Like father like daughter: sex-specific parent-of-origin effects in the transmission of liability for psychotic symptoms to offspring.

Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8-24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43-4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61-2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.

Dolutegravir: clinical and laboratory safety in integrase inhibitor-naive patients.

BACKGROUND: The efficacy of dolutegravir (DTG) has been demonstrated in 5 randomized studies in integrase inhibitor (INI)-naive adult populations. To date, a detailed safety review of DTG has not been provided in the literature. OBJECTIVE: To describe the safety and tolerability profile of DTG in adults based on 5 randomized, controlled trials and comparison with drugs in 3 major antiretroviral (ARV) classes. METHODS: Safety data from phase IIb/III/IIIb trials in ART-naive and ART-experienced, INI-naive adults were integrated. RESULTS: In 4 ART-naive (SPRING-1, SPRING-2, SINGLE, FLAMINGO) and 1 ART-experienced, INI-naive study (SAILING), 1,579 individuals received a DTG-containing regimen. The proportion of individuals from DTG treatment arms who withdrew due to adverse events (AEs) was low (≤2%) compared to raltegravir (RAL; 2% SPRING-2, 4% SAILING), efavirenz (EFV)-containing comparator arm (10% SINGLE), and darunavir + ritonavir (DRV/r; 4% FLAMINGO). The most frequently observed AEs (diarrhea, nausea, headache), typically grade 1 or 2 in severity, did not lead to study discontinuation. Psychiatric and nervous system disorders with DTG were comparable to RAL- and DRV/r-containing regimens and favorable to EFV-containing regimens. In hepatitis B and/or C coinfected ART-naive individuals, the incidence of transaminase elevations was lower with DTG versus RAL and EFV comparators, but was similar to DRV/r. In SAILING, transaminase elevations were more commonly observed with DTG, particularly in the setting of inadequate hepatitis B therapy or immune reconstitution. On DTG treatment, mild creatinine elevations occurred and stabilized early. Few cases of hypersensitivity reaction and/or severe rash were seen. Rates of these events were comparable to or lower than with RAL-, EFV-, and DRV/r-containing regimens. CONCLUSIONS: The safety profile for DTG 50 mg once daily in INI-naive individuals was comparable to RAL- and DRV/r-containing regimens and generally favorable compared with EFV-containing regimens.

Carbohydrate residues in non-malignant prostatic epithelium as revealed by lectins.

Non-neoplastic prostatic epithelium from 39 patients obtained at transurethral resection for outflow tract obstruction and 5 normal prostates from men under 35 years of age obtained at postmortem were formalin-fixed and paraffin-embedded. The distribution of 8 lectin receptors were studied using a peroxidase anti-peroxidase method and an avidin-biotin method. Con A, WGA, and PNA bound to most epithelial cells. Con A and WGA also showed major stromal binding. Approximately 5% to 10% of cells bound UEA1, GS1, DBA, SBA and BPA. No major differences in lectin receptor expression were observed between normal and hyperplastic epithelium with either of the immunohistochemical techniques except that hyperplastic cells stained more strongly than normal epithelium.

Comparison of weight, depth, and diagnostic adequacy of specimens obtained with 16 different biopsy forceps designed for upper gastrointestinal endoscopy.

The influence of endoscopic forceps variables (size, design, and make) on biopsy specimen weight, depth, and diagnostic adequacy has been studied in vitro on normal human stomach, and in vivo at endoscopy in dog and in patients. Greater pressure during the biopsy procedure yielded significantly heavier, deeper, and histologically more acceptable specimens. Standard sized forceps (diameter 2.4 mm) and those with ellipsoid cups consistently produced larger specimens than the smaller 'paediatric' forceps (1.8 mm) and those with round cups. Deeper specimens were also obtained using the standard forceps. In vitro and in vivo in the dog, the standard sized forceps also produced specimens of greater diagnostic adequacy than the paediatric forceps. At endoscopy in patients, however, we could not detect any influence of the size, shape, and presence of forceps spike or fenestration on the diagnostic adequacy of the specimens.