Evaluation of various membranes at different fluxes to enable large-volume single-use perfusion bioreactors.

The growing demand for biological therapeutics has increased interest in large-volume perfusion bioreactors, but the operation and scalability of perfusion membranes remain a challenge. This study evaluates perfusion cell culture performance and monoclonal antibody (mAb) productivity at various membrane fluxes (1.5-5 LMH), utilizing polyvinylidene difluoride (PVDF), polyethersulfone (PES), or polysulfone (PS) membranes in tangential flow filtration mode. At low flux, culture with PVDF membrane maintained higher cell culture growth, permeate titer (1.06-1.34 g/L) and sieving coefficients (≥83%) but showed lower permeate volumetric throughput and higher transmembrane pressure (TMP) (>1.50 psi) in the later part of the run compared to cultures with PES and PS membrane. However, as permeate flux increased, the total mass of product decreased by around 30% for cultures with PVDF membrane, while it remained consistent with PES and PS membrane, and at the highest flux studied, PES membrane generated 12% more product than PVDF membrane. This highlights that membrane selection for large-volume perfusion bioreactors depends on the productivity and permeate flux required. Since operating large-volume perfusion bioreactors at low flux would require several cell retention devices and a complex setup, PVDF membranes are suitable for low-volume operations at low fluxes whereas PES membranes can be a desirable alternative for large-volume higher demand products at higher fluxes.

Contributions of Chinese hamster ovary cell derived extracellular vesicles and other cellular materials to hollow fiber filter fouling during perfusion manufacturing of monoclonal antibodies.

Hollow fiber filter fouling is a common issue plaguing perfusion production process for biologics therapeutics, but the nature of filter foulant has been elusive. Here we studied cell culture materials especially Chinese hamster ovary (CHO) cell-derived extracellular vesicles in perfusion process to determine their role in filter fouling. We found that the decrease of CHO-derived small extracellular vesicles (sEVs) with 50-200 nm in diameter in perfusion permeates always preceded the increase in transmembrane pressure (TMP) and subsequent decrease in product sieving, suggesting that sEVs might have been retained inside filters and contributed to filter fouling. Using scanning electron microscopy and helium ion microscopy, we found sEV-like structures in pores and on foulant patches of hollow fiber tangential flow filtration filter (HF-TFF) membranes. We also observed that the Day 28 TMP of perfusion culture correlated positively with the percentage of foulant patch areas. In addition, energy dispersive X-ray spectroscopy-based elemental mapping microscopy and spectroscopy analysis suggests that foulant patches had enriched cellular materials but not antifoam. Fluorescent staining results further indicate that these cellular materials could be DNA, proteins, and even adherent CHO cells. Lastly, in a small-scale HF-TFF model, addition of CHO-specific sEVs in CHO culture simulated filter fouling behaviors in a concentration-dependent manner. Based on these results, we proposed a mechanism of HF-TFF fouling, in which filter pore constriction by CHO sEVs is followed by cake formation of cellular materials on filter membrane.

Physicochemical, Rheological and Sensory Evaluation of Herbal Bread Containing Turmeric, Ginger, and Black Cumin Powder.

The diversity in the global food market is expanding as thousands of new products enter the business every year, among which nutraceutical and functional foods hold important positions. The present research work aimed at the nutritional evaluation of three medicinal herbs, i.e., turmeric (Curcuma longa L.), ginger (Zingiber officinale), and black cumin (Nigella sativa). A bread formulation was enriched with the individual/combined supplementation (1-3%) of these herbs. Later, the bread was analyzed for nutritional, rheological, textural, and sensorial characteristics. The results revealed that the herbs improved the nutritional composition of bread, especially ash and fiber, as the maximum ash and fiber contents were noticed in T15 (2.0% dried powder of each plant) with values of 1.64 ± 0.04% and 4.63 ± 0.16%, respectively. The results regarding the rheological behavior showed minor variations in the rheological traits and a slight increase in dough development time up to 4.50 ± 0.20 min in T10 from 2.80 ± 0.13 min in T0. The sensorial attributes also indicated their marked suitability as external and internal characteristics were least affected by the addition of the herbs. Although some parameters like the crust and crumb colors were affected by the addition of black cumin, showing values of 6.25 ± 0.52 and 4.44 ± 0.19, respectively, in T15, and aroma characteristics were affected by the addition of ginger, supplementation with a combination of herbs at lower doses mitigated the adverse effects of other herbs. Moreover, shelf-life extension, especially with the addition of turmeric powder, was the hallmark of this research. This study concluded that medicinal herbs can be incorporated into baked products to improve the nutritional and sensorial attributes of functional herbal bread.

Intravesical mitomycin C efficacy in acidic and alkaline urinary pH: impact on recurrence-free survival rate after TURBT.

Background: Urinary bladder tumor recurrence following transurethral resection of bladder tumor (TURBT) is a common issue. This study aims to determine how urine alkalinization affects bladder tumor recurrence after surgery. Materials and methods: Sixty patients receiving mitomycin C (MMC) therapy after TURBT were divided into two groups based on mean pH values. Twenty-six patients were in group A, whose urine pH was below 5.5. However, there were 34 patients in group B, and their urine pH was higher than 5.5. Both groups of patients were given intravesical MMC once weekly for 6 weeks following TURBT. A cystoscopy was performed as a follow-up at 3, 6, and 12 months. Urine pH and the recurrence-free survival rate were compared using Kaplan-Meier survival analysis and the COX proportional hazard model. Results: The mean time to tumor recurrence in group A (intravesical MMC in acidic urine) and group B (intravesical MMC in alkaline urine) was 12.48 versus 16.84 months, respectively. Alkaline urine pH was identified as an independent predictor of preventing the recurrence of superficial bladder tumors by univariate COX regression analysis. Age, sex, and mean tumor size did not affect the likelihood of tumor recurrence. However, smoking had an association with increased tumor recurrence. Conclusion: Tumor recurrence post-TURBT is delayed in patients with alkaline urine pH. Smoking is an independent risk factor for bladder tumors.

Indigo® Aspiration System for thrombectomy in pulmonary embolism.

Anticoagulation is mainstay therapy for patients with acute pulmonary embolism while systemic thrombolysis is reserved for those with hemodynamic instability. Over the last decade, percutaneous interventional options have entered the landscape aimed to achieve rapid pharmacomechanical pulmonary artery recanalization. The Penumbra Indigo® Aspiration System (Penumbra Inc., CA, USA) is a US FDA-approved large-bore aspiration thrombectomy device for the treatment of pulmonary embolism. Recent data has demonstrated improved radiographic end points with low rates of major adverse events in cases of intermediate-risk pulmonary embolism. In this review article, we outline device technology, applications, evidence and future directions.

A pulmonary embolism, or a blood clot in the blood vessels of the lungs, can cause symptoms of chest pain and difficulty breathing. While blood thinners have been the main treatment for pulmonary embolism, procedures aimed to rapidly remove clots have become available as treatment options. In this article we review these procedural options for pulmonary embolism with a focus on the Indigo^® Aspiration System by Penumbra Inc. This device has shown that it works and is very safe compared with other similar devices. In the future, more studies need to be performed to compare how well this device works compared with blood thinners alone, and whether it can lower the chances of long-term symptoms of these clots such as chronic shortness of breath and heart failure.

Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions.

Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating mutations of the ACVR1 gene. FOP affects both the developmental and postnatal stages, resulting in musculoskeletal abnormalities and heterotopic ossification. Current treatment options for FOP are limited, emphasizing the need for innovative therapeutic approaches. Challenges in the development of management criteria for FOP include difficulties in recruitment due to the rarity of FOP, disease variability, the absence of reliable biomarkers, and ethical considerations regarding placebo-controlled trials. This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment. Gene therapy, particularly the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system, holds promise in treating FOP by specifically targeting the ACVR1 gene mutation. Another gene therapy approach being investigated is RNA interference, which aims to silence the mutant ACVR1 gene. Small molecule inhibitors targeting glycogen synthase kinase-3ß and modulation of the bone morphogenetic protein signaling pathway are also being explored as potential therapies for FOP. Stem cell-based approaches, such as mesenchymal stem cells and induced pluripotent stem cells, show potential in tissue regeneration and inhibiting abnormal bone formation in FOP. Immunotherapy and nanoparticle delivery systems provide alternative avenues for FOP treatment.

Achieving Superior Tensile Performance in Individual Metal-Organic Framework Crystals.

Rapid advances in the engineering application prospects of metal-organic framework (MOF) materials necessitate an urgent in-depth understanding of their mechanical properties. This work demonstrates unprecedented recoverable elastic deformation of Ni-tetraphenylporphyrins (Ni-TCPP) MOF nanobelts with a tensile strain as high as 14%, and a projected yield strength-to-Young's modulus ratio exceeding the theoretical limit (≈10%) for crystalline materials. Based on first-principles simulations, the observed behavior of MOF crystal can be attributed to the mechanical deformation induced conformation transition and the formation of helical configuration of dislocations under high stresses, arising from their organic ligand building blocks in the crystal structures. The investigations of the mechanical properties along with electromechanical properties demonstrate that MOF materials have exciting application potential for biomechanics integrated systems, flexible electronics, and nanoelectromechanical devices.

Using mixed models to examine the factors associated with intimate partner violence among married women in Pakistan.

Currently, the rate of intimate partner violence (IPV) in Pakistan is 29%, which is likely an underestimate. This study used mixed models to examine the effects of women empowerment, women and husband's education, number of adult women in a household, number of children 5 or under in a household, and place of residence on physical violence and controlling behavior, controlling for women's current age and wealth status. Nationally representative data collected from 3,545 currently married women in the Pakistan Demographic and Health Survey (2012-2013) was used for the current study. Mixed models were estimated separately for physical violence and controlling behavior. Logistic regression was also used to conduct additional analyses. Results indicated that women and their husband's education, and number of adult women in a household were associated with a decrease in physical violence, whereas women's empowerment, and women and their husband's education were associated with a decrease in controlling behavior. The implications and limitations of the study are discussed.

An Overview of Complete Blood Count Sample Rejection Rates in a Clinical Hematology Laboratory Due to Various Preanalytical Errors.

Introduction The Chughtai Laboratory collects blood samples for complete blood counts from various hospitals, emergency departments, ICUs, and through home sampling services all across the country. The preanalytical phase is an integral component of laboratory medicine. A laboratory report has a key role in patient treatment and the clinician's decision in the management of the disease. Preanalytical errors are most frequently caused by the absence of a sample and/or inappropriate understanding of a test request, mislabeling, contamination from the sampling site, hemolyzed, clotted, insufficient samples, storage issues, and inappropriate blood to anticoagulant proportion or inappropriate choice of anticoagulant. Objective To identify the cause of rejection rates of the complete blood count samples and reduce the rejection rates by improving the accuracy of the results and lowering pre-analytical errors. Methods This cross-sectional study was done in the Hematology Department of Chughtai Laboratory's head office in Lahore between 19-06-2021 and 19-10-2021. Simple random sampling was applied to collect the data. About 3 ml of each blood sample was received in an ethylenediaminetetraacetic acid (EDTA) vial, inspected visually, run on Sysmex XN-9000 (Sysmex Corporation, Kobe, Hyogo, Japan), and was reviewed on peripheral smears. Results Out of 231,008 blood samples, 11,897 (5.15%) samples were rejected. The most common pre-analytical mistake was storage issues due to transportation delay (19.45%) followed by wrong medical records (19.16%), diluted samples (16.35%), incorrect tubes (16.01%), hemolyzed samples (15.13%), unlabeled samples (10.01%), and clotted sample (3.88%). Conclusion In the hematology department, the total rejection rate observed during the study period was 5.15%. Recognition of preanalytical errors and avoiding them will help us lower the sample rejection rate and raise the overall quality of laboratory management.

Chylous Ascites Pointing Toward an Internal Hernia in the Setting of Roux-en-Y Gastric Bypass: A Case Report.

Chylous ascites is a rare but significant complication of a variety of surgical procedures. It is an uncommon complication of laparoscopic Roux-en-Y gastric bypass (LRGYB). The underlying etiology is assumed to be an internal hernia, in which the hernia causes lymphatic channel engorgement and lymphatic extravasation. We present the case of a 34-year-old male who had a history of LRGYB a year back and had been experiencing gradually worsening, colicky abdominal pain radiating to the right flank for the last 24 hours. Laparoscopic exploration revealed chylous ascites due to internal herniation owing to the complication of LRYGB. Classic signs of internal hernias such as mesenteric swirl were absent on the computed tomography scan of the abdomen.

Frequency of Nucleated Red Blood Cells in the Peripheral Blood of ICU-Admitted Patients.

Background Nucleated red blood cells (NRBCs) are not normally found in the peripheral blood of normal healthy individuals. The presence of NRBCs on an adult peripheral blood smear indicates that there is an extremely high demand for the bone marrow to manufacture RBCs and that immature red blood cells are being released into the bloodstream. Anemia, myelofibrosis, thalassemia, miliary tuberculosis, malignancies of the bone marrow (myelomas, leukemias, lymphomas), and prolonged hypoxemia are a few possible pathogenic reasons. Critically ill patients who have NRBCs have a high mortality rate and a worse prognosis. OBJECTIVE: To evaluate the clinical significance of NRBCs in the peripheral blood of critically ill patients admitted to the ICU to find a cut-off to predict mortality. MATERIALS AND METHODS: A cross-sectional study was carried out over a period of six months September 1, 2020, to March 31, 2021, in Lahore, Pakistan. A total of 800 critically ill patients of both sexes in the age group of 18-70 years were included. Patients younger than 18 years and patients who underwent surgery were excluded. A quantity of 3 ml of whole blood sample in an ethylenediamine tetraacetic acid (EDTA) vial from each patient was run on SYSMEX XN-9000 (Sysmex Corporation, Kobe, Hyogo, Japan) and the results were reviewed on peripheral smears. RESULTS: The incidence of NRBCs in ICU-admitted patients was 62.5% (500/800). The total number of NRBC-positive patients recovering after the treatment was 364 (72.8%). The overall mortality of NRBC-positive patients was 30% (150/500). It was significantly higher (p<0.001) than that of NRBC-negative patients (14%; 44/300). During treatment, the highest mortality rate was seen in patients due to malignancy (100%), followed by sepsis (58.8%). It was observed that the disease pattern and number of NRBCs were significantly different (p<0.001) among all disease groups. However, there was no statistically significant difference in NRBCs on the basis of gender (p >0.05). In our study, a cutoff of NRBCs of 2.50 showed a high risk of mortality with a sensitivity of 91%. CONCLUSION: The presence of NRBCs may predict mortality in critically ill ICU-admitted patients. Their presence in the blood may be regarded as a marker of severity suggesting a high risk of ICU death.

Occam's Razor Versus Hickam's Dictum: A Case Report of Junctional Epidermolysis Bullosa and Lower Urinary Tract Infection.

Epidermolysis bullosa (EB) is a rare heterogeneous group of diseases which typically presents with extensive blistering and mucocutaneous erosions. EB is mechanobullous in nature and thus commonly involves sites of trauma and friction. It is a painful and disfiguring disorder. The involvement of different internal organs and systems, such as respiratory, genitourinary, and gastrointestinal systems, has been reported in the literature depending on the type of EB. We report a case of junctional epidermolysis bullosa (JEB) with urogenital involvement in a female child in Pakistan. JEB is a rare subtype of EB which is transmitted in an autosomal recessive pattern of inheritance. It classically affects neonates. Diagnosis is established after clinical examination, and investigations are directed at the exploration of skin lesions such as histopathological and direct immunofluorescence studies. Management of patients is primarily supportive.

In Vitro and Ex Vivo Evaluation of Fluocinolone Acetonide-Acitretin-Coloaded Nanostructured Lipid Carriers for Topical Treatment of Psoriasis.

Psoriasis is chronic autoimmune disease that affects 2-5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU-ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box-Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU-ACT-coloaded NLCs. The FLU-ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU-ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of -34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU-ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU-ACT-coloaded NLCs and FLU-ACT-coloaded NLC gel compared with the FLU-ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU-ACT-coloaded NLC gel.

Diagnostic accuracy of Alvarado scoring system relative to histopathological diagnosis for acute appendicitis: A retrospective cohort study.

Background: Acute appendicitis (AA) is a surgical emergency that requires prompt diagnosis and suitable management. It may lead to complications resulting in mortality. To evaluate the diagnostic accuracy of the Alvarado scoring system (ASS) for acute appendicitis concerning histopathological data. Methodology: About 120 patients were selected for this study consisting of 96 males and 24 females age between 20 and 60. Alvarado scoring system is calculated for each patient after collecting data about demographics, laboratory findings, and clinical examination. Then, we compared it with histopathological diagnosis taking it as a gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. SPSS version 20 was used for analyzing the data. Results: About 120 patients were included in our study. The male to female ratio was 3:1. Sensitivity and specificity were 83.3% and 41% respectively. While PPV and NPV were 85% and 41% respectively. The negative appendectomy rate was 21%. The area under the curve for receiving operating characteristics is 0.628. Conclusion: ASS is a useful diagnostic tool regarding sensitivity and positive predictive value, especially in developing countries. It is cheap, reliable, and can be easily applied.

Prevalence of Dyslipidemia in Ischemic Stroke Patients: A Single-Center Prospective Study From Pakistan.

Background Stroke is a debilitating condition that adds morbidity to the patient and is an economic burden to society. Several modifiable risk factors can be identified and controlled, and dyslipidemia is one such under-diagnosed and least reported risk factor in Pakistan. We aimed to conduct this study to determine the frequency of dyslipidemia in ischemic stroke patients. Methodology We conducted a prospective cross-sectional study for seven months at Shalamar Hospital, Lahore, from November 2020 to May 2021. One hundred four patients were enrolled as per inclusion and exclusion criteria. After informed consent, a blood sample was taken from the patients and sent to a laboratory to determine dyslipidemia. Demographic details, history, and co-morbidities were also noted on a performa. All the collected data were analyzed in SPSS 20.0. Results The mean age was 53.09 ± 12.51 years. Of 104 patients, 60 (57.69%) were male, and 44 (42.31%) were females, with a male-to-female ratio of 1.4:1. The mean duration of disease in our study was 5.77 ± 3.33 hours. The mean BMI was 27.54 ± 3.03 kg/m2. In our study, the frequency of dyslipidemia in ischemic stroke patients was 39.42% (41 patients).  Conclusion This study concluded that dyslipidemia in ischemic stroke patients is very high in the Pakistani population. This highlighted the need to control this modifiable risk factor in the population. Strategic measures, including pharmacological therapy and diet modification, should be adopted, and awareness about the disease burden, control, and importance should be spread.

The Impact of Social Entrepreneurship, Corporate Social Responsibilities, and Working Capital Management Practices on the Performance of Tourism Small-Medium Enterprises (SMEs) During COVID-19: Moderating Role of Employee Behavior.

The failure or success of an enterprise depends upon its working capital management practices (WCMP) along with effective corporate social responsibilities (CSR) and social entrepreneurship (SE). These factors ensure not only the soundness of financial indicators but also the profitability of an enterprise. Therefore, the objective of this study was to determine the impact of CSR, SE, and WCMP on the performance of small-medium enterprises (SMEs) of tourism sector, during the lockdown period in Malaysia. The goals also include the investigation of moderating role of employee behavior (EB) among the nexus of CSR, SE, WCMP, and performance of SMEs. The survey was performed to find out the practices adopted by the SMEs during corona days. A quantitative research method has been adopted to get data with convenient sampling technique, and PLS-SEM has been exploited to find out the significant nexus among CSR, SE, WCMP, and the performance of SMEs. The results indicate that CSR, SE, and WCMP have a positive association with the performance of SMEs in Malaysia. The results also indicate that EB positively moderates among the nexus of CSR, SE, WCMP, and the performance of SMEs in Malaysia. Stock review strategies by the SMEs during the corona days also exhibit significant differences except for no stock review. Significant differences between the enterprises show a lack of adaptation of the financial indicators that determine enterprise soundness. The study not only provides guidelines for entrepreneurs of SMEs but also helps in maintaining standards for the evaluation of the enterprises.

Use of peripherally inserted central catheters with a dedicated vascular access specialists team versus centrally inserted central catheters in the management of septic shock patients in the ICU.

OBJECTIVES: Peripherally inserted central catheters (PICCs) are increasingly recognized as an alternative to centrally inserted central catheters (CICCs) in critical care, yet the data regarding the safety and feasibility of this choice in septic shock management is growing but still lacking. In this study, we aimed to determine the feasibility, safety, and impact on outcomes of using dedicated vascular access specialist (VAS) teams to insert PICCs versus CICCs on patients admitted to the ICU with septic shock. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic Rochester Medical ICU and Mayo Clinic Arizona Multidisciplinary ICU from 2013 to 2016. PATIENTS: All adult patients hospitalized with diagnosis of septic shock excluding patients who declined authorization for review of their medical records, mixed shock states, and readmissions. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Comprehensive data regarding septic shock diagnosis and resuscitation were abstracted from electronic medical records. A total of 562 patients with septic shock were included in the study; 215 patients were resuscitated utilizing a PICC and 347 were resuscitated using a CICC. On univariate analysis, the time to central line insertion and time to vasopressor initiation were found to be reduced in those who received PICC at time of ICU admission versus CICC. Other favorable outcomes were also observed in those who received PICC versus CICC including shorter ICU length of stay and lower unadjusted hospital mortality. A multivariable analysis for hospital mortality showed that after adjusting for important covariates, neither the time to central line insertion nor the time to vasopressor initiation was associated with a lower hospital mortality. CONCLUSIONS: Across two tertiary referral centers within the same enterprise, use of a dedicated VAS team for insertion of PICCs for initial resuscitation in patients with septic shock was feasible and associated with shorter time to central venous access and initiation of vasopressors; however, adjusted hospital mortality was not different between the two groups.

Revitalization of tourism and hospitality sector: preempting pandemics through lessons learned.

The devastating effects of the COVID-19 pandemic have left many repercussions for the tourism industry to preempt any future catastrophe of this nature. The research aims to propose recommendations for the post-COVID-19 business world to revitalize and reclaim their market space and win back their volumes without any fear of indefinite closures and continued lockdowns in the industry. Drawing from the literature, the study assumed revitalization through responsiveness, use of advanced technology, customers' and employees' willingness, enhanced skills, adherence to standard operating procedures and protective measures, and restructuring via a public-private partnership. For the purpose, survey method was employed to collect data from the industry. After confirmation of the reliability and validity, the regression analyses supported effective revitalization through government responsiveness, use of digital technology, psychological recouping of customers' willingness, enhancing technical skills through training, strict adherence to protective measures, and destination restructuring and reorganization through a public-private partnership. The study proclaimed that Pakistan's tourism and hospitality sector development has evolved through the COVID-19 situation, and is likely to revamp and revitalize into a sustainable business. Once achieving sustainability, the revamped industry will likely to increase revenue, generate employment, and alleviate poverty through thriving public-private partnerships, community involvement, and community well-being without compromising people's health.

Downside risk-return volatilities during Covid 19 outbreak: a comparison across developed and emerging markets.

This research study evaluates the impact of the Covid 19 pandemics on the downside risk-return volatilities across the four stock markets of the USA, UK, China, and Pakistan. The pandemic results in severe economic and financial consequences both at micro and macro levels as well as across the stock markets of various countries. The selected stock markets of the USA, UK, Pakistan, and China are significantly affected in terms of both investor risk and return during the pandemic time. The entire period distribution of the risk exhibited the downside risk behavior of both markets and investors' serious concern regarding their investment strategies. Using high-frequency data from January 2020 to April 2021, the findings of the study reveal more of the downside abnormal returns across both markets. The impact is larger and high in developed markets of USA and UK compared to the emerging markets of China and Pakistan. The outcomes of the various value-at-risk models disclose the higher downside risk implications for all markets, larger for developed countries. Similarly, the three stock markets of the USA, UK, and China were found to be significantly connected during a pandemic. Investors' reactions were positive and high in case of positive news outbreaks and dwindling in case of negative news and downside impact. The outcomes of the study are useful for investors, portfolio managers, investment advisors, and others to understand the dynamics of the pandemic situation and devise effective strategies to overcome the severities of downside risk.

Relationship Between High-Density Lipoprotein-Cholesterol and Red Cell Distribution Width in Patients With Coronary Artery Disease.

Background A high red cell distribution width (RDW), which indicates ongoing inflammation, and low levels of high-density lipoprotein-cholesterol (HDL-C) are associated with increased mortality and morbidity in patients with coronary artery disease (CAD). Recent studies have suggested that HDL-C possesses anti-inflammatory and antioxidant effects, which may explain its anti-atherogenic properties. This study aims to determine the relationship between HDL-C levels and RDW in patients with CAD. Materials and methods This cross-sectional study was performed on 120 patients with CAD from July 2020 to June 2021 in the Hematology Department of Chughtai Lab Lahore. Patients were graded according to the degree of coronary artery stenosis as follows: Grade 1,30%-50%; Grade 2, 51%-70%; and Grade 3,>70%. The HDL-C level was measured from venous blood samples by a fully automated Abbot Alinity analyzer. The RDW was measured by Sysmex XN-5000. The sample size was calculated using the Select Statistics calculator. The mean RDW and HDL-C of the patients were calculated, and correlation analyses were performed using the Pearson correlation coefficient. Results The HDL-C level was inversely related to the RDW. Of the 120 patients, 38, 44, and 38 had Grade 1, Grade 2, and Grade 3 stenosis, respectively. The mean HDL-C level and RDW were 30.58 ±3.77 mg/dL and 16.04% ±1.66%, respectively. The value of r was -0.8622 (strongly negative). Data were stratified based on the degree of stenosis. The values of r in Grades 1, 2, and 3 were -0.43 (moderately negative), -0.604 (moderately negative), and -0.27 (weakly negative), respectively. Conclusion The RDW can be used as an additional marker to determine the disease status in CAD patients.