3,4-Methylenedioxymethamphetamine (MDMA, ''Ecstasy'') is a widely abused recreational drug associated with multi-organ toxicity. Objective was to compare hepatic, renal, and systemic biochemical abnormalities after acute MDMA exposure alone and with alcohol. This cross-sectional pilot study was conducted at Sheikh Zayed bin Al Nahyan and Shalamar Medical and Dental Colleges, Pakistan. The study included 24 exposed participants (ecstasy-only n = 10; ecstasy and alcohol n = 14) and 20 controls. Blood samples were analyzed for AST (<37 U/L), ALT (<63 U/L), ALP (46–116 U/L), GGT (<55 U/L), LDH (81–234 U/L), Urea (10–50 mg/dl), Creatinine (0.7–1.4 mg/dL), Uric Acid (3.5–7.2 mg/dl), and CK (39–232 U/L). Marked hepatorenal biochemical injury was predefined as ALP > 3 times the laboratory specific upper limit of normal or serum urea > 150 mg/dl. Group comparison, age and sex adjusted multivariable linear regression and ROC analyses were performed. The study group exhibited significantly elevated hepatorenal biomarkers vs. controls. Median AST, ALT and ALP were117.0, 117.5 and 439.0 U/L, equivalent to 3.16, 1.86 and 3.78 x ULN, respectively. Median urea and creatinine levels were 172.5 mg/dL and 1.42 mg/dL respectively. No significant difference was found between ecstasy-only and ecstasy and alcohol after correction. Adjusted models showed significantly higher ALP, urea, and creatinine in both study groups versus controls. RSI and STI showed high apparent discrimination (AUC 1.000 and 0.890, respectively). Acute MDMA exposure was associated with marked hepatic and renal biochemical abnormalities. Alcohol co-consumption did not independently exacerbate organ damage. The RSI and STI are novel, cost-effective, and highly accurate tools for emergency triage using routine laboratory parameters.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing novel coronavirus (COVID-19) outbreak has an impact on the liver enzymes. The study aimed to determine the serum markers and liver enzymes and their association in COVID-19 patients admitted to hospital. Methods: It was a retrospective, observational study conducted at the Gastroenterology Department of Lahore General Hospital, from April 2020-July 2020. Total 495 patients were divided into two groups. Group A (318) comprised of patients with moderate symptoms and group B (177) with severe symptoms. Records were obtained from the hospital laboratory in which Lactate dehydrogenase (LDH), Aspartate aminotransferase, (AST), Alanine aminotransferase (ALT), Gamma glutamyl transferase (GGT) and Alkaline phosphatase (ALP) were assessed using an automated biochemistry analyzer. Serum C-reactive protein test was performed by the immunoturbidimetric assays. Serum Ferritin was determined using the ELISA technique. Results: The mean age of moderate cases was 48.57±16.84 years and of severe cases were 62.51±9.76 years. In both moderate and severe cases, males [200(63%), 98(55.36%)] were more affected than females [118(37.10%), 79(44.63%)]. Furthermore, 79(16%) of severe cases were associated with medical profession. The levels of CRP, Ferritin and LDH were increased significantly in severe COVID-19 cases (p<0.05) compared to moderate ones. On the other hand, liver enzymes ALT, AST, GGT and ALP were non-significantly raised in severe cases compared to moderate cases (p> 0.05). Conclusion: Serum ferritin, C-reactive protein and lactate dehydrogenase acts as prognostic biochemical parameters based on severity. In addition, levels of liver enzymes were also raised indicating liver derangement; however, the results were not significant. Keywords: Ferritin; C-Reactive Protein; Lactate Dehydrogenase; Gama Glutamyl Transferase; Covid-19.

Background:The polycystic ovarian syndrome (PCOS), a well-known endocrine-metabolic disease, is caused by the interaction of environmental, genetic and metabolic factors.A cross-sectional, comparative study was planned to evaluate high sensitivity C-reactive protein (hs-CRP), insulin and lipid profile in non-obese and obese PCOS patients.Methods: Seventy-two women diagnosed with PCOS as per Rotterdam criteria, were placed in three groups in accordance with the body mass index: Group 1 (normal weight), Group 11 (overweight), and Group 111 (obese).Blood glucose, hs-CRP, serum insulin, lipid profile was estimated and insulin resistance was calculated.Data was analyzed using version 20 of SPSS.Analysis of variance (ANOVA) was used to compare the numeric variables among three groups of PCOS women and p-value < 0.05 was considered statistically significant.Results: Significantly, higher levels of insulin (13.03 ± 0.22), triglyceride (1.74 ± 0.96) and hs-CRP (7.24±4.11)were detected in obese PCOS women.The levels of fasting blood glucose (4.61±0.54)were also raised.Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (2.69±0.79)showed insulin resistance in obese PCOS women (p=0.004).The obese group had significantly lower HDL-Cholesterol levels (0.82±0.09).Levels of total cholesterol (4.69±0.97)and LDL-Cholesterol (3.08±0.64)were increased but results were non-significant.These results indicate obesity leads to insulin resistance, dyslipidemia with low grade inflammation in PCOS. Conclusion:Frequency of insulin resistance, dyslipidemia and low-grade inflammation was found significantly higher in young obese PCOS women.Obesity may have an important role in the aetiology as well as the complications associated with PCOS.

Background: Diabetes mellitus is considered as hypercoagulable state, where hypercoagulability of blood result in acceleration of atherosclerosis and diabetic microvascular complications. Three recognized diabetic microvascular complications include diabetic neuropathy, diabetic nephropathy and diabetic retinopathy. The aim of the present study was to evaluate association of plasma fibrinogen levels with other variables in patients with any of the three-recognized diabetic microvascular complications: diabetic neuropathy, diabetic retinopathy or diabetic nephropathy. Methods: 104 patients of T2DM from in Medical unit-II and ophthalmology ward, Services Hospital, Lahore from April to October 2017 were included in present study. The patients were divided into two groups of 52 patients each. Group 1 comprised of Type 2 Diabetes Mellitus patients without any diabetic microvascular complications and Group II: Type 2 Diabetes Mellitus patients with any of three recognized diabetic microvascular complications: diabetic neuropathy, diabetic nephropathy and diabetic retinopathy (52 patients). Plasma fibrinogen levels, blood sugar fasting (BSF), HbA1c and BMI were evaluated in all patients. Results: Spearman’s rank correlation coefficient, applied for measuring correlation of variables, showed statistically significant correlation (P < 0.05) of BSF r = 0.39; HbA1c r = 0.48 to plasma fibrinogen in patients with any of the three diabetic microvascular complications. Conclusion: Higher fibrinogen levels (Clotting factor I) in plasma contribute significantly to establishment of microvascular complications in type-II diabetes mellitus patients. Fibrinogen levels were positively correlated with HbA1c and blood sugar fasting.

Background: Educational environment (EE) plays a pivotal role in the academic growth of a medical student. The objective of the study was to compare the perception of a learning environment in Basic Health Sciences by first and second-year MBBS students of private and public medical colleges in Lahore, Pakistan during Covid-19 using a questionnaire. Methods: Data was collected from students (146) through a self-reported questionnaire via Google. dox after obtaining consent. A total score between 151 and 200 was considered excellent. A score between 101 and 150 indicated a positive approach while less than 100 was considered problematic. A score >3.5 for individual items indicate the presence of the specific aspect of the educational environment, whereas, <3 score requires attention. The t-test was used for analysis and p<0.05 was considered significant. Results: Out of 146 students 84(51.21%) were from private medical colleges while 62(42.46%) were from public medical colleges. The students of private medical colleges who follow the integrated curriculum found the learning sessions (27.84±7.40) were more student-centered with supporting online classes (2.75 ± 1.01) (p<0.05). Multiple softwares found that the tutorial sessions improved their problem-solving skills (>2.5). Teachers were helpful in stress management during the pandemic (>3). Proper counselors were employed by the private medical schools to cater to the needs of students who required assistance. Conclusion: A significantly high mean score was obtained from private-sector medical students regarding students’ perception of learning (SPL), students’ perception of teachers (SPT), and students’ academic self-perception (SASP), compared to public medical colleges. Keywords: Learning Environment; Questionnaire; Medical Students; Perception; Integrated.

