Embryo development is impaired by sperm mitochondrial-derived ROS

Background Basal energetic metabolism in sperm, particularly oxidative phosphorylation, is known to condition not only their oocyte fertilising ability, but also the subsequent embryo development. While the molecular pathways underlying these events still need to be elucidated, reactive oxygen species (ROS) could have a relevant role. We, therefore, aimed to describe the mechanisms through which mitochondrial activity can influence the first stages of embryo development. Results We first show that embryo development is tightly influenced by both intracellular ROS and mitochondrial activity. In addition, we depict that the inhibition of mitochondrial activity dramatically decreases intracellular ROS levels. Finally, we also demonstrate that the inhibition of mitochondrial respiration positively influences sperm DNA integrity, most likely because of the depletion of intracellular ROS formation. Conclusion Collectively, the data presented in this work reveals that impairment of early embryo development may result from the accumulation of sperm DNA damage caused by mitochondrial-derived ROS.

Escala de Respuestas Emocionales por Estrés al Traslado en Transporte Público / Scale of Emotional Responses due to Commuting Stress in Public Transport

Resumen El traslado cotidiano entre la casa y el trabajo demanda un importante uso de recursos personales y puede llegar a ser estresante. El objetivo fue construir y evaluar una escala de respuestas emocionales por el estrés en el traslado en transporte público para la Zona Metropolitana del Valle de México de manera exploratoria. Método: Se realizó un estudio cualitativo a través de entrevistas semi estructuradas con el propósito de identificar emociones asociadas a la experiencia de estrés por el traslado para desarrollar los reactivos de acuerdo con el contexto. Posteriormente, dos estudios cuantitativos permitieron evaluar las propiedades psicométricas. Participaron 196 y 298 personas respectivamente. La aplicación de la escala se realizó en línea en septiembre de 2020 y abril de 2021. Resultados: la escala incluyó 26 respuestas emocionales asociadas al estrés. En el Análisis Factorial Exploratorio se redujo a nueve emociones negativas (X2=1183, gl=36, p=.001, KMO=.94, 60% de varianza explicada, Alfa ordinal=.93), corroboradas en el Análisis Factorial Confirmatorio (X2=41.87, gl=26, X2/gl=1.61, p=.025; RMR=.036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conclusión: la propuesta exploratoria de la escala para evaluar las respuestas emocionales por el estrés en el traslado presenta valores adecuados para aplicarse en la Zona Metropolitana del Valle de México.

Abstract The stress in urban settings is related to a greater request for personal resources to face situations of daily life, such as the commuting, since in big cities, people spend a lot of time on it, and sometimes is uncomfortable and annoying, which can cause stress. Commuting stress has been assessed, through commuting daily hassles, commuting stressful features and physiological responses, but it is possible assess it through emotional responses. The aim of this study was to develop and assess an exploratory scale of emotional responses for the study of commuting stress by public transport in an urban area of México that is densely populated. Method, a cross sectional design was used, in which a qualitative exploratory study was carried out through 23 individual semi-structured interviews and two focus group, where it was identified the main emotions experienced during the commuting stress to develop the items in the language of the population. Subsequently, those emotions were compared with emotions proposed in previous studies to complement the scale. Thus, 26 emotions were included to assess the commuting stress through emotional responses. Finally, two quantitative studies were carried out to assess the psychometric properties of the scale, in which 196 and 298 people participated, respectively. The scale was applied online in September 2020 and in April 2021. Results, from the 26 emotional stress responses were reduced to nine negative emotions in an Exploratory Factor Analysis (X2=1183, df=36, p=.001, KMO= .94, 60% variance, Alfa ordinal=.93). This solution was corroborated with a Confirmatory Factor Analysis (X2=41.87, d.f.=26, X2/d.f.=1.61, p=.025; RMR= .036, SRMR=.036, RMSEA=.045; GFI=.997, CFI=.999, TLI=.998). Conserve only nine negative emotions is due to statistical analysis but also because some emotions referred to conditions of physical exhaustion or body energy level. On the other hand, positive emotions were related with pleasant commuting situations, not with the commuting stress experience. Conclusion, the exploratory scale to assess the commuting stress through emotional responses presents acceptable values to be applied in this urban area of Mexico.

Evaluación de la capacidad de centrado y transporte apical de los sistemas Reciproc Blue y XP-endo Shaper / Evaluation of the centering and apical transport capacity of Reciproc Blue and XP-endo Shaper systems

Resumen Objetivo: Comparar la capacidad de centrado y el transporte apical de los sistemas Reciproc Blue y XP-endo Shaper en bloques de resina con fotografías pre y posoperatorias yuxtapuestas, mediante un programa de análisis de imágenes. Materiales y Métodos: Se dividieron al azar 20 tacos de resina en dos grupos (n=10) preparados con XP-endo Sha- per y Reciproc Blue respectivamente. Se tomaron fotografías digitales de los tacos, antes y después de la preparación con cada sistema en una misma posición. Luego las fotografías obtenidas fueron yuxtapuestas mediante el software Photo shop. Se midieron las desviaciones del centro del conducto con respecto a la pared interna y externa del mismo en diversos puntos de referencia preestablecidos. Estos datos fueron analizados estadísticamente con el test de ANOVA. Resultados: Ambos sistemas produjeron transporte y desviación respecto a la trayectoria original del conducto radicular, pero el análisis estadístico (ANOVA Factorial 2x8) no cuantificó diferencias significativas entre ambos sistemas (p=0,4044) Conclusiones: Bajo las condiciones de este trabajo, ambos sistemas producen transporte y desviación respecto a la trayectoria original del conducto radicular.

Abstract Aim: To compare the centering capacity and apical transport of the Reciproc Blue and X-Pendo Shaper system in resin blocks with juxtaposed pre and postoperative photographs, using the Photoshop software. Materials and methods: 20 resin plugs were randomly divided into two groups (n=10) that were prepared with XP-endo Shaper and Reciproc Blue respectively. Digital photographs of the blocks were taken, before and after preparation, with each system in the same position. Then the obtained photographs were juxtaposed using Photoshop software. The deviations of the center of the canal, with respect to its inter nal and external wall, were measured at various pre-established reference points. These data were statistically analysed with the ANOVA test. Results: Both systems produced transport and deviation from the original trajectory of the root canal, but the statistical analysis (2x8 Factorial ANOVA) did not quantify significant differences between both systems (p=0.4044) Conclusions: Under the conditions of this work, both systems produce transport and deviation with respect to the original trajectory of the root canal.

Influence of garlic extract on larval performance and survival of juvenile angelfish Pterophyllum scalare during transport / Influência do extrato de alho no desempenho larval e na sobrevivência durante o transporte de juvenis de acará bandeira Pterophyllum scalare

Abstract The objective of this study was to evaluate the properties of garlic as a growth promoter in larvae of angelfish Pterophyllum scalare and its benefits during transport of juveniles of this species. The experiment was conducted in recirculation aquaculture system, consisting of 20 tanks of 40 L equipped with independent water input and output. We used 1,400 larvae distributed among five treatments, with four repetitions, which totaled 20 experimental units. The treatments were 0, 50, 100, 200, and 400 mg of garlic extract per kilo of feed. The results showed that the inclusion of levels of garlic extract in the feed did not significantly effect the fish's development or their transport. Neither did the inclusion of levels of garlic extract affect the survival of the larvae during the trial period. New research with extracts of higher dosages should be performed to elucidate the effect of garlic extract as a growth promoter.

Resumo O estudo teve como objetivo avaliar as propriedades do alho como promotor de crescimento em larvas de acará bandeira Pterophyllum scalare e seus benefícios no transporte de juvenis da mesma espécie. O experimento foi conduzido em sistema de recirculação composto por 20 aquários de 40 L de volume útil, dotado de entrada e saída de água independentes e teve a duração de 40 dias. O delineamento experimental adotado foi o inteiramente casualizado (DIC), com cinco tratamentos e quatro repetições, totalizando 20 unidades experimentais. Foram utilizadas 1.400 larvas de acará bandeira (Pterophyllum scalare) divididas entre os tratamentos. Os tratamentos consistiram em: 0, 50, 100, 200 e 400 mg de extrato de alho por quilo de ração. Os resultados mostraram que não houve efeito significativo dos níveis de inclusão do extrato do alho sobre os índices zootécnicos avaliados e posteriormente no transporte dos juvenis. Também não foi observado influência na sobrevivência das larvas durante o período experimental. Novas pesquisas com dosagens maiores de extratos devem ser realizados para melhor elucidação do efeito do extrato de alho como promotor de crescimento.

