Risk factors and prognosis for supraclavicular lymph node metastasis in patients with thoracic esophageal cancer. Distant or regional metastasis?

We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs. The efficacy index (EI), calculated from the frequency of LN metastases and survival rates, was used as prognostic value of each LN station dissection for patient survival. Risk factors for #104 LN metastasis were determined by multivariable logistic regression. The frequency of #104 LN metastasis was 11.6% overall, 31.7% in upper and 8.3% in middle/lower third lesion. Neoadjuvant chemotherapy was administered to 71% of patients and chemo-radiation to 11%. The 5-year overall survival was 45.8%. The EI for #104 LNs (5.3) was similar to that for #101 LNs. Risk factors were age < 65 years, upper third lesion, clinical N2-3, #101/106rec LN metastasis and poorly differentiated carcinoma. The 5-year overall survival of patients with middle/lower lesions was 38% (EI 3.1), similar to that for #101 and #8/9/11 LNs. The prognosis of patients with #104 LN metastases is similar to that of patients with metastases in other regional LN stations. Therefore, we recommend 3FL exclusively for patients at a high risk of #104 LN metastasis due to the overall metastatic rate not being high.

Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery : A Retrospective Cohort Study.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

Neurotensin induces sustainable activation of the ErbB-ERK1/2 pathway, which is required for developmental competence of oocytes in mice.

Purpose: LH induces the expression of EGF-like factors and their shedding enzyme (ADAM17) in granulosa cells (GCs), which is essential for ovulation via activation of the ErbB-ERK1/2 pathway in cumulus cells (CCs). Neurotensin (NTS) is reported as a novel regulator of ovulation, whereas the NTS-induced maturation mechanism in oocytes remains unclear. In this study, we focused on the role of NTS in the expression of EGF-like factors and ErbBs, and ADAM17 activity, during oocyte maturation and ovulation in mice. Methods: The expression and localization in GC and CC were examined. Next, hCG and NTS receptor 1 antagonist (SR) were injected into eCG-primed mice, and the effects of SR on ERK1/2 phosphorylation were investigated. Finally, we explored the effects of SR on the expression of EGF-like factors and ErbBs, and ADAM17 activity in GC and CC. Results: NTS was significantly upregulated in GC and CC following hCG injection. SR injection suppressed oocyte maturation and ERK1/2 phosphorylation. SR also downregulated part of the expression of EGF-like factors and their receptors, and ADAM17 activity. Conclusions: NTS induces oocyte maturation through the sustainable activation of the ERK1/2 signaling pathway by upregulating part of the EGF-like factor-induced pathway during oocyte maturation in mice.

Surgical tips and tricks for laparoscopic intragastric surgery for submucosal tumors relative to the esophagogastric junction.

Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ. Fourteen patients with gastric SMTs < 2 cm of the EGJ and underwent l-IGS were eligible for this study. We examined the tumor location, operative time, intraoperative hemorrhage, degree of deformation, gastroesophageal reflux disease, perioperative complications, and recurrence. Furthermore, we compared patients with tumors in the EGJ with those with tumors near the EGJ and patients in whom three-port l-IGS was performed with those who underwent single-incision laparoscopic surgery. The average tumor size, operative time, intraoperative hemorrhage, and postoperative hospitalization of the 14 patients were 30.9 ± 21.3 mm, 125.2 ± 31.1 min, 30.7 ± 103.3 mL, and 9.2 ± 3.1 d, respectively. No differences in these parameters according to the type of l-IGS or tumor location were observed. All patients underwent l-IGS without complications and were free from EGJ deformation or esophagitis. We believe that l-IGS is useful for gastric SMTs located < 2 cm of the EGJ as it can be safely performed for difficult tumor locations and does not cause deformation of the EGJ.

Pre-culture with transferrin-Fe3+ before in vitro maturation improves the developmental competence of porcine oocytes matured in vitro.

Purpose: Since the developmental competence of oocytes cultured after in vitro maturation (IVM) is low, it is necessary to improve the IVM method for efficient offspring production. In this study, we revealed that transferrin (TF)-Fe3+ was accumulated in follicular fluid with increasing the follicular diameter, and that TF receptor (TFR1) was localized in granulosa cells of pig. Thus, we hypothesized that TF-Fe3+ would be a factor in the induction of developmental competence of porcine oocytes. Methods: To mimic the follicular development environment, cumulus-oocyte complexes (COCs) were cultured in pre-IVM medium (low dose of FSH) without or with Holo-TF (monoferric or diferric TF) or Apo-TF (non-iron bond TF). After pre-IVM without or with Holo-TF, COCs were cultured in IVM medium (high dose of FSH and EGF) without or with Holo-TF. Results: Cultivation with Holo-TF increased the expression of follicular development maker (Cyp19a1 and Ccnd2), E2 production, and proliferative activity of cumulus cells, whereas cultivation with Apo-TF did not show these positive effects. The treatment with Holo-TF during pre-IVM, but not during IVM, dramatically induced oocyte maturation with increasing the blastocyst rate. Conclusion: We succeeded in showing for the first time that the cultivation with Holo-TF in pre-IVM can produce embryos in pig with high efficiency.

Efficacy of palliative surgery for gastric cancer patients with peritoneal metastasis who still have residual peritoneal dissemination after chemotherapy.

PURPOSE: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy. The purpose of this study was to investigate the efficacy of palliative surgery for gastric cancer patients with PM who still have residual peritoneal dissemination after chemotherapy. METHODS: Twenty-five gastric cancer patients with PM confirmed by laparoscopy and who had received chemotherapy but who still had residual PM were included in this study. Among the 25 patients, palliative surgery was performed in 20 patients (PS group) and chemotherapy was continued in 5 patients (CTx group), and their therapeutic outcomes were compared. RESULTS: In the PS group, total and distal gastrectomies were performed. Clavien-Dindo grade I postoperative complications occurred in two patients (10%). There were no treatment-related deaths. Postoperative chemotherapy was performed all cases. In the PS group, the median survival time (MST) reached 22.5 months, with 1- and 2-year overall survival (OS) rates of 95% and 45%, respectively, whereas in the CTx group, the MST was 15.8 months, and the 1- and 2-year OS rates were 60% and 0%, respectively. The PS group had significantly longer OS than the CTx group (P=0.044). CONCLUSIONS: Palliative surgery is safe and may prolong survival in gastric cancer patients with residual PM after chemotherapy.

Lipopolysaccharide (LPS) suppresses follicle development marker expression and enhances cytokine expressions, which results in fail to granulosa cell proliferation in developing follicle in cows.

Postpartum endometritis is known to be associated with ovarian dysfunction in cows. Lipopolysaccharide (LPS) generated by Gram-negative bacteria is recognized by toll-like receptor 4 (TLR4), which leads to an inflammatory response by the generation of cytokines such as tumor necrosis factor-α (TNF-α) and interleukins. In this study, we investigated the effect of endometrial LPS on granulosa cell functions during early follicular development in cows. Uteri and follicles were obtained from a slaughterhouse and classified into either clinical endometritis (CE) or normal groups by vaginal mucus test. TLR4 mRNA and protein in normal cows were expressed in granulosa cells collected from follicles measuring 1-3 and 4-7 mm in a diameter, respectively. LPS content in endometrium and follicular fluid of CE cows was significantly higher than that in normal cows. Compared to normal cows, CE cows showed lower expression of follicular development markers (FSHR, CYP19A1, CCND2, and LHCGR) in granulosa cells, lower estradiol-17ß concentrations in follicular fluid, and lower granulosa cell proliferation. CE contraction significantly increased cytokine expressions (TNF, IL-1A, and IL-1B) in granulosa cells and suppressed apoptosis of granulosa cells compared to normal cows. LPS significantly suppressed the expression of follicular development markers and the production of estradiol-17ß in granulosa cells and reduced granulosa cells proliferation compared to cells cultured without LPS. LPS significantly increased cytokine expressions and suppressed granulosa cell apoptosis. Thus, the present results suggest that the existence of LPS in developing follicles is one of the causes of ovarian quiescence in cows.

Para-Sports can Promote Functional Reorganization in the Ipsilateral Primary Motor Cortex of Lower Limbs Amputee.

Background. Drastic functional reorganization was observed in the ipsilateral primary motor cortex (M1) of a Paralympic long jumper with a unilateral below-knee amputation in our previous study. However, it remains unclear whether long-term para-sports are associated with ipsilateral M1 reorganization since only 1 athlete with amputation was investigated. Objective. This study aimed to investigate the relationship between the long-term para-sports and ipsilateral M1 reorganization after lower limb amputation. Methods. Lower limb rhythmic muscle contraction tasks with functional magnetic resonance imaging and T1-weighted structural imaging were performed in 30 lower limb amputees with different para-sports experiences in the chronic phase. Results. Brain activity in the ipsilateral primary motor and somatosensory areas (SM1) as well as the contralateral dorsolateral prefrontal cortex, SM1, and inferior temporal gyrus showed a positive correlation with the years of routine para-sports participation (sports years) during contraction of the amputated knee. Indeed, twelve of the 30 participants who exhibited significant ipsilateral M1 activation during amputated knee contraction had a relatively longer history of para-sports participation. No significant correlation was found in the structural analysis. Conclusions. Long-term para-sports could lead to extensive reorganization at the brain network level, not only bilateral M1 reorganization but also reorganization of the frontal lobe and visual pathways. These results suggest that the interaction of injury-induced and use-dependent cortical plasticity might bring about drastic reorganization in lower limb amputees.

Cortical Re-organization After Traumatic Brain Injury Elicited Using Functional Electrical Stimulation Therapy: A Case Report.

Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up. In total, 36 sessions of FEST were applied to enable upper-limb grasping and reaching movements. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), indicating cortical and/or subcortical inhibition after each intervention. At the same time, no changes in motor evoked potentials (MEPs) were observed. Long-term assessments showed increased MEP corticospinal excitability after 12-weeks of FEST, which seemed to remain during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, functional magnetic resonance imaging (fMRI) data showed M1 activations increased during hand grip and finger pinch tasks after 12-weeks of FEST, while gradual reduction of activity compared to after the intervention was seen during follow-ups. Widespread changes were seen not only in the M1, but also sensory, parietal rostroventral, supplementary motor, and premotor areas in both contralateral and ipsilateral hemispheres, especially during the finger pinch task. Drawing test performance showed improvements after the intervention and during follow-ups. Our findings suggest that task-specific and repetitive FEST can effectively increase cortical activations by integrating voluntary motor commands and sensorimotor network through functional electrical stimulation (FES). Overall, our results demonstrated cortical re-organization in an individual with chronic TBI after FEST.

Insights of neurophysiology on unconscious state using combined transcranial magnetic stimulation and electroencephalography: A systematic review.

Unconscious state has been investigated in numerous studies so far, but pathophysiology of this state is not fully understood. Recently, combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been developed to allow for non-invasive assessment of neurophysiology in the cerebral cortex. We conducted a systematic literature search for TMS-EEG studies on human unconscious state using PubMed with cross-reference and manual searches. The initial search yielded 137 articles, and 19 of them were identified as relevant, including one article found by manual search. This review included 10 studies for unresponsive wakefulness syndrome (UWS), 9 for minimally conscious states (MCS), 5 for medication-induced unconscious states, and 6 for natural non-rapid eye movement states. These studies analyzed TMS-evoked potential to calculate perturbational complexity index (PCI) and OFF-periods. In particular, PCI was found to be a potentially useful marker to differentiate between UWS and MCS. This review demonstrated that TMS-EEG could represent a promising neuroscientific tool to investigate various unconscious states. Further TMS-EEG research may help elucidate the neural basis of unconscious state.

LH Induces De Novo Cholesterol Biosynthesis via SREBP Activation in Granulosa Cells During Ovulation in Female Mice.

In the liver, the sterol response element binding protein (SREBP) and the SREBP cleavage-activated protein (SCAP) complex upregulate cholesterol biosynthesis by gene induction of de novo cholesterol synthetic enzymes (Hmgcr, Cyp51, and Dhcr7). Insulin induced gene 1 (INSIG1) negatively regulates cholesterol biosynthesis by the inhibition of de novo cholesterol biosynthetic gene expression. In the ovary, cholesterol is de novo synthesized; however, the roles of SREBP and its regulators (SCAP and INSIG1) are not well understood. In this study, when immature mice were treated with gonadotropins (eCG followed by hCG), eCG induced and hCG maintained the expression of SREBP-1a, -2, and SCAP granulosa cells, whereas INSIG1 expression was dramatically downregulated after hCG injection. Downregulation of INSIG1 led to generate the SREBPs active form and translocate the SREBPs active form to nuclei. Inhibition of generation of the SREBPs active form by fatostatin or Scap siRNA in both in vivo and in vitro significantly decreased the expressions of de novo cholesterol biosynthetic enzymes, cholesterol accumulation, and progesterone (P4) production compared with the control group. Fatostatin treatment inhibited the ovulation and increased the formation of abnormal corpus luteum which trapped the matured oocyte in the corpus luteum; however, the phenomenon was abolished by P4 administration. The results showed that decreasing INSIG1 level after hCG stimulation activated SREBP-induced de novo cholesterol biosynthesis in granulosa cells of preovulatory follicles, which is essential for P4 production and the rupture of matured oocyte during ovulation process.

Cortisol induces follicle regression, while FSH prevents cortisol-induced follicle regression in pigs.

During follicular development, a few dominant follicles develop to large antral dominant follicles, whereas the remaining follicles undergo atretic degeneration. Because vascularization on the follicular surface is a morphological feature of dominant follicles, we previously classified these follicles as vascularized follicles (VFs) and non-VFs (NVFs). In NVFs, progesterone producing genes were expressed similarly to that in VFs; however, the progesterone concentration in follicular fluid was low in large NVFs. Therefore, we estimated that progesterone is converted to cortisol, which induces the loss of follicular functions. In this study, we comparative analyzed the expression of genes for progesterone converting enzymes (Cytochrome (CYP)11B1, CYP21A2, Hydroxysteroid (HSD)11B2) and cortisol receptor (NR3C1) in VF and NVF granulosa cells. In NVFs, expression of cortisol producing genes (CYP11B1 and CYP21A2) was higher than in VFs. Expression of the gene for the cortisol metabolizing enzyme HSD11B2 in NVFs was significantly lower than in VFs. In NVFs, accompanied by increasing cortisol concentration in follicular fluid, apoptosis of granulosa and cumulus cells was observed. Cultivation with FSH and metyrapone (a CYP11B1 inhibitor) of NVF cumulus-oocyte complexes inhibited apoptosis of cumulus cells and induced cumulus cell proliferation and oocyte maturation. Cortisol-induced CYP11B1 and CYP21A2 expression, whereas FSH-induced HSD11B2 mRNA expression in VF granulosa cells in the presence of cortisol. Furthermore, an addition of 18ß-glycyrrhetinic acid (18-GA; a HSD17B2 inhibitor) to cortisol and FSH-containing medium increased apoptosis of VF granulosa cells. These results suggested that cortisol is a stimulatory factor that induces follicular atresia; furthermore, inhibition of cortisol production by FSH might increase the number of healthy preovulatory follicles in pigs.

Specific Brain Reorganization Underlying Superior Upper Limb Motor Function After Spinal Cord Injury: A Multimodal MRI Study.

BACKGROUND: We recently discovered that individuals with complete spinal cord injury (SCI) have a higher grip force control ability in their intact upper limbs than able-bodied subjects. However, the neural basis for this phenomenon is unknown. OBJECTIVE: This study aimed to investigate the neural basis of the higher grip force control in the brains of individuals with SCI using multimodal magnetic resonance imaging (MRI). METHODS: Eight SCI subjects and 10 able-bodied subjects performed hand grip force control tasks at 10%, 20%, and 30% of their maximal voluntary contraction during functional MRI (fMRI). Resting-state fMRI and T1-weighted structural images were obtained to investigate changes in brain networks and structures after SCI. RESULTS: SCI subjects showed higher grip force steadiness than able-bodied subjects (P < .05, corrected), smaller activation in the primary motor cortex (P < .05, corrected), and deactivation of the visual cortex (P < .001, uncorrected). Furthermore, SCI subjects had stronger functional connectivity between the superior parietal lobule and the left primary motor cortex (P < .001, uncorrected), as well as larger gray matter volume in the bilateral superior parietal lobule (P < .001, uncorrected). CONCLUSIONS: The structural and functional reorganization observed in the superior parietal lobule of SCI subjects may represent the neural basis underlying the observed higher grip force control, and is likely responsible for the smaller activation in the primary motor cortex observed in these individuals. These findings could have applications in the fields of neurorehabilitation for improvement of intact limb functions after SCI.

Methyl-beta cyclodextrin and creatine work synergistically under hypoxic conditions to improve the fertilization ability of boar ejaculated sperm.

Although successful fertilization is completed by only 150 sperm in the pig oviduct, more than 50,000 sperms are required to achieve a fertilization rate of more than 70% by pig in vitro fertilization (IVF). In this study, to improve the efficiency of pig IVF, the effects of hypoxic conditions and treatment with creatine and methyl-beta cyclodextrin (MßCD) on the glycolytic pathway were investigated. Under low O2 conditions, zig-zag motility was strongly induced within 30 min; however, the induction disappeared at 60 min. Although caffeine suppressed zig-zag motility under low O2 conditions, creatine induced and sustained zig-zag motility until 120 min. Additionally, pretreatment with MßCD for 15 min greatly enhanced zig-zag motility via ATP production in sperm incubated with creatine under low O2 conditions. Sperm pretreated with MßCD were used for IVF in medium containing creatine under low O2 conditions. A fertilization rate of approximately 70% was achieved with only 1.0 x 104 sperms/mL, and there were few polyspermic embryos. Therefore, our novel method was beneficial for efficient production of pig embryos in vitro. Moreover, the zig-zag motility may be a novel movement which boar capacitated sperm exhibit in the culture medium.

Iron deficiency induces female infertile in order to failure of follicular development in mice.

Iron is important for many cellular functions, including ATP synthesis and cell proliferation. Insufficient of iron in the diet causes iron deficiency anemia (IDA), which often occurs in people living in the world. Since 50% of women with IDA show amenorrhea, the relationship of between iron deficiency and reproductive function was assessed using mice fed a low Fe diet (LFD). The estrous cycle in the LFD mice was blocked at diestrus, which impair follicle development, and fertility. Further, even LFD mice were injected with exogenous pregnant mare serum gonadotropin (PMSG), follicular development was ceased at the secondary follicle stage, and preovulatory follicles were not observed. Amount of ATP decreased in the ovary of the LFD mice, and expression of follicle development markers (Fshr, Cyp19a1, Ccnd2) and estradiol-17ß (E2) was low level compared to levels mice fed a normal diet. Feeding a normal diet with sufficient iron to the LFD mice for an additional 3 weeks completely reversed absence the effects of iron insufficient on the estrous cycle and infertility. Thus, iron restriction depresses ovary functions, especially follicular development from secondary follicle to antral follicles and infertility. These effects are fully reversible by supplementation of a normal diet containing iron.

Cortical reorganization of lower-limb motor representations in an elite archery athlete with congenital amputation of both arms.

Despite their disabilities, top Paralympic athletes have better motor skills than able-bodied athletes. However, the neural underpinnings of these better motor skills remain unclear. We investigated the reorganization of the primary motor cortex (M1) in a Paralympic athlete with congenital amputation of both arms who holds the world record for the farthest accurate shot in archery (Amputee Archer: AA). We recorded brain activity during contraction of right toe, ankle, knee, and hip joint muscles in the AA and 12 able-bodied control subjects using functional magnetic resonance imaging. The results revealed that M1 activation was more widespread in the AA compared with control subjects during all tasks, and shifted towards the lateral part of the M1 during contraction of toe and knee muscles. We also conducted a motor mapping experiment using navigated transcranial magnetic stimulation. The M1 area receiving stimulation elicited motor-evoked potentials from the toe, lower-leg, and thigh muscles, which were larger in the AA compared with 12 control subjects. Furthermore, the AA's motor maps were shifted towards the lateral side of M1. These results suggest an expansion of lower-limb M1 representation towards the lateral side of M1, including the trunk and upper-limb representations, and an expansion of the area of corticomotor neurons innervating the lower limb muscles in the AA. This unique M1 reorganization could underpin the AA's excellent archery performance in the absence of upper limbs. The current results suggest that Paralympic athletes may exhibit extreme M1 plasticity, which could arise through a combination of rigorous long-term motor training and compensatory M1 reorganization for missing body parts.

Remarkable hand grip steadiness in individuals with complete spinal cord injury.

Although no damage occurs in the brains of individuals with spinal cord injury, structural and functional reorganization occurs in the sensorimotor cortex because of the deafferentation of afferent signal input from below the injury level. This brain reorganization that is specific to individuals with spinal cord injury is speculated to contribute to the improvement of the motor function of the remaining upper limbs. However, no study has investigated in detail the motor function above the injury level. To clarify this, we designed an experiment using the handgrip force steadiness task, which is a popular technique for evaluating motor function as the index of the variability of common synaptic input to motoneurons. Fourteen complete spinal cord injury (cSCI) individuals in the chronic phase, fifteen individuals with lower limb disabilities, and twelve healthy controls participated in the study. We clarified that the force steadiness in the cSCI group was significantly higher than that in the control groups, and that sports years were significantly correlated with this steadiness. Furthermore, multiple analyses revealed that force steadiness was significantly predicted by sports years. These results suggest that brain reorganization after spinal cord injury can functionally affect the remaining upper limb motor function. These findings may have implications in the clinical rehabilitation field, such as occupational rehabilitation of the upper limbs. They also indicate that individuals with complete spinal cord injury, based on their enhanced force adjustment skills, would excel at fine motor tasks such as manufacturing and handicrafts.

Alternating Sequence Control for Carboxylic Acid and Hydroxy Pendant Groups by Controlled Radical Cyclopolymerization of a Divinyl Monomer Carrying a Cleavable Spacer.

By utilizing features of the hemiacetal ester (HAE) bond: easy formation from vinyl ether and carboxylic acid and easy cleavage into different functional groups (-COOH and -OH), we achieved control of the alternating sequence of two functional pendant groups of a vinyl copolymer. Methacrylate- and acrylate-based vinyl groups were connected through HAE bonds to prepare a cleavable divinyl monomer, which was cyclo-polymerized under optimized conditions in a ruthenium-catalyzed living radical polymerization. Subsequent cleavage of the HAE bonds in the resultant cyclo-pendant led to a copolymer consisting of alternating methacrylic acid and 2-hydroxyethyl acrylate units as analyzed by 13 C NMR spectroscopy. The alternating sequence of -COOH and -OH pendants specifically provided a lower critical solution temperature (LCST) in an ether solvent, which was not observed with the random copolymer of same composition ratio.

Iterative Radical Addition with a Special Monomer Carrying Bulky and Convertible Pendant: A New Concept toward Controlling the Sequence for Vinyl Polymers.

Herein we propose a new concept to control sequence for vinyl polymers. A tertiary alkyl methacrylate monomer carrying both adamantyl and isopropyl groups (IPAMA) is very unique to allow control of single unit addition with an alkyl halide initiator for metal-catalyzed living radical polymerization due to the exceptional bulkiness. After control of the single unit addition, the bulkiness can be removed via acidolysis to further convert into the ester pendant with less bulky and nontertiary alcohol. The resultant adduct can be used as an initiator for the next single unit addition of IPAMA and the terminal ester can be selectively hydrolyzed followed by esterification similar to the first process. Namely, the cycle consisting of "radical addition of IPAMA", "acidolysis of the IPAMA side group", and "esterification of resultant carboxylic acid" can be repeated to construct sequence well-defined poly(oligo-)methacrylates. In this letter, results of the cycle and the iterative process with the special methacrylate monomer are actually demonstrated as well as the scope of applicable alcohols for the esterification process toward sequence control with functional units.