Molecular-based study of scrub typhus in Kerala, South India from 2014 to 2021: a laboratory-based study.

Scrub typhus (ST) is a neglected acute, febrile, infectious disease caused by the intracellular parasite Orientia tsutsugamushi, a gram-negative coccobacillus of the family Rickettsiaceae. Early and precise diagnosis is crucial to reduce the risk of developing disease complications. However, IgM antibody enzyme-linked immunosorbent assay (IgM ELISA) and indirect immunofluorescence assay (IFA) remain essential for diagnosis. However, it could be more helpful for early diagnosis due to the need for uniformity of approach in the diagnostic accuracy studies to determine appropriate ELISA cut-offs for various geographic locations. Hence, we aim to study the O. tsutsugamushi type-specific 56 kilodalton (kDa) protein gene using nested PCR (nPCR) and DNA sequence analysis as a molecular marker for early diagnosis. Out of 10,439 suspected cases, 1147/10,439 (11%) patients were positive for IgM ELISA. A total of 1044/10,439 (10%) samples were randomly tested after nPCR and compared with IgM ELISA results and DNA sequence analysis. Using nested PCR and IgM ELISA methods, 13% (134/1044) and 12% (125/1044) of the samples were positive, respectively. The serology method could not replicate the substantial number of positive cases demonstrated by nPCR; therefore, significant mutual exclusivity of the two techniques requires further investigation. Furthermore, our phylogenetic analysis revealed a clustering of isolates with Karp-related strains, providing insight into the transmission dynamics. Therefore, molecular diagnostic methods may aid in the early diagnosis of infection and enable prompt treatment of ST in endemic regions. Our results show that IgM ELISA can provide complete diagnostic advantages in conjunction with nPCR and can be an essential tool for accurate diagnosis. In addition, the DNA sequencing analysis of the samples showed that Karp-related strains were the main strains. Furthermore, research with samples from various regions in combination with the entire genome sequencing of O. tsutsugamushi is required to understand the infection mechanism better and develop robust early detection methods. Supplementary Information: The online version contains supplementary material available at 10.1007/s00580-023-03443-8.

Comparative performance of CDC-modified SARS-CoV-2 real-time PCR assay with four different commercial assays: laboratory-based study.

The coronavirus infectious disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses. The pandemic has emerged as a global public health crisis, and the threat of fast-spreading of the latest variants of the coronavirus (such as omicron, delta) is rampant. Therefore, a fast and reliable diagnostic assay is needed to make the clinical decision for further treatment. The study aims to develop a Centers for Disease and Prevention (CDC)-modified qualitative real-time reverse transcriptase PCR (RT-qPCR) assay and parallel assessment of commercially available RT-qPCR assay (Altona, Seegene, BD, and GBC) to detect SARS-CoV-2. Two hundred nine samples were chosen randomly out of around two hundred thousand samples. The panel consisted of SARS-CoV-2-positive (n = 156) and SARS-CoV-2-negative (n = 52) nasopharyngeal swab specimens for a primary clinical evaluation. Furthermore, 29 positive samples were sequenced using Oxford Nanopore Minion technology. Two hundred nine patient sample data of the cycle threshold (Ct) readings for target genes of five assays are 100% sensitive for Ct values. Mean Ct values for N1, N2, RdRp, S, and E of the positive controls in CDC assay, RealStar®, Allplex, GBC, and SD Biosensor were 17.5 ± 0.49, 16.9 ± 0.51, 20 ± 0.49, 21.7 ± 0.38, and 23.1 ± 0.43, respectively. F test value shows ≥ 1, which was statistically significant. All assays showed an efficiency of < 120% and R squares were < 0.99, which is well above the required threshold value. Thus, when taking the CDC-modified assay as a gold standard, the other four assays demonstrated a p value of 0.0000, concordance at 100%, and a Kappa at 1.000. A maximum-likelihood (ML) tree was constructed and compared based on full-length SARS-CoV-2 with Wuhan isolate. These isolates are closely related to the B.1.617 lineage and reference sequences. Therefore, we conclude that all RT-PCR kits assessed in this study shall be used for routine diagnostics of COVID-19 in patients. Supplementary information: The online version contains supplementary material available at 10.1007/s00580-022-03356-y.

Pharmacogenetics Based Dose Prediction Model for Initial Tacrolimus Dosing in Renal Transplant Recipients.

Tacrolimus, an immunosuppressant used in solid organ transplantation, has a narrow therapeutic index and exhibits inter-individual pharmacokinetic variability. Achieving and maintaining a therapeutic level of the drug by giving appropriate doses is crucial for successful immunosuppression, especially during the initial post-transplant period. We studied the effect of CYP3A5, CYP3A4, and ABCB1 gene polymorphisms on tacrolimus trough concentrations in South Indian renal transplant recipients from Kerala to formulate a genotype-based dosing equation to calculate the required starting daily dose of tacrolimus to be given to each patient to attain optimal initial post-transplant period drug level. We also investigated the effect of these genes on drug-induced adverse effects and rejection episodes and looked into the global distribution of allele frequencies of these polymorphisms. One hundred forty-five renal transplant recipients on a triple immunosuppressive regimen of tacrolimus, mycophenolate mofetil, and steroid were included in this study. Clinical data including tacrolimus daily doses, trough levels (C0) and dose-adjusted tacrolimus trough concentration (C0/D) in blood at three time points (day 6, 6 months, and 1-year post-transplantation), adverse drug effects, rejection episodes, serum creatinine levels, etc., were recorded. The patients were genotyped for CYP3A5*3, CYP3A4*1B, CYP3A4*1G, ABCB1 G2677T, and ABCB1 C3435T polymorphisms by the PCR-RFLP method. We found that CYP3A5*3 polymorphism was the single most strongly associated factor determining the tacrolimus C0/D in blood at all three time points (p < 0.001). Using multiple linear regression, we formulated a simple and easy to compute equation that will help the clinician calculate the starting tacrolimus dose per kg body weight to be administered to a patient to attain optimal initial post-transplant period tacrolimus level. CYP3A5 expressors had an increased chance of rejection than non-expressors (p = 0.028), while non-expressors had an increased risk for new-onset diabetes mellitus after transplantation (NODAT) than expressors (p = 0.018). Genotype-guided initial tacrolimus dosing would help transplant recipients achieve optimal initial post-transplant period tacrolimus levels and thus prevent the adverse effects due to overdose and rejection due to inadequate dose. We observed inter-population differences in allele frequencies of drug metabolizer and transporter genes, emphasizing the importance of formulating population-specific dose prediction models to draw results of clinical relevance.

Molecular-genetic characterization of human parvovirus B19 prevalent in Kerala State, India.

BACKGROUND: Human parvovirus B19V is a DNA virus, and a member of the family Parvoviridae, that causes various clinical manifestations, from asymptomatic to persistent infection that is associated with different autoimmune diseases. The parvovirus B19 evolves with a very high mutation rate that is closer to those of existing RNA viruses. Globally circulating B19V is currently classified into three genotypes, but their distribution is not spatially and temporally correlated. Except for a few recent reports on B19V entry into the human host and its genetic diversity, there is a lack of sufficient studies on this virus from distinct geographical locations and no clear understanding of its evolution has been documented. METHODS: To better understand the evolution of the Human parvo B19V virus from India's southern part, a geographically distinct location with no reports of B19V genomes, we have screened for B19V in 456 suspected cases using VP1/2 surface marker genes, and its characteristics were studied in detail. Amongst 456 clinically suspected B19V samples, 7.2% (33/456) were found positive by nested PCR (nPCR) were subsequently validated by real-time PCR, Sanger sequencing, and metagenome analysis. RESULTS: Human parvovirus B19 infection was shown among 33 of 456 patients when tested by nPCR; 30 among these were also positive by qPCR and were subsequently confirmed by sequencing 75% nPCR positive samples and 76% qPCR positive samples were from patients with age. ≥ 50 years respectively (Additional file 1: Table S1). The complete VP1/2 gene assembly from the South Indian strain showed three novel mutations (T122A, V128I, I283V), which might significantly impact the stability and virulence of the B19V virus circulating in this part of the world. These mutations might be crucial for its adaptive evolutionary strategies facilitating the spread and infectivity potential of the virus. In maximum likelihood phylogeny of VP1/2 sequences, the South Indian B19V strain forms a separate clade closer to the existing genotype two strains circulating worldwide. CONCLUSION: Our study contributes to a better understanding of the human parvovirus's genetic and evolutionary characteristics in South India. Also, it highlights the possibility that a positive selection pressure acting on VP1/2 could increase the survival and replication capabilities of the viruses.

Combined in vitro and in silico approach to evaluate the inhibitory potential of an underutilized allium vegetable and its pharmacologically active compounds on multidrug resistant Candida species.

Candida infections and related mortality have become a challenge to global health. Nontoxic and natural bioactive compounds from plants are regarded as promising candidates to inhibit these multidrug resistant strains. In the present study, in vitro assays and in silico molecular docking approach was combined to evaluate the inhibitory effect of crude extracts from Allium ampeloprasum and its variety A. porrum on Candida pathogens. Phytochemical screening revealed the presence of phenolic acids and flavonoids in higher quantity. Spectral studies of the extracts support the presence of phenols, flavonoids and organosulfur compounds. Aqueous extract of A. ampeloprasum showed a total antioxidant capacity of 68 ± 1.7 mg AAE/ g and an IC50 value of 0.88 ± 2.1 mg/ml was obtained for DPPH radicals scavenging assay. C. albicans were highly susceptible (19.9 ± 1.1 mm) when treated with aqueous A. ampeloprasum extract. Minimum inhibitory concentrations were within the range of 19-40 µg/ml and the results were significant (p ≤ 0.05). In silico molecular docking studies demonstrated that bioactive phytocompounds of A. ampeloprasum and A. porrum efficiently interacted with the active site of Secreted aspartyl proteinase 2 enzyme that is responsible for the virulence of pathogenic yeasts. Rosmarinic acid and Myricetin exhibited low binding energies and higher number of hydrogen bond interactions with the protein target. Thus the study concludes that A. ampeloprasum and A. porrum that remain as underutilized vegetables in the Allium genus are potential anti-candida agents and their pharmacologically active compounds must be considered as competent candidates for drug discovery.

Structural and Functional Implications of Non-synonymous Mutations in the Spike protein of 2,954 SARS-CoV-2 Genomes

Protein-protein interactions between virus and host are crucial for infection. SARS-CoV-2, the causative agent of COVID-19 pandemic is an RNA virus prone to mutations. Formation of a stable binding interface between the Spike (S) protein Receptor Binding Domain (RBD) of SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) of host actuates viral entry. Yet, how this binding interface evolves as virus acquires mutations during pandemic remains elusive. Here, using a high fidelity bioinformatics pipeline, we analysed 31,403 SARS-CoV-2 genomes across the globe, and identified 444 non-synonymous mutations that cause 49 distinct amino acid substitutions in the RBD. Molecular phylogenetic analysis suggested independent emergence of these RBD mutants during pandemic. In silico structure modelling of interfaces induced by mutations on residues which directly engage ACE2 or lie in the near vicinity revealed molecular rearrangements and binding energies unique to each RBD mutant. Comparative structure analysis using binding interface from mouse that prevents SARS-CoV-2 entry uncovered minimal molecular determinants in RBD necessary for the formation of stable interface. We identified that interfacial interaction involving amino acid residues N487 and G496 on either ends of the binding scaffold are indispensable to anchor RBD and are well conserved in all SARS-like corona viruses. All other interactions appear to be required to locally remodel binding interface with varying affinities and thus may decide extent of viral transmission and disease outcome. Together, our findings propose the modalities and variations in RBD-ACE2 interface formation exploited by SARS-CoV-2 for endurance. ImportanceCOVID-19, so far the worst hit pandemic to mankind, started in January 2020 and is still prevailing globally. Our study identified key molecular arrangements in RBD-ACE2 interface that help virus to tolerate mutations and prevail. In addition, RBD mutations identified in this study can serve as a molecular directory for experimental biologists to perform functional validation experiments. The minimal molecular requirements for the formation of RBD-ACE2 interface predicted using in silico structure models may help precisely design neutralizing antibodies, vaccines and therapeutics. Our study also proposes the significance of understanding evolution of protein interfaces during pandemic.

