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Ynamide, a unique species with inherited polarization of nitrogen lone pair electron to triple bond, has been largely used for the developement of novel synthetic methods and the construction of unusual N-bearing heterocycles. The reaction versatility of ynamide on umpolung reactivity, radical reactions and asymmetric synthesis have been recently reviewed. This review provides an overall scenic view into the gold catalyzed transformation of ynamides. The ynamides reactivity towards nitrogen-transfer reagents, such as azides, nitrogen ylides, isoxazoles, and anthranils; oxygen atom-transfer reagents, like nitrones, sulfoxides, and pyridine N-oxides; and carbon nucleophiles under gold catalysis are herein uncovered. The scope as well the mechanistic insights of each reaction is also briefed., (© 2021 The Chemical Society of Japan & Wiley-VCH GmbH.)

We employed an Illumina-based high-throughput metagenomics sequencing approach to unveil the rhizosphere and root endosphere microbial community associated with an organically grown Camellia population located at the Experimental Garden for Plantation Crops, Assam (India). The de novo assembled tea root endosphere metagenome contained 24,231 contigs (total 7,771,089 base pairs with an average length of 321 bps), while tea rhizosphere soil metagenome contained 261,965 sequences (total 230,537,174 base pairs, average length 846). The most prominent rhizobacteria belonged to the genera, viz., Bacillus (10.35%), Candidatus Solibacter (6.36%), Burkholderia (5.19%), Pseudomonas (3.9%), Streptomyces (3.52%), and Bradyrhizobium (2.77%), while the root endosphere was dominated by bacterial genera, viz., Serratia (46.64%), Methylobacterium (8.02%), Yersinia (5.97%), Burkholderia (2.05%), etc. The presence of few agronomically important bacterial genera, Bradyrhizobium, Rhizobium (each 0.93%), Sinorhizobium (0.34%), Azorhizobium, and Flavobacterium (0.17% each), was also detected in the root endosphere. KEGG pathway mapping indicated the presence of microbial metabolic pathway genes related to tyrosine metabolism, tryptophan metabolism, glyoxylate, and dicarboxylate metabolism which play important roles in endosphere activities, including survival, growth promotion, and host adaptation. The root endosphere microbiome also contained few important plant growth promoting traits related to phytohormone production, abiotic stress alleviation, mineral solubilization, and plant disease suppression., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs., Methods: Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis., Findings: 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks., Interpretation: Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks., Funding: UKRI-MRC and NIHR., Competing Interests: KK is Director of the University of Leicester Centre for Black Minority Ethnic Health, Trustee of the South Asian Health Foundation, Chair of the Ethnicity Subgroup of the UK Government Scientific Advisory Group for Emergencies (SAGE) and Member of Independent SAGE. SC is Deputy Medical Director of the General Medical Council, UK Honorary Professor, University of Leicester. MP reports grants from Sanofi, grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work. KW, ICM, CAM, LBN, ALG, CM, LB, MG, FW, AAO, OH, AG, CJ, MDT, SS, BG, AA, SZ, RR and LJG have no competing interests to declare., (© 2021 The Authors.)

Introduction: As the world continues to grapple with the COVID-19 pandemic, emerging evidence suggests that individuals from ethnic minority backgrounds may be disproportionately affected. The United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) project has been initiated to generate rapid evidence on whether and why ethnicity affects COVID-19 diagnosis and clinical outcomes in healthcare workers (HCWs) in the UK, through five interlinked work packages/work streams, three of which form the basis of this protocol. The ethico-legal work (Work Package 3) aims to understand and address legal, ethical and acceptability issues around big data research; the HCWs' experiences study (Work Package 4) explores their work and personal experiences, perceptions of risk, support and coping mechanisms; the stakeholder engagement work (Work Package 5) aims to provide feedback and support with the formulation and dissemination of the project recommendations., Methods and Analysis: Work Package 3 has two different research strands: (A) desk-based doctrinal research; and (B) empirical qualitative research with key opinion leaders. For the empirical research, in-depth interviews will be conducted digitally and recorded with participants' permission. Recordings will be transcribed, coded and analysed using thematic analysis. In Work Package 4, online in-depth interviews and focus groups will be conducted with approximately 150 HCWs, from across the UK, and these will be recorded with participants' consent. The recordings will be transcribed and coded and data will be analysed using thematic analysis. Work Package 5 will achieve its objectives through regular group meetings and in-group discussions., Ethics and Dissemination: Ethical approval has been received from the London-Brighton & Sussex Research Ethics Committee of the Health Research Authority (Ref No 20/HRA/4718). Results of the study will be published in open-access journals, and disseminated through conference presentations, project website, stakeholder organisations, media and scientific advisory groups., Trial Registration Number: ISRCTN11811602., Competing Interests: Competing interests: MP reports grants and personal fees from Gilead Sciences and personal fees from QIAGEN, outside the submitted work. IA reports personal fees from House of Lords, grants from Bill & Melinda Gates Foundation and grants from NIHR, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Type 2 immunity helps protect the host from infection, but it also plays key roles in tissue homeostasis, metabolism, and repair. Unfortunately, inappropriate type 2 immune reactions may lead to allergy and asthma. Group 2 innate lymphoid cells (ILC2s) in the lungs respond rapidly to local environmental cues, such as the release of epithelium-derived type 2 initiator cytokines/alarmins, producing type 2 effector cytokines such as IL-4, IL-5, and IL-13 in response to tissue damage and infection. ILC2s are associated with the severity of allergic asthma, and experimental models of lung inflammation have shown how they act as playmakers, receiving signals variously from stromal and immune cells as well as the nervous system and then distributing cytokine cues to elicit type 2 immune effector functions and potentiate CD4 + T helper cell activation, both of which characterize the pathology of allergic asthma. Recent breakthroughs identifying stromal- and neuronal-derived microenvironmental cues that regulate ILC2s, along with studies recognizing the potential plasticity of ILC2s, have improved our understanding of the immunoregulation of asthma and opened new avenues for drug discovery.

Type 2 innate lymphoid cells (ILC2) contribute to immune homeostasis, protective immunity and tissue repair. Here we demonstrate that functional ILC2 cells can arise in the embryonic thymus from shared T cell precursors, preceding the emergence of CD4 + CD8 + (double-positive) T cells. Thymic ILC2 cells migrated to mucosal tissues, with colonization of the intestinal lamina propria. Expression of the transcription factor RORα repressed T cell development while promoting ILC2 development in the thymus. From RNA-seq, assay for transposase-accessible chromatin sequencing (ATAC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq) data, we propose a revised transcriptional circuit to explain the co-development of T cells and ILC2 cells from common progenitors in the thymus. When Notch signaling is present, BCL11B dampens Nfil3 and Id2 expression, permitting E protein-directed T cell commitment. However, concomitant expression of RORα overrides the repression of Nfil3 and Id2 repression, allowing ID2 to repress E proteins and promote ILC2 differentiation. Thus, we demonstrate that RORα expression represents a critical checkpoint at the bifurcation of the T cell and ILC2 lineages in the embryonic thymus.

A nickel(II) terephthalate complex, viz. [Ni(C 6 H 4 N 2 ) 2 (H 2 O) 4 ](O 2 CC 6 H 4 CO 2 )·4H 2 O, has been synthesized and studied by single-crystal X-ray diffraction. It crystallizes in the triclinic space group P . The crystal structure shows an approximately octa-hedral coordination environment of the complex with the [Ni(H 2 O) 4 (3-NCpy) 2 ] 2+ (3-NCpy is pyridine-3-carbo-nitrile) cation associated with four free water mol-ecules and hydrogen bonded to a terephthalate dianion [graph set R 2 2 (8)]. The supra-molecular structure of the compound is stabilized by a three-dimensional array of O-H⋯O and O-H⋯N hydrogen bonds, along with π-π stacked pyridine-3-carbo-nitrile rings and C-H⋯O inter-actions., (© Gogoi and Das 2021.)

Type-2 immunity is characterised by interleukin (IL)-4, IL-5 and IL-13, eosinophilia, mucus production, IgE, and alternatively activated macrophages (AAM). However, despite the lack of neutrophil chemoattractants such as CXCL1, neutrophils, a feature of type-1 immunity, are observed in type-2 responses. Consequently, alternative mechanisms must exist to ensure that neutrophils can contribute to type-2 immune reactions without escalation of deleterious inflammation. We now demonstrate that type-2 immune-associated neutrophil infiltration is regulated by the mouse RNase A homologue, eosinophil-associated ribonuclease 11 (Ear11), which is secreted by AAM downstream of IL-25-stimulated ILC2. Transgenic overexpression of Ear11 resulted in tissue neutrophilia, whereas Ear11-deficient mice have fewer resting tissue neutrophils, whilst other type-2 immune responses are not impaired. Notably, administration of recombinant mouse Ear11 increases neutrophil motility and recruitment. Thus, Ear11 helps maintain tissue neutrophils at homoeostasis and during type-2 reactions when chemokine-producing classically activated macrophages are infrequently elicited.

Aims: Our aim is to develop 3D printed chitosan-gelatin-alginate scaffolds using a costeffective in house designed 3D printer followed by its characterization. To observe chondrocyte differentiation on 3D printed scaffolds as part of scaffold application., Background: Cartilage is considered to be a significant tissue in humans. It is present in between the rib cage, the lobe of the ear, nasal septum in the form of hyaline cartilage, in between ribs costal cartilage, intervertebral discs in the form of fibrocartilage, meniscus, larynx, epiglottis and between various joints of bones. To replace or repair damaged tissues due to disorders or trauma, thousands of surgical procedures are performed daily. 3D printing plays a crucial role in the development of controlled porous architectures of scaffolds for cartilage tissue regeneration. Advancement in 3D printing technology like inkjet, micro- extrusion in 3D bioprinting, Laser-assisted 3D Bioprinting (LAB), stereolithography combination with biomaterials plays a crucial role in the quick development of patient-specific articulating cartilage when need in a short period frame., Objective: Our objective is to develop different compositions of chitosan-gelatin-alginate composite hydrogel scaffolds with controlled porosity and architectures with the application of 3D printing and observe the growth of cartilage on it. To achieve as proposed, an in-house 3D paste extruder printer was developed, which is capable of printing porous composite chitosan hydrogel scaffolds of desired architecture layer by layer. After the characterization of 3D printed chitosan composite scaffolds, the differentiation of chondrocyte was observed using hMSC., Methods: In present paper process for the development of chitosan-alginate-gelatin composite hydrogel, 3D printing, morphological characterization, and observation for differentiation of chondrocytes cells on 3D printed chitosan composite hydrogels is presented. The present study is divided into three parts: in first part development of composite chitosan-alginate-gelatin hydrogel with the utilization of in house customized assembled paste extruder based 3D printer, which is capable of printing chitosan composite hydrogels. In the second part, the characterization of 3D printed chitosan composite scaffolds hydrogel is performed for evaluating the morphological, mechanical, and physical properties. The prepared composite scaffolds were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction(XRD), Scanning Electron Microscopy SEM, swelling property, mechanical testing, porosity, etc. In the last part of the study, the differentiation of chondrocytes cells was observed with human Mesenchymal Stem Cells (hMSC) on 3D printed scaffolds and showed positive results for the same., Results: Stereolithography (STL) files of 3D models for porous chitosan composite were developed using Computer-Aided Design (CAD) and printed with a hydrogel flow rate within the range of 0.2-0.25 ml/min. The prepared scaffolds are highly porous, having optimum porosity, optimal mechanical strength to sustain the cartilage formation. The 3D printed chitosan composite scaffolds show supports for the differentiation of chondrocytes. The above study is helpful for in-vivo regeneration of cartilage for patients having related cartilage disorders., Conclusion: This method helps in regeneration of degenerated cartilage for patient-specific and form above experiment we also concluded that 3D printed chitosan scaffold is best suited for the regeneration of chondrocyte cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The 2019 novel coronavirus disease (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to global public health. Although primarily, the infection causes lung injury, liver enzyme abnormalities have also been reported to occur during the course of the disease. We conducted an extensive literature review using the PubMed database on articles covering a broad range of issues related to COVID-19 and hepatic injury. The present review summarizes available information on the spectrum of liver involvement, the possible mechanisms and risk factors of liver injury due to SARS-CoV-2 infection, and the prognostic significance of the presence of liver injury. Hopefully, this review will enable clinicians, especially the hepatologists, to understand and manage the liver derangements they may encounter in these patients better and provide guidance for further studies on the liver injury of COVID-19., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The 4-methyl-pyridine (4-Mepy) based dimeric copper(II) carboxyl-ate complex [Cu 2 (C 10 H 19 O 2 ) 4 (C 6 H 7 N) 2 ] or [Cu 2 ( μ -O 2 CC 9 H 19 ) 4 (4-Mepy) 2 ] crystallizes with triclinic ( P ) symmetry. The two Cu II ions exhibit a distorted square-pyramidal environment and are connected into a centrosymmetric paddle-wheel dinuclear cluster [Cu⋯Cu = 2.6472 (8) Å] via four bridging carboxyl-ate ligands arranged in the syn-syn coordination mode. The apical positions around the paddle-wheel copper centers are occupied by the N atoms of the 4-methyl-pyridine ligands. The structure exhibits disorder of the terminal alkyl carbon atoms in the deca-noate chains., (© Gogoi and Das 2020.)

