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Globally, zoonoses have serious consequences due to their socioeconomic impacts. Ngorongoro District is home to a diverse range of wildlife and domestic animals, including rodents and dogs, which often coexist in close proximity with humans. The aim of the study was to identify the zoonotic bacteria present in wild rodents, domestic dogs, and humans using metagenomics next-generation sequencing technology. A cross-sectional study was conducted in 2022. This study used both Illumina and Oxford Nanopore sequencing technologies to identify bacteria in 530 blood samples collected from humans (n = 200), wild rodents (n = 230), and dogs (n = 100). Several zoonotic airborne/contagious bacteria, including Mycobacterium spp., Mycoplasma spp., Bordetella spp., and Legionella spp., were detected in wild rodents, domestic dogs, and humans. Arthropod-borne zoonotic bacteria such as Bartonella spp., Borrelia spp., and Rickettsia spp. were detected in all three hosts, while Orientia spp. was found in wild rodents and domestic dogs. Yersinia pestis, Streptobacillus spp. and Anaplasma spp. were found only in wild rodents. Other zoonotic bacteria found shared among wild rodents, domestic dogs, and humans are Leptospira spp., Brucella spp., and Salmonella spp. Generally, wild rodents had the highest prevalence of zoonotic bacterial species when compared to domestic dogs and humans. The detection of zoonotic bacteria in rodents, dogs, and humans supports the hypothesis that infections can spread between animals and humans sharing the same environment.

Abstract Background Cartilage is a mechanically highly stressed tissue in the human body and an important part of synovial joints. The joint cartilage is lubricated by synovial fluid with hyaluronic acid (HA) as main component. However, in joints with osteoarthritis HA has a lower concentration and molecular weight compared to healthy joints. In recent years, the intra-articular injection of therapeutic HA lubricant, has become a popular therapy. The effect of HA application on the friction of a complete joint with physiological movement needs to be further determined. Methods The aim of the present study was to evaluate the lubrication effect of the joint by three lubricants (NaCl, fetal calf serum (FCS) and HA) and their effect on the friction in nine complete ovine carpo-metacarpal joints. The joints were mounted on a material testing machine and a physiological movement with 10° rotation was simulated with ascending axial load (100 – 400 N). Specimens were tested native, with cartilage damage caused by drying out and relubricated. Dissipated energy (DE) as a measure of friction was recorded and compared. Results Investigating the effect of axial load, we found significant differences in DE between all axial load steps (p

Epidemics of Rift Valley fever (RVF), a mosquito-borne zoonotic disease caused by RVF virus, have been linked to exceptionally heavy rainfall and widespread flooding. The disease is endemic in most African countries and pose a major global health risk. Given that the disease was reported in various districts of Tanzania, we hypothesized a lack of knowledge about RVF epidemiology among agropastoral and pastoral communities. The research took place in a period of 7 months, from July, 2021 to January, 2022. The aim of this study was to assess the knowledge, attitudes, and practices (KAP) among the agropastoral and pastoral communities of Ngorongoro district towards RVF. The survey employed a mixed method system, which included 3 focus groups (each comprised 12 individuals), 20 key informant interviews and administration of questionnaire (N = 352) in agropastoral and pastoral community members of Ngorongoro district. The relationship between demographic characteristics and communities' knowledge, attitudes, and practices regarding RVF was observed using a multiple logistic regression model. A total of 352 participants were interviewed, with the majority (67.61%) being male and 32.39% being female, majority (39.5%) attending primary school, and majority (58.2%) being pastoralists. The findings showed that only 36.1%, 38.64% and 16.19% of participants had good knowledge, positive attitude and good practices regarding RVF respectively. Significant demographic factors related with knowledge included: gender (OR = 1.9, CI = 1.03-3.56, P = 0.041), education levels (primary: OR = 3.97, CI = 2-8.16, P = 0.000; secondary: OR = 15.27, CI = 5.5-46.23, P = 0.000 and college: OR = 34. 23, CI = 5.4-67.22, P = 0.000), and locality (Pinyinyi: OR = 0.14, CI = 0.05-0.38, P = 0.000 and Sale: OR = 0.14, CI = 0.04-0.44, P = 0.001). Male participants showed significant positive attitude towards RVF compared to female (OR = 2.37, CI = 1.35-4.17, P = 0.003). Individuals with formal education showed a significant positive attitude toward RVF compared to informal (OR>1, P

Abstract Background Anti-malarial drug resistance remains a key concern for the global fight against malaria. In Ghana sulfadoxine-pyrimethamine (SP) is used for intermittent preventive treatment of malaria in pregnancy and combined with amodiaquine for Seasonal Malaria Chemoprevention (SMC) during the high malaria season. Thus, surveillance of molecular markers of SP resistance is important to guide decision-making for these interventions in Ghana. Methods A total of 4469 samples from uncomplicated malaria patients collected from 2009 to 2018 was submitted to the Wellcome Trust Sanger Institute, UK for DNA sequencing using MiSeq. Genotypes were successfully translated into haplotypes in 2694 and 846 mono infections respectively for pfdhfr and pfdhps genes and the combined pfhdfr/pfdhps genes across all years. Results At the pfdhfr locus, a consistently high (> 60%) prevalence of parasites carrying triple mutants (IRNI) were detected from 2009 to 2018. Two double mutant haplotypes (NRNI and ICNI) were found, with haplotype NRNI having a much higher prevalence (average 13.8%) than ICNI (average 3.2%) across all years. Six pfdhps haplotypes were detected. Of these, prevalence of five fluctuated in a downward trend over time from 2009 to 2018, except a pfdhps double mutant (AGKAA), which increased consistently from 2.5% in 2009 to 78.2% in 2018. Across both genes, pfdhfr/pfdhps combined triple (NRNI + AAKAA) mutants were only detected in 2009, 2014, 2015 and 2018, prevalence of which fluctuated between 3.5 and 5.5%. The combined quadruple (IRNI + AAKAA) genotype increased in prevalence from 19.3% in 2009 to 87.5% in 2011 before fluctuating downwards to 19.6% in 2018 with an average prevalence of 37.4% within the nine years. Prevalence of parasites carrying the quintuple (IRNI + AGKAA or SGEAA) mutant haplotypes, which are highly refractory to SP increased over time from 14.0% in 2009 to 89.0% in 2016 before decreasing to 78.9 and 76.6% in 2017 and 2018 respectively. Though quintuple mutants are rising in prevalence in both malaria seasons, together these combined genotypes vary significantly within season but not between seasons. Conclusions Despite high prevalence of pfdhfr triple mutants and combined pfdhfr/pfdhps quadruple and quintuple mutants in this setting SP may still be efficacious. These findings are significant as they highlight the need to continuously monitor SP resistance, particularly using deep targeted sequencing to ascertain changing resistance patterns.

Abstract Background Lateral tibial split fractures (LTSF) usually require surgical therapy with screw or plate osteosynthesis. Excellent anatomical reduction of the fracture is thereby essential to avoid post-traumatic osteoarthritis. In clinical practice, a gap and step of 2 mm have been propagated as maximum tolerable limit. To date, biomechanical studies regarding tibial fractures have been limited to pressure measurement, but the relationship between dissipated energy (DE) as a friction parameter and reduction accuracy in LTSF has not been investigated. In past experiments, we developed a new method to measure DE in ovine knee joints. To determine weather non-anatomical fracture reduction with lateral gap or vertical step condition leads to relevant changes in DE in the human knee joint, we tested the applicability of the new method on human LTSFs and investigated whether the current limit of 2 mm gap and step is durable from a biomechanical point of view. Methods Seven right human, native knee joint specimens were cyclically moved under 400 N axial load using a robotic system. During the cyclic motion, the flexion angle and the respective torque were recorded and the DE was calculated. First, DE was measured after an anterolateral approach had been performed (condition “native”). Then a LTSF was set with a chisel, reduced anatomically, fixed with two set screws and DE was measured (“even”). DE of further reductions was then measured with gaps of 1 mm and 2 mm, and a 2 mm step down or a 2 mm step up was measured. Results We successfully established a measurement protocol for DE in human knee joints with LTSF. While gaps led to small though statistically significant increase (1 mm gap:ΔDE compared with native = 0.030 J/cycle, (+ 21%), p = 0.02; 2 mm gap:ΔDE = 0.032 J/cycle, (+ 22%), p = 0.009), this increase almost doubled when reducing in a step-down condition (ΔDE = 0.058 J/cycle, (+ 56%), p = 0.042) and even tripled in the step-up condition (ΔDE = 0.097 J/cycle, (+ 94%), p = 0.004). Conclusions Based on our biomechanical findings, we suggest avoiding step conditions in the daily work in the operating theatre. Gap conditions can be handled a bit more generously.