Can Mobile Health Improve Depression Treatment Access and Adherence Among Rural Indian Women? A Qualitative Study.

Major Depressive Disorder (MDD) is associated with low rates of treatment and medication non-adherence, more so in low- and middle-income countries (LMICs). Mobile mental health (mHealth) interventions offer promise as a tool to address these problems. However, the feasibility and acceptability of mHealth interventions among rural women in LMICs is unknown. We examined barriers to accessing mental health treatment, reasons for non-adherence, and attitudes towards mHealth solutions among women with MDD in rural south India. Six focus groups were conducted among women with MDD (n = 69) who had been in treatment at a rural community health center. The discussion was transcribed and analyzed using a modified grounded-theory approach. Women perceived limited autonomy within their family structure, and experienced financial and systemic barriers as contributing to poor treatment access and non-adherence. Illiteracy, limited personal access to mobile phones, and preference for in-person clinical consultation were identified as barriers to use of mHealth. This is the first qualitative study, to our knowledge, that examines attitude towards mHealth among women with MDD in a rural setting in India. The study identified contextual barriers that will be important to address before implementing mHealth interventions.

CD1a+ and CD207+ cells are reduced in oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: The objective of this study investigated the distribution of immature dendritic cells (DCs), Langerhans cells and plasmacytoid DCs in oral submucous fibrosis (OSMF), OSMF associated with oral squamous cell carcinoma (OSMF-OSCC), oral leukoplakia (OL), and oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Fourteen cases of OSMF, 9 of OSMF-OSCC, 8 of OL¸ 45 of OSCC and 8 of normal epithelium were retrospectively retrieved and their diagnoses confirmed. Immunoreactions against CD1a, CD207 e CD303 were performed and the number of positive cells quantified. RESULTS: A significant decrease of CD1a+ was found in OSMF (p≤0.05), OSMF-OSCC (p ≤ 0.01), and OSCC (p ≤ 0.001) when compared to normal epithelium. For CD207+ the significance decrease was observed in OSMF-OSCC (p ≤ 0.05), and OSCC (p ≤ 0.01) when compared with normal epithelium, and in OSMF when compared with OL (p ≤ 0.05). There was no significant difference for CD303, but increased in CD303+ was observed in OSCC when compared with normal epithelium. CONCLUSION: The decrease in the number of CD1a+ and CD207+ cells may be associate to the development of oral OSCC, and in OPMDs they might be indicators of malignant transformation.

Psidium guajava Leaf Extracts and Their Quercetin Protect HepG2 Cell Lines Against CCL4 Induced Cytotoxicity.

The present study was carried out to evaluate the in vitro cytoprotective effects of Psidium guajava and their isolated quercetin fraction to reduce the CCl4 (carbon tetrachloride) induced toxicity in HepG2 cell lines (Hepatocellular carcinoma G2). Silymarin was used as a standard drug to compare the protective effects of plant extracts in infected cell lines. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay, cell viability assay, leakage parameters [Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Lactate dehydrogenase (LDH)], lipid peroxidation and reduced glutathione (GSH) levels were used to find out the protection of human derived HepG2 cells against CCl4-induced damage. The levels of cytotoxicity, viability and GSH were reduced. While the activities of AST, ALT, LDH and lipid peroxidation was increased in CCl4-treated groups. The treatment of P. guajava and their isolated quercetin fractions (100, 200, 300 µg/mL) decreased the elevated levels of all these parameters. The results of the present study suggest that the ethanolic extract of P. guajava leaf and their isolated quercetin fractions can able to reduce the CCl4-induced cytotoxicity in HepG2 cell lines.

Wavefront sensing applied to determine the temperature dependence of the refractive index of liquids.

A method based on wavefront sensing is described to determine the temperature dependence of the refractive index of liquids. The technique only implies measuring the wavefront of a light beam passing through a micro-vessel containing the liquid. Here, this vessel is a crater made by CO2 laser processing in a fused silica plate. From the wavefront analysis, the optical path that is related to the refractive index of the liquid can be determined. This measurement can be done at different temperatures to obtain the temperature dependence of the refractive index. This method is applied to three liquids: water, ethanol, and cyclohexane at λ=630 nm. The results show a linear dependence in the range of 17°C-50°C and give coefficients dndT that are in good agreement with values from the literature.

Comparative Study of Molecular Approaches for the Detection of Influenza Virus from Patient Samples Using Real-time PCR: Prospective Disease Burden Study in Kerala (India) from 2010 to 2016.

PURPOSE OF REVIEW: Acute respiratory infections caused by influenza virus are a major cause of viral respiratory diseases globally. Surveillance of circulating subtypes and estimation of disease burden is of utmost clinical importance. Molecular surveillance and proper disease burden estimates are scarce in India although clinical influenza infections are on the rise. Our study aims to delineate the prevalent influenza subtypes in a South Indian population from cases requiring hospital visits. Using real-time polymerase chain reaction (RT-PCR), 2154 throat/nasopharyngeal swabs from patients attending Government Medical College, Thiruvananthapuram, Kerala, India, with suspected influenza-like illness, were tested for the presence of different influenza subtypes. RESEARCH FINDINGS: Forty-three percent of specimens were positive for the influenza virus. Among these, prevalence of influenza A(H3N2), influenza B, and H1N1pdm09 was 26.7, 6.3, and 10%, respectively. Nominal co-infections were detected. An easy to use commercial kit was used for the majority of the study after proper evaluation for sensitivity and specificity against a gold standard protocol. Specific diagnosis using molecular tools caters to the urgency, and a precise measure of the disease burden and management actions are needed, especially in developing countries like India. Infection rate estimation using a sensitive RT-PCR assay signified that influenza was highly prevalent in the region. The study data generated will help understand the epidemiology of influenza in India as well as generate information for global influenza surveillance and disease burden.

Role of brain-derived neurotrophic factor in the pathogenesis of distention-associated abdominal pain in bowel obstruction.

BACKGROUND: Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress-induced expression of BDNF in smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity in BO by altering voltage-gated K+ channel (Kv ) activity in sensory neurons. METHODS: Partial colon obstruction was maintained in rats for 7 days. Colon-projecting neurons in the dorsal root ganglia (DRG, T13 to L2) were isolated for electrophysiological and gene expression studies. KEY RESULTS: Compared to controls, membrane excitability of colon-projecting DRG neurons was markedly enhanced in BO. The densities of total Kv and transient A-type (IA ) K+ currents, but not sustained delayed IK current, were significantly reduced in the neurons in BO. The mRNA expression of IA subtype Kv 1.4 in colon neurons was down-regulated in BO. Expression of BDNF mRNA and protein was dramatically increased in colonic smooth muscle of the distended segment, but not in the non-distended aboral segment. Mechanical stretch of colon SMC in vitro increased BDNF expression. Treatment with anti-BDNF antibody restored total Kv and IA currents of neurons from BO rats. Administration of Trk B inhibitor ANA-12 blocked BO-associated changes of neuronal excitability, Kv activity and gene expression in obstruction. CONCLUSIONS AND INFERENCES: Mechanical stress-induced expression of BDNF in colon SMC plays a critical role in visceral hypersensitivity in BO by suppressing A-type K+ currents and gene expression in sensory nerve. These findings help to identify therapeutic targets for distention-associated abdominal pain in the gut.

