Hematuria duration does not predict kidney function at 1 year in ANCA-associated glomerulonephritis

Objectives

Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.

Methods

We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.

Results

Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3] mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥90 days) was not predictive of eGFR at 1 year (p = 0.93).

Conclusions

In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression.     

Utility of snout wipe samples for influenza A virus surveillance in exhibition swine populations

Background

Sporadic influenza A virus (IAV) outbreaks in humans and swine have resulted from commingling of large numbers of people and pigs at agricultural fairs in the United States. Current antemortem IAV surveillance strategies in swine require collecting nasal swabs, which entails restraining pigs with snares. Restraint is labor-intensive for samplers, stressful for pigs, and displeasing to onlookers because pigs often resist and vocalize.

Objective

To evaluate the utility of snout wipes in exhibition swine as a method to make IAV surveillance efforts less intrusive, less labor-intensive, and more widely accepted among pig owners and exhibition officials.

Methods

Three materials (rayon/polyester gauze, cotton gauze, and Swiffer® Sweeper dry cloths) were inoculated with IAV, and viral recoveries from these materials were quantified using qRT-PCR and TCID₅₀ assays. In a field trial, paired cotton gauze snout wipes and gold standard polyester-tipped nasal swabs were collected from 553 pigs representing 29 agricultural fairs and the qualitative results of rRT-PCR and viral isolation were compared.

Results and Conclusions

Viral recoveries from potential snout wipe materials ranged from 0·26 to 1·59 log₁₀ TCID₅₀/ml less than that of the positive control in which no substrate was included; rayon/polyester gauze performed significantly worse than the other materials. In the field, snout wipes and nasal swabs had high levels of agreement for both rRT-PCR detection and virus isolation. Although further investigation and refinement of the sampling method is needed, results indicate that snout wipes will facilitate convenient and undisruptive IAV surveillance in pigs at agricultural fairs.     

Change Patterns of Homeless Individuals with Mental Illness: A Multiple Case Study

This multiple case study illuminates the individual change trajectories of four homeless men with mental illnesses who participated in a manualized life skills intervention to improve housing retention. Readiness-to-change, life skills knowledge and trauma symptoms were measured at baseline, post-intervention and at 3–6 months follow-up. Cluster analysis identified two patterns of readiness-to-change: engaged and pre-engaged. Change is non-linear and baseline readiness is not necessary to benefit from the intervention. Examining individuals’ lives in context illuminated the change process and demonstrated that varied patterns can lead to successful outcomes for housing stability and community reintegration.     

The Role of Parental Perceptions of Tic Frequency and Intensity in Predicting Tic-Related Functional Impairment in Youth with Chronic Tic Disorders

Tic severity is composed of several dimensions. Tic frequency and intensity are two such dimensions, but little empirical data exist regarding their relative contributions to functional impairment in those with chronic tic disorders (CTD). The present study examined the relative contributions of these dimensions in predicting tic-related impairment across several psychosocial domains. Using data collected from parents of youth with CTD, multivariate regression analyses revealed that both tic frequency and intensity predicted tic-related impairment in several areas; including family and peer relationships, school interference, and social endeavors, even when controlling for the presence of comorbid anxiety symptoms and Attention Deficit Hyperactivity Disorder diagnostic status. Results showed that tic intensity predicted more variance across more domains than tic frequency.     

Tic-related activity restriction as a predictor of emotional functioning and quality of life

Objectives

Tourette Syndrome (TS) is a chronic neuropsychiatric condition that frequently persists into adulthood. Existing research has identified demographic and symptom-level variables associated with psychopathology and poor quality of life in TS. However, behavior patterns associated with enhanced or adaptive psychological and global functioning among adults with TS have yet to be empirically identified. The current study examined whether tic-specific activity restriction is related to emotional functioning and quality of life in adults with TS.

Methods

Participants were 509 adults from the Tourette Syndrome Impact Survey who completed self-report measures of demographics, tic severity, emotional functioning, quality of life, and tic-related general and social activity restriction.

Results

Partial correlations controlling for tic severity indicated that tic-related general and social activity restriction were significantly correlated with lower quality of life and poorer emotional functioning. Hierarchical linear regression models indicated that activity restriction significantly predicted lower quality of life and poorer emotional functioning when controlling for tic severity and demographic variables.

