Response of leuprolide on gonadal functions of women with overt hypothyroidism: a tertiary care centre study from Uttar Pradesh, India

Background: Hypothyroidism can cause menstrual disturbances mainly oligoanovualtory cycles and sometimes menorrhagia. It has also been seen to cause subfertility and pregnancy related complications. Various studies have been done to evaluate gonadal dysfunctions in overt hypothyroidism but very few studies are there which have done using a gonadotrophin response in that subset of patients. Present study evaluates the response of leuprolide on gonadal functions of women with overt hypothyroidism in a tertiary care centre at Meerut.Methods: In this study 50 females of age 20 to 40 years with newly diagnosed overt hypothyroidism were taken as cases and age and Body Mass Index (BMI) matched healthy females were taken as controls. Both in cases and controls, basal FSH, LH, estradiol was measured on 2nd day to 5th day of menstrual cycle. Thereafter Leuprolide 20 mcg/kg was given subcutaneously on the same day. Post leuprolide test, stimulated LH, FSH and estradiol were measured. Basal and stimulated values were compared between both groups.Results: Basal LH was significantly higher in controls (8.2±3.2 mIU/L) when compared to cases (6.45±2.75 mIU/L) with a p value 0.03(<0.05). Basal estradiol and FSH levels were found to be nearly similar and non-significant in cases and controls. No significant differences were found between stimulated mean LH and estradiol in both the groups. Leuprolide response after stimulation test was found to be sluggish in patients with overt hypothyroidism compared to normal euthyroid controls. This study is the rare one done on human subject in tertiary care centre of India, however large sample and multicentric trials are necessary before establishing the biochemical results.Conclusions: Pituitary and gonadal (ovarian) response to leuprolide was found to have impaired (decreased) in overt hypothyroidism cases. This is the first study to be done in overt hypothyroid subjects to asses both basal and stimulated gonadotropin levels

Validated HPLC and HPTLC Methods for Simultaneous Determination of Some α1 -Adrenoreceptor Blockers

Alpha-blockers (alfuzosin, tamsulosin, doxazosin, prazosin and terazosin) relax the smooth muscles in the prostate and are indicated for the symptomatic treatment of benign prostatic hyperplasia due to evidence of their positive and rapid effect on lower urinary tract symptoms. Our objective was to develop and validate simultaneous estimation of these drugs. Same class of drugs may have almost same functional groups and therefore research focused on development of RPLC and HPTLC method for simultaneous quantitative determination. The separation was achieved in HPLC method on a C18 column, a UV detector at 230 nm and a elution was performed under a gradient mobile phase composed of (A) ACNdiethylamine (0.05 mL), (B) methanol, (C) 10 mM ammonium acetate and (D) Water. For HPTLC method separation was achieved by using mobile phase chloroform and methanol in the ratio 9.5:0.5. Both of the validated methods can be utilized for the assay of these α1 adrenoreceptors in pharmaceutical industries.Colegio de Farmacéuticos de la Provincia de Buenos Aire

ASSESSMENT OF FEASIBILITY AND COMPLICATIONS OF LAPAROSCOPIC CHOLECYSTECTOMY IN CIRRHOTIC PATIENTS

Abstract :Introduction: From the era of absolute contraindication to the phase of preferred treatment, the technique of laparoscopic cholecystectomy advances with time. Here, we report our experience of laparoscopic cholecystectomy in 20 patients of liver cirrhosis. In our institute, laparoscopic cholecystectomy is the preferred choice for cholelithiasis in cirrhotic patient.Methods: In last 2 years, 180 laparoscopic cholecystectomies were performed and 20 patients were cirrhotic. Their data analyzed retrospectively in terms of preoperative optimization, operative technique and results.Results: Laparoscopic cholecystectomy was completed successfully in 19 patients and one was converted to open. Mean operative time was 54 minutes. No additional port was required in all cases. Calot's first dissection was performed in 18 patients and fundus first technique was used in 2 patients due to unclear anatomy. Liver bed bleeding was present in 16 patients, which was controlled effectively. Subhepatic drain was placed in 12 patients. There was no mortality. Morbidity  in two patients was worsening of ascites in one; and incisional hernia in other patient which was converted to open. Port site complications were not noted in any patient and there was no evidence of intraabdominal bleeding or bile leak postoperatively. Blood and component transfusion was required in 2 patients. Average length of hospital stay was 4.8 days.Conclusion: Though laparoscopic cholecystectomy may be difficult in cirrhotic patients but it is feasible and relatively safe. It offers many advantages in cirrhotic patients and associated with low morbidity when compared with open surgery.Keywords: cirrhosis, laparoscopic cholecystectomy, difficult cholecystectom

Unraveling the temperature dependence of the yield strength in single-crystal tungsten using atomistically-informed crystal plasticity calculations

We use a physically-based crystal plasticity model to predict the yield strength of body-centered cubic (bcc) tungsten single crystals subjected to uniaxial loading. Our model captures the thermally-activated character of screw dislocation motion and full non-Schmid effects, both of which are known to play a critical role in bcc plasticity. The model uses atomistic calculations as the sole source of constitutive information, with no parameter fitting of any kind to experimental data. Our results are in excellent agreement with experimental measurements of the yield stress as a function of temperature for a number of loading orientations. The validated methodology is then employed to calculate the temperature and strain-rate dependence of the yield strength for 231 crystallographic orientations within the standard stereographic triangle. We extract the strain-rate sensitivity of W crystals at different temperatures, and finish with the calculation of yield surfaces under biaxial loading conditions that can be used to define effective yield criteria for engineering design models

PARTICLE SWARM OPTIMIZED RANDOM FOREST FOR SURVIVAL PREDICTION: A LEAKAGE -AWARE, NOISE ROBUSTNESS STUDY USING SEER PROSTATE CANCER DATA

Survival prediction in prostate cancer is both clinically vital and methodologically challenging due to risks of data leakage and the impact of real-world noise. This study presents a novel, leakage-aware- noise robustness machine learning pipeline, where all post-outcome and treatment-related features are rigorously excluded to ensure fair modeling. We employed Particle Swarm Optimization (PSO) to optimize Random Forest (RF) hyperparameters for survival prediction using the SEER prostate cancer dataset. Data are label- encoded and MinMax normalized and model evaluation is performed via stratified 5-fold cross-validation, repeated twice for reliability. To systematically assess robustness, Gaussian noise is injected into all numeric features at levels of 0%, 10%, 20%, 30%, and 40% standard deviation. Our framework achieves exceptional performance at 0% noise: accuracy 0.9915, precision 0.9979, recall 0.9656, F1-score 0.9814, and ROC-AUC 0.9984. Even as noise increases to 30%, the PSO-tuned RF maintains F1 &gt; 0.92 and ROC-AUC &gt; 0.95, evidencing high resilience. At 40% noise, performance declines only modestly (F1 &gt; 0.89, ROC-AUC &gt; 0.94). This explicit combination of leakage prevention and noise stress testing demonstrates that metaheuristic-optimized RF models deliver robust and trustworthy survival predictions, even under challenging data conditions. Our approach establishes a reproducible benchmark for future clinical AI and provides a blueprint for robust model development in other biomedical prediction domains where data integrity is essential

Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Prazosin, Terazosin, and Doxazosin in Pharmaceutical Formulations

The current study was carried out with an attempt to separate similarly structured title drugs by liquid chromatography. Spectrophotometric techniques were generally insufficient under these conditions because of the spectral overlapping of drugs with similar functional groups. The pharmaceutical drugs prazosin, terazosin, and doxazosin contain the same parent quinazoline nucleus, thus making it especially difficult to separate the former two drugs because of their very similar structures. A simple and sensitive method for the routine determination of these drugs in pharmaceutical formulations was attempted. We found that the mobile phase consisting of A: ACN–diethylamine (0.05 ml), B: methanol, and C: 10 mM Ammonium acetate separated these drugs effectively. Separations were carried out on a new Kromasil C18 column (250 × 4.6 mm, 5.0 μm) at 254 nm wavelength. The calibration curve was found to be linear in the range of 2–500 μg/ml. The stated method was then validated in terms of specificity, linearity, precision, and accuracy. Additionally, the proposed method reduced the duration of the analysis

Methods for the determination of limit of detection and limit of quantitation of the analytical methods

The quality of an analytical method developed is always appraised in terms of suitability for its intended purpose, recovery, requirement for standardization, sensitivity, analyte stability, ease of analysis, skill subset required, time and cost in that order. It is highly imperative to establish through a systematic process that the analytical method under question is acceptable for its intended purpose. Limit of detection (LOD) and limit of quantification (LOQ) are two important performance characteristics in method validation. LOD and LOQ are terms used to describe the smallest concentration of an analyte that can be reliably measured by an analytical procedure. There has often been a lack of agreement within the clinical laboratory field as to the terminology best suited to describe this parameter. Likewise, there have been various methods for estimating it. The presented review provides information relating to the calculation of the limit of detection and limit of quantitation. Brief information about differences in various regulatory agencies about these parameters is also presented here