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BackgroundPsychosis is associated with many forms of adversity, deprivation and living in urban areas.AimsTo investigate whether psychosis is part of a syndemic of multiple adversities.MethodDrawing on UK Biobank (UKBB) data (Project ID: 57601), we sought to understand mechanisms by which childhood, recent/contemporary and place-based adversities might cluster and interact to be implicated in pathways by which psychoses evolve. We investigated the associations between adversities, potential mediating inflammatory markers and ICD-10 diagnoses (F20–F31) of psychotic disorders. We fitted logistic regression models initially including all relevant candidate variables and used backwards deletion to retain theoretically plausible and statistically significant (P < 0.05) associations with psychotic disorders. The candidate variables were entered in a partial least squares structural equation model (PLS-SEM) to test for syndemic interactions between risk factors. We tested whether the findings were sensitive to demographics, gender and ethnicity.ResultsWe fitted a PLS-SEM including psychosis as a syndemic outcome, and identified three latent constructs: lifetime adversity, current adversity and biomarkers. Factor loadings were above 0.30, and all structural paths were significant (P < 0.05). There were moderate associations between lifetime adversity and current adversity (standardised coefficient s.c. = 0.178) and between current adversity and biomarkers (s.c. = 0.227). All three latent constructs showed small but significant associations with psychosis (s.c. < 0.04). Lifetime adversity and current adversity were more strongly associated among ethnic minorities (combined) than White British people.ConclusionsOur findings stress the importance of interactions between childhood and contemporary adversities in preventive and therapeutic interventions for psychotic disorders, especially among ethnic minorities.

The authors would like to thank Luneau Technology Portugal for lending the Visionix VX120., Purpose: To study the effect of near-vision reading task on optical quality of the eye when performed on a computer monitor and on printed paper, and to identify which of the two results in greater changes. Methods: Two groups of subjects performed a 30-min reading task in two different conditions: on a computer monitor and on printed paper. Ocular, corneal, and internal wavefront aberrations (Zernike coefficients up to 6th order), root-mean-square of low- and high-order aberrations, spherical equivalent, vectoral components of ocular astigmatism ( J45 and J0), and the compensation factor between internal and corneal aberrations were measured before and after the tasks. Their changes were analyzed in each group and between groups. Results: Statistically significant changes in wavefront aberrations and in root mean square of low- and high-order aberrations were observed in both groups which was significantly greater when the task was performed on printed paper. Partial loss of compensation mechanism and variation in spherical equivalent in a negative direction occurred after both reading tasks; however, it was statistically significant only with printed paper reading task. The vectoral components of ocular astigmatism did not show statistically significant changes in either groups. Conclusion: Near-vision reading tasks can change the optical quality of the eye, especially when the task is performed on printed paper., This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2019 and by the project PTDC/FIS-OTI/ 31486/2017.

Cancer is one of the leading causes of death in the world. It is very important to find drugs with high efficiency, low toxicity, and low side effects for the treatment of cancer. Flavonoids and their derivatives with broad biological functions have been recognized as anti-tumor chemicals. 8-Formylophiopogonanone B (8-FOB), a naturally existed homoisoflavonoids with rarely known biological functions, needs pharmacological evaluation. In order to explore the possible anti-tumor action of 8-FOB, we used six types of tumor cells to evaluate in vitro effects of this agent on cell viability and tested the effects on clone formation ability, scratching wound-healing, and apoptosis. In an attempt to elucidate the mechanism of pharmacological action, we examined 8-FOB-induced intracellular oxidative stress and -disrupted mitochondrial function. Results suggested that 8-FOB could suppress tumor cell viability, inhibit cell migration and invasion, induce apoptosis, and elicit intracellular ROS production. Among these six types of tumor cells, the nasopharyngeal carcinoma CNE-1 cells were the most sensitive cancer cells to 8-FOB treatment. Intracellular ROS production played a pivotal role in the anti-tumor action of 8-FOB. Our present study is the first to document that 8-FOB has anti-tumor activity in vitro and increases intracellular ROS production, which might be responsible for its anti-tumor action. The anti-tumor pharmacological effect of 8-FOB is worthy of further investigation.

N, N-Dimethylformamide (DMF) can cause liver damage in occupationally exposed workers, but the molecular mechanism of DMF-induced liver damage has not been fully elucidated. Researches have proved that lncRNA plays a major function in chemical-induced liver toxicity and can be used as a biomarker and therapeutic target for liver injury. In order to verify that lncRNA also participates in DMF-induced liver damage, we treated HL-7702 cells with 75 or 150 mM DMF, and obtained lncRNA expression profiles through high-throughput sequencing. Among the differentially expressed lncRNAs, lncRNA SNHG12 was proved to be significantly downregulated in DMF-treated HL-7702 cells and participate in DMF-mediated apoptosis, even under long-term low-dose DMF exposure (5–10 mM, 8 weeks). In addition, according to bioinformatics analysis, miR-218-5p is expected to be a potential target of SNHG12, which was verified by the dual luciferase reporter assay in HEK293FT cells. MiR-218-5p mimic can induce apoptosis in HL-7702 cells. Among the predicted targets of miR-218-5p, protein kinase C epsilon (PRKCE) was reported to be involved in apoptosis, and was indeed downregulated by miR-218-5p mimic in our study. Further experiments showed that changes of the expression of SNHG12 can affect the expression of PRKCE. In the epidemiological study of occupational population, we also found that SNHG12 was downregulated in the serum exosomes of workers exposed to DMF. These results indicated that SNHG12 can mediate DMF-induced apoptosis of HL-7702 cells through miR-218-5p/PRKCE pathway.

Thalidomide causes teratogenic effects in several animal species and in humans. Accordingly, the World Health Organization banned thalidomide when mothers who took thalidomide during pregnancy delivered abnormal fetuses. After four decades, thalidomide underwent drug “re-purposing” since its antiangiogenic and immunomodulatory effects were therapeutic for multiple myeloma. There are no reports of thalidomide’s effects on prokaryotes, but it showed teratogenic effects in Arabidopsis thaliana, an ancestor of the plant kingdom. This proof of concept study clearly shows that thalidomide caused a significant and reproducible decrease in germination rate, nitric oxide (NO) production, and chlorophyll content of fennel plantlets. Thalidomide also induced the formation of abnormal fennel plantlets with stunting, wrinkling, and curling of fennel shoots and leaves. Notably, quantitative analysis showed that thalidomide caused a 50% increase in the formation of abnormal fennel plantlets and that these negative effects of thalidomide showed a 2.50- to 4-fold decrease when fennel seeds were co-incubated with an NO donor (Spermine NoNoate) or a stable cGMP analog 8-bromo Guanosine 3′,5′-cyclic monophosphate (8-Bromo-cGMP). This study is important because it confirms that thalidomide’s negative effects on fennel seed germination and growth are mediated by attenuation of NO and disruption of NO signaling. This reproducible model of thalidomide-induced, NO-dependent damage in a plant system can be used to further investigate the molecular mechanisms of thalidomide action in plants. Importantly, this study establishes a link between the evolution of development of higher plants and mammals.

Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5–0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries， include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration.

Malaria and leishmaniasis are the public health problems in southern Iran. The main activity of vector control is indoor residual spraying using pyrethroids, using different insecticides as larviciding and impregnated bednets. The aim of study was to evaluate the biological assays of bendiocarb wettable powder (WP) at different surfaces of wall. The residual effect of bendiocarb WP80 at 400 milligram/meter square (mg/m2) was evaluated on various local surfaces of rooms such as mud and plaster as well as thatch roofs and wooden. World Health Organization standard cones using contact bioassays were carried out using laboratory reared sugar-fed, 48–72 h old females of Anopheles stephensi. Contact bioassays were carried out on sprayed surfaces for 150 days. Contact bioassay on surfaces treated with bendiocarb WP80 at different surfaces was estimated about 2 months. Fumigant tests of bendiocarb WP80 at 400 mg/m2 revealed 50–93.83% mortality with 1 month persistency. The results showed that carbamate insecticide could be used as rotation with pyrethroids for malaria vector control. Monitoring and evaluation of environmental toxicology of pesticides is important for decision making for choosing appropriate pesticides for disease vector control.

Homocysteine (Hcy) is an excitatory amino acid that contains thiol group and derives from the methionine metabolism. It increases vulnerability of the neuronal cells to excitotoxic and oxidative damage. This study aimed to investigate the hyperhomocysteinemia (hHcy) effects on rat cerebellum and the possible protective role of quercetin administration in Hcy-treated rats, using behavioral and biochemical analyzes. To this end, the adult male rats were divided randomly into the control group that received vehicle, Hcy group received Hcy (400 μg/kg), Hcy + Que group received Hcy + quercetin (50 mg/kg), quercetin group received quercetin for 14 days. On Day 14 after the final treatment, lipid peroxidation level, the superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were evaluated in the cerebellum. After completion of treatment, the rat’s performance on rotarod and locomotor activity was evaluated. The results showed that Hcy treatment elicited cerebellar lipid peroxidation, impaired locomotor activity and increased latency to fall on the rotarod. Quercetin failed to attenuate significantly motoric impairment, increased significantly the cerebellar lipid peroxidation and GPx activity in the Hcy + Que group. Our results suggest that Hcy induced cerebellar toxicity and quercetin had no significant protective effects against Hcy toxicity in the cerebellum of adult rats.

Diabetic nephropathy (DN) is becoming a worldwide public health problem and its pathophysiological mechanism is not well understood. Emerging evidences indicated that cadmium (Cd), an industrial material but also an environmental toxin, may be involved in the development and progression of diabetes and diabetes-related kidney disease. However, the underlying mechanism is still unclear. Herein, a DN animal model was constructed by exposing to Cd, the metabolomic profiling of DN mice were obtained by using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), pattern recognition and pathway analysis were performed to screen potential biomarker. Moreover, western blotting was employed to verify the possible mechanism involved in the occurrence of Cd-induced DN. A total of 66 metabolites in serum have been screened out and identified as biomarkers, including free fatty acids, phospholipids, sphingomyelins, glycerides, and others. Significant differences were demonstrated between the metabolic profiles, including decreased levels of phospholipid and increased content of triglyceride, diacylglycerols, ceramide, lysophosphatidylcholine in Cd-induced DN mice compared with control. Protein expression level of p38 MAPK and Wnt/β-catenin were significantly increased. UPLC-Q-TOF/MS-based serum metabolomics coupled with pattern recognition methods and pathway analysis provide a powerful approach to identify potential biomarkers and is a new strategy to predict the underlying mechanism of disease caused by environmental toxicant.

BackgroundRecovery in schizophrenia is a complex process, involving clinical, societal and personal recovery. Until now, studies analysed these domains separately, without examining their mutual relations and changes over time.AimsThis study aimed to examine different states of recovery and transition rates between states.MethodThe Pharmacotherapy Monitoring and Outcome Survey (2006–2017) yearly assesses patients with schizophrenia in the Northern Netherlands. Data from 2327 patients with one up to 11 yearly measurements on clinical, societal and personal recovery were jointly analysed with a mixture latent Markov model (MLMM).ResultsThe selected MLMM had four states that differed in degree and pattern of recovery outcomes. Patients in state 1 were least recovered on any domain (16% of measurements), and partly recovered in states 2 (25%; featured by negative symptoms) and 3 (21%; featured by positive symptoms). Patients in state 4 (38%) were most recovered, except for work, study and housekeeping. At the subsequent measurement, the probability of remaining in the same state was 77–89%, transitioning to a better state was 4–12% and transitioning to a worse state was 4–6%; no transitions occurred between states 1 and 4. Female gender, shorter illness duration and less schizophrenia were more prevalent in better states.ConclusionsQuite a high recovery rate was present among a substantial part of the measurements (38%, state 4), with a high probability (89%) of remaining in this state. Transition rates in the other states might increase to a more favourable state by focusing on adequate treatment of negative and positive symptoms and societal problems.

BackgroundClozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences.AimsTo examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects.MethodA retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined.ResultsOf 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation.ConclusionsSuspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The ‘critical period’ for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.

The aim of this study is to implement lifetime attributable risk (LAR) predictions for radiation induced cancers for Swedish cohorts of patients of various age and sex, undergoing diagnostic investigations by nuclear medicine methods. Methods: Calculations are performed on Swedish groups of patients with Paget's disease and with bone metastases from prostatic cancer and diagnosed with bone scintigraphy with an administration of 500 MBq 99mTc-phosphonate. Results: The inclusion of patient survival rates into the calculations lowers the induced radiation cancer risk, as it takes into account that cohorts of patients have shorter predicted survival times than the general population. Conclusion: LAR estimations could be valuable for referring physicians, nuclear medicine physicians, nurses, medical physicists, radiologists, and oncologists and as well as ethical committees for risk estimates for specific subgroups of patients. Caution is however advised with respect to application of LAR predictions to individuals (because of individual sensitivities, circumstances, etc.).

Mono-2-ethyhexyl phthalate (MEHP), an environmental xenoestrogen, is widely used in the production of polyvinyl chloride materials and can be easily accumulated in human body. MBP is the active monoester metabolite of di butyl phthalate that is widely used as plasticizer in many products such as plastic toys, food packaging, personal care products, as well as an additive in lubricants, eliminating foams, and lotions. The presented in-vitro cytotoxicity study focused on time-dependent and combinatory exposure scenarios. We chose these phthalates because they are posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. All experiments performed in INS-1 pancreatic beta cells show moderate cytotoxicity with a time-dependent increase in effectiveness. INS-1 cells were treated with 0.001, 0.01, 0.1, 1, or 10-μM MEHP and MBP for 24, 48, and 72 h. Our results showed that cell viability was decreased and total oxidant levels were increased. Also, mRNA expression levels with asscociated beta cells were measured and for MBP dose groups, all mRNA expression levels were decreased. In conclusion, these findings suggest that, MEHP and MBP are have a negative and distruptor role on pancreatic beta cells and it will be linked with insulin resistance and type 2 diabetes.

Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.

IntroductionSparse data and conflicting evidence exist on the prevalence and prognosis of organophosphate (OP)-related cardiac toxicity. We aimed to characterize the cardiac abnormalities of OP after an acute cholinergic crisis in adults without previous cardiovascular conditions.Patients and MethodsWe did a prospective observational study in a tertiary-care hospital of north India (Postgraduate Institute of Medical Education and Research, Chandigarh) in 74 patients aged ≥ 13 years admitted with acute OP poisoning after self-ingestion. A systemic evaluation, including clinical characteristics, electrocardiography, and echocardiography, was performed to estimate the prevalence and prognosis of cardiac injury. A rate-corrected QT interval was calculated using Bazett’s method, and >440 milliseconds was used to define prolongation.ResultsChlorpyrifos was the most commonly ingested OP (n = 29). The patients had a similar occurrence of hypotension (n = 10) and hypertension (n = 9) at admission, and electrocardiography demonstrated sinus tachycardia in 38 (51.3%) and sinus bradycardia in one case. During the hospital stay, 3 out of 74 patients had a prolonged rate-corrected QT interval (457, 468, and 461 milliseconds), and one patient developed supraventricular tachycardia. Eight (10.8%) patients developed the intermediate syndrome, and six (8.1%) died. None of the hemodynamic or electrocardiographic abnormalities was associated with in-hospital mortality or intermediate syndrome development on univariant analysis. Baseline echocardiography at hospital discharge was performed in 27 patients (admitted during 2018) and normal in all except mild tricuspid regurgitation in one. At a 6-month follow-up, 23 cases were available for cardiovascular screening (including echocardiography) and had a normal evaluation.ConclusionCardiac toxicity is uncommon after acute OP self-ingestion and lacks prognostic significance.

Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.

Purpose: Digital tomosynthesis (DTS) is currently undergoing validation for potential clinical implications. The aim of this study was to investigate the potential for DTS as a low-dose alternative to computed tomography (CT) in imaging of pulmonary pathology in patients with cystic fibrosis (CF). Methods: DTS and CT were performed as part of the routine triannual follow-up in 31 CF patients. Extent of disease was quantified according to modality-specific scoring systems. Statistical analysis included Spearman’s rank correlation coefficient (r) and Krippendorff’s alpha (α). Major findings: The median effective dose was 0.14 for DTS and 2.68 for CT. Intermodality correlation was very strong for total score and the subscores regarding bronchiectasis and bronchial wall-thickening (r = 0.82–0.91, P

BackgroundInfluential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes.AimsTo test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network.MethodWe employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation.ResultsNeural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network.ConclusionsThis supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.

Objectives To estimate the frequency, clinical approaches and risk factors of hypoadrenocorticism in dogs under UK primary veterinary care. Materials and methods Dogs diagnosed with hypoadrenocorticism were identified from the UK VetCompass™ programme by searching anonymised electronic patient records. Pre-existing and newly diagnosed cases of disease during 2016 were included. Cases were further sub-categorised as having a laboratory-confirmed or presumed diagnosis of hypoadrenocorticism based on the information recorded in the electronic patient records. Descriptive data were manually extracted. Multivariable logistic regression methods were used to identify demographic risk factors. Results There were 177 hypoadrenocorticism cases identified from 905,543 dogs in 2016; 72 laboratory-confirmed and 105 presumed. The 1-year period prevalence for hypoadrenocorticism in all dogs was 0.06% (95% confidence interval: 0.05-0.07%). The most common presenting clinical signs in laboratory-confirmed dogs were lethargy (51/66, 77.3%), anorexia (48/66, 66.7%) and vomiting (48/66, 66.7%). Hyperkalaemia was reported in 47 of 53 (88.7%), hyponatraemia in 46 of 53 (86.8%). Median sodium: potassium ratio was 19.00 (interquartile range: 16.20-20.60). Breed, age, neuter status and insurance status were associated with a laboratory-confirmed diagnosis of hypoadrenocorticism. No sex association with hypoadrenocorticism was observed in the multivariable model. The standard poodle had 51.38 times the odds (95% CI: 14.49-182.18) of hypoadrenocorticism compared with crossbreeds. The labradoodle and West Highland white terrier also had increased odds. Clinical significance This is the first epidemiological study to report on hypoadrenocorticism in dogs within the UK primary-care population. These results provide benchmark data of current veterinary activity relating to hypoadrenocorticism in primary-care practices.

