Novel human recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in a glyco-engineered Escherichia coli strain.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Previously, it was reported the production of an active human recombinant GALNS (rGALNS) in E. coli BL21(DE3). However, this recombinant enzyme was not taken up by HEK293 cells or MPS IVA skin fibroblasts. Here, we leveraged a glyco-engineered E. coli strain to produce a recombinant human GALNS bearing the eukaryotic trimannosyl core N-glycan, Man3GlcNAc2 (rGALNSoptGly). The N-glycosylated GALNS was produced at 100 mL and 1.65 L scales, purified and characterized with respect to pH stability, enzyme kinetic parameters, cell uptake, and KS clearance. The results showed that the addition of trimannosyl core N-glycans enhanced both protein stability and substrate affinity. rGALNSoptGly was capture through a mannose receptor-mediated process. This enzyme was delivered to the lysosome, where it reduced KS storage in human MPS IVA fibroblasts. This study demonstrates the potential of a glyco-engineered E. coli for producing a fully functional GALNS enzyme. It may offer an economic approach for the biosynthesis of a therapeutic glycoprotein that could prove useful for MPS IVA treatment. This strategy could be extended to other lysosomal enzymes that rely on the presence of mannose N-glycans for cell uptake.

Identification of Orthosteric and Allosteric Pharmacological Chaperones for Mucopolysaccharidosis Type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal inherited disease caused by mutations in gene encoding the lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU). These mutations result in reduced NAGLU activity, preventing it from catalyzing the hydrolysis of the glycosaminoglycan heparan sulfate (HS). There are currently no approved treatments for MPS IIIB. A novel approach in the treatment of lysosomal storage diseases is the use of pharmacological chaperones (PC). In this study, we used a drug repurposing approach to identify and characterize novel potential PCs for NAGLU enzyme. We modeled the interaction of natural and artificial substrates within the active cavity of NAGLU (orthosteric site) and predicted potential allosteric sites. We performed a virtual screening for both the orthosteric and the predicted allosteric site against a curated database of human tested molecules. Considering the binding affinity and predicted blood-brain barrier permeability and gastrointestinal absorption, we selected atovaquone and piperaquine as orthosteric and allosteric PCs. The PCs were evaluated by their capacity to bind NAGLU and the ability to restore the enzymatic activity in human MPS IIIB fibroblasts These results represent novel PCs described for MPS IIIB and demonstrate the potential to develop novel therapeutic alternatives for this and other protein deficiency diseases.

Comparison of the Stress and Anxiety to Viral Epidemic-9 and SAVE-6 scales among healthcare workers in Peru.

Introduction: Peru is a country that has a high incidence of viral outbreaks and epidemics, which is why it is necessary to validate a scale that measures anxiety and stress in professionals who are on the front lines of these events. Therefore, our objective was to validate the Peruvian-Spanish version of the Stress and Anxiety to Viral Epidemics-9 items (SAVE-9) scale and to concurrently compare its validity and internal consistency with the SAVE-6 scale among healthcare workers (HCWs). Materials and methods: We conducted a cross-sectional study based on data collected from a self-reported survey in paper-and-pencil format between April and July 2023. A total of 203 HCWs participated in the research. We developed a confirmatory factor analysis (CFA) and item response theory (IRT). We calculated Cronbach's α coefficient and McDonald's ω to assess the internal consistency of the scales. Results: The results show that SAVE-9 (a two-factor model) and SAVE-6 (a one-factor model) provided an excellent fit in the confirmatory factor analysis. Both scales demonstrated strong internal consistency (Cronbach's α 0.85 and 0.86, respectively). Significant correlations were found between the SAVE-9 and SAVE-6 scales and Generalized Anxiety Disorder-7 items scale (r = 0.44 and r = 0.38, respectively, p < 0.001) as well as the Patient Health Questionnaire-9 items (r = 0.39 and r = 0.35, respectively, p < 0.001). The optimal cutoff points for SAVE-9 and SAVE-6 were identified for assessing anxiety, aligned with a GAD-7 score ≥5 points. Conclusion: The Peruvian-Spanish SAVE-9 and SAVE-6 scales are reliable and valid rating scales to assess the anxiety response of HCWs in response to viral epidemics. Though COVID-19 is diminished, these scales will be useful for other viral epidemics in the future.

Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.

Simultaneous Detection of Carbon Quantum Dots as Tracers for Interwell Connectivity Evaluation in a Pattern with Two Injection Wells.

This study aimed to develop and implement a nanotechnology-based alternative to traditional tracers used in the oil and gas industry for assessing interwell connectivity. A simple and rapid hydrothermal protocol for synthesizing carbon quantum dots (CQDs) using agroindustry waste was implemented. Three commercial CQDs were employed (CQDblue, CQDgreen, and CQDred); the fourth was synthesized from orange peel (CQDop). The CQDs from waste and other commercials with spherical morphology, nanometric sizes less than 11 nm in diameter, and surface roughness less than 3.1 nm were used. These tracers demonstrated high colloidal stability with a negative zeta potential, containing carbonyl-type chemical groups and unsaturations in aromatic structures that influenced their optical behavior. All materials presented high colloidal stability with negative values of charge z potential between -17.8 and -49.1. Additionally, individual quantification of these tracers is feasible even in scenarios where multiple CQDs are present in the effluent with a maximum percentage of interference of 15.5% for CQDop in the presence of the other three nanotracers. The CQDs were injected into the field once the technology was insured under laboratory conditions. Monitoring the effluents allowed the determination of connectivity for five first-line producer wells. This study enables the application of CQDs in the industry, particularly in fields where the arrangement of injector and producer wells is intricate, requiring the use of multiple tracers for a comprehensive description of the system.

Peri-ictal psychiatric manifestations in people with epilepsy: An umbrella review.

OBJECTIVE: We aimed to conduct an umbrella review to summarize the existing evidence regarding the prevalence of peri-ictal psychiatric manifestations (PM) in people with epilepsy (PWE) including pre-ictal, ictal, and postictal stages. METHODS: Databases were searched up to June 2023 for systematic reviews (SR) of observational studies that included patients with epilepsy peri-ictal PM. Data selection, data extraction, and risk of bias assessment (with the AMSTAR-2 instrument) were performed by two independent reviewers. We performed a narrative synthesis using previous guidelines. We used a self-developed decision table according to the GRADE system adapted for narrative outcomes if the certainty of outcomes was not determined by systematic review authors. RESULTS: Four SRs were included comprising 66 primary studies (n = 10 217). Three SRs evaluated one period (pre-ictal, ictal, and postictal), and one did not determine it. During the pre-ictal period, the more prevalent symptom was confusion, although with a low certainty (due to the heterogeneity and serious risk of bias). One systematic review that only included case reports evaluated the ictal period, finding mood/anxiety disorders, psychosis, and personality changes. The postictal period included the most PM (anxiety: 45.0% and depressive symptoms: 43.0%), with very low certainty, due to risk of bias, potential publication bias, heterogeneity, and failure to report the confidence intervals. SIGNIFICANCE: With very low certainty, epileptic periods are characterized by a wide spectrum of PM, being postictal symptoms the most prevalent, predominantly anxiety, and depressive symptoms. Further understanding of these PM of epilepsy could improve the attention of the people with epilepsy. PLAIN LANGUAGE SUMMARY: In this review of reviews, we summarize the frequency in which psychiatric manifestations occur in relation to an epileptic seizure. A total of 10 217 patients were reported in the reviews. The most common manifestations included symptoms of anxiety and depression, as well as changes in the normal behavior of the patient. These manifestations occurred most frequently right after the seizure finished.

Rescue and rehabilitation of maned wolf (Chrysocyon brachyurus) in Paraguay: Case description.

