Do children in India grow well into adolescents? Longitudinal analysis of growth transitions from Young Lives panel survey in India.

OBJECTIVES: Studies that examined the growth during late childhood and early adolescence beyond 8 years of age are very limited. Further, most studies have used dichotomized classification of stunting, thereby limiting the understanding of moderate stunting in childhood growth trajectory. We aimed to examine the course of stunting from childhood to adolescence by undertaking robust analyses of the Young Lives Survey (YLS) longitudinal data from India using multilevel categorization of stunting. STUDY DESIGN: Retrospective cohort analysis was undertaken from YLS in India among 1827 children from the younger cohort born in 2001-02 with complete follow-up data in all five rounds of YLS collected in 2002, 2006, 2009, 2013, and 2016. METHODS: A three-state multistate Markov model (not stunted, moderate, severe) was performed to estimate annual transition probabilities, mean sojourn-time, and transition-specific risk factors. RESULTS: Between Round-one and Round-five, cross-sectional prevalence of severe stunting decreased from 10.4% (95% confidence interval [CI]: 7.8%, 13.7%) to 5.3% (95% CI: 3.8%, 7.3%), while moderate stunting increased from 19.9% (95% CI: 16.3%,23.9%) to 21.7% (95% CI: 18.4%, 24.9%). Mean Sojourn time estimation indicated a relatively concise state for moderate stunting. The stunting trajectory had shown gender differential where more faltering to severe stunting and lower recovery to the normal state was observed among girls between 8 and 12 years and among boys between 12 and 15 years. Compared with boys, girls had 40% excess likelihood (Hazard Ratio: 1.40; 95% CI 1.00 to 1.95) for moderate-to-severe stunting transition and also had 19% excess likelihood (Hazard Ratio: 1.19; 95% CI 1.01 to 1.40) of favorable transition (moderate-to-non-stunted). CONCLUSIONS: The transition trajectory highlights preadolescence, especially among girls, as an additional window of opportunity to ensure better nutrition in adolescent life. With a fifth of adolescents living in India, study findings call for coordinated, multisectoral, age-appropriate, and gender-responsive approach to take India closer to meeting SDG-2.

The effect of COVID-19 on a Major Trauma Network. An analysis of mechanism of injury pattern, referral load and operative case-mix.

PURPOSE: The aim of this study was to evaluate changes in both mechanism and diagnoses of injuries presenting to the orthopaedic department during this lockdown period, as well as to observe any changes in operative case-mix during this time. METHODS: A study period of twelve weeks following the introduction of the nationwide "lockdown period", March 23rd - June 14th, 2020 was identified and compared to the same time period in 2019 as a "baseline period". A retrospective analysis of all emergency orthopaedic referrals and surgical procedures performed during these time frames was undertaken. All data was collected and screened using the 'eTrauma' management platform (Open Medical, UK). The study included data from a five NHS Foundation Trusts within North West London. A total of 6695 referrals were included for analysis. RESULTS: The total number of referrals received during the lockdown period fell by 35.3% (n=2631) compared to the same period in 2019 (n=4064). Falls remained proportionally the most common mechanism of injury across all age groups in both time periods. The proportion sports related injuries compared to the overall number of injuries fell significantly during the lockdown period (p<0.001), however, the proportion of pushbike related accidents increased significantly (p<0.001). The total number of operations performed during the lockdown period fell by 38.8% (n=1046) during lockdown (n=1732). The proportion of patients undergoing operative intervention for Neck of Femur (NOF) and ankle fractures remained similar during both study periods. A more non-operative approach was seen in the management of wrist fractures, with 41.4% of injuries undergoing an operation during the lockdown period compared to 58.6% at baseline (p<0.001). CONCLUSION: In conclusion, the nationwide lockdown has led to a decrease in emergency orthopaedic referrals and procedure numbers. There has been a change in mechanism of injuries, with fewer sporting injuries, conversely, there has been an increase in the number of pushbike or scooter related injuries during the lockdown period. NOF fractures remained at similar levels to the previous year. There was a change in strategy for managing distal radius fractures with more fractures being treated non-operatively.

Advanced therapeutic options and importance of rebiopsy in epidermal growth factor receptor-tyrosine kinase inhibitor-progressed nonsmall cell lung carcinoma patients: An expert opinion.

Advanced nonsmall cell lung cancer (NSCLC) treatment is primarily based on platinum-based chemotherapy. Although epidermal growth factor receptor (EGFR) targeting has shifted the treatment paradigm toward personalized tyrosine kinase inhibitors (TKIs), resistance develops inevitably and EGFR T790M is the most common acquired resistance mechanism. Rebiopsy of resistant NSCLC cases can provide additional information on the underlying resistant mechanisms and therefore can help clinicians in taking better management decisions. An expert panel meeting of renowned cancer oncologists was held to discuss the management of advanced-stage NSCLC. The present paper is based on the recommendations made by the expert panel and is supported by an exhaustive literature search. It was suggested that identification of driver mutation leads to better treatment decisions. TKIs have proven to be better treatment option in EGFR-positive patients as compared to chemotherapy. Third-generation TKIs (osimertinib) promise to bring optimal and improved care for NSCLC cases failing first-line TKI treatment.

