Efficacy of amoxicillin/clavulanic acid after surgical drainage of perianal abscess in the prevention of the development of anal fistula (PERIQxA study): study protocol for a multicenter randomized, double-blind clinical trial.

BACKGROUND: Anorectal fistula, which is a relatively common pathology, is the chronic manifestation of the acute perirectal process that forms an anal abscess. The development of a fistula after incision and drainage of an anal abscess is seen in approximately 26-37%. Its treatment is a relevant topic, and the role of the use of antibiotic therapy in its prevention remains controversial, after the publication of several studies with contradictory results and several methodological limitations. Our hypothesis is that the combination of amoxicillin and clavulanic acid will reduce the incidence of anal fistula. METHOD: The aim of this study is to evaluate the efficacy of antibiotherapy after surgical drainage of perianal abscess in the development of perianal fistula. The PERIQxA study is a multicenter, randomized, double-blind controlled trial. The study has been designed to include 286 adult patients who will be randomly (1:1) assigned to either the experimental (amoxicillin/clavulanic acid 875/125 mg TDS for 7 days) or the control arm (placebo). The primary outcome measure is the percentage of patients that develop perianal fistula after surgery and during follow-up (6 months). DISCUSSION: This clinical trial is designed to evaluate the efficacy and safety of amoxicillin/clavulanic in the prevention of perianal fistula. The results of this study are expected to contribute to stablish the potential role of antibiotherapy in the therapeutics for anal abscess. TRIAL REGISTRATION: EudraCT Number: 2021-003376-14. Registered on November 26, 2021.

Escobar syndrome, difficult airway management in pediatrics: A case report / Síndrome de Escobar, manejo de vía aérea difícil pediátrica: a propósito de un caso

Abstract Escobar syndrome is a rare, autosomal recessive disease of unknown incidence. It is characterized by multiple skeletal, genitourinary and orofacial abnormalities. The multiple malformations (mainly orofacial) and restricted mobility of these patients pose a challenge to the anesthesia team, especially as regards airway management. We describe the clinical case of a pediatric patient diagnosed with Escobar syndrome who underwent two consecutive anesthesia interventions, with evidence of progressive airway anomalies that characterize this syndrome. The case required adaptation, according to the clinical stage of the disease, of the current algorithms used to approach an anticipated difficult airway in pediatrics, and the incorporation of new devices, not described so far in patients with this pathology, as part of the planning and execution phases.

Resumen El síndrome de Escobar es una enfermedad rara, autosómica recesiva, de incidencia desconocida. Se caracteriza por múltiples anomalías esqueléticas, genitourinarias y orofaciales. Las múltiples malformaciones (principalmente orofaciales) y la restricción de la movilidad de estos pacientes determinan un desafío para el equipo anestésico, especialmente en el manejo de la vía aérea. Se describe el caso clínico de una paciente pediátrica con diagnóstico de síndrome de Escobar que fue sometida a dos anestesias consecutivas, en el que se evidencia una progresión de las anomalías de la vía aérea propias del síndrome, por lo que se requiere adecuar, según el estadío clínico de la enfermedad, los algoritmos actuales de abordaje de vía aérea difícil pediátrica anticipada y la incorporación de nuevos dispositivos en la planificación y ejecución para su manejo que no han sido descritos en pacientes con esta patología.

Shortened Automatic Lung Recruitment Maneuvers in an In Vivo Model of Neonatal ARDS.

BACKGROUND: The aim of this study was to assess the safety and efficacy of 2 protocols for automatic lung recruitment maneuvers (LRMs) using stepwise increases in PEEP in a neonatal ARDS model. These protocols were designed with lower maximum opening pressures than traditional methods and differ each one in the duration of the opening phases (short vs prolonged). We described hemodynamic changes through invasive monitoring, and we analyzed if the behavior of the variables depends on the duration of the opening phase of the LRM. METHODS: We designed a prospective, experimental study with 10 Landrace x Large White pigs < 48 h old. Under general anesthesia, tracheal intubation, invasive hemodynamic monitoring with a pediatric arterial thermodilution catheter was performed. An ARDS model was developed with bronchoalveolar lavages. Two types of LRMs were performed in each piglet, with a maximum peak inspiratory pressure (PIP) of 30 cm H2O and a PEEP 15 cm H2O applied during 8.5 s in the short LRM and 17 s in the prolonged LRM. A comparative analysis by virtue of the Wilcoxon signed-rank test and a regression analysis using generalized estimation equation were performed. RESULTS: We found that both LRMs were effective regarding oxygenation and respiratory mechanics. Shortening the duration of the opening phase and lowering the maximum opening pressures to PIP 30 and PEEP 15 cm H2O were above the critical opening pressure to reverse alveolar collapse in our neonatal ARDS model. Although we observed hemodynamic variations during both types of LRMs, these were well tolerated. CONCLUSIONS: Our LRM protocols exceeded critical opening pressures to reverse alveolar collapse in our neonatal ARDS model. This range of pressures might involve less hemodynamic disturbance. Duration of the maximum opening pressure step is a determining factor for hemodynamic alterations.

Calidad de vida relacionada con la salud bucal y factores asociados en pacientes con bruxismo / Quality of life related to oral health and associated factors in patients with bruxism

RESUMEN Introducción: El bruxismo es una actividad parafuncional que puede tener impacto en la calidad de vida de las personas. Su etiología es diversa y por ello puede tener influencia de diferentes factores. Objetivo: Evaluar el impacto en la calidad de vida relacionada con la salud bucal y factores asociados en pacientes con bruxismo, atendidos en clínicas de practica de la Facultad de Odontología sede Medellín-Envigado, de la Universidad Cooperativa de Colombia. Métodos: Estudio observacional transversal y analítico con una muestra no probabilística de 51 pacientes entre 18 y 60 años que acudieron a consulta programada, atendidos en clínicas de practica de la Facultad de Odontología en Envigado, de la Universidad Cooperativa de Colombia, se realizaron exámenes clínicos, anamnesis y encuesta sociodemográfica, posteriormente se aplicó cuestionario OHIP-14 sobre calidad de vida relacionada con la salud bucal. Se realizó un análisis univariado y bivariado. Resultados: en los pacientes con bruxismo el índice OHIP-14 evidenció que la limitación funcional y el dolor físico obtuvieron un valor máximo de 6.00 puntos. Además, los ítems de discapacidad y malestar psicológico presentaban puntuación medianamente alta (4.00 y 5.00 puntos respectivamente). Al evaluar otros factores, solo se encuentran diferencias con significación estadística para los aspectos demográficos y socioeconómicos en algunos dominios (Vp=0,012). Conclusión: Los pacientes con bruxismo tuvieron un impacto negativo en la calidad de vida relacionada con la salud bucal.

ABSTRACT Introduction: Bruxism is a parafunctional activity that can have an impact on people's quality of life. Its etiology is diverse and therefore it can be influenced by different factors. Objective: To evaluate the impact on the quality of life related to oral health and associated factors in patients with bruxism, attended in the practices clinics of the Faculty of Dentistry, at the Universidad Cooperativa de Colombia sectional Medellín-Envigado. Methods: Cross-sectional and analytical observational study with a non-probability sample of 51 patients between 18 and 60 years of age who attended a scheduled consultation, attended in the practices clinics of the Faculty of Dentistry, at the Cooperative University of Colombia, Medellin-Envigado. Clinical exams, anamnesis and sociodemographic survey were carried out, subsequently an OHIP-14 survey on quality of life related to oral health was applied. A univariate and bivariate analysis was performed. Results: in patients with bruxism the OHIP-14 index showed that functional limitation and physical pain obtained a maximum value of 6.00 points. In addition, the items of disability and psychological distress presented a fairly high score (4.00 and 5.00 points respectively). When evaluating other factors, differences with statistical significance were found only for demographic and socioeconomic aspects in some domains (Vp = 0.012). Conclusion: Patients with bruxism had a negative impact on quality of life related to oral health.

