Usefulness of non-surgical treatment without weight bearing restriction versus surgical treatment for maintaining activities of daily living in patients with peri-prosthetic femoral fractures.

PURPOSE: Non-surgical treatment without weight-bearing restriction, even in the early post-injury phase, may have a favourable effect on the activities of daily living (ADLs) in elderly patients with peri-prosthetic femoral fractures (PFFs). This study aimed to assess the effectiveness of surgical and non-surgical treatments for PFFs in terms of ADL maintenance and clinical safety. METHODS: This retrospective cohort study included 44 patients with PFFs proximal to the stem fixation site without stem loosening. Rehabilitation with weight bearing was initiated after internal fixation of the fracture site in the surgical group (n = 12) and immediately after the injury in the non-surgical group (n = 32). Clinical and radiological outcomes, including time until the first weight-bearing exercise, time until independent walking, ADL deterioration, and bone union rate, were compared between groups. Independent risk factors for ADL deterioration were also evaluated. RESULTS: The time until first weight-bearing exercise was shorter and the ADL deterioration rate was smaller in the non-surgical group than in the surgical group (8.8 ± 9.2 vs. 21 ± 13 days, P = 0.004; 6.2% vs. 12.5%, P = 0.04, respectively). Bone union rates were similar between groups (91% vs. 83%, P = 0.42), and aseptic loosening of the stem was not observed. Time until first weight-bearing exercise was identified as an independent risk factor for ADL deterioration (odds ratio, 1.13; 95% confidence interval, 1.01-1.26; P = 0.03). CONCLUSION: Non-surgical treatment of PFFs proximal to the stem fixation site without stem loosening, which does not restrict early weight-bearing exercise after injury, is an effective and safe treatment procedure that maintains ADL performance in elderly patients.

[A Case of Curative Resection of the Local Advanced Gastric Cancer after SOX plus Nivolumab Chemotherapy, and the Pathological Diagnosis Was Complete Response].

A-78-year-old woman presented with difficulty swallowing. She was diagnosed as having advanced upper gastric cancer with invasion to the esophagus and the diaphragm. Biopsy examination of the tumor showed MSI-high and HER2-negative. The patient received 4 courses of SOX plus nivolumab in combination. After the chemotherapy, the size of the tumor decreased remarkably. We performed total gastrectomy with D2 lymph node dissection. Pathological examination revealed no residual cancer at the primary tumor location and the regional lymph nodes. The patient has shown no recurrence for 9 months without adjuvant chemotherapy. We conclude that SOX plus nivolumab in combination as first-line chemotherapy is an effective strategy against advanced gastric cancer.

Dietary scallop oil prepared from the internal organs of Japanese giant scallop (Patinopecten yessoensis) improved mite allergen-induced atopic dermatitis-like symptoms on the dorsal skin of NC/Nga mice.

This study aimed to investigate the effects of scallop oil (SCO) on atopic dermatitis (AD)-like symptoms induced by mite allergens in the dorsal and ear skins of NC/Nga mice compared to those of refined corn oil and krill oil (KO). SCO, rich in n-3 polyunsaturated fatty acids and phospholipids, was prepared from the internal organs of Japanese giant scallop, an underutilized fishery resource in Japan. Results showed that SCO intake improved AD-like symptoms, including ear edema, ear thickness, and transepidermal water loss of dorsal skin, and tended to decrease the scratching behavior, whereas KO intake did not. Further, SCO intake decreased the degranulated mast cell count and increased the tight junction protein claudin-1 expression, which is important for the barrier function, in the dorsal skin compared to refined corn oil intake. SCO improved the AD-like symptoms by suppressing mast cell degranulation and strengthening the barrier function of dorsal skin in NC/Nga mice.

Accuracy of tibial component placement in unicompartmental knee arthroplasty performed using an accelerometer-based portable navigation system.