This paper reports the first ever green synthesis of silver nanoplates using plant leaves having the special feature of showing the lotus effect. Eichhornia crassipes and Colocasia esculenta plant leaves were chosen for the purpose. The aqueous leaf extract of these plants was used as a reducing as well as stabilizing agent in the hydrothermal synthesis of silver nanoplates using silver nitrate as the precursor. Well dispersed silver nanoplates were formed. The appearance of two SPR (Surface Plasmon Resonance) bands corresponding to in-plane and out of plane vibration confirmed the formation of anisotropic nanostructures. The blue shift in peaks of the nanostructures in UV-visible spectra gave information about the stability of the nanoplates with time. Dynamic Light Scattering (DLS) and powder XRD were used to evaluate the ultimate average diameter and crystal structure of these nanostructures respectively. FESEM/EDX and HRTEM/SAED images also confirmed the formation of silver nanoplates. The FT-IR spectra helped to identify the reducing and stabilizing component of plant leaves extract in the formation of 2-D nanostructures. Preliminary antibacterial activity was examined using these nanoplates. A significant zone of inhibition was observed for S. aureus , a Gram positive bacterium., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Textile industries are currently not showing much interest in Ramie fibers due to the difficulties associated with their post-harvest downstream processing. The degumming chemicals are often detrimental to the environment upon discharged. Chemical degumming alone results in fibril-released coarse and brittle fibers. This problem has been addressed by combining partial chemical treatment with microbial degumming of the fibers for 72 h at 37 °C using a novel microbial formulation with Bacillus thuringiensis MCC2138 and Bacillus subtilis ABDR01. The extracellular microbial enzyme-based degumming without the release of fibrils produced a durable, soft, and lustrous fiber with higher tensile strength while utilizing fewer chemicals, thereby leading to lower discharge toxicity. The improved texture and strength compared to complete chemical treatment are attributed to even degumming of the fiber ensuring proper spinnability. Through this approach, Ramie is expected to gain visibility in the global textile market, thereby leading to Ramie cultivators' economic benefits., Competing Interests: The authors report no declarations of interest., (© 2020 The Authors.)

Brucellosis is a neglected zoonotic disease caused by alpha proteobacterial genus Brucella comprising of facultative intracellular pathogenic species that can infect both animals and humans. In this study, we aimed to identify genome-wide unique insertion sequence (IS) elements among Brucella abortus, B. melitensis, B. ovis, B. suis and B. canis for use in species differentiation by conducting an intensive in silico-based comparative genomic analysis. As a result, 25, 27, 37, 86 and 3 unique ISs were identified respectively and they had a striking pattern of distribution among them. To explain, a particular IS would be present in four species with 100% identity whereas completely absent in the fifth species. However, flanking regions of that IS element would be highly identical and conserved in all five species. Species-specific primers designed on these flanking conserved regions resulted in two different amplicons grouping the species into two: one that possesses IS and the other that lacks it. Seeking for species-specific amplicon size for particular species was sufficient to identify it irrespective of biovar. A multiplex PCR developed using these primers resulted in successful differentiation of the five species irrespective of biovars with significant specificity and sensitivity when examined on clinical samples.

Tea is a highly cross-pollinated, woody, perennial tree. High heterozygosity combined with a long gestational period makes conventional breeding a cumbersome process. Therefore, marker-assisted breeding is a better alternative approach when compared with conventional breeding. Considering the large genome size of tea (~3 Gb), information about simple sequence repeat (SSR) is scanty. Thus, we have taken advantage of the recently published tea genomes to identify large numbers of SSR markers in the tea. Besides the genomic sequences, we identified SSRs from the other publicly available sequences such as RNA-seq, GSS, ESTs and organelle genomes (chloroplasts and mitochondrial) and also searched published literature to catalog validated set of tea SSR markers. The complete exercise yielded a total of 935 547 SSRs. Out of the total, 82 SSRs were selected for validation among a diverse set of tea genotypes. Six primers (each with four to six alleles, an average of five alleles per locus) out of the total 27 polymorphic primers were used for a diversity analysis in 36 tea genotypes with mean polymorphic information content of 0.61-0.76. Finally, using all the information generated in this study, we have developed a user-friendly database (TeaMiD; http://indianteagenome.in:8080/teamid/) that hosts SSR from all the six resources including three nuclear genomes of tea and transcriptome sequences of 17 Camellia wild species. Database URL: http://indianteagenome.in:8080/teamid/., (© The Author(s) 2020. Published by Oxford University Press.)

The feasibility of bortezomib (BZB) in induction and reduced cytarabine doses in intensification was evaluated in children with relapsed acute lymphoblastic leukaemia (rALL) at a single centre in India. Of 55 children with rALL, 23 received supportive care and 7 refused treatment, with a median survival of 2 (interquartile range 1-6) months. Twenty-two (88%) of 25 children who were treated achieved second remission and 9 (69%) of 13 had end-of-induction minimal residual disease of <10 -4 . The lower cytarabine dose was associated with decreased hospitalisation. One-year event-free and overall survival for the treated group was 74·7% (95% confidence interval 52-88) and 79·6% (58-91) respectively., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Safe sleep recommendations for infants have been evolving over the past three decades. It has been shown that physicians' recommendations strongly influence parents' choice of infant sleep position. However, the proportion of physicians and/or nurses giving infant sleep advice to parents is reportedly low., Methods: A survey was conducted in South Dakota to evaluate pediatricians' and family practitioners' knowledge of safe sleep recommendations for infants. Survey questions assessed their beliefs regarding risk factors for sudden infant death syndrome (SIDS) and their recommendations for safe sleep environments provided to parents/caregivers., Results: Among the respondents, 98 percent felt that it is important to discuss SIDS with every parent and 80 percent of them indicated a need within their profession to have further information on the topic of SIDS. However, 31 percent of physicians with 16 years or more since training and 64.5 percent of those with less than 16 years since training did provide safe sleep advice to parents and caregivers., Conclusions: Despite the knowledge of SIDS risk factors, gaps were seen in dissemination of information regarding all risk factors to parents. While sleep position, postnatal exposures and breast feeding were more likely to be addressed, other elements of a safe sleep environment such as bedding surface, bed sharing, pacifier use and room ventilation were less likely to be covered. These findings indicate the need for improved health care provider education/communication in South Dakota., (Copyright© South Dakota State Medical Association.)

Group 2 innate lymphoid cells (ILC2) increase in frequency in eczema and allergic asthma patients, and thus represent a new therapeutic target cell for type-2 immune-mediated disease. The bromodomain and extra-terminal (BET) protein family of epigenetic regulators are known to support the expression of cell cycle and pro-inflammatory genes during type-1 inflammation, but have not been evaluated in type-2 immune responses. We isolated human ILC2 and examined the capacity of the BET protein inhibitor, iBET151, to modulate human ILC2 activation following IL-33 stimulation. iBET151 profoundly blocked expression of genes critical for type-2 immunity, including type-2 cytokines, cell surface receptors and transcriptional regulators of ILC2 differentiation and activation. Furthermore, in vivo administration of iBET151 during experimental mouse models of allergic lung inflammation potently inhibited lung inflammation and airways resistance in response to cytokine or allergen exposure. Thus, iBET151 effectively prevents human ILC2 activation and dampens type-2 immune responses.

Salmonella is a major cause of morbidity and mortality in the developing and underdeveloped nations. Being a foodborne disease, Salmonella infection is primarily contracted through the ingestion of contaminated food or water, or due to close contact with infected/carrier individuals. It is an intracellular pathogen, which can survive and replicate in various cells including macrophages, dendritic cells, epithelial cells, and other white blood cells. Once Salmonella crosses the intestinal barrier, it disseminates to various systemic sites by circulation via immune cells. One of the major cell types which are involved in Salmonella infection are host macrophages. They are the niche for intracellular survival and proliferation of Salmonella and a mode of dissemination to distal systemic sites. These cells are very crucial as they mediate the mounting of an appropriate innate and adaptive anti-Salmonella immune response. In this review, we have tried to concise the current knowledge of complex interactions that occur between Salmonella and macrophages., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Salmonella being a successful pathogen, employs a plethora of immune evasion mechanisms. This contributes to pathogenesis, persistence and also limits the efficacy of available treatment. All these contributing factors call upon for new drug targets against Salmonella. For the first time, we have demonstrated that Salmonella upregulates sirtuin 2 (SIRT2), an NAD+ dependent deacetylase in dendritic cells (DC). SIRT2 upregulation results in translocation of NFκB p65 to the nucleus. This further upregulates NOS2 transcription and nitric oxide (NO) production. NO subsequently shows antibacterial activity and suppresses T cell proliferation. NOS2 mediated effect of SIRT2 is further validated by the absence of effect of SIRT2 inhibition in NOS2-/- mice. Inhibition of SIRT2 increases intracellular survival of the pathogen and enhances antigen presentation in vitro. However, in vivo SIRT2 inhibition shows lower bacterial organ burden and reduced tissue damage. SIRT2 knockout mice also demonstrate reduced bacterial organ burden compared to wild-type mice. Collectively, our results prove the role of SIRT2 in Salmonella pathogenesis and the mechanism of action. This can aid in designing of host-targeted therapeutics directed towards inhibition of SIRT2., Competing Interests: The authors have declared that no competing interests exist.

Background: Helicobacter pylori, the gastric bacterium, is widely known to be one of the most genetically diverse group of organisms whose pathogenesis as well as the diversity in infection outcome may be attributed to a variety of virulent genes., Aim: This study aimed to study the molecular profile of H. pylori vacA gene by determining the phylogenetic relatedness and genetic diversity of the strains isolated in this region with those of other geographical regions., Materials and Methods: A total of twenty H. pylori clinical strains were isolated from randomly selected 100 patients suffering from gastroduodenal diseases as well as endoscopically normal patients in a cross-sectional hospital-based setting from January 2016 to May 2017. VacA signal sequence and mid regions of H. pylori were amplified by polymerase chain reaction followed by DNA sequencing and phylogenetic analysis., Results: VacA s1m1 allelic variant was more prevalent in our study, regardless of the clinical outcomes. Phylogenetic analysis of VacA s1 strains revealed clustering of most of the strains. VacA m1 strains clustered with Bangladesh strains which is a country nearest to India., Conclusion: Prevalence of VacA s1m1 strains may account for high risk of transmission of this gastric pathogen and the overall risk of acquiring infection. Phylogenetic analysis results suggests the prevalence of high genetic diversity in our region. Our findings may aid in developing a better understanding of the genetic structure of H. pylori and the pathophysiology of associated diseases, thus facilitating the implementation of various treatment options., Competing Interests: There are no conflicts of interest

