Asymptomatic Healthy Controls Research Articles

390 Opioids Interfere With Deglutitive Inhibition Assessed by Response to Multiple Rapid Swallows During High Resolution Esophageal Manometry

INTRODUCTION: We previously showed an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and Jackhammer esophagus. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during MRS followed by an augmented contraction with higher vigor than single swallows. Hypothesis: during MRS, opioids may interfere with deglutitive inhibition and may enhance post MRS contraction. Aim: compare response to MRS in opioid users, non-users and healthy controls. METHODS: Response to MRS was evaluated in 200 patients with esophageal symptoms (100 chronic opioid users on oxycodone, hydrocodone, or tramadol for ≥3 months, 100 not on opioids), and 19 asymptomatic healthy controls that underwent HRM. Patients with prior gastroesophageal surgery, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, esophageal stricture, achalasia type I or II, and scleroderma were excluded. Demographic and symptom data were extracted from a prospectively maintained motility database. Response to MRS was evaluated for complete versus incomplete inhibition (contractility with DCI >100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than mean DCI for single swallows). Categorical variables were analyzed by chi square. RESULTS: Patients were older than controls (Table 1). HRM indications are shown in Table 2. Incomplete inhibition during MRS was significantly more frequent in chronic opioid users compared to patients not on opioids and healthy controls (26% vs 11% vs 0% P = 0.002; Figure 1). There was a significant difference in the rate of incomplete MRS inhibition for patients on oxycodone, hydrocodone, and tramadol (27% vs 34% vs 22% P = 0.002). The proportion of patients with augmentation post MRS was similar for opioid users, non-opioid users and healthy controls (P = 0.05). CONCLUSION: Impaired deglutitive inhibition during MRS was significantly more frequent among opioid users compared to non-opioid users and healthy controls. This was more common with stronger opioids (oxycodone and hydrocodone) compared to tramadol. These findings support our hypothesis that opioids interfere with inhibitory signals in the esophagus.

434 Response to Multiple Rapid Swallows Shows Impairment of Inhibitory Pathways in Patients With Distal Esophageal Spasm

INTRODUCTION: Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during the MRS sequence. We hypothesize that deglutitive inhibition is impaired in DES patients. Aim: compare response to MRS in DES patients and healthy controls. METHODS: Response to MRS was evaluated in 19 DES patients and 24 asymptomatic healthy controls. Demographic and symptom data were extracted from a prospectively maintained motility database. Patients with history of prior gastroesophageal surgery, endoscopic myotomy (POEM), pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, and esophageal stricture were excluded. HRM was performed with a solid state catheter with 36 circumferential pressure sensors 1-cm apart; ten 5-ml liquid swallows were given followed by MRS sequence, analyzed with Manoview software (Medtronic). Esophagogastric junction integrated relaxation pressure (IRP), distal contractile integral (DCI), and distal latency (DL) were calculated, and Chicago Classification v3.0 was applied to diagnose DES (defined by ≥ 2 swallows with DL ≤ 4.5 sec). Response to MRS was evaluated for complete versus impaired inhibition (contractility with DCI > 100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than single-swallow mean DCI). Chi-Square and Fisher’s exact test were used for statistical analysis. RESULTS: Demographics and symptom data are shown in Table 1. Patients with DES were older and more symptomatic than controls. Impaired inhibition of peristalsis during MRS was significantly more frequent in DES compared to controls (89% vs 0%, P < 0.001, Figure 1). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3788 vs 1239, P = 0.013). CONCLUSION: Impaired deglutitive inhibition during MRS is present in the majority of patients with DES, supporting impaired inhibitory pathways in the esophagus as a mechanism of action in this disorder.

Down regulation of RANTES in pleural site is associated with inhibition of antigen specific response in tuberculosis

Tuberculosis is the most common infectious reason for death and a major cause of pleural effusion globally. To understand the role of chemokines in trafficking of cells during TB pleurisy, we studied the responses to MTB, Ag85A in cells from pleural fluids and peripheral blood. Patients with TB pleural effusions, malignant effusions and asymptomatic healthy controls were enrolled. High expression (p < 0.05) of IP-10, MCP-1, MIG, IL-8, IFN-γ and IL-23 were observed in pleural fluids of TB patients compared to their plasma where expression of RANTES was significantly higher (p < 0.05). On specific stimulation of PFMCs with Ag85A, expression of RANTES was significantly lower in TB compared to NTB patients. We also observed increased expression of T regs and PD1 on CD8+T cells in PFMC of TB patients. Though some of the inflammatory chemokine/cytokines were up-regulated in pleura of TB patients, antigenic stimulation failed to induce them indicating poor antigenic responses at the site. Low expression of RANTES might be a reason for decreased trafficking of cells to the site and dissemination of infection into pleural site. The pattern of RANTES expression in pleural fluid vs serum is interesting. The observations necessitate further studies to investigate the levels of RANTES for its potential biological relevance in TB immunity and its use as a biomarker for diagnosis of pleural TB.

Upper esophageal sphincter metrics on high-resolution manometry differentiate etiologies of esophagogastric junction outflow obstruction.

Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM), particularly nadir UES residual pressure (UES-RP), are abnormal in achalasia and may help characterize the underlying mechanism or predict management outcome in esophagogastric junction outflow obstruction (EGJOO). A database of consecutive patients undergoing esophageal HRM from 2008 to 2013 yielded 134 patients (59.8±1.4years, 68% F) with EGJOO. Final clinical diagnoses and treatment response were extracted from chart review. Esophageal body, UES, and lower esophageal sphincter (LES) metrics were compared between EGJOO and asymptomatic healthy controls (n=16, 27.7±0.7years, 56% F). Logistic regression evaluated differences between HRM metrics amongst etiologies of EGJOO grouped into motor versus mechanical disorders. Distal contractile integral, distal latency, and nadir UES-RP were significantly different between EGJOO subgroups (P≤0.01 for each comparison), but only nadir UES-RP remained independently predictive of subgroups (adjusted odds ratio 1.15, 95% confidence intervals 1.05-1.27, P<0.01). Nadir UES-RP was highest in achalasia variants, and lowest in mechanical EGJOO and controls (P<0.001). Of 19 patients who underwent LES myotomy, durable benefit was reported by 68.4% over mean 3.6years of follow-up. Significantly higher nadir UES-RP was noted with symptom relief (3.4 vs -0.7mmHg with symptom recurrence, 95% confidence intervals of difference=1.35-6.83). A threshold UES-RP of ≥2.0mmHg yielded a sensitivity of 84.6% and specificity of 83.3% in predicting symptom resolution following myotomy. Nadir UES-RP offers clues to differentiation of subtypes within EGJOO and may predict symptom outcome from myotomy.

Correlations between masticatory muscle activity, quality of life, and dysfunction severity in women with chronic temporomandibular disorder

ABSTRACT BACKGROUND AND OBJECTIVES: Assessing the possible interactions between the activity of masticatory muscles and quality of life and severity of the temporomandibular disorder can help clarify how changes in muscle activity can be associated with a chronic temporomandibular disorder in women. This study aimed to investigate the correlations between masticatory electrical activity during mandibular resting, maximum voluntary contraction, the severity of the temporomandibular disorder, and quality of life in women with chronic temporomandibular disorder and to compare these parameters with healthy asymptomatic controls. METHODS: Sixty women, 30 with temporomandibular disorder and 30 asymptomatic, participated in this case-control observational study. Diagnostic Criteria for Temporomandibular Disorder was used to identify the presence or absence of temporomandibular disorder. The SF-36 questionnaire was used to assess the quality of life in participants, and ProTMDmulti-part-II was applied to assess the severity of signs and symptoms of temporomandibular disorder. RESULTS: During jaw clenching, the masticatory activity of the right temporal and left masseter muscles, the symmetry of the masseter muscles, and anteroposterior coefficient were significantly smaller in the temporomandibular disorder group than in the asymptomatic group. Masticatory activity at rest, signs and symptoms of chronic temporomandibular disorder, and impairment of the quality of life were correlated using Spearman coefficient (p<0.05). CONCLUSION: Our results contribute to findings on the associations between the masticatory activity in chronic signs and symptoms of the temporomandibular disorder, impairment in quality of life, and differences in the masticatory activity during clenching in patients with temporomandibular disorder and controls.

Impact of asymptomatic hypertension on left and right ventricular functions by echocardiography

Background: Hypertension generally has no symptoms and is called the silent killer as the first warning presentation may itself be a cardiac failure or myocardial infarction, which is often massive and fatal. Hypertension many times remains asymptomatic for several years and is detected on regular health check-ups. Aims and Objective: The objective of this study is to study the cardiac changes in both right and left ventricles by echocardiography in asymptomatic hypertensive participants. Materials and Methods: Twenty-five asymptomatic cases and 29 normotensive controls (total 54 participants) were studied. All the participants were male aged between 20 years and 60 years and above. Clinical evaluation was done by determining their age, systolic and diastolic blood pressures, heart rate, and symptoms. Cardiac structural and functional changes were studied by echocardiogram. Cardiac output, stroke volume, left ventricular (LV) mass, right ventricular thickness, LV systolic and diastolic dimensions and functions, fractional fiber shortening, and ejection fraction were studied in both cases and controls. Results: There was a change in LV mass in asymptomatic hypertensive participants when compared with control participants. There was a statistically significant change in LV mass measured in grams (weight) showing P < 0.001 (0.00 vs. 0.00) in asymptomatic cases and healthy normotensive controls, and the LV posterior wall also showed a statistically significant change with P < 0.001 (0.008 vs. 0.009) in asymptomatic cases and normotensive controls. Conclusions: There is increased cardiac mortality and morbidity in asymptomatic hypertensive participants in whom the cardiac damage is concealed, compared with symptomatic hypertensives who consult a physician as soon as symptoms are felt.

A pilot study investigating circulating trimethylamine N-oxide and its precursors in dogs with degenerative mitral valve disease with or without congestive heart failure.

BackgroundPathophysiologic mechanisms for the development and progression of degenerative mitral valve disease (DMVD) remain elusive. Increased concentrations of circulating trimethylamine N‐oxide (TMAO) and its precursors choline and l‐carnitine are associated with the presence and severity of heart disease in people.ObjectivesTo determine if differences exist in plasma concentrations of TMAO, choline, or l‐carnitine among dogs with DMVD and congestive heart failure (CHF), dogs with asymptomatic DMVD, and healthy control dogs.AnimalsThirty client‐owned dogs: 10 dogs with CHF secondary to DMVD, 10 dogs with asymptomatic DMVD, and 10 healthy control dogs.MethodsA pilot cross‐sectional study in which echocardiography was performed and fasting plasma concentrations of TMAO, choline, and l‐carnitine (total and fractions) were measured.ResultsTMAO (P = .03), total l‐carnitine (P = .03), carnitine esters (P = .05), and carnitine esters to free carnitine ratio (E/F ratio; P = .05) were significantly higher in dogs with CHF compared to those with asymptomatic DMVD. TMAO (P = .02), choline (P = .01), total l‐carnitine (P = .01), carnitine esters (P = .02), free carnitine (P = .02), and E/F ratio (P = .009) were significantly higher in dogs with CHF compared to healthy controls.Conclusions and Clinical ImportanceDogs with CHF secondary to DMVD had higher concentrations of TMAO compared to both asymptomatic DMVD dogs and healthy controls. Larger prospective studies are warranted to determine if TMAO plays a role in the development or progression of DMVD or CHF.

Association between gastric myoelectric activity disturbances and dyspeptic symptoms in gastrointestinal cancer patients

PurposeDyspeptic symptoms present a severe problem in gastrointestinal (GI) cancer patients. The aim of the study was to analyze an association between gastric myoelectric activity changes and dyspeptic symptoms in gastrointestinal cancer patients. Material and MethodsThe study included 80 patients (37 men and 43 women, mean age 61.2 ± 7.8 years) diagnosed with GI tract malignancies: colon (group A), rectal (group B) and gastric cancers (group C). Gastric myoelectric activity in a preprandial and postprandial state was determined by means of a 4-channel electrogastrography. Autonomic nervous system was studied based on heart rate variability analysis. The results were compared with the data from healthy asymptomatic controls. ResultsIn a fasted state, GI cancer patients presented with lesser percentages of normogastria time (A:44.23 vs. B:46.5 vs. C:47.10 vs. Control:78.2%) and average percentage slow wave coupling (ACSWC) (A:47.1 vs. B:50.8 vs. C:47.2 vs. Control:74.9%), and with higher values of dominant power (A:12.8 vs. B:11.7 vs. C:12.3 vs. Control:10.9) than the controls. Patients did not show an improvement in the percentage of normogastria time, dominant power, dominant frequency and ACSWC in response to food. The severity of dyspeptic symptoms correlated with the values of electrogastrography parameters. Patients showed lower values of heart rate variability parameters than the healthy controls, that indicate abnormal autonomic nervous system activity. ConclusionGI cancers affect the gastric myoelectric activity, decreasing normogastria and slow wave coupling. These patients do not show adequate gastric motility response to food. Impaired gastric electric motility may result from cancer-induced autonomic disturbances.

Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease.

Background: Archaeal genes present in Trypanosoma cruzi may represent symbionts that would explain development of heart failure in 30% of Chagas disease patients. Extracellular vesicles in peripheral blood, called exosomes (< 0.1 μm) or microvesicles (>0.1 μm), present in larger numbers in heart failure, were analyzed to determine whether they are derived from archaea in heart failure Chagas disease.Methods: Exosomes and microvesicles in serum supernatant from 3 groups were analyzed: heart failure Chagas disease (N = 26), asymptomatic indeterminate form (N = 21) and healthy non-chagasic control (N = 16). Samples were quantified with transmission electron microscopy, flow cytometer immunolabeled with anti-archaemetzincin-1 antibody (AMZ 1, archaea collagenase) and probe anti-archaeal DNA and zymography to determine AMZ1 (Archaeal metalloproteinase) activity.Results: Indeterminate form patients had higher median numbers of exosomes/case vs. heart failure patients (58.5 vs. 25.5, P < 0.001), higher exosome content of AMZ1 antigens (2.0 vs. 0.0; P < 0.001), and lower archaeal DNA content (0.2 vs. 1.5, P = 0.02). A positive correlation between exosomes and AMZ1 content was seen in indeterminate form (r = 0.5, P < 0.001), but not in heart failure patients (r = 0.002, P = 0.98). Higher free archaeal DNA (63.0 vs. 11.1, P < 0.001) in correlation with exosome numbers (r = 0.66, P = 0.01) was seen in heart failure but not in indeterminate form (r = 0.29, P = 0.10). Flow cytometer showed higher numbers of AMZ1 microvesicles in indeterminate form (64 vs. 36, P = 0.02) and higher archaeal DNA microvesicles in heart failure (8.1 vs. 0.9, P < 0.001). Zymography showed strong% collagenase activity in HF group, mild activity in IF compared to non-chagasic healthy group (121 ± 14, 106 ± 13 and 100; P < 0.001).Conclusions: Numerous exosomes, possibly removing and degrading abnormal AMZ1 collagenase, are associated with indeterminate form. Archaeal microvesicles and their exosomes, possibly associated with release of archaeal AMZ1 in heart failure, are future candidates of heart failure biomarkers if confirmed in larger series, and the therapeutic focus in the treatment of Chagas disease.

Subjects with medial and lateral tibiofemoral articular cartilage defects do not alter compartmental loading during walking

BackgroundHealthy cartilage is essential for optimal joint function. Although, articular cartilage defects are highly prevalent in the active population and hamper joint function, the effect of articular cartilage defects on knee loading is not yet documented. Therefore, the present study compared knee contact forces and pressures between patients with tibiofemoral cartilage defects and healthy controls. Potentially this provides additional insights in movement adaptations and the role of altered loading in the progression from defect towards OA. MethodsExperimental gait data collected in 15 patients with isolated cartilage defects (8 medial involvement, 7 lateral-involvement) and 19 healthy asymptomatic controls was processed using a musculoskeletal model to calculate contact forces and pressures. Differences between two patient groups and controls were evaluated using Kruskal-Wallis tests and individually compared using Mann-Whitney-U tests (alpha <0.05). FindingsThe patients with lateral involvement walked significantly slower compared to the healthy controls. No movement adaptations to decrease the loading on the injured condyle were observed. Additionally, the location of loading was not significantly affected. InterpretationThe current results suggest that isolated cartilage defects do not induce significant changes in the knee joint loading distribution. Consequently, the involved condyle will capture a physiological loading magnitude that should however be distributed over the cartilage surrounding the defect. This may cause local degenerative changes in the cartilage and in combination with inflammatory responses, might play a key role in the progression from articular cartilage defect to a more severe OA phenotype.

Eficacia diagnóstica de la impedancia basal nocturna media, un nuevo parámetro para el estudio de la enfermedad por reflujo gastroesofágico

Introducción y objetivos: el análisis de la impedancia basal nocturna media (IBNM) se ha propuesto para incrementar la precisión diagnóstica de enfermedad por reflujo erosiva (ERGE). Nuestro objetivo fue evaluar el rendimiento diagnóstico de esta prueba en un grupo de pacientes con ERGE conocida.Materiales y métodos: incluimos 123 individuos (58 con ERGE y 65 controles sanos) a quienes se les realizó pH-impedanciometría (pH-IMM) consecutiva entre enero de 2015 y junio de 2017. Todos los pacientes tenían endoscopia tomada en los 6 meses previos. El tiempo de exposición ácida (TEA) anormal (&gt;4,2%) y la presencia de pirosis y/o regurgitación en los 6 meses previos fueron los criterios para el diagnóstico de ERGE. Se encontraron 58 pacientes con ERGE, 24 con enfermedad por reflujo erosiva (ERE) y 34 con enfermedad por reflujo no erosiva (ERNE). Los 65 restantes fueron controles sanos (CS) asintomáticos con EGD y pH-IMM normales. Todos los trazos de pH-IMM se reanalizaron para medir la IBNM por un segundo observador que desconocía los datos previos. El análisis estadístico incluyó pruebas múltiples de Bonferroni para comparar los grupos; regresión lineal para variables continuas; y análisis de curva ROC para buscar valor IBNM con mayor rendimiento. Para los diferentes parámetros de precisión diagnóstica se utilizó el punto de corte de la IBNM. Se usó significancia estadística con valor de p &lt;0,01 e intervalos de confianza de 95% (IC 95%) para todos los cálculos.Resultados: los pacientes con ERE y ERNE presentaron valores de IBNM significativamente más bajos que el grupo control (p &lt;0,01). Se observó una correlación negativa entre los valores de la IBNM y TEA (r = 0,59; p = &lt;0,001), y también entre la IBNM y número de eventos de reflujo (r = 0,37; p = &lt;0,001). En el análisis de curva ROC, el área bajo la curva de la IBNM fue de 0,941 (IC 95%: 0,894-0,987) y el punto de corte con mayor eficiencia 1102 ohms (sensibilidad 98,5%; especificidad 84,5%). Usando este valor (&lt;1,102), la IBNM tuvo una sensibilidad para detectar ERGE de 91% (ERNE 86% y ERE 100%) y una especificidad de 98%.Conclusión: la IBNM tiene alta sensibilidad y especificidad para el diagnóstico de la ERGE. Adicionar esta prueba al análisis convencional de la pH-impedancia y a los métodos actuales de estudio de la ERGE puede mejorar significativamente nuestra capacidad para diagnosticar la enfermedad.

Mo1521 - Examining the Deglutitive Integrated Relaxation Pressure (IRP) of the Lower Esophageal Sphincter (LES) in 60 Healthy Asymptomatic Controls and 69 Achalasia Patients

Mo1521 - Examining the Deglutitive Integrated Relaxation Pressure (IRP) of the Lower Esophageal Sphincter (LES) in 60 Healthy Asymptomatic Controls and 69 Achalasia Patients

Paper #11 - Scapular Kinematics in Asymptomatic Rotator Cuff Tears and Healthy Controls

Paper #11 - Scapular Kinematics in Asymptomatic Rotator Cuff Tears and Healthy Controls

Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy

Leber’s hereditary optic neuropathy (LHON) is the maternally inherited mitochondrial disease caused by homoplasmic mutations in mitochondrial electron transport chain Complex I subunit genes. The mechanism of its incomplete penetrance is still largely unclear. In this study, we created the patient-specific human induced pluripotent stem cells (hiPSCs) from MT-ND4 mutated LHON-affected patient, asymptomatic mutation carrier and healthy control, and differentiated them into retinal ganglion cells (RGCs). We found the defective neurite outgrowth in affected RGCs, but not in the carrier RGCs which had significant expression of SNCG gene. We observed enhanced mitochondrial biogenesis in affected and carrier derived RGCs. Surprisingly, we observed increased NADH dehydrogenase enzymatic activity of Complex I in hiPSC-derived RGCs of asymptomatic carrier, but not of the affected patient. LHON mutation substantially decreased basal respiration in both affected and unaffected carrier hiPSCs, and had the same effect on spare respiratory capacity, which ensures normal function of mitochondria in conditions of increased energy demand or environmental stress. The expression of antioxidant enzyme catalase was decreased in affected and carrier patient hiPSC-derived RGCs as compared to the healthy control, which might indicate to higher oxidative stress-enriched environment in the LHON-specific RGCs. Microarray profiling demonstrated enhanced expression of cell cycle machinery and downregulation of neuronal specific genes.

Anxiety and Insomnia in Young and Middle-Aged Adult Hip Pain Patients With and Without Femoroacetabular Impingement and Developmental Hip Dysplasia

BackgroundIn young and middle-aged adults with and without hip deformity, hip pain receives treatment focused primarily related to hip structure. Because this hip pain may be chronic, these patients develop other coexisting, modifiable disorders related to pain that may go undiagnosed in this young and active population, including insomnia and anxiety. ObjectiveThe objective of this study was to compare assessments of insomnia and anxiety in young and middle-aged adults presenting with hip pain with no greater than minimal osteoarthritis (OA) compared to asymptomatic healthy controls. Comparisons between types of hip deformity and no hip deformity in hip pain patients were performed to assess whether patients with specific hip deformities were likely to have insomnia or anxiety as a cofounding disorder to their hip pain. DesignProspective case series with control comparison. SettingTwo tertiary university physiatry outpatient clinics. ParticipantsA total of 50 hip pain patients aged 18-40 years and 50 gender- and age-matched healthy controls. MethodsPatients were enrolled if 2 provocative hip tests were found on physical examination and hip radiographs had no or minimal OA. Radiographic hip deformity measurements were completed by an independent examiner. Comparisons of insomnia and anxiety were completed between 50 hip pain patients and 50 controls and between patients with different types of hip deformity. Main Outcome MeasuresInsomnia Severity Index (ISI) and Pain Anxiety Symptoms Scale (PASS). ResultsA total of 50 hip pain patients (11 male and 39 female) with mean age of 31.2 ± 8.31 years enrolled. Hip pain patients slept significantly less (P = .001) per night than controls. Patients experienced significantly greater insomnia (P = .0001) and anxiety (P = .0001) compared to controls. No differences were found in insomnia and anxiety scores between hip pain patients with and without hip deformity or between different types of hip deformity. ConclusionHip pain patients with radiographs demonstrating minimal to no hip arthritis with and without hip deformity experience significant cofounding yet modifiable disorders of sleep and anxiety. If recognized early in presentation, treatment of insomnia and anxiety ultimately will improve outcomes for hip patients treated either conservatively or surgically for their hip disorder. Level of EvidenceII

