Understanding the rise in traditional contraceptive methods use in Uttar Pradesh, India.

BACKGROUND: The sustainable development goals (SDG) aim at satisfying three-fourths of family planning needs through modern contraceptive methods by 2030. However, the traditional methods (TM) of family planning use are on the rise, along with modern contraception in Uttar Pradesh (UP), the most populous Indian state. This study attempts to explore the dynamics of rising TM use in the state. METHODS: We used a state representative cross-sectional survey conducted among 12,200 Currently Married Women (CMW) aged 15-49 years during December 2020-February 2021 in UP. Using a multistage sampling technique, 508 primary sampling units (PSU) were selected. These PSU were ASHA areas in rural settings and Census Enumeration Blocks in urban settings. About 27 households from each PSU were randomly selected. All the eligible women within the selected households were interviewed. The survey also included the nearest public health facilities to understand the availability of family planning methods. Univariate and bivariate analyses were conducted. Appropriate sampling weights were applied. RESULTS: Overall, 33.9% of CMW were using any modern methods and 23.7% any TM (Rhythm and withdrawal) at the time of survey. The results show that while the modern method use has increased by 2.2 percentage points, the TM use increased by 9.9 percentage points compared to NFHS-4 (2015-16). The use of TM was almost same across women of different socio-demographic characteristics. Of 2921 current TM users, 80.7% started with TM and 78.3% expressed to continue with the same in future. No side effects (56.9%), easy to use (41.7%) and no cost incurred (38.0%) were the main reasons for the continuation of TM. TM use increased despite a significant increase (66.1 to 81.3%) in the availability of modern reversible methods and consistent availability of limiting methods (84.0%) in the nearest public health facilities. CONCLUSION: Initial contraceptive method was found to have significant implications for current contraceptive method choice and future preferences. Program should reach young and zero-parity women with modern method choices by leveraging front-line workers in rural UP. Community and facility platforms can also be engaged in providing modern method choices to women of other parities to increase modern contraceptive use further to achieve the SDG goals.

In Uttar Pradesh, the use of traditional methods of contraception is on the rise, observed similarly in many other Indian states in recent times. The emphasis on modern contraceptive methods and the rise and high prevalence of traditional method use in the state call for a systematic assessment to understand the dynamics such as patterns, prevalence and reasons for traditional method use for better family planning programming. Using a state representative cross-sectional survey data from Uttar Pradesh, we attempted to understand the dynamics of increasing traditional methods use. We found no significant variations in use of traditional methods by their socio-demographic characteristics. Not only that, most current traditional method users reported that their first method was a traditional method and an overwhelming proportion of women (4/5 traditional methods users) expressed to continue with the same method in future. Also the findings reveal that more than half of the traditional method users used the method consistently over the three-years calendar period. Among those who had unmet need at the time of survey, a considerable proportion of them intend to use traditional methods in future. This emphasized the importance of initial contraceptive method choice on current contraceptive use and future preference. Traditional methods use increased in the state despite a significant increase (66.1 to 81.3% during 2018 to 2021) in availability of modern reversible methods and consistent availability of limiting method (84.0%) in public health facilities.

Hypoxia-driven metabolic heterogeneity and immune evasive behaviour of gastrointestinal cancers: Elements of a recipe for disaster.

Gastrointestinal (GI) cancers refer to a group of malignancies associated with the GI tract (GIT). Like other solid tumors, hypoxic regions consistently feature inside the GI tumor microenvironment (TME) and contribute towards metabolic reprogramming of tumor-resident cells by modulating hypoxia-induced factors. We highlight here how the metabolic crosstalk between cancer cells and immune cells generate immunosuppressive environment inside hypoxic tumors. Given the fluctuating nature of tumor hypoxia, the metabolic fluxes between immune cells and cancer cells change dynamically. These changes alter cellular phenotypes and functions, resulting in the acceleration of cancer progression. These evolved properties of hypoxic tumors make metabolism-targeting monotherapy approaches or immunotherapy-measures unsuccessful. The current review highlights the advantages of combined immunometabolic treatment strategies to target hypoxic GI cancers and also identifies research areas to develop better combinational therapeutics for future.

