Cortico-cerebellar connectivity underlying motor control in chronic post-stroke individuals.

The robust, reciprocal anatomical connections between the cerebellum and contralateral sensorimotor cerebral hemisphere underscores the strong physiological interdependence between these two regions in relation to human behavior. Previous studies have shown that damage to sensorimotor cortex can result in a lasting reduction of cerebellar metabolism, the magnitude of which has been linked to poor rehabilitative outcomes. A better understanding of movement-related cerebellar physiology as well as cortico-cerebellar coherence (CCC) in the chronic, post-stroke state may be key to developing novel neuromodulatory techniques that promote upper limb motor rehabilitation. As a part of the first in-human phase-I trial investigating the effects of deep brain stimulation of the cerebellar dentate nucleus (DN) on chronic, post-stroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG in subjects (both sexes) with middle cerebral artery stroke during a visuo-motor tracking task. We investigated the excitability of ipsilesional cortex, DN and the their interaction as a function of motor impairment and performance. Our results indicate that 1) event-related oscillations in the ipsilesional cortex and DN were significantly correlated at movement onset in the low-ß band, with moderately and severely impaired subjects showing desynchronization and synchronization, respectively. 2) Significant CCC was observed during isometric 'hold' period in the low-ß band, which was critical for maintaining task accuracy. Our findings support a strong coupling between ipsilesional cortex and DN in the low-ß band during motor control across all impairment levels which encourages the exploitation of the cerebello-thalamo-cortical pathway as a neuromodulation target to promote rehabilitation.Significance Statement:Cerebral infarct due to stroke can lead to lasting reduction in cerebellar metabolism resulting in poor rehabilitative outcomes. Thorough investigation of the cerebellar electrophysiology as well as cortico-cerebellar connectivity in humans that could provide key insights to facilitate development of novel neuromodulatory technologies, has been lacking. As a part of the first in-human phase-I trial investigating deep brain stimulation of the cerebellar dentate nucleus (DN) for chronic, post-stroke motor rehabilitation, we collected invasive recordings from DN and scalp EEG while stroke patients performed a motor task. Our data indicate strong coupling between ipsilesional sensorimotor cortex and DN in the low-ß band across all impairment levels encouraging the exploration of electrical stimulation of the DN.

Development of near-infrared imaging agents for detection of junction adhesion molecule-A protein.

INTRODUCTION: Prostate and breast cancer are the most prevalent primary malignant human tumors globally. Prostatectomy and breast conservative surgery remain the most common definitive treatment option for the >500,000 men and women newly diagnosed with localized prostate and breast cancer each year only in the US. Morphological examination is the mainstay of diagnosis but margin under-sampling of the excised cancer tissue may lead to local recurrence. In despite of the progress of non-invasive optical imaging, there is still a clinical need for targeted optical imaging probes that could rapidly and globally visualize cancerous tissues. METHODS: Elevated expression of junctional adhesion molecule-A (JAM-A) on tumor cells and its multiple pro-tumorigenic activity make the JAM-A a candidate for molecular imaging. Near-infrared imaging probe, which employed anti-JAM-A monoclonal antibody (mAb) phthalocyanine dye IR700 conjugates (JAM-A mAb/IR700), was synthesized and used to identify and visualize heterotopic human prostate and breast tumor mouse xenografts in vivo. RESULTS: The intravenously injected JAM-A mAb/IR700 conjugates enabled the non-invasive detection of prostate and breast cancerous tissue by fluorescence imaging. A single dose of JAM-A mAb/IR700 reduced number of mitotic cancer cells in vivo, indicating theranostic ability of this imaging agent. The JAM-A mAb/IR700 conjugates allowed us to image a specific receptor expression in prostate and breast tumors without post-image processing. CONCLUSION: This agent demonstrates promise as a method to image the extent of prostate and breast cancer in vivo and could assist with real-time visualization of extracapsular extension of cancerous tissue.

Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells. When exposed to alternating low-power radiofrequency (RF) fields, the nanoparticle's mechanical tumbling releases the entrapped drug molecules from the pores of the silica shell. After directing the nanoparticle to target the near-perivascular regions and altered endothelium of the brain tumor via fibronectin-targeting ligands, rapid drug release from the nanoparticles is triggered by RF facilitating wide distribution of drug delivery across the blood-brain tumor interface.

