, the guided-care arm demonstrated statistically significant benefit over TAU when the HAM-D6 (∆ = 4.4%, p = 0.023) was used as the continuous measure of symptom improvement, but not when using the HAM-D17 (∆ = 3.2%, p = 0.069). Response rates increased significantly for guided-care compared with TAU when evaluated using both HAM-D6 (∆ = 7.0%, p = 0.004) and HAM-D17 (∆ = 6.3%, p = 0.007). Remission rates also were significantly greater for guided-care versus TAU using both measures (HAM-D6 ∆ = 4.6%, p = 0.031; HAM-D17 ∆ = 5.5%, p = 0.005). Patients in the guided-care arm who at baseline were taking medications predicted to have gene-drug interactions showed further increased benefit over TAU at week 8 for symptom improvement (∆ = 7.3%, p = 0.004) response (∆ = 10.0%, p = 0.001) and remission (∆ = 7.9%, p = 0.005) using HAM-D6. All outcomes showed continued improvement through week 24. Mokken scale analysis demonstrated the homogeneity and unidimensionality of HAM-D6, but not of HAM-D17, across treatment arms. Conclusions The HAM-D6 scale identified a statistically significant difference in symptom improvement between combinatorial pharmacogenomics-guided care and TAU, whereas the HAM-D17 did not. The demonstrated utility of pharmacogenomics-guided treatment over TAU as detected by the HAM-D6 highlights its value for future biomarker-guided trials comparing active treatment arms. Trial registration Clinicaltrials.gov: NCT02109939. Registered 10 April 2014.

Introduction: The prevalence of cardiovascular disease in sub-Saharan Africa is substantial and growing. Much remains to be learned about the relative burden of acute coronary syndrome (ACS), heart failure, and stroke on emergency departments and hospital admissions. Methods: A retrospective chart review of admissions from September 2017 through March 2018 was conducted at the emergency department of a tertiary care center in northern Tanzania. Stroke admission volume was compared to previously published data from the same hospital and adjusted for population growth. Results: Of 2418 adult admissions, heart failure and stroke were the two most common admission diagnoses, accounting for 294 (12.2%) and 204 (8.4%) admissions, respectively. ACS was uncommon, accounting for 9 (0.3%) admissions. Of patients admitted for heart failure, uncontrolled hypertension was the most commonly identified etiology of heart failure, cited in 124 (42.2%) cases. Ischemic heart disease was cited as the etiology in only 1 (0.3%) case. Adjusting for population growth, the annual volume of stroke admissions increased 70-fold in 43 years, from 2.9 admissions per 100,000 population in 1974 to 202.2 admissions per 100,000 in 2017. Conclusions: The burden of heart failure and stroke on hospital admissions in Tanzania is substantial, and the volume of stroke admissions is rising precipitously. ACS is a rare diagnosis, and the distribution of cardiovascular disease phenotypes in Tanzania differs from what has been observed outside of Africa. Further research is needed to ascertain the reasons for these differences. Keywords: Acute coronary syndrome, Heart failure, Stroke, Sub-Saharan Africa

ABSTRACT Black morel is a widely prized ascomycetous mushroom with culinary value. It was once uncultivable but can now be cultivated routinely in ordinary farmland soils. Large-scale morel farming sometimes encounters nonfructification for unknown reasons. In spring 2020, many morel farms in the area of Chengdu-Plain, China, exhibited no fructification at all, causing disastrous economic loss to the farmers. To determine potential ecological factors associated with the different performance of morel production in these farms, 21 affected sites versus 11 sites with normal fructification performance were analyzed to compare soil microbiota and physiochemical characteristics during fructification. The results indicated that soil physiochemical characteristics were unlikely to be a major reason for the difference between successful fructification and nonfructification. The soils with successful fructification had significantly higher diversity in both the fungal and bacterial communities than those with nonfructification. Morel yield was positively correlated with the α-diversity of fungal communities. The higher diversity of the successfully fructified soils was contributed by community evenness rather than taxonomic richness. In contrast, most nonfructification soils were dominated by a high proportion of a certain fungal genus, typically Acremonium or Mortierella, in the fungal communities. Our findings demonstrate the importance of microbial ecology to the large-scale agroindustry of soil-cultivated mushrooms. IMPORTANCE Saprotrophic mushrooms cultivated in soils are subject to complex influences from soil microbial communities. Research on growing edible mushrooms has revealed connections between fungi and a few species of growth-promoting bacteria colonizing the mycosphere. The composition and diversity of the whole microbial community may also have an influence on the growth and production of soil-saprotrophic mushrooms. Morel mushrooms (Morchella spp.) are economically and culturally important and are widely prized throughout the world. This study used the large-scale farming of morels as an example of an agroecosystem for soil-saprotrophic mushroom cultivation. It demonstrated a typical pattern of how the microbial ecology in soil agroecosystems, especially the α-diversity level and community evenness among soil fungal taxa, could affect the production of high-value cash crops and the income of farmers.

Fe2O3/TiO2 nanocomposites were fabricated via a facile impregnation/calcination technique employing different amounts iron (III) nitrate onto commercial TiO2 (P25 Aeroxide). The as-prepared Fe2O3/TiO2 nanocomposites were characterized by X-ray diffraction (XRD), Raman spectroscopy (RS), scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDXS), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller analysis (BET), electron impedance spectroscopy (EIS), photoluminescence spectroscopy (PL), and diffuse reflectance spectroscopy (DRS). As a result, 5% (w/w) Fe2O3/TiO2 achieved the highest photocatalytic activity in the slurry system and was successfully immobilized on glass support. Photocatalytic activity under visible-light irradiation was assessed by treating pharmaceutical amoxicillin (AMX) in the presence and absence of additional oxidants: hydrogen peroxide (H2O2) and persulfate salts (PS). The influence of pH and PS concentration on AMX conversion rate was established by means of statistical planning and response surface modeling. Results revealed optimum conditions of [S2O82−] = 1.873 mM and pH = 4.808; these were also utilized in presence of H2O2 instead of PS in long-term tests. The fastest AMX conversion possessing a zero-order rate constant of 1.51 × 10−7 M·min−1 was achieved with the photocatalysis + PS system. The AMX conversion pathway was established, and the evolution/conversion of formed intermediates was correlated with the changes in toxicity toward Vibrio fischeri. Reactive oxygen species (ROS) scavenging was also utilized to investigate the AMX conversion mechanism, revealing the major contribution of photogenerated h+ in all processes.

Background: A better understanding of the influence of genetic factors on the response to lifestyle interventions in people with obesity may allow the development of more personalised, effective and efficient therapeutic strategies. We sought to determine the influence of six obesity-related genetic risk scores on the magnitude of weight lost by patients with severe obesity who completed a dietary intervention. Methods: In this single-centre prospective cohort study, participants with severe and complicated obesity who completed a 24-week, milk-based meal replacement programme were genotyped to detect the frequency of common risk alleles for obesity and type 2 diabetes-related traits. Genetic risk scores (GRS) for six of these traits were derived. Participants with a potentially deleterious monogenic gene variant were excluded from the analysis. Results: In 93 patients completing the programme who were not carrying a known obesity-related gene mutation, 35.5% had diabetes, 53.8% were female, mean age was 51.4 ± 11 years, mean body mass index was 51.5 ± 8.7 and mean total weight loss percent at 24 weeks was 16 ± 6.3%. The waist–hip ratio (WHR) GRS was inversely associated with percentage total weight loss at 24 weeks (adjusted β for one standard deviation increase in WHR GRS −11.6 [−23.0, −0.3], p = 0.045), and patients in the lowest tertile of WHR GRS lost more weight. Conclusions: Patients with severe and complicated obesity with a genetic predisposition to central fat accumulation had less weight loss in a 24-week milk-based meal replacement programme, but there was no evidence for influence from the five other obesity-related genetic risk scores on the response to dietary restriction.

