Epicatechin Provides Antioxidant Protection to Bovine Spermatozoa Subjected to Induced Oxidative Stress.

Epicatechin (EPI) is a natural flavonoid with antibacterial, anti-inflammatory and anti-cancer properties. Furthermore, the molecule exhibits powerful reactive oxygen species (ROS) scavenging and metal-chelating properties. In this study, we assessed the efficiency of EPI to reverse ROS-mediated alterations to the motility, viability, DNA integrity and oxidative profile of bovine spermatozoa. For the first experiment, spermatozoa were washed out of fresh semen and exposed to 12.5 µmol/L EPI, 25 µmol/L EPI, 50 µmol/L EPI and 100 µmol/L EPI in the presence of ferrous ascorbate (FeAA) during a 6 h in vitro culture. For the second experiment, the ejaculates were split into aliquots and cryopreserved with a commercial semen extender supplemented with 12.5 µmol/L EPI, 25 µmol/L EPI, 50 µmol/L EPI, 100 µmol/L EPI or containing no supplement. Sperm motility was assessed using the computer-aided sperm analysis and the cell viability was studied with the metabolic activity test. ROS production was quantified using luminometry, and DNA fragmentation was evaluated using the chromatin dispersion test. Cell lysates were prepared at the end of the culture in order to assess the concentration of protein carbonyls and malondialdehyde. Exposure to FeAA led to a significantly reduced sperm motility (p < 0.001), mitochondrial activity (p < 0.001), but increased the generation of ROS (p < 0.001), as well as oxidative damage to proteins (p < 0.001), DNA (p < 0.001) and lipids (p < 0.001). EPI supplementation, particularly at a concentration range of 50-100 µmol/L, resulted in higher preservation of the spermatozoa vitality (p < 0.001). Furthermore, 50-100 µmol/L EPI were significantly effective in the prevention of oxidative damage to sperm proteins (p < 0.001), lipids (p < 0.001) and DNA (p < 0.01 in relation to 50 µmol/L EPI; p < 0.001 with respect to 100 µmol/L EPI). In the case of the cryopreserved spermatozoa, the administration of 50-100 µmol/L EPI resulted in higher sperm motility (p < 0.001) and mitochondrial activity (p < 0.001). ROS production, the number of protein carbonyls, lipid peroxidation as well as oxidative DNA damage were found to be significantly decreased particularly in samples cryopreserved in the presence of 100 µmol/L EPI (p < 0.001). Our results suggest that EPI could behave as an effective antioxidant which may prevent oxidative insults to spermatozoa, and thus, preserve their vitality and functionality. Nevertheless, its potential to achieve higher fertilization rates in reproductive technologies needs to be validated.

Identifying patients using antidepressants for the treatment of depression: A predictive algorithm for use in pharmaceutical and medical claims data.

PURPOSE: Records of antidepressant dispensings are often used as a surrogate measure of depression. However, as antidepressants are frequently prescribed for indications other than depression, this is likely to result in misclassification. This study aimed to develop a predictive algorithm that identifies patients using antidepressants for the treatment of depression. METHODS: Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) claims data were linked to follow-up questionnaires (completed in 2012-2013) for participants of the 45 and Up Study-a cohort study of residents of New South Wales, Australia, aged 45 years and older. The sample composed participants who were dispensed an antidepressant in the 30 days prior to questionnaire completion (n = 3162). An algorithm based on patient characteristics, pharmaceutical dispensings, and claims for mental health services was built using group-lasso interaction network (glinternet), with self-reported receipt of treatment for depression as the outcome. The predictive performance of the algorithm was assessed via bootstrap resampling. RESULTS: The algorithm composes 15 main effects and 11 interactions, with type of antidepressant dispensed and claims for mental health services the strongest predictors. The ability of the algorithm to discriminate between antidepressant users with and without depression was 0.73. At a predicted probability cut-off of 0.6, specificity was 93.8% and sensitivity was 23.6%. CONCLUSIONS: Using this algorithm with a high probability cut-off yields high specificity and facilitates the exclusion of individuals using antidepressants for indications other than depression, thereby mitigating the risk of confounding by indication when evaluating the outcomes of antidepressant use.

Overcoming the data drought: exploring general practice in Australia by network analysis of big data.

