Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Hidden danger: The long-term effect of ultrafine particles on mortality and its sociodemographic disparities in New York State.

Although previous studies have shown increased health risks of particulate matters, few have evaluated the long-term health impacts of ultrafine particles (UFPs or PM0.1, ≤ 0.1 µm in diameter). This study assessed the association between long-term exposure to UFPs and mortality in New York State (NYS), including total non-accidental and cause-specific mortalities, sociodemographic disparities and seasonal trends. Collecting data from a comprehensive chemical transport model and NYS Vital Records, we used the interquartile range (IQR) and high-level UFPs (≥75 % percentile) as indicators to link with mortalities. Our modified difference-in-difference model controlled for other pollutants, meteorological factors, spatial and temporal confounders. The findings indicate that long-term UFPs exposure significantly increases the risk of non-accidental mortality (RR=1.10, 95 % CI: 1.05, 1.17), cardiovascular mortality (RR=1.11, 95 % CI: 1.05, 1.18) particularly for cerebrovascular (RR=1.21, 95 % CI: 1.10, 1.35) and pulmonary heart diseases (RR=1.33, 95 % CI: 1.13, 1.57), and respiratory mortality (borderline significance, RR=1.09, 95 % CI: 1.00, 1.18). Hispanics (RR=1.13, 95 % CI: 1.00, 1.29) and non-Hispanic Blacks (RR=1.40, 95 % CI: 1.16, 1.68) experienced significantly higher mortality risk after exposure to UFPs, compared to non-Hispanic Whites. Children under five, older adults, non-NYC residents, and winter seasons are more susceptible to UFPs' effects.

Regulatory role of miR-125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses.

OBJECTIVES: Studies have investigated miR-125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3. METHODS: The present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR-125a was conducted by quantitative real-time PCR (qPCR). RESULTS: The expression of miR-125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56-fold, P < 0.0001). Among the target gene of miR-125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58-fold, P = 0.04; 1.87-fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR-125a cases depicted a significant association (P = 0.0005). Kaplan-Meier survival analysis revealed cases with low miR-125a expression had significantly shorter time to miscarriages, (log-rank P = 0.02). Also, decreased expression of miR-125a significantly conferred >2-fold increased risk for RPL (HR = 2.34: P < 0.05). CONCLUSION: The overall conclusion of the study was that altered miR-125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy.

Mysteriously rapid rise in Legionnaires' disease incidence correlates with declining atmospheric sulfur dioxide.

Legionnaires' disease (LD) is a severe form of pneumonia (∼10-25% fatality rate) caused by inhalation of aerosols containing Legionella, a pathogenic gram-negative bacteria. These bacteria can grow, spread, and aerosolize through building water systems. A recent dramatic increase in LD incidence has been observed globally, with a 9-fold increase in the United States from 2000 to 2018, and with disproportionately higher burden for socioeconomically vulnerable subgroups. Despite the focus of decades of research since the infamous 1976 outbreak, substantial knowledge gaps remain with regard to source of exposure and the reason(s) for the dramatic increase in LD incidence. Here, we rule out factors indicated in literature to contribute to its long-term increases and identify a hitherto unexplored explanatory factor. We also provide an epidemiological demonstration that the occurrence of LD is linked with exposure to cooling towers (CTs). Our results suggest that declining sulfur dioxide air pollution, which has many well-established health benefits, results in reduced acidity of aerosols emitted from CTs, which may prolong the survival duration of Legionella in contaminated CT droplets and contribute to the increase in LD incidence. Mechanistically associating decreasing aerosol acidity with this respiratory disease has implications for better understanding its transmission, predicting future risks, and informed design of preventive and interventional strategies that consider the complex impacts of continued sulfur dioxide changes.

Incidental pulmonary nodules may lead to a high proportion of early-stage lung cancer: but it requires more than a high CT volume to achieve this.