The Use of Commas in Secondary-Education Students and Its Relationship with Reading Comprehension: The Case of Spanish.

The correct use of punctuation marks in secondary-school students is essential for the comprehension of written texts and, therefore, for the students' academic success. However, the examination of this issue has often been overlooked in the literature. In the present study, we focused on the progression of comma usage (i.e., a punctuation mark that is often challenging to master) and examined its relation to reading comprehension. A sample of first- and fourth-year secondary-education students from Spain (N = 115) punctuated brief texts in which commas had been previously omitted. The original texts included various types of mandatory commas in Spanish. We also obtained a reading comprehension score from a standardized reading test. Results show that secondary-education students often did not correctly place the commas, with first-year secondary-education students only succeeding in the correct placement of commas 54.5% of the time in (Year 8 in the UK system). This figure increased to 80.9% in fourth-year secondary-education students (Year 11 in the UK system). As a control, this figure rose to 91.5% in first-year university students. Critically, better comprehenders were the ones with better use of punctuation marks (r = 0.33). These results are useful for developing teaching methods to improve writing/reading skills in secondary-school students.

Impacto en la salud mental en residentes de tres programas de especialización médica de la Universidad de Valparaíso durante la pandemia por COVID-19 / Impact of the COVID-19 pandemic on the mental health of residents of three specialty medical programs

BACKGROUND: COVID-19 pandemic disturbed mental health of healthcare personnel. Residents of the specialization programs could be at risk, since they were reassigned in their functions. Aim: To describe the impact of COVID-19 pandemic on symptoms of depression, stress, anxiety and resilient coping in residents of Anesthesiology, Internal Medicine and Emergency Medicine MATERIAL AND METHODS: Residents were invited to answer an online survey containing the DASS-21 scale for anxiety, stress and depression symptoms and the Brief Resilient Coping Scale (BRCS) for resilience skills. RESULTS: Fifty four out of 90 residents answered the survey. Eighteen to 24% of respondents had symptoms of depression, anxiety and stress at severe and extremely severe levels. Those with severe and extremely severe symptoms had also the lowest score on the BRCS resilience scale. We did not find an association between severity of symptoms and gender. Discussion: A proportion of respondent residents had severe psychological symptoms and lower resilience scores during the COVID-19 pandemic.

Safe Inspiratory Pressures Threshold in Lung Recruitment Maneuvers: An In Vivo Neonatal ARDS Model.

BACKGROUND: The aim of this study was to define the level of peak inspiratory pressure (PIP) and mean airway pressure ([Formula: see text]) at which a pneumothorax is produced in an in vivo ARDS neonate model. In addition, we analyzed the hemodynamic response and cerebral parameters during the progressive increase of intrathoracic pressure. METHODS: We designed a prospective, experimental study with 11 Landrace × Large White pigs < 48 h from their birth. With the pigs under general anesthesia, tracheal intubation, invasive hemodynamic monitoring with a pediatric arterial thermodilution catheter, intracranial pressure, cerebral oximetry through near-infrared spectroscopy, and bilateral chest tube catheterization were performed. The ARDS model was developed with bronchoalveolar lavages. The rise in inspiratory pressure was performed achieved by increasing PEEP in stepwise increments at a constant driving pressure. PEEP was increased 5 cm H2O every 2 min until a pneumothorax was observed. A descriptive analysis, a Kaplan-Meier curve, and a regression analysis by using a generalized estimation equation were performed. RESULTS: A pneumothorax was observed in a median (interquartile range [IQR]) [Formula: see text] of 54 (46-56) cm H2O and median (IQR) PIP of 65 (58-73) cm H2O; asystole at median (IQR) [Formula: see text] of 49 (36-54) cm H2O and median (IQR) PIP of 60 (48-65) cm H2O. Hemodynamic changes in the median artery pressure, cardiac output, and myocardial contractility were observed above the range of [Formula: see text] of 14 cm H2O (PIP 25 and PEEP 10 cm H2O). Disturbances in intracranial pressure and cerebral oximetry through near-infrared spectroscopy appeared when deep hypotension and asystole occurred. CONCLUSIONS: A progressive increase of PEEP at a constant driving pressure did not increase severe adverse events at the range of pressures that we routinely use in neonates with ARDS. Asystole, pneumothorax, and cerebral compromise appeared at high intrathoracic ranges of pressure. Hemodynamics must be strictly monitored in all patients during the performance of lung recruitment maneuvers because hemodynamic deflections emerge early, at a range of pressures commonly used in ventilated neonates with ARDS.

[Impact of the COVID-19 pandemic on the mental health of residents of three specialty medical programs]. / Impacto en la salud mental en residentes de tres programas de especialización médica de la Universidad de Valparaíso durante la pandemia por COVID-19.

BACKGROUND: COVID-19 pandemic disturbed mental health of healthcare personnel. Residents of the specialization programs could be at risk, since they were reassigned in their functions. AIM: To describe the impact of COVID-19 pandemic on symptoms of depression, stress, anxiety and resilient coping in residents of Anesthesiology, Internal Medicine and Emergency Medicine Material and Methods: Residents were invited to answer an online survey containing the DASS-21 scale for anxiety, stress and depression symptoms and the Brief Resilient Coping Scale (BRCS) for resilience skills. RESULTS: Fifty four out of 90 residents answered the survey. Eighteen to 24% of respondents had symptoms of depression, anxiety and stress at severe and extremely severe levels. Those with severe and extremely severe symptoms had also the lowest score on the BRCS resilience scale. We did not find an association between severity of symptoms and gender. DISCUSSION: A proportion of respondent residents had severe psychological symptoms and lower resilience scores during the COVID-19 pandemic.

Safety and efficacy evaluation of the automatic stepwise recruitment maneuver in the neonatal population: An in vivo interventional study. Can anesthesiologists safely perform automatic lung recruitment maneuvers in neonates?

BACKGROUND: A new software has recently been incorporated in almost all new anesthesia machines to enable automatic lung recruitment maneuvers. To date, no studies have assessed the safety and efficacy of these automatic software programs in the neonatal population. AIMS: We aimed to evaluate the safety and efficacy of the lung recruitment maneuver performed using the automatic stepwise recruitment maneuver software of the FLOW-i 4.3 Anesthesia System® in a healthy and live neonatal model. METHODS: Eight male newborn piglets were included in the study. The lung recruitment maneuver was performed in pressure-controlled ventilation with a constant driving pressure (15 cmH2 O) in a stepwise increasing positive end-expiratory pressure (PEEP) model. The target peak inspiratory pressure (PIP) was 30 cmH2 O and PEEP was 15 cmH2 O. The maneuver lasted for 39 seconds. The hemodynamic variables were monitored using the PICCO® system. The following respiratory parameters were monitored: oxygen saturation, fraction of inspired oxygen, partial pressure of oxygen and carbon dioxide in the arterial blood, end-tidal carbon dioxide pressure, PIP, plateau pressure, PEEP, static compliance (Cstat ), and dynamic compliance (Cdyn ). Safety was evaluated by assessing the accuracy of the software, need for not interrupting the maneuver, hemodynamic stability, and absence of adverse respiratory events with the lung recruitment maneuver. Efficacy was evaluated by improvement in Cstat and Cdyn after performing the lung recruitment maneuver. RESULTS: All lung recruitment maneuvers were safely performed as scheduled without any interruptions. No pneumothorax or other side effects were observed. Hemodynamic stability was maintained during the lung recruitment maneuver. We observed an improvement of 33% in Cdyn and 24% in Cstat after the maneuver. CONCLUSIONS: The automatic stepwise recruitment maneuver software of the FLOW-i 4.3 Anesthesia System® is safe and efficacious in a healthy neonatal model. We did not observe any adverse respiratory or hemodynamic events during the implementation of the lung recruitment maneuver in the pressure-controlled ventilation mode using a stepwise increasing PEEP (30/15 cmH2 O) approach.

