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Abstract The COVID-19 pandemic has been marked by novel viral variants, posing challenges to global public health. Recombination, a viral evolution mechanism, is implicated in SARS-CoV-2's ongoing evolution. The XBB recombinant lineage, known for evading antibody-mediated immunity, exhibits higher transmissibility without increased disease severity. We investigated the prevalence and genomic features of XBB in SARS-CoV-2-positive cases in Rio Grande do Sul (RS), Brazil. We sequenced 357 samples from epidemiological weeks (EW) 47/2022 to 17/2023, and included 389 publicly available sequences. Clinical and epidemiological data were obtained from DATASUS, e-SUS, and SIVEP GRIPE (data recording systems of the Brazilian Ministry of Health). Of these, 143 were classified as XBB and 586 were other Omicron lineages. In March 2023 (EW 10), XBB became dominant, accounting for 83.3% of cases. 97.7% of XBB-infected patients successfully recovered from the infection, with a low mortality rate (2.3%). Even after receiving three vaccine doses and having been previously infected, 59.5% of the patients experienced reinfection with XBB. However, for 54% of the individuals, the interval between their XBB infection and the last vaccine dose exceeded one year, potentially leading to a decline in antibody levels. In addition, we identified 90 mutations in RS circulating XBB, spread throughout the genome, notably in the Spike protein region associated with immune resistance. This study provides insights into the dynamics and impact of a recombinant variant becoming predominant for the first time in the state. Continued surveillance of SARS-CoV-2 genomic evolution is crucial for effective public health management.

Abstract Cerebrospinal fluid (CSF) core biomarkers of Alzheimer’s disease (AD), including amyloid peptide beta-42 (Aβ42), Aβ42/40 ratio, and phosphorylated tau (pTau), are precious tools for supporting AD diagnosis. However, their use in clinical practice is limited due to the invasiveness of CSF collection. Thus, there is intensive research to find alternative, noninvasive, and widely accessible biological matrices to measure AD core biomarkers. In this study, we measured AD core biomarkers in saliva and plasma by a fully automated platform. We enrolled all consecutive patients with cognitive decline. For each patient, we measured Aβ42, Aβ40, and pTau levels in CSF, saliva, and plasma by Lumipulse G1200 (Fujirebio). We included forty-two patients, of whom 27 had AD. Levels of all biomarkers significantly differed in the three biofluids, with saliva having the lowest and CSF the highest levels of Aβ42, Aβ40, and pTau. A positive correlation of pTau, Aβ42/40 ratio, and pTau/Aβ42 ratio levels in CSF and plasma was detected, while no correlation between any biomarker in CSF and saliva was found. Our findings suggest that plasma but not saliva could represent a surrogate biofluid for measuring core AD biomarkers. Specifically, plasma Aβ42/40 ratio, pTau/Aβ42 ratio, and pTau could serve as surrogates of the corresponding CSF biomarkers.

Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.

There is a lack of standardized measurement tools globally to assess knowledge, attitudes, and perceptions of expecting women toward prenatal screening. The purpose of this systematic review was to identify reasons women pursue or decline prenatal screening and compare the strengths and limitations of available measurement tools used to assess pregnant women’s perceptions, knowledge, and attitudes toward prenatal screening. This review followed the five-step York methodology by Arksey and O’Malley and incorporated recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist for the extraction, analysis, and presentation of results. The five steps consisted of: (1) identification of the research questions; (2) searching for relevant studies; (3) selection of studies relevant to the research questions; (4) data charting; and (5) collation, summarization, and reporting of results. Four online databases (PubMed, Embase, Web of Science, and Cochrane Library) were selected after the librarian’s development of a detailed search strategy. The Rayyan platform was used between June 2023 and August 2023 to epitomize the articles produced from our search. A total of 68 eligible studies were included in the analysis. The top five major reasons for declining prenatal screening uptake included (1) being unsure of the risk of prenatal screening and harm to the baby or miscarriage ( n = 15), (2) not considering action such as termination of pregnancy for prenatal screening to be considered as necessary ( n = 14), (3) high cost ( n = 12), (4) lack of knowledge about testing procedures and being anxious about the test ( n = 10), and (5) being worried about probability of false negative or false positive results ( n = 6). Only 32 studies utilized scientifically validated instruments. Difficulties in capturing representative, adequately sized samples inclusive of diverse ethnicities and demographics were pervasive. Findings highlight the need for rigorous validation of research measurement methodologies to ensure the accuracy and applicability of resulting data regarding the assessment of prenatal screening perceptions, knowledge, and attitudes across diverse female populations. Registration: N/A.

