Fractures in older people - incidence, predictors and consequences

In older populations, fractures are common and the consequences of fractures may be serious both for an individual and for society. However, information is scarce about the incidence, predictors and consequences of fractures in population-based unselected cohorts including both men and women and a long follow-up. The objective of this study was to analyse the incidence and predictors of fractures as well as functional decline and excess mortality due to fractures, among 482 men and 695 women aged 65 or older in the municipality of Lieto, Finland from 1991 until 2002. In analyses, Poisson’s, Cox proportional Hazards and Cumulative Logistic regression models were used for the control of several confounding variables. During the 12-year follow-up with a total of 10 040 person-years (PY), 307 (26%) persons sustained altogether 425 fractures of which 77% were sustained by women. The total incidence of fractures was 53.4 per 1000 PY (95% confidence intervals [95% CI]: 47.9 - 59.5) in women and 24.9 per 1000 PY (95% CI: 20.4 - 30.4) in men. The incidence rates of fractures at any sites and hip fractures were associated with increasing age. No significant changes in the ageadjusted incidence rates of fractures were found in either gender during the 12-year follow-up. The predictors of fractures varied by gender. In multivariate analyses, reduced handgrip strength and body mass index (BMI) lower than 30 in women and a large number of depressive symptoms in men were independent predictors of fractures. A compression fracture in one or more thoracic or upper lumbar vertebras on chest radiography at baseline was associated with subsequent fractures in both genders. Lower body fractures independently predicted both short- (0-2 years) and long-term (up to 8 years) functional decline in mobility and activities of daily living (ADL) performance during the 8-year follow-up. Upper body fractures predicted decline in ADL performance during longterm follow-up. In the 12-year follow-up, hip fractures in men (Hazard Ratio [HR] 8.1, 95% CI: 4.4-14.9) and in women (HR 3.0, 95% CI: 1.9-4.9), and fractures at the proximal humerus in men (HR 5.4, 95% CI: 1.6-17.7) were independently associated with excess mortality. In addition, leisure time inactivity in physical exercise predicted independently both functional decline and excess mortality. Fractures are common among older people posing serious individual consequences. Further studies about the effectiveness of preventing falls and fractures as well as improving care and rehabilitation after fractures are needed.

Thyroid function in the elderly and sex hormones in elderly men: reference intervals and associations with health

Aims: The aims were to create clinically feasible reference intervals for thyroidstimulating hormone (TSH) and free thyroxine (FT4) and to analyze associations between thyroid function and self-rated health, neuropsychiatric symptoms, depression and dementia in the elderly. The second aim was also to establish reference intervals for sex hormones and to analyze associations between sex hormone levels and self-rated health, symptoms, depression and dementia in elderly men. Subjects and methods: The study population comprised 1252 subjects aged 65 years or over, living in the municipality of Lieto, south-western Finland. Self-rated health, life satisfaction, symptoms, depression, and dementia were assessed with specific questions, clinical examination and tools such as the Zung Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH, FT4 or sex hormone levels were assessed. Levels of TSH and FT4 in thyroid disease–free women and women treated with thyroxine were also compared. Results: Elevated concentrations of thyroid peroxidase antibodies (TPOAb) or thyroglobulin antibodies (TgAb) were found to have a marked effect on the upper reference limit for TSH among women, who were thyroid antibody positive more higher than suggested in several recent guidelines. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most neuropsychiatric symptoms in the thyroid disease-free population. Although women with thyroxine treatment for primary hypothyroidism had far higher TSH levels than thyroid disease-free women, there were no differences between thyroid-disease free women and women with stable thyroxine treatment regarding self-rated health, life satisfaction or symptoms. Age had a significant positive association with luteinizing hormone (LH), follicle 2 practice, one range in men aged 65 years or over can be used for T, E2 and FSH measured with the AutoDelfia method, but two separate reference intervals should be used for fT, LH and SHBG. After adjustment for age, higher levels of T and fT were associated with better self-rated health (SRH) in the reference population. After adjustment for age and body mass index (BMI), there were no associations between sex hormone concentrations and self-rated health, life satisfaction or most symptoms in concentration. Conclusion: Age-specific reference intervals were derived for thyroid function and sex hormones based on comprehensive data from a community-dwelling population with a high participation rate. The results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. Older age or being overweight symptoms among elderly men. The associations of single symptoms with T levels were inconsistent among elderly men, although the association of low T level with diagnosed depression might be clinically significant.

