Result Baseline and follow-up data were available for 19 pharmacy staff members and 48 parents who attended a counseling session in the pharmacy. In both groups there was as decrease in negative beliefs and worries towards TCS (p  less then  0.05). Mean total TOPICOP scores decreased from 42 to 35% and from 33 to 25% for parents and pharmacy staff respectively. Conclusion Our results show the prevalence of corticophobia among parents. Education of pharmacy staff and targeted patient counseling seems to be effective in reducing corticophobia.The present study aimed to clarify the process of peer support formation and the promotion of recovery in people using psychiatric day care. From January to March 2014, semi-structured interviews were conducted with 18 participants with mental illness living in the community in Japan. The qualitative data were analyzed using a modified grounded theory approach. The results described a two-stage process (1) awareness of peers with similar disability and distress and (2) formation and utilization of peer support. These results suggest that adjusting the environment and engaging in activities assisting others are useful for facilitating peer support and promoting the recovery of users in psychiatric day care.The estuarine firefly, Pteroptyx tener, aggregates in the thousands in mangrove trees lining tidal rivers in Southeast Asia where they engage one another in a nocturnal, pre-mating ritual of synchronised courtship flashes. Unfortunately, populations of the species by virtue of being restricted to isolated estuarine rivers systems in the region, are at risk of genetic isolation. Because of this concern we undertook the task of sequencing and characterising the mitochondrial DNA genome of P. tener, as the first step towards helping us to characterise and better understand their genetic diversity. We sequenced and assembled the mitochondrial DNA genome of P. tener from two male and female specimens from the district of Kuala Selangor in Peninsular Malaysia and announce the molecules in this publication. We also reconstructed the phylogenetic trees of all available lampyrids mitogenomes and suggest the need to re-examine our current understanding of their classification which have largely been based on morphological data and the cox1 gene. Separately, our analysis of codon usage patterns among lampyrid mitogenomes showed that the codon usage in a majority of the protein-coding genes were non-neutral. Codon usage patterns between mitogenome sequences of P. tener were, however, largely neutral. Our findings demonstrate the usefulness of mitochondrial genes/mitogenomes for analysing both inter- and intra- specific variation in the Lampyridae to aid in species discovery in this highly variable genus; and elucidate the phylogenetic relationships of Pteroptyx spp. from the region.Inorganic-organic optical probe based on lanthanide emission will provide a new way for specific applications. In this work, sarcosine and urea are selected as raw materials to synthesize carbon dots with cyan-emissive color. In the next step, indicator components (Ethylene Diamine Tetraacetic Acid and lanthanide ions) are incorporated onto carbon quantum dots (CQDs) and the flexible alginate hydrogel is employed as the host to accommodate the emissive species. The soft material can exhibit typical red and green emissions. Its luminescence is responsive to calcium ions and the detection limit has been calculated to be 0.84 μM and 0.92 μM respectively. Such optical device can be employed as a portable probe in a variety of scientific fields due to its convenience and flexibility.The present study demonstrates, development of ssDNA aptamers against whole cell of S. flexneri employing a whole bacterium-based Systemic Evolution of Ligands by Exponential Enrichment (SELEX). After ten rounds of SELEX, cell surface specific aptamer pool was cloned, sequenced and divided based on sequence similarities and secondary structure. Binding affinity of FITC labelled aptamer from different group were carried out by flow cytometry analysis. The dissociation constant (Kd) values for specific and higher binder were evaluated to range from 144 to 329 nM. Six high binding aptamers with lower dissociation constant was chosen for selectivity study. Aptamer SHI 23, SHI 37 and SHI 42 showed higher selectivity towards S. flexneri in comparison with other related bacteria. Further applicability of selected aptamer was proven by fluorescence assay for convenience detection of target cell from spiked water sample and natural contaminated water samples. Altogether, aptamer generated in this study can be alternative DNA ligands for detection of S. flexneri compared to available ligands.Glioma is the most common brain tumor of the central nervous system. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified to play a vital role in the initiation and progression of glioma, including tumor cell proliferation, survival, apoptosis, invasion, and therapy resistance. New documents emerged, which indicated that the interaction between long non-coding RNAs and miRNAs contributes to the tumorigenesis and pathogenesis of glioma. LncRNAs can act as competing for endogenous RNA (ceRNA), and molecular sponge/deregulator in regulating miRNAs. These interactions stimulate different molecular signaling pathways in glioma, including the lncRNAs/miRNAs/Wnt/β-catenin molecular signaling pathway, the lncRNAs/miRNAs/PI3K/AKT/mTOR molecular signaling pathway, the lncRNAs-miRNAs/MAPK kinase molecular signaling pathway, and the lncRNAs/miRNAs/NF-κB molecular signaling pathway. In this paper, the basic roles and molecular interactions of the lncRNAs and miRNAs pathway glioma were summarized to better understand the pathogenesis and tumorigenesis of glioma.Obesity is a risk factor for Barrett’s oesophagus and oesophageal adenocarcinoma. Adipose tissue secretes the hormone leptin. Leptin is a growth factor for several cell types, including Barrett’s cells and oesophageal adenocarcinoma cells. Statins are associated with reduced rates of Barrett’s oesophagus and oesophageal cancer and exhibit anti-cancer effects in vitro. The mechanisms of these effects are not fully established. We have examined the effects of leptin and the lipid-soluble statin, atorvastatin, on signalling via monomeric GTP-binding proteins and Akt. Proliferation and apoptosis were assessed in OE33 cells. Akt activity was quantified by cell-based ELISA and in vitro kinase assay. Specific small-molecule inhibitors and a dominant-negative construct were used to reduce Akt activity. Small GTPases were inhibited using transfection of dominant-negative plasmids, prenylation inhibitors and pretreatment with atorvastatin. Leptin stimulated Akt activity and cell proliferation and inhibited camptothecin-induced apoptosis in an Akt-sensitive manner. Leptin induced phosphorylation of Bad and FOXO1 in an Akt-sensitive manner. Leptin activated Ras, Rac, RhoA and cdc42. Transfection of dominant-negative plasmids confirmed that leptin-induced Akt activation required Ras, RhoA cdc42 but not Rac. Atorvastatin inhibited leptin-induced activation of Ras, RhoA, cdc42 and Akt. Co-treatment with mevalonate prevented these effects of atorvastatin. The protein kinase Akt is essential to the growth-promoting and anti-apoptotic effects of leptin in oesophageal adenocarcinoma cells. Akt is activated via Ras-, Rho- and cdc42-dependant pathways. Atorvastatin reduces leptin-induced Akt activation by inhibiting prenylation of small GTPases. This may explain the reduced incidence of oesophageal adenocarcinoma in statin-users.TWIST1 (Twist) is a basic helix-loop-helix transcription factor that is overexpressed in many cancers and promotes tumor cell invasion, metastasis, and recurrence. In this study, we demonstrate that Twist upregulates expression of microRNA 22 (miR-22) which, in turn, downregulates estrogen receptor alpha (ER) expression in breast cancer. Initial analysis of miR-22 and Twist expression in a panel of breast cancer cell lines showed a direct correlation between Twist and miR-22 levels with miR-22 being highly expressed in ER negative cell lines. Overexpressing Twist caused increased miR-22 levels while downregulating it led to decreased miR-22 expression. To characterize the upstream promoter region of miR-22, we utilized rapid amplification of cDNA ends and identified the transcription start site and the putative promoter region of miR-22. Mechanistically, we determined that Twist, in combination with HDAC1 and DNMT3B, transcriptionally upregulates miR-22 expression by binding to E-boxes in the proximal miR-22 promoter. We also established that miR-22 causes an increase in growth in 3D but not 2D cultures. Importantly, we observed a direct correlation between increased breast cancer grade and Twist and miR-22 expression. We also identified two potential miR-22 binding sites in the 3′-UTR region of ER and confirmed by promoter assays that miR-22 regulates ER expression by binding to both target sites. These results reveal a novel pathway of ER suppression by Twist through miR-22 activation that could potentially promote the ER negative phenotype in breast cancers.Research demonstrates that Black parents attempt to suppress children’s expressions of negative emotions (e.g., anger, fear), in part, to protect them from experiencing racial bias from authority figures. The goal of this study was to examine whether the effectiveness of parental suppression strategies in reducing behavior problems depends on whether parents talk to children about the potential of experiencing racism (i.e., preparation for bias) and children’s resting cardiac vagal tone as indexed by baseline respiratory sinus arrhythmia (RSA). Ninety-four parents (97% mothers) who identified their child as Black (56% girls) completed questionnaires about their punitive and minimizing responses to their child’s negative emotions and their child’s internalizing and externalizing problems at ages 5 and 6. Children’s baseline RSA was assessed at age 5. Results indicated that parents’ suppression of children’s negative emotions predicted decreased externalizing behaviors (e.g., acting out) only when parents talked to their children about racism. When parents did not contextualize their restrictions on children’s emotional expressions with discussions about race, children with higher baseline RSA demonstrated increased externalizing behaviors, whereas those with lower baseline RSA were unaffected. Parental suppression strategies led to increased internalizing symptoms (e.g., anxiety, withdrawal) among children with higher baseline RSA regardless of whether parents discussed racism. Black parents face a conundrum in which suppressing their children’s negative emotions, in hopes of subverting racism, may reduce their children’s externalizing problems under some circumstances, but may increase the risk of their children developing internalizing problems. Implications for systemic policy change to combat racism are discussed.Most adolescents experiment with alcohol, but a smaller percentage advance to heavy alcohol use (AU) and AU disorder (AUD). Understanding for whom and how early risk leads to AUD is of interest to prevention, treatment, and etiology of AUD. Informed by developmental and behavioral neuroscience theory, the current study tested whether temperament (effortful control, surgency, and negative affect), peer AU (multi-reporter), and AU with parents’ permission interacted to distinguish youth who experiment with alcohol from those who escalate to AUD. Community adolescents (N = 765, 53% female) were assessed annually for seven years (Mage = 11.8, range 10-13 at Year 1; Mage = 18.7; range = 17-20 at year 7). Temperament by early experience interactions were expected to predict amount of AU. Amount of AU was expected to mediate the relationship between the interactions and AUD symptoms (assessed at Years 3 and 7, Mage = 13.8 and 18.7) above and beyond a range of confounds (e.g., problem behavior and parental AU and AUD). Supporting hypotheses, effortful control and surgency interacted with AU with parents’ permission and peer AU, respectively, to predict higher amount of AU (R2 = 0.47) and AUD symptoms (R2 = 0.03). Results support developmental and behavioral neuroscience theory. High surgency and low effortful control in conjunction with peer AU and AU with parents’ permission were associated with large effects on AU and moderate mediated effects through AU to AUD. AU with parents’ permission was risky at low and high effortful control and protective when peers used alcohol.The low-rank matrix approximation (LRMA) is an efficient image denoising method to reduce additive Gaussian noise. However, the existing low-rank matrix approximation does not perform well in terms of Rician noise removal for magnetic resonance imaging (MRI). To this end, we propose a novel MR image denoising approach based on the extended difference of Gaussian (DoG) filter and nonlocal low-rank regularization. In the proposed method, a novel nonlocal self-similarity evaluation with the tight frame is exploited to improve the patch matching. To remove the Rician noise and preserve the edge details, the extended DoG filter is exploited to the nonlocal low-rank regularization model. The experimental results demonstrate that the proposed method can preserve more edge and fine structures while removing noise in MR image as compared with some of the existing methods.Imbalance in the autonomic nervous system can lead to orthostatic intolerance manifested by dizziness, lightheadedness, and a sudden loss of consciousness (syncope); these are common conditions, but they are challenging to diagnose correctly. Uncertainties about the triggering mechanisms and the underlying pathophysiology have led to variations in their classification. This study uses machine learning to categorize patients with orthostatic intolerance. We use random forest classification trees to identify a small number of markers in blood pressure, and heart rate time-series data measured during head-up tilt to (a) distinguish patients with a single pathology and (b) examine data from patients with a mixed pathophysiology. Next, we use Kmeans to cluster the markers representing the time-series data. We apply the proposed method analyzing clinical data from 186 subjects identified as control or suffering from one of four conditions postural orthostatic tachycardia (POTS), cardioinhibition, vasodepression, anfrom syncope and control patients. Results show that machine learning can provide accurate classification of disease groups for 98% of patients and we identified two subgroups within the control patients differentiated by their BP response.In recent years, cadmium (Cd) contamination in agricultural soils and its subsequent transfer to crops is one of the high-priority environmental and public health issues of global concern, especially in densely populated developing countries like Bangladesh. However, no effective strategy has been introduced or implemented yet to manage Cd-contaminated soils in order to sustain agricultural production with no human health risks. In this study, agricultural soil samples were collected from 60 locations of 10 upazilas from Tangail district to assess the extent of soil Cd contamination. The Cd concentration ranged from 0.83 to 4.08 mg kg-1 with a mean of 2.17 mg kg-1 in topsoil (0-15 cm), and from 0.67 to 3.74 mg kg-1 with a mean of 2.10 mg kg-1 in subsoil (16-30 cm). The values of contamination factor (CF) indicated that all the sampling locations were found to be highly contaminated with Cd. Pot trials with the application of different doses of biochar and vermicompost in Cd-contaminated soil (0.8 mg kg-1 Cd) revealed that integrated application of biochar (5 t ha-1) and vermicompost (5 t ha-1) was the best treatment that significantly (p  less then  0.05) reduced plant Cd concentration (72%) and increased the biomass of experimental crop, Red amaranth (Amaranthus cruentus). This combined treatment also significantly reduced the uptake of Cr (37%) when co-contamination was present. The study suggests the application of biochar (5 t ha-1) in combination with vermicompost (5 t ha-1) to reduce human health risk and increase crop production when the soil is loamy sand in texture.Various hydrogeochemical processes can modify the quality of river water during riverbank filtration (RBF). Identifying the subsurface processes responsible for the bank-filtered water quality is challenging, but essential for predicting water quality changes and determining the necessity of post-treatment. However, no systematic approach for this has been proposed yet. In this study, the subsurface hydrogeochemical processes that caused the high concentrations of total iron (Fe) and sulfate (SO42-) in the bank-filtered water were investigated at a pilot-scale RBF site in South Korea. For this purpose, water quality variations were monitored in both the extraction well and the adjacent river over five months. The volumetric mixing ratio between the river water and the native groundwater in the RBF well was calculated to understand the effect of mixing on the quality of water from the well and to assess the potential contribution of subsurface reactions to water quality changes. To identify the subsurface processes responsible for the evolution of Fe and SO42- during RBF, an inverse modeling based on the chemical mass balance was conducted using the water quality data and the calculated volumetric mixing ratio. The modeling results suggest that pyrite oxidation by abundant O2 present in an unsaturated zone could be a primary process explaining the evolution of total Fe and SO42- during RBF at the study site. The presence of pyrite in the aquifer was indirectly supported by iron sulfate hydroxide (Fe(SO4)(OH)) detected in oxidized aquifer sediments.The aim of this study was to comprehensively assess the prevalence of goiter and thyroid nodules (TNs) in relation to China’s iodine nutrition level over the past 20 years and provide an effective reference for developing health policies. PubMed, EMBASE, Chinese National Knowledge Infrastructure, Chongqing VIP, and Chinese Wan Fang databases were searched for relevant studies from Jan 1996 to Feb 2020. Two reviewers extracted valid data from the eligible citations to determine the morbidity of TNs in different urinary iodine concentrations (UICs) and in patients of different genders, of different ages, who live in different geographic regions, and who live at different altitudes, as well as the P values of interactions between groups. There were 26 articles (34 studies) included in this analysis. The overall morbidity of TNs in mainland China was 23.4%. Morbidity was higher in urban areas (P less then 0.001) than in rural and mixed areas. Coastal areas (P less then 0.001), female patients (P less then 0.001), high-altitude areas (P less then 0.001), and residence in south China (P less then 0.001) were all associated with higher morbidity of TNs. The lowest morbidity value of TNs, 16%, was in the more-than-adequate iodine subgroup. The highest morbidity, 27.2%, was in the adequate iodine subgroup. The morbidity of TNs increases with age, and women are more likely to have TNs. We also need to perform more epidemiological studies, and in the future, we should cultivate better understanding of the relationship between other thyroid diseases and provide more comprehensive and useful information for other researchers.