Hypolipidemic Effect of Psidium guajava Leaf Extract Against Hepatotoxicity in Rats.

BACKGROUND: Plant-based natural extracts cure several diseases in human. However, the extract of Psidium guajava leaf is not yet evaluated on changes of lipid profile in hepatic disease affected rats. OBJECTIVE: The present study was aimed to evaluate the mitigation effect of the ethanolic extract of P. guajava leaf and its isolated quercetin fraction on hepatotoxic rats. MATERIALS AND METHODS: Carbon tetrachloride (CCl4) was injected to rats for hepatic disease induction and silymarin drug was used as positive control to compare plant ethanolic extract. The lipid profiles were assessed in both plasma and liver tissue of diseased and control rats. RESULTS: Levels of total cholesterol, triglycerides, free fatty acids, phospholipids, and low-density lipoprotein cholesterol were increased and the level of high-density lipoprotein cholesterol (HDL-C) was decreased in CCl4-induced hepatotoxic rats. The treatment of P. guajava (100, 200, and 300 mg/kg, bw) and isolated quercetin fraction (20 mg/kg, bw) doses decreased the elevated levels of all these parameters in diseased rats and restored the normal concentration of HDL-C. CONCLUSION: The results of the present study concluded that the P. guajava leaf and its isolated quercetin fraction can significantly regulate lipid metabolism in CCl4-induced hepatotoxic rats and decrease the disease rate. SUMMARY: Psidium guajava leaf extract reduces the hepatotoxicity and disease rate in ratsQuercetin fraction of leaf extract significantly regulates lipid profile in hepatic diseased rats. Abbreviations used: CCl4: Carbon tetrachloride; FFA: Free fatty acids; HDL-C: High-density lipoprotein cholesterol; LCAT: Lecithin cholesterol acyltransferase; LDL-C: Low-density lipoprotein cholesterol; PL: Phospholipids; TC: Total cholesterol; TG: Triglycerides; VLDL-C: Very low-density lipoprotein cholesterol.

Generating multibreather vector solitons by influencing the Manakov model and its modified forms with the linear self and cross coupling parameters.

We have realized for the first time the multibreather vector multi-solitons supporting collision dynamics with many interaction effects (namely reflection, attraction, beating, etc., effects) associated with the coupled nonlinear Schrödinger family equations having multiple applications. Such effects can be suppressed or enhanced by using the soliton parameters. Here each colliding multibreather vector one-soliton is composed with many soliton and antisoliton parts. Our solutions have freedom to control the number of soliton and antisoliton parts used to compose a vector one-soliton with a definite breathing length. It is also interesting to observe that the breathing maps associated with the obtained solutions depend on their free parameters and also the system parameters. All such investigations help us to realize different breathing mechanisms (namely pedaling, toggling, symmetric compression, symmetric elongation, asymmetric compression, asymmetric elongation, etc.) supported by the colliding one-solitons. An existing breathing mechanism of a given vector breather one-soliton can be suppressed or switched into another mechanism by tuning certain parameters appropriately. Because of such features we believe that this kind of study will further give impetus on the Lindner-Fedyanin system in the continuum limit, and find the potential applications in fiber coupler and also in Bose-Einstein condensates.

Osteoporotic fractures in patients with systemic lupus erythematosus and end stage renal disease.

Background The incidence of end stage renal disease (ESRD) in patients with systemic lupus erythematosus (SLE) is rising. However, the relationship between osteoporotic fractures and SLE in the setting of ESRD remains uninvestigated. The purpose of this study was to compare the frequency of incident osteoporotic fractures in patients with ESRD with and without SLE, to identify risk factors for fractures in patients with SLE and ESRD, and to examine the contribution of these fractures to mortality. Methods Retrospective cohort study of patients with SLE ( n = 716) and a 5% random sample of controls without SLE ( n = 4176) in the United States Renal Data System (USRDS) from years 2006-2008 enrolled in Medicare Part D. Results Fractures occurred in 10.6% ( n = 76) of patients with SLE and ESRD and 12.1% ( n = 507) of patients with ESRD without SLE ( p = 0.24). Older age (adjusted relative risk 1.02, 95% confidence interval 1.01-1.04) was associated with an increased risk for fracture in patients with SLE and ESRD. In multivariable analyses, vertebral and hip fractures more than doubled the risk for mortality. Conclusions The frequency of osteoporotic fractures in patients with SLE and ESRD is similar to the general population of patients with ESRD. Vertebral and hip fractures are significant contributors to mortality in patients with SLE and ESRD. Fracture prevention, in particular, for elderly patients with SLE and ESRD, should be considered. Summary SLE is not an independent risk factor for fractures in patients with ESRD. However, among patients with SLE and ESRD, vertebral and hip fractures are significant contributors to mortality.

Prenatal Factors Associated with Postnatal Brain Injury in Infants with Congenital Diaphragmatic Hernia.

BACKGROUND AND PURPOSE: Approximately 60% of infants with congenital diaphragmatic hernia have evidence of brain injury on postnatal MR imaging. It is unclear whether any brain injury is present before birth. In this study, we evaluated fetal MR imaging findings of brain injury and the association of congenital diaphragmatic hernia severity with postnatal brain injury. MATERIALS AND METHODS: Fetal MR imaging and postnatal brain MR imaging were retrospectively evaluated in 36 cases of congenital diaphragmatic hernia (from 2009 to 2014) by 2 pediatric neuroradiologists. Brain injury on postnatal MR imaging and brain injury and congenital diaphragmatic hernia severity on fetal MR imaging were recorded. Correlations between brain abnormalities on fetal and postnatal brain MR imaging were analyzed. Postnatal brain injury findings correlating with the severity of congenital diaphragmatic hernia were also assessed. RESULTS: On fetal MR imaging, enlarged extra-axial spaces (61%), venous sinus distention (21%), and ventriculomegaly (6%) were identified. No maturational delay, intracranial hemorrhage, or brain parenchymal injury was identified on fetal MR imaging. On postnatal MR imaging, 67% of infants had evidence of abnormality, commonly, enlarged extra-axial spaces (44%). Right-sided congenital diaphragmatic hernia was associated with a greater postnatal brain injury score (P = .05). Low observed-to-expected lung volume was associated with postnatal white matter injury (P = .005) and a greater postnatal brain injury score (P = .008). Lack of liver herniation was associated with normal postnatal brain MR imaging findings (P = .03). CONCLUSIONS: Fetal lung hypoplasia is associated with postnatal brain injury in congenital diaphragmatic hernia, suggesting that the severity of lung disease and associated treatments affect brain health as well. We found no evidence of prenatal brain parenchymal injury or maturational delay.

Motion of a nano-spheroid in a cylindrical vessel flow: Brownian and hydrodynamic interactions.

We study the motion of a buoyant or a nearly neutrally buoyant nano-sized spheroid in a fluid filled tube without or with an imposed pressure gradient (weak Poiseuille flow). The fluctuating hydrodynamics approach and the deterministic method are both employed. We ensure that the fluctuation-dissipation relation and the principle of thermal equipartition of energy are both satisfied. The major focus is on the effect of the confining boundary. Results for the velocity and the angular velocity autocorrelations (VACF and AVACF), the diffusivities and the drag and the lift forces as functions of the shape, the aspect ratio, the inclination angle and the proximity to the wall are presented. For the parameters considered, the boundary modifies the VACF and AVACF such that three distinct regimes are discernible - an initial exponential decay followed by an algebraic decay culminating in a second exponential decay. The first is due to the thermal noise, the algebraic regime is due both to the thermal noise and the hydrodynamic correlations, while the second exponential decay shows the effect of momentum reflection from the confining wall. Our predictions display excellent comparison with published results for the algebraic regime (the only regime for which earlier results exist). We also discuss the role of the off-diagonal elements of the mobility and the diffusivity tensors that enable the quantifications of the degree of lift and margination of the nanocarrier. Our study covers a range of parameters that are of wide applicability in nanotechnology, microrheology and in targeted drug delivery.

Efficacy of corrective exercise strategy in subjects with hyperkyphosis.

BACKGROUND: Age-related hyperkyphosis causes deleterious effects on health, physical function, and quality of life. Recently, health care providers recognized it as a major health concern. OBJECTIVE: To identify the effect of corrective exercise strategy on hyperkyphosis and compare it with that of conventional exercise. METHODS: Subjects were randomly categorized into two groups. Each group comprised 30 subjects. Group A received the corrective exercise strategy, and group B received conventional exercises for 8 weeks of the study duration (15 repetitions of each exercise for three sessions/day for a total duration of 45 min and 4 days/week. Pre- and post-interventional hyperkyphosis were analyzed according to posture number using the Posture Pro 8 postural analysis software. In addition, pectoralis minor flexibility was assessed using the ruler scale method in centimeters. RESULTS: Both groups showed highly significant postural alteration and changes in pectoralis minor muscle length (p< 0.001)CONCLUSIONS:The corrective exercise strategy seems to promote scapular stability and produce a more upright posture of the upper thoracic spine.

Implication of Posture Analysing Software to Evaluate the Postural Changes after Corrective Exercise Strategy on Subjects with Upper Body Dysfunction-A Randomized Controlled Trial.

INTRODUCTION: The postural adaptation is very common now a days in school going children, office desk oriented job, computer users and frequent mobile users, and in all major industrial workers. Several studies have documented a high incidence of postural abnormalities in a given population; however, methods of postural measurement were poorly defined. The implication of postural pro software to analyse the postural imbalance of upper body dysfunction is very rare and literature studies says that the kinematic changes in particular segment will produce pain/discomfort and thereby lesser productivity of subjects. AIM: To evaluate the postural changes in subjects with upper body dysfunction after a corrective exercise strategy using postural analysis software and pectoralis minor muscle length testing. MATERIALS AND METHODS: After explaining the procedure and benefits, informed consent was taken from the participating subjects (age 25-55 years). Subjects with upper body dysfunction were randomly allocated into two groups (each group 30 subjects). The Group-A received the corrective exercise strategy and Group-B received the conventional exercise for eight weeks of study duration (15 reps each exercise, total duration of 40 min; four days/week. Pre and Post posture analysis were analysed using posture pro software along with flexibility of pectoralis minor was assessed using ruler scale method. RESULTS: After interpretation of data, both the group showed the postural alteration and pectoralis minor muscle length changes, p-value (p<0.01) of both group showed highly significant changes. But comparing the both groups, the subjects who received the corrective exercise strategy shown more percentage of improvement in posture alteration (56.25%), pectoralis minor muscle length changes (68.69%) than the conventional exercise received subjects in posture alteration (24.86%) and pectoralis minor muscle length changes (21.9%). CONCLUSION: Altered postural changes and pectoralis minor muscle flexibility before and after the corrective exercise strategy evaluated by postural analysis software method shown to be a significant tool in clinical practice, which is easier and reproducible method.

Whole-Genome Sequences of Influenza A(H1N1)pdm09 Virus Isolates from Kerala, India.

We report here the whole-genome sequence of six clinical isolates of influenza A(H1N1)pdm09, isolated from Kerala, India. Amino acid analysis of all gene segments from the A(H1N1)pdm09 isolates obtained in 2014 and 2015 identified several new mutations compared to the 2009 A(H1N1) pandemic strain.