One pot synthesis of 5-hydroxyalkylated thiadiazine thiones: Implication in pain management and bactericidal properties.

The synthesis of a new series of thiadiazine thiones including 5-(2-hydroxyethyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (1-5), 5-(2-hydroxypropyl)-3-alkyl/aryl-1, 3, 5-thiadiazine-2-thiones (6-8), 3,5-dipropyl-1, 3, 5-thiadiazine-2-thione (9) and (2-(5-alkyl/aryl-6-thioxo-1, 3, 5-thiadiazine-3-yl) alkyl acetate/benzoate) (10-17) was accomplished via one pot reaction. The structures of the synthesized compounds were characterized through NMR and Mass spectrometry. The anti-nociceptive activity of compounds was performed on BALB/C mice by hot plate method, where compounds 3, 5 (50 µg/kg), and 8 (50, 100 µg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time of 15, 30, and 60 min, while compounds 6 and 16 (100 µg/kg) exhibited significant effect (P < 0.01, P < 0.05) in latency time interval of 15 and 30 min. Compounds 1, 12-13, and 15 showed moderate activity. Among the tested hits, compounds 5 (17.3 ± 2.2), 11 (16.2 ± 2.1), and 8 (16.1 ± 2.1) showed significant anti-nociceptive potential. Molecular docking studies on the most active anti-nociceptive hits indicated that the activity might be attributed to the ability of the compounds to target µ-opioid receptor (µOR) effectively. Furthermore, compounds 14 and 11 showed anti-bacterial activity against Pseudomonas aeruginosa and MSRA with MIC of 40.97 and 54.77 µg/mL, respectively. In addition, the predicted ADMET profile of 5, 9, and 11 indicates that these molecules follow the drug-likeness criteria, and their activity can be enhanced through structural optimization.

Seroprevalence of SARS-CoV-2: Insights into the epidemiology of the pandemic.

AIM: This study aimed to assess the seroprevalence of SARS-CoV-2 and disease symptoms in Malakand, Pakistan. MATERIALS & METHOD: 623 samples with suspected SARS-CoV-2 were collected from different regions of Malakand and analyzed to detect SARS-CoV-2 IgG antibodies using ELISA. RESULTS: 306 (49.1%) 0 f 623 patients were anti-SARS-CoV-2 IgG reactive, with a higher prevalence in males (75%) than females (25%). In this study, we enrolled two groups, subjects working in a non-medical setting and subjects working in a medical setting. Clinical symptoms were statistically linked with SARS-CoV-2. Four weeks of follow-up analysis of IgG titers in health care workers showed an increase in IgG antibodies titer. CONCLUSION: This study gives insights into the community-based spread of SARS-CoV-2 infection, associated immunity, and herd immunity in the studied population. This study can provide insights to the government about early vaccination of this population as most of the population is not yet vaccinated.

Suburethral Endometriosis as Clinical Finding of Extensive Disease.

Objective: Endometriosis spreading to the vagina is rare, present in only 0.02% of women with symptomatic endometriosis. Suburethral lesion site is exceptional. In an extensive literature review only 4 cases of suburethral endometriosis were identified. Our objective is to present a case of primary vaginal suburethral endometriosis in a 31-year old patient who underwent laparoscopic evaluation and to perform a literature review on this topic. Methods and Procedures: Case report presentation based on information extracted from patient database. A review of literature with a Medline search using key words urethral endometriosis, suburethral endometriosis, or urethral diverticulum was undertaken. Results: This case report describes a case of a 31-year old female patient referred for severe pelvic pain, worsening during menstruation. On physical examination a 2 cm suburethral endometriotic lesion was found as the initial presentation. Her examination was also significant for enlarged, tender uterus and adnexa. Based on examination and imaging, adenomyosis and endometriosis were suspected. Surgical evaluation revealed extensive endometriosis with lymph node involvement at laparoscopic exploration. The review of literature revealed only 4 cases where suburethral endometriosis was previously identified. Conclusion: Primary vaginal suburethral endometriosis, although rare, could be an indication of extensive endometriosis. This case highlights the importance of careful clinical examination, surgical excision, and laparoscopic evaluation when identifying suburethral vaginal endometriotic lesions.

Neutrophilia and mortality in women with uterine carcinosarcoma.

