Emergence of selectivity and specificity in a coarse-grained model of the nuclear pore complex with sequence-agnostic FG-Nups.

The role of hydrophobicity of phenylalanine-glycine nucleoporins (FG-Nups) in determining the transport of receptor-bound cargo across the nuclear pore complex (NPC) is investigated using Langevin dynamics simulations. A coarse-grained, minimal model of the NPC, comprising a cylindrical pore and hydrophobic-hydrophilic random copolymers for FG-Nups was employed. Karyopherin-bound receptor-cargo complexes (Kaps) were modeled as rigid, coarse-grained spheres without (inert) and with (patchy) FG-binding hydrophobic domains. With a sequence-agnostic description of FG-Nups and the absence of any anisotropies associated with either NPC or cargo, the model described tracer transport only as a function of FG-Nup hydrophobicity, f. The simulations showed the emergence of two important features of cargo transport, namely, NPC selectivity and specificity. NPC selectivity to patchy tracers emerged due to hydrophobic Kap-FG interactions and despite the sequence-agnostic description of FG-Nups. Furthermore, NPC selectivity was observed only in a specific range of FG-hydrophobic fraction, 0.05 ≤ f ≤ 0.20, resulting in specificity of NPC transport with respect to f. Significantly, this range corresponded to the number fraction of FG-repeats observed in both S. cerevisiae and H. sapiens NPCs. This established the central role of the FG-hydrophobic fraction in determining NPC transport, and provided a biophysical basis for conservation of the FG-Nup hydrophobic fraction across evolutionarily distant NPCs. Specificity in NPC transport emerged from the formation of a hydrogel-like network inside the pore with a characteristic mesh size dependent on f. This network rejected cargo for f > 0.2 based on size exclusion, which resulted in enhanced translocation probability for 0.05 ≤ f ≤ 0.20. Extended brush configurations outside the pore resulted in entropic repulsion and exclusion of inert cargo in this range. Thus, our minimal NPC model exhibited a hybrid cargo translocation mechanism, with aspects of both virtual gate and selective-phase models, in this range of FG-hydrophobic fraction.

Helical intermediate formation and its role in amyloids of an amphibian antimicrobial peptide.

Helical intermediates appear to be crucial in the amyloid formation of several amyloidogenic peptides, including Aß, that are implicated in different neurodegenerative diseases. Intermediate species of amyloid formation have been reported to be more toxic than mature amyloid fibrils. Hence, the current work focuses on understanding the mechanistic roles of the helical intermediates in the early stages of amyloid self-assembly in amyloidogenic peptides. Molecular dynamics (MD) simulations and the adaptive biasing force (ABF) method were utilized to investigate structural changes that lead to amyloid formation in amphibian peptide uperin-3.5 (U3.5), an antimicrobial and amyloidogenic peptide. Microsecond time-scale MD simulations revealed that peptide aggregation, into ß-sheet dominated aggregates, is centred on two important factors; evolution of α-helical intermediates and the critical role of local peptide concentration inside these aggregates. Electrostatic attraction between the oppositely charged aspartate (D) and arginine (R) residues located near the N-terminus induced hydrogen bonding resulting in the formation of precursor 310-helices close to the N-terminus. The 310-helices transitioned into α-helices, thereby imparting partial helical conformations to the peptides. In the initial stages of aggregation, U3.5 peptides with amphipathic, partial helices were driven closer by hydrophobic interactions to form small clusters of helical intermediates. These helices imparted stability to the helical intermediates, which promoted the growth of clusters by further addition of peptides. This led to an increase in the local peptide concentration, which enabled stronger peptide-peptide interactions and triggered a ß-sheet transition in these aggregates. Thus, this study emphasized that the helical intermediates may be crucial to the evolution of ß-sheet-rich amyloid structures.

Combined effect of ZnO nanoripples and solvent additive on the nanomorphology and performance of PTB7-Th: PC71BM organic solar cells.

In bulk heterojunction organic solar cells (OSCs), nanomorphology of the photoactive layer plays a crucial role in determining photocurrent and fill factor (FF) of OSCs, and therefore it is essential to control the nanomorphology of the photoactive layer to fabricate devices with high power conversion efficiency (PCE). We demonstrate the combined effects of a ZnO nanorippled electron transport layer (ETL) and solvent additive (1,8-diiodooctane (DIO)) on the nanomorphology and performance of a model OSC in an inverted geometry. The photoactive layer in the model OSC is composed of Poly [4,8-bis (5-(2-ethylhexyl)thiophen-2-yl)benzo[1,2-b;4,5-b']dithiophene-2,6-diyl-alt-(4-(2-ethylhexyl)-3-fluorothieno[3,4-b]thiophene-)-2-carboxylate-2-6-diyl] (PTB7-Th):phenyl-C71-butyric acid methyl ester (PC71BM) blend. It is observed that the use of ZnO nanoripples as an ETL and DIO as a solvent additive facilitates the formation of near ideal nanomorphology of bi-continuous interpenetrating network of donor and acceptor. This is confirmed by morphological studies using atomic force microscopy, scanning electron microscopy and transmission electron microscopy. Photo-electrochemical impedance spectroscopy measurements confirm that obtained nanomorphology of bicontinuous interpenetrating network is contributing to the improved device performance. The device with 3 vol% DIO, with underneath ZnO nanoripples exhibited improved current density (J sc), FF, open circuit voltage (V oc) and PCE of 15.57 mA cm-2, 64.50%, 0.81V and 8.20%, respectively.

Scaling relations for the interactions between curved graphene sheets in water.

The effect of curvature and relative orientation between two curved graphene sheets in aqueous media is quantified by calculating the potential of mean force using molecular dynamics simulations and thermodynamic perturbation. The potential of mean force between two curved graphene sheets is found to scale as UCG ∼ R0.5d-4.5, where R is the sheet radius of curvature and d is the inter-sheet distance. Further, a simple analytical calculation based on classical Hamaker theory and the Derjaguin approximation also arrives at the same scaling of interaction energy with respect to R and d. For the case where a misorientation, θ, exists between the two curved graphene sheets, the simulation results strongly suggest an inverse dependence of the potential of mean force on sin θ for θ > 30°. This result is very similar to the scaling predicted by the Derjaguin approximation for two cylinders crossed at an angle θ with respect to each other.

A Comparison of the Intracerebral Hemorrhage Score and the Acute Physiology and Chronic Health Evaluation II Score for 30-Day Mortality Prediction in Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The intracerebral hemorrhage (ICH) score is well established as a reliable prognostic score in ICH, whereas recently, Acute Physiology and Chronic Health Evaluation II (APACHE II) has been observed to have a better discrimination in predicting mortality in primary pontine hemorrhage. Further, physiological parameters of APACHE II have been associated with outcome in ICH. This study is the first to observe a direct comparison between APACHE II and ICH scores in predicting 30-day mortality in spontaneous intracerebral hemorrhage (SICH). MATERIALS AND METHODS: This study was a prospective observational study where we compared the receiver operating characteristic (ROCs) of baseline ICH and APACHE II scores in patients with SICH for predicting 30-day mortality outcome. RESULTS: We observed that both APACHE II and ICH scores were good for predicting 30-day mortality with both having an area under the ROC curve of more than .8 (.831 [95% confidence interval {CI}, .740-.922; P <.001] and .892 [95% CI, .757-.932; P <.001], respectively). However, the ICH score was better discriminative (area under the curve AUC, .892 versus .831; P = .040) and better calibrated (P = .037 versus P = .089, Hosmer-Lemeshow goodness-of-fit test for logistic regression) for the same. Both APACHE II and ICH scores had a sensitivity of 87% at cutoff values of 19 and 3, respectively; however, the ICH score had a better specificity (90% versus 76.5%). CONCLUSION: The ICH score was observed to have a better discrimination and calibration for predicting 30-day mortality in SICH.

Deagglomeration of multi-walled carbon nanotubes via an organic modifier: structure and mechanism.

We have investigated the agglomeration behaviour of two types of multi-walled carbon nanotubes (MWNTs; N-MWNTs and D-MWNTs), which have different chemical functionalities, average diameter, varying extent of agglomeration and agglomerations. The properties were altered by varying the agglomerated structure. The strength of the MWNT agglomerates was estimated via nanoindentation. The work done to indent D-MWNT agglomerates (3910.3 × 10(-8) erg) was higher than for N-MWNTs agglomerates (2316.4 × 10(-8) erg). An organic modifier, the Li salt of 6-aminohexanoic acid (Li-AHA), was used to deagglomerate the MWNTs in an aqueous medium. The stability of the aqueous dispersion of Li-AHA-modified MWNTs was analyzed by UV-vis spectroscopy and zeta potential measurements. An increase in Li-AHA concentration increased the dispersion of MWNTs in the aqueous medium. Furthermore, the mechanism of dispersion of the two types of MWNTs in the aqueous medium in the presence of Li-AHA was determined based on the electrostatic charge repulsion between the negatively charged species. A fluorescence-activated cell sorting technique was used to assess the debundling of MWNT agglomerates in the aqueous medium. We examined the morphology-property relationship in Li-AHA-modified MWNTs.

Influence of non-covalent modification of multiwalled carbon nanotubes on the crystallization behaviour of binary blends of polypropylene and polyamide 6.

Blends of polypropylene (PP) and polyamide 6 (PA6) with multiwalled carbon nanotubes (MWNTs) were prepared using different processing strategies in a twin-screw micro-compounder. The effect of MWNTs on the crystallization behaviour of the PP phase and the PA6 phase of the blend has been investigated through non-isothermal crystallization studies by differential scanning calorimetric analysis. Furthermore, the effect of the addition of the compatibilizer (PP-g-MA) and the modification of MWNTs (m-MWNTs) with a non-covalent organic modifier (Li-salt of 6 amino hexanoic acid, Li-AHA) has also been studied in context to the crystallization behaviour of the PP and PA6 phase in the blend. The crystallization studies have indicated a significant increase in bulk crystallization temperature of the PP phase in the blend in the presence of MWNTs. Moreover, the formation of 'trans-lamellar crystalline' structure consisting of PA6 'trans-crystalline lamellae' on MWNTs surface was facilitated in the case of blends prepared via 'protocol 2' as compared to the corresponding blends prepared via 'protocol 1'. Wide angle X-ray diffraction analysis has showed the existence of a ß-polymorph of the PP phase due to incorporation of the PA6 phase in the blend. Addition of MWNTs in the blends has facilitated further ß-crystalline structure formation of the PP phase. In the presence of m-MWNTs, a higher ß-fraction was observed in the PP phase as compared to the blend with pristine MWNTs. Addition of PP-g-MA has suppressed the ß-phase formation in the PP phase in the blend. X-ray bulk texture analysis revealed that incorporation of PA6 as well as pristine/modified MWNTs has influenced the extent of orientation of the PP chains towards specific crystalline planes in various blend compositions of PP and PA6.

Influence of hybrid nano-filler on the crystallization behaviour and interfacial interaction in polyamide 6 based hybrid nano-composites.

Expanded graphite (EG) and multiwalled carbon nanotubes (MWNTs) based hybrid nano-composites were prepared with polyamide 6 (PA6) matrix via melt-mixing technique using a conical twin-screw micro-compounder. A novel organic modifier (lithium salt of 6-aminohexanoic acid; Li-AHA) was employed to modify MWNTs, which was utilized to intercalate Li-AHA modified MWNTs into the partially exfoliated EG gallery. Morphological investigation showed the intercalation of Li-AHA modified MWNTs into a partially exfoliated EG gallery in an EG/MWNTs-m2h hybrid, whereas the unmodified EG/MWNTs-h hybrid mixture exhibited a separate identity in the mixture. Improved interaction via melt-interfacial reaction between the acid end group of PA6 and the amine functionality of Li-AHA in the EG/MWNTs-m2h hybrid filler was confirmed by Fourier transform infrared spectroscopic analysis. The extent of melt-interfacial reaction was increased as a function of Li-AHA concentration in the filler. Wide angle X-ray diffraction analysis showed the existence of the α-crystalline phase of PA6. The incorporation of MWNTs, EG and EG/MWNTs hybrid in the PA6 matrix has favoured an α-crystalline structure of the PA6 phase. Crystallization studies have indicated a significant increase in the bulk crystallization temperature of the PA6 phase in the presence of MWNTs, EG and the EG/MWNTs hybrid filler. Moreover, the formation of PA6 'trans-crystalline lamellae' on the MWNTs surface was facilitated in the case of composites with MWNTs and the EG/MWNTs hybrid filler. An attempt has been made to investigate the role of the EG/MWNTs hybrid filler in influencing the crystallization behaviour of the PA6 phase in the hybrid nano-composites.

Transgenic mice overexpressing mutant TDP-43 show aberrant splicing of neurological disorders-associated gene Zmynd11 prior to onset of motor symptoms.

