Impact of combined intermittent fasting and high-intensity interval training on apoptosis and atrophy signaling in rat fast- and slow-twitch muscles.

This study aimed to evaluate the influence of combined intermittent fasting (IF) and high-intensity interval training (HIIT) on morphology, caspase-independent apoptosis signaling pathway, and myostatin expression in soleus and gastrocnemius (white portion) muscles from healthy rats. Sixty-day-old male Wistar rats (n = 60) were divided into four groups: control (C), IF, high-intensity-interval training (T), and high-intensity-interval training and intermittent fasting (T-IF). The C and T groups received ad libitum chow daily; IF and T-IF received the same standard chow every other day. Animals from T and T-IF underwent a HIIT protocol five times a week for 12 weeks. IF reduced gastrocnemius mass and increased pro-apoptotic proteins apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in soleus and cleaved-to-non-cleaved PARP-1 ratio and myostatin expression in gastrocnemius white portion. HIIT increased AIF and apoptosis repressor with caspase recruitment domain expression in soleus and cleaved-to-total PARP-1 ratio in gastrocnemius muscle white portion. The combination of IF and HIIT reduced fiber cross-sectional area in both muscles, increased EndoG and AIF expression, and decreased cleaved-to-non-cleaved PARP-1 ratio in gastrocnemius muscle white portion. Muscle responses to IF and HIIT are directly impacted by the muscle fiber type composition and are modulated, at least in part, by myostatin and caspase-independent apoptosis signaling.

Loss of Lkb1 cooperates with BrafV600E and ultraviolet radiation, increasing melanoma multiplicity and neural-like dedifferentiation.

The mechanisms that work alongside BRAFV600E oncogene in melanoma development, in addition to ultraviolet (UV) radiation (UVR), are of great interest. Analysis of human melanoma tumors [data from The Cancer Genome Atlas (TCGA)] revealed that 50% or more of the samples expressed no or low amounts of serine/threonine protein kinase STK11 (also known as LKB1) protein. Here, we report that, in a mouse model, concomitant neonatal BrafV600E activation and Lkb1 tumor suppressor ablation in melanocytes led to full melanoma development. A single postnatal dose of UVB radiation had no effect on melanoma onset in Lkb1-depleted mice compared with BrafV600E-irradiated mice, but increased tumor multiplicity. In concordance with these findings and previous reports, Lkb1-null irradiated mice exhibited deficient DNA damage repair (DDR). Histologically, tumors lacking Lkb1 were enriched in neural-like tumor morphology. Genetic profiling and gene set enrichment analyses of tumor sample mutated genes indicated that loss of Lkb1 promoted the selection of altered genes associated with neural differentiation processes. Thus, these results suggest that the loss of Lkb1 cooperates with BrafV600E and UVR, impairing the DDR and increasing melanoma multiplicity and neural-like dedifferentiation.

The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease.

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

ß-lactamase expression induces collateral sensitivity in Escherichia coli.

Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, ß-lactam resistance genes -encoding ß-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the ß-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile ß-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that ß-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of ß-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Exercise, mTOR Activation, and Potential Impacts on the Liver in Rodents.

The literature offers a consensus on the association between exercise training (ET) protocols based on the adequate parameters of intensity and frequency, and several adaptive alterations in the liver. Indeed, regular ET can reverse glucose and lipid metabolism disorders, especially from aerobic modalities, which can decrease intrahepatic fat formation. In terms of molecular mechanisms, the regulation of hepatic fat formation would be directly related to the modulation of the mechanistic target of rapamycin (mTOR), which would be stimulated by insulin signaling and Akt activation, from the following three different primary signaling pathways: (I) growth factor, (II) energy/ATP-sensitive, and (III) amino acid-sensitive signaling pathways, respectively. Hyperactivation of the Akt/mTORC1 pathway induces lipogenesis by regulating the action of sterol regulatory element binding protein-1 (SREBP-1). Exercise training interventions have been associated with multiple metabolic and tissue benefits. However, it is worth highlighting that the mTOR signaling in the liver in response to exercise interventions remains unclear. Hepatic adaptive alterations seem to be most outstanding when sustained by chronic interventions or high-intensity exercise protocols.

Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/µm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.

Frailty, Sarcopenia and Osteoporosis. / Fragilidad, sarcopenia y osteoporosis.

Frailty, sarcopenia and osteoporosis are entities specific to the elderly, who share some risk factors. For this reason, their relationship has been studied in different works, which have provided disparate results, probably because these studies have not always focused on the same aspects. This article reviews the relationship of frailty and sarcopenia with osteoporosis.

Nivel de comunicación familiar y autoeficacia en pacientes con Diabetes Mellitus tipo 2 en atención primaria de salud / Level of family communication and self-efficacy in patients with type 2 Diabetes Mellitus in primary health care primary health care

Objetivo principal: establecer la relación entre el nivel de comunicación familiar y autoeficacia en pacientes con Diabetes Mellitus Tipo 2 que asisten a un centro de salud primaria. Metodología: Estudio analítico de corte transversal, con una muestra de 238 pacientes con DM2 a los que se les aplicó la Escala de Comunicación Familiar de FACES IV y la Escala de Autoeficacia en Diabetes. Resultados principales: El 75,6% identificó un nivel de comunicación familiar “muy alto” relacionado significativamente con el “apoyo de parientes” (p=0,001). La autoeficacia percibida presentó un puntaje general de 8,2 con correlación altamente significativa entre nivel de comunicación y los ítems de autoeficacia (p < 0,05). Los mayores puntajes de autoeficacia se concentraron en niveles “muy alto” de comunicación familiar. Conclusión principal: Una alta comunicación familiar puede impactar positivamente en la autopercepción y el empoderamiento del paciente en el manejo de su DM2.(AU)

Objective: to establish the relationship between the level of family communication and self-efficacy in patients with Type 2 Diabetes Mellitus attending a primary health center. Methodology: Cross-sectional analytical study. A sample of 238 patients with T2DM was obtained and administered the FACES IV Family Communication Scale and the Diabetes Self-Efficacy Scale. Results: 75.6% identified a "very high" level of family communication significantly related to "support from relatives" (p=0.001). Perceived self-efficacy had an overall score of 8.2 with a highly significant correlation between level of communication and self-efficacy items (p-value < 0.05). The highest self-efficacy scores were concentrated in "very high" levels of family communication. Conclusion: High family communication can positively impact the patient’s self-perception and empowerment in the management of their T2DM.(AU)

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy.

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1ß release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1ß release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers.

From Chronodisruption to Sarcopenia: The Therapeutic Potential of Melatonin.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria and organelle, where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

ACOD frente a AVK en pacientes con fibrilación auricular y bioprótesis: revisión sistemática y metanálisis / DOAC versus VKA in patients with atrial fibrillation and bioprosthetic valves: a systematic review and meta-analysis

Introducción y objetivos: Los anticoagulantes orales directos (ACOD) se han mostrado eficaces y seguros en pacientes con fibrilación auricular; sin embargo, los pacientes con FA y bioprótesis están infrarrepresentados en los ensayos clínicos, por lo que la evidencia en este grupo es menor. Nuestro objetivo fue analizar la seguridad y eficacia de los ACODs en esta población revisando la información existente en la literatura. Métodos: Se realizó una búsqueda y revisión sistemática con los ensayos clínicos aleatorizados y estudios observacionales comparativos desde 2017 a enero de 2022, que comparasen ACODs y antagonistas de vitamina K (AVK) en pacientes con FA y bioprótesis. Se utilizó la hazard ratio al 95% del intervalo de confianza para comparar ambos grupos en términos de mortalidad total y cardiovascular, ictus/embolia sistémica y hemorragia mayor. Se realizó un metanálisis combinando los resultados de los estudios incluidos. Resultados: Se incluyeron 12 estudios (un total de 30.283 pacientes). Los ACODs se asociaron a una reducción significativa del 9% de la mortalidad total (HR=0,91; IC95%, 0,85-0,97; p=0,0068; I2=8%), sin diferencias significativas en el riesgo de ictus/embolismo sistémico (HR=0,87; IC95%, 0,67-1,14; p=0,29; I2=45%) o hemorragia mayor (HR=0,82; IC95%, 0,67-1,00; p=0,054; I2=48.7%). Conclusiones: En pacientes con FA portadores de bioprótesis, los ACODs podrían asociarse a una reducción de la mortalidad total sin reducción de eficacia en la prevención de ictus/embolia sistémica o aumento del riesgo de hemorragia mayor.(AU)