The maned wolf, Chrysocyon brachyurus, is the largest South American canid, with a natural distribution that stretches across Peru, Bolivia, Brazil, Argentina, Paraguay and Uruguay. The present study reports the case of a rescued specimen of maned wolf that underwent a rehabilitation process in Paraguay, starting in October 2020 with its rescue, and finalising in May 2021 with the reintroduction. Herein, we document findings regarding the general management, biometrics, feeding and environmental enrichment; chemical immobilisation and monitoring; haematology, blood biochemistry and specific serology-relevant pathogens; skin examination and bone marrow cytology; orthopaedic, ophthalmological and dental evaluation; abdominal and cardiac ultrasonography; radiology and copro-parasitology. Main findings include the feeding habits of the individual and enrichment opportunities. The animal weighed 7 kg on arrival, with an estimated age of 5 months, and 18 kg on reintroduction, with an estimated age of 1 year. The animal tested negative to serologic tests for Brucella canis, Dirofilaria, canine distemper, Toxoplasmosis and canine parvovirus. Leptospira testing showed antibodies against L. grippotyphosa on both samplings, L. wolffi and L. ictero on the first sampling, and L. pomona on the second sampling. Abdominal organs were examined and measured through ultrasound evaluation and kidneys showed no alterations. Echocardiography showed preserved mitral, tricuspid and aortic valve flows, but turbulent pulmonary valve flow. Copro-parasitology reported the presence of Lagochilascaris sp. and Balantidium sp. All the information gathered aided in diagnosing the health status of the individual, and the response to environmental enrichment helped assess the behaviour, which led to the suggestion of reintroducing the animal. These data constitute the first published health check of a maned wolf in Paraguay, which can contribute to the species' conservation in the country. The protocol presented in this study can serve as a basis for developing an action plan for the maned wolf in Paraguay.

Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS in recent decades, underscoring their high potential of infectivity in humans. Insights from previous outbreaks of SARS and MERS have played a significant role in developing effective strategies to mitigate the global impact of SARS-CoV-2. As of January 7, 2024, there have been 774,075,242 confirmed cases of COVID-19 worldwide. To date, 13.59 billion vaccine doses have been administered, and there have been 7,012,986 documented fatalities (https://www.who.int/) Despite significant progress in addressing the COVID-19 pandemic, the rapid evolution of SARS-CoV-2 challenges human defenses, presenting ongoing global challenges. The emergence of new SARS-CoV-2 lineages, shaped by mutation and recombination processes, has led to successive waves of infections. This scenario reveals the need for next-generation vaccines as a crucial requirement for ensuring ongoing protection against SARS-CoV-2. This demand calls for formulations that trigger a robust adaptive immune response without leading the acute inflammation linked with the infection. Key mutations detected in the Spike protein, a critical target for neutralizing antibodies and vaccine design -specifically within the Receptor Binding Domain region of Omicron variant lineages (B.1.1.529), currently dominant worldwide, have intensified concerns due to their association with immunity evasion from prior vaccinations and infections. As the world deals with this evolving threat, the narrative extends to the realm of emerging variants, each displaying new mutations with implications that remain largely misunderstood. Notably, the JN.1 Omicron lineage is gaining global prevalence, and early findings suggest it stands among the immune-evading variants, a characteristic attributed to its mutation L455S. Moreover, the detrimental consequences of the novel emergence of SARS-CoV-2 lineages bear a particularly critical impact on immunocompromised individuals and older adults. Immunocompromised individuals face challenges such as suboptimal responses to COVID-19 vaccines, rendering them more susceptible to severe disease. Similarly, older adults have an increased risk of severe disease and the presence of comorbid conditions, find themselves at a heightened vulnerability to develop COVID-19 disease. Thus, recognizing these intricate factors is crucial for effectively tailoring public health strategies to protect these vulnerable populations. In this context, this review aims to describe, analyze, and discuss the current progress of the next-generation treatments encompassing immunotherapeutic approaches and advanced therapies emerging as complements that will offer solutions to counter the disadvantages of the existing options. Preliminary outcomes show that these strategies target the virus and address the immunomodulatory responses associated with COVID-19. Furthermore, the capacity to promote tissue repair has been demonstrated, which can be particularly noteworthy for immunocompromised individuals who stand as vulnerable actors in the global landscape of coronavirus infections. The emerging next-generation treatments possess broader potential, offering protection against a wide range of variants and enhancing the ability to counter the impact of the constant evolution of the virus. Furthermore, advanced therapies are projected as potential treatment alternatives for managing Chronic Post-COVID-19 syndromeand addressing its associated long-term complications.

