Effect of inhibition of estrogen synthesis or blocking its receptors on male rabbit reproduction

Purpose: The present aimed to study the effects of tamoxifen and fadrozole on semen characteristics and fertility, besides we emphasized the relationship between brain estrogen and sexual behavior in male rabbits. Methods: Eighty rabbits allocated into four equal groups. The control injected with sesame oil; the second injected with estradiol; the third injected with tamoxifen and the fourth injected with fadrozole. Treatments done daily for 60 days. Ten rabbits from each group served artificial vagina for evaluation of semen and sexual behavior. The other ten served female rabbits for fertility test. Reproductive organ and brain weights recorded. Serum and testicular testosterone, serum and brain estradiol and testicular zinc and cholesterol levels assayed. Results: Tamoxifen caused decrease in all estimated parameters except it increased both sperm ab normalities percentage; testicular cholesterol content; time of reaction and time between two consecutive ejaculations. Fadrozole results were opposite to that of tamoxifen except it increased the time between two consecutive ejaculations and decreased brain estradiol level. Conclusion: Fadrozole may be improve male rabbits performance along with elevated testosterone evident highlighting the important played by testosterone in regulating male rabbit fertility and advocacy the postulate that testosterone effect is mediated in part by its aromatization to estradiol

Development of HDAC Inhibitors Exhibiting Therapeutic Potential in T-Cell Prolymphocytic Leukemia

Epigenetic targeting has emerged as an efficacious therapy for hematological cancers. The rare and incurable T-cell prolymphocytic leukemia (T-PLL) is known for its aggressive clinical course. Current epigenetic agents such as histone deacetylase (HDAC) inhibitors are increasingly used for targeted therapy. Through a structure-activity relationship (SAR) study, we developed an HDAC6 inhibitor KT-531, which exhibited higher potency in T-PLL compared to other hematological cancers. KT-531 displayed strong HDAC6 inhibitory potency and selectivity, on-target biological activity, and a safe therapeutic window in nontransformed cell lines. In primary T-PLL patient cells, where HDAC6 was found to be overexpressed, KT-531 exhibited strong biological responses, and safety in healthy donor samples. Notably, combination studies in T-PLL patient samples demonstrated KT-531 synergizes with approved cancer drugs, bendamustine, idasanutlin, and venetoclax. Our work suggests HDAC inhibition in T-PLL could afford sufficient therapeutic windows to achieve durable remission either as standalone or in combination with targeted drugs.Peer reviewe

Terabit indoor laser-based wireless communications : LiFi 2.0 for 6G

This paper provides a summary of available technologies required for implementing indoor laser-based wireless networks capable of achieving aggregate data-rates of terabits per second as widely accepted as a sixth generation (6G) key performance indicator. The main focus of this paper is on the technologies supporting the near infrared region of the optical spectrum. The main challenges in the design of the transmitter and receiver systems and communication/networking schemes are identified and new insights are provided. This paper also covers the previous and recent standards as well as industrial applications for optical wireless communications (OWC) and LiFi

Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography

© 2016 The Author(s). This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1β: 2678 compared with 4631 pg/ml, P= 0.04 and IL-6: 3442 compared with 6157 pg/ml, P= 0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1β: 2025 compared with 3332 pg/ml, P= 0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1β: 2150 compared with 2520 pg/ml, P= 0.03 and IL-6: 2488 compared with 3250 pg/ml, P= 0.01). Occludin expression (85 compared with 95%, P= 0.004) and mean duodenal villus height (334 compared with 404 μm, P= 0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P= 0.04) and CD86 (P= 0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease