Biopuncture, A Multitarget Therapy in the Treatment of Individuals with Knee Osteoarthritis: state of the art.

Objectives: The objective of this manuscript was to carry out a comprehensive review of the published information on the use of Biopuncture in patients with knee osteoarthritis. Methods: A scientific search was performed using online databases following the terms (Biopuncture) and (Knee Osteoarthritis) to identify scientific manuscripts that were related to the use of Biopuncture in the treatment of individuals with knee osteoarthritis. Results: With the information found, a theoretical framework was integrated that describes the components of Biopuncture, its mechanism of action and practical topics for the application of the technique. Conclusion: Biopuncture appears to be a potential, simple and low-risk therapeutic strategy in the treatment of knee osteoarthritis, which is applied through periarticular subcutaneous injections, with multitarget mechanisms of action at various physiopathological levels such as the modulation of the inflammatory process, decreased peripheral sensitization, and stimulation of antidegenerative and trophic mechanisms. Perhaps it can be part of the integrative treatments for knee osteoarthritis.

New Advances in the Study of CMTM6, a Focus on Its Novel Non-Canonical Cellular Locations, and Functions beyond Its Role as a PD-L1 Stabilizer.

CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it has non-canonical subcellular localizations in cell lines derived from cervical cancer. Our objective was to determine whether CMTM6 is found in plasma derived from cervical cancer patients and its subcellular localization in cell lines. Patient plasma was separated into exosome-enriched, exosome-free, and total plasma fractions. The levels of CMTM6 in each fraction were determined using ELISA and Western blot. Finally, for the cellular model, HeLa, SiHa, CaSki, and HaCaT were used; the subcellular locations of CMTM6 were determined using immunofluorescence and flow cytometry. Soluble CMTM6 was found to be elevated in plasma from patients with cervical cancer, with a nearly three-fold increase in patients (966.27 pg/mL in patients vs. 363.54 pg/mL in controls). CMTM6 was preferentially, but not exclusively, found in the exosome-enriched plasma fraction, and was positively correlated with exosomal PD-L1; CMTM6 was identified in the membrane, intracellular compartments, and culture supernatant of the cell lines. These results highlight that CMTM6, in its various presentations, may play an important role in the biology of tumor cells and in immune system evasion.

Agave-Laurate-Bioconjugated Fructans Decrease Hyperinsulinemia and Insulin Resistance, Whilst Increasing IL-10 in Rats with Metabolic Syndrome Induced by a High-Fat Diet.

Metabolic syndrome (MetS) comprises a cluster of metabolic risk factors, which include obesity, hypertriglyceridemia, high blood pressure, and insulin resistance. The purpose of this study was to evaluate the effects of laurate-bioconjugated fructans on pro- and anti-inflammatory cytokines in Wistar rats with MetS induced by a high-fat diet. Laurate-bioconjugated fructans were synthesized with agave fructans, immobilized lipase B, and vinyl laureate as the acylant. Groups were fed a standard diet (NORMAL), a high-fat diet (HFD), or a high-fat diet plus laurate-bioconjugated fructans (FL PREV) for 9 weeks. A fourth group received a high-fat diet for 6 weeks, followed by simultaneous exposure to a high-fat diet and laurate-bioconjugated fructans for 3 additional weeks (FL REV). The dose of laurate-bioconjugated fructans was 130 mg/kg. Laurate-bioconjugated fructans reduced food and energy intake, body weight, body mass index, abdominal circumference, adipose tissue, adipocyte area, serum triglycerides, insulin, insulin resistance, and C-reactive protein but they increased IL-10 protein serum levels and mRNA expression. The impact of laurate-bioconjugated fructans on zoometric and metabolic parameters supports their potential as therapeutic agents to improve obesity, obesity comorbidities, insulin resistance, type 2 diabetes mellitus, and MetS.

GPS Data and Machine Learning Tools, a Practical and Cost-Effective Combination for Estimating Light Vehicle Emissions.

This paper focuses on the emissions of the three most sold categories of light vehicles: sedans, SUVs, and pickups. The research is carried out through an innovative methodology based on GPS and machine learning in real driving conditions. For this purpose, driving data from the three best-selling vehicles in Ecuador are acquired using a data logger with GPS included, and emissions are measured using a PEMS in six RDE tests with two standardized routes for each vehicle. The data obtained on Route 1 are used to estimate the gears used during driving using the K-means algorithm and classification trees. Then, the relative importance of driving variables is estimated using random forest techniques, followed by the training of ANNs to estimate CO2, CO, NOX, and HC. The data generated on Route 2 are used to validate the obtained ANNs. These models are fed with a dataset generated from 324, 300, and 316 km of random driving for each type of vehicle. The results of the model were compared with the IVE model and an OBD-based model, showing similar results without the need to mount the PEMS on the vehicles for long test drives. The generated model is robust to different traffic conditions as a result of its training and validation using a large amount of data obtained under completely random driving conditions.

Human TIMP1 Is a Growth Factor That Improves Oocyte Developmental Competence.

Oocyte developmental competence is the ability of a mature oocyte to be fertilized and subsequently support embryonic development. Such competence is gained during folliculogenesis and is facilitated by the bidirectional communication into a compacted cumulus-oocyte complex (COC). Human tissue inhibitor of metalloproteinases-1 (TIMP1) participates in biological processes, including cell growth, differentiation, and apoptosis. This study aimed to evaluate the influence of TIMP1 as a growth factor on the in vitro maturation (IVM) culture of bovine COCs to improve oocyte developmental competence. All TIMP1 treatments (50, 100, and 150 ng/mL) favored the COCs' compaction structure (p < 0.05). TIMP1 at 150 ng/mL produced more oocytes in metaphase II compared to the other treatments (p < 0.05). The 150 ng/mL TIMP1 generated oocytes with the most (p < 0.05) cortical granules below the plasma membrane (pattern I). In a parthenogenesis assay, oocyte IVM in 50 ng/mL of TIMP1 produced the most blastocyst compared to the other treatments (p < 0.05). The Principal Component Analysis (PCA) showed that 50 ng/mL of TIMP1 was the best condition to develop oocyte competence because it was associated with the COC compact and cortical granule pattern I. TIMP1 influences the development of oocyte competence when added to the IVM culture medium of COCs.

Acute pulmonary artery dissection in an adult with chronic pulmonary hypertension secondary to congenital heart disease: a case report.

Background: D-Transposition of the great arteries (d-TGA) is characterized by the aorta positioned above the right ventricle and the pulmonary artery above the left ventricle. Acute pulmonary artery dissection (PAD) is a rare and often lethal condition. We present a case report of acute PAD in an adult with d-TGA and pulmonary hypertension. Case summary: A 49-year-old male with history of d-TGA palliated with an atrial switch (Mustard) operation, pulmonary venous baffle stenosis treated percutaneously, chronic pulmonary hypertension (mixed group 1 and 2), and severe dilatation of pulmonary arteries (pulmonary trunk of 75 mm) presented to the emergency department with chest pain and acute respiratory failure. Blood pressure was 106/78 mmHg, heart rate 93 b.p.m., and oxygen saturation 88% on room air. A computed tomography (CT) scan showed acute right PAD. He was not considered suitable for surgery nor percutaneous procedure. Epoprostenol was initiated to reduce parietal stress, but after initial stabilization, pulmonary venous stent baffle gradient increased and acute pulmonary oedema occurred. Epoprostenol was withdrawn, and furosemide was initiated, with good clinical response. A follow-up CT scan showed dissection morphological stabilization and false lumen thrombosis, and the patient was discharged. Discussion: Pulmonary hypertension and previous pulmonary artery dilatation are reported as the main underlying conditions leading to PAD. No previous cases of PAD are described in patients with history of d-TGA and atrial switch procedure. Evidence regarding the best treatment of PAD is lacking, but it seems reasonable to reduce parietal stress using pulmonary vasodilators. Nevertheless, in patients with post-capillary pulmonary hypertension, pulmonary vasodilatation may cause important pulmonary congestion.

AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis.

The development of several vaccines against the SARS-CoV2 virus and their application in millions of people have shown efficacy and safety in the transfer of genes to muscle turning this tissue into a protein-producing factory. Established advanced liver fibrosis, is characterized by replacement of hepatic parenchyma by tissue scar, mostly collagen type I, with increased profibrogenic and proinflammatory molecules gene expression. Matrix metalloproteinase 8 (MMP-8) is an interstitial collagen-degrading proenzyme acting preferentially on collagen type I when activated. This study was carried out to elucidate the effect of an intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) in male Wistar rats with experimental advanced liver fibrosis induced by thioacetamide. Therapeutic effects were monitored after 1, 2, or 3 weeks of a single dose (3 × 1011 vp/kg) of AdhMMP8. Circulating and liver concentration of MMP-8 protein remained constant; hepatic fibrosis decreased up to 48%; proinflammatory and profibrogenic genes expression diminished: TNF-α 2.28-fold, IL-1 1.95-fold, Col 1A1 4-fold, TGF-ß1 3-fold and CTGF 2-fold; and antifibrogenic genes expression raised, MMP-9 2.8-fold and MMP-1 10-fold. Our data proposes that the administration of AdhMMP8 in muscle is safe and effective in achieving liver fibrosis regression at a comparable extent as when the adenoviral vector is delivered systemically to reach the liver, using a minimally invasive procedure.

Low-diversity microbiota and an increased metabolism of arginine and aromatic amino acids: a hallmark of hepatic encephalopathy in western Mexican patients with alcohol-associated cirrhosis.

AIMS: To evaluate the composition and functions of the gut microbiota in patients with decompensated alcohol-associated cirrhosis, with and without hepatic encephalopathy (HE). METHODS AND RESULTS: Faecal samples from 31 inpatients (20 with HE, 11 without HE), and from 18 age-balanced healthy controls (HC), were included. Microbial composition was determined by 16S rRNA amplicon sequencing and analysed using QIIME2. Metabolic pathways were inferred by PICRUSt2, and short-chain fatty acids (SCFAs) quantification was performed by gas chromatography. The gut microbiota of patients with HE was characterized by a diminished α-diversity, compared to no-HE (P < 0.01) and HC (P < 0.001) groups; ß-diversity also differed between HE vs no-HE patients (P < 0.05), and between HE vs HC (P < 0.001). In patients with HE, Escherichia/Shigella, Burkholderiales and Lactobacillales taxa predominated. In contrast, patients without HE were characterized by Veillonella and Bacteroides. Reduced levels of faecal SCFAs in both groups correlated with a depletion of beneficial taxa, such as Ruminococcus or Faecalibacterium. PICRUSt2 analysis showed both an enhanced catabolism of arginine through ammonia-producing pathways and chorismate biosynthesis in HE patients, a key precursor of aromatic amino acids. CONCLUSIONS: The gut microbiota of HE patients exhibits a proinflammatory dysbiotic profile, plus metabolic pathways that produce potentially neurotoxic byproducts.

Pregnancy-related aortic complications in women with bicuspid aortic valve.

