Search

Abstract Background The significance of perineural invasion (PNI) in prostate cancer (PC) is unclear. A recent report of patients with pT2N0R0 PC found that PNI at prostatectomy was independently associated with higher Gleason score and more diffuse prostatic disease. We aimed to test our hypothesis that PNI on prostate biopsy in pT2N0R0 patients is associated with increased Gleason score upgrading at prostatectomy. Methods We identified 2892 patients status post prostatectomy with pT2N0R0 PC from three institutions, diagnosed between 1 January 2008 and 31 December 2014. Multivariable logistic regression (MVA) was used to evaluate the association between prostate biopsy PNI status and surgical Gleason upgrading, while controlling for potential confounders. Results Of the 2892 patients identified, 14% had PNI on biopsy, of whom 21% had surgical Gleason upgrading, while 28% without PNI on biopsy had such upgrading (P 4 ng/mL (OR 1.26, P = .02). Conclusions In post‐prostatectomy patients with favorable‐risk PC, PNI on prostate biopsy was not associated with surgical Gleason score upgrading. This may be due to the association of PNI with more diffuse disease, leading to increased biopsy tumor yield and grading accuracy. These findings suggest that in this setting, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision‐making for men debating active surveillance, radiation, and surgery.

Globoid cell leukodystrophy (Krabbe disease) is a fatal neurodegenerative, demyelinating disease caused by dysfunctional activity of galactosylceramidase (GALC), leading to the accumulation of glycosphingolipids including psychosine. While oligodendrocytes have been extensively studied due to their high levels of GALC, the contribution of astrocytes to disease pathogenesis remains to be fully elucidated. In the current study, we generated induced pluripotent stem cells (iPSCs) from two donors with infantile onset Krabbe disease and differentiated them into cultures of astrocytes. Krabbe astrocytes recapitulated many key findings observed in humans and rodent models of the disease, including the accumulation of psychosine and elevated expression of the pro-inflammatory cytokine IL-6. Unexpectedly, Krabbe astrocytes had higher levels of glucosylceramide and ceramide, and displayed compensatory changes in genes encoding glycosphingolipid biosynthetic enzymes, suggesting a shunting away from the galactosylceramide and psychosine pathway. In co-culture, Krabbe astrocytes negatively impacted the survival of iPSC-derived human neurons while enhancing survival of iPSC-derived human microglia. Substrate reduction approaches targeting either glucosylceramide synthase or serine palmitoyltransferase to reduce the sphingolipids elevated in Krabbe astrocytes failed to rescue their detrimental impact on neuron survival. Our results suggest that astrocytes may contribute to the progression of Krabbe disease and warrant further exploration into their role as therapeutic targets.

Ca2+ signaling is a major contributor to sensory hair cell function in the cochlea. Oncomodulin (OCM) is a Ca2+ binding protein (CaBP) preferentially expressed in outer hair cells (OHCs) of the cochlea and few other specialized cell types. Here, we expand on our previous reports and show that OCM delays hearing loss in mice of two different genetic backgrounds: CBA/CaJ and C57Bl/6J. In both backgrounds, genetic disruption of Ocm leads to early progressive hearing loss as measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). In both strains, loss of Ocm reduced hearing across lifetime (hearing span) by more than 50% relative to wild type (WT). Even though the two WT strains have very different hearing spans, OCM plays a considerable and similar role within their genetic environment to regulate hearing function. The accelerated age-related hearing loss (ARHL) of the Ocm KO illustrates the importance of Ca2+ signaling in maintaining hearing health. Manipulation of OCM and Ca2+ signaling may reveal important clues to the systems of function/dysfunction that lead to ARHL.

Adolescent bulimia nervosa (BN) remains relatively understudied, and the complex interaction between core eating psychopathology and emotional regulation difficulties provides ongoing challenges for full symptom remission. In an open pilot trial, we aimed to investigate the efficacy of a program integrating family-based treatment (FBT) and dialectical behavior therapy (DBT) in treating adolescent BN, without exclusion criteria. Participants were 35 adolescents who underwent partial hospital treatment for BN, and outcomes included measures of core BN pathology and emotional regulation difficulties, as well as parental measures of self-efficacy, completed at intake and discharge. Results indicate significant improvements in overall eating disorder pathology, t(68) = 4.52, p = .002, and in core BN symptoms, including objective binge episodes, t(68) = 2.01, p = .041, and self-induced vomiting, t(68) = 2.90, p = .005. Results also illustrated a significant increase in parental efficacy throughout the course of treatment, t(20) = .081, p = .001, although no global improvement in difficulties in emotion regulation was noted, t(68) = 1.12, p = .285. These preliminary findings support the utility of this integration of FBT and DBT, although raise interesting questions as to the mechanism of symptom remission.

An increasing body of evidence supports the use of family-based treatment (FBT) in medically stable outpatient presentations of adolescent anorexia nervosa, although there is relatively less research on adapting evidence-based treatment approaches in more intensive levels of patient care. The integration of FBT, which centrally leverages parental involvement in more intensive levels of care which typically require greater clinical management, requires careful consideration. We provide an overview of several key practical and theoretical considerations when adjusting the delivery of FBT across more intensive levels of patient care, providing clinical guidelines for the delivery of FBT while ensuring fidelity to the core theoretical tenets. Implications for clinical practice and future research are discussed.

Dialectical behavior therapy (DBT) and family-based treatment (FBT) are two evidence-based interventions that have been applied in the treatment of bulimia nervosa (BN) in adolescents. While DBT focuses on providing skills for coping with emotion dysregulation that often co-occurs with BN, FBT targets the normalization of eating patterns. The purpose of the current article is to introduce an integration of both treatments to provide a more comprehensive approach that targets the full scope of the disorder. We provide a review of the conceptual similarities and differences between FBT-BN and DBT along with strategies to guide a blended treatment approach. Given the strengths and limitations of either independent treatment, DBT and FBT-BN complement one another and together can address the range of symptoms and behaviors typically seen in adolescent BN.

Drawing from a content analysis of publicly traded companies' privacy notices, a survey of managers, a field study, and five online experiments, this research investigates how consumers respond to privacy notices. A privacy notice, by placing legally enforceable limits on a firm's data practices, communicating safeguards, and signaling transparency, might be expected to promote confidence that personal data will not be misused. Indeed, most managers expected a privacy notice to make customers feel more secure (Study 1). Yet, consistent with the analogy that bulletproof glass can increase feelings of vulnerability despite the protection offered, formal privacy notices undermined consumer trust and decreased purchase interest even when they emphasized objective protection (Studies 2, 3, and 5) or omitted any mention of potentially concerning data practices (Study 6). These unintended consequences did not occur, however, when consumers had an a priori reason to be distrustful (Study 4) or when benevolence cues were added to privacy notices (Studies 5 and 6). Finally, Study 7 showed that both the presence and conspicuous absence of privacy information are sufficient to trigger decreased purchase intent. Together, these results provide actionable guidance to managers on how to effectively convey privacy information (without hurting purchase interest). [ABSTRACT FROM AUTHOR]

The Mars2020 Perseverance Rover landed successfully on the Martian surface on the Jezero Crater floor (18.44°N, 77.45°E) at Martian solar longitude, Ls, ∼5° in February 2021. Since then, it has produced highly valuable environmental measurements with a versatile scientific payload including the MEDA (Mars Environmental Dynamics Analyzer) suite of environmental sensors. One of the MEDA systems is the PS pressure sensor system, which weighs 40 g and has an estimated absolute accuracy of better than 3.5 Pa and a resolution of 0.13 Pa. We present initial results from the first 414 sols of Martian atmospheric surface pressure observations by the PS, whose performance was found to meet its specifications. Observed sol‐averaged atmospheric pressures follow an anticipated pattern of pressure variation in the course of the advancing season and are consistent with data from other landing missions. The observed daily pressure amplitude varies by ∼2%–5 % of the sol‐averaged pressure, with absolute amplitude 10–35 Pa in an approximately direct relationship with airborne dust. During a regional dust storm, which began at Ls ∼ 135°, the daily pressure amplitude roughly doubled. The daily pressure variations were found to be remarkably sensitive to the seasonal evolution of the atmosphere. In particular, analysis of the daily pressure signature revealed diagnostic information likely related to the regional scale structure of the atmosphere. Comparison of Perseverance pressure observations with data from other landers reveals the global scale seasonal behavior of Mars' atmosphere. Plain Language Summary: Mars2020 Perseverance Rover successfully arrived on Mars in February 2021. It landed in an early Martian spring afternoon in a crater north of Mars' equator called Jezero crater. The rover is equipped with meteorological instruments that have so far produced extensive and valuable data for understanding the Martian atmosphere. One of the meteorological instruments is an accurate and precise pressure sensor. The pressure sensor has revealed large changes in the pressure over the seasons that are related to large changes in the actual mass of the Martian atmosphere. This is in line with seasonal pressure changes measured during previous Mars missions and can be explained as the condensation of the atmosphere onto the Martian poles and its subsequent sublimation. On a shorter time scale, the pressure sensor revealed complex pressure changes over a Martian day. These variations are thought to be related to atmospheric dust, whose ubiquitous nature is known to have a strong influence on the Martian climate. As the seasons progressed, the daily pressure variations morphed to exhibit different patterns likely related to the large‐scale regional changes in the atmosphere. Comparison of Perseverance pressure observations with other landers revealed the global nature of the atmosphere. Key Points: The atmospheric pressure observations by Perseverance Rover have proved to be of excellent quality fulfilling expectationsJezero crater pressure exhibits significant differences to other Martian areas likely due to varying regional geography and solar forcingOverall, the diurnal and seasonal atmospheric pressure cycles at Jezero Crater follow an anticipated pattern of pressure variation [ABSTRACT FROM AUTHOR]