An update on the potential for male contraception : emerging options

The human population continues to grow and is estimated to rise to 10.1 billion by the end of the century. Therefore, there is still an unmet need for safe and highly effective contraceptive options for both men and women. Current options available to men include withdrawal, condoms, and vasectomy. Methods in development fall into two categories: hormonal and nonhormonal. This review will provide an overview of the testosterone combinations and immunocontraception of hormonal targets. Nonhormonal immunocontraception of sperm proteins will also be examined, together with the use of agents to disrupt other sperm-associated targets and pathways. The categories focused on include epididymal proteins, testicular kinases, epigenetic reader proteins, opioids, lonidamine derivatives, retinoic acid, microRNAs associated with spermatogenesis, and plant extracts. Considering these developments, the number of options available to men is likely to increase in the near future

Cybersecurity Enhancement through Hybrid Encryption: Combining RSA and Vigenère Algorithms in the Cypher-X System

لا يزال أمن البيانات مصدر قلق في عصرنا الرقمي، مع فشل العديد من أنظمة التشفير بسبب تعقيدها وقابليتها للتهديدات السيبرانية. Cypher-X، هو نظام تشفير وفك تشفير متطور، يدمج الخوارزميات الكلاسيكية، RSA وVigenère، لحماية سرية البيانات. ويسعى مشروعنا إلى معالجة هذه المخاوف من خلال التركيز على ثلاثة أهداف رئيسية: تعزيز أمن البيانات، وتقييم كفاءة النظام، وتحديد نقاط الضعف التي يستغلها القراصنة. تؤكد النتائج التي توصلنا إليها قدرات التشفير القوية لـ Cypher-X، مع احتمالات تعزيزها بشكل أكبر من خلال تكامل المصادقة متعددة العوامل وآليات التحكم في الوصول. بينما نتعامل مع المشكلة المتمثلة في أمن البيانات، تبرز Cypher-X كمنارة للأمل، حيث تقدم حلاً واعدًا لحماية المعلومات الحساسة في المشهد الرقمي.In the contemporary digital landscape, the imperative issue of data security continues to be a prominent concern. Numerous encryption systems have faced challenges stemming from their intricate nature and susceptibility to cyber threats. This study introduces Cypher-X, an advanced encryption and decryption system that adeptly integrates classical algorithms, namely RSA and Vigenère, to fortify data confidentiality. This research endeavors to address prevailing concerns by focusing on three primary objectives: augmenting data security measures, evaluating system efficiency, and identifying vulnerabilities exploited by cyber adversaries. The outcomes of our investigation affirm the robust encryption capabilities of Cypher-X, underscoring its potential for further enhancement through the incorporation of multi-factor authentication and access control mechanisms. In the realm of data security, Cypher-X emerges as a beacon of hope, offering a promising solution to safeguard sensitive information in the digital sphere. It is essential to acknowledge the ongoing necessity for elucidating our research question, methodology, key findings, and practical implications as we navigate the complex landscape of data protection

Delivering natural products and biotherapeutics to improve drug efficacy

Due to the increasing problem of drug resistance, new and improved medicines are required. Natural products and biotherapeutics offer a vast resource for new drugs; however, challenges, including the cost and time taken for traditional drug discovery processes and the subsequent lack of investment from the pharmaceutical industry, are associated with these areas. New techniques are producing compounds with appropriate activity at a faster rate. While the formulation of these combined with drug-delivery systems offers a promising approach for expanding the drug developments available to modern medicine. Here, various classes of drug-delivery systems are described and the advantages they bring to small molecule and biotherapeutic targeting are highlighted. This is an attractive approach to the pharmaceutical industry and the rising trend in research in this area is examined in brief

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Non-ionic surfactant vesicles as a delivery system for cisplatin

Cisplatin is a leading anti-cancer drug used in the treatment of various cancers. However, its clinical use is limited by its undesirable toxic side effect profile and the potential of certain tumours to be or to develop resistance to cisplatin. Encapsulation of cisplatin within a vesicular structure such as non-ionic surfactant vesicles (NIVs) was developed to overcome these limitations. Characterisation studies showed that the size and negative surface charge of cisplatin NIVs could be exploited in enhancing their uptake by the mononuclear phagocytic system present in the lungs, liver and spleen. Physicochemical stability of the systems over a 15 month time period was demonstrated in relation to vesicle size and surface charge; the absence of colloidal aggregation and chemical stability of the lipid components. Vesicle entrapment efficiency of cisplatin was improved with increasing cisplatin concentrations used for lipid hydration but subsequent precipitation of drug limited the usefulness of such an approach. Removal of unentrapped cisplatin by the use of diafiltration and resuspension in lower concentrations of cisplatin solution overcame this problem but resulted in drug leakage from the vesicles over time. Preliminary in vitro and in vivo studies were used to evaluate NIVs. In vitro studies confirmed the potential of NIVs in enhancing the anti-cancer effect of cisplatin in comparison to free drug in a murine B16-F0 murine melanoma cell line. In vivo rodent studies compared cisplatin NIVs with free drug solution administered as single doses by intravenous or pulmonary routes of delivery. Intravenous delivery demonstrated more representable results with greater accumulation of cisplatin in the lungs when administered as a NIVs formulation in comparison to free drug solution. In conclusion, NIVs have great potential to be a viable delivery platform for the administration of cisplatin.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

High performance liquid chromatography with evaporative light scattering detection for the characterisation of a vesicular delivery system during stability studies

A normal phase high performance liquid chromatography method with evaporative light scattering detection was developed for the simultaneous quantification of the lipid constituents of a non-ionic surfactant vesicle (NIV) delivery system consisting of tetra-ethylene glycol mono n-hexadecyl ether, cholesterol and dicetyl phosphate. An accelerated stability study performed at 25°C/60% relative humidity (RH) and 40°C/75% RH indicated that the NIV were chemically stable. Similar results were observed when stored at 4°C for 469 days. This chromatographic method developed is a sensitive, robust and high throughput analytical technique that offers the potential for rapid quantification of lipids in liposomal and vesicular systems. The results of the chromatographic studies were supported by parallel size and zeta potential measurements

Respiratory Distress in Full Term Outborn Neonates: A Hospital Based Study

Summary: Background: Respiratory distress remains a major problem post adaptation and one of the most common reasons for admission of neonates to Intensive Care. Objectives: To study the causes and short term outcomes of respiratory distress in full term neonates and its correlation to mode of delivery. Patients and Methods: A cross sectional study was carried out on 100 full termoutborn neonates with respiratory distress admitted to Neonatal care unit of Children Welfare Teaching Hospital, Medical City, Baghdad from 1st of April to 31st of August 2011. Results: Hundred full term neonateswerestudied, 66% were boys and 81% born by cesarean section (elective cesarean sectionin 62%). In both sexes, Transient TachypneaofNewbornand pneumothorax ranked the 1st and 2nd among other causes.Among boys, early onset sepsis/pneumonia ranked 3rd, whereas late pneumonia and hyaline membrane disease among girls.The proportion ofTransient TachypneaofNewborn was higher in those who were delivered by cesarean section(86.66%).There was no significant correlation between the mode of delivery and respiratory distress in congenital heartdisease, birth asphyxia, meconium aspiration andtracheoesophagel fistula.The case fatality was 100% in birth asphyxia, 16.66% in sepsis/pneumonia, 9.09% in hyaline membrane disease and 5.88%in pneumothorax. Conclusions:Transient tachypnea was the commonest cause of hospitalizations among term neonates with respiratory distress. Elective cesarean sectionwas correlated with neonatal respiratory distress. Key Words: Respiratory Distress, Full Term Outborn neonate

Methods of sterilization and contraception in mammals

This article examines a range of sterilization methods used in male and female mammals. It includes permanent surgical methods and the desire for reversible and non-surgical methods, depending on the type of animal (human, companion, farm, pest, wild). Steroidal and non-steroidal products are considered, as well as developments in hormonal and gamete-based immunocastration. Recent targets are described and indicate that this field is still very active

Optimizing efficacy of mucosal vaccines

In general, there are only a few vaccines administered via mucosal routes, as the mucosal immune system presents numerous hurdles, including diversity in mucosal surface structure, complexity in immune cell interaction and limitations in experimental methodology. This therefore necessitates a range of strategies to be used for each target area. With reference to the three main routes of delivery and associated mucosal surfaces (oral/intestinal, nasal/respiratory and female genital tract), this review examines how coadministration of immune-stimulatory molecules, adjuvants, delivery systems and mucoadhesives are used to improve mucosal vaccine efficacy. Key considerations to the development of next-generation mucosal vaccines include improved efficacy and safety, technological advancements in medical devices to enable convenience and better administration, as well as reduced manufacturing costs

Assessment of the antigen-specific antibody response induced by mucosal administration of a GnRH conjugate entrapped in lipid nanoparticles

Vaccines administered parenterally have been developed against gonadotrophin releasing hormone (GnRH) for anti-fertility and anti-cancer purposes. The aim of this study was to demonstrate whether mucosal delivery using GnRH immunogens entrapped in lipid nanoparticles (LNP) could induce anti-GnRH antibody titres. Immunogens consisting of KLH (keyhole limpet haemocyanin) conjugated to either GnRH-I or GnRH-III analogues were entrapped in LNP. Loaded non-ionic surfactant vesicles (NISV) were administered subcutaneously, while nasal delivery was achieved using NISV in xanthan gum and oral delivery using NISV containing deoxycholate (bilosomes). NISV and bilosomes had similar properties: they were spherical, in the nanometre size range, with a slightly negative zeta potential and surface properties that changed with protein loading and inclusion of xanthan gum. Following immunisation in female BALB/c mice, systemic antibody responses were similar for both GnRH-I and GnRH-III immunisation. Only nasal delivery proved to be successful in terms of producing systemic and mucosal antibodies