Bilateral sixth nerve palsy with subdural hematoma: a unique presentation of B12 deficiency.

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae.

A survey of patients visiting an Ayurvedic teaching hospital for factors influencing the decision to choose ayurveda as a health care provider.

STUDY BACKGROUND: In a pluralistic health care delivery model, it is important to assess whether the individual's health care choices are based upon evidences of efficacy and safety. Since the essence of medical pluralism lies in the fact that all such systems are equally accessible to a seeker, in such situation, it is highly relevant to check what defines such choices in real life. OBJECTIVE: To identify the factors influencing the health care choices in a subpopulation seeking Ayurveda health care in an Ayurvedic teaching hospital. MATERIALS AND METHOD: The study was an all-inclusive cross sectional survey, done on randomly selected out patients visiting an Ayurveda teaching hospital. The data was collected using a 21 items questionnaire refined through pilot testing from 7.9.2017 to 30.9.2017. RESULTS: The data of 289 respondents who have given their consent were included in statistical analysis. Out of 21 variables studied for their agreement or disagreement in the study population 8 were found to have a significant proportion in favour of agreement. Among these relative safety (Item 9); disease eradicating potential (Item 14); belief (Item 3) and indirect evidences of efficacy (Item 4) were found to have high significance (p < 0.001). CONCLUSION: Participants chose Ayurveda treatment due to its perceived safety and probability of helping in a particular clinical condition. Contrary to the common perception, enabling factors like availability, accessibility and affordability were given less importance by the participants in making health care choices related to Ayurveda.

Taurine and/or inorganic potassium as dietary osmolyte counter the stress and enhance the growth of GIFT reared in ion imbalanced low saline water.

The effects of dietary osmolytes for alleviating osmotic stress and enhancing growth are not well elucidated in fish reared in inland saline water. The present study evaluated the effects of dietary taurine or potassium (K+) individually or in combination on growth, ionic homeostasis, and stress response of GIFT tilapia reared in potassium deficient low saline water (PDLSW, 10 ppt salinity) mimicking inland saline water. Isonitrogenous and isoenergetic diets supplemented with five potassium concentrations (0, 0.3, 0.45, 0.6 and 0.75 %), two taurine (T) concentrations (0.5 and 1.0 %) and two combinations of both (K+ 0.1 % + T 0.5 % and K+ 0.2 % + T 0.5 %) were fed to GIFT juveniles (4.4 ± 0.02 g body weight) and reared in PDLSW for 45 days. The fish fed on the diet fortifying with K+ 0.2 % + T 0.5 % showed the highest growth performance among the controls and other treatment groups. Dietary supplementation had no effects on PDLSW induced increase in osmoregulatory endpoints. The optimum dietary potassium requirement of GIFT reared in PDLSW was 0.57 and 0.599 g/100 g diet. Dietary K+ down-regulated the PDLSW induced expression of NKAa1, AQP1, and ClC2, whereas inhibited taurine-induced up-regulation of AQP1 and CLC2, which is the first report in tilapia. In addition, dietary K+ and taurine modulated antioxidant and metabolic enzyme activities for easing stress and balancing energy requirements. Thus, blending of potassium (0.2 %) and taurine (0.5 %) in the diet appears best to mitigate stress and enhance GIFT growth reared in inland saline water.

Extra-Fortification of Zinc Upsets Vitellogenin Gene Expression and Antioxidant Status in Female of Clarias magur brooders.

The present experiment was designed to evaluate the effect of graded level of zinc on Vitellogenin gene (Vtg) expression and antioxidant enzymes in threatened catfish, Clarias magur (C. magur). One hundred and eighty female C. magur with an average weight of 145 ± 5 g were allocated in twelve cemented tanks with dimension 4.5 × 2 × 1 m for a period of 60 days. Fish were distributed in four groups with three replicates following the completely randomised design. The first group treated as control (C) fed with basal diet contained normal zinc level, and remaining groups were fed with basal diets having 50, 200 and 300 mg/kg zinc acetate and treated as T1, T2 and T3 respectively. To evaluate the effect of dietary zinc supplementation on Vtg gene expression, three sampling were carried out, I sampling (April, before starting the experimental trail), II sampling (May, after 1 month of feeding trail) and III sampling (June before breeding season). In the present study, a dose-dependent relationship between Vtg gene expression and zinc inclusion in the diet of threatened catfish, C. magur, was reported. Vtg gene expression increased in all groups from I sampling to II sampling but the highest Vtg gene expression was found in T1 group and the lowest in T3 group at II sampling. Vtg gene expression among the treatments differs significantly (P < 0.05) in each sampling. Accumulation of zinc was measured by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) in C. magur and it was reported that the significantly higher (P < 0.05) zinc was accumulated in the liver and ovary of T3 group as compared to other groups. The antioxidant enzyme activities (superoxide dismutase, SOD, catalase and GST) were also measured in different tissues (liver, gill and ovary) to evaluate the effect of extra-supplementation of zinc on the antioxidant status. In T3 group, SOD, catalase and GST activities were significantly higher than those in other groups. In the current study, serum glucose level was also measured and it was found in increasing trend with inclusion of zinc in the diet of C. magur. In the present study, it can be concluded that the zinc exhibits beneficial effect only up to 50 mg/kg. Thus, it is concluded that supplementation of zinc at 200 mg/kg or more disrupts Vtg gene expression and antioxidant status.

Time Taken for Symptom Recognition, First Consultation, Diagnosis and First Definitive Treatment and Its Associated Factors among Women with Breast Cancer.

BACKGROUND: Breast cancer patients in Malaysia often present late, delaying diagnosis and treatment. Decisions on health-seeking behaviour are influenced by a complex interplay of several factors. Early detection and subsequent successful treatment are the main goal in order to reduce breast cancer mortality. The aims of this study were to identify the time taken by women with breast cancer for consultation, diagnosis and first definitive treatment and the factors associated with the initiation of definitive treatment. METHODS: In this cohort study, we interviewed 328 women with histologically confirmed breast cancer at five medical centres in Malaysia. Times were measured from recognition of symptoms to first consultation to diagnosis and to the first definitive treatment. The event was initiation of definitive treatment. Data was analysed using multivariable Cox proportional hazards regression. RESULTS: The mean age was 47.9 (standard deviation 9.4) years and 79.9% were ethnic Malays. The median follow-up time was 6.9 months. The median times for first doctor consultation, diagnosis and initiation of treatment were 2 months, 5.5 months and 2.4 weeks, respectively. The percentage of consultation delay more than a month was 66.8%, diagnosis delay more than three months was 73.2% and treatment delay more than one month was 11.6%. Factors associated with not initiating the definitive treatment were pregnancy (adjusted hazard ratio (AHR) 1.75; 95% Confidence Interval (CI): 1.07, 2.88), taking complementary alternative medicine (AHR 1.45; 95% CI: 1.15, 1.83), initial refusal of mastectomy (AHR 3.49; 95% CI: 2.38, 5.13) and undergoing lumpectomy prior to definitive treatment (AHR 1.62; 95% CI: 1.16, 2.28). CONCLUSIONS: Delays in diagnosis and consultation were more serious than treatment delays. Most respondents would accept treatment immediately after diagnosis. Respondents themselves were responsible for a large proportion of the delays. This study was successful in understanding the process of breast cancer patients' experience, from symptoms recognition to consultation, diagnosis and treatment.

Institutional library reforms are needed to improve ayurveda education, practice and research: Inferences from a case study.

Libraries have always been the integral components of the academic institutions world over. Earlier known for housing the spectrum of books permitting their ready access to knowledge seekers, libraries of current age are no more confined spaces with limited functions. With the advancing information technology, the conventional definition of a library is changing to accommodate newer roles and challenges. Twenty-first century academic libraries are extending beyond the walls of their individual institutions and are evolving as open access information spaces, dealing with intelligent sharing through social communication and networking technologies. Despite such massive changes in the information storage and retrieval patterns across the globe, libraries at Ayurveda institutions in India seem by and large unbothered and unaffected. Poor educational and research standards in Ayurveda seem to have direct links with libraries contributing minimally to academic exchange and progress. An SCONUL survey conducted for the first time in any ayurvedic library setting in the country came as an eye opener stating clearly that Ayurveda institutional libraries require a major reform first to bring them at par with other academic libraries and subsequently to evolve them as the nucleus of knowledge fostering. These setups direly need a hand of help to become eligible for contributing what they are really meant to.

Responses of Corpuscles of Stannius to intra-peritoneal vitamin-D3 administration in teleost Labeo rohita (Hamilton, 1822) reared in water with two different levels of calcium concentration.

This study assessed the responses of vitamin-D3 intraperitoneally injected to Rohu, Labeo rohita @ of 0 IU/kg bw (only solvent), 100 IU/kg bw and 500 IU/kg bw reared in 20 and 40 ppm of calcium (Ca) enriched water. The cellular changes in Corpuscles of Stannius (CS) gland, serum Ca, and inorganic phosphate (Pi) level were analysed up to the 60th day. Rohu administered with 100 IU/kg bw D3 and exposed to 40 ppm Ca-rich water exhibited notable hyperplasia of CS compared with their control groups. Notable changes with high serum Ca level (13.87 ± 0.3 mg/dl) was detected on the 5th day in fish exposed to 40 ppm Ca-rich water, while related values attained (13.74 ± 0.1 mg/dl) only after 7 days in 20 ppm Ca-rich water of 500 IU/kg bw vitamin D3 injection. Similarly, high serum Pi level (7.66 ± 0.2 mg/dl) in 40 ppm Ca injected with D3 at 500 IU/kg bw. The results demonstrated that the Ca homeostasis of Labeo rohita is influenced by intra-peritoneal vitamin D3. Progressive studies should be conducted by increasing the dose of vitamin D3 to investigate optimum dose/supplement in feed for commercially important aquaculture teleost Labeo rohita for maximum and sustainable absorption of Ca from the variable water Calcium levels to maintain Ca2+ homeostasis.

Expression of Growth and Hunger Related Genes and Physio-Biochemical Responses in Labeo rohita (Hamilton, 1822) Fed with Lysine and Betaine.

BACKGROUND/AIMS: The growth promoting effect of lysine and betaine as well as the expression of candidate genes reflecting their efficacy, such as ghrelin, leptin, Growth Hormone Secretagogue Receptor (GHS-R), Insulin like Growth Factor (IGF- 1) and Growth Hormone Releasing Hormone (GHRH) was examined in Labeo rohita fingerlings. METHODS: One hundred eighty healthy juveniles from a homologous population were randomly distributed to 15 rectangular tanks of 150 litres capacity. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. The experiment was carried out for 60 days with five treatment groups consisting T1 (0.25% Betaine), T2 (0.5% Betaine), T3 (0.75% Lysine) and T4 (1.5% Lysine) and control group. At the end of trial, the growth parameters such as weight gain, SGR, PER were estimated from the weight of the triplicate groups. The digestive, metabolic and antioxidant enzymes were analysed using spectrophotometric methods. The intestine, brain and liver were sampled from the treatments and expression of different genes ghrelin, leptin, GHSR, IGF-1 and GHRH was also performed by realtime PCR. RESULTS: A significant (P<0.05) increase in weight gain, SGR, PER and lowest FCR was found in T4 group which was significantly (p < 0.05) different from other experimental groups. The highest mRNA expression levels of expression were found in T4 group which was similar to that of ghrelin gene mRNA of T2 group. The significantly (p<0.05) highest GHSR, GHRH and IGF-1 gene expression levels were found in T4 treatment group compared to other groups. CONCLUSION: The present study reveals that the lysine and betaine stimulate growth and expression of ghrelin GHRH, GHS-R and IGF-1 genes. The increase of IGF-I mRNA expression with lysine and betaine supplementation revealed that these compounds act as growth modulators. However, lysine was found to be a more potent modulator of growth compared to betaine.

Gene structure and comparative and phylogenetic analyses of Catla catla CYP1A full-length cDNA and its responsiveness to benzo(a)pyrene and copper sulphate at early developmental stages.

In the present study, full-length CYP1A cDNA from Catla catla (Catla) has been identified, and its real-time quantitative reverse transcription PCR (qRT-PCR) expression has been evaluated in different tissues, developmental stages (0, 3, 6, 12 and 24 h and 5, 7 and 9 days post-fertilization) and copper sulphate and benzo(a)pyrene (BaP)-treated 5-day post-fertilization (dpf) larvae (6 to 6.5 mm). Various structural, comparative and phylogenetic analyses of the deduced amino acid sequence revealed that the identified gene of Catla belongs to the CYP1A1 subfamily. Among different tissues of Catla, the highest CYP1A expression was observed in the kidney followed by the liver, muscle, gill, intestine and brain. CYP1A mRNA expression was detected during all the larval developmental stages, including the unfertilized egg with the highest expression on 9 dpf. BaP (3.5 ppb) and copper sulphate (sublethal dose 0.516 ppm) challenge test for 96 h to Catla larvae revealed the highest CYP1A1 expression at 48 h post-challenge. CYP1A1 transcript also showed a concentration-dependent increase in expression following exposure at 1.75 and 3.5 ppb of BaP for 48 h. Its expression profiling indicates that it is functional at early developmental stages. It can also be used to develop a specific biomarker tool for monitoring environmental pollution.

