Incidence and risk factors for perineal hernia after robotic abdominoperineal resection: a single-center, retrospective cohort study.

BACKGROUND: Perineal hernia (PH) is a late complication of abdominoperineal resection (APR) that may compromise a patient's quality of life. The frequency and risk factors for PH after robotic APR adopting recent rectal cancer treatment strategies remain unclear. METHODS: Patients who underwent robotic APR for rectal cancer between December 2011 and June 2022 were retrospectively examined. From July 2020, pelvic reinforcement procedures, such as robotic closure of the pelvic peritoneum and levator ani muscles, were performed as prophylactic procedures for PH whenever feasible. PH was diagnosed in patients with or without symptoms using computed tomography 1 year after surgery. We examined the frequency of PH, compared characteristics between patients with PH (PH+) and without PH (PH-), and identified risk factors for PH. RESULTS: We evaluated 142 patients, including 53 PH+ (37.3%) and 89 PH- (62.6%). PH+ had a significantly higher rate of preoperative chemoradiotherapy (26.4% versus 10.1%, p = 0.017) and a significantly lower rate of undergoing pelvic reinforcement procedures (1.9% versus 14.0%, p = 0.017). PH+ had a lower rate of lateral lymph node dissection (47.2% versus 61.8%, p = 0.115) and a shorter operative time (340 min versus 394 min, p = 0.110). According to multivariate analysis, the independent risk factors for PH were preoperative chemoradiotherapy, not undergoing lateral lymph node dissection, and not undergoing a pelvic reinforcement procedure. CONCLUSIONS: PH after robotic APR for rectal cancer is not a rare complication under the recent treatment strategies for rectal cancer, and performing prophylactic procedures for PH should be considered.

Observation of Nonlinear Spin-Charge Conversion in the Thin Film of Nominally Centrosymmetric Dirac Semimetal SrIrO_{3} at Room Temperature.

Spin-charge conversion via spin-orbit interaction is one of the core concepts in the current spintronics research. The efficiency of the interconversion between charge and spin current is estimated based on Berry curvature of Bloch wave function in the linear-response regime. Beyond the linear regime, nonlinear spin-charge conversion in the higher-order electric field terms has recently been demonstrated in noncentrosymmetric materials with nontrivial spin texture in the momentum space. Here, we report the observation of the nonlinear charge-spin conversion in a nominally centrosymmetric oxide material SrIrO_{3} by breaking inversion symmetry at the interface. A large second-order magnetoelectric coefficient is observed at room temperature because of the antisymmetric spin-orbit interaction at the interface of Dirac semimetallic bands, which is subject to the symmetry constraint of the substrates. Our study suggests that nonlinear spin-charge conversion can be induced in many materials with strong spin-orbit interaction at the interface by breaking the local inversion symmetry to give rise to spin splitting in otherwise spin degenerate systems.

TGFß1 synergizes with FLT3 ligand to induce chemoresistant quiescence in acute lymphoblastic leukemia with MLL gene rearrangements.

Fms-like tyrosine kinase 3 (FLT3) is highly expressed in mixed-lineage leukemia (MLL) gene-rearranged acute lymphoblastic leukemia (MLL+ALL) with a dismal prognosis. We previously reported that FLT3 ligand (FL) stimulation induced cell cycle arrest in MLL+ALL cells leading to resistance against anti-leukemic agents. Given that FL stimulation enhanced transforming growth factor (TGF)ß1 mRNA levels in MLL+ALL cells, we extensively examined the effect of TGFß1 on the cell cycle progression and chemosensitivity in MLL+ALL cells, and found that TGFß1 stimulation induced MLL+ALL cells into cell cycle arrest resistant to arabinosyl cytosine; its effect was markedly enhanced in synergy with FL. Thus, it is likely that TGFß1 and FL, both abundantly produced by bone marrow stromal cells, function in a coordinated manner to render MLL+ALL cells chemoresistant, which should lead to the development of minimal residual disease (MRD) resulting in relapse. The use of inhibitors against FLT3 and TGFß1 may become a useful strategy for eradicating MRD in MLL+ALL.

Diversity of knockdown resistance alleles in a single house fly population facilitates adaptation to pyrethroid insecticides.

