Total Hip Arthroplasty in Dyggve-Melchior-Clausen Syndrome: Literature Review and Case Report.

Dyggve-Melchior-Clausen (DMC) disease is a rare spondyloepiphyseal autosomal recessive disorder characterized by skeletal dysplasia and intellectual disability. Hip arthritis, often secondary to hip dysplasia, presents at an early age. Current literature suggests that osteotomies do not benefit DMC syndrome-associated hip disease but reports of total hip arthroplasty in these patients are lacking. We present a case of bilateral hip replacement in a 31-year-old patient with DMC syndrome. After planning the operation with the use of computed tomography, we chose to use a small-dimension porous cup along with an appropriately sized version control stem in order to address the unique acetabular and femoral deformities. In conclusion, we consider total hip replacement in DMC syndrome to be safe and effective in addressing a challenging hip pathology.

Connecting Clinical Capacity and Intervention Sustainability in Resource-Variable Pediatric Oncology Centers in Latin America.

Clinical capacity for sustainability, or the clinical resources needed to sustain an evidence-based practice, represent proximal determinants that contribute to intervention sustainment. We examine the relationship between clinical capacity for sustainability and sustainment of PEWS, an evidence-based intervention to improve outcomes for pediatric oncology patients in resource-variable hospitals. We conducted a cross-sectional survey among Latin American pediatric oncology centers participating in Proyecto Escala de Valoración de Alerta Temprana (EVAT), an improvement collaborative to implement Pediatric Early Warning Systems (PEWS). Hospitals were eligible if they had completed PEWS implementation. Clinicians were eligible to participate if they were involved in PEWS implementation or used PEWS in clinical work. The Spanish language survey consisted of 56 close and open-ended questions about the respondent, hospital, participants' assessment of clinical capacity to sustain PEWS using the clinical sustainability assessment tool (CSAT), and perceptions about PEWS and its use as an intervention. Results were analyzed using a multi-level modeling approach to examine the relationship between individual, hospital, intervention, and clinical capacity determinants to PEWS sustainment. A total of 797 responses from 37 centers in 13 countries were included in the analysis. Eighty-seven percent of participants reported PEWS sustainment. After controlling for individual, hospital, and intervention factors, clinical capacity was significantly associated with PEWS sustainment (OR 3.27, p < .01). Marginal effects from the final model indicate that an increasing capacity score has a positive influence (11% for every additional CSAT point) of predicting PEWS sustainment. PEWS is a sustainable intervention and clinical capacity to sustain PEWS contributes meaningfully to PEWS sustainment.

[Clinical evolution of patients with infection associated with orthopedic devices in treatment with continuous negative pressure]. / Evolución clínica de los pacientes con infección asociada a dispositivos ortopédicos en tratamiento con presión negativa continua.

Objective: To describe the use of negative pressure therapy with (TPNi) and without instillation (TPNs) as adjuvant treatment in the management of orthopedic device-associated infections (IADO). Method: Analytic observational study of records of patients with IADO managed with TPNi and TPNs with 0.9% saline solution, in patients > 18 years, operated on in 2018-2021. Clinical characteristics of infection, infectious agent as well as sociodemographic variables were evaluated. TPN was performed with the V.A.C. VERAFLO™ system. Analysis with χ2, Fisher and t-Student. Statistically accepted value p < 0.05. Results: Sample 40 patients. 75% male. Fractures 42.5% exposed and 57.5% closed. 92.5% applied prophylactic antibiotic (30-120 min). 35% plate implants, 12.5% centromedullary nail, 10% knee prosthesis and 12.5% hip. 47.5% bleeding < 500 ml. 72.5% surgical time of 2-4 hours. Previous hospitalization time, TPNs 3 weeks 55.9% and 4 weeks 26.5%; TPNi, 3 weeks 50% and 4 weeks 33.3%. Conservation of the implant 73.5% TPNs and 50% TPNi (p = 0.341). Wound closure 91.2% with TPNs and 100% with TPNi (p = 1.000). Conclusions: The use of TPNs and TPNi were useful as adjuvant treatments in the management of IADO, in addition they allowed to preserve the implant and wound closure in a large part of the patients.

