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Alcohol use disorder (AUD) and affective disorders are frequently comorbid and share underlying mechanisms that could be targets for comprehensive treatment. Post-traumatic stress disorder (PTSD) has high comorbidity with AUD, but comprehensive models of this overlap are nascent. We recently characterized a model of comorbid AUD and PTSD-like symptoms, wherein stressed rats receive an inhibitory avoidance (IA)-related footshock on two occasions followed by two-bottle choice (2BC) voluntary alcohol drinking. Stressed rats received the second footshock in a familiar (FAM, same IA box as the first footshock) or novel context (NOV, single-chambered apparatus); the FAM paradigm more effectively increased alcohol drinking in males and the NOV paradigm in females. During abstinence, stressed males displayed avoidance-like PTSD symptoms, and females showed hyperarousal-like PTSD symptoms. Rats in the model had altered spontaneous action potential-independent GABAergic transmission in the central amygdala (CeA), a brain region key in alcohol dependence and stress-related signaling. However, PTSD sufferers may have alcohol experience prior to their trauma. Here, we therefore modified our AUD/PTSD comorbidity model to provide 3 weeks of intermittent extended alcohol access before footshock and then studied the effects of NOV and FAM stress on drinking and PTSD phenotypes. NOV stress suppressed the escalation of alcohol intake and preference seen in male controls, but no stress effects were seen on drinking in females. Additionally, NOV males had decreased action potential-independent presynaptic GABA release and delayed postsynaptic GABAA receptor kinetics in the CeA compared to control and FAM males. Despite these changes to alcohol intake and CeA GABA signaling, stressed rats showed broadly similar anxiogenic-like behaviors to our previous comorbid model, suggesting decoupling of the PTSD symptoms from the AUD vulnerability for some of these animals. The collective results show the importance of alcohol history and trauma context in vulnerability to comorbid AUD/PTSD-like symptoms.

Background The effect of COVID-19 on Health-Care Professionals’ mental health has received increased attention in the last year’s literature. However, previous studies essentially evaluated psychopathological symptoms and not the presence of positive mental health. Therefore, the first objective of the present research is to evaluate health-care professionals’ mental illness (i.e., anxiety and traumatic intensity) and positive mental health (i.e., well-being) using the Complete State Model of Health. Our second objective is to study the effect of Personal Protection Equipment availability on professionals’ mental health. Methods Two-hundred and thirty-two health-care professionals working in Spain in the first line of COVID-19 patient care participated in the study. To measure anxiety, traumatic intensity and well-being participants completed the State Trait Anxiety Inventory, the Davidson Trauma Scale, and the Mental Health Continuum-Short Form. Pearson correlations were used to examine the relationships between all scales. In order to test the two continua model of mental health, we used parallel analysis and exploratory factor analysis. To analyze anxiety, traumatic intensity, and well-being differences between health-care professionals with and without Personal Protection Equipment availability we conducted different ANOVAS. To test our hypothesis regarding the moderating role of Personal Protection Equipment availability in the effect of mental illness on positive mental health, data were subjected to a hierarchical regression analysis. Results As in previous studies, health-care professionals showed high levels of anxiety and traumatic intensity. They also presented low levels of well-being indicators. According to our hypothesis, results of parallel analysis and exploratory factorial analysis indicated that the measures of mental illness and positive mental health loaded on separate but correlated factors. Finally, Personal Protection Equipment availability moderated the effects of state anxiety and traumatic intensity on professionals’ well-being. Conclusions Health-care professionals’ mental illness and positive mental health reflect distinct continua, rather than the extreme ends of a single spectrum. Therefore, it is essential to measure both psychopathology and the presence of positive health to comprehensively evaluate professionals’ mental health. Finally, our results indicated that Personal Protection Equipment availability is essential not only for professionals’ physical health, but also for their mental health.

Resumen: Introducción: La enfermedad por coronavirus 2019 (COVID-19) es una infección viral causada por un nuevo coronavirus que está afectando a todo el mundo. Hay estudios previos de pacientes en hemodiálisis en centro, pero hay pocos datos sobre población en diálisis domiciliaria. Nuestro objetivo es estudiar la incidencia y evolución de la COVID-19 en una unidad de diálisis domiciliaria (UDD) durante el pico de la pandemia. Métodos: Estudio observacional y retrospectivo que incluye todos los pacientes diagnosticados de COVID-19 de la UDD del Hospital Universitario La Paz (Madrid, España) entre el 10 de marzo y el 15 de mayo de 2020. Se recogieron los datos clínicos de la UDD (57 pacientes en diálisis peritoneal y 22 pacientes en hemodiálisis domiciliaria) y comparamos las características clínicas y la evolución de los pacientes con o sin infección por COVID-19. Resultados: Doce pacientes fueron diagnosticados de COVID-19 (9 diálisis peritoneal, 3 hemodiálisis domiciliaria). No hubo diferencias estadísticamente significativas entre las características clínicas de los pacientes con COVID-19 y el resto de la unidad. La edad media fue 62 ± 18,5 años; la mayoría eran varones (75%). Todos los pacientes menos uno necesitaron hospitalización. Diez pacientes (83%) fueron dados de alta tras una media de 16,4 ± 9,7 días de hospitalización. Dos pacientes fueron diagnosticados durante su hospitalización por otro motivo y fueron los únicos que fallecieron. Los fallecidos eran de mayor edad que los supervivientes. Conclusión: La incidencia de COVID-19 en nuestra UDD en Madrid durante el pico de la pandemia fue alto, especialmente en los pacientes en diálisis peritoneal, sin observarse un potencial beneficio para prevenir la infección en los pacientes en diálisis domiciliaria. La edad avanzada y la transmisión nosocomial fueron los principales factores relacionados con peor pronóstico. Abstract: Introduction: The 2019 coronavirus (COVID-19) is a viral infection caused by a new coronavirus that is affecting the entire world. There have been studies of patients on in-center hemodialysis, but home dialysis population data are scarce. Our objective is to study the incidence and course of COVID-19 in a home dialysis unit (HDU) at the height of the pandemic. Methods: An observational, retrospective study enrolling all patients diagnosed with COVID-19 from the HDU of Hospital Universitario La Paz (La Paz University Hospital) (Madrid, Spain) between March 10 and May 15, 2020. We collected clinical data from the HDU (57 patients on peritoneal dialysis and 22 patients on home hemodialysis) and compared the clinical characteristics and course of patients with and without COVID-19 infection. Results: Twelve patients were diagnosed with COVID-19 (9 peritoneal dialysis; 3 home hemodialysis). There were no statistically significant differences in terms of clinical characteristics between patients with COVID-19 and the rest of the unit. The mean age was 62 ± 18.5 years; most were men (75%). All patients but one required hospitalization. Ten patients (83%) were discharged following a mean of 16.4 ± 9.7 days of hospitalization. Two patients were diagnosed while hospitalized for other conditions, and these were the only patients who died. Those who died were older than those who survived. Conclusion: The incidence of COVID-19 in our HDU in Madrid at the height of the pandemic was high, especially in patients on peritoneal dialysis. No potential benefit for preventing the infection in patients on home dialysis was observed. Advanced age and nosocomial transmission were the main factors linked to a worse prognosis.

Aims Alcohol use disorder (AUD) is linked to hyperactivity of brain stress systems, leading to withdrawal states which drive relapse. AUD differs among the sexes, as men are more likely to have AUD than women, but women progress from casual use to binge and heavy alcohol use more quickly and are more likely to relapse into repetitive episodes of heavy drinking. In alcohol dependence animal models of AUD, the central amygdala (CeA) functions as a hub of stress and anxiety processing and gamma-Aminobutyric acid (GABA)ergic signaling within the CeA is involved in dependence-induced increases in alcohol consumption. We have shown dysregulation of CeA GABAergic synaptic signaling in alcohol dependence animal models, but previous studies have exclusively used males. Methods Here, we used whole-cell patch clamp electrophysiology to examine basal CeA GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) and the effects of acute alcohol in both naïve and alcohol dependent rats of both sexes. Results We found that sIPSC kinetics differ between females and males, as well as between naïve and alcohol-dependent animals, with naïve females having the fastest current kinetics. Additionally, we find differences in baseline current kinetics across estrous cycle stages. In contrast to the increase in sIPSC frequency routinely found in males, acute alcohol (11–88 mM) had no effect on sIPSCs in naïve females, however the highest concentration of alcohol increased sIPSC frequency in dependent females. Conclusion These results provide important insight into sex differences in CeA neuronal function and dysregulation with alcohol dependence and highlight the need for sex-specific considerations in the development of effective AUD treatment.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by the recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin-releasing factor (CRF)-CRF1 receptor and Gamma-Aminobutyric Acid (GABA)-ergic signaling dysregulation occurring in alcohol-dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch-clamp electrophysiology to examine the effects of alcohol dependence on the CRF modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared to males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had fewer CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike in males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

The class IIa histone deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express Hdac4, 5, and 7 but not Hdac9. Here, we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when Hdac4 and 5 are knocked-out from Schwann cells in mice, a JUN-dependent mechanism induces the compensatory overexpression of Hdac7 permitting, although with a delay, the formation of the myelin sheath. When Hdac4, 5, and 7 are simultaneously removed, the myocyte-specific enhancer-factor d (MEF2D) binds to the promoter and induces the de novo expression of Hdac9, and although several melanocytic lineage genes are misexpressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa Hdac family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury., This work has been funded by grants from the Ministerio de Economía y Competitividad (BFU2016-75864R and PID2019-109762RB-I00), ISABIAL (UGP18-257 and UGP-2019–128) to H Cabedo, and Conselleria Educació Generalitat Valenciana (PROMETEO 2018/114) to J Gallar and H Cabedo. Predoctoral fellowships ACIF/2 017/169 from Generalitat Valenciana (to L Frutos-Rincón) and FPU16/00283from Ministerio de Universidades are also acknowledged. The Instituto de Neurociencias is a 'Center of Excellence Severo Ochoa' (Ministerio de Economía y Competitividad SEV-2013-0317).

Poor knowledge and management of menstruation impacts girls’ school attendance and academic performance. This paper aims to explore how menstrual hygiene management practices and related factors influence school absenteeism and drop-out among primary and secondary school girls in rural Gambia. Mixed-method studies were conducted among students and key informants from 19 schools from July 2015–December 2017. Focus group discussions, in-depth interviews, cross-sectional surveys, menstrual diaries, and school water, sanitation and hygiene (WASH) facility observations were used. Key findings from the interviews were that menstrual pain, cultural beliefs, fear of peers knowing menstrual status, and poor school WASH facilities led to school absenteeism, however, they had no impact on school drop-out. Of the 561 girls surveyed, 27% reported missing at least one school day per month due to menses. Missing school during the most recent menstrual period was strongly associated with menstrual pain (extreme pain adjusted odds ratio (AOR) = 16.8 (95% CI: 7.29–38.74)), as was having at least one symptom suggestive of urinary tract infection (AOR = 1.71 (95% CI: 1.16–2.52)) or reproductive tract infection (AOR = 1.99 (95% CI: 1.34–2.94)). Clean toilets (AOR = 0.44 (95% CI: 0.26–75)), being happy using school latrines while menstruating (AOR = 0.59 (95% CI: 0.37–0.93)), and soap availability (AOR = 0.46 (95% CI: 0.3–0.73)) were associated with reduced odds of school absenteeism. This study suggests menstrual pain, school WASH facilities, urogenital infections, and cultural beliefs affected school attendance among menstruating girls in rural Gambia.

Key summary points Aim According to age, there are differences in the clinical profile, presentation, management, and short-term outcomes of patients with COVID-19 admitted to the Emergency Department. Findings A statistically significant association was found between demographic data, comorbidities, clinical, radiographic, analytical, and therapeutic variables and short-term results according to age-dependent categories. Age was a prognostic factor for hospital admission and in-hospital and 30-day mortality, and was associated with not being admitted to intensive care. Message Clinical presentation, management, and short-term outcomes differ according to age among patients with COVID-19 admitted to the Emergency Department. Electronic supplementary material The online version of this article (10.1007/s41999-020-00359-2) contains supplementary material, which is available to authorized users., Purpose To determine the differences by age-dependent categories in the clinical profile, presentation, management, and short-term outcomes of patients with laboratory-confirmed COVID-19 admitted to a Spanish Emergency Department (ED). Methods Secondary analysis of COVID-19_URG-HCSC registry. We included all consecutive patients with laboratory-confirmed COVID-19 admitted to the ED of the University Hospital Clinico San Carlos (Madrid, Spain). The population was divided into six age groups. Demographic, baseline and acute clinical data, and in-hospital and 30-day outcomes were collected. Results 1379 confirmed COVID-19 cases (mean age 62 (SD 18) years old; 53.5% male) were included (18.1%

Proficient bilinguals use two languages actively, but the contexts in which they do so may differ dramatically. The present study asked what consequences the contexts of language use hold for the way in which cognitive resources modulate language abilities. Three groups of speakers were compared, all of whom were highly proficient Spanish-English bilinguals who differed with respect to the contexts in which they used the two languages in their everyday lives. They performed two lexical production tasks and the "AX" variant of the Continuous Performance Task (AX-CPT), a nonlinguistic measure of cognitive control. Results showed that lexical access in each language, and how it related to cognitive control ability, depended on whether bilinguals used their languages separately or interchangeably or whether they were immersed in their second language. These findings suggest that even highly proficient bilinguals who speak the same languages are not necessarily alike in the way in which they engage cognitive resources. Findings support recent proposals that being bilingual does not, in itself, identify a unique pattern of cognitive control. An important implication is that much of the controversy that currently surrounds the consequences of bilingualism may be understood, in part, as a failure to characterize the complexity associated with the context of language use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background Identification of the culprit artery can be helpful in the management of inferior infarction with ST-segment elevation myocardial infarction. Some studies suggest that previously published algorithms intended to help identify the infarct-related artery are suboptimal. Our aim is to develop a better method to localise the culprit artery on the basis of the 12-lead ECG. Patients and methods We analysed the ECG and coronary angiograms of two different cohorts of patients with inferior ST-segment elevation myocardial infarction. Patients from the first cohort were labelled the derivative cohort (group A), whereas patients in the second cohort were labelled the validation cohort (group B). ST-segment elevation was measured in each lead, and a multiple logistic regression analysis was carried out to determine the best equation to predict the culprit artery. A derived algorithm was then applied to the validation cohort. Next, our algorithm was applied to the total cohort of both groups and compared with four different previously published algorithms. We analysed differences in sensitivity, specificity and area under the curve (AUC). Results We included 252 patients in the derivative group and 90 in the validation group. The multiple models analysis concluded that the best model should include five leads. This model was validated by internal bootstrapping with 1000 repetitions in group A and externally in group B. The resultant algorithm was as follows: (ST-elevation in III + aVF + V3) - (ST-elevation in II + V6) less than 0.75 mm means that the culprit artery is the left circumflex artery (Cx). If the result is at least 0.75, the culprit artery is the right coronary artery. The total group of both cohorts comprised 342 patients, aged 61.2 ± 12.4 years, of whom 19.6% were female and 80.4% were male. The Cx was the culprit artery in 67 (19.6%) patients. Our algorithm had a sensitivity of 72.3, a specificity of 80.9 and an AUC of 0.766. The AUC value was better compared with the other algorithms. Conclusion The best algorithm to localise the culprit artery includes ST-elevation in leads II and V6 related to Cx, and ST-elevation in leads III, aVF and V3 related to right coronary artery. Our algorithm has been validated internally and externally, and works better than other previously published algorithms.

Objective Investigate whether there are differences in the drugs involved, symptomatology and severity of drug intoxication in patients with co-ingestion of alcohol attended in hospital emergency departments (ED). Method Patients attended in 11 Spanish EDs due to drug intoxication were included. Sociodemographic and clinical characteristics were collected. A combined adverse event of cardiorespiratory arrest, need for intubation, and admission to intensive care or death was considered as the primary indicator of severity. The symptomatology and severity were compared adjusted for age, sex and type of drug based on whether or not ethanol had been co-ingested. Results 3925 patients (alcohol co-ingestion: 2290, 58.3%) with a mean age of 33 (±11) years were included, and 25% were women. Co-ingestion of alcohol was observed in younger patients, in EDs in areas with high leisure tourism, on holidays and during the early morning hours. It was also more frequent in individuals intoxicated by amphetamine derivatives (66.2%) and cocaine (65.7%), and was more frequently associated with a reduction in consciousness (odds ratio [OR] = 2.13, 95% confidence interval [CI] 1.69–2.67) and agitation/aggressiveness (OR = 1.22, 95% = 1.04–1.43). A combined adverse event was observed in 114 patients (2.9%) with no differences between individuals co-ingesting or not ethanol (3.1% vs. 2.7%; OR = 1.11, 95% CI = 0.74–1.65). Conclusion Co-ingestion of alcohol is more frequent in individuals intoxicated by cocaine and amphetamines and predisposes a greater reduction in the level of consciousness or agitation, although there are no differences in the severity of the episodes of drug intoxication.

Accumulating evidence from preclinical and clinical studies has implicated a role for the cytokine IL-6 in a variety of CNS diseases including anxiety-like and depressive-like behaviors, as well as alcohol use disorders. Here we use homozygous and heterozygous transgenic mice expressing elevated levels of IL-6 in the CNS due to increased astrocyte expression and non-transgenic littermates to examine a role for astrocyte-produced IL-6 in emotionality (response to novelty, anxiety-like, and depressive-like behaviors). Our results from homozygous IL-6 mice in a variety of behavioral tests (light/dark transfer, open field, digging, tail suspension, and forced swim tests) support a role for IL-6 in stress-coping behaviors. Ex vivo electrophysiological studies of neuronal excitability and inhibitory spontaneous GABAergic synaptic transmission in the central nucleus of the amygdala (CeA) of the homozygous transgenic mice revealed increased inhibitory GABAergic signaling and increased excitability of CeA neurons, suggesting a role for astrocyte produced IL-6 in the amygdala in exploratory drive and depressive-like behavior. Furthermore, studies in the hippocampus of activation/expression of proteins associated with IL-6 signal transduction and inhibitory GABAergic mechanisms support a role for astrocyte produced IL-6 in depressive-like behaviors. Our studies indicate a complex and dose-dependent relationship between IL-6 and behavior and implicate IL-6 induced neuroadaptive changes in neuronal excitability and the inhibitory GABAergic system as important contributors to altered behavior associated with IL-6 expression in the CNS.

The class IIa histone deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express

The long‐term evolution of COVID‐19 is unknown, making it necessary to study the persistence of symptoms over time and their impact on quality of life in people who have had the disease. We analyzed these aspects 1 year after admission for COVID‐19 and explored the influence of treatment with systemic corticosteroids during the acute phase of the illness. This observational cohort study took place in a tertiary hospital in March and April 2021 and included people admitted due to infection with SARS‐CoV‐2 in March, April, or May 2020. We excluded patients who had died, were unreachable or had substantial cognitive impairment. A telephone survey was undertaken to assess the presence of symptoms related to COVID‐19 and to administer the SF‐36 quality of life questionnaire. Other variables collected were demographic and clinical data along with the treatment received and the evolution over time. We analyzed 76 patients, including 44 who did not receive corticosteroids and 32 who did. Most symptoms were less frequent in the group that received corticosteroids, with statistically significant differences for headache, dysphagia, chest pain, and depression. These patients also showed significantly better outcomes in the SF‐36 domains for “bodily pain” and “mental health.” Corticosteroids administered in the acute phase of COVID‐19 could attenuate the presence of long‐term symptoms and improve patients’ quality of life.

Research on collaborative memory shows that people recalling in groups rarely achieve optimal performance. Collaborative groups typically recall less than nominal groups, where performance for the latter is derived by pooling the non-overlapping information recalled by the same number of individuals working alone. While behavioural evidence has widely replicated this collaborative inhibition in free recall, little evidence speaks to the neurophysiological signatures of this counterintuitive phenomenon. Behavioural evidence also indicates that disruption to one's preferred recall strategy, resulting from processing others' recalled information, is a key mechanism underlying this effect. We aimed to identify the neural signatures indexing the recollection process and their disruption during collaborative recall. In three experiments, we replicated the standard collaborative inhibition effect with an EEG-adapted procedure (Experiment 1), and recorded EEG while people recalled in groups or in isolation (Experiments 2a, 2b). Comparisons showed increments in N400 and theta power, the neurophysiological components associated with interference, at shorter intervals for the collaborative compared to the nominal groups. Stronger theta power for collaborative than nominal recall, and for speakers than non-speakers in collaborative groups, were also evident at longer intervals and suggest demanding reinstatement of memory associated with collaborative recall. Together, the results suggest distinct neural processes underlying collaborative inhibition, with neural responses at shorter intervals signaling processes that are consistent with strategy disruption (stronger interference signaled by N400 and theta power increments), and further increments in theta at later times suggesting more demanding reinstatement processes during collaborative remembering.

Integration of information across the senses is critical for perception and is a common property of neurons in the cerebral cortex, where it is thought to arise primarily from corticocortical connections. Much less is known about the role of subcortical circuits in shaping the multisensory properties of cortical neurons. We show that stimulation of the whiskers causes widespread suppression of sound-evoked activity in mouse primary auditory cortex (A1). This suppression depends on the primary somatosensory cortex (S1), and is implemented through a descending circuit that links S1, via the auditory midbrain, with thalamic neurons that project to A1. Furthermore, a direct pathway from S1 has a facilitatory effect on auditory responses in higher-order thalamic nuclei that project to other brain areas. Crossmodal corticofugal projections to the auditory midbrain and thalamus therefore play a pivotal role in integrating multisensory signals and in enabling communication between different sensory cortical areas., In the primary auditory cortex, visual or tactile stimuli can modulate acoustically-driven activity. Here, the authors show that circuits linking the primary somatosensory cortex to both the auditory midbrain and thalamus allow tactile inputs to modulate auditory thalamocortical processing.

Background Scabies is a neglected tropical disease of the skin, causing severe itching, stigmatizing skin lesions and systemic complications. Since 2015, the DerMalawi project provide an integrated skin diseases clinics and Tele-dermatology care in Malawi. Clinic based data suggested a progressive increase in scabies cases observed. To better identify and treat individuals with scabies in the region, we shifted from a clinic-based model to a community based outreach programme. Methodology/Principal findings From May 2015, DerMalawi project provide integrated skin diseases and Tele-dermatological care in the Nkhotakota and Salima health districts in Malawi. Demographic and clinical data of all patients personally attended are recorded. Due to a progressive increase in the number of cases of scabies the project shifted to a community-based outreach programme. For the community outreach activities, we conducted three visits between 2018 to 2019 and undertook screening in schools and villages of Alinafe Hospital catchment area. Treatment was offered for all the cases and school or household contacts. Scabies increased from 2.9% to 39.2% of all cases seen by the DerMalawi project at clinics between 2015 to 2018. During the community-based activities approximately 50% of the population was assessed in each of three visits. The prevalence of scabies was similar in the first two rounds, 15.4% (2392) at the first visit and 17.2% at the second visit. The prevalence of scabies appeared to be lower (2.4%) at the third visit. The prevalence of impetigo appeared unchanged and was 6.7% at the first visit and 5.2% at the final visit. Conclusions/Significance Prevalence of scabies in our setting was very high suggesting that scabies is a major public health problem in parts of Malawi. Further work is required to more accurately assess the burden of disease and develop appropriate public health strategies for its control., Author summary Scabies is an infestation of the skin caused by a mite. There is limited data on how common scabies is in sub-Saharan Africa, including Malawi. The DerMalawi project has been providing care for dermatological conditions in rural Malawi since 2015. Between 2015 and 2018 we observed an increase in patients with scabies attending for treatment. In response the project shifted from providing care at clinics to an approach using community-based outreach. Between 2018 and 2019 we conducted community-based activities on three occasions in an area of approximately 30,000 individuals. The DerMalawi team visited schools and villages to identify and treat cases of scabies and their contacts. We were able to examine about 50% of the population on each visit. Initially a large proportion of the population had scabies (15%) and this was similar during our second community survey. At our third survey this appeared to have decreased to 2% but it is difficult for us to know if this is because of treatment given in the previous rounds. Scabies is a major problem in rural populations in Malawi and public health strategies are needed to reduce the disease burden.

The iPTH upper reference limit (URL) reported by our laboratory provider (Abbott Laboratories) at Tor Vergata University Hospital was evaluated by internal verification procedures as not representative of our population and resulting as underestimated. In this study, a new reference interval has been investigated and established by comparing a direct and an indirect method based on a statistical reduction from results stored in the laboratory database.For reference interval calculation from the healthy population, we analyzed a cohort of 100 blood donors (84% males and 16% females) screened with no bone-related and malabsorption diseases. We analyzed a cohort of 495 patients retrieved from more than 800 iPTH results by excluding subjects with pathological measurement for calcium, phosphorus, and creatinine for the reference interval evaluation. Patients with vitamin D results were included in the analysis. Vitamin D sufficiency status during the period from January to September 2020 was also evaluated by investigating 3,050 patients.The iPTH reference interval of a healthy blood donor population was measured as 25.2-109.1 pg/mL (2.7-11.6 pmol/L) at 2.5 and 97.5 distribution percentile. The iPTH reference interval from data stored in the laboratory database was 19.3-112.5 pg/mL (2.0-11.9 pmol/L). Furthermore, 60% of the whole population had prevalently insufficient vitamin D concentration (30 ng/dL;75 nmol/L). The impact of vitamin D concentration on the iPTH reference interval was measured for insufficient vitamin D (30 ng/dL;75 nmol/L) as 15.2-127.7 pg/mL (1.6-13.5 pmol/L), desirable vitamin D (30-40 ng/ml; 75-100 nmol/L) as 25.6-105 pg/mL (2.7-10.7 pmol/L) and optimal vitamin D (40 ng/ml;100 nmol/L) as 26.2-89.2 pg/mL (2.8-9.4 pmol/L), respectively.The URL reported in manufacturer datasheets likely refers to a normal population with non-pathological vitamin D levels. On the contrary, the considered population was mostly vitamin D insufficient, resulting in a URL shift. On this basis, we suggest describing in medical reports the iPTH range for vitamin D deficiency for diagnosis of primary hyperparathyroidism even when a specific vitamin D request is lacking. On the other hand, reporting optimal vitamin D-based iPTH reference interval could be clinically relevant in supplemented patients as a marker of treatment efficacy.

Peritoneal catheter dysfunction is a frequent complication of peritoneal dialysis (PD). Traditionally, dysfunction has been attributed to catheter malposition, but whether the location of the catheter tip in the small pelvis really determines proper function is unclear. We reviewed 900 abdominal X-ray images of PD patients from a 7-year period in two PD units that use different catheter types (straight and Swan Neck Curled). In 52% of the images, the dialysis catheter tip was located in the ideal position in the small pelvis and in 48% in other sites. Peritoneal catheter function was normal at the time of imaging in 87% of those with ideal catheter tip position, and in 74% of those with other than ideal position. The tip was located in small pelvis in 35% of images performed during catheter dysfunction and in 56% of those performed during normal catheter function. There were no differences between two catheter types. The positive predictive value of abdominal X-ray images to predict catheter function was 26%, and the negative predictive value 87%. We also found a significant positive correlation between polycystic kidney disease and normal catheter function. In contrast, obese patients were more likely to have catheter malfunction. Previous abdominal surgery was not associated with catheter dysfunction. Our data showed a higher probability of normal function of peritoneal catheters whose tips were located in the small pelvis. However, also malpositioned catheters generally functioned well, and malpositioning of the PD catheter did not in itself explain its malfunction.

Patients with end-stage kidney disease (ESKD) are at high risk of malnutrition and subsequent related mortality when starting dialysis. However, there have been few clinical studies on the effect of nutritional interventions on long-term patient survival. A 2-year longitudinal study was conducted from January 2012 to December 2016. A total of 186 patients with non-dialysis ESKD started the nutritional education program (NEP), and 169 completed it. A total of 128 patients participated in a NEP over 6 months (personalized diet, education and oral supplementation, if needed). The control group (n = 45) underwent no specific nutritional intervention. The hospitalization rate was significantly lower for the patients with NEP (13.7%) compared with the control patients (26.7%) (p = 0.004). The mortality odds ratio for the patients who did not receive NEP was 2.883 (95% CI 0.993–8.3365, p = 0.051). The multivariate analysis showed an independent association between mortality and age (OR, 1.103, 95% CI 1.041–1.169, p = 0.001) and between mortality and the female sex (OR, 3.332, 95% CI 1.054–10.535, p = 0.040) but not between mortality and those with NEP (p = 0.051). Individualized nutrition education has long-term positive effects on nutritional status, reduces hospital admissions and increases survival among patients with advanced CKD who are starting dialysis programs.

BACKGROUND Renal parenchymal damage and scarring usually is associated with urinary tract infection (UTI), whereas the impact of vesicoureteral reflux (VUR) on the kidneys is unclear. We aimed to compare kidneys with all grades of VUR (grades Io- V) and those without VUR by using direct radionuclide cystography, voiding cystourethrography, and findings from 99mTc-DMSA scintigraphy (DMSA scan). MATERIAL AND METHODS The present analysis included 253 renal ureteral units (RUU) from 129 children with VUR and recurrent UTI and children with a single febrile UTI associated with abnormal ultrasonographic findings. The 6 grades of VUR (Io, I, II, III, IV, and V) and 35 RUUs without VUR were divided into 4 groups: 1. Non-dilated VUR (grades Io-II) ; 2. Mildly dilated VUR (grade III) ; 3. Dilated VUR (grades IV-V) ; and 4. The control group. RESULTS DMSA scanning showed significant differences between the groups with non-dilated VUR, grade III VUR, grades IV-V VUR, and the control group in kidney width (χ²=30.5 ; P

Proteïna TDP-43; Esclerosi lateral amiotròfica; Demència frontotemporal Proteína TDP-43; Esclerosis lateral amiotrófica; Demencia frontotemporal TDP-43 protein; Amyotrophic lateral sclerosis; Frontotemporal dementia Cognitive impairment and behavioral changes in amyotrophic lateral sclerosis (ALS) are now recognized as part of the disease. Whether it is solely related to the extent of TDP-43 pathology is currently unclear. We aim to evaluate the influence of age, genetics, neuropathological features, and concomitant pathologies on cognitive impairment in ALS patients. We analyzed a postmortem series of 104 ALS patients and retrospectively reviewed clinical and neuropathological data. We assessed the burden and extent of concomitant pathologies, the role of APOE ε4 and mutations, and correlated these findings with cognitive status. We performed a logistic regression model to identify which pathologies are related to cognitive impairment. Cognitive decline was recorded in 38.5% of the subjects. Neuropathological features of frontotemporal lobar degeneration (FTLD) were found in 32.7%, explaining most, but not all, cases with cognitive impairment. Extent of TDP-43 pathology and the presence of hippocampal sclerosis were associated with cognitive impairment. Mutation carriers presented a higher burden of TDP-43 pathology and FTLD more frequently than sporadic cases. Most cases (89.4%) presented some degree of concomitant pathologies. The presence of concomitant pathologies was associated with older age at death. FTLD, but also Alzheimer’s disease, were the predominant underlying pathologies explaining the cognitive impairment in ALS patients. In sum, FTLD explained the presence of cognitive decline in most but not all ALS cases, while other non-FTLD related findings can influence the cognitive status, particularly in older age groups. SBE is a recipient of the Rio-Hortega post-residency grant from the Instituto de Salud Carlos III, Spain. This study was partially funded by Fundació Marató de TV3 (grant no. 20141610 to EG and no. 20143710 to RRG) and Fondo Europeo de Desarrollo Regional (FEDER) (PI15/01618 to RRG). AA is funded by Departament de Salut de la Generalitat de Catalunya, Pla estratègic de recerca i innovació en salut (PERIS) 2016–2020 (SLT002/16/00329). JG is recipient of the Instituto de Salud Carlos III-FEDER grants (PI16/01673 and PI19/00593)

Background: Fluoropyrimidines 5-fluorouracil (5- FU) and capecitabine are antimetabolite drugs used for the treatment of colorectal, breast, head, and neck malignancies. Different clinical manifestations of fluoropyrimidine-induced cardio- toxicity (FIC) have been reported in the literature. Case report: A 46-year-old female patient with a history of colorectal adenocarcinoma presented to the Emergency Department due to chest pain and mildly elevated cardiac serum troponin levels. Three days earlier, she had received a first adjuvant chemotherapy treatment with oral capecitabine. After the exclusion of obstructive coronary artery disease (CAD), acute myopericarditis was suspected. Conclusion: Capecitabine-induced myopericarditis is an extremely rare but important clinical condition to be recognized and treated promptly in order to prevent potentially lethal consequences of cardiac dysfunction.

A system for sorbent‐assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single‐lumen peritoneal catheter with the regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by the maintenance of a high plasma‐to‐dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8‐hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance the clearance of phosphate and organic waste solutes during the day. Uremic pigs (n = 3) were treated with the day‐ (n = 3) and nighttime system (n = 15) for 4–8 hr per treatment. Plasma clearance (Cl), MTAC, and total mass transport (MT) of urea, creatinine, phosphate, and potassium were compared with a static dwell (n = 28). Cl, MTAC, and MT of urea, creatinine, phosphate, and potassium were low in the pig as compared to humans due to the pig's low peritoneal transport status and could be enhanced only to a limited extent by SAPD treatment compared with a static dwell (nighttime system: Cl urea: ×1.5 (p = .029), Cl creatinine: ×1.7 (p = .054), Cl phosphate: ×1.5 (p = .158), Cl potassium: ×1.6 (p = .011); daytime system: Cl creatinine: ×2.7 (p = .040), Cl phosphate: ×2.2 (p = .039)). Sorbent‐assisted peritoneal dialysis treatment in a uremic pig model is safe and enhances small solute clearance as compared to a static dwell. Future studies in humans or animal species with higher peritoneal transport should elucidate whether our SAPD system enhances clearance to a clinically relevant extent as compared to conventional PD., A system for sorbent‐assisted peritoneal dialysis (SAPD) has been developed that continuously recirculates dialysate via a tidal mode using a single lumen peritoneal catheter with regeneration of spent dialysate by means of sorbents. SAPD treatment may improve plasma clearance by maintenance of a high plasma‐to‐dialysate concentration gradient and by increasing the mass transfer area coefficient (MTAC) of solutes. The system is designed for daily 8‐hr treatment (12 kg, nighttime system). A wearable system (2.3 kg, daytime system) may further enhance clearance of phosphate and organic waste solutes during the day.

It is known that a subpopulation of T cells expresses two T cell receptor (TCR) clonotypes, though the extent and functional significance of this is not established. To definitively evaluate dual TCRα cells, we generated mice with green fluorescent protein and red fluorescent protein reporters linked to TCRα, revealing that ∼16% of T cells express dual TCRs, notably higher than prior estimates. Importantly, dual TCR expression has functional consequences, as dual TCR cells predominated response to lymphocytic choriomeningitis virus infection, comprising up to 60% of virus-specific CD4(+) and CD8(+) T cells during acute responses. Dual receptor expression selectively influenced immune memory, as postinfection memory CD4(+) populations contained significantly increased frequencies of dual TCR cells. These data reveal a previously unappreciated contribution of dual TCR cells to the immune repertoire and highlight their potential effects on immune responses.

Frailty screening can be performed with different tools and in multiple settings. Among the different evaluation systems, gait speed (GS) and Timed Up-and-Go (TUG) are postulated as simple and easy to apply systems. There are few data on the prevalence of frailty in intermediate care centre inpatients.Descriptive study to determine the applicability of GS and TUG as frailty screening tools in an intermediate care hospital, as well as an estimate of frailty prevalence at discharge. Frailty was considered when GS1m/s and / or TUG12seconds. The study included all patients attending the rehabilitation unit of the centre throughout 2015.A total of 909 patients were included (mean age of 80.12 years). Only 205 (22.6%) were able to perform GS and TUG at discharge from the rehabilitation unit. Frailty prevalence for this group was between 89.8% (GS) and 92.2% (TUG), with no statistical differences between both tools (P=.25).The applicability of GS and TUG for frailty screening in intermediate care hospitals is limited. Despite this, the results obtained suggest a high prevalence of frailty. More studies will be necessary to corroborate this data.

Intestinal barrier dysfunction is a marker of disease progression during chronic viral infections, but its causes remain mostly unknown. This study demonstrates essential roles for type I IFN signaling and CD8 T cell responses in increasing intestinal permeability during chronic viral infection., Intestinal barrier leakage constitutes a potential therapeutic target for many inflammatory diseases and represents a disease progression marker during chronic viral infections. However, the causes of altered gut barrier remain mostly unknown. Using murine infection with lymphocytic choriomeningitis virus, we demonstrate that, in contrast to an acute viral strain, a persistent viral isolate leads to long-term viral replication in hematopoietic and mesenchymal cells, but not epithelial cells (IECs), in the intestine. Viral persistence drove sustained intestinal epithelial barrier leakage, which was characterized by increased paracellular flux of small molecules and was associated with enhanced colitis susceptibility. Type I IFN signaling caused tight junction dysregulation in IECs, promoted gut microbiome shifts and enhanced intestinal CD8 T cell responses. Notably, both type I IFN receptor blockade and CD8 T cell depletion prevented infection-induced barrier leakage. Our study demonstrates that infection with a virus that persistently replicates in the intestinal mucosa increases epithelial barrier permeability and reveals type I IFNs and CD8 T cells as causative factors of intestinal leakage during chronic infections., Graphical Abstract

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV., This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI15/00120 to R.S, PI18/00882 to M.A.B, PI17/00119 to M.R.-O. and Red de Investigación Renal (REDINREN): RD16/0009, to R.S and M.R-O); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.-O. and M.L-C. Spanish Ministry of Science and Innovation/Fondo Europeo de Desarrollo Regional (MICINN/FEDER) (PID2019-110132RB-I00) to M.L.-C.

Understanding neural physiopathology requires advances in nanotechnology-based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer-size features for stimulation and recording as in cell-non-invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au-based electrodes behave similarly to controls. Contrarily, Ni-based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au-based electrodes perform superiorly compared to Ni-based ones. Under electrical stimulation, Au-based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarization.

Studies of Spanish grammatical gender have shown that native speakers exploit gender cues in determiners to facilitate speech processing and are sensitive to gender mismatches. However, past research has not considered attested distributional asymmetries between masculine and feminine gender, collapsing performance on trials with one or the other gender into a single analysis. We use event-related potentials to investigate whether masculine and feminine grammatical gender elicit qualitatively different brain responses. Forty monolingual Spanish speakers read sentences that were well-formed or contained determiner-noun gender violations. Half of the nouns were masculine and the other half were feminine. Consistent with previous research, brain responses varied along a continuum between LAN- and P600-dominant effects for both gender categories. However, results showed that individuals’ ERP response dominance (LAN/P600) systematically differed across the two genders: participants who showed a LAN-dominant response to masculine-noun violations were more likely to show a P600 effect in response to feminine-noun violations. Correlations with individual difference measures further revealed that responses to masculine-noun violations were modulated by performance on the AX-CPT, a measure of cognitive control, whereas responses to feminine-noun violations were modulated by lexical knowledge, as indexed by verbal fluency. Together, the results demonstrate that even when processing features of language that belong to the same “natural class,” native speakers can exhibit patterns of brain activity attuned to distributional patterns of language use. The inherent variability in native speaker processing is, therefore, an important factor when explaining purported deviations from the “native norm” reported in other types of populations.

Previous research has shown that giving an instruction to forget part of a studied list of items impairs the subsequent retrieval of these items compared with those not cued to be forgotten. This selective directed forgetting (SDF) effect has been found with slightly different procedures and in adolescents and young adults. While recent research has suggested that executive control might underlie SDF, alternative explanations that rely on procedural issues still have not been investigated. Specifically, SDF might essentially reflect output interference from the items cued to be remembered, so that the earlier recalled items interfere with the later recalled items. The effect could also result from demand characteristics: Participants might withhold the to-be-forgotten items to comply with the experimenter’s implicit goals or might not be willing to engage in the effort of retrieving all studied information. The results from two experiments showed that (1) the to-be-forgotten items were less accessible and were not influenced by output interference from to-be-remembered items (Experiment 1), and (2) SDF was still present when participants were offered monetary reward for retrieving as many items as possible (Experiment 2). Hence, the findings do not provide support to explanations of SDF based on output interference and demand characteristics.

STUDY QUESTION Does the oestrogen receptor isoform, ER46, contribute to regulation of endometrial function? SUMMARY ANSWER ER46 is expressed in endometrial tissues, is the predominant ER isoform in first trimester decidua and is localised to the cell membrane of uterine natural killer (uNK) cells where activation of ER46 increases cell motility. WHAT IS KNOWN ALREADY Oestrogens acting via their cognate receptors are essential regulators of endometrial function and play key roles in establishment of pregnancy. ER46 is a 46-kDa truncated isoform of full length ERα (ER66, encoded by ESR1) that contains both ligand- and DNA-binding domains. Expression of ER46 in the human endometrium has not been investigated previously. ER46 is located at the cell membrane of peripheral blood leukocytes and mediates rapid responses to oestrogens. uNK cells are a phenotypically distinct (CD56brightCD16−) population of tissue-resident immune cells that regulate vascular remodelling within the endometrium and decidua. We have shown that oestrogens stimulate rapid increases in uNK cell motility. Previous characterisation of uNK cells suggests they are ER66-negative, but expression of ER46 has not been characterised. We hypothesise that uNK cells express ER46 and that rapid responses to oestrogens are mediated via this receptor. STUDY DESIGN, SIZE, DURATION This laboratory-based study used primary human endometrial (n = 24) and decidual tissue biopsies (n = 30) as well as uNK cells which were freshly isolated from first trimester human decidua (n = 18). PARTICIPANTS/MATERIALS, SETTING, METHODS Primary human endometrial and first trimester decidual tissue biopsies were collected using methods approved by the local institutional ethics committee (LREC/05/51104/12 and LREC/10/51402/59). The expression of ERs (ER66, ER46 and ERβ) was assessed by quantitative PCR, western blot and immunohistochemistry. uNK cells were isolated from first-trimester human decidua by magnetic bead sorting. Cell motility of uNK cells was measured by live cell imaging: cells were treated with 17β-oestradiol conjugated to bovine serum albumin (E2-BSA, 10 nM equivalent), the ERβ-selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10 nM) or dimethylsulphoxide vehicle control. MAIN RESULTS AND THE ROLE OF CHANCE ER46 was detected in proliferative and secretory phase tissues by western blot and was the predominant ER isoform in first-trimester decidua samples. Immunohistochemistry revealed that ER46 was co-localised with ER66 in cell nuclei during the proliferative phase but detected in both the cytoplasm and cell membrane of stromal cells in the secretory phase and in decidua. Triple immunofluorescence staining of decidua tissues identified expression of ER46 in the cell membrane of CD56-positive uNK cells which were otherwise ER66-negative. Profiling of isolated uNK cells confirmed expression of ER46 by quantitative PCR and western blot and localised ER46 protein to the cell membrane by immunocytochemistry. Functional analysis of isolated uNK cells using live cell imaging demonstrated that activation of ER46 with E2-BSA significantly increased uNK cell motility. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Expression pattern in endometrial tissue was only determined using samples from proliferative and secretory phases. Assessment of first trimester decidua samples was from a range of gestational ages, which may have precluded insights into gestation-specific changes in these tissues. Our results are based on in vitro responses of primary human cells and we cannot be certain that similar mechanisms occur in situ. WIDER IMPLICATIONS OF THE FINDINGS E2 is an essential regulator of reproductive competence. This study provides the first evidence for expression of ER46 in the human endometrium and decidua of early pregnancy. We describe a mechanism for regulating the function of human uNK cells via expression of ER46 and demonstrate that selective targeting with E2-BSA regulates uNK cell motility. These novel findings identify a role for ER46 in the human endometrium and provide unique insight into the importance of membrane-initiated signalling in modulating the impact of E2 on uNK cell function in women. Given the importance of uNK cells to regulating vascular remodelling in early pregnancy and the potential for selective targeting of ER46, this may be an attractive future therapeutic target in the treatment of reproductive disorders. STUDY FUNDING/COMPETING INTEREST(S) These studies were supported by Medical Research Council (MRC) Programme Grants G1100356/1 and MR/N024524/1 to PTKS. H.O.D.C. was supported by MRC grant G1002033. The authors declare no competing interests related to the published work.

