Segmental duplications and gene conversion: Human luteinizing hormone/chorionic gonadotropin beta gene cluster

Segmental duplicons (>1 kb) of high sequence similarity (>90%) covering >5% of the human genome are characterized by complex sequence variation. Apart from a few well-characterized regions (MHC, β-globin), the diversity and linkage disequilibrium (LD) patterns of duplicons and the role of gene conversion in shaping them have been poorly studied. To shed light on these issues, we have re-sequenced the human Luteinizing Hormone/Chorionic Gonadotropin β (LHB/CGB) cluster (19q13.32) of three population samples (Estonians, Mandenka, and Han). The LHB/CGB cluster consists of seven duplicated genes critical in human reproduction. In the LHB/CGB region, high sequence diversity, concentration of gene-conversion acceptor sites, and strong LD colocalize with peripheral genes, whereas central loci are characterized by lower variation, gene-conversion donor activity, and breakdown of LD between close markers. The data highlight an important role of gene conversion in spreading polymorphisms among duplicon copies and generating LD around them. The directionality of gene-conversion events seems to be determined by the localization of a predicted recombination “hotspot” and “warm spot” in the vicinity of the most active acceptor genes at the periphery of the cluster. The data suggest that enriched crossover activity in direct and inverted segmental repeats is in accordance with the formation of palindromic secondary structures promoting double-strand breaks rather than fixed DNA sequence motifs. Also, this first detailed coverage of sequence diversity and structure of the LHB/CGB gene cluster will pave the way for studying the identified polymorphisms as well as potential genomic rearrangements in association with an individual's reproductive success.     

Personal Values that Support and Counteract Utilization of a Screening Test for Prostate Cancer

The main aim of the current research was to discover the personal values that may support men's prostate cancer screening decisions in the future. We asked for participants’ past behavior and future behavioral intentions, and also considered their real-life behavior. The sample consisted of 371 men, of which 93 were first-time patients at the Andrology Unit. The results show that Security value was related to past participation, while Achievement, Stimulation, and Traditions counteracted this. Present prostate-testing behavior was related only to higher Security values. Predictors of future behavioral intentions were Security, Self-direction, and Benevolence, which described 21% of the total variability. Considering informed decision-making processes, our results suggest that men who hold Security, Self-direction, and Benevolence values are more likely to participate in office-based initial screening. The study indicates the need to offer office-based initial screening to those age-eligible men whose values do not support participation.     

The strength of primary care in Europe: an international comparative study

Background

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking.

Aim

Evaluation of strength of primary care in Europe.

Design and setting

International comparative cross-sectional study performed in 2009–2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey.

Method

Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts’ consultations.

Results

Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries.

Conclusion

Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.     

Compliance with treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, progressive, debilitating disease that demands continuous therapy with multiple medications. Noncompliance with disease-modifying drugs may cause disease flares, preventable functional impairment, unnecessary treatment changes, and loss of health care resources. The aim of the current study was to explore self-reported compliance with treatment and the factors contributing to this compliance using a representative sample of an RA patient population in Estonia. Two thousand patients diagnosed with RA were randomly selected from the Estonian Health Insurance Fund database. The eligible response rate of the study was 60%. Using prestructured questionnaires, the following information about the disease and treatment was evaluated: self-reported compliance with treatment, reasons for noncompliance, disease history, sociodemographic variables, health care utilization, and satisfaction with health care providers. The self-reported compliance rate was 80.3%, reflecting the percentage of patients who reported that they always took their medications exactly as described. The most often reported reasons for noncompliance were side effects and fear of side effects. Compliance was found to be the lowest in a group of younger and active patients with higher income. Higher frequency of visits to the rheumatologist, satisfaction with health care providers, and sufficient information about RA treatment correlated with better compliance.     

Semen quality and associated reproductive indicators in middle-aged males: the role of non-malignant prostate conditions and genital tract inflammation

Purpose

To compare the associations between non-malignant prostate conditions, genital tract inflammation, and reproductive function in middle-aged men.

Methods

Three-hundred and eighty-two voluntary male subjects who underwent the screening for prostate health were recruited for the study. Semen quality and associated reproductive indicators, seminal inflammation, and prostate-related pathologies were evaluated.

Results

Sperm motility and prostate-related parameters were significantly impaired in patients with chronic prostatitis syndromes and lower urinary tract symptoms in comparison with controls. Elevated seminal markers of inflammation were in positive association with body mass index, prostate-specific antigen, and estradiol level in serum while in negative association with semen volume, total sperm count, and sperm motility. According to WHO reference limits, speculative cutoff values for WBC and IL-6 in semen to detect reduced sperm parameters were 0.342 M/mL and 56.8 ng/L, respectively.

Conclusions

According to our data, one of the possible pathways for impaired reproductive quality in male subjects >45 years could be related to infection and inflammation in the genital tract with subsequent (partial) obstruction and damage of prostate and other male accessory glands.     

Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study

Summary

We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits.

Introduction

Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear.

Methods

We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40–79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (_aBMD, n?=?527) and performed radius peripheral quantitative computed tomography (pQCT, n?=?595).

Results

MetS was present in 975 men (31.2 %). Men with MetS had lower β C-terminal cross-linked telopeptide (β-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P?<?0.0001) and higher total hip, femoral neck, and lumbar spine _aBMD (P?≤?0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and β-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip _aBMD and radius cross-sectional area (CSA) and stress–strain index. HOMA-S was similarly associated with PINP and β-CTX, BUA, and radius CSA in BMI-adjusted models.

Conclusions

Men with MetS have higher _aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone’s failure to adapt to increasing bodily loads in men with MetS.

     

Intracellular energetic units in healthy and diseased hearts

BACKGROUND:

The present review examines the role of intra-cellular compartmentation of energy metabolism in vivo.

OBJECTIVE:

To compare the kinetics of the activation of mitochondrial respiration in skinned cardiac fibres by exogenous and endogenous adenine nucleotides in dependence of the modulation of cellular structure and contraction.

METHODS:

Saponin-permeabilized cardiac fibres or cells were analyzed using oxygraphy and confocal microscopy.

RESULTS:

Mitochondria respiration in fibres or cells was upregulated by cumulative additions of ADP to the medium with an apparent K_m of 200 μM to 300 μM. When respiration was stimulated by endogenous ADP produced by intracellular ATPases, a near maximum respiration rate was achieved at an ADP concentration of less than 20 μM in the medium. A powerful ADP-consuming system, consisting of pyruvate kinase and phosphoenolpyruvate, that totally suppressed the activation of respiration by exogenous ADP, failed to abolish the stimulation of respiration by endogenous ADP, but did inhibit respiration after the cells were treated with trypsin. The addition of up to 4 μM of free Ca²⁺ to the actively respiring fibres resulted in reversible hypercontraction associated with a decreased apparent K_m for exogenous ADP. These changes were fully abolished in fibres after the removal of myosin by KCl treatment.

CONCLUSIONS:

Mitochondria and ATPases, together with cytoskeletal proteins that establish the structural links between mitochondria and sarcomeres, form complexes – intracellular energetic units (ICEUs) – in cardiac cells. Within the ICEUs, the mitochondria and ATPases interact via specialized energy transfer systems, such as the creatine kinase- and adenylate kinase-phosphotransfer networks, and direct ATP channelling. Disintegration of the structure and function of ICEUs results in dyscompartmentation of adenine nucleotides and may represent a basis for cardiac diseases.     

Daily usage and efficiency of remote home monitoring in hypertensive patients over a one-year period

We evaluated daily self-monitored blood pressure (BP) data collected over one year using remote home monitoring. Fifty treated, moderately hypertensive subjects (26 males, mean age 50 years; 17 females, mean age 54 years; seven exclusions) were recruited for the study in which semi-automatic arm-cuff BP measurement devices were used. The daily self-monitoring regimen had two phases of usage: one of initial enthusiasm (the first one to two months) followed by a phase of lower usage (89% versus 64%, P<0.01). Monitoring was missed more often (P < 0.01) during weekends (7.3 instances per patient) compared with workdays (5.0). Lack of motivation was not considered to be a major barrier. Approximately half of the study population was willing to continue the trial at the end of the one-year study. The occurrence of extreme BP values dropped significantly after the initial study month (P = 0.02). In conclusion, routine remote BP monitoring is capable of collecting consistent and accurate data, with sufficient sensitivity to reveal trends.