The relationship between BCG immunotherapy and oxidative stress parameters in patients with nonmuscle invasive bladder cancer.

INTRODUCTION: Environmental chemicals have been associated with the regulation of oxidative stress markers, which have the potential for the development of bladder cancer. However, limited studies on the function of oxidative stress parameters and nonmuscle invasive bladder cancer (NMIBC) in therapy response are available. Here we studied the oxidative stress parameters in response to BCG immunotherapy in NMIBC patients. MATERIAL AND METHODS: A total of 120 patients with NMIBC and treatment with BCG were enrolled and categorized into 2 groups on BCG response, 50 patients were BCG-responsive (BCG-R) and 70 were BCG-nonresponsive (BCG-N). BCG-R have no evidence of tumor recurrence or advancement after 1 year of BCG immunotherapy, but BCG-N has a recurrence of tumor after 3 to 6 months cycles of BCG instillation, as determined by cystoscopy. In all groups, we measured the levels of oxidative stress markers- malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT). RESULTS: The levels of oxidative stress markers viz. MDA, NO, and SOD in the BCG-N group were significantly higher (P < 0.001) than in the BCG-R group. Furthermore, the data demonstrated a significant correlation between oxidative stress marker and NMIBC T1 high grade and tumor size >2.5 cm. However, no statistically significant difference was found between studied groups with CAT. CONCLUSION: The findings suggest that the carcinogenesis of NMIBC is associated with oxidative damage of biomolecules and indicates the involvement of oxidative stress markers in the development and recurrence of NMIBC.; Therefore, it is critical to ensure the management for T1 high grade and tumor size of >2.5 cm for antioxidant protection.

Effect of Meditation and Breathing Exercises on the Well-being of Patients with SARS-CoV-2 Infection under Institutional Isolation: A Randomized Control Trial.

OBJECTIVES: The corona virus disease-19 (COVID-19) pandemic has affected every domain of human health be it physical or mental. The uncertainty of disease progression in patients with SARS-CoV-2 infection can lead to major psychological and psychiatric concerns that should not be overlooked. The interventions should be directed to the vulnerable population to help them mitigate the stress and anxiety caused by the infection and isolation. We evaluated the effect of meditation and breathing exercises on the well-being of patients with SARS-CoV-2 infection under institutional isolation. MATERIALS AND METHODS: We conducted a randomized control trial on 84 subjects, 18 years and above, asymptomatic, or mildly symptomatic SARS-CoV-2 infected patients under institutional isolation. Subjects were randomly and equally divided into a control group and interventional group. We measured the depression, anxiety, and stress levels as well as quality of sleep in patients after 7 days of meditation and breathing exercises in the intervention group versus standard care in the control group. RESULTS: Meditation and breathing exercises had a statistically significant effect on the depression level (P < 0.001), stress level (P = 0.004), and the quality of sleep [trouble falling asleep (P = 0.007), trouble staying asleep (P = 0.004), and feel tired after waking up in the morning (P = 0.003)]. Further, the positive effect of intervention on the level of anxiety in patients under isolation was also observed; however, the difference was not found to be statistically significant (P = 0.528). CONCLUSION: Meditation and breathing exercises have positive effects on depression, stress levels, and quality of sleep in COVID-19 positive patients under strict institutional isolation.

Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.

Occupational exposure to pesticides in female tea garden workers and adverse birth outcomes.

Pesticides are globally used to eliminate pests from crops and plants. The increased use of pesticides has posed a serious threat to human health. This study evaluates the effects of pesticide exposure on pregnancy outcomes in tea garden workers (TGW). The acetylcholinesterase (AChE) activity was measured in the maternal blood, placenta, and cord blood of TGW and housewives (HWs). The placental structure and expression of hypoxia-inducible factor (HIF)-1α were also analyzed in TGW and HW groups delivering low birth weight (LBW) and normal birth weight (NBW) babies. A significantly decreased AChE activity was observed in maternal blood and cord blood in TGW as compared with HW in the LBW group. However, it did not change significantly in the NBW group (p < .05). The adjusted regression analysis of birth outcomes (birth weight, head circumference, infant's length, and ponderal index) revealed a significant and positive association with the levels of AChE activity in maternal blood, placenta, and cord blood in TGW (p < .05). The histological analysis showed significantly higher placental syncytial knots, chorangiosis, fibrinoid deposition, necrosis, and stromal fibrosis in the LBW group of TGW. Microinfarction, increased fibrinoid deposition, and atypical villi characteristics, such as mushroom-like structures, were observed during scanning electron microscopy along with increased HIF-1α expression in placental tissues of TGW exposed to pesticides. Results suggest that occupational pesticide exposure during pregnancy may decrease AChE activity and cause in utero pathological changes accompanied by an increased HIF-1α expression, which also contributes to placental insufficiency and fetal growth restriction.

The Efficacy of Scrambler Therapy for the Management of Head, Neck and Thoracic Cancer Pain: A Randomized Controlled Trial.

BACKGROUND: Pain is still a common feature in all types of cancers including head and neck and thoracic cancer. Neuromodulatory techniques have gained popularity over opioids in recent times because of the risks associated with chronic opioid therapy. There are no clinical trials evaluating the efficacy of scrambler therapy (ST) for the management of pain due to head and neck and thoracic cancer. OBJECTIVE: This trial was undertaken to evaluate the efficacy of scrambler therapy (ST) for pain relief and to assess the possible effect of ST on the dosage of opioids in patients suffering from cancer pain. STUDY DESIGN: A randomized control trial (RCT) was performed. SETTING: The trial was conducted at the Pain and Palliative Care Unit of the Dr. B.R. Ambedkar Institute Rotary Cancer Hospital of All India Institute of Medical Sciences, New Delhi, India. METHOD: Forty patients were included in each of the 2 arms, control and Intervention. In both arms, patients were given pain management drugs. In the intervention group, patients additionally received 10 consecutive sessions of ST with one follow-up after 7 days. A numeric rating scale (NRS-11) was used to measure pain. Drug dosage was also recorded. RESULTS: Overall, pain decreased in both arms. However, pain decreased more in the intervention arm as compared to the control arm. The total change in the mean score of the NRS-11 from baseline to follow-up was 3.1 and 6.19 in the control and ST arms, respectively. Differences between pain scores in both arms became significant from day 3 onwards. Mean morphine dose was significantly lower in the intervention arm from day 7 onwards. LIMITATIONS: The study followed the patients until one week after the last treatment session and encouraged patients to return for treatment if their pain returned to previous levels within 10 days. Moreover, patients in the control arm received the standard of care in the form of pharmacological treatment but did not receive either transcutaneous electrical nerve stimulation (TENS) or a sham (placebo) procedure. CONCLUSIONS: The trial showed that ST is an effective treatment for the management of pain due to head and neck and thoracic cancer. On the basis of this study, the use of ST for the management of refractory cancer pain in head and neck and thoracic cancer is recommended.

Unveiling molecular associations of polymorphic variants of VDR gene (FokI, BsmI and ApaI) in multiple myeloma patients of Indian population.

Multiple myeloma (MM) is a plasma cell malignancy frequently accompanied with skeletal co-morbidity. Vitamin D (1,25(OH)2D) is an important mediator of skeletal homeostasis that mediates its effect by binding to vitamin D receptor (VDR), a steroid family receptor and modulates various downstream pathways. Multiple polymorphisms have been determined in VDR gene that witnessed significant association with cancer development and progression. Therefore, in this maiden study, we recruited 75 newly diagnosed MM patients and 75 control subjects. 25-hydroxy vitamin D (25(OH)D) levels were measured in all recruited study subjects. Further, PCR-RFLP was performed in DNA samples of recruited study subjects. Results demonstrated significantly decreased 25(OH)D levels in MM patients compared to controls. Additionally, decreased 25(OH)D levels in MM patients inversely associated with disease severity. Further, single nucleotide polymorphism (SNP) analysis of VDR gene showed significantly higher risk of MM disease development in Ff + ff, Aa + aa, and Bb + bb genotypes. Additionally, FokI f, ApaI a and BsmI b alleles were significantly associated with MM occurrence. In conclusion, this study provided initial evidences of association between 25(OH)D insufficiency, VDR gene polymorphism and MM development. Thus, we suggest that a study involving assessment of 25(OH)D levels and VDR gene polymorphism in large patients' cohort might substantiate their role in MM development which would further provide impetus to give 25(OH)D supplementation along with conventional chemotherapeutic agents for myeloma treatment in future.

Fisetin attenuates isoproterenol-induced cardiac ischemic injury in vivo by suppressing RAGE/NF-κB mediated oxidative stress, apoptosis and inflammation.

BACKGROUND: The therapeutic options for the reducing the damage caused by myocardial ischemia are limited and not devoid of adverse effects. The role of the flavanoid, fisetin, predominantly found in strawberry and apple, is yet to be explored in the heart. STUDY DESIGN: Male Wistar rats (n = 48) were administered fisetin (10, 20 & 40 mg/kg/day, orally) or vehicle for 28 days while ISO, 85 mg/kg, subcutaneously, was also administered at 24 h interval on the 27th and 28th day. On the 29th day, rats were anaesthetized and right carotid artery was cannulated to record hemodynamic parameters. Subsequently, blood sample was collected and heart was removed to evaluate various parameters. RESULTS: Fisetin at doses of 10 and 20 mg/kg reversed ISO induced detrimental alterations in blood pressure and left ventricular pressures and reduced the myocardial injury markers CK-MB and LDH in the serum. These findings were supported by amelioration of ISO induced histological and ultrastructural damage by fisetin. The disequilibrium in the levels of pro and anti oxidants in the myocardial tissue caused by ISO was also normalized Furthermore, apoptosis was evident from enhanced DNA fragmentation and raised pro-apoptotic proteins (bax, caspase-3, cytochrome-c) as well as suppressed anti-apoptotic protein (Bcl-2) in case of ISO treatment which again was reversed by fisetin. A molecular mechanism for this protection was elucidated as downregulation of RAGE and NF-κB However fisetin at 40 mg/kg revealed a deteriorating effect which was similar to ISO group of rats. CONCLUSION: Hence, through our study, the role of fisetin in cardioprotection has been uncovered via a molecular pathway.

Vesicovaginal fistula due to vaginal herb for primary infertility: could it be devastating?

Vesicovaginal fistula (VVF) is a very commonly encountered urogynaecological entity in developing countries such as India. The most common cause of VVF in developing counties is secondary to obstructive labour. We report a very unusual case of VVF in a young woman that developed due to insertion of an unknown vaginal herb for treatment of primary infertility. Cystoscopy showed a single trigonal fistula measuring 3×2 cm just near the bladder neck. Vaginoscopy revealed cicatrised less capacious vagina and unhealthy vaginal mucosa. She was treated with transvaginal VVF repair using Martius flap interposition which leaked on 10th postoperative day. She underwent re-evaluation and another transvaginal fistula repair for small trigonal residual fistula after 3 months. She is doing well during the follow-up of 2 years. She attained sexual activity after 3 months of surgical repair but could not conceive.

Grading complications after transurethral resection of prostate using modified Clavien classification system and predicting complications using the Charlson comorbidity index.

PURPOSE: To retrospectively report and grade the peri-operative complications of transurethral resection of the prostate (TURP) using the modified Clavien classification system (MCCS) and validate whether Charlson comorbidity index (CCI) predicts the complications after TURP. MATERIALS AND METHODS: Between September 2006 and 2012, data of 722 patients who underwent TURP were analyzed after excluding patients with incomplete data (n = 40). Data recorded included the age, prostate volume, operative time, mean prostatic tissue removed and duration of hospitalization while complications were recorded using the MCCS. Preexisting comorbidities were evaluated using the CCI, and patients were classified into 3 CCI score categories (0, 1, ≥ 2). RESULTS: Two hundred and forty-four complications were seen in 145 (20 %) patients. CCI score was "0" for 480 patients (66.5 %), "1" for 184 patients (25.5 %) and "≥ 2" for 58 patients (8 %). Significant difference was observed between patient groups with CCI score 0, 1 and ≥ 2 for mean age, prostatic weight, operative time, weight of prostatic chips and duration of hospitalization. Similarly, a significant difference in occurrence of various MCCS grades of complication among patients groups with different CCI score was observed. CONCLUSION: Grades I, II and III complications constituted the main bulk (90 %) while grade IV were less common (<8 %) and grade V was rare (1 %) after TURP. Men with higher CCI score had a significantly higher rate of morbidity than those with a lower score. The present study is the first to validate that CCI can predict complications of TURP recorded according to the MCCS.

Outcome of simultaneous transurethral resection of bladder tumor and transurethral resection of the prostate in comparison with the procedures in two separate sittings in patients with bladder tumor and urodynamically proven bladder outflow obstruction.

BACKGROUND AND PURPOSE: A prospective randomized study was undertaken wherein transurethral resection of bladder tumor (TURBT) was performed along with transurethral resection of the prostate (TURP) in the same sitting (group A) in patients with bladder tumor and urodynamically proven bladder outflow obstruction. The outcome (recurrence and progression of superficial transitional cell carcinoma) was compared with patients who underwent TURBT and TURP in two separate sittings (group B) approximately 6 months apart. PATIENTS AND METHODS: Between January 2002 and December 2007, 48 patients were randomized for this study. The inclusion and exclusion criteria are described below. The patients were followed up according to standard protocols. The two groups were compared for the recurrence and progression of the bladder tumor. RESULTS: Mean age in both the groups were similar (group A = 56.06 +/- 4.45 years, group B = 57.36 +/- 3.65 years). The mean duration of follow-up was also similar between the two groups (group A, 35.71 +/- 12.8 months; group B, 37.55 +/- 14.12 months; P > 0.05). In group A, 12 (50%) patients had recurrence, while in group B, 11 (42.85%) patients had recurrence. The differences in recurrence, mean elapsed time to recurrence, and progression of tumor between the two groups were statistically insignificant. CONCLUSION: TURBT and TURP can be performed simultaneously without any increased risk of recurrence and progression of tumor, if performed in a properly selected group of patients.

Withania somnifera Improves Semen Quality in Stress-Related Male Fertility.

Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.