OBJECTIVE: The objective of this study was to investigate the relationship between pre-treatment absolute neutrophil count and clinical outcomes in patients with uterine carcinosarcoma. METHODS: In an Institutional Review Board approved, retrospective cohort study of 103 patients with uterine carcinosarcoma, the pre-treatment absolute neutrophil count data were obtained from the medical records, along with clinical, pathologic, treatment, and outcome data. Kaplan-Meier survival estimates were calculated and compared by the log rank test. Univariable and multivariable Cox proportional hazard regression models were used to examine the relationship of pre-treatment absolute neutrophil count with progression-free survival and overall survival. RESULTS: Uterine carcinosarcoma patients in the highest quartile of pre-treatment absolute neutrophil count had significantly reduced progression-free survival (p<0.001, log rank test), and overall survival (p<0.001, log rank test), compared with patients in the lower absolute neutrophil count quartiles. On multivariable analysis, high absolute neutrophil count was an independent poor prognostic factor for disease recurrence, HR 2.97 (95% CI 1.35 to 6.53, p=0.007) for highest versus lowest quartile absolute neutrophil count, and for mortality, HR 4.43 (95% CI 1.64 to 12.00, p= 0.003). CONCLUSIONS: High pre-treatment absolute neutrophil count is an independent poor prognostic factor in patients with uterine carcinosarcoma and may be useful as a potential biomarker in clinical trials. The mechanistic relationship of neutrophilia and uterine carcinosarcoma progression merits further investigation.

Epidemiology of Second Primary Tumors in Women With Ovarian Cancer.

OBJECTIVE: The last large study of second primary tumors (SPTs) in women with ovarian cancer was published in 1996, prior to major changes in the differential diagnosis and treatment. The present study reports on the incidence of SPTs in a contemporary cohort of patients with a diagnosis of ovarian cancer. METHODS: Ovarian cancer patients with a diagnosis of an ovarian malignancy between 1992 and 2012 were identified and characterized from 13 registries of the Surveillance, Epidemiology, and End Results database. RESULTS: Of 41,073 women with a diagnosis of an ovarian malignancy between 1992 and 2012, 1831 (4.5%) developed a microscopically confirmed SPT. There was no significant difference in the risk of developing an SPT at all sites between women with an ovarian cancer and the general population. There was an elevated risk of site-specific SPTs of the small intestine, vagina, thyroid gland, and acute nonlymphocytic leukemia in ovarian cancer patients compared with the general Surveillance, Epidemiology, and End Results population. Conversely, the risk of lung and non-Hodgkin lymphoma was significantly decreased in women with ovarian cancer. An elevated risk of SPTs was observed in women with mucinous, endometrioid, and germ cell tumors. White women had an overall decreased risk of developing a second primary solid tumor, whereas American Indian and Asian/Pacific Islander women had an overall increased risk of an SPT at any site. CONCLUSIONS: The incidence of SPTs in women with ovarian cancer was not significantly different as compared with the general population. However, divergent rates of SPTs in relation to histology, latency, age, and race were observed.

Chlamydia Peritonitis and Ascites Mimicking Ovarian Cancer.

Background. Pelvic inflammatory disease (PID) rarely results in diffuse ascites. Severe adhesive disease secondary to PID may lead to the formation of inclusion cysts and even pelvic peritoneal nodularity due to postinflammatory scarring and cause an elevation of serum CA-125 levels. The constellation of these findings may mimic an ovarian neoplasm. Case. We report a case of a 22-year-old female who presented with multiple pelvic cysts and diffuse ascites due to Chlamydia trachomatis infection. The initial gynecologic exam did not reveal obvious evidence of PID; however, a positive Chlamydia trachomatis test, pathologic findings, and the exclusion of other etiologies facilitated the diagnosis. Conclusion. Chlamydia trachomatis and other infectious agents should be considered in the differential diagnosis of a young sexually active female with abdominal pain, ascites, and pelvic cystic masses. Thorough workup in such a population may reduce the number of more invasive procedures as well as unnecessary repeat surgical procedures.

Supraumbilical primary trocar insertion for laparoscopic access: the relationship between points of entry and retroperitoneal vital vasculature by imaging.

OBJECTIVES: Advances in laparoscopy have demonstrated that supraumbilical primary ports can be desirable in complex cases with large masses. This study evaluated distances to vital retroperitoneal vasculature that were encountered with 45- and 90-degree angle entry from the umbilicus and 2 commonly described supraumbilical entry points at 3 and 5 cm cephalad from the umbilicus. STUDY DESIGN: Retrospective analysis of computed tomography scans of the abdomen and pelvis from 100 randomly selected women who were 18-50 years old with normal anatomy was performed. Three-dimensional models of sagittal sections were generated using IMPAX software. Measurements from the abdominal wall at the umbilicus and 3 and 5 cm cephalad with 45- and 90-degree angles to retroperitoneal structures were performed. RESULTS: With 90-degree angle entry, the abdominal wall thickness (AWT) was thinnest at the umbilicus; however, the thickness at 3 and 5 cm was similar. AWT increased at all sites with 45-degree angle entry, and the same pattern was observed. AWT and intraperitoneal distance positively correlated with body mass index and supraumbilical entry points. With 90-degree angle entry, the aorta was 1.9 cm (95% confidence interval [CI], 1.4-2.4) and 2.5 cm (95% CI, 2.0-2.9) farther away at 3 and 5 cm cephalad compared with umbilical entry. In one-third of the cases, regardless of port placement, a vascular structure other than the aorta was the most anterior vessel. With 45-degree angle entry at the umbilicus, no vessels were encountered. With 45-degree angle entry at 3 and 5 cm cephalad, the aorta was the most anterior vessel in 1% and 2% of cases, respectively, and was noted to be 1.0 cm (95% CI, 1.0-1.0) and 2.3 cm (95% CI, 1.2-3.3) farther away than with 90-degree angle entry. A vessel other than the aorta was encountered in 4% and 7% of cases at 3 and 5 cm, respectively. CONCLUSION: According to theoretic modeling, supraumbilical primary port placement can be implemented safely in laparoscopy. With supraumbilical entry, the distance to retroperitoneal vessels was greater than at the umbilicus. Compared with a 90-degree angle, with a 45-degree angle entry, it was uncommon to encounter vasculature, and all measured distances were greater.

Surgical site infection in women undergoing surgery for gynecologic cancer.

OBJECTIVES: The objectives of this study were to describe the rate and predictors of surgical site infection (SSI) after gynecologic cancer surgery and identify any association between SSI and postoperative outcome. MATERIALS AND METHODS: Patients with endometrial, cervical, or ovarian cancers from 2005 to 2011 were identified from the American College of Surgeons National Surgical Quality Improvement Program. The extent of surgical intervention was categorized into modified surgical complexity scoring (MSCS) system. Univariate and multivariate logistic regression analyses were used. Odds ratios were adjusted for patient demographics, comorbidities, preoperative laboratory values, and operative factors. RESULTS: Of 6854 patients, 369 (5.4%) were diagnosed with SSI. Surgical site infection after laparotomy was 3.5 times higher compared with minimally invasive surgery (7% vs 2%; P < 0.001). Among laparotomy group, independent predictors of SSI included endometrial cancer diagnosis, obesity, ascites, preoperative anemia, American Society of Anesthesiologists class greater than or equal to 3, MSCS greater than or equal to 3, and perioperative blood transfusion. Among laparoscopic cases, independent predictors of SSI included only preoperative leukocytosis and overweight. For patients with deep or organ space SSI, significant predictors included hypoalbuminemia, preoperative weight loss, respiratory comorbidities, MSCS greater than 4, and perioperative blood transfusion for laparotomy and only preoperative leukocytosis for minimally invasive surgery. Surgical site infection was associated with longer mean hospital stay and higher rate of reoperation, sepsis, and wound dehiscence. Surgical site infection was not associated with increased risk of acute renal failure or 30-day mortality. These findings were consistent in subset of patients with deep or organ space SSI. CONCLUSIONS: Seven percent of patients undergoing laparotomy for gynecologic malignancy developed SSI. Surgical site infection is associated with longer hospital stay and more than 5-fold increased risk of reoperation. In this study, we identified several risk factors for developing SSI among gynecologic cancer patients. These findings may contribute toward identification of patients at risk for SSI and the development of strategies to reduce SSI rate and potentially reduce the cost of care in gynecologic cancer surgery.

Prevalence and prognostic impact of lymphadenectomy and lymph node metastasis in clinically early-stage ovarian clear cell carcinoma.

OBJECTIVES: The objective of this study was to estimate the prevalence and prognostic impact of lymphadenectomy and lymph node involvement in patients with ovarian clear cell carcinoma (OCCC) grossly confined to the ovary. METHODS: Patients with a diagnosis of OCCC grossly confined to the ovary were identified from Surveillance, Epidemiology, and End Results program from 1988 to 2007. Only surgically treated patients were included. Statistical analysis using Student t test, Kaplan-Meier survival methods, and Cox proportional hazards regression were performed. RESULTS: One thousand eight hundred ninety-seven patients with OCCC who have undergone surgical treatment and deemed at time of the surgery to have disease grossly confined to the ovary were included: 538 (28.3%) had no lymphadenectomy (LND -1), and 1359 (71.7%) had lymphadenectomy. Of the 1359 patients who had lymphadenectomy, 1298 (95.5%) were International Federation of Gynecology and Obstetrics (FIGO) surgical stage I (LND +1), and 61 (4.5%) were upstaged to FIGO stage IIIC due to nodal metastasis (LND +3C). The 5-year disease-specific survival was 84.9% for LND -1, 88.0% for LND +1, and 65.0% for LND +3C (P < 0.001). Among those with histologically negative lymph nodes, the 5-year disease-specific survival was 85% for patients with 1 to 10 nodes removed, and 91% for those with more than 10 nodes removed (P = 0.054). On multivariate analysis after controlling for stage, age, and race, lymph node metastasis was an independent predictor of poor disease-specific survival (hazard ratio, 3.1; 95% confidence interval, 1.86-5.28; P < 0.001). On other hand, there was a trend toward an improved survival when more extensive lymphadenectomy is performed in patients with histologically negative nodes (1-10 vs >10 nodes), but it did not reach statistical significance (hazard ratio, 0.71; 95% confidence interval, 0.49-1.02; P = 0.064). CONCLUSIONS: Lymph node metastasis was uncommon in patients diagnosed with OCCC grossly confined to the ovary; however, patients with positive nodes were more likely to die compared to those with negative nodes. More extensive lymphadenectomy plays an important role in providing accurate staging and prognostic information.

Lanostane-type triterpenoid and steroid from the stem bark of Klainedoxa gabonensis.

A new lanostane triterpenoid, 2-hydroxy-24-methylenelanostan-1,8-dien-3-one named klainedoxalanostenone (1) with one new steroid, 6-O-acyl-ß-d-glucosyl-ß-sitosterol named klainedoxasterol (2) together with ten known compounds including six triterpenoids (3-8), two steroids (9, 10) and two tanins (11, 12) were isolated from the stem bark of Klainedoxa gabonensis. To the best of our knowledge, this is the first report of lanostane-type triterpenoids from this genus. Their structures were determined by extensive analysis of spectroscopic data (1D and 2D NMR, MS) and by comparison with literature data. The xanthine oxidase inhibitory activity of nine compounds (1-6, 8, 10 and 11) were evaluated. Compound 5 showed a good xanthine oxidase inhibitory activity; the other tested compounds were moderately active.

Ceramide and Cerebroside from the stem bark of Ficus mucuso (Moraceae).

Two new sphingolipids mucusamide (1) and mucusoside (2) have been isolated from methanol soluble part of the stem bark of Ficus mucuso WELW., together with fifteen known secondary metabolites including cellobiosylsterol (3), ß-sitosterol (4), stigmasterol (5), ß-sitosterol 3-O-ß-D-glucopyranoside (6), lupeol acetate (7), ursolic acid (8), procatechuic acid (9), 2-methyl-5,7-dihydroxychromone 8-C-ß-D-glucoside (10), apigenin (11), (-)-epicatechin (12), (+)-catechin (13), N-benzoyl-L-phenylalanilol (14), α-acetylamino-phenylpropyl α-benzoylamino-phenylpropionate (15), asperphenamate (16) and bejaminamide (17). Structures of compounds 1 and 2 were elucidated by spectroscopic analysis and chemical methods.