Re-Emergence of Poliovirus in the United States: Considerations and Implications.

The first case of paralytic poliomyelitis in nearly a decade in the US was discovered in a 20-year-old unvaccinated man from Rockland County, New York, in July 2022, who developed acute flaccid myelitis. The isolated virus from stool sampling was found to be a circulating vaccine-derived poliovirus type 2, derived from the oral polio vaccine. Since the discovery of this case, local wastewater surveillance has revealed evidence of circulating vaccine-derived poliovirus type 2 in local counties, as well as in New York City, representing community transmission. In the wake of the coronavirus disease 2019 pandemic, routine vaccination administration has declined globally, with increasing numbers of communities not vaccinated for poliovirus. Now, with evidence of local community transmission, the clinical implication for at-risk unvaccinated individuals is significant. Here, we review the epidemiological origin of this discovered strain of poliovirus, national and international methods of surveillance for poliovirus, and neurological features of poliovirus. We also highlight the opportunities and challenges involved in monitoring suspected cases, as well as the unique role neurologists might play in national and global poliomyelitis surveillance. ANN NEUROL 2022;92:725-728.

Behavioral activation therapy during transcranial magnetic stimulation for major depressive disorder.

BACKGROUND: Behavioral Activation (BA) Therapy and Transcranial Magnetic Stimulation (TMS) have each been shown to be effective in the treatment of adult outpatients with major depressive disorder (MDD). Combining both treatments may produce synergistic antidepressant outcomes. METHODS: We developed a new protocol for incorporating a simplified version of BA during a standard 6-week course of TMS and it was pilot tested in 11 consecutively treated outpatients with treatment resistant depression (TRD). BA was delivered in a 5-10 min interval daily prior to the start of TMS. Engagement in BA was measured by tracking the setting and attainment of between session "goals" during the course of TMS treatment. The Inventory of Depressive Symptoms (IDS-SR), the 9-item Patient Health Questionnaire (PHQ-9), and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to measure overall symptom improvement. RESULTS: Patients who underwent a combined BA + TMS protocol demonstrated an average goal completion rate of 77% along with overall symptom improvement as demonstrated by an average decrease of 47%, 55%, and 39% in IDS-SR, PHQ-9, and SHAPS scores respectively. BA was easily incorporated into the daily routine of administering TMS procedures. LIMITATIONS: There is inadequate power in this current investigation to compare treatment efficacy of BA + TMS to TMS alone. CONCLUSION: Incorporation of a modified version of BA therapy into a standard acute course of TMS therapy is feasible, well tolerated, and holds potential for augmenting the efficacy of TMS treatment for patients with TRD.

MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation.

Neurogenesis is a highly-regulated process occurring in the dentate gyrus that has been linked to learning, memory, and antidepressant efficacy. MicroRNAs (miRNAs) have been previously shown to play an important role in the regulation of neuronal development and neurogenesis in the dentate gyrus via modulation of gene expression. However, this mode of regulation is both incompletely described in the literature thus far and highly multifactorial. In this study, we designed sensors and detected relative levels of expression of 10 different miRNAs and found miR-338-3p was most highly expressed in the dentate gyrus. Comparison of miR-338-3p expression with neuronal markers of maturity indicates miR-338-3p is expressed most highly in the mature neuron. We also designed a viral "sponge" to knock down in vivo expression of miR-338-3p. When miR-338-3p is knocked down, neurons sprout multiple primary dendrites that branch off of the soma in a disorganized manner, cellular proliferation is upregulated, and neoplasms form spontaneously in vivo. Additionally, miR-338-3p overexpression in glioblastoma cell lines slows their proliferation in vitro. Further, low miR-338-3p expression is associated with increased mortality and disease progression in patients with glioblastoma. These data identify miR-338-3p as a clinically relevant tumor suppressor in glioblastoma.

Clinical characteristics and outcomes of patients with recurrence 5 years after nephrectomy for localized renal cell carcinoma.

PURPOSE: We analyzed characteristics in patients with recurrent renal cell carcinoma 5 years or later after nephrectomy and determined predictors of survival after recurrence. MATERIALS AND METHODS: From July 1989 to October 2008 at total of 2,368 nephrectomies were done for clinically localized, unilateral renal cell carcinoma at our institution. Of 256 patients with disease recurrence 44 had recurrence 5 years or more after nephrectomy. We compared clinicopathological characteristics in patients with disease recurrence before vs after 5 years. Survival from time of recurrence was assessed based on Memorial Sloan-Kettering Cancer Center risk score, symptoms at recurrence, metastasectomy, tumor diameter, and recurrence stage and site. RESULTS: Patients with late recurrence tended to have fewer symptoms at presentation, smaller tumors (median 8.5 vs 7 cm) and less aggressive disease (pT1 in 18% vs 39%). Median overall survival was 6.1 years from time of recurrence. Five-year actuarial survival was 85% in 28 patients at favorable risk and 14% in 10 at intermediate risk (log rank p <0.001). The 5-year estimated overall survival rate was 72% in 31 patients with incidentally detected recurrence and 39% in 11 with symptoms at recurrence (log rank p = 0.01). CONCLUSIONS: Data suggest that patients with cancer recurrence 5 years after nephrectomy are at favorable risk and have long-term median survival. A favorable Memorial Sloan-Kettering Cancer Center risk score and absent symptoms related to metastasis are associated with longer survival in these patients.