Evidence for widespread translation of 5' untranslated regions.

Ribosome profiling experiments support the translation of a range of novel human open reading frames. By contrast, most peptides from large-scale proteomics experiments derive from just one source, 5' untranslated regions. Across the human genome we find evidence for 192 translated upstream regions, most of which would produce protein isoforms with extended N-terminal ends. Almost all of these N-terminal extensions are from highly abundant genes, which suggests that the novel regions we detect are just the tip of the iceberg. These upstream regions have characteristics that are not typical of coding exons. Their GC-content is remarkably high, even higher than 5' regions in other genes, and a large majority have non-canonical start codons. Although some novel upstream regions have cross-species conservation - five have orthologues in invertebrates for example - the reading frames of two thirds are not conserved beyond simians. These non-conserved regions also have no evidence of purifying selection, which suggests that much of this translation is not functional. In addition, non-conserved upstream regions have significantly more peptides in cancer cell lines than would be expected, a strong indication that an aberrant or noisy translation initiation process may play an important role in translation from upstream regions.

Carbon-phosphorus cycle models overestimate CO2 enrichment response in a mature Eucalyptus forest.

The importance of phosphorus (P) in regulating ecosystem responses to climate change has fostered P-cycle implementation in land surface models, but their CO2 effects predictions have not been evaluated against measurements. Here, we perform a data-driven model evaluation where simulations of eight widely used P-enabled models were confronted with observations from a long-term free-air CO2 enrichment experiment in a mature, P-limited Eucalyptus forest. We show that most models predicted the correct sign and magnitude of the CO2 effect on ecosystem carbon (C) sequestration, but they generally overestimated the effects on plant C uptake and growth. We identify leaf-to-canopy scaling of photosynthesis, plant tissue stoichiometry, plant belowground C allocation, and the subsequent consequences for plant-microbial interaction as key areas in which models of ecosystem C-P interaction can be improved. Together, this data-model intercomparison reveals data-driven insights into the performance and functionality of P-enabled models and adds to the existing evidence that the global CO2-driven carbon sink is overestimated by models.

Cardiopulmonary Complications after Pulmonary Embolism in COVID-19.

Although pulmonary embolism (PE) is a frequent complication in COVID-19, its consequences remain unknown. We performed pulmonary function tests, echocardiography and computed tomography pulmonary angiography and identified blood biomarkers in a cohort of consecutive hospitalized COVID-19 patients with pneumonia to describe and compare medium-term outcomes according to the presence of PE, as well as to explore their potential predictors. A total of 141 patients (56 with PE) were followed up during a median of 6 months. Post-COVID-19 radiological lung abnormalities (PCRLA) and impaired diffusing capacity for carbon monoxide (DLCOc) were found in 55.2% and 67.6% cases, respectively. A total of 7.3% had PE, and 6.7% presented an intermediate-high probability of pulmonary hypertension. No significant difference was found between PE and non-PE patients. Univariate analysis showed that age > 65, some clinical severity factors, surfactant protein-D, baseline C-reactive protein, and both peak red cell distribution width and Interleukin (IL)-10 were associated with DLCOc < 80%. A score for PCRLA prediction including age > 65, minimum lymphocyte count, and IL-1ß concentration on admission was constructed with excellent overall performance. In conclusion, reduced DLCOc and PCRLA were common in COVID-19 patients after hospital discharge, but PE did not increase the risk. A PCRLA predictive score was developed, which needs further validation.

Vitamins and fatty acids against chemotherapy-induced intestinal mucositis.

Chemotherapy has allowed an increase in cancer survivorship, but it causes important adverse effects. Mucositis affecting the gastrointestinal tract is one of the main problems acutely caused by many antineoplastic drugs, such as 5-fluorouracil or methotrexate. Mucositis may cause pain, diarrhea, anorexia, weight loss, systemic infections and even death. This narrative review focuses on intestinal mucositis and the role that some nutraceuticals, namely vitamins (both lipid- and water-soluble) as well as fatty acids (FAs) and lipid-based products, can have in it. In preclinical (cell cultures, animal models) and/or human studies, vitamins A, D, E, B2, B9 and C, omega-3 long-chain FAs (eicosapentaenoic, docosahexaenoic, conjugated linoleic acid), short-chain FAs (mainly butyrate), medium-chain FAs (capric acid), and different lipid-based products (emu oil, extra-virgin olive oil, lipid replacement therapy), enriched in beneficial FAs and natural antioxidants, were shown to exert beneficial effects (both preventative and palliative) against chemotherapy-induced intestinal mucositis. Although the exact mechanisms of action involved in these effects are not yet well known, our review highlights the interest of investigating on diet and nutrition to implement scientifically robust strategies to improve protection of cancer patients against chemotherapy-induced adverse effects.

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.

