Exploring the role of anticipatory postural adjustment duration within APA2 subphase as a potential mediator between clinical disease severity and fall risk in Parkinson's disease.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk.

Investigating spatiotemporal and kinematic gait parameters in individuals with Parkinson's disease with a history of freezing of gait and exploring the effects of dopaminergic therapy on freezing of gait subtypes.

Introduction: Freezing of Gait (FOG) is a prevalent and debilitating symptom in idiopathic Parkinson's disease (PD). This study evaluated spatiotemporal and kinematic gait parameters in individuals with PD with a history of FOG and explored the effects of dopaminergic therapy on FOG subtypes. Methods: One hundred and nine individuals with PD underwent clinical assessments and quantitative biomechanical measures during walking cycles before and after dopaminergic therapy. Individuals with FOG were classified into levodopa-responsive and levodopa-unresponsive groups. Results: Individuals with FOG displayed longer disease duration and higher Unified Parkinson's Disease Rating Scale (UPDRS) II, III, IV scores, and total scores and levodopa equivalent dose, than those without FOG (all p < 0.0001). Following propensity score matching of 15 pairs based on UPDRS total score and disease duration during the off-medication state, the analysis comparing the FOG and non-FOG groups revealed no significant differences in spatiotemporal and kinematic parameters. In 39 cases of FOG, dopaminergic therapy improved gait performance in individuals with PD, enhancing spatiotemporal parameters (speed, stride length, step length, step variability) and kinematic parameters (shoulder and elbow flexion/extension range of motion (ROM), pelvic rotation, and hip abduction/adduction ROM) regardless of FOG responsiveness to dopaminergic therapy. A significant difference in trunk sway ROM (p = 0.029) remained before and after dopaminergic therapy, even after adjusting for disease duration and clinical severity. Discussion: Dopaminergic therapy had varying effects on PD with FOG, improving several spatiotemporal and kinematic gait parameters but being less effective in levodopa-unresponsive cases. Quantitative biomechanical measures offer detailed insights into gait performance, aiding personalized fall risk assessment and guiding individualized rehabilitation programs.

Efficacy and Safety of Xylitol Nasal Irrigation after Functional Endoscopic Sinus Surgery: A Randomized Controlled Study.

Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.

Effect of Age and Gender on Taste Function as Measured by the Waterless Empirical Taste Test.

The effect of age and gender on taste function is rarely investigated. Therefore, we tried to study the effect of age and gender on taste function as evaluated by the Waterless Empirical Taste Test (WETT®). The WETT® consists of 40 strips that are coated with one of five tastants (sucrose, citric acid, sodium chloride, caffeine, or monosodium glutamate). Each tastant is prepared with four different concentrations. These 40 strips are interspersed with an additional 13 tasteless strips. To implement the WETT®, a strip was placed on the middle portion of the tongue. The subjects closed their mouth and tasted the strip. They then chose one of six answers (sweet, sour, salty, bitter, brothy, or no taste at all). If the answer was correct, one score was acquired. One-hundred-and-twenty healthy men and women were collected in this study. Among them, there were 40 subjects in each age group of 20-39 years, 40-59 years, and ≥60 years. The overall taste and individual tastant function decreased with age, particularly between subjects aged 20-39 years and those aged ≥60 years. The overall taste and individual tastant function were better in females than in males, especially for subjects aged older than 59 years. Our results show that taste function is affected by both age and gender.

Influence of Age and Gender on Nasal Airway Patency as Measured by Active Anterior Rhinomanometry and Acoustic Rhinometry.

In this study, we aimed to investigate the influences of age and gender on nasal airway patency, as measured by both active anterior rhinomanometry (AAR) and acoustic rhinometry (AR). The nasal airway patency of healthy subjects was evaluated using AAR and AR. In AAR, the subjects generated airflow actively through inspiration and expiration in repetitions of 10, while nasal patency was measured at an inspiratory and expiratory reference pressure of 75 Pa. In AR, we assessed the geometry of the nasal cavity through the analysis of sound waves reflected from the nasal cavities in order to measure both cross-sectional areas and nasal volumes. The subjects were divided by gender, with all males and females then grouped by ages of 20-39 years, 40-59 years and ≥60 years. There were 40 subjects in each group. The mean resistance measured by AAR and the cross-sectional areas and nasal volumes measured by AR were not different between the different age groups; however, the cross-sectional areas and nasal volumes were found to be lesser in females than in males. Our results showed that nasal airway patency was not affected by age, while females were shown to have wider nasal passages than males.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History.