Microarray analysis of gene expression in parthenotes and in vitro-derived goat embryos.

The present work was carried out to investigate the global gene expression profile to search differentially expressed candidate transcripts between parthenogenetic and in vitro-fertilized (IVF) caprine morula. For this study, total RNA was isolated from diploid parthenogenetic and IVF embryos, and complementary DNA was synthesized. Microarray and relative real-time polymerase chain reaction analysis were performed to check global gene expression profile and validation, respectively. According to the microarray analysis, the total number of upregulated (UR) and downregulated (DR) genes was 613 and 220, respectively in diploid parthenogenetic morula as compared with IVF morula. The number of genes showing about two-, two- to five-, five- to 10-, 10- to 20-, and above 20-fold UR and DR genes was 147, 229, 122, 59, and 56 and 94, 73, 18, 13, and 22, respectively. Five UR genes validated (PTEN, PHF3, CTNNB1, SELK, and NPDC1) and all of them were significantly higher in parthenotes, which was in accordance with microarray results, whereas the expression of DR (AURKC and KLF15) genes were downregulated in parthenotes as observed in microarray results but the difference was not significant (P < 0.05). In conclusion, our findings demonstrate differential expression of a large number of genes in parthenotes compared with IVF embryos, which may be the reason for aberrant parthenogenetic embryo development in caprine species.

Isolation and characterization of neural stem cells from buffalo.

Neural stem cells (NSCs) are primordial, uncommitted cells postulated to give rise to the array of more specialized cells of the central nervous system (CNS). NSCs can self-renew and give rise to neurons, astrocytes and oligodendrocytes. NSCs are found in the CNS of mammalian organisms, and represent a promising resource for both fundamental research and CNS repair. Animal models of CNS damage have highlighted the potential benefit of NSC-based approaches. Present study described that buffalo neural stem cells (Bu-NSCs) were isolated and expanded rapidly from buffalo fetal brain in adherent culture. They were capable of multidifferentiation into neurons, astrocytes, and oligodendrocytes. Bu-NSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 128.16 h. Normal buffalo karyotype was unchanged throughout the in vitro culture period. Together, we have isolated and cultured Bu-NSC from fetal brain that showed self-renewal, rapid proliferation and ability to differentiate into cells of nervous system. The availability of such cells may hold great interest for basic and applied neuroscience.

Availability of doctors at primary health centres of Andhra Pradesh, India.

BACKGROUND: Availability of doctors at primary health centres (PHCs) is a major concern. We measured the operational availability of doctors in PHCs and examined the effect of residential distance and private practice. METHODS: Thirty-six health centres, consisting of six randomly selected PHCs from six purposively chosen districts in Andhra Pradesh were studied. Cross-sectional data on residential distance, private practice and attendance pattern of 38 operationally available medical officers were analysed. RESULTS: About 80% of doctors residing within 20 km attended their PHC on all 6 days of a week, compared with only 33% for those staying >40 km away. Among those staying >20 km away from their PHC, the odds of absenteeism by privately practising doctors was 3-24 times more than for those not practising privately. CONCLUSION: Residential distance seems to affect the operational availability of doctors. Private practice by doctors living within 20 km from the PHC does not seem to affect their operational availability. However, private practice by doctors staying >20 km away from their PHC may affect their availability.

Gradient of reduced glutathione in the tail of Hemidactylus leschenaultii (Sauria: Gekkonidae).

A proximo-distal gradient of reduced glutathione (GSH), a non enzymatic antioxidant was observed in the original tails of the lizard, H. leschenaultii. In the regenerating tails, a gradual increase in the level of GSH was noted with tail elongation. In the newly regenerated tails also the level of GSH remained higher in the proximal part than the corresponding distal parts.

Current density in generalized Fibonacci superlattices under a uniform electric field.

We present an exhaustive study on tunneling and electrical conduction in an electrically biased GaAs-Al(y)Ga(1-y)As generalized Fibonacci superlattice. The study is based on transfer matrix formalism using an Airy function approach and provides an exact calculation of the current density in the case of quasi-periodic multibarrier systems. The results suggest the use of such quasi-periodic systems in perfect band-pass or band-eliminator (of extremely low width) circuitry. We have clearly demonstrated the resonance-type peaks and negative differential conductivity regimes in such systems. It has also been found that quasi-periodicity favors sharp negative differential conductivity peaks compared to those in periodic superlattices and thus have profound importance in device applications.

