National athletic trainers' association position statement: management of the athlete with type 1 diabetes mellitus

OBJECTIVE: To present recommendations for the certified athletic trainer in the management of type 1 diabetes in the athlete. BACKGROUND: In managing diabetes, the most important goal is to keep blood glucose levels at or as close to normal levels as possible without causing hypoglycemia. This goal requires the maintenance of a delicate balance among hypoglycemia, euglycemia, and hyperglycemia, which is often more challenging in the athlete due to the demands of physical activity and competition. However, effectively managing blood glucose, lipid, and blood pressure levels is necessary to ensuring the long-term health and well-being of the athlete with diabetes. RECOMMENDATIONS: These recommendations are intended to provide the certified athletic trainer participating in the management of an athlete with type 1 diabetes mellitus with the specific knowledge and problem-solving skills needed. Athletic trainers have more contact with the athlete with diabetes than most members of the diabetes management team do and so must be prepared to assist the athlete as required.     

Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions

It is generally accepted that nitric oxide (NO) donors, such as sodium nitroprusside (SNP), or phosphodiesterase 5 (PDE5) inhibitors, including sildenafil, each impact human platelet function. Although a strong correlation exists between the actions of NO donors in platelets and their impact on cGMP, agents such as sildenafil act without increasing global intra-platelet cGMP levels. This study was undertaken to identify how PDE5 inhibitors might act without increasing cGMP. Our data identify PDE5 as an integral component of a protein kinase G1β (PKG1β)-containing signaling complex, reported previously to coordinate cGMP-mediated inhibition of inositol-1, 4, 5-trisphosphate receptor type 1 (IP₃R1)-mediated Ca²⁺-release. PKG1β and PDE5 did not interact in subcellular fractions devoid of IP₃R1 and were not recruited to IP₃R1-enriched membranes in response to cGMP-elevating agents. Activation of platelet PKG promoted phosphorylation and activation of the PDE5 fraction tethered to the IP₃R1-PKG complex, an effect not observed for the nontethered PDE5. Based on these findings, we elaborate a model in which PKG selectively activates PDE5 within a defined microdomain in platelets and propose that this mechanism allows spatial and temporal regulation of cGMP signaling in these cells. Recent reports indicate that sildenafil might prove useful in limiting in-stent thrombosis and the thrombotic events associated with the acute coronary syndromes (ACS), situations poorly regulated with currently available therapeutics. We submit that our findings may define a molecular mechanism by which PDE5 inhibition can differentially impact selected cellular functions of platelets, and perhaps of other cell types.     

Fexofenadine effects on cognitive performance in aviators at ground level and simulated altitude

INTRODUCTION: Antihistamines are used for the treatment of allergic rhinitis (AR) symptoms. However, the cognitive effects of some antihistamines can dramatically impair individuals in occupations that require sustained vigilance. METHODS: The cognitive effects of fexofenadine were compared to a placebo (passive control) and cetirizine (active control) in healthy naval flight personnel. All subjects received one dose of each treatment in one of six possible sequences with two washout periods in between, and were assessed for aviation-related cognitive skills using the Aeromedical Vigilance Test (AVT) at both ambient atmospheric conditions and normobaric hypoxic conditions. Drowsiness was self-assessed by participants using a visual analog scale (VAS). RESULTS: There was no significant difference between fexofenadine and placebo over the entire 60-min test period, under ambient atmospheric conditions, or under either hypoxic condition. Compared with placebo, cetirizine significantly increased AVT errors over the entire 60-min test period, at 10,000 ft, and at 15,000 ft. No statistical difference was found between treatments under ambient atmospheric conditions, although cetirizine treatment resulted in a greater change from baseline in adjusted average number of AVT errors (0.2124 +/- 0.06) than fexofenadine treatment (0.1989 +/- 0.07) and placebo (0.0745 +/- 0.07). Furthermore, at 10,000 ft there were significantly more AVT errors with cetirizine than with fexofenadine. There were no significant increases in self-reported drowsiness (VAS) for both cetirizine and fexofenadine compared with placebo. CONCLUSION: Fexofenadine is comparable to placebo in its effect on the cognitive skills important for piloting an aircraft, while cetirizine impairs cognition and may affect piloting ability.     

Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection,donor selection algorithms and conditioning protocols

Allogeneic haemopoietic stem cell transplantation offers a potentially curative treatment option for a wide range of life‐threatening malignant and non‐malignant disorders of the bone marrow and immune system in patients of all ages. With rapidly emerging advances in the use of alternative donors, such as mismatched unrelated, cord blood and haploidentical donors, it is now possible to find a potential donor for almost all patients in whom an allograft is indicated. Therefore, for any specific patient, the transplant physician may be faced with a myriad of potential choices, including decisions concerning which donor to prioritize where there is more than one, the optimal selection of specific umbilical cord blood units and which conditioning and graft‐versus‐host disease prophylactic schedule to use. Donor choice may be further complicated by other important factors, such as urgency of transplant, the presence of alloantibodies, the disease status (homozygosity or heterozygosity) of sibling donors affected by inherited disorders and the cytomegalovirus serostatus of patient and donor. We report UK consensus guidelines on the selection of umbilical cord blood units, the hierarchy of donor selection and the preferred conditioning regimens for umbilical cord blood transplantation, with a summary of rationale supporting these recommendations.     

Assessing cerebrovascular reactivity by the pattern of response to progressive hypercapnia

Cerebral blood flow responds to a carbon dioxide challenge, and is often assessed as cerebrovascular reactivity, assuming a linear response over a limited stimulus range or a sigmoidal response over a wider range. However, these assumed response patterns may not necessarily apply to regions with pathophysiology. Deviations from sigmoidal responses are hypothesised to result from upstream flow limitations causing competition for blood flow between downstream regions, particularly with vasodilatory stimulation; flow is preferentially distributed to regions with more reactive vessels. Under these conditions, linear or sigmoidal fitting may not fairly describe the relationship between stimulus and flow. To assess the range of response patterns and their prevalence a survey of healthy control subjects and patients with cerebrovascular disease was conducted. We used a ramp carbon dioxide challenge from hypo‐ to hypercapnia as the stimulus, and magnetic resonance imaging to measure the flow responses. We categorized BOLD response patterns into four types based on the signs of their linear slopes in the hypo‐ and hypercapnic ranges, color coded and mapped them onto their respective anatomical scans. We suggest that these type maps complement maps of linear cerebrovascular reactivity by providing a better indication of the actual response patterns. Hum Brain Mapp 38:3415–3427, 2017. © 2017 Wiley Periodicals, Inc.     

The prediction of hospital admission in children with acute asthma

Objective : To determine whether a single assessment of children at the time of presentation to the emergency department would discriminate accurately between those requiring admission and those who could be managed at home and to examine the appropriateness of these decisions.
Methodology : Fifty-three children were assessed using a table recommended by Australian and New Zealand respiratory paediatricians, which categorizes children as probably being able to manage at home (group 1), may need admission to hospital (group 2) and certainly need admission to hospital (group 3) on the basis of oximetry, presence of wheeze and pulsus paradoxus.
Results : Nine out of 11 children assigned to group 1 were managed at home and 15/17 who were predicted to require admission were admitted. No individual component of the assessment dominated the decision made. Of the 25 children allocated to group 2, 18 were admitted.
Conclusions : The method employed was highly predictive of outcome for half of the children who presented with asthma. However, 25/53 (47%) were assigned by the table to a recommendation for further assessment; this limits its usefulness.     

Care co‐ordination for older people in the third sector: scoping the evidence

The third sector has played a significant role internationally in the delivery of adult social care services for many years. Its contribution to care co‐ordination activities for older people, however, in England and elsewhere, is relatively unknown. A scoping review was therefore conducted to ascertain the character of the literature, the nature and extent of third sector care co‐ordination activity, and to identify evidence gaps. It was undertaken between autumn 2013 and summer 2014 and updated with additional searches in 2016. Electronic and manual searches of international literature using distinct terms for different approaches to care co‐ordination were undertaken. From a total of 835 papers, 26 met inclusion criteria. Data were organised in relation to care co‐ordination approaches, types of third sector organisation and care recipients. Papers were predominantly from the UK and published this century. Key findings included that: a minority of literature focused specifically on older people and that those doing so described only one care co‐ordination approach; third sector services tended to be associated with independence and person‐centred practice; and working with the statutory sector, a prerequisite of care co‐ordination, was challenging and required a range of features to be in place to support effective partnerships. Strengths and weaknesses of care co‐ordination practice in the third sector according to key stakeholder groups were also highlighted. Areas for future research included the need for: a specific focus on older people's experiences; an investigation of workforce issues; detailed examination of third sector practices, outcomes and costs; interactions with the statutory sector; and an examination of quality assurance systems and their appropriateness to third sector practice. The main implication of the findings is a need to nurture variety within the third sector in order to provide older people and other adults with the range of service options desired.