P wave duration and dispersion in Holter electrocardiography of patients with obstructive sleep apnea

Purpose

The underlying mechanisms of the association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) remained unclear. We investigated P wave parameters as indicators of atrial conduction status among OSA patients.

Methods

We studied 42 untreated OSA patients, categorized into mild (6), moderate (18), and severe (18) OSA based on the apnea/hypopnea index (AHI) and 18 healthy controls. Twenty-four-hour Holter electrocardiography was applied to measure P wave parameters including P wave duration and P wave dispersion; difference between the maximum (P-max) and minimum (P-min) measured P wave duration.

Results

Mean P wave duration ranged from 110.2?±?9.3 ms in mild OSA patients to 121.1?±?15.4 ms in severe OSA patients and was 113.4?±?10.0 ms in controls with no significant difference among the groups, P?=?0.281. P wave dispersion and P-max were significantly longer in those with moderate OSA (68.0?±?9.3 and 154.2?±?9.3 ms) and those with severe OSA (71.6?±?13.7 and 157.2?±?13.3 ms) than controls (52.6?±?15.3 and 142.1?±?15.4 ms), P?r?=?0.407, P?=?0.012) and P wave dispersion (r?=?0.431, P?=?0.008). With linear regression analysis controlling for age, gender, and BMI, the AHI was independently associated with P wave dispersion (β?=?0.482, P?=?0.002).

Conclusions

Using Holter monitoring for measurement of P wave parameters, this study showed an association of OSA with prolonged P-max and P wave dispersion. These results indicate that patients with OSA have disturbances in atrial conduction associated with OSA severity. Repeating this study in a larger sample of patients is warranted.     

Combined inhibition of the BMP pathway and the RANK-RANKL axis in a mixed lytic/blastic prostate cancer lesion

The purpose of this study was to investigate the influence of combined inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) and bone morphogenetic protein (BMP) activity in a mixed lytic/blastic prostate cancer lesion in bone. Human prostate cancer cells (C4 2b) were injected into immunocompromised mice using an intratibial injection model to create mixed lytic/blastic lesions. RANK-Fc, a recombinant RANKL antagonist, was injected subcutaneously three times a week (10mg/kg) to inhibit RANKL and subsequent formation, function and survival of osteoclasts. Inhibition of BMP activity was achieved by transducing prostate cancer cells ex vivo with a retroviral vector expressing noggin (retronoggin; RN). There were three treatment groups (RANK-Fc treatment, RN treatment and combined RN and RANK-Fc treatment) and two control groups (untreated control and empty vector control for the RN treatment group). The progression of bone lesion and tumor growth was evaluated using plain radiographs, hindlimb tumor size, (18)F-Fluorodeoxyglucose and (18)F-fluoride micro PET-CT, histology and histomorphometry. Treatment with RANK-Fc alone inhibited osteolysis and transformed a mixed lytic/blastic lesion into an osteoblastic phenotype. Treatment with RN alone inhibited the osteoblastic component in a mixed lytic/blastic lesion and resulted in formation of smaller osteolytic bone lesion with smaller soft tissue size. The animals treated with both RN and RANK-Fc demonstrated delayed development of bone lesions, inhibition of osteolysis, small soft tissue tumors and preservation of bone architecture with less tumor induced new bone formation. This study suggests that combined inhibition of the RANKL and the BMP pathway may be an effective biologic therapy to inhibit the progression of established mixed lytic/blastic prostate cancer lesions in bone.     

Grape Seed Extract to Improve Liver Function in Patients with Nonalcoholic Fatty Liver Change

Background/Aim:

Therapeutic interventions in nonalcoholic fatty liver disease are limited, while antioxidative materials have shown benefi ts in animal models. This study aimed to evaluate grape seed extract as an anti-oxidative material in this process. Therapeutic effects of grape seed extract were evaluated in comparison to vitamin C in a double-blind setting.

Materials and Methods:

Fifteen patients were enrolled in each group. Liver function tests were done; also, grade of steatosis and pattern of echogenicity of the liver were determined. Patients were followed up by the same evaluation repeated in first, second and third months.