Introduction This study aimed to determine the prevalence of diabetic kidney disease (DKD) and rapid renal function decline and to identify indices associated with this decline among adults attending a diabetes center in Northern Europe.Research design and methods This is a retrospective cohort study of 4606 patients who attended a diabetes center in Ireland between June 2012 and December 2016. Definition/staging of chronic kidney disease used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification based on data from the most recently attended appointment. Relevant longitudinal trends and variabilities were derived from serial records prior to index visit. Rapid renal function decline was defined based on per cent and absolute rates of estimated glomerular filtration rate (eGFR) change. Multiple linear regression was used to explore the relationships between explanatory variables and per cent eGFR change.Results 42.0% (total), 23.4% (type 1 diabetes), 47.9% (type 2 diabetes) and 32.6% (other diabetes) had DKD. Rapid decline based on per cent change was more frequent in type 2 than in type 1 diabetes (32.8% vs 14.0%, p

Ectomycorrhizal fungi establish a mutualistic symbiosis in roots of most woody plants. The molecular underpinning of ectomycorrhizal development was only explored in a few lineages. Here, we characterized the symbiotic transcriptomes of several milkcap species (Lactarius, Russulales) in association with different pine hosts. A time-course study of changes in gene expression during the development of L. deliciosus–Pinus taeda symbiosis identified 6 to 594 differentially expressed fungal genes at various developmental stages. Up- or down-regulated genes are involved in signaling pathways, nutrient transport, cell wall modifications, and plant defenses. A high number of genes coding for secreted proteases, especially sedolisins, were induced during root colonization. In contrast, only a few genes encoding mycorrhiza-induced small secreted proteins were identified. This feature was confirmed in several other Lactarius species in association with various pines. Further comparison among all these species revealed that each Lactarius species encodes a highly specific symbiotic gene repertoire, a feature possibly related to their host-specificity. This study provides insights on the genetic basis of symbiosis in an ectomycorrhizal order, the Russulales, which was not investigated so far.

IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Background Rigorous incidence data for acute myocardial infarction (AMI) in sub‐Saharan Africa are lacking. Consequently, modeling studies based on limited data have suggested that the burden of AMI and AMI‐associated mortality in sub‐Saharan Africa is lower than in other world regions. Methods and Results We estimated the incidence of AMI in northern Tanzania in 2019 by integrating data from a prospective surveillance study (681 participants) and a community survey of healthcare‐seeking behavior (718 participants). In the surveillance study, adults presenting to an emergency department with chest pain or shortness of breath were screened for AMI with ECG and troponin testing. AMI was defined by the Fourth Universal Definition of AMI criteria. Mortality was assessed 30 days following enrollment via in‐person or telephone interviews. In the cluster‐based community survey, adults in northern Tanzania were asked where they would present for chest pain or shortness of breath. Multipliers were applied to account for AMI cases that would have been missed by our surveillance methods. The estimated annual incidence of AMI was 172 (207 among men and 139 among women) cases per 100 000 people. The age‐standardized annual incidence was 211 (263 among men and 170 among women) per 100 000 people. The estimated annual incidence of AMI‐associated mortality was 87 deaths per 100 000 people, and the age‐standardized annual incidence was 102 deaths per 100 000 people. Conclusions The incidence of AMI and AMI‐associated mortality in northern Tanzania is much higher than previously estimated and similar to that observed in high‐income countries.

We report a case of a 66-year-old male who presented with a locally advanced primary mucinous adenocarcinoma arising from a fistula-in-ano. The presentation was typical for perianal sepsis and fistula-in-ano with anal pain and chronic discharge. Initial treatments with fistula debridement and seton were performed. Subsequent review of histology revealed underlying adenocarcinoma, while magnetic resonance imaging (MRI) showed local invasion into the prostate. The patient received neoadjuvant chemoradiotherapy followed by pelvic exenteration to maximize the chance of achieving cure. Features of this case are discussed together with its implications, including treatment guidelines and typical MRI findings.

Background: Hand Hygiene (HH) is widely recognized to be one of the most successful and cost-effective measures for reducing the incidence of healthcare-associated infections (HAIs). The hand hygiene behavior of hospital healthcare workers (HCWs) is not well-documented in Benin. Therefore, Theoretical Domains Framework (TDF) was used to identify the behavioral determinants that may impact HCWs’ hand-hygiene compliance in a public hospital. Methods: A qualitative design comprising face-to-face semi-structured interviews with nine HCWs. The interviews included questions on transmission of infections, hand-hygiene practices, problems with their implementation; and ways to improve hand hygiene compliance. Two pharmacists independently coded interviews into behavioral domains using the TDF and then subdivided them into several themes. Interview transcripts were analyzed following 3-steps approach: coding, generation of specific beliefs, and identification of relevant domains. Results: Almost all interviewees have cited the environmental context and resources (such as lack of water) as a barrier to HH practice. They also believed that role models had a significant impact on the good practices of others HCWs. Fortunately, they were confident of their capabilities to perform appropriate HH behaviors. The majority (7/9) reported having the necessary knowledge and skills and believed they could carry out appropriate HH behavior. In all cases, the participants were motivated to carry out HH behavior, and it was recognized that HH remains the cornerstone to reduce health care associated infections. Conclusion: This study identified several behavioral constructs aligned with the TDF that can be targeted and help for the development of new hand-hygiene interventions. These may increase the likelihood of a successful intervention, thereby improving HH compliance and patient safety, especially in hospitals.

Chronic kidney disease (CKD) is one of the most life-threatening disorders. To improve survivability, early discovery and good management are encouraged. In this paper, CKD was diagnosed using multiple optimized neural networks against traditional neural networks on the UCI machine learning dataset, to identify the most efficient model for the task. The study works on the binary classification of CKD from 24 attributes. For classification, optimized CNN (OCNN), ANN (OANN), and LSTM (OLSTM) models were used as well as traditional CNN, ANN, and LSTM models. With various performance matrixes, error measures, loss values, AUC values, and compilation time, the implemented models are compared to identify the most competent model for the classification of CKD. It is observed that, overall, the optimized models have better performance compared to the traditional models. The highest validation accuracy among the tradition models were achieved from CNN with 92.71%, whereas OCNN, OANN, and OLSTM have higher accuracies of 98.75%, 96.25%, and 98.5%, respectively. Additionally, OCNN has the highest AUC score of 0.99 and the lowest compilation time for classification with 0.00447 s, making it the most efficient model for the diagnosis of CKD.

Trypanosoma cruzi, the causative agent of Chagas disease, faces changes in redox status and nutritional availability during its life cycle. However, the influence of oxygen fluctuation upon the biology of T. cruzi is unclear. The present work investigated the response of T. cruzi epimastigotes to hypoxia. The parasites showed an adaptation to the hypoxic condition, presenting an increase in proliferation and a reduction in metacyclogenesis. Additionally, parasites cultured in hypoxia produced more reactive oxygen species (ROS) compared to parasites cultured in normoxia. The analyses of the mitochondrial physiology demonstrated that hypoxic condition induced a decrease in both oxidative phosphorylation and mitochondrial membrane potential (ΔΨm) in epimastigotes. In spite of that, ATP levels of parasites cultivated in hypoxia increased. The hypoxic condition also increased the expression of the hexokinase and NADH fumarate reductase genes and reduced NAD(P)H, suggesting that this increase in ATP levels of hypoxia-challenged parasites was a consequence of increased glycolysis and fermentation pathways. Taken together, our results suggest that decreased oxygen levels trigger a shift in the bioenergetic metabolism of T. cruzi epimastigotes, favoring ROS production and fermentation to sustain ATP production, allowing the parasite to survive and proliferate in the insect vector.

An alarming worldwide increase in antimicrobial resistance is complicating the management of surgical site infections (SSIs), especially in low-middle income countries. The main objective of this study was to describe the pattern of carbapenem-resistant bacteria in hospitalized patients and to highlight the challenge of their detection in Benin. We collected pus samples from patients suspected to have SSIs in hospitals. After bacterial identification by MALDI-TOF mass spectrometry, antimicrobial susceptibility was performed according to the Kirby–Bauer method. Carbapenem-resistant strains were characterized using, successively, the Modified Hodge Test (MHT), the RESIST-5 O.K.N.V.I: a multiplex lateral flow and finally the polymerase chain reaction. Six isolates were resistant to three tested carbapenems and almost all antibiotics we tested but remained susceptible to amikacin. Four (66.7%) of them harbored some ESBL genes (blaCTX-M-1 and blaTEM-1). The MHT was positive for Carbapenems but not for Pseudomonas aeruginosa and Acinetobacter baumannii. As surgical antimicrobial prophylaxis, five of the six patients received ceftriaxone. The following carbapenems genes were identified: bla OXA-48(33.3%, n = 2), blaNDM (33.3%, n = 2) and blaVIM (33.3%, n = 2). These findings indicate a need for local and national antimicrobial resistance surveillance and the strengthening of antimicrobial stewardship programs in the country.

