Clinical manifestations of human brucellosis : a systematic review and meta-analysis

BACKGROUND: The objectives of this systematic review, commissioned by WHO, were to assess the frequency and severity of clinical manifestations of human brucellosis, in view of specifying a disability weight for a DALY calculation. METHODS/PRINCIPAL FINDINGS: Thirty three databases were searched, with 2,385 articles published between January 1990-June 2010 identified as relating to human brucellosis. Fifty-seven studies were of sufficient quality for data extraction. Pooled proportions of cases with specific clinical manifestations were stratified by age category and sex and analysed using generalized linear mixed models. Data relating to duration of illness and risk factors were also extracted. Severe complications of brucellosis infection were not rare, with 1 case of endocarditis and 4 neurological cases per 100 patients. One in 10 men suffered from epididymo-orchitis. Debilitating conditions such as arthralgia, myalgia and back pain affected around half of the patients (65%, 47% and 45%, respectively). Given that 78% patients had fever, brucellosis poses a diagnostic challenge in malaria-endemic areas. Significant delays in appropriate diagnosis and treatment were the result of health service inadequacies and socioeconomic factors. Based on disability weights from the 2004 Global Burden of Disease Study, a disability weight of 0.150 is proposed as the first informed estimate for chronic, localised brucellosis and 0.190 for acute brucellosis. CONCLUSIONS: This systematic review adds to the understanding of the global burden of brucellosis, one of the most common zoonoses worldwide. The severe, debilitating, and chronic impact of brucellosis is highlighted. Well designed epidemiological studies from regions lacking in data would allow a more complete understanding of the clinical manifestations of disease and exposure risks, and provide further evidence for policy-makers. As this is the first informed estimate of a disability weight for brucellosis, there need for further debate amongst brucellosis experts and a consensus to be reache

Towards a one health food safety strategy for palestine: a mixed-method study

Introduction: Foodborne diseases, together with increasing antimicrobial resistance (AMR), pose a threat to public health in an era of huge challenges with climate change and the risks of zoonotic epidemics. A One Health approach to foster food safety is a key for improvement, particularly in complex socio-ecological systems such as in Palestine, to examine human-animal-environment interfaces and promote intersectoral action. Objectives: This study aimed to assess food safety from farm to public health toward an operational One Health strategy for Palestine. This study evaluates the food production (broiler production) and monitoring system to better understanding the zoonotic foodborne illnesses transmission and their resistance to antimicrobials. Methods: The transdisciplinary approach included multi-stakeholder discussion groups and field visits to broiler farms, slaughterhouses, and meat stores in the Ramallah and Al-Bireh and Jerusalem districts using a semi-structured observational tool. A survey with 337 poultry producers and workers in slaughterhouses and meat stores was conducted to assess hygiene knowledge, attitudes, and practices during broiler meat production. Results: The stakeholders point out various challenges along the food production chain in Palestine, such as a striking scarcity of public slaughterhouses, insufficient coordination between authorities, a gap between public and private sectors, and inconsistent application of the law. From observations, it appears that, unlike traditional broiler production, the public slaughterhouses and meat markets have effective hygiene, while large-scale farms implement biosecurity measures. Overall, surveyed participants reported that they are aware of zoonotic disease transmission routes and value hygiene standards. Semi-structured observations and survey results are contradictory. Observations indicate poor hygiene practices; however, the vast majority of broiler meat production chain workers claim that hygiene standards are met. Discussion and Conclusions: Our study found that the overuse of antimicrobials, system fragmentation, insufficient infrastructure, a lack of regulations and controls, and poor hygiene practices are among the main obstacles to improving food safety in Palestine. Considering the risk of an important human health burden of food-related illnesses, enhancing food safety in Palestine is required using an integrated One Health approach. It is crucial to develop an integrated quality control system for food production along with promoting on-farm biosecurity and antimicrobial stewardship. Infrastructure, especially slaughterhouses and laboratories, must be built, training and education provided, and consumer awareness raised. As an important added value within a One Health strategy for better food safety in Palestine, research should be reinforced and accompany any future development of the food production monitoring system

