Explore the vast range of titles available.

Simplified treatment regimens for HIV-1 may have advantages. In this open-label, randomized, controlled trial, patients with HIV-1 infection who had not previously received antiretroviral therapy were given oral induction therapy, then treated with either monthly injections of long-acting cabotegravir and rilpivirine or standard treatment. At 48 weeks, similar viral suppression was observed with the two regimens.

Simplified treatment regimens for HIV management may increase adherence. In this open-label, randomized, controlled trial, longer-acting (monthly) injectable cabotegravir plus rilpivirine was compared with standard oral treatment. At 48 weeks, similar viral suppression was seen with the two regimens.

The need for new therapies to treat multidrug-resistant (MDR) tuberculosis is great. The new compound TMC207, a diarylquinoline that inhibits mycobacterial ATP synthase, shows promising activity against MDR tuberculosis. In this study involving 47 patients, the administration of TMC207, as compared with placebo, resulted in a shorter time to sputum-culture conversion and a significant increase in the proportion of patients achieving culture conversion to negative. The new compound TMC207, a diarylquinoline that inhibits mycobacterial ATP synthase, shows promising activity against MDR tuberculosis. In this study, the administration of TMC207 resulted in a shorter time to sputum-culture conversion and a significant increase in the proportion of patients achieving culture conversion to negative. Tuberculosis is a leading cause of death from infectious disease, second only to human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). 1 In 2006, there were 9.2 million new cases of tuberculosis and 1.7 million deaths, with the burden of the disease occurring predominantly in the developing world. 2 It is estimated that one third of the world's population is infected with latent Mycobacterium tuberculosis, providing an enormous reservoir for future disease. 3 Treatment of tuberculosis is protracted and burdensome. 4 Tuberculosis control is further complicated by the synergy between tuberculosis and HIV/AIDS and by the emergence of multidrug-resistant strains of M. tuberculosis . . . .

Objective Biometric identification techniques for pediatric use are limited. This investigation studied iris scanning in minors aged 1–4 in two exploratory studies in Belgium (n = 197) and Sierra Leone (n = 230), and in a subsequent clinical study in Sierra Leone (n = 635). Images of participants’ irises were captured using a camera, while a survey assessed the ease of use with children. Results The image capture success rate per individual was high; 86.0% of the participants had ≥ 2 successful captures. Iris scan quality and surface were similar in all age groups and in the matching population database. When including feasibility in the analysis of minors aged 3–4, sensitivity and specificity were non-inferior compared to using the biometric of a guardian. However, the quality of iris scanning in minors aged 1–4 was worse than the iris scanning reference quality in adults. A mean total usability score of 1.55 ± 0.27 was calculated; a usability threshold of 1.45 is required for routine use. Overall, this technique is feasible in minors aged 3–4, replacing the use of guardian biometrics. Additional work is ongoing to improve this technique further, striving for uniformity from the age of 1.

Preventing HIV-1 infection, especially with female-controlled approaches, is a high priority. In this trial in South Africa and Uganda, a dapivirine vaginal ring was associated with a rate of acquisition of HIV-1 infection that was approximately 30% lower than that with placebo. In 2014, approximately 36.9 million people worldwide were living with human immunodeficiency virus (HIV) infection. 1 Rates of new HIV infection among adolescent girls and young women remain high in Eastern and Southern Africa, 2 which underscores the need for the development of safe and effective tools against HIV infection that women initiate themselves. 3 – 5 Self-inserted vaginal rings, which provide a sustained release of antiretroviral drugs over time, have the potential to offer women a prevention option that does not require daily or pericoital use. 6 The International Partnership for Microbicides (IPM) developed a monthly self-administered vaginal ring that contains the nonnucleoside reverse-transcriptase . . .

Apolipoprotein E (APOE) has been extensively demonstrated to be a genetic risk factor for Alzheimer’s disease (AD). Associations of APOE genotype have been reported with age at AD onset, rate of decline, and responsiveness to therapy. This study aimed to test these hypotheses in a large study population of AD patients. APOE genotype was determined from 1,528 Caucasian subjects, diagnosed by NINCDS/ADRDA criteria as probable AD patients, enrolled in four international placebo-controlled clinical trials of 3–12 months duration, designed to evaluate efficacy of treatment with galantamine or sabeluzole. In addition to patient demographics and baseline scores for Mini Mental State Examination, scores on the Disability Assessment for Dementia (DAD) and the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) were recorded at the start, during, and at the end of the study. APOE Ε4 homozygotes had a significantly lower age at disease onset compared to patients with other APOE genotypes. The Ε4 allele was significantly over-represented in females compared to males, and in the group of subjects with an AD family history. Based on longitudinal data of 504 placebo-treated AD patients, the linear annual rate of change in score was 5 points on the ADAS-cog scale and 11 on the DAD scale. The Ε4 allele copy number did not influence these rates of decline. Sabeluzole treatment was not effective in the overall group compared to the placebo-treated group, nor in any subgroup stratified by Ε4 allele count. Galantamine produced cognitive and functional improvement that were not affected by Ε4 allele count. In conclusion, our data confirm a strong association between Ε4 homozygotes and age at onset of AD but do not support an effect of Ε4 allele copy number on rate of cognitive and functional decline nor on the efficacy of galantamine in patients with AD.

