Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor.

Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to show that cancer cells release succinate into their microenvironment and activate succinate receptor (SUCNR1) signaling to polarize macrophages into TAM. Furthermore, the results from in vitro and in vivo studies revealed that succinate promotes not only cancer cell migration and invasion but also cancer metastasis. These effects are mediated by SUCNR1-triggered PI3K-hypoxia-inducible factor 1α (HIF-1α) axis. Compared with healthy subjects and tumor-free lung tissues, serum succinate levels and lung cancer SUCNR1 expression were elevated in lung cancer patients, suggesting an important clinical relevance. Collectively, our findings indicate that the secreted tumor-derived succinate belongs to a novel class of cancer progression factors, controlling TAM polarization and promoting tumorigenic signaling.

A Noninferiority Trial Comparing 2 Days vs 5 Days of Terlipressin and Ceftriaxone in Terms of 5-Day Rebleeding for Patients With Acute Gastroesophageal Variceal Hemorrhage.

INTRODUCTION: This trial was to shorten the duration of both vasoconstrictors and prophylactic antibiotics to only 2 days in the therapy of acute gastroesophageal variceal hemorrhage. METHODS: After successful endoscopic hemostasis of gastroesophageal variceal hemorrhage, eligible patients were randomized to receive terlipressin infusion 1 mg per 6 hours and ceftriaxone 1 g daily for 5 days (group A) or a similar regimen for 2 days (group B). Primary end points were very early rebleeding at 5 days, and secondary end points included 48-hour hemostasis, 42-day rebleeding, and hospitalization days. RESULTS: Group A comprised 48 patients, and group B comprised 52 patients. Both groups were comparable in the severity of liver disease. Forty-eight-hour initial hemostasis was 95.8% in group A and 100% in group B ( P = 0.13). Very early rebleeding between 3 and 5 days occurred in 1 patient (2.1%) in group A and 2 patients (3.8%) in group B ( P = 0.60). The difference was 1.8% and the 95% confidence interval was -1.31% to 2.08%, which demonstrated noninferiority. Forty-two-day rebleeding occurred in 5 patients (10.4%) in group A and 4 patients (7.7%) in group B ( P = 0.63). The median hospitalization days were 8.5 ± 3.8 days in group A vs 5.6 ± 2.6 days in group B ( P < 0.001). DISCUSSION: After successful endoscopic hemostasis of acute variceal bleeding, combination of 2-day terlipressin infusion and ceftriaxone therapy was not inferior to the 5-day regimen in terms of very early rebleeding, with the advantage of shortening hospitalization stay.

The Effects of Light Therapy on Sleep, Depression, Neuropsychiatric Behaviors, and Cognition Among People Living With Dementia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms significantly impact sleep, emotional, and cognitive functions, with its synchronization depending on light exposure. We performed a meta-analysis to evaluate the effects of light therapy on sleep, depression, neuropsychiatric behaviors, and cognition among PLWD. METHODS: A systematic search was conducted in Cochrane, ClinicalTrials.gov, Embase, EBSCOhost, Ovid-MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The pooled effect size was calculated using the Hedges' g with random-effects model adopted in comprehensive meta-analysis software. The Cochrane risk of bias (RoB 2.0) tool evaluated the quality of studies, while Cochrane's Q and I² tests assessed heterogeneity. RESULTS: A total of 24 studies with 1,074 participants were included. Light therapy demonstrated small-to-medium effects on improving sleep parameters: total sleep time (Hedges' g = 0.19), wake after sleep onset (Hedges' g = 0.24), sleep efficiency (Hedges' g = 0.31), sleep latency (Hedges' g = 0.35), circadian rhythm (acrophase: Hedges' g = 0.36; amplitude: Hedges' g = 0.43), number of night awakenings (Hedges' g = 0.37), sleep disturbance (Hedges'g = 0.45), and sleep quality (Hedges' g = 0.60). Light therapy showed small-to-medium effect on reducing depression (Hedges' g = -0.46) with medium-to-large effect on cyclical function (Hedges' g = -0.68) and mood-related signs and symptoms (Hedges' g = -0.84) subscales. Light therapy also demonstrated small effect on reducing neuropsychiatric behaviors (Hedges' g = -0.34) with medium-to-large effect on agitation (Hedges' g = -0.65), affective symptom (Hedges' g = -0.70), psychosis (Hedges' g = -0.72), and melancholic behavior (Hedges' g = -0.91) subscales. Additionally, light therapy also improved cognition (Hedges' g = 0.39). CONCLUSION: Light therapy could be used as a supportive therapy to improve sleep, depression, cognition, and neuropsychiatric behaviors among PLWD.