Glutamate binding triggers monomerization of unliganded mGluR2 dimers.

The Metabotropic glutamate receptor 2 (mGluR2) is involved in several neurological and psychiatric disorders and is an attractive drug target. It is believed to form a strict dimer and the dimeric assembly is necessary for glutamate induced activation. Although many studies have focused on glutamate induced conformational changes, the dimerization propensity of mGluR2 with and without glutamate has never been investigated. Also, the role of the unstructured loop in dimerization of mGluR2 is not clear. Here, using Forster Resonance Energy Transfer (FRET) based assay in live cells we show that mGluR2 does not form a "strict dimer" rather it exists in a dynamic monomer-dimer equilibrium. The unstructured loop moderately destabilizes the dimers. Furthermore, binding of glutamate to mGluR2 induces conformational change that promotes monomerization of mGluR2. In the absence of an unstructured loop, mGluR2 neither undergoes conformational change nor monomerizes upon binding to glutamate.

Ru-TsDPEN catalysts and derivatives in asymmetric transfer hydrogenation reactions.

This review summarizes current developments, novel synthetic routes for Ruthenium tethered chiral catalyst, and its derivatives along with its application in asymmetric synthesis. The review also covers derivatization in tethering unit, modification in N-monofunctionalized ligand as well as ligation of other ligand with Ru metal in chiral catalyst. Apparently, the effect of a modified tethered catalyst in the enantioselective synthesis of chiral products as well as in synthetic chemistry is also discussed in detail.

Interaction of apoptosis and pluripotency related transcripts for developmental potential of ovine embryos produced in vitro at different oxygen concentrations.

The present study in sheep model was to find out the interaction of apoptotic transcripts, that is, Bcl2, Bax, Casp3, PCNA and p53 and pluripotency related transcripts, that is, Sox2, Nanog and Oct4 in ovine embryos produced in vitro at different O2 concentrations (20% and 5% O2) to compare their developmental potential. Oxygen concentrations did not influence the maturation and cleavage rate but the percentage of morula and blastocysts was significantly more at 5% as compared to 20% O2. A significant upregulated expression of Bcl2 and PCNA genes and significantly downregulated expression of Casp3 and p53 were observed in the blastocysts at 5% than those at 20% O2. The expression of Bax was not influenced by the O2 concentration. Among the pluripotency related transcripts, the expression of Oct4 was significantly upregulated and the expression of Sox2 and Nanog was significantly downregulated in embryos at 5% than at 20% O2. The study concluded that the embryos produced in vitro at low O2 (5%) concentration regulate the expression of developmental genes related to apoptosis and pluripotency to improve the developmental potential of embryos as compared to high O2 (20%) concentration.

Unstructured loop is essential for the activation of mGluR2.

Metabotropic Glutamate Receptors (mGluRs) are Class C G-protein coupled receptors (GPCRs) that are expressed throughout the central nervous system and are involved in several neurological and psychiatric disorders. Although, many studies focused on Glutamate induced activation of mGluR2, however, the role of unstructured loop (or "BC loop") in activation of metabotropic Glutamate receptors is currently unknown. Here, using Förster Resonance Energy Transfer (FRET) based assay in live cells we show that unstructured loop is required for Glutamate induced conformation and hence the activation of the receptor.

Harnessing the Phytotherapeutic Treasure Troves of the Ancient Medicinal Plant Azadirachta indica (Neem) and Associated Endophytic Microorganisms.

Azadirachta indica, commonly known as neem, is an evergreen tree of the tropics and sub-tropics native to the Indian subcontinent with demonstrated ethnomedicinal value and importance in agriculture as well as in the pharmaceutical industry. This ancient medicinal tree, often called the "wonder tree", is regarded as a chemical factory of diverse and complex compounds with a plethora of structural scaffolds that is very difficult to mimic by chemical synthesis. Such multifaceted chemical diversity leads to a fantastic repertoire of functional traits, encompassing a wide variety of biological activity and unique modes of action against specific and generalist pathogens and pests. Until now, more than 400 compounds have been isolated from different parts of neem including important bioactive secondary metabolites such as azadirachtin, nimbidin, nimbin, nimbolide, gedunin, and many more. In addition to its insecticidal property, the plant is also known for antimicrobial, antimalarial, antiviral, anti-inflammatory, analgesic, antipyretic, hypoglycaemic, antiulcer, antifertility, anticarcinogenic, hepatoprotective, antioxidant, anxiolytic, molluscicidal, acaricidal, and antifilarial properties. Notwithstanding the chemical and biological virtuosity of neem, it has also been extensively explored for associated microorganisms, especially a class of mutualists called endophytic microorganisms (or endophytes). More than 30 compounds, including neem "mimetic" compounds, have been reported from endophytes harbored in the neem trees in different ecological niches. In this review, we provide an informative and in-depth overview of the topic that can serve as a point of reference for an understanding of the functions and applications of a medicinal plant such as neem, including associated endophytes, within the overall theme of phytopathology. Our review further exemplifies the already-noted current surge of interest in plant and microbial natural products for implications both within the ecological and clinical settings, for a more secure and sustainable future.

Sexing of pre-implantation ovine embryos through polymerase chain reaction-based amplification of GAPDH, SRY and AMEL genes.

The ability to identify the sex of embryo and control of sex ratio has a great commercial importance to livestock industry. Prediction of embryonic sex could be useful in the management decisions of sex selection in breeding programs. Several methods have been attempted to determine the sex but the polymerase chain reaction (PCR)-based sexing method is generally favoured, as it is cost effective, simple and reliable. The aim of the present study was to identify sex of sheep embryos produced in vitro through amplification of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), sex-determining region Y (SRY) and amelogenin genes present in genomic DNA (gDNA) of embryos through PCR. To avoid false interpretation of the result by no amplification of SRY in female embryos, a duplex PCR was approached to amplify combinedly SRY and GAPDH genes. Sex-specific blood was used in PCR as positive control. In vitro sheep embryos were produced as per standardized protocol of laboratory. Sexing of sex-specific blood and in vitro produced embryos were approached though PCR to amplify the respective genes using gDNA present in the sample without its traditional isolation. The accuracy of sex prediction for embryos was 100% by this procedure.

The Roles of Microtubules and Membrane Tension in Axonal Beading, Retraction, and Atrophy.

Axonal beading, or the formation of a series of swellings along the axon, and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here, we report controlled experiments that can induce either beading or retraction and follow the time evolution of these responses. By making quantitative analysis of the shape modes under different conditions, measurement of membrane tension, and using theoretical considerations, we argue that membrane tension is the main driving force that pushes cytosol out of the axon when microtubules are degraded, causing axonal thinning. Under pharmacological perturbation, atrophy is always retrograde, and this is set by a gradient in the microtubule stability. The nature of microtubule depolymerization dictates the type of shape transformation, vis-à-vis beading or retraction. Elucidating the mechanisms of these shape transformations may facilitate development of strategies to prevent or arrest axonal atrophy due to neurodegenerative conditions.

Nickel, Cobalt and Palladium Catalysed C-H Functionalization of Un-Activated C(sp3 )-H Bond.

This review represents nickel, cobalt and palladium catalyzed C-H activation of sp3 carbon, with special emphasis on methyl C-H activation. The importance of directing group assistance and effect of ligand on ß- or γ- C(sp3 )-H activation is summarized in this review. The mechanistic study for Ni, Co and Pd catalyzed sp3 C-H bond functionalization also discussed in detail.

Liver paired exchange: Can the liver emulate the kidney?

