Nevin Manimala

Int J Fertil Steril. 2022 Aug 21;16(3):180-183. doi: 10.22074/ijfs.2021.141690.1050.

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is known as the most common endocrine and metabolic disorder in the reproductive-age women. Due to the effects of PCOS on the physical and mental health, the investigation of the factors affecting the development of PCOS is crucial. Hexose-6-phosphate dehydrogenase (H6PD) is a microsomal enzyme that catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway. The present study examined the polymorphisms of the H6PD gene (R453Q and D151A) in PCOS patients of Iranian Kurdish women.<br />Materials and Methods: In this case-control study, a total, of 200 female volunteers in two equal groups participated in our study. The PCOS patients were selected based on the Rotterdam diagnostic criteria. The association of H6PD gene polymorphisms, D151A and R453Q, with the development of PCOS were investigated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. Statistical analysis was applied by the SPSS (version 16) software.<br />Results: Statistically significant lower frequencies of AA+AG genotype (37% vs. 55%, P=0.01) and A allele (22.5%<br />vs. 34%, P=0.01) of R453Q were observed in the patients compared to the controls. In the case of D151A, no significant<br />differences were observed in the frequency of genotypes and alleles between the two groups.

CONCLUSION: The findings of this study suggest that variants of H6PD R453Q affect the risk of PCOS.

PMID:36029054 | DOI:10.22074/ijfs.2021.141690.1050

Int J Fertil Steril. 2022 Aug 21;16(3):162-166. doi: 10.22074/ijfs.2021.532311.1141.

ABSTRACT

Few studies have so far been done about the role of follicle stimulating hormone (FSH) in final oocyte<br />maturation. However, none of these studies have been performed solely on normoresponder patients. This study aimed<br />to determine whether oocyte maturation, as well as fertilization and pregnancy rates, could be improved in normoresponder women with concomitant FSH and human chorionic gonadotropin (hCG) trigger compared to those with the hCG trigger alone.<br />Materials and Methods: In this prospective randomized clinical trial, 117 normoresponder women, aged 19-40 years<br />who were candidates for the gonadotropin-releasing hormone (GnRH) antagonist protocol at Avicenna Infertility<br />treatment Center, were enrolled and claasified in two groups. Final oocyte maturation was triggered using 10000 IU of<br />hCG plus 450 IU of FSH in the first group (59 subjects) and 10000 IU of hCG alone in the second group (58 subjects).<br />The primary outcome was clinical pregnancy rate.<br />Results: Mean age of the patients was 33.21 ± 4.41 years. There was no difference in clinical pregnancy among the<br />two groups (30.9% vs. 25.5%, P=0.525). There was no statistically significant difference in fertilization rate (80.0%<br />vs. 74.1%, P=0.106), implantation rates (18.9% vs. 16.7%, P=0.352), and chemical pregnancy rates (38.2% vs. 32.7%,<br />P=0.550). Oocyte maturation rate (84.2% vs. 73.6%, P<0.001), 2 pronuclei (2PNs) (6.53 ± 2.54 vs. 5.36 ± 2.85,<br />P=0.021) and total embryos (5.85 ± 2.43 vs. 4.91 ± 2.58, P=0.046) were significantly higher in the first group.<br />Conclusion: Adding FSH to hCG for oocyte triggering, significantly improved oocyte maturation rates and total embryos.<br />While there was no significant difference in the clinical and chemical pregnancy rates, between these two groups<br />(registration number: IRCT20190108042285N1).

PMID:36029051 | DOI:10.22074/ijfs.2021.532311.1141

Int J Fertil Steril. 2022 Aug 21;16(3):156-161. doi: 10.22074/ijfs.2021.532258.1140.

ABSTRACT

Accurate etiology of azoospermia is required for optimal management of patients. The aim of this<br />study was the determination of serum hormonal levels and testicular long axis cut off points to distinguish obstructive<br />azoospermia (OA) from non-OA (NOA) in Iranian patients as well as the evaluation of the necessity of diagnostic<br />testis biopsy in azoospermic patients.<br />Materials and Methods: In this retrospective study, data of 471 azoospermic patients such as history and physical<br />examination, serum hormonal level, semen fluid parameter, and testicular long axis based on ultrasound were<br />evaluated from 2016 to 2020. All patients were examined by a single urologist and underwent a diagnostic testis<br />biopsy for a definite diagnosis. The diagnostic parameters were analyzed using Statistical Package for the Social<br />Sciences (SPSS) version 16 with t test and chi-square test and receiver operating characteristic (ROC) curves to<br />distinguish NOA from OA.<br />Results: A total of 127 patients with OA and 284 with NOA were included in this study. The mean serum testosterone<br />level was significantly higher in OA than NOA (4.2 vs. 3.4 ng/ml), whereas the mean serum follicular stimulating hormone<br />(FSH, 5.3 vs. 19.1 mIU/ml) and luteinizing hormone (LH, 5.3 vs. 11 mIU/ml) were lower in OA. ROC curve analysis<br />showed that FSH and testicular long axis were the best diagnostic predictors. Using a combination of serum FSH (8.9<br />mIU/ml) and testicular long axis (39 mm), the positive predictive value for NOA was 97.02% and for OA was 78.8%.<br />Conclusion: Combination of serum FSH higher than 8.9 mIU/ml and testicular long axis lower than 39 mm were<br />strong predictors to distinguish NOA from OA in Iranian participants in this study. In addition, diagnostic testicular<br />biopsy seems to be necessary for patients with OA and NOA characteristics.

PMID:36029050 | DOI:10.22074/ijfs.2021.532258.1140

Acta Neurol Scand. 2022 Aug 27. doi: 10.1111/ane.13676. Online ahead of print.

ABSTRACT

Vestibular neuritis is a common neuro-otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta-analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970-2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta-analysis using a commercially available software program (www.meta-analysis.com). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2-7.8; p = .015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4-23). The odds ratio (OR) for restoration of vestibular function in the follow-up was 2.4 (95% CI 1.3-4.4; p = .004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5-18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3-93.8; p = .015) and an estimated number needed to harm (NNH) = 4 (95% CI 3-19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non-randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low-grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well-designed randomized controlled trial to re-evaluate the effectiveness of corticosteroids.

PMID:36029039 | DOI:10.1111/ane.13676

Chem Biol Drug Des. 2022 Aug 4. doi: 10.1111/cbdd.14125. Online ahead of print.

ABSTRACT

Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver and key therapeutic target for human cancers. Current therapies targeting HER2 are primarily based on overexpression of the wild-type form of HER2. However, kinase domain mutations have been identified that can increase the activity of HER2 even when expressed at basal levels. Using purified enzymes, we confirmed the hyperactivity of two HER2 mutants (D769Y and P780insGSP). To identify small molecule inhibitors against these cancer-associated variants, we used a combined approach consisting of biochemical testing, similarity-based searching, and in silico modeling. These approaches resulted in the identification of a candidate molecule that inhibits mutant forms of HER2 in vitro and in cell-based assays. Our structural model predicts that the compound takes advantage of water-mediated interactions in the HER2 kinase binding pocket.

PMID:36029027 | DOI:10.1111/cbdd.14125

Urol J. 2022 Aug 13:7160. doi: 10.22037/uj.v19i.7160. Online ahead of print.

ABSTRACT

PURPOSE: To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted.

MATERIALS AND METHODS: The retrieval time was from January 1947 to May 2021，without language restriction. Stata 12.0 was used for the meta-analysis.

RESULTS: A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: – 0.55 to – 0.06, SMD = – 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001).

CONCLUSION: Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.

PMID:36029025 | DOI:10.22037/uj.v19i.7160

Orthop Surg. 2022 Aug 26. doi: 10.1111/os.13446. Online ahead of print.

ABSTRACT

OBJECTIVE: Musculoskeletal pain is having growing impacts worldwide with clinical challenge in pain management. The purpose of the present study is to investigate the preferences of orthopedic surgeons of China for using medicine in musculoskeletal pain.

METHODS: A questionnaire was developed, including the following domains, personal information, medication preference for pain treatment, and perceptions of topical medicine. Ten participants were selected to confirm the consistency of questionnaire. A cross-sectional survey was conducted in orthopedic physicians with different specialties in different regions of China via the online survey platform. The participants’ survey results were analyzed one-way and multi-way using chi-square test and logistic regression.

RESULTS: The pre-survey analysis results of 10 randomly selected investigators were a mean weighted kappa coefficient of 0.76 (range 0.61-0.89), which indicated the substantial consistency of the present questionnaire. A total of 1099 orthopedic surgeons (mean age, 41.67 ± 8.31 years) responded to our survey, most of whom were male (90.72%), and most of whom worked in level III hospitals (63.24%) and trained in modern medicine (71.43%). Most surgeons who participated in the survey had used topical analgesics in their clinical work (95.81%), and most preferred to use topical analgesics (39.50%) or a combination of oral analgesics (28.87%). Primary reasons for preferring topical analgesics were as follows: less adverse reactions (68.01%); ease of use (60.90%); and not interfering with other oral medications (49.60%). The preference for prescribing topical analgesics increased with the education level of the respondent, where statistically significant differences were seen (P < 0.05). In addition, the level of the respondent’s hospital, type of hospital, the respondent’s profession, and their participation in surgical work influenced their preferences for topical analgesics (P < 0.05).

CONCLUSION: Orthopedic surgeons across China have different medication preferences in the treatment of musculoskeletal pain. The educational background of the physician largely influences the preference when selecting medications. To better improve the treatment of musculoskeletal pain, there is a need to improve the overall medical education of practitioners and to disseminate clinical practice guidelines.

PMID:36029012 | DOI:10.1111/os.13446

Cancer Med. 2022 Aug 26. doi: 10.1002/cam4.5116. Online ahead of print.

ABSTRACT

BACKGROUNDS: We aimed to test whether the prediction of presurgical metabolic syndrome for postsurgical survival outcomes of gastric cancer hinges upon cigarette smoking status.

METHODS: This study is a part of the ongoing Fujian prospective investigation of cancer (FIESTA) study. Patients with gastric cancer received radical resection of primary gastric cancer between January 2000 and December 2010, with the latest follow-up ended in December 2015. The 1:1 propensity score matching analysis was adopted to balance confounders between smokers and never-smokers. Effect-size estimates are expressed as hazard ratio (HR) with 95% confidence interval (CI). Model performance was evaluated using the Hosmer and Lemeshow test and 10-fold cross-validated area under the receiver operating characteristic curve (AUROC). Statistical analyses were completed with SAS software (v9.4).

RESULTS: Total 2779 patients with gastric cancer were analyzed, including 2223 smokers and 556 never-smokers. Median follow-up time was 45.6 months. Cigarette smoking was not associated with postsurgical survival differences. Presurgical metabolic syndrome complication was significantly associated with increased gastric cancer-specific mortality in smokers (HR [95% CI]: 2.73 [1.53-4.89], p < 0.001), but not in never-smokers. Relative excess risk due to interaction was estimated to be 2.43 (95% CI: 0.40-4.45). After constructing a risk assessment score, one unit increment was associated with 10% reduced risk of gastric cancer-specific mortality (HR [95% CI]: 0.90 [0.88-0.91], p < 0.001), with 10-fold cross-validated AUROC being 0.82 (95% CI: 0.74-0.92).

CONCLUSIONS: Our findings showed that the prediction of presurgical metabolic syndrome for gastric cancer-specific mortality was more evident in smokers. Practically, this study provides evidence base for future personalized prediction and helped risk-stratify gastric cancer patients who might experience serious postsurgical consequences.

PMID:36028993 | DOI:10.1002/cam4.5116

Int J Neurosci. 2022 Aug 26:1-12. doi: 10.1080/00207454.2022.2118599. Online ahead of print.

ABSTRACT

Background: Platelets are crucial players in thrombus formation during ischemic stroke. Platelet (PLT) count and Mean platelet volume (MPV) are important parameters that affect platelet functions. The current study has been carried out with an aim to evaluate the association of MPV and PLT count with ischemic stroke in a population from the Malwa region of Punjab.Material and Methods: The study included one hundred and fifty ischemic stroke patients. The extent of disability occurs by stroke was measured by mRS. MPV and PLT was evaluated using cell counter. Further, PLT count was confirmed in 50% of patients using flow cytometer. Clot formation rate was evaluated using Sonoclot Coagulation and Platelet Function Analyzer. All the statistical analysis was carried out using SPSS.Results: A significant association of increased MPV (p < 0.02) was found with the ischemic stroke. However, PLT count did not show a significant association with the disease (p < 0.07). Further, a stepwise multiple logistic regression (MLR) analysis controlling the other confounding risk factors evaluated the association of hypertension and MPV with the disease. Patients with higher mRS were found to have high MPV values confirming that higher MPV is correlated with disability occurs by ischemic stroke. MPV was also found to was found to significantly associated with large artery atherosclerosis (LAA) (p < 0.001). Clot formation analysis revealed that ischemic stroke patients bear higher clot rate (CR) and Platelet function (PF) values.Conclusions: Elevated MPV is an independent risk factor for Ischemic stroke along with hypertension. In addition, higher MPV associated significantly with stroke disability as well.

PMID:36028984 | DOI:10.1080/00207454.2022.2118599

Protein Pept Lett. 2022 Aug 25. doi: 10.2174/0929866529666220825150025. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. Clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), that compose the classical pathway of the renin-angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as a promise therapeutic targets in neuropsychiatric disorders, leading to neuroprotection.

OBJECTIVE: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice.

METHODS: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. Student’s t test was applied for statistical analysis.

RESULTS: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus, compared with controls.

CONCLUSION: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.

PMID:36028967 | DOI:10.2174/0929866529666220825150025