Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study

Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P 相似文献   

New predictors of outcome in idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension (PAH) is a rare disease with a poor prognosis. New therapies have improved the outcome of this condition; accordingly, the factors that determine outcome may have changed. We aimed to identify determinants of survival in a cohort of consecutive patients with PAH: which was idiopathic, familial, or associated with anorexigen use. We performed a retrospective cohort study of 84 consecutive patients with PAH who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. Survival at 1, 3, and 5 [corrected] years was 87%, 75%, and 61%, respectively. Multivariate analysis showed that being of African-American or Asian descent was associated with an increased risk of death. Warfarin use was associated with a reduced risk of death. Higher serum albumin and cardiac index and acute vasoreactivity were independently associated with improved survival. These data suggest that the determinants of outcome have changed. Race is identified as a new risk factor, which may be attributable to biologic or socioeconomic differences. Cardiac function and acute reactivity of the pulmonary vascular bed remain strong independent predictors of outcome.     

Cardiovascular effects of hemoglobin response in patients receiving epoetin alfa and oral iron in heart failure with a preserved ejection fraction

Background Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with heart failure with a preserved ejection fraction （HFPEF） and anemia randomized to treatment with epoetin alfa （erythro-poiesis-stimulating agents, ESA） vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular （LV） structure, functional capacity, or quality of life （QOL）. However, several patients randomized to the treatment arm were non-responders with a subop-timal increase in hemoglobin. All patients in the trial also received oral ferrous gluconate, which could have contributed to increases in he-moglobin observed in those receiving placebo. Accordingly, we performed an analysis separating patients into responders vs. non-responders in order to determine if measured improvement in anemia would have any effect on clinical endpoints. Methods A total of 56 patients （age 77 ± 11 years, 68%female） were recruited who had anemia defined as a hemoglobin of≤12 g/dL （average, 10.4 ± 1 g/dL） with HFPEF defined as having NHANES-CHF （National Health And Nutrition Examination Survey：Congestive Heart Failure） criteria score of≥3 and an ejection fraction of＆gt;40%（average EF=63%±15%）. Patients were randomly allocated to receive either ESA and ferrous gluconate or ferrous gluconate only. In this analysis, a responder was defined as a patient with an increase of 1 g/dL in the first 4 weeks of the trial. Re-sults Nineteen subjects were classified as responders compared to 33 non-responders. While the average hemoglobin increased signifi-cantly at the end of 6 months for responders （1.8 ± 0.3 vs. 0.8 ± 0.2 g/dL, P = 0.004）, 50% of the subjects assigned to ESA were non-responders. Left ventricular function including ejection fraction （P=0.32） and end diastolic volume （P=0.59） was unchanged in res-ponders compared to non-responders. Responders also showed no significant improvements in New York Heart Association （NYHA） class, Six Minute Walk Test （6 MWT） and peak VO2. Though QOL improved significantly within each group, there was no difference between the two. Conclusions A significant hemoglobin response to anemia treatment with ESA and oral iron does not lead to differences in LV re-modeling, functional status, or QOL. Additionally, a significant percent of older adults with HFPEF and anemia do not respond to ESA ther-apy. Given the results of this small trial, it appears as though using objective improvements in anemia as a marker in older adult subjects with HFPEF does not have significant clinical utility.     

Offering prenatal diagnostic tests: European guidelines for clinical practice

For over four decades, it has been possible to offer prenatal diagnostic testing for fetal abnormalities. Prenatal testing is now available for a wide range of monogenic disorders as well as chromosomal abnormalities and should be provided within the ethical framework of informed consent and autonomous choice. However, there are no published guidelines for health professionals from varied disciplines who offer prenatal diagnosis (PND) in a range of possible settings including departments of maternity, obstetrics and clinical genetics. We used an Expert Group technique to develop a set of guidelines for provision of prenatal diagnostic services. Thirteen European health professionals, all experts in PND, participated in a workshop to develop the guidelines, which were then subjected to a wide consultation process. The objective of PND was defined as providing prenatal diagnostic testing services (for genetic conditions) that enable families to make informed choices consistent with their individual needs and values and which support them in dealing with the outcome of such testing. General principles, logistical considerations, clinical care and counselling topics are all described and are equally applicable to invasive and non-invasive testing. These guidelines provide a framework for ethical clinical care; however, they are flexible enough to enable practitioners to adapt them to their particular setting. Ideally, an individualised approach to each family is required to ensure autonomous choice and informed consent regarding prenatal diagnostic testing within the local ethical and legal framework.     

Two-photon imaging of Zn2+ dynamics in mossy fiber boutons of adult hippocampal slices

Mossy fiber termini in the hippocampus accumulate Zn²⁺, which is released with glutamate from synaptic vesicles upon neural excitation. Understanding the spatiotemporal regulation of mobile Zn²⁺ at the synaptic level is challenging owing to the difficulty of visualizing Zn²⁺ at individual synapses. Here we describe the use of zinc-responsive fluorescent probes together with two-photon microscopy to image Zn²⁺ dynamics mediated by NMDA receptor-dependent long-term potentiation induction at single mossy fiber termini of dentate gyrus neurons in adult mouse hippocampal slices. The membrane-impermeant fluorescent Zn²⁺ probe, 6-CO₂H-ZAP4, was loaded into presynaptic vesicles in hippocampal mossy fiber termini upon KCl-induced depolarization, which triggers subsequent endocytosis and vesicular restoration. Local tetanic stimulation decreased the Zn²⁺ signal observed at individual presynaptic sites, indicating release of the Zn²⁺ from vesicles in synaptic potentiation. This synapse-level two-photon Zn²⁺ imaging method enables monitoring of presynaptic Zn²⁺ dynamics for improving the understanding of physiological roles of mobile Zn²⁺ in regular and aberrant neurologic function.Although most cellular Zn²⁺ is sequestered within proteins, stores of loosely bound Zn²⁺ are present in many kinds of cells. This mobile Zn²⁺ pool is believed to mediate cellular processes, including neurotransmission (1). Within the hippocampus, mossy fibers connecting the dentate gyrus (DG) and the CA3 regions contain Zn²⁺ in glutamatergic synaptic vesicles. The precise concentration of Zn²⁺ within the neuronal vesicles is unknown, with upper estimates ranging in the low millimolar range (2, 3). Upon stimulation, Zn²⁺ is believed to be coreleased with glutamate and to modulate glutamatergic synaptic transmission (4, 5). Despite this recent finding, however, much remains to be understood about the dynamics and functional roles of synaptic Zn²⁺.Numerous fluorescent Zn²⁺ probes have been developed for use in biological systems (6, 7), including 6-methoxy-(8-p-toluenesulfonamido)quinoline (8), Zinquin (9), Zinbo-5 (10), and the Zinpyr (ZP) and ZnAF families of probes (11–14). Despite the abundance of fluorescent Zn²⁺ probes, analysis of Zn²⁺ in vivo remains problematic. Many probes bind Zn²⁺ to form complexes with dissociation constants in the nanomolar range; these tight binding affinities lead to rates of Zn²⁺ release that are too slow for time-resolvable measurements. These probes also may act as Zn²⁺ traps, sequestering Zn²⁺ in one region of the cell, and then collecting elsewhere to yield a faulty image of native Zn²⁺ distributions within cells. Reductions in binding affinity can be accomplished via two strategies. First, steric bulk can be installed near the chelating atoms, as was done with two series of methylated Zn²⁺ probes (15, 16). Second, chelating atoms can be removed from the ligand systematically, as was done for probes in the ZnAF series (16), as well as those in the QZ, Zinspy, and ZinAlkylPyr (ZAP) families (17–19).Here we present the synthesis of the probe ZinAlkylPyr-4 (ZAP4) and its 6-carboxylic acid derivative (6-CO₂H-ZAP4). The molecular structure of ZAP4 was modeled after earlier ZAP probes (17), with pentafluorobenzyl groups chosen as the alkyl groups to reduce the basicity of the probe and minimize proton-induced enhancement of the emission. The 6-CO₂H-ZAP4 probe was constructed as a membrane-impermeant Zn²⁺ probe, analogous to the previously reported 6-CO₂H-ZP1 (20).Previous attempts to monitor presynaptic Zn²⁺ dynamics in living brain tissues used membrane-permeant probes to detect intracellular Zn²⁺ from populations of presynaptic terminals at relatively low spatial resolution at the tissue level (21, 22). In addition, activity-dependent extracellular Zn²⁺ release has been monitored with membrane-impermeant probes (16, 23–30). These tissue level-averaged Zn²⁺ imaging methods have limited spatial and temporal resolution and fail to specify the precise location of the relevant synapses.We describe intracellular Zn²⁺ imaging at the single-synapse level in mossy fiber termini of neurons in acute hippocampal slices from adult mice. The technique relies on the membrane-impermeant fluorescent Zn²⁺ probe 6-CO₂H-ZAP4 and two-photon fluorescence microscopy.     

Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

Objective

Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

Methods

AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

Results

Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue.

Conclusions

The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.     

Comparision of blood loss between computer assisted and conventional total knee arthroplasty

Background:

Bleeding during total knee arthroplasty (TKA) can cause significant morbidity and mortality. One proposed benefit of computer assisted TKA is decreased bleeding as the femoral canal is not invaded. This study assessed blood loss between computer assisted surgery (CAS) and conventional TKA.

Materials and Methods:

73 consecutive patients (37 males, 36 females) underwent primary TKA between 2006 and 2009. Thirty eight patients underwent navigated TKA and 35 underwent conventional TKA for symptomatic osteoarthritis of the knee. These patients were matched for age, gender, and body mass index (BMI). Average age was 70.3 years (range 47-91 years). Mean BMI was 30 (range 17-49). Average preoperative hemoglobin was 13.26 g/dL (range 8.7-18.4 g/dL) in the navigated group and 13.47 g/dL (range 9.6-15.8 g/dL) in the conventional group (P = 0.9). Average tourniquet time was 110 min (range 90-150 min) in the navigated group and 96.7 min (range 60-145 min) in the conventional group (P = 0.77).

Results:

Average postoperative hemoglobin in the navigated group was 10.34 g/dL (range 7.5-14.8 g/dL) and in the conventional group was 10.03 g/dL (range 7.5-12.2 g/dL) (P = 0.17). Six patients in both groups required blood transfusions. The mean drain collection was 599 mL (range 150-1370 mL) in the navigated group and 562 mL (range 750-1000 mL) in the conventional group (P = 0.1724). These results suggest that there is no significant reduction in blood loss in CAS TKA.

Conclusion:

These results suggest that there is no significant difference in blood loss in CAS TKA and conventional TKA. This study also highlights the heterogeneity of methods used in studies related to CAS TKA. We believe that there is a need for a large multicenter prospective randomized controlled trial to be performed before a consensus can be reached on the influence of CAS techniques on blood loss during primary TKA.