Mutations in TDP-43 are known to cause Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). TDP-43 binds to and regulates splicing of several RNA including Zmynd11 . Zmynd11 is a transcriptional repressor and a potential E3 ubiquitin ligase family member, known for its role in neuron and muscle differentiation. Mutations in Zmynd11 have been associated with autism with significant developmental motor delays, intellectual disability, and ataxia. Here, we show that Zmynd11 is aberrantly spliced in the brain and spinal cord of transgenic mice overexpressing a mutant human TDP-43 (A315T), and that these changes occur before the onset of motor symptoms.

The COMT Val158 allele is associated with impaired delayed-match-to-sample performance in ADHD.

BACKGROUND: This study explored the association between three measures of working memory ability and genetic variation in a range of catecholamine genes in a sample of children with ADHD. METHODS: One hundred and eighteen children with ADHD performed three working memory measures taken from the CANTAB battery (Spatial Span, Delayed-match-to-sample, and Spatial Working Memory). Associations between performance on working memory measures and allelic variation in catecholamine genes (including those for the noradrenaline transporter [NET1], the dopamine D4 and D2 receptor genes [DRD4; DRD2], the gene encoding dopamine beta hydroxylase [DBH] and catechol-O-methyl transferase [COMT]) were investigated using regression models that controlled for age, IQ, gender and medication status on the day of test. RESULTS: Significant associations were found between performance on the delayed-match-to-sample task and COMT genotype. More specifically, val/val homozygotes produced significantly more errors than did children who carried a least one met allele. There were no further associations between allelic variants and performance across the other working memory tasks. CONCLUSIONS: The working memory measures employed in the present study differed in the degree to which accurate task performance depended upon either the dynamic updating and/or manipulation of items in working memory, as in the spatial span and spatial working memory tasks, or upon the stable maintenance of representations, as in the delay-match-to-sample task. The results are interpreted as evidence of a relationship between tonic dopamine levels associated with the met COMT allele and the maintenance of stable working memory representations required to perform the delayed-match-to-sample-task.

Secondary Structure Transitions for a Family of Amyloidogenic, Antimicrobial Uperin 3 Peptides in Contact with Sodium Dodecyl Sulfate.

Secondary structure changes are an inherent part of antimicrobial (AMP) and amyloidogenic peptide activity, especially in close proximity to membranes, and impact the peptides' function and dysfunction roles. The formation, and stability of α-helical components are regarded as essential 'intermediates' for both these functions. To illuminate the conformational transitions leading to amyloid formation we use short cationic AMPs, from an Australian toadlet, Uperoleia mjobergii, (Uperin 3 family, U3) and assess the impact on secondary structural elements in the presence of a membrane mimetic surfactant, sodium dodecyl sulfate (SDS). Specifically, Uperin 3.x, where x=4, 5, 6 wild-type peptides and position seven variants for each, R7A or K7A, were investigated using a combination of experimental and simulation approaches. In water, U3 peptides remain largely unstructured as random coils, with the addition of salts initiating structural transitions leading to assembly towards amyloid. Solution NMR data show that an unstructured U3.5 wt peptide transitions in the presence of SDS to a well-defined α-helical structure that spans nearly the entire sequence. Circular dichroism (CD) and ThT fluorescence studies show that all six U3 peptides aggregate in solution, albeit with vastly varying rates, and a dynamic equilibrium between soluble aggregates rich in either α-helices or ß-sheets may exist in solution. However, the addition of SDS leads to a rapid disaggregation for all peptides and stabilisation of predominantly α-helical content in all the U3 peptides. Molecular dynamics (MD) simulations show that the adsorption of U3.5 wt/R7A peptides onto the SDS micelle is driven by Coulombic attraction between peptide cationic residues and the negatively charged sulfate head-groups on SDS. Simulating the interactions of various kinds of ß-sheet dimers (of both U3.5 wt and its variant U3.5 R7A) with SDS micelles confirmed ß-sheet content decreases in the dimers after their attachment to the SDS micelle. Adsorbed peptides interact favourably with the hydrophobic core of the micelle, promoting intramolecular hydrogen bonds leading to stabilisation of the α-helical structure in peptides, and resulting in a corresponding decrease in intermolecular hydrogen bonds responsible for ß-sheets.

Lessons Learned from a Fulminant Case of Reversible Cerebral Vasoconstriction Syndrome: Past Medical History Misleads the Diagnosis and Intra-Arterial Milrinone Offers Diagnostic Utility.

