Cadaveric and CT angiography study of vessels around the transverse colon mesentery.

BACKGROUND: Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse colon. Although the vessels of the right colon have been investigated, middle colic artery (MCA) variation and the relationship with vessels around the transvers colon are unknown. We investigated variation of the MCA using computed tomography angiography (CTA) and cadaver specimen and the relationship between the superior mesenteric vein (SMV) and MCA using CTA. The classification of vessels around the transverse colon may lead to safer and reliable surgery. METHODS: This study included 505 consecutive patients who underwent CTA in our institution from 2014 to 2020 and 44 cadaver specimens. Vascular anatomical classifications and relationships were analyzed using CT images. RESULTS: The MCA was defined as the arteries arising from the superior mesenteric artery (SMA) that flowed into the transverse colon at the distal ends. The classifications were as follows: type I, branching right and left from common trunk; type II, the right and left branches bifurcated separately from the SMA; and type III, the MCA branched from a vessel other than the SMA. Type II was subclassified into two subtypes, type IIa with one left branch and type IIb with two or more left branches from SMA. In the CTA and cadaver studies, respectively, the classifications were as follows: type I, n = 290 and n = 31; type IIa, n = 211 and n = 13; type IIb, n = 3 and n = 0; and type III, n = 1 and n = 0. We classified the relationship between the MCA and left side of the SMV into three types: type A, a common trunk runs along the left edge of the SMV (n = 173; 59.7%); type B, a right branch of the MCA runs along the left edge of the SMV (n = 116; 40.0%); and type C, the MCA runs dorsal of the SMV (n = 1; 0.3%). CONCLUSIONS: This study revealed that The MCA branching classifications and relationship between the SMV and MCA. Preoperative CT angiography may be able to reliably identify vessel variation, which may be useful in clinical practice.

Joint gap produced by manual stress is dependent on the surgeon's experience and is smaller in flexion in robotic-assisted total knee arthroplasty.

PURPOSE: This study aimed to retrospectively investigate (1) the reproducibility of gap measurements by manual stress using the Z-shaped retractor depending on the surgeon's experience with this maneuver and (2) the consistency of the gap distraction force produced by manual stress throughout the range of motion (ROM) in the robotic-assisted total knee arthroplasty (TKA). It was hypothesized that the joint gap produced by manual stress is not reproducible depending on the surgeon's experience, and the distraction force applied by manual stress throughout the ROM is not constant. METHODS: Medial and lateral joint gaps were obtained throughout the ROM by manual stress or a tensioner by two surgeons with different levels of experience in robotic-assisted TKA. The association between the differences in gap measurement by the two surgeons and the preoperative radiographic parameters, including the hip-knee-ankle (HKA) angle and absolute and relative varus/valgus laxities were analyzed. RESULTS: The experienced surgeon produced significantly greater gaps than the inexperienced surgeon from 0° to 100° flexion, with a mean difference of 0.35 ± 0.12 mm in the medial gap (p < 0.0001), and from 10° to 120° flexion with a mean difference of 0.57 ± 0.13 mm in the lateral gap (p < 0.0001). The tensioner produced a significantly greater medial gap from 70° to 110° flexion with a mean difference of 0.32 ± 0.01 mm in the medial gap (p < 0.0001) and from 0° to 110° flexion with a mean difference of 1.12 ± 0.26 mm in the lateral gap (p < 0.0001). The differences in gap distance by manual stress between experienced and inexperienced surgeons were moderately correlated with the HKA angle in the lateral gap (r = 0.40, p = 0.01). The gap differences due to manual stress and a tensioner showed moderate negative correlation with the HKA angle in the medial gap (r = - 0.50, p = 0.001) and weak negative correlation with the absolute valgus laxity in the lateral gap (r = - 0.35, p = 0.03). CONCLUSIONS: The joint distraction force by manual stress may differ depending on the surgeon's experience and tended to be smaller in deep flexion; therefore, the flexion gap may be underestimated. Surgeons should determine implant positioning considering gap balance by manual stress, taking into account these characteristics of the manual stress maneuver. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Impact of Gestational Haloperidol Exposure on miR-137-3p and Nr3c1 mRNA Expression in Hippocampus of Offspring Mice.