Background Rating of perceived exertion (RPE) is considered a valid method for prescribing prolonged aerobic steady-state exercise (SSE) intensity due to its association with physiological indicators of exercise intensity, such as oxygen uptake (V̇O2) or heart rate (HR). However, these associations between psychological and physiological indicators of exercise intensity were found during graded exercise tests (GXT) but are currently used to prescribe SSE intensity even though the transferability and validity of the relationships found during GXT to SSE were not investigated. The present study aims to verify whether (a) RPE-HR or RPE-V̇O2 relations found during GXTs are valid during SSEs, and (b) the duration and intensity of SSE affect these relations. Methods Eight healthy and physically active males (age 22.6 ± 1.2 years) were enrolled. On the first visit, pre-exercise (during 20 min standing) and maximal (during a GXT) HR and V̇O2 values were measured. Then, on separate days, participants performed 4 SSEs on the treadmill by running at 60% and 80% of the HR reserve (HRR) for 15 and 45 min (random order). Individual linear regressions between GXTs’ RPE (dependent variable) and HRR and V̇O2 reserve (V̇O2R) values (computed as the difference between maximal and pre-exercise values) were used to predict the RPE associated with %HRR (RPEHRR) and %V̇O2R (RPEV̇O2R) during the SSEs. For each relation (RPE-%HRR and RPE-%V̇O2R), a three-way factorial repeated measures ANOVA (α = 0.05) was used to assess if RPE (dependent variable) was affected by exercise modality (i.e., RPE recorded during SSE [RPESSE] or GXT-predicted), duration (i.e., 15 or 45 min), and intensity (i.e., 60% or 80% of HRR). Results The differences between RPESSE and GXT-predicted RPE, which were assessed by evaluating the effect of modality and its interactions with SSE intensity and duration, showed no significant differences between RPESSE and RPEHRR. However, when RPESSE was compared with RPEV̇O2R, although modality or its interactions with intensity were not significant, there was a significant (p = 0.020) interaction effect of modality and duration yielding a dissociation between changes of RPESSE and RPEV̇O2R over time. Indeed, RPESSE did not change significantly (p = 0.054) from SSE of 15 min (12.1 ± 2.0) to SSE of 45 min (13.5 ± 2.1), with a mean change of 1.4 ± 1.8, whereas RPEV̇O2R decreased significantly (p = 0.022) from SSE of 15 min (13.7 ± 3.2) to SSE of 45 min (12.4 ± 2.8), with a mean change of −1.3 ± 1.5. Conclusion The transferability of the individual relationships between RPE and physiological parameters found during GXT to SSE should not be assumed as shown by the results of this study. Therefore, future studies modelling how the exercise prescription method used (e.g., RPE, HR, or V̇O2) and SSE characteristics (e.g., exercise intensity, duration, or modality) affect the relationships between RPE and physiological parameters are warranted.

Abstract Objective A reliable taxonomic identification of species from molecular samples is the first step for many studies. For researchers unfamiliar with programming, running a BLAST analysis, filtering, and organizing results for hundreds of sequences through the BLAST web interface can be difficult. Additionally, sequences deposited in GenBank can have outdated taxonomic identification. The use of reliable Reference Sequences Library (RSL) containing accurate taxonomically-identified sequences facilitates this task. Pending the availability of a RSL with the user, we developed a tool that automates the molecular taxonomic identification of sequences. Results We developed PARSID, a Python script running through the command-line that automates the routine workflow of blasting an input sequence file against the user’s RSL, and retrieves the matches with the highest percentage of identity in five steps. PARSID accepts cut-off parameters and supplementary information in a.csv file for filtering the results. The final output is visualized in a spreadsheet. We tested its functioning using 10 input sequences simulating different situations of the molecular taxonomic identification of sequences against an example RSL containing 25 sequences. Step-by-step instructions and test files are publicly available at https://github.com/kokinide/PARSID.git .

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p

Abstract Antimicrobial-resistant Klebsiella pneumoniae is a global threat to healthcare and an important cause of nosocomial infections. Antimicrobial resistance causes prolonged treatment periods, high mortality rates, and economic impacts. Whole Genome Sequencing (WGS) has been used in laboratory diagnosis, but there is limited evidence about pipeline validation to parse generated data. Thus, the present study aimed to validate a bioinformatics pipeline for the identification of antimicrobial resistance genes from carbapenem-resistant K. pneumoniae WGS. Sequences were obtained from a publicly available database, trimmed, de novo assembled, mapped to the K. pneumoniae reference genome, and annotated. Contigs were submitted to different tools for bacterial (Kraken2 and SpeciesFinder) and antimicrobial resistance gene identification (ResFinder and ABRicate). We analyzed 201 K. pneumoniae genomes. In the bacterial identification by Kraken2, all samples were correctly identified, and in SpeciesFinder, 92.54% were correctly identified as K. pneumoniae, 6.96% erroneously as Pseudomonas aeruginosa, and 0.5% erroneously as Citrobacter freundii. ResFinder found a greater number of antimicrobial resistance genes than ABRicate; however, many were identified more than once in the same sample. All tools presented 100% repeatability and reproducibility and > 75% performance in other metrics. Kraken2 was more assertive in recognizing bacterial species, and SpeciesFinder may need improvements.

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

Key Clinical Message Fibromyalgia is a rare disease, difficult to diagnose and to treat. We think that hyperbaric oxygen therapy could improve its signs and symptoms although more evidences have to be accumulated.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1–17, interquartile range (IQR) 8–15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42–64, IQR 18–81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3–9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

Objetivo: avaliar a intensidade e o desconforto provocados pela sede em pacientes em pós-operatório imediato. Método: estudo exploratório-descritivo, desenvolvido com pacientes internados na sala de recuperação pós-anestésica de um hospital público paranaense. Avaliaram-se indivíduos maiores de 18 anos, de ambos os sexos, com cognitivo preservado, internados de junho de 2021 a janeiro de 2022. A intensidade e o desconforto da sede foram mensurados por escalas específicas. Resultados: avaliaram-se 150 pacientes, com média de 43,9 anos. A maioria era do sexo masculino (65,3%), sem comorbidades (68,7%), submetida à raquianestesia (58%) e cirurgia ortopédica (59,3%), com soroterapia em curso (92,7%). O tempo médio de cirurgia foi 1,5 hora e 14,6 horas de jejum; 72,7% da amostra verbalizou sede, sendo que 37,6% queixaram-se de forma espontânea. Conclusão: os participantes de pesquisa apresentaram intensidade (6,6) e desconforto (7,6) moderados de sede no pós-operatório, tornando-se necessário discutir protocolos institucionais de intervenção para diminuir tal evento.

