Long COVID: Factors influencing persistent symptoms and the impact of gender.

OBJECTIVE: This study aimed to characterize the prevalence as well as clinical and epidemiological features of persistent symptoms after acute COVID-19, focusing on gender-specific differences in a primary care setting. METHODS: A total of 1542 individuals with confirmed SARS-CoV-2 infection were enrolled. The study population comprised 55.77% females (mean age: 45.04 years). Risk factors for persistent COVID-19 were analyzed, revealing disparities between men and women. Symptom clusters and their prevalence were assessed over time, along with functional status using the post-COVID-19 functional status scale. RESULTS: The prevalence of persistent COVID-19 was 12.38%, with females exhibiting a 1.5 times higher risk. Females displayed a higher number of visits and persistent symptoms at 90 days, decreasing after one year. Symptom clusters varied between genders, with females experiencing more dermatological issues. Functional status analysis revealed that females had a better pre-infection status, similar status to males at 90 days, and improved status at 180-, 270-, and 365-days post-infection. Logistic regression analysis showed significant associations between persistence, gender, hospitalization, radiological abnormalities, age, and immunosuppression. CONCLUSION: This study provides insights into the prevalence and clinical characteristics of persistent COVID-19 in a primary care population. Females exhibited a higher risk of persistent symptoms and displayed distinct patterns in symptom clusters and functional status compared to males. These findings contribute to a better understanding of the long-term effects of COVID-19 and highlight the importance of gender-specific considerations in post-acute care.

Discovery of potential protein biomarkers of lung adenocarcinoma in bronchoalveolar lavage fluid by SWATH MS data-independent acquisition and targeted data extraction.

UNLABELLED: Lung cancer currently ranks as the neoplasia with the highest global mortality rate. Although some improvements have been introduced in recent years, new advances in diagnosis are required in order to increase survival rates. New mildly invasive endoscopy-based diagnostic techniques include the collection of bronchoalveolar lavage fluid (BALF), which is discarded after using a portion of the fluid for standard pathological procedures. BALF proteomic analysis can contribute to clinical practice with more sensitive biomarkers, and can complement cytohistological studies by aiding in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. The range of quantitative proteomics methodologies used for biomarker discovery is currently being broadened with the introduction of data-independent acquisition (DIA) analysis-related approaches that address the massive quantitation of the components of a proteome. Here we report for the first time a DIA-based quantitative proteomics study using BALF as the source for the discovery of potential lung cancer biomarkers. The results have been encouraging in terms of the number of identified and quantified proteins. A panel of candidate protein biomarkers for adenocarcinoma in BALF is reported; this points to the activation of the complement network as being strongly over-represented and suggests this pathway as a potential target for lung cancer research. In addition, the results reported for haptoglobin, complement C4-A, and glutathione S-transferase pi are consistent with previous studies, which indicates that these proteins deserve further consideration as potential lung cancer biomarkers in BALF. Our study demonstrates that the analysis of BALF proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), combining a simple sample pre-treatment and SWATH DIA MS, is a useful method for the discovery of potential lung cancer biomarkers. SIGNIFICANCE: Bronchoalveolar lavage fluid (BALF) analysis can contribute to clinical practice with more sensitive biomarkers, thus complementing cytohistological studies in order to aid in the diagnosis, prognosis, and subtyping of lung cancer, as well as the monitoring of treatment response. Here we report a panel of candidate protein biomarkers for adenocarcinoma in BALF. Forty-four proteins showed a fold-change higher than 3.75 among adenocarcinoma patients compared with controls. This report is the first DIA-based quantitative proteomics study to use bronchoalveolar lavage fluid (BALF) as a matrix for discovering potential biomarkers. The results are encouraging in terms of the number of identified and quantified proteins, demonstrating that the analysis of BALF proteins by a SWATH approach is a useful method for the discovery of potential biomarkers of pulmonary diseases.

¿Qué factores ayudan a explicar la satisfacción con la Atención Primaria en España? / What factors help to explain satisfaction with Primary Health care in Spain?