Chronic immune activation has been considered as the driving force for CD4+ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4+ and CD8+ subsets. In addition, it is accompanied by low CD4+ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.

Black morel, a widely prized culinary delicacy, was once an uncultivable soil-saprotrophic ascomycete mushroom that can now be cultivated routinely in farmland soils. It acquires carbon nutrients from an aboveground nutritional supplementation, while it remains unknown how the morel mycelium together with associated microbiota in the substratum metabolizes and accumulates specific nutrients to support the fructification. In this study, a semi-synthetic substratum of quartz particles mixed with compost was used as a replacement and mimic of the soil. Two types of composts (C1 and C2) were used, respectively, plus a bare-quartz substratum (NC) as a blank reference. Microbiota succession, substrate transformation as well as the activity level of key enzymes were compared between the three types of substrata that produced quite divergent yields of morel fruiting bodies. The C1 substratum, with the highest yield, possessed higher abundances of Actinobacteria and Chloroflexi. In comparison with C2 and NC, the microbiota in C1 could limit over-expansion of microorganisms harboring N-fixing genes, such as Cyanobacteria, during the fructification period. Driven by the microbiota, the C1 substratum had advantages in accumulating lipids to supply morel fructification and maintaining appropriate forms of nitrogenous substances. Our findings contribute to an increasingly detailed portrait of microbial ecological mechanisms triggering morel fructification.

We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines.

Abstract Background Adherence to tuberculosis (TB) treatment is challenging because of many factors. The World Health Organization has recommended the use of digital adherence monitoring technologies in its End TB Strategy. However, evidence on improving adherence is limited. EvriMED is a real-time medication-monitoring device which was found to be feasible and acceptable in a few studies in Asia. In Tanzania, however, there may be challenges in implementing evriMED due to stigmatization, network and power access, accuracy, and cost effectiveness, which may have implications for treatment outcome. We propose a pragmatic cluster randomized trial to investigate the effectiveness of evriMED with reminder cues and tailored feedback on adherence to TB treatment in Kilimanjaro, Tanzania. Methods/design We will create clusters in Kilimanjaro based on level of health care facility. Clusters will be randomized in an intervention arm, where evriMED will be implemented, or a control arm, where standard practice directly observed treatment will be followed. TB patients in intervention clusters will take their medication from the evriMED pillbox and receive tailored feedback. We will use the ‘Stages of Change’ model, which assumes that a person has to go through the stages of pre-contemplation, contemplation, preparation, action, and evaluation to change behavior for tailored feedback on adherence reports from the device. Discussion If the intervention shows a significant effect on adherence and the devices are accepted, accurate, and sustainable, the intervention can be scaled up within the National Tuberculosis Programmes. Trial registration Pan African Clinical Trials Registry, PACTR201811755733759. Registered on 8 November 2018.

Abstract Background Ambient temperature is an important determinant of malaria transmission and suitability, affecting the life-cycle of the Plasmodium parasite and Anopheles vector. Early models predicted a thermal malaria transmission optimum of 31 °C, later revised to 25 °C using experimental data from mosquito and parasite biology. However, the link between ambient temperature and human malaria incidence remains poorly resolved. Methods To evaluate the relationship between ambient temperature and malaria risk, 5833 febrile children (

A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team.

We consider a binary mixture of two polymers with different architecture, consisting of linear and cyclic chains. We study this system by performing extensive molecular dynamics computer simulations of bead-spring models, which possess the open-chain and loop topology. The system is confined between two walls, and we consider both the case of attractive- and repulsive polymer-wall interactions. By changing the chain length of the two polymers so as to encompass two regimes with low and high degree of polymerization, we show the effect on the structural properties at the interface. Our results provide some physical insight on the competition between polymer architecture and chain length in determining the surface adsorption. 2000 MSC: 41A05, 41A10, 65D05, 65D17, Keywords: Adsorption, Polymer architecture, Wall-fluid potential

Abstract Background There are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitaemia. Methods We used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for 8 years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (≥ 8) or low (