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Nipah virus (NiV) is a novel zoonotic pathogen that belongs to the

KDM5A over-expression mediates cancer cell proliferation and promotes resistance toward chemotherapy through epigenetic modifications. As its complete mechanism of action is still unknown, there is no KDM5A specific drug available at clinical level. In the current study, lead compounds for KDM5A were determined through pharmacophore modeling and high-throughput virtual screening from Asinex libraries containing 0.5 million compounds. These virtual hits were further evaluated and filtered for ADMET properties. Finally, 726 compounds were used for docking analysis against KDM5A. On the basis of docking score, 10 top-ranked compounds were selected and further evaluated for non-central nervous system (CNS) and CNS drug-like properties. Among these compounds, N-{[(7-Methyl-4-oxo-1,2,3,4-tetrahydrocyclopenta [c] chromen-9-yl) oxy]acetyl}-l-phenylalanine (G-score: -11.363 kcal/mol) was estimated to exhibit non-CNS properties while 2-(3,4-Dimethoxy-phenyl)-7-methoxy-chromen-4-one (G-score: -7.977 kcal/mol) was evaluated as CNS compound. Docked complexes of both compounds were finally selected for molecular dynamic simulation to examine the stability. This study concluded that both these compounds can serve as lead compounds in the quest of finding therapeutic agents against KDM5A associated cancers.

Recently, graphene quantum dots (GQDs), zero-dimensional flat nanomaterials with distinct optical, electrical, and optoelectric properties, have attracted significant attention, owing to their non-toxicity and physiological inertness. A variety of top-down and bottom-up methodologies have been exploited for the synthesis of these materials, including electrochemical oxidation, hydrothermal or solvothermal, microwave-assisted, controllable synthesis and carbonization from organic molecules or polymers. This review focuses on the synthesis and applications of GQDs in solar cells, supercapacitors, LEDs, and Li/Na ion batteries. Herein, we summarized in detail the synthesis methods for GQDs employed in energy storage applications with enhanced capacitance, power conversion, retention capability, and stability, achieved by adjusting many synthesis parameters, including annealing temperature, growth time, substrate concentration, and catalyst. The conclusion highlights the potential opportunities and challenges related to future research on GQDs.

Mixed matrix membranes (MMMs) fabricated with porous metal organic frame works have enhanced the separation performance of polymer membranes. In this context microporous 3D Tb(BTC)(H2O).(DMF)1.1 MOF was incorporated into pristine Matrimid® with loadings of 10, 20 and 30 weight percentages. SEM micrographs indicated proper distribution of filler in the Matrimid and no interfacial voids were observed. Gas permeation studies evidenced the CO2 permeability to be 13.2 (82.32%) and 18.34 (153.31%) and 25.86 Barrer for 10, 20 and 30 wt% MMMs respectively. The 257.18% increase in CO2 permeability of 30 wt% MMM than methane was attributed to polar nature of CO2, its smaller kinetic diameter, condensability, and larger solubility within the Matrimid matrix than non – polar and larger CH4 molecules. Addition of filler influenced the pure gas selectivity of all MMMs positively. So, 30 wt% MMM exhibited the highest 58.04% increase in selectivity that was attributed to the molecular sieving property of the filler and the size exclusion phenomena as followed by CH4 and CO2. The high values of mixed and pure gas selectivity were obtained upon increasing filler concentration. The commercial applicability of these MMMs was tested by checking their selectivity under increased feed concentrations of CO2 and checking permeability and selectivities at high temperatures. The study depicted that, competitive sorption of gases, prevalence of size exclusion phenomena and polymer chains relaxation at higher temperature were responsible for low gas selectivity. MMM with 30 wt% of MOF lied close to Robson’s Upper bound 2008 that indicated its good separation potential.

Hepatitis B causes major deathly infections in developing countries. The surface antigen preS1, hepatocytes attachment site, plays a crucial role in development and progression of disease. The present study was, therefore, an effort to develop an efficient expression system for PreS1 gene in Esherishia coli. PreS1 gene was amplified and cloned in pTZ57R/T vector. Following confirmation through restriction enzyme digestion and sequencing, it was subcloned in pET22b(+). E. coli BL21 (DE3) CodonPlus cells were transformed with the recombinant plasmid. PreS1 gene was induced using IPTG, the protein was expressed and quantified with Bradford assay and analyzed on SDS-PAGE. Enzyme Linked Immunosorbent Assay and Western Blot analysis were performed for protein integrity and conformation.

Aim: To detect the clinical presentation, biopsy and surgery of breast cancer in women at tertiary care hospital in Gujrat, Pakistan. Study design: Cross sectional descriptive study. Place and duration of study: This study was conducted in 06 years April 2014 to March 2020 at Aziz Bhatti Shaheed Teaching Hospital Gujrat, Pakistan. Methods: Total 138 women were selected for study that was having breast lump, breast ulcer or abnormal breast (nipple) discharge. Women were admitted for investigations and further plan for treatment. Breast cancer was diagnosed on history, examination and investigations. Complete blood count, serum studies, ultra-sonography of breast, mammography and breast biopsy was planned. Results: Total 138 women were enrolled in the study. Women 25-85 years of age were included in the study. Youngest woman was 27 years of age and the oldest was 85 years of age. Thirty two (23.18%) women were less than 50 years of age and 106(76.81%) women were more than 50 years of age. Conclusions: Breast cancer is the commonest cancer of women and most frequent cause of cancer related deaths. Early diagnosis and appropriate treatment offers the best chance for cure. Histological diagnosis and staging is mandatory prior to treatment. The best treatment of breast cancer is carried out by multidisciplinary team. Keywords: Breast lump, mammography, nipple discharge

Aim: To detect the frequency of confirmed corona infection (covid-19) in children in affected families in Gujrat. Study design; cross sectional study. Place and duration of study: This study was conducted from January 2020 to 10 June 2020 at Gujrat Pakistan. Methods: Total 214 children were included in the study from 141 families in which at least one family member was confirmed positive for corona virus infection (COVID-19). This study was started in the beginning of year 2020 but in Gujrat first positive case was reported in March 2020. First of all a family was decided where a confirmed positive case was there. This particular family was included and decided for testing if there was abroad travelling history within 14 days or there was a contact with a confirmed positive patient for corona infection (COVID-19). Results: Total 214 children were included from January 2020 to June 2020. Out of total 214 children, 78 children were positive for (COVID-19) corona infection. Out of 78 (COVID-19) corona infection positive children, 46(58.97%) were female children whereas 32(41.02%) were male children. 37 children (47.44%) were from 1 to 6 years of age whereas 41 (52.56%) were 7-15 years of age. Conclusions: Children can acquire corona virus infection (COVID-19) from adults. Though the severity of corona virus infection (COVID-19) is mild in children, in spite of all this the children should not come in contact with positive person for corona virus infection (COVID-19). Keywords: COVID-19, affected family, contact with positive patients

Objective To determine whether surge conditions were associated with increased mortality. Design Multicenter cohort study. Setting U.S. ICUs participating in STOP-COVID. Patients Consecutive adults with COVID-19 admitted to participating ICUs between March 4 and July 1, 2020. Interventions None Measurements and Main Results The main outcome was 28-day in-hospital mortality. To assess the association between admission to an ICU during a surge period and mortality, we used two different strategies: (1) an inverse probability weighted difference-in-differences model limited to appropriately matched surge and non-surge patients and (2) a meta-regression of 50 multivariable difference-in-differences models (each based on sets of randomly matched surge- and non-surge hospitals). In the first analysis, we considered a single surge period for the cohort (March 23 – May 6). In the second, each surge hospital had its own surge period (which was compared to the same time periods in matched non-surge hospitals). Our cohort consisted of 4342 ICU patients (average age 60.8 [sd 14.8], 63.5% men) in 53 U.S. hospitals. Of these, 13 hospitals encountered surge conditions. In analysis 1, the increase in mortality seen during surge was not statistically significant (odds ratio [95% CI]: 1.30 [0.47-3.58], p = .6). In analysis 2, surge was associated with an increased odds of death (odds ratio 1.39 [95% CI, 1.34-1.43], p Conclusions Admission to an ICU with COVID-19 in a hospital that is experiencing surge conditions may be associated with an increased odds of death. Given the high incidence of COVID-19, such increases would translate into substantial excess mortality.

Background: COVID-19 is a severe respiratory disease, started in China. For diagnosis, we need swabs from different regions of respiratory tract. Nasopharyngeal swab is the preferred method. Rt-PCR for Corona virus is the gold standard lab test for diagnosis. Objective: To determine frequency of positive PCR tests and complications in total number of nasopharyngeal samples taken at ENT department of Allied Hospital, Faisalabad Pakistan. Study Design: Descriptive cross-sectional study. Settings: ENT department, Allied Hospital, Faisalabad Pakistan. Duration: 1st May 2020 to 31st August 2020. Methodology: Nasopharyngeal swabs of suspected cases, their contacts, and healthcare workers were taken at ENT department of Allied Hospital. All samples were sent to BSL-LAB. The complication related to procedure were also noted. The result was labelled as detected and non-detected. Results: Total sample taken were 2909 out of which 627 (22%) cases were positive for Corona virus while 2282 (78%) were negative. Pain was most frequent complication (68%) followed by blood staining of swab (31%) and epistaxis (1%). Conclusion: Frequency of positive corona virus case presenting to allied Hospital is 22%. Nasopharyngeal swabs are a safe and effective method of sampling in suspected Corona Virus cases. Pain during the procedure is the most frequent complication.

