Portable Prehospital Methods to Treat Near-Hypothermic Shivering Cold Casualties.

OBJECTIVE: To compare the effectiveness of a single-layered polyethylene survival bag (P), a single-layered polyethylene survival bag with a hot drink (P+HD), a multi-layered metalized plastic sheeting survival bag (MPS: Blizzard Survival), and a multi-layered MPS survival bag with 4 large chemical heat pads (MPS+HP: Blizzard Heat) to treat cold casualties. METHODS: Portable cold casualty treatment methods were compared by examining core and skin temperature, metabolic heat production, and thermal comfort during a 3-hour, 0°C cold air exposure in 7 shivering, near-hypothermic men (35.4°C). The hot drink (70°C, ~400 ml, ~28 kJ) was consumed at 0, 1, and 2 hours during the cold air exposure. RESULTS: During the cold air exposure, core rewarming and thermal comfort were similar on all trials (P = .45 and P = .36, respectively). However, skin temperature was higher (10%-13%; P < .001; large effect sizes d > 2.7) and metabolic heat production lower (15%-39%; P < .05; large effect sizes d > .9) on MPS and MPS+HP than P and P+HD. The addition of heat pads further lowered metabolic heat production by 15% (MPS+HP vs MPS; P = .05; large effect size d = .9). The addition of the hot drink to polyethylene survival bag did not increase skin temperature or lower metabolic heat production. CONCLUSIONS: Near-hypothermic cold casualties are rewarmed with less peripheral cold stress and shivering thermogenesis using a multi-layered MPS survival bag compared with a polyethylene survival bag. Prehospital rewarming is further aided by large chemical heat pads but not by hot drinks.

Is this elderly patient dehydrated? Diagnostic accuracy of hydration assessment using physical signs, urine, and saliva markers.

OBJECTIVES: Dehydration in older adults contributes to increased morbidity and mortality during hospitalization. As such, early diagnosis of dehydration may improve patient outcome and reduce the burden on healthcare. This prospective study investigated the diagnostic accuracy of routinely used physical signs, and noninvasive markers of hydration in urine and saliva. DESIGN: Prospective diagnostic accuracy study. SETTING: Hospital acute medical care unit and emergency department. PARTICIPANTS: One hundred thirty older adults [59 males, 71 females, mean (standard deviation) age = 78 (9) years]. MEASUREMENTS: Participants with any primary diagnosis underwent a hydration assessment within 30 minutes of admittance to hospital. Hydration assessment comprised 7 physical signs of dehydration [tachycardia (>100 bpm), low systolic blood pressure (<100 mm Hg), dry mucous membrane, dry axilla, poor skin turgor, sunken eyes, and long capillary refill time (>2 seconds)], urine color, urine specific gravity, saliva flow rate, and saliva osmolality. Plasma osmolality and the blood urea nitrogen to creatinine ratio were assessed as reference standards of hydration with 21% of participants classified with water-loss dehydration (plasma osmolality >295 mOsm/kg), 19% classified with water-and-solute-loss dehydration (blood urea nitrogen to creatinine ratio >20), and 60% classified as euhydrated. RESULTS: All physical signs showed poor sensitivity (0%-44%) for detecting either form of dehydration, with only low systolic blood pressure demonstrating potential utility for aiding the diagnosis of water-and-solute-loss dehydration [diagnostic odds ratio (OR) = 14.7]. Neither urine color, urine specific gravity, nor saliva flow rate could discriminate hydration status (area under the receiver operating characteristic curve = 0.49-0.57, P > .05). In contrast, saliva osmolality demonstrated moderate diagnostic accuracy (area under the receiver operating characteristic curve = 0.76, P < .001) to distinguish both dehydration types (70% sensitivity, 68% specificity, OR = 5.0 (95% confidence interval 1.7-15.1) for water-loss dehydration, and 78% sensitivity, 72% specificity, OR = 8.9 (95% confidence interval 2.5-30.7) for water-and-solute-loss dehydration). CONCLUSIONS: With the exception of low systolic blood pressure, which could aid in the specific diagnosis of water-and-solute-loss dehydration, physical signs and urine markers show little utility to determine if an elderly patient is dehydrated. Saliva osmolality demonstrated superior diagnostic accuracy compared with physical signs and urine markers, and may have utility for the assessment of both water-loss and water-and-solute-loss dehydration in older individuals. It is particularly noteworthy that saliva osmolality was able to detect water-and-solute-loss dehydration, for which a measurement of plasma osmolality would have no diagnostic utility.

Physical activity energy expenditure and glucose control in pregnant women with type 1 diabetes: is 30 minutes of daily exercise enough?