GAMES Investigators., [Background] Enterococcal endocarditis (EE) is a growing entity in Western countries. However, quality data from large studies is lacking., [Objectives] The purpose of this study was to describe the characteristics and analyze the prognostic factors of EE in the GAMES cohort., [Methods] This was a post hoc analysis of a prospectively collected cohort of patients from 35 Spanish centers from 2008 to 2016. Characteristics and outcomes of 516 cases of EE were compared with those of 3,308 cases of nonenterococcal endocarditis (NEE). Logistic regression and Cox proportional hazards regression analysis were performed to investigate risk factors for in-hospital and 1-year mortality, as well as relapses., [Results] Patients with EE were significantly older; more frequently presented chronic lung disease, chronic heart failure, prior endocarditis, and degenerative valve disease; and had higher median age-adjusted Charlson score. EE more frequently involved the aortic valve and prosthesis (64.3% vs. 46.7%; p < 0.001; and 35.9% vs. 28.9%; p = 0.002, respectively) but less frequently pacemakers/defibrillators (1.5% vs. 10.5%; p < 0.001), and showed higher rates of acute heart failure (45% vs. 38.3%; p = 0.005). Cardiac surgery was less frequently performed in EE (40.7% vs. 45.9%; p = 0.024). No differences in in-hospital and 1-year mortality were found, whereas relapses were significantly higher in EE (3.5% vs. 1.7%; p = 0.035). Increasing Charlson score, LogEuroSCORE, acute heart failure, septic shock, and paravalvular complications were risk factors for mortality, whereas prior endocarditis was protective and persistent bacteremia constituted the sole risk factor for relapse., [Conclusions] Besides other baseline and clinical differences, EE more frequently affects prosthetic valves and less frequently pacemakers/defibrillators. EE presents higher rates of relapse than NEE.

Background. Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. Methods. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). Results. After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10-6 (95% CI 3.3 × 10-7-1.1 × 10-5)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Conclusions. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD. © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Serum anti-heart autoantibodies (AHAs) and anti-intercalated disk autoantibodies (AIDAs) are autoimmune markers in myocarditis. Myocarditis has been reported in arrhythmogenic right ventricular cardiomyopathy (ARVC). To provide evidence for autoimmunity, we searched for AHAs and AIDAs in ARVC. Methods: We studied: 42 ARVC probands, 23 male, aged 42, interquartile range 33–49, 20 from familial and 22 nonfamilial pedigrees; 37 clinically affected relatives (ARs), 24 male aged 35, interquartile range 18–46; and 96 healthy relatives, 49 male, aged 27, interquartile range 17–45. Serum AHAs and AIDAs were tested by indirect immunofluorescence on human myocardium and skeletal muscle in 171 of the 175 ARVC individuals and in controls with noninflammatory cardiac disease (n=160), ischemic heart failure (n=141), and healthy blood donors (n=270). Screening of 5 desmosomal genes was performed in probands; when a sequence variant was identified, cascade family screening followed, blind to immunologic results. Results: AHA frequency was higher (36.8%) in probands, ARs (37.8%), and healthy relatives (25%) than in noninflammatory cardiac disease (1%), ischemic heart failure (1%), or healthy blood donors (2.5%; P =0.0001). AIDA frequency was higher in probands (8%, P =0.006), in ARs (21.6%, P =0.00001), and in healthy relatives (14.6%, P =0.00001) than in noninflammatory cardiac disease (3.75%), ischemic heart failure (2%), or healthy blood donors (0.3%). AHA-positive status was associated with higher frequency of palpitation ( P =0.004), implantable cardioverter defibrillator implantation ( P =0.021), lower left ventricular ejection fraction ( P =0.004), AIDA-positive status with both lower right ventricular and left ventricular ejection fractions ( P =0.027 and P =0.027, respectively). AHA- and/or AIDA-positive status in the proband and at least one of the respective relatives was more common in familial (17/20, 85%) than in sporadic (10/22, 45%) pedigrees ( P =0.007). Conclusions: The presence of AHAs and AIDAs provides evidence of autoimmunity in the majority of familial and in almost half of sporadic ARVC. In probands and in ARs, these antibodies were associated with features of disease severity. Longitudinal studies are needed to clarify whether they may predict ARVC development in healthy relatives or if they be a result of manifest ARVC.

Alcohol use disorder (AUD) and anxiety disorders are frequently comorbid and share mechanisms that could be therapeutic targets. To facilitate mechanistic studies, we adapted an inhibitory avoidance-based "2-hit" rat model of posttraumatic stress disorder (PTSD) and identified predictors and biomarkers of comorbid alcohol (ethanol)/PTSD-like symptoms in these animals. Stressed Wistar rats received a single footshock on two occasions. The first footshock occurred when rats crossed into the dark chamber of a shuttle box. Forty-eight hours later, rats received the second footshock in a familiar (FAM) or novel (NOV) context. Rats then received 4 weeks of two-bottle choice (2BC) ethanol access. During subsequent abstinence, PTSD-like behavior responses, GABAergic synaptic transmission in the central amygdala (CeA), and circulating cytokine levels were measured. FAM and NOV stress more effectively increased 2BC drinking in males and females, respectively. Stressed male rats, especially drinking-vulnerable individuals (≥0.8 g/kg average 2-h ethanol intake with >50% ethanol preference), showed higher fear overgeneralization in novel contexts, increased GABAergic transmission in the CeA, and a profile of increased G-CSF, GM-CSF, IL-13, IL-6, IL-17a, leptin, and IL-4 that discriminated between stress context (NOV > FAM > Control). However, drinking-resilient males showed the highest G-CSF, IL-13, and leptin levels. Stressed females showed increased acoustic startle and decreased sleep maintenance, indicative of hyperarousal, with increased CeA GABAergic transmission in NOV females. This paradigm promotes key features of PTSD, including hyperarousal, fear generalization, avoidance, and sleep disturbance, with comorbid ethanol intake, in a sex-specific fashion that approximates clinical comorbidities better than existing models, and identifies increased CeA GABAergic signaling and a distinct pro-hematopoietic, proinflammatory, and pro-atopic cytokine profile that may aid in treatment.

Background Adolescent girls and young women living with HIV in resource-limited settings have the poorest health outcomes of any age group, due in part to poor retention in care. Differentiated models of HIV care that target the specific challenges of young people living with HIV are urgently needed. Methods The FANMI study is an unblinded randomized controlled trial designed to evaluate the efficacy of an adolescent-specific model of HIV care in Port-au-Prince, Haiti. The FANMI intervention places newly young women living with HIV who are not currently on ART or on ART ≤ 3 months, in cohorts of 5–10 peers to receive monthly group HIV care in a community location. In contrast, participants in the standard care arm receive routine HIV care and individual counseling each month in GHESKIO’s Adolescent Clinic. A total of 160 participants ages 16–23 years old are being randomized on a 1:1 basis. The primary outcome is retention in HIV care defined as being alive and in care at 12 months after enrollment. Secondary outcomes include viral suppression at 12 months, sexual risk behaviors, acceptability of the FANMI intervention, and health care utilization and costs. Discussion The FANMI study evaluates a novel community-based cohort model of HIV care aimed at improving retention in care and reducing risk behaviors for HIV transmission among adolescent girls and young women living with HIV. Specifically, the FANMI model of care addresses social isolation by placing participants in cohorts of 5–10 peers to provide intensified peer support and makes HIV health management a group norm; reduces stigma and improves convenience by providing care in a community setting; and integrates clinical care and social support by the same providers to streamline care and promote long-term patient-provider relationships. If shown to be effective, the FANMI intervention may serve as a model of HIV care for improving retention among hard-to-reach adolescents and young adults in Haiti and could be adapted for other high-risk groups globally. Trial registration Identifier: NCT03286504, Registered September 18, 2017.

Objective: To investigate the rate of colorectal neoplasms (CRNs) in patients who have Enterococcus faecalis infective endocarditis (EFIE) with available colonoscopies and to assess whether this is associated with the identification of a focus the infection. Patients and Methods: Retrospective analysis of data from a prospective multicenter study involving 35 centers who are members of the Grupo de Apoyo para el Manejo de la Endocarditis en Espana [Support Group for the Management of Infective Endocarditis in Spain] cohort. A specific set of queries regarding information on colonoscopy and histopathology of colorectal diseases was sent to each participating center. Four-hundred sixty-seven patients with EFIE were included from January 1, 2008, to December 31, 2017, from whom data on colonoscopy performance and results were available in 411 patients. Results: One hundred forty-two (34.5%) patients had a colonoscopy close to the EFIE episode. The overall rate of colorectal diseases was 70.4% (100 of 142), whereas the prevalence of CRN (advanced adenomas and colorectal carcinoma) was 14.8% (21 of 142), with no significant differences between the group of EFIE of unknown focus and that with an identified focus. Conclusion: Our study adds to prior evidence suggesting a much higher rate of CRN among patients with EFIE than in the general population of the same age and sex. In addition, our findings suggest that this phenomenon might take place both in EFIE with an unknown and an identified source of infection.

Purpose: To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE). Methods: From January 2008 to September 2016, 334 patients with definite SPVE were attended in the participating hospitals. Ninety-four patients (28.1%) received treatment based on β-lactam or vancomycin plus rifampicin and were included in the study. Variables were analyzed which related to patient survival during admission, including having received treatment with gentamicin. Results: Seventy-seven (81.9%) were treated with cloxacillin (or vancomycin) plus rifampicin plus gentamicin, and 17 patients (18.1%) received the same regimen without gentamicin. The causative microorganism was Staphylococcus aureus in 40 cases (42.6%) and coagulase-negative staphylococci in 54 cases (57.4%). Overall, 40 patients (42.6%) died during hospital admission, 33 patients (42.9%) in the group receiving gentamicin and 7 patients in the group that did not (41.2%, P = 0.899). Worsening renal function was observed in 42 patients (54.5%) who received gentamicin and in 9 patients (52.9%) who did not (p = 0.904). Heart failure as a complication of endocarditis (OR: 4.58; CI 95%: 1.84–11.42) and not performing surgery when indicated (OR: 2.68; CI 95%: 1.03–6.94) increased mortality. Gentamicin administration remained unrelated to mortality (OR: 1.001; CI 95%: 0.29–3.38) in the multivariable analysis. Conclusions: The addition of gentamicin to a regimen containing vancomycin or cloxacillin plus rifampicin in SPVE was not associated to better outcome.

Objective To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Method Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006–February 2007), E2 (April 2008–January 2009) and E3 (July 2010–May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Results Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD] = 1.15) in E1; 6.90 (SD = 1.60) in E2; and 6.52 (SD = 1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P = .0008), whereas level of tension (P = .0119) and mood (P = .0451) decreased significantly. Conclusions In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment.

The neuropathological hallmark of the C9orf72 intronic hexanucleotide expansion in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the presence of small ubiquitin/p62-positive and transactive response DNA binding protein 43 kDa (TDP-43)-negative cytoplasmic inclusions in several brain areas. The identification of this histopathological signature is highly predictive of an underlying mutation. In this study, we screened 1800 cases of the Barcelona IDIBAPS Brain Bank, independently of the clinical and final neuropathological diagnosis of the brain donor, for the presence of ubiquitin/p62-positive inclusions in the cerebellum (UPPI). Positive cases were also stained for dipeptide repeats. We identified a total of 21 donors with UPPI and in all of them the C9orf72 hexanucleotide expansion was genetically confirmed. Most donors had an FTLD or to a lesser extent ALS clinico-pathological phenotype. However, 3 cases had been previously classified as having clinically and neuropathologically Lewy body disease. Other co-existing pathologies, especially of the PART-type, were also frequently encountered. This study highlights the importance of the evaluation of ubiquitin/p62-positive cytoplasmic inclusions in all neurodegenerative diseases as a good screening method for the detection of C9orf72 expansion mutation, since this mutation is not rare and can overlap with other neurodegenerative entities.

Background/Aims: Peritoneal protein loss (PPL) is associated with cardiovascular disease and mortality in peritoneal dialysis (PD). Controversial results have been published about the effect of paricalcitol in PPL among PD patients. This study intends to analyze the relationship between paricalcitol and PPL in PD. Methods: In a retrospective study, prevalent PD patients were divided into 2 groups: “with paricalcitol” and “without paricalcitol”. X2-test, Student’s t test, Pearson correlation coefficient and Logistic Regression analysis were applied. Results: Eighty-two patients were included. PPL was lower among patients medicated with paricalcitol (5.17 ± 1.71 vs. 6.79 ± 2.10 g/24 h, p = 0.0001). In multivariate analysis, paricalcitol and dialysate/plasma ratio of creatinine (D/P creatinine) were independently related to PPL (OR 4.270 [1.437–12.684], p = 0.009 and OR 0.205 [0.064–0.659], p = 0.008, respectively), adjusted for diabetes. Conclusion: Paricalcitol and D/P creatinine were independently related to PPL. Paricalcitol may have an effect on PPL in PD patients

To investigate the associations between the Neuro-Quality of Life (NQOL) Depression and Anxiety measures with an objective emotional inventory (Personality Assessment Inventory; PAI), and demonstrate the clinical utility of the NQOL as screening measures for depression and anxiety in persons with epilepsy (PWE).PWE (N=72) were concurrently administered the NQOL Depression and Anxiety measures and the PAI. Pearson product moment correlations were used to determine the relationships between the NQOL measures and the respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted comparing NQOL scores between patients with elevated levels of depression and anxiety (T-score≥65 on the PAI) to profiles that were within normal limits. Using sensitivity and specificity analyses, optimal cut-scores on the NQOL measures were determined.Participants were primarily Caucasian (89%), female (60%), and ~35 years old. The NQOL Depression measure was significantly correlated with the PAI Depression total score (r=.747; p0.001) and its subscales (p's0.001). Similarly, the NQOL Anxiety measure was significantly correlated with the PAI Anxiety total score (r=.750; p0.001) and its subscales (p's0.001). Compared to profiles that were within normal limits, individuals with elevated depressive symptoms on the PAI had significantly higher NQOL Depression scores (F(1,71)=48.2, p0.001, d=1.6). Similarly, those who endorsed elevated anxiety on the PAI had significantly higher NQOL Anxiety scores (F(1,71)=32.2, p0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and 24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67; specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77; specificity=0.82; PPV=0.81; NPV=0.78) in PWE.The NQOL Depression and Anxiety measures evidenced strong associations with the PAI Depression and Anxiety scales and may be effective in detecting depressive and anxiety symptoms in PWE using the provided cut-scores.

The aim of this study was to investigate cognitive and emotional factors associated with the presence and clinical course of confabulation. 24 confabulating participants were compared with 11 brain injured and 6 healthy controls on measures of temporal context confusions, mood state (elation, depression) and lack of insight. Measures of autobiographical memory and executive function were also available. Changes in confabulation and these other measures were monitored over 9 months in the confabulating group. We found that temporal context confusions were more common in confabulating patients than in healthy controls, and that the decline in these errors paralleled the recovery from confabulation. However, temporal context confusions were not specific to the presence of confabulation in brain injury; and their decline was not correlated with change in confabulation scores over 9 months. We found that elated mood and lack of insight discriminated between confabulating and non-confabulating patients, but these measures did not correlate with either the severity of confabulation or change in confabulation scores through time. What seems to have been most strongly associated with the severity of confabulation scores at ‘baseline’ and changes through time (over 9 months) were the severity of memory impairment (especially on autobiographical memory) and errors on executive tests (particularly in making cognitive estimates). Greater autobiographical memory and executive impairment were associated with more severe confabulation. The findings were consistent with the view that confabulation results from executive dysfunction where autobiographical memory is also impaired; and that it resolves as these impairments subside.