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This report describes a newborn who presents high pressure values and absence of pulses in inferior extremities in his 4th day of life. Posterior to placement of umbilical arterial catheter, confirming diagnostic of thrombosis in aorta and left renal artery. A gamagraphy with MAG 3 was performed that gave evidence of left renal exclusion and aorta and left renal angioresonance. A management with no fractional heparin and streptokinase during 6 hours was initiated. The compromise in lower extremities was totally recovered, improving presure values in a few days. Following studies of renal function and growth give evidence of left renal artery flow and some function. This report describes an improvement with anticoagulant and thrombolitic treatment of a newborn kidney depite of a prolonged ischemia. [ABSTRACT FROM AUTHOR]

O ciúme patológico (CP) é um problema importante para a psiquiatria, que envolve riscos e muito sofrimento, podendo ocorrer em diversos transtornos mentais. Psicopatologicamente pode se apresentar de formas distintas, tais como idéias obsessivas, prevalentes ou delirantes sobre infidelidade. Entretanto, sua apresentação no transtorno obsessivo-compulsivo (TOC), como uma obsessão em geral associada a rituais de verificação, é relativamente pouco documentada. Para discutir esse aspecto específico do CP, este trabalho é ilustrado com quatro casos clínicos selecionados, em que o CP tem tais características, abordando aspectos de diagnóstico e tratamento. A compreensão de alguns casos de CP como uma manifestação do TOC, mesmo quando não claramente egodistônica, amplia as possibilidades terapêuticas e pode melhorar o prognóstico.

Abstract Background A major outbreak of bloody diarrhea associated with Shiga toxin-producing Escherichia coli O104:H4 occurred early in 2011, to which an unusual number of hemolytic uremic syndrome cases were linked. Due to limited information regarding pathogenesis and/or virulence properties of this particular serotype, we investigated the contribution of the aerobactin iron transport system during in vitro and in vivo conditions. Results A bioluminescent reporter construct was used to perform real-time monitoring of E. coli O104:H4 in a mouse model of infection. We verified that our reporter strain maintained characteristics and growth kinetics that were similar to those of the wild-type E. coli strain. We found that the intestinal cecum of ICR (CD-1) mice was colonized by O104:H4, with bacteria persisting for up to 7 days after intragastric inoculation. MALDI-TOF analysis of heat-extracted proteins was performed to identify putative surface-exposed virulence determinants. A protein with a high similarity to the aerobactin iron receptor was identified and further demonstrated to be up-regulated in E. coli O104:H4 when grown on MacConkey agar or during iron-depleted conditions. Because the aerobactin iron acquisition system is a key virulence factor in Enterobacteriaceae, an isogenic aerobactin receptor (iutA) mutant was created and its intestinal fitness assessed in the murine model. We demonstrated that the aerobactin mutant was out-competed by the wild-type E. coli O104:H4 during in vivo competition experiments, and the mutant was unable to persist in the cecum. Conclusion Our findings demonstrate that bioluminescent imaging is a useful tool to monitor E. coli O104:H4 colonization properties, and the murine model can become a rapid way to evaluate bacterial factors associated with fitness and/or colonization during E. coli O104:H4 infections.

Abstract Background Although most HTLV infections in Spain have been found in native intravenous drug users carrying HTLV-2, the large immigration flows from Latin America and Sub-Saharan Africa in recent years may have changed the prevalence and distribution of HTLV-1 and HTLV-2 infections, and hypothetically open the opportunity for introducing HTLV-3 or HTLV-4 in Spain. To assess the current seroprevalence of HTLV infection in Spain a national multicenter, cross-sectional, study was conducted in June 2009. Results A total of 6,460 consecutive outpatients attending 16 hospitals were examined. Overall, 12% were immigrants, and their main origin was Latin America (4.9%), Africa (3.6%) and other European countries (2.8%). Nine individuals were seroreactive for HTLV antibodies (overall prevalence, 0.14%). Evidence of HTLV-1 infection was confirmed by Western blot in 4 subjects (prevalence 0.06%) while HTLV-2 infection was found in 5 (prevalence 0.08%). Infection with HTLV types 1, 2, 3 and 4 was discarded by Western blot and specific PCR assays in another two specimens initially reactive in the enzyme immunoassay. All but one HTLV-1 cases were Latin-Americans while all persons with HTLV-2 infection were native Spaniards. Conclusions The overall prevalence of HTLV infections in Spain remains low, with no evidence of HTLV-3 or HTLV-4 infections so far.

Abstract Background Community-Associated Methicillin Resistant Staphylococcus aureus (CA-MRSA) has traditionally been related to skin and soft tissue infections in healthy young patients. However, it has now emerged as responsible for severe infections worldwide, for which vancomycin is one of the mainstays of treatment. Infective endocarditis (IE) due to CA-MRSA with heterogeneous vancomycin-intermediate susceptibility-(h-VISA) has been recently reported, associated to an epidemic USA 300 CA-MRSA clone. Case Presentation We describe the occurrence of h-VISA phenotype in a case of IE caused by a strain belonging to an epidemic CA-MRSA clone, distinct from USA300, for the first time in Argentina. The isolate h-VISA (SaB2) was recovered from a patient with persistent bacteraemia after a 7-day therapy with vancomycin, which evolved to fatal case of IE complicated with brain abscesses. The initial isolate-(SaB1) was fully vancomycin susceptible (VSSA). Although MRSA SaB2 was vancomycin susceptible (≤2 μg/ml) by MIC (agar and broth dilution, E-test and VITEK 2), a slight increase of MIC values between SaB1 and SaB2 isolates was detected by the four MIC methods, particularly for teicoplanin. Moreover, Sab2 was classified as h-VISA by three different screening methods [MHA5T-screening agar, Macromethod-E-test-(MET) and by GRD E-test] and confirmed by population analysis profile-(PAP). In addition, a significant increase in cell-wall thickness was revealed for SaB2 by electron microscopy. Molecular typing showed that both strains, SaB1 and SaB2, belonged to ST5 lineage, carried SCCmecIV, lacked Panton-Valentine leukocidin-(PVL) genes and had indistinguishable PFGE patterns (subtype I2), thereby confirming their isogenic nature. In addition, they were clonally related to the epidemic CA-MRSA clone (pulsotype I) detected in our country. Conclusions This report demonstrates the ability of this epidemic CA-MRSA clone, disseminated in some regions of Argentina, to produce severe and rapidly fatal infections such as IE, in addition to its ability to acquire low-level vancomycin resistance; for these reasons, it constitutes a new challenge for the Healthcare System of this country.

Abstract Background Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated E. coli pathotype. Results We sequenced the complete genome of E. coli NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic E. coli causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal E. coli allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype. Conclusions Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.

Abstract Background Burkholderia mallei is a zoonotic Gram negative bacterium which primarily infects solipeds but can cause lethal disease in humans if left untreated. The effect of two antibiotics with different modes of action on Burkholderia mallei strain ATCC23344 was investigated by using in vitro and in vivo studies. Results Determination of minimal inhibitory concentrations (MICs) in vitro was done by the agar diffusion method and the dilution method. The MICs of levofloxacin and ceftazidime were in the similar range, 2.5 and 5.0 μg/ml, respectively. Intracellular susceptibility of the bacterium to these two antibiotics in J774A.1 mouse macrophages in vitro was also investigated. Macrophages treated with antibiotics demonstrated uptake of the drugs and reduced bacterial loads in vitro. The efficacy of ceftazidime and levofloxacin were studied in BALB/c mice as post-exposure treatment following intranasal B. mallei infection. Intranasal infection with 5 × 105 CFUs of B. mallei resulted in 90% death in non-treated control mice. Antibiotic treatments 10 days post-infection proved to be effective in vivo with all antibiotic treated mice surviving to day 34 post-infection. The antibiotics did not result in complete clearance of the bacterial infection and presence of the bacteria was found in lungs and spleens of the survivors, although bacterial burden recovered from levofloxacin treated animals appeared reduced compared to ceftazidime. Conclusion Both antibiotics demonstrated utility for the treatment of glanders, including the ability for intracellular penetration and clearance of organisms in vitro.

Abstract Background We performed initial cell, cytokine and complement depletion studies to investigate the possible role of these effectors in response to vaccination with heat-killed Burkholderia mallei in a susceptible BALB/c mouse model of infection. Results While protection with heat-killed bacilli did not result in sterilizing immunity, limited protection was afforded against an otherwise lethal infection and provided insight into potential host protective mechanisms. Our results demonstrated that mice depleted of either B cells, TNF-α or IFN-γ exhibited decreased survival rates, indicating a role for these effectors in obtaining partial protection from a lethal challenge by the intraperitoneal route. Additionally, complement depletion had no effect on immunoglobulin production when compared to non-complement depleted controls infected intranasally. Conclusion The data provide a basis for future studies of protection via vaccination using either subunit or whole-organism vaccine preparations from lethal infection in the experimental BALB/c mouse model. The results of this study demonstrate participation of B220+ cells and pro-inflammatory cytokines IFN-γ and TNF-α in protection following HK vaccination.

Prior studies have identified various determinants of differential immune responses to COVID-19. This study focused on the Ig-G anti-RBD marker, analyzing its potential correlations with sex, vaccine type, body fat percentage, metabolic risk, perceived stress, and previous COVID-19 exposure. In this study, data (available in S1 Data) were obtained from 108 participants from the ESFUERSO cohort, who completed questionnaires detailing their COVID-19 experiences and stress levels assessed through the SISCO scale. IgG anti-RBD concentrations were quantified using an ELISA assay developed by UNAM. Multiple regression analysis was employed to control for covariates, including sex, age, body fat percentage, body mass index (BMI), and perceived stress. This sample comprised young individuals (average age of 21.4 years), primarily consisting of females (70%), with a substantial proportion reporting a family history of diabetes, hypertension, or obesity. Most students had received the Moderna or Pfizer vaccines, and 91% displayed a positive anti-RBD response. A noteworthy finding was the interaction between body fat percentage and sex. In males, increased adiposity was associated with decreased Ig-G anti-RBD concentration; in females, the response increased. Importantly, this pattern remained consistent regardless of the vaccine received. No significant associations were observed for dietary habits or perceived stress variables. This research reports the impact of sex and body fat percentage on the immune response through Ig-G anti-RBD levels to COVID-19 vaccines. The implications of these findings offer a foundation for educational initiatives and the formulation of preventive policies aimed at mitigating health disparities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Perales-Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: nutritional interventions (IN) in schoolchildren allow for health promotion, physical activity, and nutrition actions for the prevention of malnutrition., Objective: to evaluate the effect of an IN on the nutrient content in school snacks (ER) in public education schools in Mexico., Methods: descriptive, longitudinal, and prospective study with a sample of 812 children were classified into intervention group (IG) and control group (GC). Anthropometric measurements (weight, height, waist circumference) were made to identify nutritional status (EN); to evaluate the ER, the food and beverages that the children took from home to consume during the break were recorded on a checklist; the IN was performed in the GI for 12 weeks with a 6-week reinforcement and the final evaluation was carried out that included EN and SP in both groups., Results: a 1.4 % increase in overweight (SP) and obesity (OB) was observed in the GI, while in the GC it increased 5.5 %. In the CR, the GC showed a higher consumption of calories, carbohydrates, and sugars. In the intragroup analysis, the GI decreased carbohydrates, sugars. This intervention showed a small effect on the decrease of calories, carbohydrates and polyunsaturated acids of the GI compared to the GC., Conclusion: IN had a positive effect on the decrease in the energy and carbohydrate content of school snacks and therefore a slower trend in the prevalence of SP and OB in the GI compared to the GC.

