Changes in peripheral oxytocin and vasopressin during a silent month-long Insight meditation retreat.

Background: Given its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators. Methods: Plasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes. Results: The retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat. Conclusion: These preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU): Trial Satisfaction and Attitudes towards Future Clinical Trials.

BACKGROUND: Clinical trial satisfaction is increasingly important for future trial designs and is associated with treatment adherence and willingness to enroll in future research studies or to recommend trial participation. In this post-trial survey, we examined participant satisfaction and attitudes toward future clinical trials in the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU). METHODS: We developed an anonymous, participant satisfaction survey tailored to participants enrolled in the DIAN-TU-001 double-blind clinical trial of solanezumab or gantenerumab and requested that all study sites share the survey with their trial participants. A total of 194 participants enrolled in the trial at 24 study sites. We utilized regression analysis to explore the link between participants' clinical trial experiences, their satisfaction, and their willingness to participate in upcoming trials. RESULTS: Survey responses were received over a sixteen-month window during 2020-2021 from 58 participants representing 15 study sites. Notably, 96.5% of the survey respondents expressed high levels of satisfaction with the trial, 91.4% would recommend trial participation, and 96.5% were willing to enroll again. Age, gender, and education did not influence satisfaction levels. Participants reported enhanced medical care (70.7%) and pride in contributing to the DIAN-TU trial (84.5%). Satisfaction with personnel and procedures was high (98.3%). Respondents had a mean age of 48.7 years, with most being from North America and Western Europe, matching the trial's demographic distribution. Participants' decisions to learn their genetic status increased during the trial, and most participants endorsed considering future trial participation regardless of the DIAN-TU-001 trial outcome. CONCLUSION: Results suggest that DIAN-TU-001 participants who responded to the survey exhibited high motivation to participate in research, overall satisfaction with the clinical trial, and willingness to participate in research in the future, despite a long trial duration of 4-7 years with detailed annual clinical, cognitive, PET, MRI, and lumbar puncture assessments. Implementation of features that alleviate barriers and challenges to trial participation is like to have a high impact on trial satisfaction and reduce participant burden.

Tailoring cytomegalovirus prophylaxis based on T cell immunity panel assessment in kidney transplant patients at high risk of cytomegalovirus.

BACKGROUND: Valganciclovir prophylaxis against cytomegalovirus (CMV) is recommended for solid organ transplant recipients, but is associated with drawbacks, including expense and leukopenia. Our center adopted a strategy of serial assessment with a CMV-specific T cell immunity panel (CMV-TCIP) and cessation of valganciclovir prophylaxis upon demonstration of adequate CD4+ responses in kidney transplant patients at high risk of CMV disease. METHODS: We retrospectively reviewed adult recipients of a kidney or pancreas transplant between August 2019 and July 2021 undergoing serial CMV-TCIP monitoring. Included patients were considered high risk for CMV, defined by donor positive (D+)/recipient negative (R-) CMV IgG serostatus, or recipient positive (R+) patients who received induction with a lymphocyte-depleting agent. Prophylaxis was discontinued after a patient's first CMV-specific CD4+ T cell value of ≥0.20%. Risk of clinically significant CMV infection (csCMVi) in those who underwent early discontinuation of CMV prophylaxis and predictors of CMV T cell immunity were analyzed. RESULTS: Of 54 included patients, 22 stopped prophylaxis early due to CMV-specific CD4+ T cell immunity at a median of 4.7 (IQR: 3.8-5.4) months after transplant. No instances of csCMVi were observed in the 22 patients who had prophylaxis discontinued early, of whom 19/22 were CMV R+ and 3/22 were CMV D+/R-. Donor/recipient CMV serostatus was predictive of immunity (p <.001). CONCLUSION: Early discontinuation of valganciclovir prophylaxis in patients with CMV CD4+ T cellular immunity appears safe and potentially beneficial in this preliminary series, especially in R+ patients. Further study is warranted, given that truncated prophylaxis may yield patient-level benefits.

Impact of OPTN policy 3.7D providing waiting time modification for candidates affected by race-inclusive eGFR calculations: Early results from a single center.

INTRODUCTION: OPTN Policy 3.7D, implemented January 5, 2023, mandates that all kidney transplant programs modify waiting time for candidates affected by race-inclusive eGFR calculations. We report the early impact of this policy change. METHODS: Our transplant program reviewed all listed transplant candidates and identified patients potentially eligible for waiting time modification. Eligible candidates received waiting time modification after submission of supporting evidence to the OPTN. We reviewed the impact on waiting time and transplant activity through October 1, 2023. RESULTS: Forty-six adult patients on our center's active waiting list self-identified as Black/African American. 25 (54.3%) candidates qualified for waiting time modification. A median 451 (321, 1543.5) additional days of waiting time was added for qualifying patients. Of the 25 patients who qualified for waiting time modification, 11 patients received a deceased donor kidney in the early period following waiting time modification, including 5 patients transplanted within 1 month after modification. CONCLUSIONS: Policy 3.7D is one of few national mandates to address specifically structural racism within transplantation. Implementation has yielded near immediate effects with greater than 40% of time-adjusted patients at our center receiving a deceased donor kidney transplant in the initial months after policy enactment. Early assessment demonstrates great potential impact for this policy.

Improved Early Post-Transplant Outcomes and Organ Use in Kidney Transplant Using Normothermic Regional Perfusion for Donation after Circulatory Death: National Experience in the US.

BACKGROUND: Normothermic regional perfusion (NRP) is a technique that is intended to enhance organ transplant outcomes from donation circulatory death (DCD) donors. STUDY DESIGN: A retrospective analysis of data from the Scientific Registry of Transplant Recipients was performed. DCD donors were screened for inclusion based on date of donation 2020 or later, and whether the heart was also recovered for transplantation. We grouped donors as either donation after brain death or DCD. DCD donors were further divided into groups including those in which the heart was not recovered for transplant (Non-Heart DCD) and those in which it was, based on recovery technique (thoracoabdominal-NRP [TA-NRP] Heart DCD and Super Rapid Recovery Heart DCD). RESULTS: A total of 219 kidney transplant recipients receiving organs from TA-NRP Heart DCD donors were compared to 436 SRR Super Rapid Recovery DCD, 10,630 Super Rapid Recovery non-heart DCD, and 27,820 donations after brain death recipients. Kidney transplant recipients of TA-NRP DCD allografts experienced shorter length of stay, lower rates of delayed graft function, and lower serum creatinine at the time of discharge when compared with recipients of other DCD allografts. CONCLUSIONS: Our analysis demonstrates superior early kidney allograft function when TA-NRP is used for DCD organ recovery.

Metabolic Remodeling during Early Cardiac Lineage Specification of Pluripotent Stem Cells.

Growing evidence indicates that metabolites and energy metabolism play an active rather than consequential role in regulating cellular fate. Cardiac development requires dramatic metabolic remodeling from relying primarily on glycolysis in pluripotent stem cells (PSCs) to oxidizing a wide array of energy substrates to match the high bioenergetic demands of continuous contraction in the developed heart. However, a detailed analysis of how remodeling of energy metabolism contributes to human cardiac development is lacking. Using dynamic multiple reaction monitoring metabolomics of central carbon metabolism, we evaluated temporal changes in energy metabolism during human PSC 3D cardiac lineage specification. Significant metabolic remodeling occurs during the complete differentiation, yet temporal analysis revealed that most changes occur during transitions from pluripotency to mesoderm (day 1) and mesoderm to early cardiac (day 5), with limited maturation of cardiac metabolism beyond day 5. Real-time metabolic analysis demonstrated that while hPSC cardiomyocytes (hPSC-CM) showed elevated rates of oxidative metabolism compared to PSCs, they still retained high glycolytic rates, confirming an immature metabolic phenotype. These observations support the opportunity to metabolically optimize the differentiation process to support lineage specification and maturation of hPSC-CMs.

