Effects of Androgen Treatment on the Male Rat Aorta

Androgen was given to male rats to determine if it exerted effects on the aortic wall distinct from those of estrogen deficit. Although a general anabolic effect was avoided, significant vascular effects were observed. The amounts of mural fibrous proteins, elastin and collagen, were significantly increased in treated animals; noncollagenous, alkali-soluble protein, thought to reflect the cellular component, was unchanged with treatment. These effects were not detectable on microscopic examination and measurement of the vessel wall despite attempts to duplicate closely in vivo wall dimensions before study. These findings of distinct and marked effects of androgen on vascular metabolism extend the growing evidence for an important role of sex hormones in vessel wall structure and function.     

Risk factors for non-haemorrhagic stroke in patients with coronary heart disease and the effect of lipid-modifying therapy with pravastatin

OBJECTIVE: To determine the relative importance of recognised risk factors for non-haemorrhagic stroke, including serum cholesterol and the effect of cholesterol-lowering therapy, on the occurrence of non-haemorrhagic stroke in patients enrolled in the LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease) study. DESIGN: The LIPID study was a placebo-controlled, double-blind trial of the efficacy on coronary heart disease mortality of pravastatin therapy over 6 years in 9014 patients with previous acute coronary syndromes and baseline total cholesterol of 4-7 mmol/l. Following identification of patients who had suffered non-haemorrhagic stroke, a pre-specified secondary end point, multivariate Cox regression was used to determine risk in the total population. Time-to-event analysis was used to determine the effect of pravastatin therapy on the rate of non-haemorrhagic stroke. RESULTS: There were 388 non-haemorrhagic strokes in 350 patients. Factors conferring risk of future non-haemorrhagic stroke were age, atrial fibrillation, prior stroke, diabetes, hypertension, systolic blood pressure, cigarette smoking, body mass index, male sex and creatinine clearance. Baseline lipids did not predict non-haemorrhagic stroke. Treatment with pravastatin reduced non-haemorrhagic stroke by 23% (P = 0.016) when considered alone, and 21% (P = 0.024) after adjustment for other risk factors. CONCLUSIONS: The study confirmed the variety of risk factors for non-haemorrhagic stroke. From the risk predictors, a simple prognostic index was created for non-haemorrhagic stroke to identify a group of patients at high risk. Treatment with pravastatin resulted in significant additional benefit after allowance for risk factors.     

Mental health carers’ experiences of an Australian Carer Peer Support program: Tailoring supports to carers’ needs

Carer Peer Support Workers (CPSWs) are people who have lived experience as carers/family members of persons with a mental illness, and are employed to provide support to other carers/family members. This qualitative study aimed to explore carers’ experiences within a community‐based CPSW pilot program in an Australian mental health service. Semi‐structured phone interviews were conducted with 20 carer participants in 2015, 5–10 months following their last contact with the service. Thematic analysis uncovered that carers were generally positive about the CPSW's emotional support, practical support, shared lived experience and mutual understanding, and the “ripple effect” the support had on service users. Some carers, on the other hand, felt that the support was unnecessary; either because they believed that it did not have a lasting effect, the focus should have been on the service user, or that they had previously received enough support. Nevertheless, the study highlighted how mental health services could best utilise and benefit from CPSWs. Moreover, to be most useful, the nature of the carer peer support work should be tailored to the specific needs of the carers; which may vary according to their culture, years of caring experience, and previous experiences with mental health services.     

Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action

Benzimidazole nucleosides have been shown to be potent inhibitors of human cytomegalovirus (HCMV) replication in vitro. As part of the exploration of structure-activity relationships within this series, we synthesized the 2-isopropylamino derivative (3322W93) of 1H-beta-D-ribofuranoside-2-bromo-5,6-dichlorobenzimidazole (BDCRB) and the biologically unnatural L-sugars corresponding to both compounds. One of the L derivatives, 1H-beta-L-ribofuranoside-2-isopropylamino-5,6-dichlorobenzimidazole (1263W94), showed significant antiviral potency in vitro against both laboratory HCMV strains and clinical HCMV isolates, including those resistant to ganciclovir (GCV), foscarnet, and BDCRB. 1263W94 inhibited viral replication in a dose-dependent manner, with a mean 50% inhibitory concentration (IC(50)) of 0.12 +/- 0.01 microM compared to a mean IC(50) for GCV of 0.53 +/- 0.04 microM, as measured by a multicycle DNA hybridization assay. In a single replication cycle, 1263W94 treatment reduced viral DNA synthesis, as well as overall virus yield. HCMV mutants resistant to 1263W94 were isolated, establishing that the target of 1263W94 was a viral gene product. The resistance mutation was mapped to the UL97 open reading frame. The pUL97 protein kinase was strongly inhibited by 1263W94, with 50% inhibition occurring at 3 nM. Although HCMV DNA synthesis was inhibited by 1263W94, the inhibition was not mediated by the inhibition of viral DNA polymerase. The parent benzimidazole D-riboside BDCRB inhibits viral DNA maturation and processing, whereas 1263W94 does not. The mechanism of the antiviral effect of L-riboside 1263W94 is thus distinct from those of GCV and of BDCRB. In summary, 1263W94 inhibits viral replication by a novel mechanism that is not yet completely understood.     

A word-recognition task in multitalker babble using a descending presentation mode from 24 dB to 0 dB signal to babble

A speech-in-multitalker-babble test instrument was developed for use in a Department of Veterans Affairs (VA) multicenter study examining the effects of hearing loss on self-perceived quality of life. Word recognition in quiet and in multitalker babble was measured on 24 listeners with normal hearing and 24 listeners with sensorineural hearing loss. The protocol involved the presentation of 10 monosyllabic words (each in a unique babble segment) at each of seven signal-to-babble (S/B) ratios from 24 dB to 0 dB, with the babble fixed at 60 dB HL (hearing loss). Word recognition in quiet at 60 dB and 80 dB HL for both groups was >90% correct. Two trials on the task were conducted. In babble, the 50% correct points were at 4.1 dB and 9.4 dB S/B for the listeners with normal hearing and hearing loss, respectively, with the 90th percentile for the listeners with normal hearing at 6 dB S/B. Twenty-two of the twenty-four listeners with hearing loss had 50% correct points outside of the 90th percentile for listeners with normal hearing. Test-retest reliability was excellent.