The application value of tibial transverse transport microvascular reconstruction combined with antibiotic bone cement in the limb salvage of diabetic foot / 中国医师进修杂志

Objective:To analyze the application value of tibial transverse transport (TTT) microvascular reconstruction combined with antibiotic bone cement in the limb salvage of diabetic foot.Methods:Seventy-seven patients with diabetic foot admitted to the Traditional Chinese Medicine Hospital of Zhongshan from January 2018 to January 2021 were enrolled retrospectively, and they were divided into the control group (performed TTT microvascular reconstruction, 47 cases) and the combined group (performed TTT microvascular reconstruction combined with antibiotic bone cement, 30 cases) according to the surgical method. Wound healing rate, limb salvage rate, the ulcer healing time, bone window healing time, wound infection control status, affected side lower limb vascular blood supply situation, and peripheral nerve function recovery were compared between the two groups.Results:The amputation rate between the two groups had no significant difference ( P>0.05), but the healing rate in the combined group was higher than that in the control group: 90.00%(27/30) vs. 68.08%(32/47); and the ulcer healing time, bone window healing time in the combined group were shorter than those in the control group: (12.55 ± 2.14) weeks vs. (15.01 ± 3.17) weeks, (17.47 ± 2.09) weeks vs. (19.00 ± 2.58) weeks, there were statistical differences ( P<0.05). The positive percentage of bacteria culture in wound secretions in the combined group after the surgery for 6 d was lower than that in the control group: 20.00%(6/30) vs. 44.68%(21/47), there was statistical difference ( P<0.05). After the surgery for 3 months, the dorsal skin temperature and ankle brachial index in the combined group were higher than those in the control group: (31.05 ± 1.74) ℃ vs. (29.27 ± 1.66) ℃, 0.93 ± 0.29 vs. 0.80 ± 0.19, there were statistical differences ( P<0.05), but the scores of visual analog scale (VAS) and 10 g nylon line test values between the two groups had no significant differences ( P>0.05). Conclusions:TTT combined with antibiotic bone cement can achieve better wound healing and infection control effect in the limb salvage of diabetic foot, and the blood supply improvement of the affected limb is more significant.

Clinical value of neonatal transport team participating in the management of twin neonates before transport / 中国小儿急救医学

Objective:To investigate and analyze the necessity and clinical significance of professional neonatal transport team participating in post-natal resuscitation, management and transport of twin neonates after birth.Methods:A total of 298 cases of twin neonates admitted to the Department of Neonatology at the Fifth Medical Center of PLA General Hospital from January 2017 to December 2021 were selected.According to whether the neonatal transport team participated in birth resuscitation and management, they were divided into participation group ( n=136) and case group ( n=162). The resuscitation measures taken after birth, Apgar score, respiratory support during transport, basic information at admission, the first arterial blood gas after admission, complications during hospitalization, length of stay and outcome of the two groups of twins were retrospectively analyzed. Results:Compared with twins in case group, the proportion of tracheal intubation before transport was significantly higher in participation group(5.88% vs.0.62%, χ2=6.997, P=0.013), hospital admissions were significantly shorter[48(7, 115) min vs.87(47, 425) min, Z=-11.593, P<0.001], and significantly lower rates of hypoxia on admission(9.56% vs.17.90%, χ2=4.250, P=0.039), significantly higher percutaneous oxygen saturation[96(86, 100)% vs.95(85, 100)%, Z=-7.274, P<0.001], and higher blood-gas-oxygen partial pressure on admission[(91.02±25.77)mmHg vs.(87.82±25.23)mmHg, t=1.076, P=0.008] were found.The incidence of hypothermia on admission was significantly lower(36.03% vs.47.53%, χ2=4.008, P=0.045), and the differences between two groups were statistically significant( P<0.05). The proportion of critically ill neonates(40.44% vs.24.07%, χ2=9.172, P=0.002), length of hospital-stay[11(4, 76)d vs.9(3, 72) d, Z=-2.684, P=0.014] as well as the intravenous nutrition time[7(0, 42)d vs.5(0, 40) d, Z=-2.470, P=0.014] in participaton group were significantly higher than those in case group, and there were statistically significant differences between two groups( P<0.05). Conclusion:Professional neonatal transport teams play a positive role in neonatal resuscitation and later hospitalization during the pre-transport management of twin neonates.It can improve success rate of tracheal intubation in asphyxia resuscitation of twin neonates.Neonatal transport to the NICU for management takes less time, reducing the incidence of hypoxemia during transport, hypoxia status and hypothermia after admission.Obstetric pediatric medical staff in midwifery hospitals should strengthen the professional training of neonatal asphyxiation resuscitation, improve the skill of neonatal asphyxiation resuscitation and tracheal intubation, and strengthen the post-birth care for twin neonates.

