A genetic exploration of the relationship between Posttraumatic Stress Disorder and cardiovascular diseases.

Background and Aims: Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. Methods: We leveraged summary-level data of genome-wide association studies (PTSD: N= 1,222,882; atrial fibrillation (AF): N=482,409; coronary artery disease (CAD): N=1,165,690; hypertension: N=458,554; heart failure (HF): N=977,323). First, we estimated genetic correlations and utilized genomic structural equation modeling to identify a common genetic factor for PTSD and CVD. Next, we assessed biological, behavioural, and psychosocial factors as potential mediators. Finally, we employed multivariable Mendelian randomization to examine causal pathways between PTSD and CVD, incorporating the same potential mediators. Results: Significant genetic correlations were found between PTSD and CAD, HT, and HF (rg =0.21-0.32, p≤ 3.08 · 10-16), but not between PTSD and AF. Insomnia, smoking, alcohol dependence, waist-to-hip ratio, and inflammation (IL6, C-reactive protein) partly mediated these associations. Mendelian randomization indicated that PTSD causally increases CAD (IVW OR=1.53, 95% CIs=1.19-1.96, p=0.001), HF (OR=1.44, CIs=1.08-1.92, p=0.012), and to a lesser degree hypertension (OR=1.25, CIs=1.05-1.49, p=0.012). While insomnia, smoking, alcohol, and inflammation were important mediators, independent causal effects also remained. Conclusions: In addition to shared genetic liability between PTSD and CVD, we present strong evidence for causal effects of PTSD on CVD. Crucially, we implicate specific lifestyle and biological mediators (insomnia, substance use, inflammation) which has important implications for interventions to prevent CVD in PTSD patients.

Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: an in-depth genetic exploration of population samples.

Background: An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. While arrhythmic disorders play an important role in this, the nature of the relation between schizophrenia and arrhythmia is not fully understood. Methods: We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53,386 cases 77,258 controls), arrhythmic disorders (atrial fibrillation, 55,114 cases 482,295 controls; Brugada syndrome, 2,820 cases 10,001 controls) and electrocardiogram traits (heart rate (variability), PR interval, QT interval, JT interval, and QRS duration, n=46,952-293,051). First, we examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Next, we explored bidirectional causal relations between schizophrenia and arrhythmic disorders and electrocardiogram traits using Mendelian randomization. Outcomes: There was no evidence for global genetic correlations, except between schizophrenia and Brugada (rg=0·14, p=4·0E-04). In contrast, strong positive and negative local genetic correlations between schizophrenia and all cardiac traits were found across the genome. In the strongest associated regions, genes related to immune system and viral response mechanisms were overrepresented. Mendelian randomization indicated a causal, increasing effect of liability to schizophrenia on Brugada syndrome (OR=1·15, p=0·009) and heart rate during activity (beta=0·25, p=0·015). Interpretation: While there was little evidence for global genetic correlations, specific genomic regions and biological pathways important for both schizophrenia and arrhythmic disorders and electrocardiogram traits emerged. The putative causal effect of liability to schizophrenia on Brugada warrants increased cardiac monitoring and potentially early medical intervention in patients with schizophrenia. Funding: European Research Council Starting Grant.

Advanced zirconia ceramics stabilized with yttria and magnesia: Structure and Vickers microhardness.

The samples 8YSZ containing 70, 75, 80 mol% ZrO2 and other oxides were prepared by. a high temperature solid state reaction process. Using X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and spectroscopic methods were evaluated the effect of oxide addition on the properties of yttria-doped zirconia. X-ray data shows the formation of zirconia (Y-doped), YSZ and/or tetragonal zirconia crystalline phases in all samples. IR data indicate the stretching vibrations of the Si-O bonds from tetrahedral [SiO4] units and the stretching vibrations of the Fe-O bonds from [FeO6] structural units, respectively. EPR results indicate the destroying of the local ordering of the Fe+3 ion vicinities situated in the rhombic distorted octahedral geometries by the increasing of ZrO2 content in the host ceramic. The highest values of Vickers hardness were recorded for the ceramics containing 70 and 75 mol% ZrO2. This superior performance can be explained considering the presence of a smaller amount of monoclinic ZrO2 crystalline phase in the ceramic structure. The analysis of the X-ray Absorption Near Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS) data shows the presence of Fe+2 and Fe+3 ions. In the ceramics with higher ZrO2 contents the iron atoms adopt a randomly structure due to the highly distorted [FeO6] structural units and non-equivalent Fe-O distances in the first coordination shell.

