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.

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 post-lateral 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 "Non-Beneficial" 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 Δwalking 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 post-surgery. 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.

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.

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.

Evaluating the Efficacy of IL-6 as Predictors of Lateral Lumbar Interbody Fusion Success: Insights From Pain Scores and JOABPEQ Assessments.

STUDY DESIGN: A prospective study. OBJECTIVES: This study aims to explore the correlation between interleukin (IL)- 6 levels in intervertebral disc (IVD) tissue and clinical outcomes in patients undergoing lumbar surgery for lumbar degenerative disease (LDD). METHODS: This prospective study analyzed 32 patients (22 men and 10 women, average age 69.6 years) who underwent lateral lumbar interbody fusion (LLIF). IL-6 gene expression in IVD tissues collected during surgery was measured and correlated with pre- and postoperative clinical outcomes, including pain intensity assessed via Numeric Rating Scales (NRS) and quality of life (QOL) evaluated through the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). RESULTS: IL-6 levels showed statistical correlations with postoperative intensity of low back pain (LBP) and several JOABPEQ domains. Patients with higher expression of IL-6 levels experienced more severe postoperative LBP and lower scores in lumbar function, walking ability, social life function, and mental health. The effectiveness rate of JOABPEQ scores was exceptionally high for low back pain (.548), walking ability (.677), and social functioning (.563), demonstrating the effectiveness of LLIF. The average operation time was 105.6 minutes, and the estimated blood loss was 85.6 mL. CONCLUSIONS: The study underscores IL-6 as a potential biomarker for predicting surgical outcomes in LDD. High IL-6 levels correlate with worse postoperative LBP and lower QOL scores. Integrating molecular markers like IL-6 with patient-reported outcomes could provide a more comprehensive approach to postoperative care in spinal disorders, aiming to improve the overall QOL for LDD patients undergoing LLIF surgery.

Preoperative Body Composition Correlates with Postoperative Muscle Volume and Degeneration after Total Hip Arthroplasty.

Impaired muscle recovery after total hip arthroplasty (THA) may affect gait and activities of daily living. Bioelectrical impedance analysis (BIA) can assess body composition and muscle volume, and computed tomography (CT) can assess muscle volume and the fatty degeneration of muscle. This study aimed to explore the effectiveness of BIA, and the correlation between preoperative body composition and postoperative muscle volume and degeneration after THA using BIA and CT. Thirty-eight patients who underwent THA and had BIA and CT performed pre- and postoperatively were retrospectively assessed. The BIA-derived measurements of preoperative body composition (fat mass index, fat-free mass index, and phase angle) were correlated with the CT-derived measurements (pre- and postoperative muscle volume and gluteus maximus and quadriceps Hounsfield Units of the affected hip). The preoperative fat mass index negatively correlated with the postoperative muscle volume of the gluteus maximus (p = 0.02) and quadriceps (p < 0.001) and the Hounsfield Units of the gluteus maximus (p = 0.03) and quadriceps (p = 0.03). The preoperative fat-free mass index positively correlated with the postoperative muscle volume of the quadriceps (p = 0.02). The preoperative phase angle positively correlated with the postoperative muscle volume of the quadriceps (p = 0.001) and the Hounsfield Units of the gluteus maximus (p = 0.03) and quadriceps (p = 0.001). In patients who underwent THA, preoperative body composition correlated with postoperative muscle volume and the fatty degeneration of the affected lower limb. Preoperative body composition may help predict postoperative muscle volume and fatty degeneration and thus, postoperative recovery.

Cholinergic Control of GnRH Neuron Physiology and Luteinizing Hormone Secretion in Male Mice: Involvement of ACh/GABA Cotransmission.

Gonadotropin-releasing hormone (GnRH)-synthesizing neurons orchestrate reproduction centrally. Early studies have proposed the contribution of acetylcholine (ACh) to hypothalamic control of reproduction, although the causal mechanisms have not been clarified. Here, we report that in vivo pharmacogenetic activation of the cholinergic system increased the secretion of luteinizing hormone (LH) in orchidectomized mice. 3DISCO immunocytochemistry and electron microscopy revealed the innervation of GnRH neurons by cholinergic axons. Retrograde viral labeling initiated from GnRH-Cre neurons identified the medial septum and the diagonal band of Broca as exclusive sites of origin for cholinergic afferents of GnRH neurons. In acute brain slices, ACh and carbachol evoked a biphasic effect on the firing rate in GnRH neurons, first increasing and then diminishing it. In the presence of tetrodotoxin, carbachol induced an inward current, followed by a decline in the frequency of miniature postsynaptic currents (mPSCs), indicating a direct influence on GnRH cells. RT-PCR and whole-cell patch-clamp studies revealed that GnRH neurons expressed both nicotinic (α4ß2, α3ß4, and α7) and muscarinic (M1-M5) AChRs. The nicotinic AChRs contributed to the nicotine-elicited inward current and the rise in firing rate. Muscarine via M1 and M3 receptors increased, while via M2 and M4 reduced the frequency of both mPSCs and firing. Optogenetic activation of channelrhodopsin-2-tagged cholinergic axons modified GnRH neuronal activity and evoked cotransmission of ACh and GABA from a subpopulation of boutons. These findings confirm that the central cholinergic system regulates GnRH neurons and activates the pituitary-gonadal axis via ACh and ACh/GABA neurotransmissions in male mice.

Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety.

Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum. Biochemical studies in the mouse cortex confirmed that GluK3 subunits do not assemble with GluK4 and GluK5 subunits, that can be activated by lower concentration of agonists. Overall, we found that GluK3-containing KARs function to express anxiety, which may represent promising anti-anxiety medication targets.

Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation.

In the central nervous system, astrocytes enable appropriate synapse function through glutamate clearance from the synaptic cleft; however, it remains unclear how astrocytic glutamate transporters function at peri-synaptic contact. Here, we report that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synapse formation and function in the developing cerebellum. Dscam-mutant mice show defects in CF synapse translocation as is observed in loss of function mutations in the astrocytic glutamate transporter GLAST expressed in Bergmann glia. These mice show impaired glutamate clearance and the delocalization of GLAST away from the cleft of parallel fibre (PF) synapse. GLAST complexes with the extracellular domain of DSCAM. Riluzole, as an activator of GLAST-mediated uptake, rescues the proximal impairment in CF synapse formation in Purkinje cell-selective Dscam-deficient mice. DSCAM is required for motor learning, but not gross motor coordination. In conclusion, the intercellular association of synaptic and astrocyte proteins is important for synapse formation and function in neural transmission.

Risk factors for anastomotic leakage after low anterior resection for obese patients with rectal cancer.

PURPOSE: We aimed to analyze the risk factors for anastomotic leakage (AL) after low anterior resection (LAR) in obese patients (body mass index [BMI] ≥ 25 kg/m2) with rectal cancer. METHODS: Data were collected from four hundred two obese patients who underwent LAR for rectal cancer in 51 institutions. RESULTS: Forty-six (11.4%) patients had clinical AL. The median BMI (27 kg/m2) did not differ between the AL and non-AL groups. In the AL group, comorbid respiratory disease was more common (p = 0.025), and the median tumor size was larger (p = 0.002). The incidence of AL was 11.5% in the open surgery subgroup and 11.4% in the laparoscopic surgery subgroup. Among the patients who underwent open surgery, the AL group showed a male predominance (p = 0.04) in the univariate analysis, but it was not statistically significant in the multivariate analysis. Among the patients who underwent laparoscopic surgery, the AL group included a higher proportion of patients with comorbid respiratory disease (p = 0.003) and larger tumors (p = 0.007). CONCLUSION: Comorbid respiratory disease and tumor size were risk factors for AL in obese patients with rectal cancer. Careful perioperative respiratory management and appropriate selection of surgical procedures are required for obese rectal cancer patients with respiratory diseases.

ISSLS PRIZE in Basic Science 2024: superiority of nucleus pulposus cell- versus mesenchymal stromal cell-derived extracellular vesicles in attenuating disc degeneration and alleviating pain.

PURPOSE: To investigate the therapeutic potential of extracellular vesicles (EVs) derived from human nucleus pulposus cells (NPCs), with a specific emphasis on Tie2-enhanced NPCs, compared to EVs derived from human bone marrow-derived mesenchymal stromal cells (BM-MSCs) in a coccygeal intervertebral disc degeneration (IDD) rat model. METHODS: EVs were isolated from healthy human NPCs cultured under standard (NPCSTD-EVs) and Tie2-enhancing (NPCTie2+-EVs) conditions. EVs were characterized, and their potential was assessed in vitro on degenerative NPCs in terms of cell proliferation and senescence, with or without 10 ng/mL interleukin (IL)-1ß. Thereafter, 16 Sprague-Dawley rats underwent annular puncture of three contiguous coccygeal discs to develop IDD. Phosphate-buffered saline, NPCSTD-EVs, NPCTie2+-EVs, or BM-MSC-derived EVs were injected into injured discs, and animals were followed for 12 weeks until sacrifice. Behavioral tests, radiographic disc height index (DHI) measurements, evaluation of pain biomarkers, and histological analyses were performed to assess the outcomes of injected EVs. RESULTS: NPC-derived EVs exhibited the typical exosomal morphology and were efficiently internalized by degenerative NPCs, enhancing cell proliferation, and reducing senescence. In vivo, a single injection of NPC-derived EVs preserved DHI, attenuated degenerative changes, and notably reduced mechanical hypersensitivity. MSC-derived EVs showed marginal improvements over sham controls across all measured outcomes. CONCLUSION: Our results underscore the regenerative potential of young NPC-derived EVs, particularly NPCTie2+-EVs, surpassing MSC-derived counterparts. These findings raise questions about the validity of MSCs as both EV sources and cellular therapeutics against IDD. The study emphasizes the critical influence of cell type, source, and culture conditions in EV-based therapeutics.

SOD2 orchestrates redox homeostasis in intervertebral discs: A novel insight into oxidative stress-mediated degeneration and therapeutic potential.

Low back pain (LBP) is a pervasive global health concern, primarily associated with intervertebral disc (IVD) degeneration. Although oxidative stress has been shown to contribute to IVD degeneration, the underlying mechanisms remain undetermined. This study aimed to unravel the role of superoxide dismutase 2 (SOD2) in IVD pathogenesis and target oxidative stress to limit IVD degeneration. SOD2 demonstrated a dynamic regulation in surgically excised human IVD tissues, with initial upregulation in moderate degeneration and downregulation in severely degenerated IVDs. Through a comprehensive set of in vitro and in vivo experiments, we found a suggestive association between excessive mitochondrial superoxide, cellular senescence, and matrix degradation in human and mouse IVD cells. We confirmed that aging and mechanical stress, established triggers for IVD degeneration, escalated mitochondrial superoxide levels in mouse models. Critically, chondrocyte-specific Sod2 deficiency accelerated age-related and mechanical stress-induced disc degeneration in mice, and could be attenuated by ß-nicotinamide mononucleotide treatment. These revelations underscore the central role of SOD2 in IVD redox balance and unveil potential therapeutic avenues, making SOD2 and mitochondrial superoxide promising targets for effective LBP interventions.

Hounsfield Unit Values as an Adjunct Diagnostic Tool: Investigating Its Relationship with Bone Mineral Density and Vertebral Bone Quality in Lumbar Degenerative Disease Patients.

OBJECTIVE: With an increasing prevalence of osteoporosis due to demographic shifts, accurate diagnostic methods are vital, particularly before spinal surgeries. This research investigated the correlation between bone mineral density T-scores of the lumbar spine and femoral neck, Hounsfield Unit (HU) values from computed tomography (CT), and vertebral bone quality (VBQ) scores from Magnetic Resonance Imaging (MRI) in patients with lumbar degenerative disease. METHODS: We analyzed data from 100 patients with lumbar degenerative disease who underwent CT, dual-energy X-ray absorptiometry (DXA), and MRI between 2019 and 2023. HU values were measured individually from L1 to L4, while T-scores were obtained from DXA scans of the lumbar spine and the femoral neck. The VBQ scores were derived from T1-weighted MRIs. RESULTS: A notable association between the lumbar and femoral neck T-scores and HU values was found. The VBQ score had a faint correlation with HU values and lacked any with the T-score. Notably, the HU values derived via the Youden index and regression closely matched. Lumbar spine HU values related to T-scores of 85.6 and 84.4 and femoral neck T-scores of 98.9 and 103.6, with a low T-score at 98.9 and 104.6. CONCLUSIONS: This study underscores a strong correlation between bone mineral density and HU values from CT scans in lumbar degenerative disease patients, suggesting the utility of HU measurements as an adjunct diagnostic tool for osteoporosis. However, the correlation with the VBQ score remains weak. Further multicenter studies are essential for more robust validation.

Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143-/y ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143-/y mice. The phenotypic defect in Gpr143-/y mice was mimicked in cholinergic interneuron-specific Gpr143-/y (Chat-cre;Gpr143flox/y ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser240/244 in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143flox/y mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143flox/y mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs.

Standardization of robot-assisted pelvic lymph node dissection-Development of a common understanding of regional anatomy and surgical technique based on cross-disciplinary discussion among colorectal surgery, urology, and gynecology.

BACKGROUND: Pelvic lymph node dissection is a procedure performed in gastroenterological surgery, urology, and gynecology. However, due to discrepancies in the understanding of pelvic anatomy among these departments, cross-disciplinary discussions have not been easy. Recently, with the rapid spread of robotic surgery, the importance of visual information in understanding pelvic anatomy has become even more significant. In this project, we attempted to clarify a shared understanding of pelvic anatomy through cross-disciplinary discussions. METHOD: From May 2020 to November 2021, a total of 11 discussions were held entirely online with 5 colorectal surgery specialists, 4 urologists, and 4 gynecologists. The discussions focused on evidence from each specialty and surgical videos, aiming to create a universally understandable pelvic anatomical illustration. RESULTS: The common area of dissection recognized across the three departments was identified as the obturator lymph nodes. A dynamic illustration of pelvic anatomy was created. In addition to a bird's-eye view of the pelvis, a pelvic half view was developed to enhance understanding of the deeper pelvic anatomy. The following insights were incorporated into the illustration: (1) the cardinal ligament in gynecology partly overlaps with the vesicohypogastric fascia in colorectal surgery; (2) the obturator lymph nodes continue cephalad into the fossa of Marcille in urology; and (3) the deep uterine vein in gynecology corresponds to the inferior vesical vein in colorectal surgery. CONCLUSION: Based on the dynamic illustration of pelvic anatomy from cross-disciplinary discussions, we anticipate advancements in pelvic lymph node dissection aiming for curative and safe outcomes.

MPFL Reconstruction Combined with a Modified Elmslie-Trillat Procedure for Recurrent Patellofemoral Instability.

Several combined procedures have been reported for treating recurrent patellofemoral instability (RPI) with various types and severity of morphological abnormalities, but none have identified absolute threshold values as indications for surgery. We performed medial patellofemoral ligament (MPFL) reconstruction combined with a modified Elmslie-Trillat (ET) procedure on 24 knees (10 male and 11 female patients) to treat RPI with morphological abnormalities corresponding to elevated tibial tubercle-trochlear groove (TT-TG) distance, significant patella alta, and trochlear dysplasia. The inclusion criteria were RPI with morphological abnormalities corresponding to one or more of the following: sulcus angle > 160 degrees, trochlear dysplasia of Dejour classification C or D, Caton-Deschamps index > 1.5, lateral shift ratio > 50%, congruence angle > 15 degrees, or TT-TG distance > 20 mm, including habitual dislocation of the patella. Skeletally immature patients and those with congenital dislocation of the patella were excluded. The Kujala score, International Knee Documentation Committee subjective score, Knee Injury and Osteoarthritis Outcome score (KOOS), and each item of the KOOS improved significantly after surgery. Patellar apprehension sign was present preoperatively in all cases, but all disappeared postoperatively. No instance of postoperative redislocation was observed. On radiographic examination, the mean Q angle, tilting angle, lateral shift ratio, congruence angle, Caton-Deschamps index, Insall-Salvati index, and TT-TG distance improved significantly after surgery. There were no significant differences in sulcus angle after surgery. These results suggest MPFL reconstruction combined with a modified ET procedure provides satisfactory outcomes based on radiological and clinical evaluations for RPI with morphological abnormalities corresponding to elevated TT-TG distance, significant patella alta, and trochlear dysplasia.

Recombinant Laminin-511 Fragment (iMatrix-511) Coating Supports Maintenance of Human Nucleus Pulposus Progenitor Cells In Vitro.

The angiopoietin-1 receptor (Tie2) marks specific nucleus pulposus (NP) progenitor cells, shows a rapid decline during aging and intervertebral disc degeneration, and has thus sparked interest in its utilization as a regenerative agent against disc degeneration. However, the challenge of maintaining and expanding these progenitor cells in vitro has been a significant hurdle. In this study, we investigated the potential of laminin-511 to sustain Tie2+ NP progenitor cells in vitro. We isolated cells from human NP tissue (n = 5) and cultured them for 6 days on either standard (Non-coat) or iMatrix-511 (laminin-511 product)-coated (Lami-coat) dishes. We assessed these cells for their proliferative capacity, activation of Erk1/2 and Akt pathways, as well as the expression of cell surface markers such as Tie2, GD2, and CD24. To gauge their regenerative potential, we examined their extracellular matrix (ECM) production capacity (intracellular type II collagen (Col2) and proteoglycans (PG)) and their ability to form spherical colonies within methylcellulose hydrogels. Lami-coat significantly enhanced cell proliferation rates and increased Tie2 expression, resulting in a 7.9-fold increase in Tie2-expressing cell yields. Moreover, the overall proportion of cells positive for Tie2 also increased 2.7-fold. Notably, the Col2 positivity rate was significantly higher on laminin-coated plates (Non-coat: 10.24% (±1.7%) versus Lami-coat: 26.2% (±7.5%), p = 0.010), and the ability to form spherical colonies also showed a significant improvement (Non-coat: 40.7 (±8.8)/1000 cells versus Lami-coat: 70.53 (±18.0)/1000 cells, p = 0.016). These findings demonstrate that Lami-coat enhances the potential of NP cells, as indicated by improved colony formation and proliferative characteristics. This highlights the potential of laminin-coating in maintaining the NP progenitor cell phenotype in culture, thereby supporting their translation into prospective clinical cell-transplantation products.

Brain-enriched guanylate kinase-associated protein, a component of the post-synaptic density protein complexes, contributes to learning and memory.

Brain-enriched guanylate kinase-associated protein (BEGAIN) is highly enriched in the post-synaptic density (PSD) fraction and was identified in our previous study as a protein associated with neuropathic pain in the spinal dorsal horn. PSD protein complexes containing N-methyl-D-aspartate receptors are known to be involved in neuropathic pain. Since these PSD proteins also participate in learning and memory, BEGAIN is also expected to play a crucial role in this behavior. To verify this, we first examined the distribution of BEGAIN in the brain. We found that BEGAIN was widely distributed in the brain and highly expressed in the dendritic regions of the hippocampus. Moreover, we found that BEGAIN was concentrated in the PSD fraction of the hippocampus. Furthermore, immunoelectron microscopy confirmed that BEGAIN was localized at the asymmetric synapses. Behavioral tests were performed using BEGAIN-knockout (KO) mice to determine the contribution of BEGAIN toward learning and memory. Spatial reference memory and reversal learning in the Barns circular maze test along with contextual fear and cued fear memory in the contextual and cued fear conditioning test were significantly impaired in BEGAIN-KO mice compared to with those in wild-type mice. Thus, this study reveals that BEGAIN is a component of the post-synaptic compartment of excitatory synapses involved in learning and memory.

[Strychnine, in The Mysterious Affair at Styles: Blocking Glycinergic Synaptic Transmission].

Strychnine is a poison that often appears in classical mysteries and has been used for medicine and various purposes. Clearly, its point of action is glycine receptors, and it inhibits glycinergic synaptic transmission. Because of its powerful stimulant effect on the nervous system, if taken orally, characteristic symptoms that are intense and agonizing, such as tonic convulsions, opisthotonus or posterior arch tension, and convulsive laughter, appear. These symptoms are linked to the pathological basis of tetanus, and the drug is an important topic ranging from neuroscience to medical care.