Up-regulation of transient receptor potential vanilloid (TRPV) and down-regulation of brain-derived neurotrophic factor (BDNF) expression in patients with functional dyspepsia (FD).

The role of immune activation in Functional Dyspepsia (FD) patients without previous infection is unclear. We compare the gastric and circulating brain-derived neurotropic factor (BDNF), receptor potential vanilloid type (TRPV) families and various cytokines in FD patients. Consecutive adult FD patients (Rome III) with no recent history of gastroenteritis and asymptomatic healthy controls were recruited for upper endoscopy. Subjects with GERD and IBS as predominant symptoms, diabetes mellitus, current or previous Helicobacter pylori infection, psychiatric illness and recent use of NSAID or PPI were excluded. Corpus biopsies and serum samples were collected. Forty three [M:F=8:35, mean age: 35.0 (9.3)] FD patients were compared with 23 healthy controls [M:F=8:15, mean age: 36.6 (10.2)]. FD patients had postprandial distress syndrome (PDS) as predominant sub-type (PDS: 36, EPS: 2). There was no significant difference in the median inflammation score (FD:0 (0-1) vs Control:0 (0-1), P=.79). However, FD patients had significantly higher mRNA expression of TRPV1 (FD:0.014±0.007, Control:0.003±0.001, 4.6 fold, P=.02) and TRPV2 (FD:0.012±0.006, Control:0.003±0.001, 4 fold, P=.02) compared to controls. The serum (FD:258.0±12.3ngml-1 , Control:319.7±18.1ngml-1 , P<.01) and gastric BDNF mRNA (FD:0.06±0.008, Control:0.092±0.01, 0.65 fold, P=.02)levels significantly lower in FD patients. Secretion of cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, G-CSF, TGF-β2, MCP-1)was also highly correlated with dyspeptic symptoms in patients with FD. Despite lacking gastric mucosal inflammation, up-regulation of TRPV1 and TRPV2, down-regulation of BDNF were observed in FD patients. These suggest that immune alteration may contribute to the pathogenesis of FD without any previous infection.

19. Amygdala Subnuclei Volumes Differ among PTSD, Asymptomatic Trauma-Exposed and Healthy Individuals

The clinical consequences of trauma differ across individuals: while some develop post-traumatic stress disorder (PTSD), others may not present with significant psychopathology. A growing body of evidence is pointing to the anatomical and physiological properties of the fear conditioning circuitry, and the amygdala in particular, as the substrate that explains different trauma-related clinical trajectories. In this study we use validated atlas-based methods to assess differences in the volumes of key amygdala subnuclei across patients with PTSD, asymptomatic trauma-expose individuals and healthy controls.

Hip biomechanics during stair ascent and descent in people with and without hip osteoarthritis.

