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PurposeDominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.MethodsWe used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.ResultsWe found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity. Loss-of-function variants disrupted RARB function through a dominant-negative effect, possibly by disrupting ligand binding and/or coactivators' recruitment. By reviewing clinical data from 52 affected individuals, we found that disruption of RARB is associated with a more variable phenotype than initially suspected, with the absence in some individuals of cardinal features of MCOPS12, such as developmental eye anomaly or motor impairment.ConclusionOur study indicates that pathogenic variants in RARB are functionally heterogeneous and associated with extensive clinical heterogeneity.

Aesthetic sensitivity in people with high sensory processing sensitivity (SPS) reflects the positive perception of life, especially aspects related to the arts and nature. This study is focused on the analysis of the effect of aesthetic sensitivity in relation to indicators of health-related quality of life (general health, mental health and emotional role), the personality traits openness to experience and agreeableness, and coping strategies in people with SPS. The adult participants (N = 10,520, mean age = 33.61) completed the Spanish versions of the High Sensitivity Person Scale (HSPS-S), Short Form Health Survey (SF-36), NEO Five Factor Inventory (NEO-FFI) and Coping Strategies Inventory (CSI). It was observed that people with high aesthetic sensitivity presented greater openness and agreeableness, tended to use adaptive coping strategies and showed a slightly poorer functioning in different areas of daily living. Moreover, health-related quality of life, mental health and adaptive coping strategies occupied central positions in the correlations between variables, with a positive impact between mental health and adaptive coping strategies with openness and agreeableness. Lastly, the level of aesthetic sensitivity did not play a moderator role, and it exerted no differential influence on its relationship with the analysed variables. Now, it has been found that people with high levels of aesthetic sensitivity cope more adequately, which would cushion the effect that high SPS can have on mental health, specifically on anxious and depressive symptoms. It is concluded that these findings are relevant and useful for future propositions of prevention and clinical intervention, as well as for counselling in the psychoeducational, labour and family scopes, amongst others.

Abstract SRAM and DRAM memory technologies have been dominant in the implementations of memory subsystems. In recent years, and mainly driven by the huge memory demands of big data applications, NVRAM technology has emerged as a denser memory technology, enabling the design of new hybrid DRAM/NVRAM memory hierarchies that combine multiple memory media technologies to balance memory capacity, latency, cost, and endurance. Two main approaches are being applied to the design of hybrid memory hierarchies: the hybrid address space approach, which relies on the programmer or the operating system to choose the memory technology where each memory page should be stored; and the (only) NVM address space approach, where a faster technology (e.g. commodity DRAM) is needed to acts as a cache of NVRAM to boost the performance. This approach presents architectural challenges such the organization of metadata (e.g. cache tags) and the selection of the proper technology for each memory component. In contrast to existing approaches, this work proposes a memory controller that leverages novel memory technologies such as eDRAM and MRAM to mitigate NVRAM bus contention and improve the performance of the NVM address space. The devised solution proposes a two-level cache hierarchy in the memory controller: a SRAM sector cache and a (x)RAM cache. The (x)RAM cache, much denser, helps significantly reduce the number of accesses to NVRAM. Experimental results show that implementing the (x)RAM cache with eDRAM or MRAM is the best performing approach. Moreover, the eRAM is able to improve the SRAM cache miss penalty by up to 50% and 80%, and overall system performance by 15% and 23%.

Faunas of oceanic islands have a high proportion of endemic species which contribute to the uniqueness of island communities. Island species are particularly naïve and vulnerable to alien predators, such as cats (Felis catus). On large, inhabited islands, where the complete eradication of feral cat populations is not considered feasible, control represents the best management option to lower their detrimental effects on native fauna. The first objective of our study was to investigate population genetics of feral cats of Réunion Island. The second objective was to understand the space use of feral cats established near the breeding colonies of the two endemic and endangered seabirds of Réunion Island, the Barau’s Petrel (Pterodroma baraui) and the Mascarene Petrel (Pseudobulweria aterrima). We evaluated genetic diversity, population structure and gene flow amongst six groups of feral cats located at a maximum of 10 km from known petrel colonies. We also analysed the behaviour and space use of one of these feral cat groups using camera-trap data and Spatially Explicit Capture-Recapture (SECR) models. Genetic analyses revealed that feral cats were structured in three genetic clusters explained mostly by the island topography. Two clusters were observed at five sampled sites, suggesting high connectivity amongst these sites. The last cluster was found in only one site, suggesting high isolation. This site was a remote mountain area located in the vicinity of one of the main Barau’s Petrel colonies. The behavioural study was conducted on this isolated feral cat population. Mark recapture analysis suggested that feral cats were present at low density and had large home ranges, which is probably explained by reduced food availability. Finally, we make several recommendations for refining feral cat management programmes on inhabited islands.