BACKGROUND: Schizophrenia is a mental disorder caused by both environmental and genetic factors. Prenatal exposure to antipsychotics, an environmental factor for the fetal brain, induces apoptotic neurodegeneration and cognitive impairment of offspring similar to schizophrenia. The aim was to investigate molecular biological changes in the fetal hippocampus exposed to haloperidol (HAL) by RNA expression as a model of the disorder. METHODS: HAL (1 mg/kg/d) was administered to pregnant mice. Upregulated and downregulated gene expressions in the hippocampus of offspring were studied with RNA-sequencing and validated with the qPCR method, and micro-RNA (miR) regulating mRNA expressional changes was predicted by in silico analysis. An in vitro experiment was used to identify the miRNA using a dual-luciferase assay. RESULTS: There were significant gene expressional changes (1370 upregulated and 1260 downregulated genes) in the HAL group compared with the control group on RNA-sequencing analysis (P < .05 and q < 0.05). Of them, the increase of Nr3c1 mRNA expression was successfully validated, and in silico analysis predicted that microRNA-137-3p (miR-137-3p) possibly regulates that gene's expression. The expression of miR-137-3p in the hippocampus of offspring was significantly decreased in the first generation, but it increased in the second generation. In vitro experiments with Neuro2a cells showed that miR-137-3p inversely regulated Nr3c1 mRNA expression, which was upregulated in the HAL group. CONCLUSIONS: These findings will be key for understanding the impact of the molecular biological effects of antipsychotics on the fetal brain.

Medial proximal tibial angle at the posterior tibial plateau represents the pre-arthritic constitutional medial proximal tibial angle in anterior cruciate ligament-intact, advanced osteoarthritis of the knee.

PURPOSE: In kinematically aligned total knee arthroplasty (TKA), it is necessary to infer the pre-arthritic constitutional medial proximal tibial angle (MPTA) in advanced osteoarthritis (OA) of the knee with bone loss. The aim of this study was to investigate whether MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in anterior cruciate ligament (ACL)-intact, advanced OA knees. It was hypothesized that MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA of ACL-intact, advanced knee OA. METHODS: One hundred varus, anterior cruciate ligament (ACL)-intact, advanced OA knees were analysed. The hip-knee-ankle (HKA) angle and MPTA were assessed on computed radiography (CR) and MPTAs at the anterior, middle, and posterior part of the tibial plateau were assessed on computed tomography (CT) images. The association between these parameters was also analysed. RESULTS: CR images showed an HKA angle of 172.4 ± 4.1° and MPTA of 84.3 ± 2.5°. CT images showed different MPTAs in the three regions, ranging from 83.9 ± 2.4° to 85.9 ± 2.8°. The middle MPTA was the lowest at 83.9 ± 2.4°. HKA angle correlated with the middle MPTA (r = 0.3355, 95% confidence interval [CI] 0.1489-0.4991, p = 0.0006) and ΔMPTA (Middle-Posterior) (r = 0.5128, 95% CI 0.3518-0.6443, p < 0.0001). CONCLUSION: The MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in ACL-intact, advanced OA knees. LEVEL OF EVIDENCE: III, retrospective cohort study.

Inhibition of low-density lipoprotein uptake by Helicobacter pylori virulence factor CagA.

Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years, several studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, mechanisms underlying this association has not been defined. In this study, we carried out a large-scale genetic screen using Drosophila and identified a novel CagA target low-density lipoprotein receptor (LDLR), which aids in the clearance of circulating LDL. We showed that CagA physically interacted with LDLR via its carboxy-terminal region and inhibited LDLR-mediated LDL uptake into cells. Since deficiency of LDLR-mediated LDL uptake has been known to increase plasma LDL and accelerate atherosclerosis, our findings may provide a novel mechanism for the association between infection with CagA-positive H. pylori and hypercholesterolemia leading to atherosclerotic cardiovascular diseases.

Prosaposin in the rat oviductal epithelial cells.

Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.

Differentiation of schizophrenia using structural MRI with consideration of scanner differences: A real-world multisite study.

AIM: Neuroimaging studies have revealed that patients with schizophrenia exhibit reduced gray matter volume in various regions. With these findings, various studies have indicated that structural MRI can be useful for the diagnosis of schizophrenia. However, multisite studies are limited. Here, we evaluated a simple model that could be used to differentiate schizophrenia from control subjects considering MRI scanner differences employing voxel-based morphometry. METHODS: Subjects were 541 patients with schizophrenia and 1252 healthy volunteers. Among them, 95 patients and 95 controls (Dataset A) were used for the generation of regions of interest (ROI), and the rest (Dataset B) were used to evaluate our method. The two datasets were comprised of different subjects. Three-dimensional T1-weighted MRI scans were taken for all subjects and gray-matter images were extracted. To differentiate schizophrenia, we generated ROI for schizophrenia from Dataset A. Then, we determined volume within the ROI for each subject from Dataset B. Using the extracted volume data, we calculated a differentiation feature considering age, sex, and intracranial volume for each MRI scanner. Receiver-operator curve analyses were performed to evaluate the differentiation feature. RESULTS: The area under the curve ranged from 0.74 to 0.84, with accuracy from 69% to 76%. Receiver-operator curve analysis with all samples revealed an area under the curve of 0.76 and an accuracy of 73%. CONCLUSION: We moderately successfully differentiated schizophrenia from control using structural MRI from differing scanners from multiple sites. This could be useful for applying neuroimaging techniques to clinical settings for the accurate diagnosis of schizophrenia.

Revisiting the infracardiac bursa using multimodal methods: topographic anatomy for surgery of the esophagogastric junction.

In embryology, the infracardiac bursa (ICB) is a well-known derivative separated from the omental bursa. During surgeries around the esophagogastric junction (EGJ), surgeons often encounter a closed space considered to be equivalent to the ICB, but the macroscopic anatomy in adults is hardly known. This study aimed to revisit the ICB using multimodal methods to show its development from the embryonic to adult stage and clarify its persistence and topographic anatomy. Histological sections of 79 embryos from Carnegie stage (CS) 16 to 23 and magnetic resonance (MR) images of 39 fetuses were examined to study the embryological development of the ICB. Horizontal sections around the EGJ obtained from three adult cadavers were examined to determine the topographic anatomy and histology of the ICB. Further, 32 laparoscopic surgical videos before (n = 16) and after (n = 16) the start of this study were reviewed to confirm its remaining rate and topographic anatomy in surgery. The ICB was formed in 1 out of 10 CS17 samples, and in 8 out of 10 CS18 samples. Further, it was observed in all CS19-23 except one CS23 sample and in 25 (64%) out of 39 fetus samples. Three-dimensional reconstructed MR images of fetuses revealed that the ICB was located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. In one adult cadaver, the caudal end of the ICB arose from the level of the esophageal hiatus and the cranial end reached up to the level of the pericardium. The inner surface cells of the space consisted of the mesothelium. In laparoscopic surgery, the ICB was identified in only 11 (69%) out of 16 surgeries before. However, subsequently we were able to identify the ICB reproducibly in 15 (94%) out of 16 surgeries. Thus, the ICB is the structure commonly remaining in almost all adults as a closed space located at the right alongside the esophagus and the cranial side of the diaphragmatic crus. It may be available as a useful landmark in surgery of the EGJ.

Precise Three-Dimensional Morphology of the Male Anterior Anorectum Reconstructed From Large Serial Histologic Sections: A Cadaveric Study.