OBJECTIVE: To test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history. DESIGN: Prospective cross-sectional study. SETTING: Largest medical center in southern Taiwan. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Plantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states. PARTICIPANTS: A total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125). RESULTS: Plantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71). CONCLUSIONS: FOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.

The Effect of Chinese Herbal Medicine on Traumatic Anosmia: A Prospective, Randomized Clinical Trial.

OBJECTIVE: Chinese herbal medicine (CHM) has been implemented as a form of treatment for olfactory dysfunction. In this study, we aimed to use a tailored Guizhi decoction for the treatment of traumatic olfactory dysfunction. METHODS: Patients who had lost olfactory function after experiencing head trauma and whose olfactory function was anosmic were selected. The eligible patients were randomly assigned to two groups. In the CHM group, a tailored Guizhi decoction was prescribed, with patients also undergoing olfactory training (OT). In the OT group, patients performed OT only. The olfactory function of each patient was evaluated by both the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (TC-UPSIT), at both 3 and 6 months after the completion of treatment. RESULTS: A total of 38 patients in the CHM group and 40 in the OT group completed the study. The TC-UPSIT scores of patients slightly rose after treatment in both the CHM and OT groups. Nevertheless, there were no significant differences in TC-UPSIT scores before and after treatment in both groups. However, the PEA thresholds improved significantly in both CHM and OT groups (p = 0.005 and 0.016, respectively). Of note, there were no significant differences in threshold or identification scores between the CHM and OT groups. CONCLUSION: Our results show that adding a tailored Guizhi decoction to OT conferred a limited benefit to the olfactory function of patients experiencing traumatic anosmia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:1473-1479, 2023.

Assessing the Feasibility of Using Electrochemical Skin Conductance as a Substitute for the Quantitative Sudomotor Axon Reflex Test in the Composite Autonomic Scoring Scale and Its Correlation with Composite Autonomic Symptom Scale 31 in Parkinson's Disease.

The Composite Autonomic Scoring Scale (CASS) is a quantitative scoring system that integrates the sudomotor, the cardiovagal, and the adrenergic subscores, and the Composite Autonomic Symptom Scale 31 (COMPASS 31) is based on a well-established comprehensive questionnaire designed to assess the autonomic symptoms across multiple domains. We tested the hypothesis that electrochemical skin conductance (Sudoscan) can be a substitute for the quantitative sudomotor axon reflex test (QSART) in the sudomotor domain and assessed its correlation with COMPASS 31 in patients with Parkinson's disease (PD). Fifty-five patients with PD underwent clinical assessment and cardiovascular autonomic function tests and completed the COMPASS 31 questionnaire. We compared the modified CASS (integrating the Sudoscan-based sudomotor, adrenergic, and cardiovagal subscores) and CASS subscores (the sum of the adrenergic and cardiovagal subscores). The total weighted score of COMPASS 31 was significantly correlated with both the modified CASS and the CASS subscore (p = 0.007 and p = 0.019). The correlation of the total weighted score of COMPASS 31 increased from 0.316 (CASS subscores) to 0.361 (modified CASS). When we added the Sudoscan-based sudomotor subscore, the case numbers for autonomic neuropathy (AN) increased from 22 (40%, CASS subscores) to 40 (72.7%, modified CASS). The modified CASS not only better reflects the exact autonomic function, but also improves the characterization and quantification of AN in patients with PD. In areas in which a QSART facility is not easily available, Sudoscan could be a time-saving substitution.

Nasal Mycology of Chronic Rhinosinusitis Revealed by Nanopore Sequencing.

BACKGROUND: Nanopore sequencing (NS) is a third-generation sequencing technology capable of generating reads of long sequences. In this study, we used NS to investigate nasal mycology in patients with chronic rhinosinusitis (CRS). METHODS: Nasal cavities of 13 CRS patients were individually irrigated with 20 mL of distilled water. The irrigant was forcefully blown by the patient into a basin. The collected fluid was placed into a centrifuge tube and processed using the method of Ponikau et al. The collected specimens were used for traditional fungal culture and sequenced for total DNA using NS. RESULTS: Traditional fungal culture successfully grew fungi in the specimens of 11 (84.6%) patients. Aspergillus sp. and Penicillium sp. were found in four (30.8%) patients, Cladosporium sp. in three (23.1%) patients, and Candida albicans, Mucor sp. and Chaetomium sp. in one patient. NS revealed fungi abundance ranged from 81 to 2226, with the Shannon species diversity ranging from 1.094 to 1.683 at the genus level. Malassezia sp. was sequenced in 13 patients, Aspergillus sp. in 12 (92.3%) patients, Candida albicans in 11 (84.6%) patients, and Penicillium sp. in 10 (76.9%) patients. CONCLUSION: Our results showed that NS was sensitive and fast in detecting nasal fungi in CRS patients.

