Differentiating the roles of Mycobacterium tuberculosis substrate binding proteins, FecB and FecB2, in iron uptake.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, poses a great threat to human health. With the emergence of drug resistant Mtb strains, new therapeutics are desperately needed. As iron is critical to the growth and survival of Mtb, mechanisms through which Mtb acquires host iron represent attractive therapeutic targets. Mtb scavenges host iron via Mtb siderophore-dependent and heme iron uptake pathways. While multiple studies describe the import of heme and ferric-siderophores and the export of apo-siderophores across the inner membrane, little is known about their transport across the periplasm and cell-wall environments. Mtb FecB and FecB2 are predicted periplasmic binding proteins implicated in host iron acquisition; however, their precise roles are not well understood. This study sought to differentiate the roles FecB and FecB2 play in Mtb iron acquisition. The crystallographic structures of Mtb FecB and FecB2 were determined to 2.0 Å and 2.2 Å resolution, respectively, and show distinct ligand binding pockets. In vitro ligand binding experiments for FecB and FecB2 were performed with heme and bacterial siderophores from Mtb and other species, revealing that both FecB and FecB2 bind heme, while only FecB binds the Mtb sideophore ferric-carboxymycobactin (Fe-cMB). Subsequent structure-guided mutagenesis of FecB identified a single glutamate residue-Glu339-that significantly contributes to Fe-cMB binding. A role for FecB in the Mtb siderophore-mediated iron acquisition pathway was corroborated by Mycobacterium smegmatis and Mtb pull-down assays, which revealed interactions between FecB and members of the mycobacterial siderophore export and import machinery. Similarly, pull-down assays with FecB2 confirms its role in heme uptake revealing interactions with a potential inner membrane heme importer. Due to ligand preference and protein partners, our data suggest that Mtb FecB plays a role in siderophore-dependent iron and heme acquisition pathways; in addition, we confirm that Mtb FecB2 is involved in heme uptake.

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Mycobacterium tuberculosis Infection Induces BCSFB Disruption but No BBB Disruption In Vivo: Implications in the Pathophysiology of Tuberculous Meningitis.

Central nervous system (CNS) tuberculosis is the most lethal and devastating form among the diseases caused by Mycobacterium tuberculosis. The mechanisms by which M. tuberculosis bacilli enter the CNS are still unclear. However, the BBB and the BCSFB have been proposed as possible routes of access into the brain. We previously reported that certain strains of M. tuberculosis possess an enhanced ability to cause secondary CNS infection in a mouse model of progressive pulmonary tuberculosis. Here, we evaluated the morphostructural and molecular integrity of CNS barriers. For this purpose, we analyzed through transmission electron microscopy the ultrastructure of brain parenchymal microvessels and choroid plexus epithelium from animals infected with two mycobacterial strains. Additionally, we determined the expression of junctional proteins and cytokines by immunological techniques. The results showed that the presence of M. tuberculosis induced disruption of the BCSFB but no disruption of the BBB, and that the severity of such damage was related to the strain used, suggesting that variations in the ability to cause CNS disease among distinct strains of bacteria may also be linked to their capacity to cause direct or indirect disruption of these barriers. Understanding the pathophysiological mechanisms involved in CNS tuberculosis may facilitate the establishment of new biomarkers and therapeutic targets.

Identifying contamination of heavy metals in soils of Peruvian Amazon plain: use of multivariate statistical techniques.