Background: The management of pulmonary nodules plays a critical role in early detection of lung cancer. Computed tomography (CT) has led to a stage-shift towards early-stage lung cancer, but regional differences in survival rates have been reported in Denmark. This study aimed to evaluate whether variations in nodule management among Danish health regions contributed to these differences. Material and Methods: The Danish Health Data Authority and Danish Lung Cancer Registry provided data on CT usage and lung cancer stage distribution, respectively. Auditing of lung cancer stage IA patient referrals and nodule management of stage IV lung cancer patients was conducted in seven Danish lung cancer investigation centers, covering four of the five Danish health regions. CT scans were performed up to 2 years before the patients' diagnosis from 2019 to 2021. Results: CT usage has increased steadily in Denmark over the past decade, with a simultaneous increase in the proportion of early-stage lung cancers, particularly stage IA. However, one Danish health region, Region Zealand, exhibited lower rates of early-stage lung cancer and overall survival despite a CT usage roughly similar to that of the other health regions. The audit did not find significant differences in pulmonary nodule management or a higher number of missed nodules by radiologists in this region compared to others. Conclusion: This study suggests that a high CT scan volume alone is not sufficient for the early detection of lung cancer. Factors beyond hospital management practices, such as patient-related delays in socioeconomically disadvantaged areas, may contribute to regional differences in survival rates. This has implications for future strategies for reducing these differences.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

BACKGROUND: Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. AIM: To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. MATERIALS AND METHODS: 129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). RESULTS: The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. CONCLUSION: EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.

BACKGROUND: Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease. METHOD: Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein. RESULTS: Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05). CONCLUSION: Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.

A numerical study of spatio-temporal COVID-19 vaccine model via finite-difference operator-splitting and meshless techniques.

In this paper, a new spatio-temporal model is formulated to study the spread of coronavirus infection (COVID-19) in a spatially heterogeneous environment with the impact of vaccination. Initially, a detailed qualitative analysis of the spatio-temporal model is presented. The existence, uniqueness, positivity, and boundedness of the model solution are investigated. Local asymptotical stability of the diffusive COVID-19 model at steady state is carried out using well-known criteria. Moreover, a suitable nonlinear Lyapunov functional is constructed for the global asymptotical stability of the spatio-temporal model. Further, the model is solved numerically based on uniform and non-uniform initial conditions. Two different numerical schemes named: finite difference operator-splitting and mesh-free operator-splitting based on multi-quadratic radial basis functions are implemented in the numerical study. The impact of diffusion as well as some pharmaceutical and non-pharmaceutical control measures, i.e., reducing an effective contact causing infection transmission, vaccination rate and vaccine waning rate on the disease dynamics is presented in a spatially heterogeneous environment. Furthermore, the impact of the  aforementioned interventions is investigated with and without diffusion on the incidence of disease. The simulation results conclude that the random motion of individuals has a significant impact on the disease dynamics and helps in setting a better control strategy for disease eradication.

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Safety outcomes of anti-platelet therapy post coronary artery bypass graft surgery: A systematic review and network meta-analysis of randomized control trials.

BACKGROUND: Antiplatelet therapy is used to decrease the risk of graft failure post coronary artery bypass graft surgery. We aimed to compare dual antiplatelet therapy (DAPT) with monotherapy along with a comparison of Aspirin, Ticagrelor, Aspirin+Ticagrelor (A+T) and Aspirin+Clopidogrel (A+C) to determine the major and minor bleeding risk, risk of postoperative myocardial infarction (MI), stroke, and all-cause mortality (ACM). METHODS: Randomized Controlled Trials comparing the four groups were included. Odds ratio (OR) and Absolute Risk (AR) were employed to assess the mean and standard deviation (SD) with 95% confidence intervals (CI). The Bayesian random-effects model was used for statistical analysis. Risk difference and Cochran Q tests were used to calculate rank probability (RP) and heterogeneity, respectively. RESULTS: We included 10 trials, consisting of 21 arms and 3926 patients. For the risk of major and minor bleed, A + T and Ticagrelor showed the lowest mean value of 0.040 (0.043) and 0.067 (0.073), respectively, and the highest RP of being the safest group. While a direct comparison between DAPT and monotherapy resulted in an OR of 0.57 [0.34, 0.95] for the risk of minor bleed. A + T was found to have the highest RP and the lowest mean value in terms of ACM, MI, and stroke. CONCLUSION: No significant difference was found between monotherapy or dual-antiplatelet therapy for the major bleeding risk safety outcome, however DAPT was found to have a significantly higher rate of minor bleeding complications post-CABG. DAPT should be considered as the antiplatelet modality of choice post-CABG.

COVID-19 associated multisystemic mucormycosis from India: a multicentric retrospective study on clinical profile, predisposing factors, cumulative mortality and factors affecting outcome.

