Primary cilia as a targetable node between biliary injury, senescence and regeneration in liver transplantation.

BACKGROUND & AIMS: Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly-specialised sensory organelle, in biliary injury leading to post-transplant biliary complications. METHODS: Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (N=7) in comparison with recipients without biliary complications (N=12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERTKif3aflox/flox mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used in vitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers. RESULTS: Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury. CONCLUSIONS: Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation. IMPACT AND IMPLICATIONS: Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.

Unlocking the specificity of antimicrobial peptide interactions for membrane-targeted therapies.

Antimicrobial peptides (AMPs) are increasingly recognized as potent therapeutic agents, with their selective affinity for pathological membranes, low toxicity profile, and minimal resistance development making them particularly attractive in the pharmaceutical landscape. This study offers a comprehensive analysis of the interaction between specific AMPs, including magainin-2, pleurocidin, CM15, LL37, and clavanin, with lipid bilayer models of very different compositions that have been ordinarily used as biological membrane models of healthy mammal, cancerous, and bacterial cells. Employing unbiased molecular dynamics simulations and metadynamics techniques, we have deciphered the intricate mechanisms by which these peptides recognize pathogenic and pathologic lipid patterns and integrate into lipid assemblies. Our findings reveal that the transverse component of the peptide's hydrophobic dipole moment is critical for membrane interaction, decisively influencing the molecule's orientation and expected therapeutic efficacy. Our approach also provides insight on the kinetic and dynamic dependence on the peptide orientation in the axial and azimuthal angles when coming close to the membrane. The aim is to establish a robust framework for the rational design of peptide-based, membrane-targeted therapies, as well as effective quantitative descriptors that can facilitate the automated design of novel AMPs for these therapies using machine learning methods.

Incidence, Risk Factors, and Survival of Bone Metastases and Skeletal-Related Events in Melanoma Patients: A Systematic Review and Quality Assessment of 29 Studies.

Background: Skeletal metastases make up 17% of all metastases from advanced-stage melanoma. Bone metastases are associated with increased morbidity and mortality and decreased quality of life due to their association with skeletal-related events (SREs), including pathological fracture, spinal cord compression, hypercalcemia, radiotherapy, and surgery. The study aimed to determine the incidence of bone metastases and SREs in melanoma, identify possible risk factors for the development of bone metastases and SREs, and investigate survival rates in this patient population. Methods: A computer-based literature search was conducted using Pubmed, Embase, and Cochrane Central Register of Controlled Trials up to July 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was utilized for quality assessment. Study characteristics, patient information, risk factors for developing bone metastases and SREs, and characteristics for survival were recorded. Results: We included 29 studies. The average bone metastasis-free interval ranged from four to 72 months. Incidence of bone metastases varied from 2 % to 49 % across 14 studies. 69 % (20/29) of studies described the location of bone metastases, with 24 % (7/29) focusing solely on spinal metastases. In one study, 129 SREs were recorded in 71 % (59/83) of the patient cohort, with various manifestations. The use of bone-directed agents was independently associated with lower risk of SREs. Survival after detection of bone metastasis ranged from three to 13 months. Factors associated with survival included clinical, tumor-related, and treatment features. Conclusion: This review highlights the notable prevalence and risk factors of developing bone metastases and subsequent SREs in patients with melanoma. The surge in bone metastases poses a challenge in complication management, given the high prevalence of SREs. While this study offers a comprehensive overview of the incidence, risk factors, and outcomes associated with bone metastases and SREs in melanoma patients that may guide patient and physician decision-making, a notable gap lies in the limited availability of high-quality data and the heterogeneous design of the existing literature. Future research should address predictive factors for bone metastases and SREs in melanoma to facilitate patient and physician decision-making and ultimately improve outcomes in this patient population.

Immunotherapy time of infusion impacts survival in head and neck cancer: A propensity score matched analysis.

The adaptive immune response is physiologically regulated by the circadian rhythm. Data in lung and melanoma malignancies suggests immunotherapy infusions earlier in the day may be associated with improved response; however, the optimal time of administration for patients with head and neck squamous cell carcinoma (HNSCC) is not known. We aimed to evaluate the association of immunotherapy infusion time with overall survival (OS) and progression free survival (PFS) in patients with HNSCC in an Institutional Review Board-approved, retrospective cohort study. 113 patients met study inclusion criteria and 98 patients were included in a propensity score-matched cohort. In the full unmatched cohort (N = 113), each additional 20 % of infusions received after 1500 h conferred an OS hazard ratio (HR) of 1.35 (95 % C.I.1.2-1.6; p-value = 0.0003) and a PFS HR of 1.34 (95 % C.I.1.2-1.6; p-value < 0.0001). A propensity score-matched analysis of patients who did or did not receive ≥20 % of infusions after 1500 h showed that those who were administered ≥20 % of infusions after 1500 h trended towards a shorter OS (HR = 1.35; p-value = 0.26) and a shorter PFS (HR = 1.57, 95 % C.I. 1.02-2.42, p-value = 0.04). Each additional 20 % of infusions received after 1500 h remained robust in the matched cohort multivariable analysis and was associated with shorter OS (adjusted HR = 1.4 (95 % C.I.1.2-1.8), p-value < 0.001). Patients with advanced HNSCC who received more of their infusions in the afternoon were associated with shorter OS and PFS and scheduling immunotherapy infusions earlier in the day may be warranted.

Unraveling lipid and inflammation interplay in cancer, aging and infection for novel theranostic approaches.

The synergistic relationships between Cancer, Aging, and Infection, here referred to as the CAIn Triangle, are significant determinants in numerous health maladies and mortality rates. The CAIn-related pathologies exhibit close correlations with each other and share two common underlying factors: persistent inflammation and anomalous lipid concentration profiles in the membranes of affected cells. This study provides a comprehensive evaluation of the most pertinent interconnections within the CAIn Triangle, in addition to examining the relationship between chronic inflammation and specific lipidic compositions in cellular membranes. To tackle the CAIn-associated diseases, a suite of complementary strategies aimed at diagnosis, prevention, and treatment is proffered. Our holistic approach is expected to augment the understanding of the fundamental mechanisms underlying these diseases and highlight the potential of shared features to facilitate the development of novel theranostic strategies.

Comparing the Diagnostic Performance of Quantitative PCR, Digital Droplet PCR, and Next-Generation Sequencing Liquid Biopsies for Human Papillomavirus-Associated Cancers.

Human papillomavirus (HPV)-associated cancers, including oropharyngeal squamous cell carcinoma (HPV + OPSCC), cervical cancer, and squamous cell carcinoma of the anus (HPV + SCCA), release circulating tumor HPV DNA (ctHPVDNA) into the blood. The diagnostic performance of ctHPVDNA detection depends on the approaches used and the individual assay metrics. A comparison of these approaches has not been systematically performed to inform expected performance, which in turn affects clinical interpretation. A meta-analysis was performed using Ovid MEDLINE, Embase, and Web of Science Core Collection databases to assess the diagnostic accuracy of ctHPVDNA detection across cancer anatomic sites, detection platforms, and blood components. The population included patients with HPV + OPSCC, HPV-associated cervical cancer, and HPV + SCCA with pretreatment samples analyzed by quantitative PCR (qPCR), digital droplet PCR (ddPCR), or next-generation sequencing (NGS). Thirty-six studies involving 2986 patients met the inclusion criteria. The sensitivity, specificity, and quality of each study were assessed and pooled for each analysis. The sensitivity of ctHPVDNA detection was greatest with NGS, followed by ddPCR and then qPCR when pooling all studies, whereas specificity was similar (sensitivity: ddPCR > qPCR, P < 0.001; NGS > ddPCR, P = 0.014). ctHPVDNA from OPSCC was more easily detected compared with cervical cancer and SCCA, overall (P = 0.044). In conclusion, detection platform, anatomic site of the cancer, and blood component used affects ctHPVDNA detection and must be considered when interpreting results. Plasma NGS-based testing may be the most sensitive approach for ctHPVDNA overall.

Lactoferrin as a Component of Pharmaceutical Preparations: An Experimental Focus.

Lactoferrin is an 80 kDa monomeric glycoprotein that exhibits multitask activities. Lactoferrin properties are of interest in the pharmaceutical field for the design of products with therapeutic potential, including nanoparticles and liposomes, among many others. In antimicrobial preparations, lactoferrin has been included either as a main bioactive component or as an enhancer of the activity and potency of first-line antibiotics. In some proposals based on nanoparticles, lactoferrin has been included in delivery systems to transport and protect drugs from enzymatic degradation in the intestine, favoring the bioavailability for the treatment of inflammatory bowel disease and colon cancer. Moreover, nanoparticles loaded with lactoferrin have been formulated as delivery systems to transport drugs for neurodegenerative diseases, which cannot cross the blood-brain barrier to enter the central nervous system. This manuscript is focused on pharmaceutical products either containing lactoferrin as the bioactive component or formulated with lactoferrin as the carrier considering its interaction with receptors expressed in tissues as targets of drugs delivered via parenteral or mucosal administration. We hope that this manuscript provides insights about the therapeutic possibilities of pharmaceutical Lf preparations with a sustainable approach that contributes to decreasing the resistance of antimicrobials and enhancing the bioavailability of first-line drugs for intestinal chronic inflammation and neurodegenerative diseases.

Regionalized analysis of gut barrier components in the small intestine of BALB/c mice following chronic immobilization stress.

BACKGROUND: Microbiota and tight junction proteins (TJPs) are components of the gut barrier, and are considered stress targets that have deleterious effects on intestinal homeostasis. OBJECTIVES: This study aimed to evaluate the effects of chronic immobilization stress on selected small intestine homeostasis parameters. MATERIAL AND METHODS: Female BALB/c mice were divided into a stress group that underwent short-term immobilization for 2 h per day for 4 consecutive days, and a non-stressed control group (n = 6 per group). Proximal and distal small intestine samples were excised to assess colony-forming units per gram (CFU/g) of total bifidobacteria in selective agar plates, luminal albumin was assessed using immune-enzymatic assay, pro-inflammatory cytokines were evaluated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and TJPs (pore-forming, claudin (Cld)-2; pore-sealing, Cld-4; ambiguous, Cld-7, -12 and -15) were assessed with RT-qPCR and western blotting. RESULTS: Compared with the control group, the stress group had lower body weight and energy intake. In the distal region, the stressed mice had lower bifidobacteria count and messenger ribonucleic acid (mRNA) expression of Cld-2, Cld-4 and Cld-12, though they had more albumin and higher interleukin (IL)-6 mRNA expression. Within the proximal region, the stressed mice had higher mRNA expression of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), IL-6, Cld-7, Cld-12, and Cld-15, along with lower levels of IL-10 and Cld-4. However, mRNA and protein expression of TJPs were discordant. CONCLUSIONS: These findings indicate divergent stress-induced outcomes in the small intestine, evidenced by the elicitation of a pro-inflammatory response and decreased anti-inflammatory response in the duodenum, and by increased albumin transudation and decreased bifidobacterial growth in the distal region.

Minimally invasive lateral single-position surgery for multilevel degenerative lumbar spine disease: feasibility and perioperative results in a single Latin-American spine center.

INTRODUCTION: Within advances in minimally invasive spine surgery, the implementation of lateral single position (LSP) increases efficiency while limiting complications, avoiding intraoperative repositioning and diminishing surgical time. Most literature describes one-level instrumentation of the lumbar spine; this study includes the use of LSP for multilevel degenerative disease. OBJECTIVE: The objective of the article is to analyze initial clinical results and complications in the use of LSP for multiple level instrumentation in adults with lumbar degenerative disease. METHODS: A retrospective early clinical series was performed for patients who had multiple level instrumentation in LSP between August 2019 and September 2022 at the Hospital Universitario San Ignacio in Bogota, Colombia. Inclusion criteria were patients older than 18 years with symptomatic lumbar degenerative disease, undergoing any combination of multilevel anterior lumbar interbody fusion, lateral lumbar interbody fusion (LLIF) and pedicle screw fixation. RESULTS: Forty patients with an average age of 61.3 years were included, with diagnosis of multilevel degenerative spondylotic changes. Four-, three- and two-level interventions were performed in 52.5, 35 and 12.5%, respectively. Average time per level was 68.9 min, and length of hospital stay had an average of 2.4 days, with all patients starting ambulation within the first postoperative day. CONCLUSION: Procedural time and blood loss were similar to those reported in literature. No severe lesions, postoperative infections or reinterventions took place. Although it was a small number of patients and further clinical trials are needed, LSP for multiple levels is apparently safe with adequate outcomes which may improve efficiency in the operating room.

Ambiente escolar: una necesidad de aprendizaje por el médico de familia / School environment: a learning need for the family doctor

El Ministerio de Salud Pública cubano tiene orientada la realización de los controles médicos a los estudiantes y trabajadores que en su centro no cuentan con equipo básico de salud, en el consultorio médico de la comunidad. En el presente artículo los autores se proponen compartir con la comunidad científica los basamentos teóricos concernientes al proceso de superación, el cual responde a las necesidades de aprendizaje y constituye una vía primordial para que, gradualmente, los médicos de familia coadyuven a la solución de las insuficiencias académicas en determinados temas relacionados con el ambiente escolar y favorezcan el bienestar social desde su desempeño profesional y humano.

The Cuban Ministry of Public Health is oriented to carry out medical controls for students and workers who do not have basic health equipment in their center, in the community doctor's office. In this article the authors intend to share with the scientific community the theoretical foundations concerning the improvement process, which responds to the learning needs and constitutes a primary way for Gps to gradually contribute to the solution of the academic insufficiencies in certain topics related to the school environment and favor social well-being from their professional and human performance.

Long-Term Outcome of Prostatic Artery Embolization for Patients with Benign Prostatic Hyperplasia: Single-Centre Retrospective Study in 1072 Patients Over a 10-Year Period.

PURPOSE: Assess long-term outcomes of prostatic artery embolization (PAE) for patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Single centre retrospective study from 2009-2019 including 1072 patients who received PAE and had available follow-up. Patients were evaluated yearly at 1-10 years post PAE using the International Prostate Symptom Score (IPSS) and quality of life (QoL), prostate volume (PV), prostate-specific antigen (PSA), peak urinary flow rate (Qmax) and postvoid residual (PVR) volume. The need for prostatic medication, re-intervention rates, repeat PAE and prostatectomy rates were assessed with Kaplan-Meier survival analysis and compared between different embolic agents using Cox regression analysis. RESULTS: Mean follow-up time was 4.39 ± 2.37 years. At last follow-up visit, mean IPSS and QoL improvements were - 10.14 ± 8.34 (p < .0001) and - 1.87 ± 1.48 (p < .0001) points, mean PV reduction was - 6.82 ± 41.11 cm3 (p = 0.7779), mean PSA reduction was - 1.12 ± 4.60 ng/mL (p = 0.9713), mean Qmax increase was 2.72 ± 6.38 mL/s (p = 0.0005), mean PVR reduction was - 8.35 ± 135.75 mL (p = 0.6786). There were 335 patients (31.3%) needing prostatic medication after PAE. Re-intervention rates were 3.4% at 1 year, 21.1% at 5 years and 58.1% at 10 years. Repeat-PAE rates were 2.3% at 1 year, 9.5% at 5 years and 23.1% at 10 years. Prostatectomy rates were 1.1% at 1 year, 11.6% at 5 years and 35.0% at 10 years. No significant differences were found between polyvinyl alcohol particles, Bead Block, Embospheres and Embozenes. CONCLUSION: PAE induces durable long-term LUTS relief, with re-intervention rates of 20% in the first 5 years and 30%-60% > 5 years post-PAE.

Microbiota y sepsis

La sepsis es la respuesta desordenada del organismo a la infección y se caracteriza por un daño a los órganos que puede ser irreversible y mortal. El microbioma intestinal regula a un grupo de mecanismos homeostáticos en el huésped, como la función inmunológica y la protección de la barrera intestinal, la pérdida de la estructura y la función microbiana intestinal normal; además, se ha asociado con el inicio de enfermedades de características diversas. La evidencia reciente ha demostrado un nexo entre el microbioma intestinal y la sepsis: la alteración del microbioma intestinal aumenta la susceptibilidad a la sepsis a través de varios mecanismos como la expansión de bacterias intestinales patógenas, la respuesta proinflamatoria marcada y la disminución de la formación de productos microbianos beneficiosos como los ácidos grasos de cadena corta. Una vez establecida la sepsis, la alteración del microbioma intestinal empeora y aumenta la susceptibilidad a la disfunción del órgano terminal. Existen pruebas limitadas de que las terapias basadas en microbiomas (que incluyen a probióticos y a la descontaminación digestiva selectiva) pueden disminuir el riesgo de sepsis y mejorar sus resultados en poblaciones de pacientes seleccionadas, pero las preocupaciones sobre la seguridad causan una aceptación limitada. Si bien gran parte de la evidencia que vincula el microbioma intestinal y la sepsis se ha establecido en estudios preclínicos, aún es necesaria la evidencia clínica en distintas áreas.

Sepsis is the body's overwhelming response to an infection. It is characterized by damage to the organs that may be irreversible and life-threatening. The gastrointestinal microbiome regulates a series of homeostatic mechanisms in the host, such as the immune function and the protection of the intestinal barrier, and the loss of normal intestinal microbial structure and function. Moreover, it has been associated with the onset of diseases of diverse characteristics. Recent evidence has shown a link between the gastrointestinal microbiome and sepsis: the alteration of the gastrointestinal microbiome increases the susceptibility to sepsis through various mechanisms, including the expansion of pathogenic intestinal bacteria, marked pro-inflammatory response and decreased production of beneficial microbial products such as short-chain fatty acids. Once sepsis is established, the alteration of the gastrointestinal microbiome worsens and the susceptibility to end-organ dysfunction increases. There is limited evidence that microbiome-based therapies, which include probiotics and selective digestive decontamination, can decrease the risk of sepsis and improve its outcomes in selected patient populations. However, safety concerns generate limited acceptance. While much of the evidence linking the gastrointestinal microbiome and sepsis has been established in preclinical studies, clinical evidence is still necessary in many areas.

Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease.

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.

Binational survey of personal protective equipment (PPE) pollution driven by the COVID-19 pandemic in coastal environments: Abundance, distribution, and analytical characterization.

In the present contribution, two nationwide surveys of personal protective equipment (PPE) pollution were conducted in Peru and Argentina aiming to provide valuable information regarding the abundance and distribution of PPE in coastal sites. Additionally, PPE items were recovered from the environment and analyzed by Fourier transformed infrared (FTIR) spectroscopy, Scanning electron microscopy (SEM) with Energy dispersive X-ray (EDX), and X-ray diffraction (XRD), and compared to brand-new PPE in order to investigate the chemical and structural degradation of PPE in the environment. PPE density (PPE m-2) found in both countries were comparable to previous studies. FTIR analysis revealed multiple polymer types comprising common PPE, mainly polypropylene, polyamide, polyethylene terephthalate, and polyester. SEM micrographs showed clear weathering signs, such as cracks, cavities, and rough surfaces in face masks and gloves. EDX elemental mapping revealed the presence of elemental additives, such as Ca in gloves and face masks and AgNPs as an antimicrobial agent. Other metals found on the surface of PPE were Mo, P, Ti, and Zn. XRD patterns displayed a notorious decrease in the crystallinity of polypropylene face masks, which could alter its interaction with external contaminants and stability. The next steps in this line of research were discussed.

Female Mice with Selenocysteine tRNA Deletion in Agrp Neurons Maintain Leptin Sensitivity and Resist Weight Gain While on a High-Fat Diet.

The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis. There is also evidence that selenium supports leptin signaling in the hypothalamus by maintaining proper redox balance. In this study, we generated mice with conditional knockout of the selenocysteine tRNA[Ser]Sec gene (Trsp) in an orexigenic cell population called agouti-related peptide (Agrp)-positive neurons. We found that female TrspAgrpKO mice gain less weight while on a high-fat diet, which occurs due to changes in adipose tissue activity. Female TrspAgrpKO mice also retained hypothalamic sensitivity to leptin administration. Male mice were unaffected, however, highlighting the sexually dimorphic influence of selenium on neurobiology and energy homeostasis. These findings provide novel insight into the role of selenoproteins within a small yet heavily influential population of hypothalamic neurons.

Sucrose-Responsive Intercommunicated Janus Nanoparticles Network.

Inspired by biological systems, the development of artificial nanoscale materials that communicate over a short distance is still at its early stages. This work shows a new example of a cooperating system with intercommunicated devices at the nanoscale. The system is based on the new sucrose-responsive Janus gold-mesoporous silica (Janus Au-MS) nanoparticles network with two enzyme-powered nanodevices. These nanodevices involve two enzymatic processes based on invertase and glucose oxidase, which are anchored on the Au surfaces of different Janus Au-MS nanoparticles, and N-acetyl-L-cysteine and [Ru(bpy)3]2+ loaded as chemical messengers, respectively. Sucrose acts as the INPUT, triggering the sequential delivery of two different cargoes through the enzymatic control. Nanoscale communication using abiotic nanodevices is a developing potential research field and may prompt several applications in different disciplines, such as nanomedicine.

