A young physician starting a fresh career in medicine in this millennium would hardly stop to think about the genesis of a particular biological drug that he/she will be prescribing for a patient evaluated in the morning outpatient department. For him/her, this is now routine, and the question of ‘Who’, ‘How’ and ‘When’ about these biologicals would be the last thing on their mind. However, for those who came to the medical profession in the 1950s, 1960s and 1970s, these targeted drugs are nothing short of ‘miracles’. It would be a fascinating story for the young doctor to learn about the long journey that the dedicated biomedical scientists of yesteryears took to reach the final destination of producing such wonder drugs. The story is much like an interesting novel, full of twists and turns, heart-breaking failures and glorious successes. The biologicals acting as ‘targeted therapy’ have not only changed the natural history of a large number of incurable/uncontrollable diseases but have also transformed the whole approach towards drug development. From the classical empirical process, there is now a complete shift towards understanding the disease pathobiology focusing on the dysregulated molecule(s), targeting them with greater precision and aiming for better results. Seminal advances in understanding the disease mechanism, development of remarkably effective new technologies, greater knowledge of the human genome and genetic medicine have all made it possible to reach the stage where artificially developed ‘targeted’ drugs are now therapeutically used in routine clinical medicine.

The Indian Council of Medical Research (ICMR) has been at the forefront in setting up the ethical guidance for the conduct of biomedical and health research in India. The latest version of National Guidelines for Biomedical and Health Research Involving Human Participants, 2017 was planned in order to provide a more detailed guidance to the existing topics in view of emerging ethical concerns and to add a number of newer areas in which guidance was lacking. The scope of the guidelines has been expanded to include socio-behavioural research related to health and research involving biological material and datasets. The guidelines have 12 sections which cover a wide range of topics and areas of research. The first six sections are more generic, applying to all types of biomedical and health research, while the next six sections are more subject specific. The guidelines have been revised in consultation with a large number of experts and stakeholders and went through an exhaustive process stretching over a period of two years in its drafting, review, consultation and finalisation. This commentary seeks to explain the process and key components of the Guidelines.

Background & objectives: Gemcitabine combined with non-cremophor-based paclitaxel is one of the standards of care in advanced inoperable pancreatic cancer. This study was undertaken to retrospectively evaluate real world non-trial outcomes with this combination. Methods: Patients with histologically proven advanced inoperable pancreatic adenocarcinoma (PDAC), treated with non-cremophor-based paclitaxel-gemcitabine combination (PG) (gemcitabine-nanoxel or gemcitabine-abraxane) between January 2012 and June 2015, were retrospectively analyzed. Response assessment was done every 8-12 wk with computed tomography scan and responses were measured as per the Response Evaluation Criteria in Solid Tumours 1.1 criteria where feasible. Toxicity was recorded as per the Common Terminology Criteria for Adverse Events (CTCAE) v4 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: A total of 78 patients with PDAC were treated with the combination. Of these, 83.3 per cent of patients had metastatic disease. The median number of chemotherapy cycles administered was three. The objective response rate for the whole group was 30.8 per cent. Grade III/IV toxicities were seen in 35.9 per cent of patients. Median PFS was 5.6 months and median OS was 11.6 months. Interpretation & conclusions: Non-cremophor-based paclitaxel in combination with gemcitabine appeared efficacious for advanced pancreatic cancers in routine clinical practice. Within the confines of a single-centre retrospective analysis, gemcitabine-nanoxel and gemcitabine-abraxane appeared to have similar efficacy and toxicity in advanced pancreatic cancers.

Background & objectives: Non-alcoholic fatty liver disease (NAFLD) characterized by excessive accumulation of fat in the liver, which can progress to inflammation, and cirrhosis, has emerged as an important complication of obesity in adults as well as children. This study was undertaken to assess the prevalence of NAFLD and its correlation with clinical and biochemical parameters in overweight Indian adolescents. Methods: In this cross-sectional study, 218 overweight adolescents aged 10 to 16 yr and their parents were included. Measurements included anthropometry, ultrasonography to diagnose NAFLD, fasting glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lipids for adolescents and parents, and additional parameters of blood pressure, body fat percentage (BF%), fasting insulin, apolipoprotein C3, tumour necrosis factor-α and adiponectin for adolescents. The variables were compared between adolescents with and without NAFLD, and logistic regression analysis was performed. Results: Mean age and body mass index (BMI)SD score (SDS) were 11.9±1.6 yr and 2.3±1.1, respectively. NAFLD was seen in 62.5 per cent of the adolescents. The prevalence of NAFLD in the parents was similar among the adolescents with and without NAFLD, while BMI and waist circumference SDS, BF per cent, blood pressure (BP), ALT, AST, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in the adolescents with NAFLD. On multiple logistic regression, abdominal obesity, HOMA-IR and BF per cent were independently associated with NAFLD with odds ratios (95% confidence interval) of 2.77 (1.40-5.47), 2.21 (1.16-4.21) and 2.17 (1.12-4.22), respectively. Interpretation & conclusions: NAFLD was noted among nearly two-thirds of the overweight adolescents. An independent association was observed between abdominal obesity, HOMA-IR and body fat percentage and NAFLD in overweight adolescents.

Background & objectives: Transvaginal ultrasonography (TVS) is a non-invasive procedure and can be used as a screening tool among women with abnormal uterine bleeding (AUB). Power Doppler is useful in depicting the vascular architecture better than the conventional Doppler. Hence, this study was conducted to evaluate whether addition of power Doppler to grey scale TVS can replace invasive hysteroscopy for the prediction of endometrial pathology in perimenopausal women with AUB. Methods: One hundred women (>45 yr) with perimenopausal AUB underwent evaluation with TVS, power Doppler and hysteroscopy-guided biopsy after a detailed history and examination. Histopathology was considered as gold standard and other tools such as grey scale TVS with power Doppler and hysteroscopy were compared with it. Results: Fifty six per cent women had no vascularity on power Doppler. Among those who had vascularity, the vascular patterns noted were single-vessel in 18 per cent, scattered-vessel in 15 per cent and multiple-vessel in 11 per cent. The sensitivity, specificity, positive predictive value and negative predictive value of TVS-endometrial thickness with power Doppler in detecting hyperplasia were 50, 86.5, 13.3 and 97.6 per cent, respectively, whereas the same for hysteroscopy were 100, 97.6, 88.1 and 100 per cent, respectively. Interpretation & conclusions: Addition of power Doppler to grey scale TVS improved the specificity and negative predictive value almost comparable to hysteroscopy for evaluation of AUB, but sensitivity and positive predictive value remained poor.

Background & objectives: India has recorded a marked increase in facility births due to government's conditional cash benefit scheme initiated in 2005. However, concerns have been raised regarding the need for improvement in the quality of care at facilities. Here we report the monitoring patterns during labour and delivery documented by direct observation in reference to the government's evidence-based guidelines on skilled birth attendance in five districts of India. Methods: A cross-sectional study design with multistage sampling was used for observation of labour and delivery processes of low-risk women with singleton pregnancy in five districts of the country. Trained research staff recorded the findings on pre-tested case record sheets. Results: A total of 1479 women were observed during active first stage of labour and delivery in 55 facilities. The overall frequency of monitoring of temperature, pulse and blood pressure was low at all facilities. The frequency of monitoring uterine contractions and foetal heart sounds was less than the expected norm, while the frequency of vaginal examinations was high at all levels of facilities. Partograph plotting was done in only 15.8 per cent deliveries, and labour was augmented in about half of the cases. Interpretation & conclusions: The findings of our study point towards a need for improvement in monitoring of maternal and foetal parameters during labour and delivery in facility births and to improve adherence to government guidelines for skilled birth attendance.

Background & objectives: Atopic dermatitis (AD) is one of the most common pathologic conditions of skin in children. The effect of breastfeeding on the risk of AD remains controversial. The aim of this study was to determine the counts of cytokine-producing cells in the mothers' breast milk of infants with and without AD to assess association, if any. Methods: Breast milk samples (10 ml) were obtained from mothers of 25 infants with AD and of 26 healthy infants as a control group. The number of cytokine-producing cells including interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α), interleukin-13 (IL-13) and IL-4 in the milk samples was determined using an enzyme-linked immunospot assay technique. Results: The mean of IL-13-producing cells in milk was significantly lower in mothers of AD-affected infants in comparison with mothers of normal infants (324.91±255.45 vs. 538.93±465.39, P<0.05). There were no significant differences between mothers of infants with and without AD regarding milk count of IFN-γ-, TNF-α- and IL-4-producing cells. Interpretation & conclusions: Our results showed lower number of IL-13-producing cells in milk of mothers of infants with AD. Therefore, lower count of IL-13-producing cells in mothers' milk may confer a susceptibility to AD. Further studies with a large number of samples need to be done to confirm our findings.

Background & objectives: Human papillomavirus (HPV) infections play a crucial role in the aetiology of cervical cancer (CC), and HPV16 is the primary viral genotype associated with CC. A number of variants of the HPV16 E6 gene are involved in the progression of CC, differing in their prevalence and biological and biochemical properties. This study was designed to determine the frequency of HPV types 16/18 and to identify the presence of HPV16 E6-variants in asymptomatic Mexican women. Methods: A total of 189 cervical Pap smears were collected from women attending public health services in three different cities in Sinaloa, Mexico. Viral DNA was identified by amplification of E6 viral gene fragments using polymerase chain reaction (PCR). Identification of variants was done by sequencing a DNA fragment (321bp) of the HPV16 E6 gene. Results: More than half of the women tested were HPV-positive (52.38%), with HPV16 being the most frequent genotype (21.16%), followed by HPV18 (8.99%). Sequence analysis of the E6-HPV16 PCR products showed that in all cases, the viruses corresponded to European variants. It was further observed that the E350G intra-variant was the most common (>76%). Interpretation & conclusions: This study showed a predominance of European lineage variants of HPV16 among asymptomatic women from Sinaloa, Mexico, predominantly with of the E350G variant. This variant has been shown to be associated with an increased risk of early development of CC. The use of molecular identification of carcinogenic HPV and Pap test screening may be a good strategy for monitoring women to prevent CC.

Background & objectives: Respiratory tract infections are common among Hajj and Umrah pilgrims which pose a public health risk of spread of respiratory infections. Influenza has been reported from Indian Hajj and Umrah returning pilgrims, but data on other respiratory pathogens are sparse in India. Here we report the presence of common respiratory viral pathogens in returning Hajj and Umrah pilgrims suffering from acute respiratory illness (ARI) in 2014-2015. Methods: Respiratory specimens (nasopharyngeal and throat swabs) were collected from 300 consenting pilgrims with ARI in the past one week and tested for influenza and Middle East Respiratory Syndrome coronavirus (MERS-CoV) and other respiratory viruses using in-house standardized quantitative real-time reverse-transcription polymerase chain reaction. Clinical features among the pathogen positive and negative patients were compared. The patients received symptomatic treatment and antivirals where appropriate and were followed telephonically to collect data on illness outcome. Results: Ninety seven (32.3%) of the 300 participants were tested positive for any virus, most common being influenza viruses (n=33, 11%). Other respiratory viruses that were detected included human coronaviruses [n=26, 8.7%; OC43 (n=19, 6.3%) and C229E (n=7, 2.3%)], rhinovirus (n=20, 6%), adenoviruses (n=8, 2.6%), parainfluenza viruses (n=7, 2.3%), respiratory syncytial virus (n=3, 1%) and bocaviruses (n=2, 0.6%). Clinical features observed in pathogen positive and pathogen negative patients did not differ significantly. Eighteen influenza positive patients were treated with oseltamivir. Interpretation & conclusions: Pilgrims returning from mass gatherings are often afflicted with respiratory pathogens with a potential to facilitate transmission of respiratory pathogens across international borders. The study reinforces the need for better infection prevention and control measures such as vaccination, health education on cough etiquette and hand hygiene.

Background & objectives: In sterile insect technology (SIT), mating competitiveness is a pre-condition for the reduction of target pest populations and a crucial parameter for judging efficacy. Still, current SIT trials are being hindered by decreased effectiveness due to reduced sexual performance of released males. Here, we explored the possible role of a herbal aphrodisiac in boosting the mating activity of Aedes aegypti. Methods: Males were fed one of two diets in this study: experimental extract of Eurycoma longifolia (MSAs) and sugar only (MSOs). Differences in life span, courtship latency, copulation activity and mating success were examined between the two groups. Results: No deaths occurred among MSA and MSO males. Life span of MSOs was similar to that of MSAs. The courtship latency of MSAs was shorter than that of MSOs (P<0.01). MSAs had greater copulation success than MSOs (P<0.001). In all female treatments, MSAs mated more than MSOs, but the differences in rate were significant only in the highest female density (P<0.05). In MSAs, mating success varied significantly with female density (P<0.01), with the 20-female group (P<0.01) having the lowest rate. Single MSA had better mating success at the two lowest female densities. In MSOs, there were no significant differences in mating success rate between the different female densities. Interpretation & conclusions: Our results suggested that the herbal aphrodisiac, E. longifolia, stimulated the sexual activity of Ae. aegypti and may be useful for improving the mating competitiveness of sterile males, thus improving SIT programmes.