Experimental data of the study on H-rotor with semi-elliptic shaped bladed vertical axis wind turbine.

The performance and load test data of the proposed H-rotor with semi-elliptical shaped blade vertical axis wind turbine is carried out at the laboratory using 1 m diameter axial fan. India has a long coastline and low-wind velocity ranging from 3 to 10 m/s which is available everywhere in the country irrespective of climatic conditions. The data article is carried out at different aspect ratios along with tilt of the blades and without tilting of the blades. These data sets provide the researchers to further study experimentally as well as numerically in order to enhance the performance of the proposed VAWT. The data presented here are measured at wind velocity ranging from 3 to 6 m/s. The raw data captured using data acquisition system are processed and presented in a form so as to compare it with other typical VAWT.

AEROSOL SIZE DISTRIBUTION IN URANIUM PROCESSING FACILITY FOR APPLICATION IN THE ASSESSMENT OF INTERNAL EXPOSURE.

In circumstances of inhalation exposure the radiotoxicity of radionuclide depends on the fractional deposition of inhaled activity, which is governed by the aerodynamic characteristics of the particles. Although International Commission on Radiological Protection (ICRP) provides default size distribution parameters for work place aerosols, inhaled aerosol characteristics may be different depending on the physical and chemical conditions of aerosol generation process. The present study is undertaken to determine the particle activity-size distribution during operation of various significant processes of uranium metal production facility of Bhabha Atomic Research Centre (BARC). Activity median aerodynamic diameter (AMAD) and its geometric standard deviation (GSD) were estimated for these process areas for uranium aerosol particles. The AMAD varied from 3.2 to 10.06 µm and GSD ranged from 1.5 to 3.0. Also, the obtained size distribution was tested by Pearson's chi-squared distribution test method to ascertain the assumption that the particle size distribution is best described by log-normal relationship.

One-pot synthesis of nanochain particles for targeting brain tumors.

To synthesize multi-component nanochains, we developed a simple 'one-pot' synthesis, which exhibited high yield and consistency. The nanochains particles consist of parent nanospheres chemically linked into a higher-order, chain-like assembly. The one-pot synthesis is based on the addition of two types of parent nanospheres in terms of their surface chemical functionality (e.g., decorated with PEG-NH2 or PEG-COOH). By reacting the two types of parent nanospheres at a specific ratio (∼2 : 1) for a short period of time (∼30 min) under rigorous stirring, nanochains were formed. For example, we show the synthesis of iron oxide nanochains with lengths of about 125 nm consisting of 3-5 constituting nanospheres. The chain-like shaped nanoparticle possessed a unique ability to target and rapidly deposit on the endothelium of glioma sites via vascular targeting. To target and image invasive brain tumors, we used iron oxide nanochains with the targeting ligand being the fibronectin-targeting peptide CREKA. Overexpression of fibronectin is strongly associated with the perivascular regions of glioblastoma multiforme and plays a critical role in migrating and invasive glioma cells. In mice with invasive glioma tumors, 3.7% of the injected CREKA-targeted nanochains was found in gliomas within 1 h. Notably, the intratumoral deposition of the nanochain was ∼2.6-fold higher than its spherical variant. Using MR imaging, the precise targeting of nanochains to gliomas provided images with the exact topology of the disease including their margin of infiltrating edges and distant invasive sites.

Synthesis of silver nanoparticles through green approach using Dioscorea alata and their characterization on antibacterial activities and optical limiting behavior.

In this work, we have successfully synthesized highly biocompatible and functionalized Dioscorea alata (D. alata) mediated silver nanoparticles with different quantities of its extract for the evaluation of proficient bactericidal activity and optical limiting behavior. The crystalline nature of the synthesized silver nanoparticles was confirmed by powder X-ray powder diffraction (XRD) analysis and furthermore confirmed from SAED pattern of HRTEM Analysis. The Surface Plasmon Resonance band was measured and monitored by UV-Visible spectral studies. The functional groups present in the extract for the reduction and stabilization of the nanoparticles were analyzed by Fourier transform infrared spectroscopy (FTIR) technique. Surface morphology and size of particles were determined by high-resolution transmission electron microscopy analysis (HRTEM). The elemental analysis was made by Energy Dispersive X-ray Spectroscopy (EDX). The synthesized silver nanoparticles (AgNPs) in colloidal form were found to exhibit third order optical nonlinearity as studied by closed aperture Z-scan technique and open aperture technique using 532nm Nd:YAG (SHG) CW laser beam (COHERENT-Compass 215M-50 diode-pumped) output as source. The negative nonlinearity observed was well utilized for the study of optical limiting behavior of the silver nanoparticles. D. alata mediated silver nanoparticles possess very good antimicrobial activity which was confirmed by agar well diffusion assay method.

