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Background : Meningiomas are slow-growing tumors. Grading of meningiomas based on histological features has certain limitations in predicting the exact biological behavior, necessitating ancillary techniques. Objective : To study the Ki67 labeling index (Ki67 LI) in various histological subtypes and grades of meningioma and correlate it with various parameters for recurrence. Material and Methods : All intracranial and intraspinal meningiomas diagnosed between 2005 and 2008 were graded according to WHO 2007 criteria. Immunohistochemistry was performed using Ki67 (Dako, USA 1:50) in 300 cases. Statistical analysis was performed. Results : There was female predominance. The age ranged from 2-75 years including 11 children below the age of 18 years. There were 211 Grade I, 78 Grade II and 11 Grade III meningiomas. The mean Ki67 LI increased from Grade I to II and from Grade II to III and these were statistically significant. The Ki67 LI was high for the subtypes of clear cell, chordoid, papillary and rhabdoid but there was no statistical significance between the subtypes. The difference in Ki67 LI between recurrent versus non-recurrent and brain-invasive versus non-invasive meningiomas was statistically significant. Conclusion : High Ki67 LI indicates higher grade of meningioma. The difference in KI67 LI between recurrent and non-recurrent meningiomas was statistically significant. [ABSTRACT FROM AUTHOR]

Objective: The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer., Significance: Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile., Methods: Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology., Results: LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. In vitro release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC 50 value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. In vivo pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX., The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.

The present study aimed to investigate pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis based on history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded a non-significant ( p ≥ 0.05) increase in incidences among male dogs (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), in the summer months (55%), and dogs housed in pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their lives. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin, with an increase in the levels of globulin, alanine aminotransferase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Proteinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting the p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus .

Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome., Materials and Methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence., Results: The immunogenicity of the designed, refined, and verified prospective three-dimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting non-allergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation., Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

Microsatellite markers are being used for molecular identification and characterization as well as estimation of evolution patterns due to their highly polymorphic nature. The repeats hold 40% of the entire genome of Orientia tsutsugamushi (OT), but not yet been characterized. Thus, we investigated the genome-wide presence of microsatellites within nine complete genomes of OT and analyzed their distribution pattern, composition, and complexity. The in-silico study revealed that the genome of OT enriched with microsatellites having a total of 126,187 SSRs and 10,374 cSSRs throughout the genome, of which 70% and 30% are represented within the coding and non-coding regions, respectively. The relative density (RD) and relative abundance (RA) of SSRs were 42-44.43/kb and 6.25-6.59/kb, while for cSSRs this value ranged from 7.06 to 8.1/kb and 0.50 to 0.55/kb, respectively. However, RA and RD were weakly correlated with genome size and incidence of microsatellites. The mononucleotide repeats (54.55%) were prevalent over di- (33.22%), tri- (11.88%), tetra- (0.27%), penta- (0.02%), hexanucleotide (0.04%) repeats, with poly (A/T) richness over poly (G/C). The motif composition of cSSRs revealed that maximum cSSRs were made up of two microsatellites having unique duplication patterns such as AT-x-AT and CG-x-CG. To our knowledge, this is the first study of microsatellites in the OT genome, where characterization of such variations in repeat sequences would be important in deciphering the origin, rate of mutation, and role of repeat sequences in the genome. More numbers of microsatellites represented within the coding region provide an insight into the genome plasticity that may interfere with gene regulation to mitigate host-pathogen interaction and evolution of the species., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Labeo fimbriatus is a medium carp species found throughout India's peninsular river basins and is regarded as a valuable aquaculture resource alongside Indian major carps due to its taste and nutritional value. This species has recently declined dramatically due to habitat degradation and overfishing. Because of its enormous economic importance, a selective breeding programme is likely to be in place to improve performance traits. Knowledge of genetic variation among the base population from which the broodstock will be selected is an important step in this process. A diverse genetic base of broodstock is required to achieve the best response to selection for long-term aquaculture management practices. Consequently, using mitochondrial DNA (ATPase 6 and Control region) and microsatellite markers, we have made the first step toward estimating the level of genetic variation and how it is distributed among the four populations of L. fimbriatus found in peninsular rivers in India. The ATPase 6 gene analysis in four populations revealed 15 haplotypes and 51 variable sites, in contrast to the Control region, which had 60 haplotypes together with 73 variable sites and a haplotype diversity of 0.941. Twelve microsatellite loci displayed estimated allele numbers ( N A ) ranging from 3 to 19, observed heterozygosity ( H O ), and expected heterozygosity ( H E ), respectively, of 0.705 to 0.753 and 0.657 to 0.914. Each marker type showed a significant F ST value, indicating the presence of low to moderate genetic differentiation across entire wild populations. The Godavari, Kaveri, and Mahanadi populations formed one cluster according to the UPGMA, which was based on genetic distance matrix, while the Krishna population formed a separate cluster. The comparative genetic analysis of data from different markers utilized in the current study would enable the identification of the genetic stocks of L. fimbriatus and facilitate conservation measures and selective breeding., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03369-y., Competing Interests: Conflict of interestThe authors declare that they have no conflicts of interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Enteroviruses are members of the Picornaviridae family consisting of human enterovirus groups A, B, C, and D as well as nonhuman enteroviruses. Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis, known as hand, foot, and mouth disease (HFMD), in children worldwide, especially in the Asia-Pacific region. EV71 and coxsackievirus A16 are the two viruses responsible for HFMD which are members of group A enteroviruses. The identified EV71 receptors provide useful information for understanding viral replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the respective viral genome that determine virulence remain unclear. Although a vaccine is currently approved, there is no effective therapy for treating EV71-infected patients. Therefore, understanding the host-pathogen interaction could provide knowledge in viral pathogenesis and further benefits to anti-viral therapy development. The aim of this study was to investigate the latest findings about the interaction of viral ligands with the host receptors as well as the activation of immunerelated signaling pathways for innate immunity and the involvement of different cytokines and chemokines during host-pathogen interaction. The study also examined the roles of viral proteins, mainly 2A and 3C protease, interferons production and their inhibitory effects.

Scrub typhus is a neglected tropical disease that affects one-third of the world's population. The disease is caused by Orientia tsutsugamushi (OT), an obligate intracellular Gram-negative bacterium. OT efficiently escapes from the endosomal pathway after entering the host cell and replicates inside cytosol. OT infection promotes cellular autophagy, the autonomous defense mechanism unlike other bacteria. This study has discussed the bacterial invasion process through the extracellular matrix and the immune response activated by the bacterium within the hosts. Furthermore, we have emphasized the importance of extracellular matrix and their cross-talk with the immune cells, such as, macrophages, neutrophils, and dendritic cells followed by their inflammatory response. We have also put an insight into the host factors associated with signaling pathways during scrub typhus disease with a special focus on the OT-induced stress response, autophagy, apoptosis, and innate immunity. Multiple cytokines and chemokines play a significant role in activating different immune-related signaling pathways. Due to the presence of high antigenic diversity among strains, the signaling pathways during the host-pathogen interplay of OT with its host is very complicated. Thus, it hinders to mitigate the severity of the pandemic occurred by the respective pathogen. Our investigation will provide a useful guide to better understand the virulence and physiology of this intracellular pathogen which will lead towards a better therapeutic diagnosis and vaccine development., Competing Interests: Conflict of interestThe authors have no conflict of interest to declare., (© King Abdulaziz City for Science and Technology 2022.)

Contagious pustular dermatitis is a disease that primarily infects small ruminants and possesses zoonotic potential. It is caused by orf virus (ORFV), a member of the genus Parapoxvirus. In this study, we evaluated an ORFV outbreak in goats in Madhya Pradesh, a state in central India, during 2017. The transboundary potential of this virus was evaluated by constructing phylogenetic trees. The complete genome sequence of an ORFV isolate named Ind/MP/17 was found to be 139,807 bp in length with 63.7% GC content and 132 open reading frames (ORFs) flanked by 3,910-bp inverted terminal repeats (ITRs). An investigation into evolutionary parameters such as selection pressure (θ = dN/dS) and nucleotide diversity (π) demonstrated that ORFV has undergone purifying selection. A total of 40 recombination events were identified, 21 of which were evident in the Ind/MP/17 genome, indicating its ability to generate new variants., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Microsatellite markers or Simple Sequence Repeats (SSRs) are gaining importance for molecular characterization of the virus as well as estimation of evolution patterns due to its high-polymorphic nature. The Avipoxvirus is the causative agent of pox-like lesions in more than 300 birds and one of the major diseases for the extinction of endangered avian species. Therefore, we conducted a genome-wide analysis to decipher the type, distribution pattern of 14 complete genomes derived from the Avipoxvirus genus. The in-silico screening deciphered the existence of 917-2632 SSRs per strain. In the case of compound SSRs (cSSRs), the value was obtained 44-255 per genome. Our analysis indicates that the di-nucleotide repeats (52.74%) are the most abundant, followed by the mononucleotides (34.79), trinucleotides (11.57%), tetranucleotides (0.64%), pentanucleotides (0.12%) and hexanucleotides (0.15%) repeats. The specific parameters like Relative Abundance (RA) and Relative Density (RD) of microsatellites ranged within 5.5-8.12 and 33.08-53.58 bp/kb. The analysis of RA and RD value of compound microsatellites resulted between 0.25-0.82 and 4.64-15.12 bp/kb. The analysis of motif composition of cSSR revealed that most of the compound microsatellites were made up of two microsatellites, with some unique duplicated pattern of the motif like, (TA)-x-(TA), (TCA)-x-(TCA), etc. and self-complementary motifs, such as (TA)-x-(AT). Finally, we validated forty sets of compound microsatellite markers through an in-vitro approach utilizing clinical specimens and mapping the sequencing products with the database through comparative genomics approaches., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03169-4., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© King Abdulaziz City for Science and Technology 2022.)

Scrub typhus is a bacterial zoonotic acute febrile illness (AFI) caused by the obligate intracellular bacterium Orientia tsutsugamushi, which is an antigenically diverse strain frequently observed in the tropical region of Southeast Asian countries. The recent investigation was conducted to delineate the genotype identification of Orientia tsutsugamushi predominating in the eastern zone of India such as Odisha to decipher its strain type, and evaluate its diversity as well as evolutionary pattern based on the nucleotide analysis of the immune dominant 56 KDa gene. During this study, we have investigated 100 clinical samples (2014-2018), out of which 28 were positive for scrub typhus followed by its molecular characterization and phylogenetic analysis utilizing 56 KDa partial genes. Population genetic parameters showed the presence of 287 polymorphic sites within the analyzed 56 KDa gene. The gene diversity (Hd) and sequence diversity (π) was estimated 0.638 and 0.280, respectively. Selection pressure analysis (θ = dN/dS) having the value 0.222 suggests that the gene lied under purifying selection. The present study suggested a high rate of genetic diversity within the isolates. This research study sheds light on the hereditary and evolutionary relationships of Orientia strains found in the eastern Indian population. Understanding regional genetic variation is critical for vaccine development and sero-diagnostics methods. A significant level of genetic variability was observed during this study. This information has a way to understand more about antigen diversity that leads to develop an effective vaccine candidate for this pathogen., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction Functional endoscopic sinus surgery (FESS) is one of the common surgical procedures requiring hypotensive anesthesia; many agents have been tried to reduce the amount of blood loss. This study aims at comparing the efficacy of two agents for providing deliberate hypotension. Objectives The aim of this study was to evaluate the efficacy of esmolol and of dexmedetomidine and compare which one of the two is a better agent to produce induced hypotension during FESS. Materials and methods This was a comparative study conducted in a tertiary care hospital in Odisha, India. There were two study groups with 30 participants each who were given either esmolol or dexmedetomidine (group E and group DEX, respectively). Results Esmolol is an anti-hypertensive agent with better hemodynamic stability. The amount of drug and dose requirement was low in group DEX. The emergence time, sedation score, and time to first analgesic request were found to be highly statistically significant in group DEX. Conclusion Dexmedetomidine was found to be a better agent at controlling intra-operative blood pressure than esmolol and had beneficial effects on recovery from anesthesia and analgesia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Sahu et al.)

Bovine ephemeral fever virus (BEFV) is an evolving arbovirus reported across tropical, subtropical and temperate climatic zones globally. This study reveals prominent BEFV outbreaks in India, emerging annually during monsoons in subtropical areas accompanied by a congenial abundance of the vector population. PCR-based detection of viral genomic RNA in the blood samples collected during outbreaks of 2018-2019 for the first time confirmed the presence of BEFV in India. Phylogenetic analysis based on the glycoprotein gene of BEFV showed the current isolates to have high sequence homology with Middle Eastern lineage with nearly 97%, identity to Turkey (BEFV Ad12/TUR) and Israel (Israel 2006) isolates., (© 2020 Blackwell Verlag GmbH.)

Genome-wide in-silico identification of microsatellites or simple sequence repeats (SSRs) in the Orf virus (ORFV), the causative agent of contagious ecthyma has been carried out to investigate the type, distribution and its potential role in the genome evolution. We have investigated eleven ORFV strains, which resulted in the presence of 1,036-1,181 microsatellites per strain. The further screening revealed the presence of 83-107 compound SSRs (cSSRs) per genome. Our analysis indicates the dinucleotide (76.9%) repeats to be the most abundant, followed by trinucleotide (17.7%), mononucleotide (4.9%), tetranucleotide (0.4%) and hexanucleotide (0.2%) repeats. The Relative Abundance (RA) and Relative Density (RD) of these SSRs varied between 7.6-8.4 and 53.0-59.5 bp/kb, respectively. While in the case of cSSRs, the RA and RD ranged from 0.6-0.8 and 12.1-17.0 bp/kb, respectively. Regression analysis of all parameters like the incident of SSRs, RA, and RD significantly correlated with the GC content. But in a case of genome size, except incident SSRs, all other parameters were non-significantly correlated. Nearly all cSSRs were composed of two microsatellites, which showed no biasedness to a particular motif. Motif duplication pattern, such as, (C)-x-(C), (TG)-x-(TG), (AT)-x-(AT), (TC)- x-(TC) and self-complementary motifs, such as (GC)-x-(CG), (TC)-x-(AG), (GT)-x-(CA) and (TC)-x-(AG) were observed in the cSSRs. Finally, in-silico polymorphism was assessed, followed by in-vitro validation using PCR analysis and sequencing. The thirteen polymorphic SSR markers developed in this study were further characterized by mapping with the sequence present in the database. The results of the present study indicate that these SSRs could be a useful tool for identification, analysis of genetic diversity, and understanding the evolutionary status of the virus.

Enhancing the rate of decomposition or removal of organic dye by designing novel nanostructures is a subject of intensive research aimed at improving waste-water treatment in the textile and pharmaceutical industries. Despite radical progress in this challenging area using iron-based nanostructures, enhancing stability and dye adsorption performance is highly desirable. In the present manuscript alkali cations are incorporated into iron oxide nanoparticles (IONPs) to tailor their structural and magnetic properties and to magnify methyl blue (MB) removal/decomposition capability. The process automatically functionalizes the IONPs without any additional steps. The plausible mechanisms proposed for IONPs incubated in alkali chloride and hydroxide solutions are based on structural investigation and correlated with the removal/adsorption capabilities. The MB adsorption kinetics of the incubated IONPs is elucidated by the pseudo second-order reaction model. Not only are the functional groups of -OH and -Cl attached to the surface of the NPs, the present investigation also reveals that the presence of alkali cations significantly influences the MB adsorption kinetics and correlates with the cation content and atomic polarizability.

During the years 2010-2018, avipoxvirus (APV) outbreaks were observed in the domestic chickens and pigeons present in the eastern Indian state of Odisha. Based on typical pox lesions, followed by molecular techniques, the overall morbidity was found to be 18%-19.23% and 16.92%-23% in chickens and pigeons, respectively. The cutaneous forms of the disease were observed with varied rates of mortality, being 47.36%-52.77% in chickens and 39.13%-92% in pigeons. PCR amplification targeting the viral P4b core protein-coding gene and the DNA polymerase gene confirmed the presence of APV strains in 10 birds. Subsequent phylogenetic analysis of these two genes confirmed that the circulating strains were members of APV clade A. The subclade analysis revealed the introduction of A1 and A3 subclades in Indian chickens and pigeons, respectively. This study is the first molecular record of APVs circulating in eastern Indian birds (Odisha) and involves the first use of the polymerase gene to reveal the circulating clades of Indian APVs., (© 2019 Blackwell Verlag GmbH.)

Oral squamous cell carcinoma (OSCC) is one of the common type of cancer in humans. A combinatorial approach has been done by using paclitaxel (PTX), 5-fluorouracil (5-FU) and ascorbic acid (AA) loaded solid lipid nanoparticles (SLN) for its treatment. SLN were made by high-speed homogenization and ultrasonication technique and they were used alone and in combination to check their efficacy against OSCC induced animal model. Pharmacokinetics and biodistribution study of the optimized formulations for PTX, 5-FU and AA loaded SLN was performed. The SLN shows a biphasic nature of drug release both in the in-vitro and in-vivo system. SLN loaded with PTX in combination with SLN loaded with AA shows a greater potency in the treatment of OSCC in-vivo. The Pharmacokinetic and biodistribution studies of SLN depict a better therapeutic efficacy. The combination of PTX and AA loaded SLN can be a novel approach for the treatment of OSCC.

Introduction: One of the most common tumors of the brain are metastatic lesions. They can present as cancer of unknown primary (CUP) and require careful determination of the site of origin of the primary. Histopathologic and immunohistochemical analysis helps to determine the primary site., Aim: To study the clinicopathological features of metastatic tumors of the brain., Materials and Methods: All cases of surgically resected brain metastasis (solid tumor metastasis) from January 2013 to April 2015 were included in the study. The clinical details including age, gender, clinical features, and location were taken from medical records. The histopathology slides were retrieved and reviewed along with clinical and imaging findings from medical records. Immunohistochemistry was performed wherever necessary., Results: Out of 1662 resected brain lesions during the study period, 69 accounted for central nervous system metastasis, of which 36 were brain metastasis and 33 were isolated spinal cord metastasis. In the 36 brain metastasis cases, 19 were cases with an unknown primary. Carcinoma lung (47.2%) was found to be the most common primary malignancy. Immunohistochemistry with cytokeratin (CK)7, CK20, and thyroid transcription factor (TTF) 1 as a primary panel in metastatic tumors is highly recommended., Conclusion: Metastatic tumors accounted for 4.1% of intracranial lesions. Histopathologic pattern and immunohistochemistry aid in the accurate diagnosis of the original site of malignancy., Competing Interests: There are no conflicts of interest

Objective: To evaluate the prognostic usefulness of cerebrospinal fluid (CSF) lactate in postoperative bacterial meningitis (POBM) and to establish the optimal CSF lactate cut-off values in our population to identify POBM in neurosurgical patients., Patients and Methods: A prospective study of postoperative neurosurgical patients with presumed and established bacterial meningitis in the Department of Neurosurgery, NIMS, Hyderabad, India, from September 2012 to December 2014. The diagnostic and prognostic values of CSF lactate have been evaluated and compared with other well-established CSF markers. All the patients who have undergone intradural cranial surgery with features of meningism have been included., Results: The study included 37 patients. The CSF value of the first lumbar puncture (LP) was taken to evaluate the diagnostic value of CSF lactate. Twenty three corresponded to Group A, and 14 to Group B. The mean CSF lactate in Group A was 5.94 ± 2.36, and in Group B 4.60 ± 2.31. Subsequent LPs were performed and CSF analyzed to evaluate the prognostic value of CSF lactate. The CSF markers like neutrophil count (P = 0.003), CSF/blood glucose ratio (P = 0.012), CSF lactate (P = 0.024), lymphocyte count (P = 0.046), leukocyte count (P = 0.047) have shown their prognostic value in a descending order. CSF markers like the presence of red blood cells (P = 0.540) and proteins (P = 0.757) did not show prognostic significance. The decline in CSF lactate (content and concentration) after initiation of antibiotics correlated with subsidence of fever (P = 0.0001), decrease in neck rigidity (P = 0.022) and improvement in sensorium. They were also correlated improvement in CSF/blood glucose ratio and CSF white blood cell counts., Conclusions: In our study, CSF lactate was noted to have a dependable prognostic value in POBM. As routine CSF markers can be ambiguous in POBM, CSF lactate can be considered a better alternative for both establishing the diagnosis and prognostication., Competing Interests: There are no conflicts of interest

Context: Poor grade subarachnoid hemorrhage (SAH) is usually associated with unfavorable outcomes and optimal management is deemed complicated. Most centres follow an expectant management strategy or a less aggressive approach till patients improve to good clinical grades. This approach has been associated with higher mortality and morbidity. However, not all patients with poor clinical condition fare badly. Identification and early aggressive management of this select group of patients may lead to favorable outcomes., Settings and Design: Prospective non-randomized study., Materials and Methods: We prospectively analyzed 19 cases presented in WFNS grade 4 and 5 and factors affecting their outcome at a tertiary care centre in south India. This study was aimed at identifying those few poor grade patients who are probable candidates for a good outcome., Statistical Analysis Used: All the variables were analyzed for possible correlations with the SPSS version 13 software. The Chi-square test with a P < 0.05 was taken as statistically significant., Results: Of 19 cases, 13 were operated and good outcome was seen in 53.8% of the patients who underwent surgery and aggressive management. All 7 patients who were managed conservatively died. 15.8% of the patients had low density changes ( P = 0.625). Absence of such changes was associated with a good long term outcome ( P = 0.004). 9 patients had intraventricular hemorrhage at presentation and 5 patients having hydrocephalus underwent extra-ventricular drainage. Statistically significant factors precluding good outcome were the presence of infarcts and thick SAH in the cisterns., Conclusions: Poor grade (WFNS 4 and 5) SAH patients with or without ICH, IVH, if operated within 3 days can give rise to favorable outcome in around 50%. However, presence of patchy infarcts associated with thick subarachnoid blood (Fisher grade 3) precludes long term survival or meaningful recovery. Hence, aggressive management is unlikely to alter the natural history of such patients.

Purpose: A curcumin-docetaxel co-loaded nanosuspension with increased anti-breast cancer activity was developed. Curcumin is a potential anticancer agent with p-glycoprotein (p-gp) inhibiting activity may be co-administered with docetaxel as a nanosuspension to enhance its anticancer effect by increasing the oral bioavailability and decreasing drug efflux., Methods: Nanosuspensions of curcumin and docetaxel were prepared by precipitation-homozenisation technique and evaluated for particle size, polydispersity, zeta potential and drug release. The in vitro MTT assay was conducted using MCF-7 for anti-breast cancer activity. The in vivo biodistribution by radiolabeling and tumor inhibition study was conducted in mice., Results: Homogenous nanosuspensions of 80 ± 20 nm were obtained with increased solubility. The drugs as nanosuspensions showed higher cytotoxicity on MCF-7 cell line compared to their suspensions due to the increased in vitro cellular uptake. Due to this increased solubility, sensitization of tumor cells and inhibition of p-gp the in-vivo results showed greater tumor inhibition rate of up to 70% in MCF-7 treated mice. Histopathological results showed higher apoptotic activity and reduced level of angiogenesis., Conclusions: The in vitro and in vivo study of the nanosuspensions has shown that Co-administration of Curcumin as a p-gp inhibitor with docetaxel may have the potential to increase the anti-breast cancer efficacy of both drugs.

Aims and Objectives: To describe clinicopathological features of surgically resected vascular malformations (VMs) of central nervous system (CNS)., Materials and Methods: Histologically diagnosed cases of VMs of CNS during April 2010-April 2014 were included. Demographic data, clinical and radiological features were obtained. Hematoxylin and eosin slides were reviewed along with Verhoeff-Van Gieson (VVG), Masson's trichrome, periodic acid-Schiff, and Perls' stains. Morphologically, cavernomas and arteriovenous malformations (AVMs) were distinguished on the basis of vessel wall features on VVG and intervening glial parenchyma., Results: Fifty cases were diagnosed as VMs of CNS with an age range of 14-62 years. These included 36 cavernomas, 12 AVMs, 2 mixed capillary-cavernous angiomas. Most of the cavernoma patients (15/36) presented with seizures, whereas AVM patients (8/12) had a headache as the dominant symptom. Twenty-nine patients were reliably diagnosed on radiological features. Microscopic evidence of hemorrhage was seen in 24/36 cavernomas and 6/12 AVMs, as opposed to radiologic evidence of 10 and 4, respectively. Reactive gliosis was seen in 16 cavernomas., Conclusions: Histological features are important for classifying the VMs of CNS as there are no specific clinical and radiological features. Type of VM has a bearing on management, prognosis, and risk of hemorrhage.

Linkage map with wide marker coverage is an essential resource for genetic improvement study for any species. Sex-averaged genetic linkage map of Labeo rohita, popularly known as 'rohu', widely cultured in the Indian subcontinent, was developed by placing 68 microsatellite markers generated by a simplified method. The parents and their F1 progeny (92 individuals) were used as segregating populations. The genetic linkage map spans a sex-averaged total length of 1462.2 cM, in 25 linkage groups. The genome length of rohu was estimated to be 3087.9 cM. This genetic linkage map may facilitate systematic searches of the genome to identify genes associated with commercially important characters and marker-assisted selection programmes of this species.

Anaesthesiologists are often involved in the management of patients with cervical spine disorders. Airway management is often implicated in the deterioration of spinal cord function. Most evidence on neurological deterioration resulting from intubation is from case reports which suggest only association, but not causation. Most anaesthesiologists and surgeons probably believe that the risk of spinal cord injury (SCI) during intubation is largely due to mechanical compression produced by movement of the cervical spine. But it is questionable that the small and brief deformations produced during intubation can produce SCI. Difficult intubation, more frequently encountered in patients with cervical spine disorders, is likely to produce greater movement of spine. Several alternative intubation techniques are shown to improve ease and success, and reduce cervical spine movement but their role in limiting SCI is not studied. The current opinion is that most neurological injuries during anaesthesia are the result of prolonged deformation, impaired perfusion of the cord, or both. To prevent further neurological injury to the spinal cord and preserve spinal cord function, minimizing movement during intubation and positioning for surgery are essential. The features that diagnose laryngoscopy induced SCI are myelopathy present on recovery, short period of unconsciousness, autonomic disturbances following laryngoscopy, cranio-cervical junction disease or gross instability below C3. It is difficult to accept or refute the claim that neurological deterioration was induced by intubation. Hence, a record of adequate care at laryngoscopy and also perioperative period are important in the event of later medico-legal proceedings.

Objective: Ossification of the posterior longitudinal ligament (OPLL) is a complex multi-factorial disease process having both metabolic and biomechanical factors. The role of surgical intervention as well as the choice of approach weather anterior or posterior is ambiguous. The objective of this study was to assess the surgical out come and post operative functional improvement in patients with cervical OPLL at a tertiary care centre., Patients and Methods: This prospective study included 63 patients of cervical OPLL who underwent either anterior and/or posterior surgeries in Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad between June 2009 to May 2011. Patient's data including age, sex, pre and post operative functional status, radiographic findings and OPLL subtypes were recorded and analyzed over a follow up ranging up to minimum two years., Results: The mean age of the patients was 51.1 (range 30-80 years) involving 14 women and 49 men. Out of 63 patients, 14 patients underwent surgery by anterior approach (corpectomy and fusion) and all of them improved (P = 0.52). 49 patients underwent surgery by posterior approach where decompressive laminectomy was performed in 40, laminectomy with instrumentation was done in 5, laminoplasty was done in 3 and 1 patient underwent both anterior and posterior surgeries. Of those who underwent posterior surgery, 40 patients improved, 7 remained the same as their preoperative status (who were having signal intensity changes on T2W MRI) and 2 patients deteriorated in the immediate post operative period and then showed gradual improvement. All the patients were followed up for 24 months. The mean pre-operative Nurick grade was 2.82 which later on improved to 2.03 post surgery (P < 0.05). Minor complications included wound infections in two patients (1.26%)., Conclusions: Anterior cervical decompression and reconstruction is a safe and appropriate treatment for cervical spondylitic myelopathy in the setting of single or two level OPLL. Laminectomy or laminoplasty is indicated in patients with preserved cervical lordosis having three or more levels of involvement. Younger patients with good pre operative functional status and less than 2 levels of involvement have better outcome following anterior surgery.

The purpose of this study was to develop a nanosuspension of a poorly soluble drug felodipine by nanoprecipitation to achieve superior in vitro dissolution and high oral absorption in vivo in rats. Felodipine nanosuspensions were prepared by precipitation with ultrasonication method using polyvinyl alcohol (PVA) and hydroxy propyl methyl cellulose (HPMC) as stabilizers. The particle size of nanosuspension with PVA was 60-200 nm, while with HPMC is 300-410 nm. The in vitro dissolution and pharmacokinetics of optimized nanosuspensions were studied after oral administration in male wistar rats. The results showed significant improvement during in vitro dissolution and in vivo plasma level. Dissolution studies of lyophillised nanoparticles showed that up to 93.0 % dissolved in 2 h. In the in vivo evaluation, nanosuspension exhibited significant increase in AUC0-24, C max and decrease in t max. The findings revealed that particle size reduction can influence felodipine absorption in gastrointestinal tract and nanosuspension can enhance oral bioavailability of felodipine in rats.

Background and Aims: Anesthetic management of extracranial to intracranial (EC-IC) bypass for complex intracranial aneurysms is challenging as the goals involve balancing the cerebral perfusion during parent artery clamping and avoiding factors that predispose to rupture of the unsecured aneurysm. There is very sparse literature available on anesthetic management for this procedure., Materials and Methods: A retrospective review of the records of 20 patients undergoing EC-IC bypass was performed with an objective of assessing the efficacy and outcomes of anesthetic management in the absence of advanced neurological monitoring., Results: A total of 20 patients underwent EC-IC bypass as an adjunct cerebral revascularization in the management of complex intracranial aneurysms. Intraoperatively normotension and normocarbia were maintained. During the EC-IC bypass, when the temporary clamp was applied, mild hypertension (increase from baseline by 20%) and hypervolemia (central venous pressure increased to 12 mmHg) were maintained. Cerebral protection during temporary clipping of intracranial vessel was provided using moderate hypothermia to 34°C and intravenous thiopentone. Temporary clip time ranged from 15 min to 54 min (mean-25 min). All patients except one were extubated post-operatively (19/20 = 95%). None of the patients had rupture of aneurysm in the peri-operative period. Three patients developed neurologic events (3/20 = 15%). One patient had cerebral vasospasm and two patients developed cerebral infarction. Two patient subsequently improved and one succumbed to the neurological deterioration (mortality 1/20 = 5%)., Conclusion: Adherence to the principal goals for the procedure, avoidance of hemodynamic fluctuations such as hypotension and hypertension, maintenance of normocarbia, and cerebral protection, result in favorable neurological outcome even in the absence of advanced neuromonitoring.

Background: Cervical spondyloptosis is an extreme variant of cervical spinal injury where patients usually present with disabling neurological deficits. Presentation of these patients without significant morbidity is very rare and we could only find sporadic case reports in literature involving traumatic cervical spondyloptosis without neurological deficits. Usually such patients get spared due to expansion of spinal canal after fracture of posterior vertebral elements. We report a case of traumatic C5/C6 spondyloptosis in an ambulatory patient despite having an intact posterior vertebral arch. This patient was managed successfully with anterior cervical fusion., Conclusion: To the best of our knowledge, this is the first case report of its kind as it exemplifies the rarity of such an occurrence and underlines the importance of timely management to maintain such preserved neurological status.

Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailibility of 10-90%. The aim of this study was to enhance the oral bioavailibilty of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA). These were characterized for particle size, zeta potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The average particle size of furosemide nanoparticles were found to be in the range of 150-300 nm. This was further confirmed by SEM photograph. The particle size varies with an increase in concentration of drug and stabilizer. The preparations showed negative zeta potential and polydispersity index in the range of 0.3 +/- 0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The saturation solubility of prepared furosemide nanoparticles markedly increased compared to the original drug in simulated gastric fluid. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. It may be concluded that the nanoprecipitation with ultrasonication have potential to formulate homogenous nanosuspensions with uniform sized amorphous nanoparticles of furosemide. Polyvinyl acetate can be used as a suitable steric stabilizer to prepare stable furosemide nanosuspensions. The enhanced saturation solubility in simulated gastric fluid may lead to enhanced absorption of furosemide.

Background: Meningiomas represent about 30% of primary adult central nervous system tumors. Though slow growing, they recur, causing significant morbidity and mortality., Objective: The objective of the following study is to grade meningiomas according to World Health Organization (WHO) 2007 criteria and to correlate the grade with degree of expression of epidermal growth factor receptor (EGFR) and p53., Materials and Methods: Meningiomas diagnosed in the year 2010 in the Department of Pathology of our institute, were included in the study. Clinical and radiological findings were noted from medical records. The histopathology slides were reviewed and the tumors were graded according to WHO 2007 criteria. Tissue microarrays (TMA) were prepared and immunohistochemical analysis with epithelial membrane antigen, Vimentin, Ki67, EGFR and p53 was performed on the TMA slides., Results: A total of 79 meningiomas diagnosed during the study period included 30 male and 49 female patients with an age range of 10-75 years. There was a female preponderance with M:F ratio of 1:1.63. EGFR was found to be higher in grade I (82.93%) compared with grade II (35.71%) and grade III tumors (20%) with an overall positivity of 60.81%. Mean p53 indices were higher in grade III (50%) compared with grade II (39.29%) and grade I tumors (38.46%) with an overall positivity of 39.44%. Ki67 labeling index (LI) was significantly high in grade III (16.4%) compared with grade II (6.46%) and grade I tumors (3.13%)., Conclusion: EGFR expression and Ki67 LI correlated with grade of meningioma P < 0.0001 and P < 0.0001 respectively which were statistically significant whereas p53 expression did not correlate (P - 0.90).

Primary melanocytic tumors of the central nervous system are rare. In this article the authors describe a case of C1C2 intradural extramedullary melanocytoma in a 43-year-old patient who presented with neck pain. C1-3 laminectomy was performed followed by excision of the lesion and an adjoining satellite nodule, along with the dural attachment. The histopathological features were consistent with a meningeal melanocytoma despite the presence of a satellite nodule. The patient has no evidence of recurrence during the six month follow up period. A brief review of literature pertaining to the radiological features, pathological findings, management and prognosis of this rare tumor is discussed.

Keraunoparalysis or transient weakness in limbs following a lightning strike has been well described in literature. Many times, neurosurgeons encounter patients with paraparesis secondary to trauma in the setting of a lightning strike. In these cases, it becomes imperative to find out the true cause behind such weakness in lower limbs because the prognosis differs significantly depending on the etiology. We report a case of keraunoparalysis affecting both lower limbs in a 50-year-old male, where he recovered within 48 hours of the impact. As far as our knowledge is concerned, this is the first case of keraunoparalysis reported from India. We also review the available literature and discuss the physics of lightning, its mechanism, other clinical presentations, and management strategy in the light of our case. These patients must be investigated for other possible causes of paraparesis secondary to trauma and keraunoparalysis should rather be a diagnosis of exclusion, only to be confirmed on imageology. Awareness regarding similar cases will make neurosurgeons notice this entity early, avoiding unnecessary investigation, and hence they will be able to prognosticate in the most efficient manner.

Background and Importance: The occurrence of multiple tumors of different histopathologies in the central nervous -system is rare. Here, we report a case of a child with dual neuroepithelial tumors of different histological cell types and -review the available literature for analyzing the causal hypo-thesis., Case Report: A 7-year-old girl presented with history of headaches associated with multiple episodes of early morning projectile vomiting and visual blurring. Magnetic resonance imaging (MRI) showed a well-defined lesion in the hypothalamic region. The patient underwent resection of the tumor by the transcallosal transfornicial approach. Histopathology was suggestive of pilocytic astrocytoma. After 3 years, the patient presented with low back pain radiating to the right lower limb followed by sudden onset of weakness in both lower limbs. Recent MRI brain and spine scans showed a small residual lesion at the hypothalamus with D1 to D10 syrinx. A T1 hypointense and T2 hyperintense cystic lesion from D10 to S2 with intensely enhancing solid component at the S1, S2 region was also detected. The patient underwent L4 to S2 laminectomy and the histopathological examination revealed myxopapillary ependymoma., Conclusion: The presence of multiple neuroepithelial tumors of different histopathology in the same patient is extremely rare, and we report one such case of dual gliomas with hypothalamic pilocytic astrocytoma and cauda equina myxopapillary ependymoma in a 10-year-old patient. During the course of development, displacement and dedifferentiation of primitive totipotent neuroepithelial germ cells may be a causal factor for the appearance of the different neuroepithelial tumors in neuraxis concomitantly or subsequently, which might be substantiated by common cytogenetic abnormalities in different neuroepithelial tumor histogenesis., (Copyright © 2013 S. Karger AG, Basel.)

Multiple intracranial aneurysms located bilaterally in the anterior circulation are usually clipped sequentially by separate craniotomies or a bilateral craniotomy. However, in selected patients, bilateral aneurysms can be clipped on both sides in a single sitting through a unilateral approach and unilateral craniotomy without causing morbidity. We present our technique and results of bilateral aneurysms clipped through a unilateral craniotomy from the ruptured aneurysm side. Ten patients (between 2006 and 2008) aged 20years to 67years with bilateral supratentorial anterior circulation saccular aneurysms, World Federation of Neurological Surgeons Scale (WFNS) score subarachnoid hemorrhage (SAH) grades 1 and 3, Fisher grades 2 and 3, were operated with unilateral orbito-pterional craniotomy and clipping of bilateral aneurysms. A total of 23 aneurysms, 12 located contralaterally, were successfully clipped with a good outcome in nine patients and no mortality at all. We therefore conclude that the unilateral orbito-pterional approach can be safely employed in selected patients harboring bilateral supratentorial saccular aneurysms and presenting with SAH, having WFNS grade 1 to 3, Fisher grade up to grade 3. The brain must be lax intra-operatively. Wide opening of the basal cisterns, 3rd ventriculostomy, and clipping of ruptured aneurysms are the important steps to be performed first before clipping the contralateral aneurysm thus avoiding a second craniotomy., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Numerous studies have developed a "severity score" or "risk index" for mechanical ventilation and mortality, but there are few to predict outcomes for cervical spine injury (CSI) patients. Our objective in this study was to develop a simple bedside additive predictive score for requirement for ventilation and early in-hospital mortality for patients with CSI., Methods: Multivariate logistic regression analysis of the data obtained from 101 patients (development set) after surgical stabilization of traumatic CSI was performed to identify independent predictors of the need for mechanical ventilation and of early in-hospital mortality. Predictors of respiratory insufficiency and mortality (PRIM) scores were developed separately for ventilation and mortality by using the coefficients of the logistic regression model. The model was validated using the receiver operating characteristics curve to test its discriminatory ability and by comparing the predicted and observed outcomes. Validation was performed on an independent data set of 87 consecutive patients (validation set) with traumatic acute CSI., Results: Mechanical ventilation was required in 16.8% of the patients, and the in-hospital mortality rate was 17.8% in the development set. Independent risk factors for mechanical ventilation were severe injury (American Spinal Injury Association Impairment Scale Grades A and B), breath-holding time, pulmonary infection, hemodynamic instability, and progressive neurologic deterioration. Scores of 15, 20, 25, 25, and 15 were assigned to these variables, respectively. Independent predictors of death were severe injury (American Spinal Injury Association Impairment Scale Grades A and B), hemodynamic instability, progressive neurologic deterioration, and mechanical ventilation. The scores assigned for each of the variables were 20, 20, 40, and 20, respectively. The PRIM scores for mechanical ventilation and mortality had excellent discrimination (area under receiver operating characteristics curve >0.75). There was good correlation between predicted and observed outcomes in the development set and the validation set., Conclusion: PRIM scores enable accurate prediction of individual patient risk of need for mechanical ventilation and in-hospital mortality in association with acute CSI.

Aims: To describe the pathology of central nervous system (CNS) fungal infections with particular reference to India., Methods and Results: This was a retrospective study from 1988 to 2004 constituting 130 cases. The diagnosis was based on morphology of biopsy/autopsy material. These included aspergillosis (n=73), zygomycosis (n=40), cryptococcosis (n=2), rhodotorulosis (n=1), candidiasis (n=5), maduramycosis (n=1), pheohyphomycosis (n=3) and mixed infections (n=5). Predisposing risk factors were present in 49 (38%) patients only. The majority of the patients were immunocompetent. The commonest risk factor was diabetes mellitus, the commonest route of infection was from a contiguous site and the commonest pathology was granuloma. Culture positivity was seen in only 31%., Conclusion: Environmental factors in tropical countries such as India play a significant role in the pathogenesis of CNS fungal infections.

Objective: To report three patients with isolated Rosai Dorfman disease of the central nervous system., Case Reports: We report two patients with dural-based lesions diagnosed imageologically as meningiomas, and one patient with multiple intraparenchymal lesions diagnosed imageologically as lymphoma. Two patients were males and one was female. All were above 35 years of age with no nodal or other system involvement. The diagnosis was established on surgically excised masses during histopathology. One patient died due to unrelated causes 10 years later and the other two are symptom-free at 21.5- and 11.5-year-follow-up., Conclusions: Awareness of the entity and consideration in the differential diagnosis of dural-based/intraparenchymal lesions is necessary for diagnosis and prognosis.

A seventeen year old male patient presented with clinical features suggestive of raised intracranial pressure. CT Scan and MRI of brain revealed two mass lesions, one in trigone of each lateral ventricle. They were imageologically alike, appearing as mirror image masses. Both ware totally excised through occipitoparietal transventricular approach on the respective side of the lesion. Postoperative period was uneventful. Repeat CT Scan showed no residue of the lesions. Histopathological examination showed meningioma. To the best of our knowledge this is the first published report on bilateral trigonal meningiomas.