Dual Function of the pUL7-pUL51 Tegument Protein Complex in Herpes Simplex Virus 1 Infection

The tegument of herpesviruses is a highly complex structural layer between the nucleocapsid and the envelope of virions. Tegument proteins play both structural and regulatory functions during replication and spread, but the interactions and functions of many of these proteins are poorly understood. Here we focus on two tegument proteins from herpes simplex virus 1 (HSV-1), pUL7 and pUL51, which have homologues in all other herpesviruses. We have now identified that HSV-1 pUL7 and pUL51 form a stable and direct protein-protein interaction, their expression levels rely on the presence of each other, and they function as a complex in infected cells. We demonstrate that expression of the pUL7-pUL51 complex is important for efficient HSV-1 assembly and plaque formation. Furthermore, we also discovered that the pUL7-pUL51 complex localizes to focal adhesions at the plasma membrane in both infected cells and in the absence of other viral proteins. The expression of pUL7-pUL51 is important to stabilize focal adhesions and maintain cell morphology in infected cells and cells infected with viruses lacking pUL7 and/or pUL51 round up more rapidly than cells infected with wild-type HSV-1. Our data suggest that, in addition to the previously reported functions in virus assembly and spread for pUL51, the pUL7-pUL51 complex is important for maintaining the attachment of infected cells to their surroundings through modulating the activity of focal adhesion complexes. $\textbf{IMPORTANCE}$: The $\textit{Herpesviridae }$ is a large family of highly successful human and animal pathogens. Virions of these viruses are composed of many different proteins, most of which are contained within the tegument, a complex structural layer between the nucleocapsid and the envelope within virus particles. Tegument proteins have important roles in assembling virus particles as well as modifying host cells to promote virus replication and spread. However, little is known about the function of many tegument proteins during virus replication. Our study focuses on two tegument proteins from herpes simplex virus 1 that are conserved in all herpesviruses: pUL7 and pUL51. We demonstrate that these proteins directly interact and form a functional complex that is important for both virus assembly and modulation of host cell morphology. Further, we identify for the first time that these conserved herpesvirus tegument proteins localize to focal adhesions in addition to cytoplasmic juxtanuclear membranes within infected cells.This work was supported by the Leverhulme Trust (grant RPG-2012-793 to C.M.C.), the Royal Society (University Research Fellowship UF090010 to C.M.C.), and the Royal Society and the Wellcome Trust (Sir Henry Dale Fellowship 098406/Z/12/Z to S.C.G.). L.D. was supported by Wellcome Trust Ph.D. Programme funding (086158/Z/08/Z). D.J.O. was supported by a John Lucas Walker studentship. M.F.A. was supported by a Commonwealth Scholarship Commission PhD scholarship (BDCA-2014-7)

Noxious stimulation induces self-protective behavior in bumblebees

It has been widely stated that insects do not show self-protective behavior towards noxiously-stimulated body parts, but this claim has never been empirically tested. Here, we tested whether an insect species displays a type of self-protective behavior: self-grooming a noxiously-stimulated site. We touched bumblebees (Bombus terrestris) on the antenna with a noxiously-heated (65°C) probe and found that, in the first two minutes after this stimulus, bees groomed their touched antenna more than their untouched antenna and more than bees that were touched with an unheated probe or not touched at all. Our results present evidence that bumblebees display self-protective behavior. We discuss the potential neural mechanisms of this behavior and the implications for the topic of insect pain

Whole-genome sequencing for One Health surveillance of antimicrobial resistance in conflict zones: a case study of Salmonella spp. and Campylobacter spp. in the West Bank, Palestine