Galantamine, a novel treatment for Alzheimer’s disease (AD), has a dual mechanism of action, combining allosteric modulation of nicotinic acetylcholine receptors with reversible, competitive inhibition of acetylcholinesterase. In the Phase III clinical trial programme, over 3,000 patients with mild-to-moderate AD were enrolled in one of five randomized, controlled, double-blind studies. Using the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) to assess memory and other cognitive functions, galantamine was found to be significantly superior to placebo in all five studies at doses of 16, 24 and 32 mg/day. In all studies, galantamine-treated patients maintained their cognitive function, whereas the placebo-treated patients experienced a significant deterioration in ADAS-cog scores. The 32-mg/day dose was not associated with any additional cognitive benefit. Pooled data from two 6-month studies (n = 1,269), which were of identical design, show that the therapeutic benefits of galantamine are sustained for the duration of treatment. The treatment effect (galantamine-placebo difference on ADAS-cog) for the pooled data was approximately 4 points. Clinical benefit was seen in all levels of disease severity, with a 7-point advantage over placebo on ADAS-cog for patients with moderately severe disease. Galantamine was well tolerated, with most patients completing the 6-month studies. The long-term effects of galantamine have been evaluated in a 12-month study. Patients who completed one of the pivotal 6-month studies (n = 353) were entered into a 6-month open-label extension. Cognitive and daily function were maintained throughout the 12 months in patients who received galantamine 24 mg/day. This sustained level of benefit may reflect galantamine’s dual effect on the cholinergic system. Data from a 5-month, placebo-controlled study have also shown that galantamine produces significant benefits on behavioural symptoms. The persistence and range of therapeutic effects produced by galantamine suggest that it may provide additional benefits for patients with AD.

The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1,4,5-trisphosphate receptor (IP3R), the primary Ca(2+)-release channel in the endoplasmic reticulum (ER). Bcl-2 can thereby reduce pro-apoptotic IP3R-mediated Ca(2+) release from the ER. Moreover, the Bcl-2 homology domain 4 (Bcl-2-BH4) has been identified as essential and sufficient for this IP3R-mediated anti-apoptotic activity. In the present study, we investigated whether the reported inhibitory effect of a Bcl-2-BH4 peptide on the IP 3R1 was related to the distinctive α-helical conformation of the BH4 domain peptide. We therefore designed a peptide with two glycine \"hinges\" replacing residues I14 and V15, of the wild-type Bcl-2-BH4 domain (Bcl-2-BH4-IV/GG). By comparing the structural and functional properties of the Bcl-2-BH4-IV/GG peptide with its native counterpart, we found that the variant contained reduced α-helicity, neither bound nor inhibited the IP 3R1 channel, and in turn lost its anti-apoptotic effect. Similar results were obtained with other substitutions in Bcl-2-BH4 that destabilized the α-helix with concomitant loss of IP3R inhibition. These results provide new insights for the further development of Bcl-2-BH4-derived peptides as specific inhibitors of the IP3R with significant pharmacological implications.

Host stress is well known to result in flare-ups of many bacterial, viral and parasitic infections. The mechanism by which host stress is exploited to increase pathogen loads, is poorly understood. Here we show that Salmonella enterica subspecies enterica serovar Typhimurium employs a dedicated mechanism, driven by the scsA gene, to respond to the host stress hormone cortisol. Through this mechanism, cortisol increases Salmonella proliferation inside macrophages, resulting in increased intestinal infection loads in DBA/2J mice. ScsA directs overall Salmonella virulence gene expression under conditions that mimic the intramacrophagic environment of Salmonella , and stimulates the host cytoskeletal alterations that are required for increased Salmonella proliferation inside cortisol exposed macrophages. We thus provide evidence that in a stressed host, the complex interplay between a pathogen and its host endocrine and innate immune system increases intestinal pathogen loads to facilitate pathogen dispersal.

Scientific Reports 6: Article number: 20849; published online: 09 February 2016; updated: 15 April 2016. In the Supplementary Information file originally published with this Article, Figures S1-4, Tables S1, S2, S4 and S5 were omitted. This error has been corrected in the Supplementary Information that now accompanies the Article.