Conclusions

Adults who restrict fewer activities due to tics, regardless of tic severity, experience greater quality of life and better emotional functioning. Clinically, adults with chronic tics may benefit from interventions focused on enhancing engagement in valued life activities.     

Electron tomography on γ‐aminobutyric acid‐ergic synapses reveals a discontinuous postsynaptic network of filaments

The regulation of synaptic strength at γ‐aminobutyric acid (GABA)‐ergic synapses is dependent on the dynamic capture, retention, and modulation of GABA A‐type receptors by cytoplasmic proteins at GABAergic postsynaptic sites. How these proteins are oriented and organized in the postsynaptic cytoplasm is not yet established. To better understand these structures and gain further insight into the mechanisms by which they regulate receptor populations at postsynaptic sites, we utilized electron tomography to examine GABAergic synapses in dissociated rat hippocampal cultures. GABAergic synapses were identified and selected for tomography by using a set of criteria derived from the structure of immunogold‐labeled GABAergic synapses. Tomography revealed a complex postsynaptic network composed of filaments that extend ～100 nm into the cytoplasm from the postsynaptic membrane. The distribution of these postsynaptic filaments was strikingly similar to that of the immunogold label for gephyrin. Filaments were interconnected through uniform patterns of contact, forming complexes composed of 2–12 filaments each. Complexes did not link to form an integrated, continuous scaffold, suggesting that GABAergic postsynaptic specializations are less rigidly organized than glutamatergic postsynaptic densities. J. Comp. Neurol. 522:921–936, 2014. © 2013 Wiley Periodicals, Inc.     

Sensory intolerance: Latent structure and psychopathologic correlates

Background

Sensory intolerance refers to high levels of distress evoked by everyday sounds (e.g., sounds of people chewing) or commonplace tactile sensations (e.g., sticky or greasy substances). Sensory intolerance may be associated with obsessive–compulsive (OC) symptoms, OC-related phenomena, and other forms of psychopathology. Sensory intolerance is not included as a syndrome in current diagnostic systems, although preliminary research suggests that it might be a distinct syndrome.

Objectives

First, to investigate the latent structure of sensory intolerance in adults; that is, to investigate whether it is syndrome-like in nature, in which auditory and tactile sensory intolerance co-occur and are associated with impaired functioning. Second, to investigate the psychopathologic correlates of sensory intolerance. In particular, to investigate whether sensory intolerance is associated with OC-related phenomena, as suggested by previous research.

Method

A sample of 534 community-based participants were recruited via Amazon.com's Mechanical Turk program. Participants completed measures of sensory intolerance, OC-related phenomena, and general psychopathology.

Results

Latent class analysis revealed two classes of individuals: those who were intolerant of both auditory and tactile stimuli (n = 150), and those who were relatively undisturbed by auditory or tactile stimuli (n = 384). Sensory-intolerant individuals, compared to those who were comparatively sensory tolerant, had greater scores on indices of general psychopathology, more severe OC symptoms, a higher likelihood of meeting caseness criteria for OC disorder, elevated scores on measures of OC-related dysfunctional beliefs, a greater tendency to report OC-related phenomena (e.g., a greater frequency of tics), and more impairment on indices of social and occupational functioning. Sensory-intolerant individuals had significantly higher scores on OC symptoms even after controlling for general psychopathology.

Conclusions

Consistent with recent research, these findings provide further evidence for a sensory intolerance syndrome. The findings provide a rationale for conducting future research for determining whether a sensory intolerance syndrome should be included in the diagnostic nomenclature.     

Scaling the primate lateral geniculate nucleus: Niche and neurodevelopment in the regulation of magnocellular and parvocellular cell number and nucleus volume

New stereological assessments of lateral geniculate nucleus (LGN) neuron numbers and volumes in five New World primates (Cebus apella, Saguinus midas niger, Alouatta caraya, Aotus azarae, and Callicebus moloch) and compiled LGN volumes for an additional 26 mammals were analyzed for a better understanding of visual system evolution. Both the magnocellular (M)‐ and the parvocellular (P)‐cell populations scale allometrically with brain volume in primates, P cells with a significantly higher slope such that, for every increase in M neuron number, P neuron numbers more than double (ln scale; y = 0.89x + 2.42R² = 0.664). In diurnal primates, the ratio of P to M cells was slightly but significantly higher than in nocturnal primates. For all mammals, including primates, LGN volume was unrelated to nocturnal or diurnal niche but showed marked differences in slope and intercept depending on taxonomic group. The allometric scaling of M and P cells can be related to the order of neurogenesis, with late‐generated P cells increasing with positive allometry compared with the earlier‐generated M cells. This developmental regularity links relative foveal representation to relative isocortex enlargement, which is also generated late. The small increase in the P/M cell ratio in diurnal primates may result from increased developmental neuron loss in the M‐cell population as it competes for limited termination zones in primary visual cortex. J. Comp. Neurol. 522:1839–1857, 2014. © 2013 Wiley Periodicals, Inc.     

Meta-Analysis to Assess the Quality of International Normalized Ratio Control and Associated Outcomes in Venous Thromboembolism Patients

Introduction

Patients with venous thromboembolism (VTE) frequently require vitamin K antagonists (VKAs) to prevent recurrent events, but their use increases hemorrhage risk. We performed a meta-analysis to assess the quality of international normalized ratio (INR) control, identify study-level predictors of poor control and to examine the relationship between INR control and adverse outcomes in VTE patients.

Materials and Methods

We searched bibliographic databases (1990-June 2013) for studies of VTE patients receiving adjusted-dose VKAs that reported time in range (2.0-3.0) or proportion of INRs in range and/or reported INR measurements coinciding with thromboembolic or hemorrhagic events. Meta-analysis and meta-regression analysis was performed.

Results

Upon meta-analysis, studies found 59% (95%CI: 54-64%) of INRs measured and 61% (95%CI: 59-63%) of the time patients were treated were spent outside the target range of 2.0-3.0; with a tendency for under- versus over-anticoagulation. Moreover, this poor INR control resulted in a greater chance of recurrent VTE (beta-coefficient = -0.46, p = 0.01) and major bleeding (beta-coefficient = -0.30, p = 0.02). Patients with an INR < 2.0 made up 58% (95%CI: 39-77%) of VTE cases, while those with an INR > 3.0 made up 48% (95%CI: 34-61%) of major hemorrhage cases. Upon meta-regression, being VKA-naïve (-14%, p = 0.04) and treated in the community (-7%, p < 0.001) were associated with less time in range, while being treated in Europe/United Kingdom (compared to North America) was associated with (11%, p = 0.003) greater time.

Conclusions

Strategies to improve INR control or alternative anticoagulants, including the newer oral agents, should be widely implemented in VTE patients to reduce the rate of recurrent events and bleeding.     

Spermatogonia differentiation requires retinoic acid receptor γ

Vitamin A is instrumental to mammalian reproduction. Its metabolite, retinoic acid (RA), acts in a hormone-like manner through binding to and activating three nuclear receptor isotypes, RA receptor (RAR)α (RARA), RARβ, and RARγ (RARG). Here, we show that 1) RARG is expressed by A aligned (A(al)) spermatogonia, as well as during the transition from A(al) to A(1) spermatogonia, which is known to require RA; and 2) ablation of Rarg, either in the whole mouse or specifically in spermatogonia, does not affect meiosis and spermiogenesis but impairs the A(al) to A(1) transition in the course of some of the seminiferous epithelium cycles. Upon ageing, this phenomenon yields seminiferous tubules containing only spermatogonia and Sertoli cells. Altogether, our findings indicate that RARG cell-autonomously transduces, in undifferentiated spermatogonia of adult testes, a RA signal critical for spermatogenesis. During the prepubertal spermatogenic wave, the loss of RARG function can however be compensated by RARA, as indicated by the normal timing of appearance of meiotic cells in Rarg-null testes. Accordingly, RARG- and RARA-selective agonists are both able to stimulate Stra8 expression in wild-type prepubertal testes. Interestingly, inactivation of Rarg does not impair expression of the spermatogonia differentiation markers Kit and Stra8, contrary to vitamin A deficiency. This latter observation supports the notion that the RA-signaling pathway previously shown to operate in Sertoli cells also participates in spermatogonia differentiation.