CD4+ T-cell response is vital for successful clearance of Salmonella Typhimurium infection. Efficient antigen presentation is crucial for effective CD4+ T-cell response. Previous study has reported that Salmonella abrogates antigen presentation capacity of dendritic cells in order to escape host adaptive immune response. In this study, we have elucidated the mechanism of Salmonella-mediated downregulation of the total cellular Major Histocompatibility Complex (MHC) II pool in dendritic cells. Infected dendritic cells show upregulation of E3 ubiquitin ligase, MARCH1 expression and K63-linked ubiquitination of MHC II. Salmonella infection also enhances the internalisation of ubiquitin-tagged MHC II molecules that are subsequently degraded by endosomal proteases. In addition, Salmonella regulates the activation of endosomal proteases by lowering the pH of endosomes. In infected dendritic cells, Salmonella delays NOX2 recruitment to the phagosomes thereby preventing its alkalinisation. NOX2 is a significant part of innate immune response against pathogens as it is responsible for Reactive Oxygen Species (ROS) production. In this study, we have demonstrated how Salmonella evades MHC II-mediated adaptive immune response in dendritic cells through enhanced endosomal proteolysis. To escape host CD4+T response, Salmonella delays NOX2 recruitment, an innate immune response element to the phagosomes.

Assays for the rapid detection and accurate differentiation of Burkholderia pseudomallei from near-neighbor species are urgently needed in melioidosis endemic regions due to the high associated mortality and biowarfare importance of the pathogen. PCR-based methods have revolutionized this field due to the accuracy, sensitivity, and specificity that are achievable in a rapid way. In this study, a compound molecular detection system, consisting of a duplex PCR assay, was developed for the specific identification of Burkholderia pseudomallei and differentiation from other Burkholderia species. For accurate identification of B. pseudomallei, we deciphered and adopted a novel gene termed putative fimbrial chaperone (fimC). d-beta hydroxybutyrate dehydrogenase (bdha), reported previously by our group for sequence-based differentiation of B. pseudomallei from other Burkholderia species, was employed as a genus-specific target. Enforcement of an internal amplification control in the PCR format ruled out possible false negative results in the assay. Thus, the developed PCR assay was highly specific (100%) in its detection features, and a clear detection sensitivity of 10 pg/μl for purified gDNA and 3 × 10 3  CFU/ml for B. pseudomallei spiked urine was recorded. Successful identification of B. pseudomallei from an experimental mouse model at both the genus and species level revealed the accurate diagnostic efficiency of the duplex PCR method., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Persistently high maternal mortality levels are a concern in developing countries. In India, monetary incentive schemes have increased institutional delivery rates appreciably, but have not been equally successful in reducing maternal mortality. Maternal outcomes are affected by quality of obstetric care and socio-cultural norms. In this light there is need to examine the quality of care provided to women delivering in institutions., Objective: This study aimed to examine pregnant women's expectations of high-quality care in public health facilities in Uttar Pradesh, India, and to contrast this with provider's perceptions of the same, as well as the barriers that limit their ability to provide high-quality care., Methods: A qualitative descriptive analysis was conducted on data from two studies - focus group discussions with rural women in their last trimester of pregnancy (conducted in 2014) to understand women's experience and satisfaction with maternal care services, and in-depth interviews with care providers (conducted in 2016-17) to understand provision of person-centred care. Provider perspectives were matched with themes of women's perspectives on quality of childbirth care in facilities., Results: Major themes of care prioritised by women included availability of doctors at the facility; availability of medicines; food; ambulance services; maintenance of cleanliness and hygiene; privacy; good and safe delivery with no complications; client-provider interaction; financial cost of care. Many women also voiced no expectation of care, indicating disillusionment from the existing system. Providers concurred with women on all themes of care except availability of doctors, as they felt that trained nurses were proficient in conducting deliveries., Conclusions: This study shows that women have clear expectations of quality care from facilities where they go to deliver. Understanding their expectations and matching them with providers' perspectives of care is critical for efforts to improve the quality of care and thereby impact maternal outcomes.

Magnetic liposome-mediated combined chemotherapy and hyperthermia is gaining importance as an effective therapeutic modality for cancer. However, control and maintenance of optimum hyperthermia are major challenges in clinical settings due to the overheating of tissues. To overcome this problem, we developed a novel magnetic liposomes formulation co-entrapping a dextran coated biphasic suspension of La 0.75 Sr 0.25 MnO 3 (LSMO) and iron oxide (Fe 3 O 4 ) nanoparticles for self-controlled hyperthermia and chemotherapy. However, the general apprehension about biocompatibility and safety of the newly developed formulation needs to be addressed. In this work, in vitro and in vivo biocompatibility and therapeutic evaluation studies of the novel magnetic liposomes are reported. Biocompatibility study of the magnetic liposomes formulation was carried out to evaluate the signs of preliminary systemic toxicity, if any, following intravenous administration of the magnetic liposomes in Swiss mice. Therapeutic efficacy of the magnetic liposomes formulation was evaluated in the fibrosarcoma tumour bearing mouse model. Fibrosarcoma tumour-bearing mice were subjected to hyperthermia following intratumoral injection of single or double doses of the magnetic liposomes with or without chemotherapeutic drug paclitaxel. Hyperthermia (three spurts, each at 3 days interval) with drug loaded magnetic liposomes following single dose administration reduced the growth of tumours by 2.5 fold (mean tumour volume 2356 ± 550 mm 3 ) whereas the double dose treatment reduced the tumour growth by 3.6 fold (mean tumour volume 1045 ± 440 mm 3 ) compared to their corresponding control (mean tumour volume 3782 ± 515 mm 3 ). At the end of the tumour efficacy studies, the presence of MNPs was studied in the remnant tumour tissues and vital organs of the mice. No significant leaching or drainage of the magnetic liposomes during the study was observed from the tumour site to the other vital organs of the body, suggesting again the potential of the novel magnetic liposomes formulation for possibility of developing as an effective modality for treatment of drug resistant or physiologically vulnerable cancer.

