The longitudinal outcome of canine (K9) myxomatous mitral valve disease (LOOK-Mitral) registry: Baseline treatment characteristics.

OBJECTIVES: To describe the medical treatment prescribed or modified by veterinary cardiologists at the enrollment visit in dogs included in the longitudinal outcome of canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-mitral registry) and to evaluate the influence of the EPIC trial and other selected variables on cardiologist prescription habits. ANIMALS: The medical records of 6,102 dogs enrolled in the LOOK_mitral registry between 2015 and 2018 were retrospectively reviewed and 6,016 dogs were included. RESULTS: A medical treatment was prescribed by a cardiologist to 2,599 dogs (15% Stage-B1, 90% Stage-B2 and to all dogs in Stage-C). Angiotensin converting enzyme inhibitors (Ace-i) were the treatment most commonly prescribed for dogs in Stage-B1 (n = 352, 9%). The combination of pimobendan and an Ace-i was the most common treatment in Stage-B2 dogs (n = 367, 41%). Furosemide, an Ace-i, and pimobendan was the most common cardiac medical treatment prescribed for ACVIM Stage-C dogs (n = 704, 57%). Within each stage, dogs with larger left atrial and left ventricular dimensions were more likely to receive Ace-i, pimobendan or spironolactone. There was a four-fold increase in pimobendan prescription in Stage-B2 dogs after the publication of the EPIC trial. Moreover, a 15% reduction in Ace-i prescription and a 30% reduction in spironolactone prescription occurred after EPIC. In 974 dogs, a medical treatment was prescribed by the referring veterinarian. This was not changed (12%), modified (74%), or discontinued (14%) by the cardiologist. CONCLUSIONS: The EPIC trial and the echocardiographic assessment of left atrial and ventricular dimensions influence cardiologists' prescription habits.

Arrhythmogenic right ventricular cardiomyopathy in Bulldogs: Evaluation of clinical and histopathologic features, progression, and outcome in 71 dogs (2004-2016).

OBJECTIVES: This study aimed to characterize the clinical and histopathological features of arrhythmogenic right ventricular cardiomyopathy (ARVC) in English Bulldogs, American Bulldogs, and Bulldog-type mixed breed dogs and assess affected Bulldogs for a striatin gene mutation previously reported in Boxers with ARVC. ANIMALS: Seventy-one Bulldogs fit the inclusion criteria. Genetic analysis was performed on five dogs. Cardiac post-mortem evaluations were performed on two dogs. METHODS: Medical records from a single veterinary cardiology group (CVCA) were retrospectively evaluated. Tissue and blood samples were submitted for histopathological analysis and genetic testing in select patients. RESULTS: Presenting complaints included syncope (38%), arrhythmia (81.7%), or murmur (34.2%) documented on examination. On presentation, congestive heart failure (CHF) was diagnosed in 22 (31%) dogs, and 58 (81.7%) had ventricular arrhythmias. On bivariable analyses, the two-dimensional (2D) left atrial-to-aortic root ratio (LA:Ao) was the only prognostic variable significantly associated with survival time. Dogs with 2D LA:Ao below the mean (1.41) had longer median survival to all-cause mortality (12 months; 95% confidence interval [CI] six-15 months) than those with 2D LA:Ao above the mean (four months; 95% CI two-six months; p=0.0384). Most dogs (54%) died from cardiac disease, with 42.1% experiencing sudden death. The median time from diagnosis to cardiac death was four months. CONCLUSIONS: Arrhythmogenic right ventricular cardiomyopathy affects Bulldogs with both arrhythmogenic and dilated-type phenotypes. Despite variable arrhythmia severity and predominantly right-sided involvement in many dogs, an increase in left atrial size was the only significant predictor of mortality in this sample of dogs.

The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (LOOK-Mitral registry): Baseline characteristics.

