Progression of blood-borne viruses through bloodstream: A comparative mathematical study.

BACKGROUND AND OBJECTIVES: Blood-borne pathogens are contagious microorganisms that can cause life-threatening illnesses, and are found in human blood. It is crucial to examine how these viruses spread through blood flow in the blood vessel. Keeping that in view, this study aims to determine how blood viscosity, and diameter of the viruses can affect the virus transmission through the blood flow in the blood vessel. A comparative study of bloodborne viruses (BBVs) such as HIV, Hepatitis B, and C, has been addressed in the present model. A couple stress fluid model is used to represent blood as a carrying medium for virus transmission. The Basset-Boussinesq-Oseen equation is taken into account for the simulation of virus transmission. METHODS: An analytical approach to derive the exact solutions under the assumption of long wavelength and low Reynolds number approximations is employed. For the computation of the results, a segment (wavelength) of blood vessels about 120 mm with wave velocities in the range of 49 - 190 mm/sec are considered, where the diameter of BBVs ranges from 40-120 nm. The viscosity of the blood varies from 3.5-5.5 × 10-3Ns/m2 which affect the virion motion having a density range 1.03 - 1. 25 g/m3. RESULTS: It shows that the Hepatitis B virus is more harmful than other blood-borne viruses considered in the analysis. Patients with high blood pressure are highly susceptible for transmission of BBVs. CONCLUSIONS: The present fluid dynamics approach for virus spread through blood flow can be helpful in understanding the dynamics of virus propagation inside the human circulatory system.

Alteration in membrane-based pumping flow with rheological behaviour: A mathematical model.

BACKGROUND AND OBJECTIVE: Blood is complex fluids exhibits the non-Newtonian characters and rheological properties of the blood vary person to person. Typically, the rheological properties of blood are very similar to Carreau fluids which is considered in the present model. The main objective of this study is to examine how a typical membrane-based pumping model will function with varying rheological properties (shear-thinning, Newtonian, and shear-thickening) of fluids. METHODS: A mathematical formulation is constructed for the membrane-based pumping model using the conservation principles of mass and momentum, and stress-strain relationship based on Carreau fluids model. Velocity slip condition is adopted for this model to discuss the possibility of fluids velocity at the wall surface. The perturbation method is employed to derive the series solution for the governing equations subjected to physical boundary conditions with suitable assumptions. RESULTS: From numerical results, it is found that the pressure inside the microchannel reduces for the shear-thinning fluid and increases for the shear-thickening fluid with increasing the Weissenberg. In the membrane region, the chaos of the flow field is occurred due to the local pressure gradient by the rhythmic membrane propagation. It is further reported that shear-driven flow is responsible for the decrement in fluid velocity. CONCLUSIONS: This model provides a framework for estimating the effects of rheological properties and velocity slip for membrane-based pumping model which help in designing the smart pumps for various needs in the fields of biomedical engineering and fluid industries.

Propagation of H1N1 virus through saliva movement in oesophagus: a mathematical model.

H1N1 (Swine flu) is caused by the influenza A virus which belongs to the Orthomyxoviridae family. Influenza A is very harmful to the elderly, and people with chronic respiratory disease and cardiovascular disease. Therefore, it is essential to analyse the behaviour of virus transmission through the saliva movement in oesophagus. A mathematical paradigm is developed to study the saliva movement under the applications of transverse magnetic field. Jeffrey fluid model is considered for saliva to show the viscoelastic nature. The flow nature is considered creeping and assumptions of long wavelength and low Reynolds number are adopted for analytical solutions. The Basset-Boussinesq-Oseen equation is employed to understand the propagation of H1N1 virus through saliva under the effect of applicable forces such as gravity, virtual mass, basset force, and drag forces. The suitable data for saliva, oesophagus and H1N1 virus are taken from the existing literature for simulation of the results using MATLAB software. From the graphical results, it is observed that the susceptibility to viral infections is less because the magnetic field reduces the motion of the virus particle. Further, the chances of infections in males are more as compared to females and children due to variation in viscosity of saliva. Such findings provide an understanding of the mechanics of the virus floating through the saliva (viscoelastic fluids) in the oesophagus.

