Search

OBJECTIVES The objective of this study was to investigate the role of ultrasound in the detection of early pregnancies presenting with placental molar changes. METHODOLOGY This retrospective study was carried out at Radiology department of Hayatabad Medical Complex, Peshawar, between Aug 2020 and July 2021. All cases suspected of molar changes were evaluated from 10-14 weeks of gestation. The patient were referred to our department because of fetal abnormality, maternal disease or age and family or previous pregnancy history or were identified from an ongoing ultrasound screening study for aneuploidy by measurement of fetal nuchal translucency thickness. Transabdominal or transvaginal sonography was used to examine the fetus and placenta. RESULTS Total 85 patients of molar pregnancies were enrolled in the study. Age ranged between 20-45 years with a mean age of 32.5 years. There were 60(70.6%) complete moles (CM) and 25(27.4%) partial moles (PM) were suspected on ultrasound. In case of complete mole coexisting with a normal singleton or twin pregnancy, the molar placenta was clearly separated from the normal placenta, whereas with partial moles the molar structures were dispersed inside the placental mass. CONCLUSION Ultrasound detection of molar pregnancy remains a diagnostic challenge. Data suggest that there has been an increase in both the predictive value and the sensitivity of ultrasound over time; however, the diagnostic criteria remain ill defined. Prior to managing a miscarriage, being aware of the possibility of molar pregnancy will guide treatment and allow for adequate follow-up.

ObjectiveThe differentiation of vascular smooth muscle cells (VSMCs) into an osteo-chondrogenic phenotype and consequent vascular calcification and increased extracellular matrix (ECM) stiffness are hallmarks of vascular ageing. Sox9 (SRY-Box Transcription Factor 9) is a major regulator of chondrogenesis that is also expressed in the vasculature during development and disease. Here, we investigated the relationship between VSMC ageing and Sox9-driven ECM regulation in VSMCs in vitro and in vivo.Approach and ResultsWe found that Sox9 expression in the aortic media was not associated with vascular calcification but strongly correlated with the senescence marker p16. Analysis of Sox9 expression in vitro showed that it was not a direct regulator of VSMC senescence but was highly mechanosensitive exclusively in senescent VSMCs, showing increased expression on stiff matrices. Manipulation of Sox9 via overexpression and depletion in VSMCs revealed that Sox9 regulates both ECM stiffness and organisation by orchestrating changes in collagen expression and reducing VSMC contractility. Importantly these ECM changes promoted VSMC phenotypic modulation such that senescent cells plated onto ECM synthesized from senescent cells depleted of Sox9 returned to a proliferative state and reduced p16 and p21 expression, as well as decreased the senescence associated secretory phenotype (SASP) marker IL6. We identified procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (LH3) as a novel Sox9 target, and key regulator of Sox9-driven ECM stiffness during VSMC senescence. LH3 is packaged into extracellular vesicles (EVs) and secreted into the ECM and we found that Sox9 also increases EV secretion, leading to increased LH3 deposition within the ECM.ConclusionsThese findings identify Sox9 as a key driver of increased ECM stiffness during VSMC ageing through upregulation of LH3 deposition via increased EV release. They also highlight a crucial role for ECM structure and composition in regulating VSMC phenotype and identify a novel cycle where cellular senescence and increased ECM stiffening promote Sox9 expression which acts to further enhance ECM modifications thus accelerating vascular stiffening, ageing and senescence.

Background: Ovulation induction with clomiphene citrate in women with infertility has been practiced more than 40% years but in infertile patients this treatment plan proved to be ineffective with multiple complication. Body weight plays an important role modulating reproductive development and functioning. Aim: To observe the effects on body weight of female albino rat after use of clomiphene citrate and letrozole for consecutive 1-4 estrous cycles Method: Eighty four adult female Albino rats were equally divided into three groups for this research. Body weight of each rat was measured before and after the experiment. Vaginal smear cytology of each rat was performed to study different phases of estrous cycle. Control group A was given normal saline orally , In Experimental group B rats were given letrozole (Femara) at dose 5mg/kg orally and in Experimental group C rats were given clomiphene citrate at dose 100ug/kg orally. Results: Significant weight gain is observed in rats taking clomiphene citrate as compared to letrozole Conclusion : Comiphene citrate directly affects the body weight which indirectly reduces the ovulation induction and pregnancy rate. Letrozole is good alternate for ovulation induction and for CC resistant patients. Keywords: Estrous cycle, body weight, citrate and letrozole

Vascular amyloidosis, caused when peptide monomers aggregate into insoluble amyloid, is a prevalent age-associated pathology. Aortic medial amyloid (AMA) is the most common human amyloid and is composed of medin, a 50-amino acid peptide. Emerging evidence has implicated extracellular vesicles (EVs) as mediators of pathological amyloid accumulation in the extracellular matrix (ECM). To determine the mechanisms of AMA formation with age, we explored the impact of vascular smooth muscle cell (VSMC) senescence, EV secretion, and ECM remodeling on medin accumulation. Medin was detected in EVs secreted from primary VSMCs. Small, round medin aggregates colocalized with EV markers in decellularized ECM in vitro and medin was shown on the surface of EVs deposited in the ECM. Decreasing EV secretion with an inhibitor attenuated aggregation and deposition of medin in the ECM. Medin accumulation in the aortic wall of human subjects was strongly correlated with age and VSMC senescence increased EV secretion, increased EV medin loading and triggered deposition of fibril-like medin. Proteomic analysis showed VSMC senescence induced changes in EV cargo and ECM composition, which led to enhanced EV-ECM binding and accelerated medin aggregation. Abundance of the proteoglycan, HSPG2, was increased in the senescent ECM and colocalized with EVs and medin. Isolated EVs selectively bound to HSPG2 in the ECM and its knock-down decreased formation of fibril-like medin structures. These data identify VSMC-derived EVs and HSPG2 in the ECM as key mediators of medin accumulation, contributing to age-associated AMA development.

Weeds are unwanted plants in crop that can be control by different methods among them use of aqueous extract of crop is an imperative method. To investigate the allopathic potential of aqueous extract of winter crop Papavare somniferum (opium) on summer weed Echinochloa cruss-galli (barnyard grass) laboratory experiments were conducted. The experiment coomprised seven concentrations (0, 0.25, 0.50, 1, 2, 4, and 8%) of different plant parts i.e., leaves, stem and flower of P. somniferumwere. All the tested concentrations and plant parts of P. somniferum significantly reduced mean emergence time, germination index, germination percentage, time to 50% germination as well as well growth of E. cruss-galliweed. However, maximum mean emergence time (9.07 days), time to 50% germination (3.67 days) was noted at leaves and stem extract, respectively. Application of aqueous extract of stem at 8% concentration resulted in greatest time to complete 50% germination (5.42 days) and lowest fresh weight (6.28 g), dry weight (1.00 g) and root length (0.33 cm) of E. cruss-galli. Whereas leaf extract at 8% concentration produces less shoot length (1.13 cm) and more emergence time (9.18 days). Lowest emergence percentage (6.67%) and germination index (0.89) were produced by aqueous extract of fruit at 8% concentration. On the basis of this experiment, it can be concluded that higher concentration (8%) of stem extract of P. somniferumwas used to biologically control the infestation of E. cruss-galli weed.

Background: Vascular amyloidosis, caused when peptide monomers aggregate into insoluble amyloid, is a prevalent age-associated pathology. Aortic medial amyloid (AMA) is the most common human amyloid and is composed of medin, a 50-amino acid fragment of milk fat globule EGF-factor 8 (MFGE8). Emerging evidence has implicated extracellular vesicles (EVs) as mediators of pathological amyloid metabolism and accumulation in the extracellular matrix (ECM). MFGE8 has been identified as EV cargo in several cell types, including vascular smooth muscle cells (VSMCs). To determine the mechanisms of AMA formation with age, we explored the impact of VSMC senescence, EV secretion and ECM remodelling on medin accumulation. Methods: Primary human VSMCs were used for in vitro experiments, including EV isolation and synthesis of decellularised ECM for Western blotting, immunofluorescence and mass spectrometry analysis. Results: Medin was detected in EVs secreted from VSMCs. Small, round medin aggregates colocalised with EV markers in the ECM and medin was shown on the surface of EVs deposited in the ECM. Decreasing VSMC EV secretion with an inhibitor attenuated aggregation and deposition of medin in the ECM. Medin accumulation in the aortic wall of human subjects was strongly correlated with age. VSMC senescence increased EV secretion, increased EV medin loading and triggered extracellular deposition of medin in fibrillar form. Proteomic analysis showed VSMC senescence induced changes in EV cargo and ECM composition. These changes led to enhanced EV-ECM binding in the senescent ECM and accelerated aggregation of medin into amyloid fibrils. Abundance of the proteoglycan, HSPG2, was increased in the senescent ECM and colocalised with EVs and medin. Knock-down of HSPG2 decreased medin fibril formation in the senescent ECM. Conclusions: Medin is secreted into the ECM by VSMC-derived EVs, which enhance its aggregation. Senescence induces changes in EV secretion and cargo and ECM composition. Together, these changes trigger accumulation of fibrillar medin, contributing to the age-associated development of AMA.

Objective: To determine association of body mass index with life style behaviours among students of Punjab University. Methodology: This was a cross sectional study, done among Punjab University students. Study was started after approval of Institutional Review Board of the Department of Public health and after taking informed consent. Data was collected on a self structured questionnaire. Body Mass Index (BMI) was calculated after measurements of weight and height. BMI was taken normal in the range of 18.5-24.9 kg/m2, under-weight below 18.5kg/m2 and overweight 25-29.9kg/m2. Then analysis was done using appropriate statistical tests. Results: Most of the respondent (80%) had age group 17-25 years. Majority respondents sleep late night, 93.5% were nonsmoker, 55% had good sleep 6 to 8 hours daily, 50% respondents walk 10 to 20 minutes daily, 90% did not have outdoor games activity, jogging and swimming habit. Majority (60%) respondents had normal BMI, 25% had high and 15% below normal. Demographic variable when associated with BMI age, gender, weight, height, and income were found statistically significant. Similarly, physical activities when associated with BMI then daily sleeping hours, timing of sleeping, daily walk, outdoors games, jogging and use of bike were statistically significant. Conclusion: Lifestyle of University students of young age shows that there is need to create awareness about healthy physical activities and improving their lifestyle behaviours so as to maintain a normal BMI. Descriptive statistics shows that majority of the university students do not have health lifestyle and around 25% had high BMI in spite of young age. There is need of the hour to create awareness about healthy physical activities and improving their lifestyle behaviours so as to maintain a normal BMI.

To measure and compare micro ribonucleic acid-16, survivin and tumour protein p53-regulated apoptosis-inducing protein 1 expression levels in preeclamptic and normotensive pregnancies, and to check the correlation of micro ribonucleic acid-16 with messenger ribonucleic acid expression of survivin and tumour protein p53.The observational cross-sectional comparative study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2016 to 2018, and comprised preeclamptic women in group A and normotensive women in group B. The preeclamptic patients were further categorised into early-onset preeclampsia subgroup A1and late-onset preeclampsia group A2. Expression of micro ribonucleic acid-16, messenger ribonucleic acid expression of survivin and tumour protein p53 in preeclamptic and normotensive pregnancies were analysed using real time polymerase chain reaction. Data was analysed using SPSS 22.Of the 54 patients, 27(50%) were in each of the two groups. Within group A, 14(52%) patients were in group A1 and 13(48%) in group A2. The expression of micro ribonucleic acid 16 showed significant increase in group A compared to group B (p0.05). The difference was not significant between the subgroups A1 and A2. The levels of messenger ribonucleic acid expression of survivin and tumour protein p53 were deregulated in group A, with a decrease in survivin and an increase in tumour protein p53. The messenger ribonucleic acid expression of survivin and tumour protein p53 showed statistically significant differences across subgroups A1 and A2 (p0.05). The micro ribonucleic acid-16 expression correlated negatively with messenger ribonucleic acid expression of survivin, but exhibited a positive correlation with tumour protein p53.Deregulated micro ribonucleic acid-16 along with differentially expressed apoptotic genes, survivin and tumour protein p53 might result in altered apoptosis implicated in the pathogenesis of preeclampsia.

Aim: To check the correlation of Body Mass Index (BMI) with Total Leukocyte count (TLC) and C Reactive Protein (CRP) levels in preeclamptic and normotensive pregnant women. Methods: It was a comparative cross sectional study with 120 participants divided into two groups with 60 diagnosed cases of preeclampsia and 60 healthy pregnant women with normal blood pressure. The samples were collected in the third trimester of pregnancy. All the participants were in the range of 20-40 years of age and had a BMI within 18-25kg/m2. Results: TLC and BMI were significantly high in the preeclamptic group (p value

In this study we have presented the optical detection of Hepatitis C virus and molecular changes in human serum through partial least square regression vectors obtained from their Raman spectra. 140 samples tested through enzyme-linked immunosorbent assay and PCR for confirmation were used to create a model by utilizing spectral variations in the Raman spectra of the positive and control groups. Regression coefficients of this model were obtained and analyzed. The regression vector yielded by this model is utilized to predict hepatitis C in unknown samples. This model has been evaluated by a cross-validation method, which yielded a correlation coefficient of 0.91. Moreover, 30 unknown samples were screened for hepatitis C infection using this model to test its performance. From these calculations, accuracy, specificity and sensitivity of this model were determined to be 86.67%, 93.75% and 78.57% respectively. The value of area under the ROC curve was found to be about 1 which shows that the model is accurate. Keywords: hepatitis C, partial least square (PLS) regression, multivariate analysis, Raman spectroscopy, ELISA

Single-nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ2 = 63.10; P = C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.

Cardiomyopathies are complex heart muscle diseases that can be inherited e.g. dilated cardiomyopathy resulting from LMNA gene mutations, or acquired, e.g. cardiomyopathy associated with HIV. In both cases the lamin A precursor, prelamin A, may play a central role: mutations in LMNA and certain HIV protease inhibitors acting via the enzyme ZMPSTE24 both inhibit prelamin A processing. Firstly, we show that myocardial prelamin A accumulation occurs in both these cardiomyopathies in patients. Secondly, we developed a novel mouse model of cardiac specific prelamin A accumulation which mimicked tissue and molecular features of HIV associated cardiomyopathy, including inflammation. These findings: (1) confirm a central pathological role of prelamin A common to genetic and acquired cardiomyopathies; (2) have implications for the management of HIV patients with cardiac disease in whom protease inhibitors with low/no binding to ZMPSTE24 may be preferred; and (3) suggest that targeting inflammation may be a useful treatment strategy for some forms of inherited cardiomyopathy.

Background Ageing is a major risk factor for several vascular pathologies including calcification, the deposition of hydroxyapatite crystals in the vessel wall, and amyloid deposition. Exosomes, 20–100nm secreted vesicles, have been recognised as key mediators of amyloid formation in the brain and exosomes secreted from vascular smooth muscle cells (VSMCs) have been implicated in vascular calcification. However, whether exosomes link calcification and amyloid deposition in the vasculature is unknown. Medin, forms the age-related aortic medial amyloid (AMA) and is present in the aorta of 97% of people over 50-years old. Medin is a 50 amino acid cleavage product of the protein MFGE8 however, the mechanism of AMA formation is unknown. The aims of this study were to examine 1) changes in exosome secretion and content with age, 2) amyloid protein secretion and deposition by exosomes and 3) if calcifying conditions contribute to AMA formation. Methods Western blotting, qPCR, and immunostaining were used to study medin and MFGE8 expression in primary human VSMCs, at different ages and in elevated calcium and phosphate conditions. FACS was used for quantification of exosome secretion. Exosomes were isolated by differential ultracentrifugation. Extracellular matrix (ECM) was synthesised in vitro for immunofluorescence and Western blotting. Cresolphthalein assays were used to quantify calcification. Results MFGE8, medin and calcification, shown by von Kossa staining, co-localised in the medial layer of aortas from old subjects (figure 1). Medin and calcium deposits appear predominantly extracellular. Exosome secretion is increased from senescent VSMCs and in calcifying conditions. MFGE8 was expressed by VSMCs and was secreted exclusively in exosomes and its expression and secretion increased in calcifying conditions. Immunofluorescence staining of the ECM in vitro showed medin deposits co-localise with CD63, an exosome marker. The size of medin deposits in the ECM was increased when cells were treated with calcium and phosphate and this effect was reduced with an exosome secretion inhibitor, spiroepoxide (figure 2). Treatment with spiroepoxide also decreased hydroxyapatite deposition in the ECM. Conclusion Medin and MFGE8 are abundant in aged aortas and secreted by exosomes. The von Kossa and medin staining observed in the medial layer of aged subjects indicates co-localisation of AMA and calcification. Exosome secretion is increased with age as well as in calcifying conditions, which could contribute to the age-related deposition of medin in the ECM. Blocking exosome release attenuates the effect of elevated calcium and phosphate on both the size of medin aggregates and the formation of hydroxyapatite in the ECM. This suggests VSMC-derived exosomes mediate both vascular calcification and medin aggregation; and conditions which induce vascular calcification also stimulate AMA formation. Conflict of interest No conflict of interest

