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Abstract Objective The aim of the present study was to assess the need for secondary palatal corrective surgery in a concept of palate repair that uses a protocol of anterior to posterior closure of primary palate, hard palate and soft palate. Methods A data base of patients primarily operated between 2001 and 2021 at the Craniofacial and Cleft Care Center of the University Goettingen was evaluated. Cleft lips had been repaired using Tennison Randall and Veau-Cronin procedures in conjunction with alveolar cleft repair. Cleft palate repair in CLP patients was accomplished in two steps with repair of primary palate and hard palate first using vomer flaps at the age of 10–12 months and subsequent soft palate closure using Veau/two-flap procedures 3 months later. Isolated cleft palate repair was performed in a one-stage operation using Veau/two-flap procedures. Data on age, sex, type of cleft, date and type of surgery, occurrence and location of oronasal fistulae, date and type of secondary surgery performed for correction of oronasal fistula (ONF)and / or Velophyaryngeal Insufficiency (VPI) were extracted. The rate of skeletal corrective surgery was registered as a proxy for surgery induced facial growth disturbance. Results In the 195 patients with non-syndromic complete CLP evaluated, a total number of 446 operations had been performed for repair of alveolar cleft and cleft palate repair (Veau I through IV). In 1 patient (0,5%), an ONF occurred requiring secondary repair. Moreover, secondary surgery for correction of VPI was required in 1 patient (0,5%) resulting in an overall rate of 1% of secondary palatal surgery. Skeletal corrective surgery was indicated in 6 patients (19,3%) with complete CLP in the age group of 15 – 22 years (n = 31). Conclusions The presented data have shown that two-step sequential cleft palate closure of primary palate and hard palate first followed by soft palate closure has been associated with minimal rate of secondary corrective surgery for ONF and VPI at a relatively low need for surgical skeletal correction.

BackgroundCoronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.MethodsWe performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.ResultsWe replicated 2 loci (rs9369640 and rs9349379 near PHACTR1 and rs10757278 near CDKN2B) for CAC and one locus for cIMT (rs7412 and rs445925 near APOE-APOC1) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near CSNK1A1L/LINC00547/POSTN at 13q13.3) at P=2.0×10-8 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints POSTN, encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (P

Background. Medication-related osteonecrosis of the jaw (MRONJ) is a rare, serious, and debilitating disease of unknown cause that can be associated with significant health-related quality of life (HRQOL) impairment. Hematological disease is characterized by a nonhealing exposed jawbone in patients with a history of antiresorptive or antiangiogenic agent use without radiation exposure to the head or neck. Patients and Materials and Methods. This prospective study over the period from May 2020 to December 2021 included a representative sample consisting of 27 patients with at least stage 2 MRONJ lesions who underwent surgical rehabilitation via oral and maxillofacial surgery at the University Medical Center Göttingen, Germany. Quality of life data were collected over a 6-month postoperative period using the Health-Related QOL (SF-12) and Oral Health-Related QOL (OHIP-14) questionnaires. Results. A total of 27 patients considered in the study had a total of 42 MRONJ lesions, corresponding to a mean of 1.56 necroses per patient. MRONJ lesions were downstaged in 85% of the patients. HRQOL was evaluated with the SF-12 questionnaire. Significant improvements were found in six of the eight categories (General Health (p

Localized jawbone invasion is a milestone in the progression of oral squamous cell carcinoma (OSCC). The factors that promote this process are not well understood. Sclerostin is known to be involved in bone metabolism and there are preliminary reports of its involvement in bone tumors and bone metastasis. To identify a possible involvement of sclerostin in the bone invasion process of OSCC, sclerostin expression was analyzed in vitro in two different human OSCC tumor cell lines by quantitative real-time polymerase chain reaction (qRT-PCR), and the effect of recombinant human (rh)-sclerostin treatment on tumor cell capabilities was evaluated using proliferation, migration, and invasion assays. Undifferentiated human mesenchymal stem cells (hMSCs) were osteogenically differentiated and co-cultured with OSCC tumor cells to demonstrate potential interactions and migration characteristics. Sclerostin expression was evaluated in clinical cases by immunohistochemistry at the OSCC–jawbone interface in a cohort of 15 patients. Sclerostin expression was detected in both OSCC tumor cell lines in vitro and was also detected at the OSCC–jawbone interface in clinical cases. Tumor cell proliferation rate, migration and invasion ability were increased by rh-sclerostin treatment. The migration rate of tumor cells co-cultured with osteogenically differentiated hMSCs was increased. The results presented are the first data suggesting a possible involvement of sclerostin in the bone invasion process of OSCC, which deserves further investigation and may be a potential approach for drug-based tumor therapy.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Abstract Background & Objectives Calcitonin gene-related peptide ligand/receptor (CGRP) antibodies effectively reduce headache frequency in migraine. It is understood that they act peripherally, which raises the question whether treatment merely interferes with the last stage of headache generation or, alternatively, causes secondary adaptations in the central nervous system and might thus possess disease modifying potential. This study addresses this question by investigating the nociceptive blink reflex (nBR), which is closely tied to central disease activity, before and after treatment with CGRP antibodies. Methods We enrolled 22 patients suffering episodic migraine (21 female, 46.2 ± 13.8 years of age) and 22 age-/gender-matched controls. Patients received assessments of the nBR (R2 component, 10 trials, 6 stimuli/trial) before (V0) and three months (V3) after treatment with CGRP antibodies started, controls were assessed once. The R2 area (R2a) and habituation (R2h; gradient of R2a against stimulus order) of the stimulated/non-stimulated side (_s/_ns) following repeated supraorbital stimulation provide a direct readout of brainstem excitability and habituation as key mechanisms in migraine. Results All patients showed a substantial reduction of headache days/month (V0: 12.4±3.3, V3: 6.6 ± 4.9). R2a_s (Fglobal=5.86, p

BackgroundThe burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease. We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent coronary heart disease.Methods and resultsWe studied a total of 25 109 European ancestry and African ancestry participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52 869 participants with common carotid intima-media thickness measured by ultrasonography within the CHARGE Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology). Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and carotid intima-media thickness. APOB p.Arg3527Gln was associated with 4-fold excess CAC (P=3×10-10). The APOE ε2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1×10-12) and 1.4% reduced carotid intima-media thickness (P=4×10-14) in carriers compared with noncarriers. In secondary analyses conditioning on low-density lipoprotein cholesterol concentration, the ε2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of ε2 was associated with reduced risk for coronary heart disease (odds ratio 0.77; P=1×10-11).ConclusionsExome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE ε2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease.

Background: Changes in the proteome of oral cells during periodontitis have rarely been investigated. This lack of information is partially attributed to the lack of human cell lines derived from the oral cavity for in vitro research. The objective of the present study was to create cell lines from relevant oral tissues and compare protein expression in cells cultured alone and in cells co-cultivated with periodontitis-associated bacterial strains. Methods: We established human cell lines of gingival keratinocytes, osteoblastic lineage cells from the alveolar bone, periodontal ligament fibroblasts, and cementum cells. Using state-of-the-art label-free mass spectrometry, we investigated changes in the proteomes of these cells after co-cultivation with Aggregatibacter actinomycetemcomitans and Eikenella corrodens for 48 h. Results: Gingival keratinocytes, representing ectodermal cells, exhibited decreased expression of specific keratins, basement membrane components, and cell-cell contact proteins after cultivation with the bacterial strains. Mesodermal lineage cells generally exhibited similar proteomes after co-cultivation with bacteria; in particular, collagens and integrins were expressed at higher levels. Conclusions: The results of the present study will help us elucidate the cellular mechanisms of periodontitis. Although co-cultivation with two periodontitis-associated bacterial strains significantly altered the proteomes of oral cells, future research is needed to examine the effects of complex biofilms mimicking in vivo conditions.

Personal, work, and societal concerns about obesity and body fatness have triggered research on it across multiple domains. However, the organizational literature has been hampered by a significant shortcoming in considering it solely as an objective construct, despite research in other disciplines demonstrating a critical subjective component to how body fatness is experienced. To address this conceptual and theoretical challenge, we draw on stigma theory to explore the workplace implications of subjective fatness, or how big one feels in their own mind. We utilize and extend stigma theory by integrating it with medical research. In doing so, we shed new light on the subjective nature of the self-devaluation process that occurs in stigmatized individuals. We argue that this self-devaluation process is the mechanism by which subjective body fatness influences work performance. We test these hypotheses across three studies that constructively replicate results across multiple design types (multi-rater, time-lagged, & bivariate latent-change model) and diverse geographic samples. Results consistently show that subjective fatness exerts a stronger impact on performance than objective fatness, and this influence ismediated by self-devaluation. In all, our work indicates it is not how big one is but how big one feels that most affects work performance. [ABSTRACT FROM AUTHOR]