Insecticide use exerts a tremendous selection force on house fly populations, but the frequencies of the initial resistance mutations may not reach high levels if they have a significant fitness cost in the absence of insecticides. However, with the continued use of the same (or similar) insecticides, it is expected that new mutations (conferring equal or greater resistance, but less of a fitness cost) will evolve. Pyrethroid insecticides target the insect voltage sensitive sodium channel (VSSC) and have been widely used for control of house flies at animal production facilities for more than three decades. There are three Vssc mutations known that cause resistance to pyrethroids in house flies: knockdown resistance (kdr, L1014F), kdr-his (L1014H) and super-kdr (M918T + L1014F). Whether or not there are any new mutations in house fly populations has not been examined for decades. We collected house flies from a dairy in Kansas (USA) and selected this population for three generations. We discovered multiple new Vssc alleles, including two that give very high levels of resistance to most pyrethroids. The importance of these findings to understanding the evolution of insecticide resistance, designing appropriate resistance monitoring and management schemes, and the future of pyrethroids for house fly control are discussed.

Overcoming super-knock down resistance (super-kdr) mediated resistance: multi-halogenated benzyl pyrethroids are more toxic to super-kdr than kdr house flies.

Target site insensitivity because of mutations in the voltage-sensitive sodium channel gene (Vssc) is a major mechanism of resistance to pyrethroid insecticides in the house fly, Musca domestica. There are three known Vssc alleles that confer resistance to pyrethroids in the house fly: knock down resistance (kdr; L1014F), super-kdr (M918T + L1014F) and kdr-his (L1014H), but there has been no side-by-side comparison of the resistance levels that they confer. We compared the levels of resistance conferred by the three Vssc alleles in congenic strains to 19 structurally diverse pyrethroids, and compared the full-length Vssc cDNA sequences from each strain. Generally, the levels of resistance conferred were kdr-his < kdr < super-kdr. However, there was significant variation in this pattern, especially for super-kdr, for which both high and low resistance ratios were observed for several pyrethroids. We also examined the levels of resistance in heterozygotes. Resistance in each of the hybrids was generally inherited as an incompletely recessive trait, except for the kdr-his/kdr hybrids, which showed incompletely to completely dominant resistance (ie had resistance levels comparable to kdr homozygotes). The importance of these results to understanding the frequencies of these resistance alleles in natural populations, the evolution of insecticide resistance and resistance management strategies are discussed.

Amoeba-inspired nanoarchitectonic computing implemented using electrical Brownian ratchets.

In this study, we extracted the essential spatiotemporal dynamics that allow an amoeboid organism to solve a computationally demanding problem and adapt to its environment, thereby proposing a nature-inspired nanoarchitectonic computing system, which we implemented using a network of nanowire devices called 'electrical Brownian ratchets (EBRs)'. By utilizing the fluctuations generated from thermal energy in nanowire devices, we used our system to solve the satisfiability problem, which is a highly complex combinatorial problem related to a wide variety of practical applications. We evaluated the dependency of the solution search speed on its exploration parameter, which characterizes the fluctuation intensity of EBRs, using a simulation model of our system called 'AmoebaSAT-Brownian'. We found that AmoebaSAT-Brownian enhanced the solution searching speed dramatically when we imposed some constraints on the fluctuations in its time series and it outperformed a well-known stochastic local search method. These results suggest a new computing paradigm, which may allow high-speed problem solving to be implemented by interacting nanoscale devices with low power consumption.

Specific Roles of NMDA Receptor Subunits in Mental Disorders.

N-methyl-D-aspartate (NMDA) receptor plays important roles in learning and memory. NMDA receptors are a tetramer that consists of two glycine-binding subunits GluN1, two glutamate-binding subunits (i.e., GluN2A, GluN2B, GluN2C, and GluN2D), a combination of a GluN2 subunit and glycine-binding GluN3 subunit (i.e., GluN3A or GluN3B), or two GluN3 subunits. Recent studies revealed that the specific expression and distribution of each subunit are deeply involved in neural excitability, plasticity, and synaptic deficits. The present article summarizes reports on the dysfunction of NMDA receptors and responsible subunits in various neurological and psychiatric disorders, including schizophrenia, autoimmune-induced glutamatergic receptor dysfunction, mood disorders, and autism. A key role for the GluN2D subunit in NMDA receptor antagonist-induced psychosis has been recently revealed.

Involvement of inhibitory PAS domain protein in neuronal cell death in Parkinson's disease.

Inhibitory PAS domain protein (IPAS), a repressor of hypoxia-inducible factor-dependent transcription under hypoxia, was found to exert pro-apoptotic activity in oxidative stress-induced cell death. However, physiological and pathological processes associated with this activity are not known. Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur. Activation of the PINK1-Parkin pathway attenuated IPAS-dependent apoptosis. IPAS was markedly induced in the midbrain following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, and IPAS-deficient mice showed resistance to MPTP-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). A significant increase in IPAS expression was found in SNpc neurons in patients with sporadic PD. These results indicate a mechanism of neurodegeneration in PD.