OBJECTIVES: To describe the aortic-related risks associated with pregnancy in women with bicuspid aortic valve (BAV) and to evaluate changes in aortic diameter in pregnancy. METHODS: Prospective observational study of patients with BAV from a single-site registry of pregnant women with structural heart disease between 2013 and 2020. Cardiac, obstetric and neonatal outcomes were studied. An assessment of aortic dimensions was performed during pregnancy by two-dimensional echocardiography. Aortic diameters were measured at the annulus, root, sinotubular junction and maximum ascending aorta diameter, and the largest diameter was used. Measurements of the aorta were made using the end-diastolic leading edge-to-leading edge convention. RESULTS: Forty-three women (32.9 years, IQR 29.6-35.3) with BAV were included: 9 (20.9%) had repaired aortic coarctation; 23 (53.5%) had moderate or severe aortic valve disease; 5 (11.6%) had a bioprosthetic aortic valve; and 2 (4.7%) had a mechanical prosthetic aortic valve. Twenty (47.0%) were nulliparous. The mean aortic diameter in the first trimester was 38.5 (SD 4.9) mm, and that in the third trimester was 38.4 (SD 4.8) mm. Forty (93.0%) women had an aortic diameter of <45 mm; 3 (7.0%) had 45-50 mm; and none had >50 mm. Three women (6.9%) with BAV presented cardiovascular complications during pregnancy or the postpartum period (two prosthetic thrombosis and one heart failure). No aortic complications were reported. There was a small but significant increase in aortic diameter during pregnancy (third trimester vs first trimester, 0.52 (SD 1.08) mm; p=0.03). Obstetric complications appeared in seven (16.3%) of pregnancies, and there were no maternal deaths. Vaginal non-instrumental delivery was performed in 21 (51.2%) out of 41 cases. There were no neonatal deaths, and the mean newborn weight was 3130 g (95% CI 2652 to 3380). CONCLUSIONS: Pregnancy in BAV women had a low rate of cardiac complications with no aortic complications observed in a small study group. Neither aortic dissection nor need for aortic surgery was reported. A low but significant aortic growth was observed during pregnancy. Although requiring follow-up, the risk of aortic complications in pregnant women with BAV and aortic diameters of <45 mm at baseline is low.

Oxidative and Fibrinolytic Mechanisms: Two Important Processes to Consider in Platelet Storage

Objective: Platelet-rich plasma (PRP) is used in multiple coagulation disorders. Its therapeutic effectiveness relies on technical procedures related to PRP procurement and preservation because free radicals induce platelet activation and aging. This work aims to elucidate the oxidative mechanisms involved in activation of platelets obtained from PRP during storage. Materials and Methods: One hundred ten PRP batches were obtained from healthy donors and kept under stirring at a temperature of 20-24 °C. Protein extraction was performed from platelet homogenates and plasma at different times of storage from day 1 to 20. The activities of antioxidant markers such as catalase (CAT), superoxide dismutase, and ceruloplasmin, as well as fibrinolytic protein activity metalloproteases 2 and 3, plasmin, and urokinase plasminogen activator, were analyzed by zymography assays. Oxidized proteins were also determined. Results: Significant activity of antioxidant enzymes and fibrinolytic molecules was observed on day 5 of storage in PRP homogenates, which increased over time and was concomitantly correlated with oxidized protein levels. Reverse enzymatic activity patterns were observed in plasma, except for CAT, which remained unchanged. Conclusion: Storage conditions of platelets from PRP for up to 5 days induced in vitro platelet activation by oxidative damage and proteolysis. This finding confirms the need for proper management of these blood products to preserve their viability and functionality.

Non-fitness status of peripheral NK cells defined by decreased NKp30 and perforin, and increased soluble B7H6, in cervical cancer patients.

The NKp30 receptor is one of the three natural cytotoxic receptors reported in NK cells. This receptor is codified by the NCR3 gene, which encodes three isoforms, a consequence of the alternative splicing of exon 4. A greater expression of the three isoforms (A, B, and C), along with low levels of the NKp30 ligand B7H6, has been reported as a positive prognostic factor in different cancer types. Here, in patients with cervical cancer and precursor lesions, we report an altered immune-phenotype, characterized by non-fitness markers, that correlated with increased disease stage, from CIN 1 to FIGO IV. While overall NK cell numbers increased, loss of NKp30+ NK cells, especially in the CD56dim subpopulation, was found. Perforin levels were decreased in these cells. Decreased expression of the NKp30 C isoform and overexpression of soluble B7H6 was found in cervical cancer patients when compared against healthy subjects. PBMCs from healthy subjects downregulated NKp30 isoforms after co-culture with B7H6-expressing tumour cells. Taken together, these findings describe a unique down-modulation or non-fitness status of the immune response in cervical cancer, the understanding of which will be important for the design of novel immunotherapies against this disease.

