Of patients who had GvHD, 3 needed treatment discontinuation. Overall, 12 patients suspended treatment, 8 for disease progression and 1 due to patient request. RESULTS In the prophylactic group, all patients are alive at 1 year with an event-free survival (EFS) of 95%, as only 1 patient relapsed. In the preemptive group, 1-year EFS was 54% and 1-year overall survival was 82%. CONCLUSION Low-dose AZA in posttransplantation patients with myeloid neoplasms is a well-tolerated therapy with the potential to prevent relapse and maintain stable remissions. Randomized prospective trials are needed to determine patient selection and dosage, timing, and duration of treatment. Multiple myeloma (MM) is an incurable B-cell malignancy. The immunotherapeutic approach for MM therapy is evolving. The Cd1d/invariant natural killer T-cell/glycolipid immune axis belongs to the innate immunity, and we have highlighted role in myeloma pathogenesis in the present study. The recent development of the chimeric antigen receptor (CAR19)-invariant natural killer T-cells resulted in our renewed interest in this immune system and offer new perspectives for future anti-MM immunotherapies. OBJECTIVE Venous disease is common in Latin America, with an estimated 68.11% prevalence of chronic venous disease. The diverse social, political, and economic characteristics of the many nations that make up Latin America mean that different conditions affect how these diseases are diagnosed and treated, which may differ markedly from the way they are treated by the health care systems of the United States and Europe. Our goal was to review the current state of treatment of chronic venous insufficiency (CVI) in Latin America. METHODS This is a narrative review of the medical literature on the subject and synthesizes sometimes fragmentary information on CVI across a large and diverse region. RESULTS CVI represents an unmet medical need in Latin America. Conservative treatments, such as compression stockings, may be used at first, and there are nonpharmacologic and complementary and alternative medicine approaches in use. Endovenous approaches, such as endovenous thermal ablation, have largely replaced surgical interventions. In Europe and the United States, such procedures are mainly carried out in ambulatory facilities, whereas they are mainly performed in the hospital in Latin America. https://www.selleckchem.com/products/cilengitide-emd-121974-nsc-707544.html CONCLUSIONS Recent strong economic growth in Latin America and improvements in social security and health care suggest that innovative approaches to chronic venous disease and CVI will be implemented. Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. It is characterized by deposition of extracellular matrix proteins, like collagen and fibronectin in the lung interstitium leading to respiratory failure. Our understanding of the pathobiology underlying IPF is still incomplete; however, it is accepted that aging is a major risk factor in the disease while growing evidence suggests that the mitochondria plays an important role in the initiation and progression of pulmonary fibrosis. Mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, fibroblasts, and macrophages) promoting low resilience and increasing susceptibility to activation of profibrotic responses. Here we summarize changes in mitochondrial numbers, biogenesis, turnover and associated metabolic adaptations that promote disrepair and fibrosis in the lung. Finally, we highlight new possible therapeutic approaches focused on ameliorate mitochondrial dysfunction. V.Frailty, a consequence of the interaction of the aging process and certain chronic diseases, compromises functional outcomes in the elderly and substantially increases their risk for developing disabilities and other adverse outcomes. Frailty follows from the combination of several impaired physiological mechanisms affecting multiple organs and systems. And, though frailty and sarcopenia are related, they are two different conditions. Thus, strategies to preserve or improve functional status should consider systemic function in addition to muscle conditioning. Physical activity/exercise is considered one of the main strategies to counteract frailty-related physical impairment in the elderly. Exercise reduces age-related oxidative damage and chronic inflammation, increases autophagy, and improves mitochondrial function, myokine profile, insulin-like growth factor-1 (IGF-1) signaling pathway, and insulin sensitivity. Exercise interventions target resistance (strength and power), aerobic, balance, and flexibility work. Each type improves different aspects of physical functioning, though they could be combined according to need and prescribed as a multicomponent intervention. Therefore, exercise intervention programs should be prescribed based on an individual's physical functioning and adapted to the ensuing response. V.The process of wound healing restores skin homeostasis but not full functionality; thus, novel therapeutic strategies are needed to accelerate wound closure and improve the quality of healing. In this context, tissue engineering and cellular therapies are promising approaches. Although sharing essential characteristics, mesenchymal stromal cells (MSCs) isolated from different tissues might have distinct properties. Therefore, the aim of this study was to comparatively investigate, by a mouse model in vivo assay, the potential use of dermal-derived MSCs (DSCs) and adipose tissue-derived MSCs (ASCs) in improving skin wound healing. Human DSCs and ASCs were delivered to full-thickness mouse wounds by a collagen-based scaffold (Integra Matrix). We found that the association of both DSCs and ASCs with the Integra accelerated wound closure in mice compared with the biomaterial only (control). Both types of MSCs stimulated angiogenesis and extracellular matrix remodeling, leading to better quality scars. However, the DSCs showed smaller scar size,superior extracellular matrix deposition, and greater number of cutaneous appendages. Besides, DSCs and ASCs reduced inflammation by induction of macrophage polarization from a pro-inflammatory (M1) to a pro-repair (M2) phenotype. In conclusion, both DSCs and ASCs were able to accelerate the healing of mice skin wounds and promote repair with scars of better quality and more similar to healthy skin than the empty scaffold. DSCs associated with Integra induced superior overall results than the Integra alone, whereas scaffolds with ASCs showed an intermediate effect, often not significantly better than the empty biomaterial.

C60 in only heat-adapted strains and C220 in only the naturally high heat tolerant strain were detected. These results support the hypothesis, that the consequent increase of SFA ratio is a cellular response to environmental stresses such as high temperatures, and it is able to protect the cells from acid, bile salts and osmotic conditions via cross protection. This study demonstrated that the increase in heat tolerance can be utilized as a mean to improve bacterial tolerance against various environmental stresses.Phospholipase A2 (PLA2) from Streptomyces violaceoruber is a lipolytic enzyme used in a wide range of industrial applications including production of lysolecithins and enzymatic degumming of edible oils. Thereby, we have investigated expression and secretion of PLA2 in two work-horse microbes, Pichia pastoris and Escherichia coli. The PLA2 was produced to an activity of 0.517 ± 0.012 U/mL in the culture broth of the recombinant P. pastoris. On the other hand, recombinant E. coli BL21 star (DE3) overexpressing the authentic PLA2 (P-PLA2) showed the activity of 17.0 ± 1.3 U/mL in the intracellular fraction and 21.7 ± 0.7 U/mL in the culture broth. The extracellular PLA2 activity obtained with the recombinant E. coli system was 3.2-fold higher than the corresponding value reached in a previous study, which employed recombinant E. coli BL21 (DE3) overexpressing codon-optimized PLA2. Finally, we observed that the extracellular PLA2s from the recombinant E. coli P-PLA2 culture was able to hydrolyze 31.1 g/L of crude soybean lecithin, an industrial substrate, to a conversion of approximately 95%. The newly developed E. coli-based PLA2 expression system led to an extracellular production of PLA2 to a productivity of 678 U/L·h, corresponding to 157-fold higher than that obtained with the P. pastoris-based system. This study will contribute to the extracellular production of a catalytically active PLA2.OBJECTIVE Emotional processing dysfunction evident in eating disorders (ED) such as anorexia nervosa (AN) and bulimia nervosa (BN), is considered relevant to the development and maintenance of these disorders. The purpose of the current functional magnetic resonance imaging (fMRI) study was to pilot a comparison of the activity of the fronto-limbic and fronto-striatal brain areas during an emotion processing task in persons with ED. METHODS 24 women patients with ED were scanned, while showing emotionally stimulating (pleasant, unpleasant) and neutral images from the International Affective Picture System (IAPS). RESULTS During the pleasant condition, significant differences in Dorsolateral Prefrontal Cortex (DLPFC) activations were found with AN participants presenting greater activation compared to BN and ED comorbid groups (EDc) and healthy controls also showing greater activation of this brain area compared to BN and EDc. Left putamen was less activated in EDc compared to both controls (C) and AN. During the unpleasant condition, AN participants showed hyperactivation of the Orbito-frontal Cortex (OFC) when compared to EDc. CONCLUSION This study highlights the potential functional relevance of brain areas that have been associated with self-control. These findings should help advance understanding the neural substrate of ED, though they should be considered as preliminary and be cautiously interpreted.An 82-year-old woman underwent surgery for gastric cancer at another hospital in May 2007. The pathological diagnosis was pT4a, pN2, M1, CY1, pStage Ⅳ. Although postoperative chemotherapy was administered, recurrence was observed on the abdominal wall in March 2014, and she was treated usingchemotherapy and resection. Intestinal obstruction due to peritoneal metastasis occurred in December 2017 and mid-July 2018 but symptoms improved with conservative treatment. In late August 2018, she was unable to eat and was readmitted to the hospital. https://www.selleckchem.com/products/brd3308.html Serum Na level at admission was low at 120 mEq/L, and Na correction was performed. Hyponatremia did not improve, and the serum Na level continued to decrease to 115mEq/L on the 14th day of hospitalization. Plasma osmolality was 229mOsm/kg, urine osmolality was 323mOsm/kg, and urine sodium concentration was 56mEq/L. Diagnosis of SIADH was made according to diagnosis standards. Hyponatremia improved by fluid restriction and Na correction. Subsequently, her peritoneal metastasis exacerbated, and she died in mid- October. We would like to report a case of SIADH in an elderly patient with advanced gastric cancer.BACKGROUND Aflibercept beta and FOLFIRI combination therapy were approved for metastatic colorectal cancer as secondline treatment in 2017. Aflibercept beta is a recombinant fusion protein that traps vascular endothelial growth factor(VEGF)- A, VEGF-B, and placental growth factor(PlGF). METHODS We retrospectively evaluated the efficacy and safety of aflibercept beta and FOLFIRI in metastatic colorectal cancer patients(pts)between June 2017 and April 2018 at our institution. Afliber- cept beta(4mg/kg)was administered with FOLFIRI every 2weeks. RESULTS Twenty pts received aflibercept beta and FOLFIRI. There were 11 males and 9 females, with a median age of 69.5(53-81)years. Performance status(PS)was 0 in 12 pts and 1 in the remaining 8 pts. Aflibercept beta and FOLFIRI were prescribed as second-line treatment in 8 pts and the others in 12 pts. The median number of aflibercept beta and FOLFIRI cycles was 5(1-11)cycles. Progression -free survival and overall survival have not yet been estimated. In terms of adverse events, serious adverse events of Grade 3 or higher, including Grade 5 neutropenia, were seen among all pts. CONCLUSIONS Aflibercept beta and FOLFIRI demonstrated acceptable toxicity in heavily pretreated metastatic colorectal cancer patients.The patient was a 63-year-old man with a chief complaint. Upper endoscopic examination revealed a semicircular type 2 lesion, sized 24-28 cm, on the incisor teeth and a 3 cm sized elevated lesion directly above the EGJ. When biopsy was performed, squamous cell carcinoma(SCC)was detected. In this case, lymph node metastasis and multiple liver metastases were observed, and diagnosis at the first examination was cT3N2M1(HEP), Stage Ⅳ. After 7 months of chemotherapy, he underwent right thoracic esophageal subtotal resection, 3-field lymph node dissection, posterior mediastinal gastric tube reconstruction, and partial hepatectomy. Despite receiving postoperative chemotherapy, he showed recurrence in the liver(S8). Four additional courses of chemotherapy were administered and partial hepatectomy(S8)was performed, without the appearance of new lesions. He was considered to be cured 1 year and 6months after starting the treatment and was followed- up without chemotherapy. However, 4 months later, chemotherapy was resumed when right adrenal and abdominal wall metastases and liver recurrence(S3)were found.

