The Removal of Strontium Ions from an Aqueous Solution Using Na-A Zeolites Synthesized from Kaolin.

Sr2+ ions in an aqueous solution were removed using Na-A zeolites synthesized from kaolin, a natural mineral. Na-A zeolites with high crystallinity were synthesized using NaOH/kaolin mass ratios of 0.6 (ZK06) and 0.9 (ZK09). The adsorption reached equilibrium within 120 min. The adsorption data obtained from experiments for Sr2+ using ZK06 and ZK09 were appropriately analyzed with pseudo-second-order kinetic and Langmuir isotherm models. Comparing the maximum adsorption capacities (qm) of ZK06 and ZK09 for Sr2+, the highest values were obtained at 1.90 and 2.42 mmol/g, respectively. Consequently, the Na-A zeolites synthesized from kaolin can be evaluated as adsorbents with high adsorption capacities for the removal of Sr2+, proportional to the degree of their crystallinity.

Anti-SARS-CoV-2 nucleocapsid antibody positivity 3 years after COVID-19.

The accurate identification of individuals without prior infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pivotal for seroepidemiological research and vaccine trials. Because of widespread COVID-19 vaccination, the anti-nucleocapsid antibody continues to serve as a valuable marker for individuals without a history of COVID-19. This study aimed to comprehensively assess anti-nucleocapsid antibody positivity using diverse commercial and in-house immunoassays among individuals who contracted COVID-19 more than 3 years ago. We enrolled 44 participants with laboratory-confirmed COVID-19 between January and May 2020 from Seoul National University Hospital and its community treatment centers. The results showed anti-nucleocapsid antibody positivities ranged from 45.5% to 87.9% depending upon the immunoassay used. The study highlights the importance of considering the limited anti-nucleocapsid antibody positivity in participants with a distant COVID-19 history in seroepidemiological or vaccine research.

Musculoskeletal Pain, Physical Activity, Muscle Mass, and Mortality in Older Adults: Results from the Korean Longitudinal Study on Health and Aging (KLoSHA).

Background and objectives: Musculoskeletal (MSK) pain significantly impacts physical activity and quality of life in older adults, potentially influencing mortality. This study explored the relationship between MSK pain, physical activity, muscle mass, and mortality among older adults. Material and Methods: We studied 1000 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA), a prospective, population-based cohort study of people aged 65 years or older. Survival status was tracked over a 5-year period. Correlations between low back pain (LBP), knee pain, regular exercise, appendicular skeletal muscle mass (ASM), and other variables were analyzed. Logistic regression analyses were used to identify independent risk factors for mortality. Results: Of the total participants, 829 (82.9%) survived over a 5-year period. Survivors tended to be younger, had a higher BMI, and were more active in regular exercise. In contrast, non-survivors exhibited a higher prevalence of both LBP and knee pain, along with increased instances of multiple MSK pains. Lower ASM correlated moderately with LBP and knee pain, whereas higher ASM was associated with regular exercise. There was a moderate correlation between LBP and knee pain, both of which were associated with a lack of regular exercise. Age, sex, ASM, and regular exercise were significant predictors, even though MSK pain itself did not directly predict all-cause mortality. Conclusions: This study demonstrated the independent association between ASM, regular exercise, and mortality. Although MSK pain did not directly correlate with all-cause mortality, the non-survivor group had higher levels of both single and multiple MSK pains. Recognizing the interplay of MSK pain, physical activity, and muscle mass for older adults, the research underscores the need for holistic strategies to enhance health outcomes in older individuals with MSK pain.

Clinical outcomes and immunological features of COVID-19 patients receiving B-cell depletion therapy during the Omicron era.

Background: The clinical outcomes and immunological features of coronavirus disease 2019 (COVID-19) patients receiving B-cell depletion therapy (BCDT), especially in Omicron variant era, have not been fully elucidated. We aimed to investigate the outcomes and immune responses of COVID-19 patients receiving BCDT during the Omicron period.Methods: We retrospectively compared clinical outcomes between COVID-19 patients treated with BCDT (the BCDT group) and those with the same underlying diseases not treated with BCDT (the non-BCDT group). For immunological analyses, we prospectively enrolled COVID-19 patients receiving BCDT and immunocompetent COVID-19 patients as controls. We measured humoral and cellular immune responses using the enzyme-linked immunosorbent assay and flow cytometry.Results: Severe to critical COVID-19 was more frequent in the BCDT group than in the non-BCDT group (41.9% vs. 28.3%, p = .030). BCDT was an independent risk factor for severe to critical COVID-19 (adjusted odds ratio [aOR] 2.21, 95% confidence interval [CI] 1.21-4.04, p = .010) as well as for COVID-19-related mortality (aOR 4.03, 95% CI 1.17-13.86, p = .027). Immunological analyses revealed that patients receiving BCDT had lower anti-S1 IgG titres and a tendency to higher proportions of activated CD4+ T-cells than the controls.Conclusions: BCDT was associated with worse COVID-19 outcomes in the Omicron period. Humoral immune response impairment and T-cell hyperactivation were the main immunological features of COVID-19 patients treated with BCDT, which may have contributed to the worse outcomes of COVID-19 in this population.

Tracking antigen-specific TCR clonotypes in SARS-CoV-2 infection reveals distinct severity trajectories.

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.

Malnutrition and Associated Factors in Acute and Subacute Stroke Patients with Dysphagia.

Most patients with stroke suffer from complications and these include dysphagia. Dysphagia can cause malnutrition, and malnutrition affects prognosis and recovery. However, there is a lack of accurate studies on the nutritional status of stroke patients with dysphagia and its associated factors in different phases of stroke. This study retrospectively investigated 620 stroke patients who underwent a videofluoroscopic swallowing study (VFSS) due to dysphagia, from March 2018 to February 2021. The study aimed to evaluate the nutritional state and associated factors of malnutrition in acute and subacute stroke patients with dysphagia. Serum albumin and percentage of current weight to ideal weight were used to determine nutritional status. Malnutrition was observed in 58.9 and 78.9% of acute and subacute stroke patients. Exact logistic regression analysis revealed that old age and high penetration-aspiration scale score were significantly associated factors for malnutrition in patients with acute stroke. Old age, stroke history, bilateral hemiplegia, high modified Rankin score, low Korean Mini-Mental State Examination, pneumonia, and high functional dysphagia score were significantly associated factors for malnutrition in patients with subacute stroke. Patients with these associated factors in each phase of stroke require active nutritional assessment and care to decrease the risk of malnutrition.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Background: Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. Methods: We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Results: Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Conclusions: Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

Neurophysiological Effects of Electrical Stimulation on a Patient with Neurogenic Bowel Dysfunction and Cauda Equina Syndrome after Spinal Anesthesia: A Case Report.

Neurogenic bowel dysfunction (NBD) is common in patients with cauda equina syndrome (CES). Previous studies have reported that electrical stimulation (ES) improves NBD but more neurophysiologic evidence is required. This case report describes a patient who experienced difficulty with defecation as a result of cauda equina syndrome (CES) that developed after a cesarean section performed 12 years ago under spinal anesthesia. The neurophysiological effects were assessed using the bulbocavernosus reflex (BCR) and electromyography (EMG). Two ES treatments, interferential current therapy and transcutaneous electrical stimulation, were used to stimulate the intestine and the external anal sphincter, respectively. The BCR results showed right-side delayed latency and no response on the left side. Needle EMG revealed abnormal spontaneous activities of the bilateral bulbocavernosus (BC) muscles. Electrodiagnostic testing revealed chronic bilateral sacral polyradiculopathy, compatible with CES. After treatment, the patient reported an improved perianal sensation, less strain and time for defecation than before, and satisfaction with her bowel condition. At the follow-up electrodiagnosis, the BCR latency was normal on the right side-needle EMG revealed reductions in the abnormal spontaneous activities of both BC muscles and re-innervation of the right BC muscle. Electrodiagnostic testing can offer insight into the neurophysiological effects of ES, which can help in understanding the mechanism of action and optimizing the therapy for patients with NBD.

