Efficacy of Early Intervention for Infants With Cerebral Palsy in an LMIC: An RCT.

OBJECTIVE: To test efficacy of a parent-delivered multidomain early intervention (Learning through Everyday Activities with Parents [LEAP-CP]) for infants with cerebral palsy (CP) compared with equal-dose of health advice (HA), on (1) infant development; and (2) caregiver mental health. It was hypothesized that infants receiving LEAP-CP would have better motor function, and caregivers better mental health. METHODS: This was a multisite single-blind randomized control trial of infants aged 12 to 40 weeks corrected age (CA) at risk for CP (General Movements or Hammersmith Infant Neurologic Examination). Both LEAP-CP and HA groups received 15 fortnightly home-visits by a peer trainer. LEAP-CP is a multidomain active goal-directed intervention. HA is based on Key Family Practices, World Health Organization. Primary outcomes: (1) infants at 18 months CA: Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT mobility); and (2) caregiver: Depression Anxiety and Stress Scale. RESULTS: Of eligible infants, 153 of 165 (92.7%) were recruited (86 males, mean age 7.1±2.7 months CA, Gross Motor Function Classification System at 18 m CA: I = 12, II = 25, III = 9, IV = 18, V = 32). Final data were available for 118 (77.1%). Primary (PEDI-CAT mobility mean difference = 0.8 (95% CI -1.9 to 3.6) P = .54) and secondary outcomes were similar between-groups. Modified-Intention-To-Treat analysis on n = 96 infants with confirmed CP showed Gross Motor Function Classification System I and IIs allocated to LEAP-CP had significantly better scores on PEDI-CAT mobility domain (mean difference 4.0 (95% CI = 1.4 to 6.5), P = .003) compared with HA. CONCLUSIONS: Although there was no overall effect of LEAP-CP compared with dose-matched HA, LEAP-CP lead to superior improvements in motor skills in ambulant children with CP, consistent with what is known about targeted goal-directed training.

Clinical outcome after high dose rate intracavitary brachytherapy with traditional point 'A' dose prescription in locally advanced carcinoma of uterine cervix: dosimetric analysis from the perspective of computed tomography imaging-based 3-dimensional treatment planning.

OBJECTIVE: To analyze tumour response and toxicity with respect to cumulative radiotherapy dose to target and organs at risk (OARs) with computed tomography (CT)-based image guided adaptive brachytherapy planning for locally advanced carcinoma cervix. METHODS: Patients were treated with two-dimensional concurrent chemoradiotherapy to whole pelvis followed by intracavitary brachytherapy (ICBT) with dose prescription to point 'A'. CT image-based delineation of high-risk clinical target volume (HR-CTV), urinary bladder, rectum and sigmoid colon was done with generation of dose-volume histogram (DVH) data and optimization of doses to target and OARs. Follow up assessments were done for response of disease and toxicity with generation of data for statistical analysis. RESULTS: One hundred thirty-six patients were enrolled in the study. Delineated volume of HR-CTV ranged from 20.9 to 37.1 mL, with median value of 30.2 mL. The equivalent dose in 2 Gy per fraction (EQD2) for point 'A' ranged from 71.31 to 79.75 Gy with median value of 75.1 Gy and EQD2 HR-CTV D90 ranged from 71.9 to 89.7 Gy with median value of 85.1 Gy. 69.2% of patients showed complete response and after median follow-up of 25 months, 50 patients remained disease free, of whom, 74.0% had received ≥85 Gy to HR-CTV D90 versus 26.0% receiving <85 Gy to HR-CTV D90. CONCLUSION: s Amidst the unavailability of magnetic resonance imaging facilities in low middle income countries, incorporation of CT-image based treatment planning into routine practice for ICBT provides the scope to delineate volumes of target and OARs and to generate DVH data, which can prove to be a better surrogate for disease response and toxicity.

Enhancement of Fluorescence Mediated by Silver Nanoparticles: Implications for Cell Imaging.

