Understanding and mitigating thiaminase activity in silver carp

A deficiency of thiamine (vitamin B1), an essential cofactor for enzymes involved in metabolic processes, can be caused by the enzyme thiaminase. Thiaminase in food stocks has been linked to morbidity and mortality due to thiamine depletion in many ecologically and economically important species. Thiaminase activity has been detected in certain bacteria, plants, and fish species, including carp. The invasive silver carp (Hypophthalmichthys molitrix) presents an enormous burden to ecosystems throughout the Mississippi River watershed. Its large biomass and nutritional content offer an attractive possibility as a food source for humans, wild animals, or pets. Additionally, harvesting this fish could alleviate some of the effects of this species on waterways. However, the presence of thiaminase would detract from its value for dietary consumption. Here we confirm the presence of thiaminase in several tissues from silver carp, most notably the viscera, and systematically examine the effects of microwaving, baking, dehydrating, and freeze-drying on thiaminase activity. Certain temperatures and durations of baking and microwaving reduced thiaminase activity to undetectable levels. However, caution should be taken when carp tissue is concentrated by processes without sufficient heat treatment, such as freeze-drying or dehydration, which results in concentration, but not inactivation of the enzyme. The effects of such treatments on the ease of extracting proteins, including thiaminase, and the impact on data interpretation using the 4-nitrothiophenol (4-NTP) thiaminase assay were considered

Improving Social Norms and Actions to Prevent Sexual and Intimate Partner Violence: A Pilot Study of the Impact of Green Dot Community on Youth

Sexual violence (SV) and intimate partner violence (IPV), which often cooccur with bullying, are serious public health issues underscoring the need for primary prevention. The purpose of this study was to examine the impact of a community-building SV and IPV prevention program, Green Dot Community, on adolescents’ perceptions of community social norms and their propensity to intervene as helpful actionists using two independent data sources. Green Dot Community takes place in towns and aims to influence all town members to prevent SV and IPV by addressing protective factors (i.e., collective efficacy, positive prevention social norms, and bystander helping, or actionism). In the current study, one town received Green Dot Community (the prevention-enhanced town), and two towns received prevention as usual (i.e., awareness and fundraising events by local IPV and SV advocacy centers). The program was evaluated using a two-part method: (a) A cross-sectional sample of high school students from three rural communities provided assessment of protective factors at two time points (Time 1, n = 1,187; Time 2, n = 877) and (b) Youth Risk Behavior Survey data from the state Department of Health were gathered before and after program implementation (Time 1, n = 2,034; Time 2, n = 2,017) to assess victimization rates. Youth in the prevention-enhanced town reported higher collective efficacy and more positive social norms specific to helping in situations of SV and IPV over time but did not differ on bystander behaviors or on victimization rates. Community-based prevention initiatives may be helpful in changing community norms to prevent SV/IPV

Assessment of macroalgal nitrogen limitation in a seasonal upwelling region

The relationship between nitrogen (N) availability and the growth of macroalgae in a seasonal upwelling region (Yaquina Head, Oregon, USA) was investigated. Water column nutrient concentrations were relatively high and stable during the winter, decreased in early spring, and were highly variable in the summer and early fall. Periods of high nutrient availability due to upwelling commenced in May and alternated with periods of low nutrient availability until September. Dissolved inorganic nitrogen (DIN) concentration was a poor predictor of N limitation of macroalgal growth due to the ability of macroalgae to store N for continued growth when ambient DIN concentrations were low. The relationship between growth and internal N content for Pelvetiopsis limitata (Phaeophyta:Fucaceae) and Ulva rigida (Chlorophyta:Ulvales) depended on the N source and culture conditions. Results of an in situ N enrichment experiment indicated that P. limitata growth may have been N-limited in April and May. A nitrogen budget for P. limitata indicated that NH+4 was the major N source for growth at Yaquina Head, due to its rapid uptake, despite the greater abundance of NO-3. The critical N value (tissue N level during the transition from N limiting to non-N limiting conditions) for growth of U. rigida on NO-3 (≤2.4 % dry wt) was much lower than that for growth on NH+4 (3.0 % dry wt). Ammonium was the major N source for growth of U. rigida at Yaquina Head, and growth was probably N-limited in April and May, as indicated by the critical N level for growth on NH: Growth of U. rigida may also have been intermittently N-limited between upwelling events. Problems with the use of critical N levels and nutrient monitoring to assess N limitation are discussed. Use of critical tissue N levels is complicated by variations in this parameter with the N source used for growth

Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed <2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000–2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500–3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean±standard deviation peak concentration of gentamicin was 12.3±3.7 µg/mL in infants weighing <2,000 g, 9.6±3.1 µg/mL in infants 2,000–2,249 g, and 10.0±3.4 µg/mL in infants 2,500–3,000 g. Initial peak concentration of gentamicin was >12 µg/mL in 28.8% and initial trough concentration was >2 µg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis

Past and possible future evolution of the Yukon Flats southern upland yedoma region, Alaska

The course of permafrost degradation depends on climate, vegetation, disturbance, and excess groundice content and distribution, which vary over time. The first three of these drivers are undergoing considerable change with arctic warming. Using combined lake-sediment records, field observations, aerial observations and LiDAR imagery, we reconstructed the late-Quaternary history of the marginal upland of the Yukon Flats, interior Alaska, a loess-mantled region with massive ground ice and numerous thermokarst lakes that is identified as yedoma. A switch to warmer, moister conditions during deglaciation triggered substantial thermal erosion and transport of silt, which washed into existing basins and formed widespread linear corrugations cutting across the uplands. Lakes began to form via thermokarst as early as 13,000 cal yr BP. Lakes intersect the corrugations, indicating lake formation followed initial landscape instability. Charcoal in basal sediments indicates fire may have influenced lake initiation. Small-scale surface topography revealed by LiDAR images includes deep gullies, features resembling lake drainage channels, and lowered lake shorelines. After ca 10,000 yr BP the region became colonized by dense evergreen conifer forest, which likely served to stabilize and insulate the ground surface, preventing the continuation of the high rates of permafrost degradation recorded in the earliest Holocene. Initial lake lowering and generation of steep local topography favouring drying of uplands, plus a summer water deficit, have also likely combined to shift the system to a more quiescent state through much of the Holocene. However, these changes have not prevented lake drainage events entirely. In 2013, several lakes drained or partially drained, possibly in response to fires and a high spring melt-water volume. The observed pattern of drainage is echoed in the older features preserved on the land surface. Based on the Holocene evolution of the region, increasing regional moisture and/or fire disturbance in the future could lead to an increase in permafrost degradation and lake drainage events

Patient and family involvement in adult critical and intensive care settings : a scoping review

BACKGROUND: Despite international bodies calling for increased patient and family involvement, these concepts remain poorly defined within literature on critical and intensive care settings. OBJECTIVE: This scoping review investigates the extent and range of literature on patient and family involvement in critical and intensive care settings. Methodological and empirical gaps are identified, and a future agenda for research into optimizing patient and family involvement is outlined. METHODS: Searches of MEDLINE, CINAHL, Social Work Abstracts and PsycINFO were conducted. English‐language articles published between 2003 and 2014 were retrieved. Articles were included if the studies were undertaken in an intensive care or critical care setting, addressed the topic of patient and family involvement, included a sample of adult critical care patients, their families and/or critical care providers. Two reviewers extracted and charted data and analysed findings using qualitative content analysis. FINDINGS: A total of 892 articles were screened, 124 were eligible for analysis, including 61 quantitative, 61 qualitative and 2 mixed‐methods studies. There was a significant gap in research on patient involvement in the intensive care unit. The analysis identified five different components of family and patient involvement: (i) presence, (ii) having needs met/being supported, (iii) communication, (iv) decision making and (v) contributing to care. CONCLUSION: Three research gaps were identified that require addressing: (i) the scope, extent and nature of patient involvement in intensive care settings; (ii) the broader socio‐cultural processes that shape patient and family involvement; and (iii) the bidirectional implications between patient/family involvement and interprofessional teamwork

