Response surface optimization of sludge dewatering process: synergistic enhancement by ultrasonic, chitosan and sludge-based biochar.

Due to the colloidal stability, the high compressibility and the high hydration of extracellular polymeric substances (EPS), it is difficult to efficiently dehydrate sludge. In order to enhance sludge dewatering, the process of ultrasonic (US) cracking, chitosan (CTS) re-flocculation and sludge-based biochar (SBB) skeleton adsorption of water-holding substances to regulate sludge dewaterability was proposed. Based on the response surface method, the prediction model of the specific resistance to filtration (SRF) and sludge cake moisture content (MC) was established. The US cracking time and the dosage of CTS and SBB were optimized. The results showed that the optimal parameters of the three were 5.08 s, 10.1 mg/g dry solids (DS) and 0.477 g/g DS, respectively. Meantime, the SRF and MC were 5.4125 × 1011 m/kg and 76.8123%, which significantly improved the sludge dewaterability. According to the variance analysis, it is found that the fitting degree of SRF and MC model is good, which also confirms that there is significant interaction and synergy between US, CTS and SBB, and the contribution of CTS and SBB is greater. Moreover, the process significantly improves the sludge's calorific value and makes its combustion more durable.

DNA-Guided Extracellular-Vesicle Metallization with High Catalytic Activity for Accurate Diagnosis of Pulmonary Nodules.

Sensitive and specific analysis of extracellular vesicles (EVs) offers a promising minimally invasive way to identify malignant pulmonary nodules from benign lesions. However, accurate analysis of EVs is subject to free target proteins in blood samples, which compromises the clinical diagnosis value of EVs. Here a DNA-guided extracellular-vesicle metallization (DEVM) strategy is described for ultrasensitive and specific analysis of EV protein biomarkers and classification of pulmonary nodules. The facile DEVM process mainly includes the incorporation of DNA labeled with cholesterol and thiol groups into EV membranes and subsequent deposition of Au3+ and Pt4+ to allow the DNA-functionalized EVs to be encapsulated with AuPt nanoshells. It is found that the synthesized AuPt-metallized EVs possess extrinsic peroxidase-like activity. Utilizing the feature of the catalytic metal nanoshells just growth on the EV membranes, the DEVM method enables multiparametric recognition of target proteins and EV membranes and can produce an amplified colorimetric signal, avoiding the interference of free proteins. By profiling four surface proteins of EVs from 48 patients with pulmonary nodules, the highest area under the receiver operating characteristic curve (0.9983) is obtained. Therefore, this work provides a feasible EVs analysis tool for accurate pulmonary nodules management.

Target response controlled enzyme activity switch for multimodal biosensing detection.

How to achieve delicate regulation of enzyme activity and empower it with more roles is the peak in the field of enzyme catalysis research. Traditional proteases or novel nano-enzymes are unable to achieve stimulus-responsive activity modulation due to their own structural limitations. Here, we propose a novel Controllable Enzyme Activity Switch, CEAS, based on hemin aggregation regulation, to deeply explore its regulatory mechanism and develop multimodal biosensing applications. The core of CEAS relies on the dimerizable inactivation of catalytically active center hemin and utilizes a DNA template to orderly guide the G4-Hemin DNAzyme to tightly bind to DNA-Hemin, thereby shutting down the catalytic ability. By customizing the design of the guide template, different target stimulus responses lead to hemin dimerization dissociation and restore the synergistic catalysis of G4-Hemin and DNA-Hemin, thus achieving a target-regulated enzymatic activity switch. Moreover, the programmability of CEAS allowed it easy to couple with a variety of DNA recognition and amplification techniques, thus developing a series of visual protein detection systems and highly sensitive fluorescent detection systems with excellent bioanalytical performance. Therefore, the construction of CEAS is expected to break the limitation of conventional enzymes that cannot be targetable regulated, thus enabling customizable enzymatic reaction systems and providing a new paradigm for controllable enzyme activities.

Non-invasive brain stimulation for limb motor function and daily living activity improvement in acute stroke: A meta-analysis.

