Direct and indirect pathways for heterosynaptic interaction underlying developmental synapse elimination in the mouse cerebellum.

Developmental synapse elimination is crucial for shaping mature neural circuits. In the neonatal mouse cerebellum, Purkinje cells (PCs) receive excitatory synaptic inputs from multiple climbing fibers (CFs) and synapses from all but one CF are eliminated by around postnatal day 20. Heterosynaptic interaction between CFs and parallel fibers (PFs), the axons of cerebellar granule cells (GCs) forming excitatory synapses onto PCs and molecular layer interneurons (MLIs), is crucial for CF synapse elimination. However, mechanisms for this heterosynaptic interaction are largely unknown. Here we show that deletion of AMPA-type glutamate receptor functions in GCs impairs CF synapse elimination mediated by metabotropic glutamate receptor 1 (mGlu1) signaling in PCs. Furthermore, CF synapse elimination is impaired by deleting NMDA-type glutamate receptors from MLIs. We propose that PF activity is crucial for CF synapse elimination by directly activating mGlu1 in PCs and indirectly enhancing the inhibition of PCs through activating NMDA receptors in MLIs.

The potential of an artificial intelligence for diagnosing MRI images in rectal cancer: multicenter collaborative trial.

BACKGROUND: An artificial intelligence-based algorithm we developed, mrAI, satisfactorily segmented the rectal tumor, rectum, and mesorectum from MRI data of rectal cancer patients in an initial study. Herein, we aimed to validate mrAI using an independent dataset. METHODS: We utilized MRI images collected in another nationwide research project, "Open versus Laparoscopic Surgery for Advanced Low Rectal Cancer Patients". MRIs from 467 cases with upfront surgery were utilized; six radiologists centralized the MRI evaluations. The diagnostic accuracies of mrAI and the radiologists for tumor depth were compared using pathologic diagnosis as a reference. RESULTS: For all cases, centralized diagnosis demonstrated 84.2% sensitivity, 37.7% specificity, and 73.7% accuracy; mrAI exhibited 70.6% sensitivity, 61.3% specificity, and 68.5% accuracy. After limiting MRIs to those acquired by a Philips scanner, with an inter-slice spacing of ≤ 6 mm-both conditions similar to those used in the development of mrAI-the performance of mrAI improved to 76.8% sensitivity, 76.7% specificity, and 76.7% accuracy, while the centralized diagnosis showed 81.8% sensitivity, 36.7% specificity, and 71.3% accuracy. Regarding relapse-free survival, the prognosis for tumors staged ≥ T3 was significantly worse than for tumors staged ≤ T2 (P = 0.0484) in the pathologic diagnosis. While no significant difference was observed between ≥ T3 and ≤ T2 tumors in the centralized diagnosis (P = 0.1510), the prognosis for ≥ T3 was significantly worse in the mrAI diagnosis (P = 0.0318). CONCLUSION: Proper imaging conditions for MRI can enhance the accuracy of mrAI, which has the potential to provide feedback to radiologists without overestimating tumor stage.

Prophylactic sildenafil to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis.

BACKGROUND: Bronchopulmonary dysplasia (BPD) persists as one of the foremost factors contributing to mortality and morbidity in extremely preterm infants. The effectiveness of administering sildenafil early on to prevent BPD remains uncertain. The aim of this study was to investigate the efficacy and safety of prophylactically administered sildenafil during the early life stages of preterm infants to prevent mortality and BPD. METHODS: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, and Ichushi were searched. Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated the certainty of evidence (CoE) following the Grading of Recommendations Assessment and Development and Evaluation approach. The random-effects model was used for a meta-analysis of RCTs. RESULTS: This review included three RCTs (162 infants). There were no significant differences between the prophylactic sildenafil and placebo groups in mortality (risk ratio [RR]: 1.32; 95% confidence interval [CI]: 0.16-10.75; very low CoE), BPD (RR: 1.20; 95% CI: 0.79-1.83; very low CoE), and all other outcome assessed (all with very low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: The prophylactic use of sildenafil in individuals at risk of BPD did not indicate any advantageous effects in terms of mortality, BPD, and other outcomes, or increased side effects.

Right-sided versus left-sided colorectal cancer in elderly patients: a sub-analysis of a large multicenter case-control study in Japan.

