The impact of frailty on intra-hospital survival in older patients with COVID-19 infection: the importance of early identification. SEMI-COVID National Registry.

BACKGROUND: Emerging evidence suggests that frailty may be a significant predictor of poor outcomes in older individuals hospitalized due to COVID-19. This study aims to determine the prognostic value of frailty on intrahospital patient survival. METHODS: This observational, multicenter, nationwide study included patients aged 70 years and older who were hospitalized due to COVID-19 in Spain between March 1 and December 31, 2020. Patient data were obtained from the SEMI-COVID-19 Registry of the Spanish Society of Internal Medicine. Frailty was assessed using the Clinical Frailty Scale. The primary outcome was hospital survival. Cox proportional hazards models were used to assess predictors of survival. RESULTS: A total of 1,878 participants (52% men and 48% women) were included, with 1,351 (71.9%) survivors and 527 (28.1%) non-survivors. The non-survivor group had higher mean age (83.5 vs. 81 years), comorbidities (6.3 vs. 5.3 points on the Charlson index), degree of dependency (26.8% vs. 12.4% severely dependent patients), and frailty (34.5% vs. 14.7% severely frail patients) compared to survivors. However, there were no differences in terms of sex. Our results demonstrate that a moderate-severe degree of frailty is the primary factor independently associated with shorter survival [HR 2.344 (1.437-3.823; p<0.001) for CFS 5-6 and 3.694 (2.155-6.330; p<0.001) for CFS 7-9]. CONCLUSION: Frailty is the main predictor of adverse outcomes in older patients with COVID-19. The utilization of tools such as the Clinical Frailty Scale is crucial for early detection in this population.

Screening in patients with increased risk of breast cancer (part 2). Where are we now? Actual MRI screening controversies. / Cribado en pacientes con riesgo incrementado de cáncer de mama (parte 2). ¿Dónde estamos? Controversias actuales del cribado con resonancia magnética.

For women with a high risk of breast cancer, early detection plays an important role. Due to the high incidence of breast cancer, and at a younger age than in the general population, screening begins earlier, and there is considerable evidence that magnetic resonance is the most sensitive diagnostic tool, and the principal American and European guidelines agree on the recommendation to perform annual magnetic resonance (with supplemental annual mammography) as an optimal mode of screening. In addition to the absence of current consensus on which patients should be included in the recommendation for magnetic resonance screening (widely discussed in the introduction of part 1 of this work), there are other aspects that are different between guidelines, that are not specified, or that are susceptible to change based on the evidence of several years of experience, that we have called «controversies¼, such as the age to begin screening, the possible advisability of using a different strategy in different subgroups, performing alternate versus synchronous magnetic resonance and mammography, the age at which to terminate the two techniques, or how to follow up after risk reduction surgery.The aim of the second part of the paper is, by reviewing the literature, to provide an update in relation to some of the main «controversies¼ in high risk screening with magnetic resonance. And finally, based on all this, to propose a possible model of optimal and updated screening protocol.

Occurrence of Only One Form of Glutamine Synthetase in the Green Alga Monoraphidium braunii.

Anion-exchange chromatography of crude extracts from the green alga Monoraphidium braunii yielded two glutamine synthetase (GS) activities. The ratio of activities was markedly different when crude extracts were subjected to various processing conditions but was not influenced by environmental factors of cell cultures. However, high performance liquid chromatography anion-exchange chromatograms showed only one GS if the crude extracts were processed immediately after cell disruption. Moreover, standard chromatography of crude extracts obtained in the absence of dithioerythritol, a reductant generally used in disruption buffers, yielded a single activity peak. Enzyme samples from the two activities obtained in the presence of dithioerythritol were purified for physicochemical characterization and antibody production. Both enzyme samples exhibited similar reactions to different inactivating agents and were undistinguishable by size-exclusion chromatography and native polyacrylamide gel electrophoresis. Additionally, the two GS preparations showed absolute antigenic identity as demonstrated by immunodiffusion and immunoblotting experiments. Immunocytochemistry of M. braunii cryosections evidenced a chloroplast-specific distribution of the enzyme, which rules out the existence of a cytoplasmic counterpart. All these results support the proposal that M. braunii possesses only one form of GS.

Structure of the amphibian mesonephric tubule during ontogenesis in Rana ridibunda L. tadpoles: early ontogenetic stages, renal corpuscle formation, neck segment and peritoneal funnels.

The morphological changes produced in the mesonephric tubule during ontogenesis, not previously reported in amphibians, are described in Rana ridibunda tadpoles using light and electron microscopic methods. The rudimentary nephron units do not develop synchronously along the subperitoneal nephrogenic ridged cord. The first signs of morphogenesis are the presence of round euchromatinic nuclei and mitotic figures. The subsequent developmental stages are characterized by detachment of the rudimentary nephrons from the nephrogenic cord. Renal corpuscle formation is characterized by glomerular expansion, differentiation of large fenestrated capillaries and the presence of a discrete mesangium and a small capsular space. Interstitial capillaries next to the renal corpuscle rudiments appear to induce invagination and differentiation of the capsular epithelium. Developing podocytes were cuboidal undifferentiated epithelial cells with scarce primary processes and with an extensive part of the cell surface lying flat on the glomerular basement membrane. These features reflect low or no glomerular filtration during nephron development. The ciliated neck segment and peritoneal funnels show similar structural features. The latter were not physically connected with the nephrons, but opened into renal blood vessels. Involutive peritoneal funnels were observed.

[Sampling limitations in studies of primary care: comparison of 4 sampling designs]. / Limitaciones del muestreo en estudios de atención primaria: comparación de cuatro diseños muestrales.

Different sampling methodologies have been used to avoid the great amount of information which arises in Primary Health Care. The objective of this study is to compare the estimates of four sampling schemes, analyzing variables of utilization, referral activity and diagnostic morbidity, based on data obtained from consultations in a health centre over a one-year period. The percentage of error between each sample estimation and the real value for the whole data set was obtained. Sampling schemes using week periods showed the worst results (40% of error in the estimation of chronic consultations, 18% of error in the percentage of radiology requests and more than 13% in the estimation of morbidity). The findings of this study suggest that some of the sampling schemes usually applied in primary care studies have important limitations, showing the need for more research in this field.

How to reduce avoidable admissions due to acute diabetes complications?: interrelation between primary and specialized attention in a diabetes unit.

INTRODUCTION: Type 2 Diabetes Mellitus is a serious health problem. In the year 2030 it will affect 366 million people around the world. OBJECTIVE: Evaluate the effectiveness of a mixed intervention and reducing the amount and seriousness of acute complications in diabetics from our Health Area. MATERIALS AND METHOD: Protocols of action as well as information documents were produced. Diabetes Unit coordinated educational activities in the different support levels of the Area VII of Murcia. Information talks were provided for the people in charge of the Diabetes Unit in every Care Center and Service of the Health Area. Personalized training was provided for patients treated in the different Care levels. The study comprised three stages. Information leaflets were spread and talks offered to the patient regarding in house handling of hypo and hyper glycemia. RESULTS: A reduction of 39% of the emergencies due to acute non complicated diabetes was achieved, as well as a reduction of 47.6% of hospital admissions. There was a reduction of 67.8% of the amount of total hospital stays for the group of patients under 35 years who were admitted into the hospital due to type 1 or 2 diabetes mellitus that didn't show any complications (GRD295). CONCLUSIONS: There was a reduction of more than thirty percent in the emergencies due to acute decompensations in the disease and a significant reduction in the avoidable hospital stays in the young adult, thus improving the patients' life quality and reducing the social cost of the diabetic patient.

Serum lipid responses to phytosterol-enriched milk in a moderate hypercholesterolemic population is not affected by apolipoprotein E polymorphism or diameter of low-density lipoprotein particles.

