OBJECTIVE: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells. METHODS: Sulforhodamine B (SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide (IIIM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4',6-diamidino-2-phenylindole (DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma (EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice. RESULTS: IIIM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of IIIM-067 toward A549 cells was higher among other cancer cell lines, with a selectivity index (SI) value of 2.28. IIIM-067 demonstrated concentration- and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and 0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells (SI > 1) than the parent compound colchicine (SI = 1). IIIM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. IIIM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP (100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated 78% apoptosis at 0.4 μmol/L. IIIM-067 significantly (P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore, IIIM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition (TGI) of 67.0% at a dose of 6 mg/kg (i.p.) and a reduced mortality compared to colchicine. IIIM-067 also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68% and 44.00% at doses of 5 mg/kg (i.p.), 6 mg/kg (i.p.) and 7 mg/kg (p.o.), respectively. CONCLUSION IIIM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.
Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Reactive Oxygen Species/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Colchicine/pharmacology* ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Mammals/metabolism*

Purpose: Mucormycosis is a multisystemic, aggressive, and an opportunistic fungal infection. The most common type is rhino-orbito-cerebral mucormycosis (ROCM) accounting for almost 40% of the cases. In this study, we analyzed the etiopathology, clinical features, treatment outcome, and the factors associated with outcome in ROCM. Methods: Case records of 52 patients of ROCM were analyzed. Clinical parameters, laboratory parameters, imaging findings, treatment regime, and treatment outcome details were retrieved from each case record. The outcome measures were evaluated as treatment success and treatment failure. Univariate and logistic regression analyses were performed to identify factors associated with treatment outcome. Results: On univariate analysis, factors associated with poor treatment outcome were uncontrolled blood sugar, blood urea, diabetic ketoacidosis, duration of ocular symptoms, no perception of light at presentation, ptosis, conjunctival chemosis, relative afferent pupillary defect, two or more sinus involvement, bony erosion of orbital wall, intracranial extension, intraconal invasion, etc. On subsequent logistic regression analysis, factors that maintained significant association with poor treatment outcome were uncontrolled blood sugar (adjusted odds ratio [aOR], 1.17; p = 0.018), no perception of light at presentation (aOR, 10.67; p = .006), ptosis at presentation (aOR, 3.90; p = 0.03), conjunctival chemosis (aOR, 7.11; p = 0.024), relative afferent pupillary defect (aOR, 10.60, p = 0.01), central retinal artery occlusion at presentation (aOR, 3.54; p = 0.021) and two or more sinus involvement (aOR, 4.90; p = 0.009). Conclusions The current study identified newer factors in the form of presenting ocular and radiological features as predictors for aggressive systemic disease and poor treatment outcome. Future prospective studies are, however, needed to substantiate these associations.

Background: Laser hemorrhoidoplasty (LHP) is a treatment for symptomatic internal hemorrhoids. Nevertheless, there are disparities in the technique employed, including combining it with pedicle ligation. We aimed to investigate if short-term clinical outcomes were different between patients undergoing LHP with and without pedicle. Methods: Patients who underwent LHP from a prospective registry of 3 centers were identified. Demographics, severity, symptoms, operative technique, post-operative pain, complications, and recurrence were investigated. Sub-investigation of patients with simultaneous pedicle ligation, and without, was performed. Statistical analysis was done using the χ2 test. P values <0.05 were noted as statistically significant. Results: One hundred and two patients (59.8% male) of a mean age of 45 years were assessed. Most (62.7%) had 3rd degree hemorrhoids. Median operative time was 24 minutes (10-60 minutes) minutes. Post-operative length of stay was 26 hours (2-168 hours) hours. Median pain score 24 hours post-operatively was 0/10. The general complication percentage was 26.5%, but majority complications were self-limiting. The most common complication was post-operative swelling (16 patients; 15.7%). Post-operative bleeding was seen in 9 patients (8.8%) at a median of 7 (1-14) days, 3 of whom needed operation and readmission. Then 4 patients (3.9%) had moderate-to-severe pain (pain score of more than 5/10), 2 patients (2.0%) developed ulceration and 3 patients (2.9%) had recurrence, were treated conservatively. Patients with pedicle ligation had a higher complication (33.3% vs. 14.8%; p=0.08), mainly bleeding and swelling but not statistically significant. Conclusions LHP demonstrates good short-term outcomes with minimal complication and recurrence incidences. Supplementary ligation of pedicles does not provide additional benefits, and in fact, may worsen outcomes.
Hemorrhoids

Objectives: The quality of life declines gradually as women enter menopause, owing to the various problems associated with estrogen deficiency and aging, which adds to their morbidities. This study aimed to investigate the patterns of morbidity among rural menopausal women and compare the morbidity patterns among menopausal transition group and post-menopausal women. Methods: This community-based cross-sectional study included menopausal women aged 45–55 years from rural areas of the Etawah district, Uttar Pradesh, India. To select blocks and villages of the district, multistage random sampling was performed. According to a pretested, semistructured schedule, data were collected through interviews. Results: A total of 315 women participated in the study. The most frequent complaints among the participants were of feeling tired and worn out (85.1%) and of muscle and joint pains (67.6%). Poor memory (P = 0.046) and diabetes (P = 0.024) were more common in women who were in the menopause transition phase than in those who were in the postmenopausal phase. Conclusions This study showed that majority of the menopausal women suffered from physical problems. Lifestyle modification and awareness programs will be beneficial among women in menopausal transition, to reduce the morbidity later in post-menopausal stage.Behaviour change communication, family and community support are essential in post-menopausal women, to help them cope with various morbid conditions.

Purpose: To compare the efficacy of 0.1% nepafenac and 1% prednisolone acetate eye drop in postoperative inflammation control in micro-incisional cataract surgery. Methods: We conducted a prospective, randomized, comparative, single-blind study. All the patients underwent temporal 2.2-mm micro-incisional cataract surgery. They were randomized into two groups (group A and B). Group A received 0.1% nepafenac eye drops 4 times/day for 4 weeks and group B received 1% prednisolone acetate eye drops in tapering doses for 4 weeks after surgery. Both the groups received moxifloxacin 0.5% eye drops 4 times/day for 2 weeks. Patients were examined on 1st, 7th, and 30th postoperative days and parameters of postoperative inflammation were evaluated and noted at each visit. Results: A total of 200 patients were enrolled in the study. However, five patients lost to follow up, group A had 97 and group B had 98 patients respectively. Results were statistically insignificant in terms of the difference in lid edema, conjunctival congestion, corneal edema, anterior chamber cells and flare between the two groups with p-values >0.05 for each parameter at each visit. However, the difference in mean central macular thickness between the groups was significant (205.713 ± 17.14 vs. 220.984 ± 32.83 in group A and B, respectively, p ≤ 0.001) at 1 month. Also, the mean pain score was significantly lower (p = 0.018) in the nepafenac group at day 7 of surgery. Conclusions Nepafenac is equally effective and non-inferior to prednisolone acetate in suppression and prevention of inflammation in postoperative period.

Objectives: The quality of life declines gradually as women enter menopause, owing to the various problems associated with estrogen deficiency and aging, which adds to their morbidities. This study aimed to investigate the patterns of morbidity among rural menopausal women and compare the morbidity patterns among menopausal transition group and post-menopausal women. Methods: This community-based cross-sectional study included menopausal women aged 45–55 years from rural areas of the Etawah district, Uttar Pradesh, India. To select blocks and villages of the district, multistage random sampling was performed. According to a pretested, semistructured schedule, data were collected through interviews. Results: A total of 315 women participated in the study. The most frequent complaints among the participants were of feeling tired and worn out (85.1%) and of muscle and joint pains (67.6%). Poor memory (P = 0.046) and diabetes (P = 0.024) were more common in women who were in the menopause transition phase than in those who were in the postmenopausal phase. Conclusions This study showed that majority of the menopausal women suffered from physical problems. Lifestyle modification and awareness programs will be beneficial among women in menopausal transition, to reduce the morbidity later in post-menopausal stage.Behaviour change communication, family and community support are essential in post-menopausal women, to help them cope with various morbid conditions.

Purpose: To compare the efficacy of 0.1% nepafenac and 1% prednisolone acetate eye drop in postoperative inflammation control in micro-incisional cataract surgery. Methods: We conducted a prospective, randomized, comparative, single-blind study. All the patients underwent temporal 2.2-mm micro-incisional cataract surgery. They were randomized into two groups (group A and B). Group A received 0.1% nepafenac eye drops 4 times/day for 4 weeks and group B received 1% prednisolone acetate eye drops in tapering doses for 4 weeks after surgery. Both the groups received moxifloxacin 0.5% eye drops 4 times/day for 2 weeks. Patients were examined on 1st, 7th, and 30th postoperative days and parameters of postoperative inflammation were evaluated and noted at each visit. Results: A total of 200 patients were enrolled in the study. However, five patients lost to follow up, group A had 97 and group B had 98 patients respectively. Results were statistically insignificant in terms of the difference in lid edema, conjunctival congestion, corneal edema, anterior chamber cells and flare between the two groups with p-values >0.05 for each parameter at each visit. However, the difference in mean central macular thickness between the groups was significant (205.713 ± 17.14 vs. 220.984 ± 32.83 in group A and B, respectively, p ≤ 0.001) at 1 month. Also, the mean pain score was significantly lower (p = 0.018) in the nepafenac group at day 7 of surgery. Conclusions Nepafenac is equally effective and non-inferior to prednisolone acetate in suppression and prevention of inflammation in postoperative period.

PURPOSE: Road traffic accidents (RTAs) are a public health issue and cost a lot to individuals, families, communities and nations. Trauma care systems in India are at a nascent stage of development. There is gross disparity between trauma services available in various parts of the country. Rural area in India has inefficient services for trauma care, due to the varied topography, financial constraints, and lack of appropriate health infrastructure. The present study is to study the trends of occurrence of RTA cases by month, week and time of accident occurrence as well as to research the types of vehicle involved in accidents and other various risk factors related to them. METHODS: During 1st January 2017 to 31st December 2017, a hospital-based and cross-sectional study of RTA victims was conducted. The patients were admitted in emergency department of Uttar Pradesh University of Medical Sciences, Saifai, Etawah, when stabilized, they were shifted to the orthopaedics and surgery ward. RESULTS: In the study, 654 road accident victims were included, of which the majority were males (77.5%) and the most of them belonged to rural (67%). RTA victims according to the month of occurrence majority were found in January (12.5%) and evening was time of a day with maximum accidents (32.1%). Mortality cases of RTA victims based on type of road user and it shows decreasing trend of mortality of motorcyclists (54.2%) followed by pedestrian (25.1%). CONCLUSION There should be control over people driving vehicles under the influence of alcohol and drivers over-speeding and rash driving on urban roads as well as rural village roads.
Accidental Injuries ; epidemiology ; mortality ; prevention & control ; Accidents, Traffic ; prevention & control ; statistics & numerical data ; Adolescent ; Adult ; Automobile Driving ; Cross-Sectional Studies ; Emergency Service, Hospital ; statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Risk Factors ; Seasons ; Tertiary Care Centers ; statistics & numerical data ; Time ; Young Adult

OBJECTIVE: Bergenia ciliata (Haw.) Sternb. is used in the Indian traditional system of medicine to treat various ailments including rheumatism and to heal wounds. The objective of the present study was to perform a preclinical characterization of the B. ciliata-based botanical extract IIIM-160. METHODS: IIIM-160 was chemically standardized and analyzed for heavy metal content, aflatoxins, pesticides and microbial load. The in vitro and in vivo efficacies were determined in suitable models of inflammation, arthritis and nociception. An acute oral toxicity study was performed in Swiss albino mice. A suitable oral formulation was developed and characterized. RESULTS: Bergenin was found to be the major component (9.1% w/w) of IIIM-160. The botanical lead displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6 (IL-6) and had an excellent safety-window. It showed anti-inflammatory, anti-arthritic and antinociceptive activity in animal models and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice. The gastroretentive, sustained-release capsule formulation showed sustained-release of the bergenin over the period of 24 h, resulting in improved plasma-exposure of bergenin in Sprague-Dawley rats. CONCLUSION The dual-activity of IL-6 inhibition and antinociception marks the suitability of IIIM-160 for treating rheumatoid arthritis. This study will serve as the benchmark for further research on this botanical formulation.

Pheochromocytomas are rare tumours originating from the chromaffin tissue. The clinical manifestations are variable and are not specific; as a result, pheochromocytomas often imitate other diseases. The diagnosis is usually established by biochemical studies, i.e., the measurement of catecholamines or their metabolites in urine or plasma, followed by radiographic and scintigraphic studies for localisation. Surgical removal of the tumour is the preferred treatment. We report a 30-year-old woman presenting with an adrenal incidentaloma that was 7.6 × 5.3 × 4.8 cm in size on an abdominal computed tomography scan. Investigations for adrenal hormones, including a low-dose dexamethasone suppression test, plasma aldosterone level, 24-hour urinary metanephrine and vanillylmandelic acid levels, and plasma metanephrine level were all within the normal ranges. During the surgical resection, the patient had a hypertensive spell. Surgery was postponed, and the blood pressure was adequately controlled with α blockers, followed by β blockers. After 2 weeks, the surgery was followed by a pathological biopsy that confirmed the pheochromocytoma diagnosis.