Purpose This study assessed the environmental quality of an adapted, play-based LEGO® robotics program for children and youth with disabilities to determine the degree to which the activity setting supports the therapeutic goals of the program.Materials and methods We measured the environmental qualities of a robotics program held at a paediatric rehabilitation hospital. We observed and coded video-recordings of the robotics program, specifically one session from each of five different rooms where the program took place. Using the 32-item Measure of Environmental Qualities of Activity Settings (MEQAS), we described the place- and opportunity-related qualities of these settings.Results Our observations revealed that, across all five settings, the environments support the therapeutic goals of the program, including providing opportunities for social interaction with peers and adults to a great extent. We also identified several environmental features of the robotics program that support optimal outcomes for children and youth with disabilities.Conclusions Our findings lend support for the value of examining environmental opportunities and affordances of play-based therapy within rehabilitation.IMPLICATIONS FOR REHABILITATIONAssessing the environmental opportunities and affordances of play-based activities using the Measure of Environmental Qualities of Activity Settings (MEQAS) is valuable for supporting positive outcomes in rehabilitation.The settings of an adapted LEGO® robotics program offer children with disabilities opportunities to engage in social interactions with peers and adults, to learn a new skill, and to develop a sense of self-identity.Optimal therapeutic outcomes of an adapted LEGO® robotics program can be supported by environmental features, including large tables with sufficient space for two youth and one or two adult volunteers to interact at eye-level, arranged separately with enough space to invite movement between tables, in such a way that children may also interact across tables.RATIONALE The mTOR pathway is one of the key signal cascades in the pathogenesis of idiopathic pulmonary fibrosis. Previous studies have mainly focused on this pathway in the fibroblasts and/or myofibroblasts, but not in the epithelial cells. OBJECTIVES To investigate the role of the mTOR pathway in lung epithelial cells in lung fibrosis. METHODS Using Sftpc-mTORSL1 + IT Tg mice, in which active mTOR is conditionally expressed in lung epithelial cells, we assessed the effects of chronically activated mTOR in lung epithelial cells on lung phenotypes as well as bleomycin-induced lung fibrosis. Furthermore, we isolated AEC2 from mice and performed RNA sequencing. RESULTS Sftpc-mTORSL1 + IT Tg mice had no obvious abnormal findings, but after bleomycin administration showed severer fibrotic changes and lower lung compliance than control mice. RNA sequencing revealed angiopoietin-like 4 (ANGPTL4) as a candidate downstream gene of the mTOR pathway. In vitro studies revealed that ANGPTL4 as well as mTOR promoted tight junction vulnerability and epithelial-mesenchymal transition. CONCLUSIONS mTOR activation in lung epithelial cells promoted lung fibrosis and the expression of ANGPTL4, a novel downstream target of the mTOR pathway, which could be related to the etiology of fibrosis.Aim Fusidic acid (FA) is a narrow-spectrum bacteriostatic antibiotic. We inadvertently discovered that a FA derivative modified by an amino-terminal group at the 3-OH position, namely 2, inhibited the growth of Cryptococcus neoformans. Methods & results Multiscale molecular modeling approaches were used to analyze the binding modes of 2 with eEF2. FA derivatives modified at the 3-OH position were designed based on the in silico models; seven derivatives possessing different amino-terminal groups were synthesized and tested in vitro for antifungal activity against C. https://www.selleckchem.com/products/mk-8617.html neoformans. Conclusion Compound 7 had the strongest minimum inhibitory concentration. Two protonated nitrogen atoms of 7 interacted with a negative electrostatic pocket of eEF2 likely explain the superiority of 7-2.OBJECTIVE Adnexal torsion is a rare gynecologic emergency caused by twisting of an adnexal mass. Twisted vascular pedicle is the most specific imaging finding for adnexal torsion, however, identification of twisted vascular pedicle can be challenging. The purpose of this study is to evaluate the feasibility of susceptibility-weighted MR sequence (SWS) for the diagnosis of adnexal torsion. METHODS MR imaging including SWS (SWAN susceptibility-weighted angiography) of surgically proven four benign ovarian masses with torsion (one acute and three subacute to chronic torsions) were retrospectively evaluated. Three cystic masses and one solid mass were included in this study. RESULTS High signal intensity venous thrombus within the twisted vascular pedicle on T1-weighted imaging (T1WI) was detected in three lesions with subacute to chronic torsion (75%) but not in one lesion with acute torsion, whereas susceptibility-induced signal voids within the twisted vascular pedicle on SWAN were detected in all four lesions (100%). CONCLUSION The demonstration of venous thrombus in the twisted vascular pedicle by SWS may be diagnostic for adnexal torsion. ADVANCES IN KNOWLEDGE SWS can detect blood products sensitively and can reveal venous thrombus in the twisted vascular pedicle, which may be helpful for the diagnosis of adnexal torsion.OBJECTIVES To compare the performance of arterial spin labelling (ASL) in evaluating arteriovenous malformations (AVMs) against the current gold standard of catheter angiography. METHODS We systematically reviewed the published literature using EMBASE and Medline. We included studies that compared ASL to catheter angiography in the assessment of AVMs in three outcome domains detection, angioarchitectural and haemodynamic features. RESULTS From 314 unique citations, 19 studies representing 289 patients with intracranial AVMs met our inclusion criteria. We did not pool data due to marked heterogeneity in study outcome measures. Seven studies showed high diagnostic performance of ASL in identifying arterial feeders, with sensitivity ranging from 84.6 to 100% and specificity ranging from 93.3 to 100%. Six studies showed strong ability in detecting arteriovenous shunting, with sensitivity ranging from 91.7 to 100% and specificity ranging from 90 to 100%. Seven studies demonstrated that ASL could identify nidal location and size as well as catheter angiography, while five studies showed relatively poorer performance in delineating venous drainage.