Zhu–Tokita–Takenouchi–Kim syndrome is a multisystem disorder resulting from haploinsufficiency in the SON gene, which is characterized by developmental delay/intellectual disability, seizures, facial dysmorphism, short stature, and congenital malformations, primarily in the central nervous system, along with ophthalmic, dental, pulmonary, cardiologic, renal, gastrointestinal, and musculoskeletal anomalies. In this study, we describe the first Colombian patient with ZTT harboring a novel mutation that has not been previously reported and review the clinical and molecular features of previously reported patients in the literature.

Antonio Chacón, 1 Manuela Pérez-Chacón, 1 Mercedes Borda-Mas, 2 María Luisa Avargues-Navarro, 2 Ana María López-Jiménez 3 1International School of Doctoral Studies, University of Seville, Seville, 41013, Spain; 2Department of Personality, Assessment, and Psychological Treatment, University of Seville, Seville, 41018, Spain; 3Department of Experimental Psychology, University of Seville, Seville, SpainCorrespondence: María Luisa Avargues-NavarroDepartment of Personality, Assessment, and Psychological Treatment, Faculty of Psychology, University of Seville, C/Camilo José Cela s/n, Seville, 41018, SpainTel +34 954 557 806Email avargues@us.esManuela Pérez-ChacónInternational School of Doctoral Studies, University of Seville, México Pavillion, Paseo de las Delicias s/n, Seville, 41013, SpainTel +34 672 239 205Email manpercha@alum.us.esPurpose: This article describes a cross-cultural adaptation of the Highly Sensitive Person Scale (HSPS) to the adult Spanish population, and psychometric analysis of its validation and reliability.Methods: Convenience sampling by participant accessibility was used. The original version was adapted culturally and linguistically using the back-translation method, and a pilot study was done with 88 participants. Data processing and analysis was performed with the SPSS v.25 and LISREL v.9.2 statistical packages. The psychometric properties were studied in a sample of 8358 participants using exploratory factor analysis and confirmatory factor analysis, and examining factorial invariance and internal consistency.Results: The results confirmed a Spanish version with 27 items in five-dimensions: sensitivity to overstimulation (SOS), aesthetic sensitivity (AES), low sensory threshold (LST), fine psychophysiological discrimination (FPD) and harm avoidance (HA). Invariance across gender of this factor structure was demonstrated and reliability indices were good.Conclusion: These findings demonstrate that the HSPS is an appropriate tool for evaluating high sensitivity in the adult Spanish population.Keywords: sensory processing sensitivity, sensitivity to overstimulation, aesthetic sensitivity, low sensory threshold, fine psychophysiological discrimination, harm avoidance

The aim of this study was to analyze the role of sensory processing sensitivity in the perception of stress under certain working conditions and its relationship with indicators of quality of professional life, in service sector workers. The participants (n = 3180) completed the Spanish versions of HSPS-S, CoPSoQ and ProQoL. The results show that exposure to certain working conditions represents a risk to the quality of professional life in workers of different fields, such as education, healthcare, hospitality and administration/management. The presence of high sensitivity is associated with poorer quality of professional life, specifically burnout and compassion fatigue. This study demonstrates the need to develop prevention programs aimed at managing stress by improving the working conditions, in order to adequately address sensory processing sensitivity and, consequently, promote the quality of professional life of service sector workers who present high sensitivity.

Abstract Background Lynch syndrome (LS) is a hereditary condition characterized by a high risk of colorectal cancer, endometrial cancer, and other neoplasia associated with germline alterations in DNA mismatch repair genes. The classical genetic diagnostic strategy for LS consists of the Sanger sequencing of genes associated with the suspected syndrome. Next‐generation sequencing (NGS) enables the simultaneous sequencing of a large number of hereditary cancer genes. Here, we aimed to study whether other germline pathogenic variants of hereditary cancer genes are present in patients with LS. Methods A cohort of 84 probands with a previous genetic diagnosis of LS by Sanger sequencing was reanalyzed using NGS via a commercial panel of 94 hereditary cancer genes by hybrid capture. The American College of Medical Genetics and Genomics criteria were used to classify the clinical significance of the variants. The findings of NGS were confirmed by Sanger sequencing. When possible, genetic analyses of the new findings in the proband's relatives were also performed by Sanger sequencing. Results We identified five families (6%), out of 84, with at least two germline pathogenic variants conferring to high or moderate risk in different dominant cancer‐predisposing genes: [MLH1‐BRCA2‐NBN], [MLH1‐BRCA1], [MSH2‐ATM], [MSH6‐NF1], and [MLH1‐FANCA]. Interestingly, only one out of these five families exhibited a clinical phenotype associated with the new pathogenic variants. The family with three pathogenic variants of the [MLH1‐BRCA2‐NBN] genes showed a high aggregation of tumors associated with LS and breast and ovarian cancer syndrome. Conclusions Our results showed that the co‐occurrence of more than one pathogenic variant in cancer‐predisposing genes was remarkable among cases of LS. In most cases, no clinicial manifestations were associated with the secondary pathogenic variants. Further studies are needed to confirm these findings and elucidate their clinical impact. Reanalysis of LS families should be considered only in families with mixed clinical phenotypes.

Being a housewife may already be a psychosocial risk factor leading to chronic stress and burnout, and this may be aggravated when the housewife must also become the caregiver of a family member with Alzheimer’s. The burnout syndrome and how it can affect general health and the presence of emotional disorders were studied in housewives who were family caregivers of an Alzheimer’s patient. The sample selected was made up of 193 housewives, 96 of whom were also caregivers for a family member with Alzheimer’s. Sociodemographic measures used were the Maslach Burnout Inventory and The General Health Questionnaire. Burnout was found in a significant percentage of participants. Emotional exhaustion, effect on general health, and presence of emotional disorders were higher in caregivers. Emotional exhaustion, general health, and anxiety were more influential, while depersonalization affected the appearance of depressive symptoms more. Being a caregiver and emotional exhaustion appeared to be the best predictors of emotional disorders. It was confirmed that emotional exhaustion influenced appearance of anxiety and depression equally in both groups. In the case of caregivers, an exhaustion-illness spiral was produced. In this group, emotional exhaustion seemed to become more severe as a consequence of the presence of chronic illnesses, and possibly influence the number of hours spent on care and having children living at home. Future research should analyze in greater depth and in a larger sample, the role of these variables and widen the focus of attention to personal variables that could be acting as protective factors and could be subject to intervention. The discussion concludes with some actions that should be included in prevention programs for the groups studied.

Antecedentes/Objetivo: La evidencia sobre la eficacia de intervenciones cognitivoconductuales en los Trastornos de la Conducta Alimentaria (TCA) aún presenta resultados no concluyentes respecto al papel que desempe˜nan en las conductas purgativas, más aún cuando se realizan en situaciones no controladas. Se pretende conocer la evolución tras un tratamiento multicomponente en pacientes con TCA, con presencia o ausencia de conductas purgativas, después de 30 meses del inicio del tratamiento. Método: Participaron 162 mujeres (87 purgativas y 75 no purgativas), tratadas en régimen ambulatorio o hospitalario + ambulatorio, en Espa˜na. Los instrumentos de evaluación fueron: BSQ, EAT-40, EDI, STAI, BDI y BITE. Resultados: Al inicio del tratamiento, las participantes con conductas purgativas presentaban mayor sintomatología bulímica, más insatisfacción corporal, obsesión por la delgadez, perfeccionismo e ineficacia, ansiedad y sintomatología depresiva. Tras 30 meses, en ambos grupos, la intervención produjo mejoría en las características de TCA, alteraciones emocionales y variables de desarrollo personal, siendo menor en las pacientes sin conductas purgativas. El efecto de la intervención fue mayor en las participantes purgativas y las variables con mayor tamaño de efecto: insatisfacción corporal, sintomatología bulímica y ansiedad. Conclusiones: Es importante considerar las conductas purgativas en el dise˜no de estos tratamientos de cara al pronóstico.

Our objective was to analyze the differences in posttraumatic growth in 240 liver transplant recipients based on two factors. First, self-perceived health: better (Group 1 = G1) and worse (Group 2 = G2). Second, vitality: more (Group 3 = G3) and less (Group 4 = G4). The Posttraumatic Growth Inventory, SF-36 Health Survey (Item 2) and SF-12 Health Survey (vitality dimension) were used. Firstly, analyzing main effects recipients with better (G1) compared to worse (G2) self-perceived health, showed greater posttraumatic growth. Interaction effects were found on essential posttraumatic growth domains such as new possibilities (p = 0.040), personal strength (p = 0.027), and appreciation of life (p = 0.014). Statistically significant differences showed that among transplant recipients with worse self-perceived health (G2), those with more vitality had higher levels on abovementioned posttraumatic growth dimensions. However, in transplant recipients with better self-perceived health (G1) respective dimensions were not significantly influenced by the level of vitality. Among the recipients with less vitality (G4), those with better self-perceived health showed higher scores on abovementioned posttraumatic growth dimensions. We conclude that positive self-perceived health might compensate for a lack of vitality as well as a high level of vitality may compensate for negative self-perceived health regarding the development of crucial aspects of posttraumatic growth after liver transplantation.

Background: Tubular ectasia of the rete testis (TERT) is a dilatation of the seminiferous tubules of the mediastinum testis. It tends to be asymptomatic and usually constitutes an incidental finding of imaging studies. Scrotal ultrasound (SU) shows tubules with a cystic appearance, suggesting a number of possible diagnoses, including testicular tumours. Objective: To review our experience and describe the clinical and ultrasound features. Design: Retrospective descriptive review. Setting: The images were obtained by SU on an ambulatory basis. SU was performed with the Pro Focus Ultrasound System (BK Medical®, Massachusetts, USA). The indications of the exploration, the SU findings, and the associated conditions were the variables analysed. Participants: 460 SU studies performed in our hospital between 2010 and 2013. The subjects were men, with a median age of 66 years (range 47–78). Outcome Measurements and Statistical Analysis: SPSS® version 20 (IBM, New York, USA) was used for the descriptive analysis of the data. Results and Limitations: TERT was identified in 23 out of 460 SU studies performed. SU was indicated due to the presence of scrotal swelling in 7 patients (30%), an epididymal mass in 8 patients (35%), mild testicular pain in 6 patients (26%), and post-surgical control in 2 asymptomatic patients. Within the 23 patients, 10 (43.4%) were diagnosed with an epididymal cyst, 3 (13%) with chronic epididymitis, and 9 (39%) with a hydrocoele. With regard to associated conditions, 3 (13%) had undergone ipsilateral inguinal hernia repair, 3 (13%) had undergone ipsilateral hydrocoelectomy, and 1 (4%) had a history of contralateral testicular cancer. TERT was unilateral in all cases. No malignant degeneration of the lesions was observed in our series. Conclusions: According to our experience, TERT is an incidental condition where detailed clinical history, adequate physical examination, and SU findings can lead to the diagnosis. Knowledge of this disease is therefore essential for urologists. Patient summary: In this report we analyse the clinical features and the SU findings associated with TERT, a condition incidentally found in imaging studies of men in their 60s usually performed for other reasons.

The valid assessment of the impact of transplantation on psychological well-being is highly relevant to optimize treatment. However, to date there is no standardized instrument available in Spain. The Transplant Effects Questionnaire (TxEQ) evaluates the specific problems associated with organ transplantation, such as worry about transplant, guilt regarding the donor, disclosure of having undergone transplantation, adherence to medical treatment and responsibility toward the donor, family, friends, or medical staff. Against this backdrop the English original version of the TxEQ was translated into Spanish and validated in a sample of 240 liver transplant recipients. Participants also filled in the Posttraumatic Growth Inventory (PTGI), and the 12-Item Short Form Health Survey (SF-12v.2). Confirmatory factor analysis of the TxEQ-Spanish revealed a five-factor structure equivalent to the English original version, and satisfactory internal consistency (Cronbach's alpha: worry α = 0.82, guilt α = 0.77, disclosure α = 0.91, adherence α = 0.82, responsibility α = 0.83). Results showed that better mental quality of life was associated with higher adherence and disclosure, as well as less worry and guilt. Higher posttraumatic growth was significantly associated with worry, guilt, and responsibility. Interestingly, the most powerful predictor of posttraumatic growth was worry. Analysis of variance showed an interaction effect of PTG and mental quality of life on adherence, with medium PTG being associated with significantly stronger adherence in participants with better mental quality of life. In conclusion our study could successfully adapt and validate the Spanish version of the TxEQ in a large sample of liver transplant recipients. Our findings show a complex relationship between emotional reactions to transplantation, mental quality of life, and posttraumatic growth, which give further insight into inner processes supporting psychological well-being and adherence after liver transplantation.

Hemospermia may have a broad range of functional and organic causes. It is defined as the presence of blood in seminal fluid and usually tends to resolve spontaneously within a few weeks. We present the case of a patient with a 10-year history of hemospermia associated with megacava and circumaortic renal vein. The diagnosis, treatment, and evolution of the condition are reported. Vascular anomalies are rare causes of chronic hemospermia, and the one described in our patient may constitute the first case reported in the literature.

El objetivo de este estudio ex post facto ha sido poner a prueba un modelo estructural sobre el papel mediador de la autoestima y el perfeccionismo en la relación entre los rasgos de personalidad y los trastornos de la conducta alimentaria (TCA). La muestra estuvo compuesta por 155 mujeres (18 a 31 años): 93 cumplían criterios diagnósticos DSM-IV para alguno de los tipos de TCA, 31 formaron el grupo sintomático, con alto riesgo de padecer un TCA y 31, grupo no sintomático, no presentaban patología conocida y sin alteraciones de la conducta alimentaria. Los instrumentos de evaluación utilizados fueron el MCMI-II, EDI-2, EAT-40 y BSQ. Para el análisis de los datos se utilizó el método de estimación de máxima verosimilitud mediante el programa LISREL 8.71. El modelo estimado se ajustó satisfactoriamente. Los resultados confi rman la relación de los rasgos de personalidad esquizoide, paranoide, autodestructiva y límite con los TCA, el papel de la autoestima como principal variable mediadora en el efecto ejercido por ciertos rasgos de personalidad sobre los TCA y del perfeccionismo como variable mediadora del efecto del rasgo de personalidad límite sobre dichos trastornos y sobre la autoestima.

Most clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses.

Introduction: Although lithium has a narrow therapeutic range, it is widely used in psychiatry because of its antipsychotic and antidepressant properties. During long-term treatment, the onset of nephrogenic diabetes insipidus is common, but few cases of severe hypotonic polyuria, which would be an aggravating factor, have been reported. Appropriate treatment in such cases is an open question., Case: We report a case of acute lithium poisoning in a 42-year-old man, due to chronic lithium treatment (plasma lithium=2.6 mmol/L). This patient, admitted to our intensive care unit, presented neurological disorders complicated by the early emergence of severe nephrogenic diabetes insipidus. After perfusion of hypotonic solution and intravenous treatment with ketoprofen (100 mg x 3/24 h), the polyuria improved rapidly., Comments: The beneficial action of nonsteroidal antiinflammatory drugs lies in their capacity to inhibit prostaglandin synthesis. Lithium causes excess production of prostaglandins, which decrease the ability of kidneys to reabsorb free water. Some publications report indomethacin to be effective in this case. Because it is available only in oral or rectal forms, however, its effect may be delayed. Our case suggests that intravenous ketoprofen, with its rapid onset of action, is effective in the treatment of severe lithium-induced nephrogenic diabetes insipidus. Rehydration must be strictly monitored because of the risk of renal failure connected with nonsteroidal antiinflammatory drugs.

Invasive infections by Streptococcus pyogenes continually increase both in France and in others industrialized countries. Because of the seriousness, the rapidity of the evolution and the epidemic potentialities, guidelines for managing these infections are requested by the Superior Council of Public Hygiene of France. The authors report herein a case of an adult stricken down by a violent evolution due to Streptococcus pyogenes. They point up how diagnosis, treatment and prophylaxis for family circle are difficult.

A case of neuromuscular blockade of about 200 min of duration, in a 9-year-old boy from mivacurium 0.15 mg.kg-1 is reported. The diagnosis was delayed, after onset of the first signs of recovery, due to the lack of monitoring of neuromuscular transmission. The neuromuscular blockade was reversed with neostigmine 0.04 mg.kg-1. Complete reversal required fifty minutes. The presence of an abnormal genetic variant of pseudocholinesterases was demonstrated by the measurements of pseudocholinesterase activity and dibucaine number. The importance of monitoring of neuromuscular transmission for diagnosis and treatment of mivacurium-induced neuromuscular blockade is underlined.