La educación antisísmica con estudiantes de medicina a través de un proyecto comunitario / Anti-seismic education of medical students through a community project

La prevención ante los desastres acaecidos por sismos constituye una problemática en determinadas regiones vulnerables en Cuba, y una prioridad en la formación de estudiantes de medicina. En este trabajo, las opiniones de los autores se fundamentan en la influencia que tiene un proyecto comunitario, para actuar ante situaciones sísmicas, en la preparación de los estudiantes de medicina, pues favorece una mayor calidad profesional y contribuye a enriquecer su labor preventiva con la población. Como parte del proceso, participaron 46 estudiantes de cuarto año de la Facultad de medicina No. 1, de Santiago de Cuba, en el período comprendido entre septiembre de 2016 a febrero de 2018(AU)

Prevention of earthquake disasters is a problem in certain vulnerable regions of Cuba, and a priority in the training of medical students. In this work, the authors' opinions are based on the influence that a community project has, to act in seismic situations, in the preparation of medical students, since it favours a higher professional quality and contributes to enriching their preventive work with population. As part of the process, 46 fourth-year students from the Faculty of Medicine No. 1, Santiago de Cuba, participated in the period from September 2016 to February 2018(AU)

Modulação autonômica da frequência cardíaca em crianças e jovens com paralisia cerebral / Autonomic heart rate modulation in children and youths with cerebral palsy

Introdução: A paralisia cerebral é uma doença que causa distúrbios neuromusculares, doenças cardiovasculares, além de distúrbios autonômicos e homeostáticos. Objetivo: Avaliar a modulação autonômica cardíaca de crianças e jovens com PC. Métodos: Estudo de delineamento transversal e observacional de carácter quantitativo. Foram coletados os intervalos R-R (IRR) do eletrocardiograma de 05 voluntários cadeirantes, com idade de 06 a 18 anos com PC através do cardiofrequencimetro Polar modelo V800®. Resultados: Idade média foi de 12,4 anos, ambos os gêneros, massa corpórea de 35,1 kg, estatura de 1,39 m e índice de massa corpórea 16,8 kg/m2 equivalente à desnutrição. Os dados apresentam a modulação autonômica cardíaca no domínio do tempo, as variáveis do desvio-padrão de todos os intervalos RR normais 60,0 ms, raiz-quadrada da média da soma dos quadrados das diferenças entre os IRR normais 60,3 ms, porcentagem dos IRR adjacentes maiores que 50 ms 16,1 % e no domínio da frequência a baixa frequência cardíaca (un) 55,7, a alta frequência cardíaca (un) 44,2, a razão da alta com a baixa frequência cardíaca 2,3. Conclusão: As crianças e adolescentes com paralisia cerebral têm uma baixa variabilidade da frequência cardíaca, com alta probabilidade de desenvolver doenças cardiovasculares, devido ao sedentarismo. (AU)

Introduction: Cerebral Palsy is a disease that causes neuromuscular disorders, cardiovascular diseases, in addition to disorders autonomic and homeostatic. Objective: To measure the cardiac autonomic modulation of children and young people with CP. Methods: Quantitative crosssectional and observational study. The electrocardiogram R-R intervals (IRR) were collected from 05 volunteers in wheelchairs, aged 6 to 18 years with CP through the cardiofrequencimeter Polar model V800®. Results: The average age is 12.4 years, both genders, body mass 35.1 kg, height 1.39 m and body mass index of 16.8 kg/m2 equivalent to malnutrition. The data show cardiac autonomic modulation in the time domain, the standard deviation variables of all normal RR intervals 60.0 ms, square root of the mean of the sum of squares of the differences between normal IRR 60.3 ms, percentage of adjacent IRR greater than 50 ms 16.1% and in the frequency domain, low heart rate (un) 55.7, high heart rate (un) 44.2, the ratio of discharge to low heart rate 2,3. Conclusion: Children and adolescents with cerebral palsy have a low heart rate variability, with a greater probability of developing cardiovascular diseases, due to sedentary lifestyle. (AU)

Aspectos epidemiológicos de pacientes vitimados de escalpelamento assistidos em um hospital referência na Região Amazônica / Epidemiological aspects of scalping victims attended at a hospital in the Amazon Region

Introdução: O escalpelamento é trauma que causa ferimentos e lesões por avulsão parcial ou total do couro cabeludo, provocado, principalmente, pelo contato acidental dos cabelos compridos com o eixo do motor comumente utilizado em embarcações da Região Amazônica. Objetivo: Analisar o perfil epidemiológico de pacientes internados vítimas de escalpelamento assistidos em um hospital de referência materno infantil da Região Amazônica. Métodos: Tratase de um estudo epidemiológico, transversal, retrospectivo, documental, quantitativo realizado em hospital de referência às vítimas de escalpelamento, atendidos no período de janeiro de 2016 a dezembro de 2018. Após triagem inicial dos prontuários, 40 se enquadraram nos critérios de inclusão. Resultados: Em relação aos dados sociodemográficos, constatou-se no total de prontuários a prevalência do sexo feminino (97,5%), sendo sua maioria proveniente da mesorregião do Marajó (47,5%), tendo como principal característica o escalpelamento total (65,0%) por eixo de motor (95,0%). Dentre as complicações encontradas, a infecção oriunda do escalpelamento apresentou percentual de 12,5% (<0,001). Em relação aos procedimentos cirúrgicos, com 17,5%, a reconstrução do pavilhão auricular e trepanação apresentaram maior relevância (<0,001). Conclusão: Pode-se observar que as vítimas de escalpelamento passam longos períodos em tratamento e acompanhamento, implicando em um longo processo de hospitalização sendo submetidas a diversas intervenções cirúrgicas operatórias reparadoras e plásticas. Além disso, a extensividade do tratamento pode causar traumas devido às alterações anatomofisiológicas craniofacial. (AU)

Introduction: Scalping is trauma that causes injuries due to partial or total avulsion of the scalp, caused mainly by the accidental contact of long hair with the motor shaft commonly used in vessels in the Amazon region. Objective: To analyze the epidemiological profile of scalpel victims assisted at a maternal and child referral hospital in the Amazon region. Methods: This is an epidemiological, cross-sectional, retrospective, documentary, quantitative study conducted in a referral hospital for scalpel victims, from January 2016 to December 2018. After initial screening of medical records, 40 patients met the inclusion criteria. Results: Regarding the sociodemographic data, the prevalence of females (97.5%) was found in all medical records, most of them coming from the mesoregion of Marajó (47.5%), having as main characteristic the total scalping (65.0%) per motor axis (95.0%). Among the complications found, the infection resulting from scalping presented a percentage of 12.5% (<0.001). Regarding the surgical procedures, with 17.5%, the reconstruction of the pinna and trepanning were more relevant (<0.001). Conclusion: Scalping victims spend long periods of treatment and follow-up, implying a long hospitalization process and undergoing various repair and plastic surgical interventions. In addition, the extensiveness of the treatment can cause trauma due to craniofacial and anatomophysiological changes. (AU)

Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni.

Schistosomiasis is a neglected disease caused by helminth flatworms of the genus Schistosoma, affecting over 240 million people in more than 70 countries. The treatment relies on a single drug, praziquantel, making urgent the discovery of new compounds. Aurones are a natural type of flavonoids that display interesting pharmacological activities, particularly as chemotherapeutic agents against parasites. In pursuit of treatment alternatives, the present work conducted an in vitro and in vivo antischistosomal investigation with aurone derivatives against Schistosoma mansoni. After preparation of aurone derivatives and their in vitro evaluation on adult schistosomes, the three most active aurones were evaluated in cytotoxicity and haemolytic assays, as well as in confocal laser-scanning microscope studies, showing tegumental damage in parasites in a concentration-dependent manner with no haemolytic or cytotoxic potential toward mammalian cells. In a mouse model of schistosomiasis, at a single oral dose of 400 mg/kg, the selected aurones showed worm burden reductions of 35% to 65.0% and egg reductions of 25% to 70.0%. The most active thiophenyl aurone derivative 18, unlike PZQ, had efficacy in mice harboring juvenile S. mansoni, also showing significant inhibition of oviposition by parasites, giving support for the antiparasitic potential of aurones as lead compounds for novel antischistosomal drugs.