Influence of connatural factors in shaping vaginal microflora and ensuring its health.

Vaginal canal (VC) is exposed to the external environment affected by habitual factors like hygiene and sexual behaviour as well as physiological factors like puberty, menstrual cycle, pregnancy, child birth and menopause. Healthy VC harbours beneficial microflora supported by vaginal epithelium and cervical fluid. Connatural antimicrobial peptide (AMPs) of female reproductive tract (FRT) conjunctly with these beneficial microbes provide protection from a large number of infectious diseases. Such infections may either be caused by native microbes of the VC or transitory microbes like bacteria or virus which are not a part of VC microflora. This review highlight's the role of hormones, enzymes, innate immunological factors, epithelial cells and vaginal mucus that support beneficial microbes over infectious ones thus, helping to maintain homeostasis in VC and further protect the FRT. We also discuss the prospective use of vaginal probiotics and AMPs against pathogens which can serve as a potential cure for vaginal infections.

Design of Potential IKK-ß Inhibitors using Molecular Docking and Molecular Dynamics Techniques for their Anti-cancer Potential.

AIM AND OBJECTIVE: To evaluate a set of seventy phytochemicals for their potential ability to bind the inhibitor of nuclear factor kappaB kinase beta (IKK-ß) which is a prime target for cancer and inflammatory diseases. MATERIALS AND METHODS: Seventy phytochemicals were screened against IKK-ß enzyme using DFT-based molecular docking technique and the top docking hits were carried forward for molecular dynamics (MD) simulation protocols. The ADME-Toxicity analysis was also carried out for the top docking hits. RESULTS: Sesamin, matairesinol and resveratrol were found to be the top docking hits with a total score of -413 kJ/mol, -398.11 kJ/mol and 266.73 kJ/mol, respectively. Glu100 and Gly102 were found to be the most common interacting residues. The result from MD simulation observed a stable trajectory with a binding free energy of -107.62 kJ/mol for matairesinol, -120.37 kJ/mol for sesamin and -40.56 kJ/mol for resveratrol. The ADME-Toxicity prediction observed that these compounds fall within the permissible area of Boiled-Egg and it does not violate any rule for pharmacological criteria, drug-likeness etc. Conclusion: The study interprets that dietary phytochemicals are potent inhibitors of IKK-ß enzyme with favorable binding affinity and less toxic effects. In fact, there is a gradual rise in the use of plant-derived molecules because of its lesser side effects compared to chemotherapy. The study has also provided an insight by which the phytochemicals inhibited the IKK-ß enzyme. The investigation would also provide in understanding the inhibitory mode of certain dietary phytochemicals in treating cancer.

Assessing the economic value of maintained improvements in Type 1 diabetes management, in terms of HbA1c , weight and hypoglycaemic event incidence.

AIMS: Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment-related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA1c , BMI and hypoglycaemia incidence among the UK Type 1 diabetes population. METHODS: The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life-years and quality-adjusted life-years (QALYs) for individuals with Type 1 diabetes at different baseline HbA1c , BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per-person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates. RESULTS: Modelled subjects with an HbA1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per-person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per-person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per-person net monetary benefit, and up to £197 for the avoidance of one non-severe hypoglyceamic event. CONCLUSIONS: Maintained reductions in HbA1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.

The cost-utility of sodium oxybate as narcolepsy treatment.

AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted of adult patients treated for narcolepsy with cataplexy. Healthcare utilization and quality-adjusted life years (QALYs) for each treatment alternative were calculated assuming no treatment effect on survival. Sensitivity analyses were performed for treatment effectiveness and healthcare cost parameters. RESULTS: The cost per additional quality-adjusted life year was estimated at SEK 563,481. The cost-effectiveness measure was demonstrated to be particularly sensitive to the duration of the relative quality-of-life improvements accruing to patients treated with sodium oxybate. CONCLUSIONS: The estimated cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio as potentially beneficial effects on productivity of treatment with sodium oxybate were not included (due to lack of data).

Patterns of antiepileptic drug prescription in Sweden: A register-based approach.

OBJECTIVES: To determine drug utilization pathways from the incident healthcare visit due to epilepsy and three years onward. MATERIAL AND METHODS: Anti-epileptic drug utilization was calculated using individual information on inpatient- and outpatient care utilization and drug sales. Throughout, we used national register information pertaining to pharmaceutical sales linked to diagnosis-related healthcare utilization. Information on pharmaceutical sales was collected for the 2007-2013 period. RESULTS: For the entire studied period, a majority of new patients with epilepsy were initiated on anti-epileptic drug treatment with a monotherapy (98%); most of these patients remained on that first treatment (64%). The three most frequently prescribed drugs accounted for 72% of the initiated AED treatments. Patients with epilepsy (ICD-10: G40/41) were most commonly prescribed carbamazepine, lamotrigine and valproate. The most common second-line monotherapy was levetiracetam. About 12% of new patients with epilepsy who were initiated on AED treatment during the period eventually switched to an add-on therapy. The proportion of patients who were initiated on treatment with carbamazepine or valproate decreased, and the proportion of patients who remained on their initial monotherapy increased between 2007 and 2013. CONCLUSIONS: A limited number of anti-epileptic drugs accounted for the treatment of a majority of new patients with epilepsy (carbamazepine, lamotrigine and valproate accounted for more than 70%). Add-on therapies showed the same pattern, as the most frequently prescribed add-on regimens were the same ones that accounted for most of the monotherapies. There was a tendency towards fewer patients being initiated on AED treatment with either carbamazepine or valproate.

Cellulolytic potential of probiotic Bacillus Subtilis AMS6 isolated from traditional fermented soybean (Churpi): An in-vitro study with regards to application as an animal feed additive.

The aim of the present study is to evaluate the probiotic attributes of Bacillus subtilis AMS6 isolated from fermented soybean (Churpi). This isolate exhibited tolerance to low pH (pH 2.0) and bile salt (0.3%), capability to autoaggregate and coaggregate. AMS6 also showed highest antibacterial activity against the pathogenic indicator strain Salmonella enterica typhimurium (MTCC 1252) and susceptibility towards different antibiotics tested. The isolate was effective in inhibiting the adherence of food borne pathogens to Caco-2 epithelial cell lines, and was also found to be non-hemolytic which further strengthen the candidature of the isolate as a potential probiotic. Further studies revealed B. subtilis AMS6 showed cellulolytic activity (0.54±0.05 filter paper units mL(-1)) at 37°C. The isolate was found to hydrolyze carboxymethyl cellulose, filter paper and maize (Zea mays) straw. The maize straw digestion was confirmed by scanning electron microscopy studies. The isolate was able to degrade filter paper within 96h of incubation. A full length cellulase gene of AMS6 was amplified using degenerate primers consisting of 1499 nucleotides. The ORF encoded for a protein of 499 amino acids residues with a predicted molecular mass of 55.04kDa. The amino acids sequence consisted of a glycosyl hydrolase family 5 domain at N-terminal; Glycosyl hydrolase catalytic core and a CBM-3 cellulose binding domain at its C terminal. The study suggests potential probiotic B. subtilis AMS6 as a promising candidate envisaging its application as an animal feed additive for enhanced fiber digestion and gut health of animal.

Patterns of finasteride use in the male populations of four Nordic countries: A cross-national drug utilization study.

Objective Finasteride 5 mg is a drug used to treat prostate hyperplasia. Little is known about its pattern of usage. This cross-national analysis of individual-level data from Denmark, Finland, Norway and Sweden was undertaken to appraise its usage and describe cross-national differences. Materials and methods Individual-level data from nationwide prescription registers in Denmark (1995-2009), Finland (1997-2010), Norway (2004-2009) and Sweden (July 2005-2011) were used to examine cross-national finasteride utilization patterns in the adult male population (≥15 years). The study presents period prevalences, incidence rates, waiting time distributions and Lorenz curves. Results During the study period, 295,620 men had at least one prescription redemption of finasteride 5 mg, and there were approximately 3 million dispensing events of finasteride prescriptions in the four Nordic countries. Different patterns of finasteride use were observed among the four Nordic countries. The period prevalence was markedly higher in Finland and Sweden than in Denmark and Norway. In 2009, period prevalences were 18.2/1000 males in Finland and 12.0/1000 males in Sweden compared to 6.7/1000 males in Norway and 4.9/1000 males in Denmark. Incidence rates of finasteride use for Finland, Norway and Sweden were about three times that for Denmark in 2008-2009. Long-term use of finasteride was found in all four Nordic countries with a high ratio between prevalent and incident users. Conclusion Despite resemblances regarding political systems and healthcare services in the Nordic countries, differences in finasteride utilization were found across Denmark, Finland, Norway and Sweden.

In vitro evaluation of celluloytic Bacillus amyloliquefaciens AMS1 isolated from traditional fermented soybean (Churpi) as an animal probiotic.

A microorganism showing probiotic attributes and hydrolyzing carboxymethylcellulose was isolated from traditional fermented soybean (Churpi) and identified as Bacillus amyloliquefaciens by analysis of 16S rRNA gene sequence and named as B. amyloliquefaciens AMS1. The potentiality of this isolate as probiotic was investigated in vitro and it showed gastrointestinal transit tolerance, cell surface hydrophobicity, cell aggregation and antimicrobial activity. The isolate was found to be non-hemolytic which further strengthens its candidature as a potential probiotic. The maize straw digestion was confirmed by scanning electron microscopy studies. The isolate was able to degrade filter paper within 96 hours of incubation. This study explores the possibility of combining the cellulase degrading ability of a microbe with its probiotic attributes to enhance gut health of animal and digestibility of the feed.

Prevalence and cost of epilepsy in Sweden--a register-based approach.

OBJECTIVES: To estimate the prevalence of epilepsy, costs associated with in- and outpatient care, drug utilization and productivity losses due to epilepsy in Sweden for the years 2005 and 2011. METHODS: Cost components were calculated using registry data on inpatient- and outpatient-care utilization, drug sales and early pensions granted due to permanent disability and mortality. Moreover, by cross-identification of information in healthcare and pharmaceutical registries, we were able to distinguish between pharmaceuticals prescribed for epilepsy and non-epilepsy indications. RESULTS: The prevalence of epilepsy was estimated at 0.62% in 2005 and 0.88% in 2011. The total cost of epilepsy increased during the same period, while the per-patient cost decreased from €2929 to €1729. Direct medical costs accounted for about 36% of the estimated total cost in 2005 and 60% in 2011. The estimated healthcare cost due to epilepsy as a share of total healthcare costs for all illnesses was about the same in 2005 as in 2011 (0.2%), while the corresponding pharmaceutical cost increased from about 0.5% in 2005 to almost 1% in 2011. CONCLUSIONS: The per-patient cost of epilepsy is substantial, implying a significant aggregated cost incurred on society (despite a prevalence < 1%). Our results suggest that the per-patient pharmaceutical utilization increased, while the per-patient physician visits and hospitalizations decreased, between 2005 and 2011. Moreover, we demonstrate that the 2005 prevalence measure was underestimated the true prevalence in 2005.

Regional variation in prevalence and healthcare utilization due to epilepsy in Sweden.

OBJECTIVE: To estimate the regional differences in the prevalence of epilepsy and the associated costs due to inpatient and outpatient care and anti-epileptic drug (AED) utilization for the years 2005 and 2011 in Sweden. METHODS: Region-specific estimates of the prevalence of epilepsy were obtained using a method based on a linkage of the healthcare and pharmaceutical registries and the cause of death registry. Regional cost components were estimated using registry data by region on inpatient and outpatient care utilization, AED sales, and mortality. Per-patient utilization and monetary costs were calculated. RESULTS: Estimated prevalence of epilepsy varied substantially across the regions in 2011, from 0.76% in Jämtland to 1.08% in Gotland. The national prevalence was 0.88%. The average number of hospitalizations per patient and year decreased at the national level between 2005 and 2011. At the national level, the per-patient specialized care (outpatient) utilization also decreased between 2005 and 2011. However, at the regional level, the decrease was not uniform, and in some counties, the per-patient utilization increased during the period studied. The per-patient utilization of AEDs increased in all counties, except Kronoberg, between 2005 and 2011. Moreover, between-region differences in healthcare and AED utilization, and significant differences between regions and national averages were revealed. Similarly, regional per-patient costs were shown to deviate from the national average in 13 of 21 regions. CONCLUSIONS: There is significant variation in the prevalence of epilepsy and the provision of health care for patients with epilepsy across the different regions of Sweden.

Lacosamide as treatment of epileptic seizures - cost utility results for Sweden.

OBJECTIVES: To calculate cost per additional quality-adjusted life-year (QALY) for lacosamide as adjunctive treatment for patients with uncontrolled partial-onset seizures as compared to no adjunctive treatment. MATERIALS AND METHODS: A decision-tree simulation model was constructed to calculate the number of seizures and health-care utilization for treated and untreated with lacosamide, respectively. Prices from 2007 were used for all costs. RESULTS: All results were calculated for a 24-, 18-, 12- and 6-months follow-up. The cost per additional QALY was estimated to euro 27,641 (24 months). Using a willingness-to-pay threshold for a QALY of euro 50,000 the net marginal value of using lacosamide was estimated to about euro 850,000 per 1000 patients. CONCLUSIONS: The estimated cost per QALY gained falls within the range of reported estimates of the willingness-to-pay for an additional QALY. The results imply that lacosamide is cost-effective in the treatment of uncontrolled partial-onset seizures (1 euro approximately 9.6 SEK).

Diabetes, healthcare cost and loss of productivity in Sweden 1987 and 2005--a register-based approach.

AIM: The aim of this study was to estimate healthcare cost and productivity losses as a result of diabetes and diabetes-related chronic complications in Sweden in 1987 and 2005. RESEARCH DESIGN AND METHODS: Published estimates on relative risks and Swedish age-specific diabetes-prevalence rates were used to calculate the proportions of diabetes-related chronic complications that are attributable to diabetes. These attributable risks were applied to cost estimates for diabetes-related chronic complications based on data from Swedish population registers. RESULTS: The estimated total costs for Sweden in 1987 and 2005 were EUR439m and EUR920m, respectively. The increase of 110% was as a result of a 69% increase in the estimated prevalence from 150 000 (1.8% of the population) to 254 000 (2.8%) and of an increase in the estimated annual cost per person diagnosed with diabetes by 24%. Healthcare accounted for 45% of the estimated cost in 1987 and for 37% in 2005. The estimated diabetes-related healthcare cost accounted for approximately 1.0% of total healthcare cost in Sweden in 1987 and for 1.4% in 2005. Diabetes per se accounted for 57% of the healthcare cost in 1987 and for 50% in 2005. The most important chronic complication was cardiovascular disease. CONCLUSIONS: The cost of diabetes is substantial and increasing even in a fairly low-prevalence country such as Sweden. Measures to curb the increase in prevalence and to improve individual control of his or her diabetes seem to be the most important challenges.

Your next of kin or your own career? Caring and working among the 50+ of Europe.

An increasing demand for both formal and informal care is likely to result from the ongoing demographic transition at the same time as there is a further move away from the traditional domestic division of labour. Public policy-making that aims at increasing the supply of informal care necessitates knowledge about the relative importance of various incentives for individual care providers. This paper takes as a point of departure that the willingness to supply informal care is partly explained by the extent to which it adversely affects labour-market outcomes and analyses the effect on labour-market outcomes of providing informal care to one's elderly parent(s) among the 50+ of Europe. Data from SHARE (Survey of Health, Ageing, and Retirement in Europe) was used to examine the association between, on the one hand, hours of informal care provided and, on the other, (1) the probability of employment, (2) hours worked, and (3) wages, respectively. The results suggest that giving informal care to one's elderly parents is associated with significant costs in terms of foregone labour-market opportunities and that these adverse effects vary between countries.

Informal and formal care among single-living elderly in Europe.

The aims of this study were to analyse (1) whether informal care, provided by children or grandchildren to their elderly parents, and formal care are substitutes or complements, and (2) whether this relationship differs across Europe. The analyses were based on cross-sectional data from the newly developed SHARE (Survey of Health, Ageing, and Retirement in Europe) database. We found (1) that informal and formal home care are substitutes, while informal care is a complement to doctor and hospital visits, and (2) that these relationships in some cases differ according to a European north-south gradient. Instrumental variable methods were used and the results highlight the importance of accounting for the endogeneity of informal care.

Asthma and allergy: the significance of chronic conditions for individual health behaviour.