Hydrocarbons and heavy metals in fine particulates in oil field air: possible impacts on production of natural silk.

Analyses of fine particulates (PM2.5) from the upper Assam oil fields of India indicated considerable presence of higher hydrocarbons (C22-C35) and heavy metals, Cd, Co, Cr, Cu, Ni, Pb, and Zn. This has raised serious concern for the sustainability of the exotic Muga (Antheraea assama) silk production, which has been a prime activity of a large number of people living in the area. The Muga worm feeds on the leaves of Machilus bombycina plant, and the impacts of air quality on its survival were further investigated by analyzing the leaves of the plant, the plantation soil, and the Muga cocoons. PM2.5 content in the air was much more during the winter due to near calm conditions and high humidity. Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and gas chromatography-mass spectrometer (GC-MS) analysis of PM2.5 showed the presence of higher alkanes (C22-C35) that could be traced to crude oil. Cr, Ni, and Zn were found in higher concentrations in PM2.5, M. bombycina leaves, and the plantation soil indicating a common origin. The winter has been the best period for production of the silk cocoons, and the unhealthy air during this period is likely to affect the production, which is already reflected in the declining yield of Muga cocoons from the area. SEM and protein analyses of the Muga silk fiber produced in the oil field area have exhibited the deteriorating quality of the silk. This is the first report from India on hydrocarbons and associated metals in PM2.5 collected from an oil field and on their possible effects on production of silk by A. assama.

Understanding barriers to Malaysian women with breast cancer seeking help.

Delay in help-seeking behaviour which is potentially preventable has a major effect on the prognosis and survival of patients with breast cancer. The objective of this study was to explore reasons for delay in seeking help among patients with breast cancer from the East Coast of peninsular Malaysia. A qualitative study using face- to-face in-depth interview was carried out involving 12 breast cancer patients who had been histo-pathologically confirmed and were symptomatic on presentation. Respondents were selected purposely based on their history of delayed consultation, diagnosis or treatment. All were of Malay ethnicity and the age range was 26-67 years. Three were in stage ll, seven in stage lll and two in stage lV. At the time of interview, all except one respondent had accepted treatment. The range of consultation time was 0.2-72.2 months with a median of 1.7 months, diagnosis time was 1.4-95.8 months( median 5.4 months )and treatment time was 0-33.3 months (median 1.2 months). The themes derived from the study were poor knowledge or awareness of breast cancer, fear of cancer consequences, beliefs in complementary alternative medicine, sanction by others, other priorities, denial of disease, attitude of wait and see and health care system weakness. Help-seeking behaviour was influenced by a complex interaction of cognitive, environmental, beliefs, culture and psycho-social factors. Breast cancer awareness and psychological counselling are recommended for all patients with breast symptoms to prevent delay in seeking clinical help.

Pharmacokinetics of different dosing strategies of oral posaconazole in patients with compromised gastrointestinal function and who are at high risk for invasive fungal infection.

The aim of this study was to assess different dosing strategies that may result in increased posaconazole bioavailability in patients with compromised gastrointestinal function and at high risk for invasive fungal infections. Patients undergoing chemotherapy and at risk for compromised gastrointestinal function received open-label posaconazole at 200 mg three times daily (TID) on days 1 to 8. Patients were randomized to one of three open-label dosing regimens of posaconazole on days 9 to 15: 200 mg TID, 400 mg twice daily (BID), or 400 mg TID. The plasma concentrations of interest on days 8 and 15 were 500 and 700 ng/ml, respectively; day 2 plasma concentrations of 250 and 350 ng/ml were chosen as levels that might result in steady-state concentrations of >500 and >700 ng/ml, respectively. A total of 75 patients enrolled; 52/75 (69%) completed the study, and 49/75 were included in the pharmacokinetic analyses. Mean plasma concentrations were 230, 346, and 637 ng/ml on days 2, 3, and 8, respectively. The day 15 values were 660, 930, and 671 ng/ml for 200 mg TID, 400 mg BID, and 400 mg TID, respectively. In 12 patients with a day 8 posaconazole concentration of <250 ng/ml, an overall benefit of the higher two doses was not apparent, suggesting that a subset of patients has low steady-state plasma concentrations. A change in dosing regimen on day 9 did not lead to higher exposures in these "poor absorbers" on day 15. Poor absorption may be enhanced with a high-fat meal, a nutritional supplement, or acidification.

Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers.

A four-part, randomized, crossover study with healthy subjects evaluated the effects of gastric pH, the dosing frequency and prandial state, food consumption timing, and gastric motility on the absorption of posaconazole. In part 1, a single dose (SD) of posaconazole (400 mg) was administered alone or with an acidic beverage or a proton pump inhibitor (PPI), or both. In part 2, posaconazole (400 mg twice daily and 200 mg four times daily) was administered for 7 days with and without a nutritional supplement (Boost). In part 3, an SD of posaconazole (400 mg) was administered while the subjects were fasting and before, during, and after a high-fat meal. In part 4, an SD of posaconazole (400 mg) and the nutritional supplement were administered alone, with metoclopramide, and with loperamide. Compared to the results obtained with posaconazole alone, administration with an acidic beverage increased the posaconazole maximum concentration in plasma (C(max)) and the area under the concentration-time curve (AUC) by 92% and 70%, respectively, whereas a higher gastric pH decreased the posaconazole C(max) and AUC by 46% and 32%, respectively. Compared to the results obtained with posaconazole alone, posaconazole at 400 mg or at 200 mg plus the nutritional supplement increased the posaconazole C(max) and AUC by 65% and 66%, respectively, and by up to 137% and 161%, respectively. Administration before a high-fat meal increased the C(max) and the AUC by 96% and 111%, respectively, while administration during and after the meal increased the C(max) and the AUC by up to 339% and 387%, respectively. Increased gastric motility decreased the C(max) and the AUC by 21% and 19%, respectively. Strategies to maximize posaconazole exposure in patients with absorption difficulties include administration with or after a high-fat meal, with any meal or nutritional supplement, with an acidic beverage, or in divided doses and the avoidance of proton pump inhibitors.

Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers.

We conducted a randomized, crossover study in healthy adults to examine the effects of a nutritional supplement (Boost Plus) on posaconazole pharmacokinetics. In this study, coadministration of posaconazole with Boost Plus increased the maximum concentration of posaconazole in serum and area under the concentration-time curve from 0 to 72 h values 3.4- and 2.6-fold, respectively, compared to those for the fasted state.

Pharmacodynamics of a new triazole, posaconazole, in a murine model of disseminated candidiasis.

Previous in vivo studies have characterized the pharmacodynamic characteristics of two triazole compounds, fluconazole and ravuconazole. These investigations demonstrated that the 24-h area under the concentration-time curve (AUC)/MIC ratio is the critical pharmacokinetic-pharmacodynamic (PK-PD) parameter associated with treatment efficacy. Further analysis demonstrated that a free-drug triazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success in both experimental models and clinical trials. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the time course activity of the new triazole, posaconazole. The PK-PD parameters (percent time above MIC, AUC/MIC ratio, and peak serum drug level/MIC ratio) were correlated with in vivo efficacy, as measured by organism number in kidney cultures after 48 h of therapy. Kinetics and protein binding following oral posaconazole dosing were performed in neutropenic infected mice. Peak levels and AUC from 0 h to infinity values were nonlinear over the 16-fold dose range studied. Serum drug elimination half-life ranged from 12.0 to 17.7 h. Protein binding was 99%. Single dose postantifungal effect studies demonstrated prolonged suppression of organism regrowth after serum posaconazole levels had fallen below the MIC. Treatment efficacy with the four dosing intervals studied was similar, supporting the AUC/MIC ratio as the PK-PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (AUC/MIC ratio R(2) = 83%; peak serum drug/MIC ratio R(2) = 85%; time that serum levels of posaconazole remained above the MIC R(2) = 65%). Similar studies were conducted with 11 additional C. albicans isolates with various posaconazole susceptibilities (MIC, 0.015 to 0.12 micro g/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The posaconazole free-drug AUC/MIC ratios were similar for all of the organisms studied (6.12 to 26.7, mean +/- SD = 16.9 +/- 7.8, P value, 0.42). These free-drug AUC/MIC ratios are similar to those observed for other triazoles in this model.