OBJECTIVE: To evaluate the effect of non-invasive brain stimulation (NIBS) in improving limb motor dysfunction and daily living activity during at the phase of acute stroke. MATERIALS AND METHODS: Randomized controlled trials about the effect of NIBS on hemiparesis in acute stroke were retrieved from databases of China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, CBM, PubMed, Embase, Cochrane Library, and Web of Science from inception until January 3rd 2022. The quality of the trials was assessed, and the data were extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. A statistical analysis was carried out using Review Manager 5.3 and STATA 14. The effect size was evaluated by using the weighed mean difference (WMD) and a 95% confidence interval (CI). The stability and sensitivity of the results and sources of heterogeneity were also analyzed. RESULTS: 12 studies involving 639 patients were included. Our meta-analysis showed that NIBS could improve the Fugl-Meyer Assessment (weighed mean difference = 3.96, 95% confidence interval = 3.45 to 4.48) and Barthel Index (weighed mean difference = 12.29, 95% confidence interval = 4.93 to 19.66), while reducing the National Institutes of Health Stroke Scale (weighed mean difference = -2.37, 95% confidence interval = -3.43 to -1.31). CONCLUSION: NIBS is effective in improving paretic limb motor function and activities of daily living in patients during at the phase of acute stroke.

Decursin ameliorates carbon-tetrachloride-induced liver fibrosis by facilitating ferroptosis of hepatic stellate cells.

Decursin possesses the potential to alleviate transforming growth factor (TGF)-ß-induced hepatic stellate cells (HSCs) activation. However, the mechanisms by which decursin alleviates hepatic fibrosis remain not fully understood. Our aim is to explore the function of decursin on regulating HSCs' activation and hepatic fibrosis. The anti-fibrotic effect of decursin was evaluated by Masson and Sirius red staining, and immunohistochemical (IHC) and quantitative real-time PCR (qRT-PCR) analyses for alpha-smooth muscle actin (α-SMA) and collagen type I (Col1α1) expression. Ferroptosis was assessed by measuring iron concentration, glutathione peroxidase 4 (Gpx4), and prostaglandin endoperoxide synthase 2 (Ptgs2) expression, glutathione (GSH) level, lipid peroxidation, and reactive oxygen species (ROS) level. We found that decursin treatment decreased carbon tetrachloride (CCl4)-induced liver fibrosis. The primary HSCs isolated from decursin-treated group showed an increased Fe2+, lipid ROS level, and decreased Gpx4 and GSH levels compared with HSCs from the model group. Moreover, decursin promoted ferroptosis in activated HSCs in vitro, as evidenced by declined Gpx4 and GSH levels, increased Fe2+, ROS, and Ptgs2 levels compared with control. More important, ferroptosis inhibitor destroyed the anti-fibrosis effect of decursin on HSCs. In summary, these data suggest that decursin has potential to treat hepatic fibrosis.

Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1.

Recent evidence suggests potential benefits of applying local anesthetics in cancer patients. Specifically, tetracaine has a potent antitumor effect in diverse cancers, including neuroblastoma, breast cancer, and melanoma; however, the underlying molecular mechanisms remain unclear. Here, we reported that tetracaine hydrochloride inhibited the growth of melanoma cells and arrested melanoma cells in the G0/G1 phase. Tetracaine hydrochloride treatment resulted in translocation of hnRNPA1 from the nucleoplasm to the nuclear envelope and reduced the protein stability of hnRNPA1 possibly by disrupting the dynamic balance of ubiquitination and neddylation. Elevated hnRNPA1 upregulated cyclin D1 to promote cell cycle in melanoma. The hnRNPA1 overexpression attenuated the effect of tetracaine hydrochloride on melanoma cell growth suppression and cell cycle arrest. Furthermore, melanoma homograft experiments demonstrated that tetracaine hydrochloride suppressed melanoma growth, while hnRNPA1 overexpression alleviated tetracaine's antitumor effect on melanoma. Taken together, our findings suggest that tetracaine hydrochloride exerts a potent antitumor effect on melanoma both in vitro and in vivo, and the effect involves cell cycle arrest induction via downregulation of hnRNPA1.

DUSP3 regulates phosphorylation-mediated degradation of occludin and is required for maintaining epithelial tight junction.

BACKGROUND: Tight junctions (TJ) are multi-protein complexes that hold epithelial cells together and form structural and functional barriers for maintaining proper biological activities. Dual specificity phosphatase 3 (DUSP3), a suppressor of multiple protein tyrosine (Tyr) kinases, is decreased in lung cancer tissues. Here we demonstrated the role of DUSP3 in regulation of epithelial TJ. METHODS: Barrier functions of TJ were examined in wild-type or DUSP3-deficient lung epithelial cells. Animal and clinical data were analyzed for the association between DUSP3 deficiency and lung cancer progression. Proximity ligation assay, immunoblotting, and phosphatase assay were performed to study the effect of DUSP3 on the TJ protein occludin (OCLN). Mutations of Tyr residues on OCLN showed the role of Tyr phosphorylation in regulating OCLN. RESULTS: Compared to those of the DUSP3-expressing cells, we found the expression and distribution of ZO-1, a TJ-anchoring molecule, were abnormal in DUSP3-deficient cells. OCLN had an increased phosphorylation level in DUSP3-deficient cells. We identified that OCLN is a direct substrate of DUSP3. DUSP3 regulated OCLN ubiquitination and degradation through decreasing OCLN tyrosine phosphorylation directly or through suppressing focal adhesion kinase, the OCLN kinase. CONCLUSION: Our study revealed that DUSP3 is an important TJ regulatory protein and its decrease may be involved in progression of epithelial cancers.

Burden of schizophrenia among Japanese patients: a cross-sectional National Health and Wellness Survey.

BACKGROUND: Schizophrenia places a great humanistic and financial burden to patients, families, and societies, and the burden is substantially impacted by comorbid conditions. This study aimed to estimate the lifetime prevalence of schizophrenia and to assess the health-related quality of life (HRQoL), work productivity, and indirect cost among schizophrenia patients with and without comorbidities (depressive symptoms, sleep disturbances, and anxiety problems). METHODS: This is a secondary analysis of existing data collected in 2019 from the Japan National Health and Wellness Survey. The schizophrenia patients were categorized based on their Patient Health Questionnaire-9 score, self-reported experience of sleep disturbances, and anxiety problems. The lifetime prevalence was estimated using the total number of diagnosed schizophrenia patients as the numerator and the total number of respondents as the denominator. The HRQoL was evaluated through the Short Form 12-Item (version 2) Health Survey and EuroQoL 5-dimensions scale. Work productivity and annual indirect costs were evaluated through the Work Productivity and Activity Impairment instrument and monthly wage rates. Multivariate analyses included the comparison of outcomes using generalized linear models. RESULTS: The study was conducted with 178 schizophrenia patients with an average age of 42.7 years old and an estimated lifetime prevalence of 0.59% (95% CI: 0.51%, 0.68%). Patients who experienced sleep disturbances, more severe depressive symptoms, and anxiety problems had lower HRQoL, higher levels of absenteeism, presenteeism, total work productivity and activity impairment, and almost twice more indirect costs, compared to those without these conditions. CONCLUSION: Comorbid conditions among patients with schizophrenia impact significantly on their quality of life, work productivity as well as indirect costs.

Hsa-miR-1290 is associated with stemness and invasiveness in prostate cancer cell lines by targeting RORA.

This work examined microRNA-1290 (miR-1290)'s effect on regulating the malignant phenotype of prostate cancer (PC) cells. We detected miR-1290 expression within PC based on open-sourced datasets as well as in cancer cells and tissues. Loss-of-function experiments by miR-1290 knockdown in PC cell lines were performed. We performed CCK-8, clone forming, Transwell, and sphere formation assays for examining PC cells' malignant phenotypes following miR-1290 knockdown. We estimated miR-1290's target genes using online resources including miRDB, miRbase, miRTarBase and TargetScan. We also performed in vivo studies for validating how miR-1290 affected tumour formation within the mouse model. According to findings in this work, miR-1290 showed overexpression within PC cells and tissues. miR-1290 was indispensable for PC cell growth, stemness and invasion as well as mesenchymal status. Further, we identified RORA (retinoic acid receptor-related orphan receptor A) as miR-1290's target gene for mediating miR-1290 within PC cells. To sum up, this work suggests that miR-1290 up-regulation enhances PC cell growth and invasion by regulating RORA expression.

A Maize CBM Domain Containing the Protein ZmCBM48-1 Positively Regulates Starch Synthesis in the Rice Endosperm.

Starch directly determines the grain yield and quality. The key enzymes participating in the process of starch synthesis have been cloned and characterized. Nevertheless, the regulatory mechanisms of starch synthesis remain unclear. In this study, we identified a novel starch regulatory gene, ZmCBM48-1, which contained a carbohydrate-binding module 48 (CBM48) domain. ZmCBM48-1 was highly expressed in the maize endosperm and was localized in the plastids. Compared with the wild type lines, the overexpression of ZmCBM48-1 in rice altered the grain size and 1000-grain weight, increased the starch content, and decreased the soluble sugar content. Additionally, the transgenic rice seeds exhibited an alterant endosperm cell shape and starch structure. Meanwhile, the physicochemical characteristics (gelatinization properties) of starch were influenced in the transgenic lines of the endosperm compared with the wild type seeds. Furthermore, ZmCBM48-1 played a positive regulatory role in the starch synthesis pathway by up-regulating several starch synthesis-related genes. Collectively, the results presented here suggest that ZmCBM48-1 acts as a key regulatory factor in starch synthesis, and could be helpful for devising strategies for modulating starch production for a high yield and good quality in maize endosperm.

Saikosaponin-d protects against liver fibrosis by regulating the estrogen receptor-ß/NLRP3 inflammasome pathway.

Liver fibrosis is the most common pathway in most types of chronic liver damage, characterized by an imbalance of ECM degradation and synthesis. Saikosaponin-d (SSd) possesses anti-inflammatory and anti-fibrotic effects. However, the underlying mechanism by which SSd represses hepatic stellate cell (HSC) activation remains unclear. Here, we found that SSd remarkably alleviated carbon tetrachloride (CCl4)-induced liver fibrosis, as evidenced by decreased collagen levels and profibrotic marker (COl1a1 and α-smooth muscle actin (SMA)) expression. SSd repressed CCl4-induced NOD-like receptor family pyrin-domain-containing-3 (NLRP3) activation in fibrotic livers, as suggested by decreased levels of NLRP3, IL-18, and IL-ß. The primary HSCs of CCl4 mice exhibited a significant increase in profibrotic marker expression and NLRP3 activation, but SSd treatment reversed this effect. SSd also repressed TGF-ß-induced profibrotic marker expression and NLRP3 activation in vitro. Mechanistically, TGF-ß decreased the expression of estrogen receptor-ß (ERß) in HSCs, whereas SSd treatment reversed this effect. ERß inhibition enhances NLRP3 activation in HSCs. More importantly, ERß or NLRP3 inhibition partially destroyed the function of SSd in liver fibrosis. In summary, the current data suggest that SSd prevents hepatic fibrosis by regulating the ERß/NLRP3 inflammasome pathway and suggests SSd as a potential agent for treating liver fibrosis.

Saikosaponin-d alleviates hepatic fibrosis through regulating GPER1/autophagy signaling.

BACKGROUND: Hepatic fibrosis is the final pathway of chronic liver disease characterized by excessive accumulation of extracellular matrix (ECM), which eventually develop into cirrhosis and liver cancer. Emerging studies demonstrated that Saikosaponin-d (SSd) exhibits a protective role in liver fibrosis. However, the mechanism underlying anti-liver fibrosis of SSd in vivo and in vitro remains unclear. METHODS AND RESULTS: Transforming growth factor (TGF)-ß and carbon tetrachloride (CCl4) were used for creating liver fibrosis model in vitro and in vivo, respectively. The role of SSd in regulating liver fibrosis was assessed through Sirius red and Masson staining, and IHC assay. We found that SSd attenuated remarkably CCl4-induced liver fibrosis as evidenced by decreased collagen level, and decreased expression of fibrotic markers Col 1 and α-SMA. Meanwhile, SSd repressed autophagy activation as suggested by decreased BECN1 expression and increased p62 expression. Compared with HSCs from CCl4-treated group, the primary HSCs from SSd-treated mice exhibited a marked inactivation of autophagy. Mechanistically, SSd treatment enhanced the expression of GPER1 in primary HSCs and in TGF-ß-treated LX-2 cells. GPER1 agonist G1 repressed autophagy activation, whereas GPER1 antagonist G15 activated autophagy and G15 also damaged the function of SSd on suppressing autophagy, leading to subsequent increased levels of fibrotic marker level in LX-2 cells. CONCLUSIONS: Our findings highlight that SSd alleviates hepatic fibrosis by regulating GPER1/autophagy pathway.

Impact of chronic constipation on health-related quality of life and work productivity in Japan.

BACKGROUND AND AIM: The impact of chronic constipation on health-related quality of life (HRQoL), work productivity, and healthcare resource use in Japan is not well understood. This study aimed to evaluate and compare the humanistic burden of respondents with chronic constipation to respondents without chronic constipation and to respondents with type 2 diabetes mellitus (T2DM), irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD), respectively. METHODS: This cross-sectional study collected demographic and general health data and HRQoL data as measured by the Short Form 12-Item (Version 2) Health Survey and EuroQol 5-dimension health surveys. Health impacts on employment-related activities and indirect costs were measured using the Work Productivity and Activity Impairment questionnaire. Propensity score matching was used to identify a control group without chronic constipation. Multivariate generalized linear models were used to identify potential factors that may impact the outcomes of respondents. RESULTS: A total of 30 001 individuals responded to the Japan National Health and Wellness Survey 2017, whereof 3373 (11.2%) reported having chronic constipation; 963 were physician diagnosed. Compared with matched controls, patients with physician-diagnosed chronic constipation had lower mean HRQoL scores and higher mean absenteeism, presenteeism, total Work Productivity and Activity Impairment, and indirect costs. Physician-diagnosed chronic constipation was associated with a higher health burden than T2DM, IBS, and GERD. CONCLUSIONS: Chronic constipation is associated with a considerable health burden, which is higher compared with T2DM, IBS, and GERD. These results suggest an urgent need for effective treatment of Japanese patients with chronic constipation to improve their quality of life.

Analgesic efficacy of postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane block for laparoscopic colorectal cancer surgery: a randomized, prospective, controlled study.

BACKGROUND: We assessed whether a postoperative bilateral, ultrasound-guided, posterior transversus abdominis plane (TAP) block could reduce 24 h rescue tramadol requirement compared with placebo in patients undergoing elective laparoscopic colorectal cancer surgery. METHODS: Patients scheduled to undergo elective laparoscopic surgery following the diagnosis of colorectal cancer were included in this study and randomized into Group and Group Control. The patients received a postoperative bilateral, ultrasound-guided, posterior TAP block in either 20 mL of 0.5% ropivacaine (Group TAP) per side or an equivalent volume of normal saline (Group Control). The primary outcome was the cumulative consumption of rescue tramadol within 24 h after the surgery. Secondary endpoints included (1) resting and movement numerical rating scale (NRS) pain scores at 2, 4, 6, 12, 24, 48, and 72 h; (2) incidences of related side effects; (3) time to the first request for rescue tramadol; (4) patient satisfaction regarding postoperative analgesia; (5) time to restoration of intestinal function; (6) time to mobilization; and (7) the length of hospital stay. RESULTS: In total, 92 patients were randomized, and 82 patients completed the analysis. The total rescue tramadol requirement (median [interquartile range]) within the first 24 h was lower in Group TAP (0 [0, 87.5] mg) than in Group Control (100 [100, 200] mg), P < 0.001. The posterior TAP block reduced resting and movement NRS pain scores at 2, 4, 6, 12, and 24 h after surgery (all P < 0.001) but showed similar scores at 48 h or 72 h. A higher level of satisfaction with postoperative analgesia was observed in Group TAP on day 1 (P = 0.002), which was similar on days 2 (P = 0.702) and 3 (P = 0.551), compared with the Group Control. A few incidences of opioid-related side effects (P < 0.001) and a lower percentage of patients requiring rescue tramadol analgesia within 24 h (P < 0.001) were observed in Group TAP. The time to the first request for rescue analgesia was prolonged, and the time to mobilization and flatus was reduced with a shorter hospital stay in Group TAP as compared with Group Control. CONCLUSIONS: A postoperative bilateral, ultrasound-guided, posterior TAP block resulted in better pain management and a faster recovery in patients undergoing laparoscopic colorectal cancer surgery, without adverse effects. TRIAL REGISTRATION: The study was registered at http://www.chictr.org.cn ( ChiCTR-IPR-17012650 ; Sep 12, 2017).

