Prealbumin level is a predictor of activities of daily living at discharge in older patients with heart failure who became ADL-independent after hospitalization: - Acute and early recovery cardiac rehabilitation trials.

Chiba T, Yokota J, Takahashi R, Sasaki K, Suzuki H. Prealbumin level is a predictor of activities of daily living at discharge in older patients with heart failure who became ADL-independent after hospitalization - Acute and early recovery cardiac rehabilitation trials. Jpn J Compr Rehabil Sci 2023; 14: 69-77. Objective: To determine the relationship between prealbumin level and activities of daily living (ADL) at discharge in patients with heart failure (HF) and assess the usefulness of prealbumin measurement in predicting discharge Barthel Index (BI) in older patients with HF who become non-independent in ADL after hospital admission. Methods: Patients with HF, aged ≥75 years, who were admitted to an acute hospital and underwent acute and early recovery cardiac rehabilitation (CR) were studied retrospectively. The exclusion criteria were non-independent ADL before admission (BI < 85 points) and independent ADL at the start of CR (BI ≥ 85 points). The usefulness of prealbumin level in predicting discharge BI was compared between four models. Albumin and Controlling Nutritional Status (CONUT) were used as comparison variables. The models and independent variables were model 1 (covariates only), model 2 (prealbumin + covariates), model 3 (albumin + covariates), and model 4 (CONUT score + covariates). Adjusted R2, a measure of model fit, was used to compare predictive ability. Results: A total of 152 patients were included in the analysis. Prealbumin level was a significant variable for BI at discharge but not albumin or CONUT. The adjusted R2 was higher in model 2 with the addition of prealbumin than that in model 1 (0.362 vs. 0.347). Conclusion: Prealbumin levels are useful in predicting discharge BI in older patients with HF who become non-independent in ADL after hospitalization.

Physiological ER stress caused by amylase production induces regulated Ire1-dependent mRNA decay in Aspergillus oryzae.

Regulated Ire1-dependent decay (RIDD) is a feedback mechanism in which the endoribonuclease Ire1 cleaves endoplasmic reticulum (ER)-localized mRNAs encoding secretory and membrane proteins in eukaryotic cells under ER stress. RIDD is artificially induced by chemicals that generate ER stress; however, its importance under physiological conditions remains unclear. Here, we demonstrate the occurrence of RIDD in filamentous fungus using Aspergillus oryzae as a model, which secretes copious amounts of amylases. α-Amylase mRNA was rapidly degraded by IreA, an Ire1 ortholog, depending on its ER-associated translation when mycelia were treated with dithiothreitol, an ER-stress inducer. The mRNA encoding maltose permease MalP, a prerequisite for the induction of amylolytic genes, was also identified as an RIDD target. Importantly, RIDD of malP mRNA is triggered by inducing amylase production without any artificial ER stress inducer. Our data provide the evidence that RIDD occurs in eukaryotic microorganisms under physiological ER stress.

Improving physical performance reduces dysphagia via improvement of tongue strength in patients with acute heart failure: a two-wave cross-lagged mediation model analysis.

BACKGROUND: Physical performance improvement through whole-body exercise may have a positive impact on dysphagia via improvement of maximum tongue pressure (MTP). AIMS: The present study aimed to quantitatively analyze whether improvement in physical performance reduces dysphagia by improving MTP in patients with acute heart failure (AHF). METHODS: A total of 146 patients with AHF and dysphagia were included. Dysphagia was defined as a functional oral intake scale (FOIS) score < 6. The short physical performance battery (SPPB) indexed physical performance. A two-wave cross-lagged mediation model was used to examine whether an improvement in SPPB results improves the FOIS score via an improvement in MTP. The SPPB, MTP, and FOIS scores (T1: baseline, T2: hospital discharge) were included in the model. RESULTS: A total of 146 patients were included in the final analysis. The SPPB result at T1 positively affected MTP (ß = 0.150, P = 0.030) and the FOIS score (ß = 0.249, P = 0.002) at T2. MTP at T1 also positively affected the FOIS score at T2 (ß = 0.189, P = 0.026). Furthermore, the SPPB result indirectly affected the FOIS score by affecting the MTP (indirect effect = 0.028; 95% CI = 0.010, 0.078). DISCUSSION: This study contributes to the knowledge base regarding the potential of exercise therapy as a new treatment strategy for dysphagia in patients with AHF. CONCLUSION: An improvement in SPPB results improved the FOIS score by improving the MTP in patients with AHF.

Dysphagia is an independent predictor of hospital-acquired disability in older patients with heart failure: a propensity score-matched analysis : Predictors of HAD in older HF patients.

This study aims to identify the relationship between dysphagia and developing hospital-acquired disability (HAD) in older patients with heart failure (HF). This single-center retrospective cohort study included 360 patients (median age, 84 years: 58.1% female, 41.9% male) who had undergone rehabilitation and were aged 65 years and older. Patients were divided into dysphagia and non-dysphagia groups and compared based on the Functional Oral Intake Scale score. HAD was defined as a decline in the Barthel Index score (indication of daily activity levels) at discharge relative to that before admission. The relationship between dysphagia and HAD was analyzed using bivariate analysis after adjusting for age, sex, body mass index, medical history, clinical and laboratory data, short physical performance battery (SPPB), and cognitive function at the start of rehabilitation, using propensity score matching. HAD was observed in 38.1% of the patients. Patients with dysphagia were significantly older, and had lower body mass index and physical and cognitive function than those without. After propensity score matching, the prevalence of HAD was significantly higher in the dysphagia group than in the non-dysphagia group (61.9% vs. 42.9%, P = 0.032). Dysphagia at the start of rehabilitation was an independent predictor of HAD. The results of this study may contribute to risk stratification of HAD.

Physical performance and maximum tongue pressure associated with oral intake independence: a retrospective study on hospitalized patients with heart failure.

Dysphagia in patients with heart failure leads to poorer outcomes during hospitalization and after discharge. Therefore, addressing dysphagia is critical for improving patient prognosis. This retrospective observational study aimed to evaluate associations between improvements in swallowing dysfunction at the time of hospital discharge and the physical function, cognitive function, nutritional status, and maximum tongue pressure (MTP). Overall, 111 patients who underwent cardiac rehabilitation and were deemed to have oral intake impairment were included. The exclusion criteria comprised the following: pre-admission diagnosis of dysphagia, in-hospital death, and missing data. Patients were categorized based on whether they did (n = 65) or did not (n = 46) exhibit improvements in oral intake impairment, which were determined from the functional oral intake scale (FOIS) score at discharge. Associations between potential explanatory variables and the FOIS score at discharge were assessed using a linear regression model. After adjusting for covariates, such as age, sex, heart failure severity, short physical performance battery score, Mini-Mental State Examination score, transthyretin level, and provision of swallowing therapy, the FOIS score at discharge was significantly associated with the MTP (P = 0.024, confidence interval: 0.006-0.046). In conclusion, the MTP was independently associated with improvements in FOIS in patients with heart failure.

Mild cognitive impairment in patients with acute heart failure does not limit the effectiveness of early phase II cardiac rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is commonly performed in patients with heart failure (HF) with mild cognitive impairment (MCI). However, whether MCI diminishes the benefit of early phase II CR is unclear. AIM: This study aimed to clarify whether MCI diminishes the benefit of early phase II CR in patients hospitalized for HF. DESIGN: The design of the work is a case-control study. SETTING: All HF patients who underwent CR in acute care hospitals in Japan from April 2016 to March 2021. POPULATION: Among the 574 patients who underwent CR, 204 were included in this study. Exclusion criteria were age <65 years, dependence for activities of daily living (ADLs) prior to admission, diagnosis of dementia or delirium, mini-mental state examination (MMSE) score at the commencement of CR<19, missing data, in-hospital death, and transfer to another department during hospitalization. METHODS: Patients were divided into two groups, those with MCI (MCI group, N.=134) and those without MCI (non-MCI group, N.=70), based on MMSE score at the commencement of CR. Cognitive impairment was defined as a score of <19. MCI was defined as an MMSE score between 19 and 26, and normal cognitive function was defined as MMSE >26. The primary outcomes were the 6-minute walking distance (6MWD), Barthel Index (BI), and Short Physical Performance Battery (SPPB). All patients underwent guideline-based CR programs. RESULTS: On admission, MCI patients had significantly lower BI (P<0.01, confidence interval [CI]: 4.9-20.4) and SPPB (P<0.01, CI: 1.1-3.1), despite being independent for ADLs before admission. In addition, 6MWD (P<0.01, CI: 31.2-97.2), BI (P=0.01, CI: 1.0-8.4), and SPPB (P<0.01, CI: 0.6-2.5) were significantly lower in the MCI group at the time of discharge. However, after propensity score matching to adjust for baseline characteristics, no significant differences in any primary outcome were found between the two groups. CONCLUSIONS: The BI, SPPB, and 6MWD improvements due to CR were similar, regardless of MCI. CLINICAL REHABILITATION IMPACT: Our results may inform the selection of appropriate rehabilitation interventions for patients with HF and MCI.

Dysphagia and malnutrition limit activities of daily living improvement in phase i cardiac rehabilitation: a prospective cohort study for acute phase heart failure patients.

Dysphagia and malnutrition combinations in hospitalized patients with acute heart failure (AHF) may affect activities of daily living (ADL) after hospital discharge more than dysphagia or malnutrition alone. The aim of the present study to clarify the impact of the combination of dysphagia and malnutrition on ADL in hospitalized patients with acute phase heart failure who have undergone cardiac rehabilitation (CR). Prospective cohort study. Acute care hospital. Participants were 224 AHF patients undergoing CR. Barthel index (BI), functional oral intake scale (FOIS), controlling nutritional status (CONUT), short physical performance battery (SPPB), and mini-mental state examination were evaluated at baseline. We examined primary effects of predictors (CONUT) and the moderator (FOIS) and the interaction effect of FOIS and CONUT (FOIS × CONUT) using hierarchical linear regression model and simple-slope tests. The ADL independence dropped in 29.5% of the patients on hospitalization; however, 82.6% of the patients successfully regained their independence at discharge. Based on the FOIS score and nutritional status on admission, 58.5% of the patients were classified into the non-dysphagia and non-malnutrition categories, 21.0% into non-dysphagia and malnutrition, 15.2% into dysphagia and non-malnutrition, and 5.3% into dysphagia and malnutrition. Lower FOIS and SPPB scores as well as the FOIS × CONUT interaction predicted a significantly lower BI but not CONUT. Simple slope test revealed a negative association between CONUT and BI with low-level FOIS (B = - 2.917, P < .001) but not with high-level FOIS (B = .476, P = .512). Thus, patients with dysphagia and malnutrition in combination had a greater risk of failed recovery of ADL after cardiac rehabilitation than those without this combination. In hospitalized AHF patients, FOIS and CONUT had an interactive effect on BI at hospital discharge in cases with low-level FOIS. Early detection of dysphagia might improve the accurate identification of hospitalized AHF patients at higher risk of ADL dependence at discharge.

Examination of independent predictors of discharge disposition in acute phase hospitalized heart failure patients undergoing phase I cardiac rehabilitation.

BACKGROUND: Increasing acute heart failure (HF) population is very common. Discharge disposition is one of the major cardiac rehabilitation (CR) outcomes. However, there were few data exist on home discharge criteria in acute phase HF patients who were underwent CR. AIM: The aim of this study was to clarify the predictors of home discharge in acute phase hospitalized HF patients who were underwent guideline-based CR. DESIGN: The study was designed as an intervention study. SETTING: This study took place in acute-hospital setting. POPULATION: Participants were 320 hospitalized acute phase HF patients who were underwent Japanese guideline-based CR. METHODS: Knee extension strength (KES), exercise tolerance, short physical performance battery (SPPB), Barthel Index (BI), mini-mental state examination (MMSE) and controlling nutritional status (CONUT) were evaluated on hospital admission and at hospital discharge, respectively. At hospital discharge, patients were divided into the home group (N.=255) and the non-home group (N.=65) based on discharge disposition. The independent predictors of home discharge and cut-off value were evaluated using logistic regression analysis and receiver operating curve. RESULTS: At the time of hospital admission, KES, exercise tolerance, SPPB, BI and MMSE is significantly higher in the home group. However, there were no significant differences in HF severity and CONUT on hospital admission between the groups. At hospital discharge, KES, exercise tolerance, SPPB, BI and MMSE were significantly higher and CONUT was significantly lower in the home group than in the non-home group. Multivariate analysis showed KES and SPPB on hospital admission, length of hospital stay and BI at hospital discharge were the independent predictors of home discharge. Cut-off values for predicting home discharge were KES on hospital admission ≥12.1 kg, SPPB on hospital admission ≥3 points, and BI at hospital discharge ≥80 points. CONCLUSIONS: The present study suggested that KES and SPPB on hospital admission may contributed to early detection of the patients who are difficult to return home. Additionally, there is a possibility that CR goal setting of BI ≥80 points is effective to home discharge in acute phase hospitalized HF patients. CLINICAL REHABILITATION IMPACT: This study may contribute to early detection of the patients who are predicted to be difficult to return home and to appropriate rehabilitation goals setting.

Dysphagia worsens short-term outcomes in patients with acute exacerbation of heart failure.

Dysphagia, defined as a dysfunction in any stage or process of eating, is common in patients with acute exacerbation of heart failure (HF). In some diseases, dysphagia worsens in-hospital mortality, length of hospital stay, and discharge disposition. However, it remains unclear whether dysphagia is associated with poor short-term outcomes in HF patients. The objective of the present study was to determine whether dysphagia affects short-term outcomes in patients with acute exacerbation of HF. A total of 327 patients hospitalized with acute exacerbation of HF were eligible for the study. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (NDG) based on results of the functional oral intake scale (FOIS), which evaluates a patient's ability of eating and swallowing. FOIS is a 7-point scale, with a level of ≤ 5 indicating dysphagia. Following the withdrawal of 16 patients, short-term outcomes such as in-hospital mortality, length of hospital stay, and discharge disposition, of 311 patients were analyzed. All indexes of short-term outcomes were significantly worse in the DG than in the NDG. After propensity score matching, which was performed to adjust for baseline characteristics such as age, sex, height, weight, body mass index, medical history, complications, HF severity, ejection fraction, and biochemical data excluding nutritional status, all short-term outcomes remained significantly worse in the DG than in the NDG. Multivariate analysis showed that FOIS was an independent predictor of in-hospital survival, length of hospital stay, and discharge to home. The present study suggested that dysphagia affected short-term outcomes in patients with acute exacerbation of HF. Therefore, early detection and intervention of dysphagia in HF patients are important.

Dysphagia Hinders Hospitalized Patients with Heart Failure from Being Discharged to Home.

Dysphagia, defined as a dysfunction in any stage or process of eating, is common among heart failure (HF) patients. In some diseases state, dysphagia hinders patients from being discharged to home. However, it remains unclear whether dysphagia affects discharge disposition of HF patients. This study aimed to identify the impact of dysphagia on discharge disposition of HF patients. A total of 323 patients, hospitalized with acute exacerbation of HF, were eligible for the study (excluding patients who lived at nursing care facilities before admission). Following the withdrawal of 37 patients, a total of 286 patients were analyzed. Dysphagia was determined using the functional oral intake scale (FOIS), which evaluates a patient's ability to swallow. The FOIS is a 7-point scale, with a level of ≤ 5 indicating dysphagia. Of the 286 patients analyzed, 231 (80.8%) were discharged to home, and 55 were discharged to nursing care facilities or rehabilitation hospitals (non-home). FOIS level was significantly lower, and dysphagia incidence was significantly higher among patients discharged to non-home than among those discharged to home. Multivariate analysis showed that FOIS level was an independent predictor of discharge disposition. Additionally, after propensity score matching, which was performed to adjust for baseline characteristics, FOIS level remained significantly lower in patients discharged to non-home than in those discharged to home. In conclusion, dysphagia hinders patients hospitalized with HF from being discharged to home. We conclude that evaluating dysphagia and its severity on admission is useful for predicting discharge disposition in patients hospitalized with HF.

Cellular responses to the expression of unstable secretory proteins in the filamentous fungus Aspergillus oryzae.

Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi. More recently, however, even highly expressed endogenous secretory proteins were found to evoke the UPR. These findings raise the question of whether the unfolded or misfolded state of proteins is selectively recognized by quality control mechanisms in filamentous fungi. In this study, a fungal secretory protein (1,2-α-D-mannosidase; MsdS) with a mutation that decreases its thermostability was expressed at different levels in Aspergillus oryzae. We found that, at moderate expression levels, wild-type MsdS was secreted to the medium, while the mutant was not. In the strain with a deletion for the hrdA gene, which is involved in the endoplasmic reticulum-associated degradation pathway, mutant MsdS had specifically increased levels in the intracellular fraction but was not secreted. When overexpressed, the mutant protein was secreted to the medium to a similar extent as the wild-type protein; however, the mutant underwent hyperglycosylation and induced the UPR. Deletion of α-amylase (the most abundant secretory protein in A. oryzae) alleviated the UPR induction by mutant MsdS overexpression. These findings suggest that misfolded MsdS and unfolded species of α-amylase might act synergistically for UPR induction.

Cognitive Dysfunction and Malnutrition Are Independent Predictor of Dysphagia in Patients with Acute Exacerbation of Congestive Heart Failure.

Early detection and intervention for dysphagia is important in patients with congestive heart failure (CHF). However, previous studies have focused on how many patients with dysphagia develop CHF. Studies focusing on the comorbidity of dysphagia in patients with CHF are rare. Additionally, risk factors for dysphagia in patients with CHF are unclear. Thus, the aim of this study was to clarify risk factors for dysphagia in patients with acute exacerbation of CHF. A total of 105 patients, who were admitted with acute exacerbation of CHF, were enrolled. Clinical interviews, blood chemistry analysis, electrocardiography, echocardiography, Mini-Mental State Examination (MMSE), exercise tolerance tests, phonatory function tests, and evaluation of activities of daily living (ADL) and nutrition were conducted on admission. After attending physicians permitted the drinking of water, swallowing screening tests were performed. Patients were divided into a dysphagia group (DG) or a non-dysphagia group (non-DG) based on Functional Oral Intake Scale level. Among the 105 patients, 38 had dysphagia. A greater number of patients had history of aspiration pneumonia and dementia, and there was a higher age, N-terminal pro-B-type natriuretic peptide level in the DG compared with the non-DG. MMSE scores, exercise tolerance, phonatory function, status of ADL, nutrition, albumin, and transthyretin were lower in the DG compared with the non-DG. In multivariate analysis, after adjusting for age and sex, MMSE, BI score, and transthyretin was independently associated with dysphagia. Comorbidity of dysphagia was 36.1% in patients with acute exacerbation of CHF, and cognitive dysfunction and malnutrition may be an independent predictor of dysphagia.

[Neuro-otological Studies of Patients Suffering from Dizziness with Cerebrospinal Fluid Hypovolemia after Traffic Accident-associated Whiplash Injuries].

Vertigo and dizziness are common clinical manifestations after traffic accident-associated whiplash injury. Recently, Shinonaga et al. (2001) suggested that more than 80% of patients with whiplash injury complaining of these symptoms showed cerebrospinal (CSF) hypovolemia on radioisotope (RI) cisternography (111In-DTPA). However, neuro-otological studies to investigate the pathophysiological mechanisms underlying these symptoms have been insufficient. In the present study, patients complaining of these symptoms with CSF hypovolemia after traffic accidents were investigated with posturography and electronystagmography (ENG). Fourteen patients (4 men, 10 women; 24-52 yr) were examined with posturography and showed parameters (tracking distance & area) significantly (p<0.01) larger than those of healthy subjects. Among them, five cases (1 man, 4 women; 31-52 yr) were further investigated with ENG. The slow phase peak velocities of optokinetic nystagmus (OKN) and optokinetic-after nystagmus (OKAN) were significantly (p<0.01) reduced (62.64±6.9 SD deg/sec, 60.76±10.74 SD deg/sec, respectively) and frequencies of OKN were reduced (139.7±10.75 SD), while the ocular smooth pursuit was relatively preserved. Magnetic resonance images (sagittal view) of these five patients demonstrated the downward displacement of the cerebellar tonsils and flattening of the pons, which are characteristic features of CSF hypovolemia, called "brain sagging." Our results suggest that brain sagging due to CSF hypovolemia impairs vestibular and vestibulocerebellar functions, which may cause dizziness and vertigo.