BACKGROUND: Deep anatomic knowledge of the male anterior anorectum is important to avoid urethral injury and rectal perforation in intersphincteric resection or abdominoperineal resection for very low rectal cancer. However, its structure is difficult to understand, because the anorectum, muscles, and urogenital organs are complicatedly and 3-dimensionally arranged. OBJECTIVE: The purpose of this study was to revisit the anatomic information of the male anterior anorectum for intersphincteric resection and abdominoperineal resection with a focus on the spatial muscular morphology. DESIGN: This was a descriptive cadaveric study. SETTINGS: The study was conducted at Ehime and Kyoto universities. PATIENTS: Tissue specimens from 9 male cadavers were included. MAIN OUTCOME MEASURES: Specimens around the anterior anorectum were serially sectioned in the horizontal, sagittal, or frontal plane; large semiserial histologic sections were created at 250-µm intervals. The series were stained with Elastica van Gieson, and some sections from the series were studied by immunohistochemistry to detect smooth and striated muscles. Two series were digitalized and reconstructed 3-dimensionally. RESULTS: Two regions without a clear anatomic border were elucidated: 1) the anterior region of the external anal sphincter, where the external anal sphincter, bulbospongiosus muscle, and superficial transverse perineal muscle were intertwined; and 2) the rectourethralis muscle, where the smooth muscle of the longitudinal muscle continuously extended to the posteroinferior area of the urethra, which became closest to the anorectum at the prostatic apex level. A tight connection between the striated and smooth muscles was identified at the anterior part of the upper external anal sphincter and anterolateral part of the puborectalis muscle level. LIMITATIONS: This study involved a small sample size of elderly cadavers. CONCLUSIONS: This study clarified the precise spatial relationship between smooth and striated muscles. The detailed anatomic findings will contribute more accurate step-by-step anterior dissection in intersphincteric resection and abdominoperineal resection, especially with the transanal approach, which can magnify the muscle fiber direction and contraction of striated muscle by electrostimulation. MORFOLOGÍA TRIDIMENSIONAL PRECISA DEL ANORRECTO ANTERIOR MASCULINO RECONSTRUIDO A TRAVÉS DE SECCIONES MAYORES HISTOLÓGICAS EN SERIE: UN ESTUDIO CADAVÉRICO: El conocimiento anatómico amplio del anorrecto anterior masculino es importante para evitar lesiones de uretra y perforación de recto en la resección interesfinterica o la resección abdominoperineal para cáncer de recto bajo. Sin embargo, su estructura es difícil de entender porque el anorrecto, los músculos y los órganos urogenitales están aliñados en forma complexa tridimensional. OBJETIVO: Revisar de nuevo el conocimiento anatómico del anorrecto anterior masculino relevante a la resección interesfinterica y la resección abdominoperineal con un enfoque en la morfología muscular espacial. DISEÑO:: Estudio descriptivo cadavérico. ENTORNO: Ehime y la Universidad de Kyoto. SUJETOS: Tejido especímenes de nueve cadáveres masculinos. PUNTOS FINALES DE VALORACIÓN:: Las muestras alrededor del anorrecto anterior se seccionaron en serie en planos horizontal, sagital y coronal. Se crearon mayores secciones histológicas en serie a intervalos de 250 µm. Los especímenes fueron teñidos con Elástica van Gieson, y algunas secciones de la serie se estudiaron mediante inmunohistoquímica para detectar músculos lisos y estriados. Dos series fueron digitalizadas y reconstruidas tridimensionalmente. RESULTADOS: Se demostraron dos regiones sin un borde anatómico definido: (i) la región anterior del esfínter anal externo, donde se entrelazaron el esfínter anal externo, el músculo bulbospongoso y el músculo perineal transverso superficial; y (ii) músculo rectouretral, donde el músculo liso del músculo longitudinal se extiende continuamente a la zona posteroinferior de la uretra, que se acerca más al anorrecto a nivel del ápice prostático. La conexión estrecha entre los músculos estriados y lisos se identificó en la parte anterior del esfínter anal externo superior y la parte anterolateral del nivel del músculo puborrectal. LIMITACIÓN:: Este estudio incluyó una muestra pequeña de cadáveres ancianos. CONCLUSIÓN:: Este estudio aclaró la relación espacial precisa entre los músculos lisos y estriados. Los hallazgos anatómicos detallados ayudarán para una disección anterior paso a paso más precisa en la resección interesfintérica y la resección abdominoperineal, especialmente con el abordaje transanal, que puede magnificar la dirección de las fibras musculares y la contracción del músculo estriado utilizando electroestimulación.

Prosaposin and its receptors are differentially expressed in the salivary glands of male and female rats.

Salivary glands produce various neurotrophins that are thought to regulate salivary function during normal and pathological conditions. Prosaposin (PSAP) is a potent neurotrophin found in several tissues and various biological fluids and may play roles in the regulation of salivary function. However, little is known about PSAP in salivary glands. As the functions of salivary glands are diverse based on age and sex, this study examines whether PSAP and its receptors, G protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the salivary glands of rats and whether sex and aging affect their expression. Immunohistochemical analysis revealed that PSAP and its receptors were expressed in the major salivary glands of rats, although their expression varied considerably based on the type of gland, acinar cells, age and sex. In fact, PSAP, GPR37 and GPR37L1 were predominantly expressed in granular convoluted tubule cells of the submandibular gland and the intensity of their immunoreactivity was higher in young adult female rats than age-matched male rats, which was more prominent at older ages (mature adult to menopause). On the other hand, weak PSAP, GPR37 and GPR37L1 immunoreactivity was observed mainly in the basal layer of mucous cells of the sublingual gland. Triple label immunofluorescence analysis revealed that PSAP, GPR37 and GPR37L1 were co-localized in the basal layer of acinar and ductal cells in the major salivary glands. The present findings indicate that PSAP and its receptors, GPR37 and GPR37L1, are expressed in the major salivary glands of rats and their immunoreactivities differ considerably with age and sex.

Assessment of leg muscle activity using toe tapping in patients with Parkinson's disease: comparison of two types of toe tapping.

[Purpose] This study investigates two types of toe tapping, i.e., "closed," with both feet on the floor, and "open," in which the foot does not touch the ground, and evaluates their usefulness in combination with monitoring of muscle activity during toe tapping. [Subjects and Methods] The study enrolled 11 patients with Parkinson's disease (PD) and 9 controls (Controls). The tibialis anterior (TA) and gastrocnemius (GS) muscle activity during toe tapping was measured using surface electromyography. [Results] In closed tapping, the minima in GS activation with the first tap was significantly higher in patients with PD than in Controls. In open tapping, the coefficient of variation (CV) of local maxima in TA activation was significantly higher in patients with PD than in Controls. In both types of tapping, the CV of extrema in GS activities increased with disease duration, but this may be due to the long-term administration of Levodopa, which itself tends to cause excessive GS activities. [Conclusion] Closed tapping is suitable for the assessment of GS activity and can detect excessive activities, which is observed as visible movement. Open tapping, on the other hand, is suitable for assessment of TA activity.

Differential expression of the alternatively spliced forms of prosaposin mRNAs in rat choroid plexus.

Prosaposin has two distinct profiles. One is a precursor form that is processed into saposins thus promoting lysosomal sphingolipid hydrolase function, whereas the other is an intact form that is not processed into saposins but is abundant in certain tissues and secretory fluids, including the cerebrospinal fluid. In rats, alternative splicing in the prosaposin gene generates mRNAs with and without a 9-base insertion (Pro+9 and Pro+0 mRNAs, respectively). Pro+9 mRNA is reported to be preferentially expressed in tissues in which the intact form of prosaposin dominates, whereas Pro+0 mRNA is preferentially expressed in tissues in which the precursor dominates. The expression patterns of Pro+9 and Pro+0 mRNAs in the rat choroid plexus are examined in the present study. The specificities of 36-mer oligonucleotide probes used to detect the 9-base insertion by in situ hybridization were demonstrated by dot-blot hybridization. Next, these probes were used for in situ hybridization, which showed predominant expression of Pro+0 mRNA and weak expression of Pro+9 mRNA in the choroid plexus. These expression patterns were confirmed by reverse transcription plus the polymerase chain reaction with AlwI restriction enzyme treatment. Expression of the intact form of prosaposin in the choroid plexus was assessed by Western blotting and immunohistochemistry. Because the choroid plexus is responsible for the generation of cerebrospinal fluid containing the intact form of prosaposin, the present study raises the possibility that Pro+0 mRNA is related to the intact form in the choroid plexus and that the alternatively spliced forms of mRNAs do not simply correspond to the precursor and intact forms of prosaposin.

Increase in the Posterior Tibial Slope Provides Better Joint Awareness and Patient Satisfaction in Cruciate-Retaining Total Knee Arthroplasty.

The effect of the posterior tibial slope (PTS) in cruciate-retaining total knee arthroplasty (CR-TKA) on clinical outcomes remains unclear. We aimed to investigate (1) the effect of alteration of the PTS on clinical outcomes, including patient satisfaction and joint awareness, and (2) the relationship between the patient-reported outcomes, the PTS, and compartment loading. Based on the alteration of the PTS after CR-TKA, 39 and 16 patients were stratified into increased and decreased PTS groups, respectively. Clinical evaluation was performed by the Knee Society Score (KSS) 2011 and the Forgotten Joint Score-12 (FJS-12). Compartment loading was intraoperatively assessed. KSS 2011 (symptoms, satisfaction, and total score) was significantly higher (p = 0.018, 0.023, and 0.040, respectively), and FJS ("climbing stairs?") was significantly lower (p = 0.025) in the increased PTS group compared with the decreased PTS group. The decrease in both medial and lateral compartment loading of Δ45°, Δ90°, and ΔFull was significantly greater in the increased PTS group than in the decreased PTS group (p< 0.01 for both comparisons). Medial compartment loading of Δ45°, Δ90°, and ΔFull significantly correlated with KSS 2011 for "symptom" (r = - 0.4042, -0.4164, and -0.4010, respectively; p = 0.0267, 0.0246, and 0.0311, respectively). ΔPTS significantly correlated with medial compartment loading differentials of Δ45°, Δ90°, and ΔFull (r = - 0.3288, -0.3792, and -0.4424, respectively; p = 0.0358, 0.01558, and 0.0043, respectively). Patients with increased PTS showed better symptoms and higher patient satisfaction compared with those with decreased PTS following CR-TKA, possibly due to a greater decrease in compartment loading during knee flexion.Level of evidence:level IV, therapeutic case series.

