Protein phosphatase 2A impairs IFNα-induced antiviral activity against the hepatitis C virus through the inhibition of STAT1 tyrosine phosphorylation.

Mammalian cells have developed several mechanisms to sense viruses and initiate adequate responses such as production of interferons. Interferons activate the antiviral response through the Jak-STAT signalling pathway. To establish a chronic infection, viruses need to counteract this barrier of defence. The hepatitis C and hepatitis B viruses are known to up-regulate the expression of protein phosphatase 2A (PP2A). In this study, we show that PP2Ac associates with Jak1/Tyk2/STAT1 and reduces Jak1/Tyk2/STAT1 phosphorylation resulting in an impairment of the IFNα-induced HCV antiviral response. Using the fully infectious HCV cell culture system (HCVcc), we demonstrate that the PP2A catalytic activity is not required to block the antiviral effect of IFNα, although it is needed to support HCVcc replication. Our data suggest an important contribution of virus-induced PP2Ac up-regulation in the establishment of a chronic infection.

Highly luminescent-paramagnetic nanophosphor probes for in vitro high-contrast imaging of human breast cancer cells.

Highly luminescent-paramagnetic nanophosphors have a seminal role in biotechnology and biomedical research due to their potential applications in biolabeling, bioimaging, and drug delivery. Herein, the synthesis of high-quality, ultrafine, europium-doped yttrium oxide nanophosphors (Y(1.9)O(3):Eu(0.1)(3+)) using a modified sol-gel technique is reported and in vitro fluorescence imaging studies are demonstrated in human breast cancer cells. These highly luminescent nanophosphors with an average particle size of ≈6 nm provide high-contrast optical imaging and decreased light scattering. In vitro cellular uptake is shown by fluorescence microscopy, which visualizes the characteristic intense hypersensitive red emission of Eu(3+) peaking at 610 nm ((5)D(0)-(7)F(2)) upon 246 nm UV light excitation. No apparent cytotoxicity is observed. Subsequently, time-resolved emission spectroscopy and SQUID magnetometry measurements demonstrate a photoluminescence decay time in milliseconds and paramagnetic behavior, which assure applications of the nanophosphors in biomedical studies.

Highly efficient luminescence from hybrid structures of ZnO/multi-walled carbon nanotubes for high performance display applications.

We report an interesting observation on strong enhancement in green luminescence from hybrid ZnO/multi-walled carbon nanotubes (MWCNTs). The hybrid structures were synthesized via a high temperature sintering method. The strong green emission at 510 nm has been attributed to surface defects of ZnO, originating from interactions between ZnO and the MWCNT surface, which has been confirmed by high resolution transmission electron microscopy and x-ray photoelectron spectroscopy. Furthermore, the two-dimensional (2D) layer of this hybrid material shows a high degree of homogeneity and 82% transparency. Time resolved emission spectroscopy measurement shows a photoluminescence decay time in microseconds, which is suitable for making optoelectronic devices.

Synthesis and characterization of ultra-fine Y2O3:Eu3+ nanophosphors for luminescent security ink applications.

We report a simple method for the synthesis of ultra-fine Eu(3+)-doped yttria (Y(2)O(3)) nanophosphors with an average diameter of approximately 5 nm for development of a transparent colloid that could be used as a luminescent security ink. This has been achieved by suitably substituting Eu(3+) ions at the favorable C(2) symmetry sites of Y(3+) ions and quantum mechanically confining the growth of the nanophosphor using a novel acid-catalyzed sol-gel technique. This is one of the few reports that depict the development of a transparent aqueous-stable Y(2)O(3):Eu(3+) colloidal solution for strategic applications related to security codes. High resolution transmission electron microscopy images showed excellent lattice fringes that in turn support the presence of better crystal quality and enhanced photoluminescence (PL) emission from the Y(1.9)O(3)Eu(0.1)(3+) nanophosphor system. Time resolved emission spectroscopy measurement indicated a PL decay time in the range of a few milliseconds, suitable for making luminescent security ink and other advanced applications in optoelectronic devices and bio-labeling.

Self-catalytic synthesis, structure and properties of ultra-fine luminescent ZnO nanostructures for field emission applications.

A facile method to produce high-quality ZnO nanostructures; either tetrapod (TP), nanotetraneedle (NTN) or multipod (MP) with a high degree of homogeneity for advanced field emission (FE) applications is presented. Among these nanostructures, NTN has been successfully employed to demonstrate enhanced current densities (2.6 mA cm(-2)), turn-on field (1.5 V microm(-1)) and field-enhancement factors (6930) over conventional multiwalled carbon nanotubes (MWCNTs), TP, MP and ZnO-spheroids. A comparative study of FE from various ZnO nanostructures, morphologies and site densities has lead to the conclusion that diameter of the tip is one of the vital parameters in enhancing the overall FE properties.

Investigation of confinement effects in ZnO quantum dots.

We report a simple method for the synthesis of Na(+) doped and stable zinc oxide quantum dots, using the quantum confinement atom method. An intense broad green photoluminescence (PL) was observed with a maximum located at approximately 535 nm when excited by UV radiation of 332 nm. The PL peak intensity is found to be highly dependent on the size of the quantum dots (QDs). Electron microscopy observation revealed that the radius of the QD was approximately 1 nm, which clearly indicated that the QDs are in the strong quantum confinement region (exciton Bohr radius, r(B), for bulk ZnO is 1.8 nm). Phase purity of ZnO and the presence of Na(+) was confirmed by x-ray diffraction (XRD) and atomic absorption spectroscopy (AAS), respectively. The results are well incremented by x-ray photoelectron spectroscopy (XPS) studies. Intentional ageing of QDs for several days under controlled experimental conditions such as temperature, relative humidity and pH etc, facilitated the formation of various nanostructures with a slight red shift in the PL peak position. Time resolved emission spectroscopy measurements indicated that PL decay time changes from 35 ns for QDs to 1660 micros for nanocrystals. The observed high-intensity and stable green PL emissions have been analyzed and thoroughly discussed.

Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts.

Mucocutaneous findings in 150 HIV+ve cases (F, 79; M, 71) were evaluated over a one-year period. Mucocutaneous manifestations were seen in 96% with 2.9 mean number of dermatoses and mean cluster of differentiation (CD4) count of 196.33 cells/mm(3). The highest number of mean dermatoses, 3.29, was seen in individuals with severe immunosuppression. The most common mucocutaneous manifestation seen was candidiasis (35.33%), followed by seborrhoeic dermatitis (31.33%), oral pigmentation (29.33%), xerosis/ichthyosis (22.67%), pyodermas (22%), periodontitis (17.33%) and nail pigmentation (16.67%). Patient stratification according to the WHO immunological staging, according to CD4 counts, showed a statistically significant association (P < 0.05) for candidiasis, scabies, paronychia, oral pigmentation and diffuse hair loss. Nail and oral pigmentary changes, trichomegaly and subcutaneous fungal infections caused by dermatophytes were highlights of the study. Incidences of xerosis/ichthyosis, pyodermas, scabies and molluscum contagiosum reported in our study were higher and pruritic popular eruptions was lower than those in previous Indian studies. Cutaneous neoplasms were not seen in the present study.

Severe form of type 2 reaction in patients of Hansen's disease after withdrawal of thalidomide: case reports.

Thalidomide, a racemic glutamic acid analogue, was first developed in 1954 and subsequently marketed in Europe, Australia and Canada as a sedative and anti-emetic. It was approved by the Food and Drug Administration (FDA) in the USA in 1998 for the treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and suppression of the cutaneous manifestations of ENL recurrences. It is a good choice for management in patients who are dependent on corticosteroids. Common side effects of thalidomide are teratogenicity, peripheral neuropathy, sedation and constipation. We report 4 cases of Hansen's disease with recurrent ENL who were adequately managed on thalidomide. On sudden withdrawal of thalidomide, they relapsed with severe type 2 reaction including necrotic ENL.

Clinico-epidemiological trends of leprosy in Himachal Pradesh: a five year study.

This retrospective study was done to determine the epidemiological and clinical profile of leprosy patients in a tertiary care centre, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India. In this study, we included patients registered from January 2004 to December 2008 with the urban leprosy clinic of our tertiary care centre. Data regarding demographic details, clinical features, treatment and complications was extracted from the records of the leprosy clinic. 163 patients attended the clinic during this period with male to female ratio of 3:1. Majority of patients (47.8%) were in the middle age group (20-40 years) and 13.49% patients were < 20 years of age. In the clinical disease spectrum, 53.98% patients were in the borderline spectrum followed by lepromatous leprosy (33.12%) and polar tuberculoid leprosy (5.52%). Pure neuritic and indeterminate leprosy accounted for 3.06% each. Histoid lesions were present in 7.4% of lepromatous leprosy patients. 9.2% patients had definite history of contact in the family or neighborhood. 28.22% patients were immigrants either from Nepal or adjoining states of Himachal Pradesh. Epidemiological studies and contact tracing can decrease the disease burden and morbidity associated with the disease. Multidrug therapy (MDT) helps preventing and reducing the disease progression, severity and disabilities.

Facial lupus vulgaris of bilateral periorbital skin and conjunctiva: a case report and brief review.

A 22-year-old male presented to the Dermatology Department with bilateral plaque lesions distributed symmetrically over malar area, bridge of nose and upper eyelids progressing over 1 year 3 months. Lesion remained unhealed after antibiotic treatment. Microscopy and culture for fungal and mycobacterial infections were negative. The Mantoux test showed an exaggerated response and PCR was positive for Mycobacterium tuberculosis complex. Patient was treated successfully with anti-tubercular therapy.

Hypertrophic osteitis of the medial end of the clavicle.

A 9-year-old boy had a spontaneous onset of enlargement of the medial end of the clavicle due to extensive sclerosis and periosteal reaction. There was no clinical or laboratory evidence of infection. Biopsy revealed an inflammatory exudate, and histochemical staining for Langerhans'-cell histiocytosis was negative. Hypertrophic sclerosis causing painful enlargement of the medial end of the clavicle in isolation should be distinguished from condensing osteitis and chronic recurrent multifocal osteomyelitis. An early biopsy to exclude neoplasia is recommended.

Slipped capital femoral epiphysis: is the displacement always posterior?

The initial direction of displacement on slipped capital femoral epiphysis is generally accepted to be posterior as a consequence of retroversion of the femoral neck. We report the case of a 15-year-old boy with slipped capital femoral epiphysis in the medial direction, confirmed by three-dimensional computerized imaging. This was associated with an elongated neck without retroversion of the femoral neck. We suggest a correlation between elongated femoral neck with increased offset of the hip and the medial direction of slip. This case also underlines the need for precise definition of deformity prior to undertaking surgical treatment.

Effect of dietary restriction with and without leucine supplementation on hepatic protein status in rats.

In the present study effect of dietary restriction with and without leucine supplementation was observed on body and liver weights, and liver protein status, in adult rats. Animals were fed on two diets ad lib or were on 50 per cent and 25 per cent intakes. Dietary restriction resulted in loss of body and liver weights, hepatic protein, free-alpha-amino nitrogen and RNA contents and liver cell size (liver weight/DNA ratio). When compared with the control group, the decrease in these parameters was more in the dietary restricted leucine supplemented group. However, hepatic DNA content was not changed with the change in dietary regimen. The results suggest that leucine supplementation with dietary restriction may be more harmful for the animal than dietary restriction alone.

Cognitive and Antipsychotic Medication Use in Monoallelic GBA-Related Parkinson Disease.

Mutations in glucosidase, beta, acid (GBA) are associated with cognitive impairment in Parkinson disease (PD) as well as dementia with Lewy bodies. For both of these diseases, dementia and hallucinations are typically treated with cholinesterase inhibitors and antipsychotics. However, in some lysosomal storage disorders certain antipsychotic medications are poorly tolerated. This study examined cholinesterase inhibitor and antipsychotic use in monoallelic GBA-related PD to explore potential pharmacogenetic relationships. Monoallelic GBA mutation carriers with PD (GBA-PD) with at least two clinic visits (n = 34) were matched for age-of-onset and gender to GBA and leucine-rich repeat kinase 2 (LRRK2) mutation negative idiopathic PD subjects (IPD) (n = 60). Information regarding cholinesterase inhibitor and antipsychotic use as well as impaired cognition (UPDRS Mentation >1) and hallucinations (UPDRS Thought Disorder >1) were obtained. GBA-PD more frequently reported hallucinations (HR = 5.0; p = 0.01) and they were more likely to have cognitive impairment but this was not statistically significant (HR 2.2, p = 0.07). Antipsychotic use was not significantly different between GBA-PD and IPD (HR = 1.9; p = 0.28), but GBA-PD were more likely to have sustained cholinesterase inhibitor use (HR = 3.1; p = 0.008), even after adjustment for cognition and hallucinations. Consistent with reports of worse cognition, GBA-PD patients are more likely to use cholinesterase inhibitors compared to IPD. While there was no difference in antipsychotic use between IPD and GBA-PD, persistent use of quetiapine in GBA-PD suggests that it is tolerated and that a significant interaction is unlikely. Further prospective study in larger samples with more extensive cognitive assessment is warranted to better understand pharmacogenetic relationships in GBA-PD.

Accommodative spasm with bilateral vision loss due to untreated intermittent exotropia in an adult.

