Local governments and community-based rehabilitation for developmental disabilities: leaving no one behind.

SETTING: The BUDS (not an acronym) institutions comprise a community-based rehabilitation initiative for children and families affected by developmental disabilities in Kerala, India. OBJECTIVE: To explore the role of local governments in the establishment and functioning of BUDS institutions. DESIGN: We used qualitative approaches comprising document review and in-depth interviews with trainers, parents of children with developmental disabilities and elected representatives. RESULTS: BUDS was created by Kudumbasree, a decentralised women empowerment and poverty alleviation initiative. Our findings illustrate the role of local governments in facilitating expansion through the establishment of infrastructure, therapy equipment, transportation and financial allocation for these, as well as through the development of human resources, assistance with enrolment for financial assistance and insurance programmes, and coordination with education and health sectors. Programme implementation varied considerably regarding available infrastructure, staffing and services among the institutions studied. The institutions were physically closed during the COVID-19 pandemic but continued to function in alternative ways. CONCLUSION: Despite variable implementation, local governments have supported the expansion of BUDS institutions, thereby creating more spaces for inclusive and integrated education and rehabilitation of persons with disabilities in Kerala. The expansion over the past two decades and measures during the COVID-19 pandemic suggest resilience and sustainability of the model.

CONTEXTE: Les institutions BUDS (ceci n'est pas un acronyme) ont mis en place une initiative communautaire pour la réhabilitation des enfants et familles touchés par des troubles du développement au Kérala, Inde. OBJECTIF: Analyser le rôle des gouvernements locaux dans la fondation et le fonctionnement des institutions BUDS. MÉTHODES: Nous avons utilisé des approches qualitatives fondées sur une analyse documentaire et sur des entretiens approfondis avec des formateurs, des parents d'enfants atteints de troubles du développement et des représentants élus. RÉSULTATS: BUDS a été créé dans le cadre d'une initiative décentralisée de réduction de la pauvreté et d'autonomisation des femmes, dénommée Kudumbasree. Nos résultats illustrent le rôle des gouvernements locaux dans la facilitation de l'expansion par la mise à disposition d'infrastructures, d'équipements thérapeutiques, de transports et l'allocation de fonds pour ceux-ci, ainsi que par le développement des ressources humaines, l'inclusion dans des programmes d'assistance financière et d'assurances, et la coordination avec les secteurs de l'éducation et de la santé. De grandes différences de mise en œuvre du programme ont été observées entre les institutions à l'étude, en matière d'infrastructures disponibles, de personnel et de services. Les institutions ont fermé leurs portes pendant la pandémie de COVID-19, mais elles continuaient de fonctionner de manière alternative. CONCLUSION: En dépit d'une mise en œuvre variable, les gouvernements locaux ont soutenu le développement des institutions BUDS et ainsi élargi l'espace pour une éducation et une réhabilitation inclusives et intégrées des personnes porteuses de handicaps au Kérala. Le développement de ces institutions au cours des 20 dernières années et les mesures instaurées pendant la pandémie de COVID-19 laissent transparaître la résilience et le caractère durable du modèle.

Health inequities around gender, disability and internal migration: are local governments doing enough.

SETTING: The Kerala health system in India has more than 25 years of decentralised implementation experience. Decentralization could assist in addressing health disparities such as gender, disability, and migration. OBJECTIVE: To explore how inequity issues comprising gender, disability and internal migrations were being addressed at present by the decentralised Kerala health system. DESIGN: Our approach was qualitative, using document review, key informant interviews and in-depth interviews with policy makers, health staff and other stakeholders. RESULTS: Gender aspects were incorporated into planning and budgeting, with 10% funds earmarked for women. Projects were gender-specific to women, and within conventional social roles of livelihood, welfare or reproductive health. Recently, transgender focused projects were also initiated. Schemes for people with disabilities remained welfare-centric and driven by top-down policies. The local governments performed beneficiary identification and benefit disbursal. Migrant health aspects were focused on infectious diseases surveillance and later living conditions of migrant workers. CONCLUSION: The importance that health systems place on socioeconomic determinants of health and fundamental human rights is reflected in the health interventions for marginalised communities. In Kerala, there is now a passive application of central rules and a reluctance to utilise local platforms. Changing this is a necessary condition for achieving equal development.