Prevalence of swallowing disorder in different dementia subtypes among older adults: a meta-analysis.

BACKGROUND: Ageing process and abnormal protein accumulation in dementia damage neural pathways affecting the swallowing process and leading to swallowing disorder. OBJECTIVE: To estimate the prevalence of swallowing disorder among older adults with different dementia subtypes. METHODS: We conducted a systematic search across multiple databases, including PubMed, Embase, Scopus, Web of Science and OVID Medline. The meta-analysis employed R (version 4.0.2) and utilised a generalised linear mixed model with a random-effect approach to estimate the pooled prevalence of swallowing disorder among older adults, considering various dementia subtypes. The quality of included studies was assessed using Hoy's criteria. Heterogeneity was identified through Cochrane's Q and I2 statistics. To further explore heterogeneity, moderator analysis was performed to identify the contributing variables among the included studies. RESULTS: Eighteen studies with 12,532 older adults with different dementia subtypes were enrolled in our meta-analysis. The pooled prevalence of swallowing disorder among older adults with dementia was 58%, with 46.5% for Alzheimer's dementia, 34.9% for Parkinson's dementia, 18.8% for vascular dementia, 16.3% for mixed dementia and 12.2% for Lewy body dementia. According to assessment tools, Alzheimer's dementia had the highest prevalence, with 58% in instrumental assessments and 39% in clinical assessments. Medical history, Alzheimer's dementia, moderate-to-severe Clinical Dementia Rating, delayed oral phase, delayed pharyngeal phase and poor tongue motility contributed to the heterogeneity of the included studies. CONCLUSIONS: More than half of older adults with dementia demonstrate to have swallowing disorder. Our findings offer valuable insights to healthcare professionals for the identification of swallowing disorder in ageing population with dementia.

Percutaneous transluminal angioplasty and stenting of post-irradiated stenosis of subclavian artery: A matched case-control study.

BACKGROUND: Although radiotherapy is common for head/neck and chest cancers (HNCC), it can result in post-irradiation stenosis of the subclavian artery (PISSA). The efficacy of percutaneous transluminal angioplasty and stenting (PTAS) to treat severe PISSA is not well-clarified. AIMS: To compare the technical safety and outcomes of PTAS between patients with severe PISSA (RT group) and radiation-naïve counterparts (non-RT group). METHODS: During 2000 and 2021, we retrospectively enrolled patients with severe symptomatic stenosis (>60%) of the subclavian artery who underwent PTAS. The rate of new recent vertebrobasilar ischaemic lesions (NRVBIL), diagnosed on diffusion-weight imaging (DWI) within 24 h of postprocedural brain MRI; symptom relief; and long-term stent patency were compared between the two groups. RESULTS: Technical success was achieved in all 61 patients in the two groups. Compared with the non-RT group (44 cases, 44 lesions), the RT group (17 cases, 18 lesions) had longer stenoses (22.1 vs 11.1 mm, P = 0.003), more ulcerative plaques (38.9% vs 9.1%, P = 0.010), and more medial- or distal-segment stenoses (44.4% vs 9.1%, P<0.001). The technical safety and outcome between the non-RT group and the RT group were NRVBIL on DWI of periprocedural brain MRI 30.0% vs 23.1%, P = 0.727; symptom recurrence rate (mean follow-up 67.1 ± 50.0 months) 2.3% vs 11.8%, P = 0.185; and significant in-stent restenosis rate (>50%) 2.3% vs 11.1%, P = 0.200. CONCLUSION: The technical safety and outcome of PTAS for PISSA were not inferior to those of radiation-naïve counterparts. PTAS for PISSA is an effective treatment for medically refractory ischaemic symptoms of HNCC patients with PISSA.

Effectiveness of respiratory rehabilitation in patients with COVID-19: A meta-analysis.

AIM: Examine effectiveness of respiratory rehabilitation and moderating factors on lung function and exercise capacity in post-COVID-19 patients. DESIGN: Meta-analysis. METHODS: R software 4.0.2 assessed the effectiveness of respiratory rehabilitation adopting the random-effects model and presenting standardised mean differences (SMDs). Heterogeneity was determined by Cochran's Q and I2 . The Cochrane Risk of Bias 2.0 and MINORS evaluated quality of the included studies. DATA SOURCES: A comprehensive search was undertaken in Cochrane, Embase, Ovid-MEDLINE, Scopus, NCBI SARS-CoV-2 Resources, ProQuest, Web of Science and CINAHL until March 2022. RESULTS: Of the 5703 identified studies, 12 articles with 596 post-COVID-19 patients were included. Eleven of our twelve studies had moderate to high quality and one study had high risk of bias assessed with MINORS and RoB 2 tool. Overall, respiratory rehabilitation was effective in improving forced expiratory volume in 1 s (1.14; 95%CI 0.39-1.18), forced vital capacity (0.98; 95%CI 0.39-1.56), total lung capacity (0.83; 95%CI 0.22-1.44), 6-minute walk distance (1.56; 95%CI 1.10-2.02) and quality of life (0.99; 95%CI 0.38-1.60). However, no significant differences were observed for ratio of the forced expiratory volume in 1 s to the forced vital capacity of the lungs, anxiety and depression. Respiratory rehabilitation for post-COVID-19 patients was effective in those without comorbidities, performed four types of exercise programs, frequency ≥3 times/week and rehabilitation time 6 weeks. CONCLUSIONS: Respiratory rehabilitation improved lung function, exercise capacity and quality of life in post-COVID-19 patients. The findings suggest rehabilitation programs for post-COVID-19 patients should use multiple respiratory exercise programs with frequency of ≥3 times per week for longer than 6 weeks. IMPACT: These findings will help improve the implementation of respiratory rehabilitation programs for post-COVID-19 patients. IMPLICATIONS FOR THE PROFESSION: Our findings can be used to develop patient-centred respiratory rehabilitation interventions by nurses and clinicians for post-COVID-19 patients. REPORTING METHOD: PRISMA guideline was followed. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Percutaneous transluminal angioplasty and stenting of post-irradiation stenosis of the vertebral artery.

BACKGROUND: The outcomes of percutaneous transluminal angioplasty and stenting (PTAS) in patients with medically refractory post-irradiation stenosis of the vertebral artery (PISVA) have not been clarified. AIM: This retrospective study evaluated the safety and outcomes of PTAS in patients with severe PISVA compared with their radiation-naïve counterparts (non-RT group). METHODS: Patients with medically refractory severe symptomatic vertebral artery stenosis and undergoing PTAS between 2000 and 2021 were classified as the PISVA group or the non-RT group. The periprocedural neurological complications, periprocedural brain magnetic resonance imaging, the extent of symptom relief, and long-term stent patency were compared. RESULTS: As compared with the non-RT group (22 cases, 24 lesions), the PISVA group (10 cases, 10 lesions) was younger (62.0 ± 8.6 vs 72.4 ± 9.7 years, P = 0.006) and less frequently had hypertension (40.0% vs 86.4%, P = 0.013) and diabetes mellitus (10.0% vs 54.6%, P = 0.024). Periprocedural embolic infarction was not significantly different between the non-RT group and the PISVA group (37.5% vs 35.7%, P = 1.000). At a mean follow-up of 72.1 ± 58.7 (3-244) months, there was no significant between-group differences in the symptom recurrence rate (0.00% vs 4.55%, P = 1.000) and in-stent restenosis rate (10.0% vs 12.5%, P = 1.000). CONCLUSION: PTAS of severe medically refractory PISVA is effective in the management of vertebrobasilar ischemic symptoms in head and neck cancer patients. Technical safety and outcome of the procedure were like those features in radiation-naïve patients.

Underestimated Subsequent Sensorineural Hearing Loss after Septicemia.