Research progress on the structure and function of the type IX secretion system of Porphyromonas gingivalis / 口腔疾病防治

@#The Porphyromonas gingivalis type IX secretion system (T9SS) is a recently discovered protein secretion system that is widely distributed in Bacillus cereus. The T9SS is structurally complex and powerful. More than 20 T9SS components have been verified, and more than 30 virulence factors can be secreted by Porphyromonas gingivalis alone, which contributes significant to the pathogenicity of Porphyromonas gingivalis. T9SS is a large protein complex spanning the inner cell membrane, periplasm, and outer cell membrane. Through the structural and functional connections among its components, it forms a sophisticated functional complex that includes power provision, energy transduction, inner and outer membrane translocation, outer membrane modification, and regulatory systems to recognize, translocate, shear, and modify cargo proteins and translocate bacterial intracellular cargo proteins to the cell surface. In recent years, with advancements in X-ray diffraction and in situ cryoelectron microscopy, the exploration of T9SS has evolved from the functional study of single components to the in situ structural study of multiprotein complexes. Still, the structural resolution of the protein still has shortcomings such as low resolution and an inability to capture dynamic functional structures. Future research directions should focus more on exploring how T9SS interacts and functions with cargo proteins. In this paper, we review the research progress on Porphyromonas gingivalis T9SS on X-ray diffraction and cryoelectron microscopy structure resolution in order to gain a deeper understanding of the transport mechanism of T9SS.

The modulation and mechanisms of high-altitude hypoxia in drug transport across the blood-brain barrier / 药学学报

The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

The feasibility of oral targeted drug delivery: Gut immune to particulates?

Targeted drug delivery is constantly updated with a better understanding of the physiological and pathological features of various diseases. Depending on high safety, good compliance and many other undeniable advantages, attempts have been undertaken to complete an intravenous-to-oral conversion of targeted drug delivery. However, oral delivery of particulates to systemic circulation is highly challenging due to the biochemical aggressivity and immune exclusion in the gut that restrain absorption and access to the bloodstream. Little is known about the feasibility of targeted drug delivery via oral administration (oral targeting) to a remote site beyond the gastrointestinal tract. To this end, this review proactively contributes to a special dissection on the feasibility of oral targeting. We discussed the theoretical basis of oral targeting, the biological barriers of absorption, the in vivo fate and transport mechanisms of drug vehicles, and the effect of structural evolution of vehicles on oral targeting as well. At last, a feasibility analysis on oral targeting was performed based on the integration of currently available information. The innate defense of intestinal epithelium does not allow influx of more particulates into the peripheral blood through enterocytes. Therefore, limited evidence and lacking exact quantification of systemically exposed particles fail to support much success with oral targeting. Nevertheless, the lymphatic pathway may serve as a potentially alternative portal of peroral particles into the remote target sites via M-cell uptake.

Mechanism of gigantol in transmembrane transport in human lens epithelial cells / 中国中药杂志

Gigantol is a phenolic component of precious Chinese medicine Dendrobii Caulis, which has many pharmacological activities such as prevent tumor and diabetic cataract. This paper aimed to investigate the molecular mechanism of gigantol in transmembrane transport in human lens epithelial cells(HLECs). Immortalized HLECs were cultured in vitro and inoculated in the laser scanning confocal microscopy(LSCM) medium at 5 000 cells/mL. The fluorescence distribution and intensity of gigantol marked by fluorescence in HLECs were observed by LSCM, and the absorption and distribution of gigantol were expressed as fluorescence intensity. The transmembrane transport process of gigantol in HLECs were monitored. The effects of time, temperature, concentration, transport inhibitors, and different cell lines on the transmembrane absorption and transport of gigantol were compared. HLECs were inoculated on climbing plates of 6-well culture plates, and the ultrastructure of HLECs was detected by atomic force microscopy(AFM) during the transmembrane absorption of non-fluorescent labeled gigantol. The results showed that the transmembrane absorption of gigantol was in time and concentration-dependent manners, which was also able to specifically target HLECs. Energy and carrier transport inhibitors reduced gigantol absorption by HLECs. During transmembrane process of gigantol, the membrane surface of HLECs became rougher and presented different degrees of pits, indicating that the transmembrane transport of gigantol was achieved by active absorption of energy and carrier-mediated endocytosis.

