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.

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.

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.

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.

Mucormycosis in patients without cancer: a case series from A tertiary care hospital in South India.

BACKGROUND: Mucormycosis (Zygomycosis) is a life-threatening infection. We attempted to analyse clinical features and risk factors of Mucormycosis cases in a tertiary care referral institution in India, in patients without underlying malignancy. METHODS: We retrospectively analyzed data of patients diagnosed as having Mucormycosis over a 10 year period of 2000-2010. Patients with a histopathology report and/or a Microbiology report of Zygomycetes or Mucor from a biopsy specimen were included in the study. RESULTS: Out of the 27 cases, rhino-orbital/rhino-cerebral involvement occurred in 12 (44.4%) patients, pulmonary involvement in 3 (11.1%) cases, soft tissue involvement in 11 (40.7%) cases and gastrointestinal involvement in one patient (3.7%). Diabetes mellitus is the main risk factor, followed by renal failure and trauma. Mean ESR value of these patients was 118 mm/1 hour. Mean WBC count was 20 x 10(9)/L, and neutrophil count 82%. The mean absolute neutrophil count (ANC) was 16.8 x 10(9)/L. CONCLUSION: The interesting finding in our study was the presence of neutrophilic leucocytosis and high ESR in most of the patients. In a predisposed individual, especially in a diabetic, in countries with high environmental fungal burden; presence of high ESR and neutrophilic leucocytosis with a compatible clinical presentation should raise suspicion of Mucormycosis.

Bis(tetra-ethyl-ammonium) bis-(hydrogen l-tartrate) l-tartaric acid monohydrate.

In the title compound, 2C(8)H(20)N(+)·2C(4)H(5)O(6) (-)·C(4)H(6)O(6)·H(2)O, the presence of the two tetra-ethyl-ammonium cations is balanced by two hydrogen l-tartrate anions. Also present in the asymmetric unit are a mol-ecule of l-tartaric acid and a water mol-ecule. The various components are linked by O-H⋯O hydrogen bonds. In the crystal, two-dimensional networks are formed via O-H⋯O hydrogen bonds and C-H⋯O inter-actions involving the water mol-ecule, the hydrogen l-tartrate anions and the l-tartaric acid mol-ecules. These layers, which stack along [001], are separated by tetra-ethyl-ammonium cations. The latter are also involved in C-H⋯O inter-actions with the anions and the l-tartaric acid and water mol-ecules participating in the two-dimensional network.

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.

Stromal-derived factor-1alpha (CXCL12) levels increase in periodontal disease.

BACKGROUND: The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell-derived factor-1 (SDF-1alpha or CXC chemokine ligand 12) are involved in the trafficking of leukocytes into and out of extravascular tissues. The purpose of this study was to determine whether SDF-1alpha secreted by host cells plays a role in recruiting inflammatory cells into the periodontia during local inflammation. METHODS: SDF-1alpha levels were determined by enzyme-linked immunosorbent assay in gingival crevicular fluid (GCF) of 24 individuals with periodontitis versus healthy individuals in tissue biopsies and in a preclinical rat model of Porphyromonas gingivalis lipopolysaccharide-induced experimental bone loss. Neutrophil chemotaxis assays were also used to evaluate whether SDF-1alpha plays a role in the recruitment of host cells at periodontal lesions. RESULTS: Subjects with periodontal disease had higher levels of SDF-1alpha in their GCF compared to healthy subjects. Subjects with periodontal disease who underwent mechanical therapy demonstrated decreased levels of SDF-1alpha. Immunohistologic staining showed that SDF-1alpha and CXCR4 levels were elevated in samples obtained from periodontally compromised individuals. Similar results were observed in the rodent model. Neutrophil migration was enhanced in the presence of SDF-1alpha, mimicking immune cell migration in periodontal lesions. CONCLUSIONS: SDF-1alpha may be involved in the immune defense pathway activated during periodontal disease. Upon the development of diseased tissues, SDF-1alpha levels increase and may recruit host defensive cells into sites of inflammation. These studies suggest that SDF-1alpha may be a useful biomarker for the identification of periodontal disease progression.

Factor group analysis and hyperpolarizability studies of nonlinear optical L-asparaginium picrate (LASP) crystals.

The factor group analysis and the hyperpolarizability study were carried out for the L-asparaginium picrate (LASP) single crystals to explore the possible vibrational modes and the microscopic nonlinearity by the density functional triply parameter hybrid model DFT/B3LYP using GAUSSIAN 98W, respectively. The HF/6-31G (d,p) basis set has been employed. The calculated first order hyperpolarizability of LASP is 4.815 x 10(-29)esu. The Fourier transform infrared (FTIR) spectroscopic studies were performed for identifying different functional groups present in the compound.

A comparative study on the growth and characterization of nonlinear optical amino acid crystals: L-alanine (LA) and L-alanine alaninium nitrate (LAAN).

A comparative study on the properties of L-alanine and LAAN crystals has been made and discussed. It may be concluded that the protonation of the amino group in the L-alanine molecule is the key factor in increasing the relative SHG efficiency of LAAN. The protonation is justified by the crystal structure analysis, FTIR and photoluminescence studies. The factor group vibrations are compared and found that there is an increase in vibrational modes of LA when reacted with nitric acid forming LAAN.

Growth and characterization of sodium pentaborate [Na(H4B5O10)] single crystals.

The bulk single crystals of sodium pentaborate [Na(H4B5O10)] were grown by slow evaporation solution growth technique using deionized water as solvent. The grown crystal was confirmed by single crystal X-ray diffraction studies. The structural perfection of the grown crystals has been analyzed by high resolution X-ray diffraction (HRXRD) studies by recording rocking curve. The photoluminescence (PL), UV-vis spectral studies were performed and the optical bandgap of the material was calculated. The presence of the functional groups was identified by FT-IR measurement. The factor group analysis was done on Na(H4B5O10) to reveal the vibrational optical modes. The thermal and mechanical properties of the grown crystal were studied by TG-DTA and Vickers microhardness tester, respectively. The dielectric behavior of Na(H4B5O10) was investigated with different frequencies and temperatures.

Studies on the growth, optical, electrical and spectral properties of potassium pentaborate (KB5) single crystals.

The bulk single crystals of nonlinear optical material potassium pentaborate (KB5) have been grown by slow evaporation solution growth technique using water as solvent. The grown crystal was confirmed by single crystal X-ray diffraction studies. The structural perfection of the grown crystals has been analyzed by high resolution X-ray diffraction (HRXRD) studies by recording rocking curve. The photoluminescence (PL), UV-vis spectral studies were performed and the optical bandgap of the material was calculated. FTIR and FT-Raman measurements enumerate the functional groups present in the compound. The factor group analysis on KB5 reveals that there are 117 vibrational optical modes. The dielectric behavior of KB5 was investigated with different frequencies and temperatures.

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.

Modification of WO(3) thin films by MeV N(+)-ion beam irradiation.

In this paper, we report on modification of the structural, optical, vibrational, and surface morphological properties of 2 MeV N(+)-ion irradiated WO(3) thin films at different fluences (up to 1 × 10(15) ions cm(-2)). Although we observe irradiation induced grain growth, no structural phase transition takes place in the WO(3) films. These are accompanied by a systematic reduction in the optical band gap of the films. These observations are corroborated by our independent micro-Raman and optical absorption spectroscopy studies. We have made an attempt to correlate these results with MeV ion-matter interaction.

Growth and characterization of organic nonlinear optical crystal of 1-chloro-2,4-dinitrobenzene (CDNB).

Organic nonlinear optical crystal of 1-chloro-2,4-dinitrobenzene has been successfully grown by low temperature solution growth technique. Good optical quality single crystals of size 28 mm x 11 mm x 5mm are obtained. Grown crystals were subjected to X-ray powder diffraction analysis, FT-IR, FT-Raman, proton nuclear magnetic resonance (PNMR) and etching studies. Thermal properties of the grown crystals were studied by thermo gravimetric analysis (TGA) and differential thermal analysis (DTA). UV-vis studies show the cutoff wavelength is less than 400 nm. Nonlinear optical property of the crystal was studied by Kurtz powder technique using Nd:YAG laser and the crystal exhibits second harmonic generation property.

Refractory hyperkalaemia due to trimethoprim, successfully treated with fludrocortisone.

We report a case of intractable hyperkalaemia in an elderly patient with myeloma, who received conventional dose of trimethoprim-sulfamethoxazole and hyperkalaemia resolved following therapy with fludrocortisone. We recommend monitoring of serum potassium in high-risk patients receiving conventional doses of trimethoprim-sulfamethoxazole for 5 or more days.