The Peruvian Amazon plain has abundant natural resources and is home to great biodiversity, which makes it an area with high economic potential. However, the use of its resources through various activities has contributed to the release of heavy metals (HMs) into its soils, generating severe pollution problems which have mainly affected the health of local populations and their ecosystems. Currently, there are no comprehensive studies that have identified the specific sources of contamination by HMs in the soils of this part of the Peruvian territory. In this sense, this research aims to identify the possible sources of contamination by HMs in the soils of the Peruvian Amazon plain to focus efforts on the establishment of adequate measures for the protection of the health of people and the ecosystem. In the present study, samples of topsoils (0-20 cm depth) and subsoils (100-150 cm depth) were collected for the analysis of 11 HMs (Co, Cr, Cu, Fe, Mn, Ni, Pb, V, Zn, Be, and Hg) in 48 sites located in four regions of the Peruvian Amazon plain (Loreto, Amazonas, San Martín, and Ucayali), over the year 2019. The enrichment factor and geoaccumulation index were applied to assess contamination levels of HMs. The results indicated that topsoils and subsoils presented a greater enrichment by the elements Be and Pb, and were classified as moderately contaminated. Likewise, the integral analysis of these indexes together with principal component analysis, hierarchical cluster analysis, correlation analysis, and coefficient of variation allowed the identification of potential sources of contamination by HMs. As a result, Fe, Co, Zn, Ni, V, and Cr were associated with natural or lithogenic sources (parent material, crude oil deposits, and organic matter decomposition). Hg was attributed to anthropogenic sources (illegal gold mining, atmospheric deposition, and vehicle emissions). Be, Pb, Cu, and Mn originated from natural sources (parent material, crude oil deposits, decomposition of organic matter, and forest fires) and anthropogenic (areas degraded by solid waste, illegal gold mining, agriculture, and hydrocarbons). These findings provide essential information to establish regulations and prevent and control HM contamination in soils of the Peruvian Amazon plain.

Validation of the QLQ-CX24 questionnaire for the assessment of quality of life in Mexican women with cervical cancer.

OBJECTIVE: Cervical cancer is the fourth most frequent neoplasm among women in terms of incidence and mortality. Health-related quality of life (HRQL) is an important outcome in oncology. The QLQ-CX24 instrument was developed to measure HRQL in patients with cervical cancer, and its Mexican-Spanish version had not been validated. METHODS: Between March 2018 and May 2019, Mexican women older than 18, with any-stage cervical cancer were invited to participate in the study. Patients answered the QLQ-C30 and QLQ-CX24 questionnaires. Current tests for psychometric and clinical validation were performed. RESULTS: Three hundred and thirty patients with cervical cancer were included in this study. All women invited to participate accepted and were included. The QLQ-CX24 internal consistency test demonstrated adequate convergent (Spearman correlation coefficient 0.001-0.847) and divergent validity (Spearman correlation coefficient <0.0001-0.45). Cronbach's alpha coefficients of the three multi-item scales were >0.7 (minimum 0.76, maximum 0.89). Four scales of the QLQ-CX24 distinguished patients in different clinical stages. The evaluation of responsiveness demonstrated that the peripheral neuropathy scale was sensitive to change over time during chemo-radiation therapy. Six scales of the QLQ-CX24 instrument were associated with survival. CONCLUSION: The Mexican-Spanish version of the QLQ-CX24 questionnaire is reliable and valid for the assessment of HRQL in patients with cervical cancer.

Prevalence and determinants of violence against health care in the metropolitan city of Peshawar: a cross sectional study.