A family presenting with multiple endocrine neoplasia type 2B: A case report

<p>Abstract</p> <p>Introduction</p> <p>Multiple endocrine neoplasia 2B, a rare autosomal dominant syndrome, is characterized by early onset of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and mucosal neuromas of the tongue, lips, inner cheeks and inner eyelids. Gangliomatosis of the gastrointestinal tract and its complications may also occur in patients with this disease.</p> <p>Case presentation</p> <p>We present the case of a 16-year-old Persian man diagnosed as having a non-invasive form of multiple endocrine neoplasia 2B (medullary thyroid cancer, mucosal neuroma of the tongue, lips and inner eyelids). Our patient, who had a positive family history of medullary thyroid cancer, was of normal height with no signs of marfanoid habitus.</p> <p>Conclusions</p> <p>Ophthalmological and oral manifestations of multiple endocrine neoplasia 2B, as in the case of our patient, are rare presentations of the disease; unfortunately in the case of our patient his condition had not been noted and acted upon until he presented to our department. The diagnosis in our patient's case was made only after his mother presented with the same condition. As a result, we emphasize that physicians should pay more attention to the oral and ocular signs of multiple endocrine neoplasia 2B in order to diagnose this fatal syndrome at an earlier phase.</p

Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells

Inhibition of the electron transport chain (ETC) prevents the regeneration of mitochondrial NAD+, resulting in cessation of the oxidative tricarboxylic acid (TCA) cycle and a consequent dependence upon reductive carboxylation for aspartate synthesis. NAD+ regeneration alone in the cytosol can rescue the viability of ETC-deficient cells. Yet, how this occurs and whether transfer of oxidative equivalents to the mitochondrion is required remain unknown. Here, we show that inhibition of the ETC drives reversal of the mitochondrial aspartate transaminase (GOT2) as well as malate and succinate dehydrogenases (MDH2 and SDH) to transfer oxidative NAD+ equivalents into the mitochondrion. This supports the NAD+-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis—the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.P.A.-M was supported by a Marie Skłodowska-Curie Actions individual fellowship and the Beug Foundation. A.V. was supported by Fonds Wetenschappelijk Onderzoek (FWO Vlaanderen). J.E.-H. was supported by an MRC studentship. J.C.A was supported by a Cancer Research UK Career Development Fellowship (C47559/A16243). S.-M.F. acknowledges funding from the European Research Council under the ERC Consolidator grant agreement no. 771486–MetaRegulation, FWO Projects, Fonds Baillet Latour, KU Leuven-FTBO/Internal Funding, Stichting Tegen Kanker and the King Baudouin Foundation. Work in the A.J.F. group was supported by a Wellcome Trust-ISSF grant, funding from Barts Charity (MGU0404), and by a Cancer Research UK Centre Grant to Barts Cancer Institute (C355/A25137). The illustrations in the graphical abstract and Figure 5F were created using BioRender.com

The Impact of Official Development Aid on Maternal and Reproductive Health Outcomes: A Systematic Review

BACKGROUND: Progress toward meeting Millennium Development Goal 5, which aims to improve maternal and reproductive health outcomes, is behind schedule. This is despite ever increasing volumes of official development aid targeting the goal, calling into question the distribution and efficacy of aid. The 2005 Paris Declaration on Aid Effectiveness represented a global commitment to reform aid practices in order to improve development outcomes, encouraging a shift toward collaborative aid arrangements which support the national plans of aid recipient countries (and discouraging unaligned donor projects). METHODS AND FINDINGS: We conducted a systematic review to summarise the evidence of the impact on MDG 5 outcomes of official development aid delivered in line with Paris aid effectiveness principles and to compare this with the impact of aid in general on MDG 5 outcomes. Searches of electronic databases identified 30 studies reporting aid-funded interventions designed to improve maternal and reproductive health outcomes. Aid interventions appear to be associated with small improvements in the MDG indicators, although it is not clear whether changes are happening because of the manner in which aid is delivered. The data do not allow for a meaningful comparison between Paris style and general aid. The review identified discernible gaps in the evidence base on aid interventions targeting MDG 5, notably on indicators MDG 5.4 (adolescent birth rate) and 5.6 (unmet need for family planning). DISCUSSION: This review presents the first systematic review of the impact of official development aid delivered according to the Paris principles and aid delivered outside this framework on MDG 5 outcomes. Its findings point to major gaps in the evidence base and should be used to inform new approaches and methodologies aimed at measuring the impact of official development aid

Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi Neonates

Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed &lt;2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000-2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500-3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean\ub1standard deviation peak concentration of gentamicin was 12.3\ub13.7 \u3bcg/mL in infants weighing &lt;2,000 g, 9.6\ub13.1 \u3bcg/mL in infants 2,000-2,249 g, and 10.0\ub13.4 \u3bcg/mL in infants 2,500-3,000 g. Initial peak concentration of gentamicin was &gt;12 \u3bcg/mL in 28.8% and initial trough concentration was &gt;2 \u3bcg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis