Key Features of SARS-CoV-2 and Available Therapies for COVID-19

The disease caused by severe acute respiratory syndrome (SARS-CoV2) is highly pathogenic and communicable infection, progressed in Wuhan city of China and then goes viral around the globe. The Genomic investigations exposed that Phylogenetically SARS-CoV2 resembles the other SARS-like bat viruses, therefore bats were also considered as the possible potential reservoir for SARS-CoV2. There are 2 prevalent types of SARS-CoV2, L type (~70%) and S type (~30%).The L strains are considered more infectious and virulent than the ancestral S strain. The positive sense single-stranded RNA genetic material contains 29891 nucleotides which codes for 9860 amino acids. The ORF1a/b is involved in carrying the translation of two (2) polyproteins, pp1a and pp1ab as well as the encoding of 16 NSPs (Non-structural proteins), and the leftover ORFS can bring about the encoding of non-essential and structural proteins. The origination source and transmission to humankinds is still not clear, but the intermediate hosts are supposed to have a significant role in the transfer and emergence of SARS-CoV2 from bats to humans. There is still no approved drug or vaccine available for Covid-19. In the current review, we condense and fairly evaluate the emergence and pathogenicity of SARS-CoV2, SARS-CoV and MERS-CoV. Moreover, we also discuss the treatment and vaccine developments strategies for Covid-19

TRANSFORMATIONAL LEADERSHIP AND PROJECT SUCCESS: THE ROLES OF SOCIAL CAPITAL AND SELF-EFFICACY

Transformational leaders must constantly monitor their environments to identify and develop significant internal and external exposure to multiple points of view. Transformational leaders serve as role models for bridging organizational boundaries and proactive outreach to external stakeholders to communicate information, develop inter-organizational cooperation, establish coalitions, and harness resources. The major goal of this article is to examine the dynamics that drive organizational project success, specifically the impact of transformational leadership on external and internal social capital in management teams. This research analyzed transformational leadership and project success relationships in Pakistan’s construction industry setting along with the moderating role of the project manager subordinate’s social capital and the mediating role of the project manager subordinate’s self-efficacy. The data were collected from196 subordinates of project managers of different private organizations. Data were examined through correlation, regression, and the Hayes model through SPSS. According to the results, transformational leadership is positively associated with project success and substantially associated with social capital. Additionally, self-efficacy is positively associated with transformational leadership and project success, and it mediates the relationship between transformational leadership and project success. Social capital moderates the relationship between transformational leadership and project success, according to additional findings. This study sheds light on the relationship between transformational leadership and self-efficacy in the context of project success.

Evaluation of prescription behavior of tuberculosis patients in comparison with WHO guidelines

The present study was designed to evaluate the prescribing trend among the tuberculosis (TB) patients in different hospitals of Pakistan. In this study under directly observed therapy (DOT) programme, 38 patients including adults and children of both sexs who admitted suffering with either pulmonary or extra pulmonary TB, were selected. The majority of the patients were from rural areas (64 %) and the rest of patients from urban cities. The selected patients included both of initial phase (39 %) and continuation phase (61 %) and were receiving once daily dosing of rifampicin, isoniazid, pyrazinamide, and ethambutol combination (RHZE), and ethambutol and isoniazid (EH), respectively. Two patients (5 %) were of category 2 (relapsed patients) while thirty six patients (95 %) were of category 1 (new cases). Family history, medication errors, and prescribing trends were observed and compared the treatment plan with the World Health Organization (WHO) and Pakistan Chest Society (PCS) guidelines. It was observed that WHO and PCS guidelines were followed in the hospitals and all the prescription trend was found rationale with no drug-drug interaction but yet the treatment period was more than 6 months due to poor patient compliance to the anti tuberculosis medication and ineffective DOT program in Pakistan.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation and Optimization of Prolonged Release Mucoadhesive Tablets of Dexamethasone for Wound Healing: In Vitro-In Vivo Profiling in Healthy Volunteers

The aim of the projected study was to design and develop a novel strategy for evaluating the mucoadhesive potential of polymeric tablets of dexamethasone (DXM) for local delivery against wounds. Therefore, formulations (Q1-Q7) were synthesized via direct compression method by varying the concentrations of polymers, i.e., ethyl cellulose (EC) and agar extract (AG). Moreover, the mucoadhesive polymeric tablets were characterized via physicochemical, in vitro, ex vivo and in vivo experiments. However, physicochemical characteristics such as FTIR showed no interaction with different polymeric combination. Surface pH of all formulations was normal to slightly alkaline. Highest hydration of up to 6.22% and swelling index was comprehended with maximum concentration of AG (50% of total tablet weight). Whereas, ex vivo and in vivo residence time and mucoadhesion were attributed to the increased concentrations of polymers. Moreover, Q7, (optimized formulation), containing 10% of EC and 40% of AG, exhibited maximum release of DXM (100%) over 8 h, along with sufficient mucoadhesive strength up to 11.73 g, following first-order kinetics having r(2) value of 0.9778. Hemostatic effects and epithelialization for triggering and promoting wound healing were highly pronounced in cases of Q7. Furthermore, in vivo residence time was 7.84 h followed by salivary drug concentration (4.2 mu g/mL). However, mucoadhesive buccal tablets showed stability for 6 months, thus following the standardization (ICH-Iva) stability zone. In summary, DXM mucoadhesive tablets seem to be an ideal candidate for eradication of wound infections via local targeted delivery

Comparative bioavailability analysis of oral alendronate sodium formulations in Pakistan

Alendronate sodium, a bisphosphonate drug, it is used to treat osteoporosis and other bone diseases. The present study was designed to conduct comparative bioavailability analysis of oral formulations of alendronate sodium through an open-label, randomized, 2-sequence, 2-period crossover study. Healthy adult male Pakistani volunteers received a single 70 mg dose of the test or reference formulation of alendronate sodium followed by a 7 day washout period. Plasma drug concentrations were determined using a validated HPLC post column fluorescence derivatization method. AUC0-t, AUC0-8, Cmax and Tmax were determined by non-compartmental analysis and were found within the permitted range of 80% to 125% set by the US Food and Drug Administration (FDA). Results show that both in vitro and in vivo assays of all test brands were within the specification of the US Pharmacopoeial limits and were statistically bioequivalent. No adverse events were reported in this study

An Efficient Channel Access Scheme for Vehicular Ad Hoc Networks

Vehicular Ad Hoc Networks (VANETs) are getting more popularity due to the potential Intelligent Transport Systems (ITS) technology. It provides many efficient network services such as safety warnings (collision warning), entertainment (video and voice), maps based guidance, and emergency information. VANETs most commonly use Road Side Units (RSUs) and Vehicle-to-Vehicle (V2V) referred to as Vehicle-to-Infrastructure (V2I) mode for data accessing. IEEE 802.11p standard which was originally designed for Wireless Local Area Networks (WLANs) is modified to address such type of communication. However, IEEE 802.11p uses Distributed Coordination Function (DCF) for communication between wireless nodes. Therefore, it does not perform well for high mobility networks such as VANETs. Moreover, in RSU mode timely provision of data/services under high density of vehicles is challenging. In this paper, we propose a RSU-based efficient channel access scheme for VANETs under high traffic and mobility. In the proposed scheme, the contention window is dynamically varied according to the times (deadlines) the vehicles are going to leave the RSU range. The vehicles with shorter time deadlines are served first and vice versa. Simulation is performed by using the Network Simulator (NS-3) v. 3.6. The simulation results show that the proposed scheme performs better in terms of throughput, backoff rate, RSU response time, and fairness

Role of Flavonoids as Wound Healing Agent

Flavonoids are found as the most abundant bioactive compounds all around the world. It is found in a number of medicinal plants that are used as wound healing agents in traditional medicinal uses such as Buddleja globosa, Moringa oleifera, Lam, Butea monosperma, Parapiptadenia rigida and Ononis spinosa. Flavonoids nowadays are being used in different formulation and wound healing dressings. Inflammation, proliferation and reepithelialization are involved in wound healing. Most of the wound healing medicinal plants possess multiple flavonoids that act as synergistic effect or combined effect. This chapter briefly reviews the role of flavonoids as wound healing agent in traditional and modern medicine

Study of erythrocytes as a novel drug carrier for the delivery of artemether

Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation