Sensory processing, and auditory processing in particular, is altered in individuals with neurodevelopmental disorders such as autism spectrum disorders (ASDs). The typical maturation of the auditory system is perturbed in these individuals during early development, which may underlie altered auditory reactivity that persists in later life. Of the many genes that regulate the auditory system development, loss-of-function mutations in the gene are strongly associated with language processing deficits and ASD. Therefore, using a novel knock-out rat model, we tested the impact of loss on auditory processing, filtering, and reactivity throughout development and young adulthood in male and female animals. Although hearing thresholds were not altered in knock-out animals, we found a reduction in response amplitudes and a delay in response latency of the auditory brainstem response (ABR) in juvenile knock-out rats compared with age-matched controls. Amplitudes and latency of the ABR largely normalized by adulthood, indicating a delayed maturation of auditory processing pathways in knock-out rats. Despite the reduced ABR amplitudes, adolescent knock-out animals displayed increased startle reactivity accompanied by disruptions in sensory filtering and sensorimotor gating across various conditions, most of which persisted in adulthood. All of these observations show striking parallels to disruptions reported in ASD. Our results also imply that developmental disruptions of sensory signal processing are associated with persistent changes in neural circuitries responsible for implicit auditory evoked behavior, emphasizing the need for interventions that target sensory processing disruptions early during development in ASD. This is the first study of brainstem auditory processing in a novel knock-out rat model with very high construct and face validity for autism spectrum disorders. Electrophysiological and behavioral measures of implicit auditory-evoked responses were systematically taken across developmental stages. Auditory processing, filtering, and reactivity disruptions show striking similarities to observations in autism. We also show for the first time that, whereas auditory brainstem responses normalize by adulthood, disruptions in brainstem-mediated auditory-evoked behavior persist. This indicates that early developmental perturbations in sensory processing can cause permanent maladaptive changes in circuitries responsible for auditory reactivity, underlining the importance for interventions early during development aiming at normalizing sensory processing.

Background: Renal cell carcinoma (RCC) is the most common cancer of the kidney. The most common histotype is clear-cell (cc) RCC. Hydrogen sulfide (H 2 S) is an angiogenic and anti-apoptotic gasotransmitter that is elevated under pseudohypoxic conditions. H 2 S is endogenously produced by three enzymes: Cystathionine γ-lyase (CSE), cystathionine βsynthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MPST). Seeing as increased expression of these enzymes has been observed in other human cancer types, this study aimed to quantify H 2 S-producing enzyme expression in human RCC samples and evaluate whether it correlated with clinical outcomes. Patients and Methods: Eighty-eight human kidney tissue specimens, with healthy and cancerous tissue components, were immunohistochemically stained for CSE, CBS, and MPST. The mean pixel intensity of positively stained areas was quantified. A retrospective analysis was conducted to obtain patient demographics, rates of metastasis/recurrence, and prognostic characteristics. Statistical correlations between enzyme expressions and subsequent patient outcomes were evaluated. Results: There was significantly greater expression of CSE, CBS, and MPST in cc-RCC compared to paired healthy tissue (p<0.0001). The difference in expression of CSE in cancerous versus normal tissue was significantly greater than that for CBS and MPST (p<0.0001 and p<0.01, respectively). Enzyme expression patterns in cancerous versus normal tissue did not correlate with nuclear grade, stage, histological type or cancer recurrence/metastasis. Conclusion: To our knowledge, this is the first report of the differential increase in expression of CSE, CBS, and MPST in human RCC. Although these patterns do not appear to correlate with cancer recurrence, metastasis, size or nuclear grade, their differential increase suggests a potential therapeutic target. Renal cell carcinoma (RCC) is the most common cancer of the kidney. It accounts for 80-90% of all kidney cancer cases and has a cancer-specific mortality rate of 30-40% (1, 2). Incidence rates of RCC have increased over the past few decades, and this is largely attributed to increased detection by diagnostic tools (1, 3). RCC is subdivided into various histotypes based on tumour morphology, genetic signature, clinical manifestation, and area of the nephron where the tumour is present. The most common type of RCC is clearcell (cc) RCC, accounting for 80% of all cases. Other types included papillary, chromophobe and others, which can be classified as non-cc-RCC (4).

Introduction: Kidney and simultaneous pancreas-kidney (SPK) transplant recipients can have prolonged postoperative hospitalization due to edema. Thrombo-embolic-deterrent (TED) stockings with intermittent pneumatic compression devices (TED+IPC) have been used to improve venous return during the perioperative period. The objective of this trial was to evaluate the effects of TED+IPC vs. muscle pump activator (MPA) devices on factors that could reduce postoperative complications and duration of hospitalization. Methods: In this single-center, prospective, randomized, controlled trial, 221 kidney and SPK transplant recipients were randomized to either wearing TED+IPC or MPA for six days postoperatively. Groups were compared with respect to postoperative urine output, lower limb edema, weight, days in hospital, mobility, serum creatinine, delayed graft function, need for dialysis, and lower extremity blood flow. Results: Patients in the MPA group had significantly higher urine output and less increase in mid-calf leg circumference and weight gain compared to the TED+IPC group (p=0.003, p=0.001, and p=0.003, respectively). The MPA group also experienced shorter hospitalization (p=0.038), higher femoral vein velocity (p=0.001), and took more steps (p=0.009). Incidence of delayed graft function (p=0.72) and number of dialysis runs (p=0.39) was not different between study groups. Subgroup analysis of primary endpoints in donation after cardiac death recipients and SPK recipients did not yield any significance between the study arms. Conclusions: Postoperative use of the MPA device increases urine output, decreases leg edema, minimizes weight gain, and decreases duration of hospitalization after kidney transplantation. A larger and longer-term trial is needed to evaluate the impact on graft function.

Introduction: We aimed to evaluate the impact of thrombo-embolic-deterrent + intermittent pneumatic compression (TED + IPC) vs. muscle pump activator (MPA) on incisional wound healing in kidney and simultaneous pancreas- kidney (SPK) transplant recipients. Methods: We conducted a single-centre, randomized controlled trial in which 104 patients (kidney n=94; SPK n=10) were randomly assigned to wear TED + IPC (n= 52) or MPA (n=52) for the first six days following surgery. Patient demographics, postoperative outcomes, and incisional wound images were taken using a HIPAA-compliant application on postoperative days (POD) 3, 5, and 30, and assessed using the validated Southampton Wound Care Score. Results: There were no demographic differences between the groups. The MPA group had a significant improvement in wound healing on POD 3 (p=0.04) that persisted until POD 5 (p=0.0003). At POD 30, both groups were similar in wound healing outcomes (p=0.51). Bayesian inferential analysis revealed that the use of TED + IPC following transplantation had inferior outcomes compared to the use of MPA with sequential moderate evidence. The rate of complex wound infections was significantly greater in the TED + IPC group compared to the MPA group (29% vs. 12%, respectively; p=0.03). Patients were more satisfied with the use of a MPA device than TED + IPC. No major complications were encountered in either group. Conclusions: The use of a MPA device in the immediate postoperative period leads to a significant improvement in immediate and early wound healing, and decreased number of complex wound infections following kidney and SPK transplantation compared to standard TED + IPC therapy. Patients were more satisfied with the use of a MPA device than TED + IPC.