BACKGROUND: In health economics, health is regarded as part of an individual's human capital. As such it depreciates over time, and investments in health are made in order to keep the stock of health capital at the desired level. Using this framework for analysis of health-related behaviour and Swedish panel data, we examined whether the presence of asthma or allergy affects perceived health and investments in health. METHODS: A set of panel data for approximately 3800 individuals interviewed repeatedly in 1980/81, 1988/89, and 1996/97 was created from the Swedish biannual survey of living conditions. Self-assessed health was chosen as the indicator of health capital and the reported number of sick days as the indicator of health investment. The presence of asthma or allergy, age, wage rate, wealth, marital status, number of children, exercise and smoking habits, gender, and geographic location of household were all chosen as explanatory variables. An ordered probit model was estimated for the health equation and a Poisson model for the investment equation. RESULTS: We found that both asthmatics and those who suffer from allergy invested more in their health than the general population. We also found that asthmatics reported significantly lower self-assessed health than the general population, while those who suffered from allergy did not differ significantly from the general population regarding their self-assessed health. CONCLUSION: The human capital approach was found suitable for studying the impact of asthma and allergy on individual health behaviour. Health policy measures, which reduce the individual's costs of investing in his or her health, would improve health levels. Because asthmatics were found less healthy than those suffering from allergy, the potential gains would be larger for patients with asthma than for patients with allergy. The issue of whether this would be a cost-effective policy or not would require a different design and, hence, could not be solved within the present study.

High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein.

The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic (appetite-stimulating) activity. The cysteine-rich C-terminal domain of this protein, corresponding to AGRP(87-132), contains five disulfide bonds and exhibits receptor binding affinity and antagonism equivalent to that of the full-length protein. The three-dimensional structure of this domain has been determined by 1H NMR at 800 MHz. The first 34 residues of AGRP(87-132) are well-ordered and contain a three-stranded antiparallel beta sheet, where the last two strands form a beta hairpin. The relative spatial positioning of the disulfide cross-links demonstrates that the ordered region of AGRP(87-132) adopts the inhibitor cystine knot (ICK) fold previously identified for numerous invertebrate toxins. Interestingly, this may be the first example of a mammalian protein assigned to the ICK superfamily. The hairpin's turn region presents a triplet of residues (Arg-Phe-Phe) known to be essential for melanocortin receptor binding. The structure also suggests that AGRP possesses an additional melanocortin-receptor contact region within a loop formed by the first 16 residues of its C-terminal domain. This specific region shows little sequence homology to the corresponding region of the agouti protein, which is an MC1R antagonist involved in pigmentation. Consideration of these sequence differences, along with recent experiments on mutant and chimeric melanocortin receptors, allows us to postulate that this loop in the first 16 residues of its C-terminal domain confers AGRP's distinct selectivity for MC3R and MC4R.

The family as the health producer--when spouses are Nash-bargainers.

The Grossman model is extended to a situation in which the family is regarded as the producer of individual health and spouses are Nash-bargainers. The model has implications for the interaction between family structure, income and the stocks of health capital and the bargaining strength of different family members. The main insight is that the possibility of divorce affects the distribution of health capital between family members. We analyse, inter alia, the impact on the distribution of health (particularly regarding child health) of changes in family policies related to the dissolution of the family.

NMR structure of a minimized human agouti related protein prepared by total chemical synthesis.

The structure of the chemically synthesized C-terminal region of the human agouti related protein (AGRP) was determined by 2D 1H NMR. Referred to as minimized agouti related protein, MARP is a 46 residue polypeptide containing 10 Cys residues involved in five disulfide bonds that retains the biological activity of full length AGRP. AGRP is a mammalian signaling molecule, involved in weight homeostasis, that causes adult onset obesity when overexpressed in mice. AGRP was originally identified by homology to the agouti protein, another potent signaling molecule involved in obesity disorders in mice. While AGRP's exact mechanism of action is unknown, it has been identified as a competitive antagonist of melanocortin receptors 3 and 4 (MC3r, MC4r), and MC4r in particular is implicated in the hypothalamic control of feeding behavior. Full length agouti and AGRP are only 25% homologous, however, their active C-terminal regions are approximately 40% homologous, with nine out of the 10 Cys residues spatially conserved. Until now, 3D structures have not been available for either agouti, AGRP or their C-terminal regions. The NMR structure of MARP reported here can be characterized as three major loops, with four of the five disulfide bridges at the base of the structure. Though its fold is well defined, no canonical secondary structure is identified. While previously reported structural models of the C-terminal region of AGRP were attempted based on Cys homology between AGRP and certain toxin proteins, we find that Cys spacing is not sufficient to correctly determine the 3D fold of the molecule.