Background and Objectives: Hearing loss after septicemia has been found in mice; the long-term risk increased 50-fold in young adults in a previous study. Hearing loss after septicemia has not received much attention. The aim of this study was to assess the relationship between septicemia and subsequent hearing loss. Materials and Methods: Inpatient data were obtained from the Taiwan Insurance Database. We defined patients with sensorineural hearing loss and excluded patients under 18 years of age. Patients without hearing loss were selected as controls at a frequency of 1:5. The date of admission was defined as the date of diagnosis. Comorbidities in the 3 years preceding the date of diagnosis were retrieved retrospectively. Associations with hearing loss were established by multiple logistic regression and forward stepwise selection. Results: The odds ratio (OR) for the association between sepsis and hearing loss was 3.052 (95% CI: 1.583-5.884). Autoimmune disease (OR: 5.828 (95% CI: 1.906-17.816)), brain injury (OR: 2.264 (95% CI: 1.212-4.229)) and ischemic stroke (OR: 1.47 (95% CI: 1.087-1.988)) were associated with hearing loss. Conclusions: Our study shows that hearing loss occurred after septicemia. Apoptosis caused by sepsis and ischemia can lead to hair cell damage, leading to hearing loss. Clinicians should be aware of possible subsequent complications of septicemia and provide appropriate treatment and prevention strategies for complications.

Underestimated Ischemic Heart Disease in Major Adverse Cardiovascular Events after Septicemia Discharge.

Background and Objectives: Sepsis increases cardiovascular disease and causes death. Ischemic heart disease (IHD) without acute myocardial infarction has been discussed less, and the relationship between risk factors and IHD in septicemia survivors within six months is worthy of in-depth study. Our study demonstrated the incidence of IHD and the possible risk factors for IHD in septicemia patients within six months. Materials and Methods: An inpatient dataset of the Taiwanese Longitudinal Health Insurance Database between 2001 and 2003 was used. The events were defined as rehospitalization of stroke and IHD after discharge or death within six months after the first septicemia hospitalization. The relative factors of major adverse cardiovascular events (MACEs) and IHD were identified by multivariate Cox proportional regression. Results: There were 4323 septicemia survivors and 404 (9.3%) IHD. New-onset atrial fibrillation had a hazard ratio (HR) of 1.705 (95% confidence interval (C.I.): 1.156-2.516) for MACEs and carried a 184% risk with HR 2.836 (95% C.I.: 1.725-4.665) for IHD by adjusted area and other risk factors. Conclusions: This study explored advanced-aged patients who experienced more severe septicemia with new-onset atrial fibrillation, which increases the incidence of IHD in MACEs within six months of septicemia. Therefore, healthcare providers must identify patients with a higher IHD risk and modify risk factors beforehand.

Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy.

Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.

Hemogram parameters can predict in-hospital mortality of patients with Myasthenic crisis.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease involving the neuromuscular junction. Myasthenic crisis (MC), which is characterized by respiratory failure and the requirement of mechanical ventilation in patients with MG, is still a medical emergency despite the decrease in mortality with the advances in acute management. Hemogram is a cost-effective test for evaluating hematological complications and systemic inflammation, and hemogram data have been used to predict various clinical outcomes of several diseases. The relationship between hemogram and MG has been discussed, but the role of hemogram data in predicting the prognosis of MC patients has not been established. METHODS: To identify whether hemogram data can predict in-hospital mortality in patients with MC, we retrospectively investigated 188 myasthenic crisis events from the Chang Gung Research Database between April 2001 and March 2019. Demographic and clinical characteristics were collected, as well as hemogram data before intubation and extubation. The endpoints were mortality during mechanical ventilation and mortality after extubation. RESULTS: The overall in-hospital mortality rate was 22%. Multivariate logistic regression analysis for predicting mortality during mechanical ventilation showed that old age at MC onset (OR = 1.039, p = 0.022), moderate-to-severe anemia (OR = 5.851, p = 0.001), and extreme leukocytosis (OR = 5.659, p = 0.022) before intubation were strong predictors of mortality, while acute management with plasma exchange or double-filtration plasmapheresis (PE/DFPP) significantly decreased mortality (OR = 0.236, p = 0.012). For predicting mortality after extubation, moderate-to-severe anemia before extubation (OR = 8.452, p = 0.017) and non-treated with disease-modifying therapy before MC (OR = 5.459, p = 0.031) were crucial predictive factors. CONCLUSION: This study demonstrated that both old age at MC onset and moderate-to-severe anemia are important predictors of in-hospital mortality in patients with MC, and extreme leukocytosis is another crucial predictor of mortality during mechanical ventilation. The suggested mechanism is that anemia-induced hypoxia may enhance the release of proinflammatory cytokines, exacerbate systemic inflammation, and lead to multiple organ dysfunction syndrome and, finally, mortality.

