Receptor modification as a therapeutic approach against viral diseases

Poliovirus causes flaccid paralysis through the destruction of motor neurons in the CNS. Susceptibility to its infection is mainly due to the interaction in between the surface capsid proteins and its receptors on the host cell surface, important for binding, penetration and other necessary events during early infection. Receptor modification is a new approach to treat viral diseases by the modification of target proteins structure. Binding domains are modified in an effective way to make it difficult for the virus to recognize it. In this study, tolerant and intolerant induced mutations in the poliovirus receptor, VP1 and VP2 were identified and substituted in the seed sequence to get the modified versions. Substitutions causing changes in initial folding were short listed and further analyzed for high level folding, physiochemical properties and interactions. Highest RMSD values were observed in between the seed and the mutant K90F (3.265 Å) and Q130W (3.270Å) respectively. The proposed substitutions were found to have low functional impact and thus can be further tested and validated by the experimental researchers. Interactions analyses proved most of the substitutions having decreased affinity for both the VP1 and VP2 and thus are of significant importance against poliovirus. This study will play an important role for bridging computational biology to other fields of applied biology and also will provide an insight to develop resistance against viral diseases. It is also expected that same approach can also be applicable against other viruses like HCV, HIV and other in near future

Abberent expression analysis of LMNA gene in hutchinson-gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is caused by de novo dominant point mutations of the genes encoding nuclear lamina proteins, leading towards premature aging. A protein sequence is subjected to mutations in nature which can affect the function and folding pattern of the protein by different ways. Mutations involved in HGPS were identified and were substituted in the seed sequence retrieved from the UniProt database to get the mutated versions. Tertiary structure of the Lamin A protein was previously unpredicted so was performed for all the mutated as well as for the seed protein to analyze the effects of mutations on the protein structure, folding and interactions. All the predicted models were refined and validated through multiple servers for multiple parameters. The validated 3D structure of seed protein was then successfully submitted to the Protein Model Database and was assigned with the PMDB ID PM0077829. All the predicted structures were superimposed with a root mean square deviation value of 7.0 Å and a high Dali Z-score of 1.9. It was observed that mutations affected physiochemical properties as well as instability index and thus is affecting the domains in specific and the whole structure in general. It was further analyzed that HGPS is the result of affected Lamin a protein interactions with other integral and binding proteins in the inner nuclear membrane affecting the link in between the nuclear membrane and the network of the lamina

Association of Type D personality with cardiovascular disease and its prognosis

Objective: To evaluate the association of Type D personality with cardiovascular disease and its prognosis. Methodology: This cross sectional study study was conducted in cardiology department of MBBS medical college Mirpur, from February 2019 to February 2020 in a period of one year. A total of 281 patients with cardiovascular diseases were included. Demographic information and risk factors were noted. Screening for metabolic syndrome was done using international diabetes federation criteria based upon central obesity. The assessment of type D personality was made through DS-14, type D scale, which is the most widely used instrument for type D personality measurement. In which all the 14 items are score on a 5-point Likert scale. Results: There were 77 (27.40%) patients having type D personality, with significantly less mean age (45.36 ± 6.2 vs. 53.45 ± 9.6) in comparison to patients without type D personality. No significant (p-value > 0.05) difference was noted in gender, education, occupation and marital status of the patients having type D personality. The rate of diabetes mellitus (44.46% vs. 37.25%), hypertension (59.74% vs. 47.06%), smoking status (62.34% vs. 53.43%) and metabolic syndrome (48.05% vs. 40.69%) were similar in both groups. The mean values of systolic (124.53 ± 12.35 vs. 116.28 ± 14.30, p-value = 0.000) and diastolic (78.44 ± 6.92 vs. 74.62 ± 7.48, p-value = 0.0001) blood pressure were significantly higher in patients having type D personality. Conclusions: A considerable number of cardiac patients in our study had type D personality trait. This trait was more common in younger age and male patients showing raised levels of blood pressure and HDL cholesterol. Key words: Cardiovascular disease, Type D personality, low HDL cholesterol, Prognosi

Sequence and structure based assessment of nonsynonymous SNPs in hypertrichosis universalis

Hairs are complex structures, making a protective layer and serves different biological functions. TRPS1, a transcription factor is one of the candidate genes causing congenital hypertrichosis, an excessive hair growth at inappropriate body parts. SNPs of TRPS1 were retrieved from dbSNP which were screened by SIFT and PolyPhen servers based on their functional impacts. Out of the screened SNPs, rs181507248 and rs146506752 were predicted as intolerant and damaging by both the servers. The predicted tertiary structure of the native TRPS1 after refinement and validation was successfully submitted to the Protein Model Database and was assigned with PMDB ID PM0077843, as it was previously unpredicted. It was observed through the structure based analysis that, the SNPs rs181507248 and rs146506752 caused significant changes in the secondary and tertiary structures as well as the physiochemical properties of TRPS1 protein. It can thus be concluded that the changed properties due to these single nucleotide polymorphisms effect the interactions of TRPS1 which result in congenital hypertrichosis

Ferritin Is a Marker of Inflammation rather than Iron Deficiency in Overweight and Obese People