Neck Muscle Function and Adolescent Headache

Muscular function of the neck region may be of importance for the etiology of headache, especially of tension-type headache. However, very few data exist on the association of neck muscle function with different types of headache in adolescents. The main aim of the study was to examine the association of neck muscle function with adolescent headache. The associations between leisure time activities, endurance strength of the upper extremities (UE endurance) and mobility of the neck-shoulder region and adolescent headache were studied. In addition, the associations of force production, EMG/force ratio, co-activation and fatigue characteristics, and cross-sectional area (CSA) of neck muscles with adolescent headache were studied. The study is part of a population-based cohort study of 12-year-old children with and without headache. The study had five phases (years 1998-2003). At the age of 13 years, a sample of 183 adolescents (183/311) participated in endurance strength and mobility measurements of the neck-shoulder region. In addition, the type and level of physical and other leisure activity were elicited with open and structured questions. At the age of 17 years, a random sample of 89 adolescents (89/202) participated in force and EMG measurements of the neck-shoulder muscles. In addition, at the age of 17 years, a sample of 65 adolescents (65/89) participated in CSA measurements of the neck muscles. At the age of 13 years, intensive participation in overall sports activity was associated with migraine. Frequent computer use was associated both with migraine and tension-type headache. The type of sports or other leisure activity classified them on the basis of body loading was not associated with headache type. In girls, low UE endurance of both sides, and low cervical rotation of the dominant side, were associated with tension-type headache, and low UE endurance of non-dominant side with migraine. In boys, no associations occurred between UE endurance and mobility variables and headache types. At the age of 17 years, in girls, high EMG/force ratios between the EMG of the left agonist sternocleidomastoid muscle (SCM) and maximal neck flexion and neck rotation force to the right side as well as high co-activation of right antagonist cervical erector spinae (CES) muscles during maximal neck flexion force were associated with migraine-type headache. In girls, neck force production was not associated with headache types but low left shoulder flexion force was associated with tension-type headache. In boys, no associations were found between EMG and force variables and headache. Increased SCM muscles fatigue of both sides was associated with tension-type headache. In boys, the small CSA of the right SCM muscle and, in girls, of combined right SCM and scalenus muscles was associated with tension-type headache. Similarly, in boys, the large CSA of the right SCM muscle, of the combined right SCM and scalenus muscles, of the left semispinalis capitis muscle, of the combined left semispinalis and splenius muscles was associated with migraine. No other differences in the CSA of neck flexion or extension muscles were found. Differences in the neuromucular function of the neck-shoulder muscles were associated with adolescent headache, especially in girls. Differences in the cross-sectional area of unilateral neck muscles were associated with headache, especially in boys. Differences in the neuromuscular function and in the cross-sectional area of the neck muscles also occurred between different types of headache. It remains to be established whether the findings are primary or secondary to adolescent migraine and tension headache. Keywords: adolescent, cross-sectional area, electromyography, endurance strength, fatigue, force, headache, leisure time activity, migraine, mobility, neck muscles, tension-type headache

Regulation of Spermatogenesis: Differentiation of GFP-labeled Stem Cells and the Function of Cytoplasmic Bridges

During spermatogenesis, different genes are expressed in a strictly coordinated fashion providing an excellent model to study cell differentiation. Recent identification of testis specific genes and the development of green fluorescence protein (GFP) transgene technology and an in vivo system for studying the differentiation of transplanted male germ cells in infertile testis has opened new possibilities for studying the male germ cell differentiation at molecular level. We have employed these techniques in combination with transillumination based stage recognition (Parvinen and Vanha-Perttula, 1972) and squash preparation techniques (Parvinen and Hecht, 1981) to study the regulation of male germ cell differentiation. By using transgenic mice expressing enhanced-(E)GFP as a marker we have studied the expression and hormonal regulation of beta-actin and acrosin proteins in the developmentally different living male germ cells. Beta-actin was demonstrated in all male germ cells, whereas acrosin was expressed only in late meiotic and in postmeiotic cells. Follicle stimulating hormone stimulated b-actin-EGFP expression at stages I-VI and enhanced the formation of microtubules in spermatids and this way reduced the size of the acrosomic system. When EGFP expressing spermatogonial stem cells were transplanted into infertile mouse testis differentiation and the synchronized development of male germ cells could be observed during six months observation time. Each colony developed independently and maintained typical stage-dependent cell associations. Furthermore, if more than two colonies were fused, each of them was adjusted to one stage and synchronized. By studying living spermatids we were able to demonstrate novel functions for Golgi complex and chromatoid body in material sharing between neighbor spermatids. Immunosytochemical analyses revealed a transport of haploid cell specific proteins in spermatids (TRA54 and Shippo1) and through the intercellular bridges (TRA54). Cytoskeleton inhibitor (nocodazole) demonstrated the importance of microtubules in material sharing between spermatids and in preserving the integrity of the chromatoid body. Golgi complex inhibitor, brefeldin A, revealed the great importance of Golgi complex i) in acrosomic system formation ii) TRA54 translation and in iii) granule trafficking between spermatids.

Airway surgery for obstructive sleep apnea and partial upper airway obstruction during sleep

This study analyzed the feasibility and efficacy of surgical therapies in patients with sleep-disordered breathing ranging from partial upper airway obstruction during sleep to severe obstructive sleep apnea syndrome. The surgical procedures evaluated were tracheostomy, laser-assisted uvulopalatoplasty (LUPP) and uvulopalatopharyngoplasty (UPPP) with laser or ultrasound scalpel. Obstructive sleep apnea and partial upper airway obstruction during sleep were measured with the static charge-sensitive bed (SCSB) and pulse oximeter. The patients with severe obstructive sleep apnea syndrome were treated with tracheostomy. Palatal surgery was performed only if the upper airway narrowing occurred exclusively at the soft palate level in patients with partial upper airway obstruction during sleep. The ultrasound scalpel technique was compared to laser-assisted UPPP. The efficacy of LUPP to reduce partial upper airway obstruction during sleep was assessed and histology of uvulopalatal specimen was compared to body fat distributional parameters and sleep study findings. Tracheostomy was effective therapy in severe obstructive sleep apnea. Partial upper airway obstruction and arterial oxyhemoglobin desaturation index during sleep decreased significantly after LUPP. The minimal retropalatal airway dimension increased and soft palate collapsibility decreased at the level where the velopharyngeal obstruction had occurred before the surgery. Ultrasound scalpel did not offer any significant benefits over the laser-assisted technique, except fewer postoperative haemorrhage events. The loose connective tissue as a manifestation of edema was the only histological finding showing correlation with partial upper airway obstruction parameters of SCSB. Tracheostomy remains a life-saving therapy and also long-term option when adherence to CPAP fails in patients with obstructive sleep apnea syndrome. LUPP effectively reduces partial upper airway obstruction during sleep provided that obstruction at the other levels than the soft palate and uvula were preoperatively excluded. Technically the ultrasound scalpel or laser surgeries are equal. In patients with partial upper airway obstruction the loose connective tissue is more important than fat accumulation in the soft palate. This supports the hypothesis that edema is a primary trigger for aggravation of upper airway narrowing during sleep at the soft palate level and evolution towards partial or complete upper airway obstruction during sleep.

Chromatoid body mediated RNA regulation in mouse male germline

Male germ cell differentiation, spermatogenesis is an exceptional developmental process that produces a massive amount of genetically unique spermatozoa. The complexity of this process along with the technical limitations in the germline research has left many aspects of spermatogenesis poorly understood. Post-meiotic haploid round spermatids possess the most complex transcriptomes of the whole body. Correspondingly, efficient and accurate control mechanisms are necessary to deal with the huge diversity of transcribed RNAs in these cells. The high transcriptional activity in round spermatids is accompanied by the presence of an uncommonly large cytoplasmic ribonucleoprotein granule, called the chromatoid body (CB) that is conjectured to participate in the RNA post-transcriptional regulation. However, very little is known about the possible mechanisms of the CB function. The development of a procedure to isolate CBs from mouse testes was this study’s objective. Anti-MVH immunoprecipitation of cross-linked CBs from a fractionated testicular cell lysate was optimized to yield considerable quantities of pure and intact CBs from mice testes. This protocol produced reliable and reproducible data from the subsequent analysis of CB’s protein and RNA components. We found that the majority of the CB’s proteome consists of RNA-binding proteins that associate functionally with different pathways. We also demonstrated notable localization patterns of one of the CB transient components, SAM68 and showed that its ablation does not change the general composition or structure of the CB. CB-associated RNA analysis revealed a strong accumulation of PIWI-interacting RNAs (piRNAs), mRNAs and long non-coding RNAs (lncRNAs) in the CB. When the CB transcriptome and proteome analysis results were combined, the most pronounced molecular functions in the CB were related to piRNA pathway, RNA post-transcriptional processing and CB structural scaffolding. In addition, we demonstrated that the CB is a target for the main RNA flux from the nucleus throughout all steps of round spermatid development. Moreover, we provided preliminary evidence that those isolated CBs slice target RNAs in vitro in an ATPdependent manner. Altogether, these results make a strong suggestion that the CB functions involve RNA-related and RNA-mediated mechanisms. All the existing data supports the hypothesis that the CB coordinates the highly complex haploid transcriptome during the preparation of the male gametes for fertilization. Thereby, this study provides a fundamental basis for the future functional analyses of ribonucleoprotein granules and offers also important insights into the mechanisms governing male fertility.

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonance