Heterocellular cadherin connections: coordinating adhesive cues in homeostasis and cancer

This short insight covers some of the recent topics relevant to the field of cadherin-catenin adhesion in mediating connections between different cell types, so-called heterotypic or heterocellular connections, in both homeostasis and cancer. These scientific discoveries are increasing our understanding of how multiple cells residing in complex tissues can be instructed by cadherin adhesion receptors to regulate tissue architecture and function and how these cadherin-mediated heterocellular connections spur tumor growth and the acquisition of malignant characteristics in tumor cells. Overall, the findings that have emerged over the past few years are elucidating the complexity of the functional roles of the cadherin-catenin complexes. Future exciting research lies ahead in order to understand the physical basis of these heterotypic interactions and their influence on the behavior of heterogeneous cellular populations as well as their roles in mediating phenotypic and genetic changes as cells evolve through complex environments during morphogenesis and cancer.The Perez-Moreno lab is supported by grants from the Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (ERDF), European Union (BFU2015-71376-R), and the Worldwide Cancer Research UK Foundation (15-1219 to Mirna Perez-Moreno). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes

Epidermal homeostasis is tightly controlled by a balancing act of self-renewal or terminal differentiation of proliferating basal keratinocytes. An increase in DNA content as a consequence of a mitotic block is a recognized mechanism underlying keratinocyte differentiation, but the molecular mechanisms involved in this process are not yet fully understood. Using cultured primary keratinocytes, here we report that the expression of the mammalian microtubule and kinetochore-associated protein Clasp2 is intimately associated with the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation. Clasp2-deficient keratinocytes exhibit increased centrosomal numbers and numerous mitotic alterations, including multipolar spindles and chromosomal misalignments that overall result in mitotic stress and a high DNA content. Such mitotic block prompts premature keratinocyte differentiation in a p53-dependent manner in the absence of cell death. Our findings reveal a new role for Clasp2 in governing keratinocyte undifferentiated features and highlight the presence of surveillance mechanisms that prevent cell cycle entry in cells that have alterations in the DNA content.This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) [BFU2012-33910 and BFU2015-71376-R (MINECO/ European Regional Development Fund (ERDF), European Union) to M.P.-M.]. Deposited in PMC for immediate release.S

Facores de risco de infecção puerperal no Hospital Geral Universitario " Agostinho Neto", Guantánamo 2016-2018

Introduction: the prevention of puerperal infection is a social requirement.Objective: to specify the association between rupture of ovular membranes, cervicovaginal infection and chorioamnionitis and the presentation of puerperal infection in puerperal women attended in the Obstetrics Service of the Hospital Dr. Agostinho Neto during the years 2016-2018.Method: a study was conducted of cases and controls. The universe was formed by all puerperal puerperal infections (n=622), and of the latter a sample was selected for convenience of 60 patients, which constituted the group of cases; a group of patients without puerperal infection (n=120) who formed the control group was chosen. The following variables were studied: age in years, time of rupture of ovular membranes, diagnosis of cervicovaginal infection and chorioamnionitis and birth pathway.Results: ages between 20 and 29 years predominated in cases (41.7%) and controls (48.3%). There was statistically significant evidence, with a reliability of 95%, that the rupture of membranes over 24 hours, cervicovaginal infection and chorioamnionitis were risk factors for puerperal infection. The vaginal route predominated in the cases (60%) and controls (61.7%), which was not statistically significant associated with puerperal infection.Conclusions: puerperal women with ruptured ovular membranes over 24 hours, cervicovaginal infection and chorioamnionitis presented a higher risk of puerperal infection.Introducción: la prevención de la infección puerperal es una exigencia social. Objetivo: precisar la asociación entre rotura de membranas ovulares, infección cervicovaginal y corioamnionitis, y presentación de infección puerperal en puérperas atendidas en el servicio de Obstetricia del Hospital General Docente "Dr. Agostinho Neto" durante los años 2016-2018. Método: se realizó un estudio de casos y controles. El universo se conformó por todas las puérperas con infección puerperal  (n=622), y de estas últimas se seleccionó una muestra por conveniencia de 60 pacientes, las que constituyeron el grupo de casos; y se eligió un grupo de pacientes sin infección puerperal (n=120) que conformaron el grupo control. Se estudiaron las siguientes variables: edad en años, tiempo de rotura de membranas ovulares, diagnóstico de infección cervicovaginal y corioamnionitis y vía del parto.Resultados: predominaron las edades entre 20 y 29 años en los casos (41,7 %) y controles (48,3 %). Existieron evidencias estadísticamente significativas, con una confiabilidad del 95 %, de que la rotura de membranas de más de 24 horas, la infección cervicovaginal y la corioamnionitis fueron factores de riesgo de infección puerperal. Predominó la vía vaginal en los casos (60 %) y controles (61,7  %), que no resultó estadísticamente significativa asociada a la infección puerperal.Conclusiones: las puérperas con rotura de membranas ovulares de más de 24 horas, infección cervicovaginal y corioamnionitis presentaron mayor riesgo de infección puerperal.Introdução: a prevenção da infecção puerperal é uma exigência social.Objetivo: Para esclarecer a associação entre a ruptura de membranas, infecção cérvico-vaginal e corioamnionite e apresentação de infecção puerperal em puérperas atendidas no Departamento de Obstetrícia Dr. Agostinho Neto Hospital durante os anos de 2016-2018.Método: foi realizado um estudo de casos e controles. O universo foi formado por todas as infecções puerperais no puerpério (n=622) e, deste último, uma amostra foi selecionada por conveniência de 60 pacientes, constituindo o grupo de casos; um grupo de pacientes sem infecção puerperal (n=120) que formou o grupo controle foi escolhido. As seguintes variáveis foram estudadas: idade em anos, tempo de ruptura das membranas ovulares, diagnóstico de infecção cervicovaginal e corioamnionite e via de nascimento.Resultados: as idades entre 20 e 29 anos predominaram nos casos (41,7%) e controles (48,3%). Houve evidência estatisticamente significativa, com uma confiança de 95%, que a ruptura das membranas durante mais de 24 horas, a infecção genital do corioamniotite e eram factores de risco infecção puerperal. A via vaginal predominou nos casos (60%) e controles (61,7%), o que não foi estatisticamente significante associado à infecção puerperal.Conclusões: puérperas com ruptura de membranas ovulares por 24 horas, infecção cervicovaginal e corioamnionite apresentaram maior risco de infecção puerperal

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the Second Latinos and Alzheimer's Symposium

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD

Circulating Strains of Human Respiratory Syncytial Virus in Central and South America

Human respiratory syncytial virus (HRSV) is a major cause of viral lower respiratory tract infections among infants and young children. HRSV strains vary genetically and antigenically and have been classified into two broad subgroups, A and B (HRSV-A and HRSV-B, respectively). To date, little is known about the circulating strains of HRSV in Latin America. We have evaluated the genetic diversity of 96 HRSV strains by sequencing a variable region of the G protein gene of isolates collected from 2007 to 2009 in Central and South America. Our results show the presence of the two antigenic subgroups of HRSV during this period with the majority belonging to the genotype HRSV-A2

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The role of a specific response of media in the Vavilov-Cherenkov effect

It is shown that the condition upsilon > upsilon(p) (omega), which is necessary in order to trigger the Vavilov-Cherenkov effect, determines the interval of radiated frequencies and it alone cannot establish a strong restriction to the velocity of the particle. It is exhibited that it is possible to define a general lower bound for the velocity of the particle, which does not depend on the frequency when both, a specific response of the medium is taken into account and the mentioned condition is considered. The minimum value of the phase velocity of light in the medium determines the existence of such general lower bound