Reporting trigger factors for (hypo)manic episodes in bipolar disorder: association with personality and prognosis.

OBJECTIVE: To investigate external factors that trigger manic and hypomanic relapses and how this is associated with personality and clinical outcome measured as number of affective episodes over a 7-year period. METHOD: This is a prospective cohort study of 204 meticulously characterized Swedish bipolar disorder patients. Personality was evaluated at baseline using the Swedish universities Scales of Personality in 170 patients, and 90 patients were followed up after approximately 7 years in order to evaluate clinical outcomes. RESULTS: We found that 44% of the patients reported trigger factors, including sleep disturbance, work- or family-related issues, medication, and illicit drug use. There were no significant differences in any of the personality traits when comparing the 74 patients that reported triggers with the 90 patients that did not. At 7-year follow-up, there was no difference between the groups in number of affective episodes (depressive, hypomanic, manic, or mixed), involuntary commitments, suicide attempts, or self-harm incidents since baseline. CONCLUSIONS: Around 40% of the patients reported external triggers for manic and hypomanic episodes. However, this was neither associated with personality traits nor number of affective episodes at 7-year follow-up.

Initial single centre experiences of a radiographer advanced practitioner led nephrostomy exchange programme.

INTRODUCTION: To evaluate the technical success, radiation dose, complications and costs from the introduction of a radiographer-led nephrostomy exchange service. METHODS: Post-graduate qualified interventional radiographers with several years' experience in performing other interventional procedures began performing nephrostomy exchanges. Training was provided by an interventional radiologist. Each radiographer performed ten procedures under direct supervision followed by independent practice with remote supervision. Each radiographer was then responsible for the radiological report, discharge, re-referral for further exchange and, where indicated, sending urine samples for culture and sensitivity. Data extraction included the time interval between exchanges, radiation dose/screening time and complications. RESULTS: Thirty-eight long-term nephrostomy patients had their histories interrogated back to the time of the initial insertion. The mean (range) age at nephrostomy insertion was 67 (35-93) years and 65% were male. Indications for nephrostomy were prostatic or gynaecological malignancy, ureteric injury, bulky lymphoma and post-transplant ureteric stricture. A total of 170 nephrostomy exchanges were performed with no statistically significant differences in the radiation dose, fluoroscopy time nor complication rates between consultants and radiographers. There was, however, a statistically significant reduction in the time interval between nephrostomy exchanges for the radiographer group (P = 0.022). CONCLUSION: Interventional radiographers can provide a safe, technically successful nephrostomy exchange program with radiation doses equivalent to radiologists. This is a cost-effective solution to the capacity issues faced in many departments, whilst providing career progression, job satisfaction and possibly improved care. IMPLICATIONS FOR PRACTICE: Radiographer-led interventional services should be considered by other institutions as a means of providing effective nephrostomy exchanges.

PPP1R21 homozygous null variants associated with developmental delay, muscle weakness, distinctive facial features, and brain abnormalities.

We present 3 children with homozygous null variants in the PPP1R21 gene. A 3-year-old girl had profound developmental delay, hypotonia and weakness, poor feeding, recurrent chest infections and respiratory failure, rotatory nystagmus, absent reflexes, and a homozygous nonsense variant c.2089C>T (p.Arg697*). A 2-year-old boy had profound developmental delay, weakness and hypotonia, recurrent chest infections and respiratory distress, undescended testes, rotatory nystagmus, hyporeflexia, and a homozygous nonsense variant c.427C>T (p.Arg143*). An 11-year-old girl with profound developmental delay, weakness and hypotonia, stereotypic movements, growth failure, hyporeflexia, and a homozygous frameshift variant c.87_88delAG (p.Gly30Cysfs*4). In addition, these children shared common facial features (thick eyebrows, hypertelorism, broad nasal bridge, short nose with upturned nasal tip and broad low-hanging columella, thick lips, low-set ears, and coarse facies with excessive facial hair), and brain abnormalities (cerebellar vermis hypoplasia, ventricular dilatation, and reduced white matter volume). Although PPP1R21 has not yet been linked to human disease, the consistency in the phenotype of individuals from unrelated families, the nature of the variants which result in truncated proteins, and the expected vital role for PPP1R21 in cellular function, all support that PPP1R21 is a novel disease-associated gene responsible for the phenotype observed in these individuals.

TASP1 is deleted in an infant with developmental delay, microcephaly, distinctive facial features, and multiple congenital anomalies.

We report a 20p12.1 homozygous deletion including exons 5-10 of the TASP1 gene in an infant with developmental delay, acquired microcephaly, distinctive facial features, and multiple congenital anomalies involving skeletal, cardiac, and renal systems. TASP1 encodes taspase 1 which is responsible for cleaving, thus activating, a number of transcription factors including the mixed lineage leukemia 1 (MLL1). Taspase 1-deficient mice showed early lethality, skeletal abnormalities, and growth failure, which support a potentially causal role of TASP1 deletion in this infant. Furthermore, the infant reported here had many of the features seen in Wiedemann-Steiner syndrome which is caused by MLL1 defects. Such observation further supports that TASP1 is a novel disease-related gene that is associated with a disease phenotype overlapping with Wiedemann-Steiner syndrome as both are caused by defects in the same pathway.

Multiple sclerosis or "inflammatory CADASIL?": Case Report and review of the literature.

BACKGROUND: Multiple sclerosis (MS) and CADASIL presenting together is exceedingly rare. As more cases of "inflammatory" CADASIL emerge, diagnostic challenges for clinicians increase. We report an individual with MS and CADASIL presenting with cognitive decline at age 25. She presented with gadolinium enhancing lesions on MRI and inflammatory cerebrospinal fluid raising the question of whether these patients should be given a diagnosis of "inflammatory CADASIL" or both MS and CADASIL. METHODS: A literature review was conducted on reports of inflammatory CADASIL or MS and CADASIL, clinical presentations including spinal cord lesions and CSF inflammatory markers. RESULTS: Nine cases in the literature of individuals with CADASIL and inflammatory presentations were found with treatment varying from intravenous steroids to MS immunomodulatory therapy. CONCLUSIONS: If individuals with CADASIL present with immune mediated inflammatory components they may benefit from immunomodulatory therapy. This is discussed with a review of the inflammatory CADASIL/MS cases in the literature and report of a case.

WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome.

The advancement in genomic sequencing has greatly improved the diagnostic yield for neurodevelopmental disorders and led to the discovery of large number of novel genes associated with these disorders. WDR45B has been identified as a potential intellectual disability gene through genomic sequencing of 2 large cohorts of affected individuals. In this report we present 6 individuals from 3 unrelated families with homozygous pathogenic variants in WDR45B: c.799C>T (p.Q267*) in 1 family and c.673C>T (p.R225*) in 2 families. These individuals shared a similar phenotype including profound development delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations. Neuroimaging showed ventriculomegaly, reduced cerebral white matter volume, and thinning of cerebral gray matter. The consistency in the phenotype strongly supports that WDR45B is associated with this disease.

Chromosomal microarray in a highly consanguineous population: diagnostic yield, utility of regions of homozygosity, and novel mutations.

Chromosomal microarray (CMA) has significantly improved diagnosing copy number variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional utility in detecting regions of homozygosity (ROH). Investigating ROH for genes associated with recessive disorders for follow-up sequencing can aid in diagnosis. In this study, we performed a retrospective review of clinical and molecular data for 227 individuals from a highly consanguineous population who previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25 (11%) individuals were diagnosed with recessive disorders caused by mutations in ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%. Among the 25 individuals with recessive diseases, 18 had novel mutations in 16 genes (ASPM, SPINK5, QARS, MEGF10, SPATA7, GMPPA, ABCA4, SRD5A2, RPGRIP1L, MET, SLC12A6, ALDH1A3, TNFRSF11A, FLNB, PHGDH, and FKBP10) including five with phenotypic expansion.

FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.

Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in 10 new subjects with a total of 7 novel deleterious variants; 5 null and 2 missense substitutions. All patients exhibited congenital lactic acidemia, most of them with severe encephalopathic presentation, and global developmental delay. Overall, FBXL4 defects account for at least 0.7% (6 out of 808) of subjects suspected to have a mitochondrial disorder, and as high as 14.3% (4 out of 28) in young children with congenital lactic acidosis and clinical features of mitochondrial disease. Including FBLX4 in the mitochondrial diseases panel should be particularly important for patients with congenital lactic acidosis.

[Clowns in the pediatric intensive care unit in France]. / Les clowns en réanimation pédiatrique : état des lieux en France.

INTRODUCTION: In recent years, in children's hospitals, clowns are involved in pediatric intensive care units (PICUs), at the bedside of the most severely ill children. This study is the first that addresses the work of professional clowns in the PICU. Its aim is to describe this practice in French hospitals. METHODS: This study is a descriptive and prospective study conducted in December 2013 involving all the pediatric PICUs in French hospitals. A survey was emailed to all the PICU department heads in France. RESULTS: Questionnaires were sent to 32 PICUs (21 pediatric and neonatal intensive care units and 11 pediatric intensive care units). The response rate was 81.2% (26 questionnaires completed). Among the 26 units that responded to the survey, clowns intervened in 13 of them (50%). Eight had an exclusive pediatric activity and five had both pediatric and neonatal activities. The clown visit was twice a week in six units and once in seven (missing data: one unit). The head doctor was satisfied or very satisfied in 92.3% of the cases (n=12/13). Medical clowns were trained and professional artists in all of the units. They worked in duo in most units (n=12/13) and solo in one unit. The clown rounds were preceded by a meeting with a healthcare worker in 12 of the 13 PICUs in which the clowns worked. They dialogued with a doctor in four and a nurse (or head nurse) in eight. DISCUSSION: Prior to implementation, the clowns' work should be understood, accepted, and supported by each PICU team, to be validated in the overall care plan for each child. CONCLUSION: Despite the severity of the situations met in the PICU, the instability of patients and the technical environment, clowning in PICUs appears to be a common and worthwhile practice in most French pediatric hospitals.

Physical abuse in basic-education schools in Aden governorate, Yemen: a cross-sectional study.

Physical abuse in school has lifelong consequences affecting child health and educational achievements. A study was designed to assess the prevalence of physical abuse experienced by pupils in basic-education schools in Aden, Yemen, and to examine the risk factors associated with it. A cross-sectional study covering 1066 pupils in 7th-9th grades from 8 schools in different districts of Aden governorate were randomly selected. Answering an anonymous self-administered questionnaire, 55.7% of pupils reported physical abuse at least once in their school lifetime (73.2% of males versus 26.6% of females). Teachers were the main perpetrators (45.4%). A statistically significant association was found between physical abuse and sex, age group, family type and father's education. Significant predictors of physical abuse on multivariate regression were male sex (OR=7.89) and extended family type (OR=1.36). Physical abuse in basic-education schools requires serious consideration by educational authorities, families and the community at large.

[Desmoid tumor of mediastinum revealed by superior vena cava syndrome and tamponade]. / Syndrome cave supérieur et tamponnade révélant une tumeur desmoïde du médiastin.

Desmoid tumors are rare forms of low grade malignancies. They are characterized by a strong potential of local invasion. Although they are considered histologically benign they behave aggressive locally. They typically occur in the abdominal wall or within the abdomen. Mediastinal localisation is very rare. The only curative treatment is wide surgical excision but the surgery is difficult and the risk of local recurrence is high.

Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development.

We report an ~1.3 Mb tandem duplication at Xp11.23p11.3 in an 11-year-old boy with pleasant personality, hyperactivity, learning and visual-spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X-linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over-expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams-Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co-localize to presynaptic active zones, and play important roles in neurotransmitter release.

First cigarette smoking experience among secondary-school students in Aden, Republic of Yemen.

The objectives of this study were first to estimate the prevalence of cigarette smoking among secondary-school students and then to identify and analyse the demographic, social and cultural risk factors associated with the first cigarette smoking experience. A sample comprising 1000 students was selected randomly. Results showed that 19.6% of the total sample smoked; 15.5% among females and 21.9% among males. Family and/or friends appeared to influence the first cigarette experience and thus prevention strategies should involve not only the students themselves but the home, school and social environments also.

[Proximal tibial osteotomy for osteoarthritis of the knee (author's transl)]. / Die proximale Tibiaosteotomie bei Behandlung der Arthrosis deformans des Kniegelenkes

One hundred and seventeen cases of osteoarthritis of the knee-joint, were treated with tibia osteotomy. The result of the different types of the osteotomy are discussed. The proximal tibial osteotomy without metal-fixation has the best results.