C-reactive protein-complement factor H axis as a biomarker of activity in early and intermediate age-related macular degeneration.

Purpose: To determine and compare the serum levels of complement Factor H (FH), monomeric C-Reactive Protein (mCRP) and pentameric C-Reactive protein (pCRP) in patients with age-related macular degeneration (AMD) and to correlate them with clinical, structural and functional parameters. Methods: Cross-sectional observational study. One hundred thirty-nine individuals (88 patients and 51 healthy controls) from two referral centers were included and classified into three groups: early or intermediate AMD (n=33), advanced AMD (n=55), and age and sex matched healthy controls (n=51). Serum levels of FH, mCRP, and pCRP were determined and correlated with clinical and imaging parameters. Results: Patients with intermediate AMD presented FH levels significantly lower than controls [186.5 (72.1-931.8) µg/mL vs 415.2 (106.1-1962.2) µg/mL; p=0.039] and FH levels <200 µg/mL were associated with the presence of drusen and pigmentary changes in the fundoscopy (p=0.002). While no differences were observed in pCRP and mCRP levels, and mCRP was only detected in less than 15% of the included participants, women had a significantly higher detection rate of mCRP than men (21.0% vs. 3.8%, p=0.045). In addition, the ratio mCRP/FH (log) was significantly lower in the control group compared to intermediate AMD (p=0.031). Visual acuity (p<0.001), macular volume (p<0.001), and foveal thickness (p=0.034) were significantly lower in the advanced AMD group, and choroidal thickness was significantly lower in advanced AMD compared to early/intermediate AMD (p=0.023). Conclusion: Intermediate AMD was associated in our cohort with decreased serum FH levels together with increased serum mCRP/FH ratio. All these objective serum biomarkers may suggest an underlying systemic inflammatory process in early/intermediate AMD patients.

Restrictive diets are unnecessary for colonoscopy: Non-inferiority randomized trial.

Background and study aims In colonoscopy, preparation is often regarded as the most burdensome part of the intervention. Traditionally, specific diets have been recommended, but the evidence to support this policy is insufficient. The aim of this study was to evaluate the impact of the decision not to follow a restrictive diet on bowel preparation and colonoscopy outcomes. Patients and methods This was a multicenter, controlled, non-inferiority randomized trial with FIT-positive screening colonoscopy. The subjects were assigned to follow the current standard (1-day low residue diet [LRD]) or a liberal diet. The allocation was balanced for the risk of inadequate cleansing using the Dik et al. score. All participants received the same instructions for morning colonoscopy preparation. The primary outcome was the rate of adequate preparations as defined by the Boston Bowel Preparation Scale. Secondary outcomes included tolerability and measures of colonoscopy performance and quality. Results A total of 582 subjects were randomized. Of these, 278 who received the liberal diet and 275 who received the 1-day LRD were included in the intent-to-treat analysis. Non-inferiority was demonstrated with adequate preparation rates of 97.8% in the 1-day LRD and 96.4% in the liberal diet group. Tolerability was higher with the liberal diet (94.7% vs. 83.2%). No differences were found with respect to cecal intubation time, aspirated volume, or length of the examination. Global and right colon average adenoma detection rates per colonoscopy were similar. Conclusions The liberal diet was non-inferior to the 1-day LRD, and increased tolerability. Colonoscopy performance and quality were not affected. (NCT05032794).

Assessment of short forms of recurrent atrial extra systoles by echocardiography with left atrial strain in ambulatory patients without organic cardiopathy / Evaluación de formas cortas de extrasístoles auriculares recurrentes mediante ecocardiografía con deformación auricular izquierda en pacientes ambulatorios sin cardiopatía orgánica

Abstract Aim: To analyse the potential usefulness and clinical relevance of the assessment by echocardiography with left atrial strain, based on the myocardial atrial deformation curves with speckle-tracking velocity vector imaging (VVI), in the analysis of short-form recurrent atrial extra systoles in ambulatory patients not suffering from organic cardiopathy. Methods: We designed a descriptive, prospective, and observational study including 270 patients between the ages of 18 and 75 assessed during an outpatient cardiology consultation attended due to palpitations over a period of two years. Using ambulatory electrocardiographic monitoring, we selected cases with short forms of repetitive atrial extrasystole, isolated or recurrentatrial fibrillation and a control group formed by those patients without repetitive ectopia. All patients underwent a thorough echocardiographic study during their first cardiological visit. Results: The analysis of the dynamic curves segmental deformation generated after an atrial extrasystole can reveal different points of origin of the extrasystole and detect specific anatomical alterations in the interatrial conduction at the level of the Bachmann's fascicle showing different models of electro anatomical activation possibly involved in the appearance of repetitive forms. Higher values of dyssynchrony between the septal and lateral wall and elongation in the time of interatrial electromechanical conduction could also be related to the existence of repetitive ectopic beats. Conclusions: Our ambulatory study employing the left atrial longitudinal strain, particularly in its segmental analysis, provides new insights into its the usefulness and potential clinical relevance.

Resumen Objetivo: Analizar la utilidad y relevancia clínica de la evaluación mediante ecocardiografía basada en las curvas de deformación auricular miocárdica con imágenes vectoriales de velocidad (VVI) de speckle-tracking, en el análisis de las extrasístoles auriculares recurrentes de corta duración en pacientes ambulatorios sin cardiopatía orgánica. Métodos: Se diseñó un estudio descriptivo, prospectivo y observacional que incluyó a 270 pacientes de entre 18 y 75 años evaluados durante una consulta externa de cardiología a la que acudieron por palpitaciones durante un periodo de dos años. Mediante el uso de monitorización electrocardiográfica ambulatoria, se seleccionaron casos con formas cortas de extrasistolia auricular repetitiva, fibrilación auricular aislada o repetitiva y un grupo control formado por aquellos pacientes sin ectopia repetitiva. Todos los pacientes se sometieron a un estudio ecocardiográfico exhaustivo durante su primera visita cardiológica. Resultados: El análisis de las curvas dinámicas de deformación segmentaria generadas tras un extrasístole auricular diferentes modelos de activación electroanatómica posiblemente implicados en la aparición de formas repetitivas. Valores mayores de disincronía entre la pared septal y lateral y el alargamiento en el tiempo de conducción electromecánica intraauricular pudieran también relacionarse con la existencia de latidos ectópicos repetitivos. Conclusiones: Nuestro estudio ambulatorio empleando la deformación longitudinal auricular izquierda, particularmente en su análisis segmentario, proporciona nuevas perspectivas sobre su utilidad y potencial relevancia clínica.

Assessment of short forms of recurrent atrial extra systoles by echocardiography with left atrial strain in ambulatory patients without organic cardiopathy.

Aim: To analyse the potential usefulness and clinical relevance of the assessment by echocardiography with left atrial strain, based on the myocardial atrial deformation curves with speckle-tracking velocity vector imaging (VVI), in the analysis of short-form recurrent atrial extra systoles in ambulatory patients not suffering from organic cardiopathy. Methods: We designed a descriptive, prospective, and observational study including 270 patients between the ages of 18 and 75 assessed during an outpatient cardiology consultation attended due to palpitations over a period of two years. Using ambulatory electrocardiographic monitoring, we selected cases with short forms of repetitive atrial extrasystole, isolated or recurrentatrial fibrillation and a control group formed by those patients without repetitive ectopia. All patients underwent a thorough echocardiographic study during their first cardiological visit. Results: The analysis of the dynamic curves segmental deformation generated after an atrial extrasystole can reveal different points of origin of the extrasystole and detect specific anatomical alterations in the interatrial conduction at the level of the Bachmann's fascicle showing different models of electro anatomical activation possibly involved in the appearance of repetitive forms. Higher values of dyssynchrony between the septal and lateral wall and elongation in the time of interatrial electromechanical conduction could also be related to the existence of repetitive ectopic beats. Conclusions: Our ambulatory study employing the left atrial longitudinal strain, particularly in its segmental analysis, provides new insights into its the usefulness and potential clinical relevance.

