Treatment with anabolic steroids increases the activity of the mitochondrial outer carnitine palmitoyltransferase in rat liver and fast-twitch muscle

Treatment of male rats with the anabolic steroids fluoxymesterone or methylandrostanolone increased the activity of the outer carnitine palmitoyltransferase in liver and fast-twitch muscle mitochondria. This effect was not potentiated by physical exercise and was not observed in heart and slow-twitch muscle mitochondria. Anabolic steroids did not affect the sensitivity of the liver enzyme to inhibition by malonyl-CoA. The data presented herein suggest that androgens may have an important physiological role in the regulation of fatty acid oxidation in liver and fast-twitch muscle mitochondria. In addition, our results are at odds with the notion that (most of) the metabolic effects of anabolic steroids on muscle are only evident when physical training is parallely performed.     

Stent placement in patients with acute subarachnoid haemorrhage: when is it justified?

Purpose

Endovascular stents are widely used for the elective treatment of cerebral aneurysms. Acute stenting is performed in the management of dissections, pseudo-aneurysms, broad-based aneurysms or as a ‘bail out’ measure after coil migration. The purpose of this study is to review the safety of using stents in acute subarachnoid haemorrhage.

Methods

The stent registry of our institution was reviewed for procedures in patients with acute subarachnoid haemorrhage. Imaging studies were reviewed on the hospital’s PACS system and the patients’ notes were retrieved to assess complications and clinical outcomes. Procedures were analysed according to the type of stent, treatment indication, antiplatelet regime, complications and outcomes.

Results

Between 2008 and 2016, 51 stents were placed during 50 stenting procedures in 49 patients with acute subarachnoid haemorrhage. This included 24 patients with saccular aneurysms, 10 with blister aneurysms, 10 dissections and five fusiform aneurysms. Stents were deployed in ‘bail out’ situations on eight occasions. In six cases, flow-diverting stents were used. Eighteen patients (37%) in the cohort suffered a stroke. Nine patients (18%) suffered persistent clinical deficits as a result of the stenting procedure, all but one of which occurred within 24 h. Two patients had a transient ischaemic episode, and there was evidence of asymptomatic ischaemia on imaging in four cases (8%). Five patients died, three (6%) as a result of procedural complications. Twelve patients (25%) required a further embolisation procedure.

Conclusion

The use of stents in acute subarachnoid haemorrhage incurs a considerable complication risk and should be reserved for exceptional circumstances.

     

Monitoring cerebral blood flow change through use of arterial spin labelling in acute ischaemic stroke patients after intra-arterial thrombectomy

Objectives

To evaluate the ability of arterial spin labelling perfusion-weighted imaging (ASL-PWI) to identify reperfusion status and to predict the early neurological outcome of acute ischaemic stroke patients after intra-arterial (IA) thrombectomy.

Methods

A total of 51 acute ischaemic stroke patients who underwent IA thrombectomy were retrospectively reviewed. Asymmetrical index before and after IA thrombectomy (AICBF_pre and AICBF_post) and volume ratio of the reperfused territory to the baseline perfusion abnormality (reperfusion volume ratio) were calculated on ASL-PWI. A paired t-test was used to compare AICBF_pre and AICBF_post. Pearson correlation and multiple linear regression were performed to evaluate correlations between the imaging parameters and NIHSS scores.

Results

Mean AICBF_post was significantly higher than mean AICBF_pre (0.923±0.352 vs. 0.312±0.191, p<0.001). AICBF_pre had a significant correlation with NIHSS_pre (pr=–0.430, p=.004). ?AICBF had significant correlations with NIHSS_{24 h}, NIHSS_{5-7 days} and ?NIHSS_{5-7 days} (r=–0.356, p=0.028; r=–0.597, p<0.001; r=–0.346, p=0.033, respectively). ?AICBF, reperfusion volume ratio and baseline infarct volume were significant independent predictors for NIHSS_{5-7 days}.

Conclusions

ASL-PWI has the potential to serve as a non-invasive imaging tool to monitor the reperfusion status and predict the early neurological outcome of acute ischaemic stroke patients after IA thrombectomy.

Key Points

? CBF change on ASL-PWI after IA thrombectomy correlated with NIHSS scores. ? ASL-PWI can non-invasively monitor reperfusion in AIS patients after IA thrombectomy. ? ASL-PWI may predict early outcome of AIS patients after IA thrombectomy.

     

Comparison between stimulated in-vitro fertilization and stimulated intrauterine insemination for the treatment of unexplained and mild male factor infertility

A prospective trial was undertaken to evaluate the efficacy of stimulated in-vitro fertilization (SIVF) and stimulated intrauterine insemination (SIUI) in couples with unexplained and mild male factor infertility. In all, 80 couples were allocated to treatment with SIVF or SIUI, both treatments following the same protocol [clomiphene citrate and follicle stimulating hormone (FSH) injection], except that higher doses of FSH were used in the SIVF treatment cycles. Initially, 41 couples were allocated to and started treatment with SIVF but eight cases were eventually converted to SIUI because of under-response. Similarly, although 39 couples were initially allocated to SIUI treatment, five of these converted to SIVF because of over-response. The treatment cycles that were converted either to SIUI or to SIVF were not considered as treatment failures but as treatment changes and so were included in the analyses. Of the final 38 SIVF cycles, four were cancelled (dysfunctional response), failed fertilization occurred in five cycles and 29 subjects reached embryo transfer. There were two biochemical pregnancies [positive human chorionic gonadotrophin (HCG) only], two clinical abortions and seven live births. Of the final 42 SIUI cycles, only two were cancelled, insemination being performed in the remaining 40 cases. The result was one clinical abortion, three ectopics and eight live births. The proportion of cycles with positive HCG was identical (28.9% per cycle treated for SIVF and 28.6% for SIUI) and the livebirth rates were also not different (18.4% per cycle treated for SIVF and 19.0% for SIUI). The cost per maternity of SIUI was approximately half that of SIVF (Pounds Sterling 1923 versus Pounds Sterling 4611) and so we conclude that, as SIUI had an efficacy that was not significantly different from SIVF (using similar protocols) but was more cost-effective, it must be considered the more appropriate form of management for the treatment of unexplained and mild male factor infertility. Indeed, it is hard to justify the routine use of IVF, as a first approach, in unexplained infertility.      

Cytokines and immuno-endocrine factors in recurrent miscarriage

Recurrent miscarriage remains an enigma. The main aetiologiesare endocrinological, immunological and unexplained. With thegrowth in molecular biology, it is now possible to look at theeffect of these aetiologies in more detail, allowing greaterunderstanding of the underlying pathogenesis. Keywords: cytokines/recurrent miscarriage     

Human alpha 1-antitrypsin therapy induces fatal anaphylaxis in non-obese diabetic mice

Previous studies have shown that human alpha-1 antitrypsin (hAAT) gene delivery prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. Furthermore, hAAT protein administration prolongs acceptance of islet allografts. Therefore, we evaluated the use of purified hAAT protein therapy to prevent T1D in NOD mice. Female NOD, non-obese resistant (NOR), Balb/c and C57BL/6 mice were injected intraperitoneally with vehicle alone or vehicle containing hAAT, human albumin or mouse albumin (or mg/injection/mouse; 2x/week). Preparations of clinical-grade hAAT included API(R), Aralast, Prolastin and Zemaira. Surprisingly, hAAT administration was associated with a high rate of fatal anaphylaxis. In studies seeking T1D prevention at 4 weeks of age, 100% mice died after six injections of hAAT. When administrated at 8-10 weeks of age, most (80-100%) NOD mice died following the fourth injection of hAAT, while 0% of Balb/c and C57BL/6 mice and 10% of NOR mice died. Interestingly, repeated injections of human albumin, but not mouse albumin, also induced sudden death in NOD mice. Antibodies to hAAT were induced 2-3 weeks after hAAT administration and death was prevented by treatment with anti-platelet-activating factor along with anti-histamine. In studies of disease reversal in NOD mice, using the four pharmaceutical grade formulations of hAAT, anaphylactic deaths were observed with all hAAT preparations. The propensity for fatal anaphylaxis following antigenic administration appears to be NOD- but not hAAT-specific. The susceptibility of NOD mice to hypersensitivity provides a significant limitation for testing of hAAT. Development of strategies to avoid this unwanted response is required to use this promising therapeutic agent for T1D.     

Sexual behavior, condom use, and human papillomavirus: pooled analysis of the IARC human papillomavirus prevalence surveys.

Human papillomavirus (HPV) is a sexually transmitted infection but it is unclear whether differences in transmission efficacy exist between individual HPV types. Information on sexual behavior was collected from 11 areas in four continents among population-based, age-stratified random samples of women of ages > or = 15 years. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) of being HPV positive and corresponding 95% confidence intervals (95% CI). Variables were analyzed categorically. When more than two groups were compared, floating confidence intervals were estimated by treating ORs as floating absolute risks. A total of 11,337 women (mean age, 41.9 years) were available. We confirmed that lifetime number of sexual partners is associated with HPV positivity (OR for > or = 2 versus 1, 1.86; 95% CI, 1.63-2.11) but the association was not a linear one for HPV18, 31, and 33 (i.e., no clear increase for > or = 3 versus 2 sexual partners). Women who had multiple-type infection and high-risk HPV type infection reported a statistically nonsignificant higher number of sexual partners than women who had single-type and low-risk type infections, respectively. Early age at sexual debut was not significantly related to HPV positivity. Husband's extramarital sexual relationships were associated with an OR of 1.45 (95% CI, 1.24-1.70) for HPV positivity in their wives after adjustment for age and lifetime number of women's sexual partners. We did not observe a significant association with condom use. Our study showed an effect of both women's and their husbands' sexual behavior on HPV positivity. Furthermore, it suggests some differences in the pattern of the association between sexual behavior and different HPV types.     

Classrooms in Peace Within Violent Contexts: Field Evaluation of <Emphasis Type="Italic">Aulas en Paz</Emphasis> in Colombia

Classrooms in Peace (Aulas en Paz) is an elementary school-based multicomponent program for prevention of aggression and promotion of peaceful relationships. Inspired by international programs and socio-emotional research, it includes (1) a classroom universal curriculum, (2) parent workshops and home visits to parents of the 10% most aggressive children, and (3) extracurricular peer groups of two aggressive and four prosocial children. Activities seek to promote socio-emotional competencies such as empathy, anger management, creative generation of alternatives, and assertiveness. A 2-year quasi-experimental evaluation was conducted with 1154 students from 55 classrooms of seven public schools located in neighborhoods with the presence of youth gangs, drug cartels, and high levels of community violence in two Colombian cities. Despite several implementation (e.g., about half of the activities were not implemented) and evaluation (e.g., randomization problems, large number of missing data, and changes between treatment and control groups) challenges, positive results were found in prosocial behavior and in reduction of aggressive behavior, according to teacher reports, and in assertiveness and reduction of verbal victimization, according to student reports. Furthermore, implementation cost (25 US dollars per student per year) was very low compared to other programs in developed countries. This study shows that the Classrooms in Peace program has an important potential to generate positive results and highlights the challenges of implementing and evaluating prevention programs in highly violent environments.