Cancer and heart disease are the leading causes of mortality in the USA. Advances in cancer therapies, namely, the development and use of chemotherapeutic agents alone or in combination, are becoming increasingly prevalent.

Many chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system. MTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.

Many chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system. MTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.Italy and the United States are two of the countries most affected by SARS-CoV-2 (COVID-19), with more than 240,760 confirmed cases in Italy and 2,699,658 in the United States (as of July 2, 2020). The current COVID-19 pandemic has led to substantial changes in many fields of medicine, specifically in the forensic discipline. Medicolegal activities related to conducting autopsies have been largely affected by the COVID-19 pandemic. Postmortem examinations are generally discouraged by government regulations due to the risk of spreading the disease further through the handling and dissection of bodies from patients who succumbed to COVID-19 infection. There is a paucity of data regarding the persistence of SARS-CoV-2 in bodies, as well as concerning the reliability of swabbing methods in human remains. On the other hand, the autopsy is an essential tool to provide necessary information about the pathophysiology of the disease that presents useful clinical and epidemiological insights. On this basis, we aim to address issues concerning general medical examiner/coroner organization, comparing the Italian and American systems. We also discuss the pivotal roles of forensic pathologists in informing infectious disease surveillance. Finally, we focus on the impact of COVID-19 emergency on medicolegal practices in Italy and the United States, as well as the responses of the forensic scientific community to the emerging concerns related to the pandemic. We believe that stronger efforts by authorities are necessary to facilitate completing postmortem examinations, as data derived from such assessments are expected to be paramount to improving patient management and disease prevention.The importance of the main protease (Mpro) enzyme of SARS-CoV-2 in the digestion of viral polyproteins introduces Mpro as an attractive drug target for antiviral drug design. This study aims to carry out the molecular docking, molecular dynamics studies, and prediction of ADMET properties of selected potential antiviral molecules. The study provides an insight into biomolecular interactions to understand the inhibitory mechanism and the spatial orientation of the tested ligands and further, identification of key amino acid residues within the substrate-binding pocket that can be applied for structure-based drug design. In this regard, we carried out molecular docking studies of chloroquine (CQ), hydroxychloroquine (HCQ), remdesivir (RDV), GS441524, arbidol (ARB), and natural product glycyrrhizin (GA) using AutoDock 4.2 tool. To study the drug-receptor complex’s stability, selected docking possesses were further subjected to molecular dynamics studies with Schrodinger software. The prediction of ADMET/toxicity properties was carried out on ADMET Prediction™. The docking studies suggested a potential role played by CYS145, HIS163, and GLU166 in the interaction of molecules within the active site of COVID-19 Mpro. In the docking studies, RDV and GA exhibited superiority in binding with the crystal structure of Mpro over the other selected molecules in this study. Spatial orientations of the molecules at the active site of Mpro exposed the significance of S1-S4 subsites and surrounding amino acid residues. Among GA and RDV, RDV showed better and stable interactions with the protein, which is the reason for the lesser RMSD values for RDV. Overall, the present in silico study indicated the direction to combat COVID-19 using FDA-approved drugs as promising agents, which do not need much toxicity studies and could also serve as starting points for lead optimization in drug discovery.The abdominal aorta is the largest artery in the abdominal cavity that supplies blood flows to vital organs through the complex visceral arterial branches, including the celiac trunk (the liver, stomach, spleen, etc.), the renal arteries (the kidneys) and the superior and inferior mesenteric arteries (the small and large intestine, pancreas, etc.). An accurate simulation of blood flows in this network of arteries is important for the understanding of the hemodynamics in various organs of healthy and diseased patients, but the computational cost is very high. As a result, most researchers choose to focus on a portion of the artery or use a low-dimensional approximation of the artery. In the present work, we introduce a parallel algorithm for the modeling of pulsatile flows in the abdominal aorta with branches to the primary organs, and an organ-based two-level method for calculating the resistances for the outflow boundary conditions. With this highly parallel approach, the simulation of the blood flow for a cardiac cycle of the anatomically detailed aorta can be obtained within a few hours, and the blood distribution to organs including liver, spleen and kidneys are also computed with certain accuracy. Moreover, we discuss the significant hemodynamic differences resulted from the influence of the peripheral branches. In addition, we examine the accuracy of the results with respect to the mesh size and time-step size and show the high parallel scalability of the proposed algorithm with up to 3000 processor cores.

Anaplastic thyroid carcinoma is a type of thyroid carcinoma with the most aggressive biological behaviour amongst thyroid cancer. Here, we review the current genomic and the impacts of advances in therapies to improve the management of patients with the cancer.

Common mutations being identified in anaplastic thyroid carcinoma are p53 and TERT promoter mutations. Other common mutated genes included BRAF, RAS, EIF1AX, PIK3CA, PTEN and AKT1, SWI/SNF, ALK and CDKN2A. Changes in expression of different microRNAs are also involved in the pathogenesis of anaplastic thyroid carcinoma. Curative resection combined with radiotherapy and combination chemotherapies (such as anthracyclines, platins and taxanes) has been shown to have effects in the treatment of some patients with anaplastic thyroid carcinoma. Newer molecular targeted therapies in clinical trials target mostly the cell membrane kinase and downstream proteins. These include targeting the EGFR, FGFR, VEGFR, c-kit, PDGFR and RET on the cell membrane as welbrane as well as VEGF itself and the downstream targets such as BRAF, MEK and mTOR. Immunotherapy is also being tested in the cancer. Updated knowledge of genomic as well as clinical trials on novel therapies is needed to improve the management of the patients with this aggressive cancer.Oxidative stress in the hypothalamic paraventricular nucleus (PVN) contributes greatly to the development of hypertension. The recombinant nuclear respiratory factor 1 (Nrf1) regulates the transcription of several genes related to mitochondrial respiratory chain function or antioxidant expression, and thus may be involved in the pathogenesis of hypertension. Here we show that in the two-kidney, one-clip (2K1C) hypertensive rats the transcription level of Nrf1 was elevated comparing to the normotensive controls. Knocking down of Nrf1 in the PVN of 2K1C rats can significantly reduce their blood pressure and level of plasma norepinephrine (NE). Analysis revealed significant reduction of superoxide production level in both whole cell and mitochondria, along with up-regulation of superoxide dismutase 1 (Cu/Zn-SOD), NAD(P)H quinone oxidoreductase 1 (NQO1), thioredoxin-dependent peroxiredoxin 3 (Prdx3), cytochrome c (Cyt-c) and glutathione synthesis rate-limiting enzyme (glutamyl-cysteine ligase catalytic subunit (Gclc) and modifier subunit (Gclm)), and down-regulation of cytochrome c oxidase subunit VI c (Cox6c) transcription after Nrf1 knock-down. In addition, the reduced ATP production and elevated mitochondrial membrane potential in the PVN of 2K1C rats were reinstated with Nrf1 knock-down, together with restored expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitochondrial transcription factor A (Tfam), coiled-coil myosin-like BCL2-interacting protein (Beclin1), and Mitofusin 1 (Mfn1), which are related to the mitochondrial biogenesis, fusion, and autophagy. Together, the results indicate that the PVN Nrf1 is associated with the development of 2K1C-induced hypertension, and Nrf1 knock-down in the PVN can alleviate hypertension through intervention of mitochondrial function and restorement of the production-removal balance of superoxide.This study is part of a large project carried out at the Cairo University, Egypt, and focused on assessing physiological and biochemical changes in Aiolopus thalassinus under the influence of environmental pollution with heavy metals (Pb, Cd, Cu, and Zn). The study aimed to investigate parameters related to maintaining redox balance, with particular emphasis on stage-, sex- and tissue-dependent differences in H2O2 and glutathione (GSH) levels and activity of selected enzymes involved in GSH metabolism. A noticeable increase in the concentration of H2O2 was found, especially in the gut of 5th instar nymphs and females from the highly polluted site. An increase in GSH concentration was significant, especially in the gut of adult A. thalassinus from the high polluted site. However, recycling of reduced form of glutathione in the gut by glutathione reductase (GR) was relevant only for females from the high polluted site. Nymphs and females generally showed higher glutathione S-transferase (GST) activity, especially in the gut. These stage- and sex-related differences can result from different growth dynamic and various reproductive functions of nymphs and both sexes. The digestive track is in direct contact with xenobiotics consumed with food. Nymphs are characterized by vigorous growth, they feed intensively, and their development processes are associated with substantial oxygen consumption. Also, maintaining the antioxidant system at a high level can be more important for females than males due to egg production over a long period. It appears that de novo GSH synthesis is a favorable and cost-effective adaptation mechanism for A. thalassinus living in the high polluted site.This study investigates the comprehension of spoken-Arabic idioms by Jordanian children aged five to 12 years. It examines the effects of age, semantic transparency, context, and task type on understanding six familiar transparent and opaque idioms in and out of context. The children are requested to verbally explain the meanings of each idiom. They are then asked to select the picture they think shows the idiom’s meaning. Finally, they are directed to choose the appropriate response from three possible options. The results show that older children are better at comprehending the idiomatic meanings of idioms than younger children. Furthermore, transparent idioms are understood earlier and easier than opaque ones. Moreover, context has a more evident effect on younger children. Older children, in contrast, show equal understanding of both idiom types in and out of context. Task type also plays a significant role in comprehension. Children’s performance on the multiple-choice task is much better when compared to their performance on explanation and picture-matching tasks.

Grocery food taxes represent a stable tax revenue stream for state and municipal government during times of adverse economic shocks such as that observed under the coronavirus disease 2019 (COVID-19) pandemic. Previous research, however, suggests a possible mechanism through which grocery taxes may adversely affect health. Our objectives are to document the spatial and temporal variation in grocery taxes and to empirically examine the statistical relationship between county-level grocery taxes and obesity and diabetes.

We collect and assemble a novel national dataset of annual county and state-level grocery taxes from 2009 through 2016. We link this data to three-year, county-level estimates based on data from the Centers for Disease Control and Prevention on rates of obesity and diabetes and provide a nation-wide spatial characterization of grocery taxes and these two health outcomes. Using a county-level fixed effects estimator, we estimate the effect of grocery taxes on obesity and diabetes rates, also controlling for a subset of potential confounders that vary over time.

We find a 1 percentage point increase in grocery taxes is associated with 0.588 and 0.215 percentage point increases in the county-level obesity and diabetes rates.

Counties with grocery taxes have increased prevalence of obesity and diabetes. We estimate the economic burden of increased obesity and diabetes rates resulting from grocery taxes to be $5.9 billion. Based on this estimate, the benefit-cost ratio of removing grocery taxes across the United States only considering the effects on obesity and diabetes rates is 1.90.

Counties with grocery taxes have increased prevalence of obesity and diabetes. We estimate the economic burden of increased obesity and diabetes rates resulting from grocery taxes to be $5.9 billion. Based on this estimate, the benefit-cost ratio of removing grocery taxes across the United States only considering the effects on obesity and diabetes rates is 1.90.

Mutations in kirsten rat sarcoma viral oncogene homolog (KRAS) are the most frequently observed genomic alterations in human cancers. No KRAS targeting therapy has been approved despite more than three decades of efforts. Encouraging progress has been made in targeting KRAS

with KRAS

specific covalent inhibitors in the past few years. Herein, we review the recent breakthroughs in KRAS targeting.

KRAS

mutation was found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal cancer. Recently, highly potent KRAS

specific inhibitors have been developed and demonstrated potent activity in preclinical models. Early results from phase 1 clinical trials with sotorasib and MRTX849 show promising antitumor activity in NSCLC, colorectal cancer and other solid tumors harboring KRAS

mutation. For the first time, the preclinical success of targeting KRAS has translated into clinical benefits, which holds the potential of transforming clinical management of KRAS mutated solid tumors. Additional efforts are needed to identify biomarkers that predict response to KRAS inhibition in patients with KRAS

as well as to develop strategies to overcome resistance.

KRASG12C mutation was found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal cancer. Recently, highly potent KRASG12C specific inhibitors have been developed and demonstrated potent activity in preclinical models. Early results from phase 1 clinical trials with sotorasib and MRTX849 show promising antitumor activity in NSCLC, colorectal cancer and other solid tumors harboring KRASG12C mutation. For the first time, the preclinical success of targeting KRAS has translated into clinical benefits, which holds the potential of transforming clinical management of KRAS mutated solid tumors. Additional efforts are needed to identify biomarkers that predict response to KRAS inhibition in patients with KRASG12C as well as to develop strategies to overcome resistance.This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1β and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.The correlations between shear wave velocity (SWV) calculated from virtual touch tissue imaging quantification (VTIQ) technique and histological prognostic factors of invasive ductal carcinoma was investigated. A total of 76 breast tumors histologically confirmed as invasive ductal carcinomas were included in this study. SWV values were measured by VTIQ for each lesion preoperatively or prior to breast biopsy. The maximum values were recorded for statistical analysis. Medical records were reviewed to determine tumor size, histological grade, lymph node status and immunohistochemical results. Tumor subtypes were categorized as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and triple negative. The correlations between SWV and histological prognostic factors were analyzed. It was found that tumor size showed positive association with SWV (r=0.465, P less then 0.001). Larger tumors had significantly higher SWV than smaller ones (P=0.001). Histological grade 1 tumors had significantly lower SWV values than those with higher histological grade (P=0.015). The Ki67 expression, tumor subtypes and lymph node status showed no statistically significant correlations with SWV, although triple negative tumors and lymph node-positive tumors showed higher SWV values. It was concluded that tumor size was significantly associated with SWV. Higher histological grade was associated with increased SWV. There was no statistically significant correlations between SWV and other histological prognostic factors.The purpose of this work was to demonstrate the feasibility of neurite orientation dispersion and density imaging (NODDI) in characterizing the brain tissue microstructural changes of middle cerebral artery occlusion (MCAO) in rats at 3T MRI, and to validate NODDI metrics with histology. A multi-shell diffusion MRI protocol was performed on 11 MCAO rats and 10 control rats at different post-operation time points of 0.5, 2, 6, 12, 24 and 72 h. NODDI orientation dispersion index (ODI) and intracellular volume fraction (Vic) metrics were compared between MCAO group and control group. The evolution of NODDI metrics was characterized and validated by histology. Infarction was consistent with significantly increased ODI and Vic in comparison to control tissues at all time points (P less then 0.001). Lesion ODI increased gradually from 0.5 to 72 h, while its Vic showed a more complicated and fluctuated evolution. ODI and Vic were significantly different between hyperacute and acute stroke periods (P less then 0.001). The NODDI metrics were found to be consistent with the histological findings. In conclusion, NODDI can reflect microstructural changes of brain tissues in MCAO rats at 3T MRI and the metrics are consistent with histology. This study helps to prepare NODDI for the diagnosis and management of ischemic stroke in translational research and clinical practice.Myocardial fiber deformation measurements have been reported to be associated with adverse outcomes in patients with acute heart failure and those with myocardial infarction. However, few studies have addressed the prognostic value of global circumferential strain (GCS) in dilated cardiomyopathy (DCM) patients with severely impaired systolic function. This study aimed to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived GCS in DCM patients with severely reduced ejection. Consecutive DCM patients with severely reduced ejection fraction (EF less then 35%) who underwent CMR were included. GCS was calculated from CMR cine images. The clinical endpoint was a composite of all-cause mortality, heart transplantation, implantable cardioverter defibrillator (ICD) implantation and aborted sudden cardiac death (SCD). A total of 129 patients with a mean EF of 15.33% (11.36%-22.27%) were included. During a median follow-up of 518 days, endpoint events occurred in 50 patients. Patients with GCS ≥ the median (-5.17%) had significantly reduced event-free survival as compared with those with GCS less then the median (P less then 0.01). GCS was independently associated with adverse events after adjusting for clinical and imaging risk factors including extent of late gadolinium enhancement (LGE) (P less then 0.05). Adding GCS into the model including the extent of LGE resulted in significant improvements in the C-statistic (from 0.706 to 0.742; P less then 0.05) with a continuous net reclassification improvement (NRI) of 29.71%. It was concluded that GCS derived from CMR could be useful for risk stratification in DCM patients with severely reduced EF, which may increase common imaging risk factors including LGE.K+ cycling in the cochlea is critical to maintain hearing. Many sodium-potassium pumps are proved to participate in K+ cycling, such as Na/K-ATPase. The α2-Na/K-ATPase is an important isoform of Na/K-ATPase. The expression of α2-Na/K-ATPase in the cochlea is not clear. In this study, we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR, and the α2-Na/K-ATPase expression pattern was confirmed in the inner ear. It was found α2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging (4-, 14-, 26- and 48-weeks old mice). We suspected that, the down-regulation of α2-Na/K-ATPase expression might be associated with the remodeling of K+ cycling, degeneration of morphological structure and decrease of hearing function in aging C57 mice. In conclusion, we speculated that the reduction of α2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.Diabetic retinopathy (DR) is a common cause of blindness all over the world. Bone marrow mesenchymal stem cells (BMSCs) have been considered as a promising strategy for retinal regeneration in the treatment of DR. However, the poor viability and low levels of BMSCs engraftment limit the therapeutic potential of BMSCs. The present study aimed to examine the direct induction of BMSCs differentiation into the cell types related to retinal regeneration by using soluble cytokine ciliary neurotrophic factor (CNTF). We observed remarkably increased expression of cellular retinaldehyde-binding protein (CRALBP) and retinoid isomerohydrolase (RPE65) in BMSCs treated with CNTF in vitro, indicating the directional differentiation of BMSCs into the retinal pigment epithelium (RPE) cells, which are crucial for retinal healing. In vivo, the diabetic rat model was established by use of streptozotocin (STZ), and animals treated with BMSCs+CNTF exhibited better viability and higher delivery efficiency of the transplanted cells than those treated with BMSCs injection alone. Similar to the in-vitro result, treatment with BMSCs and CNTF combined led to the differentiation of BMSCs into beneficial cells (RPE cells), and accelerated retinal healing characterized by the activation of rod photoreceptor cells and phagocytosis function of RPE cells. In conclusion, CNTF contributes to the differentiation of BMSCs into RPE cells, which may help overcome the current stem cell therapy limitations in the field of retinal regeneration.The effect of preoperative Double-J (DJ) ureteral stenting before flexible ureterorenoscopy (FURS) in the treatment for urinary stones was evaluated. We retrospectively enrolled 306 consecutive patients who underwent FURS from Jan. 2014 to Dec. 2017. All the patients were classified into two groups according to whether they had DJ ureteral stenting before FURS. Baseline characteristics (age, sex, stone location, stone size, surgical success rate, operation time, stone-free rate of the first day after surgery, stone-free rate of the first month after surgery, total complication rate) were compared using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. In total, 306 patients were included in this study. The group of DJ stenting before FURS included 203 (66.3%) patients, and non-DJ stenting before FURS was observed in 103 (33.7%) patients. The group of DJ stenting before FURS was significantly associated with a shorter operation time (53.8 vs. 59.3 min, P less then 0.001), a higher stone-free rate of the first day after surgery (69.0% vs. 51.5%, P=0.003). However, statistical significant differences were not found in the age, sex, stone location, stone size, surgical success rate, stone-free rate of the first month after surgery (89.2% vs. 81.6%, P=0.065) and total complication rate (5.4% vs. 9.7%, P=0.161) between the two groups. Preoperative DJ ureteral stenting before FURS could reduce the operation time and increase stone-free rate of the first day after surgery. However, it might not benefit the stone-free rate of the first month after surgery and reduce the complication rate. Preoperative DJ stenting should be not routinely performed.Triptolide, a component of the Chinese herb Tripterygium wilfordii Hook F, has been proved to be effective in the treatment of rheumatoid arthritis (RA). However, its underlying mechanisms on RA have not yet been well established. We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes (FLS) induced by the complex of interleukin-6 (IL-6) and the soluble form of the IL-6 receptor (sIL-6R). Furthermore, to clarify the underlying mechanisms, we treated FLS with the Janus-activated kinase 2 (JAK2) inhibitor/signal transducer and activator of transcription 3 (STAT3) activation blocker AZD1480. In this study, immunohistochemical staining was used to identify vimentin (+) and CD68 (-) in FLS. The FLS proliferation was measured by cell proliferation assay, and the cell cycles were analyzed by flow cytometry. Furthermore, ELISA was used to detect the expression of the inflammatory factors in culture solution. The expression levels of p-JAK2, JAK2, p-STAT3 and STAT3 were investigated through Western blotting analysis. The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines, including IL-6, interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF). Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3. The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway. It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.The stemness of different side population (SP) cell subtypes in ovarian cancer cells was studied, and the heterogeneity of ovarian cancer stem cells was analyzed. The cisplatin-resistant human serous ovarian cancer cell line C13 was stained with the bisbenzimide Hoechst 33342. A flow cytometry-based fluorescence-activated sorting method was used to obtain lower-SP (LSP) cells, upper-SP (USP) cells, and non-SP cells (NSP) based on their sensitivity to the staining time and Hoechst dye concentration. The sphere-forming capability, expression levels of stem cell markers, resistance to high concentrations of cisplatin, and subcutaneous tumorigenicity in NOD/SCID mice of the different cell subtypes were evaluated. The C13 cells contained SP cells with stemness characteristics, and the LSP cell subtype expressed higher levels of stem cell markers, had higher in vitro sphere-forming capability, higher cisplatin resistance and higher in vivo subcutaneous tumorigenesis than USP cells (P less then 0.05). NSP cells had no stemness. In conclusion, different subtypes of ovarian cancer SP cells have different stemness levels, and ovarian cancer stem cells may be heterogeneous.The incidence of colorectal cancer (CRC) is increasing in China, with high mortality. Here, we aimed to evaluate the latest clinicopathological features and prognostic value of the KRAS/NRAS/BRAF mutation status in CRC patients in Central China. The clinical data of 1549 CRC patients with stage I-IV disease diagnosed at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from 2015 to 2017 were collected and analyzed retrospectively. KRAS/NRAS/BRAF mutations were detected by real-time quantitative polymerase chain reaction (q-PCR) in 410 CRC patients, with mutation frequencies of KRAS, NRAS and BRAF of 47.56%, 2.93% and 4.15%, respectively. The gene mutation status and clinicopathological characteristics of 410 patients with CRC who underwent qPCR were analyzed. The KRAS and BRAF gene mutations were related to the pathological differentiation and number of metastatic lymph nodes. The BRAF gene mutation was also associated with cancer thrombosis in blood vessels. Cox regression analysis showed that there was no statistically significant difference in the overall survival (OS) between patients with KRAS, NRAS mutants and wild-type CRC patients, while the BRAF gene mutation was negatively correlated with the OS rate of CRC patients. It is suggested that the BRAF gene mutation may be an independent risk factor for the prognosis of CRC.