The impact of the COVID-19 pandemic on nursing home professionals: results of the RESICOVID project.

OBJECTIVES: The situation caused by the COVID-19 pandemic has had an impact on the mental, physical, and social health of nursing home staff. The operations and protocols of long-term care facilities had to be adapted to a new, unforeseen, and unknown situation in which a devastating and highly contagious disease was causing large numbers of deaths. The aim of this study was to determine the cumulative impact of the COVID-19 pandemic on care, technical, coordinating-supervisory, and managerial staff working in nursing homes. METHODS: Correlation analysis and between-group comparisons were carried out to study the relationship between burnout scores, emotional balance, and organic and behavioral symptoms. RESULTS: The results indicate high levels of burnout and psychological exhaustion. Management professionals displayed higher levels of organic and behavioral symptoms than other professional categories in the same care settings. Despite this negative symptomatology, most professionals showed a positive emotional balance. CONCLUSION: The need to develop intervention programs to improve the mental, physical, and occupational health of the staff in nursing homes, considering the needs of different professional categories, is emphasized.

Bovine Peripheral Blood-Derived Mesenchymal Stem Cells (PB-MSCs) and Spermatogonial Stem Cells (SSCs) Display Contrasting Expression Patterns of Pluripotency and Germ Cell Markers under the Effect of Sertoli Cell Conditioned Medium.

In vitro gamete derivation has been proposed as an interesting strategy for treatment of infertility, improvement of genetic traits, and conservation of endangered animals. Spermatogonial stem cells (SSCs) are primary candidates for in vitro gamete derivation; however, recently, mesenchymal stem cells (MSCs) have also been proposed as candidates for germ cell (GCs) differentiation mainly due to their transdifferentiating capacity. The objective of the present study was to compare the potential for GC differentiation of bovine peripheral blood-derived MSCs (PB-MSCs) and SSCs under the effect of conditioned medium (CM) derived from Sertoli cells (SCs/CM). Samples were collected every 7 days for 21 days and analyzed for pluripotent, GC, and MSC marker expression. The absence of OCT4 and the increased (p < 0.05) expression of NANOG seems to play a role in SSC differentiation, whereas the absence of NANOG and the increased expression (p < 0.05) of OCT4 may be required for PB-MSC differentiation into GCs. SSCs cultured with SCs/CM increased (p < 0.05) the expression of PIWIL2 and DAZL, while PB-MSCs cultured under the same condition only increased (p < 0.05) the expression of DAZL. Overall, the patterns of markers expression suggest that PB-MSCs and SSCs activate different signaling pathways after exposure to SCs/CM and during differentiation into GCs.

Evidence of epigenetic landscape shifts in mucopolysaccharidosis IIIB and IVA.

Lysosomal storage diseases (LSDs) are a group of monogenic diseases characterized by mutations in genes coding for proteins associated with the lysosomal function. Despite the monogenic nature, LSDs patients exhibit variable and heterogeneous clinical manifestations, prompting investigations into epigenetic factors underlying this phenotypic diversity. In this study, we focused on the potential role of epigenetic mechanisms in the pathogenesis of mucopolysaccharidosis IIIB (MPS IIIB) and mucopolysaccharidosis IVA (MPS IVA). We analyzed DNA methylation (5mC) and histone modifications (H3K14 acetylation and H3K9 trimethylation) in MPS IIIB and MPS IVA patients' fibroblasts and healthy controls. The findings revealed that global DNA hypomethylation is present in cell lines for both diseases. At the same time, histone acetylation was increased in MPS IIIB and MPS IVA cells in a donor-dependent way, further indicating a shift towards relaxed open chromatin in these MPS. Finally, the constitutive heterochromatin marker, histone H3K9 trimethylation, only showed reduced clustering in MPS IIIB cells, suggesting limited alterations in heterochromatin organization. These findings collectively emphasize the significance of epigenetic mechanisms in modulating the phenotypic variations observed in LSDs. While global DNA hypomethylation could contribute to the MPS pathogenesis, the study also highlights individual-specific epigenetic responses that might contribute to phenotypic heterogeneity. Further research into the specific genes and pathways affected by these epigenetic changes could provide insights into potential therapeutic interventions for these MPS and other LSDs.

Comamonas testosteroni as the cause of mortality in embryonated chicken eggs of breeding broiler hens in Costa Rica.

Mortality of chicken embryos and first-week chickens was reported in a commercial incubator company in Costa Rica. Six 1-day-old Cobb chickens and twenty-four embryonated chicken eggs were examined in the Laboratory of Avian Pathology and the Laboratory of Bacteriology of the National University of Costa Rica. Twelve dead-in-shell embryos showed maceration and were immersed in a putrid, turbid, slightly thick brown liquid. Additionally, the other 12 embryonated eggs had milky yellow-orange content. The livers of those embryos had congestion, haemorrhages and multifocal cream foci of necrosis. Granulocytic infiltration was observed in the bursa of Fabricius, myocardium, liver, lung and kidney. Livers and egg yolks from six embryonated chickens and all 1-day-old chickens were aseptically collected and cultured. In addition, tissues from six better conserved embryos and all 1-day-old chickens were fixed in buffered formalin and embedded in paraffin. Biochemical and molecular tests identified Comamonas testosteroni as the cause of the early, middle and late embryo mortality. As all the eggshells from the sampled embryonated eggs were dirty with soiled a fecal matter, contamination after manipulating the eggs was considered the source of infection. C. testosteroni is an environmental microorganism that has rarely been reported to cause human disease. To our knowledge, this is the first report of C. testosteroni causing mortality in a hatchery. Cleaning and disinfection using ozone were implemented in the hatchery to eliminate the embryo mortality associated with C. testosteroni.

The impact of the COVID-19 pandemic on nursing home professionals: results of the RESICOVID project

Abstract Objectives The situation caused by the COVID-19 pandemic has had an impact on the mental, physical, and social health of nursing home staff. The operations and protocols of long-term care facilities had to be adapted to a new, unforeseen, and unknown situation in which a devastating and highly contagious disease was causing large numbers of deaths. The aim of this study was to determine the cumulative impact of the COVID-19 pandemic on care, technical, coordinating-supervisory, and managerial staff working in nursing homes. Methods Correlation analysis and between-group comparisons were carried out to study the relationship between burnout scores, emotional balance, and organic and behavioral symptoms. Results The results indicate high levels of burnout and psychological exhaustion. Management professionals displayed higher levels of organic and behavioral symptoms than other professional categories in the same care settings. Despite this negative symptomatology, most professionals showed a positive emotional balance. Conclusion The need to develop intervention programs to improve the mental, physical, and occupational health of the staff in nursing homes, considering the needs of different professional categories, is emphasized.

Short-, mid-, and long-term complications after multisystem inflammatory syndrome in children over a 24-month follow-up period in a hospital in Lima-Peru, 2020-2022.

Objective: To determine the short-, mid-, and long-term complications after multisystem inflammatory syndrome in children (MIS-C) over a 24-month follow-up period in a hospital in Lima, Peru, 2020-2022, and to explore differences according to the immunomodulatory treatment received and type of SARS-CoV-2 virus circulating. Methods: Ambispective 24-month follow-up study in children <14 years of age diagnosed with MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (HNERM). Results: A total of 62 children were admitted with MIS-C. The most common short-term complications and serious events were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) due to respiratory failure, and shock; predominantly during the second pandemic wave (lambda predominance) and in children that received intravenous immunoglobulin (IVIG) plus a corticosteroid. Two patients died during the first wave due to MIS-C. During prospective follow-up (median of 24 months; IQR: 16.7-24), only 46.7% of patients were followed for >18-24 months. Of the total, seven (11.3%) patients were identified with some sequelae on discharge. Among the 43 remaining children, sequelae persisted in five (11.6%) cases (neurological, hematological, and skin problems). Six patients (13.9%) presented with new onset disease (hematologic, respiratory, neurological, and psychiatric disorders). One patient died due to acute leukemia during the follow-up period. None of them were admitted to the ICU or presented with MIS-C reactivation. Two patients presented persistence of coronary aneurysm until 8- and 24-month post-discharge. Conclusion: In our hospital, children with MIS-C frequently developed short-term complications and serious events during the acute phase, with less frequent complications in the mid- and long-term. More studies are required to confirm these findings.

Iron oxide-coupled CRISPR-nCas9-based genome editing assessment in mucopolysaccharidosis IVA mice.

Mucopolysaccharidosis (MPS) IVA is a lysosomal storage disorder caused by mutations in the GALNS gene that leads to the lysosomal accumulation of keratan sulfate (KS) and chondroitin 6-sulfate, causing skeletal dysplasia and cardiopulmonary complications. Current enzyme replacement therapy does not impact the bone manifestation of the disease, supporting that new therapeutic alternatives are required. We previously demonstrated the suitability of the CRISPR-nCas9 system to rescue the phenotype of human MPS IVA fibroblasts using iron oxide nanoparticles (IONPs) as non-viral vectors. Here, we have extended this strategy to an MPS IVA mouse model by inserting the human GALNS cDNA into the ROSA26 locus. The results showed increased GALNS activity, mono-KS reduction, partial recovery of the bone pathology, and non-IONPs-related toxicity or antibody-mediated immune response activation. This study provides, for the first time, in vivo evidence of the potential of a CRISPR-nCas9-based gene therapy strategy for treating MPS IVA using non-viral vectors as carriers.

Association between weight status and migraine in the paediatric population: a systematic review and meta-analysis.

Introduction: An association between weight status and migraine has been previously reported; however, this relationship has only been studied in adults, not in the paediatric population. Objective: To evaluate the association between weight status and migraine in the paediatric population. Methods: We searched PubMed/Medline, Scopus, Web of Science, Ovid Medline, and Embase using a cut-off date of May 2023. We included observational studies that evaluated the association between weight status (underweight, overweight, obese, and excess weight) and migraine in the paediatric population (children and adolescents). Normal weight was the comparator. The outcome was migraine (all types, episodic and chronic). We performed meta-analyses using a random-effects model to estimate the pooled effects for each outcome. Sensitivity analysis was performed based on study design and risk of bias (using the Newcastle-Ottawa Scale). Certainty of evidence was assessed using the GRADE approach. Results: Eight studies (6 cross-sectional, 1 case-control and 1 cohort) covering 16,556 patients were included. The overall certainty of evidence was very low for the association between overweight, obesity, and excess weight with migraine. In the sensitivity analysis, meta-analyses of studies with a low risk of bias found that the overweight population probably had an increased odds of migraine (OR: 1.70; 95% CI: 1.14 to 2.53; I2 = 32.3%, p = 0.224) and that excess weight may increase the odds of migraine (OR: 1.58; 95% CI: 1.06 to 2.35; I2 = 83.7%, p = 0.002). Additionally, cohort and case-control studies found that obesity probably increases the odds of migraine. No studies analysed the association between underweight and migraine. Conclusion: The associations between overweight, obesity, excess weight and migraine were uncertain, but studies with better methodological quality reported increased odds. Future longitudinal studies with proper confounding control are needed to disentangle their causal relationship. Systematic review registration: PROSPERO, identifier CRD42021271533.