Objetivos. Conocer los determinantes de la satisfacción con la atención primaria pública en España. En el trabajo se considera un amplio conjunto de potenciales determinantes de dicha satisfacción, que se agrupan en 3 bloques de variables: las relacionadas con la calidad percibida de la atención recibida, las socioeconómicas y las relativas al estado de salud. Material y métodos. Se emplearon los microdatos del Barómetro Sanitario (BS) del año 2013, que son representativos a nivel nacional. Tras un primer análisis descriptivo previo, se estimaron 2 modelos multivariantes, uno en el que se consideraba que la satisfacción tiene un carácter cardinal (modelo de regresión) y otro en el que se consideraba que tiene un carácter ordinal (modelo probit ordenado). Resultados. No existieron prácticamente diferencias entre los resultados obtenidos con uno u otro modelo multivariante. No todas las variables consideradas fueron estadísticamente significativas. De los 3 bloques de variables consideradas, el de las relacionadas con la calidad percibida de la atención en el centro de salud fue el que mayor relevancia tuvo en la explicación de la satisfacción. Conclusiones. Los resultados obtenidos muestran que, mediante el manejo de las variables relacionadas con la percepción de la calidad de la atención en los centros de salud, los gestores públicos y los profesionales sanitarios pueden incidir muy favorablemente sobre los niveles de satisfacción de los pacientes de la atención primaria (AU)

Objectives. To find out the factors that determine satisfaction with public primary health care in Spain. The work has considered a wide group of potential determining factors of that satisfaction, which are organised into 3 blocks of variables: Those related to the perceived quality in the care received, socioeconomic, and those relative to the state of health. Material and methods. The micro data of the Barómetro Sanitario (BS) of 2013, which are representative at a national level, were employed. After a prior first descriptive analysis, 2 multivariate models were estimated: One in which satisfaction is considered as being of a cardinal nature (regression model), and another in which it is contemplated as being of an ordinal nature (ordered probit model). Results. There were practically no differences between the results obtained with one or other of the multivariate models. Not all the variables considered were statistically significant. Of the 3 blocks of variables studied, the one related to the perceived quality in the care received in the health centre exerts the greatest relevance in the explanation of satisfaction. Conclusions. The results obtained show that, by means of the management of the variables related to the perception of quality of care in health centres, public administrators and health professionals may have a highly favourable influence on the levels of satisfaction of primary health care patients (AU)

[What factors help to explain satisfaction with Primary Health care in Spain?]. / ¿Qué factores ayudan a explicar la satisfacción con la Atención Primaria en España?

OBJECTIVES: To find out the factors that determine satisfaction with public primary health care in Spain. The work has considered a wide group of potential determining factors of that satisfaction, which are organised into 3 blocks of variables: Those related to the perceived quality in the care received, socioeconomic, and those relative to the state of health. MATERIAL AND METHODS: The micro data of the Barómetro Sanitario (BS) of 2013, which are representative at a national level, were employed. After a prior first descriptive analysis, 2 multivariate models were estimated: One in which satisfaction is considered as being of a cardinal nature (regression model), and another in which it is contemplated as being of an ordinal nature (ordered probit model). RESULTS: There were practically no differences between the results obtained with one or other of the multivariate models. Not all the variables considered were statistically significant. Of the 3 blocks of variables studied, the one related to the perceived quality in the care received in the health centre exerts the greatest relevance in the explanation of satisfaction. CONCLUSIONS: The results obtained show that, by means of the management of the variables related to the perception of quality of care in health centres, public administrators and health professionals may have a highly favourable influence on the levels of satisfaction of primary health care patients.

[Immunomodulatory role of dietary lipids in an immunosuppressed mouse model and infected with listeria monocytogenes]. / Papel inmunomodulador de las dietas lipídicas en un modelo murino inmunosuprimido e infectado con Listeria monocytogenes.

INTRODUCTION: Dietary fatty acids immunomodulatory capacity in immunosuppression conditions may differ according to the type of fatty acid present in the diet. OBJECTIVE: To analyze the effect of different types of dietary lipids on the immune resistance of immunosuppressed and immunocompetent animals, against experimental infection with a virulent strain of Listeria monocytogenes. METHODS: Balb/c mice were divided into four experimental groups, according to their immunosuppressive treatment: control (PBS), cyclophosphamide (CPA), GK 1.5 and RB6-8C5. Each group was subdivided into four groups according to the lipid diet used which: control, with corn oil 5% (BG); olive oil 20% (AO); fish oil 20% (AP) and sunflower oil 20% (AG). The animals were fed for a month before treatment and subsequently infected with L. monocytogenes. RESULTS: We show increases in the number of viable bacteria in spleen and liver, and low survival rates in all groups of immunosuppressed mice and also in the PBS group and fed with AP. Furthermore, increases in the lymphocyte proliferation were observed, in the spleen of mice fed with AO and treated with CPA. DISCUSSION: The AP diet produces a significant decrease the host resistance in situations of immunosuppression. On the contrary, the AO and AG diets show major efficiency in the elimination of L. monocytogenes and major immunological advantages in immunosuppressed mice. Treatment with RB6-8C5, produces a reduction in the survival of the mice in all groups studied, which leads us to establish that granulocytes play a key role in the control of infection.

Introducción: La capacidad inmunomoduladora de los ácidos grasos de la dieta en situaciones de inmunosupresión puede diferir de acuerdo con el tipo de ácido graso presente. Objetivo: Analizar el efecto de diferentes tipos de dietas lipídicas, en la resistencia de animales inmunosuprimidos o no, frente a una infección experimental con Listeria monocytogenes. Métodos: Ratones Balb/c fueron divididos en cuatro grupos experimentales, según su tratamiento inmunosupresor: control (PBS), Ciclofosfamida (CPA), GK 1.5 y RB6-8C5. Cada grupo fue subdividido en cuatro subgrupos según la dieta lipídica utilizada: control con aceite de maíz 5% (BG); aceite de oliva 20% (AO); aceite de pescado 20% (AP) y aceite de girasol 20% (AG). Los animales se alimentaron durante un mes antes del tratamiento y posteriormente infectados con L. monocytogenes. Resultados: Mostramos incrementos en el número de bacterias viables en bazo e hígado, y bajos porcentajes de supervivencia en todos los grupos de ratones inmunosuprimidos y también en el grupo PBS alimentado con AP. Además, se observaron incrementos en la linfoproliferación, de bazos de ratones alimentados con AO y tratados con CPA. Discusión: La dieta AP, produce una disminución en la resistencia del hospedador en situaciones de inmunosupresión. Por el contrario, las dietas AO y AG muestran mayor eficacia en la eliminación de L. monocytogenes y mayores ventajas en animales inmunosuprimidos. El tratamiento con RB6-8C5, produce una reducción en la supervivencia de los ratones de los grupos estudiados, lo que induce a establecer que los granulocitos juegan un papel fundamental en el control de la infección.

Papel inmunomodulador de las dietas lipídicas en un modelo murino inmunosuprimido e infectado con Listeria monocytogenes / Immunomodulatory role of dietary lipids in an immunosuppressed mouse model and infected with listeria monocytogenes