[Evidence-Based Nursing Care of Older Adult Patient With Postoperative Delirium and Hip Fracture].

Hip fracture commonly occurs in adult patients over 65 years old at a prevalence rate that is estimated to be 756 per 100 thousand cases. Thus, hip fracture surgery is one of the most common emergency operations in older adult populations. In addition, the incidence rate in older adults of post-operative delirium, which leads to symptoms of disturbance related to cognition, attention, perception, logic, memory, psychological activities, mood, and sleep, has been reported as 5%-61%. The many possible complications of post-operative delirium, including death, increase medical costs and family burdens if not managed properly. Proper management involves healthcare providers initiating early assessments, reducing accelerated factors, and providing appropriate care. As diagnosing and differentiating post-operative delirium in clinical practice is difficult, this condition is easily neglected by healthcare teams, resulting in adequate care not being provided to this population. The aim of this paper was to review the definition, relevant physiological and pathological mechanisms and etiologies, and medical management and nursing care of post-operative delirium using an evidence-based literature review. Suggestions for healthcare providers to improve the detection and management of post-operative delirium include using appropriate evaluation tools to detect and diagnose high-risk patients as early as possible, implementing older-adult life planning strategies, and conducting medical consultations. Furthermore, healthcare providers may initiate pain control, nutrient and body fluid supplementation, and sensory/cognition enhancement therapies to reduce the incidence of delirium, length of hospital stay, complications, and in-hospital mortality, thereby improving the quality of care provided to older adult patients with hip fractures and their caregivers.

Diffusion-weighted MRI versus FDG-PET/CT for diagnosing pancreatic cancer: an indirect comparison meta-analysis.

BACKGROUND: Fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DWI or DW-MRI) are tools for the diagnosis of pancreatic cancer. However, comparison of their diagnostic performance remains unknown. PURPOSE: To indirectly compare the diagnostic value of DWI and FDG-PET/CT in the detection of pancreatic cancer. MATERIAL AND METHODS: A literature search of PubMed, Embase, and Cochrane Library electronic databases for articles published through May 2018 yielded 875 articles. For the meta-analysis, we included 26 studies evaluating the efficacy of DWI and FDG-PET/CT for determining pancreatic cancer with a total of 1377 patients. QUADAS (Quality Assessment of Diagnostic Accuracy Studies) was used to assess the study quality. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) with their 95% confidence intervals were calculated for each individual study. RESULTS: There were no significant differences between DWI and FDG-PET/CT for sensitivity, specificity, PLR, NLR, or DOR, while DWI AUC was higher than that of FDG-PET/CT for the detection of pancreatic cancer. CONCLUSION: The diagnostic value of both DWI and FDG-PET/CT were comparable and, hence, both techniques seem to be equally useful tools for the diagnosis of pancreatic cancer.

Burden of migraine among Japanese patients: a cross-sectional National Health and Wellness Survey.

BACKGROUND: Limited studies have measured the burden of migraine in Japan. This study aimed at estimating the disease burden of migraine in Japan and identifying factors associated with the burden using the 2017 National Health and Wellness Survey. METHODS: Migraine patients were defined by ICHD-3 like criteria with ≥4 monthly headache days (MHDs), and non-migraine respondents were selected using 1:4 propensity score matching. Multivariate analyses were conducted to compare Health-related Quality of Life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HRU) and costs between the two groups, and to identify factors associated with these outcomes in migraine patients. RESULTS: In 30,001 respondents, 378 migraine patients were identified. Compared to matched controls (N = 1512), migraine patients had lower physical (45.17 vs. 49.89), mental (42.28 vs. 47.71) and role/social (37.91 vs. 44.19) component summary scores (p < 0.001). Migraine patients had higher absenteeism (6.4% vs. 2.2%), presenteeism (40.2% vs. 22.5%), total work productivity impairment (44.3% vs. 24.5%), total activity impairment (45.0% vs. 23.9%), indirect costs (1,492,520 JPY vs. 808,320 JPY) and more visits to healthcare providers in the past 6 months (7.23 vs. 3.96) (p < 0.001). More MHDs was associated with worse HRQoL, and higher HRU and indirect costs. CONCLUSIONS: Japanese migraine patients experience an incremental burden. This demonstrates the unmet needs among Japanese migraine patients.