Background: It has been demonstrated that infection with human parvovirus B19 (B19V) is associated with rashâfever illnesses. The present study aimed to investigate B19V as an aetiological agent of rashâfever syndromes in Congolese children confirmed as measles and rubella IgM-negative. An ELISA IgM test and PCR were performed to screen for B19V. Methods: A total of 177 archived serum samples were randomly selected from the measles biobank of the National Institute for Biomedical Research (INRB). Samples were investigated for anti-B19V IgM and B19V DNA. These samples originated from children

Abstract Background Drug resistance is one of the greatest challenges of malaria control programmes, with the monitoring of parasite resistance to artemisinins or to Artemisinin Combination Therapy (ACT) partner drugs critical to elimination efforts. Markers of resistance to a wide panel of antimalarials were assessed in natural parasite populations from southwestern Cameroon. Methods Individuals with asymptomatic parasitaemia or uncomplicated malaria were enrolled through cross-sectional surveys from May 2013 to March 2014 along the slope of mount Cameroon. Plasmodium falciparum malaria parasitaemic blood, screened by light microscopy, was depleted of leucocytes using CF11 cellulose columns and the parasite genotype ascertained by sequencing on the Illumina HiSeq platform. Results A total of 259 participants were enrolled in this study from three different altitudes. While some alleles associated with drug resistance in pfdhfr, pfmdr1 and pfcrt were highly prevalent, less than 3% of all samples carried mutations in the pfkelch13 gene, none of which were amongst those associated with slow artemisinin parasite clearance rates in Southeast Asia. The most prevalent haplotypes were triple mutants Pfdhfr I 51 R 59 N 108 I 164(99%), pfcrt- C72V73 I 74 E 75 T 76 (47.3%), and single mutants PfdhpsS436 G 437K540A581A613(69%) and Pfmdr1 N86 F 184D1246 (53.2%). Conclusions The predominance of the Pf pfcrt CVIET and Pf dhfr IRN triple mutant parasites and absence of pfkelch13 resistance alleles suggest that the amodiaquine and pyrimethamine components of AS-AQ and SP may no longer be effective in their role while chloroquine resistance still persists in southwestern Cameroon.