INTRODUCTION: The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-Mitral registry) was established to describe the natural history and predictors of outcome in dogs affected by MMVD. This study was intended to describe the baseline characteristics of dogs in the LOOK-mitral registry. ANIMALS: Dogs with echocardiographic evidence of MMVD were prospectively enrolled by thirteen referral centers. RESULTS: A total of 6102 dogs with MMVD were included. The median age was 10 years (1-19 years), and mixed breed was the most common breed (n = 1,360, 22%). Concomitant diseases were reported in 2459 dogs with chronic respiratory diseases occurring most frequently (14%), followed by the presence of azotemia (6%) and orthopedic diseases (5%). Regarding disease severity, 65% of dogs were in ACVIM Stage-B1, 15% in Stage-B2, and 20% in Stage-C. Dogs in Stage-B1 were younger (p<0.001) than dogs in other stages. Murmur intensity, heart rate during physical examination, and radiographic vertebral heart score were positively associated with the stage. Dogs in Stage-C were more likely to have tachypnea (p<0.001), dyspnea (p<0.001), cough (p<0.001), syncopal episodes (p<0.001), and tachyarrhythmias (p<0.001) compared to dogs in Stage-B1 and B2. Echocardiographic indices of left atrial and ventricular size were positively correlated with the ACVIM stage. Interestingly, 4% of dogs that weighed <20 kg had an increased normalized end-systolic left ventricle internal diameter (>1.26). CONCLUSIONS: This study contributes to a better understanding of the clinical characteristics of dogs affected by MMVD and provides new findings that may be of clinical relevance.

Predictors of reoccurrence of congestive signs within 180 days after successful treatment of the first episode of congestive heart failure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cause of left-sided congestive heart failure in dogs. We sought to identify predictors of first reoccurrence of congestive signs (CS) within 180 days in dogs with MMVD and clinically stable heart failure. ANIMALS: A total of 445 dogs affected by stable American College of Veterinary Internal Medicine (ACVIM)-Stage-C MMVD were included, 106 in the reoccurrence group (RG) and 339 in no reoccurrence group (NRG). Patients were considered "stable" if medical treatment had been unchanged for at least 4 weeks since the first identification of CS. METHODS: Medical records of dogs with stable ACVIM-Stage-C MMVD included in a registry of dogs affected by MMVD were reviewed. Follow-up was required for inclusion in this investigation. Logistic regression was used to identify clinical and echocardiographic variables that independently predict first reoccurrence of CS. RESULTS: Baseline left atrial-aortic ratio (p=0.022, OR: 1.89, 90% CI: 1.20-2.98), left ventricular internal diameter at end-diastole (LVIDd_N) (p=0.014, OR: 2.84, 90% CI: 1.41-5.77), peak velocity of early diastolic transmitral flow (p=0.049, OR: 1.81, 90% CI: 1.10-3.00) and furosemide daily dosage (p=0.039, OR: 1.19, 90% CI: 1.04-1.37) were associated with reoccurrence of CS in univariable analyses. The LVIDd_N (p=0.014) remained significant in the multivariable analysis, but the area under the receiver operator characteristic curve was 0.57. CONCLUSION: This study failed to identify accurate predictors of reoccurrence of CS. However, dogs with larger value of LVIDd_N are more likely to have reoccurrence of CS within 180 days.

Use of Gonadotropin-Releasing Hormone Analogs in Children: Update by an International Consortium.

This update, written by authors designated by multiple pediatric endocrinology societies (see List of Participating Societies) from around the globe, concisely addresses topics related to changes in GnRHa usage in children and adolescents over the last decade. Topics related to the use of GnRHa in precocious puberty include diagnostic criteria, globally available formulations, considerations of benefit of treatment, monitoring of therapy, adverse events, and long-term outcome data. Additional sections review use in transgender individuals and other pediatric endocrine related conditions. Although there have been many significant changes in GnRHa usage, there is a definite paucity of evidence-based publications to support them. Therefore, this paper is explicitly not intended to evaluate what is recommended in terms of the best use of GnRHa, based on evidence and expert opinion, but rather to describe how these drugs are used, irrespective of any qualitative evaluation. Thus, this paper should be considered a narrative review on GnRHa utilization in precocious puberty and other clinical situations. These changes are reviewed not only to point out deficiencies in the literature but also to stimulate future studies and publications in this area.

On entropy and information in gene interaction networks.

MOTIVATION: Modern biological experiments often produce candidate lists of genes presumably related to the studied phenotype. One can ask if the gene list as a whole makes sense in the context of existing knowledge: Are the genes in the list reasonably related to each other or do they look like a random assembly? There are also situations when one wants to know if two or more gene sets are closely related. Gene enrichment tests based on counting the number of genes two sets have in common are adequate if we presume that two genes are related only when they are in fact identical. If by related we mean well connected in the interaction network space, we need a new measure of relatedness for gene sets. RESULTS: We derive entropy, interaction information and mutual information for gene sets on interaction networks, starting from a simple phenomenological model of a living cell. Formally, the model describes a set of interacting linear harmonic oscillators in thermal equilibrium. Because the energy function is a quadratic form of the degrees of freedom, entropy and all other derived information quantities can be calculated exactly. We apply these concepts to estimate the probability that genes from several independent genome-wide association studies are not mutually informative; to estimate the probability that two disjoint canonical metabolic pathways are not mutually informative; and to infer relationships among human diseases based on their gene signatures. We show that the present approach is able to predict observationally validated relationships not detectable by gene enrichment methods. The converse is also true; the two methods are therefore complementary. AVAILABILITY AND IMPLEMENTATION: The functions defined in this paper are available in an R package, gsia, available for download at https://github.com/ucsd-ccbb/gsia.

Advance provision of emergency contraception to young men: An exploratory study in a clinic setting.

PURPOSE: To explore the acceptability of advance provision of emergency contraceptive pills (ECPs) to young men seeking health care. METHODS: For this exploratory study in a clinic setting, we approached young men aged 16-35 to participate in a survey eliciting socio-demographics, sexual and contraceptive history, and knowledge about ECPs. We offered young men advance provision of ECPs and compared characteristics of 126 young men who did and did not accept the ECPs. RESULTS: Most (76%) of the participants accepted advance provision and left with an ECP pack, with even higher proportions among males whose sexual histories were suggestive of increased risk of involvement in an unintended pregnancy. CONCLUSIONS: This study holds promise to inform scale up of advance provision of ECPs among young men.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Endocrine treatment of gender-dysphoric/gender-incongruent persons: an Endocrine Society clinical practice guideline

OBJECTIVE: To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009. PARTICIPANTS: The participants include an Endocrine Society-appointed task force of nine experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: Group meetings, conference calls, and e-mail communications enabled consensus. Endocrine Society committees, members and cosponsoring organizations reviewed and commented on preliminary drafts of the guidelines. CONCLUSION: Gender affirmation is multidisciplinary treatment in which endocrinologists play an important role. Gender-dysphoric/gender-incongruent persons seek and/or are referred to endocrinologists to develop the physical characteristics of the affirmed gender. They require a safe and effective hormone regimen that will (1) suppress endogenous sex hormone secretion determined by the person's genetic/gonadal sex and (2) maintain sex hormone levels within the normal range for the person's affirmed gender. Hormone treatment is not recommended for prepubertal gender-dysphoric/gender-incongruent persons. Those clinicians who recommend gender-affirming endocrine treatments-appropriately trained diagnosing clinicians (required), a mental health provider for adolescents (required) and mental health professional for adults (recommended)-should be knowledgeable about the diagnostic criteria and criteria for gender-affirming treatment, have sufficient training and experience in assessing psychopathology, and be willing to participate in the ongoing care throughout the endocrine transition. We recommend treating gender-dysphoric/gender-incongruent adolescents who have entered puberty at Tanner Stage G2/B2 by suppression with gonadotropin-releasing hormone agonists. Clinicians may add gender-affirming hormones after a multidisciplinary team has confirmed the persistence of gender dysphoria/gender incongruence and sufficient mental capacity to give informed consent to this partially irreversible treatment. Most adolescents have this capacity by age 16 years old. We recognize that there may be compelling reasons to initiate sex hormone treatment prior to age 16 years, although there is minimal published experience treating prior to 13.5 to 14 years of age. For the care of peripubertal youths and older adolescents, we recommend that an expert multidisciplinary team comprised of medical professionals and mental health professionals manage this treatment. The treating physician must confirm the criteria for treatment used by the referring mental health practitioner and collaborate with them in decisions about gender-affirming surgery in older adolescents. For adult gender-dysphoric/gender-incongruent persons, the treating clinicians (collectively) should have expertise in transgender-specific diagnostic criteria, mental health, primary care, hormone treatment, and surgery, as needed by the patient. We suggest maintaining physiologic levels of gender-appropriate hormones and monitoring for known risks and complications. When high doses of sex steroids are required to suppress endogenous sex steroids and/or in advanced age, clinicians may consider surgically removing natal gonads along with reducing sex steroid treatment. Clinicians should monitor both transgender males (female to male) and transgender females (male to female) for reproductive organ cancer risk when surgical removal is incomplete. Additionally, clinicians should persistently monitor adverse effects of sex steroids. For gender-affirming surgeries in adults, the treating physician must collaborate with and confirm the criteria for treatment used by the referring physician. Clinicians should avoid harming individuals (via hormone treatment) who have conditions other than gender dysphoria/gender incongruence and who may not benefit from the physical changes associated with this treatment.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

[Therapy of ANCA-associated vasculitis with severe renal manifestation under routine conditions]. / Therapie der ANCA-assoziierten Vaskulitis mit schwerer renaler Beteiligung unter Routinebedingungen.

INTRODUCTION: In the MEPEX trial the poor prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with severe renal manifestation (AAVr) could be significantly improved in the first year by plasmapheresis. How and to what extent is this knowledge of AAVr therapy implemented into routine practice and what effectiveness and adverse events resulted? METHODS: This was a retrospective cohort study in which all patients who received remission induction therapy for AAVr under routine clinical conditions (RCC) in this hospital from 2009 to 2014 after publication of the MEPEX trial (n = 22) were compared with those in the plasmapheresis arm of the MEPEX trial (n = 70). Endpoints were dialysis-dependent chronic kidney disease and mortality after 3 and 12 months and severe life-threatening adverse events during the first 12 months. RESULTS: All patients with AAVr were treated by plasmapheresis under RCC. The two groups showed no differences with respect to the rate of dialysis dependency (after 3 months RCC 14 % versus MEPEX 16 %, P = 1.00 and after 12 months RCC 23 % versus MEPEX 14 %, P = 0.55) or mortality (after 3 months RCC 18 % versus MEPEX 16 %, P = 0.75 and after 12 months RCC 18 % versus MEPEX 27 %, P = 0.57). The rate of severe life-threatening adverse events was similar under RCC and under controlled study conditions (64 % versus 69 %, P = 0.87). CONCLUSION: Under RCC there is a high quality of medical treatment for AAVr. All patients received plasmapheresis for remission induction with comparable effectiveness and safety compared to controlled study conditions.

Experimental Demonstration of the Stabilizing Effect of Dielectric Coatings on Magnetically Accelerated Imploding Metallic Liners.

Enhanced implosion stability has been experimentally demonstrated for magnetically accelerated liners that are coated with 70 µm of dielectric. The dielectric tamps liner-mass redistribution from electrothermal instabilities and also buffers coupling of the drive magnetic field to the magneto-Rayleigh-Taylor instability. A dielectric-coated and axially premagnetized beryllium liner was radiographed at a convergence ratio [CR=Rin,0/Rin(z,t)] of 20, which is the highest CR ever directly observed for a strengthless magnetically driven liner. The inner-wall radius Rin(z,t) displayed unprecedented uniformity, varying from 95 to 130 µm over the 4.0 mm axial height captured by the radiograph.

