Association diastolic function by echo and infarct size by magnetic resonance imaging after STEMI

Objectives. Left ventricular (LV) diastolic dysfunction is a predictor of increased morbidity and mortality; however, little is known about diastolic function and the degree of myocardial damage after myocardial infarction (MI). The aim was to assess the association between diastolic dysfunction by echocardiography and myocardial salvage assessed with cardiac magnetic resonance (CMR) imaging in patients with ST-segment elevation MI (STEMI). Design. In a prospective study, echocardiography and CMR were performed in STEMI patients in the early post-MI phase assessing diastolic dysfunction according to E/A and E/e’_average and area at risk, and after three months with measurement of final infarct size and salvage index. Linear regression analyses were performed testing the association of diastolic dysfunction with area at risk, final infarct size and salvage index. Results. A total of 193 patients (61?±?11 years) were included. Median system delay (first medical contact to primary PCI) was 185?min, 123 patients (63%) had TIMI 0/1 flow before intervention and 85 (46%) sustained an anterior MI. In 74 patients (38%), diastolic function was normal. The presence of diastolic dysfunction was associated with larger area at risk of median 6.6% (p?<?0.001), larger final infarct size of 4.5% (p?<?0.001), and lower salvage index of ?5.9% (p?=?0.02) compared with patients with normal diastolic function. Conclusion. Diastolic dysfunction in the early phase after STEMI is associated with more extensive myocardial damage and significantly poorer myocardial salvage after three months, and the presence of diastolic dysfunction acutely after STEMI may therefore be used as a marker of worse myocardial outcome.     

Subfecundity in overweight and obese couples

BACKGROUND: Recent studies indicate that not only women's but also men's obesity has adverse effects on fecundity and since fecundity is a couple concept, we examined fecundity in relation to overweight and obesity of the couple. We also examined the association between weight changes and fecundity over time. METHODS: Between 1996 and 2002, 64 167 pregnant women enrolled in the Danish National Birth Cohort were interviewed during and 18 months after pregnancy. Information on body mass index (BMI) and waiting time to pregnancy (TTP) was available for 47 835 couples. RESULTS: Among men and women with a BMI of 18.5 kg/m(2) or more, we found a dose-response relationship between increasing BMI group and subfecundity (a TTP of more than 12 months): Odds ratio (OR) = 1.32 (95% CI: 1.26-1.37) for women and OR = 1.19 (95% CI: 1.14-1.24) for men. Among 2374 women with an initial BMI of 18.5 kg/m(2) or more, who participated more than once in the Danish National Birth Cohort, each kilogram increment in weight between the two pregnancies was associated with a 2.84 (95% CI: 1.33-4.35) days longer TTP. CONCLUSIONS: Couples have a high risk of being subfecund if they are both obese.     

Pre-conceptual and prenatal supplementary folic acid and multivitamin intake,behavioral problems,and hyperkinetic disorders: A study based on the Danish National Birth Cohort (DNBC)

Objective: To evaluate whether early folic acid or multivitamin supplementation during pregnancy prevents diagnosis of hyperkinetic disorders (HKD), treatment for attention deficit hyperactivity disorder (ADHD), and ADHD-like behaviors reported by parents participating in the DNBC for children at age 7.

Methods: HKD diagnosis and ADHD medication use data were obtained from the Danish National Hospital, Central Psychiatric and Pharmaceutical registers. We estimated hazard ratios (HRs) for HKD diagnosis and ADHD medication use and risk ratios (RRs) for parent-reported ADHD behavior collected with the Strength and Difficulties Questionnaire (SDQ), comparing children whose mothers took folic acid or multivitamin supplements early in pregnancy defined as starting periconceptionally (4 weeks prior to their last menstrual period (LMP)) through 8 weeks after their LMP (4–8 weeks), to children whose mothers indicated no supplement use for the same entire period.

Results: We identified 384 children (1.1%) with a hospital diagnosis for HKD and 642 children (1.8%) treated with ADHD medication. We found no association between risk of HKD diagnosis or intake of ADHD medication and early maternal folic acid use. However, early multivitamin use was associated with an approximately 30% reduction in risk for HKD diagnosis (aHR: 0.70, 95% CI: 0.52–0.96) and 21% reduction in treatment with ADHD medication (aHR: 0.79, 95% CI: 0.62–0.98). We observed a reduced risk in parent-reported ADHD behaviors, but these results were attenuated after adjustment.

Conclusion: Our data suggest that multivitamin use in early pregnancy may reduce risk for HKD diagnosis and treatment for ADHD in the offspring.     

No certain predictors for mutation status in a Danish cohort with familial hypercholesterolemia: a descriptive study

OBJECTIVE: In order to enable clinicians to refer the right persons suspected of familial hypercholesterolemia (FH) for mutation screening, a retrospective study was conducted in a Danish FH cohort. DESIGN AND METHODS: The study comprised 643 probands and 395 relatives, of which 421 individuals had a pathogenic mutation, and 211 had cardiovascular disease (CVD). Logistic regression, Cox regression, and receiver operating characteristics (ROC) curves were used to find optimal predictive variables for mutation status and evaluate risk factors for CVD. RESULTS: Age alone had significant predictive power in both genders. ROC curves and area under the curve plots found no parameters capable of predicting mutation status. The only significant risk factor for CVD in both genders was mutation carrier status. CONCLUSIONS: No parameters could decipher mutation status a priori. All individuals fulfilling the FH criteria should therefore be referred in order to facilitate family tracing and genetic counseling.     

Cognitive impairment and associations with structural brain networks,endocrine status,and risk genotypes in newly orchiectomized testicular cancer patients

Brain Imaging and Behavior - A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the...     

Self-disorders and Schizophrenia: A Phenomenological Reappraisal of Poor Insight and Noncompliance

Poor insight into illness is considered the primary cause of treatment noncompliance in schizophrenia. In this article, we critically discuss the predominant conceptual accounts of poor insight, which consider it as an ineffective self-reflection, caused either by psychological defenses or impaired metacognition. We argue that these accounts are at odds with the phenomenology of schizophrenia, and we propose a novel account of poor insight. We suggest that the reason why schizophrenia patients have no or only partial insight and consequently do not comply with treatment is rooted in the nature of their anomalous self-experiences (ie, self- disorders) and the related articulation of their psychotic symptoms. We argue that self-disorders destabilize the patients’ experiential framework, thereby weakening their basic sense of reality (natural attitude) and enabling another sense of reality (solipsistic attitude) to emerge and coexist. This coexistence of attitudes, which Bleuler termed “double bookkeeping,” is, in our view, central to understanding what poor insight in schizophrenia really is. We suggest that our phenomenologically informed account of poor insight may have important implications for early intervention, psychoeducation, and psychotherapy for schizophrenia.Key words: compliance, phenomenology, double bookkeeping, vulnerability     

Management of persistent postsurgical inguinal pain

Purpose

Severe persistent pain is a major postsurgical complication affecting 2–4 % of patients following inguinal hernia repair and may cause critical physical and socioeconomic disability. This review introduces relevant criteria and analyses the current evidence base underlying recommended management strategies.

Results

Development of persistent postsurgical pain (PPP) following inguinal hernia repair cannot automatically be considered to follow a simple trajectory from acute to chronic pain. Surgical management comprising neurectomy with or without meshectomy was described in 25 studies. Local anesthetic blocks, pharmacological management, and treatment with sensory stimulation methods were presented in seven studies. In spite of shortcomings, the data on surgical management demonstrate that neurectomy with or without mesh removal may provide long-lasting analgesic effects in most patients with severe PPP following inguinal hernia repair. The evidence base for other management methods is still fragile, although promising results appear in the neuromodulation studies.

Conclusions

There is a need for improved study designs and, launching of large multicenter collaborative studies supplying the necessary long-term data for recommendation of future management strategies.     

Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase

Maintaining stable tryptophan levels is required to control neuronal and immune activity. We report that tryptophan homeostasis is largely controlled by the stability of tryptophan 2,3-dioxygenase (TDO), the hepatic enzyme responsible for tryptophan catabolism. High tryptophan levels stabilize the active tetrameric conformation of TDO through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan. In low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four–amino acid degron that triggers TDO polyubiquitination by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of TDO and rapid interruption of tryptophan catabolism. The nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric TDO and thereby stably reduces tryptophanemia. Our results uncover a mechanism allowing a rapid adaptation of tryptophan catabolism to ensure quick degradation of excess tryptophan while preventing further catabolism below physiological levels. This ensures a tight control of tryptophanemia as required for both neurological and immune homeostasis.

Blood levels of essential amino acids are remarkably constant despite large variations in diet supply, but the mechanisms ensuring amino acid homeostasis remain poorly understood (1). Systemic homeostasis is particularly important for tryptophan given its key roles as a neurotransmitter precursor and a regulator of immune responses (2–5). In humans, tryptophanemia is stably maintained around 60 ± 15 µM (mean ± SD) (6). Tryptophan catabolism involves dioxygenation leading to the production of kynurenine and derivatives (7, 8). This first and rate-limiting step can be catalyzed by two enzymes: TDO and indoleamine 2,3-dioxygenase (IDO1). Despite functional homology, these two enzymes differ in sequence, structure, expression, and physiological role. TDO (gene name TDO2) is a tetrameric enzyme expressed in the liver and responsible for degradation of excess dietary tryptophan (7, 9, 10). IDO1 is monomeric, only expressed in immune and inflammatory sites and mostly involved in immunoregulation (7, 11–13). Tryptophan catabolism by IDO1 can locally suppress T lymphocyte responses by depleting tryptophan and producing kynurenine. This immunosuppressive effect is exploited by tumors to resist immune rejection, and IDO1 inhibitors have been developed for cancer immunotherapy (3, 14). While IDO1 activity produces detectable levels of kynurenine in the blood, TDO does not as the kynurenine produced by TDO undergoes further degradation in the liver along the kynurenine pathway, leading to NAD and/or quinolinic acid (8). However, TDO activity is needed to control tryptophanemia. TDO-knockout (TDO-KO) mice and TDO-deficient humans have plasmatic tryptophan concentrations eight- to ninefold higher than wild-type mice or healthy humans (9, 15). As a result, TDO-KO mice better reject tumors and have higher levels of serotonin and other tryptophan metabolites in the brain, resulting in anxiolytic modulation and increased neurogenesis (9, 16). TDO is also expressed in some human tumors and may contribute to tumoral immune resistance (10, 16–18).     

Identification of Cellular Voids in the Human Otic Capsule

Journal of the Association for Research in Otolaryngology - The otic capsule consists of dense highly mineralized compact bone. Inner ear osteoprotegerin (OPG) effectively inhibits perilabyrinthine...