Cadmium (Cd) is one of the most prevalent toxic metals widely found in the environment. Cd induces toxicity and apoptosis in various organs and cells. The nervous system is one of the primary organs targeted by Cd. Cd toxicity is correlated with induction of severe oxidative stress. Myricetin, a natural product, has been found to exert protective effects against various disease conditions. The present study aimed to evaluate the potential protective effects of myricetin on Cd-induced neurotoxicity in PC12 cells. The cells were pretreated with myricetin in the absence and presence of Cd. The viability of cells was assessed using the MTT assay. Markers of oxidative stress were investigated by the lipid peroxidation (LPO), glutathione (GSH) content, and total antioxidant capacity (TAC). Moreover, activation of caspase 3 was examined by Western blot analysis. Myricetin could significantly enhance the viability of PC12 cells. Pretreatment of the cells with myricetin, prior to Cd exposure, showed a significant decrease in the levels of LPO whereas GSH and TAC levels were increased. In addition, the activity of caspase-3 was notably prevented by myricetin. These findings revealed that myricetin has protective effects on Cd-induced neurotoxicity in PC12 cells, which can be linked to its antioxidant potential, inhibition of LPO, and prevention of caspase-3 activation.

Traumatic brain injury (TBI) is an insult to the brain from an external mechanical force, leading to temporary/permanent secondary injuries, i.e. impairment of cognitive, physical, and psycho-social functions with altered consciousness. The leading mechanism responsible for neuronal damage following TBI is an increase in oxidative reactions initiated by free radicals generated by the injury along with various other mechanisms. Nerolidol is reported to have potent antioxidant and anti-neuroinflammatory properties. The present study was designed to explore the neuroprotective effect of nerolidol in weight-drop-induced TBI in rats. Animals were injured on the 1st day by dropping a free-falling weight of 200 gm from a height of 1 m through a guide pipe onto the exposed skull. After 14 days of injury, nerolidol (25, 50, and 100 mg/kg, i.p.) treatment was given for the next 14 days. Locomotor activity and motor coordination were evaluated using an actophotometer and rotarod, respectively. Cognitive impairment was observed through the Morris Water Maze and Object Recognition Test. On the 29th day, animals were sacrificed, and their brains were collected for the biochemical estimation. The weight drop model significantly decreased locomotor activity, motor coordination, increased Acetylcholinesterase (AChE) activity, oxidative stress, and induced cognitive deficits in TBI rats. Nerolidol significantly improved locomotor activity, reversed motor incoordination and cognitive impairment, and reduced the AChE activity and oxidative/nitrosative stress. The present study demonstrates the promising neuroprotective effects of nerolidol, which might improve the quality of life of TBI patients.

Intracellular copper [Cu(I)] has been hypothesized to play role in the differentiation of the neurons. This necessitates understanding the role of Cu(I) not only in the neurons but also in the glia considering their anatomical proximity, contribution towards ion homeostasis, and neurodegeneration. In this study, we did a systematic investigation of the changes in the cellular copper homeostasis during neuronal and glial differentiation and the pathways triggered by them. Our study demonstrates increased mRNA for the plasma membrane copper transporter CTR1 leading to increased Cu(I) during the neuronal (PC-12) differentiation. ATP7A is retained in the trans-Golgi network (TGN) despite high Cu(I) demonstrating its utilization towards the neuronal differentiation. Intracellular copper triggers pathways essential for neurite generation and ERK1/2 activation during the neuronal differentiation. ERK1/2 activation also accompanies the differentiation of the foetal brain derived neuronal progenitor cells. The study demonstrates that ERK1/2 phosphorylation is essential for the viability of the neurons. In contrast, differentiated C-6 (glia) cells contain low intracellular copper and significant downregulation of the ERK1/2 phosphorylation demonstrating that ERK1/2 activation does not regulate the viability of the glia. But ATP7A shows vesicular localization despite low copper in the glia. In addition to the TGN, ATP7A localizes into RAB11 positive recycling endosomes in the glial neurites. Our study demonstrates the role of copper dependent ERK1/2 phosphorylation in the neuronal viability. Whereas glial differentiation largely involves sequestration of Cu(I) into the endosomes potentially (i) for ready release and (ii) rendering cytosolic copper unavailable for pathways like the ERK1/2 activation.

BackgroundThe general health of children of parents with mental illness is overlooked.AimsTo quantify the difference in healthcare use of children exposed and unexposed to maternal mental illness (MMI).MethodThis was a retrospective cohort study of children aged 0–17 years, from 1 April 2007 to 31 July 2017, using a primary care register (Clinical Practice Research Datalink) linked to Hospital Episodes Statistics. MMI included non-affective/affective psychosis and mood, anxiety, addiction, eating and personality disorders. Healthcare use included prescriptions, primary care and secondary care contacts; inflation adjusted costs were applied. The rate and cost was calculated and compared for children exposed and unexposed to MMI using negative binomial regression models. The total annual cost to NHS England of children with MMI was estimated.ResultsThe study included 489 255 children: 238 106 (48.7%) girls, 112 741 children (23.0%) exposed to MMI. Compared to unexposed children, exposed children had a higher rate of healthcare use (rate ratio 1.27, 95% CI 1.26–1.28), averaging 2.21 extra contacts per exposed child per year (95% CI 2.14–2.29). Increased healthcare use among exposed children occurred in inpatients (rate ratio 1.37, 95% CI 1.32–1.42), emergency care visits (rate ratio 1.34, 95% CI 1.33–1.36), outpatients (rate ratio 1.30, 95% CI 1.28–1.32), prescriptions (rate ratio 1.28, 95% CI 1.26–1.30) and primary care consultations (rate ratio 1.24, 95% CI 1.23–1.25). This costs NHS England an additional £656 million (95% CI £619–£692 million), annually.ConclusionsChildren of mentally ill mothers are a health vulnerable group for whom targeted intervention may create benefit for individuals, families, as well as limited NHS resources.