BACKGROUND:Tanzania is among the Rift Valley fever (RVF) epizootic/endemic countries in sub Saharan Africa, where RVF disease outbreaks occur within a range of 3 to 17-year intervals. Detection of Rift Valley fever virus (RVFV) antibodies in animals in regions with no previous history of outbreaks raises the question of whether the disease is overlooked due to lack-of effective surveillance systems, or if there are strains of RVFV with low pathogenicity. Furthermore, which vertebrate hosts are involved in the inter-epidemic and inter-epizootic maintenance of RVFV? In our study region, the Kyela and Morogoro districts in Tanzania, no previous RVF outbreaks have been reported. METHODOLOGY:The study was conducted from June 2014 to October 2015 in the Kyela and Morogoro districts, Tanzania. Samples (n = 356) were retrieved from both the local breed of zebu cattle (Bos indicus) and Bos indicus/Bos Taurus cross breed. RVFV antibodies were analyzed by two enzyme-linked immunosorbent assay (ELISA) approaches. Initially, samples were analyzed by a RVFV multi-species competition ELISA (cELISA), which detected both RVFV IgG and IgM antibodies. All serum samples that were positive with the cELISA method were specifically analysed for the presence of RVFV IgM antibodies to trace recent infection. A plaque reduction neutralization assay (PRNT80) was performed to determine presence of RVFV neutralizing antibodies in all cELISA positive samples. FINDINGS:Overall RVFV seroprevalence rate in cattle by cELISA in both districts was 29.2% (104 of 356) with seroprevalence rates of 33% (47/147) in the Kyela district and 27% (57/209) in the Morogoro district. In total, 8.4% (30/356) of all cattle sampled had RVFV IgM antibodies, indicating current disease transmission. When segregated by districts, the IgM antibody seroprevalence was 2.0% (3/147) and 12.9% (27/209) in Kyela and Morogoro districts respectively. When the 104 cELISA positive samples were analyzed by PRNT80 to confirm that RVFV-specific antibodies were present, the majority (89%, 93/104) had RVFV neutralising antibodies. CONCLUSION:The results provided evidence of widespread prevalence of RVFV antibody among cattle during an inter-epizootic/inter-epidemic period in Tanzania in regions with no previous history of outbreaks. There is a need for further investigations of RVFV maintenance and transmission in vertebrates and vectors during the long inter-epizootic/inter-epidemic periods.

Abstract AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons.

The energy-burning capability of beige adipose tissue is a potential therapeutic tool for reducing obesity and metabolic disease, but this capacity is decreased by aging. Here, we evaluate the impact of aging on the profile and activity of adipocyte stem and progenitor cells (ASPCs) and adipocytes during the beiging process in mice. We found that aging increases the expression of Cd9 and other fibro-inflammatory genes in fibroblastic ASPCs and blocks their differentiation into beige adipocytes. Fibroblastic ASPC populations from young and aged mice were equally competent for beige differentiation in vitro, suggesting that environmental factors suppress adipogenesis in vivo. Examination of adipocytes by single nucleus RNA-sequencing identified compositional and transcriptional differences in adipocyte populations with aging and cold exposure. Notably, cold exposure induced an adipocyte population expressing high levels of de novo lipogenesis (DNL) genes, and this response was severely blunted in aged animals. We further identified Npr3, which encodes the natriuretic peptide clearance receptor, as a marker gene for a subset of white adipocytes and an aging-upregulated gene in adipocytes. In summary, this study indicates that aging blocks beige adipogenesis and dysregulates adipocyte responses to cold exposure and provides a resource for identifying cold and aging-regulated pathways in adipose tissue.

Abstract Background Shared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists. Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS). Methods We will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS. Discussion The SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS.

IntroductionThe role of personality in shaping engagement with aesthetics in science has been almost entirely unexplored. Whereas artists and arts settings (e.g., museums) are well-studied from a psychological perspective, the practice of science has often been seen as purely rational or dry. In response, this study presents novel findings on the critical role of scientists’ individual differences, which shape their engagement with aesthetics, such as the frequency of their experiences of beauty, wonder, and awe in their scientific work.MethodsBased on a very large and representative four-country study of scientists in the fields of biology and physics (N = 3,092), this study analyzed the associations of Big Five personality traits among scientists with (i) dispositional aesthetics (DPES-awe), (ii) the frequency of aesthetic experiences in scientific work, and (iii) aesthetic sensitivity in science. These survey-weighted OLS regression models included extensive statistical controls for sociodemographic factors.ResultsAs hypothesized, openness is positively, and neuroticism is negatively linked with dispositional aesthetics, the frequency of aesthetic experiences in scientific work, and aesthetic sensitivity in science. Unexpectedly, agreeableness and conscientiousness (but not extraversion) are highly significant and strong predictors of the three trait and state aesthetic engagement variables.DiscussionThe aesthetic engagement and personality framework of this paper is empirically supported and demonstrates the importance of personality types of scientists in the practice of science. The unexpectedly strong association of agreeableness with aesthetic engagement points to the importance of cooperation, collaboration, and communication to maximize scientific creativity.

Accurate measurement of angular positions on the sky requires a well-defined system of reference, something that in practice is realized by the International Celestial Reference Frame (ICRF) with observations of distant (typical redshift $\sim$1) Active Galactic Nuclei (AGN). At such great distances a subset of these objects exhibit as little as 10$-$50 $\mu$as/year observed parallax or proper motion, thus giving the frame excellent spatial and temporal stability. Until fairly recently the majority of AGN centered imaging was accomplished in the S (2.3 GHz) and X (8.4 GHz) radio frequency bands, however S-band observations for reasons such as sensitivity “plateauing”, increased source structure (jets), and radio frequency interference (RFI) have become less productive. Following spacecraft telemetry moves to higher frequencies and a desire to strengthen JPL's leadership in defining the next-generation of celestial reference frames has motivated the development of a “Quad-band” prototype receiver that operates in X, Ku, K, and Ka band in both right hand (RCP) and left hand (LCP) circular polarization. The goal of this receiver is to achieve less than a 20 % increase in noise over the Jansky Very Large Array (JVLA, NRAO) performance specification, which in such a wide bandwidth represents a revolutionary capability. To evaluate the various technical developments of the 8 GHz$-$40 GHz receiver the feedhorn optical beam was designed to interface to the US based Very Long Baseline Array (VLBA). The receiver's intermediate frequency (IF) spans 4 GHz$-$8 GHz, giving rise to up to eight 4 GHz IF channels for a fully populated instrument. This paper outlines the technical development of a 2$^{1}$/$_{2}$ octave wide (8 GHz$-$40 GHz) X-Ka band prototype receiver, fulfilling a need for super broadband technology within the VLBI network. An important additional benefit of the wideband receiver approach is its simplicity and low cost of operation.

International students, especially those studying in English language institutes at universities in the United States, often struggle to create connections with local students and the host community. Learners of non-English languages also struggle to find opportunities to practice languages that are uncommon in the surrounding community. This Practice Report describes an innovation where, instead of using English Conversation Tables to help international students practice English, professors “turned the tables” and allowed international students to become the experts, teaching local students their languages and cultures at weekly Non-English Conversation Tables held at a mid-sized rural public university. Through the Conversation Tables, both international and domestic students developed meaningful connections, deepening their on-campus engagement. These connections fostered self-growth and intercultural competence in both groups of students, some of whom had very limited prior experiences with cultural diversity. The authors identify the characteristics of the language tables that led to their success, including the location, facilitation, and promotion, to provide a model for reproducing the intervention in other contexts.

Most cases of preterm labor have unknown cause, and the burden of preterm birth is immense. Placental aging has been proposed to promote labor onset, but specific mechanisms remain elusive. We report findings stemming from unbiased transcriptomic analysis of mouse placenta, which revealed that hypoxia-inducible factor 1 (HIF-1) stabilization is a hallmark of advanced gestational timepoints, accompanied by mitochondrial dysregulation and cellular senescence; we detected similar effects in aging human placenta. In parallel in primary mouse trophoblasts and human choriocarcinoma cells, we modeled HIF-1 induction and demonstrated resultant mitochondrial dysfunction and cellular senescence. Transcriptomic analysis revealed that HIF-1 stabilization recapitulated gene signatures observed in aged placenta. Further, conditioned media from trophoblasts following HIF-1 induction promoted contractility in immortalized uterine myocytes, suggesting a mechanism by which the aging placenta may drive the transition from uterine quiescence to contractility at the onset of labor. Finally, pharmacological induction of HIF-1 via intraperitoneal administration of dimethyloxalyl glycine (DMOG) to pregnant mice caused preterm labor. These results provide clear evidence for placental aging in normal pregnancy, and demonstrate how HIF-1 signaling in late gestation may be a causal determinant of the mitochondrial dysfunction and senescence observed within the trophoblast as well as a trigger for uterine contraction.