Assembly of mixed rod-like and spherical particles from group I and II RNA bacteriophage coat proteins

The capsids of single-stranded RNA bacteriophages show remarkable structural similarity. In an attempt to test whether the coat protein (CP) from one bacteriophage could substitute for the CP of another and form mixed particles, we reassembled capsids in vitro from a mixture of different RNA phage CP dimers together with E. coli ribosomal RNA. Surprisingly, mixing CPs from phages belonging to groups I and II led to appearance of rod-like particles along with icosahedral spherical capsids, both containing a mixture of the two CPs. Rods and mixed spherical capsids containing host RNA were also obtained in vivo in bacteria expressing simultaneously fr and GA CPs. In a co-infection of the two phages, however, only authentic fr and GA virions were formed. Coat protein mutants in the FG loop were unable to assemble into rods, suggesting that these loops are involved in the formation of the aberrant particles.     

Serenoa repens monotherapy for benign prostatic hyperplasia (BPH): an updated Cochrane systematic review

What's known on the subject? and What does the study add? For the past 30 years Serenoa repens has become a widely used phytotherapy in the USA and in Europe, mostly because of positive comparisons to α‐blockers and 5α‐reductase inhibitors. During the last 4 years we have seen two very high quality trials comparing Serenoa repens to placebo and up to 72 weeks' duration. These trials found Serenoa repens no better than placebo, even (in one trial) at escalating doses.

OBJECTIVE

• ? To estimate the effectiveness and harms of Serenoa repens monotherapy in the treatment of lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS

• ? We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and other sources through to January 2012 to identify randomised trials.
• ? Trials were eligible if they randomised men with symptomatic BPH to receive Serenoa repens extract monotherapy for at least 4 weeks in comparison with placebo, and assessed clinical outcomes and urodynamic measurements.
• ? Our primary outcome was improvement in LUTS, based on change in urological symptom‐scale scores.

RESULTS

• ? In all, 17 randomised controlled trials (N= 2008) assessing Serenoa repens monotherapy (typically 320 mg/day) vs placebo met inclusion criteria, although only five reported American Urological Association Symptom Index (AUASI) or International Prostate Symptom Scores (IPSS). Trial lengths ranged from 4 to 72 weeks. The mean age of all enrolees was 64.3 years and most participants were of White race. The mean baseline total score was 14 points, indicating moderately severe symptoms. In all, 16 trials were double blinded and adequate treatment allocation concealment was reported in six trials.
• ? In a meta‐analysis of three high quality long‐to‐moderate term trials (n= 661), Serenoa repens therapy was no better than placebo in reducing LUTS based on the AUASI/IPSS (weighted mean difference [WMD]?0.16 points, 95% confidence interval [CI]–1.45 to 1.14) or maximum urinary flow rate (Q_max; WMD 0.40 mL/s, 95% CI ?0.30 to 1.09). Based on mostly short‐term studies, Q_max measured at study endpoint were also not significantly different between treatment groups (WMD 1.15 mL/s, 95% CI ?0.23 to 2.53) with evidence of substantial heterogeneity (I² 58%).
• ? One long‐term dose escalation trial (72 weeks) found double and triple doses of Serenoa repens extract did not improve AUASI compared with placebo and the proportions of clinical responders (≥3 point decrease in the AUASI) were nearly identical (43% vs 44% for Serenoa repens and placebo, respectively) with a corresponding risk ratio of 0.96 (95% CI 0.76–1.22).
• ? Long‐term, Serenoa repens therapy was no better than placebo in improving nocturia in one high‐quality study (P= 0.19). Pooled analysis of nine short‐term Permixon® trials showed a reduction in the frequency of nocturia (WMD ?0.79 times/night, 95% CI–1.28 to ?0.29), although there was evidence of heterogeneity (I² 76%)
• ? Adverse events of Serenoa repens extracts were few and mild, and incidences were not statistically significantly different vs placebo. Study withdrawals occurred in ≈10% and did not differ between Serenoa repens and placebo.

CONCLUSIONS

• ? Serenoa repens therapy does not improve LUTS or Q_max compared with placebo in men with BPH, even at double and triple the usual dose.
• ? Adverse events were generally mild and comparable to placebo.

     

Sildenafil for male erectile dysfunction: a systematic review and meta-analysis

OBJECTIVE: To determine the efficacy and safety of sildenafil citrate in the treatment of male erectile dysfunction. DATA SOURCES: The MEDLINE, HealthSTAR, Current Contents, and Cochrane Library databases (January 1, 1995, through December 31, 2000); bibliographies of retrieved articles and review articles; conference proceedings abstracts; the Food and Drug Administration Web site; and the manufacturer. STUDY SELECTION: Trials were eligible if they included men with erectile dysfunction, compared sildenafil with control, were randomized, were of at least 7 days' duration, and assessed clinically relevant outcomes. DATA EXTRACTION: Two reviewers independently evaluated study quality and extracted data in a standardized fashion. DATA SYNTHESIS: Twenty-seven trials (6659 men) met the inclusion criteria. In results pooled from 14 parallel-group, flexible as-needed dosing trials, sildenafil was more likely than placebo to lead to successful sexual intercourse, with a higher percentage of successful intercourse attempts (57% vs 21%; weighted mean difference, 33.7; 95% confidence interval [CI], 29.2-38.2; 2283 men) and a greater percentage of men experiencing at least 1 intercourse success during treatment (83% vs 45%; relative benefit increase, 1.8; 95% CI, 1.7-1.9; 2205 men). In data pooled from 6 parallel-group, fixed-dose trials, efficacy appeared slightly greater at higher doses. Treatment response appeared to vary between patient subgroups, although relative to placebo, sildenafil significantly improved erectile function in all evaluated subgroups. In trials with parallel-group design and flexible dosing, men randomized to receive sildenafil were less likely than those receiving placebo to drop out for any reason and no more likely to drop out due to an adverse event or laboratory abnormality. Specific adverse events with sildenafil included flushing (12%), headache (11%), dyspepsia (5%), and visual disturbances (3%); all adverse events were significantly less likely to occur with placebo. Sildenafil was not significantly associated with serious cardiovascular events or death. CONCLUSIONS: Sildenafil improves erectile function and is generally well tolerated. Treatment response seems to vary between patient subgroups, although sildenafil has greater efficacy than placebo in all evaluated subgroups.     

Couple and family involvement in adult mental health treatment: A systematic review

We reviewed randomized controlled trials conducted in the United States from January, 1996 through December, 2011 that examined family interventions for adult mental health conditions. We identified 51 articles (39 trials) evaluating 21 different family interventions. Findings for behavioral couple or family therapy (BCT/BFT) and community reinforcement and training (CRAFT) for substance use disorders were each pooled separately for examination in meta-analyses. Findings suggest BCT/BFT reduced substance use (small-to-moderate effects) and improved relationship adjustment (large effects) compared to individually-oriented treatments. CRAFT increased treatment initiation three-fold but did not improve substance use or family functioning over alternative family interventions. Family focused therapy for bipolar disorder improved symptoms over less intensive treatments with mixed findings when compared to equally intensive treatments. For both bipolar disorder and schizophrenia spectrum disorders, the few trials meeting our search criteria and heterogeneity among trials precluded generating broader conclusions regarding which family interventions are most effective for US populations. Overall, trials were limited in their methodological quality, and many interventions were evaluated in one trial. Future research is needed to replicate findings for these single trials, examine relationship distress as a moderator of outcome, and examine BCT/BFT among dual substance using couples and outside the research group frequently represented.