Objectively measured sedentary behavior (SB) on weekdays and weekends has been mainly assessed in white-collar workers, while data in blue-collar workers are sparse. Therefore, this study presented the difference in accelerometer-measured SB levels between weekdays and weekends, stratified by white- and blue-collar occupations. This study was a sub-analysis of accelerometer data from 73 workers (31 blue-collar and 42 white-collar) at a Japanese manufacturing plant. SB was defined as ≤1.5 metabolic equivalents estimated using an accelerometer, and compared between weekdays and weekends by using mixed models adjusted for confounders. The proportion of workers who sat for ≤8h/day on weekdays and weekends were compared using McNemar's test. In white-collar workers, SB time on weekdays was significantly longer than that on weekends (598 vs 479min/day, P<.001). In blue-collar workers, there was no significant difference in SB time between weekdays and weekends (462 vs 485min/day, P=.43). The proportion of workers who achieved the recommended SB levels (≤8h) was only 4.8% for white-collar workers on weekdays and 54.8% on weekends (P=.04), while that of blue-collar workers was 45.2% and 58.1% respectively (P>.99). White-collar workers were exposed to significantly longer SB time on weekdays than on weekends, which was not the case in blue-collar workers. It may be rather challenging for white-collar workers to limit their SB time to the level recommended by the latest guidelines for better health, especially on weekdays. White-collar workers were exposed to significantly longer SB time on weekdays than on weekends, which was not the case in blue-collar workers. It may be rather challenging for white-collar workers to limit their SB time to the level recommended by the latest guidelines for better health, especially on weekdays.Laparoscopic cholecystectomy remains the standard treatment for acute cholecystitis (AC) although it is always not suitable for patients who are poor candidates for surgery. Recently, endoscopic gallbladder (GB) drainage was found to be a potentially revolutionary alternative for cholecystectomy for the control of symptoms, definitive treatment, or bridging therapy until surgery is possible. Two endoscopic methods have been established using either the trans-mural or trans-papillary drainage approach. Endoscopic ultrasound-guided GB drainage (EUS-GBD; trans-mural approach) is a novel technique that allows stent placement between the GB and duodenum or stomach via fistula track, effectively enabling GB drainage. For endoscopic trans-papillary GB drainage (ETGBD; trans-papillary approach), attempts of selective cannulation to the cystic duct should be made to place the stent in the same manner as an endoscopic retrograde cholangiopancreatography. In comparison, EUS-GBD has higher clinical success and lower recurrence rates than ETGBD due to the use of larger-caliber stents, which allow for effective drainage when performed by skilled practitioners at high-volume centers. Advantages of ETGBD over EUS-GBD include more affordable costs and physiologic drainage, which preserves naive anatomy for possible future cholecystectomy. Although the field of endoscopic treatment for AC is rapidly advancing, important questions regarding which method improves clinical outcomes and safety more effectively remain unaddressed. Herein, the current status of endoscopic treatment for AC, including a technical review on clinical outcomes, adverse events, and advantages and disadvantages of each technique are reviewed, as well as other future prospects.Impaired mitochondrial fusion, due in part to decreased mitofusin 2 (Mfn2) expression, contributes to unrestricted cell proliferation and apoptosis-resistance in hyperproliferative diseases like pulmonary arterial hypertension (PAH) and non-small cell lung cancer (NSCLC). We hypothesized that Mfn2 levels are reduced due to increased proteasomal degradation of Mfn2 triggered by its phosphorylation at serine 442 (S442) and investigated the potential kinase mediators. Mfn2 expression was decreased and Mfn2 S442 phosphorylation was increased in pulmonary artery smooth muscle cells from PAH patients and in NSCLC cells. Mfn2 phosphorylation was mediated by PINK1 and protein kinase A (PKA), although only PINK1 expression was increased in these diseases. We designed a S442 phosphorylation deficient Mfn2 construct (PD-Mfn2) and a S442 constitutively phosphorylated Mfn2 construct (CP-Mfn2). The effects of these modified Mfn2 constructs on Mfn2 expression and biological function were compared with those of the wildtype Mfn2 construct (WT-Mfn2). WT-Mfn2 increased Mfn2 expression and mitochondrial fusion in both PAH and NSCLC cells resulting in increased apoptosis and decreased cell proliferation. Compared to WT-Mfn2, PD-Mfn2 caused greater Mfn2 expression, suppression of proliferation, apoptosis induction, and cell cycle arrest. Conversely, CP-Mfn2 caused only a small increase in Mfn2 expression and did not restore mitochondrial fusion, inhibit cell proliferation, or induce apoptosis. Silencing PINK1 or PKA, or proteasome blockade using MG132, increased Mfn2 expression, enhanced mitochondrial fusion and induced apoptosis. In a xenotransplantation NSCLC model, PD-Mfn2 gene therapy caused greater tumor regression than did therapy with WT-Mfn2. Mfn2 deficiency in PAH and NSCLC reflects proteasomal degradation triggered by Mfn2-S442 phosphorylation by PINK1 and/or PKA. Inhibiting Mfn2 phosphorylation has potential therapeutic benefit in PAH and lung cancer.The stretch-shortening cycle (SSC) assists in effective force attenuation upon landing and augments force generation at take-off during a drop vertical jump (DVJ). General performance outcomes such as jump height or peak measures have been used to assess SSC function in youth populations; however, these discrete metrics fail to provide insight into temporal jump-landing characteristics. This study assessed DVJ force-time profiles in 1013 middle and high-school female athletes (n = 279 prepubertal, n = 401 pubertal, and n = 333 postpubertal). Maturity status was determined using the Pubertal Maturation Observation Scale. https://www.selleckchem.com/products/im156.html Ground reaction force data were analyzed to extract a range of variables to characterize force-time profiles. SSC function was categorized as poor, moderate, or good dependent on the presence of an impact peak and spring-like behavior. No differences in jump height or ground contact time were observed between maturity groups (p > 0.05). Significant differences in absolute peak landing and take-off force were evident between all maturational statuses (p less then 0.