Comparable humoral and cellular immunity against Omicron variant BA.4/5 of once-boosted BA.1/2 convalescents and twice-boosted COVID-19-naïve individuals.

The fourth vaccination dose confers additional protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with no prior coronavirus disease-19 (COVID-19). However, its immunological benefit against currently circulating BA.4/5 is unclear in individuals who have received a booster shot and been infected with Omicron variant BA.1/2. We analyzed immune responses in whom had been boosted once and did not have COVID-19 (n = 16), boosted once and had COVID-19 when BA.1/2 was dominant in Korea (Hybrid-6M group, n = 27), and boosted twice and did not have COVID-19 (Vx4 group, n = 15). Antibody binding activities against RBDo BA.1 and RBDo BA.4/5 , antigen-specific memory CD4+ and CD8+ T-cell responses against BA.4/5, and B-cell responses against SARS-CoV-2 wild-type did not differ statistically between the Hybrid-6M and Vx4 groups. The humoral and cellular immune responses of the Hybrid-6M group against BA.4/5 were comparable to those of the Vx4 group. Individuals who had been boosted and had an Omicron infection in early 2022 may not have high priority for an additional vaccination.

Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice, an AD model.

BACKGROUND: Aducanumab (Adu), which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid, has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose (10 mg/kg) of the drug in Alzheimer's disease (AD) clinical trials. The purpose of this study was to investigate the effects of a lower dose of Adu (3 mg/kg) with enhanced delivery via focused ultrasound (FUS) in an AD mouse model. METHODS: The FUS with microbubbles opened the blood-brain barrier (BBB) of the hippocampus for the delivery of Adu. The combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly. Y-maze test, Brdu labeling, and immunohistochemical experimental methods were employed in this study. In addition, RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental animals. RESULTS: The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the brains. The combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS alone. Combined treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD mice. Furthermore, RNA sequencing identified that 4 enriched canonical pathways including phagosome formation, neuroinflammation signaling, CREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined treatment. CONCLUSION: In conclusion, the enhanced delivery of a low dose of Adu (3 mg/kg) via FUS decreases amyloid deposits and attenuates cognitive function deficits. FUS-mediated BBB opening increases adult hippocampal neurogenesis as well as drug delivery. We present an AD treatment strategy through the synergistic effect of the combined therapy of FUS and Adu.

Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC). Methods: In this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group. Results: All participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC. Conclusion: In the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.

Integrative analyses of genes about venous thromboembolism: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: In recent years, many studies have found possible links between gene polymorphisms and venous thromboembolism (VTE). By identifying genetic risk factors before facing environmental risk factors such as surgical interventions and COVID-19 vaccination, we could rapidly respond to the risk of VTE. The aim of this study was to perform an umbrella review of genetic variants related to VTE. Integrative gene analysis of VTE was performed to identify critical genetic variations. METHODS: This study conducted an umbrella review of systematic reviews and meta-analyses. All included studies were selected from the PubMed/MEDLINE database. To select eligible studies, the following variables were extracted: first author name; effect size of each study genetic variant; year of publication; the number of studies included in each article; ethnicity, sample size, P values, and heterogeneity estimates. To assess cumulative evidence in genetic epidemiology about effects of gene polymorphisms on VTE, Human Genome Epidemiology Network's Venice criteria were used. Methodological quality assessment was conducted with JBI Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. RESULTS: Genes provided in the present study with genetic variants associated with VTE were FVL (G1691A), Prothrombin (G20210A), MTHFR (C677T, A1298C), PAI-1 (4G/5G), factor VII activating protease (1601G > A), and endothelial protein C receptor (g.6936A_G, c.4600A_G). Among them, variants in FVL, Prothrombin, MTHFR, and PAI-1 showed high significance. Particularly, variants in Prothrombin (G20210A), MTHFR (C677T), and PAI-1 (4G/5G) had more than 2 types of model significance. CONCLUSION: The present study performed a systematic review of genetic variants associated with VTE. Our results could lead to a more comprehensive understanding of VTE etiology. These results could give a strategy of prediagnosis about evaluating individual risks of VTE who might be exposed to environmental risk factors.