Evidence for symmetry in the elementary process of bidirectional torque generation by the bacterial flagellar motor.

The bacterial flagellar motor can rotate in both counterclockwise (CCW) and clockwise (CW) directions. It has been shown that the sodium ion-driven chimeric flagellar motor rotates with 26 steps per revolution, which corresponds to the number of FliG subunits that form part of the rotor ring, but the size of the backward step is smaller than the forward one. Here we report that the proton-driven flagellar motor of Salmonella also rotates with 26 steps per revolution but symmetrical in both CCW and CW directions with occasional smaller backward steps in both directions. Occasional shift in the stepping positions is also observed, suggesting the frequent exchange of stators in one of the 11-12 possible anchoring positions around the rotor. These observations indicate that the elementary process of torque generation by the cyclic association/dissociation of the stator with every FliG subunit along the circumference of the rotor is symmetric in CCW and CW rotation even though the structure of FliG is highly asymmetric and suggests a 180° rotation of a FliG domain for the rotor-stator interaction to reverse the direction of rotation.

Effect of intracellular pH on the torque-speed relationship of bacterial proton-driven flagellar motor.

Bacterial flagella responsible for motility are driven by rotary motors powered by the electrochemical potential difference of specific ions across the cytoplasmic membrane. The stator of proton-driven flagellar motor converts proton influx into mechanical work. However, the energy conversion mechanism remains unclear. Here, we show that the motor is sensitive to intracellular proton concentration for high-speed rotation at low load, which was considerably impaired by lowering intracellular pH, while zero-speed torque was not affected. The change in extracellular pH did not show any effect. These results suggest that a high intracellular proton concentration decreases the rate of proton translocation and therefore that of the mechanochemical reaction cycle of the motor but not the actual torque generation step within the cycle by the stator-rotor interactions.

Disappearance of the angiogenic potential of endothelial cells caused by Argonaute2 knockdown.

Argonaute2 (Ago2), a component protein of RNA-induced silencing complex, plays a central role in RNA interference. We focused on the involvement of Ago2 in angiogenesis. Human umbilical vein endothelial cells (HUVECs) stimulated with several growth factors such as vascular endothelial growth factor were used for angiogenesis assays. We applied polycation liposomes for transfection of small interfering RNA (siRNA) to determine the biological effects of siRNA for Ago2 (siAgo2) on HUVECs. The proliferation study indicated that siAgo2 significantly suppressed the growth of HUVECs compared with control siRNA. TUNEL staining showed a certain population of HUVECs treated with siAgo2 underwent apoptosis. Furthermore, the treatment with siAgo2 suppressed the tube formation of HUVECs and significantly reduced the length of the tubes. These present data demonstrate that siAgo2 inhibited indispensable events of angiogenesis in vitro. This is the first report suggesting that Ago2 is required for angiogenesis.

[The medial medullary infarction (Dejerine syndrome) following chiropractic neck manipulation].

A-38-year-old man suddenly developed nausea, vomiting and vertigo during chiropractic neck manipulation. This was followed by right hemiplegia, right deep sensory disturbance and left hypoglossal nerve palsy, consistent with the medial medullary infarction (Dejerine syndrome). The MRI revealed infarction at left medial part of the medulla. The vertebral angiogram and MRA showed marked narrowing of the left vertebral artery. X-rays of the cervical spine showed no spondylosis, dislocation nor osteolysis of the odontoid process. The serological studies, including lupus anticoagulant, protein C, and protein S gave normal results. Although vascular accidents involving the brain stem after chiropractic neck manipulation have been reported since Pratt-Thomas and Berger, previous reports are still rare. In them lateral medullary infarction (Wallenberg syndrome) is probably the most common case. On the other hand, medial medullary syndrome (Dejerine syndrome) is absolutely rare. To our knowledge, the only one report has been made by Watanabe and his colleagues before our present case. The mechanism was suggested that rotation and tilting of the neck stretches and compresses the vertebral artery at the cervical joint causing injury to the vessel, with an intimal tearing, dissection, and pseudoaneurysm formation. Consequently, the present case may be caused by injury to the left vertebral artery with an intimal tearing during neck manipulation sufficient to cause disection and subsequent infarction of the brain stem.