Kidney paired exchange (KPE) constitutes 12% of all living donor kidney transplantations (LDKTs) in the United States. The success of KPE programs has prompted many in the liver transplant community to consider the possibility of liver paired exchange (LPE). Though the idea seems promising, the application has been limited to a handful of centers in Asia. In this article, we consider the indications, logistical issues, and ethics for establishing a LPE program in the United States with reference to the principles and advances developed from experience with KPE. Liver Transplantation 24 677-686 2018 AASLD.

Long-term health-related quality of life in living liver donors: A south Asian experience.

AIM: The aim of this study was to evaluate long-term health-related quality of life (HRQOL), changes in lifestyle, and complications in living liver donors at a single transplant center from southern India. METHODS: A total of 64 consecutive living liver donors from 2008 to 2011 were evaluated; 46 of 64 donors completed the short form 36 (SF-36) via telephonic interviews or clinic consultations. Mean follow-up was 48 months (range: 37-84 months). RESULTS: There was no mortality in the donors evaluated. Overall morbidity was 23%, which included wound infections (4.3%), incisional hernia (2.1%), biliary leak (4.3%), and nonspecific complaints regarding the incision site (15.2%). All 46 donors who completed the SF-36 had no change in career path or predonation lifestyle. A total of 40 of 46 (87%) donors had no limitations, decrements, or disability in any domain, while six of 46 (13%) had these in some domains of which general health (GH) was most severely affected. CONCLUSIONS: Living donor hepatectomy is safe with acceptable morbidity and excellent long-term HRQOL with no change in career path or significant alteration of lifestyle for donors.

Quaternary structures of opsin in live cells revealed by FRET spectrometry.

Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that initiates phototransduction in the retina. The receptor consists of the apoprotein opsin covalently linked to the inverse agonist 11-cis retinal. Rhodopsin and opsin have been shown to form oligomers within the outer segment disc membranes of rod photoreceptor cells. However, the physiological relevance of the observed oligomers has been questioned since observations were made on samples prepared from the retina at low temperatures. To investigate the oligomeric status of opsin in live cells at body temperatures, we utilized a novel approach called Förster resonance energy transfer spectrometry, which previously has allowed the determination of the stoichiometry and geometry (i.e. quaternary structure) of various GPCRs. In the current study, we have extended the method to additionally determine whether or not a mixture of oligomeric forms of opsin exists and in what proportion. The application of this improved method revealed that opsin expressed in live Chinese hamster ovary (CHO) cells at 37°C exists as oligomers of various sizes. At lower concentrations, opsin existed in an equilibrium of dimers and tetramers. The tetramers were in the shape of a near-rhombus. At higher concentrations of the receptor, higher-order oligomers began to form. Thus, a mixture of different oligomeric forms of opsin is present in the membrane of live CHO cells and oligomerization occurs in a concentration-dependent manner. The general principles underlying the concentration-dependent oligomerization of opsin may be universal and apply to other GPCRs as well.

Expression of Apoptotic and Antioxidant Enzyme Genes in Sheep Oocytes and In Vitro Produced Embryos.

The present study was to find out the expression pattern and relative expression level of apoptotic (Bcl2, Bax, Casp3, and PCNA) and antioxidant enzyme [(GPx, Cu/Zn-SOD (SOD1) and Mn-SOD (SOD2)] genes in sheep oocytes and developing embryos produced in vitro by conventional RT-PCR and real time qPCR, respectively. Different developmental stages of embryos were produced in vitro from oocytes collected from local slaughter house ovaries. RT-PCR amplicons showed expression of Bcl2 and PCNA in all stages except at morula. In contrast Bax and Casp3 were expressed in all stages. GPx and SOD1 were expressed in all stages but SOD2 was not expressed in 8-16 cells, although expressed in the remaining stages. The qPCR analysis reflected that Bcl2 expression was significantly (P < 0.05) downregulated in morula and maximum upregulated expression was observed in in vitro matured oocytes. Higher upregulated expression (P < 0.05) of Bax was in morula and downregulated expression was at 2-4 cells. Casp3 was significantly upregulated at 8-16 cells and downregulated in in vitro matured oocyte. PCNA expression was highest at blastocyst and least expression was at morula. GPx was expressed significantly highest in matured oocytes and least expression was at zygote. SOD1 was expressed significantly highest at 8-16 cells and least expression was at zygote. Expression of SOD2 was least among all the antioxidant enzymes but significantly higher expression of SOD2 was in immature oocyte; however, least expression was at 8-16 cells. It can be concluded from the study that the sheep embryos produced in vitro are highly sensitive to culture condition, which alters the expression level of apoptotic and antioxidant enzyme genes.

The sigma-1 receptors are present in monomeric and oligomeric forms in living cells in the presence and absence of ligands.

The sigma-1 receptor (S1R) is a 223-amino-acid membrane protein that resides in the endoplasmic reticulum and the plasma membrane of some mammalian cells. The S1R is regulated by various synthetic molecules including (+)-pentazocine, cocaine and haloperidol and endogenous molecules such as sphingosine, dimethyltryptamine and dehydroepiandrosterone. Ligand-regulated protein chaperone functions linked to oxidative stress and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and neuropathic pain have been attributed to the S1R. Several client proteins that interact with S1R have been identified including various types of ion channels and G-protein coupled receptors (GPCRs). When S1R constructs containing C-terminal monomeric GFP2 and YFP fusions were co-expressed in COS-7 cells and subjected to FRET spectrometry analysis, monomers, dimers and higher oligomeric forms of S1R were identified under non-liganded conditions. In the presence of the prototypic S1R agonist, (+)-pentazocine, however, monomers and dimers were the prevailing forms of S1R. The prototypic antagonist, haloperidol, on the other hand, favoured higher order S1R oligomers. These data, in sum, indicate that heterologously expressed S1Rs occur in vivo in COS-7 cells in multiple oligomeric forms and that S1R ligands alter these oligomeric structures. We suggest that the S1R oligomerization states may regulate its function(s).

Maturation timing and fetal bovine serum concentration for developmental potential of sheep oocytes in vitro.

The success of in vitro embryo production (IVEP) in animals has improved over time, employing a variety of culture media. Here, we assessed the maturation timing and developmental potential of sheep oocytes in vitro at different concentrations of fetal bovine serum (FBS): Cumulus oocyte complexes (COCs) were aspirated from follicles (2-6 mm) of sheep ovaries collected from local slaughter house. COCs were randomly divided into two groups and matured at 38.5'C, 5% CO2 for 24 h (Group I) and 27 h (Group II). Oocytes cultured for 27 h showed significantly (P <0.05) more maturation than those cultured for 24 h (82 vs. 76%) followed by more cleavage (35 vs. 30%), morula (53 vs. 39%) and blastocyst (17 vs. 11%) percentage. In the second experiment, oocytes were randomly divided into two groups and matured with 10% FBS (Group I) and 20% FBS (Group II) for 27 h supplemented with pyruvate, glutamine, LH, FSH and estradiol. After maturation, oocytes were fertilized by fresh semen for 18 h. Presumptive zygotes in both the groups were again divided into two groups and culturedin 10 and 20% FBS during post fertilization period, respectively. Different FBS concentration in maturation medium did not influence maturation percentage (82 vs. 79%) significantly. Out of culture groups, presumptive zygotes matured in 20% FBS and cultured in 20% FBS during post fertilization period showed significant increase in cleavage percentage (44 vs. 39, 35 and 27%) as compared to other groups but subsequent development to morula (55 vs. 53, 43 and 40%) and blastocyst (20 vs. 17, 16 and 15%) percentage were more in the group matured in 10% FBS and cultured in 20% FBS during post fertilization period.

TiO2-decorated graphite nanoplatelet nanocomposites for high-temperature sensor applications.

Temperature and/or composition mapping inside high temperature energy conversion and storage devices are challenging, yet of critical importance to improve the material design for optimum performance. Here, the great potential of TiO2 nanoparticle (NP)-decorated graphite nanoplatelet (GNP) nanocomposites as high temperature thermal senors or gas sensors is reported. Effects of the GNP substrate on phonon confinement in Raman spectrum, grain growth, and phase stability of anatase TiO2 NPs at high temperatures are systematically studied. Thermally sensitive Raman signatures, indicating the ultrafast grain growth of TiO2 NPs in response to short thermal shock treatments (0.1-25 s) at high temperatures, are exploited for high temperature thermal sensing applications. A very high accuracy of nearly 98% in temperature measurements is demonstrated for a given short-time thermal exposure. Thermal stability of anatase TiO2 NPs against transformation into the rutile phase in TiO2 -GNP nancomposites is substantially increased by controlling the surface area of the substrate, which would significantly improve the performance of TiO2 -based high temperature gas sensors.

Better innovate than compromise: a novel hepatic outflow reconstruction technique in pediatric living donor liver transplantation.

Pediatric LDLT using donors with unfavorable vascular anatomy is challenging in terms of donor safety, and complexity of reconstruction in the recipient. We describe an innovative technique of hepatic venous outflow reconstruction involving the recipient RHV, in the presence of a rudimentary RHV in the donor. The postoperative course of the donor and recipient was uneventful with satisfactory venous outflow in both. This technique avoided the use of prosthetic material, an important consideration given the recipient age and requirement for growth. This shows that donors previously considered unsuitable for donation can be utilized safely as long as principles of vascular anastomosis are adhered to. Moreover, it highlights that innovation is sometimes necessary to avoid compromise in donor safety.

Effect of acute hexavalent chromium exposure on pituitary-thyroid axis of a freshwater fish, Channa punctatus (Bloch).

Acute exposure to hexavalent chromium (10 mg L(-1) , 20 mg L(-1) , and 40 mg L(-1) potassium dichromate for 96 h) dose-dependently affected the pituitary-thyroid axis of teleost, Channa punctatus. Significant hypertrophy of the thyroid follicle was observed in 20 mg L(-1) and 40 mg L(-1) groups; the follicular epithelium was however hypertrophied only in 40 mg L(-1) group. The colloid depletion in the lumen of thyroid follicle was evident in 20 mg L(-1) and 40 mg L(-1) groups. Serum thyroid hormones (thyroxine/T4 and triiodothyronine/T3) level increased significantly at both the higher doses. Increased immunointensity and significant hypertrophy of the pituitary thyrotrophs (anti TSHß-immunoreactive cells) was observed in both 20 mg L(-1) and 40 mg L(-1) chromium-exposed fish. The increased thyroid hormones secretion observed in this study might be an adaptive response of the pituitary-thyroid axis under acute chromium-induced stress condition to maintain homeostasis. The long-term Cr(VI) exposures, however, may lead to attenuation/exhaustion of the pituitary-thyroid axis and pose serious threat to fish health and affect their population.

Acute spill-mimicking exposure effect of hexavalent chromium on the pituitary-ovarian axis of a teleost, Channa punctatus (Bloch).

Acute exposure to hexavalent chromium (as 10, 20, and 40 mg/L potassium dichromate for 96 h) adversely affected the pituitary-ovarian axis of a teleost Channa punctatus. The toxic impact of metal exposure on fish ovary was revealed in the form of increased percentage of atretic follicles, significantly in 20 mg/L and 40 mg/L exposure groups. The follicular atresia mostly occurred in vitellogenic (stage II and stage III) oocytes. Reduction of serum level of 17ß-estradiol was also significant in 20 mg/L and 40 mg/L exposure groups. The increase of LH-immunointensity of pituitary gonadotrophs (LHß-immunoreactive cells) and their hypertrophy was evident, significantly in fish of 40 mg/L exposed group. Thus, the present acute metal spill-mimicking laboratory study clearly demonstrated that short-term exposures to high doses of hexavalent chromium may disrupt reproduction of the fish and affect their population.