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Inflammation is an essential component of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and acute respiratory distress syndrome (ARDS). It is central to lung cancer, the leading cancer in terms of associated mortality that has affected millions of individuals worldwide. Inflammation and pulmonary manifestations are also the major causes of COVID-19 related deaths. Acute hyperinflammation plays an important role in the COVID-19 disease progression and severity, and development of protective immunity against the virus is greatly sought. Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection. The importance of inflammation in pulmonary manifestations, cancer and COVID-19 calls for a closer look at the underlying processes, particularly the associated increase in IL-6 and other cytokines, the dysregulation of immune cells and the coagulation pathway. Towards this end, several reports have identified epigenetic regulation of inflammation at different levels. Expression of several key inflammation-related cytokines, chemokines and other genes is affected by methylation and acetylation while non-coding RNAs, including microRNAs as well as long non-coding RNAs, also affect the overall inflammatory responses. Select miRNAs can regulate inflammation in COVID-19 infection, lung cancer as well as other inflammatory lung diseases, and can serve as epigenetic links that can be therapeutically targeted. Furthermore, epigenetic changes also mediate the environmental factors-induced inflammation. Therefore, a better understanding of epigenetic regulation of inflammation can potentially help develop novel strategies to prevent, diagnose and treat chronic pulmonary diseases, lung cancer and COVID-19.

Aim: To evaluate the application of the principles of Patient and Family-centered Care Methodology: A cross-sectional study was conducted in the Pediatric and Neonatal Intensive care unit of a tertiary care hospital in Punjab, Pakistan. IRB approval was granted, and the study spanned a period from January 2019 to June 2019. A questionnaire was created to survey the pediatric patient's parents. Data analysis was done using SPSS 25. Results: A total of 158 responses were recorded. The majority of the parents felt that patient and family-centered care was not being applied to the admitted patients' management plans in the pediatric and neonatal ICUs. Conclusion: The treatment of patients in the pediatric and neonatal ICUs was not following the principles of patient and family-centered care. Therefore, further studies are required to improve the ease of access, alongside limiting the barriers to the patient and family-centered care in Pakistan. This way, patients can benefit from improved outcomes associated with PFCC. Keywords: Neonatal intensive care unit (NICU), intensive care unit (ICU), pediatric intensive care unit (PICU), patient and family-centered care (PFCC).

Aim: To determine the viral load in the patients admitted in Covid-19 isolation and its correlation with the inflammatory markers and the following clinical outcome. Methodology: A retrospective study was conducted in the Pathology Department of Doctors Hospital and Medical Centre in Lahore, Pakistan from November 2020 to January 2021. IRB approval was granted. A total of 86 patients met the inclusion criteria for the study. Data was analyzed using research tool SPSS 24. Results: Increased serum viral load in SARS-CoV-2 infection showed positive correlation with inflammatory markers IL-6 (P =0.04) and D-dimer (P =0.029). Inflammatory markers LDH, Ferritin, Procalcitonin, D-Dimers and viral load itself (CT) all correlated with higher mortality while IL-6 did not. Conclusion: Serum viral load in patients infected with SARS-CoV-2 correlates with higher mortality rates itself and also raises certain inflammatory markers (IL-6, D-Dimers), which are independently accountable for causing higher mortality as well. Hence, increased inflammatory markers resulted in poor prognosis regardless of high or low viral load. Their correlation with mortality can still serve as prognostic indicators. Keywords: viral load, inflammatory markers, Covid-19, mortality

Pneumonia like the pandemic COVID-19 is a virus disease, first time came into light in December 2019 in the Wuhan city of China. As of today, more than two million deaths from more than 210 countries have been confirmed. This disease has modeled a great threat to human mental health, physical health, and forcefully stuck the routine life with psychosocial consequences globally. The COVID-19 disease is caused by SARS-CoV-2 which leads to acute respiratory distress. The pathogenesis of the disease started from virus entry to the host cell where it controlled the cellular system of the patient directly or indirectly. Population having cardiovascular, immunosuppressive, AIDS, and diabetes-like complications are thought to be very risky for mortality caused by the SARS-CoV-2 virus. The correlation to Noncommunicable diseases like cardiovascular disorders and diabetes has led our attention towards the management of these diseases in the corona outbreak. Thus, this review aimed to better understand the threats modeled by the disease COVID-19 to the cardiovascular system, and the medical community should share their experiences promptly. It is concluded that both published research and real-time experiences shared on social media by world experts will act as a valuable tool and will help to learn more about this disease. Several preventive and therapeutic measures including drug therapy are suggested to manage the disease in comorbidities conditions.

Objective: To find out the effective method of endotracheal intubation among patients of intracranial bleed. Methods: A quasi experimental research was performed at emergency department of Ziauddin University Hospital Karachi. 236 intracranial bleed patients were selected by consecutive sampling, half of them were intubated at upright position (45°) and remaining half at supine position. Patients of musculoskeletal deformities, ischemic stroke and previously intubated were excluded. Success or failure of endotracheal tube was confirmed by measuring oxygen saturation and audible breath sounds on chest. Results: Success rate of endotracheal placement (p-value

The 6-shogaol, is a flavanone type flavonoid that is abundant in citrus fruit and has a wide range of pharmacological effects. The present study attempted to evaluate the antiurolithic effect of 6-shogaol on ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. The efficacy of 6-shogaol 50 mg/kg and 100 mg/kg was studied in EG 0.75% (V/V) and AC 1% (W/V) experimentally induced urolithiasis in rats for 21 days. The weight difference, urine volume, the levels of calcium, phosphate, magnesium, oxalate and uric acid in urine was observed. The blood urea nitrogen, creatinine, uric acid in serum and levels of malondialdehyde (MDA) and glutathione (GSH) were also measured. Histopathological analyses in kidneys were also performed. The rats weights were higher in the 6-shogaol groups than the urolithiasis group. EG caused a significant increase in serum creatinine (p

Background: Mental Health Literacy (MHL) is the ability to recognize mental disorders, along with knowledge of professional help available, effective self-help strategies, skills to give support to others, and knowledge of how to prevent mental disorders. Adequate MHL is linked to better health-seeking behavior and management of mental illness. Aim: To assess the MHL related to depression and anxiety among adolescents of age 15 to 19 years residing in Delhi Methods: A survey was conducted among adolescents in southeast Delhi. MHL was assessed using sex-matched vignettes of Common Mental Disorders (CMDs) like depression and anxiety. MHL was assessed under domains of identifications of disorders, help-seeking behavior, knowledge about prevention, and stigmatizing attitude toward the respective illness. Statistical analysis was done in STATA and percentage of participants with adequate MHL in various domains was calculated, and difference between various groups was examined using chi-square test. Results: A total of 491 adolescents participated (response rate of 87.2%) of whom a 50.3% were girls and 57.8% were 15 to 17 years of age. Only 50 (10.2%) participants identified depression vignette as that of depression and 51 (10.4%) identified vignette of anxiety disorder as the same. No statistically significant gender differential in MHL was seen ( p value = .8). The stigmatizing attitude, assessed by asking a series of questions suggesting stigma toward the particular illness, was observed among almost all participants (depression -99.4%, and anxiety disorders -96.1%). 18.3% and 18.7% of participants reported correct knowledge about the prevention of depression and anxiety respectively. Four hundred and twenty-two (86%) identified the need to seek help for symptoms reported in vignettes. Of these, 234 (55%) preferred parents, and 62 (14.7%) look after friends for any help. Conclusion: Adolescents residing in Delhi reported poor MHL for Common Mental Disorders. High stigma and poor help-seeking behavior was also observed among the participants toward CMDs

Background: For controlling unwilling pregnancy, sustaining gorgeousness and good health, among the elite level female athletes the use of contraceptive pills is quite common. Objective: Oxidative stress in female athletes is understudied. This research study was carried out in order to assess the alteration in metabolic rate of blood urea, bilirubin and oxidative stress induced by Levonorgestrel and Ethinylestradiol (oral contraceptive pills). The outcome of the study will reveal the impact of oral contraceptive pills on the overall health of the females. Methods: User and non-user of oral contraceptive pills were included as participants of the study. Sixty elite level female athletes using Levonorgestrel and Ethinylestradiol were recruited as experimental group and twenty four female (non-users) as a control group were taken as sample of the study. Blood sample (5ml) was taken from all the subjects. Blood urea and bilirubin metabolism were estimated through kidney functional test and for the measurement of oxidative stress FRAP assay was used. The data obtained through kidney functional tests and FRAP assay were processed through statistical package for social sciences (SPSS, Version 23.0) Results: A significant difference was found between control and experimental subjects in FRAP values because (t (82) = 3.236, P

Background: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by multiple psychological and physiological impairments in young children. According to the recent reports, 1 out of every 58 newly-born children is suffering from autism. The aetiology of the disorder is complex and poorly understood, hindering the adaptation of targeted and effective therapies. There are no well- established diagnostic biomarkers for autism. Hence the analysis of symptoms by the pediatricians plays a critical role in the early intervention. Methods: In the present report, we have emphasized 24 behavioral, psychological and clinical symptoms of autism. Results: Impaired social interaction, restrictive and narrow interests, anxiety, depression; aggressive, repetitive, rigid and self-injurious behavior, lack of consistency, short attention span, fear, shyness and phobias, hypersensitivity and rapid mood alterations, high level of food and toy selectivity; inability to establish friendships or follow the instructions; fascination by round spinning objects and eating non-food materials are common psychological characteristics of autism. Speech or hearing impairments, poor cognitive function, gastrointestinal problems, weak immunity, disturbed sleep and circadian rhythms, weak motor neuromuscular interaction, lower level of serotonin and neurotransmitters, headache and body pain are common physiological symptoms. Conclusion: A variable qualitative and quantitative impact of this wide range of symptoms is perceived in each autistic individual, making him/her distinct, incomparable and exceptional. Selection and application of highly personalized medical and psychological therapies are therefore recommended for the management and treatment of autism.

Takotsubo Cardiomyopathy (TC) is a syndrome characterized by reversible left ventricular dysfunction in the presence of possible emotional or physical triggers but without evidence of obstructive coronary artery disease. It has become increasingly reported worldwide and is associated with significant morbidity and mortality. TC may present with an array of electrocardiographic (ECG) findings. These ECG findings, if accurately interpreted, can play an important role in the diagnosis and risk stratification of this syndrome. In the last three decades since the disease was first described, multiple diagnostic criteria have been established. The key diagnostic tools for TC include clinical symptomatology, cardiac biomarkers, non-invasive cardiac imaging, and coronary angiography. The ECG findings in TC can be variable, however, some ECG scores have been proposed in association with TC with reasonably good diagnostic sensitivity and specificity. This article aims to provide a succinct review of important electrocardiographic findings associated with TC and its impact on clinical outcomes.

A chronic wound in diabetic patients is a major public health concern with socioeconomic and clinical manifestations. The underlying medical condition of diabetic patients deteriorates the wound through physiological, metabolic, molecular, and cellular pathologies. Consequently, a wound enters a vicious pathological inflammatory cycle. Many therapeutic approaches are in practice to manage diabetic wounds hence ensuring the regeneration process. Polymer-based biomaterials have come up with high therapeutic promises. Many efforts have been devoted, over the years, to build an effective wound healing material using polymers. The electrospinning technique, although not new, has turned out to be one of the most effective strategies in building wound healing biomaterials due to the special structural advantages of electrospun nanofibers over the other formulations. In this review, careful integration of all electrospinning approaches has been presented which will not only give an insight into the current updates but also be helpful in the development of new therapeutic material considering pathophysiological conditions of a diabetic wound.

Aims: The aim of present investigation was to evaluate the traditional claim of Ficus retusa as an anti-diarrheal and anti-spasmodic agent using different pharmacological models. Background: Diarrhea is considered as major cause of mortality, especially in children and aged persons. Because of diarrhoea, 17% of admitted children get die. In order to treat the diarrhea, natural drugs may be useful. Objective: In order to prove the traditional claim of Ficus retusa, present work was undertaken with objective to prove antidiarrheal and antispasmodic activity. Methods: The anti-diarrhoeal activity was evaluated by magnesium sulphate induced diarrhea and 5-hydroxy tryptamine(5HT) induced diarrhea. Further, the exact were subjected to gastrointestinal motility test using standard procedure. Conclusion: The response towards bioactivity was dose dependent. It was concluded that 400mg/kg bw of ethanolic extract is most potent in antidiarrhoeal and antispasmodic activity.

Objective: 1.To determine the pattern of resistance of salmonella Typhi strains to multiple antibiotics in Islamabad and adjoining areas. 2.Suggestions regarding the regular upgradation of antibiogram according to the most susceptible strains. Method: Cross sectional study conducted for duration of one year ,recruited those patients whose blood cultures were found positive for Salmonella Typhi at Islamabad Diagnostic Center. We analyzed 100 samples and Positive culture were then assessed for sensitivity by using various antibiotics and pattern of resistance was analyzed. Results: Majority of positive patients were male and children. Sensitivity to the conventional antibiotics was found to be more in children. In all the positive isolates, 89% were sensitive to the first line treatment options.Among them, 96.6%were showing sensitivity to third generation cephalosporin. However, a few cases were having extensively drug resistant patterns (XDR). Conclusion: Despite the fact that extensively drug resistantstrains are emerging and indicating an alarming situation,its found out that more than 80% of patients are responding to the conventional therapy,making it a dire need for upgradation of antibiograms, so that the side effects of second line and advanced antibiotic can be avoided, mostly in paediatric population.

In the present work, a simple, rapid, reliable and accessible high-performance thin-layer chromatography (HPTLC) technique has been established for the concurrent quantification of plumbagin. The well-known medicinal plant, Plumbago zeylanica L., has been traditionally used to treat a variety of ailments in India and other countries. Chromatographic separation was conceded on pre-coated silica gel plates F254. The apposite mobile phase toluene‒acetic acid (9.0:0.5, V/V) was developed to expand the plates which separated components according to the marker compounds. Densitometric scanning was performed by CAMAG Scanner V and measured at wavelength 272 nm. The marker compounds were practically resolved with RF 0.44 ± 0.02 for plumbagin. Further, the antioxidant potential of the methanolic extract of P. zeylanica was also assessed with 1,1-diphenyl-2-picrylhydrazyl (DPPH) by using an ultraviolet (UV) spectrophotometer. The percentage inhibition of free radical was found to be 76.5%. The developed HPTLC method was validated for accuracy, linearity, precision and specificity. The extract has revealed considerable antioxidant activity. The reported existing phenolic and flavonoids compounds are responsible for the antioxidant activity of the plant extract as reported in the literature.

Background: The cerebellum principally the motor organ is involved in the regulation of muscular tone and skilled motor movements. The cerebellar histology consists of three layers and the middle is the Purkinje cell layer which consists of pyramidal shaped purkinje cells. Clinical research shows scanty literature on the beneficial effects of Methylcobalamin on Purkinje cells layer. Aim: Our aim was to bring to light the need for prescribing Methylcobalamin in the masses and patient suffering from motor incoordination. Method: 15 animals were given Methylcobalamin and the changes in the thickness of Purkinje cell layer ware recorded at twelve weeks Result: The morphometric analysis showed restored thickness of Purkinje cell layer Conclusion: The recorded data of the regenerated purinje cell layer thickness proved that the use of Methylcobalamin is mandatory as protective drug in damaged neuronal tissue. Key words: Proliferative, Cytostatic, Purkine cell layer

Objective Since the declaration of the coronavirus 2019 (COVID-19) outbreak as pandemic, there are reports on the increased prevalence of physical symptoms observed in the general population. We investigated the association between psychological outcomes and physical symptoms among healthcare workers. Methods Healthcare workers from 5 major hospitals, involved in the care for COVID-19 patients, in Singapore and India were invited to participate in a study by performing a self-administered questionnaire within the period of February 19 to April 17, 2020. Healthcare workers included doctors, nurses, allied healthcare workers, administrators, clerical staff and maintenance workers. This questionnaire collected information on demographics, medical history, symptom prevalence in the past month, Depression Anxiety Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) instrument. The prevalence of physical symptoms displayed by healthcare workers and the associations between physical symptoms and psychological outcomes of depression, anxiety, stress, and post-traumatic stress disorder (PTSD) were evaluated. Results Out of the 906 healthcare workers who participated in the survey, 48 (5.3%) screened positive for moderate to very-severe depression, 79 (8.7%) for moderate to extremely-severe anxiety, 20 (2.2%) for moderate to extremely-severe stress, and 34 (3.8%) for moderate to severe levels of psychological distress. The commonest reported symptom was headache (32.3%), with a large number of participants (33.4%) reporting more than four symptoms. Participants who had experienced symptoms in the preceding month were more likely to be older, have pre-existing comorbidities and a positive screen for depression, anxiety, stress, and PTSD. After adjusting for age, gender and comorbidities, it was found that depression (OR 2.79, 95% CI 1.54–5.07, p = 0.001), anxiety (OR 2.18, 95% CI 1.36–3.48, p = 0.001), stress (OR 3.06, 95% CI 1.27–7.41, p = 0.13), and PTSD (OR 2.20, 95% CI 1.12–4.35, p = 0.023) remained significantly associated with the presence of physical symptoms experienced in the preceding month. Linear regression revealed that the presence of physical symptoms was associated with higher mean scores in the IES-R, DASS Anxiety, Stress and Depression subscales. Conclusions Our study demonstrates a significant association between the prevalence of physical symptoms and psychological outcomes among healthcare workers during the COVID-19 outbreak. We postulate that this association may be bi-directional, and that timely psychological interventions for healthcare workers with physical symptoms should be considered once an infection has been excluded.

BACKGROUND & OBJECTIVE: primary Hepatitis C is a serious public health problem and is the cause of liver cirrhosis, hepatocellular carcinoma (HCC), and numerous end-stage liver disease manifestations. The management of hepatitis C is to preclude liver cirrhosis, lessen the risk of hepatocellular carcinoma or hepatoma, and curing the extra hepatic diseases. Initially, interferon was the cornerstone for treating hepatitis C, but due to its cumbersome complications, route of administration, and limited treatment access, many patients showed noncompliance. New therapies for chronic hepatitis C have been introduced based on direct antiviral effects. Several genotypes of hepatitis C have been discovered and they are responsive to different antiviral therapies. Our objective was to assess the genotypic distribution of HCV in our local setup and their pattern of response to different combination of anti-viral therapies by assessing the sustained viral response (SVR) after 12 weeks post-treatment. To determine the most prevalent genotype of hepatics C virus in our population and pattern of the response of multiple genotypes to different antiviral regimens. METHODOLOGY: It is a cross-sectional study conducted for duration of six months and recruited those patients whose polymerase chain reaction (PCR) was found positive for hepatitis C virus at Islamabad Diagnostic Center. We analyzed 100 patients, both children and adults. Patients were assessed for different genotypes and then different combinations of antiviral treatments were administered. Their clinical data, hematological parameters and viral load before and after treatment were also analyzed. RESULTS: In a total of 100 positive hepatitis C virus-infected patients, 55% were females and 45% males. The frequencies of genotypes observed were 91 %, 06%, and 03% of genotype 3, 1a, and 1b respectively. 51 out of 91 patients with type 3 genotype, who were on antiviral therapy of sofosbuvir and ribavirin, all of them achieved SVR. 30 out of 91 patients with type 3 genotype were treated with sofosbuvir alone, the percentage of failure to achieve SVR in them was 6.7%. Treatment failure percentage of 10% was observed when a combination of Interferon (INF) alpha and ribavirin was used in type 3 genotype. Remaining six patients with type 1a and three patients of type 1b genotype achieved SVR with different regimens used. CONCLUSION: Although the increased load of HCV in our setup is an alarming situation the prevalence of type 3 genotype is a blessing in disguise. The success of sustained viral response after various combinations of direct antiviral therapy and interferon-free treatment is hope for the ultimate cure of the disease and avoidance of debilitating side effects related to interferon.

The threat from deliberate or accidental exposure to halogen gases is increasing as is their industrial application and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br(2)) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br(2) and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury as indicated by BALF protein content and free bromostearic acid levels correlated with plasma cTNI levels. Thus, BFAs and cardiac injury biomarkers can identify Br(2) exposure and predict the severity of organ damage.

Diesel soot particulate is one of the main sources of air pollution, which should be eliminated effectively to minimize the carcinogenic and lethal effect of air. Herein, an effort has been made to synthesize Au–CoFe2O4 nanocomposite by a facile route and use as an effective catalyst for soot oxidation. The physicochemical properties of Au–CoFe2O4 were carried out through SEM, EDX mapping, HRTEM, XRD, XPS, hydrogen temperature-programmed reduction (H2-TPR), and NO temperature-programmed oxidation (NO-TPO). Au–CoFe2O4 catalyst showed a remarkable catalytic property for soot oxidation in both NO + O2 and O2 owing to the formation of oxygenated species that enhanced the oxidizing properties of the catalyst. The CoFe2O4 composite showed a remarkable and stable catalytic property for soot oxidation, and low T50 (50% soot conversion) 411 °C value has been achieved in the presence of O2. While as we introduced gold (Au) to form Au–CoFe2O4 then its catalytic performance for soot oxidation was found to be tremendously increased to T50 341 °C owing to the formation of surface-oxygenated species that enhanced the oxidizing properties of the catalyst surface. The durability performance of the catalyst including reusability, this catalyst showed even better soot oxidation activity after sulfur and hydrothermal aging. Owing to the tremendous soot oxidation activity, this catalyst can be used as an environmentally friendly and efficient soot oxidizer for the removal of soot.

BackgroundThe Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak.MethodsKeeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection.ResultsEvolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2.ConclusionsThe anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.

Exposure of rats to 2-chloroethyl ethyl sulfide (CEES), an analog of sulfur mustard, can cause acute lung injury (ALI), resulting in increased inflammation and coagulation and altered levels of plasma microRNAs (miRNAs). Rats were exposed to aerosolized CEES and euthanized 12 h later for collection of tissue and plasma. Profiling of miRNAs in plasma, using a TaqMan-based RT-PCR array, revealed 14 differentially expressed miRNAs. Target gene prediction and pathway analysis revealed miRNA-mediated regulation of organismal injury, inflammation, and respiratory diseases. miR-140-5p, a marker of ALI, was downregulated in the plasma, lung, liver, and kidney of CEES-exposed rats, with a concomitant increase in the expression of the inflammation markers IL-6 and IL-1α and the coagulation marker tissue factor (F3). Exposure of rat airway epithelial cells (RL-65) to CEES (0.5 mM) caused cell death and a decrease in miR-140-5p both in cells and media supernatant. This was accompanied by an increase in cellular mRNA levels of IL-6, IL-1α, and F3, as well as FGF9 and EGR2, putative targets of miR-140. Knockdown of miR-140 by specific oligos in RL-65 cells mimicked the in vivo CEES-mediated effects, leading to significantly increased mRNA levels of IL-6, IL-1α, F3, FGF9, and EGR2. Our study identifies miR-140-5p as a mediator of CEES-induced ALI, which could potentially be targeted for therapy.

Celiac disease (CD) is a gastrointestinal disorder whose genetic basis is not fully understood. Therefore, we studied a Saudi family with two CD affected siblings to discover the causal genetic defect. Through whole exome sequencing (WES), we identified that both siblings have inherited an extremely rare and deleterious CPED1 genetic variant (c.241 A > G; p.Thr81Ala) segregating as autosomal recessive mutation, suggesting its putative causal role in the CD. Saudi population specific minor allele frequency (MAF) analysis has confirmed its extremely rare prevalence in homozygous condition (MAF is 0.0004). The Sanger sequencing analysis confirmed the absence of this homozygous variant in 100 sporadic Saudi CD cases. Genotype-Tissue Expression (GTEx) data has revealed that CPED1 is abundantly expressed in gastrointestinal mucosa. By using a combination of systems biology approaches like protein 3D modeling, stability analysis and nucleotide sequence conservation analysis, we have further established that this variant is deleterious to the structural and functional aspects of CPED1 protein. To the best of our knowledge, this variant has not been previously reported in CD or any other gastrointestinal disease. The cell culture and animal model studies could provide further insight into the exact role of CPED1 p.Thr81Ala variant in the pathophysiology of CD. In conclusion, by using WES and systems biology analysis, present study for the first-time reports CPED1 as a potential causative gene for CD in a Saudi family with potential implications to both disease diagnosis and genetic counseling.

Objectives: To know about the Neurosurgical burden of Hydrocephalus in a tertiary care hospital, in developing world. Study Design: Cross sectional study. Setting: Department of Neurosurgery, MTI/LRH Peshawar. Period: September 2015 to August 2016. Material & Methods: The age, gender, indication for surgery, type of surgery and mode of surgery i.e. whether as elective or emergency, was recorded on a proforma. All patients undergoing surgery primarily for hydrocephalus due to any cause were included in the study. Patients undergoing surgery for indications other than hydrocephalus as well as patients primarily explored for other etiologies and intervened for hydrocephalus in the midst of procedure were excluded from the study. Results: During the study period a total of 2844 patients were operated and amongst them were 437 (15.34%) cases operated for hydrocephalus. Of them were 242 males and 195 females, and the male to female ratio was 1.24. The age range was one month to 68 years and the mean age was 5±4.8 years. There were 250 new shunts and 69 revisions and 13 removal procedures, 70(2.4%) endoscopic hydrocephalus related procedures, 28 external ventricular drains and 7 lumboperitoneal shunts. 189 cases were done on elective list while 248 as emergency. Conclusion: Every 3rd case done on emergency list and every 10th case done on elective list was related to hydrocephalus and accounted for 16% of all the cases done in the neurosurgery.

Sulfur mustard (SM) is a highly toxic war chemical that causes significant morbidity and mortality and lacks any effective therapy. Rats exposed to aerosolized CEES (2-chloroethyl ethyl sulfide; 10% in ethanol), an analog of SM, developed acute respiratory distress syndrome (ARDS), which is characterized by increased inflammation, hypoxemia and impaired gas exchange. We observed elevated levels of extracellular nucleic acids (eNA) in the bronchoalveolar lavage fluid (BALF) of CEES-exposed animals. eNA can induce inflammation, coagulation and barrier dysfunction. Treatment with hexadimethrine bromide (HDMBr; 10 mg/kg), an eNA neutralizing agent, 2 h post-exposure, reduced lung injury, inhibited disruption of alveolar–capillary barrier, improved blood oxygenation (PaO2/FiO2 ratio), thus reversing ARDS symptoms. HDMBr treatment also reduced lung inflammation in the CEES-exposed animals by decreasing IL-6, IL-1A, CXCL-1 and CCL-2 mRNA levels in lung tissues and HMGB1 protein in BALF. Furthermore, HDMBr treatment also reduced levels of lung tissue factor and plasminogen activator inhibitor-1 indicating reduction in clot formation and increased fibrinolysis. Fibrin was reduced in BALF of the HDMBr-treated animals. This was further confirmed by histology that revealed diminished airway fibrin, epithelial sloughing and hyaline membrane in the lungs of HDMBr-treated animals. HDMBr completely rescued the CEES-associated mortality 12 h post-exposure when the survival rate in CEES-only group was just 50%. Experimental eNA treatment of cells caused increased inflammation that was reversed by HDMBr. These results demonstrate a role of eNA in the pathogenesis of CEES/SM-induced injury and that its neutralization can serve as a potential therapeutic approach in treating SM toxicity.

Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50 mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50 mg/kg p.o., Group 4 as a STZ+UA group orally at 50 mg/kg, Group 5 as a STZ+CREE (25 mg/kg p.o.)+UA (25 mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1 mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P<0.001) reduced to 98.35±2.45 mg/dl in comparison with that in Group 2 (321.75±5.46 mg/dl). The level of plasma insulin in Group 5 increased (13.65±0.10 μU/ml) significantly (P<0.01) as compared with that in Group 2 (05.93±0.31 μU/ml). In Group 5, the level of glycogen in liver was significantly (P<0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P<0.01; P<0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.

Background/Purpose We assessed commonly reported patient- and circuit-related adverse events involving extracorporeal membrane oxygenation (ECMO) devices by analyzing post-marketing surveillance data from the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database. ECMO is a rescue therapy for critically ill patients requiring oxygenation and cardiopulmonary support. Key configurations include veno-venous (VV) ECMO for respiratory support and veno-arterial (VA) ECMO for cardio-respiratory support. Robust data on the most commonly reported complications associated with ECMO therapy are limited. Methods/Materials The MAUDE database was queried from January 1, 2009, through March 31, 2019, yielding 93 reports. After excluding duplicate reports, 82 reports were included in the final analysis. Results Percentages represent the proportion of total submitted MAUDE reports on ECMO. Of the reported cases, 24 were VV-ECMO, 8 were VA-ECMO, and the remainder were unspecified. The most commonly reported patient-related adverse events included hemodynamic decompensation of patients (12.2%), death (12.2%), atrial perforation (7.3%), and bleeding (7.3%). The most commonly reported failure modes were in the following circuit components: mechanical pump (19.5%, mostly due to technical failure or clots), membrane oxygenator (19.5%, mostly due to tear in the membrane or temperature probe), and access cannulae (18.3%, mostly due to structural damage). Conclusions Analysis of the MAUDE database demonstrates that in real-world practice, ECMO devices are associated with important complications. With broadened global utilization of ECMO devices, standard complication and failure reporting policies may improve patient selection, operator proficiency, and existing device technology. Summary An analysis of the Food and Drug Administration's Manufacturer and User Facility Device Experience database demonstrates that in real-world practice, extracorporeal membrane oxygenation devices are associated with serious complications. The most commonly reported patient-related adverse events were hemodynamic decompensation of patients and death, and the most commonly reported failure modes were in the device's mechanical pump and membrane oxygenator.

Background Comorbid chronic obstructive pulmonary disease (COPD) increases morbidity and mortality among aortic valve replacement patients undergoing conventional surgery. The impact of COPD in patients undergoing less invasive transcatheter aortic valve insertion (TAVI) is unclear. Hypothesis This study evaluates the in‐hospital outcomes of TAVI in patients with and without COPD. Methods This population‐based, retrospective study of 8466 TAVI patients (29.87% with COPD) evaluates the effects of COPD on short‐term clinical outcomes (in‐hospital mortality, length of hospital stay, and postoperative complications) using data from the National Inpatient Sample database from 2011 to 2014. Logistic regression analysis was used to determine factors associated with in‐hospital mortality and postoperative complications. Linear regression analysis was used to identify factors associated with length of hospital stay. Results COPD is significantly associated with increased risk of respiratory complications and pneumonia after TAVI (aOR = 1.43, 95% CI: 1.24‐1.64; P

The development of resistance against antibiotics used to treat bacterial infections along with the prevalence of medication residues presents significant public health problems globally. Antibiotic-resistant germs result in infections that are difficult or impossible to treat. Decreasing antibiotic effectiveness calls for rapid development of alternative antimicrobials. In this respect, nanoparticles (NPs) of copper oxide (CuO) manifest a latent and flexible inorganic nanostructure with noteworthy antimicrobial impact. Green synthesis of CuO NPs was performed in the current study, which was then doped with varying amounts of ginger (Zingiber officinale, ZO) and garlic (Allium sativum, AS) extracts. In low and high doses, the synthesized compound was used to measure the antimicrobial effectiveness against pathogenic Escherichia coli. The present research successfully demonstrated a renewable, eco-friendly synthesis technique with natural materials that is equally applicable to other green metal oxide NPs.

OBJECTIVE: To determine the frequency of sensorineural hearing loss in chronic suppurative otitis media. MATERIAL AND METHODS: A cross sectional descriptive study was done at department of ENT-B, Hayatabad Medical Complex (HMC), Peshawar, from March 2016 to September 2016. In this study a total of 174 patients were observed by using 95% confidence interval and 5% margin of error with expected frequency of sensorineural hearing loss 13% among cases with chronic suppurative otitis media with the help of WHO formula for sample size determination. More over consecutive (non-probability) sampling technique was used for sample collection. RESULTS: In this study mean age was 26 years with standard deviation ± 11.62. Forty five percent patients were male while 55% patients were female. More over the incidence of sensorineural hearing loss was found to be 18% in patients with chronic suppurative otitis media. CONCLUSION: The incidence of sensorineural hearing loss was found to be 18% in patients with chronic suppurative otitis media. KEY WORDS: Bacteriology, antibiotic sensitivity, chronic suppurative otitis media, sensory neural hearing loss

SummaryThe recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs1–4, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits5. Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D-α-tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and β-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water-soluble derivatives of α-tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV-2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp6. In summary, we conclude that solubilizing modifications to α-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection7–9.

Background: Pulmonary arterial hypertension (PAH) is a progressive proliferative vasculopathy associated with mechanical and electrical changes, culminating in increased vascular resistance, right ventricular (RV) failure, and death. With a main focus on invasive tools, there has been an underutilization of echocardiography, electrocardiography, and biomarkers to non-invasively assess the changes in myocardial and pulmonary vascular structure and function during the course of PAH.Methods: A SU5416-hypoxia rat model was used for inducing PAH. Biventricular functions were measured using transthoracic two-dimensional (2D) echocardiography/Doppler (echo/Doppler) at disease onset (0 week), during progression (3 weeks), and establishment (5 weeks). Similarly, electrocardiography was performed at 0, 3, and 5 weeks. Invasive hemodynamic measurements and markers of cardiac injury in plasma were assessed at 0, 3, and 5 weeks.Results: Increased RV systolic pressure (RVSP) and rate of isovolumic pressure rise and decline were observed at 0, 3, and 5 weeks in PAH animals. EKG showed a steady increase in QT-interval with progression of PAH, whereas P-wave height and RS width were increased only during the initial stages of PAH progression. Echocardiographic markers of PAH progression and severity were also identified. Three echocardiographic patterns were observed: a steady pattern (0–5 weeks) in which echo parameter changed progressively with severity [inferior vena cava (IVC) expiratory diameter and pulmonary artery acceleration time (PAAT)], an early pattern (0–3 weeks) where there is an early change in parameters [RV fractional area change (RV-FAC), transmitral flow, left ventricle (LV) output, estimated mean PA pressure, RV performance index, and LV systolic eccentricity index], and a late pattern (3–5 weeks) in which there is only a late rise at advanced stages of PAH (LV diastolic eccentricity index). RVSP correlated with PAAT, PAAT/PA ejection times, IVC diameters, RV-FAC, tricuspid systolic excursion, LV systolic eccentricity and output, and transmitral flow. Plasma myosin light chain (Myl-3) and cardiac troponin I (cTnI) increased progressively across the three time points. Cardiac troponin T (cTnT) and fatty acid-binding protein-3 (FABP-3) were significantly elevated only at the 5-week time point.Conclusion: Distinct electrocardiographic and echocardiographic patterns along with plasma biomarkers were identified as useful non-invasive tools for monitoring PAH progression.

Schizophrenia is a chronic, heterogeneous neurodevelopmental disorder that has complex symptoms and uncertain etiology. Mounting evidence indicates the involvement of genetics and epigenetic disturbances, alteration in gut microbiome, immune system abnormalities, and environmental influence in the disease, but a single root cause and mechanism involved has yet to be conclusively determined. Consequently, the identification of diagnostic markers and the development of psychotic drugs for the treatment of schizophrenia faces a high failure rate. This article surveys the etiology of schizophrenia with a particular focus on gut microbiota regulation and the microbial signaling system that correlates with the brain through the vagus nerve, enteric nervous system, immune system, and production of postbiotics. Gut microbially produced molecules may lay the groundwork for further investigations into the role of gut microbiota dysbiosis and the pathophysiology of schizophrenia. Current treatment of schizophrenia is limited to psychotherapy and antipsychotic drugs that have significant side effects. Therefore, alternative therapeutic options merit exploration. The use of psychobiotics alone or in combination with antipsychotics may promote the development of novel therapeutic strategies. In view of the individual gut microbiome structure and personalized response to antipsychotic drugs, a tailored and targeted manipulation of gut microbial diversity naturally by novel prebiotics (non-digestible fiber) may be a successful alternative therapeutic for the treatment of schizophrenia patients.

The development of a durable and efficient composite material that could perform a long-life antibacterial activity and radical scavenging ability is highly needed. In this paper, selenium nanostructures of different morphologies were synthesized by a wet chemical method under mild experimental setup. Silver nanoparticles were doped on the surface of these nanostructures and successfully characterized by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, and high-resolution transmission electron microscopy. The potential applications of the designed composite were investigated in multiple disciplines including antibacterial, antioxidant, and photocatalytic activities. The selenium silver (Se–Ag) nanocomposite was employed as an antibacterial agent against a Gram-positive bacterium and a Gram-negative bacterium, and our findings disclosed that the designed composite is an excellent material in inhibiting the challenged bacterial strains. The Se–Ag composite has shown excellent activity with 30-mm inhibition zone at 2 mg/ml concentration, and maintains significant antibacterial efficacy for 72 h, indicating its sustainable performance for a long-life period. Furthermore, Se–Ag nanocomposite also exhibited a significant radical scavenging property against 2,2-diphenyl-1-picrylhydrazyl free radical and an enhanced photocatalytic activity (90–95%) with complete dye decolorization in 70 min. The superior antibacterial activity (zone of inhibition 30 mm), photocatalytic (95%) and antioxidant performance (78%) of the nanocomposite are due to the combined antibacterial (17 mm), photocatalytic (~ 30%) and antioxidant potentials (15%) of the Ag and Se (16 mm, 40%, 25%), respectively.

Takotsubo syndrome is a wide spectrum disease with a dramatic clinical presentation mimicking acute coronary syndrome albeit without obstructive coronary disease and typically manifests in the backdrop of intense emotional or physical trigger. Pathophysiology is incompletely understood with multifactorial mechanistic pathways circling around a heart-brain-endocrine axis. Several anatomic and phenotypic variants exist with varied clinical manifestations. The aftermath of Takotsubo syndrome is not always benign and both short- and long-term complications can occur which may impact its prognosis. Several gaps in knowledge exist providing an impetus for tremendous future research opportunities.

Foot and Mouth disease (FMD) is economically devastating, highly contagious transboundry viral disease of livestock with 100% morbidity, rapid spread and severe production losses in animals. The FMDV has seven different serotypes. There is no vaccine that can protect animals from all serotypes. Hence, it is need of the day to develop a vaccine that protects animals from hetrologous challenge. In this study, we used immunoinformatics approach to find T and B-cell epitopes that will help to construct a universal vaccine for FMDV. For this purpose, first we constructed a consensus sequence for four structural proteins (VP1, VP2, VP3 and VP4) of aphthovirus for seven serotypes (A, O, C, Asia1, SAT1, SAT2 and SAT3). Various computational tools were used to perform multiple sequence alignment to identify the conserved regions, generation of consensus sequence through conserved regions, structures prediction and finally prediction of B and T cell epitopes. We predicted 5 B cell and 18 T cell epitopes. Finally a GPGPG spacer was used to join these epitopes to decrease binding affinity around the core binding regions. Hence, our study identified the epitopes which can be used to develop cross protective vaccines against all the fatal strains of Aphthovirus which can easily protect all the serotypes. Though, successful In vivo and In vitro studies are required to determine the genuine strength of our predicted epitopes against the fatal strains of Aphthovirus.

Introduction Musculoskeletal pain is common among Physical therapy students due to prolonged study hours and clinical practice. The objective of current study was to determine the prevalence of upper back pain among physical therapy students and its association with demographic information, length of study hours and use of cell Phones. Methods This cross sectional survey was conducted in Peshawar, Pakistan from November 2017 to March 2018. 232 students from different physical therapy institutes were included in the study through consecutive sampling. Self-administered questionnaire was used as the study conducting tool having questions regarding demographic information, Body mass index (BMI) study hours, use of cell phone and upper back pain. Results The Prevalence of upper back pain among DPT students was 44.8% (n=104) in which 33(31.7%) male students and 71(68.3%) female students had upper back pain. There was significant association between female gender and upper back pain (p-value Conclusion The frequency of upper back pain was high among physical therapy students. Female gender was highly associated with upper back pain. There was no significant association of upper back pain with BMI, study hours and use of cell phones.

Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br2 and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats. Br2-induced cardiac damage was demonstrated by acute (3–24 h) increases in circulating troponin I, heart-type fatty acid-binding protein, and NH2-terminal pro-brain natriuretic peptide. Transmission electron microscopy demonstrated acute (3–24 h) cardiac contraction band necrosis, disruption of z-disks, and mitochondrial swelling and disorganization. Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and LV tissue had increased levels of brominated fatty acids. 2-Bromohexadecanal (Br-HDA) injected into the LV cavity of a normal rat caused acute LV enlargement with extensive disruption of the sarcomeric architecture and mitochondrial damage. There was extensive infiltration of neutrophils and increased myeloperoxidase levels in the hearts of Br2- or Br2 reactant-exposed rats. Increased bromination of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased Ca2+-sensitive LV calpain activity. The calpain-specific inhibitor MDL28170 administered within 1 h after exposure significantly decreased calpain activity and acute mortality. Bromine inhalation and formation of reactive brominated species caused acute cardiac injury and myocardial damage that can lead to heart failure. NEW & NOTEWORTHY The present study defines left ventricular systolic and diastolic dysfunction due to cardiac injury after bromine (Br2) inhalation. A calpain-dependent mechanism was identified as a potential mediator of cardiac ultrastructure damage. This study not only highlights the importance of monitoring acute cardiac symptoms in victims of Br2 exposure but also defines calpains as a potential target to treat Br2-induced toxicity.

Objective: To determine the frequency and associated factors of knee and low back pain among adults with pes planus. Methods: This cross-sectional study was conducted in Hayatabad Medical Complex Peshawar, Pakistan from May 2017 to November 2017. Two hundred diagnosed Pes Planus patients were included. Questionnaire was used to collect data regarding demographic information, knee and low back pain, foot wear and severity of pes planus. Results: Out of total 200 patients, mean age of the patients was 29.14±7.69 years. Knee pain was observed in 123 (61.5%) participants, back pain in 110 (55%) whereas both knee and back pain was observed in 83 (41.5%) patients. Knee pain was significantly associated with age (p-value 0.001), gender (p-value 0.032), BMI (p-value 0.006) and occupation. Back pain was significantly associated with age (p-value 0012), gender (p-value

Despite the high morbidity and mortality among patients with extensive cutaneous burns in the intensive care unit due to the development of acute respiratory distress syndrome, effective therapeutics remain to be determined. This is primarily because the mechanisms leading to acute lung injury (ALI) in these patients remain unknown. We test the hypothesis that cutaneous chemical burns promote lung injury due to systemic activation of neutrophils, in particular, toxicity mediated by the deployment of neutrophil extracellular traps (NETs). We also demonstrate the potential benefit of a peptidyl arginine deiminase 4 (PAD4) inhibitor to prevent NETosis and to preserve microvascular endothelial barrier function, thus reducing the severity of ALI in mice. Our data demonstrated that phenylarsine oxide (PAO) treatment of neutrophils caused increased intracellular Ca2+-associated PAD4 activity. A dermal chemical burn by lewisite or PAO resulted in PAD4 activation, NETosis, and ALI. NETs disrupted the barrier function of endothelial cells in human lung microvascular endothelial cell spheroids. Citrullinated histone 3 alone caused ALI in mice. Pharmacologic or genetic abrogation of PAD4 inhibited lung injury following cutaneous chemical burns. Cutaneous burns by lewisite and PAO caused ALI by PAD4-mediated NETosis. PAD4 inhibitors may have potential as countermeasures to suppress detrimental lung injury after chemical burns.

Transposable elements (TEs), also known as jumping genes, are widely spread in the genomes of insects and play a considerable role in genomic evolution. Mariner/DD34D family belongs to class II transposable elements which is widely spread in the genomes of insects and have considerable role in genomic evolution. Mariner like elements (MLEs) were searched in the genomes of seven species of Rhus gall aphids belonging to six genera. In total, 121 MLEs were detected in the genomes of the seven investigated species of Rhus gall aphids, which showed a wide distribution in both close and distant related species. The sequences of MLEs ranged from 1 to 1.4 kb in length and the structural analysis of the MLEs showed that only five copies were potentially active with intact open reading frame (ORF) and terminal inverted repeats (TIRs). Phylogenetic analysis showed that all the 121 MLE sequences belonged to four subfamilies, i.e., Mauritiana, Drosophila, Vertumana and Irritans, among which Drosophila and Vertumana subfamilies were reported in aphids for the first time. Our present report revealed the diversity and distribution of MLEs in Rhus gall aphid genomes and expanded our understandings on the characterization of transposable elements in aphid genomes, which might be useful as genetic markers and tools and would play an important role in genomic evolution and adaptation of aphids.

Rapid ramp up of immune responses against SARS-CoV-2 during pandemic enables adequate prevention and treatment for COVID-19. Estimating levels of SARS-CoV-2 spike protein antibodies post vaccination is crucial for designing mass-vaccination strategies. The aim of this study was to evaluate effectiveness of Sputnik V first dose in Pakistan. A cross-sectional study of 2000 participants was conducted for examining Gam-COVID-Vac or Sputnik V first dose effects at 21st days post administration at Islamabad Diagnostic Center, Islamabad, Pakistan. From 100 real-time PCR negative (SARS-CoV-2 RNA) individuals, samples were collected and analyzed for antibodies to the SARS-CoV-2 spike protein using Electro-chemiluminescence immunoassay (ECLIA) (Elecsys # 09289267190 Roche, USA). 85% of the participants showed strong positive results with SARS-CoV-2 spike protein antibodies > 1.5 AU/ml. The individuals with antibody titer > 250 AU/ml were 34.9%. Among those with antibody levels > 250 AU/ml 52% had previous history of COVID-19 infection. While participants with > 100 AU/ml of antibodies were 12.7%. However 9.5% showed antibody titer of > 25 AU/ml. 27% of participants had antibody titers of > 1.5–2.5 AU/ml. While antibody titers of

Introduction: Current study was designed to evaluate the wound healing activity of a Saudi pomegranate peel extract on excision wound healing in experimentally induced diabetes in rats.Methodology: Animals were divided into three groups: diabetic excision wound with no treatment, diabetic excision wound with gel alone and diabetic excision wound with Saudi pomegranate peel extract in gel. Animals were monitored for clinical signs, weekly body weight, morbidity and mortality during entire study period. The efficacy parameters evaluated were percent wound contraction, Hydroxyproline content, estimation of Transforming Growth Factor ß1 (TGF-ß1), Vascular Endothelial Growth Factor (VEGF), and Epidermal Growth Factor (EGF) in wound lysates by ELISA, mRNA expression of TGF-ß1, VEGF, and EGF in wound lysates by qPCR, Estimation of nitric oxide (NO) and NO synthase (NOS) in Wound Lysates and histopathology of skin for reepithelization, neovascularization, and inflammation.Results: The Saudi pomegranate peel extract in gel (5.0 g extract per 100 g gel) showed significant wound healing activity when compared to the vehicle control [p < 0.05] following 21 days of treatment. Animals in the control and treatment groups were apparently normal through the study with no significant differences in body weights between groups. Expression of mRNA of TGFβ1, EGF and VEGF in wounds was the highest on day 14 post treatment 4.3, 3.5 and 0.9 fold higher respectively in the treatment group when compared to vehicle control, and on day 21, the values were 0.12, 0.3 and 0.83, respectively. No statistically significant differences were observed in TGF-ß1 levels in wounds on days 4, 7, 14 and 21 post treatment when compared to the vehicle control (p > 0.05). Significantly higher levels of VEGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Significantly higher levels of EGF were observed in treatment group on day 7 and 21 when compared to vehicle control (p < 0.05). Mean hydroxyproline levels were higher in treatment group on days 4 and 7 when compared to vehicle control. NO levels in treatment group were significantly lower on days 7, 14 and 21 when compared to vehicle control (p < 0.05). NOS activity in treatment group were significantly lower on days 4 and 7 when compared to vehicle control (p < 0.05). Histopathological changes in skin wound in the treatment group were consistent with wound healing when compared to the vehicle group.Conclusion: This study’s findings suggest that topical application of SPPE gel effectively enhanced wound healing in experimentally induced diabetic conditions.

Background: Alström syndrome (AS) is a very rare childhood disorder characterized by cardiomyopathy, progressive hearing loss and blindness. Inherited genetic variants of ALMS1 gene are the known molecular cause of this disease. The objective of this study was to characterize the genetic basis and understand the genotype–phenotype relationship in Saudi AS patients.Methods: Clinical phenotyping and whole-exome sequencing (WES) analysis were performed on six AS patients belonging to two unrelated consanguineous Saudi families. Sanger sequencing was performed to determine the mode of inheritance of ALMS1 variant in first-degree family relatives and also to ensure its rare prevalence in 100 healthy population controls.Results: We identified that Alström patients from both the families were sharing a very rare ALMS1, 3′-splice site acceptor (c.11873−2 A>T) variant, which skips entire exon-19 and shortens the protein by 80 amino acids. This disease variant was inherited by AS patients in autosomal recessive mode and is not yet reported in any population-specific genetic databases. AS patients carrying this mutation showed heterogeneity in clinical presentations. Computational analysis of the mutant centroid structure of ALMS1 mRNA revealed that exon-19 skipping enlarges the hairpin loop and decreases the free energy, eventually affecting its folding pattern, stability, and function. Hence, we propose c.11873–2A as an AS causative potential founder mutation in Saudi Arabia because it is found in two families lacking a common lineage.Conclusions: We conclude that WES analysis potentially helps in clinical phenotyping, early diagnosis, and better clinical management of Alström patients showing variable clinical expressivity.