Exploring the Relationship Between Schizophrenia and Cardiovascular Disease: A Genetic Correlation and Multivariable Mendelian Randomization Study.

Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to unravel the nature of this relationship. We obtained summary-data of genome-wide-association studies of schizophrenia (N = 130 644), heart failure (N = 977 323), coronary artery disease (N = 332 477), systolic and diastolic blood pressure (N = 757 601), heart rate variability (N = 46 952), QT interval (N = 103 331), early repolarization and dilated cardiomyopathy ECG patterns (N = 63 700). We computed genetic correlations and conducted bi-directional Mendelian randomization (MR) to assess causality. With multivariable MR, we investigated whether causal effects were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. Genetic correlations between schizophrenia and CVD were close to zero (-0.02-0.04). There was evidence that liability to schizophrenia causally increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization pattern, largely mediated by BMI and lipids. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting clinical studies. There was weak evidence that higher systolic blood pressure increases schizophrenia risk. Our finding that liability to schizophrenia increases heart failure is consistent with the notion that schizophrenia involves a systemic dysregulation of the body with detrimental effects on the heart. To decrease cardiovascular mortality among individuals with schizophrenia, priority should lie with optimal treatment in early stages of psychosis.

Insulin resistance and gray matter volume in neurodegenerative disease.

The goal of this study was to compare insulin resistance in aging and aging-related neurodegenerative diseases, and to determine the relationship between insulin resistance and gray matter volume (GMV) in each cohort using an unbiased, voxel-based approach. Insulin resistance was estimated in apparently healthy elderly control (HC, n=21) and neurodegenerative disease (Alzheimer's disease (AD), n=20; Parkinson's disease (PD), n=22) groups using Homeostasis Model Assessment of Insulin Resistance 2 (HOMA2) and intravenous glucose tolerance test (IVGTT). HOMA2 and GMV were assessed within groups through General Linear Model multiple regression. We found that HOMA2 was increased in both AD and PD compared to the HC group (HC vs. AD, p=0.002, HC vs. PD, p=0.003), although only AD subjects exhibited increased fasting glucose (p=0.005). Furthermore, our voxel-based morphometry analysis revealed that HOMA2 was related to GMV in all cohorts in a region-specific manner (p<0.001, uncorrected). Significant relationships were observed in the medial prefrontal cortex (HC), medial temporal regions (AD), and parietal regions (PD). Finally, the directionality of the relationship between HOMA2 and GMV was disease-specific. Both HC and AD subjects exhibited negative relationships between HOMA2 and brain volume (increased HOMA2 associated with decreased brain volume), while a positive relationship was observed in PD. This cross-sectional study suggests that insulin resistance is increased in neurodegenerative disease, and that individuals with AD appear to have more severe metabolic dysfunction than individuals with PD or PD dementia.

Expresión de HSP60 en infecciones murinas experimentales por Trypanosoma evansi / HSP60 expression in experimental murine infections by Trypanosoma evansi

La inducción de la síntesis de proteínas de choque térmico ha sido relacionada con la defensa del organismo frente a infecciones diversas. Este trabajo examina la acumulación de Hsp60 en Mus musculus infectados experimentalmente con un aislado equinos de Trypanosoma evansi, agente etiológico de la “derrengadera” en los Llanos venezolanos. Ratones NMRI (♀; 20 gr de peso corporal), normales e inmunosuprimidos (ciclofosfamida; 250 mg/kg) fueron inoculados intradermicamente con 1 tripomastigote/gr de peso corporal. La acumulación de Hsp60 se determinó mediante Western blot con el uso de un anticuerpo monoclonal en muestras de plasma obtenidas cada cuatro días post-inoculación. Los niveles de parasitemia también fueron registrados. Se observa acumulación diferencial y variable de Hsp60 que se correlaciona la parasitemia y la condición inmune del hospedador. Los resultados sugieren un control inmunológico en la regulación de la expresión de Hsp60, cuyos patrones de expresión dependen de la condición fisiológica del hospedador y los niveles de parasitemia.