In this study, we report the surface enhanced fluorescence (SEF) of a biologically important organic dye, fluorescein (FL), by silver nanoparticles (Ag NPs) in an aqueous medium and its implications for human cell imaging. The as-synthesized Ag NPs were characterized by dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), and UV-vis absorption spectroscopic studies. The interaction and aggregation of FL dye with Ag NPs and a cationic surfactant, namely, cetyltrimethylammonium bromide (CTAB), were explored by UV-vis absorption and steady-state and time-resolved fluorescence spectroscopic methods. The distance-dependent fluorescence enhancement of FL due to Ag NPs in the solution was also theoretically correlated by three-dimensional finite-difference time-domain (3D-FDTD) simulation. The plasmonic coupling between neighboring NPs facilitated the augmentation of the local electric field, thereby producing various "hotspots" that influence the overall fluorescence of the emitter. J-type aggregates of FL in the presence of the CTAB micelles and Ag NP mixed solution were confirmed by electronic spectroscopy. The density functional theoretical (DFT) study revealed the electronic energy levels associated with different forms of FL dye in the aqueous solution. Most interestingly, the Ag NP/FL mixed system used in fluorescence imaging of human lung fibroblast cells (WI 38 cell line) showed a significantly stronger green fluorescence signal compared to that of FL after an incubation period of only 3 h. This study confirms that the Ag NP mediated SEF phenomenon of the FL dye is also manifested in the intracellular medium of human cells giving a brighter and more intense fluorescence image. The cell viability test after exposure to the Ag NP/FL mixed system was confirmed by the MTT assay method. The proposed study may have an implication as an alternate approach for human cell imaging with higher resolution and more contrast.

Comparative and Selective Interaction of Amino Acid d-Cysteine with Colloidal Gold Nanoparticles in the Presence of a Fluorescent Probe in Aqueous Medium.

In this communication, we report the comparative and selective interaction of amino acid d-cysteine (d-Cys) with citrate caped gold nanoparticles (Au NPs) in the presence of a fluorescent dye, rhodamine B (RhB), in aqueous solution. Au NPs of size 27.5 nm could almost fully quench the steady-state fluorescence emission of RhB at their optimum concentrations in the mixed solution. The interactions of d-Cys, l-Cys, all other relevant d- and l-amino acids, neurotransmitters, and other relevant biological compounds with the Au NPs/RhB mixed solution have been explored by monitoring the fluorescence recovery efficiencies from the almost fully quenched state of RhB fluorescence via a simple steady-state spectrofluorometric method. The higher fluorescence recovery for the interaction of d-Cys with the Au NPs/RhB mixed system is accompanied by a distinct color change (red-wine to bluish-black) of the assay medium after the reaction compared to that of all other interfering compounds considered in this work. The sensitivity of this fluorometric response lies in a broad linear range of concentrations of d-Cys and the limit of detection (LOD) is found to be 4.2 nM, which is low compared to many other methods available in the literature. The different degrees of interaction of d-Cys and l-Cys with the Au NPs/RhB mixed sample have been further explored by circular dichroism (CD) spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The selective interaction of d-Cys with the proposed Au NPs/RhB mixed system is also found to be correlated with interparticle cross-linking and aggregations of nanoparticles by the analysis of ζ potential and dynamic light scattering (DLS) study, transmission electron microscopy (TEM), atomic force microscopy (AFM), UV-vis absorption spectroscopy etc. The proposed interaction mechanism is further studied with a normal human urine sample to elucidate that the optimized combination of Au NPs and RhB may be realized as an efficient platform for detection of the amino acid d-Cys in a real biosample via a simple fluorometric approach.

Exfoliated Molybdenum Disulfide-Wrapped CdS Nanoparticles as a Nano-Heterojunction for Photo-Electrochemical Water Splitting.

We developed a heterojunction photocathode, MoS2@CdS, based on the wrapping of CdS nanoparticles by the MoS2 nanocrystals. The liquid-phase exfoliation method was adopted for preparing few-layer MoS2 nanocrystals of a layer thickness of ∼7.9 nm, whereas CdS nanoparticles of an average diameter of ∼17 nm were synthesized by the one-step hydrothermal process. The synthesized nanocrystals and nanoparticles were characterized by AFM, FESEM, HRTEM, STEM, XRD, GIXRD, UV-vis absorption, fluorescence emission, and Raman spectroscopy. The difference between two modes in the Raman spectrum of MoS2 indicates the formation of few-layer MoS2. The photoelectrochemical performance of the heterojunction photocathode was excellent. The MoS2@CdS heterostructure photocathode increased the photocurrent density (JPh) under 100 mW/cm2 illumination. We obtained the maximum applied biased photoconversion efficiency (ABPE) of ∼1.2% of the MoS2@CdS heterojunction photocathode in optimum device configuration. The production of H2 was measured as ∼72 µmol/h for the MoS2@CdS heterostructure with a cyclic stability of up to 7500 s.

