Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues

A STUDY OF SEVERITY OF STROKE AND HOMOCYSTEINE LEVEL IN SOUTHERN PART OF RAJASTHAN, INDIA

Objective: Till date, a very few prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Indian populations. Methods: A prospective, case - control study of Indian subjects 10–90 years of age was conducted using frozen serum samples from 103 participants in cardiovascular risk surveys collected from December 2017 to November 2018. By the end of 103, we identified 55 incidents of severe strokes, one control subject per case was selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by Cobas c-311. Results: Compared with control subjects, total (n_206), hemorrhagic (n_106), and ischemic (n_87) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine −25.0 μ mol/L. Homocysteine was estimated after adjustment for body mass index, smoking, alcohol intake, hypertension, and other cardiovascular risk factors. The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusion: High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke) Capsuloganglionic and frontoparietal infarct (8 each)., among Indian men and women

Soft tissue augmentation of free gingival graft by cyanoacrylate adhesive in free mucosal graft surgery: a report of three cases

A free mucosal graft (FMG) technique is a periodontal surgical procedure that is commonly used for treating inadequate width of attached gingiva and gingival recession. Success of this procedure depends upon stabilization and minimum movement of graft that maintains proper vascularity during healing. Surgical sutures are conventionally used for stabilization of gingival graft but may have complications such as over strangulation of graft, trauma, dislodgement of graft, food accumulation, infection, bacterial contamination and delayed wound healing. Cyanoacrylate based chemical adhesives are very promising alternatives and used in a wide spectrum of surgery in medical and dental field. They have low toxicity and it is efficacious in reducing complications along with haemostatic and bacteriostatic property. They are easy to use, reduces operation time, post operative pain and inflammation and promotes superior tissue coverage by proper stabilization. A series of three cases are presented in this article where Cyanoacrylate based adhesives are used as stabilizing agent for graft in FMG surgery in patients presented with gingival recessions &nbsp

An Intelligent Obstacle and Edge Recognition System using Bug Algorithm

Obstacle avoidance is an important task in robotics as the autonomous robot's aim is to reach the destination without collision.  One type of autonomous robot that can detect obstacles and edges and take alternative paths free of obstacles and edges is a real-time obstacle avoiding edge detection robot. This paper proposes a robotic Robot with an intelligence built into it that guides itself whenever an obstacle comes along its way by bug algorithm. This robotic Robot is constructed using AT mega 8 families’ micro-controller (Arduino Uno R3). The ultrasonic sensor is used to detect any obstacle with edges and sends a command to the microcontroller. The micro-controller, based on the received input signal, redirects the robot to push in an alternative direction by actuating the motors that are interfaced with it via a motor driver. Depending on the situation the robot is able to choose the correct path [1]. A decision making process of obstacle avoiding edge detection occurs spontaneously here. This robot was designed to think about its day-to-day potentialities

Handoffs and transitions of care in the intensive care unit: an American Association for the Surgery of Trauma Critical Care Committee clinical consensus document.

OBJECTIVES: The American Association for the Surgery of Trauma (AAST) Critical Care Committee chose handoffs and transitions of care in the intensive care unit (ICU) as a clinically relevant topic for review. This clinical consensus document aims to provide practical guidance to the surgical intensivist on the best practices for patient handoffs and transitions of care. METHODS: A working group was formed from the committee-at-large to complete this work. The members of the working group were each assigned a subtopic to review using research to date. The research on which the recommendations are based was compiled at the discretion of the working group. Any topic with discrepant or minimal supporting literature was reviewed by the AAST Critical Care Committee through an anonymous survey. RESULTS: Recommendations for healthcare handovers include formally recognized handoffs at dedicated times, an interactive verbal exchange including all patients with a focus on what to anticipate or what is needs to be completed, tools to record and maintain information, and training to new providers on the handoff process and technology. CONCLUSION: As clinicians, we strive to provide the best evidence-based care to our patients. It is essential to study these high states, ICU handoffs to enhance the safety, efficiency, and effectiveness of patient care transitions, ultimately leading to better patient outcomes and provider satisfaction. LEVEL OF EVIDENCE: V

An advanced and secure framework for conducting online examination using blockchain method

Nowadays, the online platform has been used by many educational institutions, to conduct tests, especially for secondary to tertiary level students. The most popular online test program is run by providing a user id and password to the candidates, and subsequently, they log in to the given web page to answer the questions. However, this system has a lot of bugs, the password can be misused followed by cheating in the test. This shows the importance of a secure system being implemented to avoid such a problem. This paper presents a blockchain framework that secures the online examination system. The proposed framework has been used to secure a data management system that connects to existing educational data. Institutions can simply compile their data history without requiring a copy from the central servers. The proposed blockchain framework improves data security and removes any potential cheating between users or third-party institutions that access applications and services. In this regard, this study provides a secured framework for conducting and evaluating subject tests to ensure consistency between student and server, and secure delivery of questionnaire from the server

Review of nano-clay polymer composites for controlled nitrogen release: prospects and limitations

This review paper discusses the potential and limitations of polymer composites for smart nitrogen (N) supply to meet the needs of agricultural crops. Unlike most conventional fertilizers, nano-clay polymer composites (NCPCs) offer a slow-release mechanism that enhances nitrogen use efficiency and reduces its loss to the environment. NCPCs are normally synthesized using solution blending, melt blending and in situ polymerization. Solution blending offers a better clay dispersion in the polymer matrix than melt blending owing to its low viscosity and strong stirring force. NCPCs have been characterized by several techniques, including equilibrium water absorbency, Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and nutrient release kinetics. The potential benefits of using these composites are highlighted, including improved nitrogen use efficiency and reduced environmental impacts, as are their prospects for widespread use in agriculture and mitigation of the adverse environmental effects from conventional fertilizers. In addition, the limitations of NCPC technology, such as cost, scalability and potential negative environmental effects, are also investigated. The paper provides a wide perspective on the NCPC technology, including the regulatory environment and policy, industry trends and commercialization potential. NCPCs offer many benefits to increase nitrogen use efficiency and reduce pollution affecting water quality, air quality and climate. The main current barrier to overcome is to reduce production costs, so that farmers may also benefit financially from the higher nitrogen use efficiency and associated reduced amounts of nitrogen wasted to the environment

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research