Heat shock protein induction has been related to organism defense in diverse kinds of infection. This investigation examines Hsp60 accumulation in Mus musculus infected ex - perimentally with Trypanosoma evansi isolated from horse. This parasite is the causal agent of the “derrengadera” in Venezuelan planes. Normal and immunosupressed (cyclophosphamide( 250 mg/kg).) NMRI mice (♂; 20 gr body weight) were intra-dermal inoculated with 1 trypomastigote/ gr body weight; control groups were injected with distillated water in the same conditions. Hsp60 accumulation was analyzed by Western blot with a monoclonal antibody in plasma samples obtained each four days post-inoculation. Parasitemia levels were also registered. We observed a differential accumulation of Hsp60, which correlates with pa - rasitemia and immune conditions of the host. These results suggest an immunological control of Hsp60 expression that depends on the physiological condition of the host and parasitemia.

Transanal rectocele repair using linear stapler and bioabsorbable staple line reinforcement material: short-term results of a prospective study.

PURPOSE: This study was designed to determine the short-term results of transanal rectocele repair with use of a linear stapler and Bioabsorbable Seamguard. METHODS: Ten women (median age, 56.1 y) with obstructed defecation syndrome were enrolled in the study. The preoperative study consisted of a medical history, physical examination, anoscopy, endoanal ultrasound, and defecography. All patients completed a severity score and a visual analog scale for global quality of life, and provided the postoperative dates of complications. RESULTS: Overall, the treatment significantly improved the obstructed defecation: the severity score improved from a median of 19.8 +/- 4.2 at baseline to 6.10 +/- 8.2 at one month (P < .005), 5.9 +/- 8.3 at 6 months (P < .005), and 6 +/- 8.3 at one year after the operation (P < .005). A significant improvement was observed in the visual analog scale, which improved from a median of 1.8 +/- 1.4 at baseline to 6 +/- 1.6 at one month (P < .005), 6.6 +/- 2.1 at 6 months (P < .004), and 7 +/- 2.5 at one year (P < .004). A significant improvement was also observed in various symptoms. Only 2 patients manifested urgent defecation. CONCLUSIONS: The present study demonstrates that rectocele repair using a linear stapler and Seamguard is a safe, easy procedure, with a very low rate of complications and good immediate outcome.

Evaluation by three-dimensional anal endosonography of injectable silicone biomaterial (PTQ) implants to treat fecal incontinence: long-term localization and relation with the deterioration of the continence.

BACKGROUND: The purposes of the study were the long-term evaluation of silicone implants with three-dimensional (3D) anal endosonography and its correlation with anal incontinence. METHODS: Fifteen patients were injected with silicone because of anal incontinence and co-existing internal anal sphincter disruption (n = 8) or thinning (n = 7). The evaluation was performed with the Wexner score and 3D anal endosonographies. RESULTS: Forty-four implants were performed. The endosonography at 3 months detected that all the implants were properly located. At 24 months, it detected 37/44 implants of initially injected and 33/37 were properly located. Four of 37 implants had moved and 7/44 were neither in the anus nor in the rectum. A total of 8/15 patients had their implants correctly placed. Globally, silicone implants significantly improved fecal continence. CONCLUSIONS: The silicone implants might have moved or even be lost. The continence deterioration suffered by most patients after the first year of the injection has no relation with the localization and number of implants that the patients have.

Evaluation of the use of PTQ implants for the treatment of incontinent patients due to internal anal sphincter dysfunction.

