Sublingual immunotherapy to house dust mite as an immunological intervention in refractory atopic dermatitis

Sublingual immunotherapy (SLIT) with house dust mite (HDM) preparation has been shown to reduce disease severity in patientswith atopic dermatitis (AD). A 5-year-old girl with severe Atopic Dermatitis refractive to all possible pharmacotherapy was put onSLIT for dust mite and followed up for a period of one year. SLIT to dust mite proved highly effective in reducing the disease severityscore as well as prevention of exacerbations in this patient

CASUAL FACTROS OF CRIMINAL BEHAVIOR IN PUNJAB, PAKISTAN

This study was conducted to find out the casual factors of criminal behavior in, Punjab Pakistan. Punjab is the largest province of Pakistan and crime ratio is also highest in this province. A questionnaire of 114 items was constructed through focus group discussion, Literature and DSM-5. Five point Likert scale was used to measure the casual factors. Data was collected from 200 criminals who conducted the crime more than one time. Data was collected from District jails of Multan and Vehari from south Punjab. Mean value was selected as 2 for mentioning a factors as cause of criminal behavior which indicate the presence of a factor. In last 20 factors were mentioned as casual factors of criminal behavior including physical abuse in schools, stubbornness in childhood, feelings of hopelessness and helplessness in childhood, strict family restrictions in childhood. Failure in intimate relations, high media exposure, short temperament, feelings of revenge and deprivation in childhood. Most of the criminals found to get their primary and secondary education in schools whereas there were lowest ratio of criminals who get religious education. There is needed to make policies to reduce these casual factors to control crime in Pakistan. Key Words: Crime, Criminal Behavior, Criminal Tendency, Criminal Factors, Causes of Crime.

Significant impact of +105 A>C promoter polymorphism in IL-18 cytokine in patients with kidney stone disease

Background: Inflammation may be one cause of nephrolithiasis and the interleukin-18 (IL-18) encoding gene   polymorphisms at +105 A>C has been implicated in several inflammation related diseases. The aim of this study was to test whether IL-18+105 A>C polymorphisms could act as genetic marker for renal stone disease. A case-control study was conducted to observe the genotype distribution of IL-18+105 A>C, to elucidate the possible role of this SNP as risk factor in renal stone development and to examine its correlation with the clinico-pathologic variables.Methods: Using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique, we tested the genotype distribution of 160 nephrolithiasis patients in comparison with 200 disease free controls from the same geographical region.  Results: We observed significant differences of IL-18+105 A to C between the controls and patients with odds ratio 5.4 (P = 0.001). The prevalence of the variant genotypes AC + CC in the patients was higher than that in the controls (45% v/s 30%) and showed a significant association (P = 0.003). Moreover, the frequency per copy of the C allele of IL-18+105 A>C was found to be implicated more in patient group 0.27 as against only 0.16 in controls (P = 0.0003). Further, males and subjects with C is implicated in renal stone disease, and that the rare, C related allele is connected with higher susceptibility to nephrolithiasis.

Metabolic remodeling of white adipose tissue in obesity

Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇o2, V̇co2, and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity

Resource allocation within the National AIDS Control Program of Pakistan: a qualitative assessment of decision maker's opinions

BACKGROUND: Limited resources, whether public or private, demand prioritisation among competing needs to maximise productivity. With a substantial increase in the number of reported HIV cases, little work has been done to understand how resources have been distributed and what factors may have influenced allocation within the newly introduced Enhanced National AIDS Control Program of Pakistan. The objective of this study was to identify perceptions of decision makers about the process of resource allocation within Pakistan's Enhanced National AIDS Control Program. METHODS: A qualitative study was undertaken and in-depth interviews of decision makers at provincial and federal levels responsible to allocate resources within the program were conducted. RESULTS: HIV was not considered a priority issue by all study participants and external funding for the program was thought to have been accepted because of poor foreign currency reserves and donor agency influence rather than local need. Political influences from the federal government and donor agencies were thought to manipulate distribution of funds within the program. These influences were thought to occur despite the existence of a well-laid out procedure to determine allocation of public resources. Lack of collaboration among departments involved in decision making, a pervasive lack of technical expertise, paucity of information and an atmosphere of ad hoc decision making were thought to reduce resistance to external pressures. CONCLUSION: Development of a unified program vision through a consultative process and advocacy is necessary to understand goals to be achieved, to enhance program ownership and develop consensus about how money and effort should be directed. Enhancing public sector expertise in planning and budgeting is essential not just for the program, but also to reduce reliance on external agencies for technical support. Strengthening available databases for effective decision making is required to make financial allocations based on real, rather than perceived needs. With a large part of HIV program funding dedicated to public-private partnerships, it becomes imperative to develop public sector capacity to administer contracts, coordinate and monitor activities of the non-governmental sector

Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities

Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related pro-teins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer

Background: The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene. Materials and methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100. Results: hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare ‘A’ allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.16, p = 0.001). Conclusions: It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer

HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country