The vascular endothelium plays a role in insulin action

The endocrine system relies on the vasculature for delivery of hormones throughout the body, and the capillary microvasculature is the site where the hormones cross from the blood into the target tissue. Once considered an inert wall, various studies have now highlighted the functions of the capillary endothelium to regulate transport and therefore affect or maintain the interstitial environment. The role of the capillary may be clear in areas where there is a continuous endothelium, yet there also appears to be a role of endothelial cells in tissues with a sinusoidal structure. Here we focused on the most common endocrine disorder, diabetes, and several of the target organs associated with the disease, including skeletal muscle, liver and pancreas. However, it is important to note that the ability of hormones to cross the endothelium to reach their target tissue is a component of all endocrine functions. It is also a consideration in organs throughout the body and may have greater impact for larger hormones with target tissues containing a continuous endothelium. We noted that the blood levels do not always equal interstitial levels, which is what the cells are exposed to, and discussed how this may change in diseases such as obesity and insulin resistance. The capillary endothelium is, therefore, an essential and understudied aspect of endocrinology and metabolism that can be altered in disease, which may be an appropriate target for treatment.     

Reversal or reduction of glutamate and GABA transport in CNS pathology and therapy

A dysfunction of amino acid neurotransmitter transporters occurs in a number of central nervous system disorders, including stroke, epilepsy, cerebral palsy and amyotrophic lateral sclerosis. This dysfunction can comprise a reversal of transport direction, leading to the release of neurotransmitter into the extracellular space, or an alteration in transporter expression level. This review analyses the role of glutamate and GABA transporters in the pathogenesis and therapy of a number of acute and chronic neurological disorders.     

Improving secure messaging: A framework for support,partnership & information-giving communicating electronically (SPICE)

BackgroundPatient-centered communication benefits patients and is widely endorsed. However, it is primarily associated with face-to-face contexts, although patients are increasingly using electronic platforms, such as secure messaging in patient portals, to communicate with providers.PurposeGiven the popularity of secure messaging and its ability to impact the patient-provider relationship, this study aimed to determine which attributes of patient-centered communication are most desired by cancer patients using secure messaging.MethodsA 2⁶ balanced incomplete block design discrete choice experiment was conducted using the best-worst scaling technique. Respondents were asked to select their most and least preferred attributes of two simulated patient-provider exchanges within each of eight choice sets.Results210 respondents indicated that either level of partnership (high and low) and either level of information-giving (high and low) were most preferred, while response times greater than 24 hours and low levels of support were least favored.ConclusionsSimilar to face-to-face communication, patients value aspects of patient-centered communication in the secure messaging setting and desire them to be included in provider replies.Practice ImplicationsPatient-centered communication is important to patients using secure messaging. Providers should incorporate SPICE (Support, Partnership, and Information-giving while Communicating Electronically).     

Deficiency of complement-dependent prevention of immune precipitation in systemic sclerosis

BACKGROUND: Previous studies have indicated that complement may be activated or inherently abnormal in systemic sclerosis (SSc), and it has been suggested that immune complex deposition plays a part in the microvascular damage of this disease. OBJECTIVE: To study several aspects of the complement system in 24 patients with SSc. METHODS: Complement dependent prevention of immune precipitation (PIP) was measured by a sensitive enzyme immunoassay, levels of C1q, C4, and C3 by rocket immunoelectrophoresis, C4 allotypes by high voltage agarose electrophoresis, and C4A, C4B, and C3d by an enzyme linked immunosorbent assay (ELISA). RESULTS: PIP was markedly decreased in the patients with SSc (p<0.001). Abnormal complement activation was detected in nine patients as raised levels of the complement split product C3d. However, a relation between low PIP and complement activation was not seen. PIP was significantly lower in patients who carried the C4A*Q0 allotype (p=0.03), and a strong correlation was found between PIP and C4A concentration (p<0.00001). The PIP defect may, at least in some patients, be associated with the initial phase of the disease. CONCLUSIONS: The results show a previously unrecognised functional defect of complement in SSc; the defect correlates with low levels of classical pathway components and, in particular, C4A.     

Human thermoregulation after atropine and/or pralidoxime administration

The effects of intramuscular saline (control), atropine (2 mg), and/or pralidoxime (600 mg) on heat exchange was evaluated in four healthy males during seated, cycle exercise (55% Vo2 peak) in a temperate environment (Ta = 30.3 degrees C, Pw = 1.0 kPa). Esophageal (Tes), rectal (Tre), and mean skin temperatures (Tsk), and chest and forearm sweating (ms) were continuously measured. Skin blood flow (FBF) from the forearm was measured twice each minute by venous occlusion plethysmography. Whole body sweating was calculated from weight changes. The expected result of atropine injection, decreased eccrine sweating (-60%, p less than 0.05) and elevated esophageal (+0.4 degree C, p less than 0.05) and skin temperatures (+2.1 degrees C, p less than 0.05) was observed relative to control. Heart rate (+28 b X min-1) and FBF (+9 ml X 100 ml-1 X min-1) were higher after atropine. Pralidoxime, in general, did not affect the core and skin temperature responses to the exercise differently from control; however, a slightly elevated FBF (+3 ml X 100 cc-1 X min-1, 33%) compensated for the reduction in whole body sweating (-45%, p less than 0.05] that we observed. The combination of the drugs resulted in significantly higher esophageal (0.4 degree C) and skin (0.9 degree C) temperatures than atropine alone, as has been previously shown. The thermoregulatory disadvantage of inhibited sweating by atropine was partially compensated for by enhanced skin blood flow in this environment where Ta less than Tsk. Pralidoxime was shown to decrease whole body sweating, by a mechanism as yet unexplained.     

Your ticket to independence: a guide to getting your first Principal Investigator position

The transition to scientific independence as a principal investigator (PI) can seem like a daunting and mysterious process to postdocs and students ‐ something that many aspire to while at the same time wondering how to achieve this goal and what being a PI really entails. The FENS Kavli Network of Excellence (FKNE) is a group of young faculty who have recently completed this step in various fields of neuroscience across Europe. In a series of opinion pieces from FKNE scholars, we aim to demystify this process and to offer the next generation of up‐and‐coming PIs some advice and personal perspectives on the transition to independence, starting here with guidance on how to get hired to your first PI position. Rather than providing an exhaustive overview of all facets of the hiring process, we focus on a few key aspects that we have learned to appreciate in the quest for our own labs: What makes a research programme exciting and successful? How can you identify great places to apply to and make sure your application stands out? What are the key objectives for the job talk and the interview? How do you negotiate your position? And finally, how do you decide on a host institute that lets you develop both scientifically and personally in your new role as head of a lab?     

European consumers and health claims: attitudes, understanding and purchasing behaviour

Health claims on food products are often used as a means to highlight scientifically proven health benefits associated with consuming those foods. But do consumers understand and trust health claims? This paper provides an overview of recent research on consumers and health claims including attitudes, understanding and purchasing behaviour. A majority of studies investigated selective product-claim combinations, with ambiguous findings apart from consumers' self-reported generic interest in health claims. There are clear indications that consumer responses differ substantially according to the nature of carrier product, the type of health claim, functional ingredient used or a combination of these components. Health claims tend to be perceived more positively when linked to a product with an overall positive health image, whereas some studies demonstrate higher perceived credibility of products with general health claims (e.g. omega-3 and brain development) compared to disease risk reduction claims (e.g. bioactive peptides to reduce risk of heart disease), others report the opposite. Inconsistent evidence also exists on the correlation between having a positive attitude towards products with health claims and purchase intentions. Familiarity with the functional ingredient and/or its claimed health effect seems to result in a more favourable evaluation. Better nutritional knowledge, however, does not automatically lead to a positive attitude towards products carrying health messages. Legislation in the European Union requires that the claim is understood by the average consumer. As most studies on consumers' understanding of health claims are based on subjective understanding, this remains an area for more investigation.     

Plasma volume during heat stress and exercise in women

Summary Five women were studied during exercise and passive heating to determine whether PV dynamics were affected by the menstrual cycle. The exercise bout (80% peak) on a modified cycle ergometer and the passive heat stress were done in a hot environment (T_a=50°C, P_w=1.61kPa) during the follicular and luteal phase. Esophageal temperature (T_es) was measured continuously. Blood samples were drawn after each 0.2° C increase in T_es and was measured at that time. Initial PV was estimated at rest during the follicular phase. PV changes from rest were calculated at each T_es from Hb and Hct. During passive heating, PV decreased by a mean volume of 156 (±80) ml to 2.83 (±0.09)l in the follicular phase. During the luteal phase, there was a larger volume reduction (300±100 ml) during passive heating, and the final PV was lower than in the follicular phase and averaged 2.47±0.181. During exercise, PV decreased 463 (±90) ml to 2.50 (±0.11) l in the follicular and 381 (±70) ml to 2.50 (±0.23) l in the luteal phase. These data indicate that there is a menstrual cycle effect on PV dynamics during passive heating such that more fluid is shifted out of the vasculature during the luteal phase. During severe exercise there is a greater fluid loss during the follicular phase, yet the final PV is not different between phases.     

Heat exchange during encapsulation in a chemical warfare agent protective patient wrap in four hot environments

Tolerable encapsulation time in a Chemical Warfare Agent Protective Patient Wrap (dry insulative value = 1.44 clo; permeability index = 0.25) was determined in four hot environments including a simulated solar heat load (1152 W.m-2) for eight males. Mean body temperature (Tb), evaporative heat loss (EHL), dry heat gain (R + C), metabolic rate (M), and net heat flow (Msk) were measured or calculated from the heat balance equation. The ambient temperature (Ta) ranged from 54.7 degrees C (I) to 35.7 degrees C (IV) and the relative humidity ranged from 17% (I) to 63% (IV). EHL ranged from 173.5 W.m-2 (IV) to 277.8 W.m-2 (I) at min 30 of encapsulation. R + C ranged from -129 W.m-2 (IV) to -230 W.m-2 (I) at that time and Tb averaged 37.6(+/- 0.3) degrees C (IV) and 38.1(+/- 0.2) degrees C (I). The average time of encapsulation ranged from 61.8(+/- 0.2) degrees C (I). The average time of encapsulation ranged from 61.8(+/- 13.2) min (IV) to 38.4(+/- 5.0) min (I). A multiple linear regression equation to predict tolerable encapsulation was developed. These data show that tolerable encapsulation is severely limited in hot environments which have a marked solar heat load. A preliminary study (n = 2) indicated that encapsulation time in 54.7 degrees C/17%rh could be extended by some 23 min by covering the WRAP with wetted towels, thereby decreasing body heat storage by enhancing EHL from the surface of the WRAP.