Myonuclear alterations associated with exercise are independent of age in humans.

Age-related decline in skeletal muscle structure and function can be mitigated by regular exercise. However, the precise mechanisms that govern this are not fully understood. The nucleus plays an active role in translating forces into biochemical signals (mechanotransduction), with the nuclear lamina protein lamin A regulating nuclear shape, nuclear mechanics and ultimately gene expression. Defective lamin A expression causes muscle pathologies and premature ageing syndromes, but the roles of nuclear structure and function in physiological ageing and in exercise adaptations remain obscure. Here, we isolated single muscle fibres and carried out detailed morphological and functional analyses on myonuclei from young and older exercise-trained individuals. Strikingly, myonuclei from trained individuals were more spherical, less deformable, and contained a thicker nuclear lamina than those from untrained individuals. Complementary to this, exercise resulted in increased levels of lamin A and increased myonuclear stiffness in mice. We conclude that exercise is associated with myonuclear remodelling, independently of age, which may contribute to the preservative effects of exercise on muscle function throughout the lifespan. KEY POINTS: The nucleus plays an active role in translating forces into biochemical signals. Myonuclear aberrations in a group of muscular dystrophies called laminopathies suggest that the shape and mechanical properties of myonuclei are important for maintaining muscle function. Here, striking differences are presented in myonuclear shape and mechanics associated with exercise, in both young and old humans. Myonuclei from trained individuals were more spherical, less deformable and contained a thicker nuclear lamina than untrained individuals. It is concluded that exercise is associated with age-independent myonuclear remodelling, which may help to maintain muscle function throughout the lifespan.

Cardiorespiratory fitness not sedentary time or physical activity is associated with cardiometabolic risk in active older adults.

Sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) are associated with cardiometabolic health. Cardiorespiratory fitness (CRF) is also implicated but often overlooked in health recommendations. This study assessed the relationships between ST, MVPA, CRF, and cardiometabolic health in highly active older individuals. 125 healthy amateur cyclists aged 55 to 79 years had their ST and MVPA levels assessed by actigraphy over a 7-day period. CRF was assessed using a maximal effort cycle ergometry test to determine VO2max with results normalized to both body mass and fat-free mass measured by DXA. Markers of cardiometabolic risk (blood glucose, triglycerides, cholesterol, HDL, LDL, Insulin, HOMA IR, blood pressure, and body fat) were assessed and used to determine cumulative cardiometabolic risk. Multiple linear regression was used to assess ST, MVPA, and CRF associations with cardiometabolic health with the relationship between activity levels and CRF determined. CRF was associated with training volume (P = .003), but not ST or MVPA. A high CRF was associated with lower cumulative cardiometabolic risk, body fat percentage, triglyceride, and HDL levels (P < .05 in all cases). MVPA was negatively associated with body fat percentage, while ST was not associated with any marker of cardiometabolic risk when adjusting for activity levels. An association between CRF and cardiometabolic risk even in a group of older individuals with high fitness levels highlights the importance that CRF may have in maintaining health.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

In vitro study of enhanced photodynamic cancer cell killing effect by nanometer-thick gold nanosheets.

Photodynamic therapy (PDT) by near-infrared (NIR) irradiation is a promising technique for treating various cancers. Here, we reported the development of free-standing wafer-scale Au nanosheets (NSs) that exhibited an impressive PDT effect. The Au NSs were synthesized by ionic layer epitaxy at the air-water interface with a uniform thickness in the range from 2 to 8.5 nm. These Au NSs were found very effective in generating singlet oxygen under NIR irradiation. In vitro cellular study showed that the Au NSs had very low cytotoxicity and high PDT efficiency due to their uniform 2D morphology. Au NSs could kill cancer cells after 5 min NIR irradiation with little heat generation. This performance is comparable to using 10 times mass loading of Au nanoparticles (NPs). This work suggests that two-dimensional (2D) Au NSs could be a new type of biocompatible nanomaterial for PDT of cancer with an extraordinary photon conversion and cancer cell killing efficiency.

Enhanced Ferromagnetism from Organic-Cerium Oxide Hybrid Ultrathin Nanosheets.

Room-temperature ferromagnetism in two-dimensional (2D) oxide materials is an intriguing phenomenon for spintronic applications. Here, we report significantly enhanced room-temperature ferromagnetism observed from ultrathin cerium oxide nanosheets hybridized with organic surfactant molecules. The hybrid nanosheets were synthesized by ionic layer epitaxy over a large area at the water-air interface. The nanosheets exhibited a saturation magnetization of 0.149 emu/g as their thickness reduced to 0.67 nm. This value was 5 times higher than that for CeO2 thin films and more than 20 times higher than that for CeO2 nanoparticles. The magnetization was attributed to the high concentration (15.5%) of oxygen vacancies stabilized by surfactant hybridization as well as electron transfer between organic and oxide layers. This work brings an effective strategy of introducing strong ferromagnetism to functional oxide materials, which leads to a promising route toward exploring new physical properties in 2D hybrid nanomaterials.

Synthesis and release of proinsulin and insulin by isolated rat islets of Langerhans.

Isolated rat islets of Langerhans were incubated for 60, 120, and 180 min and the incorporation of leucine-(3)H into proinsulin and insulin moieties was followed. Synthesis and release of these hormones could be followed by separate extractions of islets and incubation media. RELEASE OF NEWLY SYNTHESIZED PROINSULIN AND INSULIN OCCURRED UNDER THE FOLLOWING CONDITIONS: (a) incubation for greater than 60 min; (b) glucose concentrations above 5.3 mmoles/liter; (c) incubation with 5 mM dibutyryl cyclic AMP or theophylline in 5.3 mM glucose (potentiated by 16 mM glucose); and (d) incubation with 5 mM tolbutamide and 16 mM glucose. Synthesis of proinsulin and insulin was enhanced by time of incubation, high glucose concentrations, by dibutyryl cyclic AMP or theophylline, and by tolbutamide only at 16 mM glucose. Synthesis was totally inhibited by tolbutamide at 5.3 mM glucose.

Studies on the biological activity of porcine proinsulin.

The biological activity of purified porcine proinsulin was investigated in rats. In vivo studies revealed that proinsulin produced a hypoglycemic response similar to insulin but of lesser magnitude. Hypophysectomized and adrenalectomized animals proved to be more sensitive to proinsulin than normal. In vitro studies with rat hemidiaphragm were consistent with the in vivo findings. No competition with insulin action could be demonstrated. Experiments were carried out to determine whether proinsulin is converted to intermediate forms or insulin as a requisite to its biological activity. Labeled proinsulin injected in vivo or incubated in vitro remained intact by a variety of techniques (Sephadex column chromatography and polyacrylamide-gel electrophoresis). An inhibitory action of Kunitz pancreatic trypsin inhibitor on proinsulin action in vitro was confirmed. No clarification of this effect could be ascertained.

Active GSK3ß and an intact ß-catenin TCF complex are essential for the differentiation of human myogenic progenitor cells.

Wnt-ß-catenin signalling is essential for skeletal muscle myogenesis during development, but its role in adult human skeletal muscle remains unknown. Here we have used human primary CD56Pos satellite cell-derived myogenic progenitors obtained from healthy individuals to study the role of Wnt-ß-catenin signalling in myogenic differentiation. We show that dephosphorylated ß-catenin (active-ß-catenin), the central effector of the canonical Wnt cascade, is strongly upregulated at the onset of differentiation and undergoes nuclear translocation as differentiation progresses. To establish the role of Wnt signalling in regulating the differentiation process we manipulated key nodes of this pathway through a series of ß-catenin gain-of-function (GSK3 inhibition and ß-catenin overexpression) or loss-of-function experiments (dominant negative TCF4). Our data showed that manipulation of these critical pathway components led to varying degrees of disruption to the normal differentiation phenotype indicating the importance of Wnt signalling in regulating this process. We reveal an independent necessity for active-ß-catenin in the fusion and differentiation of human myogenic progenitors and that dominant negative inhibition of TCF4 prevents differentiation completely. Together these data add new mechanistic insights into both Wnt signalling and adult human myogenic progenitor differentiation.

Simultaneous Enhancement of Charge Separation and Hole Transportation in a TiO2 -SrTiO3 Core-Shell Nanowire Photoelectrochemical System.

Efficient charge separation and transportation are key factors that determine the photoelectrochemical (PEC) water-splitting efficiency. Here, a simultaneous enhancement of charge separation and hole transportation on the basis of ferroelectric polarization in TiO2 -SrTiO3 core-shell nanowires (NWs) is reported. The SrTiO3 shell with controllable thicknesses generates a considerable spontaneous polarization, which effectively tunes the electrical band bending of TiO2 . Combined with its intrinsically high charge mobility, the ferroelectric SrTiO3 thin shell significantly improves the charge-separation efficiency (ηseparation ) with minimized influence on the hole-migration property of TiO2 photoelectrodes, leading to a drastically increased photocurrent density ( Jph ). Specifically, the 10 nm-thick SrTiO3 shell yields the highest Jph and ηseparation of 1.43 mA cm-2 and 87.7% at 1.23 V versus reversible hydrogen electrode, respectively, corresponding to 83% and 79% improvements compared with those of pristine TiO2 NWs. The PEC performance can be further manipulated by thermal treatment, and the control of SrTiO3 film thicknesses and electric poling directions. This work suggests a material with combined ferroelectric and semiconducting features could be a promising solution for advancing PEC systems by concurrently promoting the charge-separation and hole-transportation properties.

Determinants of condom use among junior high school students in a minority, inner-city school district.

Condoms reduce the risk of human immunodeficiency virus (HIV) transmission; however, their use among adolescents has been inconsistent. Little is known about factors which motivate consistent condom use, particularly among younger adolescents. In a study designed to identify such factors, 1899 inner-city junior high school students were surveyed. In June 1988, students completed an anonymous self-report questionnaire assessing HIV-related knowledge, attitudes, and behaviors. Among sexually active students (N = 403), logistic regression analysis evaluated the influence of demographic, psychosocial, and behavioral factors on frequency of condom use. Respondents who believe condoms are effective in preventing HIV transmission were 2.2 times more likely to report using condoms consistently during sexual intercourse; those with low perceived costs associated with condom use were 1.9 times more likely to be consistent users. Number of lifetime sexual partners was inversely related to frequency of condom use. Respondents with a history of three or more sex partners were half as likely to use condoms consistently. Factors not associated with consistent condom use include age, age at sexual debut, ethnicity, HIV knowledge, perceived efficacy to avoid HIV infection, and alcohol and drug use. School- and community-based HIV prevention programs will have to go beyond the didactic transfer of factual information and include more interactive teaching strategies to improve adolescents' attitudes toward condoms are self-efficacy to increase condom use and to counter negative peer influences and adolescents' perceptions of invulnerability. Physicians are an underutilized source of HIV prevention information. They have an important role in counseling adolescents about effective HIV-prevention methods and dispelling misperceptions which hinder consistent condom use.

Psychosocial factors in the natural history of physical activity.

We studied the association between demographic, socioeconomic, and psychosocial factors and change in level of physical activity in 4,025 persons who were interviewed in 1965 and 1974 as part of the Alameda County study. Relative declines in physical activity were found to be associated with education level (less than a college education), race (being black or non-white [women]), low income, blue-collar occupation, unmarried status, group non-membership, social isolation, depression, personal uncertainty (women), low life satisfaction, and health perceived less than "excellent." These results demonstrate the multifactorial determination of level of physical activity.

Smoking and body mass in the natural history of physical activity: prospective evidence from the Alameda County Study, 1965-1974.

The prospective effects of smoking status and body mass on change in leisure-time physical activity from 1965 to 1974 were examined in a cohort of 4,622 persons 20-94 years of age from the Alameda County Study. With adjustment for age and baseline physical activity, current smokers showed a greater nine-year decline in leisure-time physical activity than those who had never smoked. The coefficient for current smokers from a multivariate linear regression model was of a similar magnitude among women and men (coefficient = -0.27, 95% confidence interval [CI] = -0.50 to -0.05 for women; coefficient = -0.26, 95% CI = -0.54 to 0.02 for men). Larger declines in physical activity were seen with increasing number of current pack-years exposure among both women and men. Compared with women of average body mass index, women of heaviest body mass index had larger declines (coefficient = -0.70, 95% CI = -1.04 to -0.36) while women of the lightest body mass index had larger increases (or smaller declines) in physical activity (coefficient = 0.33, 95% CI = 0.00 to 0.66). Although body mass index did not initially appear to be associated with a change in physical activity among men, age-specific analyses indicated that the effect of body mass index on physical activity varied with age such that younger (20-39 years of age), thinner men increased their activity, while older (60 years of age and over), thinner men decreased their physical activity more than men of the same age with average body mass index.

The metabolism of 125I-labelled insulin by isolated Zucker rat hepatocytes.

The metabolism of 125I-labelled insulin by hepatocytes isolated from 48-h-starved Zucker lean and obese rats was studied. Hepatocytes from the lean animals bound significantly more 125I-labelled insulin and had a greater receptor number per cell than did cells from obese littermates. Hepatocytes from the lean animals degraded and internalized more hormone than did those from obese ones. Increased degradation and internalization correlated with the increased receptor number.

Factors associated with multiple sex partners among junior high school students.

Twenty-one percent of a sample of inner-city junior high school students were found to be sexually active (n = 403). Only 31% of them reported a single lifetime sexual partner, 25% reported two partners, and 43% reported three or more partners. Logistic regression analysis evaluated the influence of demographic, psychosocial, and behavioral factors on the adolescents' lifetime number of sex partners. Respondents whose sexual debut occurred before age 13 years were nine times more likely to report three or more sex partners compared with those whose first sexual intercourse was at age 15 or 16 years, blacks were four times more likely than non-Hispanic whites to report three or more sex partners; and males were four times as likely as females to report this number of sexual partners. Factors not independently associated with the number of sex partners included: age, Asian or Hispanic ethnicity, human immunodeficiency virus (HIV) knowledge, self-efficacy (belief that one can protect oneself from the virus), condom use, and alcohol and drug use. We conclude that a significant proportion of school-based middle adolescents are sexually active and that most of these are at risk for contracting HIV because of behaviors such as having multiple sexual partners. Topics often stressed in school-based HIV education, such as factual knowledge about HIV, avoiding drugs and alcohol, and condom use are not associated with adolescents' choice about their number of sex partners. Intervention programs will have to identify and then target each specific HIV risk behavior and its motivations in order to reduce adolescents' risks of contracting and transmitting the disease.

Population heterogeneity and its impact on the risk management of food safety.

Successful risk management of possible toxicological effects of chemicals in food, including novel foods, requires diverse strategies. This paper concentrates on the advisability of introducing post marketing surveillance as a key stratagem in the risk management of selected foods and food chemicals. It is argued that this stratagem is particularly applicable to those occasions when the population at risk is relatively easily identified. A key element therefore in the successful use of post marketing surveillance in selected foods, requires those agencies responsible for risk management to introduce a more thorough analysis of population heterogeneity into their strategies.

AIDS knowledge, attitudes, and behavior among inner city, junior high school students.

To gain information about AIDS knowledge, attitudes, and behavior of junior high school students, 1,967 students in three junior high schools in an inner city school district were surveyed. Ages of the participants ranged from 11-16 years, and 48% were male. Ethnically, 33% were Asian, 31% African-American, 24% Latino, and 5% white. African-American students had greater AIDS general knowledge than Asians and similar general knowledge to Latinos and whites. Most students wanted to be taught about AIDS in school. Misconceptions about casual contagion of AIDS were common. Students with these misconceptions were more likely to believe that students with AIDS should not be allowed to attend school. A high proportion of students had engaged in high-risk behavior including sexual intercourse, drinking alcoholic beverages, and using street drugs. More boys than girls reported each of these activities. Of individuals having had sexual intercourse, a positive association was found between the belief that condoms are effective in preventing HIV infection and use of condoms. These findings support the possibility that improving knowledge about HIV transmission would result in more tolerance toward students with HIV infection and would result in less high-risk behavior.

PIP: In June 1988, researchers analyzed data from 1235-1882 questionnaires concerning AIDS knowledge, attitudes, and behavior among inner city, junior high school students [90% ethnic minorities, especially Blacks (61%)] in San Francisco, California to get baseline data so educators could design relevant AIDS prevention programs geared toward minorities. Asians knew less about AIDS than Blacks (p.001), Latinos (p.001), and Whites (p.001). Most students knew what activities were high risk for acquiring HIV, but up to 50% often thought HIV could also be transmitted via casual contact. The students who had such beliefs were more likely to believe that students with AIDS should not be allowed to come to school (p.001-.05). Boys (42%) were more likely to have had sexual intercourse than girls (18%; p.001). Further they tended to use street drugs more (11% vs. 5%; p.001). More Blacks claimed to have sexual intercourse than Latinos (p.001), Asians (p.001), or Whites (p.01). On the other hand, whites reported significantly higher drug use than Blacks (p.001), Asians (p.001), and Latinos (p.01). More boys believed condoms hindered pleasure than girls regardless of level of sexual activity. 25% of the boys found it difficult to find places that sells condoms compared to 18% of girls (p.01). 59% of all students, especially girls (p.001), said that their often was disagreement about using condoms or not with their sex partners. Sexually active students who believed condoms prevent transition of HIV (80%) used them more often than those who believed they work a little (47%; p.01). 89% wanted AIDS education in school, especially those who believed it unlikely or not possible to contract AIDS from casual contact (p.001). In conclusion, AIDS education course designers should consider anxiety about peer pressure and sexual matters since anxiety could hinder acquiring and retaining information about AIDS prevention thereby preventing adolescents from planning for the consequences of sexual contact and drug use.

Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease.

OBJECTIVE: To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN: Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING: Population based study of adult residents of Alameda County, California. SUBJECTS: 2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES: Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974-84. RESULTS: There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION: Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers.

Gastroduodenal intussusception of a stromal gastric tumour.

An elderly patient presented with intermittent vomiting. The cause was a gastric tumour causing gastroduodenal intussusception. On excision and histological examination this was found to be a stromal tumour of uncertain malignant potential ('STUMP').