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Background: Pakistan has got a very high prevalence of myocardial infarction (MI). MI presents at pretty young age in this country. The objective of present study was to determine the frequency of common risk factors associated with early development of MI in middle aged adults of less than 45 years. Methods: It was a cross sectional study conducted in the Cardiology department of Ayub Teaching Hospital (ATH) Abbottabad from 23rd June 2015 – 10th July 2016. A total of 255 consecutive patients diagnosed with MI admitted to the Cardiology Unit of ATH, Abbottabad. A detailed medical history and general physical examination of the patients was carried out with an emphasis on recording the presence or absence of common risk factors of MI in these patients. All routine investigations (Blood Complete Picture, Urea, Creatinine, Blood Sugar & Lipid Profile) were done. Results: Mean age of the subjects was 39.98±4.61 SD. The frequency of risk factors in descending order was smoking in (38.8%), obesity in (29.4%) and essential hypertension in (21.6%) of the patients. Other risk factors of MI in this study were diabetes mellitus (19.2%), family history of ischemic heart disease (IHD) was (18.8%) and disproportionate dyslipidemias in (12.9%). Sex of patients (male predominance) was found to be significantly associated with diabetes, smoking and dyslipidemia (p

To examine our outpatient urologic surgery cohort for trends in opioid consumption, given the lack of consensus on opioid prescription after outpatient urologic procedures. While opioids have a role in multimodal postoperative analgesia, there is emerging data that they may not be routinely required after pediatric surgery.Data on opioid use was prospectively collected over 16 months via postoperative telephone calls to caregivers of patients undergoing outpatient urologic surgery. Patient characteristics, surgery type, analgesia, and opioid prescription and usage information were recorded. Patients were prescribed as needed oxycodone and scheduled acetaminophen and ibuprofen for 48 hours, then as needed. The relationships between the log mean of the number of opioid doses used and age, type of surgery, race, and opioid prescription were modelled using negative binomial regression with the robust standard errors.Two hundred sixty-five patients were included. They were predominantly male with median age 2.6 years. The mean number of opioid doses prescribed per patient was 5.8 (SD 2.8, range 3-20). Over half of patients used no opioids, and mean opioid use was one dose. Those prescribed5 doses took on average 3.4 times more doses compared to those prescribed5 (P = .0003), and this was the only factor significantly associated with the amount of opioid used.Our findings suggest that opioids are over-prescribed after outpatient pediatric urologic surgery, with 95% of patients having leftover medication and 54% not using any opioids at all. While opioid requirements were low across all sub-cohorts, patients who were prescribed more opioid doses used significantly more doses.

Epidemiological studies have provided varying prevalence estimates of trichotillomania (TTM) and other hair-pulling behaviors. We performed a systematic review and meta-analysis to provide data-driven prevalence estimates of TTM and hair-pulling. PubMed, PsycInfo and Embase were searched on June 2020 (updated in November 2021). Studies reporting the frequency of TTM defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria or hair-pulling behaviors were included. Prevalence data was extracted for both genders, and female-to-male odds ratios (OR) were computed for TTM and any hair-pulling behaviors. Data were pooled through random-effects meta-analyses. Of the 713 records identified through database searches, 30 studies involving 38,526 participants were included. Meta-analyses indicated TTM had a prevalence of 1.14% (95% CI 0.66%, 1.96%), while any hair-pulling behavior had a prevalence of 8.84% (95% CI 6.33%, 12.20%). Meta-analyses demonstrated females were at an increased risk of any hair-pulling when noticeable hair loss was required (OR = 2.23, 95% CI 1.60, 3.10, p 0.0001), but not of any hair-pulling when noticeable hair loss was not required (OR = 0.90, 95% CI 0.72, 1.64, p = 0.33). Meta-analyses did not indicate female preponderance in TTM (k = 10; N = 22,775; OR = 1.29; 95% CI 0.91, 1.83; I