Objective: This study examined the relationship between resilience, self-efficacy, anxiety, and depression to test whether self-efficacy affected anxiety and depression and compared how the participants in different age groups experienced anxiety, as well as the differences in anxiety between employed and unemployed participants., Method: A cross sectional web-based survey study that included adults aged 60 years or older living in Puerto Rico was performed during April and May 2020., Results: A total of 299 older adults completed the online questionnaire (14% men, 83.6% women). Of the total sample, 25.4% reported having moderate to severe symptoms of anxiety, while 20.8% reported having moderate to severe symptoms of depression. Our path analysis model suggested that while self-efficacy did not directly affect anxiety, it had an impact on resilience, thereby reducing anxiety symptoms. The participants who were 71 years old or older had lower anxiety levels than their younger counterparts did. We also confirmed that work might serve as a protective factor against anxiety., Conclusion: Our findings underscore the importance of resilience, self-efficacy, and working later in life to promote well-being and successful aging.

Background: The aim was to diagnose Candida in the oral cavity of subjects with type 2 diabetes mellitus (T2DM) using a genotyping technique and compare the results with those from conventional diagnosis by Papanicolaou (Pap) staining., Methods: Palatal mucosa smears were performed on 18 dental care patients diagnosed with T2DM and grade I, II, and III prosthetic stomatitis who met the inclusion criteria; 18 healthy control subjects were also included in the study. Hemoglobin A1c (HbA1c) levels were determined from total blood. Using exfoliative cytology, the Pap staining technique was used to diagnose candidiasis. Exfoliative cytology was also used for molecular diagnosis; DNA was obtained for Candida genotyping, and RNA was used for gene expression studies., Results: Clinical patterns indicated that all subjects were positive for Candida ; however, Pap analysis revealed only three positive subjects, whereas end-point polymerase chain reaction (PCR) analysis revealed 15 subjects with some type of Candida . The most common Candida species found were Candida guilliermondii (38.8%), Candida krusei (33.3%), Candida tropicalis , and Candida lusitaniae (22.2%). Interestingly, the coexpression of different species of Candida was found in various patients. In all patients, HbA1c levels were increased. Gene expression analysis showed a significant decrease ( p ≤ 0.05) in TLR2 expression in positive subjects, whereas TLR4 expression did not differ significantly among patients., Conclusions: The end-point PCR technique showed better sensitivity for the diagnosis of Candida when compared with the diagnosis by Pap staining. T2DM subjects showed an increased presence of C . guilliermondii that was correlated with decreased TLR2 expression.

Objective: Establish the disease burden of malignant mesothelioma (MM) in Colombia between 2015 and 2020, and its association with the subnational sociodemographic development index (SDI) and with asbestos sites., Methods: Mixed ecological study of the Colombian population diagnosed with MM (according to ICD-10) from 2015 to 2020. The global burden of disease (GBD) was estimated using the methodology proposed by Murray and Lopez, based on prevalence and mortality data obtained from official sources. The subnational (departmental level) SDI was estimated as a measure of socioeconomic development. Linear regressions were established with the GBD, SDI, and documented asbestos sites., Results: The estimated GBD of MM in Colombia during 2015-2020 was 51.71 disability-adjusted life years (DALYs) per 1 000 000 inhabitants (15 375.79 total DALYs), with predominance in people over 50 years of age (91.1%) and males (66.4%).Bogotá and Valle del Cauca were the departments with the highest number of adjusted DALYs. Bogotá had the highest SDI and Guainía and Cesar had the lowest. There was evidence of an association between DALYs and SDI, explaining 22.8% of DALYs., Conclusion: Malignant mesothelioma is the cause of a large number of DALYs, predominantly in the departments with greater socioeconomic development and with companies that used to use asbestos. However, possible underdiagnosis of MM limits analysis of the information.

Aim: Evaluate insulin resistance (IR) as a mediator of the effect of body fat distribution on liver fat infiltration and stiffness (LSt) in young adults using structural equation modeling (SEM)., Methods: We invited 500 first year students from two universities and evaluated their family history to determine the risk for cardiometabolic disease. Of these, 174 students (age 19 ± 1 years) were assessed for total body fat percentage (BF%), LSt, fat infiltration (Coefficient attenuated parameter CAP), and serum biochemical analysis. We performed a mediation analysis using two different structural equation models to determine the relationship between BMI, BF%, abdominal obesity (AO), IR, LSt, and fat infiltration using standardized β coefficients. The symbol "->" means "explains/causes"., Results: Model#1 supported that mediation analysis and had a better fit than the direct effect. AO->IR (b = 0.62, p = 0.005), AO->CAP (b = 0.63, p <0.001), and CAP->IR (b = 0.23, p = 0.007), with negligible effect of BMI on CAP and IR. Model#2 showed direct effect of BMI on LSt was a better fit than mediation. BMI->LSt (b = 0.17, p = 0.05) but no effect AO->LSt. Interestingly, LSt->IR (b = 0.18, p = 0.001), but bi-directional IR->LSt (b = 0.23, p = 0.001)., Conclusions: AO and BMI in young adults have differential phenotypic effects on liver CAP and LSt. Visceral fat had a direct effect on IR and CAP. Meanwhile, BMI was associated with LSt. Our findings shed light on the complex interplay of factors influencing liver stiffness, particularly in young individuals. Further research is needed to elucidate the precise mechanisms underlying these associations and their implications for liver health., (Copyright © 2023. Published by Elsevier Inc.)

