The cardiorenal syndrome and erythropoietin

The pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has been denoted as severe cardiorenal syndrome (SCRS). An interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide (NO) and reactive oxygen species (ROS) balance, the sympathetic nervous system (SNS), and inflammation, has been proposed as the cornerstones of the pathophysiology of SCRS. Because erythropoietin (Epo) production declinesin chronic renal failure (CRF) and Epo sensitivity might decrease by the cardiorenalconnectors in patients with the SCRS, it is not surprising thatanaemia is a commonly occurring state coinciding with CRF and chronic heart failure (CHF). Epo treatment in patients with SCRS acts via haematopoietic effects, but also may intervenes in the vicious circle of cardiorenal connectors with subsequent deteriorating effects on cardiac, renal, and vascular function. It appears that regular Epo treatment in anaemic patients with diminished renal function improves cardiac performance, delays the progression of kidney disease, and may be of clinical benefit even to patients suffering from CHF with relatively mild anaemia. Despite growing evidence about Epo having positive effects on both renal and cardiac function, little is known about the underlying mechanisms of action.     

Evaluation of 2 whole-slide imaging applications in dermatopathology

Digitization of glass slides holds great promise for increasing workflow efficiency, but current applications have not gained widespread acceptance. Applications to date have not taken into consideration pathologists' workflow patterns, and as a result many find navigation cumbersome and interpretation more challenging when compared to glass slides. We observed 3 dermatopathologists evaluate a set of cases using 2 digital applications, one of which used a novel navigation method developed in-house. We then compared their approach to the digital slides with the gold standard traditional microscopy with glass slides. Common diagnoses were identified in 3 categories: inflammatory, nonmelanocytic, and melanocytic lesions. Forty-five cases were selected representing these diagnoses. Digital slides were captured on a commercially available scanner. Sign-out was performed with a commercial viewer as well as with the in-house application. Sessions were captured on video and reviewed. Time to examine each slide, time spent at each magnification, and diagnostic concordance were measured. Average time spent per slide was least with the microscope (23 seconds) as compared with the in-house (34 seconds) or the vendor application (38 seconds). This difference was most significant in the least complex cases. Pathologists reported difficulty interpreting mitotic figures, neutrophil lobules, and eosinophil granules by digital slides. These results suggest that current applications for viewing digital slides do not yet provide a more efficient means of evaluating dermatopathology cases and reinforce the need for improvement in both the capture process and the presentation of digital slides, with particular attention paid to the interface and navigation.     

Interventions for postoperative pain in children: An overview of systematic reviews

The aim of this study was to conduct an overview of systematic reviews that summarizes the results about efficacy and safety from randomized controlled trials involving the various strategies used for postoperative pain management in children. We searched the Cochrane Database of Systematic Reviews, CINAHL, Database of Reviews of Effect, Embase, MEDLINE, and PsycINFO from the earliest date to January 24, 2016. This overview included 45 systematic reviews that evaluated interventions for postoperative pain in children. Out of 45 systematic reviews that investigated various interventions for postoperative pain in children, 19 systematic reviews (42%) presented conclusive evidence of efficacy. Positive conclusive evidence was reported in 18 systematic reviews (40%) for the efficacy of diclofenac, ketamine, caudal analgesia, dexmedetomidine, music therapy, corticosteroid, epidural analgesia, paracetamol, and/or nonsteroidal anti‐inflammatory drugs and transversus abdominis plane block. Only one systematic review reported conclusive evidence of equal efficacy that involved a comparison of dexmedetomidine vs morphine and fentanyl. Safety of interventions was reported as conclusive in 14 systematic reviews (31%), with positive conclusive evidence for dexmedetomidine, corticosteroid, epidural analgesia, transversus abdominis plane block, and clonidine. Seven systematic reviews reported equal conclusive safety for epidural infusion, diclofenac intravenous vs ketamine added to opioid analgesia, bupivacaine, ketamine, paracetamol, and dexmedetomidine vs intravenous infusions of various opioid analgesics, oral suspension and suppository of diclofenac, only opioid, normal saline, no treatment, placebo, and midazolam. Negative conclusive statement for safety was reported in one systematic review for caudal analgesia vs noncaudal regional analgesia. More than half of systematic reviews included in this overview were rated as having medium methodological quality. Of 45 included systematic reviews, 10 were Cochrane reviews and they had higher methodological quality than non‐Cochrane reviews. As evidence concerning efficacy and safety is inconclusive for most of the analyzed interventions, our review points out the need for more rigorous trials concerning pain management in children.     

