Lateral kangaroo position for thermal stability of extremely preterm: Non-inferiority randomized controlled trial.

BACKGROUND: Kangaroo care (KC) is an evidence-based best practice that can prevent major health complications in preterm infants. However, there is a lack of evidence on the feasibility and safety of placing extremely preterm infants under 28 weeks gestational age in KC position. AIM: To compare thermal stability 60 min after the first KC session in the lateral versus prone position in extremely preterm infants under 28 weeks gestational age. STUDY DESIGN: This is a single-centre, randomized, non-inferiority, parallel clinical trial. The patients were extremely preterm infants during their first 5 days of life. Infants in the intervention group received KC in the lateral position while those in the control group received KC in the prone position. All infants receiving KC were inside their polyethylene bags but maintained skin-to-skin contact. The primary outcome was the axillary temperature of the infants, and the secondary outcome was the development of intraventricular haemorrhage. RESULTS: Seventy infants were randomized (35 per group). The mean gestational age was 26 +1(1+1) in both groups. In the first KC session, the infant temperature at 60 minutes was 36.79°C (0.43) in lateral KC position, and 36.78°C (0.38) in prone KC position (p = .022). In lateral KC position, 7.69% (2) of the children who, according to the cranial ultrasound performed before the first session, had no haemorrhage presented with intraventricular haemorrhage after the first session. In prone KC position, new haemorrhages appeared after the first session in 29.17% (7) (p = .08). CONCLUSIONS: The lateral KC position is an alternative to the conventional prone KC position and maintains normothermia in infants under 28 weeks gestational age. RELEVANCE TO CLINICAL PRACTICE: Extremely preterm infants are candidates for KC. Lateral KC position is an evidence-based best practice that can be applied to preterm infants under 28 weeks GA. This evidence is particularly useful in performing umbilical catheterization on these patients.

Food Security: An Unmet Need in Outpatient Burn Care.

Nutrition is paramount for wound healing after burn injury. With rising food prices and time off work due to burn injuries, access to adequate nutrition may be a significant financial stressor. We asked patients at an outpatient burn clinic to complete the Household Food Security Module, which queries about food security over the preceding 12 months. Demographics and burn characteristics were abstracted from the medical record. We assessed the overall prevalence of food insecurity, risk factors for food insecurity, and potential effects of food insecurity on nutritional status and wound healing time. Wound healing time was assessed via Cox regression while adjusting for burn depth, total body surface area burned, and diabetes. Over 40% of participants reported experiencing food insecurity; it was more common in patients who preferred Spanish language (p=0.014) or were unemployed (p=0.049). Just over half of participants experiencing food insecurity were using any food assistance resources. Among patients more than 30 days from burn injury, patients who were food insecure had larger burns (p=0.01). Experience of food insecurity was not associated presence of malnutrition on nutrition-focused physical exam (p=0.47). Wound healing time for burns managed in the outpatient setting was associated with burn depth (p<0.001), but not food insecurity (p=0.95), burn size (p=0.17), or diabetes (p=0.14). Although food insecurity did not result in malnutrition or negatively impact wound healing time, it is important for providers to routinely screen for food insecurity due to increased nutritional requirements and loss of wages after burn injury.

Microbial competition for phosphorus limits the CO2 response of a mature forest.

The capacity for terrestrial ecosystems to sequester additional carbon (C) with rising CO2 concentrations depends on soil nutrient availability1,2. Previous evidence suggested that mature forests growing on phosphorus (P)-deprived soils had limited capacity to sequester extra biomass under elevated CO2 (refs. 3-6), but uncertainty about ecosystem P cycling and its CO2 response represents a crucial bottleneck for mechanistic prediction of the land C sink under climate change7. Here, by compiling the first comprehensive P budget for a P-limited mature forest exposed to elevated CO2, we show a high likelihood that P captured by soil microorganisms constrains ecosystem P recycling and availability for plant uptake. Trees used P efficiently, but microbial pre-emption of mineralized soil P seemed to limit the capacity of trees for increased P uptake and assimilation under elevated CO2 and, therefore, their capacity to sequester extra C. Plant strategies to stimulate microbial P cycling and plant P uptake, such as increasing rhizosphere C release to soil, will probably be necessary for P-limited forests to increase C capture into new biomass. Our results identify the key mechanisms by which P availability limits CO2 fertilization of tree growth and will guide the development of Earth system models to predict future long-term C storage.

The autophagy protein RUBCNL/PACER represses RIPK1 kinase-dependent apoptosis and necroptosis.

Mesenchymal stem cells (MSCs) are used in cell therapy; nonetheless, their application is limited by their poor survival after transplantation in a proinflammatory microenvironment. Macroautophagy/autophagy activation in MSCs constitutes a stress adaptation pathway, promoting cellular homeostasis. Our proteomics data indicate that RUBCNL/PACER (RUN and cysteine rich domain containing beclin 1 interacting protein like), a positive regulator of autophagy, is also involved in cell death. Hence, we screened MSC survival upon various cell death stimuli under loss or gain of function of RUBCNL. MSCs were protected from TNF (tumor necrosis factor)-induced regulated cell death when RUBCNL was expressed. TNF promotes inflammation by inducing RIPK1 kinase-dependent apoptosis or necroptosis. We determine that MSCs succumb to RIPK1 kinase-dependent apoptosis upon TNF sensing and necroptosis when caspases are inactivated. We show that RUBCNL is a negative regulator of both RIPK1-dependent apoptosis and necroptosis. Furthermore, RUBCNL mutants that lose the ability to regulate autophagy, retain their function in negatively regulating cell death. We also found that RUBCNL forms a complex with RIPK1, which disassembles in response to TNF. In line with this finding, RUBCNL expression limits assembly of RIPK1-TNFRSF1A/TNFR1 complex I, suggesting that complex formation between RUBCNL and RIPK1 represses TNF signaling. These results provide new insights into the crosstalk between the RIPK1-mediated cell death and autophagy machineries and suggest that RUBCNL, due to its functional duality in autophagy and apoptosis/necroptosis, could be targeted to improve the therapeutic efficacy of MSCs.

Effect of Obstructive Sleep Apnea during Pregnancy on Fetal Development: Gene Expression Profile of Cord Blood.

Obstructive sleep apnea (OSA) is quite prevalent during pregnancy and is associated with adverse perinatal outcomes, but its potential influence on fetal development remains unclear. This study investigated maternal OSA impact on the fetus by analyzing gene expression profiles in whole cord blood (WCB). Ten women in the third trimester of pregnancy were included, five OSA and five non-OSA cases. WCB RNA expression was analyzed by microarray technology to identify differentially expressed genes (DEGs) under OSA conditions. After data normalization, 3238 genes showed significant differential expression under OSA conditions, with 2690 upregulated genes and 548 downregulated genes. Functional enrichment was conducted using gene set enrichment analysis (GSEA) applied to Gene Ontology annotations. Key biological processes involved in OSA were identified, including response to oxidative stress and hypoxia, apoptosis, insulin response and secretion, and placental development. Moreover, DEGs were confirmed through qPCR analyses in additional WCB samples (7 with OSA and 13 without OSA). This highlighted differential expression of several genes in OSA (EGR1, PFN1 and PRKAR1A), with distinct gene expression profiles observed during rapid eye movement (REM)-OSA in pregnancy (PFN1, UBA52, EGR1, STX4, MYC, JUNB, and MAPKAP). These findings suggest that OSA, particularly during REM sleep, may negatively impact various biological processes during fetal development.

SERS biosensors for liquid biopsy towards cancer diagnosis by detection of various circulating biomarkers: current progress and perspectives.

Liquid biopsy has emerged as a promising non-invasive strategy for cancer diagnosis, enabling the detection of various circulating biomarkers, including circulating tumor cells (CTCs), circulating tumor nucleic acids (ctNAs), circulating tumor-derived small extracellular vesicles (sEVs), and circulating proteins. Surface-enhanced Raman scattering (SERS) biosensors have revolutionized liquid biopsy by offering sensitive and specific detection methodologies for these biomarkers. This review comprehensively examines the application of SERS-based biosensors for identification and analysis of various circulating biomarkers including CTCs, ctNAs, sEVs and proteins in liquid biopsy for cancer diagnosis. The discussion encompasses a diverse range of SERS biosensor platforms, including label-free SERS assay, magnetic bead-based SERS assay, microfluidic device-based SERS system, and paper-based SERS assay, each demonstrating unique capabilities in enhancing the sensitivity and specificity for detection of liquid biopsy cancer biomarkers. This review critically assesses the strengths, limitations, and future directions of SERS biosensors in liquid biopsy for cancer diagnosis.

Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

Racial and ethnic disparities post-hospitalization for COVID-19: barriers to access to care for survivors of COVID-19 acute respiratory distress syndrome.

Racial and ethnic health disparities in the incidence and severity of Coronavirus Disease 2019 (COVID-19) have been observed globally and in the United States. Research has focused on transmission, hospitalization, and mortality among racial and ethnic minorities, but Long COVID-19 health disparities research is limited. This study retrospectively evaluated 195 adults who survived COVID-19 associated acute respiratory distress syndrome (C-ARDS) in New York City from March-April 2020. Among survivors, 54% met the criteria for Long COVID syndrome. Hispanic/Latinx patients, were more likely to be uninsured (p = 0.027) and were less frequently discharged to rehabilitation facilities (p < 0.001). A cross-sectional telephone survey and interview were conducted with a subset of survivors (n = 69). Among these, 11% reported a lack of follow-up primary care post-discharge and 38% had subsequent emergency room visits. Notably, 38% reported poor treatment within the health care system, with 67% attributing this to racial or ethnic bias. Thematic analysis of interviews identified four perceived challenges: decline in functional status, discrimination during hospitalization, healthcare system inequities, and non-healthcare-related structural barriers. Sources of resilience included survivorship, faith, and family support. This study highlights structural and healthcare-related barriers rooted in perceived racism and poverty as factors impacting post-COVID-19 care.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Cultural adaptation of an intervention for caregivers of young autistic children: Community members' perspectives.

Caregivers of autistic children in low-to-middle-income countries experience many barriers to access resources to support their child's development. Caregiver training is considered an evidence-based practice and may be a cost-effective way to support caregivers of autistic children in such settings. This study focuses on the cultural adaptation of Parents Taking Action (PTA; Magaña et al., Family Process, 56, 57-74, 2017) to support caregivers of autistic children in Paraguay. We conducted focus groups and individual interviews with 28 caregivers, autistic individuals, and professionals in Paraguay to understand caregivers' needs and to explore needed cultural adaptations of PTA to achieve contextual fit. Participants identified caregivers' need for accurate and reliable information, strategies to support children's growth, and emotional support and strategies to manage stress. Additionally, participants provided recommendations for adapting PTA considering the dimensions within the Cultural Adaptation Checklist (Lee et al., International Journal of Developmental Disabilities, 2023). This study is the first step in the iterative process of culturally adapting an intervention and the process described in this study may be appropriate for culturally adapting other interventions.

Accidental catheter breakage during caudal epidural infiltration in an adult: An unusual complication.

Caudal epidural block is a simple and safe technique with a low complication rate commonly used for pediatric anesthesia and treatment of chronic lumbosacral pain. However, it is not exempt from some risks that, although infrequent, should be known. We describe the case of a 48-year-old female with chronic lumbosacral radicular pain who underwent caudal epidural infiltration. During the withdrawal of the catheter, accidental breakage and retention of a fragment at the level of the anterior epidural space of the sacrum occurred. We choose to have an expectant management with regular controls and a radiological lumbosacral computed tomography (CT) scan. Since the catheter was placed under sterile conditions, no prophylactic antibiotic treatment was considered. The patient showed no adverse events during the 6 months following catheter rupture. To our knowledge, there are no reports of epidural catheter breakage at the caudal level in adults. This is why there is no standardized protocol on how to proceed in these cases, and the handling of this situation must be individualized.

An undergraduate service-learning project to teach immunology concepts while increasing healthcare equity by enhancing access to stem cell donors among underrepresented populations.

Active learning has been shown to increase STEM student engagement and decrease the achievement gap among underrepresented students. As a parallel to the lack of equity in STEM education, BIPOC patients who require a life-saving hematopoietic cell transplantation (HCT) are much less likely-sometimes less than half as likely-than individuals of White-European descent to find a suitable donor when using the National Marrow Donation Program (NMDP). The Be the Match (BtM) Registry has made significant improvements in the likelihood of matching underrepresented patients, but the disparity persists. This activity uses a service-learning project to teach undergraduate students about stem cell donation and to add potential stem cell donors to the BtM Registry. A small data set of pre-/post-surveys from one cohort shows learning gains on the topic of HCT. The approach is flexible and scalable, and students overwhelmingly reported the project as a great use of class time and very rewarding.

Relevance of Comet Assay and Phosphorylated-Hsp90α in Cancer Patients' Peripheral Blood Leukocytes as Tools to Assess Cisplatin-based Chemotherapy Clinical Response and Disease Outcome.

Cisplatin (cPt) is a commonly used treatment for solid tumors. The main target of its cytotoxicity is the DNA molecule, which makes the DNA damage response (DDR) crucial for cPt-based chemotherapy. Therefore, it is essential to identify biomarkers that can accurately predict the individual clinical response and prognosis. Our goal was to assess the usefulness of alkaline comet assay and immunocytochemical staining of phosphorylated Hsp90α (p-Hsp90α), γH2AX, and 53BP1 as predictive/prognostic markers. Pre-chemotherapy peripheral blood leukocytes were exposed to cPt in vitro and collected at 0, 24 (T24), and 48 (T48) hr post-drug removal. Healthy subjects were also included. Baseline DNA damage was elevated in cancer patients (variability between individuals was observed). After cPt, patients showed increased γH2AX foci/nucleus (T24 and T48). Both in healthy persons and patients, the nuclear p-Hsp90α and N/C (nuclear/cytoplasmic) ratio augmented (T24), decreasing at T48. Favorable clinical response was associated with high DNA damage and p-Hsp90α N/C ratio following cPt. For the first time, p-Hsp90α significance as a predictive marker is highlighted. Post-cPt-DNA damage was associated with longer disease-free survival and overall survival. Our findings indicate that comet assay and p-Hsp90α (a marker of DDR) would be promising prognostic/predictive tools in cP-treated cancer patients.

Cardiometabolic risk stratification using a novel obesity phenotyping system based on body adiposity and waist circumference.

BACKGROUND: The estimation of obesity-associated cardiometabolic risk does not usually take into account body composition or the distribution of adiposity. The aim of the present study was to assess the clinical usefulness of a novel obesity phenotyping system based on the combination of actual body fat percentage (BF%) and waist circumference (WC) according to the cardiometabolic risk estimation. METHODS: A classification matrix combining BF% and WC as measures of both amount and distribution of adiposity establishing nine body phenotypes (3 BF% x 3 WC) was developed. Individuals were grouped in five different cardiometabolic risk phenotypes. We conducted a validation study in a large cohort of White subjects from both genders representing a wide range of ages and adiposity (n = 12,754; 65 % females, aged 18-88 years). RESULTS: The five risk groups using the matrix combination of BF% and WC exhibited a robust linear distribution regarding cardiometabolic risk, estimated by the Metabolic Syndrome Severity Score, showing a continuous increase between groups with significant differences (P < 0.001) among them, as well as in other cardiometabolic risk factors. An additional 24 % of patients at very high risk was detected with the new classification system proposed (P < 0.001) as compared to an equivalent matrix using BMI and WC instead of BF% and WC. CONCLUSIONS: A more detailed phenotyping should be a priority in the diagnosis and management of patients with obesity. Our classification system allows to gradually estimate the cardiometabolic risk according to BF% and WC, thus representing a novel and useful tool for both research and clinical practice.

Vaccination status and outcomes in critical COVID-19 patients.

OBJECTIVE: To analyze the clinical characteristics and outcomes of patients with COVID-19-related acute respiratory failure on the basis of their vaccination status at the time of ICU admission. METHODS: We conducted a retrospective observational study using a prospective database of patients admitted to the ICU of a university hospital in the city of Murcia, in Spain, between January 1, 2021 and September 1, 2022. Clinical, analytical, and sociodemographic data were collected and analyzed on the basis of patient vaccination status. We adjusted for confounding variables using propensity score matching and calculated adjusted ORs and 95% CIs. RESULTS: A total of 276 patients were included in the study. Of those, 8.3% were fully vaccinated, 12% were partially vaccinated, and 79.7% were unvaccinated. Although fully vaccinated patients had more comorbidities, partially vaccinated patients had higher disease severity. The proportion of patients with severe acute respiratory failure was higher in the unvaccinated group, followed by the partially vaccinated group. No significant differences were found among the different groups regarding complications, duration of ventilatory support, or length of ICU/hospital stay. In the sample selected by propensity score matching, the number of patients with severe complications and the in-hospital mortality rate were higher in unvaccinated patients, but the differences were not significant. CONCLUSIONS: This study failed to show a significant improvement in outcomes in critically ill COVID-19 patients vaccinated against SARS-CoV-2. However, the CIs were wide and the mortality point estimates favored patients who received at least one dose of COVID-19 vaccine.

From the Gut to the Brain: The Role of Enteric Glial Cells and Their Involvement in the Pathogenesis of Parkinson's Disease.

The brain-gut axis has been identified as an important contributor to the physiopathology of Parkinson's disease. In this pathology, inflammation is thought to be driven by the damage caused by aggregation of α-synuclein in the brain. Interestingly, the Braak's theory proposes that α-synuclein misfolding may originate in the gut and spread in a "prion-like" manner through the vagus nerve into the central nervous system. In the enteric nervous system, enteric glial cells are the most abundant cellular component. Several studies have evaluated their role in Parkinson's disease. Using samples obtained from patients, cell cultures, or animal models, the studies with specific antibodies to label enteric glial cells (GFAP, Sox-10, and S100ß) seem to indicate that activation and reactive gliosis are associated to the neurodegeneration produced by Parkinson's disease in the enteric nervous system. Of interest, Toll-like receptors, which are expressed on enteric glial cells, participate in the triggering of immune/inflammatory responses, in the maintenance of intestinal barrier integrity and in the configuration of gut microbiota; thus, these receptors might contribute to Parkinson's disease. External factors like stress also seem to be relevant in its pathogenesis. Some authors have studied ways to reverse changes in EGCs with interventions such as administration of Tryptophan-2,3-dioxygenase inhibitors, nutraceuticals, or physical exercise. Some researchers point out that beyond being activated during the disease, enteric glial cells may contribute to the development of synucleinopathies. Thus, it is still necessary to further study these cells and their role in Parkinson's disease.

[Efficacy of Physiotherapy Interventions on the Respiratory Musculature Through Respiratory Training Techniques in Post-operative Lung Transplant Recipients: Systematic Review]. / Eficacia de las intervenciones fisioterápicas sobre la musculatura respiratoria mediante técnicas de entrenamiento respiratorio en el postoperatorio de trasplantados pulmonares: una revisión sistemática.

Introduction: Respiratory muscles are a limiter of exercise capacity in lung transplant patients. It is necessary to know the effectiveness of specific respiratory muscle training techniques carried out in the management of adult lung transplant patients in the postoperative period. Methodology: A systematic review of clinical trials was carried out, which included adult lung transplant patients undergoing post-transplant respiratory training. A search was carried out in the databases PubMed/Medline, EMBASE, Scopus, Web of Science, Cochrane Library between January 2012 and September 2023, using the terms: "breathing exercise", "respiratory muscle training", "inspiratory muscle training", "respiratory exercise", "pulmonary rehabilitation", "lung rehabilitation"; in combination with "lung transplantation", "lung transplant", "posttransplant lung". No language limit. Results: Eleven trials were included with a total of 639 patients analyzed. Most training programs begin upon hospital discharge (more than one month post-transplant), few do so early (Intensive Care Unit). The duration varies from 1-12 months post-transplant. The interventions were based on aerobic training and peripheral muscle strength. Some of them included breathing exercises and chest expansions. The most used outcome variable was submaximal exercise capacity measured with the 6-minute walk test. Conclusions: Training the respiratory muscles of the adult transplant patient favors the improvement of exercise capacity and quality of life. Aerobic training, as well as strength training of the rest of the peripheral muscles, contribute to the improvement of respiratory muscles.