Analysis of anti-tumor effect and mechanism of GLS1 inhibitor CB-839 in colorectal cancer using a stroma-abundant tumor model.

BACKGROUND: Glutaminase 1 (GLS1), a key enzyme in glutamine metabolism in cancer cells, acts as a tumor promoter and could be a potential therapeutic target. CB-839, a GLS1-specific inhibitor, was developed recently. Herein, we aimed to elucidate the anti-tumor effects and mechanism of action of CB-839 in colorectal cancer (CRC). METHODS: Using the UCSC Xena public database, we evaluated GLS1 expression in various cancers. Immunostaining for GLS1 was performed on 154 surgically resected human CRC specimens. Subsequently, we examined the GLS1 mRNA expression levels in eight CRC cell lines and evaluated the association between GLS1 expression and CB-839 efficacy. To create a reproducible CRC model with abundant stroma and an allogeneic immune response, we co-transplanted CT26 and stem cells into BALB/c mice and treated them with CB-839. Finally, RNA sequencing of mouse tumors was performed. RESULTS: Database analysis showed higher GLS1 expression in CRC tissues than in normal colon tissues. Clinical samples from 114 of the 154 patients with CRC showed positive GLS1 expression. GLS1 expression in clinical CRC tissues correlated with vascular invasion. CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model. RNA sequencing revealed that CB-839 treatment inhibited stromal activation, tumor growth, migration, and angiogenesis. These findings were validated through in vitro and in vivo experiments and clinical specimen analysis. CONCLUSIONS: GLS1 expression in CRC plays important roles in tumor progression. CB-839 has inhibitory effects on cancer proliferation and the tumor microenvironment.

Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Novel Lewis Acid-Base Interactions in Polymer-Derived Sodium-Doped Amorphous Si-B-N Ceramic: Towards Main-Group-Mediated Hydrogen Activation.

Interest is growing in transition metal-free compounds for small molecule activation and catalysis. We discuss the opportunities arising from synthesizing sodium-doped amorphous silicon-boron-nitride (Na-doped a-SiBN). Na+ cations and 3-fold coordinated BIII moieties were incorporated into an amorphous silicon nitride network via chemical modification of a polysilazane followed by pyrolysis in ammonia at 1000 °C. Emphasis is placed on the mechanisms of hydrogen (H2) activation within Na-doped a-SiBN structure. This material design approach allows the homogeneous distribution of Na+ and BIII moieties surrounded by SiN4 units contributing to the transformation of the BIII moieties into 4-fold coordinated geometry upon encountering H2, potentially serving as frustrated Lewis acid (FLA) sites. Exposure to H2 induced formation of frustrated Lewis base (FLB) N-= sites with Na+ as a charge-compensating cation, resulting in the in situ formation of a frustrated Lewis pair (FLP) motif (≡BFLA···Hδ-···Hδ+···:N-(Na+)=). Reversible H2 adsorption-desorption behavior with high activation energy for H2 desorption (124 kJ mol-1) suggested the H2 chemisorption on Na-doped a-SiBN. These findings highlight a future landscape full of possibilities within our reach, where we anticipate main-group-mediated small molecule activation will have an important impact on the design of more efficient catalytic processes and the discovery of new catalytic transformations.

A risk scoring system for early diagnosis of anastomotic leakage after subtotal esophagectomy for esophageal cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the most critical postoperative complications after subtotal esophagectomy in patients with esophageal cancer. This study attempted to develop an optimal scoring system for stratifying the risk for AL. METHODS: The study included 171 patients who underwent subtotal esophagectomy for esophageal cancer followed by esophagogastrostomy in the cervical region from January 2011 to April 2021 at Nagoya University Hospital. AL was defined by radiologic or endoscopic evidence of anastomotic breakdown using some modalities. A risk scoring system for an early diagnosis of AL was established using factors determined in the multivariate analysis. A score was calculated for each patient, and the patients were classified into three categories according to the risk for AL: low-, intermediate- and high-risk. The trend of the risk for AL among the categories was evaluated. RESULTS: Twenty-nine patients (17%) developed AL. Multivariate analysis demonstrated that sinistrous gross features of drain fluid (P < 0.001; odds ratio (OR), 10.2), radiologic air bubble sign (P < 0.001; OR, 15.0) and the level of drain amylase ≥280 U/L on postoperative Day 7 (P < 0.001; OR, 9.0) were significantly associated with AL. According to the matching number of the above three risk factors and categorization into three risk groups, the incidence of AL was 6.1% (8/131) in the low-risk group, 45.5% (15/33) in the intermediate-risk group and 85.7% (6/7) in the high-risk group (area under curve, 0.81; 95% confidence interval, 0.72-0.90). CONCLUSIONS: The present AL-risk scoring system may be useful in postoperative patient care after subtotal esophagectomy.

Landscape Genetic Analysis for the Japanese Wild Boar in the Early Expanding Stage in the Hokuriku Region of Japan.

As a contribution to improving management of the Japanese wild boar (Sus scrofa leucomystax), which has recently expanded its range and is having some negative effects on the ecosystem, we conducted a landscape genetic study using individual-based genetic analysis and multiple landscape elements to elucidate its dispersal patterns in the early stage of its expansion. Microsatellite DNA analysis of Japanese wild boars in the Hokuriku region of Japan revealed the existence of two ancestral genetic clusters, that they had migrated via different pathways, and that they were inadequately admixed. We also inferred the most suitable habitats for Japanese wild boar using MaxEnt and concluded that lower elevation and snowfall may favor the occurrence of wild boar individuals. Landscape genetic analysis indicated regional differences in Japanese wild boar dispersal patterns, according to the spatial heterogeneity of genetic features and landscape elements. On the western side of the study area, where individuals with a high frequency of one of two ancestral clusters were more abundant, significant effects of isolation by distance and resistance due to the above two landscape factors were detected, suggesting unidirectional dispersion influenced by the alpine landscape. In contrast, on the eastern side, there was indication of resistance to dispersal of individuals predominantly possessing another ancestral cluster, suggesting the influence of irregularly arranged suitable habitats due to the complexity of the mountainous terrain. Based on our findings, we conclude that Japanese wild boar dispersal patterns may be influenced by landscape elements, such as alpine mountains.

Usefulness of Acetic Acid Spray with Narrow-Band Imaging for Identifying the Margin of Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes. AIMS: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs. METHODS: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI. RESULTS: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01). CONCLUSIONS: A-NBI may be a useful modality for identifying the margin of SSLs.

Community-based practical behavioral intervention in public transportation for people with acquired brain injury: study of two cases using a single-case experimental design study.

The purpose of this paper was to report on the progress of a behavioral approach to enable patients with acquired brain injury (age 57, male, stroke and age 36, old, female, TBI) using a community activity support center to commute alone using public transportation. In this study, two ABI patients were intervened to enable them to use public transportation. The frequency of intervention was once a month or once a week. The two community-dwelling adults each had post-ABI attention and memory deficits and anxiety. A-B-A single-case experimental design was employed for this study. The transportation route was stepped into multiple steps. Each step was scored in a unique way to determine the degree of assistance the participant received from others. This score was considered the main outcome. Tau-U analysis was used for statistical analysis. Statistically significant improvements in public transportation use were shown between baseline and intervention. There were no significant differences between the intervention and follow-up periods. The results suggest that behavioral interventions are beneficial in reacquiring the ability to use public transportation and that the intervention effects are sustained.

The efficacy and safety of pertuzumab plus trastuzumab and docetaxel as a first-line therapy in Japanese patients with inoperable or recurrent HER2-positive breast cancer: the COMACHI study.

PURPOSE: In the CLEOPATRA study of patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer, the Japanese patient subgroup did not demonstrate the improved progression-free survival (PFS) of pertuzumab plus trastuzumab and docetaxel vs. placebo that was seen in the overall population. Therefore, COMACHI was conducted to confirm the efficacy and safety of this treatment regimen in this patient subgroup. METHODS: This was a phase IV study of pertuzumab plus trastuzumab and docetaxel in Japanese patients with histologically/cytologically confirmed inoperable or recurrent HER2-positive breast cancer. All patients received pertuzumab, trastuzumab, and docetaxel intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Secondary endpoints were overall survival (OS), investigator-assessed objective response rate, and duration of response (DoR). Safety was also assessed. RESULTS: At final analysis, median investigator-assessed PFS was 22.8 months (95% CI 16.9-37.5). From first dose, OS rate at 1 year was 97.7%; and at 2 and 3 years were 88.5% and 79.1%, respectively. Of the 118 patients with measurable disease at baseline, response rate was 83.9% (95% CI 77.3-90.5) and median investigator-assessed DoR was 26.3 months (95% CI 17.1-not evaluable). Treatment was well tolerated, with no new safety signals detected. CONCLUSIONS: Our results suggest similar efficacy and safety for pertuzumab plus trastuzumab and docetaxel in Japanese patients compared with the overall population of CLEOPATRA, providing further support for this combination therapy as standard of care for Japanese patients with inoperable or recurrent HER2-positive breast cancer.

New femoral remains of Nacholapithecus kerioi: Implications for intraspecific variation and Miocene hominoid evolution.

The middle Miocene stem kenyapithecine Nacholapithecus kerioi (16-15 Ma; Nachola, Kenya) is represented by a large number of isolated fossil remains and one of the most complete skeletons in the hominoid fossil record (KNM-BG 35250). Multiple fieldwork seasons performed by Japanese-Kenyan teams during the last part of the 20th century resulted in the discovery of a large sample of Nacholapithecus fossils. Here, we describe the new femoral remains of Nacholapithecus. In well-preserved specimens, we evaluate sex differences and within-species variation using both qualitative and quantitative traits. We use these data to determine whether these specimens are morphologically similar to the species holotype KNM-BG 35250 (which shows some plastic deformation) and to compare Nacholapithecus with other Miocene hominoids and extant anthropoids to evaluate the distinctiveness of its femur. The new fossil evidence reaffirms previously reported descriptions of some distal femoral traits, namely the morphology of the patellar groove. However, results also show that relative femoral head size in Nacholapithecus is smaller, relative neck length is longer, and neck-shaft angle is lower than previously reported for KNM-BG 35250. These traits have a strong functional signal related to the hip joint kinematics, suggesting that the morphology of the proximal femur in Nacholapithecus might be functionally related to quadrupedal-like behaviors instead of more derived antipronograde locomotor modes. Results further demonstrate that other African Miocene apes (with the exception of Turkanapithecus kalakolensis) generally fall within the Nacholapithecus range of variation, whose overall femoral shape resembles that of Ekembo spp. and Equatorius africanus. Our results accord with the previously inferred locomotor repertoire of Nacholapithecus, indicating a combination of generalized arboreal quadrupedalism combined with other antipronograde behaviors (e.g., vertical climbing).

Long-Term Outcomes of Immediate Autologous Breast Reconstruction for Breast Cancer Patients.

BACKGROUND: There is limited information on the oncological outcomes of immediate autologous breast reconstruction in the Asian population. This study aimed to evaluate the oncological outcomes of immediate one-stage autologous breast reconstruction using a free perforator flap for breast cancer patients at a single institution in Japan. METHODS: We retrospectively reviewed 239 patients who underwent immediate one-stage autologous breast reconstruction using a free perforator flap after skin- or nipple-sparing mastectomy. The whole breast was pathologically analyzed in 5-mm sections. Clinical and pathological data were collected from medical records. RESULTS: For tumor stage among the 239 patients, 101 (42.3%) had stage 0, 127 (53.1%) had stage I and II, and 11 (4.6%) had stage III. Twenty-three patients (9.6%) had margin involvement in the surgical specimen. Adjuvant chemotherapy was performed in 75 patients (30%), and endocrine therapy was administered in 153 patients (64%). Radiation therapy was performed in 15 patients (6.3%) because of multiple lymph node metastases or margin involvement. With a median follow-up time of 73 mo, local recurrence was found in 3.3%, distant metastases in 2.5%, and contralateral breast cancer in 3.7%. All patients with local recurrence did not receive radiation therapy as adjuvant treatment. CONCLUSIONS: Among the patients who underwent immediate one-stage autologous reconstruction after breast surgery, 3.3% had local recurrence. For patients with margin involvement, radiation therapy is a promising option.

Effectiveness of 16S ribosomal DNA real-time PCR and sequencing for diagnosing bacterial keratitis.

PURPOSE: To evaluate the efficacy of real-time PCR for 16S ribosomal DNA (16S r-DNA) and sequencing for diagnosing microbial keratitis. METHODS: We studied 272 eyes of 272 patients with keratitis. Eyes with keratitis were classified as "definite" (N = 118), "likely" (N = 71), or "non-bacterial" (N = 83) to have bacterial keratitis. The diagnostic efficacy of real-time PCR and conventional testing was determined by receiver operating characteristic analysis. The copy numbers of bacterial DNA and clinical characteristics were retrospectively analyzed for association with concordant culture results in the "definite" cases. RESULTS: The level of bacterial DNA was significantly associated with the diagnostic probability of the three diagnostic categories. The level of bacterial DNA had comparable diagnostic efficacy with the area under the curve (AUC) at 0.67, by culture at 0.65, and by smear testing at 0.73. The efficacy was significantly improved by combining the DNA level with the conventional culture testing with an AUC of 0.81. Analysis of the "definite" cases showed culture positivity in 51.8% (58 eyes), and of these, 41 eyes (70.7%) were higher than the cutoff PCR values and 40 eyes were identified by 16S r-DNA sequencing. In the culture-negative eyes, the level of bacterial DNA was significantly lower (P = 0.0008). Eyes with higher bacterial DNA levels had significantly concordant outcomes with sequencing and culture results (P = 0.006). Previous antibiotic treatments decreased the bacterial DNA amount by 0.09-fold, and it was a significant factor for discordance (P = 0.006). CONCLUSION: Quantification of the bacterial DNA level and conventional testing improves the diagnostic efficacy of infectious bacterial keratitis.

De novo AFF3 variant in a patient with mesomelic dysplasia with foot malformation.

Mesomelic dysplasia (MD) encompasses a heterogeneous group of disorders characterized by shortening of the middle segments of the limbs. Previous studies have revealed the development of Nievergelt type-like MD accompanied by postaxial toe reduction in a patient with a ~500 kb microdeletion at 2q11.2 involving AFF3 alone, and the occurrence of Nievergelt type-like MD in mice with a ~353 kb deletion involving Aff3, together with strong expression of mouse Aff3 in the developing limbs and zeugopod. We encountered a 2 6/12-year-old Japanese girl with an unclassifiable MD associated with hypoplasia of postaxial toes, and identified a de novo likely pathogenic variant of AFF3 (NM_002285.2:c.697 G > A, p.(Ala233Thr)) by whole exome sequencing. The results provide further evidence for AFF3 being the causative gene for MD with foot malformation which may be termed "AFF3-related MD" or "Steichen-Gersdorf type MD".

The evaluation of the appropriate gentamicin use for preterm infants.

Gentamicin (GM) is used for neonates as the initial treatment for neonatal bacterial infection. An association between high trough GM levels and the elevation of the serum creatinine (sCr) level and hearing loss has been reported, although there have been no reports investigating the serial changes in the sCr level in preterm neonates treated with GM. The present study evaluated the serial changes in the sCr level and the incidence of hearing loss in preterm neonates treated with GM. This study included 56 neonates born at a gestational age of 32-36 weeks. Fifteen (group 1) and 20 (group 2) neonates were treated with 2.5 mg/kg of GM every 12 h and 4 mg/kg of GM every 36 h, respectively. Group 3 included 21 neonates without GM therapy. Serum GM levels, serial changes in the sCr levels, and the incidence of hearing loss were then compared among the three groups. The serum trough GM level in group 2 was significantly lower than that in group 1 (P < 0.001), whereas the serum peak GM levels in these groups were almost the same. The ratio of the sCr level at birth to that at the 5th day of life in group 1 was the lowest among the 3 groups. No neonates had hearing loss. GM therapy worsened the sCr level in late preterm neonates, especially those with multiple doses per day. The appropriate use of GM is needed in order to prevent the occurrence of nephrotoxicity.

Effects of green light on the growth of spotted halibut, Verasper variegatus, and Japanese flounder, Paralichthys olivaceus, and on the endocrine system of spotted halibut at different water temperatures.

We have previously shown that the somatic growth of barfin flounder, Verasper moseri, was promoted by green light. The present study was undertaken to elucidate whether growth-promoting effect of green light can be observed in other flatfishes and to understand the roles of endocrine systems in green light-induced growth. Herein, we demonstrated facilitation of growth by green light in the spotted halibut, Verasper variegatus, and Japanese flounder, Paralichthys olivaceus. Blue and blue-green light showed potencies that were similar to that of green light, while the potencies of red and white light were equivalent to that of ambient light (control). We also examined the effects of green light on growth and endocrine systems of V. variegatus at various water temperatures. Growth of the fish was facilitated by green light at four different water temperatures examined; the fish were reared for 31 days at 12 and 21 °C, and 30 days at 15 and 18 °C. Increase in condition factor was observed at 15 and 18 °C. Among the genes encoding hypothalamic hormones, expression levels of melanin-concentrating hormone 1 (mch1) were enhanced by green light at the four water temperatures. Expression levels of other genes including mch2 increased at certain water temperatures. No difference was observed in the expression levels of pituitary hormone genes, including those of growth hormone and members of proopiomelanocortin family, and in plasma levels of members of the insulin family. The results suggest that green light may generally stimulate growth of flatfishes. Moreover, it is conceivable that MCH, production of which is stimulated by green light, is a key hormone; it augments food intake, which is intimately coupled with somatic growth.

Impact of High Flow Nasal Cannula Therapy on Oral Feeding in Very Low Birth Weight Infants with Chronic Lung Disease.

Previous studies on high-flow nasal cannula (HFNC) in very-low-birth-weight infants (VLBWIs) focused on comparing HFNC with nasal continuous positive airway pressure (nCPAP) to determine the usefulness of HFNC as a backup in the case of extubation failure and nasal trauma; however, the studies did not consider oral feeding. This retrospective case-control study aimed at elucidating whether HFNC could prevent the delay in feeding and achievement of full oral feeding in VLBWIs with chronic lung disease (CLD). Forty five VLBWIs were enrolled in this study: an HFNC group (n = 11) that was supported by HFNC at oral feeding initiation, and a non-HFNC group (n = 34) that could start oral feeding without HFNC. The gestational age and birth weight of the HFNC group were lower than those in the non-HFNC group. The median duration of exposure to oxygen and neonatal intensive care unit stay were comparable in both groups. The timings of oral feeding initiation and full oral feeding achievement in both groups were not significantly different: 35.3 (33.0 - 38.1) vs. 35.5 (33.7 - 42.4) weeks (P = 0.91) for the HFNC and 38.6 (34.4 - 42.3) vs. 36.7 (34.6 - 44.4) weeks postmenstrual age (P = 0.29) for the non-HFNC. Clinically significant aspiration pneumonia during the period of oral feeding was not observed in the HFNC group. Respiratory support by HFNC in VLBWIs with CLD might prevent oral feeding delay. Initiation of oral feeding of VLBWIs on HFNC might be safe and might accelerate the achievement of oral feeding milestones.

Effects of liaison between physiotherapists and occupational therapists for home-visit rehabilitation: preliminary study.

[Purpose] Home-visit rehabilitation is used to restructure patients' home lives and involves comprehensive intervention. In Japan, liaison between physiotherapists and occupational therapists occurs, but impact of this cooperation is unclear. The present study aimed to investigate therapeutic efficacy of this liaison. [Participants and Methods] The study used a cross-sectional design. Participants were community-dwelling older adults who required long-term care and were receiving home-visit rehabilitation provided in the Chubu region. They were divided into a single-intervention group with either physiotherapy or occupational therapy alone, and a liaison-intervention group with therapy coordinated between the 2 professions. In addition to basic information, the Barthel Index, Frenchay Activities Index, Health Utility Index Mark 3, and subjective health assessments were evaluated. [Results] Eighteen participants were recruited. No significant differences were observed between groups for the Barthel Index, whereas the total Frenchay Activities Index score and items of the Frenchay Activities Index (outdoor domestic chores and outdoor activities) were significantly higher in the liaison-intervention group. The emotion item in the Health Utility Index Mark 3 and subjective health assessments were also significantly higher in the liaison-intervention group. [Conclusion] These findings suggest that this liaison is effective for improving activities of daily living and increasing quality of life. This is probably due to each therapist performing a specialized intervention and professional cooperation.

Multivariate analysis of variations in intrinsic foot musculature among hominoids.

Comparative analysis of the foot muscle architecture among extant great apes is important for understanding the evolution of the human foot and, hence, human habitual bipedal walking. However, to our knowledge, there is no previous report of a quantitative comparison of hominoid intrinsic foot muscle dimensions. In the present study, we quantitatively compared muscle dimensions of the hominoid foot by means of multivariate analysis. The foot muscle mass and physiological cross-sectional area (PCSA) of five chimpanzees, one bonobo, two gorillas, and six orangutans were obtained by our own dissections, and those of humans were taken from published accounts. The muscle mass and PCSA were respectively divided by the total mass and total PCSA of the intrinsic muscles of the entire foot for normalization. Variations in muscle architecture among human and extant great apes were quantified based on principal component analysis. Our results demonstrated that the muscle architecture of the orangutan was the most distinctive, having a larger first dorsal interosseous muscle and smaller abductor hallucis brevis muscle. On the other hand, the gorilla was found to be unique in having a larger abductor digiti minimi muscle. Humans were distinguished from extant great apes by a larger quadratus plantae muscle. The chimpanzee and the bonobo appeared to have very similar muscle architecture, with an intermediate position between the human and the orangutan. These differences (or similarities) in architecture of the intrinsic foot muscles among humans and great apes correspond well to the differences in phylogeny, positional behavior, and locomotion.

Sexual dimorphism of body size in an African fossil ape, Nacholapithecus kerioi.

Sexual size dimorphism in the African fossil ape Proconsul nyanzae (18 million years ago, 18 Ma) has been previously documented. However, additional evidence for sexual dimorphism in Miocene hominoids can provide great insight into the history of extant hominoid mating systems. The present study focused on body mass (BM) sexual dimorphism in Nacholapithecus kerioi from the Middle Miocene (16-15 Ma) in Africa. Bootstrap analysis revealed that P. nyanzae BM sexual dimorphism was lower than that in Pan troglodytes, which exhibits moderate sexual dimorphism, as reported previously. The same simulation revealed that BM sexual dimorphism of N. kerioi was comparable with that in Gorilla spp.; i.e., the males were approximately twice as large as the females. High sexual dimorphism in extant apes is usually indicative of a polygynous social structure (gorilla) or solitary/fission-fusion social system (orangutan). However, because of the high proportion of adult males in this fossil assemblage, the magnitude of dimorphism inferred here cannot be associated with a gorilla-like polygynous or oranguran-like solitary/fission-fusion social structure, and may reflect either taphonomic bias, or some other social structure. Extant hominoids have a long evolutionary history owing to their deep branching, comprising only a few existing members of the original highly successful group. Therefore, it is not surprising that the mating systems of extant hominoids fail to provide fossil apes with a perfect "model". The mating systems of extinct hominoids may have been more diverse than those of extant apes.