Characteristics and health burden of the undiagnosed population at risk of chronic obstructive pulmonary disease in China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in China. However, identifying patients has proved challenging, resulting in widespread under-diagnosis of the condition. We examined the prevalence of COPD diagnosis and COPD risk among adults in urban mainland China, the factors associated with having a COPD diagnosis or COPD risk, and the healthcare resource use and health outcomes of these groups compared with controls. METHODS: Respondents to the 2017 National Health and Wellness Survey in China (n = 19,994) were classified into three groups: 'COPD Diagnosed', 'COPD Risk (undiagnosed)', and Control (unaffected), based on their self-reported diagnosis and Lung Function Questionnaire (LFQ) score. The groups were characterised by sociodemographic, health-related quality of life (HRQoL), productivity impairment, and healthcare resource use. Pairwise comparisons (t tests and chi-squared tests) and multivariable regression analyses were used to investigate factors associated with being at risk of, or diagnosed with, COPD. RESULTS: 3320 (16.6%) respondents had a suspected risk of COPD but did not report receiving a diagnosis. This was projected to 105.3 million people, or 16.9% of adult urban Chinese. Of these respondents with an identified risk, only 554 (16.7%) were aware of COPD by name. Relative to those without COPD, those with a risk of COPD (undiagnosed) had significantly greater healthcare resource use, lower productivity and lower HRQoL not only compared to those without COPD, but also compared to people with a COPD diagnosis. Factors associated with increased odds of being at risk of COPD were older age, smoking, alcohol consumption, overweight BMI, occasional exercise, higher comorbidities, asthma diagnosis, being female, lower education, not being employed, and living in a high pollution province (p < 0.05). CONCLUSIONS: There is a substantial group of individuals, undiagnosed, but living with a risk of COPD, who have impaired HRQoL, lower productivity and elevated healthcare resource use patterns. Case-detection tools such as the LFQ may prove a quick and cost-effective approach for identifying these at-risk individuals for further definitive testing and appropriate treatment in China.

Neighbourhood level real-time forecasting of dengue cases in tropical urban Singapore.

BACKGROUND: Dengue, a vector-borne infectious disease caused by the dengue virus, has spread through tropical and subtropical regions of the world. All four serotypes of dengue viruses are endemic in the equatorial city state of Singapore, and frequent localised outbreaks occur, sometimes leading to national epidemics. Vector control remains the primary and most effective measure for dengue control and prevention. The objective of this study is to develop a novel framework for producing a spatio-temporal dengue forecast at a neighbourhood level spatial resolution that can be routinely used by Singapore's government agencies for planning of vector control for best efficiency. METHODS: The forecasting algorithm uses a mixture of purely spatial, purely temporal and spatio-temporal data to derive dynamic risk maps for dengue transmission. LASSO-based regression was used for the prediction models and separate sub-models were constructed for each forecast window. Data were divided into training and testing sets for out-of-sample validation. Neighbourhoods were categorised as high or low risk based on the forecast number of cases within the cell. The predictive accuracy of the categorisation was measured. RESULTS: Close concordance between the projections and the eventual incidence of dengue were observed. The average Matthew's correlation coefficient for a classification of the upper risk decile (operational capacity) is similar to the predictive performance at the optimal 30% cut-off. The quality of the spatial predictive algorithm as a classifier shows areas under the curve at all forecast windows being above 0.75 and above 0.80 within the next month. CONCLUSIONS: Spatially resolved forecasts of geographically structured diseases like dengue can be obtained at a neighbourhood level in highly urban environments at a precision that is suitable for guiding control efforts. The same method can be adapted to other urban and even rural areas, with appropriate adjustment to the grid size and shape.