Robot-assisted rehabilitation for total knee or hip replacement surgery patients: A systematic review and meta-analysis.

BACKGROUND: This study was performed to update the current evidence and evaluate the effects of robot-assisted rehabilitation (RAR) in comparison with conventional rehabilitation (CR) in patients following total knee (TKR) or hip replacements (THR). METHODS: PubMed Central, OVID Medline, Cochrane Collaboration Library, and EMBASE for a comprehensive search for all relevant studies, from database inception to July 2022. The following inclusion criteria were used to determine eligibility for studies: randomized and matched controlled trials recruiting men and women who underwent TKR and THR; and studies examining the effect of RAR on outcome measures of physical function and pain. RESULTS: A total of 9 studies (230 patients) were included in this review and 4 were included in the meta-analysis. The meta-analysis of 2 studies showed that Hybrid Assistive Limb (HAL) training for 5 days, significantly improved pain measured on a visual analogue scale, compared to CR in patients following TKR (SMD = 1.05, 95% confidence interval [Cl] 0.39-1.71). Heterogeneity for I2 value was lower than moderate (tau^2 = 0.0121; I2 = 5%; P = .30). There were 2 studies that assessed self-selected walking speed. The meta-analysis of these studies showed that HAL training was significantly superior to CR in patients following TKR (SMD = 48.70, 95% Cl -50.53 to 147.94) at 2 months. A high heterogeneity was detected (P < .01; I2 = 97%). CONCLUSION: The result of this systematic review and meta-analysis suggest that RAR may be an effective treatment in TKR and THR patients. However, high-quality studies are needed to verify the long-term effect on their recovery.

Effects of preoperative personal education on shoulder function and lymphedema in patients with breast cancer: A consort.

BACKGROUND: To compare the incidence and severity of ipsilateral shoulder dysfunction and lymphedema of 2 groups of patients needing to undergo unilateral breast cancer surgery, one of which had only received printed education materials and the other group which had received educational materials plus preoperative education. METHODS: We selected 61 patients who had been diagnosed with unilateral breast cancer and planned to undergo surgery. Before surgery, patients were randomly assigned, either to a control group that only received printed education materials about exercise for shoulder pain relief and lymphatic edema prevention following breast cancer surgery, or to an experimental group that received the printed education material with personal education. Participants were evaluated at 1, 3, 6, and 12 months after the surgery. To evaluate the impairment of shoulder function, we measured the passive shoulder range of motion (ROM), the degree of pain as visual analog scale (VAS), the short version of the disability of arm, shoulder, and hand (short DASH) scores, and the shoulder pain and disability index (SPADI). We checked arm circumferences to evaluate lymphedema. RESULTS: There was no significant difference in demographic or clinical variables between the control and experimental groups. The experimental group showed significantly less limitation in abduction (P = .042) and forward flexion (P = .039) in the 6 months following surgery. Change in the VAS, short DASH, and SPADI scores were 1.633 (P < .001), 2.167 (P < .001), and 4.1 (P = .003) at 1 month following surgery, respectively. These then decreased with time. These changes started before shoulder ROM and arm circumference changes had occurred, which had started 3 months following surgery. CONCLUSIONS: Preoperative education might be helpful for the prevention of a shoulder ROM limitation, and we need to focus on pain and disability in patients immediately following breast cancer surgery, and then on ROM and lymphedema.