BackgroundGrowing evidence suggests that air pollution exposure may adversely affect the brain and increase risk for psychiatric disorders such as schizophrenia and depression. However, little is known about the potential role of air pollution in severity and relapse following illness onset.AimsTo examine the longitudinal association between residential air pollution exposure and mental health service use (an indicator of illness severity and relapse) among individuals with first presentations of psychotic and mood disorders.MethodWe identified individuals aged ≥15 years who had first contact with the South London and Maudsley NHS Foundation Trust for psychotic and mood disorders in 2008–2012 (n = 13 887). High-resolution (20 × 20 m) estimates of nitrogen dioxide (NO2), nitrogen oxides (NOx) and particulate matter (PM2.5 and PM10) levels in ambient air were linked to residential addresses. In-patient days and community mental health service (CMHS) events were recorded over 1-year and 7-year follow-up periods.ResultsFollowing covariate adjustment, interquartile range increases in NO2, NOx and PM2.5 were associated with 18% (95% CI 5–34%), 18% (95% CI 5–34%) and 11% (95% CI 3–19%) increased risk for in-patient days after 1 year. Similarly, interquartile range increases in NO2, NOx, PM2.5 and PM10 were associated with 32% (95% CI 25–38%), 31% (95% CI 24–37%), 7% (95% CI 4–11%) and 9% (95% CI 5–14%) increased risk for CMHS events after 1 year. Associations persisted after 7 years.ConclusionsResidential air pollution exposure is associated with increased mental health service use among people recently diagnosed with psychotic and mood disorders. Assuming causality, interventions to reduce air pollution exposure could improve mental health prognoses and reduce healthcare costs.

Objectives: The study aimed to estimate the incidence and prevalence of feline lymphoma in cats attending primary-care practices across the UK and to identify patient-based and environmental (radon and pesticide exposure) risk factors. Materials and methods: Case records from the VetCompassTM programme from primary-care veterinary practices in the UK were searched for a diagnosis of lymphoma in cats in 2016. Cases were required to have had an external laboratory confirmed diagnosis based on cytology and/or histopathology. A nested case-control study design was used to identify risk factors for lymphoma using multivariable logistic regression. Results: From a cohort of 562,446 cats under veterinary care at VetCompass participating practices in 2016, a total of 271 lymphoma cases were identified (prevalence: 48/100,000, 95% CI 44- 56/100,000; incidence 32/100,000, 95% CI 26- 35/100,000). There was 180 incident lymphoma cases and 803 controls, all aged 2 years and older. Male (OR 1.7, 95% CI 1.2-2.4, P=0.004), insured (OR 3.6, 95% CI 2.3-5.6, P=

The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. The risk of lung cancer from radon exposure is due to the continuous radioactive decay of this gas and subsequent emission of high-energy alpha decay particles. And the bronchial epithelial cells are the main targets of radon exposure. However, there is a lack of early warning indicators of lung cancer caused by radon in the physical examination of populations involved in occupations with higher exposure to radon. To assess the potential of a molecular-based marker approach for the early detection of human lung cancer induced by radon, human bronchial epithelial cell injury models induced by alpha-particle irradiation were constructed. The results of transwell migration assay, transwell invasion assay, and the expression of the epithelial–mesenchymal transition-related proteins showed that malignant cell transformation could be triggered by alpha irradiation. Potential microRNAs (miRNAs) (hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257) were screened using miRNA chips in cell models. The pathway analyses of miRNAs selected using DIANA-miRPath v3.0 showed that miRNAs involved in malignant cell transformation were associated with cell adhesion molecules, extracellular matrix receptor interaction, and proteoglycans in cancer, among others, which are closely related to the occurrence and development of carcinogenesis. Reverse Transcription Quantitative Real-Time PCR (RT-qPCR) assay showed that five screened miRNAs were up-regulated in five lung cancer tissue samples. In conclusion, the results indicated that hsa-miR-3907, hsa-miR-6732-3p, hsa-miR-4788, hsa-miR-5001-5p, and hsa-miR-4257 may be potential early markers of the malignant transformation of bronchial epithelial cells induced by alpha-particle irradiation.

This paper summarizes the dose to the eye lens of workers of Memorial Sloan Kettering Cancer Center, a high-volume US oncologic and associated diseases facility. The doses presented in this report were collected from personal dosemeter readings using optically stimulated luminescence badges to estimate Hp(3). Doses were collected for 5950 clinical and research workers between January 2012 and December 2017. The median eye lens dose for all monitored workers was 0.23 mSv y−1. Workers performing, or supporting, fluoroscopy procedures received the highest unprotected eye lens dose of all workers with a median eye dose of 10 mSv. The use of leaded glasses by this group reduced the actual doses to the lens. Nurses and technicians involved in positron emission tomography injections received median eye lens dose of 1.2 mSv.

Many xenobiotics are known to cause hepatic damage with subsequent significant morbidity and mortality. Doxorubicin (DOX) is a broad-spectrum antineoplastic agent. DOX is reported to cause hepatocellular damage. Previous studies verified the promising role of many natural antioxidant products against various models of hepatic dysfunction. We conducted this study to evaluate the possible hepatoprotective effect of silymarin (SILY) and/or chlorogenic acid (CGA) in a rat model of DOX-induced hepatotoxicity. For this purpose, we randomly divided 30 adult male rats into five equal groups as control, DOX, co-treated DOX with SILY, co-treated DOX with GCA and co-treated DOX with SILY and CGA groups. All treatments were administered every second day for 4 weeks. Our results showed that simultaneous SILY and CGA administration caused a significant decrease in hepatic apoptosis biomarkers (hepatic caspase-3 and nuclear factor-κB levels), a significant improvement in hepatic oxidant/antioxidant status (malondialdehyde and superoxide dismutase) and significant decrease in hepatic pro-inflammatory biomarkers (tumor necrosis factor-alpha and interlukin-1β) compared with DOX treatment. We concluded that adding CGA to SILY acts as a hepatoprotective agent against DOX-induced liver injury through inhibiting apoptosis biomarkers, maintaining antioxidant enzyme levels, decreasing pro-inflammatory cytokines as well as regulating liver adenosine monophosphate-activated protein kinase signaling.

