Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis

pre-printBackground: Sepp1 transports selenium, but its complete role in selenium homeostasis is not known. Results: Deletion of Sepp1 in hepatocytes increases liver selenium at the expense of other tissues and decreases whole-bodyselenium by increasing excretion. Conclusion: Sepp1 production by hepatocytes retains selenium in the organism and distributes it from the liver to peripheral tissues. Significance: Sepp1 is central to selenium homeostasis

Adapting to Sea Level Rise: Insights from a New Evaluation Framework of Physical Design Projects

Designers and engineers are developing proposals for physical projects to adapt coastal sites to future sea level rise related threats. This puts pressure on local and regional decision makers to develop strategic frameworks for prioritizing, permitting and funding such projects. However, no systematic evaluation tools exist for the full range of these innovative designs. We build on the literature to develop an evaluation framework that synthesizes two different approaches to categorize these proposals and provide insight for coastal managers and decision makers. We apply this framework to physical projects that address sea level rise in their design around the San Francisco Bay Area, a leading region in sea level rise adaptation. We find that these projects demonstrate a shift toward more habitat-focused strategies, which likely marks the beginning of a larger transformation of the coastal zone. According to our five-part evaluation tool, we also find that the projects’ scores have improved over time, indicating that state agency work may be helping communities implement more flexible adaptation initiatives. Despite these positive signs, we also find that none of the projects achieved high marks in all five of the evaluation criteria. This finding indicates that there is a critical need for improvement in physical planning for adaptation to higher sea levels and associated impacts. Most importantly, we find that an evaluation framework such as the one used here can provide critical insights into the likely risks and benefits of proposed adaptation projects and their long-term implications for coastal zones

Altered hippocampus synaptic function in selenoprotein P deficient mice

Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS

Replenishment of selenium deficient rats with selenium results in redistribution of the selenocysteine tRNA population in a tissue specific manner

AbstractWe reported previously that the selenium status of rats influences both the steady-state levels and distributions of two selenocysteine tRNA isoacceptors and that these isoacceptors differ by a single methyl group attached to the ribosyl moiety at position 34. In this study, we demonstrate that repletion of selenium-deficient rats results in a gradual, tissue-dependent shift in the distribution of these isoacceptors. Rats fed a selenium-deficient diet possess a greater abundance of the species unmethylated on the ribosyl moiety at position 34 compared to the form methylated at this position. A redistribution of the Sec–tRNA isoacceptors occurred in tissues of selenium-supplemented rats whereby the unmethylated form gradually shifted toward the methylated form. This was true in each of four tissues examined, muscle, kidney, liver and heart, although the rate of redistribution was tissue-specific. Muscle manifested a predominance of two minor serine isoacceptors under conditions of extreme selenium-deficiency which also appeared to respond to selenium. Ribosomal binding studies revealed that one of the two additional isoacceptors decodes the serine codeword, AGU, and the second decodes the serine codeword, UCU. Interestingly, muscle and heart were the slower tissues to return to a `selenium adequate' tRNA distribution pattern

Evaluating team-based learning in a foundation training pathway for trainee pharmacists

YesA new programme incorporating online study days delivered using team-based learning (TBL) for hospital-based trainee pharmacists (TPs) in the North of England was created. To our knowledge, TBL has not previously been used in educational programmes for TPs designed to supplement their workplace learning. The project aimed to investigate the experiences of TPs learning using online TBL by exploring their perceptions on their engagement, learning, and satisfaction with TBL. Data were collected using online anonymous surveys at the end of four online TBL study days. A bespoke survey consisted of 5-point or 4-point Likert scale and two free text questions. TBL Student Assessment Instrument (SAI), a validated survey, was used to assess TPs' acceptance of TBL. Survey data was summarized descriptively, and free text comments analysed using thematic analysis. TPs developed accountability to their team, remained engaged with TBL delivery online and stated a preference for and satisfaction with this method. TPs valued opportunities to apply their knowledge in challenging scenarios and learn from discussions with their peers, the larger group, and facilitators. TBL was also perceived to be an engaging approach to learning and helped to maintain their interest with the teaching material. However, TPs struggled to engage with pre-work outside of the class due to competing work priorities. This study shows that online TBL was well accepted by TPs and can be successfully used to deliver education to large cohorts of learners. The model developed shows potential for scalability to larger numbers of learners.The teaching programme was funded by National Health Service England Workforce, Training, Education (NHSE WTE) (previously known as Health Education England)

Selenomethionine and methyl selenocysteine: multiple-dose pharmacokinetics in selenium-replete men

According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX)

Ovulation, Female Competition, and Product Choice: Hormonal Influences on Consumer Behavior

Recent research shows that women experience nonconscious shifts across dif-ferent phases of the monthly ovulatory cycle. For example, women at peak fertility (near ovulation) are attracted to different kinds of men and show increased desire to attend social gatherings. Building on the evolutionary logic behind such effects, we examined how, why, and when hormonal fluctuations associated with ovulation influenced women’s product choices. In three experiments, we show that at peak fertility women nonconsciously choose products that enhance appearance (e.g., choosing sexy rather than more conservative clothing). This hormonally regulated effect appears to be driven by a desire to outdo attractive rival women. Conse-quently, minimizing the salience of attractive women who are potential rivals sup-presses the ovulatory effect on product choice. This research provides some of the first evidence of how, why, and when consumer behavior is influenced by hormonal factors. Across cultures throughout history, women have con-sistently allocated a large portion of their resources to a very particular class of consumer goods—those that en

Promoting access to dental care in South London: adult patients' perspectives.

Objective: To evaluate patients' views on health service initiatives established to improve uptake of NHS primary dental care amongst adult patients in a socially deprived area, comparing practices with extended and regular contract capacity. Study design: Service evaluation and cross-sectional survey. Method: Questionnaire survey of patients attending a random sample of dental practices in three inner-metropolitan boroughs of south London following initiatives to improve access to dental care (across dental practices delivering regular and extended contracts for services) exploring attendance patterns and the influence and awareness of local initiatives to promote access. Results: Four hundred fifty adults across 12 dental practices completed questionnaires: 79% reported attending for routine and 21% for urgent care. Patients were most aware of banners outside practices, followed by dental advertisements in newspapers. Vouchers for free treatments were considered of the highest possible influence, followed by vouchers for reduced treatment costs and an emergency out-of-hours helpline. Awareness and influence were not aligned, and there was no evidence of difference by practice contract type whilst there were differences by age and type of attendance. Conclusion: The findings suggest that financial incentives and emergency services are considered the most influential initiatives for adult patients whose attendance patterns appear to be related to personal circumstances rather than merely being influenced by the provision of information

Family-based pediatric weight management interventions in US primary care settings targeting children ages 6-12 years old: A systematic review guided by the RE-AIM framework.

Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions