The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study

Background: Intrauterine endocrine abnormalities have profound effects on the development of physiological disorders. Objective: This study aimed to assess the effects of in utero exposure to letrozole (an aromatase inhibitor) and its late consequences on the reproductive and metabolic performance of an adult male offspring. Materials and Methods: 15 pregnant Sprague-Dawley rats (8 wk, 155 gr) were randomly assigned into 5 experimental groups (n = 3/each) and orally received either letrozole at doses of 0.25, 0.75, 1.00, and 1.25 mg/kg body weight (BW) or vehicle (control) on the gestation days of 16, 17, and 18. Pregnancy outcome, sexual behaviors on postnatal day 60, serum biochemical features, and the histopathology of testes were assessed in male offspring. Results: Compared to control group, delayed labor (21.83 vs. 24.25, p < 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p < 0.0001) were recorded in 1.25 mg/kg BW group. A reduction in high-density lipoprotein level and the elevation of testes weight, BW gain, anogenital distance, as well as the serum concentrations of testosterone, triglycerides, cholesterol, and glucose were observed in 1.25 mg/kg BW (p < 0.0001) and 1.00 mg/kg BW (p < 0.0001) groups in comparison to control. A larger number of anogenital female sniffing, pursuit, and mounting behaviors were also observed in 1.25 mg/kg BW group in comparison to control (p < 0.0001). Severe testicular defects including necrosis and disruption of the epithelium of seminiferous tubules, sloughing of epithelial cells, and spermatogenesis arrest were observed in letrozole-treated groups, in a dose-dependent manner. Conclusion: Maternal exposure to letrozole can adversely affect the reproductive and metabolic performance of male offspring rats, suggesting an incomplete sex differentiation. Key words: Androgens, Aromatase inhibitors, Rat, Sexual activities, Testes histopathology

Maternal aromatase inhibition via letrozole altered RFamide-related peptide-3 and gonadotropin-releasing hormone expression in pubertal female rats

Objective(s): Despite prevalence of polycystic ovary syndrome (PCOS) among childbearing women and development of many animal models for this syndrome, information on its etiology is still scarce. The intrauterine hyperandrogenic environment may underlie changes at the level of hypothalamus, pituitary, ovary organization in female offspring, and PCOS later in life. Letrozole has been shown to mimic reproductive and metabolic characteristics of PCOS in adult rodent models. Therefore, this research aimed to assess the condition in a prenatal letrozole-treated rat model. Materials and Methods: Twenty-eight female rats dams receiving letrozole at certain doses during late pregnancy were used in the trial. Pregnant Sprague-Dawley rats (n=21) received letrozole treatment on gestation days 16–18 at doses of 1.25, 1.0, 0.75, 0.5, and 0.25 mg/kg body weight (BW). Results: Prenatal letrozole treatment delayed parturition time and reduced the litter size in pregnant dams (P<0.0001). Late puberty onset, irregular ovarian cyclicity, increased anogenital distance (AGD), body weight gain, serum testosterone concentration, and reduced estradiol levels (P<0.0001) were observed in the female offspring of dams receiving 1.25 and 1 mg/kg BW letrozole. Furthermore, letrozole at 1.25 and 1 mg/kg BW showed increased RFRP and decreased GnRH mRNA expression (P<0.0001). Letrozole treatment at doses of 1 mg/kg BW and lower was not fetotoxic. Conclusion: It was concluded that 1 mg/kg BW letrozole may be suggested for prenatal PCOS induction. Keywords Gonadotropin-releasing hormone Hypothalamus Letrozole Polycystic ovary syndrome Prenatal Rat RFamide-related peptide-

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Pathophysiological mechanisms of gonadotropins- and steroid hormones-related genes in etiology of polycystic ovary syndrome

Objective(s): Polycystic ovary syndrome (PCOS) is an endocrinopathy in women, which, unlike its impact on fertility and health of women, there is no clear understanding about the causal mechanisms of this pathogenesis. The aim of this review paper is to investigate the pathophysiological pathways affecting the PCOS etiology, based on functions of gonadotropins– and steroid hormones–related genes. Materials and Methods: Due to different hormonal and metabolic signs of this complex disorder, different hypotheses are mentioned about etiology of this syndrome. Because of the heterogeneity of the reasons given for this syndrome and the spread of the effective genes in its pathophysiology, most of genes affected by sex-related hormonal imbalances are examined for discriminative diagnosis. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women in peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results: In previous studies, it has been well demonstrated that PCOS in some individuals have a genetic origin. Pathophysiological functions of genes are primarily responsible for the synthesis of proteins that have role in PCOS before hyperandrogenism including GnRHR, FSHβ, FSHR, LHCGR, CYP19A1, HSD17B, AR and SHBG, and their effects in PCOS of human have been confirmed. Conclusion: Hormonal imbalances are the first reason mentioned in PCOS etiology, and usually characterized with menstrual irregularities in PCOS women. Hyperandrogenism and gonadotropin secretion disorders are shown in PCOS condition, which are related to steroidogenesis pathways and hypothalamic–pituitary–ovarian axis disturbances, respectively

An IoT deep learning-based home appliances management and classification system

The rise in household energy consumption globally has increased the necessity for effective electricity consumption management and load monitoring. Smart meters can facilitate fine-grained analysis by providing consumption insights even at the level of individual appliances, for detecting deterioration of appliances, anomalous behavior, and demand response. In this work, we propose a smart home appliance classification that utilizes the deep learning architecture of Long Short-Term Memory (LSTM) trained on the latest version of the Plug-Load Appliance Identification Database (PLAID). The model achieves competitive precision, recall and F1-scores across 16 different home appliances manufactured by 330 vendors. The model is then deployed on a Raspberry Pi micro-controller and interfaced with smart meters in a home to generate almost real-time classification of appliances and transmit this to a cloud database. The results and insights are made accessible to the end user or utility provider through a mobile application connected to the same database

A Water-Energy Nexus Approach for the Co-Optimization of Electric and Water Systems

The staggering increase in water production, driven by population and economic growth, has consequently led to a massive increase in energy demand, particularly in countries that rely on desalination. Hence, the concept of the water-energy nexus has emerged as the best option to alleviate the gap between the demand and production of both water and power. This paper proposes a new approach for co-optimizing water and electric power systems by incorporating the energy-intensive equipment involved in water desalination and distribution. The proposed procedure leverages the energy flexibility of reverse osmosis (RO) desalination tracks. RO tracks can operate alternatively in conjunction with water network storage tanks with variable-speed pumps to optimal satisfy water demand at minimum energy and operating costs. The developed model takes into consideration the essential constraints of both the power and water systems to meet consumer demands. Further, a mixed-integer nonlinear programming model is proposed for the day-ahead operation of the two integrated systems. The simulation findings show that the suggested technique is successful in scheduling the energy-intensive equipment in the two systems to achieve a $\$$ 26,993 per day savings compared to a 4.6&#x0025; decrease in overall operating costs when compared to optimizing each system independently

Personal, Clinical, and Laboratory Characteristics of Women with Breast Lesions in Patients Referred to Dr. Beski Hospital in Gonbad-e Kavus, Iran

Background and Objective: Breast cancer is the most common cancer among women and ranks second in terms of mortality rate. This study was conducted in order to determine the personal, clinical, and laboratory characteristics of women with breast lesions referred to the Dr. Beski Hospital in Gonbad-e Kavus, Iran. Methods: This descriptive-analytical study was conducted on 130 women with breast lesions (benign and malignant) who were operated on in the Dr. Beski Hospital from March 2019 to March 2020. Demographic data (age, family history, and ethnicity) and pathology results (grade, lesion type, surgery type, location, and tumor size) were recorded. Results: Breast lesions were malignant in 51.53% of the patients. The most common malignant tumor was invasive ductal carcinoma (71.64%), and the most common benign tumor was fibroadenoma (69.84%). Most malignant cases were observed in patients aged 41-50 years (43.28%). Almost half of the studied population (49.15%) had no positive family history, and about a quarter of the patients had at least one first or second-degree relative with breast cancer. Most patients (44.78%) had grade II malignant tumors. In addition, 78.51% of the subjects had not undergone chemotherapy before breast surgery. About half of the patients (49.57%) did not undergo any adjuvant treatment after surgery; however, chemotherapy was the most common type of adjuvant treatment (13.68%) after surgery. Simultaneous chemotherapy and radiotherapy were performed for 24.78% of the patients after surgery. There were statistically significant relationships between age and type of lesion and adjuvant treatments after the operation, and involvement of lymph nodes was observed (P<0.05). There was a statistically significant relationship between age, tumor size, family history, and tumor malignancy (P<0.05). There was a significant correlation between age and tumor malignancy (P=0.02, F (2.48) = 4.19) so the degree of malignancy was higher in younger individuals. Conclusion: The results of this study showed the young age of developing malignant breast lesions in the study area. Most malignant lesions are invasive ductal carcinoma and grade II. There is a positive relationship between a family history of cancer and the classification of breast tumors

Experimental and Theoretical Study of O-Substituent Effect on the Fluorescence of 8-Hydroxyquinoline

The synthesis and characterization of different ether and ester derivatives of 8-hydroxyquinoline have been made. UV-visible and fluorescence spectra of these compounds have revealed spectral dependence on both solvent and O-substituent. The fluorescence intensity of ether derivatives revealed higher intensity for 8-octyloxyquinoline compared with 8-methoxyquinoline, whereas those of ester derivatives had less fluorescence than 8-hydroxyquinoline. Theoretical calculations based on Time-dependent density functional theory (TD-DFT) were carried out for the quinolin-8-yl benzoate (8-OateQ) compound to understand the effect of O-substituent on the electronic absorption of 8-hydroxyquinaline (8-HQ). The calculations revealed comparable results with those obtained from the experimental data. Optimized geometrical structure was calculated with DFT at B3LYP/6-311++G** level of theory. The results indicated that 8-OateQ is not a coplanar structure. The absorption spectra of the compound were computed in gas-phase and solvent using B3LYP and CAM-B3LYP methods with 6-311++G ** basis set. The agreement between calculated and experimental wavelengths was very good at CAM-B3LYP/6-311++G** level of theory