Schizophrenic patients' attitudes to therapists using behavioral and holistic-humanistic techniques

In a preliminary study of patients' perceptions of therapists' styles, 18 subjects with diagnoses of schizophrenia were randomly assigned either to social skills training or holistic health therapy. Four therapists conducted each treatment session in pairs, rotating between treatment conditions daily. At the end of 10 weeks of treatment, patients were able to discriminate among therapists on three interactional styles-"understanding," "independence-encouraging," and "and "critical-hostile"-and were able to differentiate between behavioral and holistic health treatments on "authoritarian" attitudes.     

Natural genetic variation caused by small insertions and deletions in the human genome

Human genetic variation is expected to play a central role in personalized medicine. Yet only a fraction of the natural genetic variation that is harbored by humans has been discovered to date. Here we report almost 2 million small insertions and deletions (INDELs) that range from 1 bp to 10,000 bp in length in the genomes of 79 diverse humans. These variants include 819,363 small INDELs that map to human genes. Small INDELs frequently were found in the coding exons of these genes, and several lines of evidence indicate that such variation is a major determinant of human biological diversity. Microarray-based genotyping experiments revealed several interesting observations regarding the population genetics of small INDEL variation. For example, we found that many of our INDELs had high levels of linkage disequilibrium (LD) with both HapMap SNPs and with high-scoring SNPs from genome-wide association studies. Overall, our study indicates that small INDEL variation is likely to be a key factor underlying inherited traits and diseases in humans.     

Body Composition Alterations,Energy Expenditure and Fat Oxidation in Elderly Males Suffering from Prostate Cancer,Pre and Post Orchiectomy

INTRODUCTION

Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects.

OBJECTIVE

This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer.

PATIENTS AND METHODS

A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63–96; median age 71) with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry.

RESULTS

Body weight (p=0.01), lean mass (p=0.004), and lipid oxidation (p=0.001) decreased significantly. Carbohydrate oxidation (p=0.02), FSH (p=0.0001) and LH (p=0.0001) levels increased significantly. Changes in fat mass (p=0.06) and bone mineral density (p=0.48) were not significant.

CONCLUSIONS

After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.     

A new role for the cellular PABP repressor Paip2 as an innate restriction factor capable of limiting productive cytomegalovirus replication

The capacity of polyadenylate-binding protein PABPC1 (PABP1) to stimulate translation is regulated by its repressor, Paip2. Paradoxically, while PABP accumulation promotes human cytomegalovirus (HCMV) protein synthesis, we show that this is accompanied by an analogous increase in the abundance of Paip2 and EDD1, an E3 ubiquitin ligase that destabilizes Paip2. Coordinate control of PABP1, Paip2, and EDD1 required the virus-encoded UL38 mTORC1 activator and resulted in augmented Paip2 synthesis, stability, and association with PABP1. Paip2 synthesis also increased following serum stimulation of uninfected normal fibroblasts, suggesting that this coregulation may play a role in how uninfected cells respond to stress. Significantly, Paip2 accumulation was dependent on PABP accrual, as preventing PABP1 accumulation suppressed viral replication and inhibited the corresponding Paip2 increase. Furthermore, depleting Paip2 restored the ability of infected cells to assemble the translation initiation factor eIF4F, promoting viral protein synthesis and replication without increasing PABP1. This establishes a new role for the cellular PABP1 inhibitor Paip2 as an innate defense that restricts viral protein synthesis and replication. Moreover, it illustrates how a stress-induced rise in PABP1 triggered by virus infection can counter and surpass a corresponding increase in Paip2 abundance and stability.     

Stankiewicz-Isidor syndrome: expanding the clinical and molecular phenotype

PurposeHaploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS.MethodsWe report 24 additional unrelated patients with STISS with various truncating single nucleotide variants or copy-number variant deletions involving PSMD12. We explore disease etiology by assessing patient cells and CRISPR/Cas9-engineered cell clones for various cellular pathways and inflammatory status.ResultsThe expressivity of most clinical features in STISS is highly variable. In addition to previously reported DD/ID, speech delay, cardiac and renal anomalies, we also confirmed preaxial hand abnormalities as a feature of this syndrome. Of note, 2 patients also showed chilblains resembling signs observed in interferonopathy. Remarkably, our data show that STISS patient cells exhibit a profound remodeling of the mTORC1 and mitophagy pathways with an induction of type I interferon-stimulated genes.ConclusionWe refine the phenotype of STISS and show that it can be clinically recognizable and biochemically diagnosed by a type I interferon gene signature.     

Premature adrenarche

Premature adrenarche refers to the presence of secondary sexual hair in girls younger than 8 years old and boys younger than 9 years old. It is a relatively common presentation to paediatricians and is more frequent in girls than boys. It is a benign diagnosis, but other causes of androgen excess such as congenital adrenal hyperplasia or adrenal tumours should be excluded first. In conjunction with history and clinical examination, first line investigations should include determination of serum androgen concentrations, along with bone age, proceeding to synacthen stimulation test (for 17OHP levels) and adrenal ultrasound if indicated. The phenotype of premature adrenarche varies considerably between populations but may be associated with low birth weight, insulin resistance, adverse cardio-metabolic risk and progression to polycystic ovarian syndrome in some populations. In the majority of cases, no specific treatment is recommended, but where there is a history of low birth weight, with associated insulin resistance, intervention with the insulin sensitising agent metformin may be considered on a case by case basis.     

Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment

We determined whether oxidative stress is an early event in the pathogenesis of sporadic Alzheimer disease (AD), and correlated oxidative stress with neuropsychological functions and neurofibrillary pathology in AD and mild cognitive impairment (MCI). Oxidative stress was measured as the percentage of astrocytes expressing heme oxygenase-1 (HO-1) in post mortem temporal cortex and hippocampus after dual HO-1/glial fibrillary acidic protein (GFAP) immunohistochemistry. Glial HO-1 expression in the MCI temporal cortex and hippocampus was significantly greater than in the non-demented group and did not differ from AD values. Astroglial HO-1 expression in the temporal cortex was associated with decreased scores for global cognition, episodic memory, semantic memory and working memory. Hippocampal astroglial HO-1 expression was associated with lower scores for global cognition, semantic memory and perceptual speed. Glial HO-1 immunoreactivity in the temporal cortex, but not hippocampus, correlated with the burden of neurofibrillary pathology. Cortical and hippocampal oxidative stress is a very early event in the pathogenesis of sporadic AD and correlates with the development of specific cognitive deficits in this condition.     

The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewater

Aims   To determine the utility of community-wide drug testing with wastewater samples as a population measure of community drug use and to test the hypothesis that the association with urbanicity would vary for three different stimulant drugs of abuse.
Design and participants   Single-day samples were obtained from a convenience sample of 96 municipalities representing 65% of the population of the State of Oregon.
Measurements   Chemical analysis of 24-hour composite influent samples for benzoylecgonine (BZE, a cocaine metabolite), methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). The distribution of community index drug loads accounting for total wastewater flow (i.e. dilution) and population are reported.
Findings   The distribution of wastewater-derived drug index loads was found to correspond with expected epidemiological drug patterns. Index loads of BZE were significantly higher in urban areas and below detection in many rural areas. Conversely, methamphetamine was present in all municipalities, with no significant differences in index loads by urbanicity. MDMA was at quantifiable levels in fewer than half the communities, with a significant trend towards higher index loads in more urban areas.
Conclusion   This demonstration provides the first evidence of the utility of wastewater-derived community drug loads for spatial analyses. Such data have the potential to improve dramatically the measurement of the true level and distribution of a range of drugs. Drug index load data provide information for all people in a community and are potentially applicable to a much larger proportion of the total population than existing measures.     

Enteroviral meningitis in neonates

We present 4 neonates with enteroviral meningitis. The cerebrospinal fluid findings were variable and posed a diagnostic problem. Immediate outcome was excellent and 3 of the 4 infants were normal at follow-up at 6 months of age. However long-term follow-up will be necessary to to determine any long-term sequelae.     

Chronic cochlear de-efferentation and susceptibility to permanent acoustic injury

The question of whether olivocochlear (OC) efferent feedback can decrease permanent damage from acoustic overexposure was investigated by comparing the chronic threshold shifts and cochlear histopathology in guinea pigs either surgically de-efferented or sham-operated and then exposed (awake and unrestrained) to a 109- or 112-dB narrow-band noise centered at 10 kHz for 2 h. Threshold shifts were estimated using compound action potentials; hair cell loss and stereocilia condition were evaluated via light-microscopic examination of plastic-embedded surface preparations, and the degree of de-efferentation was assessed by measuring OC fascicles in the tunnel of Corti. Among animals exposed to 109-dB noise, the mean permanent threshold shift (PTS) was less than 25 dB, and there were no significant differences between normal and de-efferented animals with respect to either physiological or histological measures of acoustic injury. Among animals exposed to 112 dB, the mean peak PTS was roughly 50 dB. There was a small (but statistically significant) increase in PTS for de-efferented animals, especially at frequencies above the region of peak threshold shift; however, the patterns of hair cell loss and stereocilia damage were statistically indistinguishable. Thus, for these particular exposure conditions, sound-evoked activity in the OC system does not play a major protective role in the auditory periphery, except perhaps for the extreme basal regions of the cochlea.