BACKGROUND: Intermittent exotropia (IXT) is an exodeviation intermittently controlled by fusional mechanisms. Patients with IXT may present with asthenopic symptoms, blurred vision, headaches, diplopia or visual confusion and reading difficulties; especially after prolonged periods of near work. OBJECTIVE: To report the presentation and management of a young adult with intractable accommodative spasm secondary to long standing intermittent exotropia. CASE: The patient was found to have bilateral accommodative spasm with high pseudomyopia and severe impairment of vision. There was a tendency for recurrence with discontinuation of cycloplegics. CONCLUSION: A total relief of symptoms was noticed after strabismus surgery was undertaken for the exotropia. A detailed orthoptic evaluation with emphasis on recognizing accommodative spasm as an unusual presentation of IXT, could aid in appropriate diagnosis and treatment of such cases.

Gender differences in the risk of familial parkinsonism: beyond LRRK2?

G2019S mutations in the LRRK2 gene are responsible for up to 18% of PD in individuals of Jewish descent. While a male preponderance of Parkinson disease (PD) has been consistently reported, this gender difference is not noted in LRRK2 G2019S mutation carriers. In order to test whether there is an increased genetic component in women of Jewish background in general, we examined family history of parkinsonism in 175 Jewish PD patients (82 female and 93 male) and assessed whether parkinsonism was more frequent in family members of women with PD in comparison with family members of men with PD, adjusting for LRRK2 G2019S mutations in the proband. Using Cox proportional hazard models to evaluate the risk of parkinsonism among family members of PD subjects, having a daughter with PD compared with a son was associated with increased risk of parkinsonism in the parent (HR 2.59, p=0.014) as was having a child with a LRRK2 G2019S mutation (HR 3.19, p=0.003). The increased risk among parents of women with PD persisted when adjusting for LRRK2 status (HR 2.19, p=0.023). Among individuals of Jewish descent, there is a relatively greater genetic load in women with PD, and this is not fully accounted for by the G2019S mutation. Further study that evaluates family information bias and assesses the role of glucocerebrosidase mutations is indicated.

Olfactory dysfunction in LRRK2 G2019S mutation carriers.

BACKGROUND: Olfactory dysfunction is an established nonmotor feature of idiopathic Parkinson disease (PD), which may precede disease onset. Olfaction is likely disturbed in patients with PD with leucine-rich repeat kinase (LRRK2) G2019S mutations, although the degree of impairment is debated. It is also unclear whether mutation carriers who have not yet manifested with PD have olfactory disturbances. METHODS: Thirty-one subjects with LRRK2 G2019S mutation-related PD (PD-manifesting carriers [PD-MC]), 30 subjects with PD without mutations (PD noncarriers [PD-NC]), 28 mutation carrier family members (nonmanifesting carriers [NMC]), and 46 controls completed the University of Pennsylvania Smell Identification Test (UPSIT). Generalized estimating equations were applied to determine whether olfactory score was associated with PD and LRRK2 mutation status. RESULTS: As expected, having PD was associated with impaired olfaction regardless of LRRK2 mutation status. More importantly, however, impaired olfaction was increased overall in LRRK2 carriers both with and without PD, though the impairment was only present in a subset of NMCs. Compared to controls, the mean score was lower among NMC (difference = -3.518, p = 0.006), MC (difference = -7.677, p < 0.0001), and idiopathic PD (PD-NC) (difference = -13.810, p < 0.0001). Olfaction was better among MC (PD-MC) than non-LRRK2 PD (PD-NC) (difference = 6.13, p = 0.0012). Group differences from the continuous analysis were maintained in dichotomous analysis stratifying at 15th percentile for age and gender. CONCLUSION: Olfaction is impaired in LRRK2 G2019S-mutation related PD, although less overall than other PD. Further, olfaction is impaired in a subset of LRRK2 NMC, suggesting that olfaction may be a marker for development of PD in this group, and that longitudinal studies are warranted.

Acid-base disorders in critically ill neonates.

OBJECTIVE: To study acid-base imbalance in common pediatric diseases (such as sepsis, bronchopneumonia, diarrhea, birth-asphyxia etc.) in neonates. DESIGN AND SETTING: An observational study was conducted in an emergency room of a tertiary teaching care hospital in Haryana, India. PATIENTS AND METHODS: Fifty neonates (from first hour to one month) attending pediatric emergency services with various ailments. Blood gas analysis, electrolytes, plasma lactate, and plasma albumin were estimated in neonates. RESULTS: Metabolic acidosis was the most common acid-base disorder. Hyperlactatemia was observed in more than half of such cases. Birth asphyxia was another common disorder with the highest mortality in neonates followed by bronchopneumonia and sepsis. Significant correlation between mortality and critical values of lactate was observed. CONCLUSION: Birth asphyxia with high-lactate levels in neonates constituted major alterations in acid-base disorders seen in an emergency room of a tertiary teaching care hospital. Plasma lactate concentration measurement provides an invaluable tool to assess type of metabolic acidosis in addition to predicting mortality in these neonates.