OBJECTIVES: To investigate the organisation and characteristics of general practice in Australia by applying novel network analysis methods to national Medicare claims data. DESIGN: We analysed Medicare claims for general practitioner consultations during 1994-2014 for a random 10% sample of Australian residents, and applied hierarchical block modelling to identify provider practice communities (PPCs). PARTICIPANTS: About 1.7 million patients per year. MAIN OUTCOME MEASURES: Numbers and characteristics of PPCs (including numbers of providers, patients and claims), proportion of bulk-billed claims, continuity of care, patient loyalty, patient sharing. RESULTS: The number of PPCs fluctuated during the 21-year period; there were 7747 PPCs in 2014. The proportion of larger PPCs (six or more providers) increased from 32% in 1994 to 43% in 2014, while that of sole provider PPCs declined from 50% to 39%. The median annual number of claims per PPC increased from 5000 (IQR, 40-19 940) in 1994 to 9980 (190-23 800) in 2014; the proportion of PPCs that bulk-billed all patients was lowest in 2004 (21%) and highest in 2014 (29%). Continuity of care and patient loyalty were stable; in 2014, 50% of patients saw the same provider and 78% saw a provider in the same PPC for at least 75% of consultations. Density of patient sharing in a PPC was correlated with patient loyalty to that PPC. CONCLUSIONS: During 1994-2014, Australian GP practice communities have generally increased in size, but continuity of care and patient loyalty have remained stable. Our novel approach to the analysis of routinely collected data allows continuous monitoring of the characteristics of Australian general practices and their influence on patient care.

INVERSE STABLE SUBORDINATORS.

The inverse stable subordinator provides a probability model for time-fractional differential equations, and leads to explicit solution formulae. This paper reviews properties of the inverse stable subordinator, and applications to a variety of problems in mathematics and physics. Several different governing equations for the inverse stable subordinator have been proposed in the literature. This paper also shows how these equations can be reconciled.

FRACTIONAL WAVE EQUATIONS WITH ATTENUATION.

Fractional wave equations with attenuation have been proposed by Caputo [5], Szabo [27], Chen and Holm [7], and Kelly et al. [11]. These equations capture the power-law attenuation with frequency observed in many experimental settings when sound waves travel through inhomogeneous media. In particular, these models are useful for medical ultrasound. This paper develops stochastic solutions and weak solutions to the power law wave equation of Kelly et al. [11].

Stochastic solution to a time-fractional attenuated wave equation.

The power law wave equation uses two different fractional derivative terms to model wave propagation with power law attenuation. This equation averages complex nonlinear dynamics into a convenient, tractable form with an explicit analytical solution. This paper develops a random walk model to explain the appearance and meaning of the fractional derivative terms in that equation, and discusses an application to medical ultrasound. In the process, a new strictly causal solution to this fractional wave equation is developed.

FRACTIONAL DYNAMICS AT MULTIPLE TIMES.

A continuous time random walk (CTRW) imposes a random waiting time between random particle jumps. CTRW limit densities solve a fractional Fokker-Planck equation, but since the CTRW limit is not Markovian, this is not sufficient to characterize the process. This paper applies continuum renewal theory to restore the Markov property on an expanded state space, and compute the joint CTRW limit density at multiple times.

Pretreatment staging of cervical cancer: is imaging better than palpation?: Role of CT and MRI in preoperative staging of cervical cancer: single institution results for 255 patients.

BACKGROUND: Cervical carcinoma is clinically staged according to the criteria of the International Federation of Gynecology and Obstetrics (FIGO). Computed tomography (CT) and magnetic resonance imaging (MRI) can also be used in pretreatment evaluation of tumor extension and size; however, the diagnostic value and the impact on clinical decisions of cross-sectional imaging have been questioned. METHODS: The files of 255 patients with biopsy-proven cervical carcinoma receiving primary surgical treatment at the Department of Obstetrics and Gynaecology of Ulm University between 1992 and 2003 were analyzed retrospectively. All patients had a clinical pelvic examination; additionally, 164 underwent CT, 101 had an MRI, and 90 had both CT and MRI. Surgicopathologic findings were used as the standard of reference. RESULTS: To evaluate detection of parametrial involvement, patients were divided into those with stage IIA or less disease (n = 171; 67%) and those with stage IIB or more disease (n = 84; 33%). The accuracy, sensitivity, and specificity were 75%, 66%, and 81% for clinical staging, 59%, 43%, and 71% for CT, and 58%, 52%, and 63% for MRI, respectively. After stratification for palpation, the results with CT and MRI were no better than with palpation (accuracy: CT 61% and 54%, MRI 61% and 56%, respectively). The sensitivity of CT and MRI for detecting lymph node metastasis was also poor (36% and 35%, respectively). CONCLUSION: Clinical examination was better than CT and MRI for pretreatment evaluation of early invasive cervical cancer.