Results:

Mean age ± standard deviation was 43.2 ± 10.3 years. Grape seed extract (GSE) significantly improved the grade of fatty liver change; and resulted in significant decrease in alanine aminotransferase in patients receiving the concentrate compared to those receiving vitamin C independently, from the initial grade of steatosis.

Conclusions:

This study describes the beneficial effect of using grape seed extract for three months in patients with nonalcoholic fatty liver disease. These results may improve with a longer period of follow-up.     

Personality factors and profiles in variants of irritable bowel syndrome

AIM: To study the association between irritable bowel syndrome (IBS) variants (constipation,diarrhea,or both) and personality traits in non-psychiatric patients. METHODS: IBS was diagnosed using the Rome Ⅱ diagnostic criteria after exclusion of organic bowel pathology. The entry of each patient was confirmed following a psychiatric interview. Personality traits and the score of each factor were evaluated using the NEO Five Factor Inventory. RESULTS: One hundred and fifty patients were studied. The mean age (± SD) was 33.4 (± 11.0) year (62% female). Subjects scored higher in neuroticism (26.25 ± 7.80 vs 22.92 ± 9.54,P < 0.0005),openness (26.25 ± 5.22 vs 27.94 ± 4.87,P < 0.0005) and conscientiousness (32.90 ± 7.80 vs 31.62 ± 5.64,P < 0.01) compared to our general population derived from universities of Iran. Our studied population consisted of 71 patients with Diarrhea dominant-IBS,33 with Constipation dominant-IBS and 46 with Altering type-IBS. Scores of conscientiousness and neuroticism were significantly higher in C-IBS compared to D-IBS and A-IBS (35.79 ± 5.65 vs 31.95 ± 6.80,P = 0.035 and 31.97 ± 9.87,P = 0.043,respectively). Conscientiousness was the highest dimension of personality in each of the variants. Patients with C-IBS had almost similar personality profiles,composed of higher scores for neuroticism and conscientiousness,with low levels of agreeableness,openness and extraversion that were close to those of the general population. CONCLUSION: Differences were observed between IBS patients and the general population,as well as between IBS subtypes,in terms of personality factors. Patients with constipation-predominant IBS showed similar personality profiles. Patients with each subtype of IBS may benefit from psychological interventions,which can be focused considering the characteristics of each subtype.     

Validity and reliability of a Persian translation of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS)

Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are limited in languages other than English. We aimed to translate, cross-culturally adapt, validate, and assess reliability of Minimal Assessment of Cognitive Function in MS (MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature. The battery was adapted to Persian in accordance with available guidelines. A total of 158 MS patients and 90 controls underwent neuropsychological assessment. For reliability assessment the battery was re-administered in a subset of 41 patients after a short interval using alternate forms to mitigate practice effects (approximately 10 days). Patients performed significantly worse than controls in all cognitive tests, supporting discriminant validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities Test was the most robust test by ROC analysis. All tests showed acceptable to good level of reliability. This is the first validation of gold-standard cognitive testing in Persian. The Persian MACFIMS shows nearly the same psychometrics as its English counterpart.     

Efficient ROSA26-Based Conditional and/or Inducible Transgenesis Using RMCE-Compatible F1 Hybrid Mouse Embryonic Stem Cells

The conditional Cre/loxP system and/or the doxycycline (Dox) inducible Tet-on/off system are widely used in mouse transgenesis but often require time consuming, inefficient cloning/screening steps and extensive mouse breeding strategies. We have therefore developed a highly efficient Gateway- and recombinase-mediated cassette exchange (RMCE)-compatible system to target conditional and/or inducible constructs to the ROSA26 locus of F1 hybrid Bl6/129 ESCs, called G4 ROSALUC ESCs. By combining the Cre/loxP system with or without the inducible Tet-on system using Gateway cloning, we can rapidly generate spatial and/or temporal controllable gain-of-function constructs that can be targeted to the RMCE-compatible ROSA26 locus of the G4 ROSALUC ESCs with efficiencies close to 100 %. These novel ESC-based technologies allow for the creation of multiple gain-of-function conditional and/or inducible transgenic ESC clones and mouse lines in a highly efficient and locus specific manner. Importantly, incorporating insulator sequences into the Dox-inducible vector system resulted in robust, stable transgene expression in undifferentiated ESCs but could not fully overcome transgene mosaicism in the differentiated state.