Helping in humans and other animals: a fruitful interdisciplinary dialogue.

Humans are arguably unique in the extent and scale of cooperation with unrelated individuals. While pairwise interactions among non-relatives occur in some non-human species, there is scant evidence of the large-scale, often unconditional prosociality that characterizes human social behaviour. Consequently, one may ask whether research on cooperation in humans can offer general insights to researchers working on similar questions in non-human species, and whether research on humans should be published in biology journals. We contend that the answer to both of these questions is yes. Most importantly, social behaviour in humans and other species operates under the same evolutionary framework. Moreover, we highlight how an open dialogue between different fields can inspire studies on humans and non-human species, leading to novel approaches and insights. Biology journals should encourage these discussions rather than drawing artificial boundaries between disciplines. Shared current and future challenges are to study helping in ecologically relevant contexts in order to correctly interpret how payoff matrices translate into inclusive fitness, and to integrate mechanisms into the hitherto largely functional theory. We can and should study human cooperation within a comparative framework in order to gain a full understanding of the evolution of helping

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

No Evidence for Shared Representations of Task Sets in Joint Task Switching

Action Contro

Obesity, Type 2 Diabetes and Bone in Adults.

In an increasingly obese and ageing population, type 2 diabetes (T2DM) and osteoporotic fracture are major public health concerns. Understanding how obesity and type 2 diabetes modulate fracture risk is important to identify and treat people at risk of fracture. Additionally, the study of the mechanisms of action of obesity and T2DM on bone has already offered insights that may be applicable to osteoporosis in the general population. Most available evidence indicates lower risk of proximal femur and vertebral fracture in obese adults. However the risk of some fractures (proximal humerus, femur and ankle) is higher, and a significant number fractures occur in obese people. BMI is positively associated with BMD and the mechanisms of this association in vivo may include increased loading, adipokines such as leptin, and higher aromatase activity. However, some fat depots could have negative effects on bone; cytokines from visceral fat are pro-resorptive and high intramuscular fat content is associated with poorer muscle function, attenuating loading effects and increasing falls risk. T2DM is also associated with higher bone mineral density (BMD), but increased overall and hip fracture risk. There are some similarities between bone in obesity and T2DM, but T2DM seems to have additional harmful effects and emerging evidence suggests that glycation of collagen may be an important factor. Higher BMD but higher fracture risk presents challenges in fracture prediction in obesity and T2DM. Dual energy X-ray absorptiometry underestimates risk, standard clinical risk factors may not capture all relevant information, and risk is under-recognised by clinicians. However, the limited available evidence suggests that osteoporosis treatment does reduce fracture risk in obesity and T2DM with generally similar efficacy to other patients

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

Visual attention and action: How cueing, direct mapping, and social interactions drive orienting

Despite considerable interest in both action perception and social attention over the last 2 decades, there has been surprisingly little investigation concerning how the manual actions of other humans orient visual attention. The present review draws together studies that have measured the orienting of attention, following observation of another’s goal-directed action. Our review proposes that, in line with the literature on eye gaze, action is a particularly strong orienting cue for the visual system. However, we additionally suggest that action may orient visual attention using mechanisms, which gaze direction does not (i.e., neural direct mapping and corepresentation). Finally, we review the implications of these gaze-independent mechanisms for the study of attention to action. We suggest that our understanding of attention to action may benefit from being studied in the context of joint action paradigms, where the role of higher level action goals and social factors can be investigated

Parathyroid Hormone versus Bisphosphonate Treatment on Bone Mineral Density in Osteoporosis Therapy: A Meta-Analysis of Randomized Controlled Trials

BACKGROUND: Bisphosphonates and parathyroid hormone (PTH) represent the antiresorptive and anabolic classes of drugs for osteoporosis treatment. Bone mineral density (BMD) is an essential parameter for the evaluation of anti-osteoporotic drugs. The aim of this study was to evaluate the effects of PTH versus bisphosphonates on BMD for the treatment of osteoporosis. METHODS/PRINCIPAL FINDINGS: We performed a literature search to identify studies that investigated the effects of PTH versus bisphosphonates treatment on BMD. A total of 7 articles were included in this study, representing data on 944 subjects. The pooled data showed that the percent change of increased BMD in the spine is higher with PTH compared to bisphosphonates (WMD = 5.90, 95% CI: 3.69-8.10, p<0.01,). In the hip, high dose (40 µg) PTH (1-34) showed significantly higher increments of BMD compared to alendronate (femoral neck: WMD = 5.67, 95% CI: 3.47-7.87, p<0.01; total hip: WMD = 2.40, 95%CI: 0.49-4.31, p<0.05). PTH treatment has yielded significantly higher increments than bisphosphonates with a duration of over 12 months (femoral neck: WMD = 5.67, 95% CI: 3.47-7.86, p<0.01; total hip: WMD = 2.40, 95% CI: 0.49-4.31, P<0.05) and significantly lower increments at 12 months (femoral neck: WMD = -1.05, 95% CI: -2.26-0.16, p<0.01; total hip: WMD: -1.69, 95% CI: -3.05-0.34, p<0.05). In the distal radius, a reduction in BMD was significant between PTH and alendronate treatment. (WMD = -3.68, 95% CI: -5.57-1.79, p<0.01). DISCUSSION: Our results demonstrated that PTH significantly increased lumbar spine BMD as compared to treatment with bisphosphonates and PTH treatment induced duration- and dose-dependent increases in hip BMD as compared to bisphosphonates treatment. This study has also disclosed that for the distal radius, BMD was significantly lower from PTH treatment than alendronate treatment

Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: The risedronate and alendronate (REAL) cohort study

INTRODUCTION: Randomized clinical trials have shown that risedronate and alendronate reduce fractures among women with osteoporosis. The aim of this observational study was to observe, in clinical practice, the incidence of hip and nonvertebral fractures among women in the year following initiation of once-a-week dosing of either risedronate or alendronate. METHODS: Using records of health service utilization from July 2002 through September 2004, we created two cohorts: women (ages 65 and over) receiving risedronate (n = 12,215) or alendronate (n = 21,615). Cox proportional hazard modeling was used to compare the annual incidence of nonvertebral fractures and of hip fractures between cohorts, adjusting for potential differences in risk factors for fractures. RESULTS: There were 507 nonvertebral fractures and 109 hip fractures. Through one year of therapy, the incidence of nonvertebral fractures in the risedronate cohort (2.0%) was 18% lower (95% CI 2% – 32%) than in the alendronate cohort (2.3%). The incidence of hip fractures in the risedronate cohort (0.4%) was 43% lower (95% CI 13% – 63%) than in the alendronate cohort (0.6%). These results were consistent across a number of sensitivity analyses. CONCLUSION: Patients receiving risedronate have lower rates of hip and nonvertebral fractures during their first year of therapy than patients receiving alendronate

Circadian Modulation of Gene Expression, but not Glutamate Uptake, in Mouse and Rat Cortical Astrocytes

Circadian clocks control daily rhythms including sleep-wake, hormone secretion, and metabolism. These clocks are based on intracellular transcription-translation feedback loops that sustain daily oscillations of gene expression in many cell types. Mammalian astrocytes display circadian rhythms in the expression of the clock genes Period1 (Per1) and Period2 (Per2). However, a functional role for circadian oscillations in astrocytes is unknown. Because uptake of extrasynaptic glutamate depends on the presence of Per2 in astrocytes, we asked whether glutamate uptake by glia is circadian.We measured glutamate uptake, transcript and protein levels of the astrocyte-specific glutamate transporter, Glast, and the expression of Per1 and Per2 from cultured cortical astrocytes and from explants of somatosensory cortex. We found that glutamate uptake and Glast mRNA and protein expression were significantly reduced in Clock/Clock, Per2- or NPAS2-deficient glia. Uptake was augmented when the medium was supplemented with dibutyryl-cAMP or B27. Critically, glutamate uptake was not circadian in cortical astrocytes cultured from rats or mice or in cortical slices from mice.We conclude that glutamate uptake levels are modulated by CLOCK, PER2, NPAS2, and the composition of the culture medium, and that uptake does not show circadian variations

The association between hip fracture and hip osteoarthritis: A case-control study

<p>Abstract</p> <p>Background</p> <p>There have been reports both supporting and refuting an inverse relationship between hip fracture and hip osteoarthritis (OA). We explore this relationship using a case-control study design.</p> <p>Methods</p> <p>Exclusion criteria were previous hip fracture (same side or contralateral side), age younger than 60 years, foreign nationality, pathological fracture, rheumatoid arthritis and cases were radiographic examinations were not found in the archives. We studied all subjects with hip fracture that remained after the exclusion process that were treated at Akureyri University Hospital, Iceland 1990-2008, n = 562 (74% women). Hip fracture cases were compared with a cohort of subjects with colon radiographs, n = 803 (54% women) to determine expected population prevalence of hip OA. Presence of radiographic hip OA was defined as a minimum joint space of 2.5 mm or less on an anteroposterior radiograph, or Kellgren and Lawrence grade 2 or higher. Possible causes of secondary osteoporosis were identified by review of medical records.</p> <p>Results</p> <p>The age-adjusted odds ratio (OR) for subjects with hip fracture having radiographic hip OA was 0.30 (95% confidence interval [95% CI] 0.12-0.74) for men and 0.33 (95% CI 0.19-0.58) for women, compared to controls. The probability for subjects with hip fracture and hip OA having a secondary cause of osteoporosis was three times higher than for subjects with hip fracture without hip OA.</p> <p>Conclusion</p> <p>The results of our study support an inverse relationship between hip fractures and hip OA.</p