The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

Periosteal transplantation to the rabbit patella

Autologous periosteal transplantation (without chondrocyte cell transplantation) for treating traumatic articular cartilage defects of the patella gives pain relief in uncontrolled clinical studies. To study the whole transplanted area macroscopically and microscopically, animal studies are motivated. In this pilot study, we reproduce the surgical technique for periosteum transplantation on human patella to a rabbit model. A full-thickness cartilage defect of the whole patella was created in eight adult female rabbits. The defect was treated with autologous periosteal transplantation. After surgery, the rabbits were allowed free activity. This is the difference compared to the treatment in humans, where our group uses CPM for 5 days and non-weight-bearing for 12 weeks. After 21 weeks, there was a diffuse synovitis in all transplanted knees, and in five of eight knees there were signs of osteoarthritis in the patello-femoral joint. Histologically, in three animals, small islands of hyaline cartilage surrounded by fibrocartilage were seen in the transplanted area. In the other five animals, fibrocartilage was the predominant tissue. In contrast to previous experimental studies using a rabbit model, we did not achieve hyaline cartilage resurfacing.     

Improvements to a method for determining leg length following total hip arthroplasty

Abstract

Discrepancy in leg length does frequently occur as a side effect of total hip arthroplasty and may lead to reduced patient satisfaction as well as injury in the sequalae. It is consequently important to reduce leg length discrepancy where-ever technically possible. This may be achieved by recording precise intraoperative measurements and using different sized implanted components. The aim of the given study was to improve the accuracy of a previously validated optic measurement system (OMS) to reduce leg length discrepancy. This pre-existing OMS was first trialled and based on these preliminary findings developed further. Using this improved system, measurements were taken in models and cadavers. Inter observer reliability of the improved OMS was assessed. The system is introduced in the given technical feasibility study. Its accuracy was greater in the model setup (swivel joint: 772.7?±?1.5?mm; ball joint: 770.0?±?3.7?mm; reference: 772?mm) compared to the trial using cadaveric tissues (588.8?±?5.7?mm; reference: 586?mm). Results of two examiners were similar. The third one measured significantly shorter values (p=.011). The results of the measurements with the OMS indicate that a significant increase in accuracy (p?=?2.076×¹⁰?⁶) has been achieved compared to the previously reported system, however, a further improvement to measurement accuracy is necessary for this to be applied clinically.     

Does a torn anterior cruciate ligament lead to change in the central nervous drive of the knee extensors?

Summary Integrated surface electromyograms of the three superficial parts of the quadriceps and isokinetic knee extensor maximum torque and power production were recorded simultaneously and at different angular velocities in both legs in 11 male subjects with unilateral tear of the anterior cruciate ligament. The cross-sectional area (CSA) of the thigh and its muscular components were measured by computerized tomography. The principal findings were a small but significant decrease in quadriceps CSA on the affected side; a decreased active, but not passive, range of movement; decreased mechanical output, whether or not corrected for differences in CSA; and decreased electrornyographic activity — particularly in rectus femoris. These findings suggest that the reason for the decreased maximum and total knee extensor performance seen in these patients is a change in knee joint receptor afferent inflow.     

Expression of candidate tumor markers in ovarian carcinoma and benign ovary: evidence for a link between epithelial phenotype and neoplasia

EpCAM, epithelial membrane antigen (EMA)-mucin 1 (MUC1), mesothelin, and CD9 have been reported to be overexpressed at the RNA level in ovarian carcinomas. By using immunohistochemistry, we profiled the protein expression of these gene products in ovarian carcinoma tissues and compared them with benign ovarian surface epithelium (OSE) and cortical inclusion cysts (CICs). Immunoreactivity for EMA and calretinin were used to define epithelial and mesothelial differentiation in nontumor tissues, respectively. Papillary serous (n = 16) and endometrioid (n = 10) tumors were immunopositive for EMA/MUC1 (100%), mesothelin (75% and 30%, respectively), CD9 (88% and 90%, respectively), and EpCAM (100%). All ovarian carcinomas and carcinoma cell lines tested were negative for calretinin. In nonneoplastic ovary, both OSE and CICs ranged from flat-to-cuboidal to stratified and ciliated in appearance. OSE with a cuboidal morphology had a similar immunoreactivity as omental peritoneum, expressing calretinin, mesothelin, and CD9. In contrast, CICs with stratified and ciliated epithelium show expression patterns similar to those in fallopian tubes. They frequently expressed EMA, EpCAM, mesothelin, and CD9. This immunophenotype is preserved in ovarian carcinomas, suggesting that Müllerian metaplasia signals the acquisition of these markers and that their expression is maintained in ovarian carcinomas that originate from this epithelium.     

Monoclonal antibody Leu-22 (L60) permits the demonstration of some neoplastic T cells in routinely fixed and paraffin-embedded tissue sections

Monoclonal antibody Leu-22 (L60) detects a T cell-associated antigen which is stably expressed in routinely fixed and paraffin-embedded tissue sections. We investigated the utility of monoclonal antibody Leu-22 to immunophenotype routinely processed lymphoid neoplasms by determining its reactivity in 105 archival pathologic specimens of lymphoid neoplasia that had been previously immunophenotyped by standard cell suspension and frozen tissue section techniques. Monoclonal antibody Leu-22 reacted with 69% of T cell non-Hodgkin's lymphomas (NHLs), including cases belonging to each of the major clinicopathologic categories, and with 22% of B cell NHLs, but did not react with the Reed-Sternberg (RS) cells of Hodgkin's disease (HD). We concluded that monoclonal antibody Leu-22 reacts preferentially but not exclusively with T cell NHLs. Therefore, we performed parallel analyses of the same 105 cases with monoclonal antibodies leukocyte common antigen (LCA), Leu-M1, LN1, and LN2, which detect various paraffin-resistant antigens, and of 80 of these cases with monoclonal antibody UCHL1, which detects a paraffin-resistant T cell-associated antigen. UCHL1 reacted with 61% of the T cell NHLs studied. Sixty-nine percent of T cell NHLs expressed the LCA+, Leu-22+ or Leu-M1+, LN1- phenotype and 47% of B cell NHLs expressed the LCA+, Leu-22-, Leu-M1-, LN1+ phenotype. These phenotypes had a false-positive rate of only 7%. The substitution of UCHL1 for Leu-22 or the combined use of UCHL1 and Leu-22 in this panel did not improve our ability to correctly predict the T cell phenotype of these lymphoid neoplasms. LN1 and LN2 reacted with 13% and 56% of T cell NHLs, respectively, and LN2 reacted with RS cells in 85% of cases of HD. In summary, our results demonstrate that the judicious use of monoclonal antibody Leu-22 in combination with other selected commercially available monoclonal antibodies permits the determination of the B cell or T cell origin of a high proportion of NHLs, and is helpful in the differential diagnosis between HD and NHL among cases that have been routinely fixed and paraffin-embedded.     

Inflammation and the Association of Vitamin D and Depressive Symptomatology

Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes’ PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: −0.0042) and a model including covariates (ab: −0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.     

Erratum zu: Durchimpfung von Kindern und Jugendlichen in Deutschland: Aktuelle Daten aus KiGGS Welle 2 und Trends aus der KiGGS-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Ein Erratum zu dieser Publikation wurde veröffentlicht: https://doi.org/10.1007/s00103-019-02901-5     

Coronary heart disease risk factors in black and white patients with non‐insulin‐dependent diabetes mellitus

Objective. To determine possible racial differences in risk factors for coronary heart disease (CHD) in black and white patients with noninsulin‐dependent diabetes mellitus (NIDDM).

Methods: Study of risk factors for coronary heart disease among 308 subjects who met the WHO criteria for NIDDM.

Results. Both black and white patients were found to have a high prevalence of hypertension, obesity, low high density lipoprotein (HDL) cholesterol, low leisure‐time physical activity levels, and an atherogenic dietary profile. Black males were more likely to have hypertension, reported a greater intake of dietary cholesterol, and had lower triglycerides, higher HDL cholesterol levels, a lower CHOL/HDL ratio, and a lower waist to hip ratio (WHR) than white males. Black females had higher mean arterial and diastolic blood pressures, had lower triglycerides, higher HDL cholesterol, a lower CHOL/HDL ratio, a higher subscapular/triceps ratio and lower reported leisure‐time energy expenditure compared to white females. There were no racial differences found for obesity level.

Conclusion. Our results indicate that racial differences in CHD risk factors exist among black and white patients with NIDDM. The complex genetic, sociocultural and environmental interactions involving CHD risk factors that contribute to the development of CHD may eventually provide clues to the etiology of the disease.     

Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

PURPOSE: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes. METHODS: Data were drawn from a cross-sectional face-to-face survey of randomly selected African American (n=220), Native American (n=181), and white (n=297) Medicare beneficiaries > or =65 years old with diabetes in 2 rural counties in central North Carolina. Participants were asked about utilization of a primary care doctor and of specialists (nutritionist, diabetes specialist, eye doctor, bladder specialist, kidney specialist, heart specialist, foot specialist) in the past year. FINDINGS: Virtually all respondents (99.0%) reported having a primary care doctor and seeing that doctor in the past year. About 42% reported seeing a doctor for diabetes-related care. On average, participants reported seeing 2 specialists in the past year, and 54% reported i seeing >1 specialist. Few reported seeing a diabetes specialist (5.7%), nutritionist (10.9%), or kidney specialist (17.5%). African Americans were more likely than others to report seeing a foot specialist (P < .01), while men were more likely than women to have seen bladder specialist (P = .02), kidney specialist (P = .001), and heart specialist (P = .004), after adjusting for potential confounders. Predictors of the number of specialists seen include gender, education, poverty status, diabetes medication use, and self-rated health. CONCLUSIONS: These data indicate low utilization of specialty diabetes care providers across ethnic groups and reflect the importance of primary care providers in diabetes care in rural areas.