The respiratory tract and the oral mucosa are the first areas contaminated by pesticides. The herbicide dichlorophenoxyacetic acid (2,4-D) is a widely used pesticide across the world for both crops and gardens. The aim of this study was to evaluate oral mucosal damage after an experimental simulation of chronic oral and inhalational environmental exposure to 2,4-D formulation. Eighty male Wistar rats were exposed to three distinct concentrations of 2,4-D formulation (low—187.17 mg/m3; medium—313.31 mg/m3; and high—467.93 mg/m3). Oral exposure (through contaminated feed) or inhalation exposure lasted 6 months. Rat tongues were collected for cyto- and histopathology. There was a difference between exposure groups in the intensity of tissue congestion. Most rats exposed to 2,4-D presented mucosal inflammation at both cytology and histology (P

Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P

OBJECTIVE: This waiting-list randomized controlled trial examined the effectiveness of a self-management mHealth app in improving fatigue and quality of life (QoL) in cancer patients and survivors.METHODS: Persons with cancer-related fatigue (CRF) were recruited across four English speaking countries, via social media, and randomized into intervention (n = 519) and control (n = 280) groups. Whereas the intervention group received immediate access to the Untire app, the control group received access only after 12-weeks. Primary outcomes fatigue severity and interference, and secondary outcome QoL were assessed at baseline, 4, 8, and 12-weeks. We ran generalized linear mixed models for all outcomes to determine the effects of app access (yes/no), over 12-weeks, following the intention-to-treat principle.RESULTS: Compared with the control group, the intervention group showed significantly larger improvements in fatigue severity (d = 0.40), fatigue interference (d = 0.35), and overall QoL on average (d = 0.32) (P's 56). Effects did not depend on education and cancer status. Reliable change analyses indicated that significantly more people showed full recovery for fatigue in the intervention vs the control group (P's = .02).CONCLUSIONS: The Untire app can be an effective mHealth solution for cancer patients and survivors with moderate to severe CRF.

Objective Fear of cancer recurrence (FCR) is a common psychosocial sequela among cancer survivors, but data on patients with multiple myeloma are scarce. This study calculated the prevalence of FCR and identified family and social factors that predict FCR in the study population. Methods We recruited 127 myeloma patients and their partners to participate in a cross‐sectional survey from a regional tertiary cancer centre in China. The questionnaires included items on demographic characteristics and from the fear of disease progression simplified scale, family hardiness index and Social Support Scale. Univariate and multivariate regression was used to identify predictors of FCR. Results Of the participants, 56.4% patients reported high‐level FCR, which was similar to the partner‐reported proportion. The partners' FCR was positively associated with the patients' FCR, while family hardiness and social support were statistically significant, negative predictors. Conclusions Interventions to mitigate partners' FCR and improve family hardiness and social support may help with the psychological adjustment and well‐being of myeloma patients.

Objective To explore reasons for variations in anxiety in women testing positive for human papillomavirus (HPV) with normal cytology at routine HPV primary cervical cancer screening. Methods In‐depth interviews were conducted with 30 women who had tested HPV‐positive with normal cytology, including 15 with low‐to‐normal anxiety and 15 with high anxiety. Data were analysed using Framework Analysis to compare themes between low and high anxiety groups. Results Several HPV‐related themes were shared across anxiety groups, but only highly anxious women expressed fear and worry, fatalistic cognitions about cancer, fertility‐related cognitions, adverse physiological responses and changes in health behaviour(s). In comparison to those with low anxiety, women with high anxiety more strongly voiced cognitions about the 12‐month wait for follow‐up screening, relationship infidelity, a lower internal locus of control and HPV‐related symptom attributions. Conclusions Receiving an HPV‐positive with normal cytology result related to various emotional, cognitive, behavioural and physiological responses; some of which were specific to, or more pronounced in, women with high anxiety. If our observations are confirmed in hypothesis‐driven quantitative studies, the identification of distinct themes relevant to women experiencing high anxiety can inform targeted patient communications and HPV primary screening implementation policy., Highlights To our knowledge, this is the first qualitative study to explore anxiety in women testing human papillomavirus (HPV)‐positive with normal cytology at routine HPV primary screening.Our comparative qualitative design allowed thematic nuances to emerge between women who had experienced low versus high anxiety following their result.Only highly anxious women expressed fear and worry, fatalistic cognitions about cancer, fertility‐related cognitions, adverse physiological responses and changes in health behaviour(s).Highly anxious women also more strongly voiced cognitions about the 12‐month wait for follow‐up screen, reltionship infidelity, a lower internal locus of control and HPV‐related symptom attributions.These distinct themes can be used to minimise unnecessary anxiety through the development of evidence‐based patient communications at HPV primary screening.

The purpose of this study was to quantify the proanthocyanidin content of pecan (Carya illinoinensis) pericarp extract (PPE) and to assess its useful impacts against carbon tetrachloride (CCl4)-induced hepatotoxicity. Rats were randomly divided into four groups: Group 1: received intraperitoneal injection of saline solution, Group 2: was injected with PPE (25 mg/kg body weight) for 10 consecutive days, Group 3: received CCl4 (0.5 ml/kg, subcutaneous injection), Group 4: was coadministred with PPE + CCl4. The CCl4 was administered every 3 days during 10 days. Results revealed the presence of a high amount of total proanthocyanidins in the PPE (81.01 ± 0.21 mg TAE.g−1DW). CCl4 injection induced significant reductions in hepatic antioxidants but increased hepatic lipid peroxidation (LPO) as well as serum injury biomarkers. However, cotreatment with PPE significantly (P