Application of transport ventilator in the inter-hospital transport of critically ill children / 中国当代儿科杂志

OBJECTIVES@#To study the application value of transport ventilator in the inter-hospital transport of critically ill children.@*METHODS@#The critically ill children in Hunan Children's Hospital who were transported with or without a transport ventilator were included as the observation group (from January 2019 to January 2020; n=122) and the control group (from January 2018 to January 2019; n=120), respectively. The two groups were compared in terms of general data, the changes in heart rate, respiratory rate, and blood oxygen saturation during transport, the incidence rates of adverse events, and outcomes.@*RESULTS@#There were no significant differences between the two groups in sex, age, oxygenation index, pediatric critical illness score, course of disease, primary disease, heart rate, respiratory rate, and transcutaneous oxygen saturation before transport (P>0.05). During transport, there were no significant differences between the two groups in the changes in heart rate, respiratory rate, and transcutaneous oxygen saturation (P>0.05). The incidence rates of tracheal catheter detachment, indwelling needle detachment, and sudden cardiac arrest in the observation group were lower than those in the control group during transport, but the difference was not statistically significant (P>0.05). Compared with the control group, the observation group had significantly shorter duration of mechanical ventilation and length of stay in the pediatric intensive care unit and significantly higher transport success rate and cure/improvement rate (P<0.05).@*CONCLUSIONS@#The application of transport ventilator in the inter-hospital transport can improve the success rate of inter-hospital transport and the prognosis in critically ill children, and therefore, it holds promise for clinical application in the inter-hospital transport of critically ill children.

Competencies for aeromedical evacuation practices in emergencies and disasters: a scoping review / Competencias para prácticas de evacuación aeromédica en emergencias y desastres: revisión del alcance / Competências para práticas de evacuações aeromédicas em emergências e desastres: revisão de escopo

ABSTRACT Objective: to map the competencies developed in training strategies for air transport practices for patients, in the face of emergency situations and disasters involving chemical, biological, radiological and nuclear (CBRN) agents. Method: this is a scoping review structured in accordance with the JBI and Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews recommendations. The study was carried out in five stages: search for sources in 17 databases, an information portal and two repositories of gray literature, using 125 DeCS, MeSH and Emtree descriptors, without temporal and idiomatic clipping; selection; critical reading of the texts selected by two double-blind reviewers; summary of results and presentation of mapped competencies. Results: a total of 878 studies were analyzed, of which 18 composed the sample. In all, 11 competencies were mapped, with emphasis on the technical training domain. Competencies refer especially to technical-scientific knowledge in disaster situations involving CBRN agents and the safety of patients and professionals involved. Conclusion: the operationalization of artifices to improve qualification processes based on competencies proved to be strategic to increase the quality and safety of patient air transport practices. The approach of the sources on specific aspects of the particularities of practices related to emergencies and disasters involving CBRN agents in training/training processes demonstrates the academic effort to promote the reduction of the risk of these events when, in due course, civil and military institutions and their health operators are activated.

RESUMEN Objetivo: mapear las competencias desarrolladas en estrategias de formación en prácticas de transporte aéreo de pacientes, ante situaciones de emergencia y desastres con agentes químicos, biológicos, radiológicos y nucleares (QBRN). Método: una revisión de alcance estructurada de acuerdo con las recomendaciones del JBI y la lista de verificación Elementos de informe preferidos para revisiones sistemáticas y la extensión Metanalyses para revisiones de alcance. El estudio se realizó en cinco etapas: búsqueda de fuentes en 17 bases de datos, un portal de información y dos repositorios de literatura gris, utilizando 125 descriptores DeCS, MeSH y Emtree, sin recorte temporal e idiomático; selección; lectura crítica de los textos seleccionados por dos revisores doble ciego; resumen de resultados y presentación de competencias mapeadas. Resultados: se analizaron 878 estudios, de los cuales 18 compusieron la muestra. En total, se mapearon 11 competencias, con énfasis en el dominio de formación técnica. Las competencias se refieren especialmente al conocimiento técnico-científico en situaciones de desastres que involucran a agentes QBRN y la seguridad de los pacientes y profesionales involucrados. Conclusión: la operacionalización de artificios para mejorar los procesos de calificación basados ​​en competencias demostró ser estratégica para aumentar la calidad y seguridad de las prácticas de transporte aéreo de pacientes. El abordaje de las fuentes sobre aspectos específicos de las particularidades de las prácticas relacionadas con emergencias y desastres que involucran a agentes QBRN en los procesos de formación/capacitación demuestra el esfuerzo académico por promover la reducción del riesgo de estos eventos cuando, en su momento, se activan las instituciones civiles y militares y sus operadores de salud.

RESUMO Objetivo: mapear as competências desenvolvidas em estratégias de capacitação para práticas de transporte aéreo de pacientes, diante de situações de emergência e desastres envolvendo agentes químicos, biológicos, radiológicos e nucleares (QBRN). Método: revisão de escopo estruturada conforme as recomendações do Joanna Briggs Institute e do checklist Preferred Reporting Items for Systematic reviews and Metanalyses extension for Scoping Reviews. O estudo foi desenvolvido em cinco etapas: busca de fontes em 17 bases de dados, um portal de informação e dois repositórios de literatura cinzenta, utilizando 125 descritores DeCS, MeSH e Emtree, sem recorte temporal e idiomático; seleção; leitura crítica na íntegra dos textos selecionados por dois revisores em duplo cego; síntese dos resultados e apresentação das competências mapeadas. Resultados: foram analisados 878 estudos, dos quais 18 compuseram a amostra. Ao todo, foram mapeadas 11 competências, com destaque para o domínio capacitação técnica. As competências referem-se especialmente ao conhecimento técnico-científico em situações de desastre envolvendo agentes QBRN e à segurança do paciente e dos profissionais envolvidos. Conclusão: a operacionalização de artifícios para aperfeiçoar os processos de capacitação baseados em competências mostrou-se estratégica para elevar a qualidade e a segurança das práticas de transporte aéreo de pacientes. A abordagem das fontes sobre aspectos específicos das particularidades das práticas relacionadas às emergências e desastres envolvendo agentes QBRN em processos de formação/capacitação demonstra o esforço acadêmico de promover a redução do risco desses eventos quando, oportunamente, forem acionadas instituições civis e militares e seus operadores de saúde.

Efecto del ácido deoxicólico sobre la regulación del transporte iónico intestinal en la rata / Deoxycholic acid efect on intestinal ionic transport regulation in the rat

The intestine has a very important role in the homeostasis of the internal medium. Bile acids play a regulatory role in the digestion and absorption of nutrients. Among them, deoxycholic acid, when its luminal concentration increases due to bacterial overgrowth, modifies hydroelectrolytic transport, producing an increase in the volume of water and electrolytes in stools.

El intestino tiene un papel muy importante en la homeostasis del medio interno. Los ácidos biliares cumplen una función reguladora en la digestión y absorción de nutrientes. Entre ellos el ácido deoxicólico, cuando aumenta su concentración luminal por sobrecrecimiento bacteriano, modifica el transporte hidroelectrolítico produciendo aumento del volumen de agua y electrolitos en las deposiciones.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis / Uso de elexacaftor + tezacaftor + ivacaftor em indivíduos com fibrose cística com pelo menos um alelo F508del: revisão sistemática e meta-análise

ABSTRACT Objective: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. Methods: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, −0.16; 95% CI, −0.28 to −0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, −0.03; 95% CI, −0.08 to 0.01), and none of the studies reported deaths. Conclusions: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

RESUMO Objetivo: Avaliar o efeito do tratamento com a combinação de três moduladores da proteína cystic fibrosis transmembrane conductance regulator (CFTR, reguladora de condutância transmembrana em fibrose cística) - elexacaftor + tezacaftor + ivacaftor (ETI) - sobre desfechos clínicos importantes em indivíduos com fibrose cística. Métodos: Revisão sistemática e meta-análise de ensaios clínicos randomizados que compararam o uso de ETI em indivíduos com fibrose cística com pelo menos um alelo F508del com o uso de placebo ou de um comparador ativo como outras combinações de moduladores da CFTR. O estudo foi realizado seguindo as recomendações Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) e a metodologia Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO). Foram realizadas buscas nos seguintes bancos de dados: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials e ClinicalTrials.gov, desde a sua criação até 26 de dezembro de 2022. O risco de viés foi avaliado por meio da ferramenta de risco de viés da Cochrane, e a qualidade das evidências foi determinada com base no sistema Grading of Recommendations Assessment, Development and Evaluation (GRADE). Resultados: Foram identificados 54 estudos na busca primária. Destes, 6 preencheram os critérios de inclusão e foram analisados (1.127 pacientes: 577 pacientes intervenção e 550 pacientes controle). A meta-análise revelou que o uso de ETI aumentou o VEF1 em porcentagem do previsto [diferença de risco (DR): +10,47%; IC95%: 6,88-14,06], reduziu o número de exacerbações pulmonares agudas (DR: −0,16; IC95%: −0,28 a −0,04) e melhorou a qualidade de vida (DR: +14,93; IC95%: 9,98-19,89) e o IMC (DR: +1,07 kg/m2; IC95%: 0,90-1,25). Os eventos adversos não diferiram entre os grupos (DR: −0,03; IC95%: −0,08 a 0,01), e nenhum dos estudos relatou óbitos. Conclusões: Nossos achados demonstram que o tratamento com ETI melhora substancialmente os desfechos clinicamente significativos centrados no paciente.

Elexacaftor/tezacaftor/ivacaftor-real-world clinical effectiveness and safety. A single-center Portuguese study / Elexacaftor/tezacaftor/ivacaftor-efetividade clínica e segurança no mundo real. Estudo unicêntrico português

ABSTRACT Objective: To evaluate the effectiveness of treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) and to characterize its safety profile in cystic fibrosis (CF) patients in a real-world clinical setting. Methods: This was a prospective observational study carried out in a CF referral center in Portugal involving adult CF patients who started treatment with ELX/TEZ/IVA. Clinical characteristics of the patients were collected, and effectiveness and safety data were evaluated. Results: Of the 56 patients followed in the center at the time of the study, 28 were eligible for ELX/TEZ/IVA treatment in accordance with the Portuguese National Authority for Medicines and Health Products at the time of the study. Of these, 24 met the follow-up time requirement to be included in the clinical effectiveness analysis. The mean follow-up time was 167.3 ± 96.4 days. Adverse events were generally mild and self-limited. Significant improvements in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations were observed. No significant differences in outcomes between F508del homozygous and heterozygous patients were found. The effectiveness of this new CFTR modulator combination also applied to patients with advanced lung disease. Conclusions: Treatment with ELX/TEZ/IVA showed effective improvement in real-world clinical practice, namely in lung function, BMI, sweat chloride concentration, and number of pulmonary exacerbations, with no safety concerns.

RESUMO Objetivo: Avaliar a efetividade do tratamento com elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) e caracterizar seu perfil de segurança em pacientes com fibrose cística (FC) em um cenário clínico de mundo real. Métodos: Estudo observacional prospectivo realizado em um centro de referência em FC de Portugal com pacientes adultos com FC que iniciaram o tratamento com ELX/TEZ/IVA. As características clínicas dos pacientes foram coletadas, e os dados de efetividade e segurança, avaliados. Resultados: Dos 56 pacientes acompanhados no centro na época do estudo, 28 eram elegíveis para o tratamento com ELX/TEZ/IVA de acordo com a Autoridade Nacional do Medicamento e Produtos de Saúde. Destes, 24 atenderam ao requisito de tempo de acompanhamento para inclusão na análise de efetividade clínica. O tempo médio de acompanhamento foi de 167,3 ± 96,4 dias. Os eventos adversos foram geralmente leves e autolimitados. Foram observadas melhoras significativas na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares. Não foram encontradas diferenças significativas nos resultados entre os pacientes homozigotos e heterozigotos para F508del. A efetividade dessa nova combinação de moduladores da CFRT em fibrose cística também se aplica a pacientes com doença pulmonar avançada. Conclusões: O tratamento com ELX/TEZ/IVA demonstrou melhora efetiva na prática clínica real, a saber, na função pulmonar, no IMC, na concentração de cloreto no suor e no número de exacerbações pulmonares, sem preocupações de segurança.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Sexual harassment in public transport among female students at the Federal university of technology Akure, Nigeria

Background: Every day females experience different types of sexual harassment while using public transportation worldwide. Objective: This study aims to determine the prevalence of sexual harassment amongst female students who travel by public transportation at the Federal University of Technology Akure (FUTA) Nigeria. Materials and Methods: A cross-sectional descriptive study. Data was collected using electronic questionnaires and analyzed with IBM SPSS Statistics version 21. Frequencies and percentages were used for data summary. Association between variables was determined using Chi Square test. Statistical significance was a p-value < 0.05. Results: Ninety-three percent of female students in FUTA had experienced sexual harassment. Among those who had experienced sexual harassment, 98.4% were single, 81.5% lived off campus, 79.0% used public bus, 45.4% commuted daily, 84.7% was in an overcrowded vehicle and 52.9% was in the evening. There was a significant association between sexual harassment and marital status (p = 0.033), place of residence (p = 0.019), mode of public transportation (p = 0.014), time of travel (p = 0.018). Verbal sexual harassment was most prevalent (91.1%), followed by physical sexual harassment (87.6%) and non-verbal sexual harassment (82%). Conclusion: This study found a high prevalence of sexual harassment among female university students in FUTA using public transportation, which occurs in a variety of scenarios, particularly in crowded vehicles during rush hour