Bioinspired Pumping Flow Driven by Rhythmic Membrane Propulsion in a Porous Medium.

Investigation concerning the bioinspired pumping flow of viscous fluids in the porous region using Darcy's law is demonstrated in the present article. The rhythmic membrane contraction propels fluids in the porous microchannel. The periodic contraction of the membrane is utilized in the present analysis to introduce the unique pumping mechanism. For small pattern, width to channel height ratio (i.e., the channel is substantially longer than its width) and at low Reynolds numbers, the governing equations are solved by an analytical approach. In light of porous effects, we noticed the implications of rheological limitations on pumping and trapping processes. The porosity has a dynamic role in the augmentation of membrane-based pumping. These outcomes may be productive in various bioengineering (drug delivery schemes) applications.

Evaluation of Resin Penetration Depth in Enamel Surface for Orthodontic Bonding Exposed to Five Types of Enamel Conditioning Methods: A Scanning Electron Microscopic Study.

AIMS AND OBJECTIVES: To evaluate the enamel surface depth of resin penetration for orthodontic bonding when exposed to five types of enamel conditioning methods using scanning electron microscope. MATERIALS AND METHODS: The sample comprised of 25 human extracted premolar teeth for orthodontic reasons. The samples are divided into 5 groups with each 5 teeth based on the enamel conditioning methods such as group A with 37% Phosphoric acid, group B with 10% Polyacrylic acid, group C with Self etch primer, group D with Laser etching and group E with air abrasion etching. All the samples in each group are bonded with metal brackets using Transbond XT Adhesive. After bonding, the teeth are sectioned mesiodistally using hard-tissue microtome and observed under scanning electron microscope at 500x and 3000x for the calculation of depth of resin penetration. RESULTS: The teeth etched with 37%phosphoric acid exhibited significantly greater depth of resin penetration (15.1µm) than do self-etch and polyacrylic acid. Laser etching has comparable penetration depth with that of acid etching. Air abrasion has got the least penetration of all groups. CONCLUSION: Comparing the enamel treated with these conditioning methods, the penetration of resin material into enamel are greater when it is treated with 37% Phosphoric acid than self-etch or laser etching.

Growth and liver histology of Channa punctatus exposed to a common biofertilizer.

Mustard oil cake (MOC) is widely used as biofertilizer in the field of agriculture and aquaculture. Channa punctatus was exposed to 0.42 g.L-1 sublethal concentration for 4, 7, 14, 21 and 28 days. Due to such exposure, body growth and histological changes in liver were observed. It was revealed that weight, length and breadth of fish were gradually increased with the days of exposure in compare to control fish, whereas, liver showed an increase in sinusoidal space and lipidosis during early days, followed by a recovery from the stress of MOC on the 28th day.

Validation of host-specific Bacteroidales quantitative PCR assays and their application to microbial source tracking of drinking water sources in the Kathmandu Valley, Nepal.

AIMS: To validate host-specific Bacteroidales assays to identify faecal-source contamination of drinking water sources in the Kathmandu Valley, Nepal. METHODS AND RESULTS: A total of 54 composite faecal-source samples were collected from human sewage, ruminants, pigs, dogs, chickens and ducks, which were analysed by quantitative polymerase chain reaction using human-specific (BacHum, HF183 SYBR, gyrB and HF183 TaqMan), ruminant-specific (BacCow and BacR), pig-specific (Pig2Bac and PF163) and dog-specific assays (BacCan SYBR). The BacHum, BacR and Pig2Bac assays were judged the best performing human-specific, ruminant-specific and pig-specific assays respectively. The BacCan SYBR assay highly cross-reacted with other species, resulting in poor performance. Furthermore, these validated assays were applied to microbial source tracking (MST) of 74 drinking water samples. Out of these, 20, 12 and 4% samples were judged contaminated by human, ruminant and pig faeces respectively. Detection ratios of human and ruminant faecal markers were relatively higher in built-up and agricultural areas respectively. CONCLUSION: BacHum, BacR and Pig2Bac assays were found suitable for MST and both, human and animal faecal contaminations of drinking water sources were common in the valley. SIGNIFICANCE AND IMPACT OF THE STUDY: MST could be an effective tool for preparing the faecal pollution strategies as these are site specific.

Admitting Deserving Medical Students from Rural and Disadvantaged: Patan Academy of Health Sciences' Approach.

BACKGROUND: Patan Academy of Health Sciences (PAHS) aims to produce physicians who would be able and willing to serve in the rural areas. Recognizing the critical importance of student selection strategy, among others, in achieving the program goals, it has adopted an innovative scheme for selecting medical students. This paper describes PAHS medical student selection scheme that favors enrollment of deserving applicants from rural and disadvantaged groups so as to help improve distribution of physicians in rural Nepal. METHODS: A student admission committee comprising a group of medical educators finalized a three-step student selection scheme linked with scholarships after reviewing relevant literatures and consultative meetings with experts within and outside Nepal. The committee did local validation of Personal Quality Assessment (PQA) that tested cognitive ability and personality traits, Admission OSPE (Objective Structured Performance Examination) that assessed non-cognitive attributes of applicants. It also provided preferential credits to applicants' socio-economic characteristics to favor the enrollment of deserving applicants from rural and disadvantaged groups through Social Inclusion Matrix (SIM). Three different categories of scholarship schemes namely Partial, Collaborative and Full were devised with Partial providing 50% and other two categories each providing 100% coverage of tuition fee. RESULTS: PAHS student selection scheme succeeded in enrolling more than half of its students from rural areas of Nepal, including about 10% of the students from that of the most backward region of the country. About one third of students were female and about the same were from public and community school. Sixty percent of students receive different categories of scholarships. CONCLUSIONS: Limited findings indicate the success of the selection scheme in enrolling high proportion of applicants from rural and disadvantageous groups and enable them to pursue study by providing scholarships.

Complete remission of nephrotic syndrome and acute kidney injury in crescentic IgA nephropathy: Role of mycophenolate sodium.

Optimal therapy and prognosis of crescentic-IgA nephropathy (C-IgAN) are not known. Reported treatment options for C-IgAN include combination of corticosteroids and cyclophosphamide for 6 months. The role of mycophenolate sodium in C-IgAN is unknown. We report a case of C-IgAN that was successfully treated with combination immunosuppressive therapy.

Prevalence of Extended Spectrum Beta-Lactamase Producing Klebsiella Pneumoniae Isolated From Urinary Tract Infected Patients.

BACKGROUND: Klebsiella pneumoniae, one of the bacterial agents associated with urinary tract infection has been often implicated as a major extended spectrum beta-lactamase (ESBL) producer in last few decades. This study was designed to assess the prevalence of ESBL producing Klebsiella pneumoniae in urinary isolates at a tertiary care hospital in Kathmandu, Nepal, from July to December 2014. METHODS: One thousand nine hundred eighty six mid-stream urine specimens were collected aseptically from the clinically suspected patients of urinary tract infections attending Capital Hospital and Research Center, Kathmandu. The samples were processed following standard guidelines as recommended by American Society for Microbiology (ASM) and the isolates including Klebsiella spp. were identified using the specific biochemical and sugar fermentation tests recommended by ASM. Antibiotic sensitivity testing was done by modified Kirby-Bauer disk diffusion method and interpreted following Clinical and Laboratory Standards Institute (CLSI) guidelines. Klebsiella pneumoniae isolates showing resistance upon initial screening with ceftriaxone (30 µg) disc were then confirmed for ESBL production by phenotypic confirmatory disc diffusion test (PCDDT) using ceftazidime (30 µg) and ceftazidime + clavulanic acid (30 µg + 10µg) and cefotaxime (30 µg) and cefotaxime + clavulanic acid (30 µg +10µg) disc as per CLSI guidelines. RESULTS: Out of a total 1986 specimens investigated, Escherichia coli was isolated in 309 (83.9%) and Klebsiella pneumoniae in 38 (10.3%) cases. Initial screening with ceftriaxone disc revealed 18 isolates of Klebsiella pneumoniae to be resistant. Further testing by PCDDT method confirmed 7 (18.4%) Klebsiella pneumoniae isolates to be ESBL producers. CONCLUSIONS: Compared to some earlier studies done in Nepal, higher prevalence of ESBL-producing Klebsiella pneumoniae was observed warranting a national surveillance for routine monitoring of ESBL producing Klebsiella pneumoniae isolates.

Effects of genotype, season, and nitrogen nutrition on gene expression and protein accumulation in wheat grain.

Six commercial U.K. cultivars of winter wheat selected to represent different abilities to partition nitrogen into grain protein were grown in replicated field trials at five different sites over three seasons. The proportion of LMW glutenin subunits decreased and the proportion of gliadins increased during grain development and in response to N application. Differences were observed between the proportions of LMW glutenin subunits and gliadins in low- and high-protein grain, these two fractions being decreased and increased, respectively. There was little effect of grain protein content on the proportions of either the HMW glutenin subunits or large glutenin polymers, which are enriched in these subunits, with the latter increasing during development in all cultivars. The proportion of total protein present in polymers in the mature grain decreased with increasing N level. Correlations were also observed between the abundances of gliadin protein transcripts and the corresponding proteins.

A study of viral hepatitis during pregnancy in Nepal Medical College Teaching Hospital.

The present study aimed to find out prevalence and severity of viral hepatitis during pregnancy in the department of Obstetrics and Gynaecology, Nepal Medical College Teaching Hospital. Out of 5602 pregnant women admitted in the ward from 2001-2007; viral hepatitis was seen in 29 cases. HBV was detected in 18/29 (62.0%), HEV in 6/29 (20.6%) and viral hepatitis of undetected serology was seen in 5/29 (17.2%). Serology was undetected in these cases because of financial constraints. The mortality rate was 8/29 (27.5%). Three out of eight cases who expired were HEV positive and five were of undetected serology. Seven out of 8 maternal deaths were in preterm gestation and undelivered. Fulminant hepatitis with hepatic encephalopathy was the commonest cause of death. Hepatitis E was the commonest etiological agent in those who had fulminant disease during pregnancy and was associated with high mortality rate.

Aerosol delivery of Akt controls protein translation in the lungs of dual luciferase reporter mice.

Lung cancer has emerged as a leading cause of cancer death in the world; however, most of the current conventional therapies are not sufficiently effective in altering the progression of disease. Therefore, development of novel treatment approaches is needed. Although several genes and methods have been used for cancer gene therapy, a number of problems such as specificity, efficacy and toxicity reduce their application. This has led to re-emergence of aerosol gene delivery as a noninvasive method for lung cancer treatment. In this study, nano-sized glucosylated polyethyleneimine (GPEI) was used as a gene delivery carrier to investigate the effects of Akt wild type (WT) and kinase deficient (KD) on Akt-related signaling pathways and protein translation in the lungs of CMV- LucR-cMyc-IRES-LucF dual reporter mice. These mice are a powerful tool for the discrimination between cap-dependent/-independent protein translation. Aerosols containing self-assembled nano-sized GPEI/Akt WT or GPEI/Akt KD were delivered into the lungs of reporter mice through nose-only-inhalation-chamber with the aid of nebulizer. Aerosol delivery of Akt WT caused the increase of protein expression levels of Akt-related signals, whereas aerosol delivery of Akt KD did not. Furthermore, dual luciferase activity assay showed that aerosol delivery of Akt WT enhanced cap-dependent protein translation, whereas a reduction in cap-dependent protein translation by Akt KD was observed. Our results clearly showed that targeting Akt may be a good strategy for prevention as well as treatment of lung cancer. These studies suggest that our aerosol delivery is compatible for in vivo gene delivery which could be used as a noninvasive gene therapy in the future.