Structure-Based Functional Analysis of a Hormone Belonging to an Ecdysozoan Peptide Superfamily: Revelation of a Common Molecular Architecture and Residues Possibly for Receptor Interaction.

A neuropeptide (Sco-CHH-L), belonging to the crustacean hyperglycemic hormone (CHH) superfamily and preferentially expressed in the pericardial organs (POs) of the mud crab Scylla olivacea, was functionally and structurally studied. Its expression levels were significantly higher than the alternative splice form (Sco-CHH) in the POs, and increased significantly after the animals were subjected to a hypo-osmotic stress. Sco-CHH-L, but not Sco-CHH, significantly stimulated in vitro the Na+, K+-ATPase activity in the posterior (6th) gills. Furthermore, the solution structure of Sco-CHH-L was resolved using nuclear magnetic resonance spectroscopy, revealing that it has an N-terminal tail, three α-helices (α2, Gly9-Asn28; α3, His34-Gly38; and α5, Glu62-Arg72), and a π-helix (π4, Cys43-Tyr54), and is structurally constrained by a pattern of disulfide bonds (Cys7-Cys43, Cys23-Cys39, and Cys26-Cys52), which is characteristic of the CHH superfamily-peptides. Sco-CHH-L is topologically most similar to the molt-inhibiting hormone from the Kuruma prawn Marsupenaeus japonicus with a backbone root-mean-square-deviation of 3.12 Å. Ten residues of Sco-CHH-L were chosen for alanine-substitution, and the resulting mutants were functionally tested using the gill Na+, K+-ATPase activity assay, showing that the functionally important residues (I2, F3, E45, D69, I71, and G73) are located at either end of the sequence, which are sterically close to each other and presumably constitute the receptor binding sites. Sco-CHH-L was compared with other members of the superfamily, revealing a folding pattern, which is suggested to be common for the crustacean members of the superfamily, with the properties of the residues constituting the presumed receptor binding sites being the major factors dictating the ligand-receptor binding specificity.

A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhage.

BACKGROUND: Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. METHODS: 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. RESULTS: Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P > 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P < 0.001, 95 % confidence interval [CI] 8 % - 27 %). Complications occurred in 4 (12.1 %) and 18 (51.4 %) patients in the thrombin and glue groups, respectively (P < 0.001, 95 %CI 22 % - 45 %). Two patients who received glue had post-treatment gastric ulcer bleeding. One patient in each group died. CONCLUSIONS: Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.

TLR2 Promotes Vascular Smooth Muscle Cell Chondrogenic Differentiation and Consequent Calcification via the Concerted Actions of Osteoprotegerin Suppression and IL-6-Mediated RANKL Induction.

Objective- Vascular smooth muscle cell (VSMC) transformation to an osteochondrogenic phenotype is an initial step toward arterial calcification, which is highly correlated with cardiovascular disease-related morbidity and mortality. TLR2 (Toll-like receptor 2) plays a pathogenic role in the development of vascular diseases, but its regulation in calcification of arteries and VSMCs remains unclear. We postulate that TLR2-mediated inflammation participates in mediating atherosclerotic arterial calcification and VSMC calcification. Approach and Results- We found that ApoE-/- Tlr2-/- genotype in mice suppressed high-fat diet-induced atherosclerotic plaques formation during initiation but progressively lost its preventative capacity, compared with ApoE-/- mice. However, TLR2 deficiency prohibited high-fat diet-induced advanced atherosclerotic calcification, chondrogenic metaplasia, and OPG (osteoprotegerin) downregulation in the calcified lesions. Incubation of VSMCs in a calcifying medium revealed that TLR2 agonists significantly increased VSMC calcification and chondrogenic differentiation. Furthermore, TLR2 deficiency suppressed TLR2 agonist-mediated VSMC chondrogenic differentiation and consequent calcification, which were triggered via the concerted actions of IL (interleukin)-6-mediated RANKL (receptor activator of nuclear factor κB ligand) induction and OPG suppression. Inhibition experiments with pharmacological inhibitors demonstrated that IL-6-mediated RANKL induction is signaled by p38 and ERK1/2 (extracellular signal-regulated kinase 1/2) pathways, whereas the OPG is suppressed via NF-κB (nuclear factor κB) dependent signaling mediated by ERK1/2. Conclusions- We concluded that on ligand binding, TLR2 activates p38 and ERK1/2 signaling to selectively modulate the upregulation of IL-6-mediated RANKL and downregulation of OPG. These signaling pathways act in concert to induce chondrogenic transdifferentiation of VSMCs, which in turn leads to vascular calcification during the pathogenesis of atherosclerosis.

Neuropsychiatric symptoms in Parkinson's disease: association with caregiver distress and disease severity.

OBJECTIVES: The condition of caregivers is important to the quality of care received by people with Parkinson's disease (PD), especially at the late disease stages. This study addresses the distress placed on caregivers by participants' neuropsychiatric symptoms at different stages of PD in Taiwan. METHODS: This prospective study enrolled 108 people with PD. All participants were examined with the Unified Parkinson's Disease Rating Scale (UPDRS), Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), and Clinical Dementia Rating (CDR) scale. Caregiver distress was measured using the Neuropsychiatric Inventory Caregiver Distress Scale (NPI-D). Statistical analysis was used to explore the PD-related factors that contribute to caregiver distress. RESULTS: The mean follow-up interval in the 108 PD participants were 24.0 ± 10.2 months with no participant lost to follow-up due to death. NPI-distress (the sum of NPI caregiver distress scale across the 12 domains of the NPI) was positively correlated with NPI-sum (the total score across the 12 domains of the NPI) (r = 0.787, p < 0.001), CDR (r = 0.403, p < 0.001), UPRDS (r = 0.276, p = 0.004), and disease duration (r = 0.246, p = 0.002), but negatively correlated with CASI (r = -0.237, p = 0.043) and MMSE (r = -0.281, p < 0.001). Multiple linear regression analysis showed that only NPI-sum and disease duration were independently correlated with NPI-distress. CONCLUSION: The disease duration and NPI-sum are independent predictors of caregiver distress in Taiwanese populations with PD. Early detection and reduction of neuropsychiatric symptoms in people with PD can help decrease caregiver distress.

Ion regulation in the antennal glands differs among Ocypodoidea and Grapsoidea crab species.

Gills and the antennal gland are ion-regulatory organs in crabs. Previous studies have suggested that the differences in the morphology and ion regulation of gills and accessory respiratory organs between ocypodid and grapsid species are related to their distinct evolutionary transition to land habitats. In addition, Na+, K+-ATPase (NKA) activity and Na+ and NH4+ regulation in the antennal gland differ between ocypodid and grapsid species, which had different terrestrial adaptation trajectories. This study used five Ocypodoidea species and three Grapsoidea species from the intertidal and supratidal zones to further investigate the differences in ion regulation and NKA activity in the antennal gland between these crab families in different habitats. Crabs were transferred to 5 practical salinity unit (PSU) water, and osmolality, Na+ and Cl- concentrations in the urine and hemolymph, and NKA activity in the antennal gland were examined. Phylogenetic ANOVA results showed that the NKA activity in the antennal gland was higher in the ocypodid than grapsid groups, and Moran's I autocorrelation analysis also indicated that NKA activity in the antennal gland was phylogenetically correlated among crabs. K-means clustering showed a difference among the crabs in the crabs' Na+ and Cl- concentrations in the urine/hemolymph, NKA activities in the antennal gland and gill 6, and number of pairs of gills. Crabs with relatively high antennal gland NKA activity were found not only in the Ocypode species, which are better adapted to terrestrial environments, but also in two intertidal species of Gelasiminae. In conclusion, part of the Ocypodidae lineage may have a) the ability to reabsorb Na+ and b) higher NKA activity in the antennal gland than other families, and this phenomenon is phylogenetically correlated in Ocypodoidea and Grapsoidea. The physiological diversity in osmoregulation among intertidal and costal species provides a base to further investigate their ecological niches and guilds.

Enhanced salt tolerance of euryhaline tadpoles depends on increased Na+, K+-ATPase expression after salinity acclimation.

Understanding physiological responses and osmoregulatory mechanisms for dealing with salinity stress is essential to clarify how amphibians living in coastal areas adapt to fluctuating salinity levels. Euryhaline species are rare among reported tadpole species inhabiting saline habitats, and few studies addressed the osmoregulatory mechanisms. We quantified the effects of salinity acclimation on survival, osmolality, water content, ion concentration, and gill Na+, K+-ATPase (NKA) expression of euryhaline tadpoles of Fejervarya cancrivora, to examine time-course changes of osmoregulatory responses of tadpoles subjected to salinity stress and how osmoregulatory mechanisms were involved in the process. Acclimation to 10 ppt for 24 h increased tadpole survival of F. cancrivora in 15 ppt, and it activated osmoregulatory mechanisms such as increase in NKA expression, which enabled them to maintain a stable osmolality below that of the surrounding media, to reach lower sodium and chloride concentrations of body fluid, and to modulate dehydration at higher salinities. The minimum required acclimation period is shorter than that reported previously on this species and non-euryhaline tadpoles. This study highlights that these physiological mechanisms are ecologically relevant and critical for tadpoles living in coastal brackish waters, improving their survival in coastal microhabitats with highly variable salinity levels.

Ice-associated norovirus outbreak predominantly caused by GII.17 in Taiwan, 2015.

BACKGROUND: On 5 March 2015, Taiwan Centers for Disease Control was notified of more than 200 students with gastroenteritis at a senior high school during excursion to Kenting. We conducted an outbreak investigation to identify the causative agent and possible vehicle of the pathogen. METHODS: We conducted a retrospective cohort study by using a structured questionnaire to interview all students for consumed food items during their stay at the resort. Students were defined as a gastroenteritis case while having vomiting or diarrhea after the breakfast on 4 March. We inspected the environment to identify possible contamination route. We collected stool or vomitus samples from ill students, food handlers and environmental specimens for bacterial culture for common enteropathogens, reverse transcription polymerase chain reaction (RT-PCR) for norovirus and enzyme-linked immunosorbent assay (ELISA) for rotavirus. Norovirus PCR-positive products were then sequenced and genotyped. RESULTS: Of 267 students enrolled, 144 (54%) met our case definition. Regression analysis revealed elevated risk associated with iced tea, which was made from tea powder mixed with hot water and self-made ice (risk ratio 1.54, 95% confidence interval 1.22-1.98). Ice used for beverages, water before and after water filter of the ice machine and 16 stool and vomitus samples from ill students were tested positive for norovirus; Multiple genotypes were identified including GI.2, GI.4 and GII.17. GII.17 was the predominant genotype and phylogenetic analyses showed that noroviruses identified in ice, water and human samples were clustered into the same genotypes. Environmental investigation revealed the ice was made by inadequate-filtered and un-boiled water. CONCLUSIONS: We identified the ice made by norovirus-contaminated un-boiled water caused the outbreak and the predominant genotype was GII.17. Adequately filtered or boiled water should be strongly recommended for making ice to avoid possible contamination.

Liver resection for hepatocellular carcinoma in patients with hematological malignancies.

BACKGROUND: Improvements in antimetabolite drugs have prolonged the survival of patient with hematological malignancies. However, these drugs may have hepatotoxic side effects and may induce acute liver failure, chronic liver fibrosis, cirrhosis, or even hepatocellular carcinoma (HCC). Although liver resection remains a curative option for HCC, its role in HCC with hematological malignancies has never been fully explored. METHODS: A retrospective review of 1725 patients who underwent curative liver resection for newly diagnosed HCC between 1994 and 2016 was conducted. Among these patients, 16 had a history of hematological malignancies (HM group). Their hematological malignancies were well-controlled at the time of liver resection. The clinicopathological characteristics of the HM group, along with their short- and long-term outcomes after liver resection, were compared with those of the other 1709 patients without hematological malignancy (non-HM group). RESULTS: All HM group patients were seropositive for hepatitis marker surface for hepatitis B and C. No significant differences were observed in any background characteristics between the two groups. The postoperative complication rate and 90-day mortality in the HM and non-HM groups were 25 and 20.4%, P = 0.754, and 0 and 0.6%, P = 1.000, respectively. The 5-year disease-free and overall survival rates for the HM and non-HM groups were 42.3 and 35.1%, P = 0.552, and 69.5 and 56.9%, P = 0.192, respectively. CONCLUSIONS: Hepatitis markers should be examined during chemotherapy for hematological malignancies. Regular liver imaging studies are recommended for seropositive cases. When HCC occurs secondary to a well-controlled hematological malignancy, liver resection is suggested in selected patients.