Background. In clinical practice, serum ferritin is used as a screening tool to detect iron deficiency. However, its reliability in obesity has been questioned. Objectives. To investigate the role of ferritin in overweight and obese people, either as a marker of inflammation or iron deficiency. Methods. On the basis of body mass index (BMI), 150 participants were divided into three equal groups: A: BMI 18.5–25 kg/m2, B: BMI 25–30 kg/m2, and C: BMI>30 kg/m2. Serum iron, total iron binding capacity (TIBC), transferrin saturation, ferritin, C-reactive protein, and hemoglobin (Hb) were measured for each participant and analyzed through SPSS version 16. One-way ANOVA and Pearson’s correlation tests were applied. Results. Ferritin was the highest in group C (M=163.48±2.23, P<0.001) and the lowest in group A, (M=152.78±1.81, P<0.001). Contrarily to ferritin, transferrin was the lowest in group C, (M=30.65±1.39, P<0.001) and the highest in group A, (M=38.66±2.14, P<0.001). Ferritin had a strong positive correlation with both BMI (r=0.86, P<0.001) and CRP (r=0.87, P<0.001) and strong negative correlation with Hb, iron, TIBC, and transferrin saturation (P<0.001). Conclusion. Ferritin is a marker of inflammation rather than iron status in overweight and obese people. Complete iron profile including transferrin, rather than serum ferritin alone, can truly predict iron deficiency in such people

Assessment of ICT Facilities in the Public Libraries of Khyber Pakhtunkhwa: A Descriptive Study

Purpose: This study aimed to review the ICT facilities in the public libraries of Khyber Pakhtunkhwa. The specific objectives were to see the status of ICT resources, check the ICT tools used in delivering services, and point out problems faced by the public libraries in developing ICT infrastructure. Research Design and Methodology: The study\u27s population consisted of public libraries in the province of Khyber Pakhtunkhwa. The census-based approach was employed, and data was gathered from library heads via questionnaire. The collected data was analyzed using the Statistical Package for Social Sciences version 22. Findings: It was found that most of the libraries did not have electronic information resources like e-books, theses and dissertations and access to the HEC database. Most libraries lacked ICT equipment, including microfilming machines, barcode readers, external hard drives, digital cameras, television and multimedia projectors. The majority of libraries did not use ICT applications like Twitter, YouTube, LinkedIn, Flickr and RSS for library services. The key problems identified by libraries while developing ICT infrastructure were inadequate e-resources, limited staff, lack of financial resources, insufficient IT staff and non-availability of standard library software. Implications: The study\u27s findings are beneficial to the government and higher library authorities. The critical point to be considered includes 1) LIS professionals and IT staff be recruited and trained in modern learning, education and communication skills, 2) sufficient funds should be provided to libraries to develop ICT infrastructure 3) digital resources should be acquired, and 4) the librarians should have the power and freedom to spend the budget based on the users\u27 needs. Originality: The study is unique because this is the first study in the country to assess the ICT facilities of public libraries. It will fill the literature gap and guide the researchers to do similar studies across the country. Keywords: ICT Infrastructure, ICT tools and applications, ICT Facilities, Public Libraries, Khyber Pakhtunkhwa, Pakista

Neurological health profile in pakistan – A health systems based needs assessment

The aims of our study were to develop a neurological health profile in Pakistan from a health systems perspective, ascertain the readiness of neurology with regards to Sustainable Development Goals, and proffer recommendations for policy advocacy and planning in neurology

Iris recognition Using Fast Walsh Hadamard Transform Based feature Space

The significance of Iris detection and recognition in area of bioinformatics and pattern recognition has been increased from last few decades. Looking at the importance of Iris detection and recognition, we propose a robust, stable and reliable computational model. Features are extracted from iris images using two different approaches such as Hilbert transform and Fast wavelet Hadamard Transform (FWHT).Random forest is used as a classification algorithm. 5-folds cross validation test is applied to evaluate the performance of K-nearest neighbor. Among three feature spaces, FWHT feature space has achieved promising results. The success rate of K-nearest neighbor on FWHT feature space is 94.4%. After examining the results, we have observed that our model might be useful and helpful for iris detection in future work

INCIDENCE OF NEPHROPATHY IN DIABETIC PATIENTS

Objective: To determine the burden of diabetes mellitus (type I and II) and incidence of nephropathy in diabetic patients Peshawar. Methodology: A cross-sectional study carried out on known diabetic patients in Peshawar. This study was conducted on 267 diabetic patients in duration of one year (from January 2018 to February 2019). Both diabetes mellitus type I and type II patients was included in study. Informed consent was taken from all patients before sample collection. Collected samples were further processed in pathology department. Collected data was analyzed by statistical package for social sciences software version 21. Results: Out of total 267 diabetic patients, diabetes mellitus type I was observed in 43 (16.1%) patients while diabetes mellitus type II was examined in 224 (83.9%) patients. The incidence of nephropathy was found in 33 (12.4%) patients with highest percentage in female (57.5%). Conclusion: Diabetes mellitus type II was three times more common than diabetes mellitus type I. Nephropathy incidence is manageable but high risk to female diabetic patients. Key words: Incidence, Nephropathy, Diabetes mellitus, Peshawar

Plant bioactive molecules bearing glycosides as lead compounds for the treatment of fungal infection: A review

Despite therapeutic advancement in the treatment of fungal infections, morbidity and mortality caused by these infections are still very high. There are approximately 300 fungal species that are infectious and can cause a variety of diseases. At present, several synthetic antifungal drugs are in clinical practice, many of them, however, are vulnerable to multidrug-resistant strains of microbes, and thus compromising the overall treatment outcomes. Glycosides are naturally occurring plant secondary metabolites with important therapeutic potential and clinical utility. The aim of this review was to focus on the antifungal effects of glycosides in preclinical studies with possible mechanism(s) wherein described. Published research show significant susceptibility of different fungi towards phytoglycosides, mediated through multiple mechanisms. Further detailed studies are needed to explain the clinical applications and limitations of these glycosides