OBJECTIVE: This study reports the results of injectable silicone PTQ implants for faecal incontinence due to internal anal sphincter (IAS) dysfunction. METHOD: Twenty patients (12 women) with partial faecal incontinence aged from 55 to 65 years were treated by a PTQ implant. All patients completed the Cleveland Clinic Continence and Quality of Life questionnaire. Endoluminal ultrasound and anorectal physiological testing were performed in each patient. All implants were inserted into the submucosal plane without ultrasound guidance. RESULTS: Faecal continence was significantly improved up to 1 year. The Wexner continence score fell from a median of 13.05 (range, 5-20) before treatment to 4.5 (range 2-7.7) at 1 month after (P < 0.005). This rose gradually to 6.2 (range, 0-16) at one year (P = 0.02) and 9.4 (range, 1-20) at 2 years (P = 0.127). There were no differences in resting or squeeze pressure before and at 3 months after treatment (P = 0.86 and P = 0.93). Fourteen (70%) patients experienced pruritus ani during the first few weeks after the procedure and one developed infection at the implant site. CONCLUSION: Silicone implantation is minimally invasive and technically simple. It is effective over 1 year in the treatment of faecal incontinence due to IAS dysfunction.

Use of anorectal ultrasounds in perianal Crohn's disease: consistency with clinical data.

BACKGROUND: anorectal ultrasonography (ARU) is a simple technique, and its diagnostic value for anorectal diseases either in conventional subjects or in patients with Crohn s disease (CD) is insufficiently reported. The objective of this study is to evaluate the use of ARU, its consistency with clinical orientation, and its ability to provide relevant information for patients with bowel CD and perianal involvement. METHODS: thirty ARUs were performed for 24 patients (17 male, mean age 35,7 years; range 19-59 years) with diagnosed CD (bowel and anorectal involvement). The reason to perform an ARU was to evaluate an anal fistula (15 patients, 50%), potential abscesses (9 patients, 30%), and fecal incontinence (2 patients, 6,6%), and for post-treatment monitoring purposes (4 patients, 13,3%). RESULTS: diagnostic orientation coincided for 14 patients (46,6%). An abscess was found in eight patients (26,6%), and five patients were clinically suspicious. The abscess was postanal in 3 patients. Fistulas were found in 17 patients (56,6%), and 15 patients were clinically suspicious. Transsphincterian fistulas were observed in seven patients, and abscesses were associated with fistula in six patients. Transsphincteric defects were observed in 10 patients (four internal sphincters, one external sphincter, and five both) but only two patients suffered from incontinence. ARU provided data relevant to therapeutic approach in 19 patients (63,3%). CONCLUSIONS: ARU has provided very important data for the diagnosis and treatment of anorectal diseases. Based on this technique clinical decisions can be improved, which in some instances may prove critical.

Bioabsorbable staple-line reinforcement to reduce staple-line bleeding in the transection of mesenteric vessels during laparoscopic colorectal resection: a pilot study.

BACKGROUND: Staple line hemorrhage and leak are the 2 most dreaded complications of laparoscopyassisted resection of colorectal cancer (LARCC). Recently, anastomotic staple lines have been reinforced with a range of absorbable and non-absorbable bioprosthetic reinforcement materials. This pilot prospective study used the bioabsorbable Seamguard (BSG; WL Gore & Associates, Flagstaff, AZ) for routine reinforcement of the mesenteric vascular staple transection to prevent mesenteric hemorrhage and to assess its safety and feasibility in a consecutive series of laparoscopic colonic resections. METHODS: Twenty-five patients consecutively scheduled to undergo LARCC were enrolled in the study. All operations were performed with a standard LARCC technique which included loading of the BSG sleeves onto the jaws of the cutter/stapler. RESULTS: There were 23 wholly LARCC cases and 2 open conversions. BSG was used in all 25 patients. No patient experienced staple-line bleeding or other complications during the surgical procedure. The mean number of staple-line reinforcement sleeves used was 2.6 (range, 2-4). The mean operative time was 118 minutes (range, 65-184 minutes). Additional measures to achieve hemostasis were not required in any case. The mean cost was US 475.20 dollars for the procedure. CONCLUSIONS: This small pilot study has shown the routine use of BSG mesenteric staple line reinforcement to be safe, quick and effective during LARCC.

Acetylcholinesterase inhibition in the threeridge mussel (Amblema plicata) by chlorpyrifos: implications for biomonitoring.

The effects of chlorpyrifos, an organophosphorus insecticide, were examined on the activity of the nervous system enzyme acetylcholinesterase (AChE) in the threeridge mussel Amblema plicata in a 24-day laboratory test. Thirty-six mussels in each of seven treatments (18 mussels per duplicate) were exposed to chlorpyrifos (0.1, 0.2, 0.3, 0.6, and 1.2 mg/L), a solvent (acetone), and a solvent-free (well water) control for 12, 24, or 96 h. The activity of AChE was measured in the anterior adductor muscle of eight mussels from each treatment after exposure. To assess potential latent effects, six mussels from each treatment were removed after 24 h of exposure and transferred to untreated water for a 21-day holding period; AChE activity was measured on three mussels from each treatment at 7 and 21 days of the holding period. The activity of AChE in chlorpyrifos-exposed mussels did not differ from controls after 12 or 24 h of exposure (t- test, P>0.05), but was significantly less than controls after 96 h (t- test, P=0.01). AChE activity did not vary among mussels at 24 h of exposure (i.e., Day 0 of holding period) and those at Day 7 and Day 21 of the holding period. Overall changes in AChE activity of mussels during the test were unrelated to individual chlorpyrifos concentrations and exposure times (repeated measure ANOVA; (P=0.06). A power analysis revealed that the sample size must be increased from 2 to 5 replicates (8 to 20 mussels per time interval and test concentration) to increase the probability of detecting significant differences in AChE activity. This calculated increase in sample size has potential implications for future biomonitoring studies with chlorpyrifos and unionid mussels.

[Prevalence of migraine among primary- and secondary-school students in Mérida, Venezuela]. / Prevalencia de la migraña en estudiantes de educación básica y media de Mérida, Venezuela.

OBJECTIVE: The epidemiological impact of headaches in populations is not adequately known since most of the data come from clinical studies. Therefore, we decided to survey a population of students in the municipality of Libertador, in the state of Mérida, Venezuela, to determine the prevalence of migraines, the incapacitating effect of headaches in general, and the proportion of individuals who self-medicate. METHODS: We first used stratified sampling to choose schools in the municipality, and then simple random sampling to select which classrooms to survey. A total of 1,714 students, ranging in age from 10 to 21 years old, completed a survey. RESULTS: Among the students, 84.4% of them reported having had headaches, and 16.8% of them reported experiencing migraines. We did not find a noticeable incapacitating effect of migraines in this population. Of the students who had had headaches, 69.2% of them did not request medical care, and 80.3% of them reported self-medicating. CONCLUSIONS: From these results we conclude that migraines are very frequent among this population. Judging from the levels of self-medication and the lack of medical attention for headaches, we believe there is a shortfall in health services coverage and a deficiency in public information, which together lead to an underreporting of headaches.

Mechanical stabilization in the mandibular anterior segment.

Teeth in the mandibular anterior region of the mouth, affected by years of periodontal disease and resultant bone loss, frequently require treatment for the patient to be able to chew comfortably and effectively. Often patients choose to keep compromised teeth, despite being presented with treatment options involving a fixed or removable prosthesis. In these situations, mechanical stabilization becomes necessary. Current treatment possibilities include bonding with resin composite or placement of a bonded metal mesh splint, a cast metal resin-bonded retainer, or a fiber-reinforced resin composite splint. Coupled with good oral hygiene practices, these mechanical stabilization techniques can provide increased oral comfort and improved function, especially for geriatric dental patients.

Interdisciplinary management of a common esthetic complaint.

Esthetic restoration of the maxillary anterior dentition often requires an integrated perio-restorative team approach. Careful attention to treatment planning and treatment sequencing is essential in ensuring a desirable outcome and a satisfied patient. Detailed measurements, diagnostic wax-ups, surgical mock-ups, and stents all are effective communication tools which can be used to enhance interdisciplinary communication. These concepts and treatment modalities are illustrated in this case report.