Hip osteoarthritis (OA) is often associated with pain and impaired function. Understanding biomechanical alterations in patients with hip OA during challenging activities such as stair use is important to inform treatments. The aim of this study was to determine whether kinematics and kinetics during stair ambulation differed between people with hip OA and healthy controls. Fifteen participants with symptomatic and radiographic hip OA and 15 asymptomatic healthy controls underwent 3-D motion analysis during stair ascent and descent. Trunk, pelvis, and hip kinematics as well as hip kinetics were evaluated. Analyses were performed unadjusted and adjusted for speed and leg length. In both the unadjusted and adjusted analyses, participants with hip OA ascended stairs with less hip range of motion in all three planes and a lower peak external rotation moment compared to controls. In the unadjusted analysis, hip OA participants descended stairs with greater ipsilateral trunk lean, less sagittal plane range of motion, lower peak extension moment, lower peak external rotation moment, and greater hip adduction moment impulse compared to controls. In the adjusted results, peak internal rotation moment and hip adduction moment impulse were greater in hip OA participants compared to controls. Findings show that individuals with hip OA display limited range of hip joint movement, particularly during stair ascent, and overall indicate the use of strategies (e.g., trunk lean; lower peak external rotation moment; higher adduction moment impulse) that implicate altered hip abductor function. Future research is required to further understand the implications of these findings on hip OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1505-1514, 2017.

Takotsubo syndrome and estrogen receptor genes: partners in crime?

We aimed to analyze genetic polymorphism of estrogen receptor (ESR) 1 and ESR2 in a series of postmenopausal women with Takotsubo syndrome (TS). In total, 81 consecutive white women were prospectively enrolled: 22 with TS (TS group; mean age 71.2 ± 9.8 years), 22 with acute myocardial infarction (MI group; mean age 73.2 ± 8 years), and 37 asymptomatic healthy controls (CTRL group; mean age 69 ± 4.2 years). Genotyping of ESR1 -397C>T (rs2234693) and -351A>G (rs9340799) and ESR2 -1839G>T (rs 1271572) and 1082G>A (rs1256049) genetic variants was performed. We estimated the odds ratio (OR) between the genotype of each examined locus with the occurrence of TS or MI. The risk of experiencing TS was higher for those study participants carrying the T allele at the rs2234693 locus of the ESR1 gene [OR: 2.0, 95% confidence interval (CI): 0.973-4.11, P = 0.04, TS vs. MI + CTRL; OR: 2.79, 95% CI: 1.17-6.64, P = 0.016, TS vs. MI alone]. Women carrying a T allele at the rs1271572 locus of the ESR2 gene demonstrated an even higher risk (OR: 3.23, 95% CI: 1.55-6.73, P = 0.0019, TS vs. MI + CTRL; OR: 9.13, 95% CI: 2.78-29.9, P = 0.0001, TS vs. MI alone). The study reports preliminary findings suggesting a possible link between ESR polymorphisms and the occurrence of TS. Larger studies are needed to confirm our results.

Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin

ObjectivesThe aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls.Materials and methodsApical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by multiplex assay. Marker levels were analyzed by Kruskal Wallis test, and diagnostic accuracy was analyzed with ROC curves.ResultsHigher levels of RANKL, OPG, and RANKL/OPG ratio were determined in both types of apical lesions compared to healthy periodontal ligament, whereas higher TRAP-5 levels were found only in symptomatic apical lesions (p < 0.05). OPG, RANKL, and RANKL/OPG ratio showed diagnostic potential to identify apical lesions versus healthy controls (AUC = 0.69, p < 0.05); while TRAP-5 showed a potential to discriminate symptomatic versus asymptomatic apical periodontitis (AUC = 0.71, p < 0.05) and healthy controls (AUC = 0.83, p < 0.05).ConclusionsApical lesions showed higher RANKL and OPG levels than healthy tissues. TRAP-5 levels were the highest in symptomatic apical lesions, suggesting that these represent a progressive state, and showed diagnostic potential.Clinical relevanceClinically symptomatic apical periodontitis might represent biologically progressive apical lesions based on TRAP5 levels. TRAP5 has diagnostic potential to identify these lesions, representing a candidate prognostic biomarker.