A 34-year-old post-partum female having dermatomyositis developed headache and became comatose after a seizure episode. Magnetic resonance imaging of brain showed a massive left ganglio-capsular bleed for which decompressive surgery was done. Computed tomographic angiography showed multiple foci of narrowing and irregularities in distal cerebral vessels. In view of dermatomyositis, the diagnosis of vasculitis was considered and pulse therapy of intravenous methylprednisolone was started. The patient, however, showed no improvement and developed new brain infarcts. She was subsequently taken up for a diagnostic cerebral angiography which showed multifocal severe narrowing in bilateral major cerebral arteries. These angiographic abnormalities showed excellent reversibility to intra-arterial milrinone and hence, reversible cerebral vasoconstriction syndrome (RCVS) was diagnosed. Normal angiographic findings in the first week do not rule out the disease and a repeat angiography should be considered if the clinical suspicion of the RCVS is high. Intra-arterial milrinone has a high diagnostic utility.

Changing Demographics of Stroke Mimics in Present Day Stroke Code Era: Need of a Streamlined Clinical Assessment for Emergency Physicians.

Background There is an apparently high incidence of stroke mimics in the present-day stroke code era. The reason being is the intense pressure to run with time to achieve the "time is brain"-based goals. Methods The present study was a retrospective analysis of the data collected over a duration of 6 months from April 2019 to September 2019. We observed the incidence of stroke mimics among the patients for whom rapid response stroke code was activated during the study period. We also performed a logistic regression analysis to identify the clinical features which can act as strong predictors of stroke and mimics. Results A total of 314 stroke codes were activated of which 256 (81.5%) were stroke and 58 (18.5%) were the mimics. Functional disorders and epilepsy were the most common mimics (24.1% each). Female gender ( p = 0.04; odds ratio [OR] 2.9[1.0-8.8]), isolated impairment of consciousness ( p < 0.01; OR 4.3[1.5-12.6]), and isolated dysarthria ( p < 0.001) were the strong independent predictors for a stroke mimic. Hemiparesis was the strong independent predictor for a stroke ( p < 0.001; OR 0.0[0.0-0.1]). Conclusion In the present epoch of rapid response stroke management, a streamlined assessment by the emergency physicians based on the above clinical predictors may help in avoiding the misdiagnosis of a mimic as stroke.

Exploring the Role of Peptide Helical Stability in the Propensity of Uperin 3.x Peptides toward Beta-Aggregation.

Antimicrobial peptides of the uperin 3.x family, obtained from the skin secretions of Uperoleia mjobergii, have an inherent ability to form amyloid with possible functional roles and can serve as model peptides to understand mechanistic aspects of amyloidogenesis. The substitution of a positively charged amino acid with a nonpolar alanine residue increased aggregation, fibril content, and propensity for ß-sheet formation for the uperin 3.5 R7A variant when compared with the uperin 3.5 wild-type peptides. We use molecular dynamics (MD) simulations and circular dichroism (CD) measurements on three uperin 3.x peptides and their corresponding seventh position alanine variants to understand the effect of substitution of a positively charged amino acid with a nonpolar alanine residue on the process of ß-aggregation. Both CD experiments and simulations show that the uperin 3.x wild-type peptides demonstrated lower ß-sheet content and propensity than with the corresponding alanine variants. Significantly, simulations of helix-to-coil transitions in individual peptides show an inverse relationship between the helical stability of peptides and their propensity to form structures rich in ß-sheets as observed in CD experiments. A simulation scheme based on a conformational search of helix-to-coil transition trajectories to select peptide conformers was used to assemble propagating peptide oligomers. Whereas octamers consisting of lower helical stability peptide conformers evolve into compact aggregates with a large ß-sheet component, octamers composed of high helical stability conformers disintegrate and show the least amounts of ß-sheet components. The highlight of the current work is that MD simulations are able to predict the correct order of ß-sheet propensity among the six peptides derived from the CD experiments and indicate the importance of helical intermediates in the amyloidogenesis pathway for uperin 3.x peptides.

Controlled Manipulation and Multiscale Modeling of Suspended Silicon Nanostructures under Site-Specific Ion Irradiation.

In this work, controlled bidirectional deformation of suspended nanostructures by site-specific ion irradiation is presented. Multiscale modeling of the bidirectional deformation of nanostructures by site-specific ion irradiation is presented, incorporating molecular dynamics (MD) simulations together with finite element analysis, to substantiate the bending mechanism. Strain engineering of the free-standing nanostructure is employed for controlled deformation through site-specific kiloelectronvolt ion irradiation experimentally using a focused ion beam. We report the detailed bending mechanism of suspended silicon (Si) nanostructures through ion-induced irradiations. MD simulations are presented to understand the ion-solid interactions, defects formation in the silicon nanowire. The atomic-scale simulations reveal that the ion irradiation-induced bidirectional bending occurs through the development of localized tensile-compressive stresses in the lattice due to defect formation associated with atomic displacements. With an increasing ion dose, the evolution of localized tensile to compressive stress is observed, developing the alternate bending directions calculated through finite element analysis. The findings of multiscale modeling are in excellent agreement with the bidirectional nature of bending observed through the experiments. The developed in situ approach for bidirectional controlled manipulation of nanostructures in this work can be used for nanofabrication of numerous novel three-dimensional configurations and can provide a route toward functional nanostructures and devices.

Enzyme-modulated DNA translocation through a nanopore.

We present a Langevin dynamics simulation study of enzyme-modulated translocation of a single-stranded DNA molecule through a cylindrical nanopore. The toroidal-shaped enzyme placed along the axis of the pore, threads a DNA molecule at a constant rate. As a result of this controlled release process, the length of DNA available for translocation varies with time. We examine the effect of time-dependent conformational entropy of the DNA on the translocation process. In addition, we also examine the effects of both the separation between the exonuclease and the pore, and the rate at which DNA is released by the enzyme. Our results indicate that the separation distance primarily influences the entry of the DNA into the pore. The length of the DNA released by the exonuclease that is most likely to enter the pore is nearly equal to separation distance between the pore and the exonuclease despite the flexibility of the polymer. However, the speed at which the DNA translocates through the nanopore is solely determined by the rate at which the exonuclease releases the DNA. We find that the translocation velocity is directly proportional to the rate of release.

High Prevalence of Asymptomatic Anterior Tarsal Tunnel Syndrome in Toddy Tappers of South India: A Case Series of 21 Participants.

Background Anterior tarsal tunnel syndrome (ATTS) is an uncommon entrapment neuropathy which occurs due to the compression of deep peroneal nerve under the inferior extensor retinaculum at the ankle. We observed a frequent occurrence of this syndrome in toddy palm tappers and hence, planned to study the association between the two. Materials and Methods We studied the prevalence of isolated deep peroneal neuropathy at the ankle among the asymptomatic toddy tappers enrolled over a period of 3 months. Results In our case series, 81% (17/21) of the study participants had ATTS of which 43% (9/21) had unilateral and 38% (8/21) had bilateral involvement. There was a strong inverse association (p < 0.001) of "duration of toddy tapping in years" with peroneal (extensor digitorum brevis) amplitudes on both the sides. Conclusion Our study confirms "palm tree climbing" to be an occupational etiology of ATTS.

Prevalence of vitamin D deficiency in chronic and subacute low back pain patients in India: a triple-arm controlled study.

Vitamin D is vital for musculoskeletal health and may be associated with subacute and chronic low back pain. The objective of this study was to estimate the prevalence of vitamin D deficiency among chronic low back pain (CLBP) and subacute low back pain (SLBP), and compare the same with healthy controls. This study was designed as triple-arm case-control study comprising of CLBP, SLBP, and controls. SLBP and CLBP cases were consecutively enrolled over 3 months of winter season from November 2016 to January 2017. Serum 25- (OH) vitamin D was estimated for the study subjects and categorical comparison of severity of vitamin D deficiency was done for the cases and controls. A total of 250 CLBP, 177 SLBP cases, and 248 controls were included in the study. Mean (± SD) serum vitamin D levels among CLBP, SLBP, and controls were 20.36 (± 12.56), 21.42 (± 13.20), and 20.84 (± 6.93) ng/ml respectively, the difference being statistically insignificant. There was no significant difference in the prevalence of vitamin D deficiency among CLBP, SLBP, and controls which was 53.6, 50.8, and 51.6% respectively, in the three arms. However, the categorical analysis revealed that CLBP and SLBP cases had a significantly higher prevalence of worse categories of vitamin D deficiency. Cases had significantly larger frequency (CLBP vs. controls, 43.6 vs 20.1%, P<0.001; SLBP vs. controls, 43.5 vs 20.1%, P = 0.001) of individuals with vitamin D levels ≤ 16 ng/ml (moderate deficiency upper threshold level). Thus, the severe forms of vitamin D deficiency may be causally associated with CLBP and SLBP. The results of the present study revealed that increasing severity of vitamin D deficiency may have a pathogenetic association with chronic low back pain and subacute low back pain. These results may prove to be of significance in framing of future management guidelines for the above clinical conditions.

Acute ischemic stroke thrombolysis with tenecteplase: An institutional experience from South India.

OBJECTIVE: Outcome assessment of intravenous (IV) thrombolysis with tenecteplase in acute ischemic stroke. MATERIALS AND METHODS: We consecutively enrolled acute ischemic stroke patients who underwent IV thrombolysis with tenecteplase from October 2016 to May 2017. Primary clinical efficacy outcome was defined as an improvement in the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at 24 h (h). Secondary clinical efficacy outcome was the favorable outcome on modified Rankin scale at 90 days defined as a score of 0 or 1. The safety endpoints were death rate at 90 days and symptomatic intracranial hemorrhage (SICH). RESULTS: Mean NIHSS scores at baseline and 24 h were 13 (±3.81) and 9.29 (±5.74), respectively, the difference being statistically significant (P = 0.016). In this study, nine patients (64%) met the primary clinical efficacy outcome and eleven (78.5%) patients met the secondary clinical efficacy outcome. Only 1 (7%) patient developed SICH and additionally, aspiration pneumonia with subsequent death. CONCLUSION: This study confirms the efficacy and safety of tenecteplase for stroke thrombolysis in our clinical setting. Tenecteplase appears to be a suitable option for stroke thrombolysis in resource-limited settings, considering its cost-effectiveness, and ease of administration.

Objectif: Évaluation de la thrombolyse intraveineuse (IV) par la tenecteplase lors d'un AVC ischémique aigu. Matériel et Méthodes: Nous avons inclus consécutivement les patients AVC ischémiques ayant subi une thrombolyse intraveineuse avec tenecteplase d'octobre 2016 à mai 2017. Le critère d'efficacité clinique primaire a été défini comme une amélioration du score NIHSS (National Institute of Health Stroke Scale) de 24 h (h). Le résultat d'efficacité clinique secondaire était le résultat favorable sur l'échelle de Rankin modifiée à 90 jours définie comme un score de 0 ou 1. Les critères de tolérance étaient le taux de mortalité à 90 jours et l'hémorragie intracrânienne symptomatique (SICH). Résultats: Les scores NIHSS moyens au départ et 24 h étaient respectivement de 13 (± 3,81) et de 9,29 (± 5,74), la différence étant statistiquement significative (P = 0,016). Dans cette étude, neuf patients (64%) ont atteint le critère principal d'efficacité clinique et onze patients (78,5%) ont atteint le critère d'efficacité clinique secondaire. Seulement 1 patient (7%) a développé un SICH et, en outre, une pneumonie d'aspiration avec décès ultérieur. Conclusion: Cette étude confirme l'efficacité et l'innocuité de la tenecteplase pour la thrombolyse par AVC dans notre contexte clinique. La ténectéplase semble être une option appropriée pour la thrombolyse d'accident vasculaire cérébral dans les milieux à ressources limitées, compte tenu de son rapport coût-efficacité et de sa facilité d'administration. Mots-clés: AVC ischémique aigu, alteplase, tenecteplase, thrombolyse.

Japanese Encephalitis Complicated with Obstructive Hydrocephalus.

Japanese Encephalitis (JE), caused by Japanese encephalitis virus (JEV), a flavi-virus, is the most significant aetiology of arboviral encephalitis worldwide. It has resulted in epidemics of encephalitis in the Indian subcontinent. Here, we report a case of 36-year-old female who presented with a short history of fever and headache followed by altered sensorium. Funduscopic examination revealed Papilloedema. Pyogenic or viral meningoencephalitis along with complicated malaria were kept as initial differential diagnosis. Magnetic Resonance Imaging (MRI) of brain revealed involvement of posterior limb of internal capsule and bilateral thalami in the form of haemorrhagic encephalitis along with obstructive hydrocephalus. Cerebro Spinal Fluid (CSF) serology (IgM ELISA) showed JE as the causative agent. Despite extensive literature search, we could not find a case of JE reported with hydrocephalus as a complication. This case highlights the typical and atypical features of JE including imaging findings and exemplifies the way, how diversely JE can present and would thus help in preparing management paradigms accordingly.