Introduction and objectives: Direct oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with bioprosthetic valves are unclear, as this population has been underrepresented in clinical trials. The aim of this study was to assess the safety and efficacy of DOACs in this population based on the existing published literature. Methods: A systematic search and review were conducted to identify randomized clinical trials and comparative observational studies published from 2017 to January 2022 that compared DOACs and vitamin K antagonists (VKAs) in AF patients with bioprosthetic valves. Hazard ratios (HR) were collected to compare the 2 treatments in terms of cardiovascular and all-cause mortality, stroke/systemic embolism, and major bleeding. A meta-analysis combining the results was performed. Results: We included 12 studies (30 283 patients). DOACs and VKAs were compared based on HRs at the 95% confidence interval. DOAC therapy was associated with a significant 9% reduction in all-cause mortality (HR, 0.91; 95%CI, 0.85-0.97; P=.0068; I2=8%), with no significant differences in the risk of stroke/systemic embolism (HR, 0.87; 95%CI, 0.67-1.14; P=.29; I2=45%) or major bleeding (HR, 0.82; 95%CI, 0.67-1.00; P=.054; I2=48.7%). Conclusions: DOAC therapy in AF patients with bioprosthetic valves may be associated with a significant reduction in all-cause mortality, with no reduction in the efficacy of stroke/systemic embolism prevention or increase in major bleeding risk.(AU)

Etiologia e fisiopatologia da fibromialgia / Etiology and pathophysiology of fibromyalgia

A fibromialgia é uma condição crônica de etiologia desconhecida e desvinculada de marcadores laboratoriais específicos para diagnóstico, devido à pobre caracterização da etiopatogenia. Em geral, as alterações comuns à fibromialgia também são observadas em outras condições de dor crônica, tornando a patogênese controversa entre diferentes condições patológicas. A etiologia desconhecida dificulta o diagnóstico e, consequentemente, repercute em um tratamento não tão eficaz de pacientes com fibromialgia. A restauração de desordens sistêmicas confere amplo espectro de possibilidades terapêuticas com potencial de orientar profissionais a estabelecer metas e métodos de avaliação. Diante disso, essa revisão narrativa se volta para debater hipóteses etiológicas e fisiopatológicas no desenvolvimento da fibromialgia.

Fibromyalgia is a chronic condition of unknown etiology unrelated to specific laboratory markers for diagnosis because of poor etiopathogenesis. In general, the changes common to fibromyalgia are also seen in other chronic pain conditions, making the pathogenesis controversial among different pathological conditions. The unknown etiology makes the diagnosis difficult and consequently has repercussions on a not so effective treatment of patients with fibromyalgia. The restoration of systemic disorders provides a wide spectrum of therapeutic possibilities with the potential to guide professionals in establishing goals and evaluation methods. Therefore, this narrative review discusses the etiological and pathophysiological hypotheses involved in the development of fibromyalgia.

Tratamiento de la macromastia sintomática en una unidad de mama. Resultados de la reducción mamaria evaluados mediante el cuestionario BREAST-Q / Treatment of symptomatic macromastia in a breast unit. Outcomes analysis of breast reduction using BREAST-Q

Introducción: El BREAST-Q (módulo reducción mamaria) es un cuestionario específico y validado para evaluar la reducción mamaria en el tratamiento de la macromastia sintomática, ofreciendo información sobre la calidad de vida y grado de satisfacción de las pacientes. Métodos: Estudio prospectivo de una cohorte de 34 pacientes tratadas mediante reducción mamaria bilateral, en una unidad de mama en 2017-2020, que fueron encuestadas con la versión adaptada al castellano del BREAST-Q. Las pacientes cumplimentaron el cuestionario en el mes previo a la cirugía y después de esta. Los cambios de las puntuaciones pre- y postoperatorias en los diferentes dominios se analizaron mediante la prueba de rangos con signo de Wilcoxon. La significación estadística fue determinada con valores de p<0,05. Resultados: El tiempo medio desde la cirugía a la encuesta postoperatoria fue 16 (DE 9) meses. Complicaciones o secuelas posquirúrgicas sucedieron en 14 (42%) pacientes con 23 eventos. Las puntuaciones preoperatorias, medianas y rango intercuartílico, en la satisfacción con las mamas (28, 26), bienestar psicológico (33, 14), físico (42, 19) y sexual (34, 14) mejoraron en la encuesta postoperatoria a (82, 15), (81,29), (82, 30) y (90, 38), respectivamente, con significación estadística, p<0,001. Conclusiones: La primera aplicación del BREAST-Q versión en castellano para españolas a pacientes con macromastia tratadas quirúrgicamente en una unidad de mama demuestra que la reducción mamaria mejora la calidad de vida de las pacientes y, que estas están muy satisfechas con el resultado de la cirugía y su cirujano, aunque la información recibida es mejorable. (AU)

Introduction: The BREAST-Q (breast reduction module) is a specific and validated questionnaire to evaluate breast reduction in the treatment of symptomatic macromastia, offering information on their quality of life and degree of satisfaction. Methods: Prospective study of a cohort of 34 patients treated by bilateral breast reduction in a breast unit in 2017–2020 surveyed with the Spanish version of BREAST-Q version 2. The statistical study to assess the effect of reduction, changes from the pre to postoperative scores of the domains were performed using the Wilcoxon signed rank test. Statistical significance was determined with P values <.05. Results: The mean time elapsed from surgery to the postoperative survey was 16 (SD 9) months. Post-surgical complications or sequelae occurred in 14 (42%) patients with 23 events. The preoperative scores, median and interquartile range, in satisfaction with the breasts (28, 26), psychological (33, 14), physical (42, 19) and sexual (34, 14) well-being improved in the postoperative survey to (82, 15), (81, 29), (82, 30) and (90, 38), respectively. These changes were statistically significant, P<.001. Conclusions: The first application of the BREAST-Q in its version in Spanish for Spanish women in patients with symptomatic macromastia treated surgically in a breast unit shows that breast reduction improves the quality of life of patients and that they are very satisfied with the outcome of the surgery and its surgeon, although the information received should clearly be improved. (AU)

Impacto del confinamiento por COVID-19 en la prescripción de benzodiacepinas / Impact of COVID-19 lockdown on the prescription of benzodiazepines

Objetivo: Evaluar el efecto del confinamiento por COVID-19 sobre la prescripción de benzodiacepinas según edad, sexo y zona básica de salud. Diseño: Estudio observacional longitudinal. Emplazamiento: Atención primaria. Área V de Salud del Principado de Asturias. Participantes: Mayores de 15 años a los que se prescribieron benzodiacepinas entre 2017 y 2020. Mediciones principales: Diferencia de las medias de dosis diaria definida por 1.000 habitantes (DHD) mensual de benzodiacepinas entre el periodo definido como preconfinamiento y el confinamiento. Además, se ajusta la diferencia por edad, sexo y zona básica de salud, así como por la interacción entre ellas. Resultados: La DHD media preconfinamiento fue 131,3 y 139,5 durante el confinamiento; en el análisis crudo, esta diferencia fue estadísticamente significativa (IC 95% 4,1 a 12,1). Se objetivó un aumento de DHD media en el grupo de 60-74 años (IC 95% 2,28 a 21,42) y en el de 90 años o más (IC 95% 21,31 a 40,63), así como en las mujeres (IC 95% 3,51 a 14,59). Finalmente, se observó una disminución de DHD media en las zonas básicas V11 (IC 95% -29 a -0,66) y V14 (IC 95% -54,28 a -25,04). Conclusiones: Determinados subgrupos muestran un cambio en la tendencia de dispensación de benzodiacepinas sin poder atribuirse completamente al confinamiento. Creemos que pueda existir una inercia terapéutica en la prescripción de psicofármacos, según las características biopsicosociales del paciente, que es importante detectar para evitar la medicalización de cuadros psicológicos.(AU)

Objective: To evaluate the effect of COVID-19 lockdown on the prescription of benzodiazepines by gender, age and district health departments. Design: Longitudinal observational study. Location: Primary care. Asturias (Spain) health district V. Participants: People over 15 years of age with filled benzodiazepine prescriptions in between 2017 and 2020. Main measurements: Benzodiazepine DHD (defined daily dose per 1000 habitants) mean difference between the period defined as pre-lockdown and lockdown. Additionally, the difference was adjusted for gender, sex and district health department and also with the interaction among them. Results: DHD mean pre-lockdown was 131.3 and 139.5 in the lockdown; this difference was significant in the global analysis (95% CI: 4.1–12.1). There was an increase in the DHD mean in the 60–74 age group (95% CI: 2.28–21.42), in the group over 90 years old (95% CI: 21.31–40.63) and in women (95% CI: 3.51–14.59). Finally, a decrease in the DHD mean of V11 (95% CI: -29 to -0.66) and V14 (95% CI: -54.28 to -25.04) district health departments was observed.Conclusions: Certain subgroups show a change in the pattern of benzodiazepine prescription without being able to relate this to the lockdown. We believe that there could be some inertia in the prescription of psychiatric medication according to the biopsychosocial characteristics of the patients; it is important to detect this in order to avoid the medicalization of psychological disorders.(AU)

Penfigoide ampolloso de origen idiopático

Introducción: El penfigoide ampolloso es una dermatosis vesicular ampollosa autoinmunitaria subepidérmica, asociada a la formación de autoanticuerpos que reconocen autoantígenos en la zona de la membrana basal. El tratamiento inmunomodulador con corticoides es la primera línea en el control de la enfermedad. Objetivo: Presentar el caso clínico de un paciente con diagnóstico de penfigoide ampolloso de origen idiopático. Caso clínico: Paciente masculino de 81 años con lesiones ampollosas dolorosas a la palpación de contenido serohemático, tamaño variado, bordes regulares y base eritematosa a nivel generalizado. La evaluación inicial sugiere diagnóstico de penfigoide ampolloso e infección bacteriana activa de las lesiones en la piel. Se solicitan exámenes de laboratorio e imágenes diagnósticas, se descartan etiologías infecciosas, autoinmunes o neoplásicas asociadas, se inicia tratamiento con corticosteroides intravenosos con adecuada evolución clínica. Finalmente, no se identifican enfermedades asociadas a las lesiones ampollosas del paciente. Conclusión: El penfigoide ampolloso es una entidad poco frecuente, con una elevada tasa de mortalidad si se realiza un diagnóstico y tratamiento tardío. Reconocer las principales manifestaciones y variantes clínicas de esta enfermedad permite un oportuno enfoque diagnóstico y terapéutico, este último basado en el control de la respuesta inflamatoria contra la piel y otros órganos.

Introduction: Bullous pemphigoid is a subepidermal autoimmune bullous vesicular dermatosis associated with the formation of autoantibodies that confirm autoantigens in the basement membrane area. Immunomodulatory treatment with corticosteroids is the first line in the control of the disease. Objective: To present the clinical case of a patient diagnosed with a bullous pemphigoid of idiopathic origin. Clinical case: 81-year-old male patient with blistering lesions that are painful on palpation with serohematic content, varied in size, regular borders and a generalized erythematous base; that the initial evaluation suggests a diagnosis of bullous pemphigoid and active bacterial infection of the skin. Laboratory tests and diagnostic images are requested, infectious, autoimmune or associated neoplastic etiologies are ruled out, treatment with intravenous corticosteroids is started with adequate clinical evolution. Finally, no diseases associated with the patient's blistering lesions were identified. Conclusion: Bullous pemphigoid is a rare entity, with a high mortality rate if a late diagnosis and treatment is performed. Recognizing the main manifestations and clinical variants of this disease allows for a timely diagnostic and therapeutic approach, the latter based on the control of the inflammatory response against the skin and other organs.

Telomere dynamics in human pluripotent stem cells.

Pluripotent stem cells (PSCs) are a promising source of stem cells for regenerative therapies. Stem cell function depends on telomere maintenance mechanisms that provide them with the proliferative capacity and genome stability necessary to multiply and regenerate tissues. We show here that established human embryonic stem cells (hESCs) have stable telomere length that is dependent on telomerase but not on alternative mechanisms based on homologous recombination pathways. Here, we show that human-induced pluripotent stem cells (hiPSCs) reprogrammed from somatic cells show progressive telomere lengthening until reaching a length similar to ESCs. hiPSCs also acquire telomeric chromatin marks of ESCs including decreased abundance of tri-methylated histone H3K9 and H4K20 and HP1 heterochromatic marks, as well as of the shelterin component TRF2. These chromatin features are accompanied with increased abundance of telomere transcripts or TERRAs. We also found that telomeres of both hESCs and hiPSCs are well protected from DNA damage during telomere elongation and once full telomere length is achieved, and exhibit stable genomes. Collectively, this study highlights that hiPSCs acquire ESC features during reprogramming and reveals the telomere biology in human pluripotent stem cells (hPSCs).

We show that established human embryonic stem cells (hESCs) have a maximum and stable telomere length that is dependent on telomerase but not on the alternative homologous recombination pathway or ALT. Human-induced pluripotent stem cells (hiPSCs) reprogrammed from somatic cells show progressive telomere lengthening until reaching a length similar maximum telomere length than ESCs, suggesting that telomere length is regulated by epigenetic mechanisms in human cells. In this regard, hiPSCs acquire telomeric chromatin marks characteristic of an "open chromatin" including increased abundance of telomere transcripts or TERRAs. Telomeres of both hESCs and hiPSCs are well protected during telomere elongation and exhibit stable genomes. Collectively, this study highlights that hiPSCs acquire ESC features during reprogramming and reveals the telomere biology in human pluripotent stem cells (hiPSCs).

Challenges of the Implementation of a Delirium Rate Scale in a Pediatric Intensive Care Unit: A Qualitative Approach.

INTRODUCTION: Delirium in the pediatric population admitted to intensive care is a worrying reality due to its potential complications and the increase in associated costs. This study aims to explore the experiences of nursing staff of a Pediatric Intensive Care Unit after 15 months of starting a program to fight against childhood delirium in their unit. METHODOLOGY: A qualitative study was conducted through semi-structured interviews with Pediatric Intensive Care Unit (PICU) Key Informants. The Standards for Reporting Qualitative Research (SRQR) and the consolidated criteria for Reporting Qualitative Research (COREQ) were followed as quality measures for the study. Seven nurses (33% of the eligible population) from the PICU of a referral hospital were interviewed. Text transcripts were analyzed using the Interpretative Description and Qualitative Content Analysis method. RESULTS: The interviewees indicated not identifying delirium as an important reality; with great deficiencies observed in what is related to the identification of delirium; identifying CAPD as an unreliable tool in their unit; and not sharing therapeutic objectives in this respect with the medical staff. CONCLUSIONS: The nursing staff presented a series of negative attitudes towards the phenomena of delirium in their unit, with gaps in training and in clinical management, and the diagnostic tool used, and did not see it as a priority objective of the unit, partly due to a resistance to change and a latent interprofessional communication conflict. A change at the formative, attitudinal, and relational levels is urgently needed for the success of the program and the well-being of the children in the unit.