Abstract The production of skeletal muscle constructs useful for replacing large defects in vivo, such as in congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents major limitations, such as hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the in vitro generation of diaphragmatic-like tissues as a proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A customized bioreactor for diaphragmatic muscle was designed to control mechanical stimulation and promote radial stretching during the construct engineering. In vitro tests demonstrated that both ECM remodeling and fibroblast overgrowth were positively influenced by the bioreactor culture. Mechanically stimulated constructs also increased tissue maturation, with the formation of new oriented and aligned muscle fibers. Moreover, after in vivo orthotopic implantation in a surgical CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers and hernia recurrence did not occur, suggesting the value of this approach for treating diaphragm defects.

ObjectivesCurrently, two classes of oral anticoagulants are available in nursing home residents: vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). DOACs have a higher net clinical benefit than VKAs but DOACs are about 10 times more expensive than VKAs. The objective of our study was to assess and compare the overall costs of anti-coagulant strategy (VKA or DOAC), i.e., including drugs, laboratory costs and time spent in human capital (nurses and medical time) in nursing homes in France.MethodsThis was an observational, multicenter, prospective study including nine nursing homes in France. Among these nursing homes, 241 patients aged 75 years and older and treated with VKA (n = 140) or DOAC (n = 101) therapy accepted to participate in the study.ResultsDuring the 3-month follow-up period, the adjusted mean costs per patient were higher for VKA than DOACs for nurse care (€327 (57) vs. €154 (56), pConclusionOur study showed that in nursing homes despite a higher drug cost, DOAC therapy is associated with a lower total cost and less time used by nurses and physicians for drug monitoring when compared to VKA.

Background The percentages of heart rate (%HRR) or oxygen uptake (%V̇O2R) reserve are used interchangeably for prescribing aerobic exercise intensity due to their assumed 1:1 relationship, although its validity is debated. This study aimed to assess if %HRR and %V̇O2R show a 1:1 relationship during steady-state exercise (SSE) and if exercise intensity and duration affect their relationship. Methods Eight physically active males (age 22.6 ± 1.2 years) were enrolled. Pre-exercise and maximal HR and V̇O2 were assessed on the first day. In the following 4 days, different SSEs were performed (running) combining the following randomly assigned durations and intensities: 15 min, 45 min, 60% HRR, 80% HRR. Post-exercise maximal HR and V̇O2 were assessed after each SSE. Using pre-exercise and post-exercise maximal values, the average HR and V̇O2 of the last 5 min of each SSE were converted into percentages of the reserves (%RES), which were computed in a 3-way RM-ANOVA (α = 0.05) to assess if they were affected by the prescription parameter (HRR or V̇O2R), exercise intensity (60% or 80% HRR), and duration (15 or 45 min). Results The %RES values were not affected by the prescription parameter (p = 0.056) or its interactions with intensity (p = 0.319) or duration and intensity (p = 0.117), while parameter and duration interaction was significant (p = 0.009). %HRRs and %V̇O2Rs did not differ in the 15-min SSEs (mean difference [MD] = 0.7 percentage points, p = 0.717), whereas %HRR was higher than %V̇O2R in the 45-min SSEs (MD = 6.7 percentage points, p = 0.009). Conclusion SSE duration affects the %HRR-%V̇O2R relationship, with %HRRs higher than %V̇O2Rs in SSEs of longer duration.

The COVID-19 pandemic has hampered the optimum management of retinal diseases. This study examined the impact of the pandemic on the intravitreal-injection practice in two academic centers in Italy along with the related medico-legal implications. A retrospective analysis of electronic medical records from 16 March 2020 to 14 March 2021 at the ophthalmological departments of University of Cagliari (SGD) and University Magna Græcia of Catanzaro (UMG) was conducted. The data collected between 16 March 2020 and 14 June 2020 (lockdown), 15 June 2020 and 13 September 2020 (unlock), and 14 September 2020 and 14 March 2021 (second wave) were compared with those of the same period of the previous year. Weekly data on the administered drug and the number and type of treated disease were collected and analyzed. During the lockdown, a drop of 59% at SGD (p < 0.00001) and 77% at UMG (p < 0.00001) in intravitreal injections was found. In the first year of the pandemic, the reduction in injections was approximately of 27% (p < 0.0008) and 38% (p < 0.0001) at SGD and UMG, respectively. The COVID-19-related containment measures and the health resources redistribution have led to a delay in the treatment of chronic diseases of the retina, prioritizing the undeferrable ones. The lack of management guidelines has conceived relevant ethical and medico-legal issues that need to be considered in future measures planning.

Objetivo: Caracterizar os usuários cardiopatas que acessam a Unidade de Dor Torácica (UDT) de um hospital geral no norte do Estado do Rio Grande do Sul. Métodos: Estudo transversal, descritivo, de abordagem quantitativa, que foi realizado na UDT do Hospital da Cidade de Passo Fundo, abordando pacientes com suspeita ou com diagnóstico médico de Doença Cardiovascular (DCV). Resultados: Coleta dos dados realizada com 112 pacientes. Houve o predomínio de idosos, homens com baixas condições socioeconômicas e alta incidência de diagnóstico de Síndrome Coronariana Aguda (SCA) sendo que a dor torácica esteve presente em grande parte dos pacientes.Conclusões: Conhecer a população que acessou a UDT possibilitou reflexões acerca da temática, bem como a importância do referido serviço, no qual serve como porta de entrada para pacientes em condições agudas e crônicas de DCV.

This research note introduces a new global dataset, the Citizenship, Migration and Mobility in a Pandemic (CMMP). The dataset features systematic information on border closures and domestic lockdowns in response to the COVID-19 outbreak in 211 countries and territories worldwide from 1 March to 1 June 2020. It documents the evolution of the types and scope of international travel bans and exceptions to them, as well as internal measures including limitations of non-essential movement and curfews in 27 countries. CMMP can be used to study causes and effects of policy restrictions to migration and mobility during the COVID-19 pandemic. The dataset is available through Cadmus and will be regularly updated until the last pandemic-related restriction has been lifted or become long-term.

Parasitic diseases are a neglected and serious problem, especially in underdeveloped countries. Among the major parasitic diseases, Leishmaniasis figures as an urgent challenge due to its high incidence and severity. At the same time, the indiscriminate use of antibiotics by the population is increasing together with resistance to medicines. To address this problem, new antibiotic-like molecules that directly kill or inhibit the growth of microorganisms are necessary, where antimicrobial peptides (AMPs) can be of great help. In this work, the ferrocene molecule, one active compound with low levels of in vivo toxicity, was coupled to the N-terminus of the RP1 peptide (derived from the human chemokine CXCL4), aiming to evaluate how this change modifies the structure, biological activity, and toxicity of the peptide. The peptide and the conjugate were synthesized using the solid phase peptide synthesis (SPPS). Circular dichroism assays in PBS showed that the RP1 peptide and its conjugate had a typical spectrum for disordered structures. The Fc-RP1 presented anti-amastigote activity against Leishmania amazonensis (IC50 = 0.25 μmol L-1). In comparison with amphotericin B, a second-line drug approved for leishmaniasis treatment, (IC50 = 0.63 μmol L-1), Fc-RP1 was more active and showed a 2.5-fold higher selectivity index. The RP1 peptide presented a MIC of 4.3 μmol L-1 against S. agalactiae, whilst Fc-RP1 was four times more active (MIC = 0.96 μmol L-1), indicating that ferrocene improved the antimicrobial activity against Gram-positive bacteria. The Fc-RP1 peptide also decreased the minimum inhibitory concentration (MIC) in the assays against E. faecalis (MIC = 7.9 μmol L-1), E. coli (MIC = 3.9 μmol L-1) and S. aureus (MIC = 3.9 μmol L-1). The cytotoxicity of the compounds was tested against HaCaT cells, and no significant activity at the highest concentration tested (500 μg. mL-1) was observed, showing the high potential of this new compound as a possible new drug. The coupling of ferrocene also increased the vesicle permeabilization of the peptide, showing a direct relation between high peptide concentration and high carboxyfluorescein release, which indicates the action mechanism by pore formation on the vesicles. Several studies have shown that ferrocene destabilizes cell membranes through lipid peroxidation, leading to cell lysis. It is noteworthy that the Fc-RP1 peptide synthesized here is a prototype of a bioconjugation strategy, but it still is a compound with great biological activity against neglected and fish diseases.

Chronic Kidney Disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this review, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.On behalf of the World Kidney Day Steering Committee.Members of the World Kidney Day Steering Committee are: Ph. Kam Tao Li, G. Garcia-Garcia, M. Benghanem-Gharbi, K. Kalantar-Zadeh, C. Kernahan, L. Kumaraswami, G.B. Piccoli, G. Saadi, L. Fox, E. Zakharova, S. Andreoli.

Chronic Kidney Disease affects approximately 10% of the world's adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women's Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women's health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world's population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide. Kidney Health and Women's Health: a case for optimizing outcomes for present and future generations

Late diagnosis and treatment may increase morbidity and mortality among persons with hepatitis C virus (HCV) infection. We included all participants of the Swiss Hepatitis C Cohort Study (SCCS). We used unadjusted and adjusted logistic and Cox regressions to determine the association between the geographic origin of the participants and the following outcomes: antiviral treatment status; sustained virologic response; cirrhosis at enrolment; incident cirrhosis; loss to follow-up (LTFU); and mortality. The analyses were adjusted for sex, baseline age, education, source of income, alcohol consumption, injection drug use (IDU), HCV genotype, HIV or HBV coinfection, duration of HCV infection, time since enrolment, cirrhosis, (type of) HCV treatment, and centre at enrolment. Among 5,356 persons, 1,752 (32.7%) were foreign-born. IDU was more common among Swiss- (64.1%) than foreign-born (36.6%) persons. Cirrhosis at enrolment was more frequent among foreign- than Swiss-born persons, reflecting the high frequency of cirrhosis among Italian-born persons who acquired HCV between 1950 and 1970 in Italian healthcare settings. Although antiviral treatment coverage was similar, the sustained viral response rate was increased and the mortality was lower among foreign-vs. Swiss-born persons, with the lowest mortality in persons from Asia/Oceania. LTFU was more frequent in persons from Germany, Eastern and Southern Europe, and the Americas. In conclusion, in Switzerland, a country with universal healthcare, geographic origin had no influence on hepatitis C treatment access, and the better treatment outcomes among foreign-born persons were likely explained by their lower prevalence of IDU and alcohol consumption than among Swiss-born persons.

Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))—a 3D-map juxtaposing two acceptability profiles—to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≥65 years in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets

In France, diphtheria tetanus and inactivated polio vaccine (DT-IPV) coverage and immunization are insufficient in the elderly and decrease with age. The principal objective of this study was to assess the impact of a strategy of catch-up DT-IPV vaccination during hospitalization in people over the age of 65 years in central France (the Sarthe region). We performed a prospective, single-center, cluster-randomized study (four hospital wards). We included patients aged ≥65 years, without mental impairment, contraindication and who accepted to participate, hospitalized in the internal medicine wards in Le Mans Hospital from 28 May 2018 to 27 May 2019. The DT-IPV vaccination status of the patients was determined at inclusion and the wards were randomized (intervention and control). In the intervention group, vaccination was up-dated during hospitalization. In case of temporary contraindication, vaccination was prescribed at hospital discharge. Patients hospitalized in the control wards received oral information only. Final immunization status was determined by calling the patient’s general practitioner two months after hospital discharge. One hundred and fifty seven patients were included: 73 in the intervention and 84 in the control arm. Baseline immunization coverage was 46.5%. Vaccination coverage increased from 56.2% to 80.8% in the intervention group and from 38.1% to 40.5% in the control group (p < 0.001). Having received sufficient information from the general practitioner was the only factor associated with vaccination being up-to-date in uni- and multivariate analysis: OR = 5.07 [2.45–10.51]. In a setting of low vaccination coverage DT-IPV vaccination during hospitalization is an effective catch-up strategy.

BACKGROUND The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. AIMS OF THE STUDY We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. METHODS We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. RESULTS Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92–96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94–98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87–100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87–97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76–94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. CONCLUSION In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.

Introduction: Cervical cancer is one of the most frequent cancers among Brazilian women and its relationship with the human papillomavirus (HPV) is well established. Objective: To analyze the presence of DNA/HPV using Hybrid Capture method for women in the city of Uruguaiana (RS). Methods: During the period of January to December 2015, 51 cervicovaginal samples were collected from patients who sought care at Basic Health Units in the city. After the collection, conventional and liquid-based cytological analysis was performed. Results: The results of the study indicate the prevalence of genital HPV infection in 5.9% of the samples; low-risk DNA/HPV was detected in 3.9% of patients of reproductive age (PIR); and 2.0% of PIR presented highrisk DNA/HPV. By stratifying the prevalence of HPV in age, we found positivity between 16 and 31 years. Conclusion: Conventional cytology is often inconclusive and, in such cases, using molecular biology methods that detect the DNA/HPV presence would be very useful.

In patients undergoing hematopoietic stem cell transplantation (HSCT), refractoriness to platelet transfusion has been associated with graft failure, delayed engraftment, early mortality and decreased overall survival. Therapeutic strategies include plasma exchange, immunoglobulins, rituximab, and splenectomy. We describe here three patients with refractoriness to platelet transfusion due to anti-human leukocyte antibodies who were splenectomized before HSCT (two cases) and after HSCT (one case) due to the lack of efficacy of other therapies. Splenectomy was uneventful. All three patients achieved a full donor engraftment. We suggest that splenectomy is feasible and effective in HSCT patients to reduce the risk of graft failure or delayed engraftment.

Background. There is an increasing need for admission of octogenarians to cardiac rehabilitation programs. The aim of this study was to evaluate if the Rivermead Mobility Index (RMI) (scale of mobility) is related to the functional capacity assessed by the 6 Minute Walking Test (6MWT). Methods. We selected 108 consecutive patients ≥ 80 years (M = 53, mean age 82.5 ± 2.7 years, after cardiac surgery n = 72, heart failure n = 36) enrolled to our cardiac rehabilitation unit. All patients were evaluated with the RMI and underwent 6MWT both at admission (RMI1 and 6MWT1) and after a period of daily physical training (RMI2 and 6MWT2). The RMI2/RMI1 and 6MWT2/6MWT1 ratios were calculated as indexes of functional improvement (IM). Results. The average in hospital stay was 20 ± 11 days with an average of 11.9 training sessions per patient. The average distance walked at 6MWT1 and 6MWT2 was 193 ± 116 and 278 ± 122 m, respectively (p

Objetivo: Relatar e discutir o caso de um paciente com tumor de células gigantes da nona vértebra torácica com evolução peculiar. Relato do caso: Paciente com dor torácica radicular, detectada lesão na nona vértebra torácica, foi operado e recebeu diagnóstico anatomopatológico de tumor de células gigantes (TCG). Apresentou três recorrências locais, sendo a primeira manejada com reintervenção cirúrgica em dois tempos, na segunda também foi realizada reintervenção cirúrgica, porém com fenolização do sítio cirúrgico, preenchimento com metilmetacrilato e radioterapia pós-operatória. Apresentou semeadura de tumor retroesternal, o qual foi ressecado cirurgicamente, não tendo sido realizada terapia complementar. Uma terceira recorrência foi detectada durante procedimento de correção de falência da artrodese posterior, sendo realizada ressecção da lesão e quimioterapia pós-operatória. Durante o tratamento, desenvolveu imunossupressão e evoluiu para óbito em decorrência de suas complicações. Conclusão: O TCG acometendo a coluna torácica é pouco frequente. Trata-se de uma lesão benigna, agressiva localmente e com comportamento incerto. A ressecção cirúrgica com margens amplas é o tratamento padrão-ouro, porém nem sempre factível, em decorrência da localização da lesão.

Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation.

BACKGROUND:Tuberculosis is endemic in Cape Town, South Africa where a majority of the population become tuberculosis infected before adulthood. While social contact patterns impacting tuberculosis and other respiratory disease spread have been studied, the environmental determinants driving airborne transmission have not been quantified. METHODS:Indoor carbon dioxide levels above outdoor levels reflect the balance of exhaled breath by room occupants and ventilation. We developed a portable monitor to continuously sample carbon dioxide levels, which were combined with social contact diary records to estimate daily rebreathed litres. A pilot study established the practicality of monitor use up to 48-hours. We then estimated the daily volumes of air rebreathed by adolescents living in a crowded township. RESULTS:One hundred eight daily records were obtained from 63 adolescents aged between 12- and 20-years. Forty-five lived in wooden shacks and 18 in brick-built homes with a median household of 4 members (range 2-9). Mean daily volume of rebreathed air was 120.6 (standard error: 8.0) litres/day, with location contributions from household (48%), school (44%), visited households (4%), transport (0.5%) and other locations (3.4%). Independent predictors of daily rebreathed volumes included household type (p = 0.002), number of household occupants (p = 0.021), number of sleeping space occupants (p = 0.022) and winter season (p

Objetivo: Descrever o perfil de recém-nascidos prematuros de muito baixo peso (RNMBP) internados em uma UTIN. Metodologia: Caracteriza-se como um estudo retrospectivo documental com coleta de dados nos prontuários de RNMBP. Resultados: A amostra foi composta por 153 RNMBP, os quais apresentaram peso ao nascimento (PN) de 1082,92 ± 275,73 e tempo de ventilação pulmonar mecânica (VPM) de 13,34 ± 17,23 dias. A incidência de displasia broncopulmonar esteve associada ao tempo de VPM, à presença de enterocolite necrosante e à persistência do canal arterial. O tempo de permanência em VPM esteve associado ao tempo de internação e ao peso de nascimento. A incidência de hemorragia intracraniana esteve associada ao tempo de VPM, à IG e ao PN. Conclusão: O baixo peso ao nascimento, isolado ou associado a outros fatores, contribui para o aparecimento de comorbidades que poderão influenciar na qualidade de vida desses bebês bem como aumentar a mortalidade.

UNLABELLED: The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs's cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia.

The success of a dental implant treatment requires hard and soft tissue integration and osseointegration, mechanisms that entail a direct anchorage of the implant in the bone without interposition of soft tissue. Peri-implantitis is defined as an inflammatory reaction of the tissues surrounding a functioning dental implant. During inflammation, a high incidence of autoantibodies has been reported. The hypothesis of the present study is that the occurrence of autoantibodies to self-antigens including extracellular matrix (ECM) molecules and heat shock proteins (HSPs) might affect the dental implant outcome. Therefore, we evaluated the occurrence of antibodies to ECM molecules (Collagen (C) I, III, IV, V, fibronectin, laminin) and HSPs (HSP 27, HSP 65, HSP 90) in subjects with a healthy peri-implant microenvironment (n=29) as compared to patients with peri-implantitis (n=13). We also evaluated the HSP 27 expression in gingival fibroblasts grown in an inflammatory microenvironment. Antibodies to conformational ECM epitopes of CI, CIII and laminin were observed both in subjects with healthy peri-implant conditions and peri-implantitis. Antibodies to more than one HSP linear epitope were found in patients with peri-implantitis but not with healthy peri-implant conditions (p=0.024). Gingival fibroblasts grown in an inflammatory microenvironment showed increased HSP 27 cytoplasmic and plasma membrane expression as compared to fibroblasts grown in normal conditions. Immunity to multiple linear HSPs epitopes in patients with peri-implantitis and not in patients with a healthy peri-implant microenvironment might be relevant for monitoring the implant outcome and help to understand the role of subsets of autoantibodies in implant osseointegration.

Abstract Laparoscopic ventral hernia repair (LVHR) is a widely practiced treatment for primary (PH) and incisional (IH) hernias, with acceptable outcomes. Prevention of recurrence is crucial and still highly debated. Purpose of this study was to evaluate predictive factors of recurrence following LVHR with intraperitoneal onlay mesh with a single type of mesh for both PH and IH. A retrospective, multicentre study of data collected from patients who underwent LVHR for PH and IH with an intraperitoneal monofilament polypropylene mesh from January 2014 to December 2018 at 8 referral centers was conducted, and statistical analysis for risk factors of recurrence and post-operative outcomes was performed. A total of 1018 patients were collected, with 665 cases of IH (65.3%) and 353 of PH (34.7%). IH patients were older (p

ABSTRACT Objective: To evaluate the precipitating factors of diabetic ketoacidosis (DKA) in patients with type 1 diabetes hospitalized through the emergency department of a tertiary hospital. Materials and methods: Individuals with type 1 diabetes hospitalized for DKA from January 2005 to March 2010 (first period [P1], n = 75) and from April 2010 to January 2017 (second period [P2], n = 97) were identified through a query of electronic medical records. Data were collected by reviewing medical records. Only the first hospitalization of each participant in each period was included. Results: In P2, 44 patients (45.4%) were women, mean age was 26.2 ± 14.5 years, and 74 patients (76.3%) had a previous diagnosis of type 1 diabetes. Only 1 patient had glycated haemoglobin (HbA1c) below 64 mmol/mol (8.0%). Most patients (62.2%) had had a previous episode of DKA. In P1, non-adherence was the main cause of DKA (38.7%), followed by infection (24.0%). In P2, these rates were 34.0% and 24.7%, respectively; no statistical difference was observed between the two study periods (p = 0.790). Conclusion: Over time, non-adherence remained the main precipitating factor of DKA, followed by infection, and no significant difference was observed between the two study periods. Elevated HbA1c, outside the therapeutic range, indicates suboptimal diabetes care and may explain, at least in part, poor adherence as a precipitating factor of decompensation. Health strategies, such as improved self-management of type 1 diabetes, may contribute to a future reduction in DKA episodes.

Abstract Arginine methylation has been recognized as a post-translational modification with pleiotropic effects that span from regulation of transcription to metabolic processes that contribute to aberrant cell proliferation and tumorigenesis. This has brought significant attention to the development of therapeutic strategies aimed at blocking the activity of protein arginine methyltransferases (PRMTs), which catalyze the formation of various methylated arginine products on a wide variety of cellular substrates. GSK3368715 is a small molecule inhibitor of type I PRMTs currently in clinical development. Here, we evaluate the effect of type I PRMT inhibition on arginine methylation in normal human peripheral blood mononuclear cells and utilize a broad proteomic approach to identify type I PRMT substrates. This work identified heterogenous nuclear ribonucleoprotein A1 (hnRNP-A1) as a pharmacodynamic biomarker of type I PRMT inhibition. Utilizing targeted mass spectrometry (MS), methods were developed to detect and quantitate changes in methylation of specific arginine residues on hnRNP-A1. This resulted in the development and validation of novel MS and immune assays useful for the assessment of GSK3368715 induced pharmacodynamic effects in blood and tumors that can be applied to GSK3368715 clinical trials.

ABSTRACT Two researchers conducted independent searches on five different electronic databases: PubMed/MEDLINE, Embase, SciELO, LiLACS and Web of Science. Studies were selected that covered cross-cultural adaptation methodology and validation in Brazil with type 1 and type 2 diabetes patients of any age. After reading the full-text articles, data related to psychometric characteristics were extracted from each study selected. Reliability was assessed with Cronbach’s α (Cα). The initial searches identified 2,211 studies. After exclusions, 26 were included, covering a total of 31 questionnaires. Questionnaires were grouped into 11 domains based on their main focus of interest: adherence (n = 8), quality of life (n = 7), diabetes knowledge (n = 3), hypoglycemia (n = 3), self-efficacy (n = 3), satisfaction with pharmaceutical services (n = 1), emotional stress (n = 2), hope (n = 1), attitude towards diabetes (n = 1), perception of disease severity (n=1), and risk of developing diabetes (n = 1). This study identified and reviewed all of the diabetes-specific questionnaires that have been validated for Brazilian Portuguese, which should facilitate selection of the most appropriate instrument for each domain of interest in future research and clinical settings.

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

On behalf of the World Kidney Day Steering Committee Chronic kidney disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Chronic Kidney Disease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly. Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants. In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Abstract Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) are associated with familial Parkinson’s disease (PD). LRRK2 protein contains several functional domains, including protein-protein interaction domains at its N- and C-termini. In this study, we analyzed the functional features attributed to LRRK2 by its N- and C-terminal domains. We combined TIRF microscopy and synaptopHluorin assay to visualize synaptic vesicle trafficking. We found that N- and C-terminal domains have opposite impact on synaptic vesicle dynamics. Biochemical analysis demonstrated that different proteins are bound at the two extremities, namely β3-Cav2.1 at N-terminus part and β-Actin and Synapsin I at C-terminus domain. A sequence variant (G2385R) harboured within the C-terminal WD40 domain increases the risk for PD. Complementary biochemical and imaging approaches revealed that the G2385R variant alters strength and quality of LRRK2 interactions and increases fusion of synaptic vesicles. Our data suggest that the G2385R variant behaves like a loss-of-function mutation that mimics activity-driven events. Impaired scaffolding capabilities of mutant LRRK2 resulting in perturbed vesicular trafficking may arise as a common pathophysiological denominator through which different LRRK2 pathological mutations cause disease.

Objetivo: analizar la aplicación del estudio de caso como método de investigación por la enfermería en las publicaciones científicas nacionales e internacionales. Método: revisión integrativa de literatura realizada en las bases bibliográficas electrónicas PubMed, CINAHL, LILACS y SciELO, utilizando los descriptores estudio de caso, investigación y enfermería. Se incluyeron artículos originales disponibles en su totalidad en formato online, en los idiomas portugués, inglés o español, en el recorte temporal de 2010 a 2015. Resultados: se encontraron 624 estudios, de los cuales 50 atendieron al objetivo. Los autores Yin y Stake fueron los investigadores cuyos referenciales metodológicos de estudio de caso se destacaron en el contexto de la investigación en el área de la enfermería. La aplicación del método abarcó los diferentes campos de actuación de la profesión: educación, asistencia/cuidado y gestión/administración. Conclusión: el estudio de caso como método de investigación se mostró una importante metodología que puede ser ampliamente utilizada por la enfermería en sus diversos campos de actuación al buscar comprender fenómenos relacionados a individuos, grupos u organizaciones.

Background: Tetracyclines’ use in intensive animal farming has raised some concerns regarding the biosafety for humans. Increasing evidences have revealed the presence of these drugs in processed animal by-products, such as bone, throughout the food chain. A potential off-target of tetracyclines is the bacterial-like mitochondrial translational machinery, thereby causing proteostatic alterations in mitochondrial DNA-encoded components of the oxidative phosphorylation system. Methods: The Seahorse methodology, confocal microscopy imaging of mitochondrial potential and reactive oxygen species, and q-RT-PCR analysis of the expression of genes involved in mitochondrial biogenesis and mitophagy were carried out on human lymphoblast derived K562 cell line challenged with bone powder derived from chicken treated with or without oxytetracycline and pure oxytetracycline. Results: A complex dose-dependent profile was attained with a low dosage of bone powder extracts causing a metabolic adaptation hallmarked by stimulation of the mitochondrial respiration and enhanced expression of mitochondriogenic factors in particular in cells challenged with oxytetracycline-free bone extract. Conversely, a higher dosage of bone powder extracts, regardless of their source, caused a progressive inhibition of mitochondrial respiration and glycolysis, ultimately leading to cell death. No significant effects of the pure oxytetracycline were observed. Conclusion: Bone powder, regardless of chicken treatment, contains and releases factors/chemicals responsible for the observed effects on energy metabolism. Quantitative differential effects appear to depend on biochemical alterations in the bone matrix caused by antibiotics rather than antibiotics themselves.

Blood is a fluid connective tissue of human body, where it plays vital functions for the nutrition, defense and well-being of the organism. When circulating in peripheral districts, it is exposed to some physical stresses coming from outside the human body, as electromagnetic fields (EMFs) which can cross the skin. Such fields may interact with biomolecules possibly inducing non thermal-mediated biological effects at the cellular level. In this study, the occurrence of biochemical/biological modifications in human peripheral blood lympho-monocytes exposed in a reverberation chamber for times ranging from 1 to 20 h to EMFs at 1.8 GHz frequency and 200 V/m electric field strength was investigated. Morphological analysis of adherent cells unveiled, in some of these, appearance of an enlarged and deformed shape after EMFs exposure. Raman spectra of the nuclear compartment of cells exposed to EMFs revealed the onset of biochemical modifications, mainly consisting in the reduction of the DNA backbone-linked vibrational modes. Respirometric measurements of mitochondrial activity in intact lympho-monocytes resulted in increase of the resting oxygen consumption rate after 20 h of exposure, which was coupled to a significant increase of the FoF1-ATP synthase-related oxygen consumption. Notably, at lower time-intervals of EMFs exposure (i.e. 5 and 12 h) a large increase of the proton leak-related respiration was observed which, however, recovered at control levels after 20 h exposure. Confocal microscopy analysis of the mitochondrial membrane potential supported the respiratory activities whereas no significant variations in the mitochondrial mass/morphology was observed in EMFs-exposed lympho-monocytes. Finally, altered redox homeostasis was shown in EMFs-exposed lympho-monocytes, which progressed differently in nucleated cellular subsets. This results suggest the occurrence of adaptive mechanisms put in action, likely via redox signaling, to compensate for early impairments of the oxidative phosphorylation system caused by exposure to EMFs. Overall the data presented warn for health safety of people involved in long-term exposure to electromagnetic fields, although further studies are required to pinpoint the leukocyte cellular subset(s) selectively targeted by the EMFs action and the mechanisms by which it is achieved.

BACKGROUND:For many years, long-acting intramuscular (LAI) antipsychotics have been prescribed predominantly to chronic and severe patients, as a last resort when other treatments failed. Recently, a broader and earlier use of LAIs, particularly second-generation LAIs, has been emphasized. To date, few studies attempted to frame how this change in prescribing took place in real-world practice. Therefore, this study aimed to describe the clinical features of patients prescribed with LAIs, and to explore possible prescribing differences between first- and second-generations LAIs under ordinary clinical practice in Italy. METHODS:The STAR Network "Depot" Study is an observational, longitudinal, multicenter study involving 35 centers in Italy. In the cross-sectional phase, patients prescribed with LAIs were consecutively recruited and assessed over a period of 12 months. Descriptive statistics and multivariable logistic regression analyses were employed. RESULTS:Of the 451 recruited patients, 61% were males. The level of social and working functioning was heterogeneous, as was the severity of disease. Seventy-two per cent of the patients had a diagnosis of the schizophrenia spectrum. Seventy per cent were prescribed with second-generation antipsychotic (SGA) LAIs (mostly paliperidone, aripiprazole and risperidone). Compared to first-generation antipsychotic (FGA) LAIs, patients prescribed with SGA LAIs were more often younger; employed; with a diagnosis of the schizophrenia spectrum or bipolar disorder; with higher levels of affective symptoms; with fewer LAI prescriptions in the past. DISCUSSION:LAIs' prescribing practices appear to be more flexible as compared to the past, although this change is mostly restricted to SGA LAIs.