OBJECTIVE: To describe activity patterns in pregnant women with type 1 diabetes and evaluate the impact of increased structured physical activity on glucose control. RESEARCH DESIGN AND METHODS: Physical activity energy expenditure (PAEE) and glucose levels (continuous glucose monitoring) were measured in 10 pregnant women with type 1 diabetes (age 33.2 years, gestation 20 weeks, BMI 27.9 kg/m(2), diabetes duration 16.6 years, HbA1c 6.5% [48 mmol/mol], insulin pump duration 2.4 years) during a day at home (free-living) and during a 24-h visit incorporating controlled diet and structured physical activity with light intensity activity (three 20-min self-paced walks) and moderate intensity activity (two 50-min sessions of brisk treadmill walking). PAEE was evaluated through individually calibrated combined heart rate and movement sensing. RESULTS: Free-living PAEE was comparable to that under controlled study conditions (3.8 and 5.1 kcal/kg/day, P = 0.241), with women achieving near to the recommended 30 min of moderate physical activity (median 27 min [interquartile range 14-68]). During the free-living period, more time was spent in light activity (10.3 vs. 7.2 h, P = 0.005), with less sedentary time (13.0 vs. 14.9 h, P = 0.047) and less moderate activity (27 vs. 121 min, P = 0.022). The free-living 24-h mean glucose levels by continuous glucose monitoring were significantly higher (7.7 vs. 6.0 mmol/L, P = 0.028). The effect of controlled diet and exercise persisted overnight, with significantly less time spent hyperglycemic (19 vs. 0%, P = 0.028) and less glucose variability (glucose SD 1.3 vs. 0.7 mmol/L, P = 0.022). CONCLUSIONS: A controlled diet and structured physical activity program may assist women with type 1 diabetes in achieving optimal glucose control during pregnancy.

Is whole-body hydration an important consideration in dry eye?

PURPOSE: To identify if whole-body hydration plays an important role in dry eye (DE). We hypothesized that individuals classified as DE have higher plasma osmolality (Posm), indicating suboptimal hydration, compared with those classified as non-DE. METHODS: Using a hospital-based observational cross-sectional design, assessment of DE and hydration was performed upon admission in 111 participants (N = 56 males and 55 females; mean ± SD age 77 ± 8 years). Assessments of DE included tear osmolarity (Tosm), the 5-item dry eye questionnaire (DEQ-5), rating of eye dryness using a visual analogue scale (VAS), and noninvasive tear film breakup time (NITBUT). Hydration assessment was performed by measuring Posm using freezing-point depression osmometry. RESULTS: Posm was higher in DE than control (CON), indicating suboptimal hydration when using the 316 mOsm/L Tosm cutoff for DE (mean Posm + 11 mOsm/kg versus CON, P = 0.004, Cohen's effect size [d]) = 0.83) and the more conservative Tosm classification for DE where Tosm >324 and CON <308 mOsm/L (mean Posm + 12 mOsm/kg versus CON, P = 0.006, d = 0.94). Posm was also higher in DE than CON when using composite DE assessments, including Tosm and DEQ-5 (P = 0.021, d = 1.07); Tosm and NITBUT (P = 0.013, d = 1.08); and the VAS and DEQ-5 (P = 0.034, d = 0.58). CONCLUSIONS: These are the first published data to show that individuals classified as DE have higher Posm, indicating suboptimal hydration, compared with non-DE. These findings indicate that whole-body hydration is an important consideration in DE.

Mitochondrial dysfunction in patients with primary congenital insulin resistance.

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes. It has thus been suggested that primary and/or genetic abnormalities in mitochondrial function may lead to accumulation of toxic lipid species in muscle and elsewhere, impairing insulin action on glucose metabolism. Alternatively, however, defects in insulin signaling may be primary events that result in mitochondrial dysfunction, or there may be a bidirectional relationship between these phenomena. To investigate this, we examined mitochondrial function in patients with genetic defects in insulin receptor (INSR) signaling. We found that phosphocreatine recovery after exercise, a measure of skeletal muscle mitochondrial function in vivo, was significantly slowed in patients with INSR mutations compared with that in healthy age-, fitness-, and BMI-matched controls. These findings suggest that defective insulin signaling may promote mitochondrial dysfunction. Furthermore, consistent with previous studies of mouse models of mitochondrial dysfunction, basal and sleeping metabolic rates were both significantly increased in genetically insulin-resistant patients, perhaps because mitochondrial dysfunction necessitates increased nutrient oxidation in order to maintain cellular energy levels.

Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia.

Resistance to thyroid hormone (RTH), a dominantly inherited disorder usually associated with mutations in thyroid hormone receptor beta (THRB), is characterized by elevated levels of circulating thyroid hormones (including thyroxine), failure of feedback suppression of thyrotropin, and variable tissue refractoriness to thyroid hormone action. Raised energy expenditure and hyperphagia are recognized features of hyperthyroidism, but the effects of comparable hyperthyroxinemia in RTH patients are unknown. Here, we show that resting energy expenditure (REE) was substantially increased in adults and children with THRB mutations. Energy intake in RTH subjects was increased by 40%, with marked hyperphagia particularly evident in children. Rates of muscle TCA cycle flux were increased by 75% in adults with RTH, whereas rates of ATP synthesis were unchanged, as determined by 13C/31P magnetic resonance spectroscopy. Mitochondrial coupling index between ATP synthesis and mitochondrial rates of oxidation (as estimated by the ratio of ATP synthesis to TCA cycle flux) was significantly decreased in RTH patients. These data demonstrate that basal mitochondrial substrate oxidation is increased and energy production in the form of ATP synthesis is decreased in the muscle of RTH patients and that resting oxidative phosphorylation is uncoupled in this disorder. Furthermore, these observations suggest that mitochondrial uncoupling in skeletal muscle is a major contributor to increased REE in patients with RTH, due to tissue selective retention of thyroid hormone receptor alpha sensitivity to elevated thyroid hormone levels.

Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC.

Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although rare, they are of considerable interest as they, like obesity, typically lead to ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this paper we describe a female patient with partial lipodystrophy (affecting limb, femorogluteal and subcutaneous abdominal fat), white adipocytes with multiloculated lipid droplets and insulin-resistant diabetes, who was found to be homozygous for a premature truncation mutation in the lipid droplet protein cell death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to increase the lipid droplet size in transfected cells. In mice, Cidec deficiency also reduces fat mass and induces the formation of white adipocytes with multilocular lipid droplets, but in contrast to our patient, Cidec null mice are protected against diet-induced obesity and insulin resistance. In addition to describing a novel autosomal recessive form of familial partial lipodystrophy, these observations also suggest that CIDEC is required for unilocular lipid droplet formation and optimal energy storage in human fat.

Complement abnormalities in acquired lipodystrophy revisited.

CONTEXT: Lipodystrophy is a heterogeneous condition characterized by an inherited or acquired deficiency in the number of adipocytes required for the storage of energy as triglycerides. Acquired lipodystrophy is frequently associated with other autoimmune disorders. One well-studied form is characterized by the selective loss of upper body fat in association with activation of the alternative complement pathway by C3 nephritic factor, low complement factor C3, and mesangiocapillary glomerulonephritis. OBJECTIVE: We now describe an immunologically distinct form of acquired generalized lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis. Patients and Research Design: Three unrelated patients with acquired lipodystrophy and low complement C4 levels are described. In vitro analysis of the complement pathway was undertaken to determine the reason for the low C4 complement levels. Biopsies were obtained from liver, bone marrow, and adipose tissue for histological analysis. RESULTS: All three patients manifested near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels. Additional autoimmune diseases, including severe hemolytic anemia, autoimmune thyroid disease, and polyneuropathy, were variably present. Detailed studies of complement pathways suggested constitutive classical pathway activation. CONCLUSIONS: Although the previously described syndrome, which typically results in a cephalad pattern of partial lipodystrophy, results from activation of the alternative complement pathway, this form, in which lipodystrophy is generalized, is associated with activation of the classical pathway. Future therapeutic approaches to these disorders may benefit from being tailored to their distinct immunopathogenesis.

Assessment of nutritional knowledge in female athletes susceptible to the Female Athlete Triad syndrome.

BACKGROUND: The study aimed to i) assess nutritional knowledge in female athletes susceptible to the Female Athlete Triad (FAT) syndrome and to compare with controls; and ii) to compare nutritional knowledge of those who were classified as being 'at risk' for developing FAT syndrome and those who are 'not at risk'. METHODS: In this study, participants completed General Nutritional Knowledge Questionnaire (GNKQ), the Eating Attitude Test (EAT-26) and survey measures of training/physical activity, menstrual and skeletal injury history. The sample consisted of 48 regional endurance athletes, 11 trampoline gymnasts and 32 untrained controls. Based on proxy measures for the FAT components, participants were classified being 'at risk' or 'not at risk' and nutrition knowledge scores were compared for the two groups. Formal education related to nutrition was considered. RESULTS: A considerably higher percentage of athletes were classified 'at risk' of menstrual dysfunction than controls (28.8% and 9.4%, respectively) and a higher percentage scored at or above the cutoff value of 20 on the EAT-26 test among athletes than controls (10.2% and 3.1%, respectively). 8.5% of athletes were classified 'at risk' for bone mineral density in contrast to none from the control group. Nutrition knowledge and eating attitude appeared to be independent for both athletes and controls. GNKQ scores of athletes were higher than controls but the differences between the knowledge of 'at risk' and 'not at risk' athletes and controls were inconsequential. Formal education in nutrition or closely related subjects does not have an influence on nutrition knowledge or on being classified as 'at risk' or 'not at risk'. CONCLUSION: The lack of difference in nutrition knowledge between 'at risk' and 'not at risk' athletes suggests that lack of information is not accountable for restricted eating associated with the Female Athlete Triad.