Aim. We analyzed the added value of sTfR measurement in routine clinical practice to standard parameters (SP) of iron deficiency in the detection of iron deficiency anemia (IDA) in patients with rheumatoid arthritis (RA). Methods. Blood samples from 116 patients with RA were analyzed in a prospective study. Based on biochemical parameters, patients were classified as having IDA, anemia of chronic disease (ACD), IDA with concomitant ACD (ACD/IDA), or “other anemia.” Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of sTfR and SP of iron status alone and in combination were calculated for the diagnosis of IDA in general, i.e., IDA or ACD/IDA. Results. In the whole sample, with regard to the diagnosis of iron deficiency (IDA or ACD/IDA), sTfR had a higher sensitivity compared both to the combined use of SP and to the combination of SP with sTfR (80.9% versus 66.7/54.8%). Specificity, PPV and NPV did not differ substantially. When patients were stratified in groups with high (CRP levels above the median, i.e., 24.1 mg/l) and low (CRP levels less or equal to the median) inflammation, the diagnostic superiority of sTfR was restricted to patients with high inflammation. In this group, the diagnostic performance of sTfR was superior both to the combined use of SP and the combination of SP with sTfR with higher sensitivity (100% versus 52.4%) and NPV (100% versus 77.7/76.7%) and comparable specificity and PPV. Conclusion. For the detection of iron depletion (IDA or ACD/IDA) in anemic RA patients, sTfR is superior to SP of iron deficiency only in highly inflammatory states.

Objective: Several studies revealed relations between low or high insulin -like growth factor I (IGF-I) levels and risk of cardiovascular diseases or mortality, whereas the mechanisms be hind these associations are still unknown. Design: The study aimed to explore the relations between IGF-I and cha nges in surrogate markers of cardiovascular disease including carotid intima-media thickness (IMT), left ve ntricular mass index (LVMI) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Methods: Longitudinal data of the population-based cohort Study of Heal th in Pomerania (SHIP) were used. IMT was measured by ultrasonography and LVMI was determined based on ec hocardiography. IGF-I and IGF-binding protein-3 (IGFBP-3) levels were measured by chemiluminescent immunoassays and the IGF-I/IGFBP-3 ratio was calculated. Mixed linear regression models adjusted for known cardiovascular conf ounders were performed. Results: Statistical analyses demonstrated relations between low baseli ne IGF-I levels (beta for ΔIMT per s.d. increase −0.044 (s.e. 0.012)) or IGF-I/IGFBP-3 ratio (beta −0.045 (0.012)) and a long-term IMT increase. No associations be tween IGF-I, IGFBP-3 or IGF-I/IGFBP-3 ratio and changes in LVMI were detected. With respect to NT-proBNP sex-specific associations with IGF-I were found. In women, higher baseline I GF-I levels (beta for ΔNT-proBNP per s.d. increase 5.92 (2.2)) or IGF-I/IGFBP-3 ratio (beta 4.48 (2.2)) were related to an increase in NT-proBNP levels. Among men, U-shaped relations of baseline levels of IGF-I, IGFBP-3 and the IGF-I/IG FBP-3 ratio with an increase in NT-proBNP were found. Conclusions: The study detected significant relations between IGF-I and long -term changes in IMT and NT-proBNP but not LVMI. These findings argue for different effects of the IGF-I axis with respect to various cardiovascular entities.

ABSTRACT The gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is linked to an increased risk for cardiovascular diseases. Trimethylamine (TMA), which is subsequently oxidized to TMAO in the liver, is formed by intestinal bacteria via distinct biochemical routes from dietary precursors that are enriched in animal product-based foods. To get a full picture of the entire process of the diet > gut microbiota > TMAO axis, we quantified potential TMA-forming gut bacteria and plasma metabolites using gene-targeted assays and targeted metabolomics on a subsample (n = 425) of a German population-based cohort study. We specifically compared persons reporting daily meat intake with those that rarely or never consume meat. While meat intake did not predict TMAO plasma levels in our study, two major bacterial TMA-forming pathways were linked to the metabolite’s concentration. Furthermore, advancing age was strongly associated with TMAO. Construction of a structural equation model allowed us to disentangle the different routes that promote higher TMAO levels with increasing age, demonstrating, for the first time, a functional role of gut microbiota in the process, where specific food items augmented abundances of TMA-forming bacteria that were associated with higher TMAO plasma concentrations. Analyses stratified by age showed an association between carotid intima-media thickness and TMAO only in individuals >65 of age, indicating that this group is particularly affected by the metabolite. IMPORTANCE Many cohort studies have investigated the link between diet and plasma TMAO levels, reporting incongruent results, while gut microbiota were only recently included into analyses. In these studies, taxonomic data were recorded that are not a good proxy for TMA formation, as specific members of various taxa exhibit genes catalyzing this reaction, demanding function-based technologies for accurate quantification of TMA-synthesizing bacteria. Using this approach, we demonstrated that abundances of the main components leading to TMAO formation, i.e., TMA precursors and TMA-forming bacteria, are uncoupled and not governed by the same (dietary) factors. Results emphasize that all levels leading to TMA(O) formation should be considered for accurate risk assessment, rejecting the simple view that diets rich in TMA precursors directly lead to increased plasma levels of this hazardous compound. The results can assist in developing strategies to reduce TMAO levels, specifically in the elderly, who are prone to TMAO-associated diseases.

Despite celebrations from governments, corporations and international financial institutions around increasing economic growth, the majority of the world’s urban labour force continues to work under informal conditions, lacking enforceable contracts, adequate earnings, democratic representation, secure employment and social protection. The pervasiveness of informal labour globally has given rise to numerous calls to adopt a wider and more diverse understanding of what constitutes labouring classes and what is required to organise them. Our case study assesses the outcomes and effectiveness of informal sector organising in Uganda, focusing on the transportation, market and textile sectors. Drawing on Guy Standing’s distinction between “business” and “community” unions and Benjamin Selwyn’s contrasting of “capital-centred development theory” (CCDT) and “labour-led development” (LLD), we argue that community unionist approaches are most effective in addressing the decent work deficit in the informal economy. Simultaneously, the trade unions face constant barriers to successful community organising in the informal economy that cannot be easily overcome without wider changes to the structural conditions under which union organisers must operate. KEYWORDS: Trade unionism; informal labour organising; labour-centred development; Uganda; decent work

This Phase IV placebo-controlled clinical trial was designed to demonstrate the efficacy and safety of the product Neurodoron (Kalium phosporicum comp., KPC) in patients with neurasthenia. This monocenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (registration number: DRKS00003261) was conducted in an outpatient German trial site. Women and men aged 18 and above were randomized to receive either KPC or placebo if they reported typical symptoms of neurasthenia and a severe psychiatric disorder could be excluded. The primary objectives were a reduction in characteristic symptoms of nervous exhaustion and perceived stress as well as improvement in general health status after 6 weeks of treatment. In total, 204 patients underwent screening, 78 were randomized in each treatment group, and 77 patients each received treatment (intention-to-treat (ITT) population = 154 patients). For none of the primary efficacy variables, an advantage in favor of KPC could be demonstrated in the pre-specified analysis (p-values between 0.505–0.773, Student's t-test). In a post-hoc analysis of intra-individual differences after 6 weeks treatment, a significant advantage of KPC vs. placebo was shown for characteristic symptoms of nervous exhaustion (irritability (p = 0.020); nervousness (p = 0.045), Student's t-test). Adverse event (AE) rates were similar between treatment groups, in both groups six AEs were assessed as causally related to treatment (severity mild or moderate). No AE resulted in discontinuation of treatment. Trial treatment was well tolerated with only a few and minor AEs reported, confirming the markedly good safety of KPC. A significant improvement of neurasthenia was seen for the total study population at the end of the treatment period. Superiority of KPC vs. placebo could not be demonstrated with the pre-specified analysis with regards to a sum score of 12 typical symptoms, perceived stress, or general health status. However, the explorative post-hoc analysis revealed that KPC is superior to placebo in the characteristic symptoms irritability and nervousness. KPC could therefore be a beneficial treatment option for symptomatic relief of neurasthenia. [ABSTRACT FROM AUTHOR]

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Introduction: The aim of this study was to investigate the effect of dihydrotestosterone (DHT), 17-β-estrogen (E2), genistein (GEN) and equol (EQ) on bone remodeling and bone morphology during healing of osteoporotic male rat tibiae. Materials and methods: 180 Sprague-Dawley male rats were divided in 5 groups of 36 animals. After orchidectomy (ORX) and development of osteoporosis, trepanation of the tibia was performed. Until the time of trepanation all groups received soya free food (SF), then food change occurred and treatment started. At day 95, 102 and 151, samples were taken and histomorphometry was performed to analyze changes in bone structure under treatment. At day 33 and 70 all animals received calcein respective alizarin for polychrome bone labeling. Results: The cortical bone was particularly affected. Treatment with DHT and E2 led to a significant long-term expansion of the thickness of the diaphyseal cortical bone, while the phytoestrogens EQ and GEN only had a positive short-term effect in this area. Only E2 preserved the trabecular bone for a limited time. In all groups, periosteal and endosteal bone areas showed the highest bone formation activity. The osteoporotic male injured bone shows a shift in mineral apposition rate (MAR) from periosteal to endosteal bone in the SF, DHT and E2 groups but not in the GEN and EQ phytohormones groups. An MAR decrease in trabecular bone formation was observed at day 70 in all groups except the E2 group. Conclusion: We conclude from our results that healing of cortical bone defects in a rat model of male osteoporosis are mainly influenced by the estrogen pathway. Nevertheless, effects via purely androgenic mechanisms can also be demonstrated. The role of a phytohormone therapy is only marginal and if only useful for a short-term supportive approach. The role of the periosteal to endosteal shift during male osteoporotic bone healing needs to be further examined.

Background: Cumulative evidence suggests that both traumatic stress and posttraumatic stress disorder (PTSD) are cross-sectionally and prospectively linked to cardiovascular disease (CVD). However, their association with proxy markers of atherosclerosis has hardly been investigated. Objective: The objective of this general population study was to relate traumatic stress and PTSD to carotid plaque and intima-media thickness (cIMT). Methods: 3119 adults from the general population were assessed regarding their traditional cardiovascular risk factors, and an ultrasound of the carotid arteries was performed in each participant. Based on a PTSD interview, every participant was assigned to one of three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. The sample was stratified into five age groups. Results: Trauma exposure was reported by 54.5% of the sample and 2.0% had PTSD. Traumatized participants had increased odds of self-reported CVD events compared to those without trauma exposure, even when accounted for CVD risk factors and other covariates (odds ratio [OR] = 1.51; 95% confidence interval [CI]: 1.03–2.22). This association was driven by those aged 70 years or older. Only in those aged 40 to 49 years, there was an association between cIMT and PTSD. There were no further associations between carotid plaque or cIMT and traumatic stress or PTSD. Conclusions: Our findings in concert with prior research suggest that the association between traumatic stress, PTSD and atherosclerosis as well as its clinical endpoints is complex and remains inconclusive.

Introduction: About 10,000 escalator-related injuries per year result in emergency department treatment in the United States. Since the 1990s, a steady increase has been reported, but few statistics on escalator-related injuries have been published worldwide. We have therefore analyzed escalator accident statistics in admissions to our hospital in Switzerland since 2000.Methods: Using retrospective electronic patient chart analysis, we included in our study patients >16 years treated over an 11-year period. We categorized patients in terms of gender, age and associated risk factors, and classified accidents according to day, time, location and cause. Resulting trauma was categorized according to type and location. We divided post-admission treatment into surgical and conservative, and into treatment as an outpatient, in a short-stay unit, or as a hospital admission. Women and men were compared using Fisher’s exact test. Results: We identified 173 patients with 285 discrete injuries. Of these, 87 patients (50%) were women. Fifty-three (61%) of the women and 38 (44%) of the men were >60 years old (P = 0.033). Fifty percent of the men (43/86)of the men, but only 7% (6/87) of the women showed signs of alcohol intoxication (P < 0.0001). Accidents in women occurred predominantly on Tuesdays (19/87; 22%) between 12PM and 6PM (35/87; 40%), and in men on Saturdays (16/86; 19%) between 6PM and 12AM (29/86; 34%; P = 0.0097). Sixty-two percent (44/71) of the accidents were in public transport facilities and 30% (21/71) in shopping centers. The majority of injuries in women were to the lower extremities (49/87; 56%), while most accidents in men were to the head and neck (51/86; 59%; P = 0.0052). About half (90; 52%) of the patients were treated conservatively. Almost half of all patients (76, 44%) required hospital admission. Of those, 45% left the hospital within 24 hours of admission (short stay unit) and 55% stayed longer than 24 hours.Conclusion: Escalator accidents can result in severe trauma. Significant gender differences in escalator accidents have been observed. Alcohol intoxication and age are significant risk factors in escalator-related accidents and might be possible targets for preventive measures. [West J Emerg Med 2013;14(2):141-145.]

Background Common carotid intima–media thickness (cIMT) is a biomarker for subclinical atherosclerosis and is associated with all‐cause as well as cardiovascular mortality. Higher cIMT is accompanied by a compensatory increase in lumen diameter (LD) of the common carotid arteries. Whether cIMT or LD carry more information with regard to mortality is unclear. Methods and Results A total of 2751 subjects (median age 53 years; 52% female) were included. During a median follow‐up of 14.9 years (range: 12.8–16.5) a total of 506 subjects died. At baseline, cIMT and LD were assessed by carotid ultrasound scans. Multivariable Cox regression models were used to relate cIMT, LD, LD adjusted for cIMT (LD+cIMT), and LD/cIMT ratio with all‐cause, cardiovascular, and noncardiovascular mortality. All models were ranked using Akaike's information criterion. Harrel's c statistic was used to compare the models' predictive power for mortality. A 1‐mm increase in LD was related to a higher risk for all‐cause mortality (hazard ratio [HR], 1.29; 95% CI, 1.14–1.45, P

Abstract Background Clefts in newborns are associated with severe morphological and functional impairment. Especially the lip is of importance as if the treatment result is unsatisfactory, it can lead to psychological changes in the patient. Different operative procedures have been developed over the last decades. The aim of the presented study was the comparison of the surgical techniques according to Millard and Pfeifer regarding the temporal development of the postoperative symmetry of the lip height and mouth width. Methods Digitized photographs of patients from the department of oral and maxillofacial surgery at the University of Göttingen were evaluated from 1979 to 1996. With a video analysis program, the lip height and mouth width were analyzed regarding the symmetry. We demonstrated the symmetry values over a period of 8 years in order to show the influence of growth on postoperative results. Results The development of the vertical symmetry of the Philtrum and the lip vermillion on the cleft side in comparison to the healthy side behaves differently depending on Pfeifer and Millard. The lip height of the cleft lip was shorter in both techniques than on the healthy side, but Pfeifer’s difference was significantly more pronounced. The lip vermillion height on the cleft side was slightly shorter in the Millard group and markedly larger in the Pfeifer group. Both techniques can achieve good symmetry results for the vertical dimension of the lip. According to Pfeifer, the development of the horizontal dimension on the cleft side is bigger within the first 4 years than on the healthy side; according to the Millard technique, the horizontal development is smaller. These differences are greater within the first 6 years and approach between the 6th and 8th year. Conclusions The Millard technique demonstrates better results concerning the philtrum and vermillion symmetry during growth within the first 6 years. Over the whole study period, growth corrects the philtrum and vermillion symmetry within the Pfeifer group.

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS). Here the authors find that DNA methylation at HLA-DRB1 gene mediates the effect of DRB1*15:01 and of a protective HLA variant on HLA-DRB1 expression and the risk of MS.

Abstract Introduction We sought to investigate associations of regional white matter hyperintensities (WMHs) within white matter (WM) tracts with cardiovascular risk and brain aging‐related atrophy throughout adulthood in the general population, leveraging state of the art pattern analysis methods. Methods We analyzed a large sample (n = 2367) from the Study of Health in Pomerania, Germany (range 20–90 years). WMHs were automatically segmented on T1‐weighted and fluid‐attenuated inversion recovery magnetic resonance images, and WMH volumes were calculated in WM regions defined using the John Hopkins University WM tractography atlas. Regions with the highest average WMH volume were selected. We calculated a subject‐specific index, Spatial Pattern of Alteration for Recognition of Brain Aging, to measure age‐related atrophy patterns. The Framingham cardiovascular disease risk score summarized the individual cardiovascular risk profile. We used structural equation models, independently for each region, using Spatial Pattern of Alteration for Recognition of Brain Aging as a dependent variable, age as an independent variable, and cardiovascular disease risk score and regional WMH volumes as mediators. Results Selected 12 WM regions included 75% of the total WMH burden in average. Structural equation models showed that the age effect on Spatial Pattern of Alteration for Recognition of Brain Aging was mediated by WMHs to a different extent in the superior frontal WM, anterior corona radiata, inferior frontal WM, superior corona radiata, superior longitudinal fasciculus, middle temporal WM, posterior corona radiata, superior parietal WM, splenium of corpus callosum, posterior thalamic radiation, and middle occipital WM (variance explained between 2.8% and 10.3%, P