Objective: To determine the frequency of esophageal varices cirrhotic patients presenting with new onset ascites. Methodology: This cross-sectional study was done at Gastroenterology department, LGH, Lahore fromSeptember 2016 to February 2017 and included 150 patients. Complete physical examination was performed and all laboratory studies including liver function tests and complete blood count and ascitic fluid analysis was done. For the evaluation of texture of liver tissue, portal vein diameter, splenomegaly and ascites, abdominal ultrasound was performed. Patients were evaluated for the existence of esophageal varices by endoscopy. Results: New varices in esophageal region were seen in 85 (56.7%) patients. Insignificant association was found between ages, gender duration of liver cirrhosis with new esophageal varices. Conclusion: Varices in esophageal region exists in almost 50% of cirrhotic patients. Their presence is associated with severity of liver disease. The study findings may help physicians to separate the high-risk patients with these co-morbidities.

Background: Close relatives of tuberculosis patients may be at increased risk of developing the disease as they are in close contact with them Objectives: A cross-sectional research was conducted to determine correlation of Vitamin D with monocytes and lymphocytes in individuals with active tuberculosis as well as their care takers. Material and Methods: Total of 83 subjects was divided into three groups. Of the 83 participants, 31 had active tuberculosis, while 31 were adult family members who lived with and looked after the patients. 21 healthy age matched individuals were chosen to form the control group. SWISS Max analyzer was used to evaluate the levels of lymphocytes and monocytes in the blood and Vitamin D was measured by ELISA. Results: Vitamin D levels and monocyte lymphocyte count in the three groups showed substantial variation. The patient's monocyte and lymphocyte count showed a statistically significant correlation. However there was non-significant correlation of vitamin D with both monocyte and lymphocyte. Conclusion: Caretakers of active tuberculosis patients showed increased levels of circulating monocytes, lymphocytes as well as lower vitamin D levels with increased risk of developing tuberculosis. Keywords: care taker, tuberculosis, vitamin D, monocyte and lymphocyte

Background: Coronavirus (COVID 19) pandemic has taken so many lives and has contributed to an increase in morbidity due to its complications. The research is still in infancy and much has yet to be investigated. Objective: To correlate the HRCT findings on chest with antibody testing in patients visiting tertiary care hospitals in Lahore. Methodology: Three hundred and thirty-two patients with mild, moderate and severe symptoms of COVID 19 were recruited. Those with raised CRP levels were sent for HRCT chest and PCR testing as protocol of the hospitals. All patients were tested with Rapid antibody kits for reactivity. Results: Showed that males were affected more than females. Similarly, non-health care workers were more affected. All patients with bilateral involvement of lungs on HRCT chest and positive PCR findings also tested reactive on antibody testing. However, a few people with bilateral lung involvement and negative on PCR testing got reactive results on Rapid antibody testing. Linear regression model shows significant correlation of HRCT chest findings with Ant-SARC-COV 2 antibodies. Conclusion: HRCT findings (Unilateral and bilateral lung infiltrates) correlated significantly with Anti SARC-COV 2 Antibodies.

Introduction: Coronavirus emerged as a pandemic in 2019 with the SARS COV 2 virus infecting people worldwide. Although PCR successfully detected symptomatic patients, asymptomatic patients remained undetected due to limitation of resources. The objective of the study was to determine the prevalence of IgM and IgG antibodies in the faculty, staff, and MBBS students in Medical school and tertiary care hospital, Pakistan. Material and Methods: A cross-sectional study was conducted on 500 asymptomatic healthy subjects, from September to December 2020 in Biochemistry department Shalamar Medical and Dental College (SMDC). Rapid antibody test was used to determine the presence of IgM and IgG antibodies in the subjects. Those found IgM positive were validated by COVID 19 detection by Polymerase Chain Reaction. Results: Anti-SARS-COV 2 antibodies was observed in 19.6 % of 500 asymptomatic subjects. Significant reactive cases were identified in hospital staff (27.5%) compared to hospital faculty (23.4%), medical students (21.4%), college faculty (6.12%) followed by college staff (3.06%). Significant reactive cases (47.9%) were identified in middle age group i.e. between 31 to 45 years. IgG was more prevalent than IgM and 2% of the subjects showed coagulation disorders who were both IgG and IgM positive. Conclusion: Prevalence of 19.6% of Anti-SARS-COV 2 antibodies was observed in asymptomatic subjects. Prevalence was more in males, people in the middle age group i.e. 31 to 45 years and in hospital staff and faculty. Recommendations: Based on the study it is recommended that Rapid COVID 19- SRAC-2 antibody test, which is cost effective and rapid method may be used to detect the COVID 19 in developing countries with limited resources.

Background and objectives: Coronavirus (COVID-19) is pandemic, has affected almost every country around the world. A retrospective multi-centered study was carried out to determine the frequency of COVID-19 in children and adults in Lahore, Pakistan from March 2020 to May 15 2020. The study was included 574 corona positive (PCR–positive) patients of all age groups including 147 children. Record of the patients who visited emergency with symptoms of Corona like fever, sore throat, and respiratory distress and those admitted in hospitals due to corona illness was analyzed. Travelling history was recorded and frequency determined using SPSS ver 21. Data of study showed that 54% middle aged patients were found to suffer with Corona virus followed by children and 23% old age group. The patients belong to middle / low socioeconomic status. 26 patients had international travel history while 49 travelled domestically. Study concluded that the incidence of coronavirus disease was more in middle age men followed by children and old age group. However, it is found that the incidence of virus observed in children with better recovery than other age groups. In most of the cases, the course of disease is mild to moderate with less mortality rate.

Background: Eighty percent of the Pakistani population is suffering from gastric issues due to H. Pylori associated gastritis. Objective: To evaluate the diagnostic accuracy of HpSA test for H. Pylori infection in young patients presenting with dyspepsia taking standard Endoscopic Gastric Biopsy as gold standard. Study Design: Cross sectional study. Settings: Gastroenterology Department Lahore General Hospital, Lahore Pakistan. Duration: 7 months from 20th June to 19th December 2016. Methodology: A total 110 patients (18-35 years) with dyspepsia were included after taking approval from ethics committee of LGH/PGMI. After taking consent, fecal antigen detection test and gastric biopsies were carried out on all patient. Biopsy specimens were processed and observed. Hp stool antigen test was assessed from stool samples using ELISA technique. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value was measured by 2x2 contingency table. Results: A total of 60 patients (54.5%) had H.pylori infection as determined by gold standard biopsy whereas 76 (69.1%%) patients were reported positive using fecal antigen. There was 83.3% sensitivity, 48.0% specificity, 65.8% positive predictive value, 70.6% negative predictive and 67.3% diagnostic accuracy. Conclusion: HpSA test has acceptable diagnostic accuracy in comparison with biopsy.

Objective: To compare the risk factors and the possible mode of acquisition of Hepatitis B and C in patients of different ages Methodology: A descriptive cross-sectional study was carried out at Lahore General Hospital from January 2020 to June 2020. Total 350 previously unscreened patients with ages between 16 and 55 years were included in the study after approval from the Ethical Review Committee of PGMI/LGH (095/20- 8/6/20). Patients were grouped according to age: Group 1 (16-35 years) and Group 2 (36-55 years). Screening was done by ELISA technique. Data was collected through questionnaire and was analyzed on Statistical Package for Social Sciences (SPSS) version 21. Results: Incidence of Hepatitis C Virus (HCV) was found to be more common than Hepatitis B Virus (HBV) in both genders. Risk of developing viral infection in both genders increases with age. Use of I/V drugs, barber shave (via razor), dental procedures, and body piercing were the risk factors of developing infection observed in more in Group 2. Co-infection was observed more in males in Group 2. Conclusion: Major contributors for Hepatitis B and C are the use of unsterilized injections and unscreened blood during dental procedures and blood transfusions and visits to community barbers. Awareness regarding equipment sterilization for both the age groups may help in reducing the burden of infection in this community.

Aim: To compare the serum level of homocysteine and fibrinogen in patients with controlled and uncontrolled type 2 diabetes mellitusMethods: It was a cross sectional study. Total 120 consented patients with age range 35-45 years were involved in this study. Patients were taken from LGH, Lahore General Hospital from 2016 August to January 2017. Grouping of patients was done on the values of HbA1c i.e. Group I included controlled diabetes with HbA1c <7 and Group II included uncontrolled diabetes with HbA1c >7. Level of blood HbA1c, fibrinogen and homocysteine were estimated by immunoturbidimetric, Clauss method and ELISA technique respectivelyResults: Mean age of group I and II was 44 and 46 with BMI 25 and 27 kg/m(2) respectively. Chronicity of DM in group I was 24 months and in group II was 49 months. Percentages of HbA1c was 6.25 in group I and 8.65 in group II. Level of fibrinogen and homocysteine was significantly high in group II as compared to group I.Conclusions: High level of fibrinogen along with homocysteine may be useful predictor of cardiovascular risk in uncontrolled diabetic people.

Objective: To find the probable role of Homocysteine as a prognostic indicator for women with Pregnancy-Induced Hypertension and comparison of Homocysteine Levels in Normal Versus pre-eclamptic women. Study Design: Cross Sectional Comparative study. Setting: Gynecology Unit of Lahore General Hospital, Lahore. Period: May 2017 to Oct 2017. Material & Methods: Thirty four consented pre-eclamptic pregnant women with age range 29 to 35 years were included in the study. 20 age matched pregnant women with no history of any clinical problem were taken as controls. A questionnaire based on age, obstetric details including detail of gravida, family history etc was filled by both subjects and controls. Anthropometric parameters were noted based on height and weight. Blood sample of both patients and controls was drawn for estimation of blood urea, serum creatinine, and homocysteine. Results: Mean age of women was 31 year with BMI 27.0 Kg/m2. Levels of serum homocysteine were significantly more women with pre-eclampsia in comparison with cases of controls. However the values of blood urea and serum creatinine were insignificantly high in pre-eclamptic women in comparison with their controls. Conclusion: Serum homocysteine as a biomarker may help to find out its additive importance in the prediction of pre-eclampsia and the severity of its related complications.

Early onset neonatal sepsis is invariably very common and serious problem worldwide, especially it is one of the important etiological factor for deaths of neonates in Pakistan. Acute renal failure is frequently seen in neonates with sepsis. Objectives: The aim of present study was to determine the correlation of renal function tests (Blood Urea and creatinine) with early onset neonatal sepsis. Study Design: Descriptive study. Setting: Department of Paediatric Medicine Sir Ganga Ram hospital, Lahore. Period: Six months from 20th March to 20th September 2018. Material & Methods: Total 300 cases of neonatal sepsis with acute renal failure were included in this study after taking informed consent from the parents. Cases selection was done with help of a predefined inclusion and exclusion criteria. Daily blood urea and serum creatinine were calculated from birth to first 7 days of life. If any of blood urea or serum creatinine was deranged, the neonate was labelled as having acute renal failure. Data was entered and analysed using SPSS software version 21. Results: Mean age of all cases was 2.82±1.56 days. The minimum and maximum age limits of the neonates were 1 and 7 days respectively. Gender distribution of neonate showed that 57% of the neonates were male and 43% were females. At the 2nd day of life, mean serum creatinine level was 1.12±0.39, at 3rd day 1.19±0.51, at 4th day 1.41±0.38, at 5th day 1.33±0.39, at 6th day 1.19±0.39, and at 7th day mean serum creatinine level was 1.09±0.31 respectively. At 2nd day of birth mean blood urea was 54.82±34.77, at 3rd day59.50±28.22 at 4th day 74.94±30.37, at 5th day 67.09±26.94, at 6th day 56.09±25.76, at 7th day mean blood urea level was 47.66±22.47 respectively. Frequency of acute renal failure was observed in 28.3% of the neonates while the remaining 71.7% of neonates did not suffer from acute renal failure. Conclusion: Early onset neonatal sepsis contributes significantly to development of acute renal failure in neonates.

Aim: To see serum cholesterol and triacylglycerol levels in type 2 diabetics in population of Lahore. Design: Cross sectional analytical study. Place and Duration of Study: The study was conducted at Post Graduate medical Institute, Lahore General Hospital and Sir Ganga Ram Hospital, Lahore. Methods: A total of 160 type 2 diabetics (40 - 60 years of age both sexes) were included in the study. 24 healthy controls were matched for age and sex. Prior consent of all subjects was obtained. Well diagnosed cases of type 2 diabetes were included. Diabetics with hypertension or any other disease and pregnant women were excluded. Antecubital venous blood samples were taken in morning (0800-1000), after an overnight fast. Serum was obtained for lipid profile and blood glucose. Results: There were total 84 males, 72 patients and 12 controls, and 100 females, 88 patients and 12 controls, enrolled in study. Male age ranges 45-60 years (mean 51.03 +/- 6.62) and female age ranges 40-60 years (mean 48.58 +/- 6.05). It was found out that there was a highly significant (P<0.001) increase in triacylglycerols and fasting blood glucose levels in male diabetics. In females there was a highly significant (P<0.001) increase in serum cholesterol, serum triacylglycerol and fasting blood glucose levels. Conclusion: Present study shows that the diabetic patients are more susceptible to develop hyperlipidemia. The routine assay of the lipid profile should be done in patients of type 2 diabetes.

Background: Esophageal variceal related bleeding is a lethal outcome of portal hypertension in patients with cirrhosis with mortality. Objective: To assess esophageal varices in patients with liver cirrhosis using non-invasive parameters. Study Design: Cross sectional study. Settings: Gastroenterology Department, Lahore General Hospital, Lahore Pakistan. Duration: 6 months from September 2016 to February 2017. Methodology: Data of all cirrhotic patients admitted in medical ward was collected. Liver cirrhosis was confirmed by abdominal ultrasound. Values of platelet count, serum albumin and serum ALT estimated by automated biochemistry analyzer. Serum ALT / platelet ratio index was measured by formula. Results: It is observed that esophageal varices are most common in middle to old age. 53.9 % of the cirrhosis patients of the age greater than 40 years have esophageal varices. Mean age of patients with esophageal varices (EV) was 40.94 year. Average duration of cirrhosis was 3.09 years and level of serum alanine aminotransferase (ALT) was raised with thrombocytopenia and low serum albumin. Aspartate aminotransferase / platelet ratio (APRI) index was raised as compared to patients without esophageal varices. Conclusion: Esophageal varices are most common in middle to old age and non-invasive assessment including level of serum alanine aminotransferase, aspartate aminotransferase, serum albumin, platelet count and APRI ratio may help to assess esophageal varices in patients with liver cirrhosis.

Background: Beta-Thalassaemia major (beta TM) is hemolytic congenital disorder leading to hypochromic microcytic anemia. Due to repeated blood transfusion, patients with beta TM develop iron overload and deposition in various body organs which may result in destruction of pancreatic beta cells initiating oxidative stress and hypoinsulinemia and eventually result in Type 1 Diabetes Mellitus. Immune-competent cells like macrophages release proinflammatory cytokines such as interleukin-1 beta which may be an important clinical indicator of ongoing pancreatic beta cell destruction in pre-diabetes phase. Aim: To evaluate and compare serum interleukin-1 beta levels in Beta-Thalassemia major children having normal and impaired glucose tolerance. Methods: 90 patients of Beta thalassemia major aged >= 10 years belonging to both genders were taken for study purpose. These patients were divided into 2 study groups. Group A included 45 patients having normal fasting blood glucose and glucose tolerance. Group B included 45 patients with impaired fasting blood glucose levels and glucose tolerance. The study data was then analyzed by SPSS version 21. Results: The mean age was 11.56 +/- 1.06 years and 11.56 +/- 1.06 years in group A and B respectivley. Mean BMI was 22.41 +/- 1.76 Kg/m(2) and 22.21 +/- 2.15 Kg/m(2) in group A and B respectively.With regards to gender distribution, group A comprised of 29 (64.5 %) males and 16 (35.5%) females, whereas in group B, there were 27(60%) males and 18(40%) females. Mean serum ferritin levels were 4428.04 +/- 1776.89 ng/ml and 5246.09 +/- 3073.06 ng/ml in group A and B respectively. Mean fasting blood sugar was 95.2 +/- 9.1 mg/dl and 119.13 +/- 3.92 mg/dl in group A and B respectively. Mean oral glucose tolerance was 128.2 +/- 6.94 mg/dl and 166.51 +/- 12.56 mg/dl in group A and B respectively. Mean serum interleukin-1 beta (IL-1 beta) levels were 2.91 +/- 1.30 and 5.24 +/- 2.16 pg/ml in group A and B respectively. Conclusion: Higher interleukin-1 beta levels contribute significantly to development and progression of impaired glucose tolerance in beta thalassemia major patients and hence pose a threat for Type 1 diabetes mellitus progress in these patients.