Cambios en la microbiota durante el embarazo: revisión narrativa / Changes in the microbiota during pregnancy: a narrative review

OBJETIVO: Evaluar la evidencia científica de los cambios en la microbiota durante el embarazo. METODOLOGÍA: Revisión de la bibliografía publicada entre el 2013 y el 2022 efectuada mediante la búsqueda de artículos científicos escritos en español e inglés resguardados en las bases de datos bibliográficas NICE, CENETEC-SALUD, BIREME y Portal OMS, OPS, Portal de Evidencias de la Biblioteca Virtual de Salud - BVS, LILACS, BIREME, EVIPNET, PubMed y Cochrane. La selección de artículos se basó en los descriptores: microbiota; embarazo-pregnancy; microbiota, gut microbiome, fetus-feto; microbiota, placenta; microbiota, combinadas entre sí con el operador boleano "and". RESULTADOS: Se identificaron 3038 posibles artículos y 137 se encontraron adecuados para el objetivo de la revisión en virtud de estar relacionados directamente con el embarazo y la microbiota. Se revisaron estudios transversales, ensayos, revisiones, cohortes, casos y controles, revisiones sistemáticas o matanálisis. CONCLUSIONES: La microbiota se encuentra en diversos tejidos u órganos que anteriormente se creían estériles durante el embarazo. Se sugiere que todos los cambios que implica esta etapa pueden influir en la microbiota de la madre y el feto. A pesar de las crecientes investigaciones en el área aún quedan preguntas por contestar para ayudar a solucionar el enigma de los cambios en la diversidad en las diferentes complicaciones del embarazo y saber si los probióticos tendrían efecto o no en la disminución del riesgo a padecerlas.

Abstract OBJECTIVE: to evaluate the scientific evidence on changes in the microbiota during pregnancy. METHODOLOGY: A review of the literature published between 2013 and 2022 was carried out through the search of scientific articles in Spanish and English in the bibliographic databases NICE, CENETEC-SALUD, BIREME AND PORTAL WHO, PAHO, Portal of Evidence of the Virtual Health Library - BVS, LILACS, BIREME, EVIPNET, PUBMED and COCHRANE. The selection of articles was based on the descriptors: Microbiota, pregnancy, Gut microbiome, Fetus-Microbiota, Placenta - Microbiota, combined with each other with the Boolean "and". RESULTS: A total of 3,038 possible articles were identified and 137 were found suitable for the objective of the review because they were directly related to pregnancy and microbiota. Cross-sectional studies, trials, reviews, cohorts, case-controls, systematic review, or meta-analysis were reviewed. CONCLUSIONS: Microbiota has been found in various tissues or organs that were previously believed to be sterile during pregnancy, and with this, it is suggested that all the changes that this stage entails can influence the maternal and fetal microbiota. However, despite the growing research in the area, there are still questions to be resolved to help solve the enigma of the changes in diversity in the different complications of pregnancy and whether the use of probiotics would influence reducing the risk to present them.

Milk-Gelling Properties of Proteases Extracted from the Fruits of Solanum Elaeagnifolium Cavanilles.

There is little information on the milk coagulation process by plant proteases combined with chymosins. This work is aimed at studying the capability of protease enclosed in the ripe fruits of Solanum elaeagnifolium (commonly named trompillo) to form milk gels by itself and in combination with chymosin. For this purpose, proteases were partially purified from trompillo fruits. These proteases had a molecular weight of ~60 kDa, and results suggest cucumisin-like serine proteases, though further studies are needed to confirm this observation. Unlike chymosins, trompillo proteases had high proteolytic activity (PA = 50.23 UTyr mg protein-1) and low milk-clotting activity (MCA = 3658.86 SU mL-1). Consequently, the ratio of MCA/PA was lower in trompillo proteases (6.83) than in chymosins (187 to 223). Our result also showed that milk gels formed with trompillo proteases were softer (7.03 mPa s) and had a higher release of whey (31.08%) than the milk gels clotted with chymosin (~10 mPa s and ~4% of syneresis). However, the combination of trompillo proteases with chymosin sped up the gelling process (21 min), improved the firmness of milk gels (12 mPa s), and decreased the whey release from milk curds (3.41%). Therefore, trompillo proteases could be combined with chymosin to improve the cheese yield and change certain cheese features.