Association of APOE polymorphisms and stressful life events with dementia in a Pakistani population.

Dementia is a major public health problem worldwide. Alzheimer's disease (AD) is a major form of dementia and the APOE 4 allele is an established genetic risk factor for AD. Similarly, stressful life events are also associated with dementia. The objective of this study was to examine the association of APOE 4 and stressful life events with dementia in a Pakistani sample, which to our knowledge has not been reported previously. We also tested for an interaction between stressful life events and APOE 4 on dementia risk. A total of 176 subjects (61 cases and 115 controls) were recruited. All cases and healthy controls were interviewed to assess cognition, co-morbidities, history of stressful life events and demographics. Blood genotyping for the APOE polymorphism (E2/E3/E4) was performed. APOE 4 and stressful life events were each independently and significantly associated with the risk of dementia (APOE 4: P=0.00697; stressful life events: P=5.29E-09). However, we did not find a significant interaction between APOE 4 carrier status and stressful life events on risk of dementia (P=0.677). Although the sample size of this study was small, the established association of APOE 4 with dementia was confirmed the first time in a Pakistani sample. Furthermore, stressful life events were also found to be significantly associated with dementia in this population.

Photon-enhanced thermionic emission from heterostructures with low interface recombination.

Photon-enhanced thermionic emission is a method of solar-energy conversion that promises to combine photon and thermal processes into a single mechanism, overcoming fundamental limits on the efficiency of photovoltaic cells. Photon-enhanced thermionic emission relies on vacuum emission of photoexcited electrons that are in thermal equilibrium with a semiconductor lattice, avoiding challenging non-equilibrium requirements and exotic material properties. However, although previous work demonstrated the photon-enhanced thermionic emission effect, efficiency has until now remained very low. Here we describe electron-emission measurements on a GaAs/AlGaAs heterostructure that introduces an internal interface, decoupling the basic physics of photon-enhanced thermionic emission from the vacuum emission process. Quantum efficiencies are dramatically higher than in previous experiments because of low interface recombination and are projected to increase another order of magnitude with more stable, low work-function coatings. The results highlight the effectiveness of the photon-enhanced thermionic emission process and demonstrate that efficient photon-enhanced thermionic emission is achievable, a key step towards realistic photon-enhanced thermionic emission based energy conversion.

Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial.

AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process continuing for years after presentation. We tested whether treatment with teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the new-onset period, affects the decline in C-peptide production in individuals with type 1 diabetes. METHODS: In a randomised placebo-controlled trial we treated 58 participants with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic centres in the USA. A central randomisation centre used computer generated tables to allocate treatments. Investigators, patients, and caregivers were blinded to group assignment. The primary outcome was a comparison of C-peptide responses to a mixed meal after 1 year. We explored modification of treatment effects in subgroups of patients. RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo treated groups, respectively. Thirty-one and 27, respectively, were analysed. Although the primary outcome analysis showed a 21.7% higher C-peptide response in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher (0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater proportion of placebo-treated participants lost detectable C-peptide responses at 12 months (p = 0.03). The teplizumab group required less exogenous insulin (p < 0.001) but treatment differences in HbA(1c) levels were not observed. Teplizumab was well tolerated. A subgroup analysis showed that treatment benefits were larger in younger individuals and those with HbA(1c) <6.5% at entry. Clinical responders to teplizumab had an increase in circulating CD8 central memory cells 2 months after enrolment compared with non-responders. CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin secretion may be affected by immune therapy with teplizumab after the new-onset period but the magnitude of the effect is less than during the new-onset period. Our studies identify characteristics of patients most likely to respond to this immune therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508 FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 RR024131 and UL1 RR024134 from the NIH.

Proteomic biomarkers for the early detection of acute kidney injury.

Acute kidney injury (AKI) comprises several syndromes that are associated with a sudden decrease in renal function. AKI is a common condition especially among critically ill patients. It is typically multifactorial and of great prognostic significance. The incidence of AKI has increased while the associated mortality rate has remained unchanged over the last years. Recent definitions of AKI, namely the Risk, Injury, Failure, Loss of renal function and End-stage kidney disease (RIFLE) classifycation or the Acute Kidney Injury Network (AKIN) criteria, incorporate serum creatinine and urine output as the principal markers to define and detect AKI. However, elevated serum creatinine or oliguria were demonstrated to detect AKI at late stages of renal injury when preventive strategies may be less effective. Therefore, there has recently been a great scientific interest in obtainng valuable markers for early AKI detection. In the last 5 years numerous new markers such as neutrophil-gelatinase associated lipo-calin, interleukin-18, cystatin C and kidney injury molecule 1 in the urine and/or serum have been studied and proposed as early detection markers of AKI. Persistently, these markers performed well in initial pilot trials. However, these promising results could often not be confirmed in later, larger multicentre trials and limitation of these biomarkers in the early diagnosis of renal injury were discovered. Furthermore, as AKI is multi-factorial and heterogeneous in origin, it seems likely that not one single marker but a panel of biomarkers will be required to detect all subtypes of AKI early during their evolution. This has initiated proteomic studies to develop panels of biomarkers which may facilitate early detection of AKI. The present review will focus on the most important clinical studies evaluating the ability of single AKI biomarkers and on those in clinical proteomics that attempted to establish panels of biomarkers in urine for early and accurate AKI diagnosis and prognosis.

Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells.

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans.

[Renal sonography]. / Nierensonographie.

Ultrasound is the most important non-invasive diagnostic tool for detecting morphological pathological alterations of the kidneys. With a low patient burden it permits rapid, potentially serial and highly reproducible bed-side diagnoses of postrenal acute kidney injury and chronic kidney disease. Within chronic kidney disease, polycystic kidney disease can reliably be detected and evidence can be obtained for ischemic nephropathy, diabetic nephropathy and chronic pyelonephritis by renal size and intrarenal morphological alterations. An additional domain of ultrasound is the differentiation of the dignity of solid and cystic renal lesions. Newly introduced contrast-enhanced ultrasound is of additional help as benign and malignant lesions display different perfusion patterns. Renal artery stenosis can reliably be identified and its hemodynamic effect can be assessed with a combination of direct and indirect criteria by Doppler and duplex ultrasound.

Hepatitis B in the United States: ongoing missed opportunities for hepatitis B vaccination, evidence from the Behavioral Risk Factor Surveillance Survey, 2007.

PURPOSE: In the USA, the burden of hepatitis B disproportionately affects high-risk adults who alone account for more than 75% of newly reported hepatitis B virus infections each year. Despite the localization of new infections in identifiable high-risk groups, vaccination rates in this subgroup, with the exception of health care workers, remain consistently low. The purpose of this study was to characterize those at risk for hepatitis B transmission and quantify the association between missed opportunities and hepatitis B vaccination. METHODS: Data from the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS) of adults aged 18 years and older who were at high risk for hepatitis B infection (n = 15,432) were analyzed. Multivariate regression analysis was conducted to determine factors independently associated with vaccination. RESULTS: In a nationally representative sample, 51.4% of high-risk adults remained unvaccinated against hepatitis B and more than 50% had a missed opportunity for vaccination. High-risk adults who were vaccinated against pneumonia and influenza had a higher odds ratio of being vaccinated against hepatitis B than those not vaccinated against pneumonia and influenza (OR 2.27 and 1.67, respectively). Also, high-risk adults tested for human immunodeficiency virus (HIV) at a counseling and testing site or a drug treatment facility had a higher OR of being vaccinated than those who had not been tested for HIV (OR 1.78 and 1.73, respectively). The opposite relationship was true among individuals tested for HIV at a correctional facility (OR 0.60). CONCLUSIONS: The findings of this study underscore the inadequacy of vaccination coverage in high-risk adults and highlight advantageous opportunities to bridge gaps in vaccination coverage.