PURPOSE: This study investigated the impact of sidedness of colorectal cancer (CRC) in elderly patients on the prognosis. METHODS: In a sub-analysis of a multicenter case-control study of CRC patients who underwent surgery at ≥ 80 years old conducted in Japan between 2003 and 2007, both short- and long-term outcomes were compared between right-sided colon cancers (RCCs) and left-sided colorectal cancers (LCCs). RCCs were defined as those located from the cecum to the transverse colon. RESULTS: Among the 1680 patients who underwent curative surgery, 812 and 868 had RCCs and LCCs, respectively. RCCs were more frequent than LCCs in those who were female, had renal comorbidities, and had a history of abdominal surgery. Regarding tumor characteristics, RCCs were larger, invaded more deeply, and were diagnosed as either mucinous or signet ring-cell carcinoma more frequently than LCCs. Regarding the prognosis, patients with RCCs had a significantly longer cancer-specific survival (CS-S) and cancer-specific relapse-free survival (CS-RFS) than those with LCCs. Furthermore, sidedness was determined to be an independent prognostic factor for CS-S and CS-RFS. CONCLUSION: RCCs, which accounted for half of the cases in patients ≥ 80 years old, showed better long-term outcomes than LCCs.

Local Recurrence of Rectal Cancer After Transanal Total Mesorectal Excision and Risk Factors: A Nationwide Multicenter Cohort Study in Japan.

Objective: To investigate the oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer and risk factors for local recurrence (LR). Background: A high LR rate with a multifocal pattern early after TaTME has been reported in Norway and the Netherlands, causing controversy over the oncological safety of this technique. Methods: Twenty-six member institutions of the Japan Society of Laparoscopic Colorectal Surgery participated in this retrospective cohort study. A total of 706 patients with primary rectal cancer who underwent TaTME between January 2012 and December 2019 were included for analysis. The primary endpoint was the cumulative 3-year LR rate. Results: A total of 253 patients had clinical stage III disease (35.8%) and 91 (12.9%) had stage IV. Intersphincteric resection was performed in 318 patients (45.0%) and abdominoperineal resection in 193 (27.3%). There was 1 urethral injury (0.1%). A positive resection margin (R1) was seen in 42 patients (5.9%). Median follow-up was 3.42 years, and the 2- and 3-year cumulative LR rates were 4.95% (95% confidence interval: 3.50-6.75) and 6.82% (95% confidence interval: 5.08-8.89), respectively. A multifocal pattern was observed in 14 (25%) of 56 patients with LR. Tumor height from the anal verge, pathological T4 disease, pathological stage III/IV, positive perineural invasion, and R1 resection were significant risk factors for LR in multivariable analysis. Conclusions: In this selected cohort in which intersphincteric resection or abdominoperineal resection was performed in more than half of cases, oncological outcomes were acceptable during a median follow-up of more than 3 years.

Disease-Modifying Effects of Lenvatinib, a Multiple Receptor Tyrosine Kinase Inhibitor, on Posttraumatic Osteoarthritis of the Knee.

Angiogenesis and vascular endothelial growth factor (VEGF) are involved in osteoarthritis (OA). We previously reported the inhibitory effect of bevacizumab in a rabbit model of OA. In the current study, we investigated the effects of lenvatinib, an angiogenesis inhibitor targeting the VEGF and fibroblast growth factor receptors, on synovitis, osteophyte formation, and cartilage degeneration in a rabbit OA model. Posttraumatic OA was induced by anterior cruciate ligament transection (ACLT) on one knee of each rabbit. Rabbits were placed into four groups according to the following lenvatinib doses: untreated control (n = 12), L0.3: 0.3 mg/kg/day (n = 15), L1.0: 1.0 mg/kg/day (n = 14), and L3.0: 3.0 mg/kg/day (n = 13) groups. We evaluated limb pain using the weight distribution ratio measured with an incapacitance tester, macroscopic osteophyte formation, and femoral condyle synovium and cartilage histology. For cartilage evaluation, the following distal sites of the femur were evaluated separately: femoral-tibial (FT), femoral-patellar (FP), and femoral corner (between FP and FT). The weight distribution ratio at 12 weeks after surgery was higher in the L0.3 and L1.0 groups than in the control group. Osteophyte formation and synovitis scores were significantly lower in the L0.3, L1.0, and L3.0 groups than in the control group. The Osteoarthritis Research Society International scores of the FT, corner, and FP sites in the L0.3 group were lower than in the control group. The cartilage thickness ratio at the FT and corner sites was significantly lower in the L0.3 group than in the control group. Krenn's grading system of cartilage synovitis showed that all lenvatinib-administered groups had significantly lower scores than the control group. MMP3 expression level in cartilage tissue was significantly lower in the L3.0 group compared with the other three groups. ADAMTS5 expression was lower in the L3.0 group compared with the control and L0.3 groups. Oral administration of lenvatinib inhibited synovitis, osteophyte formation, and cartilage degeneration and reduced pain in a rabbit ACLT model. Lenvatinib is an oral VEGF inhibitor that is easier to administer than other VEGF inhibitors and may have potential as a treatment of posttraumatic OA.

Feasibility of robotic-assisted surgery in advanced rectal cancer: a multicentre prospective phase II study (VITRUVIANO trial).

BACKGROUND: The potential benefits of robotic-assisted compared with laparoscopic surgery for locally advanced cancer have not been sufficiently proven by prospective studies. One factor is speculated to be the lack of strict surgeon criteria. The aim of this study was to assess outcomes for robotic surgery in patients with locally advanced rectal cancer with strict surgeon experience criteria. METHODS: A criterion was set requiring surgeons to have performed more than 40 robotically assisted operations for rectal cancer. Between March 2020 and May 2022, patients with rectal cancer (distance from the anal verge of 12 cm or less, cT2-T4a, cN0-N3, cM0, or cT1-T4a, cN1-N3, cM0) were registered. The primary endpoint was the rate positive circumferential resection margin (CRM) from the pathological specimen. Secondary endpoints were surgical outcomes, pathological results, postoperative complications, and longterm outcomes. RESULTS: Of the 321 registered patients, 303 were analysed, excluding 18 that were ineligible. At diagnosis: stage I (n = 68), stage II (n = 84) and stage III (n = 151). Neoadjuvant therapy was used in 56 patients. There were no conversions to open surgery. The median console time to rectal resection was 170 min, and the median blood loss was 5 ml. Fourteen patients had a positive CRM (4.6%). Grade III-IV postoperative complications were observed in 13 patients (4.3%). CONCLUSION: Robotic-assisted surgery is feasible for locally advanced rectal cancer when strict surgeon criteria are used.

Abundant extrasynaptic expression of α3ß4-containing nicotinic acetylcholine receptors in the medial habenula-interpeduncular nucleus pathway in mice.

Nicotinic acetylcholine receptors (nAChRs) in the medial habenula (MHb)-interpeduncular nucleus (IPN) pathway play critical roles in nicotine-related behaviors. This pathway is particularly enriched in nAChR α3 and ß4 subunits, both of which are genetically linked to nicotine dependence. However, the cellular and subcellular expression of endogenous α3ß4-containing nAChRs remains largely unknown because specific antibodies and appropriate detection methods were unavailable. Here, we successfully uncovered the expression of endogenous nAChRs containing α3 and ß4 subunits in the MHb-IPN pathway using novel specific antibodies and a fixative glyoxal that enables simultaneous detection of synaptic and extrasynaptic molecules. Immunofluorescence and immunoelectron microscopy revealed that both subunits were predominantly localized to the extrasynaptic cell surface of somatodendritic and axonal compartments of MHb neurons but not at their synaptic junctions. Immunolabeling for α3 and ß4 subunits disappeared in α5ß4-knockout brains, which we used as negative controls. The enriched and diffuse extrasynaptic expression along the MHb-IPN pathway suggests that α3ß4-containing nAChRs may enhance the excitability of MHb neurons and neurotransmitter release from their presynaptic terminals in the IPN. The revealed distribution pattern provides a molecular and anatomical basis for understanding the functional role of α3ß4-containing nAChRs in the crucial pathway of nicotine dependence.

Comparative clinical outcomes and radiological images of clavicle hook plate versus Scorpion Plate® for unstable distal clavicle fractures.

