Viral vectored transmission blocking vaccines against Plasmodium falciparum

Background: Transmission blocking vaccines (TBVs) target sexual develop¬ment of the parasite within the mosquito and aim to prevent transmission of malaria from one individual to another. Antibodies raised against Pfs48/45, Pfs230 Region C, PfHAP2, and Anopheles gambiae Alanyl Aminopeptidase N1 (AgAPN1) proteins reduce transmission i.e. have transmission blocking activity [1–5]. Recombinant simian Adenovirus (AdC63 serotype) and Modified Vaccinia Ankara (MVA) viral vectors have been shown to induce high antibody titres to asexual parasite antigens in animal studies [6]. Materials and methods: Protein sequences for each of the antigens were codon optimised for expression in humans and cloned into shuttle vectors, which were then recombined with the parental virus and purified to obtain virus expressing the antigen of interest. Mice were vaccinated with AdC63 (i.m.), sera was taken after 2 weeks, and will be followed by an MVA boost (i.d.) eight weeks after the prime. Antibodies were assayed by a standardised ELISA, and transmission blocking activity assessed using a standardised membrane feeding assay (SMFA). Conclusion: Induction of high antibody tires using this vaccine platform could be used together with other control measures to achieve elimination and/or eradication of the disease at a local or national level

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal

INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored

Melt Inclusion Vapour Bubbles: The Hidden Reservoir for Major and Volatile Elements

Olivine-hosted melt inclusions (MIs) provide samples of magmatic liquids and their dissolved volatiles from deep within the plumbing system. Inevitable post-entrapment modifications can lead to significant compositional changes in the glass and/or any contained bubbles. Re-heating is a common technique to reverse MI crystallisation; however, its effect on volatile contents has been assumed to be minor. We test this assumption using crystallised and glassy basaltic MIs, combined with Raman spectroscopy and 3D imaging, to investigate the changes in fluid and solid phases in the bubbles before and after re-heating. Before re-heating, the bubble contains CO2 gas and anhydrite (CaSO4) crystallites. The rapid diffusion of major and volatile elements from the melt during re-heating creates new phases within the bubble: SO2, gypsum, Fe-sulphides. Vapour bubbles hosted in naturally glassy MIs similarly contain a plethora of solid phases (carbonates, sulphates, and sulphides) that account for up to 84% of the total MI sulphur, 80% of CO2, and 14% of FeO. In both re-heated and naturally glassy MIs, bubbles sequester major and volatile elements that are components of the total magmatic budget and represent a “loss” from the glass. Analyses of the glass alone significantly underestimates the original magma composition and storage parameters

Black rings with fourth dipole cause less hair loss

An example of entropy enigma with a controlled CFT dual was recently studied in arXiv:1108.0411. The enigmatic bulk configurations, considered within the STU model, can be mapped under spectral flow into black rings with three monopole and dipole charges. Even though the bulk and CFT configurations existed in the same region of parameter space, the Bekenstein-Hawking entropy of the bulk configurations was found to be lower than the microscopic entropy from the CFT. While it is possible that the difference in entropy is due to the bulk and boundary configurations being at different points in the moduli space, it is also possible that the bulk configurations embeddable within the STU model are not the most entropic. New families of BPS black ring solutions with four electric and four dipole magnetic charges have recently been explicitly constructed in arXiv:1201.2585. These black rings are not embeddable within the STU model. In this paper we investigate if these black rings can be entropically dominant over the STU model black rings. We find that the new black rings are always entropically subdominant to the STU-model black rings. However, for small fourth dipole charge these black rings continue to be dominant over the BMPV in a small region of parameters and are thus enigmatic.Comment: v2: minor changes, references added, 15 pages, 9 figures (published version

Dispersal and reproductive careers of male mountain gorillas in Bwindi Impenetrable National Park, Uganda

Dispersal is a key event in the life of an animal and it influences individual reproductive success. Male mountain gorillas exhibit both philopatry and dispersal, resulting in a mixed one-male and multimale social organization. However, little is known about the relationship between male dispersal or philopatry and reproductive careers in Bwindi mountain gorillas. Here we analyze data spanning from 1993 to 2017 on social groups in Bwindi Impenetrable National Park, Uganda to examine the proportion of males that disperse, age of dispersal, pathways to attaining alpha status, fate of dispersing males and philopatric males, and male tenure length as well as make comparisons of these variables to the Virunga mountain gorilla population. We report previously undocumented cases of dispersal by immature males and old males and we also observed the only known case of a fully mature male immigrating into a breeding group. We used genetic tracking of known individuals to estimate that a minimum of 25% of males that disperse to become solitary males eventually form new groups. No differences were found between the Bwindi and Virunga population in the age of male dispersal, the proportion of males that disperse, the age of alpha male acquisition, and dominance tenure length. The lack of differences may be due to small sample sizes or because the observed ecological variability does not lead to life history differences between the populations. Males in both populations follow variable strategies to attain alpha status leading to the variable one-male and multimale social organization, including dispersal to become solitary and eventually form a group, via group fissioning, usurping another alpha male, or inheriting the alpha position when a previous group leader dies

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

<p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p

Indigenous use and bio-efficacy of medicinal plants in the Rasuwa District, Central Nepal

<p>Abstract</p> <p>Background</p> <p>By revealing historical and present plant use, ethnobotany contributes to drug discovery and socioeconomic development. Nepal is a natural storehouse of medicinal plants. Although several ethnobotanical studies were conducted in the country, many areas remain unexplored. Furthermore, few studies have compared indigenous plant use with reported phytochemical and pharmacological properties.</p> <p>Methods</p> <p>Ethnopharmacological data was collected in the Rasuwa district of Central Nepal by conducting interviews and focus group discussions with local people. The informant consensus factor (F_IC) was calculated in order to estimate use variability of medicinal plants. Bio-efficacy was assessed by comparing indigenous plant use with phytochemical and pharmacological properties determined from a review of the available literature. Criteria were used to identify high priority medicinal plant species.</p> <p>Results</p> <p>A total of 60 medicinal formulations from 56 plant species were documented. Medicinal plants were used to treat various diseases and disorders, with the highest number of species being used for gastro-intestinal problems, followed by fever and headache. Herbs were the primary source of medicinal plants (57% of the species), followed by trees (23%). The average F_IC value for all ailment categories was 0.82, indicating a high level of informant agreement compared to similar studies conducted elsewhere. High F_ICvalues were obtained for ophthalmological problems, tooth ache, kidney problems, and menstrual disorders, indicating that the species traditionally used to treat these ailments are worth searching for bioactive compounds: <it>Astilbe rivularis</it>, <it>Berberis asiatica</it>, <it>Hippophae salicifolia, Juniperus recurva</it>, and <it>Swertia multicaulis</it>. A 90% correspondence was found between local plant use and reported plant chemical composition and pharmacological properties for the 30 species for which information was available. Sixteen medicinal plants were ranked as priority species, 13 of which having also been prioritized in a country-wide governmental classification.</p> <p>Conclusions</p> <p>The <it>Tamang </it>people possess rich ethnopharmacological knowledge. This study allowed to identify many high value and high priority medicinal plant species, indicating high potential for economic development through sustainable collection and trade.</p

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background: Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings: In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation: Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Funding: Bill & Melinda Gates Foundation