Habituation of auditory responses in young autistic and neurotypical children.

Prior studies suggest that habituation of sensory responses is reduced in autism and that diminished habituation could be related to atypical autistic sensory experiences, for example, by causing brain responses to aversive stimuli to remain strong over time instead of being suppressed. While many prior studies exploring habituation in autism have repeatedly presented identical stimuli, other studies suggest group differences can still be observed in habituation to intermittent stimuli. The present study explored habituation of electrophysiological responses to auditory complex tones of varying intensities (50-80 dB SPL), presented passively in an interleaved manner, in a well-characterized sample of 127 autistic (MDQ = 65.41, SD = 20.54) and 79 typically developing (MDQ = 106.02, SD = 11.50) children between 2 and 5 years old. Habituation was quantified as changes in the amplitudes of single-trial responses to tones of each intensity over the course of the experiment. Habituation of the auditory N2 response was substantially reduced in autistic participants as compared to typically developing controls, although diagnostic groups did not clearly differ in habituation of the P1 response. Interestingly, the P1 habituated less to loud 80 dB sounds than softer sounds, whereas the N2 habituated less to soft 50 dB sounds than louder sounds. No associations were found between electrophysiological habituation and cognitive ability or participants' caregiver-reported sound tolerance (Sensory Profile Hyperacusis Index). The results present study results extend prior research suggesting habituation of certain sensory responses is reduced in autism; however, they also suggest that habituation differences observed using this study's paradigm might not be a primary driver of autistic participants' real-world sound intolerance.

The circadian clock is disrupted in pancreatic cancer.

Disruption of the circadian clock is linked to cancer development and progression. Establishing this connection has proven beneficial for understanding cancer pathogenesis, determining prognosis, and uncovering novel therapeutic targets. However, barriers to characterizing the circadian clock in human pancreas and human pancreatic cancer-one of the deadliest malignancies-have hindered an appreciation of its role in this cancer. Here, we employed normalized coefficient of variation (nCV) and clock correlation analysis in human population-level data to determine the functioning of the circadian clock in pancreas cancer and adjacent normal tissue. We found a substantially attenuated clock in the pancreatic cancer tissue. Then we exploited our existing mouse pancreatic transcriptome data to perform an analysis of the human normal and pancreas cancer samples using a machine learning method, cyclic ordering by periodic structure (CYCLOPS). Through CYCLOPS ordering, we confirmed the nCV and clock correlation findings of an intact circadian clock in normal pancreas with robust cycling of several core clock genes. However, in pancreas cancer, there was a loss of rhythmicity of many core clock genes with an inability to effectively order the cancer samples, providing substantive evidence of a dysregulated clock. The implications of clock disruption were further assessed with a Bmal1 knockout pancreas cancer model, which revealed that an arrhythmic clock caused accelerated cancer growth and worse survival, accompanied by chemoresistance and enrichment of key cancer-related pathways. These findings provide strong evidence for clock disruption in human pancreas cancer and demonstrate a link between circadian disruption and pancreas cancer progression.

Cultivating concern for others: Meditation training and motivated engagement with human suffering.

Contemplative traditions have long affirmed that compassion and kindness are trainable skills. While research on meditation practice has recently flourished, the mechanisms that might engender such changes are still poorly understood. Here, we present a motivational framework to explain why meditation training should increase concern for others and modulate empathic engagement with human suffering over time. Meditation practices are conceived as tools for enacting cognitive and emotion regulatory goals that are conditioned by the underlying ethical motivation of the training-to reduce and alleviate suffering. In support of this account, we present data from a randomized, wait-list-controlled study of intensive meditation. In Study 1, we use a novel cardiovascular index to show that 3 months of meditation training can increase the motivational salience of others' suffering, as compared to the salience of threats to oneself. In Study 2, we demonstrate that training-related changes in the ability to orient attention to suffering are mediated by the dynamic regulation of distress-related physiological arousal. Finally, in Study 3, we provide exploratory evidence suggesting that meditation training may influence how human suffering is encoded in memory, leaving lasting imprints on the recollection of emotional experience. Together, our findings suggest that meditation training can strengthen the motivational relevance of others' suffering, prompting a shift from self-focused to other-focused evaluative processing. Considering meditation training from a motivational standpoint offers an important perspective for understanding how compassion can be cultivated through intentional practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

University Coaching for Activity and Nutrition (UCAN): A weight-inclusive health coaching program.

Background: Given the body image and disordered eating struggles prevalent in young adults, weight-inclusive anti-diet programs are needed on college campuses. Such programs replace weight loss advice with changes that center physical and mental well-being. Methods/Program Design: University health and wellness programs such as University Coaching for Activity and Nutrition (UCAN) is a novel weight-inclusive health and wellness coaching program designed to support university students and faculty/staff in their development and maintenance of self-care behaviors related to physical activity, nutrition, sleep, and stress management. Specifically, we describe the program's mechanisms for participant recruitment, health coach training, session protocol, program evaluation, and supervision so other campuses can replicate the program model at their respective universities. Discussion: This work can help campuses cultivate positive self-care habits that improve physical and mental health through the lens of a weight-inclusive paradigm while also creating research and service-learning experiences for pre-health professionals.

"Neural Noise" in Auditory Responses in Young Autistic and Neurotypical Children.

Elevated "neural noise" has been advanced as an explanation of autism and autistic sensory experiences. However, functional neuroimaging measures of neural noise may be vulnerable to contamination by recording noise. This study explored variability of electrophysiological responses to tones of different intensities in 127 autistic and 79 typically-developing children aged 2-5 years old. A rigorous data processing pipeline, including advanced visualizations of different signal sources that were maximally independent across different time lags, was used to identify and eliminate putative recording noise. Inter-trial variability was measured using median absolute deviations (MADs) of EEG amplitudes across trials and inter-trial phase coherence (ITPC). ITPC was elevated in autism in the 50 and 60 dB intensity conditions, suggesting diminished (rather than elevated) neural noise in autism, although reduced ITPC to soft 50 dB sounds was associated with increased loudness discomfort. Autistic and non-autistic participants did not differ in MADs, and indeed, the vast majority of the statistical tests examined in this study yielded no significant effects. These results appear inconsistent with the neural noise account.

Shifting Baselines: Longitudinal Reductions in EEG Beta Band Power Characterize Resting Brain Activity with Intensive Meditation.

Objectives: A core assumption of meditation training is that cognitive capacities developed during formal practice will transfer to other contexts or activities as expertise develops over time. This implies that meditation training might influence domain-general neurocognitive systems, the spontaneous activity of which should be reflected in the dynamics of the resting brain. Previous research has demonstrated that 3 months of meditation training led to reductions in EEG beta band power during mindfulness of breathing practice. The current study extends these findings to ask whether concomitant shifts in power are observed during 2 min of eyes closed rest, when participants are not explicitly engaged in formal meditation. Methods: Experienced meditation practitioners were randomly assigned to practice 3 months of focused attention meditation in a residential retreat, or to serve as waitlist controls. The waitlist controls later completed their own 3-month retreat. Permutation-based cluster analysis of 88-channel resting EEG data was used to test for spectral changes in spontaneous brain activity over the course of the retreats. Results: Longitudinal reductions in EEG power in the beta frequency range were identified and replicated across the two independent training periods. Less robust reductions were also observed in the high alpha frequency range, and in individual peak alpha frequency. These changes closely mirror those previously observed during formal mindfulness of breathing meditation practice. Conclusions: These findings suggest that the neurocognitive effects of meditation training can extend beyond the bounds of formal practice, influencing the spontaneous activity of the resting brain. Rather than serving as an invariant baseline, resting states might carry meaningful training-related effects, blurring the line between state and trait change. Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-022-01974-9.

Persistent Relapsing Immune Thrombocytopenia Following COVID-19 Infection.

Immune thrombocytopenia (ITP) is a rare autoimmune disease that presents along a spectrum of disease severity, ranging from asymptomatic thrombocytopenia to potentially life-threatening bleeding complications. Recent case reports and case series suggest that a COVID-19 infection can trigger secondary ITP and may be associated with higher rates of bleeding and lower nadir platelet counts compared to patients with ITP of other etiologies. Multiple ITP relapses have also been described in some COVID-19 patients. We report the case of a 30-year-old otherwise healthy woman who presented to the hospital with fatigue, easy bruising, and a platelet count of 11 x 103/µL. She responded well to our initial treatment with prednisone and intravenous immunoglobulin (IVIG) but experienced a persistent disease course with nine ITP relapses (defined as platelet count <30 x 103/µL) over the next 10.5 months, requiring six additional hospital admissions for acute management as well as long-term maintenance medication adjustments. It is important for clinicians to recognize ITP as a potential complication of a COVID-19 infection and to initiate early therapy to prevent serious bleeding in these patients. Further studies will be needed to understand the natural history, optimal treatment, and prognosis for patients with relapsing COVID-19-associated ITP.

Multisensory integration and interactions across vision, hearing, and somatosensation in autism spectrum development and typical development.

Most prior studies of multisensory integration (MSI) in autism have measured MSI in only a single combination of modalities - typically audiovisual integration. The present study used onset reaction times (RTs) and 125-channel electroencephalography (EEG) to examine different forms of bimodal and trimodal MSI based on combinations of auditory (noise burst), somatosensory (finger tap), and visual (flash) stimuli presented in a spatially-aligned manner using a custom desktop apparatus. A total of 36 autistic and 19 non-autistic adolescents between the ages of 11-14 participated. Significant RT multisensory facilitation relative to summed unisensory RT was observed in both groups, as were significant differences between summed unisensory and multisensory ERPs. Although the present study's statistical approach was not intended to test effect latencies, these interactions may have begun as early as ∼45 ms, constituting "early" (<100 ms) MSI. RT and ERP measurements of MSI appeared independent of one another. Groups did not significantly differ in multisensory RT facilitation, but we found exploratory evidence of group differences in the magnitude of audiovisual interactions in ERPs. Future research should make greater efforts to explore MSI in under-represented populations, especially autistic people with intellectual disabilities and nonspeaking/minimally-verbal autistic people.

Changes in the expression of inflammatory and epigenetic-modulatory genes after an intensive meditation retreat.

Background: Meditation retreats are characterized by intensive or concentrated periods of meditation practice, commonly undertaken in a residential setting. Although research indicates that meditation training can positively influence physical and mental health outcomes, the biological consequences of meditation retreat interventions are relatively understudied. In this study, we examined the influence of a month-long, silent meditation retreat on the expression of genes involved in epigenetic modulation and immune processes. Method: We assessed gene expression changes in experienced meditators attending a month-long Insight meditation retreat (n = 28), as compared to a community control group (n = 34) of experienced practitioners living their everyday lives. Blood samples were collected on day two of the retreat (Time 1) and again 3 weeks later (Time 2). Control participants were also assessed across a 3-week interval, during which they maintained their regular daily routines. Results: As compared to controls, retreat participants showed differential changes in the expression of several genes involved in chromatin modulation and inflammation. The most substantive finding was downregulation of the TNF pathway in retreat participants, which was not observed in controls. Conclusions: These findings indicate that meditation retreat participation may influence some of the inflammatory mechanisms involved in the development of chronic diseases, and that this style of psychosocial intervention may have therapeutic potential, particularly in experienced practitioners.

Uncoupling of Proliferative Capacity from Developmental Stage During Directed Cardiac Differentiation of Pluripotent Stem Cells.

Lineage-specific differentiation of human-induced pluripotent stem cells (hiPSCs) into cardiomyocytes (CMs) offers a patient-specific model to dissect development and disease pathogenesis in a dish. However, challenges exist with this model system, such as the relative immaturity of iPSC-derived CMs, which evoke the question of whether this model faithfully recapitulates in vivo cardiac development. As in vivo cardiac developmental stage is intimately linked with the proliferative capacity (or maturation is inversely correlated to proliferative capacity), we sought to understand how proliferation is regulated during hiPSC CM differentiation and how it compares with in vivo mouse cardiac development. Using standard Chemically Defined Media 3 differentiation, gene expression profiles demonstrate that hiPSC-derived cardiomyocytes (hiPSC-CMs) do not progress past the equivalent of embryonic day 14.5 of murine cardiac development. Throughout differentiation, overall DNA synthesis rapidly declines with <5% of hiPSC-CMs actively synthesizing DNA at the end of the differentiation period despite their immaturity. Bivariate cell cycle analysis demonstrated that hiPSC-CMs have a cell cycle profile distinct from their non-cardiac counterparts from the same differentiation, with significantly fewer cells within G1 and a marked accumulation of cells in G2/M than their non-cardiac counterparts throughout differentiation. Pulse-chase analysis demonstrated that non-cardiac cells progressed completely through the cell cycle within a 24-h period, whereas hiPSC-CMs had restricted progression with only a small proportion of cells undergoing cytokinesis with the remainder stalling in late S-phase or G2/M. This cell cycle arrest phenotype is associated with abbreviated expression of cell cycle promoting genes compared with expression throughout murine embryonic cardiac development. In summary, directed differentiation of hiPSCs into CMs uncouples the developmental stage from cell cycle regulation compared with in vivo mouse cardiac development, leading to a premature exit of hiPSC-CMs from the cell cycle despite their relative immaturity.

A Multidimensional Investigation of Sensory Processing in Autism: Parent- and Self-Report Questionnaires, Psychophysical Thresholds, and Event-Related Potentials in the Auditory and Somatosensory Modalities.

Background: Reconciling results obtained using different types of sensory measures is a challenge for autism sensory research. The present study used questionnaire, psychophysical, and neurophysiological measures to characterize autistic sensory processing in different measurement modalities. Methods: Participants were 46 autistic and 21 typically developing 11- to 14-year-olds. Participants and their caregivers completed questionnaires regarding sensory experiences and behaviors. Auditory and somatosensory event-related potentials (ERPs) were recorded as part of a multisensory ERP task. Auditory detection, tactile static detection, and tactile spatial resolution psychophysical thresholds were measured. Results: Sensory questionnaires strongly differentiated between autistic and typically developing individuals, while little evidence of group differences was observed in psychophysical thresholds. Crucially, the different types of measures (neurophysiological, psychophysical, questionnaire) appeared to be largely independent of one another. However, we unexpectedly found autistic participants with larger auditory Tb ERP amplitudes had reduced hearing acuity, even though all participants had hearing acuity in the non-clinical range. Limitations: The autistic and typically developing groups were not matched on cognitive ability, although this limitation does not affect our main analyses regarding convergence of measures within autism. Conclusion: Overall, based on these results, measures in different sensory modalities appear to capture distinct aspects of sensory processing in autism, with relatively limited convergence between questionnaires and laboratory-based tasks. Generally, this might reflect the reality that laboratory tasks are often carried out in controlled environments without background stimuli to compete for attention, a context which may not closely resemble the busier and more complex environments in which autistic people's atypical sensory experiences commonly occur. Sensory questionnaires and more naturalistic laboratory tasks may be better suited to explore autistic people's real-world sensory challenges. Further research is needed to replicate and investigate the drivers of the unexpected association we observed between auditory Tb ERP amplitudes and hearing acuity, which could represent an important confound for ERP researchers to consider in their studies.

