Evaluation of hypertension control among hemodialysis patients in Pakistan: a prospective follow-up study.

BACKGROUND: Hypertension is highly prevalent and uncontrolled among hemodialysis patients. In Pakistan published data does not provide enough information about the management and factors associated with uncontrolled hypertension in hemodialysis patients. OBJECTIVE: This study was conducted to evaluate the factors influencing the pharmacotherapeutic management and control of hypertension in hemodialysis patients. METHODS: A prospective follow-up study was conducted on hemodialysis patients who were enrolled at study sites between 1 June 2020 and 31 December 2020. The predialysis blood pressure (BP) readings were recorded as mean SBP and DBP at baseline and for each of 6 months. Multivariate analyses were applied to analyze the factors associated with uncontrolled hypertension in hemodialysis patients. RESULTS: The average predialysis BP (SBP and DBP) of study participants at baseline visit was 158.41 and 87.22 mmHg respectively. After 6 months the study participants have 150.27 mmHg and 80.03 mmHg average predialysis SBP and DBP respectively. Only 28.1% of hemodialysis patients were on target BP after 6 months. Results of multivariate analysis have shown that the use of beta-blockers and calcium channel blockers (CCBs) were significantly associated with hypertension control at baseline [odds ratio (OR) = 1.432, P value = 0.034] (OR = 1.499, P value = 0.045) and at after 6 months (OR = 2.824, P value = 0.015) (OR = 1.883, P value = 0.032). CONCLUSION: This study revealed that among the antihypertensive drugs, CCBs and beta-blockers provided better management in controlling hypertension among hemodialysis patients.

Biological synthesis of hybrid silver nanoparticles by Periploca aphylla Dcne. From nanotechnology to biotechnology applications.

Nanotechnology is one of the advanced technologies that have almost universal implications in every field of science. The importance is due to the unique properties of nanoparticles; however, green synthesized nanoparticles are considered eco-friendly. The current project was rationalized to prepare green-synthesized biogenic Periploca aphylla Dcne. silver nanoparticles (Pe-AgNPs) and poly (ethylene glycol) methacrylate coated AgNPs nanocomposites (PEGMA-AgNPs) with higher potential for their application in plant tissue culture for enhancing the biomass of Stevia rebaudiana calli. The increased biomass accumulation (17.61 g/3 plates) was observed on a medium containing virgin Pe-AgNPs 40th days after incubation, while the maximum increase was found by supplementing virgin Pe-AgNPs and PEGMA capped AgNPs (19.56 g/3 plates), compared with control (12.01 g/3 plates). In this study, PEGMA capped AgNPs supplementation also induced the maximum increase in total phenolics content (2.46 mg GAE/g-FW), total flavonoids content (3.68 mg QE/g-FW), SOD activity (53.78 U/ml protein), GSH content (139.75 µg/g FW), antioxidant activity (54.3 mg AAE/g FW), FRAP (54 mg AAE/g FW), and DPPH (76.3%) in S. rebaudiana calli compared with the control. It was concluded that virgin Pe-AgNPs and PEGMA capped AgNPs (hybrid polymer) are potent growth regulator agents and elicitors that can be exploited in the biotechnology field for growth promotion and induction of essential bioactive compounds and secondary metabolites from various commercially important and medicinally valuable plants such as S. rebaudiana without laborious field cultivation.

Biological Synthesis of Silver Nanoparticles by Amaryllis vittata (L.) Herit: From Antimicrobial to Biomedical Applications.

The current study sought to synthesize silver nanoparticles (AgNPs) from Amaryllis vittata (L.) leaf and bulb extracts in order to determine their biological significance and use the toxic plants for human health benefits. The formation of silver nanoparticles was detected by a change in color from whitish to brown for bulb-AgNPs and from light green to dark brown for leaf-AgNPs. For the optimization of silver nanoparticles, various experimental physicochemical parameters such as pH, temperature, and salt were determined. UV-vis spectroscopy, Fourier transform infrared spectroscopy, X-ray dispersion spectroscopy, scanning electron microscopy, and energy dispersion spectroscopy analysis were used to characterize nanoparticles. Despite the fact that flavonoids in plant extracts were implicated in the reduction and capping procedure, the prepared nanoparticles demonstrated maximum absorbency between 400 and 500 nm. SEM analysis confirmed the preparation of monodispersed spherical crystalline particles with fcc structure. The bioinspired nanoparticles were found to show effective insecticidal activity against Tribolium castaneum and phytotoxic activity against Lemna aequincotialis. In comparison to plant extracts alone, the tested fabricated nanoparticles showed significant potential to scavenge free radicals and relieve pain. Antibacterial testing against human pathogenic strains, i.e., Escherichia coli and Pseudomonas aureginosa, and antifungal testing against Aspergillus niger revealed the significant potential for microbe resistance using AgNPs. As a result of the findings, the tested silver nanoparticles demonstrated promising potential for developing new and effective pharmacological and agricultural medications. Furthermore, the effects of biogenic AgNPs on an in vitro culture of Solanum tuberosum L. plants were investigated, and the findings indicated that bulb-AgNPs and leaf-AgNPs produced biomass and induced antioxidants via their active constituents. As a result, bulb-AgNPs and leaf-AgNPs may be recommended for use in Solanum tuberosum L. tissue culture for biomass fabrication and metabolic induction.