Effectiveness of Different Methods for Baroreflex Sensitivity Assessment in Determining the Severity of Cardiovascular Autonomic Neuropathy in Patients With Parkinson's Disease.

Background: Autonomic disorders are an important non-motor feature of Parkinson's disease (PD). Baroreflex sensitivity (BRS) is often used as an indicator of cardiovascular autonomic function, and it is clinically significant. Several different methods of BRS assessment have been described. We evaluated and compared the efficiency of several methods of BRS assessment for additional insight into the underlying physiology and the determination of its severity in patients with PD. Materials and Methods: Eighty-five patients with PD underwent cardiovascular autonomic testing. The Composite Autonomic Scoring Scale (CASS) was used to grade the severity of autonomic impairment and to define the presence of cardiovascular autonomic neuropathy (CAN). BRS was assessed using the Valsalva maneuver (BRS_VM). In addition, spontaneous BRS was computed using the sequence method and the spectral method. Results and Conclusion: There was considerable agreement between the different methods of BRS assessment. Nevertheless, BRS_VM exhibited a higher degree of correlation with cardiovascular autonomic function than spontaneous BRS indexes obtained by the sequence or spectral method. BRS_VM, rather than spontaneous BRS, also had a predictive value for the presence of CAN to the diagnostic criteria by CASS in patients with PD.

Clinical Disease Severity Mediates the Relationship between Stride Length and Speed and the Risk of Falling in Parkinson's Disease.

The shuffling gait with slowed speed and reduced stride length has been considered classic clinical features in idiopathic Parkinson's disease (PD), and the risk of falling increases as the disease progresses. This raises the possibility that clinical disease severity might mediate the relationship between stride length and speed and the risk of falling in patients with PD. Sixty-one patients with PD patients underwent the clinical scores as well as quantitative biomechanical measures during walking cycles before and after dopamine replacement therapy. Mediation analysis tests whether the direct effect of an independent variable (stride length and speed) on a dependent variable (three-step fall prediction model score) can be explained by the indirect influence of the mediating variable (Unified Parkinson's Disease Rating Scale (UPDRS) total scores). The results demonstrate that decreased stride length, straight walking speed, and turning speed is associated with increased three-step fall prediction model score (r = -0.583, p < 0.0001, r = -0.519, p < 0.0001, and r = -0.462, p < 0.0001, respectively). We further discovered that UPDRS total scores value is negatively correlated with stride length, straight walking, and turning speed (r = -0.651, p < 0.0001, r = -0.555, p < 0.0001, and r = -0.372, p = 0.005, respectively) but positively correlated with the fall prediction model score value (r = 0.527, p < 0.0001). Further mediation analysis shows that the UPDRS total score values serve as mediators between lower stride length, straight walking, and turning speed and higher fall prediction model score values. Our results highlighted the relationship among stride length and speed, clinical disease severity, and risk of falling. As decreased stride length and speed are hallmarks of falls, monitoring the changes of quantitative biomechanical measures along with the use of wearable technology in a longitudinal study can provide a scientific basis for pharmacology, rehabilitation programs, and selecting high-risk candidates for surgical treatment to reduce future fall risk.

Feasibility of Combining Disease-Specific and Balance-Related Measures as Risk Predictors of Future Falls in Patients with Parkinson's Disease.

Evidence supports the view that postural sway in a quiet stance increases with clinical disease severity and dopaminergic therapy in idiopathic Parkinson's disease (PD), which, in turn, increases the risk of falling. This study evaluated the feasibility of combining disease-specific and balance-related measures as risk predictors for future falls in patients with PD. The patients with PD underwent postural sway measurements (area, length, and velocity traveled by the excursion of the center of pressure) and clinical functional scores (Parkinson's Disease Rating Scale [UPDRS] and Tinetti balance and gait score assessment) in both the on- and off-states of dopaminergic therapy. The outcome was defined as the development of a new fall. The sway area, velocity, and length increased after the medication administration. The Cox proportional hazards model showed that only previous fall history, Tinetti balance and gait score (on-state), and levodopa equivalent daily dose (LEDD) were associated with the development of future falls. The cumulative risk of fall development showed that the sway length and velocity were associated with future falls after more than six months. The combined LEDD, Tinetti balance and gait score (on-state), and velocity and length of postural sway (on-state) had the highest diagnostic accuracy (area under the curve = 0.9, p < 0.0001). Dopaminergic therapy can improve clinical functional scores but worsen balance-related measures. Increased sway length and velocity during the medication state are hallmarks of future falls, particularly in advanced PD. Combining disease-specific and balance-related measures can serve as an auxiliary diagnosis as risk predictors for future falls.

Detraining Effect on Pulmonary and Cardiovascular Autonomic Function and Functional Outcomes in Patients With Parkinson's Disease After Respiratory Muscle Training: An 18-Month Follow-Up Study.

Background: The effect of 3-month respiratory muscle training (RMT) on pulmonary and autonomic function and functional outcomes has been demonstrated in patients with Parkinson's disease (PD); however, there is a paucity of information on the durability of the training effect. In this study, we monitored the pulmonary and cardiovascular autonomic function and clinical severity scales until 18 months after the cessation of RMT to elucidate the detraining effect after RMT. Methods: All patients with PD receiving RMT were assessed with clinical severity scales as well as pulmonary and autonomic function tests at four different stages (baseline on enrollment, immediately after 3 months of RMT, and 6 and 18 months after cessation of RMT). A control group of PD patients who did not receive RMT was also recruited for comparison. Pulmonary function parameters, including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP), were assessed. Cardiovascular autonomic function was assessed using measures including heart rate response to deep breathing (HRDB), Valsalva ratio, and baroreflex sensitivity. Clinical severity scores were also measured using the Hoehn and Yahr staging and the Unified Parkinson's Disease Rating Scale (UPDRS). Results: The results showed significant improvements in MIP, MEP, HRDB, and UPDRS immediately after RMT. Despite some decay, the improvements in pulmonary function (MIP and MEP) and functional outcomes (UPDRS) remained significant until 6 months of detraining (9 months after enrollment). However, the improvement in cardiovascular autonomic function (HRDB) was reversed after 6 months of detraining. Conclusions: Based on these findings, we recommend that RMT may be repeated after at least 6 months after previous session (9 months after enrollment) for patients with PD to maintain optimal therapeutic effects.

Impact of oxidative stress on treatment outcomes in adult patients with sepsis: A prospective study.

PURPOSE: Oxidative stress has been shown to reflect on the development of sepsis and disease severity. In the present study, we evaluated the effects of increased levels of oxidative stress and decreased antioxidant coactivity in patients with sepsis, and the importance of oxidative stress on treatment outcomes. METHODS: Biomarkers of oxidative stress (thiobarbituric acid-reactive substances [TBARS]) and antioxidant capacity (glutathione peroxidase [GPx] and glutathione content [thiol]) were prospectively evaluated along with biochemical and clinical data in 100 patients with sepsis on days 1, 4, and 7 after admission. RESULTS: The TBARS level of the non-survivor group was significantly higher than that of the survivor group on day 1 and day 4 and negatively correlated with thiol upon admission. However, thiol was positively correlated with lactate concentration. The TBARS and lactate levels upon admission were independent predictors of fatality. CONCLUSIONS: We conclude that a TBARS cut-off value of 18.30 µM can be used to predict fatality, and an increase in the TBARS concentration by 1 µM will increase the fatality rate by 0.94%. In the panel of biomarkers, the TBARS assay can be considered as a prognostic biomarker for the treatment of patients with sepsis.

α-1-Acid Glycoprotein Concentration as an Outcome Predictor in Adult Patients with Sepsis.

BACKGROUND: α-1-Acid glycoprotein (AGP) is an acute-phase protein that plays a role in first-line defense against infection and is therefore elevated in sepsis. We tested the hypothesis that AGP levels increase initially in sepsis and decrease after antimicrobial therapy and that these levels may predict treatment outcomes. METHODS: AGP, biomarkers widely used in clinical practice, and maximum 24-h acute physiology and chronic health evaluation (APACHE)-II scores upon emergency department (ED) admission were prospectively evaluated and compared. We further examined changes in AGP concentrations 1, 4, and 7 days after admission and determined the value of AGP that may be used to accurately and reliably predict the prognosis in patients with sepsis. RESULTS: Mechanical ventilation, white blood cell (WBC) counts, C-reactive protein (CRP) and lactate levels, maximum 24-h APACHE-II scores, and AGP concentrations were significantly higher upon admission in patients with sepsis who died. AGP and lactate concentrations were also significantly higher in non-survivors than in survivors on days 1, 4, and 7. As indicated by the stepwise logistic regression model analysis and area under the curve analysis, AGP was the best prognostic indicator, and the cut-off value for predicting fatality was 1307 µg/mL, and any increase 1-ng/mL in AGP concentration would increase the fatality rate by 0.5%. CONCLUSION: Based on our observations, AGP may be a good prognostic predictor in patients with sepsis. In addition, serial AGP levels meet the requirements for predicting outcomes in patients with sepsis.