A new magnetic resonance imaging grading system for anterior cruciate ligament myxoid degeneration in osteoarthritis of the knee.

BACKGROUND: This study aimed to investigate association between magnetic resonance imaging (MRI) and histological findings of degenerated anterior cruciate ligament (ACL) in knee osteoarthritis (OA), and based on this result, to develop a new ACL degeneration grading system by MRI that corresponds to histological findings of degenerated ACL. HYPOTHESIS: MRI signal intensity of the ACL could correspond to histological findings of collagen degeneration. PATIENTS AND METHODS: A collection of 106 ACL specimens from 85 patients who underwent primary total knee arthroplasty was investigated for signal intensity of the ACL and muscle on axial Fat-saturated proton density-weighted MRI and MRI signal intensity ratio (ACL/muscle) was calculated. The correlation between ACL histological degeneration and MRI ACL/muscle signal intensity ratio was analyzed. The ACL was stratified into 3 grades based on signal intensity relative to muscle intensity (grade 1, low; grade 2, iso; and grade 3, high), and the extent to ACL degeneration in each MRI ACL degeneration grade was evaluated. RESULTS: Collagen degeneration (53.5±24.0%) and myxoid change (25.2±18.8%) in degenerated ACL significantly correlated with MRI signal intensity ratio of the ACL/muscle (r=0.62, p<0.0001; r=0.67, p<0.0001). ACL were assigned to grade 1 (n=22 [20.8%]), grade 2 (n=56 [52.8%]), and grade 3 (n=28 [26.4%]). ACL collagen degeneration was 34.8±18.4% in grade 1, 49.3±21.7% in grade 2, and 76.6±12.0% in grade 3. ACL myxoid change was 10.0±11.3% in grade 1, 21.3±14.1% in grade 2, and 45.0±15.3% in grade 3. DISCUSSION: The ACL/muscle signal intensity ratio on MRI correlated with the extent to ACL myxoid degeneration. The new MRI ACL degeneration grade is helpful to estimate the extent to ACL myxoid degeneration in knee OA. LEVEL OF EVIDENCE: III; retrospective cohort study.

Distribution of prosaposin in rat lymphatic tissues.

Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system.

Variation in avian brain shape: relationship with size and orbital shape.

There is wide variation in brain shape among birds. Differences in brain dimensions reflect species-specific sensory capacities and behavioral repertoires that are shaped by environmental and biological factors during evolution. Most previous studies aimed at defining factors impacting brain shape have used volumetric or linear measurements. However, few have explored the quantitative indices of three-dimensional (3D) brain geometry that are absolutely imperative to understanding avian evolutionary history. This study aimed: (i) to explore the relationship between brain shape and overall brain size; and (ii) to assess the relationship between brain shape and orbital shape. Avian brain endocasts were reconstructed from computed tomography images and analyzed using 3D geometric morphometrics. Principal component analysis revealed dominant regional variations in avian brain shape and shape correlations between the telencephalon and cerebellum, between the cerebellum and myelencephalon, and between the diencephalon and optic tectum. Brain shape changes relative to total brain size were determined by multivariate regression analysis. Larger brain size was associated with a relatively slender telencephalon and differences in brain orientation. The correlation between brain shape and orbital shape was assessed by two-block partial least-squares analysis. Relatively round brains with a ventrally flexed brain base were associated with rounder orbits, while narrower brains with a flat brain base were associated with more elongated orbits. The shapes of functionally associated avian brain regions are correlated, and orbital size and shape are dominant factors influencing the overall shape of the avian brain.

Age-related learning difficulty through trial-and-error method associated with decreased default mode network integration in healthy middle-aged adults.