KDM5A over-expression mediates cancer cell proliferation and promotes resistance toward chemotherapy through epigenetic modifications. As its complete mechanism of action is still unknown, there is no KDM5A specific drug available at clinical level. In the current study, lead compounds for KDM5A were determined through pharmacophore modeling and high-throughput virtual screening from Asinex libraries containing 0.5 million compounds. These virtual hits were further evaluated and filtered for ADMET properties. Finally, 726 compounds were used for docking analysis against KDM5A. On the basis of docking score, 10 top-ranked compounds were selected and further evaluated for non-central nervous system (CNS) and CNS drug-like properties. Among these compounds, N-{[(7-Methyl-4-oxo-1,2,3,4-tetrahydrocyclopenta [c] chromen-9-yl) oxy]acetyl}-l-phenylalanine (G-score: -11.363 kcal/mol) was estimated to exhibit non-CNS properties while 2-(3,4-Dimethoxy-phenyl)-7-methoxy-chromen-4-one (G-score: -7.977 kcal/mol) was evaluated as CNS compound. Docked complexes of both compounds were finally selected for molecular dynamic simulation to examine the stability. This study concluded that both these compounds can serve as lead compounds in the quest of finding therapeutic agents against KDM5A associated cancers.

During diagnostic bronchoscopies, conscious sedation improves patient tolerance, but it can contribute to hypercapnia and hypoxia by various mechanisms including depression of ventilatory drive. This prospective study was undertaken to determine the frequency of respiratory events and associated oxygen desaturations during bronchoscopy with conscious sedation.The Nox-T3 monitoring system was placed before starting the bronchoscopy and remained in place for 30 minutes following the procedure. The primary endpoint was the occurrence of obstructive and central apneic events during bronchoscopy under conscious sedation.Obstructive events (apnea and hypopnea) occurred in 100% of patients (n=31), and central apneas occurred in 58% of patients (n=18) during the procedure with a median of 9 and 2 events per patient, respectively. During recovery, a significant proportion of patients had detectable obstructive (86%) and central (36%) events. Higher body mass index was associated with oxygen desaturation to90% and with the need for escalation of care. Furthermore, a conscious sedation regimen that included propofol was significantly associated with central apneic events.Respiratory events are common during and immediately postprocedure after conscious sedation for bronchoscopy. Most events are obstructive, and the use of propofol predisposes to central apneas during the procedure. Both types of events are associated with a higher body mass index. Oxygen desaturation to90% triggers escalation of care. A further prospective study will be required to determine the clinical significance of these apneic events and whether alleviating these events will improve the safety and outcomes of bronchoscopic procedures performed under conscious sedation.

Rationale & Objective Acute kidney injury treated with kidney replacement therapy (AKI-KRT) occurs frequently in critically ill patients with COVID-19. We examined the clinical factors that determine kidney recovery in this population. Study Design Multicenter cohort study. Setting & Participants 4221 adults with COVID-19 not receiving kidney replacement therapy who were admitted to intensive care units at 68 US hospitals with COVID-19 from March 1 to June 22, 2020 (the “ICU cohort”). Among these, 876 developed AKI-KRT after admission to the ICU (the “AKI-KRT subcohort”). Exposure(s) The ICU cohort was analyzed using AKI severity as the exposure. For the AKI-KRT subcohort, exposures included demographics, comorbidities, initial mode of KRT, and markers of illness severity at the time of dialysis initiation. Outcome(s) The outcome for the ICU cohort was estimated glomerular filtration rate (GFR) at hospital discharge. A three-level outcome including death, kidney nonrecovery, and kidney recovery at discharge, was analyzed for the AKI-KRT subcohort. Analytical approach The ICU cohort was characterized using descriptive analyses. The AKI-KRT subcohort was characterized with both descriptive analyses and multinomial logistic regression to assess factors associated with kidney nonrecovery while accounting for death. Results Among a total of 4221 patients in the ICU cohort, 2361 (56%) developed AKI, including 876 (21%) who received KRT. More severe AKI was associated with higher mortality. Among survivors, more severe AKI was associated with an increased rate of kidney nonrecovery and lower kidney function at discharge. Among the 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) had kidney nonrecovery, and 193 (22%) had kidney recovery by the time of discharge. The odds of kidney nonrecovery was greater for lower estimated GFR with odds ratios (ORs) of 2.09 (95% CI, 1.09-4.04), 4.27 (95% CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for CKD GFR categories 3, 4, and 5, respectively, compared to estimated GFR > 60 mL/min/1.73 m2. Oliguria at the time of KRT initiation was also associated with nonrecovery (OR 2.10 [95% CI, 1.14-3.88] and 4.02 [95% CI, 1.72-9.39] for patients with 50-499 and, Critically ill patients with COVID-19 often develop acute kidney injury (AKI). This study of 4221 patients demonstrated that more severe AKI was associated with greater in-hospital mortality and poorer kidney function at hospital discharge. Among the 876 patients who required dialysis for AKI, almost two-thirds died. Among those who survived to discharge, about two-thirds recovered kidney function and were discharged without the need for dialysis. Lower baseline kidney function and reduced urine output were associated with non-recovery of kidney function. Identification of such predictors is important in assessing prognosis among these critically ill patients and has implications for clinical care of individuals critically ill with COVID-19.

Evidence collected from biological fluids obtained from a crime scene is essentially important in forensic cases. A potential profile can be generated from these obtained samples and this can help in identifying the victims and/or suspects of sexual assault. The water environments selected for this study are all related to the potential crime scenes from which there is a possibility of finding a dead body or clothing of a sexual assault victim. Tap water, River water, Swimming pool water, and Canal water were selected. Fabric types selected were khaddar, linen, silk, polyester, and chiffon. Detection of seminal stains was carried out by three methods; Alternate Light Source (ALS), Acid phosphatase (AP) testing, and Kernechtrot-Picro-indigo-carmine (KPIC) testing. These tests were performed for each fabric type in each water environment after regular intervals, 24 h, 48 h, 72 h, 4 days, 7 days, and 14 days. This study aimed to compare the ability of five types of fabrics to retain seminal material after immersion in four different types of water environments. Fluorescence was only detected in tap water-soaked silk fabric after 14 days of immersion. Seminal fluid was detected in khaddar, chiffon, silk, and polyester in samples immersed for 14 days in tap water. Spermatozoa were retained by khaddar and silk immersed in tap water, Polyester fabric in tap and river water, Chiffon in only river water and Linen in swimming pool water when immersed for 14 days. However, fluorescence, seminal fluid or spermatozoa were not detected in linen fabric regardless of all the afore mentioned variables.

Variation in hospital mortality has been described for coronavirus disease 2019 (COVID-19), but the factors that explain these differences remain unclear.Our objective was to utilize a large, nationally representative dataset of critically ill adults with COVID-19 to determine which factors explain mortality variability.In this multicenter cohort study, we examined adults hospitalized in intensive care units with COVID-19 at 70 United States hospitals between March and June 2020. The primary outcome was 28-day mortality. We examined patient-level and hospital-level variables. Mixed-effects logistic regression was used to identify factors associated with interhospital variation. The median odds ratio (OR) was calculated to compare outcomes in higher- vs. lower-mortality hospitals. A gradient boosted machine algorithm was developed for individual-level mortality models.A total of 4,019 patients were included, 1537 (38%) of whom died by 28 days. Mortality varied considerably across hospitals (0-82%). After adjustment for patient- and hospital-level domains, interhospital variation was attenuated (OR decline from 2.06 [95% CI, 1.73-2.37] to 1.22 [95% CI, 1.00-1.38]), with the greatest changes occurring with adjustment for acute physiology, socioeconomic status, and strain. For individual patients, the relative contribution of each domain to mortality risk was: acute physiology (49%), demographics and comorbidities (20%), socioeconomic status (12%), strain (9%), hospital quality (8%), and treatments (3%).There is considerable interhospital variation in mortality for critically ill patients with COVID-19, which is mostly explained by hospital-level socioeconomic status, strain, and acute physiologic differences. Individual mortality is driven mostly by patient-level factors. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Summary: Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Rationale & Objective Underlying kidney disease is an emerging risk factor for more severe COVID-19 illness. We examined the clinical courses of critically ill COVID-19 patients with and without pre-existing kidney disease and investigated the association between degree of underlying kidney disease and in-hospital outcomes. Study Design Retrospective cohort study Settings & Participants 4,264 critically ill COVID-19 patients (143 dialysis patients, 521 chronic kidney disease [CKD] patients, and 3,600 patients without CKD) admitted to ICUs at 68 hospitals in the United States. Predictor(s) Presence (versus absence) of pre-existing kidney disease Outcome(s) In-hospital mortality (primary); respiratory failure, shock, ventricular arrhythmia/ cardiac arrest, thromboembolic event, major bleed, and acute liver injury (secondary) Analytical Approach We used standardized differences to compare patient characteristics (values >0.10 indicate a meaningful difference between groups) and multivariable adjusted Fine and Gray survival models to examine outcome associations. Results Dialysis patients had a shorter time from symptom onset to ICU admission compared to other groups (median [quartile 1-quartile 3] days: 4 [2-9] for dialysis patients; 7 [3-10] for CKD patients; 7 [4-10] for patients without pre-existing kidney disease). More dialysis patients (25%) reported altered mental status than those with CKD (20%, standardized difference = 0.12) and no kidney disease (12%, standardized difference = 0.36). Half of dialysis and CKD patients died within 28-days of ICU admission versus 35% of patients without pre-existing kidney disease. Compared to patients without pre-existing kidney disease, dialysis patients had a higher risk of 28-day in-hospital death (adjusted HR 1.41; 95% CI 1.09, 1.81), while patients with CKD had an intermediate risk (adjusted HR 1.25; 95% CI 1.08, 1.44). Limitations Potential residual confounding Conclusions Findings highlight the high mortality of individuals with underlying kidney disease and severe COVID-19, underscoring the importance of identifying safe and effective COVID-19 therapies for this vulnerable population., Individuals with underlying kidney disease may be particularly vulnerable to severe COVID-19 illness, marked by multi-system organ failure, thrombosis, and a heightened inflammatory response. Among 4,264 critically ill adults with COVID-19 admitted to 68 intensive care units across the U.S., we found that both chronic kidney disease and dialysis patients had a ∼50% 28-day in-hospital mortality rate. Patients with underlying kidney disease had higher in-hospital mortality than patients without kidney disease, with patients on maintenance dialysis having the highest risk. As evidenced by differences in symptoms and clinical trajectories, patients with pre-existing kidney disease may have unique susceptibility to COVID-19-related complications which warrants additional study and special consideration in the pursuit and development of targeted therapies.

Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival. Visual Abstract. Early Anticoagulation in COVID-19 Hypercoagulability may be a key mechanism of death in patients with COVID-19. This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival., Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. Setting: 67 hospitals in the United States. Participants: Adults with COVID-19 admitted to a participating ICU. Measurements: Time to death, censored at hospital discharge, or date of last follow-up. Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Limitation: Observational design. Conclusion: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. Primary Funding Source: None.

Cancer is the second biggest killer worldwide. It has been estimated that specific lifestyle and dietary measures can prevent 30–40% of all cancers. Consumption of nutrient sparse foods, such as refined flour products and concentrated sugars, consumption of red meat, low fibre intake, and disproportion of omega 3 and omega 6 fatty acids, contributes to cancer risks. Microbiological and chemical food contaminants as well as conventional and industrial food processing methods may further increase the carcinogenicity of diets while protective agents in a cancer prevention diet include folic acid, selenium, vitamin D, vitamin B-12, chlorophyll, and antioxidants such as the carotenoids, kryptoxanthin, lycopene, and lutein. Diet can also influence the gut microbes that may have positive or adverse effects on cancer risk. The authors summarize cancer prevention by functional foods and discuss the role of different dietary factors such as promoter or inhibitor in pathogenesis of different subtypes of cancer worldwide.

Background and objectives In surgical patients, coronary disease is the main cause of perioperative mortality. The incidence of serious cardiovascular complications is reported as 5% with a probability of 1-2% of death from the cardiac cause in major non-cardiac surgery. B-type natriuretic peptide (BNP) is a sensitive and specific predictor of left ventricular systolic dysfunction and predicts first cardiovascular event and death in the general population. The recent guidelines recommended the use of pro-BNP for independent perioperative prognosis in cardiac patients undergoing non-cardiac surgery. The aim of this study is to assess the predictive value of raised pro-BNP levels in patients who underwent major abdominal surgery and evaluate its relationship with cardiovascular complications and mortality occurring up to 30 days after surgery. Materials and methods We reviewed the medical records of patients undergone surgical procedures in the abdominal region lasting more than two hours, requiring postoperative high dependence or intensive care and an expected hospital stay of at least three days. All types of open or laparoscopic-assisted abdominal or pelvic surgeries that were evaluated for preoperative pro-BNP levels were included in the study. During the postoperative period, all patients were followed for cardiac complications and mortality for 30 days after surgery. Postoperative adverse cardiac events were predefined as angina pectoris, myocardial infarction, cardiogenic dyspnea, acute arrhythmias (atrial fibrillation/flutter, ventricular fibrillation/tachycardia), acute hypertensive event (hypertensive emergency or urgency), congestive heart failure, acute pulmonary edema, or primary cardiac death. While non-cardiac complications were also documented as either pulmonary, septic, postsurgical site infection, and other systemic complications. Subsequently, a survival analysis was done for the discretion of cardiovascular complications and mortality. Results The mean age of the study population was found to be 50.22 ± 14.28 years, mean pro-BNP levels were 909.29 ± 3950.04, and mean days of hospital stay were 7.43 ± 4.49 days. The 30-day postoperative all-cause mortality was found to be 9.8%. Hypertension and diabetes were frequent comorbidities amongst the study population. The mean preoperative pro-BNP levels were found higher in the male gender (p=0.071), also found higher in those with cardiovascular complications (p=0.006) and mortality (p=0.057). Receiver operating characteristic (ROC) analysis showed cardiovascular outcomes with a cut-off value of pro-BNP at 143 pg/ml, AUC of 0.891, at a sensitivity of 91%, positive predictive value (PPV) of 96%, a specificity of 75%, and negative predictive value (NPV) of 58%, while the same for mortality at a cut-off value of 164 pg/ml was found with AUC of 0.815, at a sensitivity of 84%, a specificity of 66%, PPV of 97%, and NPV of 21%. The unadjusted odds ratio for cardiovascular complications was found to be 17.857 (95% CI: 6.56-48.60) while that for mortality was 10.863 (95% Cl: 2.29-51.37). The Kaplan-Meier survival curves showing elevated pro-BNP levels were significantly associated with cardiovascular events, with 30 days mortality at a cut-off value of 164 pg/ml. Conclusion Pro-BNP is a useful marker in postoperative patients for not only predicting cardiovascular outcomes as cited by many previous studies but also mortality.

Many shreds of evidence found on the crime scenes contain a trace amount of DNA which results in insignificant profiling results for subsequent comparison. This can nullify the potential evidence material and hamper investigation process. Over the years, different strategies have been employed by various DNA testing laboratories to create interpretable DNA profiles generated from low template of DNA. This review highlights different strategies used by forensic laboratories worldwide for creating complete DNA profiles from low copy number template for comparison purposes along with its associated risks for forensic purposes Many shreds of evidence found on the crime scenes contain a trace amount of DNA which results in insignificant profiling results for subsequent comparison. This can nullify the potential evidence material and hamper investigation process. Over the years, different strategies have been employed by various DNA testing laboratories to create interpretable DNA profiles generated from low template of DNA. This review highlights different strategies used by forensic laboratories worldwide for creating complete DNA profiles from low copy number template for comparison purposes along with its associated risks for forensic purposes

Highlights • With increase in number of people suffering from COVID-19, there is a dire need to look for effective remedies against this pandemic. • In this study, we propose a single drug Paromomycin against two targets of COVID-19 i.e. Spike protein (S1) and protease domain. Based upon docking scores and MD simulation, Paromomycin was found to have strong binding affinity against both the targets of coronavirus. • 15 anti-malarial drugs including chloroquine were also investigated against both targets using in-silico approach. The results showed that no anti-malarial drug exhibited effective binding against either S1 or protease. • Paromomycin, a broad spectrum aminoglycoside antibiotic that is originally used to treat acute and chronic intestinal infection may also be potentially used to treat COVID-19. As one of the major symptoms in COVID-19 infection include GI disturbance. • Clinical trials are further needed to confirm the efficacy of Paromomycin against COVID-19., Objectives With increase in number of people suffering from COVID-19, there is a dire need to look for effective remedies against this pandemic. Drug repurposing seems to be the solution for current situation. Methods In our quest for finding potential drug against this virus, 15 anti-malarial drugs including chloroquine, and 2413 FDA approved drugs were investigated against both protease and spike proteins of COVID-19 usingin-silico approach. Molecular docking analysis followed by MD simulation was carried out to estimate the binding and stability of the complexes. Results In this study, we found a single drug Paromomycin against two targets of COVID-19 i.e. Spike protein (S1) and protease domain. Paromomycin was found to have strong binding affinity against both the targets of coronavirus. The results also showed that no anti-malarial drug exhibited effective binding against either S1 or protease. Conclusions Current study concluded that Paromomycin is an effective dual targeting drug against coronavirus, as it binds not only to the protease domain of the virion but also with the spike domain with high stability. Furthermore, none of the anti-malarial drugs showed strong binding affinity for either protease or receptor binding domain (RBD).

BACKGROUND: Long-term oxygen therapy (LTOT) delivered continuously is known to decrease mortality in patients with COPD and who are hypoxemic; however, supportive data for LTOT use in patients without COPD is lacking. In addition, many patients may be prescribed LTOT without a definitive etiology for hypoxemia. First, we investigated the diagnoses for which oxygen was prescribed to a sample of veterans and whether each diagnosis was supported by confirmatory testing. Second, we looked at the proportion of subjects who were prescribed non-continuous therapy. METHODS: We retrospectively studied subjects prescribed domiciliary oxygen at the Veterans Administration Western New York Healthcare System. The subjects who met inclusion criteria were identified by using a computerized patient record system; data were collected on subject characteristics, oxygen prescription information, diagnosis for hypoxia, and diagnostic workup. Descriptive data were presented as mean ± SD and median (range). Statistical analysis was performed by using the chi-square test and an unpaired t test. RESULTS: A total of 494 patients were included: 96.8% men, mean ± SD ages 74.2 ± 10.8 y. Most of the subjects were prescribed oxygen as out-patients (68.5%). A total of 335 (67.8%) were prescribed oxygen for continuous therapy, 72 (14.1%) for nocturnal therapy, 50 (10.1%) for exertion, and 30 (6.1%) for both exertion and nocturnal use. At 3 months, 19.6% of the initial cohort had oxygen discontinued. In those subjects with oxygen continued at 3 months, COPD was the most common diagnosis (63.6%), of which 76.1% had pulmonary function tests (PFTs), with 85.7% showing obstruction on spirometry. CONCLUSIONS: Results of our study showed a 99.4% adherence to Medicare criteria for domiciliary oxygen prescription. Also, 30.3% of the subjects were prescribed LTOT for exertional or nocturnal desaturation or both. Repeated testing at 3 months identified subjects who no longer required oxygen. COPD was the most common etiology for domiciliary oxygen. A small proportion of the subjects (6.9%) were prescribed oxygen without underlying etiology for hypoxia. Exertional and/or nocturnal oxygen prescription was common, and further research to elucidate its utility is clearly warranted.

Objective: To determine if granulocyte colony-stimulating factor (G-CSF) with empirical antibiotics therapy accelerates febrile neutropenia resolution compared with antibiotics without it. Study design: Experimental study. Place and Duration of Study: Study was conducted for a period of one year from march 2012 to february 2013 in oncology/haematology department Children Hospital Lahore (PAKISTAN). Subject and Methods: A total of 56 children with febrile neutropenia due to chemotherapy were included in the study. Two groups were made A and B. Twenty eight patients were included in each group. Patients included in the group A were given granulocyte colony stimulating factor with the dose of 5 microg/kg/day for five days and the patients included in group B were not given granulocyte colony stimulating factor. Subcutaneous administration was recommended. Patients remained on study until absolute neutrophil count (ANC) >500/microl and > or =48 hr without fever. Every child in both groups was given antibiotic treatment in the hospital whenever there is need, antibiotics changed according to the blood culture sensitivity. Admitted patients were followed daily for fever and signs of sepsis. Number of days of admission in hospital and number of days of treatment was calculated in both groups and compared with each other. Duration of febrile neutropenia and mortality was also analysed for both groups. Results: Out of 56 patients 46 had acute lymphoblastic leukemia (ALL), 06 patients were of wilm tumour and 04 patient were having rhabdomyosarcoma. Twenty eight patients were given only antibiotics(GROUP B) and 28 patients were given G-CSF plus antibiotics(GROUP A). Addition of G-CSF significantly reduced neutropenia and febrile neutropenia recovery times. Median days to febrile neutropenia resolution was 4.3 days earlier with G-CSF (5.3 vs. 9.6 days) (P < 0.0001). Resolution of fever was one day earlier in patients who were given G-CSF (GROUP A). Hospitalization was 2.1 days shorter with G-CSF (6.1 vs. 8.2 days) (P = 0.02). (Table II). There was difference of 2.2 days in the duration of IV and oral antibiotic treatment. Addition of antifungal therapy was done in 4 patients in group B and only in one patient in group A. All the patients recovered and no death occurred in the study. Conclusions: It is concluded that addition of G-CSF to empiric antibiotic therapy accelerates chemothserapy-induced febrile neutropenia resolution by 4.3 days in pediatric patients with malignancy. It is a significant difference in duration of hospitalization. By bearing expenses of G-CSF we can decrease the expenses of hospitalization and antibiotics.

Crime scene investigation is an important tool in criminal investigation process. Proper processing of crime scene is a prerequisite for successfully solving a criminal case. In Pakistan, local policemen are not properly trained and equipped with the necessary items required for systematic processing of crime scene including proper identification and collection of evidence. Certain capacity building measures and improvements must be needed for proper processing of crime scene in Pakistan. This article focuses the current situation and strategies being practiced in Pakistan followed by suggestions for capacity building measures in this field. Keywords: Pakistan, Crime scene, Investigation process, Capacity building

Lung cancer is the major contributor to overall cancer-related mortality. Biomarkers are important in early detection and prognosis, in addition to developing treatment regimes, which may improve the patient survival rates. Biomarkers may also assist in investigating the in depth metabolic pathways and in establishing a set of therapeutic agents leading to early detection of the disease. The present study was designed to identify and confirm a lung cancer protein biomarker and to correlate the differential expression of the protein to a particular histological disease type. A total of 100 lung cancer patients and 50 healthy controls were included in the present study and were categorized into the two main histological types of lung cancer; non‑small cell lung cancer (NSCLC; n=88) and small cell lung cancer (SCLC; n=12). NSCLC was further subclassified into three histological types; adenocarcinoma (n=34), squamous cell carcinoma (n=48) and large cell carcinoma (n=6). The patient and control serum samples underwent sodium dodecyl sulphate polyacrylamide gel electrophoresis characterization followed by two‑dimensional gel electrophoresis. Following mass spectrometry, human haptoglobin was identified with a mass of ~42‑46 kDa and an isoelectric point (pI) of ~5.5‑6.2. The experimental mass of the protein was found to be 45.8 kDa with a pI of 6.13. The matrix‑assisted laser desorption/ionization time‑of‑flight/time‑of‑flight data exhibited spectral peaks of 1146.134, 1724.191, 1345.339 and 2210.319 m/z and Mascot search analysis identified these peaks as haptoglobin (accession no. P00738; Mascot score 87; sequence coverage 23%). This protein was significantly overexpressed in squamous cell carcinoma and adenocarcinoma, as compared with the control. The present study described differentially expressed human haptoglobin as a lung cancer serum protein biomarker, which may serve as a diagnostic and therapeutic target and set a standard criteria for the evaluation of histological types of lung cancer compared with other disease types.

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke.

One of the major complications after subarachnoid hemorrhage (SAH) is angiographic vasospasm in the large arteries at the base of the brain. However, a clinical trial of clazosentan demonstrated a 65% relative risk reduction in angiographic vasospasm but no effect on mortality or clinical outcome, raising questions about the role of angiographic vasospasm played in outcome after SAH. The purpose of this study was to determine if reducing or reversing angiographic vasospasm with clazosentan reduced other secondary complications such as microthromboembolism, loss of long-term potentiation (LTP) and neuronal cell death in a rat model of SAH. SAH in rats was created by injection of 300 μl non-heparinized autologous blood into the pre-chiasmatic cistern. Clazosentan, 10mg/kg bolus, or vehicle control was administered 1h after SAH intravenously, followed by a continuous infusion (1mg/kg/h) into the jugular vein using an osmotic pump. Rats treated with clazosentan had less large-artery vasospsam compared to vehicle-treated controls. However, clazosentan did not prevent the formation of microthromboemboli, neuronal cell death and degeneration and loss of LTP, suggesting there is a dissociation between large-artery angiographic vasospasm and other secondary complications of SAH. This result suggests that alleviation of angiographic vasospasm alone may not be sufficient to prevent other secondary complications or that off-target drug effects after systemic administration of clazosentan counteract the beneficial effects on angiographic vasospasm.

About 50% of subarachnoid hemorrhage (SAH) survivors have cognitive or neurobehavioral dysfunction. The mechanisms are not known. This study characterized behavioral deficits in a rat SAH model, and correlated these changes with histological alterations. SAH was induced by injection of 0.3 ml blood into the prechiasmatic cistern. Cognitive and memory changes were investigated in the Morris water maze. Neuronal cell death was evaluated by fluoro-jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Vasospasm was assessed on cross-sections of middle and anterior cerebral arteries. Microthromboemboli were quantified by fibrinogen staining. Escape latency and swimming distance were significantly increased in rats with SAH as compared to controls (P

We studied whether endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled in large cerebral arteries after subarachnoid hemorrhage (SAH) and also whether this causes cerebral vasospasm in a mouse model of anterior circulation SAH. Control animals underwent injection of saline instead of blood ( n=16 SAH and n=16 controls). There was significant vasospasm of the middle cerebral artery 2 days after SAH (lumen radius/wall thickness ratio 4.3±1.3 for SAH, 23.2±2.1 for saline, P

Survivors of aneurysmal subarachnoid hemorrhage (SAH) often suffer from cognitive impairment such as memory loss. However, the underlying mechanisms of these impairments are not known. Long-term potentiation (LTP) of synapses in the hippocampus is generally regarded as a molecular substrate of memory. The purpose of this study was to examine the effect of SAH on LTP in the hippocampal Schaffer collateral (CA3-CA1) pathway in a rat model of SAH. We found SAH caused significant vasospasm of the middle cerebral artery (MCA) compared to saline injected or sham controls (P

A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. A needle was inserted stereotactically into the prechiasmatic cistern and 100 microl autologous arterial blood injected over seconds (n=10). Effects were compared to injection of saline (n=10) or to sham operation (n=7). Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P

The study focused on the distribution of trace elements in the blood samples of leukemia patients. The blood samples of 62 patients of leukemia and their age, gender and demographically matched controls were analyzed for Cu, Ni, Mg, Zn, Fe and Cr by FAAS. The study evidenced higher mean levels for all the trace elements except Zn in leukemia patients than healthy controls. Mg was the major contributor at mean levels and Cr was present at sub-ppm levels in patients. The order for mean trace element levels in patients was: Mg > Fe > Ni > Zn > Cu > Cr, in comparison to healthy controls where the order remained: Mg > Fe > Zn > Cu > Ni > Cr. In patients Ni-Mg was significantly positively correlated while Mg was significantly negatively correlated with Cu. In healthy donors no such significant correlation was observed. The age of donors was found to be significantly positively correlated with Ni depicting an increase in Ni levels with increasing age of patients. Age of patients was significantly negatively correlated with Cu and Cr and positively correlated with Mg. Cluster analysis showed an independent behavior of Mg in patients contrary to healthy donors. Gender based study evidenced different orders of mean levels of selected trace elements in the blood of male and female patients. These orders were also different from the controls. Different clustering behavior of trace elements was observed in male and female patients.

Presently existing screening approaches for lung cancer are not being proving sufficient and sensitive, so a study was conducted to identify disease related biomarker proteins for diagnostic applications. A total of 100 lung cancer patients (88 non-small cell lung cancer and 12 small cell lung cancer) and 50 healthy controls were included in this study. Serum samples of patients and healthy controls were subjected to a series of proteomic approaches and as a result of two dimensional gel electrophoresis, a ∼ 43 kDa protein was found to be differentially expressed compared to healthy controls. Quantitative profiling of two dimensional gels by Dymension software analysis displayed 3.58 fold increased expression of ∼ 43 kDa protein in squamous cell carcinoma and 2.92 fold in case of adenocarcinoma. Mass spectrometric analysis resulted in identification of 8 differentially expressed proteins, out of which human Alpha-1-acid glycoprotein 1 was targeted for further validations. This candidate protein exhibited N-linked glycosylation at five amino acid residues; 33, 56, 72, 93, and 103 with significant score of 0.66, 0.78, 0.78, 0.53 and 0.66, respectively. Sandwich ELISA quantified high serum levels of Alpha-1-acid glycoprotein 1 in squamous cell carcinoma (2.93 g/l ± 1.22) and adenocarcinoma (2.39 g/l ± 1.13) when compared with healthy controls (0.83 g/l ± 0.21). One-way ANOVA analysis predicted highly significant variation of Alpha-1-acid glycoprotein 1, among all the study types (F-value 65.37, p-value 0.000). This study may prove as a non-invasive, cost effective and sensitive scheme for diagnosis of lung cancer, by passing the expensive and painful screening procedures.

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.