BACKGROUND: Violence against healthcare personnel is a major public health problem. Healthcare personnel are at the frontline dealing with people in stressful and unpredictable situations. Therefore, this study was conducted to determine the prevalence and associated factors of violence against health care personnel. METHODS: A cross sectional study was conducted in the district Peshawar. Healthcare personnel from public and private sectors working in both the primary and tertiary levels of healthcare were invited to participate. Violence was assessed through a structured questionnaire previously used in Pakistan and was defined as experiencing and/or witnessing any form of violence in the last 12 months. Mental health was assessed through the General Health Questionnaire. Logistic regression was used to estimate the association of violence against healthcare personnel with psychological distress and demographic characteristics. Data entry and analysis were conducted in STATA 14. RESULTS: A total of 842 healthcare personnel participated in the study. The prevalence of violence experienced and/or witnessed by healthcare personnel in Peshawar was 51%. Verbal violence remained the predominant form of violence and almost half of the healthcare personnel (45%) were exposed to it. A quarter of the respondents (24%) reported physical violence alone or in combination with other forms of violence. In almost two third of the incidents the perpetrators were either attendants, relatives or the patients. The emergency unit and wards within healthcare facilities were the most common places where violent events took place. The major factors responsible for the violent incidents were communication failure, unreasonable expectations and perceived substandard care. No uniform policy/procedure existed to manage the incidents and the healthcare personnel adopted different responses in the wake of violent events targeting health care. Working in public healthcare facilities and having a larger number of co-workers/colleagues significantly increased the risk of violence in the healthcare settings while being a paramedic significantly reduced the risk as compared to physicians. CONCLUSIONS: Violence against healthcare personnel is a serious public health issue and the prevalence is quite high. A holistic effort is needed by all stakeholders including healthcare community, the administration, lawmakers, law enforcement, civil society, and international organizations.

QoE Optimization in a Live Cellular Network through RLC Parameter Tuning.

The mobile communication networks sector has experienced a great evolution during the last few years. The emergence of new services as well as the growth in the number of subscribers have motivated the search for new ways to optimize mobile networks. In this way, the objective pursued by optimization techniques has been evolving, shifting from the traditional optimization of radio parameters to the improvement of the quality perceived by users, known as quality of experience (QoE). In mobile networks, the radio link control (RLC) layer provides a reliable link between both ends of the communication and has a great impact on the QoE. In this paper, the optimization of the QoE for users based on the adjustment of the RLC layer is proposed. For this purpose, two typical services demanded by the users of mobile networks have been selected: the real-time video streaming service and file transfer service. For a broader view of the behavior of the QoE in relation to RLC, optimization tests have been carried out in scenarios with different system bandwidths. In this way, the relationship between the QoE and the optimal configuration of RLC in different network load situations has been analyzed. A proof of concept has been carried out to show the capability of this optimization. To that end, both a cellular network simulator and a live cellular network devised for research purposes have been used.

Feature Extraction for Dimensionality Reduction in Cellular Networks Performance Analysis.

Next-generation mobile communications networks will have to cope with an extraordinary amount and variety of network performance indicators, causing an increase in the storage needs of the network databases and the degradation of the management functions due to the high-dimensionality of every network observation. In this paper, different techniques for feature extraction are described and proposed as a means for reducing this high dimensionality, to be integrated as an intermediate stage between the monitoring of the network performance indicators and their usage in mobile networks' management functions. Results using a dataset gathered from a live cellular network show the benefits of this approach, in terms both of storage savings and subsequent management function improvements.

On the Capability of QoE Improvement Based on the Adjustment of RLC Parameters.

The constant evolution in mobile communications networks have led operators to seek new techniques to optimize their mobile networks with the objective of satisfying the expectations of the users. In this way, traditional optimization techniques based on improving radio indicators, have given way to new techniques based on improving the quality of experience (QoE) perceived by users. This paper is focused on analyzing the impact of the adjustment of radio link control (RLC) layer configuration parameters on the QoE perceived by the users of two different types of services. Firstly, an evaluation of the QoE experienced by the user of a real-time video streaming service with respect to the transmission buffer size of the RLC layer in unacknowledged mode (UM) has been carried out. Secondly, the QoE perceived by the user of a file transfer service in relation to the variation of the configuration parameters of the RLC layer in acknowledged mode (AM) has been evaluated. The study, which has been carried out in a simulated cellular environment, has been performed for different system bandwidth values, thus proving the relationship between the QoE perceived by the users, the optimal RLC configuration parameters values and the available bandwidth.

Online Anomaly Detection System for Mobile Networks.

The arrival of the fifth generation (5G) standard has further accelerated the need for operators to improve the network capacity. With this purpose, mobile network topologies with smaller cells are currently being deployed to increase the frequency reuse. In this way, the number of nodes that collect performance data is being further risen, so the number of metrics to be managed and analyzed is being highly increased. Therefore, it is fundamental to have tools that automatically inform the network operator of the relevant information within the vast amount of metrics collected. The continuous monitoring of the performance indicators and the automatic detection of anomalies is especially important for network operators to prevent the network degradation and user complaints. Therefore, this paper proposes a methodology to detect and track anomalies in the mobile networks performance indicators online, i.e., in real time. The feasibility of this system was evaluated with several performance metrics and a real LTE Advanced dataset. In addition, it was also compared with the performances of other state-of-the-art anomaly detection systems.

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway.

BACKGROUND: Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C-KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. METHODS: A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17-year period). Immunohistochemistry stain of C-KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi-square, Fisher's exact and the Mann-Whitney U tests were applied when necessary. The significance was set at P < 0.05. RESULTS: Sixty-two cases were included, 74% were positive for C-KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ 61R and BRAFV 600E , respectively, followed by KITK624E (3.2%). No KITL 576P , MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = -0.057, P = 0.765). CONCLUSIONS: Regardless of the high immunoexpression of C-KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C-KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.

The structure of Mycobacterium thermoresistibile MmpS5 reveals a conserved disulfide bond across mycobacteria.

The tuberculosis (TB) emergency has been a pressing health threat for decades. With the emergence of drug-resistant TB and complications from the COVID-19 pandemic, the TB health crisis is more serious than ever. Mycobacterium tuberculosis (Mtb), the causative agent of TB, requires iron for its survival. Thus, Mtb has evolved several mechanisms to acquire iron from the host. Mtb produces two siderophores, mycobactin and carboxymycobactin, which scavenge for host iron. Mtb siderophore-dependent iron acquisition requires the export of apo-siderophores from the cytosol to the host environment and import of iron-bound siderophores. The export of Mtb apo-siderophores across the inner membrane is facilitated by two mycobacterial inner membrane proteins with their cognate periplasmic accessory proteins, designated MmpL4/MmpS4 and MmpL5/MmpS5. Notably, the Mtb MmpL4/MmpS4 and MmpL5/MmpS5 complexes have also been implicated in the efflux of anti-TB drugs. Herein, we solved the crystal structure of M. thermoresistibile MmpS5. The MmpS5 structure reveals a previously uncharacterized, biologically relevant disulfide bond that appears to be conserved across the Mycobacterium MmpS4/S5 homologs, and comparison with structural homologs suggests that MmpS5 may be dimeric.

Guía mexicana para el diagnóstico y el tratamiento del hemangioma infantil.

Infantile hemangioma is a benign vascular tumor, the most common in childhood, whose natural evolution is the disappearance of the lesion in the pediatric age and which has effective and safe treatments that limit its growth and favor its disappearance at younger ages. Infantile hemangioma continues to be a reason for attention to complications, due to erroneous diagnoses, lack of knowledge of the condition, late referral or fear of the effects of the medications used for its treatment. Furthermore, its presence is normalized without taking into account that it can cause uncertainty, anxiety, feelings of guilt and, as a consequence, a significant impact on the quality of life, mainly in the parents or caregivers of the child. The need for a clinical practice guideline in our country arises from the high presentation of late-remitted complications in infantile hemangioma even with the availability of adequate treatments, the continuous evolution of medicine and the appearance of new evidence. Throughout the guide you will find recommendations regarding the diagnosis, treatment and follow-up of patients with infantile hemangioma, taking into account the paraclinical tests that can be performed, topical or systemic management options, as well as adjuvant therapies. For the first time, objective tools for patient follow-up are included in a guide for the management of infantile hemangioma, as well as to help the first contact doctor in timely referral.

El hemangioma infantil es un tumor vascular benigno, el más frecuente de la infancia, cuya evolución natural favorece la desaparición de la lesión en la misma edad pediátrica y que cuenta con tratamientos eficaces y seguros que limitan su crecimiento y favorecen su desaparición a edades más tempranas. Continúa siendo motivo de atención de complicaciones, debido a diagnósticos erróneos, desconocimiento del padecimiento, referencia tardía o temor de los efectos de los fármacos utilizados para su tratamiento. Además, se normaliza su presencia sin tomar en cuenta que puede llegar a causar incertidumbre, ansiedad, sentimientos de culpa y, como consecuencia, importante afectación de la calidad de vida, principalmente en los padres o cuidadores del niño. La necesidad de una guía de práctica clínica en nuestro país surge ante la alta presentación de complicaciones del hemangioma infantil referidas de manera tardía aun con la disponibilidad de tratamientos adecuados, la evolución continua de la medicina y la aparición de nueva evidencia. A lo largo de la guía se encontrarán recomendaciones en relación con el diagnóstico, el tratamiento y el seguimiento de los pacientes con hemangioma infantil, tomando en cuenta los paraclínicos que pueden realizarse, las opciones de manejo tópico o sistémico, y las terapias adyuvantes. Por primera vez se incluyen en una guía para el manejo del hemangioma infantil herramientas objetivas para el seguimiento de los pacientes, así como para ayudar al médico de primer contacto en su referencia oportuna.

FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy - protocol for a prospective multicentre mixed-methods feasibility study.

INTRODUCTION: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. METHODS AND ANALYSIS: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. ETHICS AND DISSEMINATION: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. TRIAL REGISTRATION NUMBER: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201).

Healthcare workers' experiences of workplace violence: a qualitative study in Lebanon.

BACKGROUND: The COVID-19 pandemic has brought unprecedented challenges to healthcare workers (HCWs) around the world. The healthcare system in Lebanon was already under pressure due to economic instability and political unrest before the pandemic. This study aims to explore the impact of COVID-19 and the economic crisis on HCWs' experiences of workplace violence in Lebanon. METHODS: A qualitative research design with an inductive approach was employed to gather data on workplace violence through Focus Group Discussions (FGDs) from HCWs in Tripoli Governmental Hospital (TGH), a governmental hospital in North Lebanon. Participants were recruited through purposive sampling. The interviews were conducted in Arabic, recorded, transcribed, and translated into English. Thematic analysis was used to analyze the data. RESULTS: A total of 27 employees at the hospital participated in the six FGDs, of which 15 females and 12 males. The analysis identified four main themes: (1) Types of violence, (2) Events witnessed, (3) Staff reactions to violence, and (4) Causes of violence. According to the interviews conducted, all the staff members, whether they had experienced or witnessed violent behavior, reported that such incidents occurred frequently, ranging from verbal abuse to physical assault, and sometimes even involving the use of weapons. The study findings suggest that several factors contribute to the prevalence of violence in TGH, including patients' financial status, cultural beliefs, and lack of medical knowledge. The hospital's location in an area with a culture of nepotism and favoritism further exacerbates the issue. The staff's collective response to dealing with violence is either to submit to the aggressor's demands or to remove themselves from the situation by running away. Participants reported an increase in workplace violence during the COVID-19 pandemic and the exacerbated economic crisis in Lebanon and the pandemic. CONCLUSION: Interventions at different levels, such as logistical, policy, and education interventions, can help prevent and address workplace violence. Community-level interventions, such as raising awareness and engaging with non-state armed groups, are also essential to promoting a culture of respect and zero tolerance for violence.

Understanding context of violence against healthcare through citizen science and evaluating the effectiveness of a co-designed code of conduct and of a tailored de-escalation of violence training in Eastern Democratic Republic of Congo and Iraq: a study protocol for a stepped wedge randomized controlled trial.

BACKGROUND: Violence against health care workers (HCWs) is a multifaceted issue entwined with broader social, cultural, and economic contexts. While it is a global phenomenon, in crisis settings, HCWs are exposed to exceptionally high rates of violence. We hypothesize that the implementation of a training on de-escalation of violence and of a code of conduct informed through participatory citizen science research would reduce the incidence and severity of episodes of violence in primary healthcare settings of rural Democratic Republic of Congo (DRC) and large hospitals in Baghdad, Iraq. METHODS: In an initial formative research phase, the study will use a transdisciplinary citizen science approach to inform the re-adaptation of a violence de-escalation training for HCWs and the content of a code of conduct for both HCWs and clients. Qualitative and citizen science methods will explore motivations, causes, and contributing factors that lead to violence against HCWs. Preliminary findings will inform participatory meetings aimed at co-developing local rules of conduct through in-depth discussion and input from various stakeholders, followed by a validation and legitimization process. The effectiveness of the two interventions will be evaluated through a stepped-wedge randomized-cluster trial (SW-RCT) design with 11 arms, measuring the frequency and severity of violence, as well as secondary outcomes such as post-traumatic stress disorder (PTSD), job burnout, empathy, or HCWs' quality of life at various points in time, alongside a cost-effectiveness study comparing the two strategies. DISCUSSION: Violence against HCWs is a global issue, and it can be particularly severe in humanitarian contexts. However, there is limited evidence on effective and affordable approaches to address this problem. Understanding the context of community distrust and motivation for violence against HCWs will be critical for developing effective, tailored, and culturally appropriate responses, including a training on violence de-escalation and a community behavioral change approach to increase public trust in HCWs. This study aims therefore to compare the effectiveness and cost-effectiveness of different interventions to reduce violence against HCWs in two post-crisis settings, providing valuable evidence for future efforts to address this issue. TRIAL REGISTRATION: ClinicalTrial.gov Identifier NCT05419687. Prospectively registered on June 15, 2022.

Violence against health care workers in a crisis context: a mixed cross-sectional study in Eastern Democratic Republic of Congo.

BACKGROUND: Health Care Workers (HCWs) in conflict zones face high levels of violence while also playing a crucial role in assisting the population in distress. For more than two decades, the eastern provinces of the Democratic Republic of the Congo (DRC), have been wracked by conflict. This study aims to describe the state of violence against HCWs and the potential prevention mechanisms in eastern DRC. METHODS: In North and South Kivu, between February 5 and 21, 2021, we conducted a mixed cross-sectional convergent study in health facilities (health centers and hospitals). An anonymized self-administered questionnaire was sent to HCWs about their experience of violence in the 12 months prior to the study. In-depth individual interviews with HCWs, present on the day of the investigation, were also done to explore their experience of violence. A descriptive analysis of the quantitative data and a thematic analysis of the qualitative data was carried out. RESULTS: Of a total of 590 participants, 276 (45.9%) reported having experienced violence in the 12 months before the study. In North Kivu, aggressors were more frequently the patients (43.7% vs. 26.5%) and armed group members (14.3% vs. 7.9%) than in South Kivu. Most respondents (93.5%) reported verbal aggression (insults, intimidation, death threats). Other forms of physical aggression including with bare hands (11.2%), firearm (1.81%), and stabbing (4.7%). Only nearly one-tenth of the attacks were officially reported, and among those reported a higher proportion of sanctions was observed in South Kivu (8.5%) than in North Kivu (2.4%). The mechanisms proposed to prevent violence against HCWs were community initiatives and actions to strength the health system. CONCLUSIONS: In Eastern DRC, HCWs face multiple and severe forms of aggression from a variety of individuals. The effects of such levels violence on HCWs and the communities they served could be devastating on the already pressured health system. Policy framework that defines the roles and responsibilities for the protection of HCWs and for the development and implementation of preparedness measures such as training on management of violence are possible solutions to this problem.

The role of TNF receptors as mediators of chronic vasculitis in possible milder forms of the CNS tuberculosis.

INTRODUCTION: Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB due to its high mortality and functional sequelae. There are several differential diagnoses for TB; and, it can also cause secondary conditions, such as vasculitis. METHODOLOGY: 155 biopsies, corresponding to 155 different patients out of 5,386 registered biopsies from 2008-2013, met the criteria of unknown etiology vasculitis and evidence of cerebral vascular disease. These were analyzed to assess the presence of central nervous system TB. The selected cases were assessed with Suzaan Marais (SM) criteria for clinical tuberculosis. After that, Ziehl-Neelsen (ZN) staining and polymerase chain reaction (PCR) were performed to amplify a fragment of the insertion sequence IS6110 of M. tuberculosis. 21 patients met the criteria for definitive tuberculosis by ZN staining and PCR, and 2 met the criteria for possible tuberculosis. Tumor necrosis factor (TNF)-α, TNF-R1, and TNF-R2 were determined by immunohistochemistry in histological sections from formalin-fixed paraffin-embedded (FF-PE) tissues in the 23 selected patients. RESULTS: Granulomatous TB was present in almost half of the cases. TNF-R1 and TNF-R2 were expressed mainly in blood vessels, histiocytes, and macrophages. TNF-R2 expression was higher than the other markers, which suggests an anti-inflammatory response against M. tuberculosis. CONCLUSIONS: The histopathological presentation of TB is not always limited to granulomas, abscesses, or meningitis; there are also clinical presentations characterized only with chronic inflammation of nervous and vascular tissue.

Development of the Early Activity Scale for Endurance for children with cerebral palsy.

PURPOSE: The Early Activity Scale for Endurance (EASE) was developed as a clinically feasible measure of endurance for physical activity in young children with cerebral palsy (CP). Validity and reliability were evaluated. METHODS: Participants included 414 children with CP and 106 without CP. Parents completed the EASE, an 11-item self-report measure. For construct validity, EASE scores were compared by Gross Motor Function Classification System levels (0 assigned for children without CP), age, and gender. In subgroups, convergent validity with the 6-minute walk test and test-retest reliability with a second EASE were evaluated. RESULTS: EASE scores differed significantly by Gross Motor Function Classification System, but not by age or gender. The EASE correlated moderately (rs = 0.57) with the 6-minute walk test. Test-retest reliability was high, intraclass correlation (2,1) = 0.95. CONCLUSION: The EASE has acceptable psychometrics for use in practice and research to estimate endurance for physical activity in young children with CP.

Exposing the Great Imitator: Proposal for a Holistic Diagnosis of Oral Secondary Syphilis in People Living with HIV.

Oral secondary syphilis may mimic various infectious, neoplastic, or immune-mediated processes; hence, its diagnosis may represent a challenge. Early diagnosis of syphilis, a disease that has increased in recent decades, is essential for adequate management, particularly in people living with HIV (PLWH). This study aimed to comprehensively characterize oral secondary syphilis in a group of 47 PLWH. A group of PLWH with oral secondary syphilis attending four HIV-referral centers in Mexico City was included (2004-2021). Clinical and laboratory data were retrieved, and an exhaustive oral examination was performed following the established criteria. Demographic, clinicopathological, immunohistochemical, and serological features of the patients were analyzed. Approximately 11% of PLWH with oral secondary syphilis demonstrated negative Venereal Disease Research Laboratory tests. A noticeable feature was the absence of symptoms in 95.7% of cases, despite the clinically evident appearance of the lesions. In contrast to previous results, 18% of ulcerations were detected to be deep, crateriform, and infiltrative, and 22% of the mucous patches were highly keratotic lesions. Most samples (77.3%) showed superficial lymphoplasmacytic infiltrates in the superficial lamina propria, with perivascular and perineural patterns, and immunohistochemistry was positive in 66.7% of the cases. The "great imitator" appears not only clinically but also histopathologically and immunohistochemically, where features may be comparable with those of chronic inflammatory processes, deep infections, or malignant processes. Although not recommended as a routine assay, IHC could be a critical tool, particularly in PLWH with atypical clinical features or with negative and/or dubious serology.