PURPOSE: There is a need for new devices to improve the accuracy of implantation in unicompartmental knee arthroplasties (UKAs). The accelerometer-based portable navigation system is expected to improve this accuracy. This study aimed to compare the accuracy of UKAs performed by the portable navigation system with that of the conventional method, and to investigate whether the portable navigation system can complement the surgeon's experience. METHODS: The study comprised of 80 Oxford UKAs. Knees were divided into two groups based on the method of tibial osteotomy: the conventional group (37 UKAs performed by an experienced surgeon using the extra-medullary guide) and the portable navigation group (43 UKAs performed by 2 unaccustomed surgeons using the navigation system). The absolute error from the target angle on the coronal and sagittal plane was measured on whole lower leg X-ray. The incidence of outliers (> 3°) was compared between the groups using Fisher's exact probability test. RESULTS: The incidences of outliers on the coronal plane were 41.0% (15 of 37 knees) in the conventional group and 9.3% (4 of 43 knees) in the portable navigation group (p < 0.0001). The incidences of outliers on the sagittal plane were 13.5% (5 of 37 knees) in the conventional group and 14.0% (6 of 43 knees) in the portable navigation group (p = 0.3772). CONCLUSION: This is the first report on the usefulness of an accelerometer-based portable navigation system in UKA. The use of this system improves the accuracy of implantation of the tibial component beyond the experience of the surgeon. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Discovery of novel 2-(4-aryl-2-methylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3ß inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3ß inhibitors from our promising compounds containing a 3-methylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3ß inhibitors. SAR studies focused on the nitrogen atom of the piperazine moiety revealed that a phenyl group afforded potent inhibitory activity toward GSK-3ß. Docking studies indicated that the phenyl group on the piperazine nitrogen atom and the methyl group on the piperazine make cation-π and CH-π interactions with GSK-3ß respectively. 4-Methoxyphenyl analogue 29 showed most potent inhibitory activity toward GSK-3ß with good in vitro and in vivo pharmacokinetic profiles, and 29 demonstrated a significant decrease in tau phosphorylation after oral administration in mice.

Discovery of novel 2-(3-phenylpiperazin-1-yl)-pyrimidin-4-ones as glycogen synthase kinase-3ß inhibitors.

We herein describe the results of further evolution of glycogen synthase kinase (GSK)-3ß inhibitors from our promising compounds containing a 2-phenylmorpholine moiety. Transformation of the morpholine moiety into a piperazine moiety resulted in potent GSK-3ß inhibitors. SAR studies focused on the phenyl moiety revealed that a 4-fluoro-2-methoxy group afforded potent inhibitory activity toward GSK-3ß. Based on docking studies, new hydrogen bonding between the nitrogen atom of the piperazine moiety and the oxygen atom of the main chain of Gln185 has been indicated, which may contribute to increased activity compared with that of the corresponding phenylmorpholine analogues. Effect of the stereochemistry of the phenylpiperazine moiety is also discussed.

Effects of oolonghomobisflavan A on oxidation of low-density lipoprotein.

Oxidation of low-density lipoprotein (LDL) by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been suggested to be involved in the onset of atherosclerosis. Oolong tea contains unique polyphenols including oolonghomobisflavan A (OFA). In this study, the effects of OFA on LDL oxidation by ROS and RNS were investigated in vitro. OFA suppressed formation of cholesterol ester hydroperoxides in LDL oxidized by peroxyl radical and peroxynitrite, and formation of thiobarbituric acid reactive substances in LDL oxidized by Cu2+. In addition, OFA inhibited fragmentation, carbonylation, and nitration of apolipoprotein B-100 (apo B-100) in the oxidized LDL, in which heparin-binding activity of apo B-100 was protected by OFA. Our results suggest that OFA exhibits antioxidant activity against both lipid peroxidation and oxidative modification of apo B-100 in LDL oxidized by ROS and RNS. Polyphenols in oolong tea may prevent atherosclerosis by reducing oxidative stress.

Multiple origins of the phenol reaction negative phenotype in foxtail millet, Setaria italica (L.) P. Beauv., were caused by independent loss-of-function mutations of the polyphenol oxidase (Si7PPO) gene during domestication.

Foxtail millet shows variation in positive phenol color reaction (Phr) and negative Phr in grains, but predominant accessions of this crop are negative reaction type, and the molecular genetic basis of the Phr reaction remains unresolved. In this article, we isolated polyphenol oxidase (PPO) gene responsible for Phr using genome sequence information and investigated molecular genetic basis of negative Phr and crop evolution of foxtail millet. First of all, we searched for PPO gene homologs in a foxtail millet genome database using a rice PPO gene as a query and successfully found three copies of the PPO gene. One of the PPO gene homologs on chromosome 7 showed the highest similarity with PPO genes expressed in hulls (grains) of other cereal species including rice, wheat, and barley and was designated as Si7PPO. Phr phenotypes and Si7PPO genotypes completely co-segregated in a segregating population. We also analyzed the genetic variation conferring negative Phr reaction. Of 480 accessions of the landraces investigated, 87 (18.1 %) showed positive Phr and 393 (81.9 %) showed negative Phr. In the 393 Phr negative accessions, three types of loss-of-function Si7PPO gene were predominant and independently found in various locations. One of them has an SNP in exon 1 resulting in a premature stop codon and was designated as stop codon type, another has an insertion of a transposon (Si7PPO-TE1) in intron 2 and was designated as TE1-insertion type, and the other has a 6-bp duplication in exon 3 resulting in the duplication of 2 amino acids and was designated as 6-bp duplication type. As a rare variant of the stop codon type, one accession additionally has an insertion of a transposon, Si7PPO-TE2, in intron 2 and was designated as "stop codon +TE2 insertion type". The geographical distribution of accessions with positive Phr and those with three major types of negative Phr was also investigated. Accessions with positive Phr were found in subtropical and tropical regions at frequencies of ca. 25-67 % and those with negative Phr were broadly found in Europe and Asia. The stop codon type was found in 285 accessions and was broadly distributed in Europe and Asia, whereas the TE-1 insertion type was found in 99 accessions from Europe and Asia but was not found in India. The 6-bp duplication type was found in only 8 accessions from Nansei Islands (Okinawa Prefecture) of Japan. We also analyzed Phr in the wild ancestor and concluded that the negative Phr type was likely to have originated after domestication of foxtail millet. It was also implied that negative Phr of foxtail millet arose by multiple independent loss of function of PPO gene through dispersal because of some advantages under some environmental conditions and human selection as in rice and barley.

Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3ß inhibitors for Alzheimer's disease.

We herein describe the results of further evolution of GSK-3ß inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3ß inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models.

NYC4, the rice ortholog of Arabidopsis THF1, is involved in the degradation of chlorophyll - protein complexes during leaf senescence.

Yellowing/chlorophyll breakdown is a prominent phenomenon in leaf senescence, and is associated with the degradation of chlorophyll - protein complexes. From a rice mutant population generated by ionizing radiation, we isolated nyc4-1, a stay-green mutant with a defect in chlorophyll breakdown during leaf senescence. Using gene mapping, nyc4-1 was found to be linked to two chromosomal regions. We extracted Os07g0558500 as a candidate for NYC4 via gene expression microarray analysis, and concluded from further evidence that disruption of the gene by a translocation-related event causes the nyc4 phenotype. Os07g0558500 is thought to be the ortholog of THF1 in Arabidopsis thaliana. The thf1 mutant leaves show variegation in a light intensity-dependent manner. Surprisingly, the Fv /Fm value remained high in nyc4-1 during the dark incubation, suggesting that photosystem II retained its function. Western blot analysis revealed that, in nyc4-1, the PSII core subunits D1 and D2 were significantly retained during leaf senescence in comparison with wild-type and other non-functional stay-green mutants, including sgr-2, a mutant of the key regulator of chlorophyll degradation SGR. The role of NYC4 in degradation of chlorophyll and chlorophyll - protein complexes during leaf senescence is discussed.

Crop Evolution of Foxtail Millet.

Studies on the domestication, genetic differentiation, and crop evolution of foxtail millet are reviewed in this paper. Several genetic studies were carried out to elucidate the genetic relationships among foxtail millet accessions originating mainly from Eurasia based on intraspecific hybrid pollen semi-sterility, isozymes, DNA markers, and single-nucleotide polymorphisms. Most studies suggest that China is the center of diversity of foxtail millet, and landraces were categorized into geographical groups. These results indicate that this millet was domesticated in China and spread over Eurasia, but independent origin in other regions cannot be ruled out. Furthermore, the evolution of genes was reviewed (i.e., the Waxy gene conferring amylose content in the endosperm, the Si7PPO gene controlling polyphenol oxidase, the HD1 and SiPRR37 genes controlling heading time, the Sh1 and SvLes1 genes involved in grain shattering, and the C gene controlling leaf sheath pigmentation), and the variation and distribution of these genes suggested complex patterns of evolution under human and/or natural selection.

Latitudinal adaptation and dispersal pathway of foxtail millet suggested by geographical distribution of transposable elements inserted in the SiPRR37 gene.

We investigated the variation and geographical distribution of the Pseudo-regulator response 37 (Setaria italica PRR37; SiPRR37) gene, which is involved in heading time (photoperiodism) in foxtail millet. An allele of the SiPRR37 gene, in which an approximately 4.9-kb transposable element (designated TE1) is inserted (a loss-of-function or reduction-of-function type), is distributed sporadically in East Asia and broadly in Southeast Asia and South Asia, implying that this gene is important in latitudinal adaptation. In addition, we found a new allele of SiPRR37 with an insertion of a 360-bp TE (TE2) at this locus and investigated the geographical distribution of this new type. This SiPRR37 allele with TE2 is distributed in Japan, Korea, Nepal, Iran and Turkey. Both TE1 and TE2 are useful markers for tracing foxtail millet dispersal pathways in Asia.

Early Postoperative Functional Recovery in Older Patients With Periprosthetic Femoral Fractures: Comparison Between Cemented and Cementless Stem Revisions.

Background: Early postoperative functional recovery is important in older patients with lower-extremity fractures to prevent disuse, and periprosthetic femoral fractures (PFFs) are no exception. This study aimed to compare the postoperative functional recovery in the early phase after revision for PFF with loose stems between cemented and cementless stems. Methods: Eighteen patients with Unified Classification System type B2 PFF were included in this retrospective cohort study with a follow-up period of about 2 years. All patients underwent stem revision and were divided into 2 groups: the cemented stem group (n = 9) and the cementless stem group (n = 9). In postrevision, functional independence measure score, independent walk rate, activities of daily living recovery rate to the original level at 2 weeks postoperatively, the Beals and Tower classification for radiological status, and survival rate for readmission as endpoints were compared between the 2 groups. Results: Patients in the cemented group recovered functional mobility earlier than in the cementless group, with higher postoperative functional independence measure functional subscale values (73 vs 50 points, P = .02), higher independent walk rate (89 vs 11%, P < .01), and more postoperative activities of daily living recovery (100% vs 44%, P = .03) at 2 weeks postoperatively. The Beals and Tower classification and survival rates were similar in both groups. Conclusions: Revision using a cemented stem for PFF in older patients was a useful surgical procedure in terms of early postoperative functional recovery. Cemented stem revision was comparable with cementless in bone union and safety at 2 years postoperatively.

Effects of Daily Consumption of Scallop Oil Prepared from Internal Organs of Japanese Giant Scallop (Patinopecten yessoensis) on Serum Lipid Composition and Its Safety: A Randomized, Double-blind, Placebo-controlled, Parallel Group Comparison Study.

Scallop oil (SCO) prepared from the internal organs of the Japanese giant scallop (Patinopecten yessoensis) contains eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and phospholipids (PL). It was previously shown that SCO consumption improves cholesterol and triacylglycerols (TG) contents in mice. The present study demonstrated the effects of daily SCO consumption (1.2 g/day, containing 376 mg of EPA, 63 mg of DHA, and 150 mg of PL) for 12 weeks in human subjects. In this randomized, doubleblind, placebo-controlled, parallel group comparison study, 70 Japanese subjects with serum TG levels ≥120 but < 200 mg/dL were recruited and randomly assigned to the SCO or placebo group. All subjects ingested six capsules per day for 12 weeks. We conducted medical interviews, body composition measurements, vital sign examinations, and blood sampling at weeks 0 (baseline), 4, 8, and 12, and measured peripheral blood flow at weeks 0 and 12. In the case of subjects with higher serum TG levels, SCO consumption decreased the changes in serum TG and malondialdehyde-low density lipoprotein (MDA-LDL) levels compared with the placebo group. Safety assessment revealed no medically significant changes due to continuous SCO consumption. The findings indicate that 1.2 g/day of SCO consumption may be beneficial for reducing serum TG and MDA-LDL levels in persons with higher TG levels.

Simultaneous Post and Cone Fractures of a Polyethylene Insert in a Mobile-Bearing Posterior-Stabilized Total Knee Arthroplasty.

We report a novel case of the simultaneous post and cone fractures of a polyethylene (PE) insert in a mobile-bearing posterior-stabilized total knee arthroplasty. Twelve years after the primary total knee arthroplasty, the 72-year-old male patient presented with a recurring right knee instability and was diagnosed with the wear of the PE insert based on physical and radiological examinations. Revision surgery was performed. The post and cone of the PE insert had fractured simultaneously. Moreover, the femoral and tibial components were in direct contact with each other. One year post-revision, knee function had improved. To diagnose a PE breakage, such as a post or cone fracture, surgeons should consider the possibility of PE breakage even in the absence of pain since patients might complain of subjective instability only.

Improvement of rotational arc during deep flexion range of a novel designed polyethylene insert for posterior-stabilised total knee arthroplasty.

BACKGROUND: One of the remaining issues in total knee arthroplasty (TKA) is achieving sufficient rotational arc during deep flexion range of the knee for specific postures such as the 'seiza' or cross-legged sitting. This study aimed to evaluate whether there was a change in the actual in vivo rotational arc during deep flexion range before and after a design change of polyethylene (PE) inserts. METHODS: In 50 posterior-stabilised TKA cases, knee kinematics, including rotational movement, were measured intraoperatively using an image-free navigation system to compare a newly designed PE insert with reduced the posterior lip with a conventional PE insert. Femoral-tibial rotational angles at 30°, 45°, 60°, 90°, 120°, and 130° knee flexion were evaluated. Varus/valgus instability, knee range of motion, and femoral rollback were also measured. Obtained parameters were compared between new and conventional PE inserts. The independent factors associated with rotational arc during deep flexion range (120° and 130° knee flexion) were analysed using multivariate analysis. RESULTS: The newly designed PE insert demonstrated a significant increase in the rotational arc at 120° (22.9 ± 8.7° vs. 30.1 ± 11.9°, P < 0.001) and 130° (24.3 ± 9.5° vs. 32.5 ± 12.4°, P < 0.001) knee flexion compared with that with the conventionally designed posterior-stabilised insert. Multivariate analysis demonstrated that using the newly designed PE insert was an independent predictor of improved rotational arc during deep flexion range: regression coefficient was 11.2 (95% confidence interval 7.1-15.3, P < 0.001). CONCLUSION: The design change, which reduced the posterior lip of the PE insert, contributed to improved rotational arc in 120° and 130° deep flexion ranges.

Association of intraoperative medial joint gap laxity in the flexion position with subjective knee instability after fixed-bearing posterior-stabilised total knee arthroplasty.

BACKGROUND: Postoperative subjective knee instability is an important clinical outcome after total knee arthroplasty (TKA), however the association with intraoperative soft tissue balance remains unclear. This study aimed to assess the association between intraoperative soft tissue balance and postoperative subjective knee instability in fixed-bearing posterior-stabilised (PS) TKA. METHODS: This retrospective case-control study included 457 patients who underwent fixed-bearing PS TKA. Intra-articular distraction force was quantitatively applied to measure the gap parameters (length and angle) during surgery. The intraoperative joint gap parameters and postoperative clinical outcomes between the patients with (n = 90) and without (n = 367) subjective knee instability were compared. The risk factors for subjective postoperative knee instability were analysed using multivariate logistic regression analysis. RESULTS: The patients with subjective knee instability demonstrated a medially wider intra-articular gap angle and worse Knee Society Score 2011 symptoms (18 vs. 21; p < 0.01), satisfaction (27 vs. 30; p < 0.01), functional activity (55 vs. 65; p < 0.01), and Forgotten Joint Score 12 items (51 vs. 65; p < 0.01) than those in the patients without subjective knee instability. The use of measured resection technique (odds ratio, 2.3; 95% CI, 1.1-4.8; p = 0.02) and the medial laxity of joint gap balance in the flexion position (odds ratio, 1.2; 95% CI, 1.0-1.4; p = 0.04) were detected as risk factors for postoperative subjective knee instability. CONCLUSION: In fixed-bearing PS TKA, intraoperative medial joint laxity in the flexion position was associated with postoperative subjective knee instability, and surgical techniques to achieve sufficient soft tissue balance contributed to improve postoperative subjective clinical outcomes. LEVEL OF EVIDENCE: Ⅲ (case-control study).

Exploring animal protein sources against prevent age-related short-term memory decline in mice: Dietary fish (Alaska Pollock) protein exhibits superior protective effects.

Dietary factors, particularly proteins, have been extensively explored to combat cognitive impairment. We have previously reported that dietary fish (Alaska Pollock) protein (APP) is more effective than casein (CAS) or fish oil in maintaining short-term memory in senescence-accelerated mice prone 10 (SAMP10). To examine the specificity of the protective effect of APP intakes against short-term memory decline, we assessed the impact of various dietary animal proteins, including APP, CAS, chicken breast protein (CP), and whey protein (WP), against age-related cognitive function in SAMP10 mice. After feeding the experimental diets for 5 months, memory was assessed using the Y-maze. The APP group exhibited a significant increase in spontaneous alternation behavior as an indicator of working memory when group compared with groups fed with other protein source. Additionally, the APP group displayed significantly higher neurofilament heavy chain positivity than the CAS and CP groups, as evidenced immunohistochemical analysis. Gut microbiota analysis indicated that dietary APP significantly enhanced the relative abundance of Lactobacillus, which positively correlated with spontaneous alternation behavior. Collectively, these findings suggest that dietary APP is more effective than CAS, CP, or WP in preventing age-related short-term memory decline and morphological abnormalities in the hippocampal axons of SAMP10 mice. Moreover, APP-mediated improvements in cognitive deficits may be associated with changes in microbiota diversity. PRACTICAL APPLICATION: This research suggests that dietary fish protein from Alaska Pollock may be more efficient in prevention short-term memory decline in mice, compared to other animal proteins. This finding has practical implications for nutritional optimization, developing the new health food products, and elucidating the relationship between the impact of specific proteins on gut microbiota and prevention of age-related cognitive decline.

6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3ß inhibitors.

The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.

2-(2-Phenylmorpholin-4-yl)pyrimidin-4(3H)-ones; a new class of potent, selective and orally active glycogen synthase kinase-3ß inhibitors.

A series of 2-(2-phenylmorpholin-4-yl)pyrimidin-4(3H)-ones was synthesized and examined for their inhibitory activity against glycogen synthase kinase-3ß (GSK-3ß). We found 21, 29 and 30 to possess potent in vitro GSK-3ß inhibitory activity with good in vitro PK profiles. 21 demonstrated significant decrease of tau phosphorylation after oral administration in mice and excellent PK profiles.