The acidic tumor microenvironment enhances PD-L1 expression via activation of STAT3 in MDA-MB-231 breast cancer cells.

Tumor acidosis, a common phenomenon in solid cancers such as breast cancer, is caused by the abnormal metabolism of cancer cells. The low pH affects cells surrounding the cancer, and tumor acidosis has been shown to inhibit the activity of immune cells. Despite many previous studies, the immune surveillance mechanisms are not fully understood. We found that the expression of PD-L1 was significantly increased under conditions of extracellular acidosis in MDA-MB-231 cells. We also confirmed that the increased expression of PD-L1 mediated by extracellular acidosis was decreased when the pH was raised to the normal range. Gene set enrichment analysis (GSEA) of public breast cancer patient databases showed that PD-L1 expression was also highly correlated with IL-6/JAK/STAT3 signaling. Surprisingly, the expression of both phospho-tyrosine STAT3 and PD-L1 was significantly increased under conditions of extracellular acidosis, and inhibition of STAT3 did not increase the expression of PD-L1 even under acidic conditions in MDA-MB-231 cells. Based on these results, we suggest that the expression of PD-L1 is increased by tumor acidosis via activation of STAT3 in MDA-MB-231 cells.

Corrigendum: Distinct Immune Response at 1 Year Post-COVID-19 According to Disease Severity.

[This corrects the article DOI: 10.3389/fimmu.2022.830433.].

Broad humoral and cellular immunity elicited by one-dose mRNA vaccination 18 months after SARS-CoV-2 infection.

BACKGROUND: Practical guidance is needed regarding the vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals in resource-limited countries. It includes the number of vaccine doses that should be given to unvaccinated patients who experienced COVID-19 early in the pandemic. METHODS: We recruited COVID-19 convalescent individuals who received one or two doses of an mRNA vaccine within 6 or around 18 months after a diagnosis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Their samples were assessed for IgG-binding or neutralizing activity and cell-mediated immune responses against SARS-CoV-2 wild-type and variants of concern. RESULTS: A total of 43 COVID-19 convalescent individuals were analyzed in the present study. The results showed that humoral and cellular immune responses against SARS-CoV-2 wild-type and variants of concern, including the Omicron variant, were comparable among patients vaccinated within 6 versus around 18 months. A second dose of vaccine did not significantly increase immune responses. CONCLUSION: One dose of mRNA vaccine should be considered sufficient to elicit a broad immune response even around 18 months after a COVID-19 diagnosis.

Distinct Immune Response at 1 Year Post-COVID-19 According to Disease Severity.

Background: Despite the fact of ongoing worldwide vaccination programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding longevity, breadth, and type of immune response to coronavirus disease-19 (COVID-19) is still important to optimize the vaccination strategy and estimate the risk of reinfection. Therefore, we performed thorough immunological assessments 1 year post-COVID-19 with different severity. Methods: We analyzed peripheral blood mononuclear cells and plasma samples at 1 year post-COVID-19 in patients who experienced asymptomatic, mild, and severe illness to assess titers of various isotypes of antibodies (Abs) against SARS-CoV-2 antigens, phagocytic capability, and memory B- and T-cell responses. Findings: A total of 24 patients (7, 9, and 8 asymptomatic, mild, and severe patients, respectively) and eight healthy volunteers were included in this study. We firstly showed that disease severity is correlated with parameters of immune responses at 1 year post-COVID-19 that play an important role in protecting against reinfection with SARS-CoV-2, namely, the phagocytic capacity of Abs and memory B-cell responses. Interpretation: Various immune responses at 1 year post-COVID-19, particularly the phagocytic capacity and memory B-cell responses, were dependent on the severity of the prior COVID-19. Our data could provide a clue for a tailored vaccination strategy after natural infection according to the severity of COVID-19.