CONTEXTE: Le système de santé du Kérala en Inde possède plus de 25 ans d'expérience de mise en œuvre décentralisée. La décentralisation pourrait aider à lutter contre les disparités en matière de santé, telles que le genre, le handicap et la migration. OBJECTIF: Examiner comment les questions d'inégalité, notamment le genre, le handicap et les migrations internes, sont actuellement abordées par le système de santé décentralisé du Kérala. MÉTHODES: Notre approche qualitative s'est appuyée sur une analyse documentaire, des entretiens avec des informateurs clés et des entretiens approfondis avec des décideurs politiques, du personnel de santé et d'autres parties prenantes. RÉSULTATS: Les aspects liés au genre ont été intégrés dans la planification et les prévisions budgétaires, en réservant 10 % des fonds aux femmes. Les projets s'adressaient uniquement aux femmes et s'inscrivaient dans le cadre des rôles sociaux conventionnels de subsistance, de bien-être ou de santé génésique. Récemment, des projets axés sur les transsexuels ont également été lancés. Les programmes destinés aux personnes porteuses de handicaps restaient axés sur l'aide sociale et dictés par des politiques descendantes. Les gouvernements locaux se chargeaient de l'identification des bénéficiaires et du versement des prestations. Les aspects de la santé des migrants étaient axés sur la surveillance des maladies infectieuses, puis sur les conditions de vie des travailleurs migrants. CONCLUSION: L'importance accordée par les systèmes de santé aux déterminants socio-économiques de la santé et aux droits fondamentaux de l'homme se reflète dans les interventions sanitaires destinées aux communautés marginalisées. Au Kérala, on constate aujourd'hui une application passive des règles centrales et une réticence à utiliser les plateformes locales. Changer cet état de fait est une condition nécessaire pour parvenir à un développement égalitaire.

Antibacterial and anticancer potential of Brassica oleracea var acephala using biosynthesised copper nanoparticles.

INTRODUCTION: Brassica oleracea var acephala was studied for preliminary phytochemical screening. The results showed that the ethanolic crude extract of the leaf contain high phytochemical activity hence B.oleracea var acephala is rich in flavonoids, phenolic compounds, carbohydrates and phytosterols. MATERIALS AND METHODS: The ethanolic extract was used to synthesise copper nanoparticles. The copper nanoparticles were successfully synthesised from copper sulphate solution which was identified by the colour change from dark green colour of the extract. Thus the B.oleracea var acephala is a good source to synthesis copper nanoparticles. The synthesised copper nanoparticles were characterised using Scanning Electron Microscope (SEM) analysis. The SEM image displayed the high-density nanoparticles synthesised by leaf extracts and that the nanoparticles were crystals in shape. RESULTS: The copper nanoparticles (CNP) bind to the leaf extract. B.oleracea var acephala also has shown the antimicrobial and antioxidant activity. A comparative study was done between ethanolic its crude extract and nanoparticles. Both extracts exhibited zone of inhibition and better antioxidant potential but the CuNPs shows major zone of inhibition and showed more antioxidant activity. Anticancer activity of B.oleracea var acephala against Cervical HeLa cell line was confirmed using ethanolic crude extract and CNP. The results showed that HeLa cells proliferation was inhibited with increasing concentration of ethanolic crude extract and copper nanoparticles. From the results, it was seen that percentage viability of the cancer cells decreased with increased concentration of the samples whereas cytotoxicity against HeLa cell lines increased with the increased concentration of the samples. CONCLUSION: Thus B.oleracea var acephala possesses anticancer activity against HeLa cell lines.

Remotely sensed thermal decay rate: an index for vegetation monitoring.

Vegetation buffers local diurnal land surface temperatures, however, this effect has found limited applications for remote vegetation characterization. In this work, we parameterize diurnal temperature variations as the thermal decay rate derived by using satellite daytime and nighttime land surface temperatures and modeled using Newton's law of cooling. The relationship between the thermal decay rate and vegetation depends on many factors including vegetation type, size, water content, location, and local conditions. The theoretical relationships are elucidated, and empirical relationships are presented. Results show that the decay rate summarizes both vegetation structure and function and exhibits a high correlation with other established vegetation-related observations. As proof of concept, we interpret 15-year spatially explicit trends in the annual thermal decay rates over Africa and discuss results. Given recent increases in availability of finer spatial resolution satellite thermal measurements, the thermal decay rate may be a useful index for monitoring vegetation.

Heterogeneous precipitation mediated heterogeneous nanostructure enhances strength-ductility synergy in severely cryo-rolled and annealed CoCrFeNi2.1Nb0.2 high entropy alloy.

Possibilities of enhancing mechanical properties of brittle intermetallic containing high entropy alloys (HEAs) using novel processing and microstructural design strategies were investigated in the present work. For this purpose, homogenized CoCrFeNi2.1Nb0.2 HEA consisting of FCC matrix and complex Laves phase particles was successfully processed by severe cold- or cryo-rolling to 90% reduction in thickness followed by annealing (800 °C/1 hour(h)). As compared to cold-rolling, cryo-rolling resulted in a finer lamellar nanostructure and decidedly greater fragmentation of the Laves phase. Upon annealing, the cold-rolled HEA showed a recrystallized FCC matrix dispersed with D019 structured ε nano-precipitates. In contrast, the finer nanostructure and greater driving force for accelerated precipitation of profuse nano-precipitates at the early stages of annealing inhibited recrystallization in the cryo-rolled HEA and resulted in the formation of heterogeneous microstructure consisting of retained deformed and recrystallized regions. The novel heterogeneous microstructure of the cryo-rolled and annealed HEA resulted in a remarkable enhancement in strength-ductility synergy. The present results indicated that cryo-rolling could be used as an innovative processing strategy for tailoring heterogeneous microstructure and achieving novel mechanical properties.

Isolation and genetic characterization of mutans streptococci associated with dental caries in rural field practice of a dental institution: In vivo study.

BACKGROUND: Streptococcus mutans is well-known causative microorganism in the development of dental caries because they drop the plaque pH and produce acids from carbohydrates and survive in the acidic environment. It is now evident that knowledge of the bacteria enforces empirical approach to therapy, then specific antimicrobial therapy that might allow more conservative treatment options. Over the past few decades, there has been a remarkable increase in the prevalence rate of dental caries among children and the elders. Genotypic methods help in the detection and manipulation of nucleic acids which allows microbial genes to be examined directly. AIM: The aim of this study is to isolate and characterize S. mutans from rural population and to obtain genomic DNA and screen DNA band pattern. METHODOLOGY: A total of 80 plaque samples were collected from the buccal surfaces of maxillary and lingual surfaces of mandibular first molar with carious teeth in patients at a rural outreach center in Chikkaballapur district, Karnataka. Among these, 48 clinical isolates of S. mutans were recovered. Further, genomic DNA was extracted from all the positively isolated strains including the standard strain (microbial type culture collection 497), and stored at 4°C in tris EDTA buffer (TE). To analyze the molecular heterogeneity of the clinical strains, polymerase chain reaction (PCR), and restriction fragment length polymorphism was performed using restriction enzymes Hind III and Hae III. Using agarose gel electrophoresis, genomic DNA band pattern was analyzed. RESULTS: Statistically significant difference was seen in the "dex" gene collected from sample DNA and standard DNA in three different parameters (S. mutans 497). CONCLUSION: Genomic DNA of S. mutans was successfully isolated from the rural population. Dex gene was successfully amplified using PCR. Hae III enzymes successfully digested PCR amplicons and the fragments exhibited visible heterogeneity.

Interrogation of a longitudinal, national pharmacy claims dataset to explore factors that predict the need for add-on therapy in older and socioeconomically disadvantaged Australians with type 2 diabetes mellitus patients (T2DM).

PURPOSE: The management of type 2 diabetes mellitus (T2DM) is complex. The aim of this work is to explore factors that predict the need for add-on therapy in patients with T2DM in the community. METHODS: We accessed longitudinal, pharmacy payment claim records from the national Pharmaceutical Benefits Scheme (PBS) (Subsidises costs of medicines: government pays difference between patient co-payments, lower in concessional patients, and additional cost of drug.) for the period January 2006 to September 2014 (EREC/MI3127) from a 10% random sample of the Australian population validated to be representative of the population by the Australian Bureau of Statistics (ABS). Likely, T2DM patients were identified as those having been dispensed a single anti-hyperglycaemic drug (monotherapy). The time taken and possible factors that might lead to the addition of a second therapy were examined. An examination was made of trends in the co-prescription of either antihypertensive or anti-hyperlipidaemic agents in relation to the time (± 3 years) of initiating an anti-hyperglycaemic agent. RESULTS: Most (83%) presumed T2DM patients were initiated with metformin. The average time until the second agent was added was 4.8 years (95% CI 4.7-4.9). Satisfactory adherence, age, male gender, initiating therapy after 2012 and initiating with a sulphonylurea drug all were significant risks for add-on therapy. There was no overall trend in the initiation of antihypertensive and/or anti-hyperlipidaemic agents with respect to the time of anti-hyperglycaemic initiation. CONCLUSION: The usefulness of a longitudinal dataset of pharmacy-claim records is demonstrated. Over half of all older and socioeconmically disadvantaged T2DM patients captured in this longitudinal claims database will be prescribed a second anti-hyperglycaemic agent within 5 years of their first drug therapy. Several factors can predict the risk of prescription of add-on therapy, and these should be considered when prescribing medications to treat T2DM.

A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function.

PURPOSE: The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CLR), and apparent non-renal clearance of metformin (CLNR/F) in patients with varying degrees of kidney function and to develop dosing recommendations. METHODS: Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CLCR; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0.55 with an estimated inter-individual variability (IIV). Simulations were performed to estimate AUC0-τ, CLR, and CLNR/F. RESULTS: The data (66 patients, 327 observations) were best described by a two-compartment model, and CLCR was a covariate for CLR. Mean CLR was 17 L/h (CV 22%) and mean CLNR/F was 1.6 L/h (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a dosage interval. When CLR increased due to improved renal function, AUC0-τ decreased proportionally, while CLNR/F did not change with kidney function. Target doses (mg/day) of metformin can be reached using CLCR/3 × 100 to obtain median AUC0-12 of 18-26 mg/L/h for metformin IR and AUC0-24 of 38-51 mg/L/h for metformin XR, with Cmax < 5 mg/L. CONCLUSIONS: The proposed dosing algorithm can be used to dose metformin in patients with various degrees of kidney function to maintain consistent drug exposure. However, there is still marked IIV and therapeutic drug monitoring of metformin plasma concentrations is recommended.

An adolescent with prolapsed omentum per rectum: Spontaneous rectal perforation managed laparoscopically.

Spontaneous rupture of the rectum is a rare occurrence. A total laparoscopic approach to rectal perforation has only occasionally been reported. We report an unusual case of a young boy who developed a spontaneous rupture of the rectum following a trivial fall. A magnetic resonance imaging revealed a tear in the rectum at the peritoneal reflection with the omentum plugging it. He denied any history of rectal instrumentation or abnormal sexual activity. He had no history of constipation or rectal prolapse. The tear was repaired laparoscopically and a covering loop sigmoid colostomy was added. He made an uneventful post-operative recovery. Spontaneous rupture of the rectum can occur in younger age groups and even in the absence of significant trauma. One needs to diligently bring out a history of rectal trauma. Equally important is to rule out any underlying pathological condition. A laparoscopic approach is feasible, especially in early cases.

High early growth response 1 (EGR1) expression correlates with resistance to anti-EGFR treatment in vitro and with poorer outcome in metastatic colorectal cancer patients treated with cetuximab.

PURPOSE: Biomarkers, such as mutant RAS, predict resistance to anti-EGFR therapy in only a proportion of patients, and hence, other predictive biomarkers are needed. The aims were to identify candidate genes upregulated in colorectal cancer cell lines resistant to anti-EGFR monoclonal antibody treatment, to knockdown (KD) these genes in the resistant cell lines to determine if sensitivity to anti-EGFR antibody was restored, and finally to perform a pilot correlative study of EGR1 expression and outcomes in a cohort of metastatic colorectal cancer (mCRC) patients given cetuximab therapy. METHODS: Comparative expression array analysis of resistant cell lines (SW48, COLO-320DM, and SNU-C1) vs sensitive cell lines (LIM1215, CaCo2, and SW948) was performed. The highest up-regulated gene in each resistant cell line was knocked down (KD) using RNA interference, and effect on proliferation was assessed with and without anti-EGFR treatment. Expression of the candidate genes in patients' tumours treated with cetuximab was assessed by immunohistochemistry; survival analyses were performed comparing high vs low expression. RESULTS: Genes significantly upregulated in resistant cell lines were EGR1 (early growth response protein 1), HBEGF (heparin-binding epidermal growth factor-like growth factor), and AKT3 (AKT serine/threonine kinase 3). KD of each gene resulted in the respective cells being more sensitive to anti-EGFR treatment, suggesting that the resistant phenotype was reversed. In the pilot study of mCRC patients treated with cetuximab, both median PFS (1.38 months vs 6.79 months; HR 2.77 95% CI 1.2-19.4) and median OS (2.59 months vs 9.82 months; HR 3.0 95% CI 1.3-23.2) were significantly worse for those patients with high EGR1 expression. CONCLUSION: High EGR1 expression may be a candidate biomarker of resistance to anti-EGFR therapy.

Trends in metformin utilisation and dose appropriateness in Australia.

PURPOSE: The study aimed to (1) determine the trends in the utilisation of metformin in Australia, (2) determine the appropriateness of metformin dosing in an Australian teaching hospital and (3) gather the opinions of prescribers on the relationship between metformin dose and renal function. METHODS: National prescription data between 1990 and 2012 were accessed. A retrospective audit (2008-2012) of metformin doses and patient renal function (20 % random sample of all in-patients prescribed metformin) was conducted at St Vincent's Hospital (SVH), Sydney. Prescribers of metformin were interviewed (semi-structured; consultants at SVH) or surveyed (Australian endocrinologists) to gather their understanding of metformin dosing in relation to renal function. RESULTS: Metformin utilisation increased fivefold nationally between 1995 and 2012. Metformin tended to be under-dosed in SVH patients with normal renal function (83.5 %) and over-dosed in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <30 mL/min, 50 %). Consultants indicated that metformin doses needed to be reduced in renal impairment. Most endocrinologists (61 %) were comfortable prescribing metformin down to eGFRs around 30 mL/min. CONCLUSION: The use of metformin increased greatly over the period of the study. Metformin is prescribed frequently for patients with eGFR values below the minimal level approved in the product label (60 mL/min). While prescribers expressed their understanding of the need to reduce metformin doses in patients with renal impairment, we found that metformin doses were higher than appropriate in patients with impaired renal function. Metformin may be used safely when renal function is poor provided dosage is appropriately reduced.

Quantitative Evaluation of Tumour--Associated Tissue Eosinophilia and Cyclo-oxegenase-2 Gene in Oral Cancer Patients with Assessment of Long Term Outcomes.

Various histopathological parameters have been extensively studied for prognostication of oral cancer but the focus is now getting diverted towards the role of inflammatory mediators in cancer progression. The present study was undertaken to evaluate two such components of the inflammatory milieu, tumor-associated tissue eosinophilia (TATE) as well as Cyclo-oxygenase-2 (COX-2) gene expression, quantitatively in oral squamous cell carcinoma (OSCC) patients in relation to treatment outcomes and patterns of recurrence. A total of forty five patients with primary OSCC matching our inclusion criteria were selected for the study and followed up over a five year period. TATE was evaluated from the invasive front of the tumor using Haematoxylin and eosin (H & E) stained sections of histopathological specimens and graded as mild, moderate or intense. COX-2 gene expression was obtained from specimens using the reverse transcriptase--polymerase chain reaction (RT-PCR) method. A statistically significant association was observed between degree of TATE and locoregional recurrence (P < 0.001). The expression of COX-2 gene ranged from 0.4326 to 0.9998 and a higher mean COX-2 score was recorded in samples with intense degree of TATE followed by moderate and mild TATE. (P < 0.001). Using the t-test, the difference in mean COX-2 was found to be statistically significant (P < 0.001) between patients who developed locoregional recurrence and those who did not. The analysis of TATE may provide an indication of future recurrence at the time of diagnosis of OSCC. Also, the increased expression of COX-2 gene in OSCC strongly suggests its possible use as a chemopreventive/chemotherapeutic target.

Characterization of Landsat-7 to Landsat-8 reflective wavelength and normalized difference vegetation index continuity.

At over 40 years, the Landsat satellites provide the longest temporal record of space-based land surface observations, and the successful 2013 launch of the Landsat-8 is continuing this legacy. Ideally, the Landsat data record should be consistent over the Landsat sensor series. The Landsat-8 Operational Land Imager (OLI) has improved calibration, signal to noise characteristics, higher 12-bit radiometric resolution, and spectrally narrower wavebands than the previous Landsat-7 Enhanced Thematic Mapper (ETM+). Reflective wavelength differences between the two Landsat sensors depend also on the surface reflectance and atmospheric state which are difficult to model comprehensively. The orbit and sensing geometries of the Landsat-8 OLI and Landsat-7 ETM+ provide swath edge overlapping paths sensed only one day apart. The overlap regions are sensed in alternating backscatter and forward scattering orientations so Landsat bi-directional reflectance effects are evident but approximately balanced between the two sensors when large amounts of time series data are considered. Taking advantage of this configuration a total of 59 million 30m corresponding sensor observations extracted from 6,317 Landsat-7 ETM+ and Landsat-8 OLI images acquired over three winter and three summer months for all the conterminous United States (CONUS) are compared. Results considering different stages of cloud and saturation filtering, and filtering to reduce one day surface state differences, demonstrate the importance of appropriate per-pixel data screening. Top of atmosphere (TOA) and atmospherically corrected surface reflectance for the spectrally corresponding visible, near infrared and shortwave infrared bands, and derived normalized difference vegetation index (NDVI), are compared and their differences quantified. On average the OLI TOA reflectance is greater than the ETM+ TOA reflectance for all bands, with greatest differences in the near-infrared (NIR) and the shortwave infrared bands due to the quite different spectral response functions between the sensors. The atmospheric correction reduces the mean difference in the NIR and shortwave infrared but increases the mean difference in the visible bands. Regardless of whether TOA or surface reflectance are used to generate NDVI, on average, for vegetated soil and vegetation surfaces (0 ≤ NDVI ≤ 1), the OLI NDVI is greater than the ETM+ NDVI. Statistical functions to transform between the comparable sensor bands and sensor NDVI values are presented so that the user community may apply them in their own research to improve temporal continuity between the Landsat-7 ETM+ and Landsat-8 OLI sensor data. The transformation functions were developed using ordinary least squares (OLS) regression and were fit quite reliably (r 2 values >0.7 for the reflectance data and >0.9 for the NDVI data, p-values <0.0001).

An analysis of medulloblastoma: 10 year experience of a referral institution in South India.

BACKGROUND: Medulloblastoma is an embryonal tumor with aggressive behavior and is more commonly seen in children than adults. The aim of this study was to determine the epidemiological patterns of medulloblastoma in a tertiary care center in Southern India. MATERIALS AND METHODS: It is a retrospective study, in which the records of all the clinically diagnosed medulloblastoma cases in the last 10 years (2002-2012) were analyzed. RESULTS: A total of 58 cases were found, with the mean age at diagnosis being 10 years. There was a slight predilection for the male sex (58.62%). The first presenting symptom was mostly related to raise intracranial pressure and the mean duration of symptoms was 200 days. Nearly, 89.6% of patients were in Stage 0 and had a central tumor location. Multimodality treatment included surgery followed by craniospinal irradiation up to 36 gray followed by posterior fossa boost up to 54 gray. Median radiation therapy duration was 6.5 weeks and concurrent single agent vincristine was the most common chemotherapy used. Most of the patients showed only a partial response to treatment, mainly because of large tumors at presentation, which could be attributed to the lack of awareness, delayed medical attention and poor follow-up. CONCLUSION: Early diagnosis and treatment is the key to management of medulloblastoma, which still needs to be achieved. Bulky tumors have a poor outcome, efforts should be aimed at complete surgery and giving risk stratification based treatment. Resources need to be allocated to make more conformal methods of radiotherapy available, which will decrease the growth abnormalities and cognitive impairments.

Patterns of care in geriatric cancer patients - An audit from a rural based hospital cancer registry in Kerala.

BACKGROUND: There is deficit of data from India on elderly patients with cancer. Comprehensive geriatric assessment may lead to a better decision making capacity in this population. However, routine implementation of such assessment is resource consuming. AIM: The aim of this study was to determine the patterns of care in elderly patients treated at a tertiary rural cancer center in India. MATERIALS AND METHODS: All patients with age 70 or above with solid tumors without any definitive treatment prior to the registration at our center and registered between 01/01/2010 and 31/12/2011 were selected for this study. The baseline demographic pattern and the pattern of care of treatment were analyzed. SPSS version 16 (IBM Inc, Armonk, New York, U.S.) was used for analysis. Descriptive data are provided. RESULTS: A total of 761 patients were evaluable subject to the aforementioned inclusion criteria. The median age of this cohort was 75 years (70-95 years). The most frequent primary sites of malignancies in 451 males were head neck (32.4%), lung (23.3%) and gastrointestinal (23.3%). In 310 females, the most common sites were head neck (31.6%), gynecological (18.4%) and gastrointestinal (24.5%). 228 (30%) of the patients had localized disease, 376 (49.4%) had loco-regionally advanced disease and 145 (19.1%) had distant metastases at presentation. 334 (46.32%) of patients were treated with curative intent. On logistic regression analysis the factors that predicted use of curative intent treatment were age <75 years, performance status 0-1, primary site and clinical extent of disease. CONCLUSION: Routine comprehensive geriatric assessment needs to be implemented in our setting as almost 50% of our geriatric patients undergo curative intent treatment.

Genetic deletion of MT1/MT2 melatonin receptors enhances murine cognitive and motor performance.

Melatonin, an indoleamine hormone secreted into circulation at night primarily by the brain's pineal gland, has been shown to have a wide variety of actions on the development and physiology of neurons in the CNS. Acting via two G-protein-coupled membrane receptors (MT1 and MT2), melatonin modulates neurogenesis, synaptic functions, neuronal cytoskeleton and gene expression. In the present studies, we sought to characterize the behavior and neuronal biology of transgenic mice lacking both of these melatonin receptors as a way to understand the hormone's receptor versus non-receptor-mediated actions in CNS-dependent activities, such as learning and memory, anxiety, general motor performance and circadian rhythmicity. Assessment of these behaviors was complemented by molecular analyses of gene expression in the brain. Our results demonstrate mild behavioral hyperactivity and a lengthened circadian period of free-running motor activity in melatonin receptor-deficient mice as compared to receptor-intact control mice beginning at an early age. Significant improvement in cognitive performance was found using the Barnes Maze and the Y-Maze. No behavioral changes in anxiety levels were found. Electrophysiological measures in hippocampal slices revealed a clear enhancement of long-term potentiation in mice lacking melatonin receptors with no significant differences in paired-pulse facilitation. Quantitative analysis of brain protein expression levels of phosphoCREB and phosphoERK1/2 and key markers of synaptic activity (synapsin, glutamate receptor 1, spinophilin, and glutamic acid decarboxylase 1) revealed significant differences between the double-knockout and wild-type animals, consistent with the behavioral findings. Thus, genetic deletion of melatonin receptors produces mice with enhanced cognitive and motor performance, supporting the view that these receptors play an important role in neurobehavioral development.

Potentiation of convergent synaptic inputs onto pyramidal neurons in somatosensory cortex: dependence on brain wave frequencies and NMDA receptor subunit composition.

N-methyl-d-aspartate receptors (NMDARs) at layer (L)1/primary whisker motor cortex synaptic inputs are distinct from thalamic/striatal (Str) synaptic inputs onto L5 pyramidal neurons in the rat somatosensory cortex. However, the consequences of differential expression of putative GluN3A-containing triheteromeric NMDARs at L1 inputs and GluN2A-containing diheteromeric NMDARs at Str inputs on plasticity of the underlying synapses at the respective inputs remain unknown. Here we demonstrate that L1, but not Str, synapses are potentiated following delta burst stimulation (dBS). This potentiation is blocked by d-serine and/or intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) suggesting that it is subunit-specific and dependent on elevations in intracellular Ca(2+). Interestingly, ifenprodil, the GluN2B-preferring antagonist, suppresses baseline L1 responses but does not prevent induction of dBS-evoked potentiation. Unlike L1, Str synapses are maximally potentiated following theta burst stimulation (tBS) and this potentiation is blocked with BAPTA and/or the GluN2A-preferring antagonist NVP-AAM077. We show further that while dBS is both necessary and sufficient to potentiate L1 synapses, tBS is most effective in potentiating Str synapses. Our data suggest distinct potentiating paradigms for the two convergent inputs onto pyramidal neurons in the somatosensory cortex and co-dependence of synaptic potentiation on brain wave-tuned frequencies of burst stimulation and subunit composition of underlying NMDARs. A model for predicting the likelihood of enhancing synaptic efficacy is proposed based on Ca(2+) influx through these receptors and integration of EPSPs at these inputs. Together, these findings raise the possibility of input-specific enhancements of synaptic efficacy in neurons as a function of the animal's behavioral state and/or arousal in vivo.

Bovine carriers of Anaplasma marginale and Anaplasma bovis in South India.

Carriers of bovine anaplasmosis in Northern Kerala, South India were detected using conventional microscopical and molecular techniques. PCR-RFLP and nested PCR techniques were used for detection of Anaplasma marginale and Anaplasma bovis respectively and the PCR products were confirmed by sequencing. Out of 150 samples tested, 25 were detected positive for A. marginale and five for A. bovis based on molecular tests. The inclusion bodies of A. marginale could be detected by microscopy in two blood smears after staining by giemsa while acridine orange staining detected three smears positive. The data clearly suggest the higher sensitivity of molecular techniques for diagnosis of these diseases.

Effect of tobacco extract on surfactant synthesis and its reversal by retinoic acid-role of cell-cell interactions in vitro.

Tobacco induces oxidative stress in the alveolar epithelium and causes its damage. Retinoic acid (RA) has a cardinal role in alveolar cell growth, differentiation, and maturation. The aim of the study was to investigate the role of cell-cell interactions and whether RA could reverse the effect of tobacco extract on epithelial function as expressed by surfactant synthesis. For this, an in vitro model, which provides multiple cell type interactions, as seen in vivo, was used. We had used the major lung cell types, alveolar epithelial and mesenchymal cells represented by the cell lines A549 (human lung adenocarcinoma cell line), and human fetal lung fibroblast-1 (HFL-1) for developing the monoculture and co-culture systems and studied the effect of tobacco extract and retinoic acid. The effect of tobacco and retinoic acid both singly and in combination on proliferation and surfactant synthesis was analyzed. Retinoic acid induced proliferation and upregulated surfactant synthesis in monocultures and co-cultures. Tobacco extract at 100 µg/ml concentration decreased A549 proliferation and upregulated surfactant protein mRNA expression. In co-cultures treated with tobacco extract (100 µg/ml), retinoic acid (1 µM), regulated cell proliferation, and surfactant protein mRNA expression vis-à-vis the monoculture system. This clearly points to the fact that cell-cell interactions modulate the effect of additives or stimulants and help in assessing the in vivo combinatorial responses in vitro and that the retinoic acid effect is regenerative.

Comparing dose prediction software used to manage gentamicin dosing.

BACKGROUND: Current Australian guidelines recommend initiating directed therapy of gentamicin if administration exceeds 48 h. Directed doses of gentamicin require the monitoring of plasma concentrations of gentamicin to determine the 24-h area under the time course of plasma gentamicin concentrations (AUC) and a dosage prediction program, for example TCIWorks or Aladdin. However, doses calculated by such programs have not been compared with an established program. AIM: To compare the directed dosage of gentamicin calculated by TCIWorks, Aladdin and an Excel-based program, with an established program, Abbottbase. METHODS: Peak and trough plasma concentrations after the first and second administered doses of gentamicin were available from three patient groups (n = 20-23) with varying creatinine clearances (<40, 40-80, >80 mL/min). The directed dose needed to produce 24-h AUC values of 80 mg.h/L was calculated using each program. RESULTS: There was a strong correlation between the directed doses predicted by each of the three programs compared with Abbottbase, following the first administered dose (r(2) > 0.97, P < 0.0001). The mean ratio (90% confidence intervals) of these directed doses of the gentamicin were: TCIWorks/Abbottbase 106% (105-107%), Aladdin/Abbottbase 102% (101-103%) and Excel/Abbottbase 108% (106-109%). The correlations and dose ratios were also similar when comparisons were made following the second administered dose. For each of the three renal function groups, all programs yielded similar directed doses. CONCLUSIONS: The four programs used in the calculation of directed doses of gentamicin yielded similar results. Any would be suitable for use in clinical practice.