ersensitivity and hyposensitivity.BACKGROUND Chondroblastoma (CB) is a rare locally aggressive bone tumor that commonly occurs in the epiphysis or apophysis of long bones. Although surgical treatment of CB carries potential risk for physeal or articular cartilage damage, risk factors for joint degeneration have not been well described. In addition, we have mainly used synthetic bone substitute (SBS) to fill the bone defect after intralesional curettage as treatment for CB. This study thus aimed to evaluate the incidence of and risk factors for adjacent-joint radiographic degeneration after SBS treatment for CB. METHODS We retrospectively reviewed 48 patients treated for CB at our institutions between 1996 and 2017. https://www.selleckchem.com/products/sar405.html Clinical data, radiographic images, treatments, and local recurrence were analyzed. RESULTS We identified 40 patients [29 males and 11 females with a mean age of 19 years (range, 8-35 years)] who received SBS to fill the defect after curettage with a minimum follow-up of 1 year. The mean follow-up period was 71 months (range, 13-239 months). A total of 8 patients (20%) developed local recurrence. Radiographic analysis showed that 5 patients (16.7%) developed radiographic joint degeneration. Joint degeneration was significantly associated with the affected joint (p = 0.004). CONCLUSIONS Curettage and SBS filling had been found to be a reasonable treatment method for CB, which commonly occurs in the epiphysis or apophysis. Radiographic joint degeneration was not uncommon after CB treatment, especially in the talus and proximal humerus.BACKGROUND The licensed doctor misdistribution is one of the major challenges faced by China. However, this subject remains underexplored as spatial distribution characteristics (such as spatial clustering patterns) have not been fully mapped out by existing studies. To fill the void, this study aims to explore the spatio-temporal dynamics and spatial clustering patterns of different subtypes of licensed doctors (i.e., clinicians, traditional Chinese medicine doctors, dentists, public health doctors, general practitioners) in China. METHODS Data on the licensed doctor quantity and population during 2012-2016 was obtained from the National Health (and Family Planning) Yearbook. Functional boxplots were used to visualize and compare the temporal trends of densities of different subtypes of licensed doctors. This study adopted two complementary spatial statistics (space-time scan statistics and Moran's I statistics) to explore the spatio-temporal dynamics and spatial clustering patterns of licensed doctor distris from disadvantaged units.BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance. METHODS The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way. RESULTS Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path00982_1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy. CONCLUSION The present study has identified a novel functional PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a linkage to therapeutic options for combating PDAC. However, the involvement of path00982_1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation. Video Abstract.BACKGROUND Chondrogenic progenitor cells (CPCs) have high self-renewal capacity and chondrogenic potential. Intra-articular delivery of purified mesenchymal stem cells (MSCs) from MRL/MpJ "superhealer" mice increased bone volume during repair and prevents post-traumatic arthritis. Recently, although extracellular vesicles released from MSCs have been used widely for treating OA, the application of extracellular vesicles secreted by CPCs from MRL/MpJ mice in OA therapy has never been reported. In this study, we evaluated the effects of extracellular vesicles secreted by CPCs from control CBA (CBA-EVs) and MRL/MpJ mice (MRL-EVs) on proliferation and migration of murine chondrocytes. We also determined here if weekly intra-articular injections of CBA-EVs and MRL-EVs would repair and regenerate surgically induced model in mice. METHODS CPC surface markers were detected by flow cytometry. CBA-EVs and MRL-EVs were isolated using an ultrafiltration method. Nanoparticle tracking analysis, transmission electron microsor therapeutic effect in comparison with CBA-EVs. The results of bioinformatics analyses revealed that the differentially expressed exosomal miRNAs participated in multiple biological processes. We identified 80 significantly upregulated and 100 downregulated miRNAs. Moreover, we found that the top 20 differentially expressed exosomal miRNAs connected OA repair to processes such as AMPK signaling, regulation of autophagy, and insulin signaling. Notably, miRNA 221-3p were highly enriched in MRL-Exos and treatment with miR 221-3p inhibitor markedly decreased chondrocyte proliferation and migration induced by CBA-EVs or MRL-EVs in vitro. CONCLUSIONS This is the first study to demonstrate MRL-EVs had a greater therapeutic effect on the treatment of OA than CBA-EVs. This study will hopefully provide new insight into the pathogenesis, prevention, and treatment of OA.

Study Design Systematic review. Objective To assess the current literature regarding the relationship between the shoulder and the spine with regard to (1) overlapping pain pathways; (2) differentiating history, exam findings, and diagnostic findings; (3) concomitant pathology and optimal treatments; and (4) cervical spine-based etiology for shoulder problems. Methods A systematic literature search was performed according to the guidelines set forth by the Cochrane Collaboration. Studies were included if they examined the clinical, anatomical, or physiological overlap between the shoulder and cervical spine. Two reviewers screened and selected full texts for inclusion according to the objectives of the study. Quality of evidence was graded using OCEBM (Oxford Center for Evidence Based Medicine) and MINORS (Methodological Index for Nonrandomized Studies) scores. Results Out of 477 references screened, 76 articles were included for review and grouped into 4 main sections (overlapping pain pathways, differentiat referral patterns, shoulder kinematics, and examination techniques are invaluable to the clinician in making an appropriate diagnosis and guiding treatment. In this review, we present an algorithm for the identification and treatment of shoulder and cervical spine pathology. © The Author(s) 2019.Study Design Narrative review. Objectives Postoperative surgical site infections (SSIs) are among the most common acute complications in spine surgery and have a devastating impact on outcomes. They can lead to increased morbidity and mortality as well as greater economic burden. Hence, preventive strategies to reduce the rate of SSIs after spine surgery have become vitally important. The purpose of this article was to summarize and critically analyze the available evidence related to current strategies in the prevention of SSIs after spine surgery. Methods A literature search utilizing Medline database was performed. Relevant studies from all the evidence levels have been included. Recommendations to decrease the risk of SSIs have been provided based on the results from studies with the highest level of evidence. Results SSI prevention occurs at each phase of care including the preoperative, intraoperative, and postoperative periods. Meticulous patient selection, tight glycemic control in diabetics, smoking cessation, and screening/eradication of Staphylococcus aureus are some of the main preoperative patient-related preventive strategies. Currently used intraoperative measures include alcohol-based skin preparation, topical vancomycin powder, and betadine irrigation of the surgical site before closure. Postoperative infection prophylaxis can be performed by administration of silver-impregnated or vacuum dressings, extended intravenous antibiotics, and supplemental oxygen therapy. Conclusions Although preventive strategies are already in use alone or in combination, further high-level research is required to prove their efficacy in reducing the rate of SSIs in spine surgery before evidence-based standard infection prophylaxis guidelines can be built. © The Author(s) 2019.Study Design Retrospective cohort. Objective To understand which patient and surgical factors are predictive of an increased odds of undergoing an admission and a prolonged stay >2 days in an intensive care unit (ICU) following corrective surgery for pediatric deformity. Methods The 2016 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Pediatric Spinal Fusion Procedure Targeted database records, merged with original 2016 ACS-NSQIP Pediatric file variables, were used for this study. Univariate and multivariate analyses were used to identify independent risk factors associated with admission, as well as a prolonged length of stay in the ICU following surgery. Results A total of 1398 (39.5%) patients required an ICU admission following the procedure-out of whom 416 (29.8%) stayed for more than 2 days. Following adjusted analysis, patient and surgical factors independently associated with an ICU admission were black/African American versus white race, anterior fusion, combined fusion, nonidiopathic scoliosis, preoperative ventilator dependence, asthma, having structural pulmonary abnormality, developmental delay, having a neuromuscular disorder, requiring nutritional support and a total operative time >270 minutes. The only significant factors associated with a prolonged length of ICU stay >2 days were preoperative ventilator dependence, nutritional support requirement, and undergoing anterior or combined fusion. Conclusions This study is the first of its kind to identify significant patient- and procedure-level factors associated with an ICU admission, and also explores predictors for a prolonged stay in the ICU. Surgeons can use this data to preoperatively counsel families and ensure postoperative course of care is appropriately planned ahead of time. © The Author(s) 2019.Study Design Retrospective cohort. Objective Facet fusion in minimally invasive spine surgery (MISS) may reduce morbidity and promote long-term construct stability. The study compares the maintenance of correction of thoracolumbar (TL) trauma patients who underwent MISS with facet fusion (FF) and without facet fusion (WOFF) and evaluates instrumentation loosening and failure. https://www.selleckchem.com/products/dooku1.html Methods TL trauma patients who underwent MISS between 2006 and 2013 were identified and stratified into FF and WOFF groups. To evaluate progressive kyphosis and loss of correction, Cobb angles were measured at immediate postoperative, short-term, and long-term follow-up. Evidence of >2 mm of radiolucency on radiographs indicated screw loosening. If instrumentation was removed, postremoval kyphosis angle was obtained. Results Of the 80 patients, 24 were in FF and 56 were in WOFF group. Between immediate postoperative and short-term follow-up, kyphosis angle changed by 4.0° (standard error [SE] 1.3°) in the FF and by 3.0° (SE 0.4°) in the WOFF group. The change between immediate postoperative and long-term follow-up kyphosis angles was 3.4° (S.E 1.1°) and 5.2° (S.E 1.6°) degrees in the FF and WOFF groups, respectively. Facet fusion had no impact on the change in kyphosis at short term (P = .49) or long term (P = .39). The screw loosening rate was 20.5% for the 80 patients with short-term follow-up and 68.8% for the 16 patients with long-term follow-up. There was no difference in screw loosening rate. Fifteen patients underwent instrumentation removal-all from the FF group. Conclusion FF in MISS does not impact the correction achieved and maintenance of correction in patients with traumatic spine injuries. © The Author(s) 2019.

Sixty-five (66%) patients were implanted for primary prevention. Dual-chamber ICDs with or without CRT were 21 and 65%, respectively. Obstructive HCM was present in 47% pacemaker patients and 25% ICD patients with available pre-implant echo. Conclusions This retrospective registry-based study provides a picture of CIED first implants in HCM patients in a Swedish tertiary university hospital. ICDs were the most commonly implanted devices, covering 59% of CIED implants. HCM patients receiving a pacemaker or an ICD had different epidemiological and clinical profiles.Introduction Migraine is a chronic neurovascular disorder characterized by recurrent headache attacks associated with neurological and autonomic symptoms. The pathophysiological mechanisms of the disease are extremely complex, involving hypothalamic and trigeminovascular activation, cortical spreading depression, release of pro-inflammatory peptides, peripheral and central sensitization. The underlying cellular and molecular mechanisms have been scarcely investigated. Recently, genetic studies have suggested that different metabolic pathways could be involved in the pathogenesis of migraine.Areas covered This review focuses on cellular and molecular mechanisms involved in migraine, suggesting a role for circadian clocks, ion channels, synaptic plasticity, vascular factors, ion metal homeostasis, and impaired glucose metabolism in the pathogenesis of the disease. Accordingly, the article proposes new therapeutic targets that may be of particular relevance for disease prevention.Expert opinion Several complex molecular mechanisms are involved in setting the genetic threshold for migraine and the pathogenesis of headache attacks. Most promising new therapeutic targets are the modulation of hypothalamic activity and ion channels involved in pain transmission. Further studies in animals and humans are necessary to enhance the elucidation of the molecular mechanisms of migraine and open new avenues for disease prevention.Although offense-supportive cognitions are related to the maintenance of contact sexual offending behavior, it is unknown whether this finding also applies to online sexual offending behavior. https://www.selleckchem.com/products/brivudine.html A few studies have examined the cognitions of men convicted for using child sexual exploitation material, but findings remain limited due to important methodological limitations. Furthermore, fewer studies have investigated the cognitions of men who use the internet to solicit sexual activities with children. The objective of this study was to examine the nature of the cognitions that support online sexual offending against children. The content of police interviews was analyzed using a thematic analysis to identify the cognitive themes present in the offense-related views expressed by 20 men who consumed child sexual exploitation material, 15 who sexually solicited children, and 18 who committed both types of online offenses. Results revealed eight cognitive themes that reflected four underlying themes related to interpersonal relationships, the sexualisation of children, perceptions of the self, and perceptions of the virtual environment. Findings indicate that while the cognitive themes of the three groups are similar, their specific content varies according to the types of offenses. Implications for future research are discussed.The spread of tobacco smoking has increased over time at the global and national levels. One of the widely spread tobacco products is waterpipe. Recent studies showed that waterpipe tobacco smoke contains toxic substances, including carbon monoxide and nicotine. Some of them are genotoxic carcinogen, such as formaldehyde. This study aims to provide comprehensive insight into the types and depth of the scientific literature on waterpipe tobacco smoke chemical content, its genotoxic effects, and waterpipe device microbial contamination. We conducted a systematic comprehensive review of articles published between 1986 and December 2018. Primary research articles focusing on the content of waterpipe smoke, including chemical, genotoxic, and microbial contaminants, were eligible for inclusion. Of the 1,286 studies generated, 22 studies were included. Twenty-three chemical families were extracted from waterpipe smoke. Aldehydes were the most identified chemical family in 6 studies, and next is polycyclic hydrocarbons, found in 5 studies. About 206 chemical compounds were identified. Flavobacterium, Pseudomonas, coagulase-negative Staphylococci, and Streptococcus were the most abundant pathogen contaminants. Waterpipe smoke had elevated levels of many DNA damage markers (8-hydroxy-2'-deoxyguanosine and cytochrome P450 1A1) and inhibited levels of many DNA repair genes (OGG1 and XRCC1) in waterpipe smokers. Waterpipe smoke is associated with the genotoxic effect, which elevates the levels of many DNA damage markers and inhibits the levels of many DNA repair genes. In addition, waterpipe smoking can expose smokers to a range of pathogenic bacteria.Hemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, and, if not treated, fatal disorder that is characterized by excessive immune system activation. This disorder can be precipitated by different triggers including malignancies, infections, and autoimmune disorders. Diagnosis is made by fulfilling criteria that was last updated in 2004, and treatment frequently includes management of the underlying trigger but can also include chemotherapy. In this article, we report a case of HLH in a 27-year-old male, who had been diagnosed with advanced untreated HIV, who presented to the hospital with fever and generalized fatigue with no obvious etiology. Infectious workup revealed cytomegalovirus viremia, and the patient met HLH criteria with impressive hyperferritinemia of 15 432 ng/mL. The patient was started on treatment for cytomegalovirus infection that led to resolution of HLH. Our report highlights the importance of early detection of HLH in special populations, and that treating the presumptive trigger can lead to resolution of HLH.Pulmonary complications from cocaine use can range from bronchospasm to vasospasm leading to pulmonary infarction. Profound vasospasm may also lead to perfusion defects presenting as pulmonary embolism on ventilation-perfusion scan. A 65-year-old patient with a past medical history of substance abuse and chronic kidney disease presents to the emergency department with sudden-onset chest pain and shortness of breath. Ventilation-perfusion scan revealed filling defect most notably in the lingual lobe. He was later discharged on warfarin for the management of pulmonary embolism. The patient presented to the emergency department 2 weeks later with similar complaints; the international normalized ratio was subtherapeutic, and urine drug screen was positive for cocaine. Repeat ventilation-perfusion scan revealed no filling defects. Follow-up bilateral venous Doppler of lower extremities and D-dimer were within normal limits.

Delirium is a psycho-organic syndrome common in hospitalized patients, especially the elderly, and is associated with poor clinical outcomes. This study aims to identify the predictors that are mostly associated with the risk of delirium episodes using a machine learning technique (MLT). A random forest (RF) algorithm was used to evaluate the association between the subject's characteristics and the 4AT (the 4 A's test) score screening tool for delirium. RF algorithm was implemented using information based on demographic characteristics, comorbidities, drugs and procedures. Of the 78 patients enrolled in the study, 49 (63%) were at risk for delirium, 32 (41%) had at least one episode of delirium during the hospitalization (38% in orthopedics and 31% both in internal medicine and in the geriatric ward). The model explained 75.8% of the variability of the 4AT score with a root mean squared error of 3.29. Higher age, the presence of dementia, physical restraint, diabetes and a lower degree are the variables associated with an increase of the 4AT score. Random forest is a valid method for investigating the patients' characteristics associated with delirium onset also in small case-series. The use of this model may allow for early detection of delirium onset to plan the proper adjustment in healthcare assistance.A large university in Queensland, Australia with a diverse staff and student community introduced a campus wide smoke-free policy in 2016. The purpose of this enquiry was to understand attitudes about a new smoke-free policy, its potential impact and the shift in social norms and organizational culture to inform the next phase of implementation. An electronic survey was distributed to all staff and students approximately 12 weeks after the smoke-free policy was implemented. The survey consisted of multiple-choice questions about demographics, smoking behaviour, attitudes towards smoking and tobacco control, awareness of the smoke-free policy, and attitudes towards the effect of a completely smoke-free campus on quality of life, learning and enrolment. The survey was completed by 641 university staff and students. Respondents reported seeking out (80.4%) and socialising in smoke-free environments (86.6%) and supported smoke-free buildings (96.1%), indoor areas (91.6%), and outdoor areas (79%). The results revealed overwhelming support for a completely smoke-free campus (83%) and minority support for designated smoking areas (31%). Overall, respondents reflected positively towards a campus wide smoke-free policy. These findings suggest Queensland's early adoption of tobacco control laws influenced the social environment, de-normalised smoking, changed behaviour, preference for smoke-free environments and shifted social norms. These findings provide convincing evidence for organisational change and suggest health promotion policy makers should progress the implementation of smoke-free policies nationally across the higher education sector.Universities are providing short-term overseas study programs for healthcare students to increase their cultural competence (i.e., capacity to work effectively in cross-cultural situations). However, there is limited empirical research evaluating the effects of these programs using well-controlled research designs. In the present research study, undergraduate healthcare students in an Australian university were selected as participants. Group 1 (n = 32) participated in a short-term overseas study program in Asia (i.e., China, Vietnam, Singapore, and Taiwan), whereas Group 2 (n = 46) stayed in Australia to continue their university education as usual. All participants completed a self-developed demographic questionnaire, Cultural Intelligence Scale, and Multicultural Personality Questionnaire. Cultural competence was surveyed pre- and post-short-term overseas programs. After controlling for prior overseas experiences and the open-mindedness trait, an ANCOVA indicated that Group 1 had a significantly higher scores than Group 2 in cultural knowledge (p less then 0.05), but not in cultural awareness, attitude, or skills. It is suggested that short-term overseas study programs may increase healthcare students' cultural knowledge, a component of competence, and that more needs to be accomplished to improve other areas of cultural competence.The use of communication technologies, e.g., mobile phones, has increased dramatically in recent years, and their use among drivers has become a great risk to traffic safety. https://www.selleckchem.com/products/au-15330.html The present study assessed the workload and road ordinary violations, utilizing driving data collected from 39 young participants who underwent a dual-task while driving a simulator, i.e., respond to a call, text on WhatsApp, and check Instagram. Findings confirmed that there are significant differences in the driving performance of young drivers in terms of vehicle control (i.e., lateral distance and hard shoulder line violations) between distracted and non-distracted drivers. Furthermore, the overall workload score of young drivers increases with the use of their mobile phones while driving. The obtained results contribute to a better understanding of the driving performance of distracted young drivers and thus they could be useful for further improvements to traffic safety strategies.The cost burdens of potentially preventable emergency department visits for pediatric asthma were estimated for Asian Americans, Pacific Islanders, and Whites using Hawai'i statewide 2015-2016 data. The cost burden of the 3234 preventable emergency department visits over the study period was over $1.9 million. Native Hawaiians had the largest proportion (36.5%) of all preventable emergency department visits and accounted for the highest costs for the two years at $709,698. After adjusting for other factors, costs for preventable pediatric-asthma-related emergency department visits differed significantly by age, insurance provider, and island of residency. Reducing potentially preventable emergency department visits would not only improve health disparities among Native Hawaiians compared to other racial or ethnic populations in Hawai'i, but could also generate cost savings for public and private insurance payers.