Objetivo: Analizar la utilidad y relevancia clínica de la evaluación mediante ecocardiografía basada en las curvas de deformación auricular miocárdica con imágenes vectoriales de velocidad (VVI) de speckle-tracking, en el análisis de las extrasístoles auriculares recurrentes de corta duración en pacientes ambulatorios sin cardiopatía orgánica. Métodos: Se diseñó un estudio descriptivo, prospectivo y observacional que incluyó a 270 pacientes de entre 18 y 75 años evaluados durante una consulta externa de cardiología a la que acudieron por palpitaciones durante un periodo de dos años. Mediante el uso de monitorización electrocardiográfica ambulatoria, se seleccionaron casos con formas cortas de extrasistolia auricular repetitiva, fibrilación auricular aislada o repetitiva y un grupo control formado por aquellos pacientes sin ectopia repetitiva. Todos los pacientes se sometieron a un estudio ecocardiográfico exhaustivo durante su primera visita cardiológica. Resultados: El análisis de las curvas dinámicas de deformación segmentaria generadas tras un extrasístole auricular diferentes modelos de activación electroanatómica posiblemente implicados en la aparición de formas repetitivas. Valores mayores de disincronía entre la pared septal y lateral y el alargamiento en el tiempo de conducción electromecánica intraauricular pudieran también relacionarse con la existencia de latidos ectópicos repetitivos. Conclusiones: Nuestro estudio ambulatorio empleando la deformación longitudinal auricular izquierda, particularmente en su análisis segmentario, proporciona nuevas perspectivas sobre su utilidad y potencial relevancia clínica.

Seroprevalence study prior and post vaccination in cancer patients in principality of Andorra (COVONCO study).

BACKGROUND: COVID-19 serologic response in patients with cancer may be lower than in the general population and may be influenced by the type of tumor or anticancer treatment. This study aims to analyze serological response prior and after vaccination of COVID-19 within the oncological population in Andorra. We set out to identify risk factors for a higher or lower serological response. PATIENTS AND METHODS: Observational, unicentric, prospective cohort study of oncologic patients in Andorra. We calculated the seroprevalence of antibodies against SARS-CoV-2 (May 2020-June 2021) and analyzed the main demographic, oncologic features and factors associated with being seropositive. RESULTS: A total of 373 patients were analyzed, mainly with solid tumours (n = 334, 89.5%). At baseline, seroprevalence was 13%, increasing during follow-up to 19%; lower seroprevalence was observed in patients with hematologic malignancies (2.6% vs 14.2%; p = 0.041) and patients receiving biological therapies (0% vs 15%, p = 0.005). In the overall seroprevalence analysis, women (23% vs 11.9%; p = 0.006) and tumour-free patients (p = 0.034) showed higher seroprevalence. The multivariable analysis showed that odds of being seropositive were higher among women (OR: 2.44, 95% CI 1.28-4.64), and patients who underwent surgery (OR: 3.35, 95% CI 1.10-10.20). About 80% of the cohort received at least one dose of COVID-19 vaccination, showing a higher seroprevalence of patients who received ChAdOx1-S than those who received BNT162b2 (24.4% vs 6.4%: p = 0.001). CONCLUSION: The seroprevalence of antibodies against SARS-COV-2 in oncologic patients in Andorra was higher among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment.

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis: Usefulness of FRAX® as a Screening Tool.

PURPOSE: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX® as a screening method to identify patients at a higher risk of fracture. METHODS: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX®) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). RESULTS: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BMI > 30 was a protective factor. A FRAX cut-off point for a major fracture > 6.6% had a sensitivity of 69% and a specificity of 85% for a diagnosis of osteoporosis. CONCLUSIONS: The prevalence of osteoporosis and fractures in patients with LC is high, particularly in older women. FRAX® may be a useful method to identify candidates for bone densitometry. A FRAX value below 6.6% without the BMD can avoid unnecessary testing.

C-reactive protein isoforms as prognostic markers of COVID-19 severity.

C-reactive protein (CRP), an active regulator of the innate immune system, has been related to COVID-19 severity. CRP is a dynamic protein undergoing conformational changes upon activation in inflammatory microenvironments between pentameric and monomeric isoforms. Although pentameric CRP is the circulating isoform routinely tested for clinical purposes, monomeric CRP shows more proinflammatory properties. Therefore, we aimed to determine the potential of monomeric CRP in serum as a biomarker of disease severity in COVID-19 patients (admission to intensive care unit [ICU] and/or in-hospital mortality). We retrospectively determined clinical and biological features as well as pentameric and monomeric CRP levels in a cohort of 97 COVID-19 patients within 72h of hospital admission. Patients with severe disease had higher levels of both pentameric and monomeric CRP. However, multivariate analysis showed increased mCRP but not pCRP to be independently associated to disease severity. Notably, mCRP levels higher than 4000 ng/mL (OR: 4.551, 95% CI: 1.329-15.58), together with number of co-morbidities, low lymphocyte count, and procalcitonin levels were independent predictors of disease severity in the multivariate model. Our results show the potential of mCRP levels as a marker of clinical severity in COVID-19 disease.

Trajectories in early rheumatoid arthritis related fatigue over 10 years: results from the ESPOIR cohort.

OBJECTIVES: In a cohort of early rheumatoid arthritis (RA) patients, we aimed to determine and characterise fatigue trajectories over 10 years of follow-up and identify predictors of trajectory membership. METHODS: We selected patients fulfilling the 2010 ACR/EULAR criteria for RA included in the ESPOIR cohort. We used a cluster analysis to obtain fatigue (assessed by fatigue visual analogue scale) trajectories over the course of 10 years from enrolment. Chi-square tests or ANOVA were performed to evaluate differences of baseline variables between fatigue trajectories. Using a multinomial logistic regression we were able to identify predictors of trajectory membership. RESULTS: We analysed 598 patients with mean disease duration at enrolment of 26.2±40.9 days. Cluster analysis revealed 3 trajectories: high (18%), moderate (52%) and low fatigue (30%). Compared to patients with moderate or low fatigue trajectory, patients with high fatigue trajectory were predominantly women and reported significantly higher duration and intensity of morning stiffness, HAQ score, tender joints count, levels of pain, number of awakenings due to arthritis, frequency of fibromyalgic RA, levels of physician and patient global assessment, more frequent sleep problems, and increased psychological distress. Female patients with pain, psychological distress and presence of sicca symptoms had a higher risk of being in the high trajectory group. CONCLUSIONS: These findings suggest that levels of fatigue are rather stable over time in each trajectory. Baseline clinical measures and baseline patient-reported measures of functional status better distinguished the three fatigue trajectories. We did not find any differences between trajectories in baseline laboratory measures. Inflammatory activity was not a predictor of being in the high trajectory fatigue group.

COVID-19 mortality risk factors in older people in a long-term care center.

PURPOSE: Despite high rates of COVID-19 infection and increased related mortality have been reported among older adults admitted in long-term care facilities, a limited amount of information is available about the natural course of this pandemic and prognostic factors in such population. In the current study, we aimed to investigate the epidemiologic, demographics, clinical, or therapeutic factors that may predict the prognosis in a cohort of COVID-19 infected institutionalized older in a nursing home. METHODS: We conducted a retrospective analysis of all COVID-19 confirmed institutionalized older in a nursing home from March 15 to June 5, 2020. Epidemiological, demographic, and frailty status before infection, and clinical, laboratory, treatment, and outcome data during infection were collected. We used bivariate analysis and multivariate logistic regression to identify risk factors for mortality. RESULTS: The analysis comprised all 100 COVID-19 confirmed cases during the study period. The median age was 85 years; 62% were female. The case fatality rate was 20%. In the bivariate analysis, male gender, fever, respiratory symptoms, severe cognitive decline, a low Barthel index, and lymphocytopenia were significantly associated with mortality. Patients treated with hydroxychloroquine plus azithromycin were related to a higher chance of survival than those without pharmacological treatment. Multivariate logistic regression analysis identified male gender, low Barthel index, no pharmacological treatment, and lymphocytopenia as independent risk factors associated with mortality. CONCLUSIONS: Male gender, low Barthel index, and lymphocytopenia are independent risk factors for COVID-19 mortality in institutionalized older patients in long-term care nursing homes. Treatment with hydroxychloroquine and azithromycin was associated with lower mortality in these patients.

Correction: Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

[This corrects the article DOI: 10.1371/journal.pone.0208112.].

Validation of the Spanish version of the questionnaire on Patient Empowerment in Long-Term Conditions.

BACKGROUND: Patient empowerment is a key factor in improving health outcomes. OBJECTIVE: To evaluate the psychometric properties of the Spanish version of the questionnaire on Patient Empowerment in Long-Term Conditions (PELC) that evaluates the degree of empowerment of patients with chronic diseases. METHODS: Three measurements were made (at baseline, 2 weeks and 12 weeks) of quality of life (QoL), self-care, self-efficacy and empowerment. Reliability was evaluated as internal consistency for the entire sample. Test-retest reproducibility was evaluated for patients who were stable from baseline to week 2 (n = 70). Validity was analysed (n = 124) as baseline correlations with QoL, self-care, self-efficacy, clinical data and psychosocial variables. Sensitivity to change was analysed in terms of effect size for patients who had improved between baseline and week 12 (n = 48). RESULTS: The study was carried out with 124 patients with a diagnosis of heart failure. Cronbach's alpha was high, at >0.9, and the interclass correlation coefficient was low, at 0.47. PELC questionnaire scores showed differences depending on New York Heart Association functional class (p<0.05) and, as posited in the a priori hypotheses, were moderately correlated with emotional dimensions of QoL (0.53) and self-efficacy (0.43). Effect size for the clinically improved subsample was moderate (0.67). CONCLUSIONS: The results suggest that the Spanish version of the PELC questionnaire has appropriate psychometric properties in terms of internal consistency and validity and is low in terms of reproducibility and sensitivity to change.

Satisfaction with Social Support Received from Social Relationships in Cases of Chronic Pain: The Influence of Personal Network Characteristics in Terms of Structure, Composition and Functional Content.

The worldwide burden of chronic illnesses, constitutes a major public health concern and a serious challenge for health systems. In addition to the strategies of self-management support developed by nursing and health organizations, an individual's personal network represents a major resource of social support in the long-term. Adopting a cross-sectional design based on personal network analysis methods, the main aim of this study is to explore the relationship between satisfaction with the social support received by individuals suffering chronic pain and the structure, composition, and functional content in social support of their personal networks. We collected personal and support network data from 30 people with chronic pain (20 person's contacts (alters) for each individual (ego), 600 relationships in total). Additionally, we examined the level of satisfaction with social support in each of the 600 relationships. Bivariate and multivariate tests were performed to analyze the satisfaction with the social support received. Using cluster analysis, we established a typology of the 600 relationships under study. Results showed that higher satisfaction was associated with a balance between degree centrality and betweenness (i.e., measures of network cohesion and network modularity, respectively). Finally, new lines of research are proposed in order to broaden our understanding of this subject.

Análisis de los índices predictores de respuesta al tratamiento con ácido ursodeoxicólico en pacientes con colangitis biliar primaria / Analysis of predictive response scores to treatment with ursodeoxycholic acid in patients with primary biliary cholangitis

Antecedentes y objetivos: La colangitis biliar primaria (CBP) es una enfermedad autoinmunitaria que afecta a los conductos biliares de pequeño y mediano tamaño. Los únicos tratamientos aprobados actualmente en nuestro país son el ácido ursodeoxicólico (AUDC) y el ácido obeticólico. Diversos índices evalúan la respuesta al año de tratamiento. El objetivo de nuestro estudio fue evaluar los diferentes índices predictivos de respuesta al tratamiento con AUDC. Material y métodos: Estudio unicéntrico retrospectivo en el que se recogieron los datos clínicos y analíticos de los pacientes diagnosticados de CBP desde enero de 1987 hasta diciembre de 2015. Se calculó la respuesta al año de inicio del tratamiento utilizando los diferentes índices de respuesta y se evaluó su grado de concordancia mediante el índice Kappa. Se calculó el area under the receiver operating characteristic curve (AUROC, «área bajo la curva ROC») para determinar la capacidad predictiva de los índices. Asimismo, se analizaron los factores pronósticos basales. Resultados: Se incluyeron 153 pacientes. El análisis bivariante demostró una relación estadísticamente significativa entre los niveles altos iniciales de fosfatasa alcalina y colesterol y la mala respuesta al tratamiento. La mejor AUROC fue del índice París-I (0,81). La concordancia entre los diferentes índices fue baja. El índice pronóstico GLOBE fue válido para evaluar el pronóstico. Conclusión: La fosfatasa alcalina y el colesterol basales fueron factores predictores de mala evolución. El índice cualitativo que mejor predijo la supervivencia fue el París-I. Se obtuvo una mala concordancia entre los diferentes índices predictivos. El índice GLOBE es válido para evaluar el pronóstico de la CBP

Background and objectives: Primary biliary cholangitis (PBC) is an autoimmune disease that affects the small bile ducts. The only treatments currently approved in our country are ursodeoxycholic acid (UDCA) and obeticholic acid. Different indices evaluate the response after one year of treatment. The aim of our study was to evaluate the different predictive scores and prognostic factors of response to UDCA. Material and methods: Retrospective single-centre study in which clinical and analytical data of patients diagnosed with PBC were collected from January 1987 to December 2015. The response after one year of treatment was evaluated using the different response scores and their concordance degree using the Kappa index. The area under the receiver operating characteristic curve (AUROC) was calculated to determine the predictive capacity of the scores. Likewise, the prognostic factors of response to treatment were analysed. Results: We included 153 patients. The bivariate analysis showed a statistically significant relationship between the initial high levels of alkaline phosphatase and cholesterol and the poor response to treatment. The best AUROC was in Paris-I score (0.81). The concordance between the different scores was low. The GLOBE score was valid to evaluate the prognosis. Conclusion: Basal alkaline phosphatase and cholesterol were predictors of poor outcome. The best predictive qualitative score in our cohort patients was Paris-I. There was a poor concordance between the different predictive scores. GLOBE score is valid to evaluate prognosis

Analysis of predictive response scores to treatment with ursodeoxycholic acid in patients with primary biliary cholangitis. / Análisis de los índices predictores de respuesta al tratamiento con ácido ursodeoxicólico en pacientes con colangitis biliar primaria.

BACKGROUND AND OBJECTIVES: Primary biliary cholangitis (PBC) is an autoimmune disease that affects the small bile ducts. The only treatments currently approved in our country are ursodeoxycholic acid (UDCA) and obeticholic acid. Different indices evaluate the response after one year of treatment. The aim of our study was to evaluate the different predictive scores and prognostic factors of response to UDCA. MATERIAL AND METHODS: Retrospective single-centre study in which clinical and analytical data of patients diagnosed with PBC were collected from January 1987 to December 2015. The response after one year of treatment was evaluated using the different response scores and their concordance degree using the Kappa index. The area under the receiver operating characteristic curve (AUROC) was calculated to determine the predictive capacity of the scores. Likewise, the prognostic factors of response to treatment were analysed. RESULTS: We included 153 patients. The bivariate analysis showed a statistically significant relationship between the initial high levels of alkaline phosphatase and cholesterol and the poor response to treatment. The best AUROC was in Paris-I score (0.81). The concordance between the different scores was low. The GLOBE score was valid to evaluate the prognosis. CONCLUSION: Basal alkaline phosphatase and cholesterol were predictors of poor outcome. The best predictive qualitative score in our cohort patients was Paris-I. There was a poor concordance between the different predictive scores. GLOBE score is valid to evaluate prognosis.

Hydroxyurea Exposure and Development of the Cerebellar External Granular Layer: Effects on Granule Cell Precursors, Bergmann Glial and Microglial Cells.

The current paper presents a histological analysis of the cell death in the cerebellar external granular layer (EGL) following the treatment with a single dose (2 mg/g) of hydroxyurea (HU). The rats were examined at postnatal days (P) 5, 10, and 15, and sacrificed at appropriate times ranging from 6 to 48 h after treatment administration. Studies were done in each cortical lobe (anterior, central, posterior, and inferior). The quantification of several parameters, such as density of 5-bromo-2'-deoxyuridine, TUNEL, vimentin, and tomato lectin-stained cells, revealed that HU compromises the viability of EGL cells. Our results indicate that P10 is a time of high vulnerability to injury. We also show here that the anterior and central lobes are the cortical regions most susceptible to the action of the HU. Additionally, our data also indicate that from 6 to 24 h after HU-exposure is a time-window of high sensibility to this agent. On the other hand, our ultrastructural analysis confirmed that HU administration produces the activation of apoptotic cellular events in the EGL, resulting in a substantial number of dying cells. Different stages of apoptosis can be observed in all cortical lobes at all investigated postnatal ages and survival times. Moreover, we observed that dying neuroblasts were covered by laminar processes of Bergmann glia, and that these unipolar astrocytes presented cytological features of phagocytes engulfing apoptotic bodies and cell debris. The electron microscopy study also revealed the participation of ameboid microglial cells in the phagocytosis of apoptotic cells in the regions of the EGL with extensive cell death.

Impact of treatment with direct-acting antivirals on anxiety and depression in chronic hepatitis C.

BACKGROUND AND AIM: Treatment of hepatitis C with direct-acting antiviral agents (DAA) has few side effects. Although pivotal studies suggested that DAA were safe in patients with psychiatric diseases who could not be treated with previous antiviral therapies, their effects on anxiety and depression have not yet been analysed in clinical practice. The aim of our study was to analyse anxiety and depression in the setting of DAA treatment in a clinical practice series. METHODS: All patients starting DAA treatment between November 1, 2014 and October 31, 2015 were eligible. Patients completed the Hospital Anxiety and Depression scale at different times during treatment. The results were plotted on line graphs and evaluated using a linear regression model with repeated measures. RESULTS: One hundred and forty-five patients were included (11% with major psychiatric disorders; 32% on psychiatric treatment). Sustained virologic response (SVR) was achieved in 97.3% of cases. Anxiety and depression measures did not differ between time points. No differences between patients on psychiatric treatment or with advanced fibrosis or cirrhosis were found at any time point analysed. CONCLUSION: DAA treatment had no impact on anxiety or depression during or after chronic hepatitis C infection treatment, even in high-risk patients with major psychiatric disorders.

Personal Network Analysis in the Study of Social Support: The Case of Chronic Pain.

In the context of chronic illness, the individual's social and relational environment plays a critical role as it can provide the informal support and care over time, beyond healthcare and social welfare institutions. Social Network Analysis represents an appropriate theoretical and methodological approach to study and understand social support since it provides measures of personal network structure, composition and functional content. The aim of this mixed method study is to present the usefulness of Personal Network Analysis to explore social support in the context of chronic pain. Personal and support network data of 30 people with chronic pain (20 alters for each ego, 600 relationships in total) were collected, obtaining measures of personal network structure and composition as well as information about social support characteristics. Also, semi-structured interviews with participants were conducted to identify the context of their experience of pain, their limitations as regards leading an autonomous life, their social support needs and other aspects concerning the effect of pain on their social and relational lives. This approach shows the importance of non-kin social support providers and the significant role of non-providers in the personal networks of people suffering chronic pain.

Autosomal Dominant Tubulointerstitial Kidney Disease: Clinical Presentation of Patients With ADTKD-UMOD and ADTKD-MUC1.

RATIONALE & OBJECTIVE: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare underdiagnosed cause of end-stage renal disease (ESRD). ADTKD is caused by mutations in at least 4 different genes: MUC1, UMOD, HNF1B, and REN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 56 families (131 affected individuals) with ADTKD referred from different Spanish hospitals. Clinical, laboratory, radiologic, and pathologic data were collected, and genetic testing for UMOD, MUC1, REN, and HNF1B was performed. PREDICTORS: Hyperuricemia, ultrasound findings, renal histology, genetic mutations. OUTCOMES: Age at ESRD, rate of decline in estimated glomerular filtration rate. RESULTS: ADTKD was diagnosed in 25 families (45%), 9 carried UMOD pathogenic variants (41 affected members), and 16 carried the MUC1 pathogenic mutation c.(428)dupC (90 affected members). No pathogenic variants were identified in REN or HNF1B. Among the 77 individuals who developed ESRD, median age at onset of ESRD was 51 years for those with ADTKD-MUC1 versus 56 years (P=0.1) for those with ADTKD-UMOD. Individuals with the MUC1 duplication presented higher risk for developing ESRD (HR, 2.24; P=0.03). The slope of decline in estimated glomerular filtration rate showed no significant difference between groups (-3.0mL/min/1.73m2 per year in the ADTKD-UMOD group versus -3.9mL/min/1.73m2 per year in the ADTKD-MUC1 group; P=0.2). The prevalence of hyperuricemia was significantly higher in individuals with ADTKD-UMOD (87% vs 54%; P=0.006). Although gout occurred more frequently in this group, the difference was not statistically significant (24% vs 7%; P=0.07). LIMITATIONS: Relatively small Spanish cohort. MUC1 analysis limited to cytosine duplication. CONCLUSIONS: The main genetic cause of ADTKD in our Spanish cohort is the MUC1 pathogenic mutation c.(428)dupC. Renal survival may be worse in individuals with the MUC1 mutation than in those with UMOD mutations. Clinical presentation does not permit distinguishing between these variants. However, hyperuricemia and gout are more frequent in individuals with ADTKD-UMOD.