Effectiveness of telerehabilitation based on real-time intervention between therapist and participants for improving physical function, activities of daily living and quality of life in people with stroke: A systematic review protocol.

BACKGROUND: There is a call for gathering more evidence on the effectiveness of telerehabilitation in stroke. In particular, a previous systematic review reported substantial variability in the types of technologies used in telerehabilitation interventions. The purpose of this study will be to summarize and synthesize findings on the effects of telerehabilitation based on real-time intervention between therapist and participants for patients with stroke. METHODS AND ANALYSIS: This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. This systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 25 May 2023 (registration number: CRD420234265527). Electronic searches will be performed in the following databases: MEDLINE, Pubmed, Web of Science, PsycINFO and CINAHL electronic databases, using a date range from inception to November 2023. We will include only randomized controlled trials for patients diagnosed with stroke who received telerehabilitation based on real-time interaction between therapist and patients. The exploration will be restricted to publications in the English language. Physical function, activities of daily living and quality of life are the outcomes. We will examine the changes of the outcomes at baseline, at the end of the intervention, and at specific time points during the follow-up after the intervention. DISCUSSION: This systematic review will provide evidence regarding telerehabilitation for people with stroke.

Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats.

Introduction: Within the realm of chemogenetics, a particular form of agonists targeting designer receptors exclusively activated by designer drugs (DREADDs) has emerged. Deschloroclozapine (DCZ), a recently introduced DREADDs agonist, demonstrates remarkable potency in activating targeted neurons at a lower dosage compared to clozapine-N-oxide (CNO). Methods: We conducted a comparative analysis of the effects of subcutaneously administered CNO (1 mg/kg) and DCZ (0.1 mg/kg) in our transgenic rats expressing hM3Dq and mCherry exclusively in oxytocin (OXT) neurons. Results and Discussion: Notably, DCZ exhibited a swift and robust elevation of serum OXT, surpassing the effects of CNO, with a significant increase in the area under the curve (AUC) up to 3 hours post-administration. Comprehensive assessment of brain neuronal activity, using Fos as an indicator, revealed comparable effects between CNO and DCZ. Additionally, in a neuropathic pain model, both CNO and DCZ increased the mechanical nociceptive and thermal thresholds; however, the DCZ-treated group exhibited a significantly accelerated onset of the effects, aligning harmoniously with the observed alterations in serum OXT concentration following DCZ administration. These findings emphasize the remarkable efficacy of DCZ in rats, suggesting its equivalent or potentially superior performance to CNO at considerably lower dosages, thus positioning it as a promising contender among DREADDs agonists.

The relationship between characteristics of gait disturbance and injury patterns of the corticospinal tract and corticoreticular pathway in post-stroke patients: A case series of 3 patients.

RATIONALE: Corticospinal tract (CST) and corticoreticular pathway (CRP) injury patterns (i.e., the continuity of the nerve fibers) are associated with gait disturbance in post-stroke patients. In this case series study, we examined the case of 3 patients with different CST and CRP injury patterns and analyzed the characteristics of gait disturbance in each patient. PATIENT CONCERNS: Patient 1 (P1) was a 73-year-old woman who presented with paralysis of the right upper and lower extremities due to a left lacunar infarction. Patient 2 (P2) was a 41-year-old man who presented with paralysis of the right upper and lower extremities due to a left putamen hemorrhage. Patient 3 (P3) was a 57-year-old man who presented with paralysis of the left upper and lower extremities due to a right putamen hemorrhage. DIAGNOSIS: In P1, the CRP in the affected hemisphere was intact, but the CST was discontinuous. In P2, the CST in the affected hemisphere was intact, but the CRP was discontinuous. P3 was discontinuous in both CST and CRP in the affected hemisphere. OUTCOMES: Over time, all 3 patients improved to the level of gait independence, but they exhibited different gait patterns. Among them, P3 showed a markedly abnormal gait pattern that included spatiotemporal gait asymmetry, lateral shift of the trunk, and hip hiking. LESSONS: This case series study demonstrated that even if both the CST and CRP were injured, gait recovered to some extent (i.e., independent level-ground gait), but the abnormal gait pattern might remain remarkable.

Importance of head movements in gaze tracking during table tennis forehand stroke.

The purpose of this study was to clarify the properties of gaze and head movements during forehand stroke in table tennis. Collegiate table tennis players (n = 12) conducted forehand strokes toward a ball launched by a skilled experimenter. A total of ten trials were conducted for the experimental task. Horizontal and vertical movements of the ball, gaze, head and eye were analyzed from the image recorded by an eye tracking device. The results showed that participants did not always keep their gaze and head position on the ball throughout the entire ball path. Our results indicate that table tennis players tend to gaze at the ball in the initial ball-tracking phase. Furthermore, there was a significant negative correlation between eye and head position especially in the vertical direction. This result suggests that horizontal VOR is suppressed more than vertical VOR in ball-tracking during table tennis forehand stroke. Finally, multiple regression analysis showed that the effect of head position to gaze position was significantly higher than that of eye position. This result indicates that gaze position during forehand stroke could be associated with head position rather than eye position. Taken together, head movements may play an important role in maintaining the ball in a constant egocentric direction in table tennis forehand stroke.

Characteristics of Older Patients with Heart Failure Readmitted due to Acute Exacerbations within the Past Year.

OBJECTIVE: We aimed to examine the relationship between physical performance and readmission among older patients with heart failure (HF) over the past year. METHODS: This retrospective cohort study included 325 patients with HF who were aged ≥65 years and were hospitalized for acute exacerbation between November 2017 and December 2021. We investigated age, sex, body mass index, length of hospital stay, initiation of rehabilitation, New York Heart Association (NYHA) class, Charlson comorbidity index (CCI) score, medications, cardiac/renal function, nutrition, maximal quadriceps isometric strength, grip strength, and Short Physical Performance Battery (SPPB) score. Data were analyzed using the χ2 test, Mann-Whitney U test, and logistic regression analysis. RESULTS: Altogether, 108 patients met the inclusion criteria and were divided into the non-readmission (n = 76) and readmission (n = 32) groups. The readmission group exhibited longer hospital stay, more severe NYHA class, higher CCI score, higher brain natriuretic peptide (BNP) levels, lower muscle strength, and lower SPPB score compared to the non-readmission group. In the logistic regression model, BNP level and SPPB score were independent factors associated with readmission. CONCLUSION: BNP level and SPPB score were associated with readmission in patients with HF within the past year.

Brain natriuretic peptide levels and short physical performance battery scores independently influence short-term readmission rates in older patients with heart failure.

The Short Physical Performance Battery (SPPB) is a well-established tool to assess the lower extremity physical performance status. The purpose of this study is to examine the impact of brain natriuretic peptide (BNP) levels and SPPB scores on short-term readmission in older patients with heart failure (HF). This prospective cohort study enrolled 325 patients with HF who were hospitalized for acute decompensated HF between November 2017 and December 2021. Variables were analyzed using the Cox proportional hazards model, receiver operating characteristic (ROC) curve, and Kaplan-Meier analysis. The 107 patients who met the inclusion criteria were divided into readmission (within 90 days of discharge; n = 25) and non-readmission (n = 82) groups. Multivariate analysis revealed that BNP level and SPPB score were independent risk factors for readmission within 90 days after discharge. Patients were classified into three groups according to the BNP and SPPB cutoff values calculated using ROC curves. The risk of readmission was significantly higher in Group 3 (BNP ≥ 384 pg/mL and SPPB ≤ 7 points) than in Group 1 (BNP < 384 pg/mL and SPPB > 7 points; hazard ratio: 27.68, 95% confidence interval: 3.672 - 208.700, P = 0.0012). Our study showed that HF patients with high BNP levels and low SPPB scores have a dramatically increased risk of readmission within 90 days of discharge.

Effect of cognitive impairment at admission on activities of daily living at discharge in older patients with heart failure.

Nonaka Y, Fujii R, Tanaka S, Tabira K. Effect of cognitive impairment at admission on activities of daily living at discharge in older patients with heart failure. Jpn J Compr Rehabil Sci 2023; 14: 78‒83. Objective: Hasegawa's Dementia Scale-Revised (HDS-R) is widely used as a screening test for cognitive function in older adults. In this study, we examined the effect of cognitive impairment (CI) at admission on activities of daily living (ADL) at discharge in older patients with heart failure (HF). Methods: This retrospective observational study included 394 patients hospitalized for acute decompensated HF between April 2016 and December 2022. Data on age, sex, body mass index, length of hospital stay, initiation of rehabilitation, New York Heart Association (NYHA) class, Charlson Comorbidity Index, medication, brain natriuretic peptide levels, left ventricular ejection fraction, renal function, hemoglobin level, serum albumin level, Geriatric Nutritional Risk Index (GNRI), Barthel Index (BI), and HDS-R score were analyzed using the χ2 test, unpaired t test, Mann-Whitney U test, and multiple linear regression. Results: Among 394 patients, 102 who met the final inclusion criteria were included in the study. Based on previous studies, patients were divided into a high BI group (N = 44) and a low BI group (N = 58). Multiple linear regression analysis showed that CI at admission independently affected BI at discharge even after adjusting for confounding effects of age, NYHA class, GNRI, and BI at admission. Conclusions: Our study showed that the presence or absence of CI may influence ADL improvement in rehabilitation interventions aimed at improving ADL in older patients with HF.

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats.

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

Ionophore Antibiotics Inhibit Type II Feline Coronavirus Proliferation In Vitro.

Feline coronaviruses (FCoVs) infect cats worldwide and cause severe systemic diseases, such as feline infectious peritonitis (FIP). FIP has a high mortality rate, and drugs approved by the Food and Drug Administration have been ineffective for the treatment of FIP. Investigating host factors and the functions required for FCoV replication is necessary to develop effective drugs for the treatment of FIP. FCoV utilizes an endosomal trafficking system for cellular entry after binding between the viral spike (S) protein and its receptor. The cellular enzymes that cleave the S protein of FCoV to release the viral genome into the cytosol require an acidic pH optimized in the endosomes by regulating cellular ion concentrations. Ionophore antibiotics are compounds that form complexes with alkali ions to alter the endosomal pH conditions. This study shows that ionophore antibiotics, including valinomycin, salinomycin, and nigericin, inhibit FCoV proliferation in vitro in a dose-dependent manner. These results suggest that ionophore antibiotics should be investigated further as potential broad-spectrum anti-FCoV agents.

Visual Strategies for Eye and Head Movements During Table Tennis Rallies.

The purpose of this study was to clarify the properties of visual strategies for gaze, eye, and head movements in skilled table tennis players during rallies. Collegiate expert and semi-expert table tennis players conducted forehand rallies at a constant tempo using a metronome. Two tempo conditions were used in the order of 130 and 150 bpm. Participants conducted a 20-stroke rally under each tempo condition. Horizontal and vertical angles between the gaze point and ball positions at the time the ball bounced (gaze-ball angle) were analyzed with the image that was recorded by an eye tracking device equipped with Gyro sensor. Eye and head movements during rallies were also recorded with the eye tracking device and Gyro sensor, respectively. The results showed that the gaze-ball angle of expert players was significantly larger than that of semi-expert players. This result indicates that expert players tended to keep their gaze position on the ball shorter than semi-expert players. We also found that eye movements of expert players were significantly smaller than that of semi-expert players. Furthermore, as the result of multiple regression analysis, the effect of eye movements on the gaze-ball angle was significantly higher than that of head movements. This result indicates that the gaze-ball angle during table tennis rallies could be associated with eye movements rather than head movements. Our findings suggest that the visual strategies used during table tennis rallies are different between expert and semi-expert players, even though they both have more than 10 years of experience.

Influence of gait exercise using a walking-assist robot for swing-leg motion in hemiplegic stroke patients: a preliminary study focusing on the immediate effect.

Fujii R, Tamari M, Nonaka Y, Tamiya F, Hosokawa H, Tanaka S. Influence of gait exercise using a walking-assist robot for swing-leg motion in hemiplegic stroke patients: A preliminary study focusing on the immediate effect. Jpn J Compr Rehabil Sci 2022; 13: 49-55. Objective: We analyzed the effect of gait training using a walking-assist robot that assists a subject's knee joint movement and leg swing to achieve toe clearance of the paralyzed-side lower limb during treadmill walking. Methods: The subjects were 10 hemiplegic stroke patients in a rehabilitation ward. The intervention consisted of gait training using the Welwalk WW-1000 (Welwalk) robot for 40 min. Immediately before and after this intervention, a gait analysis of the patients' treadmill walking was performed by a three-dimensional motion capture system. Statistical analyses compared the foot-to-floor distance and the shortening of hip-toe length (SHTL) of the paralyzed side before and after the intervention, and examined the relationship between the change of lower-limb joint kinematics and toe clearance before and after the intervention. Results: The post-intervention SHTL was significantly lower compared to before the intervention, and there was a significant negative correlation between the change in the SHTL and the knee flexion angle from before to after the intervention. Conclusion: Gait exercise using the Welwalk could contribute to the acquisition of more normal leg-swing strategies.

Chemogenetic activation of endogenous arginine vasopressin exerts anorexigenic effects via central nesfatin-1/NucB2 pathway.

We examined whether the chemogenetic activation of endogenous arginine vasopressin (AVP) affects central nesfatin-1/NucB2 neurons, using a transgenic rat line that was previously generated. Saline (1 mL/kg) or clozapine-N-oxide (CNO, 1 mg/mL/kg), an agonist for hM3Dq, was subcutaneously administered in adult male AVP-hM3Dq-mCherry transgenic rats (300-370 g). Food and water intake were significantly suppressed after subcutaneous (s.c.) injection of CNO, with aberrant circadian rhythmicity. The percentages of Fos expression in nesfatin-1/NucB2-immunoreactive neurons were significantly increased in the hypothalamus and brainstem at 120 min after s.c. injection of CNO. Suppressed food intake that was induced by chemogenetic activation of endogenous AVP was ablated after intracerebroventricularly administered nesfatin-1/NucB2-neutralizing antibody in comparison with vehicle, without any alteration of water intake nor circadian rhythmicity. These results suggest that chemogenetic activation of endogenous AVP affects, at least in part, central nesfatin-1/NucB2 neurons and may exert anorexigenic effects in the transgenic rats.

2D Photopolymerization of Liquid Crystalline Langmuir Monolayers: In Situ Observation by Reflected Polarizing Microscopy.

Photopolymerization of Langmuir monolayers composed of bifunctional acrylic liquid crystalline (LC) compounds was observed in situ by polarizing optical microscopy. In a dark state, monolayers of the LC compounds formed at an air-water or liquid-liquid interface exhibited liquid-like fluidity and in-plane optical anisotropy because of the coherent molecular tilt from the surface normal. Irradiated by UV light, the in-plane anisotropy and the liquid fluidity gradually disappeared with time, indicating the formation of the polymerized monolayers. Because the constituent molecules possess polymerizable acryloyl groups, under UV light, they are combined by acrylic polymer chains grown on the interface, which decreases the intermolecular distance and disturbs the coherent molecular tilt, resulting in the evanescence of the in-plane optical anisotropy and the fluidity. In contrast to the classical model of radical polymerization, the time taken for the monolayers to be photopolymerized was inversely proportional to the UV intensity, which is ascribed to the ideal two dimensionality of the reaction field. Because the polymerization degree is quantitatively estimated from the in-plane optical anisotropy of the LC monolayers, the process is traced, from moment to moment, by in situ microscopy observation.

Unique Retinal Binding Pocket of Primate Blue-Sensitive Visual Pigment.

The visual pigments of humans contain 11-cis retinal as the chromophore of light perception, and its photoisomerization to the all-trans form initiates visual excitation in our eyes. It is well-known that three isomeric states of retinal (11-cis, all-trans, and 9-cis) are in photoequilibrium at very low temperatures such as 77 K. Here we report the lack of formation of the 9-cis form in monkey blue (MB) at 77 K, as revealed by light-induced difference Fourier transform infrared spectroscopy. This indicates that the chromophore binding pocket of MB does not accommodate the 9-cis form, even though it accommodates the all-trans form by twisting the chromophore. Mutation of the blue-specific tyrosine at position 265 to tryptophan, which is highly conserved in other animal rhodopsins, led to formation of the 9-cis form in MB, suggesting that Y265 is one of the determinants of the unique photochemistry in blue pigments. We also found that 9-cis retinal does not bind to MB opsin, implying that the chromophore binding pocket does not accommodate the 9-cis form at physiological temperature. The unique property of MB is discussed on the basis of the results presented here.

Activation of endogenous arginine vasopressin neurons inhibit food intake: by using a novel transgenic rat line with DREADDs system.

Various studies contributed to discover novel mechanisms of central arginine vasopressin (AVP) system responsible for the behaviour albeit endogenous vasopressin activation. We established a novel transgenic rat line which expresses both human muscarinic acetylcholine receptors (hM3Dq), of which ligand is clozapine-N-oxide (CNO), and mCherry fluorescence specifically in AVP neurons. The mCherry neurons that indicate the expression of the hM3Dq gene were observed in the suprachiasmatic (SCN), supraoptic (SON), and paraventricular nuclei (PVN). hM3Dq-mCherry fluorescence was localized mainly in the membrane of the neurons. The mCherry neurons were co-localized with AVP-like immunoreactive (LI) neurons, but not with oxytocin-LI neurons. The induction of Fos, which is the indicator for neuronal activity, was observed in approximately 90% of the AVP-LI neurons in the SON and PVN 90 min after intraperitoneal (i.p.) administration of CNO. Plasma AVP was significantly increased and food intake, water intake, and urine volume were significantly attenuated after i.p. administration of CNO. Although the detailed mechanism has unveiled, we demonstrated, for the first time, that activation of endogenous AVP neurons decreased food intake. This novel transgenic rat line may provide a revolutionary insight into the neuronal mechanism regarding central AVP system responsible for various kind of behaviours.

Spectral Tuning Mechanism of Primate Blue-sensitive Visual Pigment Elucidated by FTIR Spectroscopy.

Protein-bound water molecules are essential for the structure and function of many membrane proteins, including G-protein-coupled receptors (GPCRs). Our prior work focused on studying the primate green- (MG) and red- (MR) sensitive visual pigments using low-temperature Fourier transform infrared (FTIR) spectroscopy, which revealed protein-bound waters in both visual pigments. Although the internal waters are located in the vicinity of both the retinal Schiff base and retinal ß-ionone ring, only the latter showed differences between MG and MR, which suggests their role in color tuning. Here, we report FTIR spectra of primate blue-sensitive pigment (MB) in the entire mid-IR region, which reveal the presence of internal waters that possess unique water vibrational signals that are reminiscent of a water cluster. These vibrational signals of the waters are influenced by mutations at position Glu113 and Trp265 in Rh, which suggest that these waters are situated between these two residues. Because Tyr265 is the key residue for achieving the spectral blue-shift in λmax of MB, we propose that these waters are responsible for the increase in polarity toward the retinal Schiff base, which leads to the localization of the positive charge in the Schiff base and consequently causes the blue-shift of λmax.

Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats.

Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. Nesfatin-1/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central nesfatin-1/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (180-220 g). Cumulative food intake was remarkably suppressed for at least 24 h and body weight was significantly smaller at 24 h after i.p. administration of cisplatin compared to control group. At 90 min after i.p. administration, they were perfused, followed by carrying out double-immunohistochemistry for Fos and nesfatin-1/NucB2. The percentage of nesfatin-1/NucB2 immunoreactive neurons expressing Fos was marked increased in the hypothalamus and brainstem after i.p. administration of cisplatin. Intracerebroventricularlly administered nesfatin-1/NucB2-antisense resulted in a significant attenuation of decreased food intake for 2 h after i.p. administration of cisplatin compared to nesfatin-1/NucB2-missense treated group. These results suggest that i.p. administration of cisplatin activated, at least in part, nesfatin-1/NucB2 neuron in the CNS and may exert anorexigenic effects in rats.

Inhomogeneous distribution of Chlamydomonas in a cylindrical container with a bubble plume.

Swimming microalgae show various taxes, such as phototaxis and gravitaxis, which sometimes result in the formation of a cell-rich layer or a patch in a suspension. Despite intensive studies on the effects of shear flow and turbulence on the inhomogeneous distribution of microalgae, the effect of a bubble plume has remained unclear. In this study, we used Chlamydomonas as model microalgae, and investigated the spatial distribution of cells in a cylindrical container with a bubble plume. The results illustrate that cells become inhomogeneously distributed in the suspension due to their motility and photo-responses. A vortical ring distribution was observed below the free surface when the bubble flow rate was sufficiently small. We performed a scaling analysis on the length scale of the vortical ring, which captured the main features of the experimental results. These findings are important in understanding transport phenomena in a microalgae suspension with a bubble plume.

C6-Modifications on chitosan to develop chitosan-based glycopolymers and their lectin-affinities with sigmoidal binding profiles.

Chitosan-based glycopolymers having multiple ß-lactosides exclusively at their C6-positions were successfully synthesized from partially deacetylated chitin through perfect N-deacetylation/phthaloylation and C6-selective bromination/azidation to afford 6-azide-6-deoxy-N-phthaloyl-chitosan and the subsequent Cu(+)-catalyzed Huisgen cycloadditions using alkyne-terminated ß-lactoside and/or quaternary ammonium modules followed by dephthaloylations. Lectin-affinities of the resultant chitosan-based glycopolymers were assessed through fluorescence titration assays to show their unique sigmoidal binding profiles with amplified binding constants.

Relative performance of hybrid nestlings in Ficedula flycatchers: a translocation experiment.

Ecological speciation predicts that hybrids should experience relatively low fitness in the local environments of their parental species. In this study, we performed a translocation experiment of nestling hybrids between collared and pied flycatchers into the nests of conspecific pairs of their parental species. Our aim was to compare the performance of hybrids with purebred nestlings. Nestling collared flycatchers are known to beg and grow faster than nestling pied flycatchers under favorable conditions, but to experience higher mortality than nestling pied flycatchers under food limitation. The experiment was performed relatively late in the breeding season when food is limited. If hybrid nestlings have an intermediate growth potential and begging intensity, we expected them to beg and grow faster, but also to experience lower survival than pied flycatchers. In comparison with nestling collared flycatchers, we expected them to beg and grow slower, but to survive better. We found that nestling collared flycatchers indeed begged significantly faster and experienced higher mortality than nestling hybrids. Moreover, nestling hybrids had higher weight and tended to beg faster than nestling pied flycatchers, but we did not detect a difference in survival between the latter two groups of nestlings. We conclude that hybrid Ficedula nestlings appear to have a better intrinsic adaptation to food limitation late in the breeding season compared with nestling collared flycatchers. We discuss possible implications for gene flow between the two species.