Objective: The aim of this study was to evaluate the magnetic resonance imaging (MRI) findings of caudal regression syndrome (CRS) and concomitant anomalies in pediatric patients., Materials and Methods: A hospital-based cross-sectional retrospective study was conducted. The study group comprised 21 pediatric patients presenting to the Departments of Radiodiagnosis and Pediatric Surgery in a tertiary care hospital from May 2011 to April 2016. All patients were initially evaluated clinically followed by MRI., Results: In our study, 21 pediatric patients were diagnosed with sacral agenesis/dysgenesis related to CRS. According to the Pang's classification, 2 (9.5%) patients were Type I, 5 (23.8%) patients were Type III, 7 (33.3%) patients were Type IV, and 7 (33.3%) patients were of Type V CRS. Clinically, 17 (81%) patients presented with urinary incontinence, 6 (28.6%) with fecal incontinence, 9 patients (42.9%) had poor gluteal musculatures and shallow intergluteal cleft, 7 (33.3%) patients had associated subcutaneous mass over spine, and 6 (28.6%) patients presented with distal leg muscle atrophy. MRI showed wedge-shaped conus termination in 5 (23.8%) patients and bulbous conus termination in 3 (14.3%) patients above the L1 vertebral level falling into Group 1 CRS while 7 (33.3%) patients had tethered cord and 6 (28.6%) patients had stretched conus falling into Group 2 CRS., Conclusion: MRI is the ideal modality for detailed evaluation of the status of the vertebra, spinal cord, intra- and extra-dural lesions and helps in early diagnosis, detailed preoperative MRI evaluation and assessing concomitant anomalies and guiding further management with early institution of treatment to maximize recovery.

Accurate identification of pathogens with biowarfare importance requires detection tools that specifically differentiate them from near-neighbor species. Burkholderia pseudomallei, the causative agent of a fatal disease melioidosis, is one such biothreat agent whose differentiation from its near-neighbor species is always a challenge. This is because of its phenotypic similarity with other Burkholderia species which have a wide spread geographical distribution with shared environmental niches. Melioidosis is a major public health concern in endemic regions including Southeast Asia and northern Australia. In India, the disease is still considered to be emerging. Prevalence surveys of this saprophytic bacterium in environment are under-reported in the country. A major challenge in this case is the specific identification and differentiation of B. pseudomallei from the growing list of species of Burkholderia genus. The objectives of this study included examining the prevalence of B. pseudomallei and near-neighbor species in coastal region of South India and development of a novel detection tool for specific identification and differentiation of Burkholderia species. Briefly, we analyzed soil and water samples collected from Malabar coastal region of Kerala, South India for prevalence of B. pseudomallei. The presumptive Burkholderia isolates were identified using recA PCR assay. The recA PCR assay identified 22 of the total 40 presumptive isolates as Burkholderia strains (22.72% and 77.27% B. pseudomallei and non-pseudomallei Burkholderia respectively). In order to identify each isolate screened, we performed recA and 16S rDNA sequencing. This two genes sequencing revealed that the presumptive isolates included B. pseudomallei, non-pseudomallei Burkholderia as well as non-Burkholderia strains. Furthermore, a gene termed D-beta hydroxybutyrate dehydrogenase (bdha) was studied both in silico and in vitro for accurate detection of Burkholderia genus. The optimized bdha based PCR assay when evaluated on the Burkholderia isolates of this study, it was found to be highly specific (100%) in its detection feature and a clear detection sensitivity of 10 pg/μl of purified gDNA was recorded. Nucleotide sequence variations of bdha among interspecies, as per in silico analysis, ranged from 8 to 29% within the target stretch of 730 bp highlighting the potential utility of bdha sequencing method in specific detection of Burkholderia species. Further, sequencing of the 730 bp bdha PCR amplicon of each Burkholderia strain isolated could differentiate the species and the data was comparable with recA sequence data of the strains. All sequencing results obtained were submitted to NCBI database. Bayesian phylogenetic analysis of bdha in comparison with recA and 16S rDNA showed that the bdha gene provided comparable identification of Burkholderia species., Competing Interests: The authors have declared that no competing interests exist.

Arginine is an integral part of host defense when invading pathogens are encountered. The arginine metabolite nitric oxide (NO) confers antimicrobial properties, whereas the metabolite ornithine is utilized for polyamine synthesis. Polyamines are crucial to tissue repair and anti-inflammatory responses. iNOS/arginase balance can determine Th1/Th2 response. Furthermore, the host arginine pool and its metabolites are utilized as energy sources by various pathogens. Apart from its role as an immune modulator, recent studies have also highlighted the therapeutic effects of arginine. This article sheds light upon the roles of arginine metabolism during pathological conditions and its therapeutic potential., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

MADS (Minichromosome Maintenance1 Agamous Deficiens Serum response factor) box genes encode transcription factors and they play a key role in growth and development of flowering plants. There are two types of MADS box genes- Type I (serum response factor (SRF)-like) and Type II (myocyte enhancer factor 2 (MEF2)-like). Type II MADS box genes have a conserved MIKC domain (MADS DNA-binding domain, intervening domain, keratin-like domain, and c-terminal domain) and these were extensively studied in plants. Compared to other plants very little is known about MADS box genes in Camellia sinensis. The present study aims at identifying and analyzing the MADS-box genes present in Camellia sinensis. A comparative bioinformatics and phylogenetic analysis of the Camellia sinensis sequences along with Arabidopsis thaliana MADS box sequences available in the public domain databases led to the identification of 16 genes which were orthologous to Type II MADS box gene family members. The protein sequences were classified into distinct clades which are associated with the conserved function of flower and seed development. The identified genes may be used for gene expression and gene manipulation studies to elucidate their role in the development and flowering of tea which may pave the way to improve the crop productivity.

Glyoxalase I which is synonymously known as lactoylglutathione lyase is a critical enzyme in methylglyoxal (MG) detoxification. We assessed the STM3117 encoded lactoylglutathione lyase (Lgl) of Salmonella Typhimurium, which is known to function as a virulence factor, due in part to its ability to detoxify methylglyoxal. We found that STM3117 encoded Lgl isomerises the hemithioacetal adduct of MG and glutathione (GSH) into S-lactoylglutathione. Lgl was observed to be an outer membrane bound protein with maximum expression at the exponential growth phase. The deletion mutant of S. Typhimurium (Δlgl) exhibited a notable growth inhibition coupled with oxidative DNA damage and membrane disruptions, in accordance with the growth arrest phenomenon associated with typical glyoxalase I deletion. However, growth in glucose minimal medium did not result in any inhibition. Endogenous expression of recombinant Lgl in serovar Typhi led to an increased resistance and growth in presence of external MG. Being a metalloprotein, Lgl was found to get activated maximally by Co(2+) ion followed by Ni(2+), while Zn(2+) did not activate the enzyme and this could be attributed to the geometry of the particular protein-metal complex attained in the catalytically active state. Our results offer an insight on the pivotal role of the virulence associated and horizontally acquired STM3117 gene in non-typhoidal serovars with direct correlation of its activity in lending survival advantage to Salmonella spp.

Introduction: Immunomodulators are agents, which can modulate the immune response to specific antigens, while causing least toxicity to the host system. Being part of the modern vaccine formulations, these compounds have contributed remarkably to the field of therapeutics. Despite the successful record maintained by these agents, the requirement of novel immunomodulators keeps increasing due to the increasing severity of diseases. Hence, research regarding the same holds great importance., Areas Covered: In this review, we discuss the role of immunomodulators in improving performance of various vaccines used for counteracting most threatening infectious diseases, mechanisms behind their action and criteria for development of novel immunomodulators., Expert Opinion: Understanding the molecular mechanisms underlying immune response is a prerequisite for development of effective therapeutics as these are often exploited by pathogens for their own propagation. Keeping this in mind, the present research in the field of immunotherapy focuses on developing immunomodulators that would not only enhance the protection against pathogen, but also generate a long-term memory response. With the introduction of advanced formulations including combination of different kinds of immunomodulators, one can expect tremendous success in near future.

Aim: The aim was to develop magnetic nanovesicles for chemotherapy and self-controlled hyperthermia that prevent overheating of tissues., Materials & Methods: Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles) were developed., Results: Encapsulation efficiencies of magnetic nanoparticles and paclitaxel were 67 ± 5 and 83 ± 3%, respectively. Sequential release performed at 37°C for 1 h followed by 44°C for another 1 h (as expected for intratumoral injection), showed a cumulative release of 6.6% (109.6 µg), which was above the IC50 of the drug. In an alternating current magnetic field, the temperature remained controlled at 44°C and a synergistic cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells., Conclusion: Magnetic nanovesicles containing biphasic suspensions La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential for combined self-controlled hyperthermia and chemotherapy.

We report in vivo evaluation of a thermo-responsive poly(N-isopropylacrylamide)-chitosan based magnetic nanohydrogel (MNHG) incorporated with Fe 3 O 4 nanoparticles (NPs) in mice models with expandible scope for use in localized delivery of chemotherapeutics. Biocompatibility and biodistribution of the MNHG are studied in normal Swiss mice while efficacy in tumor growth inhibition is studied in a subcutaneous fibrosarcoma tumor. The ex vivo time-dependent pattern of accumulated MNHG into vital organs; lung, liver, spleen, kidney and brain collected at 1 h, 48 h, 7 d and 14 d post intravenous administration are investigated using both a vibrating sample magnetometer (VSM) and inductively coupled plasma-atomic emission spectroscopy (ICP-AES) method. The doses of MNHG (dose I ∼ 650 and dose II ∼ 325 μg g -1 body wt) used in the study are determined based on induced thermal activation of MNHG under an AC magnetic field (AMF). Fibrosarcoma tumor bearing mice are subjected to hyperthermia with a field of 325 Oe and 265 kHz for 30 min following intratumoral administration of dose I. Tumor size measured at an interval of 72 h for a period of 2 weeks reveals that the NPs mediated therapy decelerated the growth of the transplanted tumor by about three-fold (size, 1545 ± 720 mm 3 ) as compared to the exponential growth of the tumor (size, 4510 ± 735 mm 3 ) in control mice. These results suggest the feasibility of using poly(NIPAAm)-chitosan hydrogels loaded with NPs for combined thermo-chemotherapy where the efficacy may further be improved by temperature dependent release of the drugs from the magneto hydrogels.

Paclitaxel loaded thermosensitive magnetoliposomes containing 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (PG) were prepared by thin film hydration method. Encapsulation efficiencies of paclitaxel and citric acid coated Fe(3)O(4) nanoparticles were 83±3% and 74.6±5%, respectively. Based on the release study, DPPC/PG in 9:1 (w/w) liposomes (PCPG) formulation was found to be thermosensitive and showed 46 fold higher drug release at 43 °C than at 37 °C. Drug release was done under an alternating magnetic field of intensity 10 kA/m and a fixed frequency of 423 kHz. In-vitro cytotoxicity and hyperthermia studies were carried out using a human cervical cancer cell line (HeLa). IC(50) value of the magnetoliposomes formulation was 100 nM. When the magnetoliposomes with 100 nM drug was used to treat HeLa cells in combination with hyperthermia under AC magnetic field, 89% cells were killed and were found to be more effective than either hyperthermia or chemotherapy alone. So, PCPG liposomes which co-encapsulate both Fe(3)O(4) nanoparticles and paclitaxel may be useful for combined chemotherapy and hyperthermia., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Experiments were conducted to study the dynamics of nitrous oxide (N₂O) emission from wheat varieties viz., Sonalika, HUW 468, HUW 234 and DBW 14 grown in alluvial soils of North Bank Plain Agroclimatic Zone of Assam, India. Attempts were made to find out the relationship of N₂O emission with plant morphophysiological, anatomical and soil properties. N₂O fluxes from wheat varieties ranged from 40 μg N₂O-N m⁻² h⁻¹ to 295 μg N₂O-N m⁻² h⁻¹. Soil organic carbon and soil temperature have shown significant relationship with N₂O flux. The rate of leaf transpiration recorded from the wheat varieties at different growth stages exhibited a positive correlation with N₂O emission suggesting that movement of N₂O along with the transpirational water flow may be an important mechanism of N₂O transport and emission through wheat plants. Anatomical investigation by scanning electron microscope revealed that N₂O emission has relationship with stomatal frequency of leaf and leaf sheaths. Variety HUW 234 with the highest stomatal frequency of leaf and leaf sheath also recorded higher seasonal N₂O emission compared to other varieties. Seasonal N₂O emission (E(sif)) of the varieties ranged from 3.25 to 3.81 kg N₂O-N ha⁻¹. Significant variations in E(sif) values were recorded within the varieties.

Purpose: To describe the prevalence of cataract in older people in 2 areas of north and south India., Design: Population-based, cross-sectional study., Participants: Randomly sampled villages were enumerated to identify people aged ≥ 60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination., Methods: The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III)., Main Outcome Measures: Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥ 4 for nuclear cataract, ≥ 3 for cortical cataract, and ≥ 2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract., Results: The prevalence of unoperated cataract in people aged ≥ 60 was 58% in north India (95% CI, 56-60) and 53% (95% CI, 51-55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46-50) in north India and 38% (95% CI, 37-40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20-23) and 17% (95% CI, 16-19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7-9) and 10.2% (95% CI, 9-11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002)., Conclusions: We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We present a new technique of anchoring the eyeball to the nasal periosteum using a nonabsorbable suture in acquired isolated third-nerve paresis., Methods: This was a case series of 4 consecutive adult subjects with isolated third-nerve paresis. After a 12-mm lateral rectus muscle recession in all 4 subjects, we passed 5-O double-armed polyester (NW683 Ethibond; Ethicon, Division of Johnson and Johnson Ltd., Aurangabad, India) on spatulated needles through the periosteum overlying the anterior lacrimal crest (exposed as in a Dacryocystorhinostomy procedure) at its superior part. The needles were brought anterior to the medial rectus muscle insertion and tightened enough to align the eye in 8-10 prism diopters adducted position., Results: Ocular alignment in the primary gaze was satisfactory at 6-12 months of follow up., Conclusions: The use of a nonabsorbable polyester suture to anchor the globe to the nasal periosteum is an additional technique that holds promise to align the eyes in the primary gaze.

A seldom reported causal association of two rare entities, an isolated brainstem tuberculoma and an isolated One and a half syndrome in a 12 year old girl is presented. MRI showed an isolated inflammatory granuloma in the brainstem which on empirical treatment with anti tubercular drugs resulted in complete restoration of ocular motility, along with resolution of the lesion on follow up MRI at 6 months. The diagnosis and management are discussed.

A total of 1905 subjects were randomly allocated to four types of intrauterine devices (IUDs) and were observed for 45,683 woman-months of use. While no method failure was observed with levonorgestrel (LNG) IUD, 11 women became pregnant with other devices; 4 with Copper T 380Ag, 1 with Copper T 220C, and 6 while using Copper T 200B, indicating method failure rates of 1.0, 0.3 and 1.6, respectively, at 36 months of use. These rates were within acceptable range. Continuation rates were significantly lower with LNG IUD (74.5, 58.7, 38.8 at 1 year, 2 years and 3 years, respectively) as compared to other copper devices, which ranged between 82.4 to 84.4 at 1 year, 66.6 to 69.9 at 2 years and 45.4 to 50.4 at 3 years. The difference in continuation rates was mainly due to menstrual disturbances (e.g. amenorrhoea, irregular bleeding) which were higher with LNG IUD (27.9 per 100 users) as compared to the copper devices (13.4-15.4 per 100 users) at 36 months of use. The risk of expulsion ranged between 8.3 to 10.6 per 100 users and was comparable for all the devices. The observations from the present study based on 36 months of experience with different intrauterine devices do not indicate the need to replace CuT 200, the device currently in use in the National Programme.

A total of 2388 subjects, 1181 for 60 +/- 5-day and 1207 for 90 +/- 5-day treatment regimen with norethisterone oenanthate (NET OEN) 200 mg injection, were observed for 24 months, constituting 28,513 woman-months. This clinical trial represents the largest clinical trial undertaken on NET OEN. The observations indicated that NET OEN given at 60 +/- 5-day intervals provides adequate contraceptive protection. However, as compared to the published studies elsewhere, higher method failures were seen during the first six months of NET OEN usage, when all women were receiving the drug at 60 +/- 5-day intervals. The reasons for this discrepant observation in the present study cannot be explained. The higher method failures reported with 90 +/- 5-day regimen were mainly during the third month following the injection, suggesting reduced contraceptive efficacy of the drug during this period. Thin build women (body weight less than or equal to 40 kg) were at higher risk of involuntary pregnancy. Disrupted menstrual pattern was the major reason for discontinuation ranging between 42-43 per 100 users at the end of 24 months. Amongst these, amenorrhoea was the commonest reason for discontinuation. No change in blood pressure was observed during contraceptive usage. The majority of NET OEN users did not show any change in body weight. The overall continuation rates with NET OEN were lower than those observed in similar conditions with Cu-T 200 mm2 IUCD.