Identification of the Mechanical Failure Factors with Potential Influencing Road Accidents in Ecuador.

Road traffic accidents result in injury or even death of passengers. One potential cause of these accidents is mechanical failures due to a lack of vehicle maintenance. In the quest to identify these mechanical failures, this paper aims to set up the procedure to identify the mechanical failures that contribute to traffic accidents in cities located in developing countries, including the city of Cuenca-Ecuador. For present research, a database provided by the entity responsible for the Vehicle Technical Inspection, the Empresa Pública Municipal de Movilidad, Tránsito y Transporte and for the ones responsible of managing traffic accident data, Oficina de Investigación de Accidentes de Tránsito and Sección de Investigación de Accidentes de Tránsito was used. The vehicle subcategories M1 and M3 (bus type) and N1, so named according to Ecuadorian technical standards, were considered the most relevant regarding accident rates. The database was analysed with descriptive statistics, a Pareto chart and time series with the quadratic trend. From this analysis, the most significant failures found in the VTI in all three subcategories were the alignment of the driver headlight, both horizontal and vertical, braking imbalance on the 2nd axle, insufficient tire tread and parking brake effectiveness. All these failures showed a decreasing trend over time and in the forecast at a maximum of two to three years. The most relevant causes of road accidents recorded during the period 2009-2018 related to mechanical failures were the braking system (65.5%) and the steering system (17.2%) for subcategory M1.

A Novel Method for Carbon Nanotube Functionalization Using Immobilized Candida antarctica Lipase.

Carbon nanotubes (CNTs) have been proposed as nanovehicles for drug or antigen delivery since they can be functionalized with different biomolecules. For this purpose, different types of molecules have been chemically bonded to CNTs; however, this method has low efficiency and generates solvent waste. Candida antarctica lipase is an enzyme that, in an organic solvent, can bind a carboxylic to a hydroxyl group by esterase activity. The objective of this work was to functionalize purified CNTs with insulin as a protein model using an immobilized lipase of Candida antarctica to develop a sustainable functionalization method with high protein attachment. The functionalized CNTs were characterized by scanning electron microscope (SEM), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The enzymatic functionalization of insulin on the surface of the CNTs was found to have an efficiency of 21%, which is higher in conversion and greener than previously reported by the diimide-activated amidation method. These results suggest that enzymatic esterification is a convenient and efficient method for CNT functionalization with proteins. Moreover, this functionalization method can be used to enhance the cellular-specific release of proteins by lysosomal esterases.

Nanoparticles Formulation Improves the Antifibrogenic Effect of Quercetin on an Adenine-Induced Model of Chronic Kidney Disease.

Renal fibrosis is the final stage of chronic kidney injury characterized by glomerulosclerosis and tubulointerstitial fibrosis with parenchymal destruction. Quercetin belongs to the most studied flavonoids with antioxidant, anti-inflammatory, antifibrogenic, and antitumor activity. It modifies the TGF-ß/Smad signaling pathway, decreasing profibrogenic expression molecules and inducing the expression of antioxidant, anti-inflammatory, and antifibrogenic molecules. However, quercetin exhibits poor water solubility and low absorption and bioavailability. This limitation was solved by developing a nanoparticles formulation that improves the solubility and bioavailability of several bioactive compounds. Therefore, we aimed to investigate the in vivo antifibrogenic effect of a quercetin nanoparticles formulation. Male C57BL/6 mice were induced into chronic renal failure with 50 mg/kg of adenine for four weeks. The animals were randomly grouped and treated with 25, 50, or 100 mg/kg of quercetin, either macroparticles or nanoparticles formulation. We performed biochemical, histological, and molecular analyses to evaluate and compare the effect of macroparticles versus nanoparticles formulation on kidney damage. Here, we demonstrated that smaller doses of nanoparticles exhibited the same beneficial effect as larger doses of macroparticles on preventing kidney damage. This finding translates into less quercetin consumption reaching the desired therapeutic effect.

IMD/ADM2 operates as a secretory factor that controls cumulus-oocyte complexes (COCs) conformation for oocytes in vitro maturation.

During in vitro maturation (IVM), the compact structure of cumulus-oocyte complexes (COCs) is vital for oocyte competence acquisition. Intermedin/Adrenomedullin-2 (IMD/ADM2) binds to the receptor RAMP (1, 2, or 3):CLR. Recently, it was demonstrated that IMD/ADM2 stimulates oocyte competence and improves bovine embryo quality. Therefore, this study aimed to examine the IMD/ADM2 as a secretory factor controlling COCs conformation for oocyte maturation. The results showed that traditional M-CDM medium induced in COCs the Imd/Adm2 gene expression during IVM and produced IMD/ADM2 peptide secretion. Furthermore, after IVM, in the oocytes, the expression of ramps (1, 2, or 3) and clr was demolished, and RAMPs and CLR proteins were decreased, with a negative Pearson correlation. These results suggest that RAMPs and CLR are synthesized and stored during oocyte maturation. Supplementing the M-CDM with α-RAMP1 or α-IMD/ADM2 antibodies elicits a negative effect (P < 0.05) in COCs compaction. Blocking the IMD/ADM2 signaling pathway with any α-RAMPs or α-CLR antibodies produces a similar lower yield of oocytes in metaphase II (P > 0.05) but was lower than control culture medium (P < 0.05). In conclusion, when COCs are cultured with M-CDM, the IMD/ADM2 becomes expressed and secreted. In turn, it acts as a ligand preferentially to RAMP1:CLR or RAMP3:CLR, present in cumulus cells and oocytes. Sequentially, COCs compact structure is conformed to promote an adequate bidirectional communication that conduces the oocytes' maturation.

Long-term Outcomes of Adults With Single Ventricle Physiology Not Undergoing Fontan Repair: A Multicentre Experience.

BACKGROUND: To describe long-term survival and cardiovascular events in adult patients with single ventricle physiology (SVP) without Fontan palliation, focusing on predictors of mortality and comparing groups according to their cardiovascular physiology. METHODS: Multicentre observational and retrospective study including adult patients with SVP without Fontan palliation since their first adult clinic visit. The cohort was subdivided into 3 groups: Eisenmenger, restricted pulmonary flow, and aortopulmonary shunt. Death was considered as the main end point. Other clinical outcomes occurring during follow-up were considered as secondary end points. RESULTS: A total of 146 patients, mean age 32.5 ± 11.1 years, were analysed. Over a mean follow-up of 7.3 ± 4.1 years, 33 patients (22.6%) died. Survival was 86% and 74% at 5 and 10 years, respectively. Right ventricular morphology was not associated with higher mortality. Four variables at baseline were related to a higher mortality: at least moderate atrioventricular valve regurgitation, platelet count < 150 × 103/mm3, GFR < 60 mL/min/1.73 m2, and QRS > 120 ms). A total of 34.2% of patients were admitted to the hospital due to heart failure, and 7.5% received a heart transplant. Other cardiovascular outcomes were also frequent: atrial arrhythmias in 19.2%, stroke in 15.1%, and pacemaker/implantable cardioverter-defibrillator in 6.2%/2.7%. CONCLUSIONS: Adult patients with SVP who had not undergone Fontan exhibit a high mortality rate and frequent major cardiovascular events. At least moderate atrioventricular valve regurgitation, thrombocytopenia, renal dysfunction, and QRS duration > 120 ms at baseline visit allow identification of a cohort of patients at higher risk of mortality.