Steroid-Induced Diabetic Ketoacidosis: A Case Report and Review of the Literature.

It has been well documented that corticosteroid treatment can precipitate hyperglycemia and may lead to new diagnoses of type 2 diabetes mellitus. However, steroid-induced diabetic ketoacidosis (DKA) has rarely been reported in the literature. We report the case of an obese 73-year-old man with no known history of diabetes mellitus who presented with DKA after two months of treatment with high-dose steroids. Our patient's presentation and clinical course were consistent with ketosis-prone type 2 diabetes (KPDM-2). A literature review revealed three other reports of patients with steroid-induced DKA, two of whom also had clinical and biochemical features that were consistent with KPDM-2. We postulate that high-dose steroid treatment can trigger DKA in a subgroup of obese, middle-aged patients with risk factors for KPDM-2. Physicians should suspect steroid-induced KPDM-2 in obese patients who present with new-onset DKA after initiation of steroid treatment.

Extracellular Flux Analysis of Mitochondrial Function in Pluripotent Stem Cells.

Mitochondrial function and energy metabolism are increasingly recognized not only as regulators of pluripotent stem cell function and fate, but also as critical targets in disease pathogenesis and aging. Therefore across the downstream applications of pluripotent stem cells, including development and disease modeling, drug screening, and cell-based therapies, it is crucial to be able to measure mitochondrial function and metabolism in a high-throughput, real-time and label-free manner. Here we describe the application of Seahorse extracellular flux analysis to measure mitochondrial function in pluripotent stem cells and their derivatives. Specifically, we highlight two assays, the Mitochondrial Stress Test, which quantifies overall mitochondrial function including basal, maximal and ATP-couple oxygen consumption rates, and the Electron Transport Chain Complex Specific assay, that quantifies function of individual complexes within the electron transport chain.

Extended Use of The Spanner® Temporary Prostatic Stent in Catheter-Dependent Men with Comorbidities.

PURPOSE: This US FDA investigational device exemption (IDE) study evaluated the extended use of The Spanner® Temporary Prostatic Stent in catheter-dependent men with urinary retention who were not deemed candidates for corrective surgery but demonstrated bladder contractility. MATERIALS AND METHODS: The Spanner was placed for 3 cycles of 30 days in catheter-dependent men with comorbid conditions, confirmed detrusor contractility, and catheter-associated discomfort. At each visit, postvoid residual, maximum flow rate, international prostate symptom score, quality of life, and adverse events were assessed. Voiding success was defined as PVR ≤ 150 ml at all visits. RESULTS: One hundred seven men were enrolled at 8 US sites; 82/107 (76.6%) completed the trial, and 79/107 (73.8%) successfully maintained PVR ≤ 150 ml for the trial duration. Patients were 77.1 ± 10.6 years old; 63/107 (58.9%) were dependent on Foley and 40/107 (37.4%) on intermittent catheterization for 36.0 ± 39.3 days and 30.2 ± 45.8 days, respectively. 25/107 (23.4%) discontinuations were primarily due to voluntary patient withdrawal 9/107 (8.4%), investigator-initiated withdrawal 8/107 (7.5%), or lack of effectiveness 4/107 (3.7%). During Spanner use, the mean Q max was 11.2 ± 6.6, mean IPSS was 7.5 ± 6.4, and mean QOL was 2.0 ± 1.6. The most prevalent device-related adverse events were asymptomatic bacteriuria 25/107 (23.4%), discomfort 10/107 (9.4%), and urinary urgency 8/107 (7.5%). No device-related serious AEs were reported. CONCLUSIONS: This study demonstrates that catheter-dependent men with sufficient bladder contractility can achieve volitional voiding and successful bladder drainage using The Spanner Temporary Prostatic Stent for extended periods of time.