Protein 4.1B suppresses prostate cancer progression and metastasis

Protein 4.1B is a 4.1/ezrin/radixin/moesin domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers, and breast carcinomas. However, its potential tumor-suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Down-regulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. Because expression of Protein 4.1B is frequently down-regulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.     

Linkage study of fibrinogen levels: the Strong Heart Family Study

Background

A common SNP upstream of the INSIG2 gene, rs7566605 (g.-10,1025G>C, Chr2:118,552,255, NT_022135.15), was reported to be associated with obesity (Body Mass Index, [BMI]) in a genome-wide association scan using the Framingham Heart Study but has not been reproduced in other cohorts. As BMI is a relatively insensitive measure of adiposity that is subject to many confounding variables, we sought to determine the relationship between the INSIG2 SNP and subcutaneous fat volumes measured by MRI in a young adult population.

Methods

We genotyped the INSIG2 SNP rs7566605 in college-aged population enrolled in a controlled resistance-training program, (the Functional Polymorphism Associated with Human Muscle Size and Strength, FAMuSS cohort, n = 752 volunteers 18–40 yrs). In this longitudinal study, we examined the effect of the INSIG2 polymorphism on subcutaneous fat and muscle volumes of the upper arm measured by magnetic resonance imaging (MRI) before and after 12 wks of resistance training. Gene/phenotype associations were tested using an analysis of covariance model with age and weight as covariates. Further, the % variation in each phenotype attributable to genotype was determined using hierarchical models and tested with a likelihood ratio test.

Results

Women with a copy of the C allele had higher levels of baseline subcutaneous fat (GG: n = 139; 243473 ± 5713 mm³ vs. GC/CC: n = 181; 268521 ± 5003 mm³; p = 0.0011); but men did not show any such association. Men homozygous for the G ancestral allele showed a loss of subcutaneous fat, while those with one or two copies of the C allele gained a greater percentage of subcutaneous fat with resistance training (GG: n = 103; 1.02% ± 1.74% vs. GC/CC: n = 93; 6.39% ± 1.82%; p = 0.035).

Conclusion

Our results show that the INSIG2 rs7566605 polymorphism underlies variation in subcutaneous adiposity in young adult women and suppresses the positive effects of resistance training on men. This supports and extends the original finding that there is an association between measures of obesity and INSIG2 rs7566605 and further implicates this polymorphism in fat regulation.     

Increasing sleep duration to lower beat‐to‐beat blood pressure: a pilot study

Strong evidence has accumulated over the last several years, showing that low sleep quantity and/or quality plays an important role in the elevation of blood pressure. We hypothesized that increasing sleep duration serves as an effective behavioral strategy to reduce blood pressure in prehypertension or type 1 hypertension. Twenty‐two participants with prehypertension or stage 1 hypertension, and habitual sleep durations of 7 h or less, participated in a 6‐week intervention study. Subjects were randomized to a sleep extension group (48 ± 12 years, N = 13) aiming to increase bedtime by 1 h daily over a 6‐week intervention period, or to a sleep maintenance group (47 ± 12 years, N = 9) aiming to maintain habitual bedtimes. Both groups received sleep hygiene instructions. Beat‐to‐beat blood pressure was monitored over 24 h, and 24‐h urine and a fasting blood sample were collected pre‐ and post‐intervention. Subjects in the sleep extension group increased their actigraphy‐assessed daily sleep duration by 35 ± 9 min, while subjects in the sleep maintenance condition increased slightly by 4 ± 9 min (P = 0.03 for group effect). Systolic and diastolic beat‐to‐beat blood pressure averaged across the 24‐h recording period significantly decreased from pre‐ to post‐intervention visit in the sleep extension group by 14 ± 3 and 8 ± 3 mmHg, respectively (P < 0.05). Though the reduction of 7 ± 5 and 3 ± 4 mmHg in the sleep maintenance group was not significant, it did not differ from the blood pressure reduction in the sleep extension group (P = 0.15 for interaction effect). These changes were not paralleled by pre‐ to post‐intervention changes in inflammatory or sympatho‐adrenal markers, nor by changes in caloric intake. While these preliminary findings have to be interpreted with caution due to the small sample size, they encourage future investigations to test whether behavioral interventions designed to increase sleep duration serve as an effective strategy in the treatment of hypertension.     

A novel,hydroxyapatite-based screw-like device for anterior cruciate ligament (ACL) reconstructions

Background

Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries of the knee. Common techniques for ACL reconstruction require a graft fixation using interference screws. Nowadays, these interference screws are normally made of titanium or polymer/ceramic composites. The main challenge of application of a fixation device made entirely of bioactive ceramic is in relation to the low strength of such materials. The purpose of this study was to evaluate a novel geometry for a fixation device made of pure hydroxyapatite for ACL reconstructions that can overcome some problems of the titanium and the polymer/ceramic screws.

Survival among children with “Lethal” congenital contracture syndrome 11 caused by novel mutations in the gliomedin gene (GLDN)

Biallelic GLDN mutations have recently been identified among infants with lethal congenital contracture syndrome 11 (LCCS11). GLDN encodes gliomedin, a protein required for the formation of the nodes of Ranvier and development of the human peripheral nervous system. We report six infants and children from four unrelated families with biallelic GLDN mutations, four of whom survived beyond the neonatal period into infancy, childhood, and late adolescence with intensive care and chronic respiratory and nutritional support. Our findings expand the genotypic and phenotypic spectrum of LCCS11 and demonstrate that the condition may not necessarily be lethal in the neonatal period.     

Autism: exploring historical psychiatric and psychological concepts

Autism today is a widely used term, yet what is understood by autism has changed considerably since first being introduced in scientific discourse almost 100 years ago. Autism is one example for the influence of the psychoanalytic school of Sigmund Freud on scientific psychiatry at the beginning of the 20th century. In particular psychoanalysis had an impact on Eugen Bleuler's concept of schizophrenia. The Swiss psychiatrist did not only acknowledge and follow a biological, but also a psychological approach to psychiatry and thus opened up his subject to psychoanalytic thoughts. This paper provides insights into the term's conceptual history--or, more specifically and precisely--sheds light on the expansion of the term's scope, which has gotten to be used for more and more symptoms and phenomena. When Bleuler first presented the term autism, he used it to refer to a classical schizophrenic symptom. Since, however, Bleuler was not very specific and exclusive in his definition, the term was soon used for other phenomena as well, such as to describe a schizoid symptom in the sense of today's schizoid personality disorder (schizoid autism). The concepts of autistic hebephrenia and depressive autism are further examples how the term was used and give insight into how the contents behind the term changed, got less and less specific and widened its scope. Due to its growing vagueness its suitability and usability as a psychopathological term decreased. This process further was strengthened when the word autism got more and more widely used in colloquial language for different aspects of day-to-day routine and thinking. Thus in psychiatry today, autism is exclusively used in connection with the so-called autism spectrum disorders, but has, as other formerly exclusively technical terms, different and rather unspecific meanings in everyday communication.     

"On hidden madness"--"De amentia occulta" by Ernst Platner in early 19th-century tension of medicine and jurisprudence

During the first half of the 19th century psychiatry became more and more influential in the evaluation of mentally ill offenders. "Doubtful" states of mind gained a particular importance for forensic practice. One of the mental disorders that was heavily disputed was amentia occulta (hidden madness) first described by the well-known Leipzig doctor and philosopher Ernst Platner. This publication (1797) preluded several other diagnoses to refer to non-obvious, "hidden mental derangements". Regardless of the differences in arguments as developed by the experts in question (E. T. A. Hoffmann, Merzdorff, E. Horn, J. C. A. Clarus), two case studies from the early 19 (th) century (D. Schmolling, J. C. Woyzeck) will exemplify the process of medicine, and psychiatry in particular, becoming more and more influential in everyday jurisdictional practice. The above-mentioned Ernst Platner, the author of manifold forensic studies and of "De amentia occulta", was one of the pioneers and promoters of this process. By emphasising the importance of mental states being evaluated by medical professionals he contributed a great deal to the establishment of forensic psychiatry.