This study was conducted to determine the viral responses of patients with chronic infection of Hepatitis C virus treated with sofubuvir.This Quasi experimental study was conducted at Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi from September 2014 to September 2016. 502 patients with HCV genotype 3 including treatment naive, non-responders or relapsers to previous interferon based therapy along with patients having decompensated cirrhosis (child class B or C) were included in the study. All patients were treated with Sofosbuvir 400 mg once daily along with Ribavirin for 6 months. Follow-up qualitative PCR (polymerase Chain Reaction) were performed at 4 weeks interval to assess RVR (Rapid virological Response), end of treatment to determine ETR (End of treatment response) and 3 months post treatment to determine SVR12 (Sustained viral response at 12 week).91% of the patients had become PCR negative at completion of four weeks of treatment with Sofosbuvir, whereas at completion of treatment 96.5% had attained a negative PCR. Sustained virological response at 12 weeks post therapy (SVR12) was attained in 85.5% of patients. No statistically significant associations were found with attainment status of RVR, ETR and SVR based on previous treatment status or presence of Decompensated liver disease. However, attainment of SVR was slightly more in females (p value=0.03). The serological profiles of patients whether they attained PCR at week 4, 24 of treatment or 12 weeks' post treatment did not exhibit any statistically significant difference.Sofosbuvir is effective in eradicating hepatitis C virus irrespective of previous treatment or liver fibrosis status in genotype 3 HCV Pakistani patients.

(1H-Benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), 1H-benzo[d][1,2,3]triazol-1-yl 4-methylbenzenesulfonate (Bt-OTs), and 3H-[1,2,3]triazolo[4,5-b]pyridine-3-yl 4-methylbenzenesulfonate (At-OTs) are classically utilized in peptide synthesis for amide-bond formation. However, a previously undescribed reaction of these compounds with alcohols in the presence of a base, leads to 1-alkoxy-1H-benzo- (Bt-OR) and 7-azabenzotriazoles (At-OR). Although BOP undergoes reactions with alcohols to furnish 1-alkoxy-1H-benzotriazoles, Bt-OTs proved to be superior. Both, primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling, and other chemical experiments, phosphonium and tosylate derivatives of alcohols seem to be intermediates. These then react with BtO− and AtO− produced in situ. In order to demonstrate broader utility, this novel reaction has been used to prepare a series of acyclic nucleoside-like compounds. Because BtO− is a nucleofuge, several Bt-OCH2Ar substrates have been evaluated in nucleophilic substitution reactions. Finally, the possible formation of Pd π–allyl complexes by departure of BtO− has been queried. Thus, alpha-allylation of three cyclic ketones was evaluated with 1-(cinnamyloxy)-1H-benzo[d][1,2,3]triazole, via in situ formation of pyrrolidine enamines and Pd catalysis.

Introduction: Hypercholestrolemia has a strong association with Atherosclerosis and coronary artery disease (CAD). It is amajor worldwide health problem and the incidence is rising in Pakistan. Hypocholesterolemic effect of green tea (GT) has been proven invarious research studies in the world. Objective: Present study aims to evaluate this effect in Pakistani population in the context of specificdietary and social habits prevailing here. Setting: The university of Lahore. Methodology: Sixty subjects were included in the study comprisingof thirty healthy subjects and thirty hypercholesterolemic individuals who were not taking any medication to control their serum cholesterol. Theywere all given GT in a dose of 3 gm twice daily for sixty days. Serum cholesterol levels were estimated at day 1 and then every 2nd week till the60th day. Results: Significant lowering of serum cholesterol was observed (p

DDR memory used for data storage in space applications is subjected to different errors. These errors are caused by various perturbations such as cosmic radiations, solar radiations, galactic noise, electromagnetic radiations and extreme temperature in space, which can corrupt the data stored in the DDR memory. Error detection techniques allow detecting such errors, while error correction enables reconstruction of the original data. These error detection and correction techniques enable reliable delivery of digital data over an unreliable communication channel. This paper focuses on the comparative analysis of various EDAC schemes for space applications. The analysis is done on the basis of time complexity, space complexity, error correction and detection capabilities, code rate and bit overhead. This paper includes comparison of Hamming, Hadamard, Golay, Repetition, Berger, Single Parity, Four Dimensional Parity, BCH and Reed Solomon Codes. It is concluded that 4D parity codes are best suited for DDR memories in space applications, since they are easier to implement and have highest code rate to bit overhead ratio.