A case report of secondary cutaneous cryptococcosis in a retrovirus positive patient

Cryptococcosis is a systemic mycosis caused by the capsulated yeast Cryptococcus neoformans. Cryptococcus remains an important opportunistic pathogen in HIV positive patients. It is usually acquired through inhalation of spores and by invasion of the respiratory system, and then, the organisms may spread hematogenously to other viscera mainly central nervous system. Although there are some reports of primary cutaneous cryptococcosis, cryptococcal skin disease is a rare feature of disseminated cryptococcosis and has poor outcome if undiagnosed and untreated. We present a case of secondary cutaneous cryptococcosis in a 50-year-old male, who was diagnosed as a case of retroviral disease 3 years back but not on anti-retroviral therapy

The Dynamic Effects of Fiscal Policy Shocks in Pakistan

This study investigates the dynamic effects of fiscal policy shocks in Pakistan by using structural vector auto-regressive (SVAR) model for annual time series data from 1972 to 2014. To identify the effects of fiscal shocks on macro economy, four different identification approaches has been used i.e. Recursive approach, Blanchard and Perotti approach, Sign Restriction and Event Study approach for two different lags. Both sets of impulse responses gives the same results and support Mountford and Uhlig (2005) that different lag order has no effects on the whole results. While the impulse responses of all identification approaches give different results criticized Caldara and Kamps (2006) that different identification methods given the same results. The most common results provided both government expenditure and revenue shocks showed that an expansionary fiscal policy increased output only for short and medium term at the cost of high prices and have no significant effects in the long run

The Dynamic Effects of Fiscal Policy Shocks in Pakistan

This study investigates the dynamic effects of fiscal policy shocks in Pakistan by using structural vector auto-regressive (SVAR) model for annual time series data from 1972 to 2014. To identify the effects of fiscal shocks on macro economy, four different identification approaches has been used i.e. Recursive approach, Blanchard and Perotti approach, Sign Restriction and Event Study approach for two different lags. Both sets of impulse responses gives the same results and support Mountford and Uhlig (2005) that different lag order has no effects on the whole results. While the impulse responses of all identification approaches give different results criticized Caldara and Kamps (2006) that different identification methods given the same results. The most common results provided both government expenditure and revenue shocks showed that an expansionary fiscal policy increased output only for short and medium term at the cost of high prices and have no significant effects in the long run

Effect of combined siRNA of HCV E2 gene and HCV receptors against HCV

<p>Abstract</p> <p>Background/Aim</p> <p>Hepatitis C virus (HCV) is a major threat as almost 3% of the world's population (350 million individual) and 10% of the Pakistani population is chronically infected with this virus. RNA interference (RNAi), a sequence-specific degradation process of RNA, has potential to be used as a powerful alternative molecular therapeutic approach in spite of the current therapy of interferon-α and ribavirin against HCV which has limited efficiency. HCV structural gene E2 is mainly involved in viral cell entry via attachment with the host cell surface receptors i.e., CD81 tetraspanin, low density lipoprotein receptor (LDLR), scavenger receptor class B type 1 (SR-B1), and Claudin1 (CLDN1). Considering the importance of HCV E2 gene and cellular receptors in virus infection and silencing effects of RNAi, the current study was designed to target the cellular and viral factors as new therapeutic options in limiting HCV infection.</p> <p>Results</p> <p>In this study the potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was investigated by combined treatment of siRNAs against the HCV E2 gene and HCV cellular receptors (CD81 and LDLR), which resulted in a significant decrease in HCV viral copy number.</p> <p>Conclusion</p> <p>From the current study it is concluded that the combined RNAi-mediated silencing of HCV E2 and HCV receptors is important for the development of effective siRNA-based therapeutic option against HCV-3a.</p

A Novel Nonsense Mutation in FERMT3 Causes LAD-III in a Pakistani Family

Leukocyte adhesion deficiency-III (LAD3) is an extremely rare primary immunodeficiency disorder, transmitted with autosomal-recessive inheritance. It is caused by genetic alteration in the FERMT3 gene, which leads to abnormal expression of kindlin-3. This cytoplasmic protein is highly expressed in leukocytes and platelets, and acts as an important regulator of integrin activation. LAD3 has features like bleeding syndrome of Glanzmann-type and leukocyte adhesion deficiency. FERMT3 mutation(s) have not been well characterized in Pakistani patients with LAD3. In this study, an infant and his family of Pakistani origin, presenting with clinical features of LAD, were investigated to determine the underlying genetic defect. Targeted next generation sequencing (TGS) and Sanger sequencing were performed to identify and confirm the causative mutations, respectively, and their segregation within the family. A novel, homozygous FERMT3 nonsense mutation (c.286C &gt; T, p.Q96∗) was found in the proband, and its co-segregation with LAD3 phenotype within the family was consistent with an autosomal recessive inheritance. Both parents were carriers of the same mutation. This family was offered prenatal diagnosis during first trimester of the subsequent pregnancy; the fetus carried the variant. In conclusion, our study is the first report to identify the novel homozygous variant c.286C &gt; T, p.Q96∗in the FERMT3 gene, which might be the causative mutation for LAD3 patients of Pakistani origin

HEMATOLOGICAL VARIATIONS AND ASSESMENT OF HEAVY METALS IN SINDH SPARROW (PASSER PYRRHONOTUS) AS A BIOINDICATOR IN PUNJAB AREAS OF PAKISTAN

Sindh sparrows, prevalent in Sindh region of Pakistan, are non-migratory birds abundant in human-inhabited areas globally, except Antarctica. Given their close association with human settlements, these birds serve as crucial indicators for biological monitoring in regions affected by pollution. This study focused on assessing the hematological parameters and heavy metal concentrations in various organs of Sindh sparrows in the Punjab regions of Pakistan. The collected blood samples underwent analysis for hematological indices and heavy metal concentrations. The results indicated variability in hematological analysis of sparrows. Fluctuations were observed in the concentrations of different heavy metals, with significant differences in zinc and iron, while chromium, cadmium, and nickel concentrations showed non-significant differences. The patterns of heavy metal accumulation revealed higher concentrations of chromium, nickel, and iron in the liver, contrasting with the cadmium and zinc in kidneys. In conclusion, significant correlations were observed among the concentrations of Zinc, Chromium, Cadmium, Nickel, and Iron in kidney, liver, and muscles of both male and female Sindh sparrows. The findings underscore the need for further comprehensive studies to assess heavy metal accumulation in birds, highlighting the urgency to address environmental pollution that poses risks to avian species and human populations worldwide

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Asymptomatic urinary tract infection with multidrug resistant pathogens in retro positive patients on ART

Introduction: Asymptomatic urinary tract infection refers to occurrence of bacteria in urine without causing symptoms. UTI is more prevalent among retro positive patients compared to people without HIV. Objectives – The study was done to determine prevalence of UTI, common etiologies and antibiotic susceptibility pattern of urinary isolates among HIV seropositive patients attending ART centre for CD4 counts. Materials &amp; Methods: –A total of 109 patients without any symptoms of UTI were included in the study. AST was done using Kirby Bauer disk diffusion method.CD4 count was done using FACS counter. Results: Out of the 109 cases tested, 55 were males, and 54 cases were females. No growth was seen in 60 (55.04%) samples, insignificant bacteriuria in 9(8.26%) samples. Significant growth was seen in 40 samples (36.7%). Among the 54 females, 44% had significant growth. Among 55 males, significant growth was seen in 29.1%. The isolated organisms included Escherichia coli - 9(22.5%), Staphylococcus aureus - 7(17.5%), Candida albicans - 7(17.5%). Bacterial isolates showing resistance to three or more categories of antibiotics were considered Multidrug resistant (MDR). Multidrug resistance was seen among 16 bacterial isolates (48.5%). HIV positive patients with CD4 counts of &lt;200 had higher rates of asymptomatic bacteriuria. Conclusion: Screening of HIV seropositive patients with lower CD4 counts for asymptomatic UTI helps in early diagnosis and appropriate, early management of MDR will reduce morbidity

Insulinomimetic Effect of Citrullus Colocynthis Roots in STZ Challenged Rat Model: Insulinomimetic Effect of Citrullus Colocynthis Roots

Diabetes mellitus is a metabolic disease characterized by hyperglycemia resulting from either defect in insulin secretion, insulin action, or both. Postprandial hyperglycemia is a prime characteristic of diabetes mellitus and has been a focus in the therapy for diabetes. One of the therapeutic approaches which involve decreasing hyperglycemia aims at lowering blood glucose by decreasing insulin resistance, raising insulin sensitivity at the tissues and inhibiting the carbohydrate absorbance in the intestine. Plants contain different chemical constituents with potential for insulin mimetic action, decrease in insulin resistance and of α-amylase inhibitory activity may be used as therapeutic agents in the treatment of diabetes mellitus. The present study investigates the hypoglycemic activity and insulinomimetic action of aqueous and ethanolic extracts of Citrullus colocynthis by invitro α-amylase enzyme inhibition and by histopathological studies in streptozotocin (STZ) induced diabetic rats. Male Wistar rats weighing about 180- 250g were taken and divided into fifteen groups. Diabetes was induced by giving streptozotocin (STZ) (30-50mg/kg) intraperitoneally. Rats that showed blood glucose levels &gt; 250mg/dl were selected for the study. Metformin (45mg/kg) was given as standard oral hypoglycemic agent. The aqueous and ethanolic extracts of Citrullus colocynthis (AECC and EECC) at 100mg/kg, 200mg/kg and 300mg/kg were administered to the normal and diabetic rats. The invitro α – amylase inhibitory activity was done by spectrophotometric method. Blood glucose levels were measured by glucose oxidase method. Estimation of glycogen in the lever was carried out with anthrone method. Liver and pancreas were isolated and subjected to histopathological studies. Serum insulin was monitored through chemiluminescence assay. Oral administration of both extracts showed significant inhibition of α-amylase enzyme in-vitro and decrease in blood glucose also. Glycogen and Insulin levels too were found to increase in extract treated groups which attributed for its insulinomimetic activity. The findings revealed that Citrullus colocynthis possess a very strong anti-hyperglycemic potential justifying the use of the drug for the treatment of diabetes mellitus