OBJECTIVE To perform a detailed analysis of the epidemiology, tumor biology, treatment, overall survival, and quality of life in a young patient (age ≤45 years) cohort with oral squamous cell carcinoma (OSCC). STUDY DESIGN A retrospective cohort study between 1992 and 2017 at an academic tertiary care center. RESULTS In total, 80 patients were included (36 female and 44 male) with stage I (American Joint Committee on Cancer eighth ed.) disease and lateral tongue was most common presentation. Mean follow-up was 6.28 years. The overall disease recurrence rate was 28.7% (23 of 80). Human papillomavirus was positive in 22% of patients tested. Free flap reconstruction was not associated with improved margin status (P = .62) but significant for recurrent disease (P < .04). Overall 2-year survival was significantly poorer in patients with close/positive margin status and free flap reconstruction. Patients with early-stage disease (stage II) requiring adjuvant radiotherapy, chemotherapy (all stages), or flap reconstruction (Stage III patients) had significantly worse 5-year survival rates. CONCLUSIONS OSCC in young patients (age ≤45 years) is an increasingly more common disease that occurs in patients without known risk factors. Despite their earlier presentation of disease pathology, constant vigilance and standard aggressive treatment similar to other age groups will result in similar and improved outcomes and survival.

Objective: To evaluate the effectiveness of hand-hygiene training on handwashing practices among schoolchildren. Method: The quasi-experimental study was conducted from 1st August- 2018 to 5th October- 2018 in four secondary schools in Peshawar and Kohat districts of Khyber Pakhtunkhwa, Pakistan, and comprised male students grades 5, 6, 7, 9 and 10. They were given a live demonstration about the standard steps of hand-hygiene as per the World Health Organisation checklist, and they were shown the steps in pictorial form as well to reinforce the message. Pre- and post-intervention scores were recorded on the 14- point checklist. Data analysed using SPSS 23. Results: There were 200 boys with a mean age of 13.23±0.92 years (range: 11-16 years); 87(43.5%) of them being from grade 7. Post-intervention score increased significantly compared to the baseline (p

We aimed to assess and compare autonomic function in Parkinson's disease (PD) associated with the leucine-rich repeat kinase (LRRK2) G2019S mutation (LRRK2-PD) and non-LRRK2 PD, by the study of heart rate variability (HRV) and sympathetic skin responses (SSR).In a cross-sectional three-year study, fifty LRRK2-PD and fifty clinically matched non-LRRK2 PD patients were included. Cardiac parasympathetic functions were assessed using heart rate variation to deep breathing (HR-DB), to the Valsalva maneuver (HR-V) and to standing (HR-S) and the sympathetic autonomic system by sympathetic skin responses (SSR).Neurophysiological, parasympathetic and sympathetic dysautonomia were found in 78%, 69% and 37% of all PD patients respectively. Rates of dysautonomia in the LRRK2-PD and non-LRRK2 PD patient subgroups were 76% vs 80% (p = 0.405) for neurophysiological, 62% vs 76% (p = 0.123) for parasympathetic and 38% vs 36% (p = 0.500) for sympathetic dysautonomia. HR-S was the most frequently altered parameter in both groups, and was significantly associated with the tremor-dominant (TD) motor phenotype of PD in the total cohort (p = 0.004) and in LRRK2-PD (p = 0.015). In LRRK2-PD patients, female gender was associated with parasympathetic dysfunction (p = 0.024), and with altered HR-DB (p = 0.022). Early-onset parkinsonism was also significantly associated with preserved neurophysiological autonomic functions (p = 0.044) in LRRK2-PD. In non-LRRK2 PD patients, male gender was associated with early parasympathetic (p = 0.043) and sympathetic dysfunction (p = 0.007).Our study showed a roughly similar neurophysiological autonomic profile in non-LRRK2 PD and LRRK2-PD. The latter had some peculiarities with more marked parasympathetic dysfunction and more altered HR-DB in females, more altered HR-S in the TD-motor phenotype, and preserved autonomic functions in early-onset parkinsonism. These preliminary findings would require further investigations on larger genetically homogeneous cohorts to explore the multiple facets of autonomic dysfunction in PD.

The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role.A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue.Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity-urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits.A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.

Background Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. Objective To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. Design Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tonsberg]). (ClinicalTrials.gov: NCT01778738). Setting Tertiary care obesity center in Norway. Participants 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). Intervention From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. Measurements The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. Results Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. Limitations Single-center study, short follow-up time, and lack of power for secondary outcomes. Conclusion With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. Primary funding source Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension.This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission.A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04).This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels. An interquartile range (IQR) increase of 18.12 μg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 μg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

Contamination of edible oils with aflatoxins (AFs) is a universal issue due to the detrimental effects of aflatoxins on human health and the fact that edible oils are a major source of fungal growth, particularly storage fungi (

Objective To validate the use of placenta accreta risk-antepartum (PAR-A) score as a predictive tool of clinical outcomes of placenta accreta spectrum (PAS). Methods This is a prospective study, conducted in six PAS specialized centers in six different countries. The study was conducted between October 1, 2020 and March 31, 2021. Women who were provisionally diagnosed with PAS during pregnancy were considered eligible. A machine-learning-based PAR-A score was calculated. Diagnostic performance of the PAR-A score was evaluated using a receiver operating characteristic curve, for perioperative massive blood loss and admission to intensive care unit (ClinicalTrials.gov identifier NCT04525001). Results Of 97 eligible women, 86 were included. PAS-associated massive blood loss occurred in 10 patients (11.63%). Median PAR-A scores of massive blood loss in the current cohort were 8.9 (interquartile range 6.9-14.1). In predicting massive blood loss, the area under the curve of PAR-A scores was 0.85 (95% confidence interval [CI] 0.74-0.95), which was not significantly different from the original cohort (P = 0.2). PAR-A score prediction of intensive care unit admission was slightly higher compared with the original cohort (0.88, 95% CI 0.81-0.95; P = 0.06). Conclusion PAR-A score is a novel scoring system of PAS outcomes, which showed external validity based on current data.

Background Intraparenchymal hemorrhage (IPH), possibly due to reperfusion, after evacuation of a cranial chronic subdural hematoma (cSDH) is a known phenomenon. However, it is sparingly reported and not well understood. Methods An illustrative case series is presented. A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify all previously reported cases. Results A total of 48 cases were analyzed. Males were 85.4% of the population, and the mean age was 67.5 years. Pre-existing head trauma and hypertension were the most common comorbidities. Headache was a presenting symptom in 60.4% of cases. Midline shift was explicitly stated in 54.2% of cases. Initial burr hole alone was performed 75.0% of the time, whereas craniotomy alone was performed in 16.7% of cases. Any initial craniotomy patients were associated with a modified Rankin Scale score of 5 (P = 0.03). The IPH was located in the cerebral hemisphere in 62.5% of cases and more likely to occur ipsilateral to a unilateral cSDH (P = 0.02). The IPH occurred a mean 1.9 days after surgery, and 50.0% occurred within 24 hours of initial intervention. The median modified Rankin Scale at discharge was 2. The mortality rate was 25%. Lastly, a multifactorial reperfusion pathophysiology was proposed. Conclusion IPH after cSDH evacuation is associated with significant morbidity and mortality. Prompt recognition, regulating blood pressure, controlling the amount and rate of extra-axial fluid drained, and a meticulous surgical technique are critical to optimize the care of patients with cSDH and reduce the rate of postoperative IPH.

Background/Objectives Understanding the factors that promote healthy lifestyle behaviors in women with polycystic ovary syndrome is of substantial importance. Health-promoting lifestyle behaviors (HPLB) have been observed to be effective in managing various symptoms related to PCOS. This study aimed to examine the relationship between loci of control and health-promoting lifestyle behaviors in Pakistani women with polycystic ovary syndrome and the mediating role of coping strategies. Method A correlational study was carried out with 145 unmarried women with polycystic ovary syndrome diagnosed by a gynecologist using the Rotterdam Criteria of 2003 (M age = 24.75 years). Participants were recruited from public sector hospitals in Lahore, Punjab, Pakistan and a series of hierarchical regression analyses were used to analyze results. Results Findings suggest that women with internal and powerful others locus of control use more active practical coping strategies and less active distractive coping strategies. These women also get more involved in health-promoting behaviors. On the other hand, those with a high level of chance locus of control use less active practical coping strategies and more active distractive coping strategies. In turn, they engage less in health-promoting behaviors. Conclusion Health professionals should consider the effects of different types of locus of control and coping strategies when planning interventions for women with polycystic ovary syndrome.

Objective: Several studies have focused on the use of ultrasound-stimulated microbubbles (USMB) to induce vascular damage in order to enhance tumor response to radiation. Methods: In this study, power Doppler imaging was used along with immunohistochemistry to investigate the effects of combining radiation therapy (XRT) and USMB using an ultrasound-guided focused ultrasound (FUS) therapy system in a breast cancer xenograft model. Specifically, MDA-MB-231 breast cancer xenograft tumors were induced in severe combined immuno-deficient female mice. The mice were treated with FUS alone, ultrasound and microbubbles (FUS + MB) alone, 8 Gy XRT alone, or a combined treatment consisting of ultrasound, microbubbles, and XRT (FUS + MB + XRT). Power Doppler imaging was conducted before and 24 h after treatment, at which time mice were sacrificed and tumors assessed histologically. The immunohistochemical analysis included terminal deoxynucleotidyl transferase dUTP nick end labeling, hematoxylin and eosin, cluster of differentiation-31 (CD31), Ki-67, carbonic anhydrase (CA-9), and ceramide labeling. Results: Tumors receiving treatment of FUS + MB combined with XRT demonstrated significant increase in cell death (p = 0.0006) compared to control group. Furthermore, CD31 and Power Doppler analysis revealed reduced tumor vascularization with combined treatment indicating ( P

Percutaneous closure of congenital ventricular septal defects (VSDs) represents a promising alternative to surgery with lower rate of complications and shorter hospital stay. Its main limitation is the choice of the appropriate device for each type of defect.To report the experience of the service of cardiology (Sahloul hospital, Sousse, Tunisia) in percutaneous closure of congenital VSDs with Amplatzer Duct Occluder II (ADOII).This was a retrospective, monocentric study, conducted from January 2013 to December 2017. The study included patients treated by percutaneous closure of congenital VSDs with the ADOII device.Twelve patients (6 boys; 6 girls) were included. The mean±SD of patients' age and weight were 65±41 months and 23±10 kg, respectively. VSDs were peri-membranous (n=9) and muscular (n=3), and defects were restrictive (n=11) and non-restrictive (n=1). The mean (minimum-maximum) size of VSDs was 4.72 (3-6) mm. Eleven ADOII prostheses were successfully implanted. One failure procedure was noted with migration of the device into the pulmonary artery. A second child with perimembranous defect developed transient atrioventricular block. No deaths occurred.The present early experience shows that percutaneous closure with ADOII device of perimembranous and trabecular VSDs is safe and effective.

Nitrous oxide, colloquially known as “whippets,” is a commonly abused inhalant by adolescents and young adults. There are limited data describing the adverse effects of this abuse. We present a 16-year-old girl with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and headaches. Imaging revealed extensive cerebral thrombosis. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level. She was treated with effective anticoagulation and vitamin B12 folate supplementation. To our knowledge, there are a very few cases in the medical literature of cerebral venous thrombosis following the use of nitrous oxide. The pathophysiology of the disorder appears to be linked to the metabolism of vitamin B12 inducing hyperhomocysteinemia and a procoagulant state.

The applications of exogenous hormones in different species for the induction of oocyte production, final oocyte maturation (FOM), and spawning for their reproduction is getting more attention day by day. The current preliminary research work was carried out to induce breeding in Clarias gariepinus, commonly known as African catfish, imported from Thailand. Single doses of two hormones as Ovaprim and human menopausal gonadotropin (hMG) were used and the research work was carried out at Muzaffargarh Fish Hatchery Punjab, Pakistan. A total of twenty-four (n = 24) C. gariepinus were selected having body weight approximately 2 kg and divided into two main groups based on gender as male (n = 12) and female (n = 12). For milt collection, all males were treated with Ovaprim 0.5 mg/kg body weight (b.w.) and female fish were divided into three groups as A, B, and C with four (n = 4) fish in each group. Group A was injected with only normal saline (control group) while fish in group B and group C were treated with hMG at 0.5 mg/kg b.w. and Ovaprim 0.5 mg/kg b.w., respectively. Then, after 6 h of hormone injections until 48 h, spawned eggs, eggs’ weight, fertilization rate, hatching rate, survival rate, fecundity, and deformed larvae were investigated. The results revealed that Ovaprim injection significantly (p