Quilotórax bilateral y ascitis quilosa como consecuencia de la rotura espontánea de un linfangioma retroperitoneal / Bilateral chylothorax and chylous ascites resulting from the spontaneous rupture of a retroperitoneal lymphangioma

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A non-homogeneous Markov early epidemic growth dynamics model. Application to the SARS-CoV-2 pandemic.

This work introduces a new markovian stochastic model that can be described as a non-homogeneous Pure Birth process. We propose a functional form of birth rate that depends on the number of individuals in the population and on the elapsed time, allowing us to model a contagion effect. Thus, we model the early stages of an epidemic. The number of individuals then becomes the infectious cases and the birth rate becomes the incidence rate. We obtain this way a process that depends on two competitive phenomena, infection and immunization. Variations in those rates allow us to monitor how effective the actions taken by government and health organizations are. From our model, three useful indicators for the epidemic evolution over time are obtained: the immunization rate, the infection/immunization ratio and the mean time between infections (MTBI). The proposed model allows either positive or negative concavities for the mean value curve, provided the infection/immunization ratio is either greater or less than one. We apply this model to the present SARS-CoV-2 pandemic still in its early growth stage in Latin American countries. As it is shown, the model accomplishes a good fit for the real number of both positive cases and deaths. We analyze the evolution of the three indicators for several countries and perform a comparative study between them. Important conclusions are obtained from this analysis.

SNCA and mTOR Pathway Single Nucleotide Polymorphisms Interact to Modulate the Age at Onset of Parkinson's Disease.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the α-synuclein (SNCA) gene are associated with differential risk and age at onset (AAO) of both idiopathic and Leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD). Yet potential combinatory or synergistic effects among several modulatory SNPs for PD risk or AAO remain largely underexplored. OBJECTIVES: The mechanistic target of rapamycin (mTOR) signaling pathway is functionally impaired in PD. Here we explored whether SNPs in the mTOR pathway, alone or by epistatic interaction with known susceptibility factors, can modulate PD risk and AAO. METHODS: Based on functional relevance, we selected a total of 64 SNPs mapping to a total of 57 genes from the mTOR pathway and genotyped a discovery series cohort encompassing 898 PD patients and 921 controls. As a replication series, we screened 4170 PD and 3014 controls available from the International Parkinson's Disease Genomics Consortium. RESULTS: In the discovery series cohort, we found a 4-loci interaction involving STK11 rs8111699, FCHSD1 rs456998, GSK3B rs1732170, and SNCA rs356219, which was associated with an increased risk of PD (odds ratio = 2.59, P < .001). In addition, we also found a 3-loci epistatic combination of RPTOR rs11868112 and RPS6KA2 rs6456121 with SNCA rs356219, which was associated (odds ratio = 2.89; P < .0001) with differential AAO. The latter was further validated (odds ratio = 1.56; P = 0.046-0.047) in the International Parkinson's Disease Genomics Consortium cohort. CONCLUSIONS: These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease. © 2019 International Parkinson and Movement Disorder Society.

[Medical audit guideline about rheumatoid arthritis diagnosis and treatment.] / Guía de auditoría médica sobre diagnóstico y tratamiento de la artritis reumatoidea.

Introduction: rheumatoid arthritis is a frequent inflammatory disease and a leading cause of potentially-treatable disability. Rheumatoid arthritis is associated with an increased risk of general morbidity and mortality. New therapeutic options have dramatically improved the evolution of patients. Objectives: in this joint work of the Association of Auditing and Quality of Medical Care of Córdoba (ASACAM) and the Argentine Society of Rheumatology (SAR), we generated recommendations to especially assist medical auditors in making decisions to improve the quality of the medical and life care of patients and reduce costs in the management of rheumatoid arthritis patients. in addition to medical auditors, these recommendations can be expanded to general practitioners, rheumatologists and clinicians, and eventually to the general public. Conclusions: suggestions for the diagnosis and treatment of patients with rheumatoid arthritis (including biological therapies) are described, based on the Clinical Practice Guidelines for the Treatment of Rheumatoid Arthritis (SAR, 2013), the resolutions of the Compulsory Medical Program and the Unique Reimbursement System currently used in Intended population: in addition to medical auditors, these recommendations can be expanded to general practitioners, rheumatologists and clinicians, and eventually to the general public. Conclusions: suggestions for the diagnosis and treatment of patients with rheumatoid arthritis (including biological therapies) are described, based on the Clinical Practice Guidelines for the Treatment of Rheumatoid Arthritis (SAR, 2013), the resolutions of the Compulsory Medical Program and the Unique Reimbursement System currently used in Argentina.

Introducción: la artritis reumatoidea es una patología inflamatoria frecuente, así como una causa destacada de incapacidad potencialmente tratable que se vincula con mayor riesgo de morbimortalidad general. Las nuevas opciones terapéuticas han mejorado de manera destacada la evolución de los pacientes. Objetivos: en este trabajo conjunto de la Asociación de Auditoria y Calidad de Atención Médica de Córdoba (ASACAM) y la Sociedad Argentina de Reumatología (SAR) se generaron recomendaciones para asistir especialmente a los médicos auditores en la toma de decisiones para mejorar la calidad de la atención médica y de vida de los pacientes y reducir los costos de las prestaciones en el enfoque de la artritis reumatoidea. Destinatarios: además de médicos auditores, estas recomendaciones pueden expandirse a médicos generales, reumatólogos y clínicos, y eventualmente al público en general. Conclusiones: se describen sugerencias para el diagnóstico y tratamiento de los pacientes con artritis reumatoidea, incluidas las terapias biológicas, sobe la base de las Guías de Práctica Clínica en el Tratamiento de la Artritis Reumatoidea (SAR, 2013), las resoluciones del Programa Médico Obligatorio y el denominado Sistema Único de Reintegro vigente en la Argentina.

A Long-Acting PYY3-36 Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates.

The gut hormone PYY3-36 reduces food intake in humans and exhibits at least additive efficacy in combination with GLP-1. However, the utility of PYY analogs as anti-obesity agents has been severely limited by emesis and rapid proteolysis, a profile similarly observed with native PYY3-36 in obese rhesus macaques. Here, we found that antibody conjugation of a cyclized PYY3-36 analog achieved high NPY2R selectivity, unprecedented in vivo stability, and gradual infusion-like exposure. These properties permitted profound reduction of food intake when administered to macaques for 23 days without a single emetic event in any animal. Co-administration with the GLP-1 receptor agonist liraglutide for an additional 5 days further reduced food intake with only one animal experiencing a single bout of emesis. This antibody-conjugated PYY analog therefore may enable the long-sought potential of GLP-1/PYY-based combination treatment to achieve robust, well-tolerated weight reduction in obese patients.

MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson's Disease Patients.

Dyskinesia induced by L-DOPA administration (LID) is one of the most invalidating adverse effects of the gold standard treatment restoring dopamine transmission in Parkinson's disease (PD). However, LID manifestation in parkinsonian patients is variable and heterogeneous. Here, we performed a candidate genetic pathway analysis of the mTOR signaling cascade to elucidate a potential genetic contribution to LID susceptibility, since mTOR inhibition ameliorates LID in PD animal models. We screened 64 single nucleotide polymorphisms (SNPs) mapping to 57 genes of the mTOR pathway in a retrospective cohort of 401 PD cases treated with L-DOPA (70 PD with moderate/severe LID and 331 with no/mild LID). We performed classic allelic, genotypic, and epistatic analyses to evaluate the association of individual or combinations of SNPs with LID onset and with LID severity after initiation of L-DOPA treatment. As for the time to LID onset, we found significant associations with SNP rs1043098 in the EIF4EBP2 gene and also with an epistatic interaction involving EIF4EBP2 rs1043098, RICTOR rs2043112, and PRKCA rs4790904. For LID severity, we found significant association with HRAS rs12628 and PRKN rs1801582 and also with a four-loci epistatic combination involving RPS6KB1 rs1292034, HRAS rs12628, RPS6KA2 rs6456121, and FCHSD1 rs456998. These findings indicate that the mTOR pathway contributes genetically to LID susceptibility. Our study could help to identify the most susceptible PD patients to L-DOPA in order to prevent the appearance of early and/or severe LID in a future. This information could also be used to stratify PD patients in clinical trials in a more accurate way.

El futuro del estado de Bienestar en Europa / The future of welfare state in Europe

El Estado de Bienestar en el contexto europeo en su versión actual se crea a mediados del siglo XX como un mecanismo corrector del mercado y de la mercantilización de las relaciones salariales, estando vinculado a la idea moderna de ciudadanía. En la actualidad cabe diferenciar entre cuatro regímenes de bienestar: el modelo liberal/residual, el modelo conservador, el modelo de los países del sur de Europa y el modelo socialdemócrata. Las actitudes y valores de la ciudadanía frente al Estado de Bienestar juegan un papel clave, en tanto en cuanto los ciudadanos valoran las políticas sociales como elementos básicos para mantener niveles razonables de seguridad vital. Respecto al futuro del Estado de Bienestar en Europa dependerá, en último término, de decisiones políticas

The Welfare State in the European context in its current version was created in the mid-twentieth century as a corrective mechanism of the market and the commodification of wage relations and is linked to the modern idea of citizenship. At present, it is possible to differentiate between four welfare regimes: the liberal/residual model, the conservative model, the Southern European countries model and the social-democratic model. The attitudes and values of citizenship vis-a-vis the welfare state play a key role, as one of the limitations with which governments try to cut them is that citizens value social policies as key elements for maintain reasonable levels of life safety. With regard to the future of the welfare state in Europe, it will ultimately depend on political decisions

Immunological memory to hyperphosphorylated tau in asymptomatic individuals.

Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG+ memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy.

Effects of meal size on the release of GLP-1 and PYY after Roux-en-Y gastric bypass surgery in obese subjects with or without type 2 diabetes.

Changes in gastrointestinal peptide release may play an important role in improving glucose control and reducing body weight following Roux-en-Y gastric bypass (RYGB), but the impact of low caloric intake on gut peptide release post-surgery has not been well characterized. The purpose of this study was to assess the relationships between low caloric intake and gut peptide release and how they were altered by RYGB. Obese females including ten normoglycemic (ON) and ten with type 2 diabetes mellitus (T2DM) (OD) were studied before, 1 week, and 3 months after RYGB. Nine lean, normoglycemic women were studied for comparison. Subjects were given three separate mixed meal challenges (MMCs; 75, 150, and 300 kcal). Plasma glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were analyzed. Prior to surgery, only minimal increases in GLP-1 and PYY were observed in response to the MMCs. After surgery, the peak GLP-1 concentration was progressively elevated in response to increasing meal sizes. The meal sizes had a statistically significant impact on elevation of GLP-1 incremental areas under the curve (ΔAUC) in both ON and OD at 1 week and 3 months post-surgery visits (p < 0.05 for all comparisons). The PYY ∆AUC was also significantly increased in a meal size-dependent manner in both ON and OD at both post-surgery visits (p < 0.05 for all comparisons). Meal sizes as small as 75-300 kcal, which cause minimal stimulation in GLP-1 or PYY release in the subjects before RYGB, are sufficient to provide statistically significant, meal size-dependent increases in the peptides post-RYGB both acutely and after meaningful weight loss occurred.