Background: Severe Acute Malnutrition (SAM) has become a major public health challenge in developing countries including Ethiopia, especially among the underprivileged population. Ethiopia is among the developing countries with the highest burden of acute malnutrition among under-five children. Though, plenty of studies were done on the magnitude of acute malnutrition among under-five children in Ethiopia, there is a limited evidence on time to recovery from SAM and its predictors among children aged 6–59 months in Ethiopia, particularly in the study area. Objectives: The study was aimed to assess the time to recovery from SAM and its predictors among children aged 6–59 months at Asosa general hospital (AGH), Benishangul Gumuz, Ethiopia. Methods: A Five years retrospective follow-up study design was employed among 454 children admitted with SAM in AGH from January 2015 to December 2019. The data were extracted from the patient medical records using checklist. The data were coded and entered into Epi-Data 3.1; then exported to STATA/SE-14 for analysis. Proportional Cox regression was performed to identify predictors of recovery time. A proportional hazard assumption was checked. Variables with AHR at 95% CI and P-value less than 0.05 in the multivariable Cox proportional regression was considered as significant predictors of recovery time. Findings: Among the 454 included records of children with SAM, 65.4% (95%CI: 50.1, 69.2) of them were recovered at the end of the follow-up with a median recovery time of 15 IQR(11–18)days. The incidence rate of recovery was 5.28 per 100 child days’ observations. Being HIV Negative (AHR = 2.19: 95% CI 1.28, 3.73), Marasmic (AHR = 1.69: 95% CI 1.18, 2.42), and marasmic-kwashiorkor child (AHR = 1.60: 95% CI (1.09, 2.37) independently predicted recovery time. Conclusions: Though the time to recovery from severe acute malnutrition was in the acceptable range, the proportion of recovery was found to be low in the study area compared to sphere standard. The prognosis of children with severe acute malnutrition was determined by the HIV status of the child and the type of malnutrition experienced. Further strengthening of malnutrition therapeutic centers and routine checkup of the nutritional status of HIV positive children should be emphasized to reduce child mortality and morbidity from under-nutrition.

Environmental DNA (eDNA) metabarcoding is revolutionizing the monitoring of aquatic biodiversity. The use of eDNA has the potential to enable non-invasive, cost-effective, time-efficient and high-sensitivity monitoring of fish assemblages. Although the capacity of eDNA metabarcoding to describe fish assemblages is recognised, research efforts are still needed to better assess the spatial and temporal variability of the eDNA signal and to ultimately design an optimal sampling strategy for eDNA monitoring. In this context, we sampled three different lakes (a dam reservoir, a shallow eutrophic lake and a deep oligotrophic lake) every 6 weeks for 1 year. We performed four types of sampling for each lake (integrative sampling of sub-surface water along transects on the left shore, the right shore and above the deepest zone, and point sampling in deeper layers near the lake bottom) to explore the spatial variability of the eDNA signal at the lake scale over a period of 1 year. A metabarcoding approach was applied to analyse the 92 eDNA samples in order to obtain fish species inventories which were compared with traditional fish monitoring methods (standardized gillnet samplings). Several species known to be present in these lakes were only detected by eDNA, confirming the higher sensitivity of this technique in comparison with gillnetting. The eDNA signal varied spatially, with shoreline samples being richer in species than the other samples. Furthermore, deep-water samplings appeared to be non-relevant for regularly mixed lakes, where the eDNA signal was homogeneously distributed. These results also demonstrate a clear temporal variability of the eDNA signal that seems to be related to species phenology, with most of the species detected in spring during the spawning period on shores, but also a peak of detection in winter for salmonid and coregonid species during their reproduction period. These results contribute to our understanding of the spatio-temporal distribution of eDNA in lakes and allow us to provide methodological recommendations regarding where and when to sample eDNA for fish monitoring in lakes.

Beef meat production is the key to reducing poverty, achieving food security and nutrition, promoting exports, economic growth, and industrialization. Despite a large number of beef cattle, Tanzania continues to import beef meat and its contribution to GDP is low. Thus, this study used time-series panel data to analyze the beef meat industry in Tanzania from 1990 to 2019, with a particular focus on identifying the reasons and direction of the correlation between beef meat output and its determinants in the production processes. The study applied both descriptive statistics and the Cobb-Douglas production function model, using the Ordinary Least Squares (OLS) based estimator to analyze the data. Descriptive analyses revealed that Tanzania’s beef meat production increased by 283,871 tons (59.3%-a positive trend) between 1990 and 2019. This increase was accompanied by approximately 29.75%, 53.05%, and 42.42% increases in beef cattle yield (carcass weight (hg) per head, beef cattle inventory, and the number of beef cattle slaughtered, respectively). However, the analysis further revealed that a 2.8% decrease in beef cattle extraction (low harvesting) rate due to low market participation, continues to be a critical barrier to increasing beef meat production in Tanzania. Furthermore, econometric estimates showed that the key factors that positively influenced beef meat output at a 5% significance level (P < 0.05) included beef cattle population (inventory), beef cattle yield (carcass weight (kg) per head, and the number of beef cattle slaughtered, with elasticity coefficients of 0.146, 0.469, and 0.564, respectively). While the number of beef cattle exported positively influenced beef meat production at the 10% significance level (P < 0.1) with an elasticity coefficient of 0.028. Surprisingly, invested credit to agriculture (farm credits) and imported pure-bred beef cattle had a negative impact on beef meat output but were statistically insignificant at P < 0.05. The results of this study have implications as to what factors need to be addressed to further improve beef meat production, thereby reducing its reliance on imports. We suggest that the Tanzania government and policymakers need to establish balanced policies for beef farmers and appropriately manage them so that beef meat development can be induced, contributing to poverty reduction, food security, and economic development.

Objectives: To evaluate long-term outcome using the BioMedtrix™ TPLO Curve® plate in dogs with cranial cruciate ligament disease (CrCLd) treated by tibial plateau leveling osteotomy (TPLO). Study design: Retrospective case study. Animals: Dogs (n = 323, 337 stifles). Methods: Medical records were searched for dogs presented with CrCLd and treated by TPLO with the BioMedtrix™ TPLO Curve® plate for 3.5 mm screws between March 2018 and December 2020. Tibial plateau angles (TPA) were measured on preoperative, postoperative, and follow-up radiographs. Changes in TPA between postoperative and follow-up radiographs (ModTPA) were calculated. Radiographic bone healing was scored. Complications were evaluated. Surgical site infections (SSI) were compared to a control group of dogs treated with the Synthes™ TPLO plate between January and December 2017. Owners of both groups were contacted by telephone at least 1 year postoperatively. Results: The BioMedtrix™ group was composed of 237 dogs (248 stifles), the control group was composed of 86 dogs (89 stifles). In the BioMedtrix™ group, radiographic follow-up was performed at a median of 48 days. Average ModTPA was 1.2°. Bone healing was graded as complete, good, poor, and none in 18%, 62%, 20%, and 0%, respectively. At a median of 786 days postoperatively, minor and major postoperative complications were observed in 6 (2.4%) and 32 (12.9%) cases in this group, respectively. During the first year following the surgery, 23 (9.3%) and 12 (13.5%) cases suffered a SSI, of which 12 (4.8%) and 7 (7.9%) had their implant explanted in the BioMedtrix™ group and the control group, respectively. There was no significant difference between groups for SSI and implant explantations (p = 0.31 and p = 0.29, respectively). Conclusion: The BioMedtrix™ TPLO Curve® plate provided a reliable fixation system for osteotomy healing after TPLO. Bone healing and long-term complication rates were similar to previous studies using other implants. SSI rates were similar between the BioMedtrix™ group and the control group. The antimicrobial HyProtect® coating of the plate did not reduce SSI in this study. Clinical significance: The BioMedtrix™ TPLO Curve® plate can be safely used for TPLO. The value of the antimicrobial HyProtect® coating of the plate may be questioned, as SSI rate was not lower in this study compared to the control group or previous reports.

Background: Prediction of SARS-CoV-2-induced sick leave among healthcare workers (HCWs) is essential for being able to plan the healthcare response to the epidemic. Methods: During first wave of the SARS-Cov-2 epidemic (April 23rd to June 24th, 2020), the HCWs in the greater Stockholm region in Sweden were invited to a study of past or present SARS-CoV-2 infection. We develop a discrete time Markov model using a cohort of 9449 healthcare workers (HCWs) who had complete data on SARS-CoV-2 RNA and antibodies as well as sick leave data for the calendar year 2020. The one-week and standardized longer term transition probabilities of sick leave and the ratios of the standardized probabilities for the baseline covariate distribution were compared with the referent period (an independent period when there were no SARS-CoV-2 infections) in relation to PCR results, serology results and gender. Results: The one-week probabilities of transitioning from healthy to partial sick leave or full sick leave during the outbreak as compared to after the outbreak were highest for healthy HCWs testing positive for large amounts of virus (ratio: 3.69, (95% confidence interval, CI: 2.44–5.59) and 6.67 (95% CI: 1.58–28.13), respectively). The proportion of all sick leaves attributed to COVID-19 during outbreak was at most 55% (95% CI: 50%-59%). Conclusions: A robust Markov model enabled use of simple SARS-CoV-2 testing data for quantifying past and future COVID-related sick leave among HCWs, which can serve as a basis for planning of healthcare during outbreaks.