Investigation of the binding and dynamic features of A.30 variant revealed higher binding of RBD for hACE2 and escapes the neutralizing antibody: A molecular simulation approach.

With the emergence of Delta and Omicron variants, many other important variants of SARS-CoV-2, which cause Coronavirus disease-2019, including A.30, are reported to increase the concern created by the global pandemic. The A.30 variant, reported in Tanzania and other countries, harbors spike gene mutations that help this strain to bind more robustly and to escape neutralizing antibodies. The present study uses molecular modelling and simulation-based approaches to investigate the key features of this strain that result in greater infectivity. The protein-protein docking results for the spike protein demonstrated that additional interactions, particularly two salt-bridges formed by the mutated residue Lys484, increase binding affinity, while the loss of key residues at the N terminal domain (NTD) result in a change to binding conformation with monoclonal antibodies, thus escaping their neutralizing effects. Moreover, we deeply studied the atomic features of these binding complexes through molecular simulation, which revealed differential dynamics when compared to wild type. Analysis of the binding free energy using MM/GBSA revealed that the total binding free energy (TBE) for the wild type receptor-binding domain (RBD) complex was -58.25 kcal/mol in contrast to the A.30 RBD complex, which reported -65.59 kcal/mol. The higher TBE for the A.30 RBD complex signifies a more robust interaction between A.30 variant RBD with ACE2 than the wild type, allowing the variant to bind and spread more promptly. The BFE for the wild type NTD complex was calculated to be -65.76 kcal/mol, while the A.30 NTD complex was estimated to be -49.35 kcal/mol. This shows the impact of the reported substitutions and deletions in the NTD of A.30 variant, which consequently reduce the binding of mAb, allowing it to evade the immune response of the host. The reported results will aid the development of cross-protective drugs against SARS-CoV-2 and its variants.

Hybridization of green synthesized silver nanoparticles with poly(ethylene glycol) methacrylate and their biomedical applications.

In the present research, a rapid, simple and efficient green method is used for the incorporation of silver nanoparticles (AgNPs) into poly(ethylene glycol) methacrylate (PEGMA) to create biocatalysts with excellent properties for pharmaceutical purpose. In the first phase, Caralluma tuberculata capped AgNPs (Ca-AgNPs) were prepared using green synthetic approach and in the second phase Caralluma tuberculata capped AgNPs were hybridized with poly(ethylene glycol) methacrylate to form PEGMA-AgNPs. Both the virgin (naked or uncapped) and polymer-capped materials were characterized spectroscopically and their results were compared. Fourier transform infrared spectroscopy showed no new peak after the capping procedure, showing that only physical interactions takes place during capping. After PEGMA capping, the spectra of the AgNPs red shifted (from 450 nm to 520 nm) and the overall particle size of AgNPs increased. Catalytic activity of the nanoparticles and hybrid system were tested by choosing the catalytic reduction of 4-nitrophenol (4-NP) as a model reaction. Both synthesized NPs and polymer capped NPs exhibits catalytic activity for the reduction of 4-NP to 4-aminophenol. The polymer hybrid exhibits remarkable antiproliferative, antioxidant, cytotoxic, antidiabetic and antileishmanial activities.

Expertise based skills management system to support resource allocation.

Skills Management is an essential concept of human resource management in which a skill inventory may be created for each employee and managers can assign tasks to workers based on worker's abilities. This concept is not fully practiced for two reasons: i) employee's skills are not effectively evaluated and documented, ii) tool support is deficient to manage this complex task. Ineffective skill management of an organization fizzle tasks assigned to the incompetent employees and this may lead to project failure. To fill up this gap, a survey is conducted across various software organizations to find out the best practices for the skill management and to gather requirements for skills management framework. Based on survey findings, a mathematical framework is proposed that calculates the soft and hard skills of employees automatically based on time and achievements as skill increases or decreases over time. In this framework, the Skills Calculation Engine (SCE) is developed for the managers to enhance the capacity of appropriate decisions making in assigning tasks to the rightly skilled workers. This framework is also useful for organizations as it can increase profitability as tasks are assigned to the most appropriate employees. The SCE is implemented as a Windows-based application to calculate skills, store skills in skills inventory, and assign tasks based on an employee's skills. The skills management tool is evaluated in a facilitated workshop; furthermore, a feature-wise comparison of the tool is also made with existing tools.

HantavirusesDB: Vaccinomics and RNA-based therapeutics database for the potentially emerging human respiratory pandemic agents.

Hantaviruses are etiological agents of several severe respiratory illnesses in humans and their human-to-human transmission has been reported. To cope with any potential pandemic, this group of viruses needs further research and a data platform. Therefore, herein we developed a database "HantavirusesDB (HVdb)", where genomics, proteomics, immune resource, RNAi based therapeutics and information on the 3D structures of druggable targets of the Orthohantaviruses are provided on a single platform. The database allows the researchers to effectively map the therapeutic strategies by designing multi-epitopes subunit vaccine and RNA based therapeutics. Moreover, the ease of the web interface allow the users to retrieve specific information from the database. Because of the high quality and excellent functionality of the HVdb, therapeutic research of Hantaviruses can be accelerated, and data analysis might be a foundation to design better treatment strategies targeting the hantaviruses. The database is accessible at http://hvdb.dqweilab-sjtu.com/index.php.

Genome-wide screening of vaccine targets prioritization and reverse vaccinology aided design of peptides vaccine to enforce humoral immune response against Campylobacter jejuni.

Campylobacter jejuni, gram-negative bacteria, is an infectious agent of foodborne disease-causing bloody diarrhea, abdominal pain, fever, Guillain-Barré syndrome (GBS) and Miller Fisher syndrome in humans. Campylobacter spp. with multidrug resistance to fluoroquinolones, tetracycline, and erythromycin are reported. Hence, an effective vaccine candidate would provide long-term immunity against C. jejuni infections. Thus, we used a subtractive proteomics pipeline to prioritize essential proteins, which impart a critical role in virulence, replication and survival. Five proteins, i.e. Single-stranded DNA-binding protein, UPF0324 membrane protein Cj0999c, DNA translocase FtsK, 50S ribosomal protein L22, and 50S ribosomal protein L1 were identified as virulent proteins and selected for vaccine designing. We reported that the multi-epitopes subunit vaccine based on CTL, HTL and B-cell epitopes combination possess strong antigenic properties and associates no allergenic reaction. Further investigation revealed that the vaccine interacts with the immune receptor (TLR-4) and triggered the release of primary and secondary immune factors. Moreover, the CAI and GC contents obtained through codon optimization were reported to be 0.93 and 53% that confirmed a high expression in the selected vector. The vaccine designed in this study needs further scientific consensus and will aid in managing C. jejuni infections.

The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD-ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective.

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2-RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.

Multi-objective regression test suite optimization using three variants of adaptive neuro fuzzy inference system.

In the process of software development, regression testing is one of the major activities that is done after making modifications in the current system or whenever a software system evolves. But, the test suite size increases with the addition of new test cases and it becomes in-efficient because of the occurrence of redundant, broken, and obsolete test cases. For that reason, it results in additional time and budget to run all these test cases. Many researchers have proposed computational intelligence and conventional approaches for dealing with this problem and they have achieved an optimized test suite by selecting, minimizing or reducing, and prioritizing test cases. Currently, most of these optimization approaches are single objective and static in nature. But, it is mandatory to use multi-objective dynamic approaches for optimization due to the advancements in information technology and associated market challenges. Therefore, we have proposed three variants of self-tunable Adaptive Neuro-fuzzy Inference System i.e. TLBO-ANFIS, FA-ANFIS, and HS-ANFIS, for multi-objective regression test suites optimization. Two benchmark test suites are used for evaluating the proposed ANFIS variants. The performance of proposed ANFIS variants is measured using Standard Deviation and Root Mean Square Error. A comparison of experimental results is also done with six existing methods i.e. GA-ANFIS, PSO-ANFIS, MOGA, NSGA-II, MOPSO, and TOPSIS and it is concluded that the proposed method effectively reduces the size of regression test suite without a reduction in the fault detection rate.