BACKGROUND: Although various surgical methods are available for unstable distal clavicle fractures, consensus remains lacking on the optimal technique. Therefore, the present retrospective study aimed to compare the clavicle hook plate and Scorpion Plate® in terms of clinical outcomes and radiological findings for unstable distal clavicle fractures. METHODS: Fifty-seven patients with unstable distal clavicle fractures who underwent treatment using a clavicle hook plate (Group H; 28 patients) or Scorpion Plate® (Group S; 29 patients) were included in the present study. No patients received additional augmentation and all were followed-up for >1 year (mean follow-up, 28 months). Clinical outcomes were operation time, bleeding volume, complications, range of motion (ROM) at 6 months after surgery and final follow-up, and clinical scores (Constant-Murley score and University of California, Los Angeles (UCLA) shoulder score). Radiological outcomes assessed were coracoclavicular distance (CCD), difference in CCD between affected and non-affected sides (ΔCCD), and acromioclavicular subluxation ratio (%ACS) from plain X-rays. The χ2 test and Mann-Whitney U test were used to compare each outcome. RESULTS: Complications were seen in 3 shoulders (10.7%) in Group H. ROM was significantly worse in Group H at 6 months postoperatively, but no significant differences between groups were evident at final follow-up. Moreover, no significant differences in clinical outcomes were seen between groups. In terms of radiological results, Group H showed greater improvement in CCD and ΔCCD than Group S. Further, %ACS was significantly worse in Group S. CONCLUSIONS: The clavicle hook plate allows reconstruction of a more anatomical position than the Scorpion Plate®, but carries a greater risk of complications. Conversely, the Scorpion Plate® has a low risk of complications, but acromioclavicular subluxation remains. However, no significant differences in ROM or clinical outcomes were apparent at final follow-up.

A surgical instrument motion measurement system for skill evaluation in practical laparoscopic surgery training.

This study developed and validated a surgical instrument motion measurement system for skill evaluation during practical laparoscopic surgery training. Owing to the various advantages of laparoscopic surgery including minimal invasiveness, this technique has been widely used. However, expert surgeons have insufficient time for providing training to beginners due to the shortage of surgeons and limited working hours. Skill transfer efficiency has to be improved for which there is an urgent need to develop objective surgical skill evaluation methods. Therefore, a simple motion capture-based surgical instrument motion measurement system that could be easily installed in an operating room for skill assessment during practical surgical training was developed. The tip positions and orientations of the instruments were calculated based on the marker positions attached to the root of the instrument. Because the patterns of these markers are individual, this system can track multiple instruments simultaneously and detect exchanges. However due to the many obstacles in the operating room, the measurement data included noise and outliers. In this study, the effect of this decrease in measurement accuracy on feature calculation was determined. Accuracy verification experiments were conducted during wet-lab training to demonstrate the capability of this system to measure the motion of surgical instruments with practical accuracy. A surgical training experiment on a cadaver was conducted, and the motions of six surgical instruments were measured in 36 cases of laparoscopic radical nephrectomy. Outlier removal and smoothing methods were also developed and applied to remove the noise and outliers in the obtained data. The questionnaire survey conducted during the experiment confirmed that the measurement system did not interfere with the surgical operation. Thus, the proposed system was capable of making reliable measurements with minimal impact on surgery. The system will facilitate surgical education by enabling the evaluation of skill transfer of surgical skills.

Deep sequencing of Phox2a nuclei reveals five classes of anterolateral system neurons.

The anterolateral system (ALS) is a major ascending pathway from the spinal cord that projects to multiple brain areas and underlies the perception of pain, itch, and skin temperature. Despite its importance, our understanding of this system has been hampered by the considerable functional and molecular diversity of its constituent cells. Here, we use fluorescence-activated cell sorting to isolate ALS neurons belonging to the Phox2a-lineage for single-nucleus RNA sequencing. We reveal five distinct clusters of ALS neurons (ALS1-5) and document their laminar distribution in the spinal cord using in situ hybridization. We identify three clusters of neurons located predominantly in laminae I-III of the dorsal horn (ALS1-3) and two clusters with cell bodies located in deeper laminae (ALS4 and ALS5). Our findings reveal the transcriptional logic that underlies ALS neuronal diversity in the adult mouse and uncover the molecular identity of two previously identified classes of projection neurons. We also show that these molecular signatures can be used to target groups of ALS neurons using retrograde viral tracing. Overall, our findings provide a valuable resource for studying somatosensory biology and targeting subclasses of ALS neurons.

