Agonistic and antagonistic effects of antiestrogens in different target organs.

Antiestrogens block by definition specifically the actions of estrogens. In the classical uterotropic assay in immature rodents, where estrogens cause fluid retention and cell proliferation, triphenylethylenes have also species-specific estrogen-like (agonistic) effects. 4-hydroxylated triphenylethylenes have in general less estrogenic properties than unhydroxylated ones, and ICI 164,384 has no estrogenic activity in this model. Uterus responds to estrogens by stimulation of cell proliferation. Some other tissues, like breast, liver, and bone respond by regulation of specific protein synthesis. Some of the proteins act as growth factors, and some have unknown functions. The regulation of gene expression is a complex phenomenon: estrogens may turn the responsive gene on or off. Similarly antiestrogens may participate in the gene regulation by mimicking or antagonising estrogen-like actions. This paper summarizes the estrogenic and antiestrogenic effects of classical and new antiestrogens in different tissues.     

Whole-exome sequencing of Finnish patients with vascular cognitive impairment

Cerebral small vessel disease (CSVD) is the most important cause of vascular cognitive impairment (VCI). Most CSVD cases are sporadic but familial monogenic forms of the disorder have also been described. Despite the variants identified, many CSVD cases remain unexplained genetically. We used whole-exome sequencing in an attempt to identify novel gene variants underlying CSVD. A cohort of 35 Finnish patients with suspected CSVD was analyzed. Patients were screened negative for the most common variants affecting function in NOTCH3 in Finland (p.Arg133Cys and p.Arg182Cys). Whole-exome sequencing was performed to search for a genetic cause of CSVD. Our study resulted in the detection of possibly pathogenic variants or variants of unknown significance in genes known to associate with CSVD in six patients, accounting for 17% of cases. Those genes included NOTCH3, HTRA1, COL4A1, and COL4A2. We also identified variants with predicted pathogenic effect in genes associated with other neurological or stroke-related conditions in seven patients, accounting for 20% of cases. This study supports pathogenic roles of variants in COL4A1, COL4A2, and HTRA1 in CSVD and VCI. Our results also suggest that vascular pathogenic mechanisms are linked to neurodegenerative conditions and provide novel insights into the molecular basis of VCI.Subject terms: Stroke, Sequencing, Genetics research, Dementia     

The relationship between acute stress disorder and posttraumatic stress disorder following cancer

In this study, the authors investigated the relationship between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) following cancer diagnosis. Patients who were recently diagnosed with 1st onset head and neck or lung malignancy (N=82) were assessed for ASD within the initial month following their diagnosis and reassessed (n=63) for PTSD 6 months following their cancer diagnosis. At the initial assessment, 28% of patients had ASD, and 32% displayed subsyndromal ASD. At follow-up, PTSD was diagnosed in 53% of patients who had been diagnosed with ASD and in 11% of those who had not met criteria for ASD; 36% of patients with PTSD did not initially display ASD. In this study, the authors question the use of the ASD diagnosis to identify recently diagnosed patients at risk of PTSD.     

Comparison of strength properties of poly-L/D-lactide (PLDLA) 96/4 and polyglyconate (Maxon) sutures: in vitro, in the subcutis, and in the achilles tendon of rabbits

Achilles tendon rupture is a common injury. Absorbable sutures are not commonly used because of their limited strength properties. Recently, sutures with prolonged strength retention properties have been developed. The aim of the study is to test the mechanical properties of recently developed poly-L/D-lactide (PLDLA) sutures in comparison with polyglyconate (Maxon) sutures. PLDLA (0.2 mm thick) and Maxon (4.0) sutures were studied in vitro by immersion in a buffered saline solution (pH 7.4). Tensile strength tests were done on sutures retrieved after 1-26 weeks. In vivo, they were implanted in the subcutis of 32 rabbits. Tensile strength tests were done on sutures retrieved after 1-6 weeks. The sutures were also used to repair the Achilles tendon in rabbits. Maximum force before breaking and percentage elongation of tendons were determined. Although PLDLA had a lower initial tensile strength than Maxon, PLDLA showed more prolonged tensile strength retention than Maxon. Tendons repaired with PLDLA, however, had a lower strength than Maxon-repaired tendons at six weeks (insignificant difference). PLDLA has more prolonged tensile strength properties compared with Maxon. Thus, PLDLA offers an alternative to Maxon in repair of the Achilles tendon.     

Feasibility of mobile mental wellness training for older adults

Mobile technology has been increasingly adopted in promotion of mental health among older people. This study assessed the feasibility of a mobile mental wellness training application for individual use and for group work from the perspectives of older adults and social care professionals. The older individuals recruited for the study were participants in a Circle of Friends group and family caregivers' peer support group offered by the communal senior services. The qualitative and quantitative results of interviews, questionnaires, observation, and application usage were reported. Seven older adults started using the application independently at home in parallel with the group activity. This study revealed new information regarding the barriers to the older adults' full adoption of such mobile technologies. The results indicated that there may be potential in the incorporation of mobile technologies in promotion of mental health of older people at group settings.     

Association between liver insulin resistance and cardiovascular risk factors

Abstract. Vangipurapu J, Stan?áková A, Kuulasmaa T, Soininen P, Kangas AJ, Ala‐Korpela M, Kuusisto J, Laakso M (University of Eastern Finland and Kuopio University Hospital, Kuopio; University of Oulu and Biocenter Oulu, Oulu, Finland). Association between liver insulin resistance and cardiovascular risk factors. J Intern Med 2012; 272: 402–408. Objectives. The objective of this study was to examine the associations between indices of liver insulin resistance (IR) and whole‐body insulin sensitivity and different cardiovascular disease (CVD) risk factors. Design and subjects. A total of 8750 nondiabetic men (age 57.2 ± 7.1 years, body mass index 26.8 ± 3.8 kg m^?2) were included in this study from the population‐based cross‐sectional Metabolic Syndrome In Men (METSIM) cohort. Liver IR index and Matsuda insulin sensitivity index (ISI) were used as markers of liver IR and whole‐body insulin sensitivity, respectively. Pearson correlation analysis was performed to examine the associations between these indices and various CVD risk factors. Results. Total cholesterol (r = ?0.088 vs. r = 0.020; P < 0.0019), high‐sensitivity C‐reactive protein (CRP) (r = 0.284 vs. r = ?0.219; P < 0.0019) and total triglycerides (r = 0.507 vs. r = ?0.477; P < 0.05) were more highly correlated with liver IR index than with Matsuda ISI. By contrast, Matsuda ISI was nominally more highly correlated with systolic and diastolic blood pressure (r = ?0.234 and r = ?0.275 vs. r = 0.202 and r = 0.239, respectively) compared to liver IR index. Furthermore, the variance explained by liver IR index was larger than that explained by Matsuda ISI for the majority of CVD risk factors measured. Conclusions. Liver IR index correlated more strongly than Matsuda ISI with levels of total cholesterol, CRP and triglycerides. Therefore, liver IR might be a significant indicator of CVD risk amongst men.     

Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population‐based study of 9399 Finnish men

Abstract. Wang J, Stan?áková A, Soininen P, Kangas AJ, Paananen J, Kuusisto J, Ala‐Korpela M, Laakso M (University of Eastern Finland and Kuopio University Hospital, Kuopio; Institute of Clinical Medicine, University of Oulu, Oulu; University of Eastern Finland, Kuopio; and Clinical Research Center, University of Oulu, Oulu; Finland). Lipoprotein subclass profiles in individuals with varying degrees of glucose tolerance: a population‐based study of 9399 Finnish men. J Intern Med 2012; doi: 10.1111/j.1365‐2796.2012.02562.x. Objectives. We investigated serum concentrations of lipoprotein subclass particles and their lipid components determined by proton nuclear magnetic resonance spectroscopy in a population‐based study. Design and methods. A total of 9399 Finnish men were included in the study: 3034 men with normal fasting glucose and normal glucose tolerance; 4345 with isolated impaired fasting glucose (IFG); 312 with isolated impaired glucose tolerance (IGT); 1058 with both IFG and IGT; and 650 with newly diagnosed type 2 diabetes (New DM). Lipoprotein subclasses included chylomicrons (CM) and largest VLDL particles, other VLDL particles (five subclasses), intermediate‐density lipoprotein (IDL), LDL (three subclasses) and HDL (four subclasses). The phospholipid, triglyceride (TG), cholesterol, free cholesterol and cholesterol ester levels of the lipoprotein particles were measured. Results. Abnormal glucose tolerance (especially IGT and New DM) was significantly associated with increased concentrations of VLDL subclass particles and their components (with the exception of very small VLDL particles). After further adjustment for total TGs and HDL cholesterol, increased lipid concentrations in the CM/largest VLDL particles and in most of the other VLDL particles remained significant in individuals with isolated IGT, IFG+IGT and New DM. There was a consistent trend towards a decrease in large and an increase in small HDL particle concentrations in individuals with hyperglycaemia even after adjustment for serum total TGs and HDL cholesterol. Conclusions. Abnormal glucose tolerance modifies the concentrations of lipoprotein subclass particles and their lipid components in the circulation and is also related to compositional changes in these particles.     

Effect of Comorbidity on Treatment of Anxious Children and Adolescents: Results From a Large,Combined Sample

ObjectiveThe purpose of the present study was to evaluate the influence of comorbid disorders on the degree of change and the endpoint of cognitive-behavioral treatment in anxious young people.MethodData on 750 children 6 to 18 years old were compiled from different samples within one clinic. All children had a primary anxiety disorder and were engaged in a manual-based, 10-session, cognitive-behavioral treatment program. Outcome was determined according to diagnostic status and continuous symptom measurements. Analyses compared results among four groups: no comorbidity, comorbid anxiety disorders, comorbid externalizing disorders, comorbid mood disorders. All analyses were intent-to-treat analyses.ResultsChildren with comorbid depression were the least likely to be free of their primary anxiety diagnosis at the end of treatment and follow-up. According to child and maternal reports, symptoms of anxiety decreased similarly over time in all groups, but children with comorbid mood disorders scored significantly highest at all time points. Examining the effects of anxiety treatment on comorbid disorders showed that comorbid mood disorders, but not externalizing disorders, decreased significantly over time.ConclusionsThe existence of comorbid disorders does not appear to affect the rate or extent of response to cognitive-behavioral treatment for child anxiety. However, comorbidity has a marked influence on the endpoint of treatment. Children with nonanxiety comorbidity and especially with comorbid mood disorders exhibit greater severity at the outset and remain worse after treatment. On the positive side, treatment for anxiety disorders appears to decrease comorbid mood disorders, although it has less effect on comorbid externalizing disorders.