A hydrazone Schiff base single crystal (E)-Methyl N(')-(3,4,5-trimethoxybenzylidene) hydrazine carboxylate: Physicochemical, in vitro investigation of antimicrobial activities and molecular docking with DNA gyrase protein.

Hydrazone Schiff bases have been widely explored for their antimicrobial, anticancer, anticonvulsant properties. The aim of the present work is to investigate the spectroscopic, electrochemical, thermal properties, in vitro study of antimicrobial activity and molecular docking studies of the MBHC compound. Slow evaporation solution growth technique was used to grow the single crystal of the MBHC compound. Single crystal X-ray diffraction, FTIR and FT-Raman spectroscopic studies are performed and confirmed the grown MBHC compound. UV-Vis spectroscopy and electrochemical studies deduced the absorption region and HOMO-LUMO band gap value of the compound. Resazurin reduction assay method was utilized to perform antibacterial and antifungal studies which resulted in lesser effectiveness of the MBHC compound compared to the erythromycin and fluconazole tablets. Molecular docking of the MBHC compound with the DNA gyrase protein exhibited the good binding affinity with energy of -43.196kcal/mol and docking score of -6.266 and having good interaction with aminoacids - ASP81 and ARG84.

Immunomodulatory drugs target IKZF1-IRF4-MYC axis in primary effusion lymphoma in a cereblon-dependent manner and display synergistic cytotoxicity with BRD4 inhibitors.

Primary effusion lymphoma (PEL) is an aggressive type of non-Hodgkin lymphoma localized predominantly in body cavities. Kaposi's sarcoma-associated herpes virus (KSHV) is the causative agent of PEL. PEL is an incurable malignancy and has extremely poor prognosis when treated with conventional chemotherapy. Immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are Food and Drug Administration-approved drugs for the treatment of various ailments. IMiDs display pronounced antiproliferative effect against majority of PEL cell lines within their clinically achievable concentrations, by arresting cells at G0/G1 phase of cell cycle and without any induction of KSHV lytic cycle reactivation. Although microarray examination of PEL cells treated with lenalidomide revealed activation of interferon (IFN) signaling, blocking the IFN pathway did not block the anti-PEL activity of IMiDs. The anti-PEL effects of IMiDs involved cereblon-dependent suppression of IRF4 and rapid degradation of IKZF1, but not IKZF3. Small hairpin RNA-mediated knockdown of MYC enhanced the cytotoxicity of IMiDs. Bromodomain (BRD) and extra-terminal domain (BET) proteins are epigenetic readers, which perform a vital role in chromatin remodeling and transcriptional regulation. BRD4, a widely expressed transcriptional coactivator, belongs to the BET family of proteins, which has been shown to co-occupy the super enhancers associated with MYC. Specific BRD4 inhibitors were developed, which suppress MYC transcriptionally. Lenalidomide displayed synergistic cytotoxicity with several structurally distinct BRD4 inhibitors (JQ-1, IBET151 and PFI-1). Furthermore, combined administration of lenalidomide and BRD4 inhibitor JQ-1 significantly increased the survival of PEL bearing NOD-SCID mice in an orthotopic xenograft model as compared with either agent alone. These results provide compelling evidence for clinical testing of IMiDs alone and in combination with BRD4 inhibitors for PEL.

A magnetoencephalography study of multi-modal processing of pain anticipation in primary sensory cortices.

Pain anticipation plays a critical role in pain chronification and results in disability due to pain avoidance. It is important to understand how different sensory modalities (auditory, visual or tactile) may influence pain anticipation as different strategies could be applied to mitigate anticipatory phenomena and chronification. In this study, using a countdown paradigm, we evaluated with magnetoencephalography the neural networks associated with pain anticipation elicited by different sensory modalities in normal volunteers. When encountered with well-established cues that signaled pain, visual and somatosensory cortices engaged the pain neuromatrix areas early during the countdown process, whereas the auditory cortex displayed delayed processing. In addition, during pain anticipation, the visual cortex displayed independent processing capabilities after learning the contextual meaning of cues from associative and limbic areas. Interestingly, cross-modal activation was also evident and strong when visual and tactile cues signaled upcoming pain. Dorsolateral prefrontal cortex and mid-cingulate cortex showed significant activity during pain anticipation regardless of modality. Our results show pain anticipation is processed with great time efficiency by a highly specialized and hierarchical network. The highest degree of higher-order processing is modulated by context (pain) rather than content (modality) and rests within the associative limbic regions, corroborating their intrinsic role in chronification.

Self-assembled supramolecular structure of 1-methyl piperazinium 4-nitrophenolate 4-nitrophenol monohydrate single crystal: Synthesis, growth, thermal and photo physical properties.

A new photoactive organic crystal, 1-methyl piperazinium 4-nitrophenolate-4-nitrophenol monohydrate (MP4NPM) has been synthesised at 35 °C. Good quality single crystals of MP4NPM have successfully been grown by slow evaporation solution growth technique. Single crystal X-ray diffraction analysis shows that MP4NPM belongs to monoclinic crystal system with space group P21/n. The molecular structure was further confirmed by modern spectroscopic techniques like FT-NMR (both 1D and 2D), FT-IR, UV-Vis-NIR and fluorescence. The UV-Vis-NIR spectrum was performed to understand the range of optical transparency and the results showed its suitability for nonlinear optical applications. Fluorescence emission revealed that MP4NPM can serve as a photo active material. Thermal properties of MP4NPM were investigated using simultaneous TG-DSC analysis. Frequency and temperature dependent dielectric properties were studied in the frequency range 500 Hz-5 MHz and 40-50 °C, respectively. Vicker's microhardness measurements revealed that MP4NPM belongs to the category of soft material. Kurtz and Perry powder technique shows that MP4NPM has SHG efficiency 0.89 times that of potassium dihydrogen phosphate (KDP).

Reduced MCMV Δm157 viral clearance in the absence of TSAd.

The T cell specific adapter protein (TSAd) is expressed in activated T cells and NK cells. While TSAd is beginning to emerge as a critical regulator of Lck and Itk activity in T cells, its role in NK cells has not yet been explored. Here we have examined susceptibility to virus infections in a murine model using various viral infection models. We report that TSAd-deficient mice display reduced clearance of murine cytomegalovirus (MCMV) that lack the viral MHC class I homologue m157, which is critical for Ly49H-mediated NK cell recognition of infected cells. In this infection model, NK cells contribute in the early stages of the disease, whereas CD8+ T cells are critical for viral clearance. We found that mice infected with MCMV Δm157 displayed reduced viral clearance in the spleen as well as reduced proliferation in spleen NK cells and CD8+ T cells in the absence of TSAd. Though no other immunophenotype was detected in the infection models tested, these data suggests that in the absence of the Ly49H ligand activation, NK cell and CD8+ T cell responses may be compromised in TSAd-deficient mice.

Interaction of collagen like peptides with gold nanosurfaces: a molecular dynamics investigation.

In this study, an attempt has been made to understand the interaction between collagen like peptides (CPs) with a gold nanosurface (AuNS) using a classical molecular dynamics simulation. Results reveal that the adsorption of CPs onto the gold surface depends on the amino acid composition of the collagen like peptides. It is evident from the findings that the Hyp residue of collagen interacts favorably with the AuNS. It is interesting to note that the model CP without a Hyp residue does not adsorb well on the surface. Results indicate that gold nanosurfaces or gold nanoparticles can be exploited to detect breast cancer due to the increased content of Hyp residues in the Gly-XAA-YAA triplet of collagen in breast cancer tissues. These results provide useful information for designing collagen based scaffolds for tissues engineering applications.

Salivary proteomics in bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis. SUBJECTS AND METHODS: Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157). CONCLUSIONS: Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.

Factor VIIa binding to endothelial cell protein C receptor protects vascular barrier integrity in vivo.

BACKGROUND: Recent studies have shown that factor VIIa binds to endothelial cell protein C receptor(EPCR), a cellular receptor for protein C and activated protein C. At present, the physiologic significance of FVIIa interaction with EPCR in vivo remains unclear. OBJECTIVE: To investigate whether exogenously administered FVIIa, by binding to EPCR, induces a barrier protective effect in vivo. METHODS: Lipopolysaccharide(LPS)-induced vascular leakage in the lung and kidney,and vascular endothelial growth factor (VEGF)-induced vascular leakage in the skin, were used to evaluate the FVIIa-induced barrier protective effect. Wild-type, EPCR-deficient, EPCR-overexpressing and hemophilia A mice were used in the studies. RESULTS: Administration ofFVIIa reduced LPS-induced vascular leakage in the lung and kidney; the FVIIa-induced barrier protective effect was attenuated in EPCR-deficient mice. The extent of VEGF-induced vascular leakage in the skin was highly dependent on EPCR expression levels. Therapeutic concentrations of FVIIa attenuated VEGF-induced vascular leakage in control mice but not in EPCR-deficient mice.Blockade of FVIIa binding to EPCR with a blocking mAb completely attenuated the FVIIa-induced barrier protective effect. Similarly, administration of protease activated receptor 1 antagonist blocked the FVIIa induced barrier protective effect. Hemophilic mice showed increased vascular permeability, and administration of therapeutic concentrations of FVIIa improved barrier integrity in these mice. CONCLUSIONS: This is the first study to demonstrate that FVIIa binding to EPCR leads to a barrier protective effect in vivo. This finding may have clinical relevance, as it indicates additional advantages of using FVIIa in treating hemophilic patients.

Targeting Myc in KSHV-associated primary effusion lymphoma with BET bromodomain inhibitors.

Primary effusion lymphoma (PEL) is an aggressive form of non-Hodgkin's B-cell lymphoma associated with infection by Kaposi's sarcoma-associated herpes virus (KSHV). (+)-JQ1 and I-BET151 are two recently described novel small-molecule inhibitors of BET bromodomain chromatin-associated proteins that have shown impressive preclinical activity in cancers in which MYC is overexpressed at the transcriptional level due to chromosomal translocations that bring the MYC gene under the control of a super-enhancer. PEL cells, in contrast, lack structural alterations in the MYC gene, but have deregulated Myc protein due to the activity of KSHV-encoded latent proteins. We report that PEL cell lines are highly sensitive to bromodomain and extra-terminal (BET) bromodomain inhibitors-induced growth inhibition and undergo G0/G1 cell-cycle arrest, apoptosis and cellular senescence, but without the induction of lytic reactivation, upon treatment with these drugs. Treatment of PEL cell lines with BET inhibitors suppressed the expression of MYC and resulted in a genome-wide perturbation of MYC-dependent genes. Silencing of BRD4 and MYC expression blocked cell proliferation and cell-cycle progression, while ectopic expression of MYC from a retroviral promoter rescued cells from (+)-JQ1-induced growth arrest. In a xenograft model of PEL, (+)-JQ1 significantly reduced tumor growth and improved survival. Taken collectively, our results demonstrate that the utility of BET inhibitors may not be limited to cancers in which genomic alterations result in extremely high expression of MYC and they may have equal or perhaps greater activity against cancers in which the MYC genomic locus is structurally intact and c-Myc protein is deregulated at the post-translational level and is only modestly overexpressed.

Sexual dysfunction among men in secondary care in southern India: Nature, prevalence, clinical features and explanatory models.

BACKGROUND: Sexual dysfunction, common in general medical practice, is under-recognized and inadequately managed resulting in significant morbidity and reduction in quality of life. We examined the nature, prevalence, clinical features and explanatory models of illness among men with sexual dysfunction in a general healthcare setting. METHODS: We recruited 270 consecutive men attending a general health clinic. Participants were evaluated using a structured interview. The International Index of Erectile Function-5, the Chinese Index of Premature Ejaculation-5, Short Explanatory Model Interview and the Revised Clinical Interview Schedule were used to assess sexual dysfunction, explanatory models and psychiatric morbidity. RESULTS: Premature ejaculation and erectile dysfunction were reported by 43.0% and 47.8% of men, respectively. The most common perceived causes were loss of semen due to masturbation and nocturnal emission. Popular treatments were herbal remedies and resources used were traditional healers. The factors associated with erectile dysfunction were diabetes mellitus, financial stress, past history of psychiatric treatment and common mental disorders such as depression and anxiety; those associated with premature ejaculation were common mental disorders, older age and financial debt. Sexual dysfunctions and concerns were under-diagnosed by physicians when compared to the research interview. CONCLUSION: There is a need to recognize sexual problems and effectively manage them in general medical settings. The need for sex education in schools and through the mass media, to remove sexual misconceptions, cannot be under-emphasized.

The Chennai Declaration: a roadmap to tackle the challenge of antimicrobial resistance.

"A Roadmap to Tackle the Challenge of Antimicrobial Resistance - A Joint meeting of Medical Societies in India" was organized as a pre-conference symposium of the 2 nd annual conference of the Clinical Infectious Disease Society (CIDSCON 2012) at Chennai on 24 th August. This was the first ever meeting of medical societies in India on issue of tackling resistance, with a plan to formulate a road map to tackle the global challenge of antimicrobial resistance from the Indian perspective. We had representatives from most medical societies in India, eminent policy makers from both central and state governments, representatives of World Health Organization, National Accreditation Board of Hospitals, Medical Council of India, Drug Controller General of India, and Indian Council of Medical Research along with well-known dignitaries in the Indian medical field. The meeting was attended by a large gathering of health care professionals. The meeting consisted of plenary and interactive discussion sessions designed to seek experience and views from a large range of health care professionals and included six international experts who shared action plans in their respective regions. The intention was to gain a broad consensus and range of opinions to guide formation of the road map. The ethos of the meeting was very much not to look back but rather to look forward and make joint efforts to tackle the menace of antibiotic resistance. The Chennai Declaration will be submitted to all stake holders.

Clozapine re-challenge under the cover of Filgrastim.

Rechallenge with clozapine, despite a history of clozapine-induced neutropenia is considered in patients with a good response to the drug in the past, for whom no other treatments are effective, and in cases where the risks of withholding treatment are greater than the risks of rechallenge. Dyscrasias that occur during rechallenge are reportedly earlier in onset and longer lasting. Strategies advocated during rechallenge include frequent monitoring of white blood counts, the use of lithium or Granulocyte-Colony Stimulating Factors. We report a case of a patient with treatment-resistant schizophrenia who developed neutropenia with clozapine as a result of which the drug was discontinued. However poor response to other first and second-generation antipsychotic medication and the persisting risk of harm to himself and others necessitated the reconsideration of clozapine. The patient was re-challenged with clozapine under the cover of Filgrastim, a Granulocyte-Colony Stimulating Factor.

Melioidosis :an emerging infection in India.

BACKGROUND: Melioidosis caused by the gram-negative bacterium Burkholderia pseudomallei is endemic in Southeast Asia but may be under-diagnosed and under-reported in the Indian subcontinent. This study was undertaken to analyse the clinical presentation and epidemiological risk factors for melioidosis in India. METHODS: We carried out a retrospective study of 32 culture proven cases of melioidosis at a tertiary care hospital in South India between 2005 and 2010. RESULTS: Thirty two culture confirmed cases of melioidosis were included in the study. Patient age varied from 4 to 60 years with a median age of 42.5 years. Males constituted 75% of cases and 78.12% of cases were from rural areas. Three-fourth (24 of 32) had at least one risk factor that predisposed to melioidosis: diabetes (43.75%) followed by alcoholism (21.87%) were the commonest. Fever was the most common symptom (68.75%) and mean duration of symptoms was 2.34 months before diagnosis. More than half of the cases (56.25%) presented as disseminated disease with the remainder having localised disease, usually septic arthritis or abscesses. Three fourth of patients (75%) were treated successfully on follow-up, with a regimen of parenteral ceftazidime followed by oral doxycycline and cotrimoxazole. CONCLUSION: Melioidosis is an emerging infection in India especially in males from rural areas, with diabetes and alcoholism being the commonest risk factors. Both sepsis with bacteraemia and localised disease involving joints or focal abscess were common presentations. Diagnosis is readily made by culturing the organism from appropriate clinical specimens and identifying non-fermenting Gram negative bacteria to the species level. As there was an excellent response in 75% of patients, early suspicion, culture confirmation and therapy is warranted in India.