Impact of Osteoporosis on Short-Term Surgical Outcomes in Lumbar Degenerative Disease Patients Undergoing Lateral Lumbar Interbody Fusion: A Retrospective Analysis.

OBJECTIVE: This retrospective study assesses the influence of osteoporosis on the short-term clinical outcomes of lateral lumbar interbody fusion (LLIF) surgery in patients with lumbar degenerative diseases (LDDs), focusing on complications, pain intensity, and quality of life (QOL) improvements. The primary aim of this study is to investigate the impact of osteoporosis on the short-term clinical outcomes following LLIF surgery in LDD patients, with a particular focus on the incidence of cage subsidence (CS) and overall patient well-being postoperatively. METHODS: A retrospective review was conducted on 73 patients who underwent LLIF for LDD. Patients were categorized into 2 groups based on osteoporosis status determined by dual-energy X-ray absorptiometry scans: those with osteoporosis (n = 20) and those without osteoporosis (n = 53). Data collection included demographics, surgical details, complications, magnetic resonance imaging analysis, pain intensity, and QOL (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire). RESULTS: The groups had no significant differences regarding operative time, estimated blood loss, and hospital stay duration. However, the incidence of CS was 40% in patients with osteoporosis, compared to 17% in nonosteoporotic patients. Despite this, significant improvements in spinal canal dimensions were observed in both groups. Both groups experienced significant reductions in pain intensity, with notable improvements in functional outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, indicating the overall effectiveness of LLIF in enhancing patient well-being and functionality, irrespective of osteoporosis status. CONCLUSIONS: Osteoporosis increases the risk of CS in LLIF surgery for LDD patients but does not affect short-term pain relief and QOL improvements.

Maintenance of R-loop structures by phosphorylated hTERT preserves genome integrity.

As aberrant accumulation of RNA-DNA hybrids (R-loops) causes DNA damage and genome instability, cells express regulators of R-loop structures. Here we report that RNA-dependent RNA polymerase (RdRP) activity of human telomerase reverse transcriptase (hTERT) regulates R-loop formation. We found that the phosphorylated form of hTERT (p-hTERT) exhibits RdRP activity in nuclear speckles both in telomerase-positive cells and telomerase-negative cells with alternative lengthening of telomeres (ALT) activity. The p-hTERT did not associate with telomerase RNA component in nuclear speckles but, instead, with TERRA RNAs to resolve R-loops. Targeting of the TERT gene in ALT cells ablated RdRP activity and impaired tumour growth. Using a genome-scale CRISPR loss-of-function screen, we identified Fanconi anaemia/BRCA genes as synthetic lethal partners of hTERT RdRP. Inactivation of RdRP and Fanconi anaemia/BRCA genes caused accumulation of R-loop structures and DNA damage. These findings indicate that RdRP activity of p-hTERT guards against genome instability by removing R-loop structures.

Risk factors of bleeding during rectal cancer surgery in obese patients in Japan.

BACKGROUND: According to several clinical trials for patients with rectal cancer, laparoscopic surgery significantly reduces intraoperative complications and bleeding compared with laparotomy and demonstrated comparable long-term results. However, obesity is considered one of the risk factors for increased surgical difficulty, including complication rate, prolonged operation time, and bleeding. METHODS: Patients with clinical pathological stage II/III rectal cancer and a body mass index of ≥25 kg/m2 who underwent laparotomy or laparoscopic surgery between January 2009 and December 2013 at 51 institutions participating in the Japan Society of Laparoscopic Colorectal Surgery were included. These patients were divided into major bleeding (>500 mL) group and minor bleeding (≤500 mL) group. The risk factors of major bleeding were evaluated by univariate and multivariate analyses. RESULTS: This study included 517 patients, of which 74 (19.9%) experienced major bleeding. Patient characteristics did not significantly differ between the two groups. The major bleeding group had a longer operative time (p < 0.001) and a larger tumor size than the minor bleeding group (p = 0.011). In the univariate analysis, age >65 years, laparotomy, operative time >300 min, and multivisceral resection were significantly associated with intraoperative massive bleeding. In the multivariate analysis, age >65 years (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.13-4.82), laparotomy (OR, 20.82; 95% CI, 11.56-39.75), operative time >300 min (OR, 5.39; 95% CI, 1.67-132), and multivisceral resection (OR, 10.72; 95% CI, 2.47-64.0) showed to be risk factors for massive bleeding. CONCLUSION: Age >65 years, laparotomy, operative time >300 min, and multivisceral resection were risk factors for massive bleeding during rectal cancer surgery in patients with obesity.

Advancements in pelvic ring fracture surgery: Assessing INFIX screw placement accuracy with CT navigation.

The management of unstable pelvic ring fractures, typically resulting from high-energy trauma, presents a significant clinical challenge due to the complexity of injuries. While effective in many cases, the traditional stabilization methods are fraught with various complications that can significantly impact patient recovery and quality of life (QOL). This study aims to evaluate the efficacy and precision of the anterior subcutaneous internal fixator (INFIX) technique when used with intraoperative computed tomography (CT) navigation, a novel approach intended to mitigate the limitations of conventional treatment modalities. Our retrospective case series encompasses 43 patients who sustained traumatic pelvic injuries and were subsequently treated with the INFIX technique from December 2020 to January 2024. The focus of this analysis was to assess the accuracy of INFIX screw placement facilitated by intraoperative CT navigation. A total of 81 INFIX screws were inserted, and our study findings reveal a high level of precision in screw placement, with only one screw deviating, resulting in an inaccuracy rate of merely 1.2 %. This highlights the significant advantage provided by intraoperative CT navigation. The high level of accuracy not only enhances the stability of the pelvic fixation but also substantially reduces the risk of complications commonly associated with screw misplacement, such as abdominal damage, vascular injury, and issues related to incorrect hardware positioning. In conclusion, the integration of the INFIX technique with intraoperative CT navigation in the treatment of unstable pelvic ring fractures represents a significant advancement in orthopedic trauma surgery. This study provides compelling evidence supporting the efficacy and precision of this approach, suggesting its potential as a superior alternative to traditional fixation methods. Further research, ideally through prospective studies involving larger patient cohorts, is needed to validate these findings and explore the long-term implications of this technique on patient recovery and QOL.

Quantifying Satisfaction of Degenerative Lumbar Spinal Stenosis Patients in Post-lateral Lumbar Interbody Fusion Surgery: Establishing Critical JOABPEQ Cutoff Scores.

OBJECTIVE: This retrospective study aimed to determine the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) cutoff scores for assessing patient satisfaction postlateral lumbar interbody fusion (LLIF) in degenerative lumbar spinal stenosis (DLSS) patients. METHODS: Analyzing 136 DLSS patients (83 males, 53 females), the study evaluated demographics, pain (Numeric Rating Scale), and JOABPEQ outcomes (low back pain, lumbar function, walking ability, social life, mental health). Patient satisfaction was surveyed, and based on their responses, patients were categorized into "Beneficial" and "Nonbeneficial" groups. Statistical analysis encompassed the Kolmogorov-Smirnov test, t-tests, Mann-Whitney U test, and Receiver Operating Characteristic (ROC) curve analysis for JOABPEQ cutoff determination. RESULTS: Postoperative improvements in JOABPEQ scores, especially in walking ability, social life function, and mental health, were significant. Pain intensity, assessed using the Numeric Rating Scale, also showed notable reductions. The Δ walking ability cutoff was set at 25.00, indicating substantial mobility improvement. This domain's area under the curve (AUC) was 0.815 (95% CI: 0.726-0.903), demonstrating high effectiveness in assessing patient satisfaction postsurgery. The study also found no significant differences in complication rates between groups for conditions like transient motor weakness, thigh pain/numbness, and revision surgery. CONCLUSIONS: This study underscores the value of patient-centered outcomes in evaluating LLIF surgery success for DLSS. The identified JOABPEQ cutoff values provide a quantitative tool for assessing patient satisfaction, emphasizing the necessity of comprehensive postoperative evaluations beyond traditional clinical metrics for improved patient care and life quality.

Long-term survival and functional outcomes of laparoscopic surgery for clinical stage I ultra-low rectal cancers located within 5 cm of the anal verge: A prospective phase II trial (Ultimate trial).

OBJECTIVE: To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. SUMMARY BACKGROUND DATA: Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing poorer outcomes compared to open surgery. METHODS: This single-arm, phase II trial included patients registered preoperatively from 47 institutions in Japan. The planned sample size was 300. The primary endpoint was the 3-year local recurrence rate. Anal, urinary, and sexual functions were evaluated using a prospective questionnaire. RESULTS: Three-hundred patients were registered between January 2014 and March 2017. Anus-preserving surgery was performed in 278 (93%), including 172 who underwent intersphincteric resection (58%) and 106 (36%) who underwent low anterior resection. The 3-year cumulative local recurrence rate was 6.3%. At 3 years postoperatively, 87% of patients used their own anus, and the median incontinence score improved from 12 at 3 months to 8 at 3 years. Only 5% of patients had severe incontinence (incontinence score of 16 points). Postoperative urinary function evaluation showed that International Prostate Symptom Score and Overactive Bladder Symptom Score decreased 1 week after surgery, but recovered to preoperative level 1 month after surgery. International Consultation on Incontinence Questionnaire-Sort Form remained almost stable after surgery. Sexual function evaluation using the International Index of Erectile Function-5 and International Index of Erectile Function-15 revealed that the patients had deteriorated 3 months after surgery but had recovered only slightly by 6 months. CONCLUSIONS: Laparoscopic surgery achieves feasible long-term oncological outcomes and a high rate of anus preservation with moderate anal function, and an acceptable incontinence score. While urinary function recovered rapidly, sexual function showed poor recovery.

The GLP-1 receptor agonist exenatide improves recovery from spinal cord injury by inducing macrophage polarization toward the M2 phenotype.

Although a wide variety of mechanisms take part in the secondary injury phase of spinal cord injury (SCI), inflammation is the most important factor implicated in the sequelae after SCI. Being central to the inflammation reaction, macrophages and their polarization are a topic that has garnered wide interest in the studies of SCI secondary injury. The glucagon-like peptide 1 (GLP-1) receptor agonist exenatide has been shown to enhance the endoplasmic reticulum stress response and improve motor function recovery after spinal cord injury (SCI). Since exenatide has also been reported to induce the production of M2 cells in models of cerebral infarction and neurodegenerative diseases, this study was conducted to examine the effects of exenatide administration on the inflammation process that ensues after spinal cord injury. In a rat contusion model of spinal cord injury, the exenatide group received a subcutaneous injection of 10 µg exenatide immediately after injury while those in the control group received 1 mL of phosphate-buffered saline. Quantitative RT-PCR and immunohistochemical staining were used to evaluate the effects of exenatide administration on the macrophages infiltrating the injured spinal cord, especially with regard to macrophage M1 and M2 profiles. The changes in hind limb motor function were assessed based on Basso, Beattie, Bresnahan locomotor rating scale (BBB scale) scores. The improvement in BBB scale scores was significantly higher in the exenatide group from day 7 after injury and onwards. Quantitative RT-PCR revealed an increase in the expression of M2 markers and anti-inflammatory interleukins in the exenatide group that was accompanied by a decrease in the expression of M1 markers and inflammatory cytokines. Immunohistochemical staining showed no significant difference in M1 macrophage numbers between the two groups, but a significantly higher number of M2 macrophages was observed in the exenatide group on day 3 after injury. Our findings suggest that exenatide administration promoted the number of M2-phenotype macrophages after SCI, which may have led to the observed improvement in hind limb motor function in a rat model of SCI.

Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development.

Postsynaptic proteins play crucial roles in synaptic function and plasticity. During brain development, alterations in synaptic number, shape, and stability occur, known as synapse maturation. However, the postsynaptic protein composition changes during development are not fully understood. Here, we show the trajectory of the postsynaptic proteome in developing male mice and common marmosets. Proteomic analysis of mice at 2, 3, 6, and 12 weeks of age shows that proteins involved in synaptogenesis are differentially expressed during this period. Analysis of published transcriptome datasets shows that the changes in postsynaptic protein composition in the mouse brain after 2 weeks of age correlate with gene expression changes. Proteomic analysis of marmosets at 0, 2, 3, 6, and 24 months of age show that the changes in the marmoset brain can be categorized into two parts: the first 2 months and after that. The changes observed in the first 2 months are similar to those in the mouse brain between 2 and 12 weeks of age. The changes observed in marmoset after 2 months old include differential expression of synaptogenesis-related molecules, which hardly overlap with that in mice. Our results provide a comprehensive proteomic resource that underlies developmental synapse maturation in rodents and primates.