Introducción: La capacidad inmunomoduladora de los ácidos grasos de la dieta en situaciones de inmunosupresión puede diferir de acuerdo con el tipo de ácido graso presente. Objetivo: Analizar el efecto de diferentes tipos de dietas lipídicas, en la resistencia de animales inmunosuprimidoso no, frente a una infección experimental con Listeria monocytogenes. Métodos: Ratones Balb/c fueron divididos en cuatro grupos experimentales, según su tratamiento inmunosupresor: control (PBS), Ciclofos famida (CPA), GK 1.5 yRB6-8C5. Cada grupo fue subdividido en cuatro subgrupos según la dieta lipídica utilizada: control con aceite de maíz 5% (BG); aceite de oliva 20% (AO); aceite de pescado20% (AP) y aceite de girasol 20% (AG). Los animales se alimentaron durante un mes antes del tratamiento y posteriormente infectados con L. monocytogenes. Resultados: Mostramos incrementos en el número de bacterias viables en bazo e hígado, y bajos porcentajes de supervivencia en todos los grupos de ratones inmunosuprimidos y también en el grupo PBS alimentado con AP. Además, se observaron incrementos en la linfoproliferación, de bazos de ratones alimentados con AO y tratados con CPA. Discusión: La dieta AP, produce una disminución en la resistencia del hospedador en situaciones de inmunosupresión. Por el contrario, las dietas AO y AG muestran mayor eficacia en la eliminación de L. monocytogenes y mayores ventajas en animales inmunosuprimidos. El tratamiento con RB6-8C5, produce una reducción en la supervivencia de los ratones de los grupos estudiados, lo que induce a establecer que los granulocitos juegan un papel fundamental en el control de la infección (AU)

Introduction: Dietary fatty acids immunomodulatory capacity in immunosuppression conditions may differ according to the type of fatty acid present in the diet. Objective: To analyze the effect of different types of dietary lipids on the immune resistance of immunosuppressed and immunocompetent animals, against experimental infection with a virulent strain of Listeria monocytogenes .Methods: Balb/c mice were divided into four experimental groups, according to their immunosuppressive treatment: control (PBS), cyclophosphamide (CPA), GK1.5 and RB6-8C5. Each group was subdivided into four groups according to the lipid diet used which: control, with corn oil 5% (BG); olive oil 20% (AO); fish oil 20%(AP) and sunflower oil 20% (AG). The animals were fed for a month before treatment and subsequently infected with L. monocytogenes. Results: We show increases in the number of viable bacteria in spleen and liver, and low survival rates in all groups of immunosuppressed mice and also in the PBS group and fed with AP. Furthermore, increases in the lymphocyte proliferation were observed, in the spleen of mice fed with AO and treated with CPA. Discussion: The AP diet produces a significant decrease the host resistance in situations of immunosuppression .On the contrary, the AO and AG diets show major efficiency in the elimination of L. monocytogenes and major immunological advantages in immunosuppressed mice. Treatment with RB6-8C5, produces a reduction in the survival of the mice in all groups studied, which leads us to establish that granulocytes play a key role in the control of infection (AU)

MR imaging evaluation of perianal fistulas: spectrum of imaging features.

Perianal fistulization is an inflammatory condition that affects the region around the anal canal, causing significant morbidity and often requiring repeated surgical treatments due to its high tendency to recur. To adopt the best surgical strategy and avoid recurrences, it is necessary to obtain precise radiologic information about the location of the fistulous track and the affected pelvic structures. Until recently, imaging techniques played a limited role in evaluation of perianal fistulas. However, magnetic resonance (MR) imaging now provides more precise information on the anatomy of the anal canal, the anal sphincter complex, and the relationships of the fistula to the pelvic floor structures and the plane of the levator ani muscle. MR imaging allows precise definition of the fistulous track and identification of secondary fistulas or abscesses. It provides accurate information for appropriate surgical treatment, decreasing the incidence of recurrence and allowing side effects such as fecal incontinence to be avoided. Radiologists should be familiar with the anatomic and pathologic findings of perianal fistulas and classify them using the St James's University Hospital MR imaging-based grading system.

[Coronary calcification and subclinical myocardial dysfuncion in rheumatoid arthritis]. / Calcificación coronaria y disfunción miocárdica subclínica en la artritis reumatoide.

Rheumatoid arthritis (RA) is characterized by high cardiovascular (CV) mortality, which has been related to systemic inflammation. Our aim was to analyze coronary calcification by computed tomography and subclinical myocardial dysfunction evaluated by brain natriuretic peptide (BNP) levels and an electrocardiogram in RA patients and its relationship with disease characteristics. Seventy-three RA patients and same number of controls formed by osteoarthritis patients were studied, all without a background of cardiovascular clinical events. RA patients had a higher calcium score than the control group (19.2% vs. 11%; p=0.17)), this being associated with disease duration. BNP levels (90.0 vs. 45.4; p=0.003), corrected QT length, large QT frequency and silent myocardial infarct were higher in the RA group. In conclusion, RA patients showed more coronary calcification frequency than in general population and more biochemical and electrocardiogram myocardial subclinical dysfunction signs.

Leading SU(3)-breaking corrections to the baryon magnetic moments in chiral perturbation theory.

We calculate the baryon magnetic moments using covariant chiral perturbation theory (chiPT) within the extended-on-mass-shell renormalization scheme. By fitting the two available low-energy constants, we improve the Coleman-Glashow description of the data when we include the leading SU(3)-breaking effects coming from the lowest-order loops. This success is in dramatic contrast with previous attempts at the same order using heavy-baryon chiPT and covariant infrared chiPT. We also analyze the source of this improvement with particular attention to the comparison between the covariant results.

Protein free diet feeding: effects on sympathetic activity and salivary evoked secretion in the submandibular gland of the rat.

Protein restriction impairs the salivary flow rate and composition in human and rats. The aim of the present work was to establish the effect of low protein (casein 5%) and protein free (casein 0%) isocaloric diets on sympathetic activity and salivary evoked secretion in the submandibular gland (SMG) of the rat. After 21 days, rats fed casein 0% presented: (a) a significant shift to the left of the dose-response curves (DRC) to the autonomic agonists-norepinephrine (NE), methoxamine, isoproterenol (ISO) and methacholine; (b) increased food consumption (p<0.001); (c) decreased body (p<0.001) and SMG (p<0.001) weights maintaining SMG/body (w/w) relation; (d) enhanced submandibular alpha1-adrenoceptor number without changes in the apparent dissociation constant (Kd); (e) increased submandibular NE content (p<0.05) and phosphoinositoside hydrolysis (p<0.001); (f) decreased submandibular tyrosine hydroxylase activity (TH) (p<0.01). Casein 5% feeding increased food consumption (p<0.01) and reduced body weight (p<0.05). This protein restriction increased metacholine-evoked salivation, but it altered neither submandibular sympathetic activity nor sympathetic-induced salivary secretion as compared to the Control group (C) fed a similar diet containing 25.5% protein. Present results suggest that in the adult rat, a protein free diet during 21 days lowers SMG sympathetic and cholinergic activity leading to supersensitivity as revealed by up-regulation of alpha1-adrenergic receptor number and increased autonomic-evoked salivation.

Thromboplastin Bilbao: reproducibility and sensitivity of a Spanish thromboplastin.

Prothrombin time (PT) is the control test for oral anticoagulant therapy as well as the screening test for defects of the extrinsic pathway of coagulation. Its responsiveness to decreased extrinsic clotting factors depends on the source and type of tissue factor thromboplastin extract. In 1994, a rabbit brain thromboplastin - Thromboplastin Bilbao (TBi) - was introduced as a replacement for a human brain preparation used since 1983, with the aim of establishing a national standard. The purpose of this study was to check the reproducibility, the inter-assay/intra-assay accuracy and the stability of this reagent under temperature changes and over time. A method modified from Frei et al. [World Health Organisation Regional Publications, Eastern Mediterranean Series, Alexandria, 1995] was used for the preparation of thromboplastin extract. Thirty-five batches of human TBi were prepared from 1983 to 1988, while from 1993 to 1999 13 batches of rabbit TBi were produced. The inter-assay reproducibility of rabbit TBi exhibited a coefficient of variation (CV) of 1.07-1.57% for normal plasma and of 1.25-2.56% for anticoagulated plasma. The intra-assay CV was 0.06-1.30% for normal plasma and 1.23-2.66% for anticoagulated plasma. The stability of the reagent to temperature changes and time was also estimated, with similar results for the two thromboplastins. As a result of the Oral Anticoagulant Treatment Quality Assessment Scheme in the Basque Country, an in-house rabbit thromboplastin with good sensitivity and reproducibility was developed.

Prothrombin time quality assessment scheme in the Basque Country.

The Basque Country Quality Assessment Scheme on Oral Anticoagulant Treatment (PEEC-CAV) was first launched in 1984. This project combined prothrombin time (PT) quality controls and a new in-house standard reagent called Thromboplastin Bilbao (TBi). Originally, this reagent was of human origin, but in 1994, it was replaced by one derived from rabbit brain following WHO recommendations. Nine hospitals in the area collaborated in carrying out quality controls (a) to assess different systems of PT test performance in the Basque Country and (b) to evaluate TBi response in these controls. Evaluation over the period 1994-1999 yielded an INR coefficient of variation (CV) for the plasmas used in these controls of 8.29+/-4.18% using the laboratories' routine system (reagent and coagulometer), and 9.7+/-2.70% using TBi and the manual technique. These results were similar to those obtained in the CV of PT ratio with human brain thromboplastin from 1984 to 1988 (9.26+/-2.84%).

Daily changes in beta-adrenergic sensitivity of rat submandibular gland. Correlation with beta-adrenoceptor rhythm.

Neurons from the superior cervical ganglia (SCG) innervate the submandibular gland and release noradrenaline during the dark phase of the daily photoperiod. Since in the pineal, another structure innervated by sympathetic neurons, nocturnal activation of the SCG is associated with beta-adrenergic sub- and super-sensitivity rhythms, the possible existence of similar phenomena in the rat submandibular gland was assessed. Wistar female rats, kept on a 14:10 light/dark cycle (light from 06:00 to 20:00 h), were sacrificed at 09:00, 14:00, 20:00, 24:00 and 04:00 h. beta-Adrenoceptors were studied by 3H-dihydroalprenolol binding to membrane preparations. The equilibrium dissociation constant (Kd) did not change as a function of time while significant daily variations in maximal binding values (Bmax) were observed with a peak at 20:00 h. Changes in Bmax correlated with a high response of adenylate cyclase to isoproterenol. In addition, when the response in salivary flow to isoproterenol was measured. a shift to the left (about 1 logarithmic unit) in dose-response curves was observed at 19:00-20:00 has compared to 08:00-09:00 h. These daily variations in isoproterenol responsiveness seem not to depend on the pattern of eating since a 24-h starvation or a nocturnal starvation for 16-18 days did not abolish the morning-evening differences in the salivary flow response to isoproterenol. Rather, the results suggest that the daily variations in isoproterenol response correlate with beta-adrenergic super- and sub-sensitivity phenomena associated with the circadian release of noradrenaline from SCG neurons.

Growth deceleration and bone metabolism in nutritional dwarfing rats.

Nutritional status as well as energy and protein intake are critical regulators of IGF-1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twenty-one male weanling Wistar rats (body weight = 38.20 +/- 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1:1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.

Comparative study of a portable prothrombin time monitor employing three different systems in oral anticoagulant units.

The aim of this study was to evaluate the accuracy of the portable coagulometer CoaguChek (Roche Diagnostics) as a prothrombin time (PT) monitor, and to correlate capillary blood results with those of three different routine methods used for monitoring oral anticoagulant therapy (OAT): capillary, plasma and whole blood samples. Three hospitals participated in the study with a total of 235 patients on OAT. The international normalized ratio (INR) results obtained with CoaguChek were compared with those obtained using each of the routine methods. The study presents a good correlation between the PT monitor and the three methods studied: r = 0.9745 (hospital A), r = 0.9283 (hospital B), r = 0.9136 (hospital C). A simplified concordance test of the methods results in a nine-field comparison table showing concordances of 87.2, 85.7 and 68.4%, respectively. The absolute difference (mean +/- SD) between laboratory A and CoaguChek INRs was 0.0571 +/- 0.2042, with values of 0.04286 +/- 0.3906 for laboratory B and 0.6986 +/- 0.6170 for laboratory C. These results confirm that CoaguChek could be used as a new method for oral anticoagulant monitoring, and is in best agreement with the capillary blood PT system.