BACKGROUND: The COVID-19 pandemic has exacerbated disparities in poverty and illness for people in vulnerable circumstances in ethnocultural communities. We sought to understand the evolving impacts of COVID-19 on ethnocultural communities to inform intersectoral advocacy and community action. METHODS: The Illuminate Project used participatory action research, with cultural health brokers as peer researchers, from Sept. 21 to Dec. 31, 2020, in Edmonton, Alberta. Twenty-one peer researchers collected narratives from members of ethnocultural communities and self-interpreted them as they entered the narratives into the SenseMaker platform, a mixed-method data collection tool. The entire research team analyzed real-time, aggregate, quantitative and qualitative data to identify emerging thematic domains, then visualized these domains with social network analysis. RESULTS: Brokers serving diverse communities collected 773 narratives. Identified domains illuminate the evolving and entangled impacts of COVID-19 including the following: COVID-19 prevention and management; care of acute, chronic and serious illnesses other than COVID-19; maternal care; mental health and triggers of past trauma; financial insecurity; impact on children and youth and seniors; and legal concerns. We identified that community social capital and cultural brokering are key assets that facilitate access to formal health and social system supports. INTERPRETATION: The Illuminate Project has illustrated the entangled, systemic issues that result in poor health among vulnerable members of ethnocultural communities, and the exacerbating effects of COVID-19, which also increased barriers to mitigation. Cultural brokering and community social capital are key supports for people during the COVID-19 pandemic. These findings can inform policy to reduce harm and support community resiliency.

Site-specific variation in colorectal cancer (CRC) incidence, biology and prognosis are poorly understood. We sought to determine whether common genetic variants influencing CRC risk might exhibit topographical differences on CRC risk through regional differences in effects on gene expression in the large bowel mucosa. We conducted a site-specific genetic association study (10,630 cases, 31,331 controls) to identify whether established risk variants exert differential effects on risk of proximal, compared to distal CRC. We collected normal colorectal mucosa and blood from 481 subjects and assessed mucosal gene expression using Illumina HumanHT-12v4 arrays in relation to germline genotype. Expression quantitative trait loci (eQTLs) were explored by anatomical location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects - risk of distal CRC (OR=1.20, P=8.20x10-20 ) with negligible effects on proximal CRC risk (OR=1.05, P=0.10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference=10, P=3.48x10-57 ). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest trans-eQTL signals in proximal colonic mucosa (e.g. AKAP14, beta=0.61, P=5.02x10-5 ) and opposite signals in distal mucosa (AKAP14, beta=-0.17, P=0.04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa. Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes. This article is protected by copyright. All rights reserved. Site-specific variation in colorectal cancer (CRC) incidence, biology and prognosis are poorly understood. We sought to determine whether common genetic variants influencing CRC risk might exhibit topographical differences on CRC risk through regional differences in effects on gene expression in the large bowel mucosa. We conducted a site-specific genetic association study (10,630 cases, 31,331 controls) to identify whether established risk variants exert differential effects on risk of proximal, compared to distal CRC. We collected normal colorectal mucosa and blood from 481 subjects and assessed mucosal gene expression using Illumina HumanHT-12v4 arrays in relation to germline genotype. Expression quantitative trait loci (eQTLs) were explored by anatomical location of sampling. The rs3087967 genotype (chr11q23.1 risk variant) exhibited significant site-specific effects - risk of distal CRC (OR=1.20, P=8.20x10-20 ) with negligible effects on proximal CRC risk (OR=1.05, P=0.10). Expression of 1261 genes differed between proximal and distal colonic mucosa (top hit PRAC gene, fold-difference=10, P=3.48x10-57 ). In eQTL studies, rs3087967 genotype was associated with expression of 8 cis- and 21 trans-genes. Four of these (AKAP14, ADH5P4, ASGR2, RP11-342M1.7) showed differential effects by site, with strongest trans-eQTL signals in proximal colonic mucosa (e.g. AKAP14, beta=0.61, P=5.02x10-5 ) and opposite signals in distal mucosa (AKAP14, beta=-0.17, P=0.04). In summary, genetic variation at the chr11q23.1 risk locus imparts greater risk of distal rather than proximal CRC and exhibits site-specific differences in eQTL effects in normal mucosa. Topographical differences in genomic control over gene expression relevant to CRC risk may underlie site-specific variation in CRC. Results may inform individualised CRC screening programmes. This article is protected by copyright. All rights reserved.

