Immune consequences of exercise in hypoxia: A narrative review.

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type, dose (frequency/duration, intensity), and individual characteristics. Similarly, reduced availability of ambient oxygen (hypoxia) modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia. How combined exercise and hypoxia (e.g., high-altitude training) sculpts immune responses is not well understood, although such combinations are becoming increasingly popular. Therefore, in this paper, we summarize the impact on immune responses of exercise and of hypoxia, both independently and together, with a focus on specialized cells in the innate and adaptive immune system. We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia, then we discuss how they may be modulated by nutritional strategies. Mitochondrial, antioxidant, and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism, resilience, and overall immune functions by regulating the survival, differentiation, activation, and migration of immune cells. This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions. Appropriate acclimatization, training, and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state

Frictional trajectories near a barrier: a dissipationless Newtonian approach

We address the problem of classical frictional motion under a potentialV possessing a barrier, apart from other possible confining and nonstationary terms. It is pointed out that the Green's solution of the exact equation of motion can be reduced (under suitable conditions) either to an improved Rayleigh form or a non-Rayleigh form, the latter being outside the scope of the standard large-friction treatment of the Fokker-Planck equation. The resulting dissipationless dynamics involves an appropriately scaled potential which may have promising applications to quantum stochastic phenomena. Genuine dissipative corrections in regions far away from the barrier can be accounted for by the higher-order terms in our asymptotic expansions

Protocols for BNCT of glioblastoma multiforme at Brookhaven: Practical considerations

In this report we discuss some issues considered in selecting initial protocols for boron neutron capture therapy (BNCT) of human glioblastoma multiforme. First the tolerance of normal tissues, especially the brain, to the radiation field. Radiation doses limits were based on results with human and animal exposures. Estimates of tumor control doses were based on the results of single-fraction photon therapy and single fraction BNCT both in humans and experimental animals. Of the two boron compounds (BSH and BPA), BPA was chosen since a FDA-sanctioned protocol for distribution in humans was in effect at the time the first BNCT protocols were written and therapy studies in experimental animals had shown it to be more effective than BSH

Technical aspects of boron neutron capture therapy at the BNL Medical Research Reactor

The Brookhaven Medical Research Reactor, BMRR, is a 3 MW heterogeneous, tank-type, light water cooled and moderated, graphite reflected reactor, which was designed for biomedical studies. Early BNL work in Boron Neutron Capture Therapy (BNCT) used a beam of thermal neutrons for experimental treatment of brain tumors. Research elsewhere and at BNL indicated that higher energy neutrons would be required to treat deep seated brain tumors. Epithermal neutrons would be thermalized as they penetrated the brain and peak thermal neutron flux densities would occur at the depth of brain tumors. One of the two BMRR thermal port shutters was modified in 1988 to include plates of aluminum and aluminum oxide to provide an epithermal port. Lithium carbonate in polyethylene was added in 1991 around the bismuth port to reduce the neutron flux density coming from outside the port. To enhance the epithermal neutron flux density, the two vertical thimbles A-3 (core edge) and E-3 (in core) were replaced with fuel elements. There are now four fuel elements of 190 grams each and 28 fuel elements of 140 grams each for a total of 4.68 kg of {sup 235}U in the core. The authors have proposed replacing the epithermal shutter with a fission converter plate shutter. It is estimated that the new shutter would increase the epithermal neutron flux density by a factor of seven and the epithermal/fast neutron ratio by a factor of two. The modifications made to the BMRR in the past few years permit BNCT for brain tumors without the need to reflect scalp and bone flaps. Radiation workers are monitored via a TLD badge and a self-reading dosimeter during each experiment. An early concern was raised about whether workers would be subject to a significant dose rate from working with patients who have been irradiated. The gamma ray doses for the representative key personnel involved in the care of the first 12 patients receiving BNCT are listed. These workers did not receive unusually high exposures

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Boron neutron capture therapy of glioblastoma multiforme using the p- boronophenylalanine-fructose complex and epithermal neutrons

The amino acid analogue p-boronophenylalanine (BPA) is under investigation as a neutron capture agent for BNCT of glioblastoma multiforme. A series of patients undergoing surgical removal of tumor received BPA orally as the free amino acid. Favorable tumor/blood boron concentration ratios were obtained but the absolute amount of boron in the tumor would have been insufficient for BNCT. BPA can be solubilized at neutral pH by complexation with fructose (BPA-F). Studies with rats suggest that intraperitoneal injection of BPA-F complex produces a much higher tumor boron concentration to rat intracerebral 9L gliosarcoma that were possible with oral BPA. Higher boron concentrations have allowed higher tumor radiation doses to be delivered while maintaining the dose to the normal brain vascular endothelium below the threshold of tolerance. The experience to date of the administration of BPA-F to one patient is provided in this report

TH2.2: Framework for incorporating Gender Equality and Social Inclusion (GESI) elements in Climate Information Services (CIS)

This paper proposes a Gender Equality and Social Inclusion (GESI) Framework for incorporating Climate Information Services which is increasingly becoming important due to climate change and climate variability. Our paper understands gender as a socially constructed definition of women and men. Gender inequalities seem to be pervasive in that, even with the introduction of new agricultural and climate information technologies, the gendered fault lines still appear within the new technological settings. Such gendered technological inequalities can be traced back to as early as the 1960s, where it was clear that technological solutions are grounded within the society in which they are embedded. Unless women are intentionally included in the design and development of agricultural technologies, there is a high risk that women will not benefit from agricultural innovations meant to ameliorate the impact of climate change and climate variability. According to Conway's law, any technology reflects the values of its creator. Therefore, it is of paramount importance to understand the values of those who create technological solutions and innovations. Our proposed framework has five indicators which are namely: Gender targeting by design, Sex disaggregated data collection, analysis of sex-disaggregated data, dissemination technological options and ongoing gender monitoring, and empowerment evaluation. The five indicator domains are further complemented by their respective assumptions. The five indicator domains are applied in the context of three development interventions which are namely agricultural data hub, Climate Information Services Training, and Flood and Drought Indicators which are all being implemented in Zambia as part of the Accelerating Impacts of CGIAR Climate Research for Africa Project (AICCRA) Project. The framework which is being applied in Zambia, is showing the importance of incorporating gender equality and social inclusion in the design, implementation and evaluation of climate information services

Women's leadership in the Asian Century: does expansion mean inclusion?

This paper draws on British Council commissioned research in response to concerns about women's absence from senior leadership positions in higher education in South Asia. The study sought existing knowledge from literature, policies, and available statistics and collected original interview data from 30 academics in Afghanistan, Bangladesh, India, Nepal, Pakistan, and Sri Lanka. A central finding was that gender is not a category of analysis in higher education policy, research or statistical data in the region. Our interview data suggest that leadership was frequently not an object of desire for women. Being associated with particular types of masculinities, leadership often carried a heavy affective load for those women who transgressed patriarchal socio-cultural norms and disrupted the symbolic order of women being led by men. Leadership was frequently perceived and experienced by women in terms of navigating a range of ugly feelings and toxicities that depleted aspirations, well-being and opportunities

Psychosocial implications of tubal ligation in a rural health district: A phenomenological study

<p>Abstract</p> <p>Background</p> <p>Tubal ligation is the most popular family planning method worldwide. While its benefits, such as effectiveness in protecting against pregnancies, minimal need for long-term follow-up and low side-effects profile are well documented, it has many reported complications. However, to date, these complications have not been described by residents in Congo. Therefore, the study aimed at exploring the experience of women who had undergone tubal ligation, focusing on perceptions of physical, psychological and contextual experiences of participants.</p> <p>Methods</p> <p>This qualitative study used a semi-structured questionnaire in a phenomenological paradigm to collect data. Fifteen participants were purposefully selected among sterilized women who had a ligation procedure performed, were aged between 30 and 40 years, and were living within the catchment area of the district hospital. Data were collected by two registered nurses, tape-recorded, and transcribed verbatim. Reading and re-reading cut and paste techniques, and integration were used to establish codes, categories, themes, and description.</p> <p>Results</p> <p>Diverse and sometimes opposite changes in somatic symptoms, psychological symptoms, productivity, ecological relationships, doctor-client relationships, ethical issues, and change of life style were the major problem domains.</p> <p>Conclusions</p> <p>Clients reported conflicting experiences in several areas of their lives after tubal sterilization. Management, including awareness of the particular features of the client, is needed to decrease the likelihood of psychosocial morbidity and/or to select clients in need of sterilization.</p

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible