Characteristics of higher depressive tendency in the patients with olfactory disorder.

OBJECTIVE: Most patients with olfactory dysfunction experience stress and anxiety because of the inconvenience and changes caused by the loss of olfaction. However, psychological assessment is not performed routinely in patients with olfactory dysfunction, and the characteristics of these patients with psychological depression are unclear. METHODS: In this study, we used the Self-rating Depression Scale to evaluate the degree of depression in patients who visited our clinic with olfactory dysfunction and examine the characteristics of these patients with strong depressive tendencies. Patients who visited our clinic between April 2019 and March 2020 with complaints of olfactory dysfunction were included in the study. RESULTS: A total of 180 patients (79 male and 101 female) underwent olfactory examination and completed the Self-rating Depression Scale. Eighty-six and 94 patients were included in the low depression and high depression groups, respectively. Binomial logistic regression analysis showed significant positive associations of Self-rating Depression Scale scores with female sex and the presence of parosmia/phantosmia (p < 0.05). CONCLUSION: In our study, approximately half of the patients with olfactory dysfunction had depressive tendencies especially in female and parosmia/phantosmia patients. We believe that psychological assessments, such as that with the SDS, can help identify patients with olfactory dysfunction who may be at a greater risk of developing depression.

Efficacy of Normalising Serum Zinc Level for Patients with Olfactory Dysfunction and Zinc Deficiency.

INTRODUCTION: Zinc deficiency may worsen the severity of olfactory dysfunction; however, the relationship between serum zinc levels and therapeutic effects on olfactory dysfunction remains uncertain. This study investigated the relationship between normalising serum zinc levels and the therapeutic effects on olfactory dysfunction. METHODS: Forty-two patients diagnosed with post-infectious, post-traumatic, and idiopathic olfactory dysfunction, with serum zinc levels <70 µg/dL, were included in the study. All patients were treated with mecobalamin, tokishakuyakusan, and polaprezinc. The patients were divided into 2 groups: the zinc-normalised (≥70 µg/dL) and zinc-deficient (<70 µg/dL) groups, based on their post-treatment serum zinc levels. Olfactory test results were compared in each of the 2 groups. RESULTS: The patients were treated for a median of 133 days. The zinc-normalised group had significantly better results in all olfactory tests (detection/recognition thresholds of the T&T olfactometer, odour identification test (Open Essence), Visual Analogue Scale for olfactory dysfunction, and self-administered odour questionnaire). In contrast, only the self-administered odour questionnaire showed a significant improvement in the zinc-deficient group, with no significant differences observed in the other olfactory tests. When comparing the changes in the olfactory test scores between the 2 groups, significant differences were observed in the detection/recognition thresholds of the T&T olfactometer test and Open Essence results. CONCLUSION: These findings suggest that patients with olfactory dysfunction may have difficulty improving their olfactory function if they also have zinc deficiency. Furthermore, normalisation of zinc deficiency may contribute to the improvement of olfactory dysfunction with general treatment.

Relationship between the severity of olfactory dysfunction and serum zinc levels.

PURPOSE: Although the association between zinc deficiency and olfactory dysfunction is inconclusive, zinc deficiency causes apoptosis of the olfactory ensheathing cells which is involved in olfactory nerve turnover and axon regeneration, thereby suggesting a possible relationship. We investigated the relationship between serum zinc levels and olfactory function in patients with olfactory dysfunction. METHODS: Ninety patients who had been diagnosed with post-infectious, posttraumatic, drug-induced, neurological and idiopathic olfactory dysfunction were included. Patients were divided into zinc normal group and zinc deficiency groups according to three reference values for serum zinc levels (60, 65, 70 µg/dL). The results of olfactory tests and patient backgrounds were used to compare the differences between the two groups. RESULTS: There were significantly worse detection and recognition thresholds in the T&T olfactometer and Open Essence (odor identification test) results in the zinc deficiency group (< 60 µg/dL). In addition, significant correlations between olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence results) and serum zinc levels < 65 µg/dL were observed. The zinc deficiency group < 70 µg/dL with idiopathic olfactory dysfunction had significantly worse olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence). In addition, there was a significant correlation between the detection/recognition thresholds in the T&T olfactometer and serum zinc levels in idiopathic olfactory dysfunction. CONCLUSIONS: Our findings suggest that zinc deficiency may exacerbate the severity of olfactory dysfunction. Furthermore, idiopathic olfactory dysfunction may be partly caused by zinc deficiency.

Rapid and Robust Multi-Phenotypic Assay System for ALS Using Human iPS Cells with Mutations in Causative Genes.

Amyotrophic lateral sclerosis (ALS) is a major life-threatening disease caused by motor neuron degeneration. More effective treatments through drug discovery are urgently needed. Here, we established an effective high-throughput screening system using induced pluripotent stem cells (iPSCs). Using a Tet-On-dependent transcription factor expression system carried on the PiggyBac vector, motor neurons were efficiently and rapidly generated from iPSCs by a single-step induction method. Induced iPSC transcripts displayed characteristics similar to those of spinal cord neurons. iPSC-generated motor neurons carried a mutation in fused in sarcoma (FUS) and superoxide dismutase 1 (SOD1) genes and had abnormal protein accumulation corresponding to each mutation. Calcium imaging and multiple electrode array (MEA) recordings demonstrated that ALS neurons were abnormally hyperexcitable. Noticeably, protein accumulation and hyperexcitability were ameliorated by treatment with rapamycin (mTOR inhibitor) and retigabine (Kv7 channel activator), respectively. Furthermore, rapamycin suppressed ALS neuronal death and hyperexcitability, suggesting that protein aggregate clearance through the activation of autophagy effectively normalized activity and improved neuronal survival. Our culture system reproduced several ALS phenotypes, including protein accumulation, hyperexcitability, and neuronal death. This rapid and robust phenotypic screening system will likely facilitate the discovery of novel ALS therapeutics and stratified and personalized medicine for sporadic motor neuron diseases.

Novel Platform for Predicting Drug Effects in Patients with Acromegaly: Translational Exposure-Response Evaluation of Growth Hormone-Inhibitory Effect of Octreotide after Growth Hormone-Releasing Hormone Stimulation.

Acromegaly is a chronic systemic disease characterized by facial and peripheral changes caused by soft tissue overgrowth and is associated with multiple comorbidities. Despite available surgical and medical therapies, suitable treatments for acromegaly are still lacking. Efficient drug development requires an understanding of the exposure-response (E-R) relationship based on nonclinical and early clinical studies. We aimed to establish a platform to facilitate the development of novel drugs to treat acromegaly. We evaluated the E-R relationship of the growth hormone (GH)-inhibitory effect of the somatostatin analog octreotide under growth hormone-releasing hormone + arginine stimulation in healthy participants and compared the results with historical data for patients with acromegaly. This randomized five-way crossover study included two placebo and three active-treatment periods with different doses of octreotide acetate. GH secretion in the two placebo periods was comparable, which confirmed the reproducibility of the response with no carryover effect. GH secretion was inhibited by low-, medium-, and high-dose octreotide acetate in a dose-dependent manner. We also examined the E-R relationship in monkeys as a preclinical drug evaluation study and in rats as a more convenient and simple system for screening candidate drugs. The E-R relationships and EC50 values were similar among animals, healthy participants, and patients with acromegaly, which suggests that GH stimulation studies in early research and development allowed simulation of the drug response in patients with acromegaly. SIGNIFICANCE STATEMENT: This study demonstrated similar exposure-response relationships in terms of the growth hormone-inhibitory effect of octreotide after growth hormone-releasing hormone stimulation among healthy participants, monkeys, and rats. The research methods and analyses utilized in this study will be useful for simulating the dosages and therapeutic effects of drugs for acromegaly and will facilitate the research and development of novel therapeutic agents with similar modes of action.

Effect of Care Capacity on Stroke Patients' Recovery in Activities of Daily Living: A Multi-Hospital Study.

BACKGROUND: This study aimed to investigate whether care capacity for patients following stroke contributes to improved activities of daily living (ADL) at discharge from hospital based on the degree of stroke severity. DESIGN: Retrospective, observational, longitudinal study. SETTING: Acute phase hospitals. PARTICIPANTS: From 2005 to 2011, 5006 patients with stroke at acute phase hospitals were registered in a database. There were 2501 individuals from 11 hospitals who met the following four criteria: (1) a pre-stroke modified Rankin Scale (mRS) score of 0-3; (2) admission to hospital within 7 days of suffering a stroke; (3) ischemic or hemorrhagic stroke; and (4) staying in hospital for 8-60 days. MAIN OUTCOME MEASURES: The main outcome measure was the Functional Independence Measure (FIM, version 3.0) score at discharge. The FIM is an internationally used scale, which is used as an ADL outcome assessment scale for after rehabilitation. RESULTS: Among patients with stroke, those with care capacity had higher FIM scores at hospital discharge than did those without care capacity (unstandardized coefficient = 2.3, P = 0.015). Examination of this relationship by stroke severity showed that the FIM score at discharge was only significantly higher in patients who suffered from a moderate to severe stroke (unstandardized coefficient = 7.0, P = 0.040). No associations were observed in patients who suffered from minor, moderate, or severe stroke. CONCLUSIONS: These results suggest that care capacity facilitates total recovery of the FIM, especially among patients who suffer from a moderate to severe stroke.

Encapsulation and Enhanced Luminescence Properties of IrIII Complexes within a Hexameric Self-Assembled Capsule.

Encapsulation and luminescence studies of [Ir(ppy)2 (bpy)]Cl (ppy=2-phenylpyridinate, bpy=2,2'-bipyridine) within a hexameric resorcinarene capsule are reported. One IrIII complex cation was encapsulated within the capsule, as demonstrated by NMR and dynamic light scattering (DLS) studies. The emission color of the IrIII complex was drastically changed from orange to yellow by encapsulation, in contrast with the lack of significant changes in the absorption spectrum. The hexameric capsule effectively hampers the non-radiative pathway to increase both the luminescence quantum yield and the exited state lifetime. The luminescent properties of the encapsulated IrIII complex depend on the ratio of IrIII complex to the resorcinarene monomer as well as the concentration of resorcinarene monomer owing to the reversible process of self-assembly of the hexameric capsule. Quenching experiments revealed that the IrIII complex in the capsule was effectively separated from quenchers.

Intravenous Vitamin B6 Increases Resistance to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: A Randomized Controlled Trial.

OBJECTIVE: Vitamin B6 deficiency is common in hemodialysis patients and may contribute to anemia and abnormal bone metabolism in this population. DESIGN: 6-month, open-label, randomized controlled parallel-group study in hemodialysis centers. SUBJECTS: Fifty-six maintenance hemodialysis patients with relatively high resistance to erythropoiesis-stimulating agents (ESA). INTERVENTION: Intravenous vitamin B6 (60 mg of intravenous pyridoxal 5'-phosphate after each thrice-weekly hemodialysis session). MAIN OUTCOME MEASURE: The primary and secondary outcomes were changes over time in ESA resistance index and bone turnover markers, respectively. RESULTS: The prevalence of vitamin B6 deficiency was 40% overall. Compared with the control group, the B6 group showed an upward change in ESA resistance index over time (Pinteraction = .038). At week 13 (a priori-defined time point), pyridoxal 5'-phosphate administration was associated with higher ESA resistance index by 0.97 (95% confidence interval, 0.02-1.92) ×10-2 µg ⋅darbepoetin-α/kg per g/dL⋅hemoglobin after baseline adjustment, which was not modified by baseline vitamin B6 status. There was a trend toward increase in serum erythropoietin concentrations in the B6 group after adjustment for baseline values, hemoglobin, and weekly ESA dose (Pinteraction = .06). The downward changes of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b in the B6 group relative to the control group were pronounced in patients without vitamin B6 deficiency (Pinteraction < .001 and .017, respectively), despite nonsignificant between-group difference in 1-84 parathyroid hormone. CONCLUSIONS: Thrice-weekly intravenous vitamin B6 (60 mg pyridoxal 5'-phosphate hydrate) worsens the response to ESA and may blunt the response of bone to parathyroid hormone in hemodialysis patients.

The extracellular fragment of GPNMB (Glycoprotein nonmelanosoma protein B, osteoactivin) improves memory and increases hippocampal GluA1 levels in mice.

Glycoprotein nonmelanoma protein B (GPNMB, alias osteoactivin), a type I transmembrane glycoprotein, is cleaved by extracellular proteases, resulting in release of an extracellular fragment (ECF). GPNMB is widely expressed by neurons within the CNS, including the hippocampus; however, its function in the brain remains unknown. Here, we investigated the role of GPNMB in memory and learning by using transgenic (Tg) mice over-expressing GPNMB (Tg mice on a BDF-1 background) and ECF-treated mice. In the hippocampus of both wild-type and Tg mice, GPNMB was highly expressed in neurons and astrocytes. Tg mice exhibited memory improvements in two types of learning tasks but were impaired in a passive-avoidance test. In Tg mice, the hippocampus displayed increased levels of the α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit GluA1. Intracerebroventricular administration of ECF (50 ng) to Institute of Cancer Research (ICR) mice also improved memory in a passive-avoidance test and increased hippocampal GluA1 levels 24 h after treatment. In Tg mice and ECF (0.25 µg/mL)-treated hippocampal slices, long-term potentiation was promoted. These findings suggest that GPNMB may be a novel target for research on higher order brain functions.

Glycoprotein nonmetastatic melanoma protein B ameliorates skeletal muscle lesions in a SOD1G93A mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons and subsequent muscular atrophy. The quality of life of patients with ALS is significantly improved by ameliorating muscular symptoms. We previously reported that glycoprotein nonmetastatic melanoma protein B (GPNMB; osteoactivin) might serve as a target for ALS therapy. In the present study, superoxide dismutase 1/glycine residue 93 changed to alanine (SOD1(G93A) ) transgenic mice were used as a model of ALS. Expression of the C-terminal fragment of GPNMB was increased in the skeletal muscles of SOD1(G93A) mice and patients with sporadic ALS. SOD1(G93A) /GPNMB transgenic mice were generated to determine whether GPNMB expression ameliorates muscular symptoms. The weight and cross-sectional area of the gastrocnemius muscle, number and cross-sectional area of myofibers, and denervation of neuromuscular junctions were ameliorated in SOD1(G93A) /GPNMB vs. SOD1(G93A) mice. Furthermore, direct injection of a GPNMB expression plasmid into the gastrocnemius muscle of SOD1(G93A) mice increased the numbers of myofibers and prevented myofiber atrophy. These findings suggest that GPNMB directly affects skeletal muscle and prevents muscular pathology in SOD1(G93A) mice and may therefore serve as a target for therapy of ALS.

Functional and occupational characteristics predictive of a return to work within 18 months after stroke in Japan: implications for rehabilitation.

OBJECTIVE: This study examined clinical, functional, and occupational factors associated with return to work within 18 months after stroke, specifically focusing on the impact of higher cortical dysfunction on return to work in the chronic phase. METHODS: This prospective cohort study in 21 hospitals specializing in clinical and occupational health recruited consecutive working-age inpatients receiving acute care for their first stroke (n = 351). A unified database was used to extract patient information from hospital records at the time of admission, discharge, and follow-up at 18 months post-stroke. Cox proportional hazard regression analysis was conducted to determine clinical, functional, and occupational factors influencing return to work within 18 months. RESULTS: Of 351 registered stroke patients (280 males, 71 females, mean age ± SD, 55.3 ± 7.2 years) who met inclusion criteria, 250 responded to the follow-up survey and 101 were lost to follow-up. Half (51%) succeeded in returning to work during the 18-month follow-up after stroke onset. After adjusting for age, gender, and Barthel index at initial rehabilitation, the following factors were identified as significant predictors of a return to work: white-collar versus blue-collar occupation (hazard ratio (HR) 1.5; 95% confidence interval (CI) 1.1-2.2), no aphasia (HR 3.0; 95% CI 1.5-5.9), no attention dysfunction (HR 2.0; 95% CI 1.0-4.0), and walking ability (HR 3.1; 95% CI 1.3-7.1). CONCLUSIONS: This study indicated the importance of tailored rehabilitation to alleviate the impact of higher cortical dysfunction and to support return to work by stroke survivors.

On-off system for PI3-kinase-Akt signaling through S-nitrosylation of phosphatase with sequence homology to tensin (PTEN).

Nitric oxide (NO) physiologically regulates numerous cellular responses through S-nitrosylation of protein cysteine residues. We performed antibody-array screening in conjunction with biotin-switch assays to look for S-nitrosylated proteins. Using this combination of techniques, we found that phosphatase with sequence homology to tensin (PTEN) is selectively S-nitrosylated by low concentrations of NO at a specific cysteine residue (Cys-83). S-nitrosylation of PTEN (forming SNO-PTEN) inhibits enzymatic activity and consequently stimulates the downstream Akt cascade, indicating that Cys-83 is a critical site for redox regulation of PTEN function. In ischemic mouse brain, we observed SNO-PTEN in the core and penumbra regions but found SNO-Akt, which is known to inhibit Akt activity, only in the ischemic core. These findings suggest that low concentrations of NO, as found in the penumbra, preferentially S-nitrosylate PTEN, whereas higher concentrations of NO, known to exist in the ischemic core, also S-nitrosylate Akt. In the penumbra, inhibition of PTEN (but not Akt) activity by S-nitrosylation would be expected to contribute to cell survival by means of enhanced Akt signaling. In contrast, in the ischemic core, SNO-Akt formation would inhibit this neuroprotective pathway. In vitro model systems support this notion. Thus, we identify unique sites of PTEN and Akt regulation by means of S-nitrosylation, resulting in an "on-off" pattern of control of Akt signaling.

Difference in the Dynamics of Antibody Titers between COVID-19 Vaccination and SARS-CoV-2 Infection in Healthcare Workers - A Case Study Based on Long-Term and Densely Repeated Measurements of Antibody Titers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1-2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4-8 weeks after infection, and the antibody titer remained elevated up to 16-40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.

A sigma-1 receptor antagonist (NE-100) prevents tunicamycin-induced cell death via GRP78 induction in hippocampal cells.

Endoplasmic reticulum (ER) stress is involved in various diseases such as ischemia, Alzheimer's disease, and Parkinson's disease. The widely used selective sigma-1 receptor antagonist, N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine monohydrochloride (NE-100), has been shown to suppress ischemia-induced neuronal cell death in the murine hippocampus. In the present study, we investigated whether NE-100 might suppress neuronal cell death that is induced by ER stress in ischemic injury. These studies show that NE-100 protected the ER stress-induced cell death of murine hippocampal HT22 cells, but not the oxidative stress-induced cell death. This suggests that NE-100 may have a protective effect on the ER. However, another sigma-1 receptor antagonist (BD1047) did not suppress ER stress-induced cell death. In addition, NE-100 attenuated the upregulation of C/EBP homologous protein (CHOP) induced by ER stress and upregulated the expression of both the 50-kDa activating transcription factor 6 (p50ATF6) and the 78-kDa glucose-regulated protein (GRP78). However, NE-100 did not impact the expression of phosphorylated eukaryotic initiation factor 2α (p-eIF2α) nor splicing of X-box-binding protein 1 (XBP-1). These findings suggest that NE-100 suppresses ER stress-induced cell death via CHOP expression by the upregulation of GRP78 through ATF6 pathway, independent sigma-1 receptor antagonist effect.

Discrimination of mammalian GPI-anchored proteins by hydropathy and amino acid propensities.

The glycosylphosphatidylinositol (GPI) attachment is a most important post-translational modification of proteins that plays essential roles in promoting the biochemical activities of eukaryotic cells. Described here is an analysis of the amino acid properties of mammalian GPI-anchored proteins (GPI-APs) and the development of an innovative method of detecting them. GPI-APs are characterized by two high-hydropathy regions: the signal peptide, located inside the Endoplasmic Reticulum (ER), and the GPI attachment signal, a sequence adjacent to the GPI-anchoring site (the ω-site). Especially in sequence analysis of known GPI-APs, there were some distinct aspects of the amino acid propensities around the ω-sites. Therefore, a method of detecting GPI-APs was developed based on hydropathy profiles and a position-specific scoring matrix (PSSM) calculated by position-specific amino acid propensities. First, sequences of GPI-APs and negative controls, determined by screening based on hydropathy and residue volume profiles, were aligned based on residue volume profiles in the C-terminal region, and the position-specific amino acid propensities of each group were calculated according to their alignment positions. Then, a PSSM was devised using the amino acid propensities of GPI-APs and negative controls, and discrimination scores were estimated for each dataset. Based on these scores at a threshold was fixed for each dataset. GPI-APs were detected with 81.1% sensitivity and a 0.818 success rate in an optimized calculation region determined by adjusting the window size of this region using a 5-fold dataset. The results indicate that a PSSM around the ω-site can effectively discriminate GPI-APs.

Two new species of Eriococcidae (Hemiptera: Coccomorpha) in Japan.

Two new felt scale species (Hemiptera: Coccomorpha: Eriococcidae) collected in Japan, Acanthococcus torikurai Tanaka sp. nov. and Anophococcus koguchii Tanaka sp. nov., are described and illustrated based on the morphological characteristics of the adult females. Acanthococcus torikurai is similar to A. spiraeae Borchsenius 1949 but lacks small pores on hind legs, spinulae on the meso- and metathoracic coxae, a cauda on abdominal segment VIII and capitate ventral setae. Anophococcus koguchii is similar to An. socialis (Goux 1931) but differs in having seven-segmented antennae, two different sizes of macrotubular ducts on the venter, multilocular pores mostly with five loculi rather than seven or eight, and in lacking large pores on the metathoracic coxae and a cauda on abdominal segment VIII. A key to the 17 Eriococcidae species found in Japan is also provided.

Characteristics of Extranodal NK/T-Cell Lymphoma, Nasal Type, Compared with Nasal Diffuse Large B-cell Lymphoma.

Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL), is an aggressive tumour with poor prognosis. Its early diagnosis may improve the prognosis of patients; however, it is often overlooked in many cases and misdiagnosed as an inflammatory sinus disease during its initial stage. Identifying the clinical characteristics of ENKL may aid otorhinolaryngologists in indicating cases early for a pathologic examination. In this study, we aimed to investigate the clinical characteristics of ENKL compared with that of diffuse large B-cell lymphoma (DLBCL), which is the most common nasal malignant lymphoma. Methods: The backgrounds, clinical symptoms, blood test results, and computed tomography images of patients with nasal/paranasal malignant lymphoma in our hospital between 2012 and 2017 were investigated. The characteristics of ENKL and nasal DLBCL were compared to differentiate them. Results: A total of 27 patients with nasal cavity and/or paranasal sinus lymphoma were included. Extranodal NK/T-cell lymphoma, nasal type, was diagnosed in 10 patients, while DLBCL was diagnosed in 17 patients. The median age of patients with ENKL was significantly lower than that of patients with DLBCL. All patients with ENKL had a unilateral lesion in the nasal cavity, with most located at the inferior turbinate. They also experienced nasal symptoms with significantly higher incidence of nasal obstruction and tendency of bleeding. Conclusion: ENKL was often unilateral and caused nasal obstruction, unlike DLBCL. Those who are younger in age and have sinonasal tumour with unilateral nasal obstruction and bleeding should be considered for early and repeated biopsies at multiple sites, with ENKL taken into consideration.

Impact of energy intake on the activities of daily living in patients with cervical spinal cord injury undergoing post-acute rehabilitation.

OBJECTIVE: To investigate the association between sufficient energy intake and improvement in activities of daily living (ADL) after hospitalization in patients with cervical spinal cord injury (CSCI) undergoing post-acute rehabilitation. DESIGN: Retrospective cohort study. SETTING: Post-acute care hospital from September 2013 to December 2020. PARTICIPANTS: Patients with CSCI admitted to a post-acute care hospital for rehabilitation. INTERVENTION: Not applicable. OUTCOME MEASURE(S): Multiple regression analysis was performed to investigate the relationship of sufficient energy intake to Motor Functional Independence Measure (mFIM) gain, mFIM score at discharge, and body weight change during hospitalization. RESULTS: In total, 116 patients (104 men and 12 women), median age: 55 (interquartile range [IQR] 41-65) years were included in the analysis. Then, 68 (58.6%) were in the energy-sufficient group, and 48 (41.4%) patients were classified under the energy-deficient group. The two groups did not significantly differ in terms of mFIM gain and mFIM score at discharge. The energy-sufficient group maintained body weight change during hospitalization than the energy-deficient group (0.6 [-2.0-2.0] vs. -1.9 [-4.0--0.3], P < 0.001). Multiple regression analysis showed no association between sufficient energy intake and outcomes. CONCLUSION: Sufficient energy intake within the first 3 days of admission did not affect ADL improvement during hospitalization in patients with a post-cute CSCI undergoing rehabilitation.

Symmetry-breaking host-guest assembly in a hydrogen-bonded supramolecular system.

Bio-inspired self-assembly is invaluable to create well-defined giant structures from small molecular units. Owing to a large entropy loss in the self-assembly process, highly symmetric structures are typically obtained as thermodynamic products while formation of low symmetric assemblies is still challenging. In this study, we report the symmetry-breaking self-assembly of a defined C1-symmetric supramolecular structure from an Oh-symmetric hydrogen-bonded resorcin[4]arene capsule and C2-symmetric cationic bis-cyclometalated Ir complexes, carrying sterically demanding tertiary butyl (tBu) groups, on the basis of synergistic effects of weak binding forces. The flexible capsule framework shows a large structural change upon guest binding to form a distorted resorcin[4]arene hexameric capsule, providing an asymmetric cavity. Location of the chiral guest inside the anisotropic environment leads to modulation of its Electric Dipole (ED) and Magnetic Dipole (MD) transition moments in the excited state, causing an increased emission quantum yield, longer emission lifetime, and enhancement of the dissymmetry factor (glum) in the circularly polarized luminescence.

Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia.

INTRODUCTION: Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI. METHODS: This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ). RESULTS: Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD). CONCLUSION: Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03901352.