Double seronegative myasthenia gravis with antiphospholipid syndrome: a case report.

INTRODUCTION: Myasthenia gravis is an autoimmune disease characterized by fluctuating muscle weakness. It is often associated with other autoimmune disorders, such as thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome. Many aspects of autoimmune diseases are not completely understood, particularly when they occur in association, which suggests a common pathogenetic mechanism. CASE PRESENTATION: We report a case of a 42-year-old Caucasian woman with antiphospholipid syndrome, in whom myasthenia gravis developed years later. She tested negative for both antibodies against the acetylcholine receptor and against muscle-specific receptor tyrosine-kinase, but had typical decremental responses at the repetitive nerve stimulation testing, so that a generalized myasthenia gravis was diagnosed. Her thromboplastin time and activated partial thromboplastin time were high, anticardiolipin and anti-β2 glycoprotein-I antibodies were slightly elevated, as a manifestation of the antiphospholipid syndrome. She had a good clinical response when treated with a combination of pyridostigmine, prednisone and azathioprine. CONCLUSIONS: Many patients with myasthenia gravis test positive for a large variety of auto-antibodies, testifying of an immune dysregulation, and some display mild T-cell lymphopenia associated with hypergammaglobulinemia and B-cell hyper-reactivity. Both of these mechanisms could explain the occurrence of another autoimmune condition, such as antiphospholipid syndrome, but further studies are necessary to shed light on this matter.Clinicians should be aware that patients with an autoimmune diagnosis such as antiphospholipid syndrome who develop signs and neurological symptoms suggestive of myasthenia gravis are at risk and should prompt an emergent evaluation by a specialist.

Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.

Liddle syndrome is an autosomal dominant form of hypertension resulting from deletion or missense mutations of a PPPxY motif in the cytoplasmic COOH terminus of either the beta or gamma subunit of the epithelial Na channel (ENaC). These mutations lead to increased channel activity. In this study we show that wild-type ENaC is downregulated by intracellular Na+, and that Liddle mutants decrease the channel sensitivity to inhibition by intracellular Na+. This event results at high intracellular Na+ activity in 1.2-2.4-fold higher cell surface expression, and 2.8-3.5-fold higher average current per channel in Liddle mutants compared with the wild type. In addition, we show that a rapid increase in the intracellular Na+ activity induced downregulation of the activity of wild-type ENaC, but not Liddle mutants, on a time scale of minutes, which was directly correlated to the magnitude of the Na+ influx into the oocytes. Feedback inhibition of ENaC by intracellular Na+ likely represents an important cellular mechanism for controlling Na+ reabsorption in the distal nephron that has important implications for the pathogenesis of hypertension.

Vascular postpneumonectomy syndrome: inferior vena cava and pulmonary vein compression as unusual cause for platypnea-orthodeoxia following pneumonectomy

Background: Excessive mediastinal shift into the vacated thoracic cavity after pneumonectomy can result in dyspnea without hypoxemia by compression of the tracheobronchial tree, a phenomenon called postpneumonectomy syndrome. More rarely hypoxemia in upright position (platypnea-orthodeoxia syndrome, POS) after pneumonectomy can result from re-opening of an atrial right-to-left shunt through a patent foramen ovale (PFO) due to mediastinal distorsion. Review of literature also shows a unique report of pulmonary veins stenosis resulting in POS without intracardiac shunt after pneumonectomy. Methods: We report the case of a 32-year-old woman who presented POS 6 months after right pneumonectomy for destroyed lung post tuberculosis. Results: The patient described severe dyspnea disappearing when lying. SpO2 decreased from 94% when lying to 60% sitting. Transthoracic echocardiography (TTE) suspected a possible PFO. We first tried to highlight clinical repercussions of PFO by noninvasive exams. Hyperoxia shunt quantification was not tolerated because of increased dyspnea in sitting position. Contrast bubbles TTE was difficult because of the important mediastinal shift but identified only rare left heart bubbles with/without Valsalva both in lying and sitting position, excluding a significant right-to-left shunt. A lung perfusion scintigraphy (injection while sitting) confirmed the absence of systemic isotope uptake. Computed tomographic pulmonary angiography (angio-CT) revealed a stretched but not stenosed left main bronchus, while the shift of the heart into the right cavity was major. Pulmonary angiography did not show embolism but revealed compression of the inferior vena cava (IVC) with impaired venous return to the right heart, as well as compression of the left pulmonary veins. There was no arteriovenous shunt. Cardiac MRI showed torsion of IVC at the level of the diaphragm, and strong atrial contraction contributing to a passive filling of the RV, while the right ventricle was normal. Right catheterism showed major hemodynamic disturbances with negative diastolic pressure in right heart cavities (atrium -12 mm Hg ventricle pressure -7 mm Hg). SaO2 measured in the pulmonary artery decreased from 58% when lying to 45% sitting. Conclusion: We described here an exceedingly rare and complex mechanism explaining POS after right pneumonectomy. Mediastinal repositioning with a silicone breast implant of appropriate size has been scheduled.

The burnout syndrome and associated personality disturbances. The study in three graduate programs in Dentistry at the University of Barcelona

Objective: Determine the presence of"burnout" syndrome and characteristic personality patterns in the students and faculty of three graduate programs in Dentistry at the University of Barcelona: Department of Oral Surgery and Implantology, Department of Orthodontics and Department of Integrated Dentistry. Materials and Methods: The study was carried out in 78 dentists. The level of"burnout" was evaluated using the Maslach Burnout Inventory, socio-demographic variables and, finally, the personality test. Results: Oral surgeons constituted the group of highlevel"burnout". The profile of an individual with a propensity to"burn out" is a single man, with a median age of 27, that is in the first years of the graduate program and that combines studies with 30 hours of clinical practice and/or other work (p<0,05). Narcissistic and borderline are the types of personality most frequently found in the individuals that present"burnout" syndrome (p<0,05). Conclusions: In general, no high levels of"burnout" were registered in the studied population, only 2-3%, if applying strict definition of"burnout", and 10% if these criteria were amplified. We believe it is necessary to identify the individuals with a tendency towards"burnout", in order to establish preventive measures and avoid future negative behaviour at work as well as at the personal level.

Familial occurrence of an association of multiple intestinal atresia and choanal atresia: a new syndrome?

We report on two familial cases from a non-consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post-mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high-resolution array CGH revealed no visible anomalies.

Mesurer la stigmatisation perçue chez les personnes souffrant de troubles psychiques : traduction française, validation et adaptation de la Stigma Scale [French translation, validation and adaptation of the Stigma Scale].

AIM: People suffering from mental illness are exposed to stigma. However, only few tools are available to assess stigmatization as perceived from the patient's perspective. The aim of this study is to adapt and validate a French version of the Stigma Scale (King et al., 2007 [8]). This self-report questionnaire has a three-factor structure: discrimination, disclosure and positive aspects of mental illness. Discrimination subscale refers to perceived negative reactions of others. Disclosure subscale refers mainly to managing disclosure to avoid discrimination and finally positive aspects subscale taps into how patients are becoming more accepting, more understanding toward their illness. METHOD: In the first step, internal consistency, convergent validity and test-retest reliability of the French adaptation of the 28-item scale were assessed in a sample of 183 patients. Results of confirmatory factor analyses (CFA) did not confirm the hypothesized structure. In the light of the failed attempts to validate the original version, an alternative 9-item short-form version of the Stigma Scale, maintaining the integrity of the original model, was developed based on results of exploratory factor analyses in the first sample and cross-validated in a new sample of 234 patients. RESULTS: Results of CFA did not confirm that the data fitted well to the three-factor model of the 28-item Stigma Scale (χ(2)/df=2.02, GFI=0.77, AGFI=0.73, RMSEA=0.07, CFI=0.77 and NNFI=0.75). Cronbach's α was excellent for discrimination (0.84) and disclosure (0.83) subscales but poor for potential positive aspects (0.46). External validity was satisfactory. Overall Stigma Scale total score was negatively correlated with the score on Rosenberg's Self-Esteem Scale (r=-0.49), and each subscale was significantly correlated with a visual analogue scale that referred to the specific aspect of stigma (0.43≤|r|≤0.60). Intraclass correlation coefficients between 0.68 and 0.89 indicated good test-retest reliability. The results of the CFA demonstrated that the items chosen for the short version of the Stigma Scale have the expected fit properties (χ(2)/df=1.02, GFI=0.98, AGFI=0.98, RMSEA=0.01, CFI=1.0 and NNFI=1.0). Considering the small number (three) of items in each subscale of the short version of the Stigma Scale, α coefficients for discrimination (0.57), disclosure (0.80) and potential positive aspects subscales (0.62) are considered as good. CONCLUSION: Our results suggest that the 9-item French short version of the Stigma Scale is a useful, reliable and valid self-report questionnaire to assess perceived stigmatization in people suffering from mental illness. The time of completion is really short and questions are well understood and accepted by the patients.

Sulfur isotope variations from orebody to hand-specimen scale at the Mezica lead-zinc deposit, Slovenia: a predominantly biogenic pattern

The Mississippi Valley-type (MVT) Pb-Zn ore district at Mezica is hosted by Middle to Upper Triassic platform carbonate rocks in the Northern Karavanke/Drau Range geotectonic units of the Eastern Alps, northeastern Slovenia. The mineralization at Mezica covers an area of 64 km(2) with more than 350 orebodies and numerous galena and sphalerite occurrences, which formed epigenetically, both conformable and discordant to bedding. While knowledge on the style of mineralization has grown considerably, the origin of discordant mineralization is still debated. Sulfur stable isotope analyses of 149 sulfide samples from the different types of orebodies provide new insights on the genesis of these mineralizations and their relationship. Over the whole mining district, sphalerite and galena have delta(34)S values in the range of -24.7 to -1.5% VCDT (-13.5 +/- 5.0%) and -24.7 to -1.4% (-10.7 +/- 5.9%), respectively. These values are in the range of the main MVT deposits of the Drau Range. All sulfide delta(34)S values are negative within a broad range, with delta(34)S(pyrite) < delta(34)S(sphalerite) < delta(34)S(galena) for both conformable and discordant orebodies, indicating isotopically heterogeneous H(2)S in the ore-forming fluids and precipitation of the sulfides at thermodynamic disequilibrium. This clearly supports that the main sulfide sulfur originates from bacterially mediated reduction (BSR) of Middle to Upper Triassic seawater sulfate or evaporite sulfate. Thermochemical sulfate reduction (TSR) by organic compounds contributed a minor amount of (34)S-enriched H(2)S to the ore fluid. The variations of delta(34)S values of galena and coarse-grained sphalerite at orefield scale are generally larger than the differences observed in single hand specimens. The progressively more negative delta(34)S values with time along the different sphalerite generations are consistent with mixing of different H(2)S sources, with a decreasing contribution of H(2)S from regional TSR, and an increase from a local H(2)S reservoir produced by BSR (i.e., sedimentary biogenic pyrite, organo-sulfur compounds). Galena in discordant ore (-11.9 to -1.7%; -7.0 +/- 2.7%, n=12) tends to be depleted in (34)S compared with conformable ore (-24.7 to -2.8%, -11.7 +/- 6.2%, n=39). A similar trend is observed from fine-crystalline sphalerite I to coarse open-space filling sphalerite II. Some variation of the sulfide delta(34)S values is attributed to the inherent variability of bacterial sulfate reduction, including metabolic recycling in a locally partially closed system and contribution of H(2)S from hydrolysis of biogenic pyrite and thermal cracking of organo-sulfur compounds. The results suggest that the conformable orebodies originated by mixing of hydrothermal saline metal-rich fluid with H(2)S-rich pore waters during late burial diagenesis, while the discordant orebodies formed by mobilization of the earlier conformable mineralization.

Selection of shrimp breeders free of white spot syndrome and infectious hypodermal and hematopoietic necrosis

The objective of this work was to select surviving breeders of Litopenaeus vannamei from white spot syndrome virus (WSSV) outbreak, adapted to local climatic conditions and negatively diagnosed for WSSV and infectious hypodermal and hematopoietic necrosis virus (IHHNV), and to evaluate if this strategy is a viable alternative for production in Santa Catarina, Brazil. A total of 800 males and 800 females were phenotypically selected in a farm pond. Nested-PCR analyses of 487 sexually mature females and 231 sexually mature males showed that 63% of the females and 55% of the males were infected with IHHNV. Animals free of IHHNV were tested for WSSV, and those considered double negative were used for breeding. The post-larvae produced were stocked in nine nursery tanks for analysis. From the 45 samples, with 50 post-larvae each, only two were positive for IHHNV and none for WSSV. Batches of larvae diagnosed free of virus by nested-PCR were sent to six farms. A comparative analysis was carried out in growth ponds, between local post-larvae and post-larvae from Northeast Brazil. Crabs (Chasmagnathus granulata), blue crabs (Callinectes sapidus), and sea hares (Aplysia brasiliana), which are possible vectors of these viruses, were also evaluated. The mean survival was 55% for local post-larvae against 23.4% for post-larvae from the Northeast. Sea hares showed prevalence of 50% and crabs of 67% of WSSV.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study.

BACKGROUND: Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS: Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Response to topical clonazepam in patients with burning mouth syndrome: a clinical study

Burning Mouth Syndrome (BMS) is a difficult disease for patients and clinicians. Moreover, there is not a general consensus on how to treat the disease. The main objective of this paper is to evaluate BMS patients' response to topical clonazepam treatment. A double blind study was performed. Among a total of 66 patients, 33 were treated with tablets of clonazepam and another 33 were treated with a placebo. Symptoms were evaluated after 1 month and 6 months of treatment and scored on an analogical scale from 0 to 10. Among the 33 patients treated with clonazepam, 23 showed at least a 50% reduction in symptoms after 1 month of treatment. On the contrary, only 4 in the placebo group exhibited significant improvement. After 6 months, significant differences were observed again, as 23 of the 33 patients treated with the drug reported at least a 50% reduction in symptoms, whereas only 2 among those treated with the placebo significantly improved. However, when measured in terms of a complete cure (lack of symptoms), the differences were not significant: 5 drug-treated patients and one belonging to the placebo group were asymptomatic after one month of treatment. In summary, it seems that clonazepam applied topically was effective in treating BMS in a large proportion of patients

Neonates with Bartter syndrome have enormous fluid and sodium requirements.

AIM: Managing neonatal Bartter syndrome by achieving adequate weight gain is challenging. We assessed the correlation between weight gain in neonatal Bartter syndrome and the introduction of fluid and sodium supplementations and indomethacin during the first 4 weeks of life. METHODS: Daily fluid and electrolytes requirements were analysed using linear regression and Spearman correlation coefficients. The weight gain coefficient was calculated as daily weight gain after physiological neonatal weight loss. RESULTS: We studied seven infants. The highest weight gain coefficients occurred between weeks two and four in the five neonates who either received prompt amounts of fluid (maximum 810 mL/kg/day) and sodium (maximum 70 mmol/kg/day) or were treated with indomethacin. For the two patients with the highest weight gain coefficient, water and sodium supplementations were decreased in weeks two to four leading to a significant negative Spearman correlation between weight gain and fluid supplements (r = -0.55 and -0.68) and weight gain and sodium supplementations (r = -0.96 and -0.72). The two patients with the lowest weight gain coefficient had positive Spearman correlation coefficients between weight gain and fluid and sodium supplementations. CONCLUSION: Infants with neonatal Bartter syndrome required rapid and enormous fluid and sodium supplementations or the early introduction of indomethacin treatment to achieve adequate weight gain during the early postnatal period.

Positive Emotions Program for Schizophrenia (PEPS): a pilot intervention to reduce anhedonia and apathy.