BACKGROUND/OBJECTIVES: The importance of both low-density lipoprotein cholesterol (LDLc) size and the apolipoprotein E (Apo E) in the atherogenic process is known, but there is little information with regard to the effect of phytosterols (PS) on these parameters. The aim of this study was to evaluate the influence of PS on lipid profile and LDLc size according to Apo E genotype. SUBJECTS/METHODS: This was a randomized parallel trial employing 75 mild-hypercholesterolemic subjects and consisting of two 3-month intervention phases. After 3 months of receiving a standard healthy diet, subjects were divided into two intervention groups: a diet group (n=34) and a diet+PS group (n=41) that received 2 g/day of PS. Total cholesterol (TC), triacylglycerols, LDLc, high-density lipoprotein cholesterol (HDLc), non-HDLc, Apo A-I and B-100, LDLc size and Apo E genotype were determined. RESULTS: Patients receiving PS exhibited a significant decrease in TC (5.1%), LDLc (8.1%), non-HDLc (7.4%) and Apo B-100/Apo A-I ratio (7.7%), but these effects did not depend on Apo E genotype. No significant changes were found in lipid profile according to Apo E genotype when patients following dietary recommendations were considered as a whole population or separately. No variations in LDLc size were observed in any of the intervention groups. CONCLUSION: The results of this study show that Apo E genotype does not have an impact on the lipid response to PS as a cholesterol-lowering agent in mild-hypercholesterolemic patients. Furthermore, the evidence obtained confirms that LDLc particle size is not modified when PS are added to a standard healthy diet.

[Transient apical dysfunction syndrome (Tako-Tsubo) simulating acute myocardial infarction]. / Síndrome de discinesia apical transitoria (Tako-Tsubo) que simula un infarto agudo de miocardio.

Transient apical dysfunction syndrome (TADS) is frequently misdiagnosed as an acute coronary syndrome (ACS). It is characterized by electrocardiographic alterations and elevated myocardial necrosis markers, accompanied by hypokinesia, akinesia or anteroapical dyskinesia, in absence of significant coronary disorders. It generally resolves in days or weeks with individualized support measures. We present the case of a female patient referred to our service for a myocardial perfusion imaging study due to a history suggestive of an acute coronary syndrome after a stressful event.

Levels of C3 in patients with severe, morbid and extreme obesity: its relationship to insulin resistance and different cardiovascular risk factors.

OBJECTIVE: Increased C3 has been related to body mass index (BMI) and insulin resistance, although there are not sufficient studies in subjects with morbid obesity. The purpose of this study was to evaluate the levels of C3 as a function of the BMI in subjects of both sexes, with severe, morbid and extreme obesity, and their possible relationship to insulin resistance or associated diseases such as diabetes, hypertension and dyslipidemia. SUBJECTS: The study included a total of 316 patients (110 men and 206 women) with severe obesity (17.1%), morbid obesity (54.4%) and extreme obesity (28.4%), with an average BMI of 46.70+/-7.37 kg/m2. MEASUREMENTS: The glucose and insulin levels were determined baseline, and 2 h after a 75 g of oral glucose load. The homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated. A lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein AI and apolipoprotein B100) was obtained and C3 levels determined by nephelometry. RESULTS: When distributing the patients by quartiles of BMI, we found a progressive increase in the levels of C3, and no significant differences in the rest of analytical variables studied were found; the mean values of C3 were 127.78+/-29.7 mg/dl.A significant correlation was found between C3 and the BMI (r=0.263, P<0.001), baseline insulin (r=0.237, P=0.001) and HOMA-IR (r=0.237, P=0.001). High blood pressure was found in 111 patients, type 2 diabetes in 74 patients and dyslipidemia in 139 cases. When distributing the levels of C3 according to the number of associated risk factors (hypertension, diabetes and dyslipidemia), we found significant differences between these patients and those who presented no associated diseases (P<0.01). CONCLUSION: A relationship between C3 and the progressive increase of BMI in subjects with severe, morbid or extreme obesity was established. This increase in C3 was closely related to insulin levels and the values for HOMA-IR. Furthermore, we also found an increase in C3 as more diseases related to insulin resistance, such as diabetes, hypertension and dyslipidemia, were associated with the obesity.

How to reduce avoidable admissions due to acute diabetes complications? Interrelation between primary and specialized attention in a diabetes unit / ¿Cómo reducir los ingresos evitables por complicaciones agudas de la diabetes? Interrelación entre atención primaria y especializada en una unidad de diabetes

Introduction: Type 2 Diabetes Mellitus is a serious health problem. In the year 2030 it will affect 366 million people around the world. Objective: Evaluate the effectiveness of a mixed intervention and reducing the amount and seriousness of acute complications in diabetics from our Health Area. Materials and method: Protocols of action as well as information documents were produced. Diabetes Unit coordinated educational activities in the different support levels of the Area VII of Murcia. Information talks were provided for the people in charge of the Diabetes Unit in every Care Center and Service of the Health Area. Personalized training was provided for patients treated in the differet Care levels. The study comprised three stages. Information leaflets were spread and talks offered to the patient regarding in house handling of hypo and hyper glycemia. Results: A reduction of 39% of the emergencies due to acute non complicated diabetes was achieved, as well as a reduction of 47.6% of hospital admissions. There was a reduction of 67.8% of the amount of total hospital stays for the group of patients under 35 years who were admitted into the hospital due to type 1 or 2 diabetes mellitus that didn't show any complications (GRD295). Conclusions: There was a reduction of more than thirty percent in the emergencies due to acute decompensations in the disease and a significant reduction in the avoidable hospital stays in the young adult, thus improving the patients' life quality and reducing the social cost of the diabetic patient (AU)

Introducción: La diabetes mellitus tipo 2 es un problema de salud grave. En el año 2030 afectará a 366 millones de personas en todo el mundo. Objetivo: Evaluar la eficacia de una intervención mixta y reducir la cantidad y gravedad de las complicaciones agudas de la diabetes en nuestra Área de Salud. Material y método: Se diseñaron protocolos de actuación y documentos de información. La Unidad de Diabetes coordinó las actividades educativas en los diferentes niveles de soporte de la VII Zona de Murcia. Se realizaron charlas de información para los responsables de la Unidad de Diabetes en cada Centro de Atención y Servicio del Área de Salud. Se dio formación personalizada a los pacientes tratados en los distintos niveles de atención. El estudio constó de tres etapas. Se entregaron folletos informativos y charlas al paciente con respecto a la manipulación domiciliaria de hipo e hiperglucemia. Resultados: Se logró una reducción del 39% de las emergencias debidas a diabetes aguda no complicada, así como una reducción del 39% de las emergencias debidas a diabetes aguda no complicada, así como una reducción del 47,6% de los ingresos hospitalarios. Hubo una reducción del 67,8% de la estancia hospitalaria total para el grupo de pacientes menores de 35 años que fueron ingresados en el hospital debido a diabetes tipo 1 o 2 que no mostraron ningún tipo de complicaciones (GRD295). Conclusiones: Se observó una reducción de más del treinta por ciento en los casos de urgencias por descompensaciones agudas de la enfermedad y una reducción significativa en las estancias hospitalarias evitables en el adulto joven, mejorando así la calidad de vida de los pacientes y reduciendo el costo social del paciente diabético (AU)

[Evaluation of a primary care self-management project]. / Evaluación de un proyecto de autogestión en atención primaria.

OBJECTIVE: To evaluate a "Primary Care Self-Management Project" started in 1992. DESIGN: An observational and semi-experimental study with sub-designs: post-test, pretest/post-test with one group, pre-test/post-test with a non-equivalent control group and multiple temporal series. SETTING: An urban area. PARTICIPANTS: The nine Primary Care teams (PCT) in Vitoria-Gasteiz. INTERVENTION: A decentralised budget for self-management was assigned to each PCT, which included Chapter I, staff replacements and Chapter II, Stores, Laboratory, Radiology and Maintenance. MEASUREMENTS AND MAIN RESULTS: 1. Cost control and adjustment of each PCT to the assigned budget. There was an overall saving of 1.8% of the total decentralised budget (96,959,988 pesetas). Six of the nine PCTs fulfilled their assigned budgets. 2. The increase in professional motivation was partially measured by looking at short-term spells off work in the Absence from Work index. In the PCT this index fell 31% from 1991 to 1992, from 4.2 to 2.9%. Among the County's other staff this index remained practically stable, falling only from 5.1 to 4.8%. 3. Higher productivity and better budget use was measured by looking at replacement costs, which went down 7.2% from 1991 to 1992. The proportion of cost arising from replacements for scheduled activities went from 57.9% in 1991 to 39.1% in 1992. CONCLUSIONS: Self-management, at least within the scope of this study, has positive effects on various aspects of the PCTs' work.

Immunological approach to the regulation of nitrate reductase in Monoraphidium braunii.

The effects of different culture conditions on nitrate reductase activity and nitrate reductase protein from Monoraphidium braunii have been studied, using two different immunological techniques, rocket immunoelectrophoresis and an enzyme-linked immunosorbent assay, to determine nitrate reductase protein. The nitrogen sources ammonium and glutamine repressed nitrate reductase synthesis, while nitrite, alanine, and glutamate acted as derepressors. There was a four- to eightfold increase of nitrate reductase activity and a twofold increase of nitrate reductase protein under conditions of nitrogen starvation versus growth on nitrate. Nitrate reductase synthesis was repressed in darkness. However, when Monoraphidium was grown under heterotrophic conditions with glucose as the carbon and energy source, the synthesis of nitrate reductase was maintained. With ammonium or darkness, changes in nitrate reductase activity correlated fairly well with changes in nitrate reductase protein, indicating that in both cases loss of activity was due to repression and not to inactivation of the enzyme. Experiments using methionine sulfoximine, to inhibit ammonium assimilation, showed that ammonium per se and not a product of its metabolism was the corepressor of the enzyme. The appearance of nitrate reductase activity after transferring the cells to induction media was prevented by cycloheximide and by 6-methylpurine, although in this latter case the effect was observed only in cells preincubated with the inhibitor for 1 h before the induction period.

Cytochemical characterization of leucocytes from the seawater teleost, gilthead seabream (Sparus aurata L.).

The cytochemical characterization of head-kidney and peripheral blood leucocytes of gilthead seabream (Sparus aurata L.) was studied by light and electron microscopy. Neutrophilic granulocytes show some cytoplasmic granules, which are positive for alkaline phosphatase and peroxidase but acid phosphatase negative. The scarce granules found in the cytoplasm of the circulating neutrophils and their cytochemical features seem to be indicative of an immature stage. Acidophils are also alkaline phosphatase and peroxidase positive at pH 11.0. They are strongly positive for acid phosphatase and acid phosphatase activity may thus be considered a cytochemical marker to characterize and differentiate neutrophilic from acidophilic granulocytes in this fish species. Three granule populations are characterized in the cytoplasm of the gilthead seabream acidophils: the first is positive only for peroxidase and the second contains a dense core with acid and alkaline phosphatase activities, surrounded by a thin peroxidase positive electron-dense halo. The third granule type contains an eccentric core, which is strongly positive for acid and alkaline phosphatase and peroxidase. As regards their cytochemical features, the first and second granule types seem to correspond respectively to the azurophilic and specific granules found in acidophils of mammals and could be involved in phagocytic processes, thus playing an important microbicidal role in this species. The monocytes, monocyte-macrophages and macrophages show different cytochemical features. The first have scarce acid phosphatase-positive lysosomes, while blood monocyte-macrophages and macrophages are positive for acid and alkaline phosphatases and for peroxidase; the monocyte-macrophages show scarce lysosomes.

Reticulo-endothelial stroma of the head-kidney from the seawater teleost gilthead seabream (Sparus aurata L.): an ultrastructural and cytochemical study.

BACKGROUND: Head-kidney, considered the major fish lympho-haemopoietic tissue, consists of cells of the different haemopoietic series supported by a network of stromal cells whose morphofunctional properties have not been established. We report the ultrastructure and cytochemical features of the reticulo-endothelial stroma of the head-kidney from the seawater teleost gilthead seabream (Sparus aurata L.). METHODS: Samples of head-kidney were processed for electron microscopic study. Some of the samples were incubated for acid and alkaline phosphatase, peroxidase, glucose-6-phosphatase, or ATPase. RESULTS: The reticulo-endothelial stroma of gilthead seabream head-kidney consists of sinusoidal cells (endothelial and adventitial cells) and reticular cells (macrophage-type reticulum and fibroblast-like reticular cells). Transcytosis vesicles and rounded medium electron-dense granules were observed in the cytoplasm of the endothelial cells. The adventitial cells partially covered the outside surface of the endothelial cells and were joined by desmosomes. The macrophage-type reticulum cells were characterized by their cytoplasmic processes and acid phosphatase positive lysosomes. The fibroblast-like reticular cells were joined by desmosomes and formed an extensive network between the haemopoietic parenchyma. They were peroxidase negative and acid and alkaline phosphatase, glucose-6-phosphatase, beta-glucuronidase, and ATPase positive. CONCLUSIONS: The ultrastructural and cytochemical features of the reticulo-endothelial stroma of the gilthead seabream head-kidney are similar to those of mammalian bone marrow, suggesting phylogenetic analogies between both tissues.

Blood cells of the gilthead seabream (Sparus aurata L.): light and electron microscopic studies.

The peripheral blood cells of the gilthead seabream (Sparus aurata L.) were studied by light and transmission and scanning electron microscopic methods. Acidophilic erythroblasts and mature erythrocytes, round, oval, and fusiform thrombocytes, neutrophils, acidophils and basophils, lymphocytes, plasma cells, and monocyte-macrophages were characterized. A comparison of our light and electron microscopic results was carried out. The results were discussed with those for other fish species and the main modifications from the common vertebrate haematological pattern observed being considered.

Ultrastructure of nonspecific cytotoxic cells in teleosts. I. Effector-target cell binding in a marine and a freshwater species (seabream: Sparus aurata L., and carp: Cyprinus carpio L.).

BACKGROUND: Fish cytotoxic effectors form a cell population whose ultrastructure and properties of conjugation with target cells have not been completely established. We report the ultrastructure of the nonspecific cytotoxic cells in a seawater teleost (Sparus aurata L.) and compare it to a freshwater species (Cyprinus carpio L.). METHODS: Blood leucocytes were incubated with HeLa or B16 melanoma cells. Samples were processed for transmission electron microscopic study. RESULTS: Conjugates consisting of leucocytes binding targets were regularly observed after 30 min, 1 hr, or 2 hr of incubation. In both species leucocytes binding to targets showed ultrastructural features of either monocyte-like or lymphocyte-like cells. Monocyte-like cells usually appeared flattened against the targets and seemed to enclose fragments of the target to form cytoplasmic vesicles and the content of their scarce cytoplasmic granules seemed to be delivered into these vesicles. In the seabream lymphocyte-like cells, dense cytoplasmic granules occurred only occasionally, and neither microvilli nor cell processes were present at the contact areas with the targets. In the carp, the contacts were more numerous and formed regularly interdigitating contact areas and the lymphocytes showed granules with characteristic dense and fibrillar contents. CONCLUSIONS: We conclude that seabream and carp have a leucocyte cell population with ultrastructural features of either monocytes or lymphocytes showing nonspecific cytotoxic ability.

Immunocytochemical localization of nitrite reductase in green algae.

The distribution of nitrite reductase (EC 1.7.7.1) in the green algae Chlamydomonas reinhardtii, Monoraphidium braunii, Chlorella fusca, and Scenedesmus obliquus was studied by immunoelectron microscopy. The labeling of ultrathin cryosections was performed with anti-nitrite reductase antibodies followed by gold-labeled goat anti-rabbit antibodies. In C. reinhardtii sections, gold label was mainly associated with the pyrenoid, tonoplast, and plasmalemma. Significant labeling was also detected in the thylakoid region. In all other organisms, label density was lower but distributed in the same locations, except that the plasmalemma of S. obliquus was not significantly labeled. From estimates of the relative volume of different cell regions, we found that approximately 80% of the total enzyme is located in the chloroplastic region (thylakoids plus pyrenoid) of C. reinhardtii, M. braunii, and C. fusca, and 97% in the case of S. obliquus.

Glutathione reductase directly mediates the stimulation of yeast glucose-6-phosphate dehydrogenase by GSSG.

Yeast glucose-6-phosphate dehydrogenase was inhibited by low NADPH concentrations in cell-free extracts, and de-inhibited by GSSG; extensive dialysis of the crude extract did not diminish the GSSG effect. Immunoprecipitation of glutathione reductase abolished the de-inhibition of glucose-6-phosphate dehydrogenase by GSSG. Purified glucose-6-phosphate dehydrogenase was inhibited by NADPH but not de-inhibited by GSSG, and upon addition of pure glutathione reductase GSSG completely de-inhibited the glucose-6-phosphate dehydrogenase.