Hypertonic Dextrose Prolotherapy, an Alternative to Intra-Articular Injections With Hyaluronic Acid in the Treatment of Knee Osteoarthritis: Systematic Review and Meta-analysis.

ABSTRACT: Intra-articular injections with hyaluronic acid are recommended in the treatment of knee osteoarthritis; however, hypertonic dextrose prolotherapy has been reported as effective and safe. The aim was to evaluate the effectiveness of hypertonic dextrose prolotherapy for pain reduction and improvement of function in individuals with knee osteoarthritis in comparison with hyaluronic acid by meta-analysis. The search was performed in electronic databases. Six studies were included (395 participants). No statistically significant differences were found between prolotherapy and hyaluronic acid in pain control in the short-term; however, in the subanalysis that included only the studies that used intra-articular injection within the prolotherapy scheme, an effect was found in favor of the prolotherapy groups ( d = -1.33; 95% confidence interval, -2.50 to -0.16; P ( z ) = 0.03). Also, an effect was found in favor of the prolotherapy group in the improvement in function ( d = -1.05; 95% confidence interval, -2.03 to -0.08; P ( z ) = 0.03). No major adverse reactions or side effects were reported in any of the studies. Hypertonic dextrose prolotherapy seems to be an effective intervention to decrease pain and improve function in knee osteoarthritis, with efficacy similar to intra-articular injections with hyaluronic acid in the short-term follow-up. Nonetheless, better-quality clinical trials are necessary.

Relación entre hierro y diabetes mellitus gestacional: una revisión narrativa / Relationship between iron and gestational diabetes mellitus: a narrative review

Resumen OBJETIVO: Evaluar la evidencia científica acerca de la relación entre el hierro y la diabetes mellitus gestacional. METODOLOGÍA: Revisión narrativa, fundamentada en la búsqueda de artículos publicados de 2000 a 2021 en las bases de datos de PubMed, LILACS, BIREME, NICE, SIGN y CENETEC con los MeSH: Iron, iron and diabetes, Iron overland, Gestational Diabetes y Iron overland and Gestational Diabetes. Se seleccionaron los relacionados con el tema de interés. RESULTADOS: Se encontraron 119 artículos y solo 34 se consideraron adecuados para el objetivo de la revisión porque estaban directamente relacionados con el metabolismo del hierro, diabetes gestacional y el hierro como causa de diabetes gestacional. Se obtuvieron estudios transversales, casos y controles, cohortes, ensayos, revisiones y metanálisis. CONCLUSIONES: La relación entre hierro y diabetes mellitus gestacional no está debidamente establecida; sin embargo, se ha relacionado con la capacidad oxidativa del hierro por diferentes mecanismos que acentúan la resistencia a la insulina. Se sugiere que las concentraciones elevadas de hierro podrían ser un factor de riesgo de diabetes mellitus gestacional.

Abstract OBJECTIVE: To evaluate the scientific evidence about the relationship between iron and gestational diabetes mellitus. METHODOLOGY: Narrative review, based on the search for articles published from 2000 to 2021 in the PubMed, LILACS, BIREME, NICE, SIGN and CENETEC databases with the MeSH: Iron, iron and diabetes, Iron overland, Gestational Diabetes and Iron Overland and Gestational Diabetes. Those related to the topic of interest were selected. RESULTS: 119 articles were found and only 34 were considered adequate for the purpose of the review because they were directly related to iron metabolism, gestational diabetes and iron as a cause of gestational diabetes. Cross-sectional studies, cases and controls, cohorts, trials, reviews and meta-analyses were obtained. CONCLUSIONS: The relationship between iron and gestational diabetes mellitus is not properly established; however, it has been related to the oxidative capacity of iron through different mechanisms that accentuate insulin resistance. It is suggested that high iron concentrations could be a risk factor for gestational diabetes mellitus.