Objective Patients with cancer are at high risk of depression. However, the risk of major depressive disorder (MDD) after cancer diagnosis has not been studied in a population setting in Japan. This cohort study used a Japanese medical claims database to examine time to MDD in cancer patients and the risk of MDD (hazard ratio; HR) compared with matched cancer‐free controls. Methods Primary endpoint was time to MDD (starting 6 months before cancer diagnosis) in adult (18–74 years) cancer patients; secondary endpoint was time to MDD (6 months before to 12 months after cancer diagnosis) in a matched cohort of cancer patients and cancer‐free controls. Multivariate analyses were performed to determine HRs for all cancers and for each cancer site. Results Of 35 008 cancer patients (mean age, 53.3 years), 2201 (6.3%) were diagnosed with MDD within 66 months. Matched cancer patients (n = 30 372) had an elevated risk of MDD compared with cancer‐free controls (n = 303 720; HR [95% confidence interval] 2.96 [2.77–3.16]). MDD risk was highest in patients with multiple cancers, pancreatic cancer, and brain cancer. Compared with middle‐aged patients, risk was higher in patients

Diabetes mellitus is one of the most common chronic diseases worldwide. Generally, the levels of fasting or postprandial blood glucose and other biomarkers, such as glycated albumin, glycated hemoglobin, and 1,5-anhydroglucitol, are used to diagnose or monitor diabetes progression. In the present study, we developed a sensor to simultaneously detect the glucose levels and glycation ratios of human serum albumin using a lateral flow assay. Based on the specific enzymatic reactions and immunoassays, a spiked glucose solution, total human serum albumin, and glycated albumin were measured simultaneously. To test the performance of the developed sensor, clinical serum samples from healthy subjects and patients with diabetes were analyzed. The glucose level and glycation ratios of the clinical samples were determined with reasonable correlation. The R-squared values of glucose level and glycation ratio measurements were 0.932 and 0.930, respectively. The average detection recoveries of the sensor were 85.80% for glucose and 98.32% for the glycation ratio. The glucose level and glycation ratio in our results were crosschecked with reference diagnostic values of diabetes. Based on the outcomes of the present study, we propose that this novel platform can be utilized for the simultaneous detection of glucose and glycation ratios to diagnose and monitor diabetes mellitus.

BackgroundClozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia.AimsTo investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK.MethodUsing information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use.ResultsOf 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73–3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14–2.72).ConclusionsThese findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

Cyclophosphamide (CP) is one of the most potent alkylating agents and is widely used in the treatment of numerous neoplastic conditions, autoimmune diseases and following organ transplantation. Due to its ability to induce oxidative stress and subsequent apoptosis, CP is affiliated with many adverse effects with special emphasis on the highly prevalent hepatotoxicity. Dipeptidyl peptidase 4 (DDP-IV) inhibitors are being rediscovered for new biological effects due to their ability to target multiple pathways, among which is the phosphoinositide 3–kinase (PI3K) and protein kinase B (Akt) axis. This could offer protection to multiple organs against reactive oxygen species (ROS) through modulating sirtuin 1 (SIRT1) expression and, in turn, inactivation of forkhead box transcription factor of the O class 1 (FoxO1), thus inhibiting apoptosis. Accordingly, the current study aimed to investigate the potential therapeutic benefit of alogliptin (Alo), a DPP-IV inhibitor, against CP-induced hepatotoxicity through enhancing PI3K/Akt/SIRT1 pathway. Forty male Wistar rats were randomly divided into four groups. The CP-treated group received a single dose of CP (200 mg/kg; i.p.). The Alo-treated group received Alo (20 mg/kg; p.o.) for 7 days with single CP injection on Day 2. Alo successfully reduced hepatic injury as witnessed through decreased liver function enzymes, increased phospho (p)-PI3K, p-Akt, superoxide dismutase (SOD) levels, SIRT1 expression, p-FoxO1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2). This resulted in decreased apoptosis, as witnessed through decreased caspase-3 levels and improved histopathological picture. In conclusion, the current study succeeded to elaborate, for the first time, the promising impact of Alo in ameliorating chemotherapy-induced liver injury.

Significance Prostate cancer is the most common cancer among men. An accurate diagnosis of its severity at detection plays a major role in improving their survival. Recently, machine learning models using biomarkers identified from Raman micro-spectroscopy discriminated intraductal carcinoma of the prostate (IDC-P) from cancer tissue with a ≥85 % detection accuracy and differentiated high-grade prostatic intraepithelial neoplasia (HGPIN) from IDC-P with a ≥97.8 % accuracy. Aim To improve the classification performance of machine learning models identifying different types of prostate cancer tissue using a new dimensional reduction technique. Approach A radial basis function (RBF) kernel support vector machine (SVM) model was trained on Raman spectra of prostate tissue from a 272-patient cohort (Centre hospitalier de l'Universite de Montreal, CHUM) and tested on two independent cohorts of 76 patients [University Health Network (UHN)] and 135 patients (Centre hospitalier universitaire de Quebec-Universite Laval, CHUQc-UL). Two types of engineered features were used. Individual intensity features, i.e., Raman signal intensity measured at particular wavelengths and novel Raman spectra fitted peak features consisting of peak heights and widths. Results Combining engineered features improved classification performance for the three aforementioned classification tasks. The improvements for IDC-P/cancer classification for the UHN and CHUQc-UL testing sets in accuracy, sensitivity, specificity, and area under the curve (AUC) are (numbers in parenthesis are associated with the CHUQc-UL testing set): +4 % (+8 % ), +7 % (+9 % ), +2 % (6%), +9 (+9) with respect to the current best models. Discrimination between HGPIN and IDC-P was also improved in both testing cohorts: +2.2 % (+1.7 % ), +4.5 % (+3.6 % ), +0 % (+0 % ), +2.3 (+0). While no global improvements were obtained for the normal versus cancer classification task [+0 % (-2 % ), +0 % (-3 % ), +2 % (-2 % ), +4 (+3)], the AUC was improved in both testing sets. Conclusions Combining individual intensity features and novel Raman fitted peak features, improved the classification performance on two independent and multicenter testing sets in comparison to using only individual intensity features.