Antimicrobial resistance (AMR) is a critical global concern driven by the overuse, misuse, and/or usage of inadequate antibiotics on humans, animals' agriculture, and as a result of contaminated environments. This study is the first One Health survey in the Middle East that incorporated whole-genome sequencing (WGS) to examine the spread of AMR in Campylobacter spp. and Salmonella spp. This cross-sectional study was conducted to examine the role of AMR at the human-animal-environmental interface and was performed in Ramallah/Al-Bireh and Jerusalem governorates of the central West Bank, Palestine. In 2021 and 2022, a total of 592 samples were collected and analyzed. From a total of 65 Campylobacter jejuni and 19 Salmonella spp. isolates, DNA was extracted for WGS using Oxford Nanopore Technologies MinION platform. We found that the dominant serotypes of C. jejuni and Salmonella enterica were present in chicken manure, chicken meat sold in markets, and feces of asymptomatic farm workers, with high genetic similarities between the isolates regardless of origin. Additionally, our results showed rapid strain turnover in C. jejuni from the same sites between 2021 and 2022. Most of the positive Salmonella spp. samples were multidrug-resistant (MDR) S. enterica serovar Muenchen carrying the plasmid of emerging S. infantis (pESI) megaplasmid, conferring resistance to multiple antibiotics. Our findings highlight the spread of MDR foodborne pathogens from animals to humans through the food chain, emphasizing the importance of a One Health approach that considers the interconnections between human, animal, and environmental health. IMPORTANCE Prior to this study, there existed hardly an integrated human-animal-environmental study of Salmonellosis and Campylobacteriosis and related AMR in Middle Eastern countries. The few existing studies lack robust epidemiological study designs, adequate for a One Health approach, and did not use WGS to determine the circulating serotypes and their AMR profiles. Civil unrest and war in Middle Eastern countries drive AMR because of the breakdown of public health and food security services. This study samples simultaneously humans, animals, and the environment to comprehensively investigate foodborne pathogens in the broiler chicken production chain in Palestine using WGS. We show that identical serotypes of C. jejuni and S. enterica can be found in samples from chicken farms, chicken meat sold in markets, and asymptomatic broiler chicken production workers. The most striking feature is the rapid dynamic of change in the genetic profile of the detected species in the same sampling locations. The majority of positive Salmonella spp. samples are MDR S. enterica serovar Muenchen isolates carrying the pESI megaplasmid. The results demonstrate a close relationship between the S. enterica serovar Muenchen isolates found in our sample collection and those responsible for 40% of all clinical Salmonella spp. isolates in Israel as previously reported, with a sequence identity of over 99.9%. These findings suggest the transboundary spread of MDR S. enterica serovar Muenchen strains from animals to humans through the food chain. The study underscores the importance of combining integrated One Health studies with WGS for detecting environmental-animal-human transmission of foodborne pathogens that could not be detected otherwise. This study showcases the benefits of integrated environmental-animal-human sampling and WGS for monitoring AMR. Environmental samples, which may be more accessible in conflict-torn places where monitoring systems are limited and regulations are weak, can provide an effective AMR surveillance solution. WGS of bacterial isolates provides causal inference of the distribution and spread of bacterial serotypes and AMR in complex social-ecological systems. Consequently, our results point toward the expected benefits of operationalizing a One Health approach through closer cooperation of public and animal health and food safety authorities

Association between Biological Maturation and Anterior Cruciate Ligament Injury Risk Factors during Cutting

BACKGROUND: Adolescent females are particularly susceptible to suffering anterior cruciate ligament (ACL) injuries, likely influenced by well-established maturational changes. This study investigated ACL biomechanical injury risk factors and their association with biological maturation in females. METHODS: Thirty-five adolescent females (15 ± 1 yr) completed a series of maximum-effort 90° unanticipated cutting manoeuvres. Established biomechanical ACL injury risk factors (including external knee abduction moments, knee abduction, hip abduction, knee flexion, ground reaction force) were derived from an optoelectronic motion analysis system and force platforms, with inter-limb asymmetries in these risk factors also computed. Biological maturation (percentage of predicted adult stature) was assessed using validated regression equations, incorporating anthropometric measures of participants and their biological parents. RESULTS: Significant bilateral asymmetries were observed with higher peak external knee abduction moments, higher ground reaction forces and less knee flexion (from 0-18% and 30-39% of contact) during the non-dominant vs. dominant cuts (effect sizes = 0.36, 0.63 and 0.50, respectively). Maturation did not appear to influence these asymmetries; however, less hip abduction was observed (e.g. 21-51% of contact for dominant cuts) in more biologically-mature females. CONCLUSIONS: These results highlight a potential maturation-related change in cutting technique that may explain the apparent heightened ACL injury risk in this population. As females mature, training targeted at neuromuscular control of hip abductor (e.g. gluteal) muscle groups could potentially mitigate ACL injury risk

Interactive effects of obesity and physical fitness on risk of ischemic heart disease

Background/Objectives:Obesity and low physical fitness are known risk factors for ischemic heart disease (IHD), but their interactive effects are unclear. Elucidation of interactions between these common, modifiable risk factors may help inform more effective preventive strategies. We examined interactive effects of obesity, aerobic fitness and muscular strength in late adolescence on risk of IHD in adulthood in a large national cohort.Subjects/Methods:We conducted a national cohort study of all 1 547 407 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular strength and body mass index (BMI) measurements were examined in relation to IHD identified from outpatient and inpatient diagnoses through 2012 (maximum age 62 years).Results:There were 38 142 men diagnosed with IHD in 39.7 million person years of follow-up. High BMI or low aerobic fitness (but not muscular strength) was associated with higher risk of IHD, adjusting for family history and socioeconomic factors. The combination of high BMI (overweight/obese vs normal) and low aerobic fitness (lowest vs highest tertile) was associated with highest IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31; P<0.001). These exposures had no additive and a negative multiplicative interaction (that is, their combined effect was less than the product of their separate effects). Low aerobic fitness was a strong risk factor even among those with normal BMI.Conclusions:In this large cohort study, low aerobic fitness or high BMI at age 18 was associated with higher risk of IHD in adulthood, with a negative multiplicative interaction. Low aerobic fitness appeared to account for a similar number of IHD cases among those with normal vs high BMI (that is, no additive interaction). These findings suggest that interventions to prevent IHD should begin early in life and include not only weight control but aerobic fitness, even among persons of normal weight

From reverse innovation to global innovation in animal health: a review

Reverse innovation refers to learning from or diffusion of innovations developed in low income settings and further translated to industrialized countries. There is lack of consensus regarding terminology, but the idea that innovations in low-income countries are promising for adoption in high-income contexts is not new. However, in healthcare literature globally, the vast majority of publications referring to 'disruptive innovation' were published in the last ten years. To assess the potential of innovative developments and technologies for improving animal health, we initiated a literature review in 2020. We used a combined approach, incorporating targeted searching in PubMed using a key word algorithm with a snowball technique, to identify 120 relevant publications and extract data for qualitative coding. Heterogeneity of articles precluded meta-analysis, quality scoring and risk of bias analysis. We can distinguish technical innovations like new digital devices, diagnostic tests and procedures, and social innovations of intersectoral cooperation. We profile two case studies to describe potential global innovations: an integrated surveillance and response system in Somali Regional State, Ethiopia and a blockchain secured One Health intervention to optimally provide post-exposure prophylaxis for rabies exposed people in West Africa. Innovation follows no borders and can also occur in low-income settings, under constraints of cost, lack of services and infrastructure. Lower administrative and legal barriers may contribute to produce innovations that would not be possible under conditions of high density of regulation. We recommend using the term global innovation, which highlights those emanating from international partnership to solve problems of global implications

Unionoida (Mollusca: Margaritiferidae, Unionidae) in Arkansas, Third Status Review

We analyzed stream inventories, phylogeographic studies, community and population estimates, life history and reproductive biology research, and suitable habitat investigations conducted from 1997-2008, as well as the Arkansas Natural Heritage Commission mussel database, to update the conservation status for all native freshwater unionoid bivalves thought to occur in Arkansas. Prior to this study, Harris et al. (1997) reviewed the distribution and status of 75 freshwater mussels considered native to Arkansas and ranked 22 species as endangered, threatened or special concern. We now recognize 85 mussel taxa in Arkansas; however, some of those have yet to be described or their nomenclature remains in a state of flux. The previous inclusion of Fusconaia subrotunda (I. Lea 1831) and Obovaria subrotunda (Rafinesque 1820) in the Arkansas native mussel fauna was based on misidentifications. Within the Arkansas mussel fauna, 19 species (22%) are now considered Endangered, 5 species (6%) are ranked as Threatened, 20 species (24%) are of Special Concern, and unfortunately, 1 species has probably been extirpated