PURPOSE: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). METHODS: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. RESULTS: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. CONCLUSION: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer.

Background: The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene. Materials and methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100. Results: hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare 'A' allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.14, p = 0.001). Conclusions: It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer.

Predictors of pathological complete response following neoadjuvant chemoradiotherapy for rectal cancer.

Background: Neoadjuvant chemoradiotherapy (NACRT) is an established treatment option for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NACRT have better oncological outcomes and may be subjected to wait and watch policy as well. The aim of this study was to identify predictors of pCR in LARC following NACRT. Materials and Methods: A retrospective analysis of a prospectively maintained colorectal cancer database from January 2018 to December 2019 was undertaken. A total of 129 patients of LARC who were subjected to conventional long course NACRT, followed by surgery were included in the study. Pathological response to NACRT was assessed using Mandard grading system and response was categorized as pCR or not-pCR. Correlation between various clinico pathological parameters and pCR was determined using univariate and multivariate logistic regression analysis. Results: Mean age of patients was 53.79 ± 1.303 years. Complete pathological response (Mandard Gr 1) was achieved in 24/129 (18.6%) patients. Age of patients more than 60 years (P = 0.011; odds ratio [OR] 3.194, 95% confidence interval [CI] 1.274-8.011), interval between last dose of NACRT and surgery >8 weeks (P = 0.004; OR 4.833, 95% CI 1.874-12.467), well-differentiated tumors (P < 0.0001; OR 32.00, 95% CI 10.14-100.97) and node-negative disease (P = 0.003; OR 111.0, 95% CI 2.51-48.03) proved to be strong predictors of pCR. Conclusion: Older age, longer interval between NACRT and surgery, node-negative disease and favorable tumor grade help in achieving better pCR rates. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.

Implications of Decreased Expression of miR-125a with Respect to Its Variant Allele in the Pathogenesis of Recurrent Pregnancy Loss: A Study in a High Incidence Zone.

Pregnancy is controlled by several types of genes and the regulation of their expression is tightly controlled by miRNAs. The present study was carried out to explore the association between miR-125a polymorphic sequence variation and its expression and recurrent pregnancy loss (RPL) compared to full-term healthy controls. A total of 150 women that had experienced two or more RPLs and 180 healthy controls (two or more full-term pregnancies) were recruited, along with 50 product of conception (POC) samples from the corresponding RPL patients, and evaluated for miR-125a SNPs by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), which was confirmed by high resolution melting (HRM)/DNA sequencing. Additionally, the expression of miR-125a was quantified with q−PCR in the maternal plasma of 40 corresponding RPL patients against healthy controls. The frequency of variant genotype CC was significantly higher in RPL cases (19.3%) than controls (10.5%), with an odds ratio of >2 (p = 0.025). The expression levels of miR-125a were markedly decreased in RPL cases compared to healthy controls (p < 0.05). Variant genotype CC was found significantly more often in RPL cases than controls (0.34 vs. 0.20; p < 0.05).In this study, miR-125a rs12976445 C/T revealed that the homozygous CC genotype and C allele were associated with the risk of RPL and significant expression indicates that miR-125a has an important role in RPL etiopathogenesis.

Racial Disparities in Occult Hypoxemia and Clinically Based Mitigation Strategies to Apply in Advance of Technological Advancements.

BACKGROUND: Pulse oximetry is the mainstay of patient oxygen monitoring. Measurement error from pulse oximetry is more common for those with darker skin pigmentation, yet this topic remains understudied, and evidence-based clinical mitigation strategies do not currently exist. Our objectives were to measure the rate of occult hypoxemia, defined as arterial oxygen saturation (SaO2 ) < 88% when pulse oximeter oxygen saturation was between 92-96%, in a racially diverse critically ill population; to analyze degree, direction, and consistency of measurement error; and to develop a mitigation strategy that minimizes occult hypoxemia in advance of technological advancements. METHODS: We performed a multi-center retrospective cohort study of critically ill subjects. RESULTS: Among 105,467 paired observations from 7,693 subjects, we found occult hypoxemia was more common among minority subjects. The frequency of occult hypoxemia was 7.9% versus 2.9% between Black and white subjects, respectively, (P < .001). Pulse oximeter measurement errors were inconsistent throughout a patient encounter, with 67% of encounters having a range of intra-subject measurement errors > 4 percentage points. In 75% of encounters, the intra-subject errors were bidirectional. SaO2 < 88% was less common at higher pulse oximeter oxygenation ranges (4.1% and 1.8% of observations among Black and white subjects at a pulse oximeter threshold of 94-98%). Although occult hypoxemia was further reduced at oxygenation saturation range 95-100%, the frequency of hyperoxemia (partial pressure of arterial oxygen > 110 mm Hg) became more common, occurring in 42.3% of Black and 46.0% of white observations. CONCLUSIONS: Measurement error in pulse oximetry is common for all racial groups, but occult hypoxemia occurred most commonly in Black subjects. The highly variable magnitude and direction of measurement error preclude an individualized mitigation approach. In advance of technological advancements, we recommend targeting a pulse oximetry saturation goal of 94-98% for all patients.

Evaluation of in vitro anticancer potential of pharmacological ethanolic plant extracts Acacia modesta and Opuntia monocantha against liver cancer cells.

Acacia modesta (AM) and Opuntia monocantha (OM) are distributed in Pakistan, Afghanistan and India. Both of these plants have different pharmacological properties. This study was designed to evaluate anticancer potential of Acacia modesta (AM) and Opuntia monocantha (OM). Liver cancer cell line HepG2 was used for assessment of anticancer activity. For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of apoptosis ELISA of p53 performed. Furthermore, LDH assay to find out the ability of malignant cells to metabolize pyruvate to lactate and antioxidant enzymes activity (GSH, CAT and SOD) at the end HPLC was performed to find active compound of AM and OM. Cytotoxicity (MTT), Viability assays (trypan blue, crystal viability, MUSE analysis) showed more dead, less live cells in plant treated groups with increase of concentration. Scratch assay for the anti-migratory effect of these plants showed treated groups have not ability to heal scratch/wound. ELISA of p53 for cellular apoptosis showed more release of p53 in treated groups. Antioxidant assay via glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) showed less anti-oxidative potential in treated cancer groups. LDH assay showed more lactate dehydrogenase release in treated groups compared with untreated. HPLC analysis showed the presence of phytochemicals such as steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and amino acids in AM and OM plant extracts. Based on all these findings, it can be concluded that ethanolic extracts of Acacia modesta and Opuntia monocantha have promising anti-cancer potential.

Two methodologies of the rendezvous procedure to establish ureteral continuity from a delayed ureteral leak following pelvic surgery.

BACKGROUND: Ureteral trauma recognized in the operating theater is managed, for the most part, at the same surgical procedure oftentimes with urologic consultation. A delayed urine leak presents unique problems in that direct access to the site of the leak is not possible except by a reoperative procedure. METHODS: In patients who develop delayed urine leakage following cancer surgery, the leakage may be controlled by the collaborative efforts of a urologist and interventional radiologist. Success depends on placement of a nephroureteral stent by the rendezvous procedure. RESULTS: The sequence of procedures to reestablish ureteral continuity following a delayed leak are important in the successful placement of a nephroureteral stent. In the first methodology, through a percutaneous nephrostomy, a guidewire is placed in the ureter and down to the ureteral defect. The guidewire is then recovered and advanced into the bladder using a ureteroscope and grasping forceps. A nephroureteral stent is placed over the guidewire to bridge the gap and stent the ureteral defect. In the second methodology, the urologist passed a guidewire into the distal ureter, out of the ureteral defect, and into the free peritoneal space. Under fluoroscopic control, the wire loop must snare the ureteral guidewire and pull it out at the percutaneous nephrostomy. The nephroureteral stent is passed over the ureteral wire into the bladder. CONCLUSIONS: Two different methodologies were described to complete the rendezvous procedure. It can be successful a large percentage of the time with a delayed ureteral leakage. Success requires a combined interventional radiology and urologic procedure.

Comparative analysis of IVF-ICSI outcomes between advanced and early stage of endometriosis stimulated with HMG.

INTRODUCTION: Endometriosis is a challenging disease to treat, and patients may eventually need in vitro fertilisation with Intracytoplasmic sperm injection (IVF/ICSI) to conceive after other modalities failed. There are inconsistent outcomes of IVF performance in patients with endometriosis especially with highly purified human menotropin gonadotrophin (hMG). This study was commenced to determine whether the use of hMG affects the IVF outcome in different stage of endometriosis. MATERIALS AND METHODS: This is an observational study. Eighty-seven women who had endometriosis confirmed surgically and underwent IVF/ICSI treatment, stimulated with hMG alone were included. Based on the revised American Society for Reproductive Medicine (rASRM), the participants were classified as early endometriosis (I/II) (n=39) or advanced endometriosis (III/IV) (n=35). The main outcome measures used were clinical pregnancy rate. RESULTS: Women with advanced endometriosis had a lower oocyte yield, less good quality day-3 embryos and lower clinical pregnancy rate compared with the mild endometriosis. However, higher fertilisation rate were recorded in advanced stage endometriosis compared to milder disease. CONCLUSIONS: The rASRM classification of endometriosis is valuable in predicting IVF outcome as advanced endometriosis performs poorly compared to a milder disease. Highly purified hMG could be an alternative as an ovarian stimulation in endometriosis.

Effect of intra-arterial vasodilator administration during radial artery access on systemic blood pressure in patients receiving moderate sedation.

PURPOSE: The hemodynamic effects of intra-arterial vasodilator administration for the prevention of radial artery spasm during transradial access have not been well characterized. This study evaluates the effect of intra-arterial Verapamil and Nitroglycerine administration on systemic blood pressure and its correlation with timing of moderate sedation administration. MATERIALS AND METHODS: Institutional review board approval was granted. Patients who underwent transradial access from 4/2018 to 4/2019 and received both intra-arterial vasodilators and moderate sedation were identified and their electronic medical records reviewed. Patients were divided into three cohorts based on the timing of sedation and intra-arterial vasodilator administration. Decrease in systolic blood pressure (SBP) was expressed as means with standard deviation which were then compared using Student's t-test. RESULTS: A total of 84 patients who met inclusion criteria demonstrated an overall mean decrease in SBP of 16.45 mmHg ± 15.45 mmHg. Patients receiving sedation and intra-arterial vasodilators within their expected peak SBP effect times had similar SBP change following the intra-arterial vasodilators as those in whom the interval was greater than 10 min (4.2 mmHg; 95% CI (-4.11 to 12.52), p = 0.3171). Two patients experienced asymptomatic hypotension. CONCLUSIONS: Patients undergoing transradial access for procedures utilizing moderate sedation can safely receive intra-arterial Verapamil and Nitroglycerine for prevention of radial artery spasm.

High incidences of chromosomal aberrations and Y chromosome micro-deletions as prominent causes for recurrent pregnancy losses in highly ethnic and consanguineous population.

PURPOSE: Recurrent Miscarriages (RM) commonly complicates the reproductive outcome where prominently chromosomal aberrations and molecular factors lead to recurrent miscarriages. We investigated couples with RM for cytogenetic abnormalities and Y chromosome microdeletions in males along with detection of aneuploidies de novo in the product of conception from a highly ethnic consanguineous population (Kashmir, North India) . STUDY DESIGN: Chromosomal analysis was done by Karyotyping on peripheral blood lymphocyte cultures and analyzed by Cytovision software Version 3.9. Microdeletion in Y chromosome was performed by STS-PCR and QF-PCR was used to detect aneuploidy in the product of conception. RESULTS: Of the 380 samples (190 couples) screened for cytogenetic analysis, 50 (13.1%) chromosomal aberrations were detected in both couples. Numerical aberrations were detected in 16.0%, inversions 22%, duplications 16.0% and translocations were found in 26.0% with three unique reciprocal translocations in males. The couples bonded consanguineously had 32% chromosomal changes with a significant difference in chromosomal inversions (37.5% vs. 14.7%) and translocations (37.5% vs. 20.6%) for consanguineous and non-consanguineous group, respectively (p < 0.05). Further, translocations and inversions (44.5% and 33.3%) were significantly implicated in couples with a positive family history of RM (p < 0.05). Y chromosome deletions were found in 2.1% cases of males. CONCLUSION: We conclude 15.2% couples affected either by chromosomal or Y chromosome deletions contribute hugely in the diagnosis and management of repeated pregnancy losses. It is recommended that couples that belong to consanguineous and multigenerational group of RM should be considered for cytogenetic and molecular testing after two abortions for successful pregnancy outcomes and management of RM.