The role of PCSK9 in metabolic dysfunction-associated steatotic liver disease and its impact on bariatric surgery outcomes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely tied to obesity. The degree ranges from steatosis (MASL) and steatohepatitis (MASH) to liver cirrhosis. PCSK9 controls cholesterol and lipid particle transport to the liver. PCSK9 might interfere with the pathophysiology of MASLD and bariatric surgery (BS) outcomes of patients with MASLD. OBJECTIVES: Evaluate the relationship between serum and hepatic PCSK9 levels with the degree of MASLD and the metabolic outcome of BS. SETTING: University Hospital, Spain. METHODS: A total of 110 patients with obesity undergoing BS were classified according to liver histology as controls, MAS, and MASH. PCSK9 levels in serum were measured before and 6 months after BS using enzyme-linked immunosorbent assay. PCSK9 protein and mRNA levels in liver tissue were analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. RESULTS: Hepatic PCSK9 protein levels were diminished in MASL and MASH compared with patients without MASLD and showed a strong negative association with MASLD severity scores. Liver PCSK9 mRNA was higher in MASH compared with controls and MASL and showed positive associations with MASLD severity scores. There were no differences in serum PCSK9 pre or postBS between the groups. Pre- and postsurgery serum PCSK9 positively correlated with cholesterol fold-changes and body mass index (BMI), cholesterol, and low-density lipoprotein -cholesterol fold-changes, respectively. PCSK9 fold-change positively correlated with BMI changes and was the sole variable explaining BMI fold changes in a regression model. CONCLUSIONS: PCSK9 mRNA and protein in the liver might be associated with the degree of MASLD. Serum PCSK9 may be associated with cholesterol and/or BMI fold changes. Serum changes of PCSK9 after BS could explain BMI loss outcome.

An empirical data analysis of "price runs" in daily financial indices: Dynamically assessing market geometric distributional behavior.

In financial time series there are time periods in which market indices values or assets prices increase or decrease monotonically. We call those events "price runs", "elementary uninterrupted trends" or just "uninterrupted trends". In this paper we study the distribution of the duration of uninterrupted trends for the daily indices DJIA, NASDAQ, IPC and Nikkei 225 during the period of time from 10/30/1978 to 08/07/2020 and we compare the simple geometric statistical model with [Formula: see text] consistent with the EMH to the empirical data. By a fitting procedure, it is found that the geometric distribution with parameter [Formula: see text] provides a good model for uninterrupted trends of short and medium duration for the more mature markets; however, longest duration events still need to be statistically characterized. Estimated values of the parameter p were also obtained and confirmed by calculating the mean value of p fluctuations from empirical data. Additionally, the observed trend duration distributions for the different studied markets are compared over time by means of the Anderson-Darling (AD) test, to the expected geometric distribution with parameter [Formula: see text] and to a geometric distribution with a free parameter p, making possible to assess and compare different market geometric behavior for different dates as well as to measure the fraction of time runs duration from studied markets are consistent with the geometric distribution with [Formula: see text] and in parametric free way.

Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon.

The NLRP3 inflammasome coordinates inflammation in response to different pathogen- and damage-associated molecular patterns, being implicated in different infectious, chronic inflammatory, metabolic and degenerative diseases. In chronic tendinopathic lesions, different non-resolving mechanisms produce a degenerative condition that impairs tissue healing and which therefore complicates their clinical management. Percutaneous needle electrolysis consists of the application of a galvanic current and is an emerging treatment for tendinopathies. In the present study, we found that galvanic current activates the NLRP3 inflammasome and induces an inflammatory response that promotes a collagen-mediated regeneration of the tendon in mice. This study establishes the molecular mechanism of percutaneous electrolysis that can be used to treat chronic lesions and describes the beneficial effects of an induced inflammasome-related response.

Moderate Weight Loss Modifies Leptin and Ghrelin Synthesis Rhythms but Not the Subjective Sensations of Appetite in Obesity Patients.

Obesity is characterized by a resistance to appetite-regulating hormones, leading to a misalignment between the physiological signals and the perceived hunger/satiety signal. A disruption of the synthesis rhythm may explain this situation. The aim of this study was to evaluate the effect of dietary-induced weight loss on the daily rhythms of leptin and ghrelin and its influence on the daily variability of the appetite sensations of patients with obesity. Twenty subjects with obesity underwent a hypocaloric dietary intervention for 12 weeks. Plasma leptin and ghrelin were analyzed at baseline and at the end of the intervention and in 13 normal-weight controls. Appetite ratings were analyzed. Weight loss decreased leptin synthesis (pauc < 0.001) but not the rhythm characteristics, except the mean variability value (pmesor = 0.020). By contrast, the mean ghrelin level increased after weight loss. The rhythm characteristics were also modified until a rhythm similar to the normal-weight subjects was reached. The amount of variability of leptin and ghrelin was correlated with the effectiveness of the dietary intervention (p < 0.020 and p < 0.001, respectively). Losing weight partially restores the daily rhythms of leptin and modifies the ghrelin rhythms, but appetite sensations are barely modified, thus confirming that these hormones cannot exercise their physiological function properly.

The effect of surface electromyography biofeedback on the activity of extensor and dorsiflexor muscles in elderly adults: a randomized trial.

Surface electromyography-biofeedback (sEMG-B) is a technique employed for the rehabilitation of patients with neurological pathologies, such as stroke-derived hemiplegia; however, little is known about its effectiveness in the rehabilitation of the extension and flexion of several muscular groups in elderly patients after a stroke. Therefore, this research was focused on determining the effectiveness of sEMG-B in the muscles responsible for the extension of the hand and the dorsiflexion of the foot in post-stroke elderly subjects. Forty subjects with stroke-derived hemiplegia were randomly divided into intervention or control groups. The intervention consisted of 12 sEMG-B sessions. The control group underwent 12 weeks (24 sessions) of conventional physiotherapy. Muscle activity test and functionality (Barthel index) were determined. Attending to the results obtained, the intervention group showed a higher increase in the average EMG activity of the extensor muscle of the hand and in the dorsal flexion of the foot than the control group (p < 0.001 in both cases), which was associated with an increase in the patients' Barthel index score (p = 0.006); In addition, Fugl-Meyer test revealed higher effectiveness in the lower limb (p = 0.007). Thus, the sEMG-B seems to be more effective than conventional physiotherapy, and the use of this technology may be essential for improving muscular disorders in elderly patients with physical disabilities resulting from a stroke.

Role of Kupffer cells in the progression of CRC liver metastases after the first stage of ALPPS.

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs). Interestingly, KCs expressed COX-2 (M1 polarization), while TAMs expressed mainly arginase-1 (M2 polarization). ALPPS also induced a decrease of tumor-infiltrating lymphocytes and an increase of intrahepatic T lymphocytes. Thus, ALPPS technique seems to induce a hypoxic environment, which enhances hepatic HIF1-α and VEGF expression and may promote KCs and TAMs polarization. Consequently, the regenerative stimulus seems to be driven by a pro-inflammatory and hypoxic environment, in which M1 intrahepatic macrophages expressing COX-2 and T-Lymphocytes play a key role, facts which may be related with the tumor progression observed.

Las relaciones interdisciplinarias entre la Educación Física y la Medicina Natural y Tradicional / The interdisciplinary relationships between Physical Education and Natural and Traditional Medicine

En un análisis realizado al programa de Educación Física y a la Estrategia Curricular de Medicina Natural y Tradicional, de la Universidad de Ciencias Médicas de la Habana, se pudo apreciar que la Educación Física tiene más potencialidades para vincular elementos básicos de la Medicina Natural y Tradicional, de los que tiene asignado, y, por lo tanto, se limita su desarrollo en esta esfera. También se comprobó que asignaturas como la Morfofisiología, tienen un mayor protagonismo en la Estrategia Curricular de Medicina Natural y Tradicional, y que abarcan contenidos que se pueden adecuar a los objetivos de la Educación Física. Estos pueden contribuir a elevar el nivel científico de esta disciplina y a la vez tener una mayor incidencia en la formación profesional de los estudiantes de medicina. Para lograr lo antes expuesto, se está aplicando una estrategia interdisciplinaria que permita integrar elementos básicos de la Medicina Natural y Tradicional con la Educación Física.

Dock10 regulates CD23 expression and sustains B-cell lymphopoiesis in secondary lymphoid tissue.

Dock10, a guanine nucleotide exchange factor for the Rho GTPases Rac1 and Cdc42, affects cell morphology, membrane protrusive activity, and cell movement. Dock10 is prominently expressed in lymphoid tissue and upregulated by IL-4 in B cells. To investigate the physiological role of Dock10, WT mice and Dock10 KO mice were used. KO mice showed decreased numbers of B cells in spleen, both follicular B cells and marginal zone B cells, and in peripheral blood, but not in bone marrow. The antiapoptotic effect of IL-4 in vitro, the migratory response to CXCL13 or CCL21 in vitro, and the whole genome expression profile were intact in spleen B cells from KO mice. CD23, the low-affinity receptor for immunoglobulin E, was overexpressed on follicular B cells from KO mice, suggesting that Dock10 negatively regulates membrane CD23 expression. Negative regulation of CD23 expression by Dock10 could play a role in B cell maturation and function.

Estudio cualitativo de sustancias activas presentes en la planta Adiantum capillus veneris L / Qualitative study of active substances in the plant Adiantum capillus veneris L

Se realizó un estudio experimental mediante ensayos cualitativos de tamizaje fitoquímico, con el objetivo de evaluar la presencia de sustancias activas en la droga cruda, extractos, alcohólico y acuoso, de la planta Adiantum capillus veneris L. (culantrillo de pozo), muy utilizada por la población para disminuir la caída del cabello, prevenir el catarro, la tos y combatir las enfermedades de las vías urinarias. Esta planta no está descrita farmacognósticamente en Cuba. Las muestras de la planta fueron recolectadas en el municipio Majibacoa, Las Tunas, en el período comprendido entre septiembre de 2010 y febrero de 2011. Se caracterizaron los aspectos botánicos de la planta, se realizó el extracto fluido por repercolación y el acuoso por infusión. A la droga cruda y a ambos extractos se les realizó el análisis de control de calidad correspondiente, además de la técnica de tamizaje fitoquímico establecida. Se obtuvo correspondencia en cuanto a la clasificación taxonómica de la planta recolectada y lo reportado en la literatura. La droga cruda y los extractos elaborados cumplieron los requisitos establecidos para el control de calidad químico, físico y microbiológico. Se identificó la presencia de metabolitos secundarios como flavonoides, compuestos fenólicos, triterpenos y esteroles, alcaloides, quinonas, cumarinas, compuestos lactónicos, antocianidinas, taninos, aminoácidos y azúcares reductores. En la composición cualitativa se observó diferencias entre la droga cruda y los extractos elaborados (AU)

An experimental study was carried out by means of qualitative phyto-chemical screening tests, with the objective to assess the presence of active substances in the crude drug and watery and alcoholic extracts of the plant Adiantum capillus veneris L. (maidenhair fern), widely used by the population to reduce hair loss, prevent colds and cough, and combat urinary tract diseases. There is no pharmacognostic description of the drug in Cuba. The plant samples were collected in Majibacoa municipality, Las Tunas, from September, 2010 to February, 2011. The botanical aspects of the plant were characterized by repercolation the fluid extract and infusing the watery one. The crude drug and both extracts underwent the corresponding quality control analysis, besides the phyto-chemical screening technique established. There was correspondence in relation to the taxonomic classification of the collected plant and what is reported in the specialized literature. The crude drug and the derived extracts fulfilled the requisites established for the chemical, physical and microbiological quality control. Secondary metabolites such as flavonoids, phenolic compounds, triterpenes and sterols, alkaloids, quinones, coumarins, lactonic compounds, anthocyanins, tannins, amino acids and reducing sugars were identified. Differences between the crude drug and the derived extracts were observed in its qualitative composition (AU)

Quiste gigante de ovario / Giant ovarian cyst

Un crecimiento quístico del ovario debe medir por lo menos 2,5 cm de diámetro para denominarse quiste. Se presenta el caso de una paciente de 36 años, femenina, perteneciente a la etnia Wayú, con un quiste gigante en ovario derecho, de aproximadamente 10 cm de diámetro, un peso de 3,6 Kg y torcido sobre su pedículo, que le provoca dolor intenso de más de un mes de evolución. Se practicó intervención quirúrgica y se comprobaron signos macroscópicos de necrobiosis de ovario, siendo el resultado de la biopsia un teratoma maduro. Su resultado final fue satisfactorio(AU)

By definition, a cystic growth of the ovary should measure at least 2,5 cm of diameter to be defined as a cyst. A 36 years old female patient belonging to the Wayú ethnic group is treated due to a giant ovarian cyst in the right ovary. The cyst measures approximately 10 cm of diameter, weights 3,6 Kg and is bent on its pedicle, causing intense pain for about a month. A surgical intervention was performed and there were proven macroscopic signs of ovarian necrobiosis, a mature teratoma being the result of the biopsy. The final result was satisfactory(AU)

Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women.

Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1δ, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

Profile of adipose tissue gene expression in premenopausal and postmenopausal women: site-specific differences.

OBJECTIVES: Menopause increases the risk of several pathologies, probably due to enlarged levels of visceral fat. Apart from morphological and endocrine changes, a cluster of genes, still not fully defined, may be involved in these alterations. The objectives of the present study, therefore, were to analyze differences in adipose tissue gene expression between premenopausal and postmenopausal women and to ascertain whether any differences were depot specific. METHODS: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) biopsies were taken from 7 premenopausal and 7 postmenopausal women undergoing surgery because of morbid obesity. RNA was extracted, and the overall gene expression profile was analyzed by microarray analysis. RESULTS: In general, SAT genes were overexpressed, whereas VAT genes were down-regulated in premenopausal compared with postmenopausal women. We found 724 differentially expressed genes in SAT and 327 in VAT. These differences suggest that several biological processes, such as the immune system and other metabolic processes, were altered based on menopause status. Regarding individual genes, neurexin 3, metallothionein 1E, and keratyn 7 showed the most pronounced differences. Interestingly, the expression of these genes was related to body fat distribution. CONCLUSIONS: Our results reveal that menopause influences the adipose tissue expression of many genes, especially of neurexin 3, metallothionein 1E, and keratyn 7, which are associated with the alteration of several key biological processes, such as the immune system and cell metabolism. Gene expression in adipose tissue could be used for diagnosis and the development of new therapeutic strategies against obesity and related alterations, depending on menopause status.