Major Gene Controls of Field Resistance to Spot Blotch in Wheat Genotypes 'Milan/Shanghai #7' and 'Chirya.3'.

A number of exotic wheat (Triticum aestivum) genotypes resistant to spot blotch caused by Cochliobolus sativus are being used to improve the resistance of commercial cultivars in the warm regions of South Asia. The objective of the present study was to determine the inheritance of field resistance to spot blotch in two resistant (R) wheat genotypes, 'Chirya.3' and 'Milan/Shanghai #7' (MS#7), which were crossed to a susceptible (S) commercial cultivar, 'BL1473.' The two resistant genotypes also were crossed to determine allelic relationships for resistance between them. Spot blotch severity was recorded on the parents and on F1, F2, and F3 progenies. The F1 plants from the two crosses between susceptible and resistant genotypes had low disease severity like the resistant parents, indicating that resistance in Chirya.3 and MS#7 is conditioned by dominant gene action. The F2 plants segregated in 3R:1S ratios, and the F2:3 families showed the ratio of 1R:1S:2S, segregating for R and S, suggesting that resistance in the two resistant parents is conditioned by a single, dominant gene. The F1 plants from the cross between the two resistant genotypes were resistant, whereas their F2 progenies segregated in 15R:1S, suggesting that the resistance genes in MS#7 and Chirya.3 are nonallelic. These simply inherited sources of resistance could be useful for improving spot blotch resistance in the warm regions of South Asia and also may offer useful diversity to breeding programs for developing spot-blotch-resistant wheat cultivars in other regions.

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Antimicrobial activity of crude extracts from berberis asiatica stem bark.

Different extracts from the stem bark of Berberis asiatica L. , a plant traditionally used to hasten the process of wound healing, and the alkaloid fractions derived from the commonly used aqueous extract, were tested for their putative antimicrobial activity against a battery of microorganisms by disk diffusion and agar dilution methods. The activity of the fractions was compared with that of berberine, the major alkaloid of the plant. While the methanolic extract was found to be most active, other fractions were also found to be superior to berberine, which suggests that in addition to berberine other antimicrobial agents are present in the plant.

The effects of phosphorylation of cardiac troponin-I on its interactions with actin and cardiac troponin-C.

It is known that the phosphorylation of two serine residues on the NH2-terminal extension specific to cardiac troponin-I (Tn-I) modulates the calcium-dependent activation of the myofilaments. The process by which this occurs remains an unsolved puzzle. We have applied a dissective approach to study the effect of this phosphorylation on the interactions between Tn-I and its partner proteins, actin and troponin-C (Tn-C). Using N-[14C]ethylmaleimide-labelled Tn-I in sedimentation assays with F-actin, we found that the dephosphorylated Tn-I binds to F-actin with pronounced positive cooperativity, both in the absence and the presence of tropomyosin. Phosphorylation of the protein slightly weakens the interaction in the absence of tropomyosin, but the cooperativity remained. In the presence of tropomyosin, phosphorylation of the Tn-I also appeared to slightly weaken the interaction as well but, more significantly, the cooperativity was eliminated. These data can only be explained simply by a cooperative interaction between the monomer units in the actin filament. The interactions between cardiac Tn-I and Tn-C were studied by labelling the Tn-C with the fluorescent probe dansyl aziridine. As expected, the binding of the dephosphorylated Tn-I to Tn-C was strengthened by over 20-fold upon the addition of calcium to the assay. Phosphorylation of the protein, however, had a dramatic effect on the interaction in that it appeared to desensitise the complex to the effect of calcium: the Ka values obtained for both interactions (+/- Ca2+) were almost identical. These results clearly indicate that the phosphorylation of Tn-I in the cardiac system has dramatic effects on the isolated inter-protein interactions. We also discuss the possible significance of such an effect on the interactions of the isolated proteins in their roles within the intact cardiac regulatory complex.

Direct visualization by electron microscopy of the weakly bound intermediates in the actomyosin adenosine triphosphatase cycle.

We used a novel stopped-flow/rapid-freezing machine to prepare the transient intermediates in the actin-myosin adenosine triphosphatase (ATPase) cycle for direct observation by electron microscopy. We focused on the low affinity complexes of myosin-adenosine triphosphate (ATP) and myosin-adenosine diphosphate (ADP)-Pi with actin filaments since the transition from these states to the high affinity actin-myosin-ADP and actin-myosin states is postulated to generate the molecular motion that drives muscle contraction and other types of cellular movements. After rapid freezing and metal replication of mixtures of myosin subfragment-1, actin filaments, and ATP, the structure of the weakly bound intermediates is indistinguishable from nucleotide-free rigor complexes. In particular, the average angle of attachment of the myosin head to the actin filament is approximately 40 degrees in both cases. At all stages in the ATPase cycle, the configuration of most of the myosin heads bound to actin filaments is similar, and the part of the myosin head preserved in freeze-fracture replicas does not tilt by more than a few degrees during the transition from the low affinity to high affinity states. In contrast, myosin heads chemically cross-linked to actin filaments differ in their attachment angles from ordered at 40 degrees without ATP to nearly random in the presence of ATP when viewed by negative staining (Craig, R., L.E. Greene, and E. Eisenberg. 1985. Proc. Natl. Acad. Sci. USA. 82:3247-3251, and confirmed here), freezing in vitreous ice (Applegate, D., and P. Flicker. 1987. J. Biol. Chem. 262:6856-6863), and in replicas of rapidly frozen samples. This suggests that many of the cross-linked heads in these preparations are dissociated from but tethered to the actin filaments in the presence of ATP. These observations suggest that the molecular motion produced by myosin and actin takes place with the myosin head at a point some distance from the actin binding site or does not involve a large change in the shape of the myosin head.

Dynamic quenching studies of fluorophore-labelled myosin subfragment 1 and its alkali light chain subunits.

The technique of fluorescence quenching by the non-ionic quenchers acrylamide and nicotinamide has been used to probe the accessibility of the environmentally sensitive N-(bromoacetyl)-N'-(1-sulpho-5-naphthyl) ethylenediamine (1,5-Br-AEDANS) fluorophore attached to either Cys-177 of the A1-light chain or the SH1 thiol (Cys-707) of the myosin subfragment (S1) heavy chain. Neither quencher caused any detrimental effects to the ATPase activities of S1 under the conditions of the experiments. It was found that the fluorophore on the isolated light chain was highly exposed to solvent and although this exposure was reduced on hybridization into S1(A1-AEDANS), the probe was still accessible to solvent. This exposure was unaltered by formation of binary complexes with either Mg.ATP or actin or by the formation of a weakly associated acto-S1 complex (in which the Cys-697 and Cys-707 residues of S1 were crosslinked with p-phenylenedimaleimide). The lack of corresponding change in lambda max of emission and quantum yield supported the quenching date and indicated that actin neither binds directly to this region nor induces any significant conformational changes in this locality despite the observation that the A1-Cys-707 moves some 3 nm closer to a point on actin in the weak-binding state (Trayer, H.R. and Trayer, I.P. (1988) Biochemistry, 27, 5718-5727). Parallel experiments with the fluorophore attached to the Cys-707 of the S1 indicated that this region was less accessible to solvent than the light chain thiol despite its ease of labelling. This exposure was not significantly altered by binary complex formation with actin and Mg.ATP, although spectral changes in the absence of quencher support the notion that some conformational change is occurring in this region.