Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men

OBJECTIVE: To assess the effect of a possible interaction between dietary fat and physical inactivity on whole-body insulin sensitivity and intramyocellular lipids (IMCLs). RESEARCH DESIGN AND METHODS: Eight healthy male volunteers were studied on two occasions. After 2 days of an equilibrated diet and moderate physical activity, participants remained inactive (bed rest) for 60 h and consumed either a high-saturated fat (45% fat, of which approximately 60% was saturated fat [BR-HF]) or a high-carbohydrate (70% carbohydrate [BR-HCHO]) diet. To evaluate the effect of a high-fat diet alone, six of the eight volunteers were restudied after a 2-day equilibrated diet followed by 60 h on a high-saturated fat diet and controlled physical activity (PA-HF). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and IMCL concentrations by (1)H-magnetic resonance spectroscopy. RESULTS: Insulin-mediated glucose disposal was decreased by BR-HF condition (-24 +/- 6%, P < 0.05) but did not change with BR-HCHO (+19 +/- 10%, NS). BR-HF and BR-HCHO increased IMCL levels (+32 +/- 7%, P < 0.05 and +17 +/- 8%, P < 0.0011, respectively). Although the increase in IMCL levels with PA-HF (+31 +/- 19%, P = 0.12) was similar to that during BR-HF, insulin-mediated glucose disposal (-7 +/- 9%, NS) was not decreased. CONCLUSIONS: These data indicate that physical inactivity and a high-saturated fat diet may interact to reduce whole-body insulin sensitivity. IMCL content was influenced by dietary lipid and physical inactivity but was not directly associated with insulin resistance.

Clinical predictors of prophylaxis use prior to the onset of acute venous thromboembolism in hospitalized patients SWIss Venous ThromboEmbolism Registry (SWIVTER)

BACKGROUND: We investigated clinical predictors of appropriate prophylaxis prior to the onset of venous thromboembolism (VTE). METHODS: In 14 Swiss hospitals, 567 consecutive patients (306 medical, 261 surgical) with acute VTE and hospitalization < 30 days prior to the VTE event were enrolled. RESULTS: Prophylaxis was used in 329 (58%) patients within 30 days prior to the VTE event. Among the medical patients, 146 (48%) received prophylaxis, and among the surgical patients, 183 (70%) received prophylaxis (P < 0.001). The indication for prophylaxis was present in 262 (86%) medical patients and in 217 (83%) surgical patients. Among the patients with an indication for prophylaxis, 135 (52%) of the medical patients and 165 (76%) of the surgical patients received prophylaxis (P < 0.001). Admission to the intensive care unit [odds ratio (OR) 3.28, 95% confidence interval (CI) 1.94-5.57], recent surgery (OR 2.28, 95% CI 1.51-3.44), bed rest > 3 days (OR 2.12, 95% CI 1.45-3.09), obesity (OR 2.01, 95% CI 1.03-3.90), prior deep vein thrombosis (OR 1.71, 95% CI 1.31-2.24) and prior pulmonary embolism (OR 1.54, 95% CI 1.05-2.26) were independent predictors of prophylaxis. In contrast, cancer (OR 1.06, 95% CI 0.89-1.25), age (OR 0.99, 95% CI 0.98-1.01), acute heart failure (OR 1.13, 95% CI 0.79-1.63) and acute respiratory failure (OR 1.19, 95% CI 0.89-1.59) were not predictive of prophylaxis. CONCLUSIONS: Although an indication for prophylaxis was present in most patients who suffered acute VTE, almost half did not receive any form of prophylaxis. Future efforts should focus on the improvement of prophylaxis for hospitalized patients, particularly in patients with cancer, acute heart or respiratory failure, and in the elderly.

Effects of hibernation on bone in yellow-bellied marmots

Disuse osteoporosis is a problem for people with spinal cord injury or stroke, patients confined to bed rest, and astronauts exposed to microgravity. Unlike most mammals however, bears have been shown to prevent bone loss during hibernation, a seasonal period of disuse. Similarly, studies in ground squirrels indicate preservation of whole bone strength during hibernation, though evidence suggests there may be some increased osteocytic osteolysis. Uncovering the mechanism by which these animals prevent bone loss during hibernation could lead to an improved treatment for osteoporosis in humans. Marmots are a good animal model for these studies because they are small enough to easily house in an animal facility yet still utilize intracortical remodeling like humans and bears, and unlike smaller rodents like squirrels. Marmots preserve bone mechanical and microstructural properties during hibernation. Bone mechanical and geometrical properties are not diminished in post-hibernation samples compared to pre-hibernation samples. Mineral content, measured by ash fraction, was higher in post-hibernation samples (p = 0.0003). Haversian porosity as well as remodeling cavity density were not different (p > 0.38) between pre- and post-hibernation samples. Similarly, average lacunar area, lacunar density, and lacunar porosity were all lower (p < 0.0001) in post-hibernation samples. Trabecular thickness was larger in posthibernation samples (p = 0.0058). Bone volume fraction was not different between groups, but approached significance (p = 0.0725). Further studies in marmots and other hibernators could help uncover the mechanism that allows hibernators to prevent disuse osteoporosis during hibernation.

Exploration of the role of serum factors in maintaining bone mass during hibernation in black bears

Disuse osteoporosis is a condition in which reduced mechanical loading (e.g. bed-rest, immobilization, or paralysis) results in unbalanced bone turnover. The American black bear is a unique, naturally occurring model for the prevention of disuse osteoporosis. Bears remain mostly inactive for up to half a year of hibernation annually, yet they do not lose bone mechanical strength or structural properties throughout hibernation. The long-term goal of this study is to determine the biological mechanism through which bears maintain bone during hibernation. This mechanism could pinpoint new signaling pathway targets for the development of drugs for osteoporosis prevention. In this study, bone specific alkaline phosphatase (BSALP), a marker of osteoblast activity, and tartrate resistant acid phosphatase (TRACP), a marker of osteoclast number, were quantified in the serum of hibernating and active black bears. BSALP and TRACP decreased during hibernation, suggesting a balanced reduction in bone turnover. This decrease in BSALP and TRACP were correlated positively to serum adiponectin and inversely to serum neuropeptide Y, suggesting a possible role of these hormones in suppressing bone turnover during hibernation. Osteocalcin (OCN) and undercarboxylated OCN increased dramatically in the serum of hibernating bears. These increases were inversely correlated with adiponectin, glucose, and serotonin, suggesting that OCN may have a unique role in energy homeostasis during hibernation. Finally, MC3T3-E1 osteoblasts were cultured in the serum from active and hibernating bears, and seasonal cell responses were quantified. Cells cultured in serum from hibernating bears had a reduced caspase-3/7 response, and more living cells, after apoptotic threat. The caspase-3/7 response was positively correlated to serum adiponectin and to gene expression of OCN and Runx2, suggesting that reduced caspase-3/7 activity may be related to the reduced differentiation potential of osteoblasts in hibernation serum, and that adiponectin is a potential effector hormone. In summary, the activities of osteoblasts and osteoclasts are reduced during hibernation in bears. This reduced turnover is due, in part, to hormonal control. Further study of potential effectors adiponectin and neuropeptide Y may provide insight into the biological mechanism through which bears maintain bone throughout hibernation.

Modifying Post-Operative Medical Care after EBV Implant May Reduce Pneumothorax Incidence.