Tracheo-bronchial foreign bodies: a retrospective study and review of literature.

Tracheobronchial foreign body aspiration is a common emergency in childhood constituting major cause of mortality. Although ample studies regarding airway foreign bodies are present in western literature, studies in Indian context are however lacking. The aim of the study is to present an epidemiological data regarding airway foreign bodies in Indian context thereby helping to analyze the situation with regard to our socio-economic condition. Retrospective file review of all case (n = 82) that underwent rigid bronchoscopy for suspected tracheo-bronchial foreign body over a period of 7 years (2001-2008) in the department of otolaryngology of a tertiary care centre of eastern India. Patient characteristics, history, clinical, radiographic and bronchoscopic findings were noted in an attempt to define the epidemiology, clinical presentation, management and associated morbidity. Most common age of presentation was between 1 and 3 years (56.4%). Most common symptom in our study was Cough, wheezing and respiratory distress (63.4%). Most common clinical signs at presentation were diminished breath sound in unilateral lung field seen in 36.6% cases. Most common radiological finding on chest radiograph was collapse seen in 41.65% cases. Most common type of foreign body below 3 years of age was food material (seeds, beans) removed in 48.78%. Complications were encountered in 14.6% cases of which most common complication was bronchospasm and acute respiratory distress seen in 41.6% cases.

Patterns of cancer occurrence in different regions of West Bengal--a hospital based study.

The incidence of cancer has been rising steadily in the third world countries including India. The patterns of cancer incidence reflect the racial, cultural and pharmacogenomic diversity within populations and nowhere is this diversity more striking than in the Indian subcontinent. This article shows the diversity in patterns of incidence of major cancers across three medical college hospitals in the state of West Bengal in India. All the data were collected from the period between 2001 and 2005. The results show a striking variation of incidence of major cancers in the urban, semi-urban and rural parts of the same state. Indeed the differences of the patterns are explainable by the cultural and socioeconomic differences within the populations from which the study samples are drawn. This constitutes the largest single hospital based data collected from this part of the world till date and will help in re-evaluation of cancer control programmes promulgated by the health authorities of the region.

The effect of honey on mucositis induced by chemoradiation in head and neck cancer.

The aim of this study was to evaluate the effect of pure natural honey on radiation-induced mucositis. Fifty-five patients diagnosed with head and neck cancer requiring radiation to the oropharyngeal mucosal area were divided into two groups (study arm-28 and control arm-27) to receive either chemoradiation or chemoradiation plus topical application of honey. Patients were treated using a telecobalt machine at 2 Gy per day, five times a week up to a total dose of 66 Gy. in the study arm, patients were advised to take 20 ml of honey 15 minutes before, 15 minutes after and similar amount at bed time. Patients were evaluated every week for the development of radiation mucositis using the WHO grading system. There was significant reduction in the symptomatic grades 3 and 4 mucositis in honey-treated patients compared to controls ie, 18% versus 41% for grade 3 and 4% versus 22% for grade 4 mucositis. Seventy-one per cent of patients treated with topical honey showed no change or a positive gain in body weight. In the control group also 22% had no weight loss, though none showed weight gain. Furthermore, it didn't affect blood sugar level when initial fasting blood sugar level was < 150 mg%. Honey is a cheap, simple, easily available and effective agent in reducing radiation-induced mucositis. Within the limits of this study the results showed the application of natural honey is effective in managing radiation induced mucositis, which warrants further multicentric randomised trials to validate the findings.

Dysphagia--an uncommon presentation of unnoticed snakebite.

Snakebite cases do not always present with classical features of bite, resulting in delay in diagnosis and treatment with disastrous consequences, especially when bite occurs during sleep at night. Ptosis is the most common early symptom. Dysphagia, though not uncommon in cases of snakebite but presenting solely with this, is very rare. Here a case of a young man with complaints of only severe dysphagia without any history of bite is reported. He was treated as a case of neurotoxic snakebite poisoning and found to have recovered.