Objetivo: Describir el uso de la terapia de presión negativa con (TPNi) y sin instilación (TPNs) como tratamiento adyuvante en el manejo de infecciones asociadas a dispositivo ortopédico (IADO). Método: Estudio observacional analítico de expedientes de pacientes con IADO manejados con TPNi y TPNs con solución salina al 0.9%, mayores de 18 años, operados en el periodo 2018-2021. Se evaluaron las características clínicas de infección, el agente infeccioso y las variables sociodemográficas. La TPN se realizó con sistema V.A.C.VERAFLO™. Para los análisis se emplearon las pruebas χ2, Fisher y t de Student. Valor estadísticamente aceptado: p < 0.05. Resultados: La muestra fue de 40 pacientes, el 75% masculinos. Fracturas: 42.5% expuestas y 57.5% cerradas. En el 92.5% se aplicó antibiótico profiláctico (30-120 min). Implantes: 35% placas, 12.5% clavo centromedular, 10% prótesis de rodilla y 12.5% cadera. El 47.5% con sangrado < 500 ml. En el 72.5% un tiempo quirúrgico de 2-4 horas. Tiempo de hospitalización previa: TPNs 3 semanas 55.9% y 4 semanas 26.5%; TPNi 3 semanas 50% y 4 semanas 33.3%. Conservación del implante: 73.5% TPNs y 50% TPNi (p = 0.341). Cierre de herida: 91.2% con TPNs y 100% con TPNi (p = 1.000). Conclusiones: El uso de TPNs y TPNi fue útil como tratamiento adyuvante en IADO, y además permitieron conservar el implante y el cierre de la herida en la mayoría de los pacientes.

Effect of acute altitude exposure on physiological parameters and glucose metabolism in healthy lowland Peruvians.

BACKGROUND: High altitude exposure triggers a series of physiological changes to maintain homeostasis. Although longer-term (days to years) acclimatization processes are well studied, less is known about the physiological changes upon rapid ascent. We took advantage of Peru's geography to measure the first physiological changes following rapid transport from a low to a high-altitude environment among lowlanders. METHODS: Blood glucose, insulin, C-peptide, and salivary cortisol among healthy lowland Peruvians were measured before and after glucose ingestion at 40 m and upon arrival at 3470 m. Resting heart rate, blood oxygen saturation, and blood pressure were also monitored. RESULTS: At high altitude, we find a significant ( p<0.05) increase in heart rate and a decrease in blood oxygen saturation and salivary cortisol. Additionally, baseline levels of blood glucose, plasma C-peptide, and cortisol were reduced ( p<0.05). Blood glucose, plasma insulin, and plasma C-peptide returned to baseline or below faster at high altitude after glucose ingestion. CONCLUSIONS: Although many overlapping environmental and physiological factors are present in the high-altitude environment, the first steps of acclimatization in this population appear to be caused by increased energy expenditure and glucose metabolism to maintain oxygen homeostasis until the longer-term acclimatization mechanisms become more significant.

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Courtship behavior in the knife livebearer Alfaro cultratus (Cyprinodontiformes: Poeciliidae).

The mating behavior of the knife livebearer Alfaro cultratus is described in detail. During "rubbing," the male swims to a position above the female and gently moves down repeatedly touching the dorsal part of female head with the pelvic fin tips. This courtship behavior constitutes the first report of a pelvic fin male-female contact during mating in poecilids. Based on preliminary evidence, I propose that a sensory bias mechanism could mediate the evolution of signal design/mate choice in this species, which should be tested in further studies.

Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study.

BACKGROUND: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America. METHODS: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics. FINDINGS: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29). INTERPRETATION: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer. FUNDING: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Biophysical Parameters of Plasma-Derived Extracellular Vesicles as Potential Biomarkers of Bone Disturbances in Breast Cancer Patients Receiving an Individualized Nutrition Intervention.

Extracellular vesicles (EVs) are implicated in several biological conditions, including bone metabolism disturbances in breast cancer patients (BCPs). These disorders hinder the adjustment of nutrition interventions due to changes in bone mineral density (BMD). The biophysical properties of EVs (e.g., size or electrostatic repulsion) affect their cellular uptake, however, their clinical relevance is unclear. In this study, we aimed to investigate the association between the biophysical properties of the plasma-derived EVs and BMDs in BCPs who received an individualized nutrition intervention during the first six months of antineoplastic treatment. As part of the nutritional assessment before and after the intervention, body composition including bone densitometry and plasma samples were obtained. In 16 BCPs, EVs were isolated using ExoQuick® and their biophysical properties were analyzed using light-scattering techniques. We found that the average hydrodynamic diameter of large EVs was associated with femoral neck bone mineral content, lumbar spine BMD, and neoplasms' molecular subtypes. These results provide evidence that EVs play a role in BCPs' bone disorders and suggest that the biophysical properties of EVs may serve as potential nutritional biomarkers. Further studies are needed to evaluate EVs' biophysical properties as potential nutritional biomarkers in a clinical context.

Extracellular Vesicles and Their Zeta Potential as Future Markers Associated with Nutrition and Molecular Biomarkers in Breast Cancer.

A nutritional intervention promotes the loss of body and visceral fat while maintaining muscle mass in breast cancer patients. Extracellular vesicles (EVs) and their characteristics can be potential biomarkers of disease. Here, we explore the changes in the Zeta potential of EVs; the content of miRNA-30, miRNA-145, and miRNA-155; and their association with body composition and biomarkers of metabolic risk in breast cancer patients, before and 6 months after a nutritional intervention. Clinicopathological data (HER2neu, estrogen receptor, and Ki67), anthropometric and body composition data, and plasma samples were available from a previous study. Plasma EVs were isolated and characterized in 16 patients. The expression of miRNA-30, miRNA-145, and miRNA-155 was analyzed. The Zeta potential was associated with HER2neu (ß = 2.1; p = 0.00), Ki67 (ß = -1.39; p = 0.007), estrogen positive (ß = 1.57; p = 0.01), weight (ß = -0.09; p = 0.00), and visceral fat (ß = 0.004; p = 0.00). miRNA-30 was associated with LDL (ß = -0.012; p = 0.01) and HDL (ß = -0.02; p = 0.05). miRNA-155 was associated with visceral fat (ß = -0.0007; p = 0.05) and Ki67 (ß = -0.47; p = 0.04). Our results reveal significant associations between the expression of miRNA-30 and miRNA-155 and the Zeta potential of the EVs with biomarkers of metabolic risk and disease prognosis in women with breast cancer; particularly, the Zeta potential of EVs can be a new biomarker sensitive to changes in the nutritional status and breast cancer progression.

Complicaciones hemorrágicas y trombóticas del embarazo: diagnóstico, prevención y tratamiento

Las hemorragias y la enfermedad tromboembólica venosa (ETEV) figuran entre las cinco causas más frecuentes de morbilidad y mortalidad materna en el mundo. Revisamos la evaluación y el manejo actualizado de las causas obstétricas de la hemorragia posparto (HPP), así como el diagnóstico y manejo de condiciones hematológicas que pueden causar o agravar la HPP, por ejemplo: coagulación intravascular diseminada, enfermedad de von Willebrand, trombocitopenia autoinmune y las microangiopatías trombóticas. Revisamos el rol del síndrome antifosfolípido y las trombofilias hereditarias como factores predisponentes a pérdidas fetales recurrentes y la ETEV en el embarazo y las recomendaciones actuales para la prevención de ambas complicaciones. Asimismo, repasamos el abordaje diagnóstico y líneas de manejo de la ETEV. Un objetivo adicional fue enfatizar la importancia del trabajo colaborativo multidisciplinario para lograr el manejo exitoso de las gestantes con las complicaciones obstétricas y hematológicas descritas.

Bleeding and venous thromboembolism (VTE) are among the five most common causes of morbidity and mortality in pregnant women worldwide. This review describes the current evaluation and management of the obstetric causes of postpartum hemorrhage (PPH), as well as the diagnosis and management of hematologic conditions which can cause or worsen PPH, such as disseminated intravascular coagulation, von Willebrand disease, autoimmune thrombocytopenia and the thrombotic microangiopathies. It also describes the role of the antiphospholipid syndrome and inherited thrombophilia as predisposing factors for recurrent pregnancy loses and VTE, and the current recommendations for the prevention of both complications. As well, the current diagnostic approach and management of ETEV are described. An additional objective of this Review is to emphasize the importance of a collaborative multidisciplinary approach for the successful management of the obstetric and hematologic complications herein described.

In Vitro Evaluation of Postbiotics Produced from Bacterial Isolates Obtained from Rainbow Trout and Nile Tilapia against the Pathogens Yersinia ruckeri and Aeromonas salmonicida subsp. salmonicida.

The use of antibiotics in aquaculture leads to the proliferation of multidrug-resistant bacteria, and an urgent need for developing new alternatives to prevent and control disease has, thus, arisen. In this scenario, postbiotics represent a promising tool to achieve this purpose; thus, in this study, isolation and selection of bacteria to further produce and evaluate their postbiotics antibacterial activity against fish pathogens was executed. In this respect, bacterial isolates from rainbow trout and Nile tilapia were obtained and tested in vitro against Yersinia ruckeri and Aeromonas salmonicida subsp. salmonicida. From 369 obtained isolates, 69 were selected after initial evaluation. Afterwards, additional screening was carried out by spot-on-lawn assay to finally select twelve isolates; four were identified as Pediococcus acidilactici, seven as Weissella cibaria, and one as Weissella paramesenteroides by matrix assisted laser desorption/ionization, time-of-flight mass spectrometry (MALDI-TOF MS). Selected bacteria were used to obtain postbiotic products to test their antagonistic activity through coculture challenge and broth microdilution assays. The influence of incubation time prior to postbiotic production on antagonistic behavior was also recorded. Two isolates identified as W. cibaria were able to significantly reduce (p < 0.05) A. salmonicida subsp. salmonicida's growth in the coculture challenge up to 4.49 ± 0.05 Log CFU/mL, and even though the reduction in Y. ruckeri was not as effective, some inhibition on the pathogen's growth was reported; at the same time, most of the postbiotic products obtained showed more antibacterial activity when obtained from broth cultures incubated for 72 h. Based on the results obtained, the preliminary identification of the isolates that expressed the highest inhibitory activity was confirmed by partial sequencing as W. cibaria. Through our study, it can be concluded that postbiotics produced by these strains are useful to inhibit the growth of the pathogens and could, thereby, be applicable in further research to develop suitable tools as feed additives for disease control and prevention in aquaculture.

Sociodemographic Aspects and Healthy Behaviors Associated With Perceived Life Satisfaction in Health Professionals.

BACKGROUND: Life satisfaction is a determining factor for the improvement of mental and physical health. Health care workers are a vulnerable population to suffer alterations in the factors that affect life satisfaction. Determining the influence of these factors on quality of life is important for their proper management. OBJECTIVE: To examine sociodemographic factors and healthy behaviors influencing life satisfaction in Peruvian professionals. METHODS: A cross-sectional study was conducted with 506 health care workers, who had a mean age of 40.34 years (SD = 10.39). A sociodemographic questionnaire, sleep quality, physical activity, eating habits, and life satisfaction were used. A regression model was fitted with the life satisfaction variable as the dependent variable. RESULTS: In multivariable analysis, age (ß = -.938, P < .01) and perception of poor health status (ß = -4.743, P < .001) were found to be associated with lower life satisfaction. On the other hand, higher university education level (ß = 1.667, P < .001), absence of smoking (ß = 3.202, P < .01), absence of depressive symptoms (ß = 3.390, P < .001), interest in daily activities (ß = 3.503, P < .05), good sleep quality (ß = 1.027, P < .01), a high frequency of physical activity (ß = 1.056, P < .01), and healthy eating are variables associated with higher life satisfaction. CONCLUSION: Sociodemographic aspects such as age and the perception of poor health are associated with lower life satisfaction. On the other hand, healthy behaviors such as absence of smoking, absence of depressive symptoms, interest in daily activities, good quality of sleep, high frequency of physical activity, and a healthy diet were associated with higher life satisfaction.

Rapid 40S scanning and its regulation by mRNA structure during eukaryotic translation initiation.

How the eukaryotic 43S preinitiation complex scans along the 5' untranslated region (5' UTR) of a capped mRNA to locate the correct start codon remains elusive. Here, we directly track yeast 43S-mRNA binding, scanning, and 60S subunit joining by real-time single-molecule fluorescence spectroscopy. 43S engagement with mRNA occurs through a slow, ATP-dependent process driven by multiple initiation factors including the helicase eIF4A. Once engaged, 43S scanning occurs rapidly and directionally at ∼100 nucleotides per second, independent of multiple cycles of ATP hydrolysis by RNA helicases post ribosomal loading. Scanning ribosomes can proceed through RNA secondary structures, but 5' UTR hairpin sequences near start codons drive scanning ribosomes at start codons backward in the 5' direction, requiring rescanning to arrive once more at a start codon. Direct observation of scanning ribosomes provides a mechanistic framework for translational regulation by 5' UTR structures and upstream near-cognate start codons.

Model for regional collaboration: Successful strategy to implement a pediatric early warning system in 36 pediatric oncology centers in Latin America.

BACKGROUND: Pediatric early warning systems (PEWS) aid in the early identification of deterioration in hospitalized children with cancer; however, they are under-used in resource-limited settings. The authors use the knowledge-to-action framework to describe the implementation strategy for Proyecto Escala de Valoracion de Alerta Temprana (EVAT), a multicenter quality-improvement collaborative, to scale-up PEWS in pediatric oncology centers in Latin America. METHODS: Proyecto EVAT mentored participating centers through an adaptable implementation strategy to: (1) monitor clinical deterioration in children with cancer, (2) contextually adapt PEWS, (3) assess barriers to using PEWS, (4) pilot and implement PEWS, (5) monitor the use of PEWS, (6) evaluate outcomes, and (7) sustain PEWS. The implementation outcomes assessed included the quality of PEWS use, the time required for implementation, and global program impact. RESULTS: From April 2017 to October 2021, 36 diverse Proyecto EVAT hospitals from 13 countries in Latin America collectively managing more than 4100 annual new pediatric cancer diagnoses successfully implemented PEWS. The time to complete all program phases varied among centers, averaging 7 months (range, 3-13 months) from PEWS pilot to implementation completion. All centers ultimately implemented PEWS and maintained high-quality PEWS use for up to 18 months after implementation. Across the 36 centers, more than 11,100 clinicians were trained in PEWS, and more than 41,000 pediatric hospital admissions had PEWS used in their care. CONCLUSIONS: Evidence-based interventions like PEWS can be successfully scaled-up regionally basis using a systematic approach that includes a collaborative network, an adaptable implementation strategy, and regional mentorship. Lessons learned can guide future programs to promote the widespread adoption of effective interventions and reduce global disparities in childhood cancer outcomes. LAY SUMMARY: Pediatric early warning systems (PEWS) are clinical tools used to identify deterioration in hospitalized children with cancer; however, implementation challenges limit their use in resource-limited settings. Proyecto EVAT is a multicenter quality-improvement collaborative to implement PEWS in 36 pediatric oncology centers in Latin America. This is the first multicenter, multinational study reporting a successful implementation strategy (Proyecto EVAT) to regionally scale-up PEWS. The lessons learned from Proyecto EVAT can inform future programs to promote the adoption of clinical interventions to globally improve childhood cancer outcomes.

Immobilization Systems of Antimicrobial Peptide Ib-M1 in Polymeric Nanoparticles Based on Alginate and Chitosan.

The development of new strategies to reduce the use of traditional antibiotics has been a topic of global interest due to the resistance generated by multiresistant microorganisms, including Escherichia coli, as etiological agents of various diseases. Antimicrobial peptides are presented as an alternative for the treatment of infectious diseases caused by this type of microorganism. The Ib-M1 peptide meets the requirements to be used as an antimicrobial compound. However, it is necessary to use strategies that generate protection and resist the conditions encountered in a biological system. Therefore, in this study, we synthesized alginate and chitosan nanoparticles (Alg-Chi NPs) using the ionic gelation technique, which allows for the crosslinking of polymeric chains arranged in nanostructures by intermolecular interactions that can be either covalent or non-covalent. Such interactions can be achieved through the use of crosslinking agents that facilitate this binding. This technique allows for immobilization of the Ib-M1 peptide to form an Ib-M1/Alg-Chi bioconjugate. SEM, DLS, and FT-IR were used to determine the structural features of the nanoparticles. We evaluated the biological activity against E. coli ATCC 25922 and Vero mammalian cells, as well as the stability at various temperatures, pH, and proteases, of Ib-M1 and Ib-M1/Alg-Chi. The results showed agglomerates of nanoparticles with average sizes of 150 nm; an MIC of 12.5 µM, which was maintained in the bioconjugate; and cytotoxicity values close to 40%. Stability was maintained against pH and temperature; in proteases, it was only evidenced against pepsin in Ib-M1/Alg-Chi. The results are promising with respect to the use of Ib-M1 and Ib-M1/Alg-Chi as possible antimicrobial agents.

Extracellular Vesicles from Adipose Tissue Could Promote Metabolic Adaptation through PI3K/Akt/mTOR.

Extracellular vesicles (EVs) are nanoparticles secreted by cells under physiological and pathological conditions, such as metabolic diseases. In this context, EVs are considered potential key mediators in the physiopathology of obesity. It has been reported that EVs derived from adipose tissue (ADEVs) contribute to the development of a local inflammatory response that leads to adipose tissue dysfunction. In addition, it has been proposed that EVs are associated with the onset and progression of several obesity-related metabolic diseases such as insulin resistance. In particular, characterizing the molecular fingerprint of obesity-related ADEVs can provide a bigger picture that better reflects metabolic adaptation though PI3K/Akt/mTOR. Hence, in this review we describe the possible crosstalk communication of ADEVs with metabolically active organs and the intracellular response in the insulin signaling pathway.

eIF5B and eIF1A reorient initiator tRNA to allow ribosomal subunit joining.

Translation initiation defines the identity and quantity of a synthesized protein. The process is dysregulated in many human diseases1,2. A key commitment step is when the ribosomal subunits join at a translation start site on a messenger RNA to form a functional ribosome. Here, we combined single-molecule spectroscopy and structural methods using an in vitro reconstituted system to examine how the human ribosomal subunits join. Single-molecule fluorescence revealed when the universally conserved eukaryotic initiation factors eIF1A and eIF5B associate with and depart from initiation complexes. Guided by single-molecule dynamics, we visualized initiation complexes that contained both eIF1A and eIF5B using single-particle cryo-electron microscopy. The resulting structure revealed how eukaryote-specific contacts between the two proteins remodel the initiation complex to orient the initiator aminoacyl-tRNA in a conformation compatible with ribosomal subunit joining. Collectively, our findings provide a quantitative and architectural framework for the molecular choreography orchestrated by eIF1A and eIF5B during translation initiation in humans.

Avances en el diagnóstico y tratamiento de deficiencia de hierro y anemia ferropenica / Advances in the diagnosis and treatment of iron deficiency and iron deficiency anemia

RESUMEN Deficiencia de hierro (DH) y anemia ferropénica (AF) continúan siendo problemas de salud de magnitud en el mundo y afectan especialmente a niños preescolares y mujeres embarazadas. Este artículo tiene como objetivos: a) Describir las pruebas de laboratorio diagnóstico de AF y los factores que influyen en los niveles de ferritina y otros biomarcadores del estado del hierro; b) Presentar avances en el metabolismo del hierro, i.e. el rol regulador esencial de la hepcidina en la absorción y utilización del hierro; c) Describir el impacto que estos avances han tenido en el diseño de investigaciones clínicas comparando la absorción del hierro asociada con esquemas de ingesta diaria versus días alternados; d) Describir las situaciones clínicas en las cuales hierro endovenoso está indicado como tratamiento secundario o de primera línea. Los conceptos y sugerencias expresados en este artículo están basados en literatura actualizada y la experiencia clínica de los autores.

ABSTRACT Iron deficiency (ID) and iron deficiency anemia (IDA) are still major health problems worldwide, affecting especially preschool children and pregnant women. The objectives of this article are: a) To describe the laboratory tests for diagnosing IDA and the factors that may influence results of the serum ferritin and the other iron biomarkers ; b) To present advances in iron metabolism, i.e. the critical regulatory role of hepcidin in the absorption and utilization of iron ; c) To describe the impact this new knowledge has had in the design of clinical investigations comparing the absorption of iron following oral supplementation given in consecutive days vs. alternate days schedules; and, d) To describe the clinical situations in which intravenous iron is indicated as secondary or first-line treatment. The concepts expressed and the suggestions made in this article are based on updated literature and the clinical experience of the authors.

Genetic and ecomorphological divergence between sympatric Astyanax morphs from Central America.

Intraspecific ecological and morphological polymorphism can promote ecological speciation and the build-up of reproductive isolation. Here, we evaluate correlations among morphology, trophic ecology and genetic differentiation between two divergent morphs (elongate and deep-body) of the fish genus Astyanax in the San Juan River basin in Central America, to infer the putative evolutionary mechanism shaping this system. We collected the two morphs from three water bodies and analysed: (1) the correlation between body shape and the shape of the premaxilla, a relevant trophic morphological structure, (2) the trophic level and niche width of each morph, (3) the correspondence between trophic level and body and premaxillary shape, and (4) the genetic differentiation between morphs using mitochondrial and nuclear markers. We found a strong correlation between the body and premaxillary shape of the morphs. The elongate-body morph had a streamlined body, a premaxilla with acuter angles and a narrower ascending process, and a higher trophic level, characteristic of species with predatorial habits. By contrast, the deep-body morph had a higher body depth, a premaxilla with less acute angles and a broader trophic niche, suggesting generalist habits. Despite the strong correlation between morphological and ecological divergence, the morphs showed limited genetic differentiation, supporting the idea that morphs may be undergoing incipient ecological speciation, although alternative scenarios such as stable polymorphism or plasticity should also be considered. This study provides support for the role of ecological factors promoting diversification in both lake and stream-dwelling freshwater fish.

Behavioral flexibility in Wasmannia auropunctata (Hymenoptera: Formicidae).

Worker division of labor is a defining trait in social insects. Many species are characterized by having behavioral flexibility where workers perform non-typical tasks for their age depending on the colony's needs. Worker division of labor and behavioral flexibility were examined in the little fire ant Wasmannia auropunctata (Roger, 1863), for which age-related division of labor has been found. Young workers perform nursing duties which include tending of brood and queens, and colony defense, while older workers forage. When nurses were experimentally removed from the colony, foragers were observed carrying out nursing and colony defense duties, yet when foragers were removed nurses did not forage precociously. We also administered juvenile hormone analog, methoprene, to workers. When methoprene was applied, foragers increased their nursing and defense activities while nurses became mainly idle. The behavioral flexibility of foragers of the little fire ant may be evidence of an expansion of worker's repertoires as they age; older workers can perform tasks they have already done in their life while young individuals are not capable of performing tasks ahead of time. This may be an important adaptation associated with the success of this ant as an invasive species.