BACKGROUND: Recent literature has distinguished the negative symptoms associated with a diminished capacity to experience (apathy, anhedonia) from symptoms associated with a limited capacity for expression (emotional blunting, alogia). The apathy-anhedonia syndrome tends to be associated with a poorer prognosis than the symptoms related to diminished expression. The efficacy of drug-based treatments and psychological interventions for these symptoms in schizophrenia remains limited. There is a clear clinical need for new treatments. METHODS: This pilot study tested the feasibility of a program to reduce anhedonia and apathy in schizophrenia and assessed its impact on 37 participants meeting the ICD-10 criteria for schizophrenia or schizoaffective disorders. Participants were pre- and post-tested using the Scale for the Assessment of Negative Symptoms (SANS) and the Calgary Depression Scale for Schizophrenia (CDSS). They took part in eight sessions of the Positive Emotions Program for Schizophrenia (PEPS)--an intervention that teaches participants skills to help overcome defeatist thinking and to increase the anticipation and maintenance of positive emotions. RESULTS: Thirty-one participants completed the program; those who dropped out did not differ from completers. Participation in the program was accompanied by statistically significant reductions in the total scores for Avolition-Apathy and Anhedonia-Asociality on the SANS, with moderate effect sizes. Furthermore, there was a statistically significant reduction of depression on the CDSS, with a large effect size. Emotional blunting and alogia remain stable during the intervention. DISCUSSION: Findings indicate that PEPS is both a feasible intervention and is associated with an apparently specific reduction of anhedonia and apathy. However, these findings are limited by the absence of control group and the fact that the rater was not blind to the treatment objectives. CONCLUSIONS: PEPS is a promising intervention to improve anhedonia and apathy which need to be tested further in a controlled study. TRIAL REGISTRATION NUMBER: ISRCTN registry ISRCTN74048461, registered 18 may 2015.

The consequences of burnout syndrome among healthcare professionals in Spain ans Spanish speaking Latin American countrie

Objectives: Identify the frequency and intensity of the perception of adverse professional consequences and their association with burnout syndrome and occupational variables. Methods: Cross-sectional sample of 11,530 healthcare professionals resident in Spain and Latin America. The association of negative work-related consequences on burnout, as measured by the MBI and work-related variables was analysed by multiple logistic regression. Results: The emotional exhaustion was the first variable associated with absenteeism, with intention of giving up profession, personal deterioration, and family deterioration. Depersonalization was most associated with the perception of having made mistakes. Conclusions: The findings indicate a considerable prevalence of adverse work-related consequences

Phenotypic and genotypic characteristics of cryopyrin-associated periodic syndrome: a series of 136 patients from the Eurofever Registry.

OBJECTIVE: To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. METHODS: A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. RESULTS: 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. CONCLUSIONS: Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.

Anxiety, depression, and attachment before and after the first-trimester screening for Down syndrome: comparing couples who undergo ART with those who conceive spontaneously.

OBJECTIVES: This study's aim was to describe the emotional status of parents to be before and after the first-trimester combined prenatal screening test. METHODS: One hundred three couples participated, of which 52 had undergone an in vitro fertilization/intracytoplasmic sperm injection treatment [assisted reproductive technology (ART)] and 51 had conceived spontaneously. Participants completed the state scale of the State-trait Anxiety Inventory, the Edinburgh Depression Scale, and the Maternal and Paternal Antenatal Attachment Questionnaire before the first-trimester combined prenatal screening test at around 12 weeks of gestational age (T1) and just after receiving the results at approximately 14 weeks of gestational age (T2). RESULTS: We observed a significant decrease in anxiety and depression symptoms and a significant increase in attachment from T1 to T2. Results showed no differences between groups at either time point, which suggests that ART parents are more similar to than different from parents conceiving spontaneously. Furthermore, given the importance of anxiety during pregnancy, a subsample of women with clinical anxiety was identified. They had significantly higher rates of clinical depression and lower attachment. CONCLUSIONS: These results indicate that, regardless of whether conception was through ART or spontaneous, clinical anxiety in women over the prenatal testing period is associated with more vulnerability during pregnancy (i.e. clinical depression and less attachment to fetus). © 2015 John Wiley & Sons, Ltd.