Future Doctors' Perceptions about Incorporating Nutrition into Standard Care Practice

Objective: The increasing prevalence of chronic disease has been largely attributed to long-term poor nutrition and lifestyle choices. This study investigates the attitudes of our future physicians toward nutrition and the likelihood of incorporating nutrition principles into current treatment protocols.Methods: Setting: The setting of this study was an Australian university medical school. Subjects: Subjects including year 1–4 students (n = 928) in a 4-year medical bachelor, bachelor of surgery (MBBS) degree program. Students were invited to participate in a questionnaire based on an existing instrument, the Nutrition in Patient Care Attitude (NIPC) Questionnaire, to investigate their attitudes toward nutrition in health care practices.Results: Respondents indicated that “high risk patients should be routinely counseled on nutrition” (87%), “nutrition counseling should be routine practice” (70%), and “routine nutritional assessment and counseling should occur in general practice” (57%). However, despite overall student support of nutritional counseling (70%) and assessment (86%), students were reluctant to perform actual dietary assessments, with only 38% indicating that asking for a food diary or other measure of dietary intake was important.Conclusion: These findings demonstrate that future physicians are aware of the importance of considering nutrition counseling and assessment. However, students are unlikely to adequately integrate relevant nutritional information into their treatment protocols, evidenced by their limited use of a basic nutritional assessment. This is potentially the result of a lack of formal nutrition education within their basic training.     

Clinical significance of a CYP2D6 poor metabolizer--a patient with schizophrenia on risperidone treatment

A case of a 46-year-old woman with schizophrenia who was treated with risperidone and followed up for 1 year is reported. She was genotyped as a CYP2D6 poor metabolizer (PM): CYP2D6-4*/*6, which was confirmed by a dextromethorphan (DM) test (metabolic ratio = 5.8). Genotypes of ABCB1 (MDR1) were 2677TT and 3435TT. Because risperidone is CYP2D6 and P-glycoprotein substrate, the patient might have been expected to accumulate risperidone and suffer from significant side effects. However, the patient tolerated the drug extremely well. Plasma concentration of risperidone was 73.2 nmol/L and of 9-OH-risperidone was below the limit of quantitation (6.1 nmol/L). Target range of risperidone plus 9-hydroxyrisperidone is 50-150 nmol/L. During the follow-up, patient was continuously taking 3 mg/day of risperidone. Plasma levels of risperidone and 9-OH-risperidone were 70.2 and 18.1 nmol/L, respectively. We repeated a DM test, metabolic ratio was 3.6, thus confirming that the patient remained a PM. Psychopathology was assessed with Positive and Negative Syndrome Scale, and stable remission of illness was achieved over the stated period. No adverse effects were observed or reported by the patient. We conclude that PM phenotype for CYP2D6 does not necessarily have clinical significance in regard to risperidone treatment. DM and risperidone are both CYP2D6 and P-glycoprotein substrates and significant interactions might occur with both drugs, in parallel with the possible impact of ABCB1 and CYP2D6 polymorphic gene variants.     

The Spanish “Century XXI” academy for developing elite level basketballers: design,monitoring and training methodologies

Objectives: The XXI Century Academy was a 6-year state-initiated intervention program that served as an alternative to basketball clubs for players in the u-14 and u-18 age groups in Spain, under guidelines established by the Spanish Basketball Federation. It was an important and unique project on talent development in basketball. To the best of the authors’ knowledge, no evidence has been reported on long-term athlete development programs in basketball worldwide. The main aim of this report is to describe the design and evaluation methods used for the XXI Century Academy as a long-term intervention program in the elite Spanish Basketball Academy, aiming to prepare basketball players to compete at the elite level.

Methods: The monitoring time lasted from 1996 to 2001. A total of 55 players were assigned to the intervention groups based on age, position, maturation level, and country of origin. During this process, participants competed in up to two categories in addition to playing competitive official matches worldwide in international tournaments in their categories and with the national team in the European and World Championships (u-14 - u-18). Participants included 1 NBA player, 3 national A Team players, 10 ACB (First Spanish League) players, 5 LEB (second League) players and 39 LEB-2 EBA (third League) players. Assessments took place in a High-Performance Sports Center (CPT FADURA-GETXO- Basque Government, Getxo, Vizcaya, Spain) and consisted of health questionnaires, anthropometric measures, blood parameters, maturation level, birth age, fitness tests, training volume and intensity, physical activity, technical and tactical training, dietary intake, supplementation and injuries. Each player was assessed 4 times per year (September, December, April, June) for 4 years (16 data points).

Results: This is a purely methodological paper describing the design and evaluation methods used in the XXI Century Project, which will be used as a basis for future reporting of results. Therefore, the results of the project will be reported in subsequent publications.

Conclusion: The viability of the Century XXI Project protocols has been described. This national project of training in basketball closely replicates the physical and technical match-play conditions for professionals and may constitute a useful training tool.     

Mutual interactions between telomere heterogeneity and cell culture growth dynamics shape stochasticity of cell aging

Mathematical modeling and computational simulations are often used to explain the stochastic nature of cell aging. The models published thus far are based on the molecular mechanisms of telomere biology and how they dictate the dynamics of cell culture proliferation. However, the influence of cell growth conditions on telomere dynamics has been widely overlooked. These conditions include interactions with surrounding cells through contact inhibition, gradual accumulation of non-dividing cells, culture propagation and other cell culture maintenance factors. In order to follow the intrinsic growth dynamics of normal human fibroblasts we employed the fluorescent dye DiI and FACS analysis which can distinguish cells that undergo different numbers of divisions within culture. We observed rapid generation of cell subpopulations undergoing from 0 to 9 divisions within growing cultures at each passage analyzed. These large differences in number of divisions among individual cells guarantee a strong impact on generation of telomere length heterogeneity in normal cell cultures and suggest that culture conditions should be included in future modeling of cell senescence.