Most patients (83%) had TGs < 2.26 mmol/L (< 200 mg/dL), while < 1% had TGs > 9.94 mmol/L (> 880 mg/dL). Overall, the IR of AP was low (0.08%; 95% confidence internal [CI], 0.08-0.08%), but increased with increasing TGs (0.08% in TGs < 2.26 mmol/L [< 200 mg/dL] to 1.21% in TGs > 11.29 mmol/L [> 1000 mg/dL]). In patients with a prior history of AP, the IR of AP increased dramatically; patients with ≥2 AP events at baseline had an IR of 29.98% (95% CI, 25.1-34.9%). The risk of AP increases with increasing TG strata; however, the risk increases dramatically among patients with a recent history of AP. The risk of AP increases with increasing TG strata; however, the risk increases dramatically among patients with a recent history of AP. Pseudorabies virus (PRV), a member of the Alphaherpesviruses, is one of the most important pathogens that harm the global pig industry. Accumulated evidence indicated that PRV could infect humans under certain circumstances, inducing severe clinical symptoms such as acute human encephalitis. Currently, there are no antiviral drugs to treat PRV infections, and vaccines available only for swine could not provide full protection. Thus, new control measures are urgently needed. In the present study, kaempferol exhibited anti-PRV activity in mice through improving survival rate by 22.22 %, which was higher than acyclovir (Positive control) with the survival rate of 16.67 % at 6 days post infection (dpi); meanwhile, the survival rate was 0 % at 6 dpi in the infected-untreated group. Kaempferol could inhibit the virus replication in the brain, lung, kidney, heart and spleen, especially the viral gene copies were reduced by over 700-fold in the brain, which was further confirmed by immunohistochemical examination. The pathogenic changes induced by PRV infection in these organs were also alleviated. The transcription of the only immediate-early gene IE180 in the brain was significantly inhibited by kaempferol, leading to the decreased transcriptional levels of the early genes (EPO and TK). The expression of latency-associated transcript (LAT) was also inhibited in the brain, which suggested that kaempferol could inhibit PRV latency. Kaempferol-treatment could induce higher levels of IL-1β, IL-4, IL-6, TNF-α and IFN-γ in the serum at 3 dpi which were then declined to normal levels at 5 dpi. These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection. These results suggested that kaempferol was expected to be a new alternative control measure for PRV infection. Self testing for HIV is a targeted intervention with the potential to increase the access, uptake and frequency of HIV testing and more effectively reach the undiagnosed, especially in priority populations. https://www.selleckchem.com/products/agk2.html The objectives of this study were to (1) evaluate the INSTI HIV self-test performance compared with laboratory reference testing, (2) document if intended users can perform the steps to use the HIV self-test device, and (3) document if intended users can successfully interpret contrived positive, negative, and invalid results. Study was intended to be submitted to Health Canada for review for regulatory approval purposes. The study used a cross-sectional design and recruited consenting adults who were representative of intended users of HIV self-testing from four community sites across Ontario, Québec, and Manitoba between August 2019 and March 2020. The results of the observed HIV self-test were compared with results of the Abbott Architect HIV Ag/Ab Combo test. Usability outcomes for critical (e.g., icularly when impacted by Coronavirus pandemic restrictions. Underutilization of health services among chronic non-communicable disease sufferers, especially for hypertension (HBP) and diabetes mellitus (DM), was considered as a significant contributing factor to substantial cases in terms of both avoidable morbidity and mortality. However, evidence on health services underutilization and its associated factors in poverty-stricken areas remain scarce based on previous literature. This study aims to describe health services underutilization for people diagnosed with chronic diseases in impoverished regions and to identify its associated factors, which are expected to provide practical implications for the implementations of interventions tailored to the specific needs of disadvantaged residents in rural China to achieve effective utilization of health services in a timely manner. Data were collected from a cross-sectional survey conducted through face-to-face interviews among 2413 patients from six counties in rural central China in 2019. The Anderson behavioral modaging population structures. Rhizosphere soil is a crucial niche for the diverse beneficial microbial communities in plant-microbe interactions. This study explores the antagonistic potential and diversity of the rhizosphere soil bacteria from commercial tea estates of Assam, India which comes under the Indo-Burma mega-biodiversity hotspot. Rhizosphere soil samples were collected from six different tea estates to isolate the bacteria. The bacterial isolates were subjected to evaluate for the antagonistic activity against fungal pathogens. The potential isolates were investigated for chitinase production and the presence of chitinase gene. The bacterial genetic diversity was studied by Amplified Ribosomal DNA Restriction Analysis (ARDRA) and BOX-PCR fingerprinting. A total of 217 rhizobacteria were isolated from tea rhizosphere soil, out of which 50 isolates exhibited the potential antagonistic activity against fungal pathogens. Among them, 12 isolates showed extracellular chitinase activity and the presence of chitinase genes. The che poorly explored tea rhizosphere soil could be a rich reservoir for the investigation of potential antagonistic bacterial candidates for sustainable agricultural and industrial applications. Google Trends (GT) is being used as an epidemiological tool to study coronavirus disease (COVID-19) by identifying keywords in search trends that are predictive for the COVID-19 epidemiological burden. However, many of the earlier GT-based studies include potential statistical fallacies by measuring the correlation between non-stationary time sequences without adjusting for multiple comparisons or the confounding of media coverage, leading to concerns about the increased risk of obtaining false-positive results. In this study, we aimed to apply statistically more favorable methods to validate the earlier GT-based COVID-19 study results. We extracted the relative GT search volume for keywords associated with COVID-19 symptoms, and evaluated their Granger-causality to weekly COVID-19 positivity in eight English-speaking countries and Japan. In addition, the impact of media coverage on keywords with significant Granger-causality was further evaluated using Japanese regional data. Our Granger causality-based approach largely decreased (by up to approximately one-third) the number of keywords identified as having a significant temporal relationship with the COVID-19 trend when compared to those identified by Pearson or Spearman's rank correlation-based approach.