Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.Dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc) form an important part of the basal ganglia circuitry, playing key roles in movement initiation and coordination. A hallmark of Parkinson’s disease (PD) is the degeneration of these SNpc DNs leading to akinesia, bradykinesia and tremor. There is gathering evidence that oligomeric α-synuclein (α-syn) is one of the major pathologic species in PD, with its deposition in Lewy bodies (LBs) closely correlated with disease progression. However, the precise mechanisms underlying the effects of oligomeric α-syn on DN function have yet to be fully defined. Here, we have combined electrophysiological recording and detailed analysis to characterize the time-dependent effects of α-syn aggregates (consisting of oligomers and possibly small fibrils) on the properties of SNpc DNs. The introduction of α-syn aggregates into single DNs via the patch electrode significantly reduced both the input resistance and the firing rate without changing the membrane potential. These effects occurred after 8-16 min of dialysis but did not occur with the monomeric form of α-syn. The effects of α-syn aggregates could be significantly reduced by preincubation with the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide. These data suggest that accumulation of α-syn aggregates in DNs may chronically activate KATP channels leading to a significant loss of excitability and dopamine release.Myosin Va (MyoVa) is a plus-end filamentous-actin motor protein that is highly and broadly expressed in the vertebrate body, including in the nervous system. In excitatory neurons, MyoVa transports cargo toward the tip of the dendritic spine, where the postsynaptic density (PSD) is formed and maintained. MyoVa mutations in humans cause neurologic dysfunction, intellectual disability, hypomelanation, and death in infancy or childhood. Here, we characterize the Flailer (Flr) mutant mouse, which is homozygous for a myo5a mutation that drives high levels of mutant MyoVa (Flr protein) specifically in the CNS. Flr protein functions as a dominant-negative MyoVa, sequestering cargo and blocking its transport to the PSD. Flr mice have early seizures and mild ataxia but mature and breed normally. Flr mice display several abnormal behaviors known to be associated with brain regions that show high expression of Flr protein. Flr mice are defective in the transport of synaptic components to the PSD and in mGluR-dependent long-term depression (LTD) and have a reduced number of mature dendritic spines. The synaptic and behavioral abnormalities of Flr mice result in anxiety and memory deficits similar to that of other mouse mutants with obsessive-compulsive disorder and autism spectrum disorder (ASD). Because of the dominant-negative nature of the Flr protein, the Flr mouse offers a powerful system for the analysis of how the disruption of synaptic transport and lack of LTD can alter synaptic function, development and wiring of the brain and result in symptoms that characterize many neuropsychiatric disorders.Blockade of the PD1 pathway is a broadly effective cancer therapy, but additional immune-inhibitory pathways contribute to tumor immune evasion. HERV-H LTR-associating 2 (HHLA2; also known as B7H5 and B7H7) is a member of the B7 family of immunoregulatory ligands that mediates costimulatory effects through its interaction with the CD28 family member transmembrane and immunoglobulin domain containing 2 (TMIGD2). However, HHLA2 has also been known to have inhibitory effects on T cells. Here, we report that we have identified killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) as an inhibitory receptor for HHLA2 in T cells and natural killer (NK) cells and have generated HHLA2 and KIR3DL3 antibodies that block the immune-inhibitory activity of HHLA2, preserving the costimulatory signal. It is known that HHLA2 is frequently expressed in several tumor types, including clear cell renal cell carcinoma (ccRCC). check details We found that HHLA2 expression was nonoverlapping with PDL1 expression in ccRCC, suggesting that HHLA2 mediates a mechanism of tumor immune evasion that is independent from PDL1. Blockade of both the PD1 and KIR3DL3 pathways may be a more effective way to reverse tumor immune evasion.See related Spotlight on p. 128.Pelvic exenteration combines multiple organ resections and functional reconstruction. Many techniques have been described for urinary reconstruction, although only a few are routinely used. The aim of this review is to focus beyond the technical aspects and the advantages and disadvantages of each technique, and to include a critical analysis of continent techniques in the gynecologic and urologic literature. Selecting a technique for urinary reconstruction must take into account the constraints entailed by the natural history of the disease, patient characteristics, healthcare institution, and surgeon experience. In gynecologic oncology, the Bricker ileal conduit is the most commonly employed diversion, followed by the self-catheterizable pouch and orthotopic bladder replacement. Continent and non-continent diversions present similar immediate and long-term complication rates, including lower tract urinary infections and pyelonephritis (5-50%), ureteral stricture (3-27%), urolithiasis (5-25%), urinary fistula (5%), and more rarely, vitamin B12 deficiency and metabolic acidosis. Urinary incontinence for the ileal orthotopic neobladder (50%), stoma-related complications for the Bricker ileal conduit (24%), difficulty with self-catheterization (18%) for the continent pouch, and induction of secondary malignancy for the ureterosigmoidostomy (3%) are the most relevant technique-related complications following urinary diversion. The self-catheterizable pouch and orthotopic bladder require a longer learning curve from the surgical team and demand adaptation from the patient compared with the ileal conduit. Quality of life between different techniques remains controversial, although it would seem that young patients may benefit from continent diversions. We consider that centralization of pelvic exenteration in referral centers is crucial to optimize the oncologic and functional outcomes of complex ablative reconstructive surgery.