OBJECTIVE Endoscopic lung volume reduction (ELVR) with valves has been shown to improve COPD patients with severe emphysema. However, a major complication is pneumothoraces, occurring typically soon after valve implantation, with severe consequences if not managed promptly. Based on the knowledge that strain activity is related to a higher risk of pneumothoraces, we asked whether modifying post-operative medical care with the inclusion of strict short-term limitation of strain activity is associated with a lower incidence of pneumothorax. METHODS Seventy-two (72) emphysematous patients without collateral ventilation were treated with bronchial valves and included in the study. Thirty-two (32) patients received standard post-implantation medical management (Standard Medical Care (SMC)), and 40 patients received a modified medical care that included an additional bed rest for 48 hours and cough suppression, as needed (Modified Medical Care (MMC)). RESULTS The baseline characteristics were similar for the two groups, except there were more males in the SMC cohort. Overall, ten pneumothoraces occurred up to four days after ELVR, eight pneumothoraces in the SMC, and only two in the MMC cohorts (p=0.02). Complicated pneumothoraces and pneumothoraces after upper lobe treatment were significantly lower in MMC (p=0.02). Major clinical outcomes showed no significant differences between the two cohorts. CONCLUSIONS In conclusion, modifying post-operative medical care to include bed rest for 48 hours after ELVR and cough suppression, if needed, might reduce the incidence of pneumothoraces. Prospective randomized studies with larger numbers of well-matched patients are needed to confirm the data.

Comparação entre a técnica femoral com dispositivo de hemostasia e a técnica radial em pacientes submetidos à estratégia invasiva precoce

A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial.

A sulphonate based hydrogel for nucleus pulposus repair

Introduction: Lower back pain treatment and compensation costs >$80 billion overall in the US. 75% of back pain is due to disc degeneration in the lumbar region of the spine. Current treatment comprises of painkillers and bed rest or as a more radical solution – interbody cage fusion. In the early stages of disc degeneration the patient would benefit from addition of an injectable gel which polymerises in situ to support the degenerated nucleus pulposus. This involves a material which is an analogue of the natural tissue capable of restoring the biomechanical properties of the natural disc. The nucleus pulposus of the intervertebral disc is an example of a natural proteoglycan consisting of a protein core with negatively charged keratin and chondroitin sulphate attached. As a result of the high fixed charge density of the proteoglycan, the matrix exerts an osmotic swelling pressure drawing sufficient water into support the spinal system. Materials and Methods: NaAMPs (sodium 2- acrylamido 2-methyl propane sulphonic acid) and KSPA (potassium 3- sulphopropyl acrylate) were selected as monomers, the sulphonate group being used to mimic the natural sulphate group. These are used in dermal applications involving chronic wounds and have acceptably low cytotoxicity. Other hydrophilic carboxyl, amide and hydroxyl monomers such as 2-hydroxyethyl acrylamide, ß-carboxyethyl acrylate, acryloyl morpholine, and polyethylene glycol (meth)acrylate were used as diluents together with polyethyleneglycol di(meth)acrylate and hydrophilic multifunctional macromers as cross-linker. Redox was the chosen method of polymerisation and a range of initiators were investigated. Components were packaged in two solutions each containing a redox pair. A dual syringe method of injection into the cavity was used, the required time for polymerisation is circa 3-7 minutes. The final materials were tested using a Bohlin CVO Rheometer cycling from 0.5-25Hz at 37oC to measure the modulus. An in-house compression testing method was developed, using dialysis tubing to mimic the cavity, the gels were swelled in solutions of various osmolarity and compressed to ~ 20%. The pre-gel has also been injected into sheep spinal segments for mechanical compression testing to demonstrate the restoration of properties upon use of the gel. Results and Discussion: Two systems resulted using similar monomer compositions but different initiation and crosslinking agents. NaAMPs and KSPA were used together at a ratio of ~1:1 in both systems with 0.25-2% crosslinking agent, diacrylate or methacrylate. The two initiation systems were ascorbic acid/oxone, and N,N,N,N - tetramethylethylenediamine (TEMED)/ potassium persulphate. These systems produced gelation within 3-7 and 3-5 minutes respectively. Storage of the two component systems was shown to be stable for approximately one month after mixing, in the dark, refrigerated at 1-4oC. The gelation was carried out at 37oC. Literature values for the natural disc give elastic constants ranging from 3-8kPa. The properties of the polymer can be tailored by altering crosslink density and monomer composition and are able to match those of the natural disc. It is possible to incorporate a radio-opaque (histodenz) to enable x-ray luminescence during and after injection. At an inclusion level of 5% the gel is clearly visible and polymerisation and mechanical properties are not altered. Conclusion: A two-pac injection system which will polymerise in situ, that can incorporate a radio-opaque, has been developed. This will reinforce the damaged nucleus pulposus in degenerative disc disease restoring adequate hydration and thus biomechanical properties. Tests on sheep spine segments are currently being carried out to demonstrate that a disc containing the gel has similar properties to an intact disc in comparison to one with a damaged nucleus.

Lateral positioning for critically ill adult patients

BACKGROUND: Critically ill patients require regular body position changes to minimize the adverse effects of bed rest, inactivity and immobilization. However, uncertainty surrounds the effectiveness of lateral positioning for improving pulmonary gas exchange, aiding drainage of tracheobronchial secretions and preventing morbidity. In addition, it is unclear whether the perceived risk levied by respiratory and haemodynamic instability upon turning critically ill patients outweighs the respiratory benefits of side-to-side rotation. Thus, lack of certainty may contribute to variation in positioning practice and equivocal patient outcomes. OBJECTIVES: To evaluate effects of the lateral position compared with other body positions on patient outcomes (mortality, morbidity and clinical adverse events) in critically ill adult patients. (Clinical adverse events include hypoxaemia, hypotension, low oxygen delivery and global indicators of impaired tissue oxygenation.) We examined single use of the lateral position (i.e. on the right or left side) and repeat use of the lateral position (i.e. lateral positioning) within a positioning schedule. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1950 to 23 May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to 23 May 2015), the Allied and Complementary Medicine Database (AMED) (1984 to 23 May 2015), Latin American Caribbean Health Sciences Literature (LILACS) (1901 to 23 May 2015), Web of Science (1945 to 23 May 2015), Index to Theses in Great Britain and Ireland (1950 to 23 May 2015), Trove (2009 to 23 May 2015; previously Australasian Digital Theses Program (1997 to December 2008)) and Proquest Dissertations and Theses (2009 to 23 May 2015; previously Proquest Digital Dissertations (1980 to 23 May 2015)). We handsearched the reference lists of potentially relevant reports and two nursing journals. SELECTION CRITERIA: We included randomized and quasi-randomized trials examining effects of lateral positioning in critically ill adults. We included manual or automated turns but limited eligibility to studies that included duration of body position of 10 minutes or longer. We examined each lateral position versus at least one comparator (opposite lateral position and/or another body position) for single therapy effects, and the lateral positioning schedule (repeated lateral turning) versus other positioning schedules for repetitive therapy effects. DATA COLLECTION AND ANALYSIS: We pre-specified methods to be used for data collection, risk of bias assessment and analysis. Two independent review authors carried out each stage of selection and data extraction and settled differences in opinion by consensus, or by third party adjudication when disagreements remained unresolved. We planned analysis of pair-wise comparisons under composite time intervals with the aim of considering recommendations based on meta-analyses of studies with low risk of bias. MAIN RESULTS: We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. AUTHORS' CONCLUSIONS: Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients.

Protecting skeletal muscle with protein and amino acid during periods of disuse

Habitual sedentary behavior increases risk of chronic disease, hospitalization and poor quality of life. Short-term bed rest or disuse accelerates the loss of muscle mass, function, and glucose tolerance. Optimizing nutritional practices and protein intake may reduce the consequences of disuse by preserving metabolic homeostasis and muscle mass and function. Most modes of physical inactivity have the potential to negatively impact the health of older adults more than their younger counterparts. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis are negatively affected by disuse. This contributes to reduced muscle quality and is accompanied by impaired glucose regulation. Simply encouraging increased protein and/or energy consumption is a well-intentioned, but often impractical strategy to protect muscle health. Emerging evidence suggests that leucine supplemented meals may partially and temporarily protect skeletal muscle during disuse by preserving anabolism and mitigating reductions in mass, function and metabolic homeostasis.

Stability and mobility of sand-bed channels affected by seepage

Seepage effects on the stability, mobility, and incipient motion of sand-bed particles are experimentally investigated. Seepage through a sand bed in a downward direction (suction) reduces the stability of particles, and it can even initiate their movement. The bed erosion is increased with the increased rates of suction. Whereas the seepage in an upward direction (injection) increases the stability of bed particles, it does not aid initiating their movement. The rate of bed erosion is reduced or even stopped by the increased infection rates. Hydrodynamic conditions leading to the so-called "pseudoincipient motion'' with suction (for the initiation of particles movement that are otherwise at rest under no-seepage conditions), and with injection (for only arresting the particles movement that are otherwise moving initially) are evaluated. The conventional Shields curve cannot be used to predict such pseudoincipient motion conditions with seepage. The concepts thus developed are useful for a better understanding of the sediment transport mechanics and in the design of stable alluvial channels affected by seepage.

Quality of natural coffee subjected to different rest periods during the drying process

O parcelamento da secagem pode ser eficiente tanto no que diz respeito à qualidade final do café, quanto na redução do consumo específico de energia. Diante disso, objetivou-se, com o presente trabalho, avaliar o efeito do teor de água dos frutos no momento da interrupção da secagem e do período de repouso até a retomada da secagem na qualidade do café natural, por meio da análise sensorial e dos testes de condutividade elétrica e lixiviação de potássio. Frutos de café maduros foram colhidos manual e seletivamente e, em seguida, secados ao sol em terreiros de concreto por dois dias e, então, submetidos à secagem mecânica em secadores de camada fixa. Quando o café atingiu os teores de água de 20%, 17% e 14% (base úmida, bu), a secagem foi interrompida e o café permaneceu em repouso por cinco, quinze e trinta dias e, posteriormente, foi secado em secadores mecânicos até o teor de água de 11% (bu). O controle constituiu-se na secagem completa em terreiro. Observou-se que as combinações entre o menor teor de água e o maior período de repouso e entre o maior teor de água e o menor período de repouso, proporcionam menores valores de lixiviação de potássio. A qualidade da bebida melhora progressivamente com o aumento do período de repouso. A interrupção da secagem com teores de água de 17% e 20% (bu) não altera a qualidade do café natural, comparativamente à secagem completa em terreiro.

Mechanisms in the bed nucleus of the stria terminalis involved in control of autonomic and neuroendocrine functions: A review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of the bed nucleus of the stria terminalis in cardiovascular changes following chronic treatment with cocaine and testosterone: A role beyond drug seeking in addiction?

Neural plasticity has been observed in the bed nucleus of the stria terminalis (BNST) following exposure to both cocaine and androgenic-anabolic steroids. Here we investigated the involvement of the BNST on changes in cardiovascular function and baroreflex activity following either single or combined administration of cocaine and testosterone for 10 consecutive days in rats. Single administration of testosterone increased values of arterial pressure, evoked rest bradycardia and reduced baroreflex-mediated bradycardia. These effects of testosterone were not affected by BNST inactivation caused by local bilateral microinjections of the nonselective synaptic blocker CoCl2. The single administration of cocaine as well as the combined treatment with testosterone and cocaine increased both bradycardiac and tachycardiac responses of the baroreflex. Cocaine-evoked baroreflex changes were totally reversed after BNST inactivation. However, BNST inhibition in animals subjected to combined treatment with cocaine and testosterone reversed only the increase in reflex tachycardia, whereas facilitation of reflex bradycardia was not affected by local BNST treatment with CoCl2. In conclusion, the present study provides the first direct evidence that the BNST play a role in cardiovascular changes associated with drug abuse. Our findings suggest that alterations in cardiovascular function following subchronic exposure to cocaine are mediated by neural plasticity in the BNST. The single treatment with cocaine and the combined administration of testosterone and cocaine had similar effects on baroreflex activity, however the association with testosterone inhibited cocaine-induced changes in the BNST control of reflex bradycardia. Testosterone-induced cardiovascular changes seem to be independent of the BNST. © 2013 IBRO.