Increased circulating endothelial progenitor cells and improved short-term outcomes in acute non-cardioembolic stroke after hyperbaric oxygen therapy.

BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. METHODS: The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls. RESULTS: The numbers of KDR+/CD34+ (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133+/CD34+ (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group. CONCLUSIONS: Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

Investigation of MicroRNA in Mitochondrial Apoptotic Pathway in Systemic Lupus Erythematosus.

BACKGROUND: Accumulating evidence indicates that microRNAs play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that microRNA is associated with the mitochondrial apoptotic pathway in patients with SLE. METHODS: Thirteen patients were in the clinical comparison study and microRNA study and overall 19 patients in the study of intracellular protein. Levels of microRNAs were determined by miRNeasy kit in 13 patients with SLE and 29 volunteer normal controls. Intracellular levels of caspase-9, caspase-10, MAVS, MDA5, and pIRF7 in mononuclear cells from 19 patiens and the SLE disease activity index (SLEDAI) were determined in all SLE patients. Correlation analyses were performed among microRNAs, intracellular adaptor proteins, and caspase levels and mean SLEDAI. RESULTS: The ΔCT, defined by test reading difference between the target and the internal control microRNA (miR-451a), of miR-21-5p, miR-150-5p, and miR221-3p were significantly higher in plasma from SLE patients than in normal controls. miR-150-5pΔCT was positively correlated with both CRP and SLEDAI value. miR-150-5pΔCT was negatively associated with MAVS 70 kD. Caspase-10 protein levels were negatively associated with plasma miR-22-3pΔCT and miR-21-5pΔCT levels. CONCLUSIONS: Our study confirmed the hypothesis that these microRNAs were associated with the mitochondrial apoptotic pathway in SLE. miR-150-5pΔCT was positively associated with SLE disease activity and it was negatively correlated with MAVS 70 kD, which may facilitate viral survival and further enhance inflammation. On the other hand, miR-22-3pΔCT and miR-21-5pΔCT, were negatively correlated with caspase-10 levels, which may repress extrinsic apoptosis and increase cell survival.

Concentration and value of endocan on outcome in adult patients after severe sepsis.

BACKGROUND: Endothelial dysfunction plays a central role in severe sepsis. Endocan is constitutively expressed in human endothelial cells when sepsis occurs. We tested the hypothesis that endocan concentrations are substantially increased in severe sepsis and decrease after antimicrobial therapy, and that endocan concentrations can predict treatment outcomes. METHODS: Biomarkers of the endothelium including endocan and cell adhesion molecules were prospectively evaluated in 153 patients with severe sepsis on days 1, 4, and 7 after admission along with biochemical and clinical data. RESULTS: Sepsis non-survivors had significantly higher endocan, ICAM-1, and VCAM-1 concentrations and lower platelet concentrations upon admission than the survivors. Non-survivors had significantly higher endocan and VCAM-1 concentrations than the survivors on serial analysis (days 1, 4, and 7). After stepwise logistic regression model and AUC analysis, endocan was revealed as a good predictor of outcome in severe sepsis, and the cut-off value for predicting fatality was 6.28 ng/ml. An increase in the endocan concentration by one ng/ml indicated an increase in fatality rate by 11.1%. CONCLUSIONS: Based on our results, serial endocan concentration meets the major requirements for predicting outcome in patients with severe sepsis. An assay of endocan concentration may be a good prognostic biomarker in the clinic for severe sepsis.

Impact of inflammation and oxidative stress on carotid intima-media thickness in obstructive sleep apnea patients without metabolic syndrome.

Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases, and carotid intima-media thickness (IMT) is a good indicator of the severity of atherosclerotic disease. This study tested the hypothesis that inflammation and oxidative stress determined carotid IMT in patients with OSA. The carotid IMT, mean systolic and diastolic pressure (night and morning) were significantly higher and the level of thiols and high-density lipoprotein were significantly lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea index was correlated positively with E-selectin (r = 0.222, P = 0.014), total cholesterol (r = 0.185, P = 0.042), low-density lipoprotein (r = 0.264, P = 0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high-density lipoprotein level (r = -0.203, P = 0.025) in the 121 patients with OSA. In OSA subjects, multiple linear regression analysis revealed that age, systolic blood pressure and intercellular cell adhesion molecule-1 level associated independently with carotid IMT. Besides both age and systolic blood pressure, our study demonstrated that intercellular cell adhesion molecule-1 level was associated significantly with carotid IMT in those patients who had OSA but without metabolic syndrome.