Plasma MDA and antioxidant vitamins in diabetic retinopathy.

Hyperglycemia and dyslipidemia in diabetes mellitus induce increased lipid peroxidation and peroxyl radical formation, an important mechanism in genesis of microangiopathy. We took up a study on oxidative stress, measured by plasma MDA and antioxidant vitamin status in type - 2 DM patients with and without retinopathy and compared them with a control non-diabetic group. Lipid peroxidation marker MDA was significantly elevated (p < 0.001) in both the diabetic groups whereas, serum vitamin E and vitamin C registered a significant fall (p<0.001) as compared to controls. Our correlation study revealed a significant positive association between plasma MDA with both fasting and 2hr post prandial plasma glucose (r=0.81, p < 0.001, r=0.92, p <0.001) suggesting the role of hyperglycemia in free radical production. Plasma MDA also depicted significant positive relation (p< 0.001) with all lipid parameters except serum HDLc pointing the role of dyslipidemia towards lipid peroxidation. Plasma MDA level was also found to be negatively correlated with both the vitamins (p<0.001, p<0.001) in the study group explaining their protective consumption in the oxidative process prevailing in diabetic retinopathy.

Effective post-laparoscopic treatment of endometriosis with dydrogesterone.

An open, prospective, multicenter study was designed to assess the efficacy and safety of dydrogesterone in the post-laparoscopic treatment of endometriosis in Indian patients. Ninety-eight patients suffering from minimal, mild, moderate or severe endometriosis, with or without infertility, who had undergone laparoscopy, were treated with dydrogesterone 10 mg/day (or 20 mg/day in severe cases) orally from day 5 to day 25 of each cycle for 3-6 months. Pelvic pain, dysmenorrhea and dyspareunia improved significantly (p < 0.05) after the first cycle of treatment. By the end of the sixth cycle, the reduction in pelvic pain, dysmenorrhea and dyspareunia was 95%, 87% and 85%, respectively. The amount of menstrual bleeding fell significantly (p < 0.05) after 2 months (-12%) and this significant reduction was maintained until the end of the study. The duration of bleeding was also reduced significantly (p < 0.05) throughout the study, starting after the first month of treatment (-10%). A total of 21.1% of the patients were considered cured and 66.7% showed improvement. Overall, dydrogesterone therapy was rated as excellent to good by 74% of patients and 70% of physicians. No adverse events were reported. In conclusion, dydrogesterone is an effective and safe post-laparoscopic treatment for endometriosis.

Interaction of water vapour with twenty different poly-L-amino acids and their excess hydration in presence of sodium chloride.

Using the isopiestic vapour pressure technique, the magnitudes of excess binding of water and NaCl per mole of twenty different poly-L-amino acid residues, respectively in the presence of different bulk molefractions (X2) of NaCl have been evaluated from the mathematical expressions for the Gibbs surface excesses. At certain high ranges of NaCl concentration, the plot of -Gamma1 (2) versus X1/X2 becomes linear, so that moles of water and NaCl, respectively bound per mole of amino acid residue can be evaluated. -Gamma(2)1 is the excess moles of H20 per mole of amino acid residue and X1 and X2 stand for mole fractions of the water and NaCl, respectively in the sample system. Also, using the integrated form of the Gibbs absorption equation, the values of standard free energy change (deltaG(0)) for the excess adsorption of NaCl per kg of poly-L-amino acids have been evaluated. These values are all positive as a result of positive excess hydration of polyamino acids. The standard free energy of excess hydration deltaG(0)hy (equal to -deltaG(0)) is negative due to spontaneous excess hydration of polyamino acid in the presence of a salt.

Simultaneous induction of ectopic pelvic zone and duplication of regenerated limbs in tadpoles of Polypedates maculatus by vitamin A.

With a view to determine ectopic limb developing capacity along with normal hind limb regeneration in response to vitamin A palmitate in well-differentiated hind limb stage tadpoles of P. maculatus, higher doses of vitamin A (30 IU/ml and 20 IU/ml) were administered for a longer period (120 hr) to the tadpoles following tail amputation through middle and hind limb amputation through middle of thigh. Simultaneous development of ectopic pelvic zone was observed along with hind limbs from the cut end of tail and duplication of regenerated hind limbs in the same tadpole for the first time. Besides, development of double ectopic pelvic girdle was also reported in one case. Results also indicate that induction of pelvic zone and duplication of regenerated limbs are concentration dependent.

Conformational properties of alpha-tubulin tail peptide: implications for tail-body interaction.

The carboxy-terminal segments of the alpha/beta-tubulins are flexible regions rich in acidic amino acid residues. It is generally believed that these regions play crucial roles in tubulin polymerization and interaction with many ligands, including colchicine. Exactly how these effects are exerted are not known at present. One such interesting aspect is the pH dependence of colchicine-tubulin interaction and the influence of the alpha-tail on the binding interaction. We have investigated the location of the colchicine-binding site on tubulin by docking. It has been located on the alpha/beta interface on the N-terminal side, which is also supported by much of the solution data. This location is too far from the tail regions, suggesting that influence of the tail region is transmitted by a pH-dependent conformational change. Two-dimensional NMR studies indicate that at pH 7 a 13-residue peptide corresponding to alpha-tubulin tail shows little NOE constraints, suggesting extended conformation. On the contrary, at pH 5, a relatively compact structure was deduced from the interproton NOE constraints. Pulsed field gradient measurement of diffusion constant indicates that the peptide at pH 5 is substantially faster diffusing than at pH 7. The Perrin factors calculated from diffusion data indicates that the peptide structure at pH is significantly more compact than at pH 7. Temperature coefficients of several amide protons at pH 5 fall below 5 ppb/(o)K, indicating a degree of protection. A difference is also seen in the CD spectra obtained at different pHs, consistent with the NMR data. We have investigated the probable spatial organization of the tail of the alpha-subunit of tubulin, in the high pH extended form and the low pH compact form. On the basis of correlation of pH dependence of many properties of tubulin and the conformation of the alpha-tail peptide, we propose that the intrinsic conformational preference of the tail-region modulate the tail-body interaction, which in turn has important bearing on colchicine binding properties.

Changes in oxidative stress parameters and acid phosphatase activity in the pre-regressing and regressing tail of Indian jumping frog Polypedates maculatus (Anura, Rhacophoridae).

Activities of acid phosphatase (normal and Co2+-sensitive), superoxide dismutase and catalase and levels of lipid peroxidation, hydrogen peroxide were compared in the tails of tadpoles of stage III, XVIII, XXI and XXIII, respectively, of the Indian Jumping frog Polypedates maculatus. It is noticed that acid phosphatase activity (normal and Co2+-sensitive), and levels of lipid peroxidation and hydrogen peroxide increased during tail regression. There is also an increase in the level of superoxide dismutase and catalase in the regressing tail. A positive correlation between activity of acid phosphatase and lipid peroxidation, hydrogen peroxide and lipid peroxidation, acid phosphatase and hydrogen peroxide was noticed in the tail of tadpoles during different developmental stages, suggesting a critical interaction between reactive oxygen species and lysosomal activity during metamorphosis.

A multicentric study with arteether in patients of uncomplicated falciparum malaria.

Two hundred and sixty seven patients of uncomplicated P. falciparum malaria completed study in a multicentric phase III clinical trial of Arteether. Arteether was given intramuscularly in a dose of 150 mg daily for three consecutive days. Each patient was followed upto 28 days of alpha, beta arteether therapy. The cure rate was 97% with fever clearance time between 1-7 days (24-168 hours) and parasite clearance time between 1-3 days (24-72 hours). Parasite reappearance rate was found to be 3% and reported at only three of the centres. Following the treatment no adverse effect was observed on haematological, biochemical and vital clinical parameters.

Role of the carboxy-termini of tubulin on its chaperone-like activity.

Mutational analysis and the enzymatic digestion of many chaperones indicate the importance of both hydrophobic and hydrophilic residues for their unique property. Thus, the chaperone activity of alpha-crystallin is lost due to the substitution of hydrophobic residues or upon enzymatic digestion of the negatively charged residues. Tubulin, an eukaryotic cytoskeletal protein, exhibits chaperone-like activity as demonstrated by prevention of DTT-induced aggregation of insulin, thermal aggregation of alcohol dehydrogenase, betagamma-crystallin, and other proteins. We have shown that the tubulin lost its chaperone-like activity upon digestion of its negatively charged C-termini. In this article, the role of the C-terminus of individual subunits has been investigated. We observe that the digestion of C-terminus of beta-subunit with subtilisin causes loss of chaperone-like activity of tubulin. The contribution of C-terminus of alpha-subunit is difficult to establish directly as subtilisin cleaves C-terminus of beta-subunit first. This has been ascertained indirectly using a 14-residue peptide P2 having the sequence corresponding to a conserved region of MHC class I molecules and that binds tightly to the C-terminus of alpha-subunit. We have shown that the binding of P2 peptide to alphabeta-tubulin causes complete loss of its chaperone-like activity. NMR and gel-electrophoresis studies indicate that the P2 peptide has a significant higher binding affinity for the C-terminus of alpha-subunit compared to that of beta-subunit. Thus, we conclude that both the C-termini are necessary for the chaperone-like activity of tubulin. Implications for the chaperone functions in vivo have been discussed.