Background: Dulaglutide is associated with improved cardiovascular and kidney outcomes and can be a good therapeutic option for patients with type 2 diabetes with chronic kidney disease (CKD). In this study, the effects of dulaglutide on glucose-lowering efficacy and changes in renal function were analyzed. Methods: This retrospective study involved 197 patients with type 2 diabetes with mild-to-severe CKD treated with dulaglutide for at least 3 months between January 2017 and December 2020 at two tertiary hospitals in Korea. Changes in the creatinine-based estimated glomerular filtration rate (eGFR) and HbA1c were compared before and after the use of dulaglutide in each patient. Results: The number of patients and mean eGFR (mL/min/1.73 m2) in CKD 2, 3a, 3b, and 4 were 94 (75.0 ± 8.5), 46 (54.8 ± 6.3), 31 (38.8 ± 4.4), and 26 (22.5 ± 5.4), respectively. Mean HbA1c level and body mass index (BMI) at the initiation of dulaglutide were 8.9% ± 1.4% and 29.1 ± 3.6 kg/m2, the median duration of the use of dulaglutide was 16 months. The use of dulaglutide was associated with a mean decrease in HbA1c by 0.9% ± 1.5% and the glucose-lowering efficacy was similar across all stages of CKD. Also, it was associated with a reduced decline in the eGFR; the mean eGFR change after the use of dulaglutide was –0.76 mL/min/1.73 m2 per year, whereas it was –2.41 mL/min/1.73 m2 before use (paired t-test, P = 0.003). The difference was more pronounced in patients with an eGFR < 60 mL/min/1.73 m2. Subgroup analysis showed that the renal protective effect was better in patients with proteinuria, age ≤ 65 years, and HbA1c < 9.0%, but showed no association with BMI. Conclusions: The use of dulaglutide provided adequate glycemic control irrespective of CKD stage and was associated with a reduced decline in the eGFR in the CKD population.

ESX type VII secretion systems are complex secretion machineries spanning across the mycobacterial membrane and play an important role in pathogenicity, nutrient uptake and conjugation. We previously reported the role of ESX-4 in modulating Mycobacterium abscessus intracellular survival. The loss of EccB4 was associated with limited secretion of two effector proteins belonging to the WXG-100 family, EsxU and EsxT, and encoded by the esx-4 locus. This prompted us to investigate the function of M. abscessus EsxU and EsxT in vitro and in vivo. Herein, we show that EsxU and EsxT are substrates of ESX-4 and form a stable 1:1 heterodimer that permeabilizes artificial membranes. While expression of esxU and esxT was up-regulated in M. abscessus-infected macrophages, their absence in an esxUT deletion mutant prevented phagosomal membrane disruption while maintaining M. abscessus in an unacidified phagosome. Unexpectedly, the esxUT deletion was associated with a hyper-virulent phenotype, characterised by increased bacterial loads and mortality in mouse and zebrafish infection models. Collectively, these results demonstrate that the presence of EsxU and EsxT dampens survival and persistence of M. abscessus during infection. Author summary: The evolution of bacterial secretion systems is strongly associated with the intracellular lifestyle and interactions of bacteria with their hosts. Here, we show that an ancestral type VII secretion system, ESX-4, modulates the pathophysiology of Mycobacterium abscessus infection, which is directly related to its major effectors, EsxU and EsxT. While EsxU/EsxT were found to permeabilize lipid bilayers, deletion of the esxUT genes increased the virulence of M. abscessus in animal models. In support of these observations, strictly pathogenic mycobacteria in humans and animals, such as Mycobacterium tuberculosis or Mycobacterium marinum have evolved without evidence of secretion of their respective EsxU/EsxT substrates. Together, these results underscore the possible in vivo advantage procured by the absence of EsxU and EsxT in strictly pathogenic mycobacterial species.

Objectives: The pathologic nodal stage of human papillomavirus (HPV)-related oropharyngeal cancer (OPC) patients is classified according to the number of lymph nodes (LNs), as revised in 2018. Previous studies showed that the LN ratio (LNR) could be also a significant prognostic factor in head and neck cancer, but there are few studies on the LNR in HPV-related [HPV(+)] OPC. The aim of the present study was to analyze the predictive value of the LNR for survival and recurrence in HPV(+) OPC patients. Materials and methods: HPV(+) OPC patients treated with surgery with or without postoperative radiotherapy from January 2000 to March 2019 were evaluated. The patients were divided into two sets of three groups, according to LN numbers based on pathologic nodal stages, and LNRs by a cutoff value of 0.05. The medical records were reviewed, and the overall survival (OS), disease-free survival, locoregional recurrence, and distant metastasis incidence were analyzed. Results: Ninty patients were included and the median follow-up period was 38.2 months. There were no significant differences in OS in the LN number groups. However, there was a significant difference in OS in the LNR groups (P = 0.010). The incidence of distant metastasis in the LNR groups was significantly different (P = 0.005). Conclusion: The LNR in HPV(+) OPC patients may be a more useful tool to predict survival and distant metastasis than the LN number. Additional research and consensus on surgical pathology are needed before applying the LNR to adjuvant treatment decisions and pathologic nodal staging.

