Chemical Stability and Reaction Kinetics of Two Thiamine Salts (Thiamine Mononitrate and Thiamine Chloride Hydrochloride) in Solution

Two types of thiamine (vitamin B1) salts, thiamine mononitrate (TMN) and thiamine chloride hydrochloride (TClHCl), are used to enrich and fortify food products. Both of these thiamine salt forms are sensitive to heat, alkali, oxygen, and radiation, but differences in stability between them have been noted. It was hypothesized that stability differences between the two thiamine salts could be explained by differences in solubility, solution pH, and activation energies for degradation. This study directly compared the stabilities of TMN and TClHCl in solution over time by documenting the impact of concentration and storage temperature on thiamine degradation and calculating reaction kinetics. Solutions were prepared containing five concentrations of each thiamine salt (1, 5, 10, 20, and 27 mg/mL), and three additional concentrations of TClHCl: 100, 300, and 500 mg/mL. Samples were stored at 25, 40, 60, 70, and 80 °C for up to 6 months. Degradation was quantified over time by high-performance liquid chromatography, and percent thiamine remaining was used to calculate reaction kinetics. First-order reaction kinetics were found for both TMN and TClHCl. TMN degraded significantly faster than TClHCl at all concentrations and temperatures. For example, in 27 mg/mL solutions after 5 days at 80 °C, only 32% of TMN remained compared to 94% of TClHCl. Activation energies and solution pHs were 21–25 kcal/mol and pH 5.36–6.96 for TMN and 21–32 kcal/mol and pH 1.12–3.59 for TClHCl. TClHCl degradation products had much greater sensory contributions than TMN degradation products, including intense color change and potent aromas, even with considerably less measured vitamin loss. Different peak patterns were present in HPLC chromatograms between TMN and TClHCl, indicating different degradation pathways and products. The stability of essential vitamins in foods is important, even more so when degradation contributes to sensory changes, and this study provides a direct comparison of the stability of the two thiamine salts used to fortify foods in environments relevant to the processing and shelf-life of many foods

Simulation models predict that school-age children are responsible for most human-to-mosquito Plasmodium falciparum transmission in southern Malawi

Abstract Background Malaria persists in some high-transmission areas despite extensive control efforts. Progress toward elimination may require effective targeting of specific human populations that act as key transmission reservoirs. Methods Parameterized using molecular-based Plasmodium falciparum infection data from cross-sectional community studies in southern Malawi, a simulation model was developed to predict the proportions of human-to-mosquito transmission arising from (a) children under 5 years old (U5s), (b) school-age children (SAC, 5–15 years), (c) young adults (16–30 years), and (d) adults > 30 years. The model incorporates mosquito biting heterogeneity and differential infectivity (i.e. probability that a blood-fed mosquito develops oocysts) by age and gametocyte density. Results The model predicted that SAC were responsible for more than 60% of new mosquito infections in both dry and rainy seasons, even though they comprise only 30% of this southern Malawi population. Young adults were the second largest contributors, while U5s and adults over 30 were each responsible for < 10% of transmission. While the specific predicted values are sensitive to the relative infectiousness of SAC, this group remained the most important contributor to mosquito infections under all realistic estimates. Conclusions These results suggest that U5 children play a small role compared to SAC in maintaining P. falciparum transmission in southern Malawi. Models that assume biting homogeneity overestimate the importance of U5s. To reduce transmission, interventions will need to reach more SAC and young adults. This publicly available model can be used by others to estimate age-specific transmission contributions in epidemiologically similar sites with local parameter estimates of P. falciparum prevalence and bed net use.https://deepblue.lib.umich.edu/bitstream/2027.42/143001/1/12936_2018_Article_2295.pd

Hybrid Synthetic Receptors on MOSFET Devices for Detection of Prostate Specific Antigen in Human Plasma