Changing trends in incidence of cancer sites in West Bengal--a hospital based study.

A trend of change has been observed in the incidence pattern of cancer. The incidence of cancer has been slowly declining in the developed countries, but increasing in the less developed and developing countries. Smoking prevalence in the developing countries is now much higher compared to the developed countries, contributing to almost half of all the cancers among males in developing countries. Lung cancers are increasing rapidly in Kolkata and West Bengal, whereas head and neck cancer has shown a declining trend. Proportion of gastro-intestinal cancers is increasing in West Bengal. Lifestyle change, inactivity, intake of calorie-dense food, obesity may have a reflection over some of these cancers. Breast cancers are now the commonest cancer of females of West Bengal in contrast to rest of India except Mumbai. Incidence of cancer of cervix has grossly declined in the city of Kolkata, but not in rural Bengal.

A rare case of inguinal lymph node metastasis from supraglottic laryngeal carcinoma.

Head and neck cancers are common among men in developing countries. Among head and neck cancers in the United States, supraglottic laryngeal cancer accounts for 12,500 new cases per year. It responds favorably to radiotherapy with or without chemotherapy depending on the stage of disease. Recurrence is local or locoregional. We report a unique case of carcinoma of the larynx with rare distal recurrence in the left inguinal lymph nodes.

Selective deletion of CD8(+) cells upregulated by caspases-1 via IL-18 in mice immunized with major outer membrane protein of Shigella dysenteriae 1 following infection.

INTRODUCTION: Mucosal lymphoid changes were observed in cryopreserved rectal tissues obtained from BALB/c mice infected with Shigella dysenteriae 1, immunized with 57-kDa major antigenic outer membrane protein, and infection after immunization. DISCUSSION: Our data suggested that caspase-3 is downregulated in CD4(+) cells of immunized BALB/c mice following infection with substantial increased expression of interleukin (IL)-2 and interferon (IFN)-gamma, while caspase-1 is upregulated in CD8(+) cells with decreased expression of IL-4 and IL-10. This indicated an involvement of Fas-mediated lytic pathway for selective deletion of CD8(+) cells out of CD3(+) T cells. IL-18 promotes inflammation and induces IFN-gamma and tumor necrosis factor (TNF)-alpha as the expression of IFN-gamma and TNF-alpha cytokines was evident in this study. It is assumed that the role of caspase-1 in inducing the CD4+ T cell activity increased with IL-18 rather than CD8+ suppressor cell activity. Bcl-2 is capable of inhibiting the Fas/Fas-L-mediated cell death for helper cells. Overall, the findings indicate that majority of the apoptotic cells were CD8(+) T cells in the groups of infection following immunization, and there might be a selective deletion of T lymphocytes mediated by caspase-1 via IL-18.

Pattern of cancer occurrence in rural population of West Bengal--a hospital-based study.

Incidence of cancer in India is lower than in the West and the commonly affected sites are very different. Cancers of the upper alimentary and respiratory tracts (oral cavity, pharynx, larynx) contribute more than half of the cancers in men and about a quarter in women. Indigenous habits of chewing and smoking seem to be primarily responsible for the high incidence of these cancers. During a 10-year study period, out of a total 20072 cases biopsied, 3226 (16.07%) were malignant. The maximum number of malignancies were from cervix uteri ie, 1499 (44.92%); next oral cavity and pharynx (n = 437; 13.55%) frequently found in males; breast was third in the series. Cancer of the cervix uteri is a major problem in women. Practical measures are to be taken for the prevention of these cancers common in India.

Immunofluorescence imaging as a tool for studying the pharmacokinetics of a human monoclonal single chain fragment antibody.

We have used immunofluorescence imaging to study binding of a monoclonal antibody fragment to subcutaneously implanted human melanoma cells in nude mice. The data acquired using this nontraditional approach was then analyzed using standard pharmacokinetic methods to produce estimates of k(e) (0.06h(-1)), t 1/2 (16 h), mean residency time (23.4 h) and percent exposure of the antibody to the tumor (40%). To our knowledge this is the first time standard pharmacokinetic analyzes have been conducted on immunofluorescence imaging data. The combination of this novel imaging technique and standard pharmacokinetic analytical methods should prove to be a useful tool for comparing the properties of antibody fragments in animal models.