The Naming Assessment in Multicultural Europe (NAME): Development and Validation in a Multicultural Memory Clinic.

OBJECTIVE: Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME). METHOD: We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items - e.g. from published cross-linguistic word lists and other naming tests - and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%). RESULTS: The NAME showed excellent reliability (Spearman-Brown coefficient: 0.95; Kuder-Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35-.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex. CONCLUSIONS: The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Bacteremia due to healthcare-associated urinary tract infections in children.

BACKGROUND: Epidemiological data on secondary bacteremia associated with nosocomial urinary tract infections generally include adult patients with urinary catheters. AIM: To evaluate the frequency and outcome of secondary bacteremia complicating healthcare-associated urinary tract infections. MATERIAL AND METHODS: This study was conducted between May 2013 and December 2017 at the Dr. Behçet Uz Children's Hospital and included symptomatic nosocomial urinary tract infections. A total of 117 patients with positive blood cultures were enrolled in the study. RESULTS: Six patients had bacteremia associated with nosocomial urinary tract infections yielding an incidence of 5.1%. The pathogens responsible for secondary bacteremia were: Klebsiella pneumonia in two patients, Enterococcus faecium in two patients, Klebsiella oxytoca in one patient, and Pseudomonas aeruginosa in one patient. CONCLUSION: The incidence of bacteremia associated with nosocomial urinary tract infections was not different from bacteremia associated with community-acquired urinary tract infections, and was approximately 5%.

Solar insolation in springtime influences age of onset of bipolar I disorder.

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

Role for neonatal D-serine signaling: prevention of physiological and behavioral deficits in adult Pick1 knockout mice.

NMDA glutamate receptors have key roles in brain development, function and dysfunction. Regulatory roles of D-serine in NMDA receptor-mediated synaptic plasticity have been reported. Nonetheless, it is unclear whether and how neonatal deficits in NMDA-receptor-mediated neurotransmission affect adult brain functions and behavior. Likewise, the role of D-serine during development remains elusive. Here we report behavioral and electrophysiological deficits associated with the frontal cortex in Pick1 knockout mice, which show D-serine deficits in a neonatal- and forebrain-specific manner. The pathological manifestations observed in adult Pick1 mice are rescued by transient neonatal supplementation of D-serine, but not by a similar treatment in adulthood. These results indicate a role for D-serine in neurodevelopment and provide novel insights on how we interpret data of psychiatric genetics, indicating the involvement of genes associated with D-serine synthesis and degradation, as well as how we consider animal models with neonatal application of NMDA receptor antagonists.

Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders.

Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases.

Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia.

A strong candidate gene for schizophrenia and major mental disorders, disrupted-in-schizophrenia 1 (DISC1) was first described in a large Scottish family in which a balanced chromosomal translocation segregates with schizophrenia and other psychiatric illnesses. The translocation mutation may result in loss of DISC1 function via haploinsufficiency or dominant-negative effects of a predicted mutant DISC1 truncated protein product. DISC1 has been implicated in neurodevelopment, including maturation of the cerebral cortex. To evaluate the neuronal and behavioral effects of mutant DISC1, the Tet-off system under the regulation of the CAMKII promoter was used to generate transgenic mice with inducible expression of mutant human DISC1 (hDISC1) limited to forebrain regions, including cerebral cortex, hippocampus and striatum. Expression of mutant hDISC1 was not associated with gross neurodevelopmental abnormalities, but led to a mild enlargement of the lateral ventricles and attenuation of neurite outgrowth in primary cortical neurons. These morphological changes were associated with decreased protein levels of endogenous mouse DISC1, LIS1 and SNAP-25. Compared to their sex-matched littermate controls, mutant hDISC1 transgenic male mice exhibited spontaneous hyperactivity in the open field and alterations in social interaction, and transgenic female mice showed deficient spatial memory. The results show that the neuronal and behavioral effects of mutant hDISC1 are consistent with a dominant-negative mechanism, and are similar to some features of schizophrenia. The present mouse model may facilitate the study of aspects of the pathogenesis of schizophrenia.

Transcatheter embolization of a residual congenital coronary arteriovenous fistula with a detachable balloon; superiority of interventional cardiology?

A ten-year-old girl who presented with a continuous murmur was diagnosed with a right coronary to right ventricular fistula with colored Doppler echocardiography and selective arteriography. She underwent traditional treatment-ligation of the fistula by sternotomy. Afterwards, the systolic component of the murmur persisted and repeat arteriography showed a residual shunt through the fistula, with no change in the diameter of the right coronary artery. We describe the first case in which a residual fistula was treated with a detachable balloon embolization.

Transcatheter closure of the ductus arteriosus in children and young adults.

Transcatheter occlusion of persistent patent ductus arteriosus (PDA) was attempted in 32 patients (22 female and 10 male, mean age 5.12 +/- 3.98 years, range 9 months to 19.2 years) using Rashkind's occluder device (USCI). Implantation of a second occluder device was attempted in three of the patients. Device embolization to a pulmonary artery occurred in three patients, all with the 12 mm occluder device; two of these devices were retrieved by grabber catheter and the last with thoracotomy without adverse sequelae. Embolization to the right atrium occurred in another patient during a second device implantation attempt because of fluoroscopy problems; this patient required open-heart surgery with sequala of 2 (+) tricuspid insufficiency. In another patient with a significant shunt after the implantation of a 17 mm occluder device, mechanical hemolysis developed, but surgical intervention was not required. The overall complication rate was five out of 35 implantation procedures (14.3%). Besides these, sublingual nifedipine was required for two patients whose systolic blood pressure exceeded 160 mmHg just after the implantation procedure. Sixteen 12 mm and fifteen 17 mm occluder devices were successfully and uneventfully implanted in the first procedure, except for two patients in whom a 17 mm occluder device was implanted after retrieval of an embolized 12 mm occluder. Overall early and mid-term complete occlusion was achieved in 24 patients (75%). Complete occlusion of PDA in the first days after the procedure was achieved in all patients, with the narrowest ductal diameter of less-than 3 mm with the 12 mm occluder device, and less than 6 mm with the 17 mm occluder device.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of high-dose intravenous methylprednisolone in the treatment of varicella associated thrombocytopenic purpura.

Two children with varicella associated thrombocytopenia are presented. Case 1, evidencing no mucosal or parenchymal bleeding was administered prednisone 2 mg/kg/day therapy after having been put under observation for a period of one week without medical treatment. There was an increase in the platelet count during the period of therapy culminating in a return to normal on the eighth day. Case 2, who was in poor clinical condition at presentation, was treated with high-dose intravenous methylprednisolone (HIVMP) 30 mg/kg/day, resulting in the platelet count returning to a normal level (180,000/mm3) on the second day of therapy. HIVMP therapy is recommended in the treatment of life-threatening cases of thrombocytopenia because of its rapid action, limited side-effects, and its low cost.

[Salmonella enteritidis serovar tarshyne strains isolated from fecal specimens]. / Fekal örneklerden izole edilen Salmonella enteritidis serovar tarshyne suslari.

Seven Salmonella enteritidis serovar tarshyne strains were isolated from fecal specimens in 1989 and 1990 summer months.