Acellular Human Amniotic Fluid-Derived Extracellular Vesicles as Novel Anti-Inflammatory Therapeutics against SARS-CoV-2 Infection.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 is associated with acute respiratory distress syndrome (ARDS) and fatal pneumonia. Excessive inflammation caused by SARS-CoV-2 is the key driver of ARDS and lethal disease. Several FDA-approved drugs that suppress virus replication are in clinical use. However, despite strong evidence for the role of virus-induced inflammation in severe COVID-19, no effective anti-inflammatory drug is available to control fatal inflammation as well as efficiently clear the virus. Therefore, there is an urgent need to identify biologically derived immunomodulators that suppress inflammation and promote antiviral immunity. In this study, we evaluated acellular human amniotic fluid (acAF) containing extracellular vesicles (hAF-EVs) as a potential non-toxic and safe biologic for immunomodulation during COVID-19. Our in vitro results showed that acAF significantly reduced inflammatory cytokine production in TLR2/4/7 and SARS-CoV-2 structural protein-stimulated mouse macrophages. Importantly, an intraperitoneal administration of acAF reduced morbidity and mortality in SARS-CoV-2-infected mice. A detailed examination of SARS-CoV-2-infected lungs revealed that the increased protection in acAF-treated mice was associated with reduced viral titers and levels of inflammatory myeloid cell infiltration. Collectively, our results identify a novel biologic that has potential to suppress excessive inflammation and enhance survival following SARS-CoV-2 infection, highlighting the translational potential of acAF against COVID-19.

Systematic review and meta-analysis use in the field of spinal cord injury research: A bibliometric analysis.

OBJECTIVE: To subvert issues of low sample sizes and high attrition rates and generate epidemiologically-sound evidence, collaborative research-through international consortia and multi-centric studies-and meta-analysis approaches are encouraged in spinal cord injury (SCI) research. We investigated the use of systematic reviews and meta-analyses (SRMA) methodology in SCI research and evaluated the quality of evidence across publications we identified. METHODS: We searched the Web of Science Core Collection database by topic without time or language restrictions through 16 December 2022. We identified additional relevant articles through Embase.com. SRMA including human and animal SCI populations were eligible for inclusion. We analyzed data using Bibliometrix and VOSviewer. We used the JBI tool (former Joanna Briggs Institute) to assess methodological quality of a subset of 50 randomly selected articles. RESULTS: We based our analysis on data from 1'224 documents authored by 5'237 scholars and published in 424 sources between 1985 and 2022. The use of SRMA methodology in the field gained momentum in 2009 and a steady increase followed with an annual growth rate of ≈15%. Our findings indicate major research themes in the field include recovery, SCI management, rehabilitation, and quality of life. Over the past 30 years there has been a shift from SRMA concerning functional recovery, secondary health complications, and quality of life toward biomarkers and neuro-regeneration. The major methodological issues across articles we evaluated included opaquely described search strategies, poorly reported critical appraisals, and insufficiently addressing publication bias. In addition, only one-fifth of articles reported review protocol registration. CONCLUSIONS: : Our bibliometric analysis clearly shows a rapid increase of SRMA applications in SCI research. We discuss the most important methodological concerns we identified among a randomly selected set of articles and provide guidance for improving adherence to methodological and reporting SRMA guidelines.

Brain stimulation techniques as novel treatment options for insomnia: A systematic review.

Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to available treatments. This systematic review aims to present the state of science regarding the use of brain stimulation approaches in treating insomnia. To this end, we searched MEDLINE, Embase and PsycINFO from inception to 24 March 2023. We evaluated studies that compared conditions of active stimulation with a control condition or group. Outcome measures included standardized insomnia questionnaires and/or polysomnography in adults with a clinical diagnosis of insomnia. Our search identified 17 controlled trials that met inclusion criteria, and assessed a total of 967 participants using repetitive transcranial magnetic stimulation, transcranial electric stimulation, transcutaneous auricular vagus nerve stimulation or forehead cooling. No trials using other techniques such as deep brain stimulation, vestibular stimulation or auditory stimulation met the inclusion criteria. While several studies report improvements of subjective and objective sleep parameters for different repetitive transcranial magnetic stimulation and transcranial electric stimulation protocols, important methodological limitations and risk of bias limit their interpretability. A forehead cooling study found no significant group differences in the primary endpoints, but better sleep initiation in the active condition. Two transcutaneous auricular vagus nerve stimulation trials found no superiority of active stimulation for most outcome measures. Although modulating sleep through brain stimulation appears feasible, gaps in the prevailing models of sleep physiology and insomnia pathophysiology remain to be filled. Optimized stimulation protocols and proof of superiority over reliable sham conditions are indispensable before brain stimulation becomes a viable treatment option for insomnia.

Clinical evidence for high-risk medical devices used to manage diabetes: protocol for a systematic review and meta-analysis.

INTRODUCTION: Medical devices, including high-risk medical devices, have greatly contributed to recent improvements in the management of diabetes. However, the clinical evidence that is submitted for regulatory approval is not transparent, and thus a comprehensive summary of the evidence for high-risk devices approved for managing diabetes in Europe is lacking. In the framework of the Coordinating Research and Evidence for Medical Devices group, we will, therefore, perform a systematic review and meta-analysis, which will evaluate the efficacy, safety and usability of high-risk medical devices for the management of diabetes. METHOD AND ANALYSIS: This study has been reported according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search Embase (Elsevier), Medline All (Ovid), Cochrane Library (Wiley), Science Citation Index Expanded and Emerging Sources Citation Index (Web of Science) to identify interventional and observational studies that evaluate the efficacy and/or safety and/or usability of high-risk medical devices for the management of diabetes. No language or publication dates' limits will be applied. Animal studies will be excluded. In accordance with the Medical Device Regulation in European Union, high-risk medical devices are those in classes IIb and III. The following medical devices for diabetes management are considered as having a high risk: implantable continuous glucose monitoring systems, implantable pumps and automated insulin delivery devices. Selection of studies, data extraction and quality of evidence assessment will be performed independently by two researchers. Sensitivity analysis will be performed to identify and explain potential heterogeneity. ETHICS AND DISSEMINATION: No ethical approval is needed for this systematic review, as it is based in already published data. Our findings will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022366871.

Seroprevalencia y factores de riesgo de Toxoplasma gondii en Personas que Viven con VIH/SIDA (PVVS) en el departamento de Cochabamba, Bolivia

Objetivo: determinar la seroprevalencia y los factores de riesgo de infección crónica por T. gondii en personas que viven con VIH/SIDA (PVVS) en el departamento de Cochabamba. Metodología: estudio observacional-descriptivo de corte transversal. Se emplearon 325 muestras de plasma/suero proveniente de pacientes que asistieron a LABIMED entre Julio y agosto del año 2016. La recopilación de datos se realizó en un formulario sociodemográfico. Se emplearon ensayos serológicos cualitativos de Hemaglutinación Indirecta (HAI) e Inmunoflorecencia Indirecta (IFI), este último para confirmación de casos positivos. Adicionalmente se realizó el recuento de Linfocitos T CD4+ por citómetria de flujo para determinar el estado inmunológico de los pacientes que sirve de guía en el tratamiento clínico. Los datos fueron analizados con el programa/software SPSS versión 20. Resultados: la seroprevalencia global de infección crónica por T. gondii en la población de estudio fue del 40%. El consumo de carne poco cocida (OR: 2,85; 95%IC: 1,56-5,22) y la actividad de agricultura/jardinería (OR: 1,7; IC del 95%: 1,07-2,70) fueron factores de riesgo para adquirir la infección crónica por T. gondii. El 45.6% de las PVVS positivos para toxoplasmosis tiene un recuento de Linfocitos T CD4+ < a 200 células/mm3, equivalente a una inmunodeficiencia severa. Conclusión: El estudio muestra una seroprevalencia significativa de infección crónica por T. gondii, además de presentar una inmunodeficiencia severa en PVVS

Objective: To determine the seroprevalence and risk factors for chronic infection by T. gondii in people living with HIV/AIDS (PLHA) in the department of Cochabamba. Methods: observational-descriptive cross-sectional study. 325 samples (n=325) of plasma/serum from patients who attended LABIMED between the months of July to August of the year 2016 were used. Data (age, gender and risk factors) were collected in the sociodemographic form. Qualitative serological tests of Indirect Hemaglutination (HAI) and Indirect Immunoflorescence (IFI) were used the latter for confirmation of positive cases. Additionally, the count of CD4+ T lymphocytes was performed by flow cytometry to determine the immunological status of the patients that serves as a guide in clinical treatment. The data were analyzed with the program/software SPSS version 20. Results: the global seroprevalence of chronic infection by T. gondii in the study population was 40%. Consumption of undercooked meat (AOR: 2.85; 95% CI: 1,56-5,22) and farming/gardening activity (AOR: 1,7; 95% CI: 1,07-2,70) were risk factors for chronic T. gondii infection. 45,6% of people living with the HIV/AIDS virus who are positive for toxoplasmosis have a CD4+ T lymphocyte count <200 cells/ml, equivalent to severe immunodeficiency. Conclusions: the study shows a significant seroprevalence of chronic infection by T. gondii, as well as presenting a high severe immunodeficiency in patients with the HIV/AIDS virus.

Human amniotic fluid derived extracellular vesicles attenuate T cell immune response.

Introduction: Extracellular vesicles isolated from human amniotic fluid (AF-EVs) have previously been found to modulate inflammation and macrophage infiltration in a mouse model. However, the effects of acellular amniotic fluid (acAF) or AF-EVs on the T-Cell immune response have not been explored. Methods: In this study, we investigated the effects of acAF and AF-EVs on the T cell immune response in an in vitro cell culture model. Peripheral Blood Mononuclear Cells (PBMCs) were stimulated with Phytohemagglutinin (PHA) to induce the immune response and were subsequently treated with either serum-free media (vehicle), acAF, or concentrated AF-EVs. Results: Both acAF and AF-EV treatment suppressed PHA-induced T cell proliferation and PHA-induced T cell activation; however, treatment with concentrated AF-EVs had a greater effect. Additionally, both acAF and AF-EVs reduced PBMC pro-inflammatory cytokine release. AF-EVs were found to be taken up by both CD4+ and CD8+ effector T cell subsets. Conclusion: Overall, this data demonstrates that AF-EVs have a robust immunomodulatory effect on T cells and suggests AF-EVs could be used as an immunotherapeutic tool.

Altura uterina versus ecografía obstétrica para detectar macrosomía fetal. Hospital San Juan de Kimbiri, Perú

RESUMEN Fundamento Aunque la ecografía obstétrica es ampliamente utilizada en los niveles primario y secundario de salud para la detección de macrosomía fetal, la altura uterina también puede resultar útil, sobre todo, en contextos sanitarios desprovistos de equipamiento tecnológico. Objetivo determinar la correlación entre altura uterina versus ecografía obstétrica y el diagnóstico de macrosomía fetal. Métodos estudio descriptivo, correlacional, en madres no diabéticas de partos a término con neonatos macrosómicos, realizado en un hospital público del Valle de los ríos Apurímac, Ene y Mantaro, Perú. Las variables del estudio: edad materna, índice de masa corporal pregestacional, número de embarazos, edad gestacional al parto, y vía del parto. Se emplearon los coeficientes de correlación Rho de Spearman, y Pearson, ambos con intervalos de confianza al 95 % y error del 5 %. Resultados la estimación del peso fetal y la macrosomía se correlacionaron con la altura uterina (R Pearson 0,05). Entre las características maternas asociadas a neonatos macrosómicos, se hallaron la obesidad pregestacional (Rho = 0,009) y la condición de multigesta (Rho = 0,04). La estimación del peso fetal mayor a 4000 g tuvo mayor porcentaje de acierto (26,3 %) por ecografía obstétrica. Conclusión la ecografía obstétrica mostró mayor correlación que la altura uterina con el diagnóstico de macrosomía fetal.

ABSTRACT Background Although obstetric ultrasound is widely used at primary and secondary health levels for the detection of fetal macrosomia, uterine height can also be useful, especially in health contexts lacking technological equipment. Objective to determine the correlation between uterine height versus obstetric ultrasound and the diagnosis of fetal macrosomia. Methods descriptive, correlational study in non-diabetic mothers of full-term deliveries with macrosomic neonates, carried out in a public hospital in the Valley of the Apurímac, Ene and Mantaro rivers, Peru. The study variables: maternal age, pre-pregnancy body mass index, number of pregnancies, gestational age at delivery, and route of delivery. Spearman's Rho and Pearson's correlation coefficients were used, both with 95% confidence intervals and 5% error. Results Fetal weight estimation and macrosomia correlated with uterine height (Pearson's R 0.05). Among the maternal characteristics associated with macrosomic neonates, pregestational obesity (Rho = 0.009) and multigestational condition (Rho = 0.04) were found. The estimation of fetal weight greater than 4000 g had a higher percentage of success (26.3%) by obstetric ultrasound. Conclusion obstetric ultrasound showed a higher correlation than uterine height with the diagnosis of fetal macrosomia.

Effects of radiofrequency electromagnetic fields (RF EMF) on cancer in laboratory animal studies.

BACKGROUND: The carcinogenicity of radiofrequency electromagnetic fields (RF EMF) has been evaluated by the International Agency for Research on Cancer (IARC) in 2011. Based on limited evidence of carcinogenicity in humans and in animals, RF EMF were classified as possibly carcinogenic to humans (Group 2B). In 2018, based on a survey amongst RF experts, WHO prioritized six major topics of potential RF EMF related human health effects for systematic reviews. In the current manuscript, we present the protocol for the systematic review of experimental laboratory animal studies (cancer bioassays) on exposure to RF fields on the outcome of cancer in laboratory animals. OBJECTIVE: In the framework of WHO's Radiation Program, the aim of this work is to systematically evaluate effects of RF EMF exposure on cancer in laboratory animals. STUDY ELIGIBILITY AND CRITERIA: WHO's Handbook (2014) for guideline development will be followed with appropriate adaptation. The selection of eligible studies will be based on Population, Exposures, Comparators, and Outcomes (PECO) criteria. We will include peer-reviewed articles and publicly available reports from government agencies reporting original data about animal cancer bioassays on exposure to RF EMF. The studies are identified by searching the following databases: MEDLINE (PubMed), Science Citation Index Expanded and Emerging Sources Citation Indes (Web of Science), Scopus, and the EMF Portal. No language or year-of-publication restrictions are applied. The methods and results of eligible studies will be presented in accordance with the PRISMA 2020 guidelines. STUDY APPRAISAL METHOD: Study evaluation of individual studies will be assessed using a risk of bias (RoB) tool developed by the Office of Health Assessment and Translation (OHAT) with appropriate considerations including sensitivity for evaluating RF EMF exposure in animal cancer bioassays. The final evaluation on the certainty of the evidence on a carcinogenic risk of RF EMF exposure in experimental animals will be performed using the OHAT Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach with appropriate considerations. The protocol has been registered in an open-source repository (PROSPERO). FUNDING: The study is partly financially supported by the World Health Organization. No additional funding was provided outside author salaries through their places of employment.

TNFR2 promotes Treg-mediated recovery from neuropathic pain across sexes.

Tumor necrosis factor receptor 2 (TNFR2) is a transmembrane receptor that is linked to immune modulation and tissue regeneration. Here, we show that TNFR2 essentially promotes long-term pain resolution independently of sex. Genetic deletion of TNFR2 resulted in impaired neuronal regeneration and chronic nonresolving pain after chronic constriction injury (CCI). Further, pharmacological activation of TNFR2 using the TNFR2 agonist EHD2-sc-mTNFR2 in mice with chronic neuropathic pain promoted long-lasting pain recovery. TNFR2 agonist treatment reduced neuronal injury, alleviated peripheral and central inflammation, and promoted repolarization of central nervous system (CNS)-infiltrating myeloid cells into an antiinflammatory/reparative phenotype. Depletion of regulatory T cells (Tregs) delayed spontaneous pain recovery and abolished the therapeutic effect of EHD2-sc-mTNFR2 This study therefore reveals a function of TNFR2 in neuropathic pain recovery and demonstrates that both TNFR2 signaling and Tregs are essential for pain recovery after CCI. Therefore, therapeutic strategies based on the concept of enhancing TNFR2 signaling could be developed into a nonopioid therapy for the treatment of chronic neuropathic pain.

Tumor necrosis factor receptor 1 inhibition is therapeutic for neuropathic pain in males but not in females.

Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is involved in physiological and pathological processes and has been found to be crucial for pain development. In the current study, we were interested in the effects of blocking Tumor necrosis factor receptor 1 (TNFR1) signaling on neuropathic pain after peripheral nerve injury with the use of transgenic mice and pharmacological inhibition. We have previously shown that TNFR1 mice failed to develop neuropathic pain and depressive symptoms after chronic constriction injury (CCI). To investigate the therapeutic effects of inhibiting TNFR1 signaling after injury, we delivered a drug that inactivates soluble TNF (XPro1595). Inhibition of solTNF signaling resulted in an accelerated recovery from neuropathic pain in males, but not in females. To begin exploring a mechanism, we investigated changes in N-methyl-D-aspartate (NMDA) receptors because neuropathic pain has been shown to invoke an increase in glutamatergic signaling. In male mice, XPro1595 treatment reduces elevated NMDA receptor levels in the brain after injury, whereas in female mice, NMDA receptor levels decrease after CCI. We further show that estrogen inhibits the therapeutic response of XPro1595 in females. Our results suggest that TNFR1 signaling plays an essential role in pain induction after CCI in males but not in females.

A review of reviews: Sedentary behaviour and cardiovascular disease specific to older people.

BACKGROUND: The incidence of sedentary behaviour and cardiovascular disease impacts the health of older people, potentially leading to serious and negative health consequences. AIM: The purpose of this umbrella review was to identify the systematic reviews that explore the association between sedentary behaviour and cardiovascular disease specific to older people. METHODS: An umbrella review was undertaken to systematically search five databases. Papers included were published between 2011 and 2015. RESULTS: A search yielded 2,163 results. Six reviews met the inclusion criteria. While all six systematic reviews included older people in the overall sample, only one systematic review focused on an entirely older person population. Three of the six systematic reviews provided a meta-analysis, but none of the reviews reported a separate subgroup analysis for a discrete sample of older people CONCLUSION: This umbrella review demonstrates that while sedentary behaviour is associated with cardiovascular disease, a gap exists in the analysis on the relationship specific to older persons. IMPLICATIONS FOR PRACTICE: Interventions aimed at reducing sedentary behaviour may improve cardiovascular health and well-being among older people.

The effects of spinal cord injury on bone loss and dysregulation of the calcium/parathyroid hormone loop in mice.

OBJECTIVE: To map the progression of osteoporosis following spinal cord injury in mice in specific areas and analyze changes in parathyroid hormone (PTH) and ion levels which could be responsible for overall bone loss. SUMMARY OF BACKGROUND DATA: Spinal cord injury rapidly induces severe bone loss compared to other conditions, yet the cause of this bone loss has not been identified. Studies suggest the bone loss after injury is not solely due to disuse. METHODS: To quantify bone loss we weighed individual bones and measured bone mineral density using dual energy X-ray absorptiometry at acute (1 week) and chronic (4 week) time points following a T9 contusion. An ELISA was used to measure blood PTH levels at 1 and 4 weeks after injury. Calcium and phosphate levels were also analyzed at 4 weeks following injury at the University of Miami pathology core. RESULTS: We observed a significant decrease in bone mineral density in hind limbs after an acute injury, and found this bone loss to progress over time. Furthermore, following chronic injury a decrease in bone mineral density is also observed in bones above the level of injury and in the total bone mineral density. We observed a significant decrease in parathyroid hormone levels in injured mice at the chronic time point, but not at the acute time point which suggests this could be involved in the global bone loss following injury. We also observed a significant increase in serum calcium levels following injury which could account for the imbalance of PTH levels.

A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila.

Molecular mechanisms that concordantly regulate stress, life span, and aging remain incompletely understood. Here, we demonstrate that in Drosophila, a p38 MAP kinase (p38K)/Mef2/MnSOD pathway is a coregulator of stress and life span. Hence, overexpression of p38K extends life span in a MnSOD-dependent manner, whereas inhibition of p38K causes early lethality and precipitates age-related motor dysfunction and stress sensitivity, that is rescued through muscle-restricted (but not neuronal) add-back of p38K. Additionally, mutations in p38K are associated with increased protein carbonylation and Nrf2-dependent transcription, while adversely affecting metabolic response to hypoxia. Mechanistically, p38K modulates expression of the mitochondrial MnSOD enzyme through the transcription factor Mef2, and predictably, perturbations in MnSOD modify p38K-dependent phenotypes. Thus, our results uncover a muscle-restricted p38K-Mef2-MnSOD signaling module that influences life span and stress, distinct from the insulin/JNK/FOXO pathway. We propose that potentiating p38K might be instrumental in restoring the mitochondrial detoxification machinery and combating stress-induced aging.

Estrés laboral en trabajadores del Hospital Pity Fajardo: junio 2005 febrero 2006 / Laboral stress in Pity Fajardo hospital workers: june 2005- february 2006

El estrés se conoce como uno de los factores que desempeña una función importante en la causa y evolución de ciertas enfermedades que aparecen en los primeros lugares en los cuadros de movilidad y mortalidad, por tal motivo nos propusimos realizar una investigación descriptiva con la finalidad de identificar el estrés laboral en trabajadores del Hospital Pity Fajardo Junio del 2005–Febrero 2006 del municipio de Bartolomé Masó. Para ellos se encuestan 60 trabajadores durante el periodo anteriormente mencionado. Se tomo una muestra de 30 encuestados para realizar nuestro estudio. Las enfermedades, técnicas de relajación y relación que existe entre los trabajadores con cargos y el estrés laboral donde se pudo comprobar que las edades que más predominaron en los trabajadores afectados con estrés laboral fueron de 31 a 35 años y el personal mas afectados fue enfermería ocupando el 46 por ciento de los casos la cefalea migrañosa y la gastritis fueron las enfermedades que predisponen el estrés laboral. El 63 por ciento de los encuestados consideran que la recreación sana fue la técnica de relajación que mas los ayuda a liberar estrés, además se confirmo que si existe una estrecha relajación entre el estrés y los cargos de dirección(AU)

Stress is recognized as one of the factors perforsning an import function in the etiology and evolution of certain diseases appearing in first place in morbidity and mortality that is why we propose a descriptive, prospective study to identify laboral stress in workers of Pity Fajardo hospital from June 2005 to February 2006 in bartolome maso municipality. We applied a survey to 60 workers, a sample of 30 was taken. Data were collected according to age, sex, occupation, economical status, diseases suffered, relaxation techniques, and the existing relation between management workers and laboral stress. It was proved the age of the affected workers with laboral stress were from 31 to 35 years old. Nurses were more affectes (46 per cent) with migraine and gastritis as predisposing diseases to laboral stress. Sixty three per cent of the surveyed workers consider that sane recreation was the relaxation technique more helpfull to release stress. Besides it was confirmed there is a close relation between laboral stress and management(EU)