Intramuscular fat and inflammation differ in older adults: the impact of frailty and inactivity.

OBJECTIVES: Intramuscular adipose tissue (IMAT) is recognized as a negative predictor of both muscle and mobility function in older adults, however the mechanism by which IMAT may negatively influence muscle and mobility function is currently unknown. The release of pro-inflammatory cytokines from IMAT provides a potential reason for these negative associations. To explore this hypothesis we compared IMAT and muscular inflammation in age-and BMI-matched older non-obese frail and non-frail adults. We also sought to examine the relationship between IMAT and inflammation, and muscle and mobility function in this group of older adults. DESIGN: A case-control sampling was used for this study. Age-and BMI-matched non-obese frail and non-frail individuals (<65 years) were recruited. MEASUREMENTS: MRI was used to quantify thigh IMAT and lean tissue. Unilateral muscle biopsies were used to quantify muscular inflammation as represented by interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α). Muscle and mobility function was also measured using a maximal voluntary isometric contraction, six-minute walk, and self-selected gait speed. PARTICIPANTS: 26 older (80.7 +/- 5.4 years) individuals (8 frail and 18 non-frail) were enrolled. RESULTS: The frail-group had increased IMAT (p<0.01) and decreased lean tissue (p<0.01), and elevated IL-6 muscle mRNA (p=0.02) and IL-6 protein content (p=0.02) compared to the non-frail group. IMAT was significantly associated with IL-6 mRNA (r=0.43, p=.04) and protein expression within the muscle (r=0.41, p= 0.045). IL-6 mRNA was significantly associated with six-minute walk (r=-0.63, p<0.01), and gait speed (r=-0.60, p <0.01) and IL-6 protein was significantly associated with muscle force (r=-0.54, p=0.01), six-minute walk (r=-0.66, p<0.01), and gait speed (r=-0.76, p<0.01). No significant relationships were found for any variables with TNF-a. CONCLUSION: Non-obese, older, frail individuals have increased IMAT and muscular inflammation when compared to their non-frail, age- and BMI-matched peers. A significant relationship exists between IMAT and muscle IL-6 expression as well as between IL-6 and muscle and mobility function of these older adults. This IMAT-inflammatory pathway provides a potential link between IMATs and decreased muscle and mobility function.

Regional muscle glucose uptake remains elevated one week after cessation of resistance training independent of altered insulin sensitivity response in older adults with type 2 diabetes.

BACKGROUND: Aging is associated with a decline in skeletal muscle size.Muscle is critical both for mobility and glucose disposal. While resistance exercise (RE) increases muscle mass and function in the elderly, its role in improving glucose utilization is less clear. AIMS: To investigate whether muscle size was linked with insulin sensitivity (IS) in elders with diabetes following RE and if regional muscle glucose uptake differed from systemic glucose utilization. METHODS: Seven (68.4 ± 5.9 yr) adults with diabetes participated. After 16 weeks of RE, within 24 h (post 1) and after 1 week of no exercise (post 2), lean tissue cross-sectional area (CSA) and IS via glucose infusion rate (GIR) were assessed along with a standardized 18-F fluorodeoxyglucose (FDG)-positron emission tomography uptake value (SUV). RESULTS: CSA increased between pre-test (108.5 ± 35.3 cm2) and post 1 (116.8 ± 40.9 cm2), p=0.02 and did not differ at post 2 (116.0 ± 39.3 cm2). GIR during the 40 mU/m2/min insulin clamp differed between pretest (22.0 ± 15.8 mg/kg/min) and post 1 (67.9 ± 72.8 mg/kg/min), and post 1 and post 2 (25.0 ± 27.2 mg/kg/min) but not between pre-test and post 2. GIR results during the 200 mU/m2/min insulin clamps also differed between pre-test and post 1, and post 1 and post 2 but not between pre-test and post 2. FDG-SUV increased between pre-test (1.1 ± 0.2) and post 1 (1.4 ± 0.3), and remained stable between post 1 and post 2 (1.4 ± 0.4). CONCLUSION: RE that increased muscle size and FDG-SUV improved IS 24 h but not 1 week after exercise training.

From primary photochemistry to biological function in the blue-light photoreceptors PYP and AppA.

To properly respond to changes in fluency conditions, Nature has developed a variety of photosensors that modulate gene expression, enzyme activity and/or motility. Dedicated types have evolved, which can be classified in six families: rhodopsins, phytochromes, xanthopsins, cryptochromes, phototropins and BLUF-proteins. The photochemistry of the first three families is based on cis/trans isomerization of an ethylene bond. Surprisingly, the latter three all use flavin as their chromophore, but each with very different photochemistry. In this contribution we will discuss the molecular basis of signal generation in a xanthopsin (Photoactive Yellow Protein (PYP) from Halorhodospira halophila), a photoreceptor for negative phototaxis, and in a BLUF protein (AppA from Rhodobacter sphaeroides), a transcriptional anti-repressor. PYP is activated through trans/cis isomerization of the 7,8-vinyl bond of its 4-hydroxycinnamic acid chromophore. This initiates a photocycle with multiple intermediates, like pB, which is formed after intramolecular proton transfer. The negative charge thus formed in the interior of the protein triggers formation of a partially unfolded signaling state. For AppA much less is known about the underlying photochemistry. Available evidence suggests that it is based on a light-induced change in the hydrogen-bonding of its flavin chromophore and/or a change in hydrophobic stacking between the flavin and/or nearby aromatic amino acids like Y 21. A signaling state is formed within microseconds, which recovers with a rate of approximately 10(-3) s(-1). The change in conformation between receptor- and signaling-state in AppA, however, appear to be minute as compared to those in PYP. Here we review the underlying chemistry in the various steps of the photocycle of these two photoreceptor proteins and provide new data on their mechanism and function.

Care provider assessment of intrathecal baclofen in children.

Intrathecal baclofen is used increasingly to manage severe spasticity in children. Before implanting the baclofen pump, care providers typically ask how it will benefit their child. The purpose of this study was to describe the perceptions of care providers about intrathecal baclofen for management of spasticity in 80 individuals (52 males, 28 females). The individuals were younger than 22 years at the time of implantation (mean age 11 years, SD 5 years; range 3 to 21 years). Participants had been implanted with the pump for a minimum of one year at the time of evaluation. The most common diagnoses were quadriplegic and diplegic cerebral palsy and traumatic brain injury. Most participants were at level IV and V on the Gross Motor Function Classification System. After pump implantation most participants had tone reduction on the Ashworth scale of 1 to 1.9 in the lower extremities and 0 to 0.9 in the upper extremities. Lower extremity range of motion was maintained in 43 of 51 individuals (84%) and lost in 8 participants (16%). Complications requiring surgery occurred in 63 of a larger group of 152 patients (incidence per patient-year of follow-up was 0.19). Thirty-one of the 80 children had orthopedic procedures after pump placement. Only one of these was unexpected and none had rapid progression of scoliosis. Most treatment goals were achieved. Goals most commonly chosen (decreased pain, prevention of worsening of deformity, and improved ease of care) were improved in 91%, 91%, and 88% of participants respectively. Ninety-five per cent of care providers agreed that they would have this procedure performed again (81% strongly agreed, 14% slightly agreed). All care providers reported improvement in scores on the Caregiver Questionnaire. This information has been helpful to families considering intrathecal baclofen therapy.

[Prevention of skin cancer. Necessity, implementation and success]. / Prävention von HautkrebsNotwendigkeit, Durchführung und Erfolg.

Including malignant melanoma, basal cell carcinoma, and squamous cell carcinoma, skin cancer is the cancer with the highest incidence worldwide. Its incidence is increasing more rapidly than that of all other kinds of cancer. It is necessary to slow down this trend through preventive steps in order to reduce morbidity and mortality rates and to decrease the financial burden on the health systems. This goal could be achieved through primary (prevention of risk factors) and secondary prevention (early diagnosis and screening). This essay describes the necessity, realization, and success of these kinds of intervention programs. It especially portrays the procedures in Germany as they have been practiced for the last 15 years by the Society of Dermatology Prevention and German Cancer Aid.

Complications of intrathecal baclofen pumps in children.

Intrathecal baclofen is increasingly being used to manage severe spasticity in children. Although substantial tone reduction with this treatment has been documented, complications also occur. In this study, we describe the device- and major non-device-related complications in a group of 100 consecutive children and young adults who received 117 intrathecal baclofen pumps for the management of severe spasticity. Twenty-four patients (24%) experienced a total of 48 complications. The most common complication was disconnection of the catheter at its connection to the pump, occurring in 9% of pumps implanted. This complication occurred more frequently in pumps with catheter access ports (16%) than in those without ports (2%). Catheter dislodgement from the intrathecal space was the next most common complication, occurring in 8% of pumps implanted (13% of pumps with ports, 4% of pumps without ports). To decrease the occurrence of the most common complications of intrathecal pumps, we now typically implant pumps without catheter access ports, and we use 2-piece catheters. Although the lack of an access port may be a disadvantage for troubleshooting, most complications can be detected in pumps without a port. Patient and family education is critical in preventing serious consequences of baclofen withdrawal resulting from catheter-related complications.

[Public opinion on active euthanasia. The results of a pilot project]. / Das öffentliche Meinungsbild zur aktiven Sterbehilfe. Ergebnisse eines Pilotprojekts.

BACKGROUND AND OBJECTIVE: Despite eager public interest there have been few significant studies about the views of the German population on active euthanasia. It was our purpose to investigate, before undertaking a representative enquiry about this controversial and ethically sensitive topic, to what extent public opinion and the underlying norms, values and preferences can be adequately obtained by standardized data collection. COHORT AND METHODS: An interdisciplinary project group established a standardized written form of enquiry for measuring public opinion about active euthanasia. The test was performed on an anonymized convenience [corrected] sample of 110 persons living in North Germany. The questionnaires consisted of ten hypothetical cases, 11 potentially relevant viewpoints on likely decisions and eight frequently expressed arguments used in the debate for and against euthanasia. RESULTS: The reply rate to the questionnaire was 89% (n = 98; 37 men and 59 women, average age 39.5 [21-81] years). Agreement with active euthanasia in the various case examples ranged, according to context, from 85 to 93%. Active euthanasia was accepted by a clear majority, if preconditions of a voluntary decision by a mentally sound person and incurable, terminal disease (cancer) are cumulatively fulfilled. Otherwise it was rejected by most respondents. To a clear majority, active euthanasia implied both the chance that suffering would be shortened, but also the danger of misuse. Among the persons questioned those with professional experience of euthanasia were clearly more sceptical about active euthanasia than those without such experience. CONCLUSIONS: The standardized written questionnaire made it possible to obtain a differentiated picture of public opinion on active euthanasia. However, these data represent only a moment in the dynamic process of a norm being established within a society and must on no account be used as legitimizing active euthanasia by plebiscite.