Hormonal and non-hormonal oral contraceptives given long-term to pubertal rats differently affect bone mass, quality and metabolism

IntroductionWe investigated the effects of hormonal and non-hormonal oral contraceptives (OCs) on bone mass, mineralization, composition, mechanical properties, and metabolites in pubertal female SD rats.MethodsOCs were given for 3-, and 7 months at human equivalent doses. The combined hormonal contraceptive (CHC) was ethinyl estradiol and progestin, whereas the non-hormonal contraceptive (NHC) was ormeloxifene. MicroCT was used to assess bone microarchitecture and BMD. Bone formation and mineralization were assessed by static and dynamic histomorphometry. The 3-point bending test, nanoindentation, FTIR, and cyclic reference point indentation (cRPI) measured the changes in bone strength and material composition. Bone and serum metabolomes were studied to identify potential biomarkers of drug efficacy and safety and gain insight into the underlying mechanisms of action of the OCs.ResultsNHC increased bone mass in the femur metaphysis after 3 months, but the gain was lost after 7 months. After 7 months, both OCs decreased bone mass and deteriorated trabecular microarchitecture in the femur metaphysis and lumbar spine. Also, both OCs decreased the mineral: matrix ratio and increased the unmineralized matrix after 7 months. After 3 months, the OCs increased carbonate: phosphate and carbonate: amide I ratios, indicating a disordered hydroxyapatite crystal structure susceptible to resorption, but these changes mostly reversed after 7 months, indicating that the early changes contributed to demineralization at the later time. In the femur 3-point bending test, CHC reduced energy storage, resilience, and ultimate stress, indicating increased susceptibility to micro-damage and fracture, while NHC only decreased energy storage. In the cyclic loading test, both OCs decreased creep indentation distance, but CHC increased the average unloading slope, implying decreased microdamage risk and improved deformation resistance by the OCs. Thus, reduced bone mineralization by the OCs appears to affect bone mechanical properties under static loading, but not its cyclic loading ability. When compared to an age-matched control, after 7 months, CHC affected 24 metabolic pathways in bone and 9 in serum, whereas NHC altered 17 in bone and none in serum. 6 metabolites were common between the serum and bone of CHC rats, suggesting their potential as biomarkers of bone health in women taking CHC.ConclusionBoth OCs have adverse effects on various skeletal parameters, with CHC having a greater negative impact on bone strength

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

Prevalence and Characterisation of Irregular RBC Antibodies in Antenatal Females from a Tertiary Care Center in Northern India: A Cross-sectional Study

Introduction: Haemolytic Disease of the Foetus and Newborn (HDFN) is widely known to be caused by the presence of irregular Red Blood Cell (RBC) antibodies in pregnant females. To prevent HDFN, it is crucial to identify these antibodies in pregnant women. Aim: To evaluate the prevalence of irregular red cell antibodies in pregnant women in a tertiary care hospital. Materials and Methods: A cross-sectional retrospective study was conducted in the Department of Transfusion Medicine at Indraprastha Apollo New Delhi, from November 2009 to December 2017. A total of 8,217 prenatal females were examined for irregular red cell antibodies. Antibody screening and blood grouping were performed. The Capture-R ready screen was used to confirm screen-positive tests. Adsorption, elution, and other advanced techniques were utilised as needed. Data was collected from patient records and entered into a Microsoft excel spreadsheet. The statistical analysis was conducted using Statistical Package for Social Sciences (SPSS) software version 14.0 (USA). Statistical tests, including the Chi-squared and Fisher’s exact test, were performed, with a p-value less than 0.05 considered statistically significant. Results: Out of the 8,217 prenatal females examined, 105 (1.27%) had positive screening results with the four cell panel. Red cell alloimmunisation was observed in groups that were RhD negative (n=93/105; 88.57%) and positive (n=12/105; 11.42%). The most prevalent alloantibody among RhD negative individuals was alloantibody anti-D (n= 83/93; 89.24%), followed by alloantibody anti C+ anti D (n=13/93; 13.97%). Anti-D was the most prevalent alloantibody overall (n=83/105; 79.04%). Conclusion: Alloimmunisation rates were notably high among women lacking the Rh D antigen. Individuals with a history of adverse obstetric outcomes showed a statistically significant association with alloimmunisation. Therefore, it is recommended to screen such individuals for alloantibodies to enable early detection and improve the management of HDFN

Multi-residue pesticides analysis in water samples using reverse phase high performance liquid chromatography (RP-HPLC)

India is one of the leading suppliers of agrochemicals and has the largest pesticide industry in Asia. Among various Indian states, Punjab is the primary user of pesticides. Presence of pesticide residue in water and food products of Punjab is well documented. The present study was designed to envisage the level of pesticide contamination in pond water of eleven villages of Amritsar district of Punjab, India. A rapid and concurrent method for the identification and quantification of pesticides in water samples was developed and validated. The method validation parameters exhibited high sensitivity of the developed method and the proficiency for the identification and quantification of pesticide residues in water samples. The RP-HPLC method described here • is a novel method which is applicable for simple, rapid and precise detection of pesticides. • 40.02% of water samples were found contaminated with multi-residue pesticides. • carbofuran was the most abundant pesticide which was present in 18.18% samples. Keywords: Quantitative analysis, Multi-residue pesticides, RP-HPLC, Pond water sample

Prevalence of irregular red cell antibody in healthy blood donors attending a tertiary care hospital in North India

Background: Alloantibodies may be detected in blood donors who have either been transfused previously or female donors with previous obstetric events. These antibodies can occasionally cause severe transfusion reaction, if a large amount of plasma or whole blood is transfused, as in massive transfusions and pediatric patients. Aims: The present study aims to assess the prevalence of red cell antibodies in healthy blood donors at a tertiary care hospital-based blood bank in India. Materials And Methods: A total of 82,153 donor samples were screened for irregular red cell antibodies between January 2012 and December 2015 at the Department of Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi. Antibody screening was performed by solid phase method using Immucor Capture–R ready screen (pooled cells) on fully automated immunohematology analyzer Galileo Neo (Immucor Inc., Norcross, GA, USA). Positive tests were further confirmed using Capture-R ready screen (4 cell panel). Advanced investigations to identify the antibody/ies were performed on confirmed positive samples. Antibody identification was conducted using various cell panels (Immucor Capture-R Ready-ID, Panocell-10, Ficin Treated). An advanced technique such as adsorption and elution was performed as per requirement. Results: Screening with pooled cells and 4 cell panel was positive in 227 donors (0.27%), 150 of these donors had autoantibodies, 1 had autoantibodies with underlying alloantibody anti-Jka (0.001%), and 76 had alloantibodies (0.09%) alone in their plasma. Anti-M was the most common antibody (43 donors) identified, followed by anti-D (21 donors). Anti-N was detected in 4; anti-Jka, anti-C, and anti-E in two donors each followed by anti-P1 and anti-Leb in 1 donor. Conclusion: Antibodies against red cells can be present in healthy donors detection of which is important in providing safe blood to the patient. The prevalence of red blood cell antibody in healthy donors in this study was found to be 0.27%, while the prevalence of alloantibodies was 0.09%. The majority of alloantibodies were anti-M (56.57%) and anti-D (27.63%)

Shikonin derivatives as potent xanthine oxidase inhibitors: <i>in-vitro</i> study

Induction of hypersensitivity reactions (may be fatal too) by specific XO inhibitors has led to development of new molecules that are efficacious and have safer ADME profile. Among natural compounds, biologically active Alkannin/Shikonin (A/S) derivatives have unexplored XO inhibition potential. Therefore, their iso-hexenylnaphthazarin nucleus was studied and found that the nucleus is similar to that of allopurinol, signifying the XO inhibitory potential of these derivatives. For confirmation of their potential, β,β-dimethylacrylshikonin and deoxyshikonin were successfully isolated and characterised from Arnebia euchroma (Royle.) Johnst. (Boraginaceae) and were evaluated for in vitro XO inhibitory potential. β,β-dimethylacrylshikonin and deoxyshikonin showed a good XO inhibition potential with IC50 values of 7.475 ± 1.46 µg/mL and 4.487 ± 0.88 µg/mL, respectively. Results also validated the pharmacophore hypothesis, and it was concluded that nucleus iso-hexenylnaphthazarin can be remodelled for optimising the efficacy.</p