The study reports the use of extended gate field-effect transistors (FET) for the label-free and sensitive detection of prostate cancer (PCa) biomarkers in human plasma. The approach integrates for the first time hybrid synthetic receptors comprising of highly selective aptamer-lined pockets (apta-MIP) with FETs for sensitive detection of prostate specific antigen (PSA) at clinically relevant concentrations. The hybrid synthetic receptors were constructed by immobilizing an aptamer–PSA complex on gold and subjecting it to 13 cycles of dopamine electropolymerization. The polymerization resulted in the creation of highly selective polymeric cavities that retained the ability to recognize PSA post removal of the protein. The hybrid synthetic receptors were subsequently used in an extended gate FET setup for electrochemical detection of PSA. The sensor was reported to have a limit of detection of 0.1 pg/mL with a linear detection range from 0.1 pg/mL to 1 ng/mL PSA. Detection of 1–10 pg/mL PSA was also achieved in diluted human plasma. The present apta-MIP sensor developed in conjunction with FET devices demonstrates the potential for clinical application of synthetic hybrid receptors for the detection of clinically relevant biomarkers in complex samples

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI

High prevalence of Plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern Malawi

Abstract Background In endemic areas, many people experience asymptomatic Plasmodium infections, particularly older children and adults, but their transmission contribution is unknown. Though not the exclusive determinant of infectiousness, transmission from humans to mosquitoes requires blood meals containing gametocytes. Gametocytes often occur at submicroscopic densities, challenging measurement in human populations. More sensitive molecular techniques allow better characterization of gametocyte epidemiologic patterns. Methods Approximately 30 households were selected from each of eight sites in southern Malawi during two cross-sectional surveys. Blood was sampled from 623 people during the dry season and 896 the following rainy season. Among people PCR-positive for Plasmodium falciparum, mature gametocytes were detected by qRT-PCR. Regression models evaluated predictors of gametocyte carriage and density in the total population and among those with PCR-positive infections. Results The prevalence of gametocyte carriage by molecular testing was 3.5% during the dry season and 8.6% during the rainy season, and by microscopy 0.8 and 3.3%, respectively. Nearly half of PCR-positive infections carried gametocytes, regardless of recent symptom status. Among P. falciparum-infected people, only living in unfinished houses and age were significantly associated with gametocyte presence. Infected people in unfinished houses had higher odds of carrying gametocytes (OR 2.24, 95% CI 1.16–4.31), and 31% (95% CI 3–65%) higher gametocyte density than those in finished houses. School-age children (5–15 years), had higher odds than adults (≥16 years) of having gametocytes when infected (OR 2.77, 95% CI 1.47–5.19), but 31% (95% CI 11–47%) lower gametocyte density. Children <5 years did not have significantly higher odds of gametocyte carriage or density when infected than adults. Conclusions School-age children frequently carry gametocytes in communities of southern Malawi and represent an under-recognized reservoir of infection. Malaria elimination strategies should address these frequently asymptomatic reservoirs, especially in highly endemic areas. Improved household construction may also reduce the infectious reservoir.http://deepblue.lib.umich.edu/bitstream/2027.42/134670/1/12936_2016_Article_1587.pd

Access and utilisation of maternity care for disabled women who experience domestic abuse:a systematic review

BACKGROUND: Although disabled women are significantly more likely to experience domestic abuse during pregnancy than non-disabled women, very little is known about how maternity care access and utilisation is affected by the co-existence of disability and domestic abuse. This systematic review of the literature explored how domestic abuse impacts upon disabled women’s access to maternity services. METHODS: Eleven articles were identified through a search of six electronic databases and data were analysed to identify: the factors that facilitate or compromise access to care; the consequences of inadequate care for pregnant women’s health and wellbeing; and the effectiveness of existing strategies for improvement. RESULTS: Findings indicate that a mental health diagnosis, poor relationships with health professionals and environmental barriers can compromise women’s utilisation of maternity services. Domestic abuse can both compromise, and catalyse, access to services and social support is a positive factor when accessing care. Delayed and inadequate care has adverse effects on women’s physical and psychological health, however further research is required to fully explore the nature and extent of these consequences. Only one study identified strategies currently being used to improve access to services for disabled women experiencing abuse. CONCLUSIONS: Based upon the barriers and facilitators identified within the review, we suggest that future strategies for improvement should focus on: understanding women’s reasons for accessing care; fostering positive relationships; being women-centred; promoting environmental accessibility; and improving the strength of the evidence base

Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome

Germline mutations in the DNMT3A gene can cause an overgrowth syndrome associated with behavioural and hematopoietic phenotypes. Here the authors describe a mouse model of this syndrome that recapitulates many of these features, including conserved alterations in DNA methylation in the blood cells of both species

Oral prehabilitation for patients with head and neck cancer:getting it right - the Restorative Dentistry-UK consensus on a multidisciplinary approach to oral and dental assessment and planning prior to cancer treatment

Historically, oral and dental issues for head and neck cancer patients were often not considered until after cancer treatment was complete. As a result, outcomes for oral rehabilitation were sometimes suboptimal. Inconsistencies in service delivery models and qualification, training and experience of staff delivering dental care often compounded this problem, making research and audit almost impossible. Collaborative working by consultants in restorative dentistry from all over the UK as part of a Restorative Dentistry-UK (RD UK) subgroup, renamed more recently as the RD-UK Head and Neck Cancer Clinical Excellence Network (CEN), has re-emphasised the importance of specialist restorative dentistry intervention at the outset of the head and neck cancer pathway to optimise outcomes of patient care. The CEN has driven several initiatives, reflecting Getting It Right First Time (GIRFT) principles aimed at reducing unwarranted variation. This improved consistency in approach and optimised collaborative working of the team now presents a better environment for multicentre audit and research. Ultimately, this should result in a continued improvement in patient and carer experience

What should I do and who’s to blame?:A cross-national study on youth’s attitudes and beliefs in times of COVID-19

The COVID-19 crisis has had a major impact on youth. This study examined factors associated with youth's attitudes towards their government's response to the pandemic and their blaming of individuals from certain risk groups, ethnic backgrounds, and countries or regions. In a sample of 5,682 young adults (Mage = 22) from 14 countries, lower perceived burden due to COVID-19, more collectivistic and less individualistic values, and more empathy were associated with more positive attitudes towards the government and less blaming of individuals of certain groups. Youth's social identification with others in the pandemic mediated these associations in the same direction, apart from the COVID-19 burden on attitudes, which had a positive indirect effect. No evidence of country-level moderation was found

Priorities and strategies for improving disabled women's access to maternity services when they are affected by domestic abuse:a multi-method study using concept maps

BACKGROUND: Domestic abuse is a significant public health issue. It occurs more frequently among disabled women than those without a disability and evidence suggests that a great deal of domestic abuse begins or worsens during pregnancy. All women and their infants are entitled to equal access to high quality maternity care. However, research has shown that disabled women who experience domestic abuse face numerous barriers to accessing care. The aim of the study was to identify the priority areas for improving access to maternity services for this group of women; develop strategies for improved access and utilisation; and explore the feasibility of implementing the identified strategies. METHODS: This multi-method study was the third and final part of a larger study conducted in the UK between 2012 and 2014. The study used a modified concept mapping approach and was theoretically underpinned by Andersen’s model of healthcare use. Seven focus group interviews were conducted with a range of maternity care professionals (n = 45), incorporating quantitative and qualitative components. Participants ranked perceived barriers to women’s access and utilisation of maternity services in order of priority using a 5-point Likert scale. Quantitative data exploration used descriptive and non-parametric analyses. In the qualitative component of each focus group, participants discussed the barriers and identified potential improvement strategies (and feasibility of implementing these). Qualitative data were analysed inductively using a framework analysis approach. RESULTS: The three most highly ranked barriers to women’s access and utilisation of maternity services identified in the quantitative component were: 1) staff being unaware and not asking about domestic abuse and disability; 2) the impact of domestic abuse on women; 3) women’s fear of disclosure. The top two priority strategies were: providing information about domestic abuse to all women and promoting non-judgemental staff attitude. These were also considered very feasible. The qualitative analysis identified a range of psychosocial and environmental barriers experienced by this group of women in accessing maternity care. Congruent with the quantitative results, the main themes were lack of awareness and fear of disclosure. Key strategies were identified as demystifying disclosure and creating physical spaces to facilitate disclosure. CONCLUSIONS: The study supports findings of previous research regarding the barriers that women face in accessing and utilising maternity services, particularly regarding the issue of disclosure. But the study provides new evidence on the perceived importance and feasibility of strategies to address such barriers. This is an important step in ensuring practice-based acceptability and ease with which improvement strategies might be implemented in maternity care settings