Prevalence and incidence of neuropsychiatric disorders in post hospitalized COVID-19 patients in South America: a systematic review and meta-analysis.

Introduction: There are multiple reports of neuropsychiatric disorders (NDs) such as stress, depression, post-traumatic stress disorder (PTSD), or anxiety, in patients who have survived the acute phase of COVID-19, being even more frequent in people who were hospitalized with moderate or severe disease. South America (SA) was one of the most affected continents during this time due to its health, social, political and economic context. We aimed to determine the prevalence and incidence of NDs in patients following hospitalization for COVID-19 in SA. Materials and methods: We searched in PubMed, Embase, Scopus, Web of Science, LILACS, SciELO, and Google Scholar databases up to October 2022. We performed proportion meta-analysis with a random-effect model and Freeman-Tukey Double Arcsine transformation using the STATA 16.1 program. Finally, we evaluated heterogeneity by subgroup analysis and certainty of evidence with the GRADE approach. Results: We included eight studies from four countries. We only pooled six studies with prevalence measures. The estimated prevalence of all NDs was 31.48% (two-studies, 95%CI: 25.82-37.43). Depression, anxiety, insomnia, PTSD, and memory alterations had a pooled prevalence of 16.23% (three-studies, 95%CI: 7.18-27.93, I2: 94.22), 18.72% (three-studies, 95%CI: 11.65-26.97, I2: 87.56), 43.07% (three-studies, 95%CI: 32.77-53.37, I2: 92.61), 31.78% (three-studies, 95%CI: 14.33-52.40, I2: 97.96), and 38.24% (two-studies, 95%CI: 35.5-40.97), respectively. The evidence included was deemed as moderate to high certainty. Conclusion: We suggest that NDs should be prioritized in research and care in South America with public policies that can support their identification and prompt management to improve the quality of life of patients. More studies are needed to adequately study the prevalence of NDs in South America, their associated factors, and evaluate the causes of heterogeneity. Systematic review registration: https://doi.org/10.6084/m9.figshare.21901041.v1.

Comparing typologies of violence exposure and associations with syndemic health outcomes among cisgender and transgender female sex workers living with HIV in the Dominican Republic.

Violence against women research largely excludes transgender women's experiences and violence from perpetrators other than intimate partners. This study compares patterns of violence exposure among cisgender and transgender female sex workers (FSWs) and the associations with syndemic health outcomes. We used cross-sectional surveys from samples of cisgender and transgender FSWs living with HIV in the Dominican Republic (N = 211 and 100, respectively). We used latent class analysis to identify patterns of emotional, physical, and sexual violence and harassment by partners, clients, and police. We assessed sociodemographic and occupational predictors in relation to class membership, and class membership in relation to health (HIV continuum of care outcomes, mental health, substance use), using logistic regression. Two classes were identified in cisgender sample: Low Reported Violence Exposure (Class 1) and Sex Work-related Police Harassment (Class 2). Class 2 participants had greater odds of scoring abnormal or borderline abnormal anxiety on the Hospital Anxiety and Depression Scale (HADS-A) (adjusted OR = 3.97, p<0.01), moderate-to-severe depression per the Patient Health Questionnaire-9 (PHQ-9) (aOR = 5.74, p<0.01), and any illicit drug use in the past six months (aOR = 3.06, p<0.05), compared to Class 1. The transgender sample produced three classes: Low Reported Violence Exposure (Class 1); Sex Work-related Police Harassment (Class 2); and Sex Work-related Violence and Harassment (Class 3). Class 3 participants had greater odds of having anxiety (aOR = 6.65, p<0.01) and depression (aOR = 4.45, p<0.05), while Class 2 participants had greater odds of perfect ART adherence during the previous four days (aOR = 2.78, p<0.05), compared to Class 1. The more diverse and extreme violence patterns uncovered for the transgender sample show this group's heightened risk, while similar patterns across groups regarding police abuse highlight a need for police-focused violence prevention interventions. Each sample's highest violence class was associated with poor mental health, underscoring the need for mental health interventions for all FSWs.

Humoral Immune Response of Mice against a Vaccine Candidate Composed of a Chimera of gB of Bovine Alphaherpesviruses 1 and 5.

Infectious bovine rhinotracheitis (IBR) and bovine meningoencephalitis are caused by Bovine alphaherpesvirus (BoHV) types 1 and 5, which seriously threaten the global cattle industry. Vaccination to improve immunity is the most direct and effective means to prevent these conditions. Glycoprotein B (gB) is essential for the attachment of both viruses to permissive cells, and is a major target of the host immune system, inducing a strong humoral response. The aim of this study was to evaluate, in a murine model, the immune response of a candidate vaccine formulation composed of a chimeric BoHV-1 and BoHV-5 gB (DgB), expressed in Komagataella phaffii. The chimeric DgB vaccine adjuvanted with Montanide 50 ISA V2 or aluminum hydroxide was administered intramuscularly or subcutaneously. A control group and a group that received a commercial vaccine were inoculated subcutaneously. Higher titers of neutralizing antibodies against BoHV-1, BoHV-5, and a natural BoHV-1/5 recombinant strain were obtained with the oil-based candidate vaccine formulation administered intramuscularly. The results demonstrated that the chimeric DgB conserved important epitopes that were able to stimulate a humoral immune response capable of neutralizing BoHV-1, BoHV-5, and the recombinant strain, suggesting that the vaccine antigen is a promising candidate to be further evaluated in cattle.

Virulent Brucella nosferati infecting Desmodus rotundus has emerging potential due to the broad foraging range of its bat host for humans and wild and domestic animals.

Desmodus rotundus, vampire bats, transmit dangerous infections, and brucellosis is a hazardous zoonotic disease, two adversities that coexist in the subtropical and tropical areas of the American continent. Here, we report a 47.89% Brucella infection prevalence in a colony of vampire bats inhabiting the tropical rainforest of Costa Rica. The bacterium induced placentitis and fetal death in bats. Wide-range phenotypic and genotypic characterization placed the Brucella organisms as a new pathogenic species named Brucella nosferati sp. nov., isolated from bat tissues, including the salivary glands, suggesting feeding behavior might favor transmission to their prey. Overall analyses placed B. nosferati as the etiological agent of a reported canine brucellosis case, demonstrating its potential for infecting other hosts. To assess the putative prey hosts, we analyzed the intestinal contents of 14 infected and 23 non-infected bats by proteomics. A total of 54,508 peptides sorted into 7,203 unique peptides corresponding to 1,521 proteins were identified. Twenty-three wildlife and domestic taxa, including humans, were foraged by B. nosferati-infected D. rotundus, suggesting contact of this bacterium with a broad range of hosts. Our approach is appropriate for detecting, in a single study, the prey preferences of vampire bats in a diverse area, demonstrating its suitability for control strategies where vampire bats thrive. IMPORTANCE The discovery that a high proportion of vampire bats in a tropical area is infected with pathogenic Brucella nosferati and that bats forage on humans and many wild and domestic animals is relevant from the perspective of emerging disease prevention. Indeed, bats harboring B. nosferati in their salivary glands may transmit this pathogenic bacterium to other hosts. This potential is not trivial since, besides the demonstrated pathogenicity, this bacterium possesses all the required virulent arsenal of dangerous Brucella organisms, including those that are zoonotic for humans. Our work has settled the basis for future surveillance actions in brucellosis control programs where these infected bats thrive. Moreover, our strategy to identify the foraging range of bats may be adapted for exploring the feeding habits of diverse animals, including arthropod vectors of infectious diseases, and therefore of interest to a broader audience besides experts on Brucella and bats.