Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2?=?1.06, 95% CI 0.99–1.14) or in men (HR_log2?=?0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2?=?0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR_log2?=?1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.     

The metabolism of flubendazole in human liver and cancer cell lines

Flubendazole (FLU), a benzimidazole anthelmintic drug widely used in veterinary medicine, has been approved for the treatment of gut‐residing nematodes in humans. In addition, FLU is now considered a promising anti‐cancer agent. Despite this, information about biotransformation of this compound in human is lacking. Moreover, there is no information regarding whether cancer cells are able to metabolize FLU in order to deactivate it. For these reasons, the present study was designed to identify all metabolites of Phase I and Phase II of FLU in human liver and in various cancer cells using ultra high‐performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) analysis. Precision‐cut human liver slices and 9 cell lines of different origin (breast, colon, oral cavity) were used as in vitro model systems. Our study showed that FLU with a reduced carbonyl group (FLUR) is the only FLU metabolite formed in the human liver. All human cancer cell lines were able to form FLUR. In addition, methylated FLUR was detected in breast cells MCF7 and intestinal SW480 cells. The accumulation of FLU and its reduction to FLUR markedly differed among cells. The extent of FLU reduction was in a good correlation with the detected expression level of carbonyl reductase 1. In most cases, FLU entered in a higher amount and was reduced to a lesser extent in proliferating (metastatic) cells than in differentiated (non‐cancerous, non‐metastatic) ones. These results support the promising potential of FLU in anti‐cancer therapy.     

Unfavorable hip stress distribution after Legg–Calvé–Perthes syndrome: A 25‐year follow‐up of 135 hips

To study the effect of hip and pelvis geometry on development of the hip after Perthes disease, we determined the resultant hip force and contact hip stress distribution in a population of 135 adult hips of patients who had been treated for Perthes disease in childhood. Contra‐lateral hips with no record of disease were taken as the control population. Biomechanical parameters were determined by mathematical models for resultant hip force in one‐legged stance and for contact hip stress, which use as an input the geometrical parameters assessed from anteroposterior radiographs. The mathematical model for stress was upgraded to account for the deviation of the femoral head shape from spherical. No differences were found in resultant hip force and in peak contact hip stress between the hips that were in childhood subject to Perthes disease and the control population, but a considerable (148%) and significant (p < 0.001) difference was found in the contact hip stress gradient index, expressing an unfavorable, steep decrease of contact stress at the lateral acetabular rim. This finding indicates an increased risk of early coxarthritis in hips subject to Perthes disease. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:8–16, 2014.     

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare. Therefore, event-related potentials were measured in 15 patients with schizophrenia and 15 healthy controls while rating the expression of happy, fearful and neutral faces and concurrently being distracted by emotional or neutral sounds. Compared with controls, patients with schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in response to all faces, independent of emotion or concurrent sound. Analyzing these effects with regard to audiovisual (in)congruence revealed that P1 amplitudes in patients were only reduced in response to emotionally incongruent stimulus pairs, whereas similar amplitudes between groups could be observed for congruent conditions. Correlation analyses revealed a significant negative correlation between general symptom severity (Brief Psychiatric Rating Scale-V4) and P1 amplitudes in response to congruent audiovisual stimulus pairs. These results indicate that early visual processing deficits in schizophrenia are apparent during emotion processing but, depending on symptom severity, these deficits can be restored by presenting concurrent emotionally congruent sounds.     

Haloperidol affects coupling between QT and RR intervals in guinea pig isolated heart

Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR and its changes under acute and chronic haloperidol administration. The study included 14 male guinea pigs divided into control and haloperidol-treated group. After 21-days administration of haloperidol or vehiculum, electrograms in isolated hearts were recorded. QT/RR and dQT/dRR coupling were calculated. Chronic haloperidol administration significantly decreases the coupling between QT and RR. Acute haloperidol exposure significantly decreases the dQT/dRR coupling in both treated and untreated guinea pig hearts. Flatter QT/RR relationship reveals a lack of QT adaptation to increased heart rate. It should be emphasized that in such situation ECG recording will not show significant QT prolongation evaluated according to clinical rules. However, if QT interval does not adapt to increased heart rate sufficiently, the risk of ventricular arrhythmias may be increased despite practically normal QT interval length. The results are supported by findings in biochemical analyses, which proved eligibility of the used model.     

The impact of limited English proficiency on asthma action plan use

Objective: The goal of this study was to compare rates of asthma action plan use by limited English proficiency (LEP) caregivers to English proficient (EP) caregivers. Methods: A cross-sectional bilingual survey was distributed at an urban, academic, pediatric emergency department (PED). Surveys were completed by adult caregivers of children with asthma who sought PED care for asthma related chief complaints. LEP was defined as caregiver ability to speak English less than “very well”. Data were analyzed using Fisher’s exact test and odds ratios (OR). Results: One hundred seven surveys were completed and analyzed. Fifty-one surveys (48%) were completed by LEP caregivers and 56 (52%) by EP caregivers. A 25% difference (p?=?.01) in action plan use rates between LEP caregivers (39%) and EP caregivers (64%) was observed. EP alone was associated with action plan use (OR 2.8 [95% CI 1.3–6.1]). Variables not associated with plan use included mother acting as caregiver (OR 2.1 [95% CI 0.7–7.0]), age of child >7 years (OR 1.0 [95% CI 0.5–2.4]), caregiver education?≥?associate degree (OR 1.4 [95% CI 0.6–3.0]), private insurance (OR 0.7 [95% CI 0.3–1.8]), White race (OR 0.7 [95% CI 0.2–2.2]), Latino ethnicity (OR 0.5 [95% CI 0.2–1.3]) and a federally qualified health center (OR 0.8 [95% CI 0.3–2.0]). The main caregiver reasons for plan use were feeling that a plan works/gets results, helps with symptom management and appreciation towards physician attentiveness when a plan is prescribed. The main caregiver reasons for non plan use were they were not informed/given an action plan or perceived the child’s asthma as mild/well controlled. Conclusion: Compared with EP caregivers, those with LEP experience disparate rates of asthma action plan use.     

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late‐onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late‐onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid β42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction–restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25?0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61?1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C?A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.