HPLC profiling of Mimosa pudica polyphenols and their non-invasive biophysical investigations for anti-dermatoheliotic and skin reinstating potential.

Plant-derived polyphenols are known to have promising biological activities including antioxidant and antityrosinase and may be a potential candidate for anti-dermatoheliotic remedy. The present study was performed to investigate the polyphenolic contents of Mimosa pudica (MP) seed extract and its anti-dermatoheliotic potential using non-invasive biophysical techniques after developing a stable topical emulgel formulation. Moreover, its in-vitro cytotoxicity was also evaluated using normal Human keratinocytes (HaCat cells) to rule out any cellular incompatibility. The results revealed that MP seed extract, constituted with a number of polyphenolic compounds, has very good antioxidant and anti-tyrosinase potential. There were significant positive effects (p ≤ 0.05) invoked by its topical emulgel formulation on various dermatoheliotic associated skin parameters like erythema, melanin, elasticity, hydration, and sebum as compared to placebo. In the meantime, it was also found to be biocompatible and did not show any effect on HaCat cell viability and structure. In conclusion, the topical emulgel preparation loaded with MP seed extract could be a great strategy to deal with dematoheliosis.

Erectile Dysfunction: An Underestimated Presentation in Patients with Diabetes Mellitus.

INTRODUCTION: Erectile dysfunction (ED) is a common complication of diabetes mellitus. ED, like other sexual disorders, is often under-reported and under-diagnosed, as talking about sex is considered a taboo in our society. METHODOLOGY: All the male patients with diabetes mellitus (with or without active complaints of ED) attending Medicine or Psychiatry OPD of the institute during the study period were enrolled in the study. They were investigated for their body-mass index (BMI), blood sugar and lipid profile; and were assessed on HAM-D, General Health Questionnaire-30, IIEF, sex myth checklist and QOL Instrument for Indian Diabetes Patients (QOLID). RESULT AND DISCUSSION: In the present study, a total of 138 diabetic patients were assessed, and those with severe ED were found to have poor glycemic control, worse lipid profile, higher body mass index, later age of onset, and longer duration of untreated diabetes as compared to non-ED patients. ED patients also scored higher on depression rating scale, had poorer general health and quality of life (QOL). Early attention to ED in diabetic patients can improve general health and QOL of the sufferers. CONCLUSION: DM patients with poor glycemic control and advanced age have a higher propensity of developing severe ED, which further deteriorates the already compromised health & QOL.

MR Imaging Measures of Intracranial Atherosclerosis in a Population-based Study.

Purpose To implement a magnetic resonance (MR) imaging protocol to measure intracranial atherosclerotic disease (ICAD) in a population-based multicenter study and report examination and reader reliability of these MR imaging measurements and descriptive statistics representative of the general population. Materials and Methods This prospective study was approved by the institutional review boards and compliant with HIPAA. Atherosclerosis Risk in Communities (ARIC) study participants (n = 1980) underwent brain MR imaging from 2011 to 2013 at four ARIC sites. Imaging included three-dimensional black-blood MR imaging and time-of-flight MR angiography. One hundred two participants returned for repeat MR imaging to estimate examination and reader variability. Plaque presence according to vessel segment was recorded. Quantitative measurements included lumen size and degree of stenosis, wall and/or plaque thickness, area and volume, and normalized wall index for each vessel segment. Reliability was assessed with percentage agreement, κ statistics, and intraclass correlation coefficients. Results Of the 1980 participants, 1755 (mean age, 77.6 years; 1026 women [59%]; 1234 white [70%]) completed examinations with adequate to excellent image quality. The weighted ICAD prevalence was 34.4% (637 of 1755 participants) and was higher in men than women (38.5% [302 of 729 participants] vs 31.7% [335 of 1026 participants], respectively; P = .012) and in African Americans compared with whites (41.1% [215 of 518 participants] vs 32.4% [422 of 1234 participants], respectively; P = .002). Percentage agreement of plaque identification per participant was 87.0% (interreader estimate), 89.2% (intrareader estimate), and 89.9% (examination estimate). Examination and reader reliability ranged from fair to good (κ, 0.50-0.78) for plaque presence and from good to excellent (intraclass correlation coefficient, 0.69-0.99) for quantitative vessel wall measurements. Conclusion Vessel wall MR imaging is a reliable tool for identifying and measuring ICAD and provided insight into ICAD distribution across a U.S. community-based population. (©) RSNA, 2016 Online supplemental material is available for this article.

Patterns and Implications of Intracranial Arterial Remodeling in Stroke Patients.

BACKGROUND AND PURPOSE: Preliminary studies suggest that intracranial arteries are capable of accommodating plaque formation by remodeling. We sought to study the ability and extent of intracranial arteries to remodel using 3-dimensional high-resolution black blood magnetic resonance imaging and investigate its relation to ischemic events. METHODS: Forty-two patients with cerebrovascular ischemic events underwent 3-dimensional time-of-flight magnetic resonance angiography and contrast-enhanced black blood magnetic resonance imaging examinations at 3 T for intracranial atherosclerotic disease. Each plaque was classified by location (eg, posterior versus anterior circulation) and its likelihood to have caused a stroke identified on magnetic resonance imaging (culprit, indeterminate, or nonculprit). Lumen area, outer wall area, and wall area were measured at the lesion and reference sites. Plaque burden was calculated as wall area divided by outer wall area. The arterial remodeling ratio (RR) was calculated as outer wall area at the lesion site divided by outer wall area at the reference site after adjusting for vessel tapering. Arterial remodeling was categorized as positive if RR>1.05, intermediate if 0.95≤RR≤1.05, and negative if RR<0.95. RESULTS: One hundred and thirty-seven plaques were identified in 42 patients (37% [50] posterior and 63% [87] anterior). Compared with anterior circulation plaques, posterior circulation plaques had a larger plaque burden (77.7±15.7 versus 69.0±14.0; P=0.008), higher RR (1.14±0.38 versus 0.95±0.32; P=0.002), and more often exhibited positive remodeling (54.0% versus29.9%; P=0.011). Positive remodeling was marginally associated with downstream stroke presence when adjusted for plaque burden (odds ratio 1.34, 95% confidence interval: 0.99-1.81). CONCLUSIONS: Intracranial arteries remodel in response to plaque formation, and posterior circulation arteries have a greater capacity for positive remodeling and, consequently, may more likely elude angiographic detection. Arterial remodeling may provide insight into stroke risk.

Paper eating: An unusual obsessive-compulsive disorder dimension.

There is a lot of diversity in the medical realm; where unspecified sign and symptoms might confuse and force even experienced clinicians to commit mistakes. Paper eating is presently included in pica, but certain rare compulsions may mimic this and cause confusion for unsuspecting observers. We report a case of paper eating as a manifestation of compulsion in a 15-year-old girl, and reiterate that missing on rare presentations might cause the patient sufferings from inadvertent pharmacological treatment efforts.

Superficial temporal artery calcification in patients with end-stage renal disease: Association with vascular risk factors and ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Extracranial superficial temporal artery (STA) calcification is an unusual finding seen in patients with chronic kidney disease and has unknown ramifications with respect to intracranial ischemic disease. We sought to determine the association between the risk factors for vascular calcification and this rare phenomenon, in patients with chronic renal failure, and to assess the coexistence of cerebral ischemia. MATERIALS AND METHODS: Medical records and laboratory data on risk factors for vascular calcification were retrospectively retrieved for 453 patients with a discharge diagnosis of end-stage renal disease (ESRD). CT head examinations were reviewed to identify and associate STA calcification with 1) risk factors for the vascular calcification, 2) intracranial artery calcification, and 3) cerebral ischemia (white matter and/or cortical ischemic changes). RESULTS: STA calcification was present in 9.9% (45/453) of the studied cohort. The prevalence of cerebral ischemia was 24.4% (11/45) in patients with STA calcification and 9.3% (38/408) in patients without it. Diabetes mellitus (OR: 2.56, 95% CI: 1.059-6.208; P=0.037) was independently associated with the risk of STA calcification. The risk of cerebral ischemia, however, was not related to STA calcification (P=0.221). CONCLUSION: The presence of diabetes mellitus is important in describing the risk of STA calcification in patients with ESRD, whereas age, gender, hypertension, serum calcium, serum phosphate, or serum hemoglobin levels are not. The risk of cerebral ischemia is not related to STA calcification but has the strongest association with diabetes mellitus.