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June 2019

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07 Jun

Posted at 10:42h in Blogs by

Eboigbodin K.E. et al., Diagnostic Microbiology and Infectious Disease, 2016

Recent worldwide large outbursts of the ZIKV necessitate the availability of a rapid, cost-effective and quick diagnostic method for ZIKV detection. Conventional diagnostic methods rely upon serological methods or nucleic acid amplification tests (NAATs), both of which are time consuming. The authors present an improved alternative to NAATs; the reverse transcriptase strand invasion based amplification (RT-SIBA), which has been used previously for rapid detection of DNA and RNA. RT-SIBA is essentially parallel to the PCR reaction. The investigators compared the method with conventional ones to assess the applicability, functionality (on the basis of reaction completion time and sample purity), specificity (with respect to sample source), performance (with respect to viral load) and reproducibility (in-field; on different types of in-house instruments). They established that this method was specific for the ZIKV, showed a lesser reaction completion time, independent of the degree of purity of the sample and showed comparable results when performed using in-house instruments. This method may be a powerful molecular diagnostic tool for ZIKV detection and finds an application during outbreaks, thus allowing treatment management and preventing the spread of the virus, especially in low-resource areas. Nevertheless, the assay still needs to be fully validated for direct detection of clinical specimens infected with the ZIKV.

http://www.dmidjournal.com/article/S0732-8893(16)30267-X/pdf

07 Jun

Posted at 10:41h in Blogs by

Salje H. et al., PNAS, 2016

Contraction of the disease during an infectious disease epidemic is dependent on interrelated factors, that may be directly related to the individual (age, sex), his family or the wider community of which he is a part. Advances in statistical modelling have aided studies to monitor compact communities like households or schools that help in the elucidation of the determinants of transmission in such small social structures, but have failed to include the wider context of the episode. Salje et al attempted to obtain a more comprehensive view of the risk factors associated with the contraction and spread of disease, using the case of chikungunya outbreak in a rural community in Bangladesh. Through statistical modelling, they found out that females were 1.5 times more likely to become infected by the virus, when compared to their male counterparts and attributed this to the mosquitoes being ‘lazy’ and the resultant subsequent transmission to females as they rarely moved from their households. The mosquitoes’ lazy nature allows them to get infected from an individual from a particular household, undergo the incubation period by staying in the same household and then infecting a person from the same house. The scientists also observed that the use of mosquito repellents had no impact on transmission. The result of the study showed that the complex interplay between the characteristics of an individual and his close and wider environment contributes to the shaping of infectious disease epidemics and it also offer key insights into how health officials can combat other diseases that spread the same way.

 

https://www.ncbi.nlm.nih.gov/pubmed/27821727

07 Jun

Posted at 10:40h in Blogs by

Lebel C. et al., Biological Psychiatry, 2016

 

It is well- known that perinatal maternal depression is a serious health concern, with its negative effects lasting on children. Prenatal depression is associated with altered brain gray matter in children, though the relation between postpartum depression, children’s brains and role of white matter are unclear. The study by Lebel et al, is first to report associations between maternal depression and altered brain structure in children. They observed 52 women during each trimester of pregnancy and at 3 months postpartum. Their depression was monitored both pre-and postpartum using the Edinburgh Postnatal Depression Scale (EPDS); and their children underwent MRI at the age of 2.6 years to 5.1 years. Associations between maternal depressive symptoms and MRI measures of cortical thickness and white matter structure in the children were investigated. They observed that higher maternal depressive symptoms prenatally and postpartum are associated with altered gray matter structure, with the white matter being correlated to the postpartum period. The reduced cortical thickness and diffusivity were suggestive of premature brain development in children who were exposed to higher maternal perinatal depressive symptoms. Results highlight the importance of ensuring optimal women’s mental health throughout the perinatal period, as maternal depressive symptoms appear to increase children’s vulnerability to nonoptimal brain development which predisposes them to depression and anxiety in their later age.

 

https://www.ncbi.nlm.nih.gov/pubmed/26822800

07 Jun

Posted at 10:39h in Blogs by

Marso S.P. et al., NEJM 2016

 

In order to fulfil regulatory requirement of establishing cardiovascular safety of new diabetes therapies in patients with type 2 diabetes a non inferiority trial as compared to placebo was planned for semaglutide (a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week) to evaluate its cardiovascular and other long term effects. 3297 patients with type 2 diabetes who were on a standard-care regimen were randomized to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. All participants had either established cardiovascular disease or additional cardiovascular risk factors.

The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). The mean glycated hemoglobin reduced to -1.1% and -1.4% for patients receiving 0.5 mg and1.0mg of semaglutide respectively, compared with 0.4% in the placebo group. Mean weight loss in the semaglutide group was 3.6 kg and 4.9 kg, respectively, compared with about 0.5 kg in the placebo group. Mortality rates from cardiovascular causes were similar in the two groups. New or worsening nephropathy was less common and diabetic retinopathy complications and gastrointestinal disorders were more common in the semaglutide group than in the placebo group. The trial achieved its primary end- point of showing noninferiority in safety of semaglutide compared with placebo in patients with type 2 diabetes at high cardiovascular risk. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446.)

 

 

07 Jun

Posted at 10:38h in Blogs, New and Event, Publication by

Zhang P. et al., 2017, The Lancet

 

Utidelone, a genetically engineered epothilone analogue, has emerged as a potential treatment for breast cancer in phase 1 and 2 trials. This phase III multicentre, open- label, randomized controlled trial was planned to compare the efficacy and safety of utidelone-capecitabine combination versus capecitabine alone in 270 patients with metastatic breast cancer. Patients were randomly assigned (2:1) to a 21-day cycle of either utidelone (30 mg/m2 IV once per day on days 1–5) plus capecitabine (1000 mg/m2 orally twice per day on days 1–14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1–14), until disease progression or unacceptable toxicity occurred. PFS (progression free survival) was assessed as the primary end- point. Median PFS in the combination group was 8·44 months (95% CI 7·95–9·92) compared with 4·27 months (3·22–5·68) in the capecitabine alone group. Peripheral neuropathy and Palmar-plantar erythrodysaesthesia were the most prominent grade 3 adverse event in the combination and monotherapy group respectively. 155 patients died (99 in combination therapy, 56 in monotherapy). All deaths, except one in each group were due to disease progression. This study has demonstrated that the combination was more efficacious compared to capecitabine alone, with mild toxicity and a longer PFS; thus making it an effective option for patients with metastatic breast cancer.

 

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30088-8/abstract

07 Jun

Posted at 10:37h in Blogs, New and Event, Publication by

Pradeep A. R. et al, November 2016, Journal of Periodontology

 

Gingivitis, the early stage of periodontal disease, is an infection of the tissues that surround your teeth, and is caused by a buildup of plaque.Anantiplaqueagent with minimal side effects that can be used as an effective adjunct to mechanical plaque control is needed. Recently a randomized control trial was planned to evaluate the efficacy of triphala (TRP) mouthwash in reduction of plaque and gingivitis.  Ninety individuals with chronic generalized gingivitis were randomly assigned to three groups: placebo mouthwash; TRP mouthwash; chlorhexidine (CHX) mouthwash and were instructed to rinse with their respective mouthwash twice daily. 1) Plaque index (PI); 2) gingival index (GI); 3) oral hygiene index-simplified (OHI-S); and 4) microbiologic colony counts were recorded at different time intervals. A significant difference was noticed in all four parameters in group I compared with groups II and III. However, there were no significant differences found between groups II and III for any parameters at any time intervals. From these results it was concluded that TRP mouthwash was comparable with that of CHX mouthwash for improvement in gingivitis and therefore it can be considered a potential therapeutic agent in the treatment of gingivitis.

 

http://www.joponline.org/doi/10.1902/jop.2016.130406

07 Jun

Posted at 10:36h in Blogs, New and Event, Publication by

Pradeep A. R. et al, November 2016, Journal of Periodontology

 

Since the discovery of antibiotics in the 1940s, research in this domain has been continuous, giving the world of an array of antibiotics. However, development of resistance to these antibiotics is a challenge that the researchers face on a daily basis. In a major breakthrough, scientists have discovered a fresh antibiotic, Teixobactin, produced by a screen of unculturable bacteria. Using a multichannel device, iChip, scientists cultured the unculturable bacteria in soil, screened the extracts obtained and identified Teixobactin. Further investigations into the activity spectrum and mechanism of action revealed that the antibiotic exhibited excellent activity against Gram- positive pathogens, including the drug- resistant strains; that expanded to difficult-to-treat enterococci, M. tuberculosis, C. difficle, B. anthracis and the very infamous, S. aureus MRSA. It inhibited cell wall synthesis, without affecting the DNA/ RNA and protein functions. To examine the development of resistance, Teixobactin was tested in a low dose against S. aureus and M. tuberculosis. Mutant strains did not develop, thus proposing a possible solution to antibiotic- resistance among pathogens. In vitro studies on cell lines showed no signs of apparent toxicity and in vivo efficacy studies in mouse models displayed superior efficacy. After decades of research channelled towards discovering antibiotics that do not allow for resistance development, discovery of Teixobactin has definitely given the research community hope to ‘unearth’ similar compounds.

 

http://www.nature.com/nature/journal/v517/n7535/full/nature14098.html

https://veedacr.com/2016-year-in-review/

07 Jun

Posted at 10:34h in Blogs, New and Event by

Ling L. et al, 2015, Nature

 

Since the discovery of antibiotics in the 1940s, research in this domain has been continuous, giving the world of an array of antibiotics. However, development of resistance to these antibiotics is a challenge that the researchers face on a daily basis. In a major breakthrough, scientists have discovered a fresh antibiotic, Teixobactin, produced by a screen of unculturable bacteria. Using a multichannel device, iChip, scientists cultured the unculturable bacteria in soil, screened the extracts obtained and identified Teixobactin. Further investigations into the activity spectrum and mechanism of action revealed that the antibiotic exhibited excellent activity against Gram- positive pathogens, including the drug- resistant strains; that expanded to difficult-to-treat enterococci, M. tuberculosis, C. difficle, B. anthracis and the very infamous, S. aureus MRSA. It inhibited cell wall synthesis, without affecting the DNA/ RNA and protein functions. To examine the development of resistance, Teixobactin was tested in a low dose against S. aureus and M. tuberculosis. Mutant strains did not develop, thus proposing a possible solution to antibiotic- resistance among pathogens. In vitro studies on cell lines showed no signs of apparent toxicity and in vivo efficacy studies in mouse models displayed superior efficacy. After decades of research channelled towards discovering antibiotics that do not allow for resistance development, discovery of Teixobactin has definitely given the research community hope to ‘unearth’ similar compounds.

 

http://www.nature.com/nature/journal/v517/n7535/full/nature14098.html

https://veedacr.com/2016-year-in-review/

07 Jun

Posted at 10:32h in Blogs, New and Event by

 

Mosquirix(RTS,S/ AS01) is a protein- based recombinant malaria vaccine, recently approved by the EMA. It is the first licensed vaccine, to be used for a parasitic disease. Developed by GlaxoSmithKline Vaccines, Belgium, in collaboration with the Walter Reed Army Institute of Researchand funded in part by PATH Malaria Vaccine Initiative (MVI) and with support from the Bill & Melinda Gates Foundation, it is considered as landmark achievement in the campaign against malaria. Mosquirix remains the first malaria vaccine to have completed Phase III trials, enrolling 15000 infants and young children from seven countries in sub- Saharan Africa. Efficacy was shown to range between 26- 50% in infants and children. Another set of preliminary studies indicated an efficacy of 86.7% in healthy, malaria- naive adults.

On November 2017, WHO announced the roll- out of the vaccine in pilot projects in three countries of sub-Saharan Africa. This WHO- coordinated programme is aimed to assess the vaccine’s efficacy in real- life settings. The programme will also evaluate the feasibility of delivery of the 4 required doses, the impact of the vaccines on the lives and the safety of the vaccine with respect to scheduled use.

https://www.ncbi.nlm.nih.gov/pubmed/25913272

https://www.ncbi.nlm.nih.gov/pubmed/27296848

http://www.who.int/mediacentre/news/releases/2016/funding-malaria-vaccine/en/

07 Jun

Posted at 10:29h in New and Event by

Thabit H. et al., Lancet Diabetes Endocrinology,  2017

 

An open- label, parallel- group, randomized controlled trial was conducted by Thabit H et al. to assess the safety and efficacy of fully closed-loop insulin delivery (so-called artificial pancreas), as compared to the standard subcutaneous insulin therapy in patients with type 2 diabetes mellitus. During the one year study period, 40 patients aged 18 years and above, from general ward were randomized to receive closed- loop insulin delivery (using a model-predictive control algorithm to direct subcutaneous delivery of rapid-acting insulin analogue without meal-time insulin boluses) or the conventional subcutaneous insulin delivery. The primary outcome i.e.; time spent in the target glucose concentration range of 5.6-10.0 mmol/L during the 72 hour study period; was 59·8% (SD 18·7) in the closed-loop group and 38·1% (16·7) in the control group (difference 21·8% [95% CI 10·4–33·1]; p=0·0004). No episodes of severe hypoglycaemia or hyperglycaemia with ketonaemia were observed in either group. Thus, closed- loop insulin delivery without meal-time boluses is safe and efficacious in insulin-treated adults with type 2 diabetes in the general ward.

 

https://www.ncbi.nlm.nih.gov/pubmed/27836235