Introduction: Ventilatory efficiency (VE/VCO2 slope) has been shown superior to peak oxygen consumption (VO2) for prediction of post-operative pulmonary complications in patients undergoing thoracotomy. VE/VCO2 slope is determined by ventilatory drive and ventilation/perfusion mismatch whereas VO2 is related to cardiac output and arteriovenous oxygen difference. We hypothesized pre-operative VO2 predicts post-operative cardiovascular complications in patients undergoing lung resection. Methods: Lung resection candidates from a published study were evaluated by post-hoc analysis. All of the patients underwent preoperative cardiopulmonary exercise testing. Post-operative cardiovascular complications were assessed during the first 30 post-operative days or hospital stay. One-way analysis of variance or the Kruskal–Wallis test, and multivariate logistic regression were used for statistical analysis and data summarized as median (IQR). Results: Of 353 subjects, 30 (9%) developed pulmonary complications only (excluded from further analysis), while 78 subjects (22%) developed cardiovascular complications and were divided into two groups for analysis: cardiovascular only (n = 49) and cardiovascular with pulmonary complications (n = 29). Compared to patients without complications (n = 245), peak VO2 was significantly lower in the cardiovascular with pulmonary complications group [19.9 ml/kg/min (16.5–25) vs. 16.3 ml/kg/min (15–20.3); P<0.01] but not in the cardiovascular only complications group [19.9 ml/kg/min (16.5–25) vs 19.0 ml/kg/min (16–23.1); P = 0.18]. In contrast, VE/VCO2 slope was significantly higher in both cardiovascular only [29 (25–33) vs. 31 (27–37); P = 0.05] and cardiovascular with pulmonary complication groups [29 (25–33) vs. 37 (34–42); P<0.01)]. Logistic regression analysis showed VE/VCO2 slope [OR = 1.06; 95%CI (1.01–1.11); P = 0.01; AUC = 0.74], but not peak VO2 to be independently associated with post-operative cardiovascular complications. Conclusion: VE/VCO2 slope is superior to peak VO2 for prediction of post-operative cardiovascular complications in lung resection candidates.

Selective vulnerability is an enigmatic feature of neurodegenerative diseases (NDs), whereby a widely expressed protein causes lesions in specific cell types and brain regions. Using the RiboTag method in mice, translational responses of five neural subtypes to acquired prion disease (PrD) were measured. Pre-onset and disease onset timepoints were chosen based on longitudinal electroencephalography (EEG) that revealed a gradual increase in theta power between 10- and 18-weeks after prion injection, resembling a clinical feature of human PrD. At disease onset, marked by significantly increased theta power and histopathological lesions, mice had pronounced translatome changes in all five cell types despite appearing normal. Remarkably, at a pre-onset stage, prior to EEG and neuropathological changes, we found that 1) translatomes of astrocytes indicated reduced synthesis of ribosomal and mitochondrial components, 2) glutamatergic neurons showed increased expression of cytoskeletal genes, and 3) GABAergic neurons revealed reduced expression of circadian rhythm genes. These data demonstrate that early translatome responses to neurodegeneration emerge prior to conventional markers of disease and are cell type-specific. Therapeutic strategies may need to target multiple pathways in specific populations of cells, early in disease. Author summary: Prions are infectious agents composed of a misfolded protein. When isolated from a mammalian brain and transferred to the same host species, prions will cause the same neurodegenerative disease affecting the same brain regions and cell types. This concept of selective vulnerability is also a feature of more common types of neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s. To better understand the mechanisms behind selective vulnerability, we studied disease responses of five cell types with different vulnerabilities in prion-infected mice at two different disease stages. Responses were measured as changes to mRNAs undergoing translation, referred to as the translatome. Before prion-infected mice demonstrated typical disease signs, electroencephalography (a method used clinically to characterize neurodegeneration in humans) revealed brain changes resembling those in human prion diseases, and surprisingly, the translatomes of all cells were drastically changed. Furthermore, before electroencephalography changes emerged, three cell types made unique responses while the most vulnerable cell type did not. These results suggests that mechanisms causing selective vulnerability will be difficult to dissect and that therapies will likely need to be provided before clinical signs emerge and individually engage multiple cell types and their distinct molecular pathways.