INTRODUCTION: Efficient learning is critical to adapting to different environments. There are well-known learning principles in cognitive rehabilitation, including errorless (EL) and trial-and-error (T&E) learning; however, little is known about their underlying neural mechanisms. In the current study, to understand the age-related changes in learning benefits and neural mechanisms applying EL and T&E learning methods in healthy middle-aged adults, we conducted a graph theoretical analysis using functional magnetic resonance imaging data and analyzed the relationship between learning benefits and age, as well as functional network connectivity and age, with both learning principles. METHOD: A total of 43 participants performed a color-name association task through EL and T&E learning methods. We focused on the functional connectivity patterns of the default mode network (DMN) since previous studies demonstrated this network to be more distinctive and important for the T&E learning method than EL. Within-network functional connectivity was used as the graph metric. RESULTS: Age showed significant moderate negative correlations with T&E scores and within-DMN functional connectivity in the test state following T&E learning. Conversely, age was not significantly correlated with EL scores or within-DMN functional connectivity in either the EL learning or test states. CONCLUSIONS: Our findings demonstrate the age-related learning decline associated with decreased DMN integration with aging, when applying the T&E method but not the EL method, even in healthy middle-aged adults. Relationships between the underlying neural network and age are different depending on the learning method. This suggests the need to take into consideration the remaining learning ability through the T&E learning method compared to normal aging and to utilize residual DMN functioning, in addition to the comparison between score differences between EL and T&E methods, when tailoring an individual learning approach.

Effect of medial opening wedge distal tibial tuberosity osteotomy on possible neuropathic pain in patients with osteoarthritis of the knee.

BACKGROUND: There is a paucity of literature regarding the changes and features of neuropathic pain (NP) in knee osteoarthritis (OA) following medial opening wedge distal tibial tuberosity osteotomy (OWDTO). This study aimed to investigate the effect of OWDTO on NP in knee OA; we hypothesized that OWDTO improves knee symptoms and functions and also meets patient satisfaction in those with knee OA with possible NP or without NP. METHODS: Fifty-two consecutive patients who underwent OWDTO were categorized into the unlikely NP and possible NP groups using the painDETECT questionnaire. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score and the Knee Society Score 2011 (KSS 2011) were compared between the groups preoperatively and at the 1-year follow-up. RESULTS: The number of patients having possible NP significantly decreased from 12 (23.1%) preoperatively to one (1.9%) postoperatively (p < 0.001). The patient with postoperative possible NP also had possible NP preoperatively. All preoperative sub-scores of WOMAC were significantly higher in the possible NP group than in the unlikely NP group (p = 0.018, 0.013, 0.004, and 0.005, respectively); however, the postoperative scores did not differ between the two groups. Regarding the KSS 2011, the preoperative scores for symptom and functional activities were significantly lower in the possible NP group than in the unlikely NP group (p = 0.031 and 0.024, respectively). CONCLUSIONS: OWDTO is an effective surgery for patients with possible NP; it improves symptoms and knee function as well as meets patient satisfaction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Can radiological findings detect neuropathic pain in patients with osteoarthritis of the knee undergoing surgery?

OBJECTIVES: The mechanism underlying neuropathic pain (NP) in osteoarthritis (OA) of the knee is not completely understood. This study aimed to investigate whether possible NP in patients with knee OA undergoing knee surgery is associated with specific radiological findings. METHODS: This study included 197 patients who underwent knee surgery for symptomatic knee OA. Clinical evaluation was performed using the Central Sensitization Inventory (CSI), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and PainDETECT questionnaire. Radiological evaluation was performed using the hip-knee-ankle (HKA) angle, posterior tibial slope (PTS), varus and valgus laxities, and magnetic resonance imaging OA Knee Score (MOAKS). Radiological findings were compared between patients with possible and unlikely NP. Logistic regression analysis was performed to identify the predictive factors for NP. RESULTS: There were 163 and 34 patients with unlikely NP and with possible NP, respectively. The percentage of patients with CSI score ≥ 40 was significantly higher in the possible NP group than in the unlikely NP group (17.6% vs. 6.1%). Patients with possible NP had worse WOMAC scores than patients with unlikely NP. There were no significant positive associations between the possible NP and radiological findings in knee OA. Regression analysis showed no predictive factors for possible NP. CONCLUSIONS: Possible NP is not associated with specific radiological findings in knee OA. Patients with possible NP may mediate CS and experience more severe symptoms, including decreased knee function and lower quality of life, than patients with unlikely NP.