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. Abbreviations: BAF: bafilomycin A1; CASP3: caspase 3; Caspases: cysteine-aspartic proteases; cCASP3: cleaved CASP3; CQ: chloroquine; CHX: cycloheximide; cPARP: cleaved poly (ADP-ribose) polymerase; DEPs: differential expressed proteins; ETO: etoposide; MEF: mouse embryonic fibroblast; MLKL: mixed lineage kinase domain-like; MSC: mesenchymal stem cell; MTORC1: mechanistic target of rapamycin kinase complex 1; Nec1s: necrostatin 1s; NFKB/NF-kB: nuclear factor of kappa light polypeptide gene enhancer in B cells; PLA: proximity ligation assay; RCD: regulated cell death; RIPK1: receptor (TNFRSF)-interacting serine-threonine kinase 1; RIPK3: receptor-interacting serine-threonine kinase 3; RUBCNL/PACER: RUN and cysteine rich domain containing beclin 1 interacting protein like; siCtrl: small interfering RNA nonsense; siRNA: small interfering RNA; TdT: terminal deoxynucleotidyl transferase; Tm: tunicamycin; TNF: tumor necrosis factor; TNFRSF1A/TNFR1: tumor necrosis factor receptor superfamily, member 1a.

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.

Efficiency and comparability of using new evidence platforms for updating recommendations: Experience with a type-2 diabetes guideline in Colombia.

Introduction: Updating recommendations for guidelines requires a comprehensive and efficient literature search. Although new information platforms are available for developing groups, their relative contributions to this purpose remain uncertain. Methods: As part of a review/update of eight selected evidence-based recommendationsfor type 2 diabetes, we evaluated the following five literature search approaches (targeting systematic reviews, using predetermined criteria): PubMed for MEDLINE, Epistemonikos database basic search, Epistemonikos database using a structured search strategy, Living overview of evidence (L.OVE) platform, and TRIP database. Three reviewers independently classified the retrieved references as definitely eligible, probably eligible, or not eligible. Those falling in the same "definitely" categories for all reviewers were labelled as "true" positives/negatives. The rest went to re-assessment and if found eligible/not eligible by consensus became "false" negatives/positives, respectively. We described the yield for each approach and computed "diagnostic accuracy" measures and agreement statistics. Results: Altogether, the five approaches identified 318 to 505 references for the eight recommendations, from which reviewers considered 4.2 to 9.4% eligible after the two rounds. While Pubmed outperformed the other approaches (diagnostic odds ratio 12.5 versus 2.6 to 5.3), no single search approach returned eligible references for all recommendations. Individually, searches found up to 40% of all eligible references (n = 71), and no combination of any three approaches could find over 80% of them. Kappa statistics for retrieval between searches were very poor (9 out of 10 paired comparisons did not surpass the chance-expected agreement). Conclusion: Among the information platforms assessed, PubMed appeared to be more efficient in updating this set of recommendations. However, the very poor agreement among search approaches in the reference yield demands that developing groups add information from several (probably more than three) sources for this purpose. Further research is needed to replicate our findings and enhance our understanding of how to efficiently update recommendations.

Introducción: La actualización de recomendaciones de las guías de práctica clínica requiere búsquedas bibliográficas exhaustivas y eficientes. Aunque están disponibles nuevas plataformas de información para grupos desarrolladores, su contribución a este propósito sigue siendo incierta. Métodos: Como parte de una revisión/actualización de 8 recomendaciones basadas en evidencia seleccionadas sobre diabetes tipo 2, evaluamos las siguientes cinco aproximaciones de búsqueda bibliográfica (dirigidas a revisiones sistemáticas, utilizando criterios predeterminados): PubMed para MEDLINE; Epistemonikos utilizando una búsqueda básica; Epistemonikos utilizando una estrategia de búsqueda estructurada; plataforma (L.OVE) y TRIP . Tres revisores clasificaron de forma independiente las referencias recuperadas como definitivamente o probablemente elegibles/no elegibles. Aquellas clasificadas en las mismas categorías "definitivas" para todos los revisores, se etiquetaron como "verdaderas" positivas/negativas. El resto se sometieron a una nueva evaluación y, si se consideraban por consenso elegibles/no elegibles, se convirtieron en "falsos" negativos/positivos, respectivamente. Describimos el rendimiento de cada aproximación, junto a sus medidas de "precisión diagnóstica" y las estadísticas de acuerdo. Resultados: En conjunto, las cinco aproximaciones identificaron 318-505 referencias para las 8 recomendaciones, de las cuales los revisores consideraron elegibles el 4,2 a 9,4% tras las dos rondas. Mientras que Pubmed superó a las otras aproximaciones (odds ratio de diagnóstico 12,5 versus 2,6 a 53), ninguna aproximación de búsqueda identificó por sí misma referencias elegibles para todas las recomendaciones. Individualmente, las búsquedas identificaron hasta el 40% de todas las referencias elegibles (n=71), y ninguna combinación de cualquiera de los tres enfoques pudo identificar más del 80% de ellas. Las estadísticas Kappa para la recuperación entre búsquedas fueron muy pobres (9 de cada 10 comparaciones pareadas no superaron el acuerdo esperado por azar). Conclusiones: Entre las plataformas de información evaluadas, Pubmed parece ser la más eficiente para actualizar este conjunto de recomendaciones. Sin embargo, la escasa concordancia en el rendimiento de las referencias exige que los grupos desarrolladores incorporen información de varias fuentes (probablemente más de tres) para este fin. Es necesario seguir investigando para replicar nuestros hallazgos y mejorar nuestra comprensión de cómo actualizar recomendaciones de forma eficiente.

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.

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.

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.

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.

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.

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.

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.