Onychomycosis is the most prevalent nail ailment in adults, accounting for 50% of all nail infections. Dermatophyte fungi are the primary cause, but non-dermatophyte molds (NDM) and yeasts can also cause onychomycosis. It remains important to precisely determine the fungal cause of onychomycosis since the response to current treatments may vary between fungal classes. Real-time polymerase chain reaction (qPCR) has become a widespread tool for detecting fungal organisms for diagnosis due to its sensitivity and ability to detect down to the species level. This retrospective study aims to evaluate the qPCR Onycho+ test for dermatophyte detection using remnants of toenails from a cohort of patients from Puerto Rico.  Two hundred forty-two toenail samples submitted for histological examination via Periodic acid Schiff (PAS) staining for suspected onychomycosis were analyzed by the Onycho+ test and Sanger sequencing of the internal transcribed spacer (ITS-2). Compared to the gold standard Sanger sequencing method, the Onycho+ test reported an agreement of 91.39%, a sensitivity of 100% and a specificity of 84.5% in detecting dermatophytes, superior to the histology method which had a 69.53% agreement, 85.1% sensitivity and 57.1% specificity. The distribution of fungal organisms detected in this cohort shows a dermatophyte majority but a higher-than-expected proportion of NDMs. Nails negative for the Onycho+ test and positive for histology were mostly NDMs. This study demonstrates that the clinical performance of the Onycho+ test is superior to histology in detecting dermatophytes and that a combination of Onycho+ and histology can result in a higher clinical accuracy., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest. The authors alone are responsible for the content and the writing of the paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Detection and identification of body fluids plays a crucial role in criminal investigation, as it provides information on the source of the DNA as well as corroborative evidence regarding the crime committed, scene, and/or association with persons of interest. Historically, forensic serological methods have been chemical, immunological, catalytic, spectroscopic, and/or microscopic in nature. However, most of these methods are presumptive, with few robust confirmatory exceptions. In recent years several new molecular methods (mRNA, miRNA, DNA methylation, etc.) have been proposed; although promising, these methods require high quality human DNA or RNA. Additional steps are required in RNA based methods. Additionally, RNA based methods cannot be used for old cases where only DNA extracts remain to sample from. In this study, a novel non-human DNA (microbiome) based method was developed for the identification of the majority of forensically relevant human biological samples. Eight hundred and twelve (n = 812) biological samples (semen, vaginal fluid, menstrual blood, saliva, feces, urine, and blood) were collected and preserved using methods commonly used in forensic laboratories for evidence collection. Variable region four (V4) of 16 S ribosomal DNA (16 S rDNA) was amplified using a dual-indexing strategy and then sequenced on the MiSeq FGx sequencing platform using the MiSeq Reagent Kit v2 (500 cycles) and following the manufacturer's protocol. Machine learning prediction models were used to assess the classification accuracy of the newly developed method. As there was no significant difference in bacterial communities between vaginal fluid, menstrual blood, and female urine, these were combined as female intimate samples. Except in urine, the bacterial structures associated with male and female body fluid samples were not significantly different from one another. The newly developed method accurately identified human body fluid samples with an overall accuracy of more than 88%. This newly developed bacterial signature-based method is fast (no additional steps are needed as the same DNA can be used for both body fluid identification and STR typing), efficient (consume less sample as a single test can identify all major body fluids), sensitive (needs only 5 pg of bacterial DNA), accurate, and can be easily added into a forensic high throughput sequencing (HTS) panel., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To describe the perspectives of health practitioners on the barriers, gaps, and opportunities that Venezuelan migrant women experienced to accessing sexual and reproductive health (SRH) services during the COVID-19 pandemic and how SRH services were affected in Quito, Ecuador., Methods: Health practitioners involved in SRH services at nine public health care facilities in three zones of Quito were surveyed. The Minimum Initial Service Package readiness assessment tool survey, available from the Inter-Agency Working Group on Reproductive Health in Crisis, was adapted for use and data collection in Ecuador., Results: Of 297 respondents, 227 were included in the analysis. Only 16% of the health practitioners agreed that discrimination against migrant Venezuelans women occurred in the health care system. Of those, only 2.3% described specific conditions associated with discrimination, including requiring identification documents (7.5%) and lack of empathy or responsiveness (6.6%). Most (65.2%) respondents reported that the COVID-19 pandemic affected the use of SRH services by women in the general population and by Venezuelan migrant women more so (56.3%) because of more limited access to SRH services, poverty, and vulnerability. There were no differences between perceptions by levels of health care facility, except with regard to the lack of supplies, awareness of discrimination, and the belief that Venezuelan migrant women were affected more negatively than the local population., Conclusion: The perception among health practitioners in Quito was that discrimination occurred infrequently during the COVID-19 pandemic despite affecting the health care system. However, some level of discrimination toward migrant Venezuelan migrant women seeking SRH services was acknowledged and may be underrepresented.

The topography of the extracellular matrix (ECM) is a major biophysical regulator of cell behavior. While this has inspired the design of cell-instructive biomaterials, the ability to present topographic cues to cells in a true 3D setting remains challenging, particularly in ECM-like hydrogels made from a single polymer. Herein, we report the design of microstructured alginate hydrogels for injectable cell delivery and show their ability to orchestrate morphogenesis via cellular contact guidance in 3D. Alginate was grafted with hydrophobic cyclooctyne groups (ALG-K), yielding amphiphilic derivatives with self-associative potential and ionic crosslinking ability. This allowed the formation of microstructured ALG-K H hydrogels, triggered by the spontaneous segregation between hydrophobic/hydrophilic regions of the polymer that generated 3D networks with stiffer microdomains within a softer lattice. The azide-reactivity of cyclooctynes also allowed ALG-K functionalization with bioactive peptides via cytocompatible strain-promoted azide-alkyne cycloaddition (SPAAC). Hydrogel-embedded mesenchymal stem cells (MSCs) were able to integrate spatial information and to mechano-sense the 3D topography, which regulated cell shape and stress fiber organization. MSCs clusters initially formed on microstructured regions could then act as seeds for neo-tissue formation, inducing cells to produce their own ECM and self-organize into multicellular structures throughout the hydrogel. By combining 3D topography, click functionalization, and injectability, using a single polymer, ALG-K hydrogels provide a unique cell delivery platform for tissue regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: The purpose of this study was to compare case fatality rates (CFRs) and odds for mortality by risk factors of patients with COVID-19 in Mexico, before, during and after the implementation of the national COVID-19 vaccination programme., Study Design: A large database including COVID-19 monitoring cases was used to perform an observational retrospective study., Methods: The Chi-squared test and multivariate logistic regression analyses were applied to data from COVID-19-positive patients in Mexico. Data were analysed over 3 years, 2020, 2021 and 2022, corresponding with pre-, during and post-vaccination periods. The unadjusted odds ratios and 95% confidence interval were used to estimate the risk factors for COVID-19 mortality in each of the years., Results: Statistically significant differences in CFR and odds ratio were found in the studied years, favouring postvaccination period. Significant changes in CFR by age, sex and main comorbidities indicated changes in the epidemic dynamics after the implementation of the COVID-19 vaccination campaign. The likelihood of death increased for hospitalised cases and for patients who were middle-aged or older in 2021 and 2022, whereas the odds of death associated with sex and comorbidities remained similar or reduced over the 3 years., Conclusions: Implementation of the COVID-19 vaccination programme during 2021 showed positive consequences on CFR. The increased odds of dying in hospitalised patients are likely to be due to the unvaccinated proportion of patients., (Copyright © 2022 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to evaluate office workers for symptoms of computer vision syndrome (CVS) and alterations in the tear film relate to the hours of daily computer use., Methods: Sixty-seven volunteers were divided into 2 groups: 2 to 6 and 7 to 12 hours of daily computer use. Computer vision syndrome symptoms, tear film stability by tear film break-up time test, and composition of mucin 5 AC, catalase, and IL-6 was assessed by relative gene expression of conjunctival impression cytology samples were examined., Results: All participants exhibited moderate symptoms of CVS, whereas 90% showed reduced tear film stability. For the 7- to 12-hour (vs 2- to 6-hour) group, these effects were more pronounced and overexpression of mucin 5 AC and catalase was detected., Conclusions: Prolonged computer use induced an overexpression of mucin 5 AC and catalase and instability of the tear film, associated with ocular symptoms., Competing Interests: Conflict of Interest: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Background: To date, it is still controversial whether tau phosphorylation plays a role in Huntington's disease (HD), as previous studies demonstrated either no alterations or increases in phosphorylated tau (pTau) in HD postmortem brain and mouse models., Objective: The goal of this study was to determine whether total tau and pTau levels are altered in HD., Methods: Immunohistochemistry, cellular fractionations, and western blots were used to measure total tau and pTau levels in a large cohort of HD and control postmortem prefrontal cortex (PFC). Furthermore, western blots were performed to assess tau, and pTau levels in HD and control isogenic embryonic stem cell (ESC)-derived cortical neurons and neuronal stem cells (NSCs). Similarly, western blots were used to assess tau and pTau levels in HttQ111 and transgenic R6/2 mice. Lastly, total tau levels were assessed in HD and healthy control plasma using Quanterix Simoa assay., Results: Our results revealed that, while there was no difference in total tau or pTau levels in HD PFC compared to controls, the levels of tau phosphorylated at S396 were increased in PFC samples from HD patients 60 years or older at time of death. Additionally, tau and pTau levels were not changed in HD ESC-derived cortical neurons and NSCs. Similarly, total tau or pTau levels were not altered in HttQ111 and transgenic R6/2 mice compared to wild-type littermates. Lastly, tau levels were not changed in plasma from a small cohort of HD patients compared to controls., Conclusions: Together these findings demonstrate that pTau-S396 levels increase significantly with age in HD PFC.

Extrusion bioprinted constructs for osteochondral tissue engineering were fabricated to study the effect of multi-material architecture on encapsulated human mesenchymal stem cells' tissue-specific matrix deposition and integration into an ex vivo porcine osteochondral explant model. Two extrusion fiber architecture groups with differing transition regions and degrees of bone- and cartilage-like bioink mixing were employed. The gradient fiber (G-Fib) architecture group showed an increase in chondral integration over time, 18.5 ± 0.7 kPa on Day 21 compared to 9.6 ± 1.6 kPa on Day 1 for the required peak push-out force, and the segmented fiber (S-Fib) architecture group did not, which corresponded to the increase in sulfated glycosaminoglycan deposition noted only in the G-Fib group and the staining for cellularity and tissue-specific matrix deposition at the fiber-defect boundary. Conversely, the S-Fib architecture was associated with significant mineralization over time, but the G-Fib architecture was not. Notably, both fiber groups also had similar chondral integration as a re-inserted osteochondral tissue control. While architecture did dictate differences in the cells' responses to their environment, architecture was not shown to distinguish a statistically significant difference in tissue integration via fiber push-out testing within a given time point or explant region. Use of this three-week osteochondral model demonstrates that these bioink formulations support the fabrication of cell-laden constructs that integrate into explanted tissue as capably as natural tissue and encapsulate osteochondral matrix-producing cells, and it also highlights the important role that spatial architecture plays in the engineering of multi-phasic tissue environments. STATEMENT OF SIGNIFICANCE: Here, an ex vivo model was used to interrogate fundamental questions about the effect of multi-material scaffold architectural choices on osteochondral tissue integration. Cell-encapsulating constructs resembling stratified osteochondral tissue were 3D printed with architecture consisting of either gradient transitions or segmented transitions between the bone-like and cartilage-like bioink regions. The printed constructs were assessed alongside re-inserted natural tissue plugs via mechanical tissue integration push-out testing, biochemical assays, and histology. Differences in osteochondral matrix deposition were observed based on architecture, and both printed groups demonstrated cartilage integration similar to the native tissue plug group. As 3D printing becomes commonplace within biomaterials and tissue engineering, this work illustrates critical 3D co-culture interactions and demonstrates the importance of considering architecture when interpreting the results of studies utilizing spatially complex, multi-material scaffolds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Healthcare fragmentation, a main cause for delay in cancer diagnosis and treatment, contributes to high mortality in Latin America (LA), particularly among disadvantaged populations. This research focuses on integrated care interventions, which have been limitedly implemented in the region. The objective is to evaluate the contextual effectiveness of scaling-up an integrated care intervention to improve early diagnosis of frequent cancers in healthcare networks of Chile, Colombia and Ecuador., Methods and Analysis: This research is two pronged: (A) quasi-experimental design (controlled before and after) with an intervention and a control healthcare network in each LA country, using an implementation-effectiveness hybrid approach to assess the intervention process, effectiveness and costs; and (B) case study design to analyse access to diagnosis of most frequent cancers. Focusing on the most vulnerable socioeconomic population, it develops in four phases: (1) analysis of delays and barriers to early diagnosis (baseline); (2) intervention adaptation and implementation (primary care training, fast-track referral pathway and patient information); (3) intracountry evaluation of intervention and (4) cross-country analysis. Baseline and evaluation studies adopt mixed-methods qualitative (semistructured individual interviews) and quantitative (patient questionnaire survey) methods. For the latter, a sample size of 174 patients with cancer diagnosis per healthcare network and year was calculated to detect a proportions difference of 15%, before and after intervention (α=0.05; β=0.2) in a two-sided test. A participatory approach will be used to tailor the intervention to each context, led by a local steering committee (professionals, managers, policy makers, patients and researchers)., Ethics and Dissemination: This study complies with international and national legal stipulations on ethics. It was approved by each country's ethical committee and informed consent will be obtained from participants. Besides the coproduction of knowledge with key stakeholders, it will be disseminated through strategies such as policy briefs, workshops, e-tools and scientific papers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Despite the multiple initiatives implemented to reduce stunting in Ecuador, it continues to be a public health problem with a significant prevalence. One of the most affected groups is the rural indigenous population. This study aimed to analyze the prevalence of chronic malnutrition in indigenous children under 5 years of age and its association with health determinants, focusing on one of the territories with the highest prevalence of stunting., Methods: A cross-sectional study in 1,204 Kichwa indigenous children under the age of five, residing in rural areas of the counties with the highest presence of indigenous in the province of Chimborazo-Ecuador. A questionnaire on health determinants was applied and anthropometric measurements were taken on the child and the mother. Stunting was determined by the height-for-age z-score of less than 2 standard deviations, according to the World Health Organization´s parameters. Data were analyzed using bivariate and multivariate Poisson regression., Results: 51.6% (n = 646) of the children are stunted. Height-for-age z-scores were significantly better for girls, children under 12 months, families without overcrowding, and families with higher family income. The variables that were significantly and independently associated with stunting were: overcrowding (PR 1.20, 95% CI 1-1.44), the mother required that the father give her money to buy medicine (PR 1.33, 95% CI 1.04-1.71), the father did not give her money to support herself in the last 12 months (1.58, 95% CI 1.15-2.17), mother's height less than 150 cm (PR 1.42, 95% CI 1.19-1.69) and the child was very small at birth (PR 1.75, 95% CI 1.22-2.5)., Conclusion: One out of every two rural indigenous children included in this study is stunted. The high prevalence of stunting in the indigenous and rural population is multicausal, and requires an intersectoral and multidisciplinary approach. This study identified three fundamental elements on which public policy could focus: (a) reduce overcrowding conditions, improving economic income in the rural sector (for example, through the strengthening of agriculture), (b) provide prenatal care and comprehensive postnatal care, and (c) promote strategies aimed at strengthening the empowerment of women., (© 2022. The Author(s).)

The investigation of novel hydrogel systems allows for the study of relationships between biomaterials, cells, and other factors within osteochondral tissue engineering. Three-dimensional (3D) printing is a popular research method that can allow for further interrogation of these questions via the fabrication of 3D hydrogel environments that mimic tissue-specific, complex architectures. However, the adaptation of promising hydrogel biomaterial systems into 3D-printable bioinks remains a challenge. Here, we delineated an approach to that process. First, we characterized a novel methacryloylated gelatin composite hydrogel system and assessed how calcium phosphate and glycosaminoglycan additives upregulated bone- and cartilage-like matrix deposition and certain genetic markers of differentiation within human mesenchymal stem cells (hMSCs), such as RUNX2 and SOX9. Then, new assays were developed and utilized to study the effects of xanthan gum and nanofibrillated cellulose, which allowed for cohesive fiber deposition, reliable droplet formation, and non-fracturing digital light processing (DLP)-printed constructs within extrusion, inkjet, and DLP techniques, respectively. Finally, these bioinks were used to 3D print constructs containing viable encapsulated hMSCs over a 7 d period, where DLP printed constructs facilitated the highest observed increase in cell number over 7 d (∼2.4×). The results presented here describe the promotion of osteochondral phenotypes via these novel composite hydrogel formulations, establish their ability to bioprint viable, cell-encapsulating constructs using three different 3D printing methods on multiple bioprinters, and document how a library of modular bioink additives affected those physicochemical properties important to printability., (© 2022 IOP Publishing Ltd.)

Experimental autoimmune encephalomyelitis (EAE) is a relevant animal model of multiple sclerosis (MS). Oxidative stress and chronic inflammation play a major role in the pathogenesis of MS and EAE. Melatonin, a neurohormone, has potent anti-inflammatory properties. The aim of our study was to assess the therapeutic properties of melatonin alone or in combination with interferon β-1b (IFNβ-1b) or glatiramer acetate (GA) on EAE. EAE was induced in male Sprague-Dawley rats with an intraperitoneal injection of a homogenate of spinal cord and pig brain. At day 10 post immunization, rats were euthanized, and their brains were immediately excised and processed to measure oxidative stress markers and membrane fluidity. In addition, proinflammatory cytokines were quantified in plasma. Melatonin alone or in combination with GA and IFNβ-1b inhibited the disease process of EAE and the synthesis of proinflammatory cytokines, caused a significant decrement in oxidative stress markers, and preserved the membrane fluidity in the motor cortex, midbrain, and spinal cord. The cumulative index score was significantly reduced in EAE rats treated with melatonin alone or in combination with GA and IFNβ-1b. In conclusion, our findings provide preclinical evidence for the use of melatonin as an adjuvant therapeutic treatment for MS.

The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Andrade, de Souza, Torres, de Lima, Ebram, Celano, Schattner and Chudzinski-Tavassi.)

Background: The indigenous child population in Ecuador has a high prevalence of stunting. There is limited evidence of the association between breastfeeding, feeding practices, and stunting in indigenous children. This study aimed to analyze the prevalence of breastfeeding and complementary feeding practices and explore their association with stunting in Ecuadorian indigenous children under two years of age., Methods: Cross-sectional study of secondary data analysis using the 2012 Ecuador National Health and Nutrition Study, in 625 children aged 0-23 months (48,069 expanded sample), representative for the indigenous population. Breastfeeding and complementary feeding indicators were analyzed by age groups. Timely initiation of breastfeeding (within one hour after birth), exclusive breastfeeding (infants under six months who received only breast milk for the previous day), and other indicators were measured. Chi-square test or Fisher's exact test and logistic regression for complex samples were used to explore association with demographic and socioeconomic factors and stunting., Results: Twenty-six-point eight percent of the children were stunted. Stunting occurred mainly in children with rural residence, on poor households, and where there were four or more children. Most of the children had a timely initiation of breastfeeding (69.5% for 0-12 months and 75.5% for 13-23 months) and exclusive breastfeeding up to six months (78.2%). Among children between 6-12 months of age, 99.3% continued to be breastfed. In children from ages 6 to 12 months, 32.5% received food with adequate dietary diversity. Lower percentages of complementary feeding occurred in the poorest, adolescent mothers or those with less education. Children who did not receive the minimum frequency of meals for their age had higher odds of stunting (OR 3.28; 95% CI 1.3, 8.27). Children from age 19 to 23 months who consumed foods rich in iron showed lower probabilities of stunting (OR 0.04; 95% CI 0.00, 0.51)., Conclusions: Breastfeeding practices reached a prevalence of 70% or more, without being associated with stunting. Complementary feeding practices showed differences by socioeconomic condition. Not reaching the minimum meal frequency between 6 and 12 months of age was associated with stunting. Plans and strategies are necessary to promote adequate feeding and breastfeeding practices in the indigenous population., (© 2022. The Author(s).)

Healthcare-associated infections (HAI) are one of the major concerns worldwide, posing significant challenges to healthcare professionals' education and training. This study intended to measure nursing students' perceptions regarding their learning experiences on HAI prevention and control. In the first phase of the study, a cross-sectional and descriptive study with a convenience sample composed of undergraduate nursing students from Portugal, Spain, Poland, and Finland was conducted to develop the InovSafeCare questionnaire. In the second phase, we applied the InovSafeCare scale in a sample of nursing students from two Portuguese higher education institutions to explore which factors impact nursing students' adherence to HAI prevention and control measures in clinical settings. In phase one, the InovSafeCare questionnaire was applied to 1326 students internationally, with the instrument presenting adequate psychometric qualities with reliability results in 14 dimensions. During phase two, the findings supported that Portuguese nursing students' adherence to HAI prevention and control measures is influenced not only by the curricular offerings and resources available in academic settings, but also by the standards conveyed by nursing tutors during clinical placements. Our findings support the need for a dedicated curricular focus on HAI prevention and control learning, not only through specific classroom modules, innovative resources, and pedagogical approaches, but also through a complementary and coordinated liaison between teachers and tutors in academic and clinical settings.

Modular tissue engineering approaches open up exciting perspectives for the biofabrication of vascularized tissues from the bottom-up, using micro-sized units such as spheroids as building blocks. While several techniques for 3D spheroid formation from multiple cell types have been reported, strategies to elicit the extra-spheroid assembly of complex vascularized tissues are still scarce. Here we describe an injectable approach to generate vascularized dermal tissue, as an example application, from spheroids combining fibroblasts and endothelial progenitors (OEC) in a xeno-free (XF) setting. Short-term cultured spheroids (1 day) were selected over mature spheroids (7 days), as they showed significantly higher angiogenic sprouting potential. Embedding spheroids in fibrin was crucial for triggering cell migration into the external milieu, while providing a 3D framework for in-gel extra-spheroid morphogenesis. Migrating fibroblasts proliferated and produced endogenous ECM forming a dense tissue, while OEC self-assembled into stable capillaries with lumen and basal lamina. Massive in vitro interconnection between sprouts from neighbouring spheroids rapidly settled an intricate vascular plexus. Upon injection into the chorioallantoic membrane of chick embryos, fibrin-entrapped pre-vascularized XF spheroids developed into a macrotissue with evident host vessel infiltration. After only 4 days, perfused chimeric capillaries with human cells were present in proximal areas, showing fast and functional inosculation between host and donor vessels. This method for generating dense vascularized tissue from injectable building blocks is clinically relevant and potentially useful for a range of applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Distinct microbial signatures associated with specific human body sites can play a role in the identification of biological materials recovered from the crime scene, but at present, methods that have capability to predict origin of biological materials based on such signatures are limited. Metagenomic sequencing and machine learning (ML) offer a promising enhancement to current identification protocols. We use ML for forensic source body site identification using shotgun metagenomic sequenced data to verify the presence of microbiomic signatures capable of discriminating between source body sites and then show that accurate prediction is possible. The consistency between cluster membership and actual source body site (purity) exceeded 99% at the genus taxonomy using off-the-shelf ML clustering algorithms. Similar results were obtained at the family level. Accurate predictions were observed for genus, family, and order taxonomies, as well as with a core set of 51 genera. The accurate outcomes from our replicable process should encourage forensic scientists to seriously consider integrating ML predictors into their source body site identification protocols., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Healthcare-associated infections are one of the major concerns worldwide. This study presents the development and the validation process of the InovSafeCare scale and aimed at identifying and measuring the ecosystem variables related to healthcare-associated infection (HCAI) prevention and control practices in European nurse students. Qualitative and quantitative approaches were used to (1) elaborate an item pool related to the educational environment, the healthcare setting environment, and the attitudes, beliefs, and performance of the nursing students regarding HCAI prevention and control and (2) analyze psychometric properties of the scale using factor analysis. The validated InovSafeCare scale was applied to undergraduate nursing students of five European Higher Education Institutions. The partial least square structural equation modeling (PLS-SEM) method with SMART-PLS3 software was used. The study sample consists of 657 nursing students, who responded a self-report inventory. From the analyzed data were identified 14 factors. The InovSafeCare scale reveals good validity and reliability of the dimensions in different European countries., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yurrebaso Macho, Ward Mayens, Picado Valverde, Guzmán Ordaz, Juanes Méndez, Pérez Iglesias, Mirón Canelo, Pinto, Costa Reis, Simões, Torres, Silén-Lipponen, Korhonen, Koponen, Myllymäki, Jankowiak-Bernaciak, Patrzała, Bączyk, Basa, Costa, Serambeque, Oliveira, Pardal, Graveto and Parreira.)

Introduction: Social capital is considered an important determinant of health and overall wellbeing; however, to the best of the authors' knowledge, literature relating social capital to malnutrition in developing countries is still relatively small. This article examines the relationships between social capital and chronic malnutrition and anemia in a population of rural coastal children in Ecuador., Methods: A cross-sectional study in two groups of 246 and 282 children under 5 years and their families was performed. Anemia and chronic malnutrition were analyzed as outcome variables. Variables about social capital were identified on the basis of the Social Capital Assessment Tool of the World Bank. Bivariate and multivariate logistic regression analyses were conducted., Results: The prevalences of anemia and chronic malnutrition in the children were 15.0% and 12.8%, respectively. At the multivariate analysis, the variable 'mother has borrowed money' had an inverse association with chronic malnutrition (prevalence ratio (PR) 0.43, 95% confidence interval (CI) 0.20-0.90). Receiving and providing help after the earthquake of 2016 was significantly associated with a lower prevalence of chronic malnutrition (PR 0.52, 95%CI 0.28-0.97), but not with anemia. However, a mother being part of a community organization was associated with a 1.90 times higher prevalence of anemia (95%CI 1.04-3.48) in children than mothers who were not part of a community organization., Conclusion: The relationship between maternal social capital and the nutritional status of their children in rural communities seems to be positively related. However, a mother's participation in community organizations increases the prevalence of anemia in the children. These mixed results highlight the need for further studies focused on the different types of social capital and how they impact on health in deprived areas.

Background: Even though targeted therapies are available for cancers expressing oncogenic epidermal growth receptor (EGFR) and (or) human EGFR2 (HER2), acquired or intrinsic resistance often confounds therapy success. Common mechanisms of therapy resistance involve activating receptor point mutations and (or) upregulation of signaling downstream of EGFR/HER2 to Akt and (or) mitogen activated protein kinase (MAPK) pathways. However, additional pathways of resistance may exist thus, confounding successful therapy., Methods: To determine novel mechanisms of EGFR/HER2 therapy resistance in breast cancer, gefitinib or lapatinib resistant variants were created from SKBR3 breast cancer cells. Syngenic therapy sensitive and resistant SKBR3 variants were characterized for mechanisms of resistance by mammosphere assays, viability assays, and western blotting for total and phospho proteins., Results: Gefitinib and lapatinib treatments reduced mammosphere formation in the sensitive cells, but not in the therapy resistant variants, indicating enhanced mesenchymal and cancer stem cell-like characteristics in therapy resistant cells. The therapy resistant variants did not show significant changes in known therapy resistant pathways of AKT and MAPK activities downstream of EGFR/HER2. However, these cells exhibited elevated expression and activation of the small GTPase Rac, which is a pivotal intermediate of GFR signaling in EMT and metastasis. Therefore, the potential of the Rac inhibitors EHop-016 and MBQ-167 to overcome therapy resistance was tested, and found to inhibit viability and induce apoptosis of therapy resistant cells., Conclusions: Rac inhibition may represent a viable strategy for treatment of EGFR/HER2 targeted therapy resistant breast cancer.