Background Rates of depression among Pakistani mothers are high, leading to poor developmental outcomes in their children. This study tested the effectiveness of a manualized integrated parenting program; Learning through Play Plus (LTP+) for maternal depression in Karachi, Pakistan. Methods A cluster randomized control trial conducted from January 2014 to December 2015 across 120 villages in Karachi. A total of 774 depressed mothers aged 18-44 years with children aged 0-30 months old, were included. Villages were randomized to receive LTP+ added to treatment as usual (TAU) or TAU alone. Primary outcomes were severity of maternal depression at 3 and 6 months measured by the Edinburgh Postnatal Depression Scale and child socio-emotional development at 6 months measured by the Ages and Stages Questionnaire (ASQ). Secondary outcomes included maternal anxiety, quality of life, social support, parenting competence, and knowledge about child development. Results Mothers in the LTP+ group reported significantly lower depression scores compared to those in the TAU group (6.6 vs. 13.8, effect size [ES]: -7.2; 95% confidence interval [CI]: -8.2, -6.1) at 3 and 6 months (7.2 vs. 12.00; ES: -4.6; 95% CI: -5.9, -3.4). Child socio-emotional development at 6 months was significantly better in the LTP+ group on all domains of the ASQ. There were also statistically significant improvements on all secondary outcomes at 3- and 6-month follow-up. Conclusion In low-resource settings like Pakistan, low-cost integrated parenting interventions delivered by lay health workers can provide effective treatment for depressed mothers, leading to improvements in child development.

Targeted surveillance strategies following initial primary lung cancer (IPLC) treatment are currently limited. One hundred twenty patients diagnosed with IPLC who did not develop second primary lung cancer (SPLC) were matched to 121 patients who developed SPLC. Our analysis found IPLC surgical resection increases SPLC emergence risk regardless of procedure type. Increased survival after IPLC resection warrants close SPLC monitoring. Background: Increased patient survivorship following initial primary lung cancer (IPLC) diagnosis and treatment has uncovered new clinical challenges as individuals post-IPLC are at growing subsequent risk of developing second primary lung cancer (SPLC). Proper SPLC surveillance guidelines aimed at monitoring IPLC survivors are crucial to enhancing health outcomes. This study aims to categorize risk factors associated with SPLC emergence in IPLC survivors for clinical use following IPLC treatment. Materials and Methods: Using the Karmanos Cancer Institute Tumor Registry, patients diagnosed with IPLC from 2000 to 2017 were identified. Patients diagnosed with SPLC were matched to individuals who did not develop SPLC. Logistic and Cox regression analyses were performed to identify risk factors for SPLC emergence and overall survival (OS). Results: One hundred twenty-one patients diagnosed with IPLC who later developed SPLC were identified and compared with 120 patients with IPLC who did not develop SPLC. Several factors such as stage at first diagnosis, histology, age, and smoking history were not associated with SPLC risk. The median time to SPLC was 1.79 years. Patients who were treated with surgical resection had a significantly higher probability of developing SPLC. After correcting for potential immortal time bias, the median OS was 3.63 years (95% confidence interval [CI], 3.05–5.00) and 7.31 years (95% CI, 4.62–10.90) for SPLC and no SPLC groups, respectively. Conclusion: This study uncovered notable associations and lack thereof between several competing SPLC risk factors, as well as mortality. Further characterization of SPLC risk factors is essential for enhancing surveillance recommendations.

Background We evaluated short- and mid-term outcomes with use of aortic valve-sparing root replacement to treat bicuspid aortic valves. Methods From December 2007 to January 2022, all patients with bicuspid aortic valves who underwent aortic root replacement using Tirone’s procedure were included. This study based on department database information for retrospective and follow-up data. Results Among 51 adults undergoing aortic root replacement using Tirone’s procedure, the mean age was 47.4±12.5 years, and most were men (92.2%). Three presented with a dysmorphic syndrome and one had Marfan’s syndrome. All patients were alive at 30 days, and as of January 2022, 45 were alive, two were lost to follow-up, and there were four noncardiac deaths. Two patients had infectious endocarditis and needed a Bentall’s procedure. One patient had a double biologic valve replacement in the context of severe mitral insufficiency with moderate aortic stenosis at 4.5 years post-procedure. Echocardiographic follow-up showed a left ventricular ejection fraction of 63±7% (n=36), V 2±0.6 m/s (n=17), and a mean gradient of 9.4±5.4 mmHg (n=27). No patients had grade 3 or 4 aortic regurgitation, one patient had grade 2, and four had grade 1. Conclusion Tirone’s procedure is an option for bicuspid aortic valve surgery, with good safety and outcomes, especially in younger patients.

Background: The COVID-19 pandemic is a viral infection that spreads through different mediums and has a high rate of mortality. At its initial stages, there is no particular medicine that can cure patients of COVID -19. The aim of the present study was to understand the COVID-19 knowledge, perception, and its effects in terms of anxiety and depression among frontline health care workers of Ayub Teaching Hospital, Abbottabad. Methods: This cross-sectional study was conducted in Ayub Teaching Hospital, Abbottabad from June 2021 to Jul 2021 in which data was collected from 200 hospital healthcare workers who have performed duties in COVID isolation wards through standard questionnaire. SPSS version 24.0 was used for data analysis. Results: Out of 200 participants in the study 100 (50.0%) were male. Regarding safety measures taken during COVID -19, 144(72.0%) individuals reported that they have not been given training to handle known or suspected cases of COVID -19. Moderate anxiety and depression was found in 153 (76.5%) healthcare workers, mild in 25 (12.5%) and 22(11.0%) had severe anxiety and depression at the time of COVID -19 pandemic. Conclusion: This study revealed that a significant anxiety and depression was found in frontline healthcare workers during the COVID-19 pandemic. In addition, a more extensive study should be conducted which involves many other hospitals like Ayub Teaching Hospital.

Objective To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. Methods A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. Results The median of age [14 (10–18) vs. 15 (10–18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091–3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001–1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206–0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981–0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. Conclusion Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

Ovary development is an important determinant of the procreative capacity of female animals. Here, we performed genome-wide sequencing of long non-coding RNAs (lncRNAs) and mRNAs on ovaries of 1, 3 and 8 months old Hu sheep to assess their expression profiles and roles in ovarian development. We identified 37,309 lncRNAs, 45,404 messenger RNAs (mRNAs) and 330 novel micro RNAs (miRNAs) from the transcriptomic analysis. Six thousand, seven hundred and sixteen (6716) mRNAs and 1972 lncRNAs were significantly and differentially expressed in ovaries of 1 month and 3 months old Hu sheep (H1 vs H3). These mRNAs and target genes of lncRNAs were primarily enriched in the TGF-β and PI3K-Akt signalling pathways which are closely associated with ovarian follicular development and steroid hormone biosynthesis regulation. We identified MSTRG.162061.1, MSTRG.222844.7, MSTRG.335777.1, MSTRG.334059.16, MSTRG.188947.6 and MSTRG.24344.3 as vital genes in ovary development by regulating CTNNB1, CCNA2, CDK2, CDC20, CDK1 and EGFR expressions. A total of 2903 mRNAs and 636 lncRNAs were differentially expressed in 3 and 8 months old ovaries of Hu sheep (H3 vs H8); and were predominantly enriched in PI3K-Akt, progesterone-mediated oocyte maturation, estrogen metabolism, ovulation from the ovarian follicle and oogenesis pathways. These lncRNAs were also found to regulate FGF7, PRLR, PTK2, AMH and INHBA expressions during follicular development. Our result indicates the identified genes participate in the development of the final stages of follicles and ovary development in Hu sheep.

Sajjad Ahmad,1 Mater H Mahnashi,2 Bandar A Alyami,2 Yahya S Alqahtani,2 Farhat Ullah,1 Muhammad Ayaz,1 Muhammad Tariq,3 Abdul Sadiq,1 Umer Rashid4 1Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmaceutical Chemistry, College of Pharmacy, Najran University, Najran, Saudi Arabia; 3Department PCB, Rokhan University, Jalalabad, Nangrahar, Afghanistan; 4Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanCorrespondence: Abdul SadiqDepartment of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), Khyber Pakhtunkhwa, PakistanTel +92 301 2297 102Email sadiquom@yahoo.comUmer RashidDepartment of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, PakistanTel +92-334 5171999Email umerrashid@cuiatd.edu.pkBackground: Organocatalytic asymmetric Michael addition is a strong approach for C-C bond formation. The objective of the study is to design molecules by exploiting the efficiency of Michael Adducts. We proceeded with the synthesis of Michael adducts by tailoring the substitution pattern on maleimide and trans-β-nitro styrene as Michael acceptors. The synthesized compounds were evaluated for dual cyclooxygenases (COX) and lipoxygenase (LOX) inhibition.Methods: The compounds (4, 9– 11) were synthesized through Michael additions. The cyclooxygenases (COX-1 and 2) and lipoxygenase (5-LOX) assays were used for in vitro evaluations of compounds. After the acute toxicity studies, the in vivo analgesic potential was determined with acetic acid induced writhing, tail immersion, and formalin tests. Furthermore, the possible roles of adrenergic and dopaminergic receptors were also studied. Extensive computational studies were performed to get a better understanding regarding the binding of this compound with protein target.Results: Four Michael adducts (4, 9– 11) were synthesized. Compound 4 was obtained in enantio- and diastereopure form. The stereopure compound 4 showed encouraging COX-1 and-2 inhibitions with IC50 values of 128 and 65 μM with SI of 1.94. Benzyl derivative 11 showed excellent COX-2 inhibition with the IC50 value of 5.79 μM and SI value 7.96. Compounds 4 and 11 showed good results in in vivo models of analgesia like acetic acid test, tail immersion, and formalin tests. Our compounds were not active in dopaminergic and adrenergic pathways and so were acting centrally. Through extensive computational studies, we computed binding energies, and pharmacokinetic predictions.Conclusion: Our findings conclude that our synthesized Michael products (pyrrolidinedione 4 and nitroalkane 11) can be potent centrally acting analgesics. Our in silico predictions suggested that the compounds have excellent pharmacokinetic properties. It is concluded here that dual inhibition of COX/LOX pathways provides a convincing step towards the discovery of safe lead analgesic molecules.Keywords: Michael products, succinimides, cyclooxygenase, lipoxygenase, analgesic, molecular docking, adrenergic and dopaminergic

BACKGROUND: In women with a bad obstetric history (BOH), infection is an established cause of recurrent fetal loss. A common infecting agent is the protozoan parasite Toxoplasma gondii (T. gondii). The aim of this study was to measure the prevalence of toxoplasmosis in women with recurrent fetal loss from the Khyber Pakhtunkhwa province of Pakistan. METHODS: The study included 360 females aged 16–40 years, of which 180 had a bad obstetric history (study group) and the other 180 had no such history (control group). Blood serum samples were tested for toxoplasma IgM antibodies by Enzyme Linked Immunosorbent Assay and for toxoplasma IgG antibodies using an Immunochromatographic technique. RESULTS: The overall seroprevalence of toxoplasma infection in study group females was 40.6% and in control group females it was 7.2%. Specifically, IgM prevalence was 12.8% in the study group and 1.1% in the control group. IgG prevalence was 23.9% in the study group and 6.1% in the control group. IgM and IgG combined prevalence was 3.9% in the study group cases. There is a statistically significant association between BOH and seropositivity for T. gondii (p

Previous studies using additive genetic models failed to identify robust evidence of associations between colorectal cancer (CRC) risk variants and survival outcomes. However, additive models can be prone to false negative detection if the underlying inheritance mode is recessive. Here, we tested all currently known CRC-risk variants (n = 129) in a discovery analysis of 5675 patients from a Scottish cohort. Significant associations were then validated in 2474 CRC cases from UK Biobank. We found that the TT genotype of the intron variant rs7495132 in the CRTC3 gene was associated with clinically relevant poorer CRC-specific survival in both the discovery (HR = 1.97, 95% CI = 1.41-2.74, P = 6.1x10-5 ) and validation analysis (HR = 1.69, 95% CI = 1.03-2.79, P = 0.038). In addition, the GG genotype of rs10161980 (intronic variant of AL139383.1 lncRNA) was associated with worse overall survival in the discovery cohort (HR = 1.24, 95% CI = 1.10-1.39, P = 3.4x10-4 ) and CRC-specific survival in the validation cohort (HR = 1.26, 95% CI = 1.01-1.56, P = 0.040). Our findings show that common genetic risk factors can also influence CRC survival outcome. This article is protected by copyright. All rights reserved.