Influence of garlic extract on larval performance and survival of juvenile angelfish Pterophyllum scalare during transport / Influência do extrato de alho no desempenho larval e na sobrevivência durante o transporte de juvenis de acará bandeira Pterophyllum scalare

The objective of this study was to evaluate the properties of garlic as a growth promoter in larvae of angelfish Pterophyllum scalare and its benefits during transport of juveniles of this species. The experiment was conducted in recirculation aquaculture system, consisting of 20 tanks of 40 L equipped with independent water input and output. We used 1,400 larvae distributed among five treatments, with four repetitions, which totaled 20 experimental units. The treatments were 0, 50, 100, 200, and 400 mg of garlic extract per kilo of feed. The results showed that the inclusion of levels of garlic extract in the feed did not significantly effect the fish’s development or their transport. Neither did the inclusion of levels of garlic extract affect the survival of the larvae during the trial period. New research with extracts of higher dosages should be performed to elucidate the effect of garlic extract as a growth promoter.

O estudo teve como objetivo avaliar as propriedades do alho como promotor de crescimento em larvas de acará bandeira Pterophyllum scalare e seus benefícios no transporte de juvenis da mesma espécie. O experimento foi conduzido em sistema de recirculação composto por 20 aquários de 40 L de volume útil, dotado de entrada e saída de água independentes e teve a duração de 40 dias. O delineamento experimental adotado foi o inteiramente casualizado (DIC), com cinco tratamentos e quatro repetições, totalizando 20 unidades experimentais. Foram utilizadas 1.400 larvas de acará bandeira (Pterophyllum scalare) divididas entre os tratamentos. Os tratamentos consistiram em: 0, 50, 100, 200 e 400 mg de extrato de alho por quilo de ração. Os resultados mostraram que não houve efeito significativo dos níveis de inclusão do extrato do alho sobre os índices zootécnicos avaliados e posteriormente no transporte dos juvenis. Também não foi observado influência na sobrevivência das larvas durante o período experimental. Novas pesquisas com dosagens maiores de extratos devem ser realizados para melhor elucidação do efeito do extrato de alho como promotor de crescimento.

Influence of garlic extract on larval performance and survival of juvenile angelfish Pterophyllum scalare during transport

Abstract The objective of this study was to evaluate the properties of garlic as a growth promoter in larvae of angelfish Pterophyllum scalare and its benefits during transport of juveniles of this species. The experiment was conducted in recirculation aquaculture system, consisting of 20 tanks of 40 L equipped with independent water input and output. We used 1,400 larvae distributed among five treatments, with four repetitions, which totaled 20 experimental units. The treatments were 0, 50, 100, 200, and 400 mg of garlic extract per kilo of feed. The results showed that the inclusion of levels of garlic extract in the feed did not significantly effect the fishs development or their transport. Neither did the inclusion of levels of garlic extract affect the survival of the larvae during the trial period. New research with extracts of higher dosages should be performed to elucidate the effect of garlic extract as a growth promoter.

Resumo O estudo teve como objetivo avaliar as propriedades do alho como promotor de crescimento em larvas de acará bandeira Pterophyllum scalare e seus benefícios no transporte de juvenis da mesma espécie. O experimento foi conduzido em sistema de recirculação composto por 20 aquários de 40 L de volume útil, dotado de entrada e saída de água independentes e teve a duração de 40 dias. O delineamento experimental adotado foi o inteiramente casualizado (DIC), com cinco tratamentos e quatro repetições, totalizando 20 unidades experimentais. Foram utilizadas 1.400 larvas de acará bandeira (Pterophyllum scalare) divididas entre os tratamentos. Os tratamentos consistiram em: 0, 50, 100, 200 e 400 mg de extrato de alho por quilo de ração. Os resultados mostraram que não houve efeito significativo dos níveis de inclusão do extrato do alho sobre os índices zootécnicos avaliados e posteriormente no transporte dos juvenis. Também não foi observado influência na sobrevivência das larvas durante o período experimental. Novas pesquisas com dosagens maiores de extratos devem ser realizados para melhor elucidação do efeito do extrato de alho como promotor de crescimento.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.