Significance: Peripheral pitting edema is a clinician-administered measure for grading edema. Peripheral edema is graded 0, 1 + , 2 + , 3 + , or 4 + , but subjectivity is a major limitation of this technique. A pilot clinical study for short-wave infrared (SWIR) molecular chemical imaging (MCI) effectiveness as an objective, non-contact quantitative peripheral edema measure is underway. Aim: We explore if SWIR MCI can differentiate populations with and without peripheral edema. Further, we evaluate the technology for correctly stratifying subjects with peripheral edema. Approach: SWIR MCI of shins from healthy subjects and heart failure (HF) patients was performed. Partial least squares discriminant analysis (PLS-DA) was used to discriminate the two populations. PLS regression (PLSR) was applied to assess the ability of MCI to grade edema. Results: Average spectra from edema exhibited higher water absorption than non-edema spectra. SWIR MCI differentiated healthy volunteers from a population representing all pitting edema grades with 97.1% accuracy (N = 103 shins). Additionally, SWIR MCI correctly classified shin pitting edema levels in patients with 81.6% accuracy. Conclusions: Our study successfully achieved the two primary endpoints. Application of SWIR MCI to monitor patients while actively receiving HF treatment is necessary to validate SWIR MCI as an HF monitoring technology.

Significance: Early detection of oral cancer is vital for high-risk patients, and machine learning-based automatic classification is ideal for disease screening. However, current datasets collected from high-risk populations are unbalanced and often have detrimental effects on the performance of classification. Aim: To reduce the class bias caused by data imbalance. Approach: We collected 3851 polarized white light cheek mucosa images using our customized oral cancer screening device. We use weight balancing, data augmentation, undersampling, focal loss, and ensemble methods to improve the neural network performance of oral cancer image classification with the imbalanced multi-class datasets captured from high-risk populations during oral cancer screening in low-resource settings. Results: By applying both data-level and algorithm-level approaches to the deep learning training process, the performance of the minority classes, which were difficult to distinguish at the beginning, has been improved. The accuracy of “premalignancy” class is also increased, which is ideal for screening applications. Conclusions: Experimental results show that the class bias induced by imbalanced oral cancer image datasets could be reduced using both data- and algorithm-level methods. Our study may provide an important basis for helping understand the influence of unbalanced datasets on oral cancer deep learning classifiers and how to mitigate.

Quantum dots (QDs) have recently attracted considerable attention in the biomedical fields because of their unique and excellent optical properties. However, information on their health effects, particularly in the reproductive system, is limited. The present study focuses on the effects of intravenous injection of CdSe/ZnS QDs on the reproductive system and embryo development at various stages of pregnancy in mice. The CdSe/ZnS QDs intravenously injected in mice during pregnancy accumulated in the maternal liver, uterus and placenta. This accumulation affected the growth and development of the embryo during the early and middle stages of pregnancy. Moreover, genotoxicity to the placenta after exposure to CdSe/ZnS QDs was demonstrated by the increased expression levels of genes related to oxidative stress and apoptosis and the reduced expression levels of genes related to the nutrient and waste transportation. Alterations in the gene expression levels have hindered the transport of metabolites across the placenta, which in turn affected the ability of the fetus to obtain nutrients.

There is widespread acknowledgement of the presence of vitamin D deficiency in the community and the pressing need to address this. From a public health perspective, emphasis has been placed on addressing vitamin D deficiency through dietary means. However, naturally rich food sources of vitamin D are few and infrequently consumed, and nutrition survey data from various countries have indicated that habitual vitamin D intakes in the community are much lower than the current vitamin D dietary guidelines. This review will briefly overview the extent of vitamin D deficiency within the community, its causes, and how our food chain, once its embraces the evidence-based practise of food fortification and potentially biofortification, can cater for meeting the dietary vitamin D needs of the community. Finally, international authorities, briefed with establishing vitamin D dietary guidelines over the past decade, have struggled with uncertainties and gaps in our understanding of the relative contribution of sunshine and diet to vitamin D status and vitamin D requirements for health maintenance. The review will also consider how emerging evidence of a possible minimal-risk UVB radiation exposure relative to skin cancer that also enables vitamin D production could greatly inform future vitamin D dietary guidelines.

Triple negative breast carcinoma (TNBC) is an aggressive form of cancer, with high rates of morbidity, mortality, poor prognosis and limited therapeutic options. The objective of the present study was to elaborate the anticancer activity of Troxerutin (TXN) in TNBC/MDA-MB-231 cells. Herein, we demonstrated the inhibitory effects of TXN on the breast cancer cell growth via induction of apoptosis. Mitochondrial membrane potential (∆Ψm), DNA damage and apoptotic nuclear changes were analyzed by flowcytometry, AO/EtBr and Hoechst staining, respectively. Furthermore, apoptotic protein and gene expressions were analyzed by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. Our results indicated that TXN induces apoptosis as evidenced by inhibit the cell proliferation, enhanced apoptotic activation, altered mitochondrial membrane potential and elevated level of DNA damage in TNBC cells. Furthermore, the TXN inhibit anti-apoptotic protein expression with the subsequent upregulation of Cytochrome c, Caspase-9 and Caspase-3. Thus, TXN induces apoptosis in TNBC cells through inducing nuclear damage and altered apoptotic marker expressions. Therefore, TXN might be used as a potential therapeutic agent for the treatment of triple negative breast cancer.

Objectives To report clinical features, gross post mortem and histopathological findings from an investigation into sudden or unexpected death in rabbits that was undertaken during an outbreak of rabbit haemorrhagic disease. Materials and methods Using a standard protocol, veterinarians were invited to submit case histories and results of their post mortem examination of pet rabbits that died unexpectedly. Histopathological examination of heart, lungs, liver, spleen and kidney samples was collated with macroscopic appearance and clinical details. Results Hepatocellular necrosis, characteristic of rabbit haemorrhagic disease, was observed in 185 of 300 (62%) submissions, often accompanied by glomerular thrombosis and changes in other organs. Evidence of rabbit haemorrhagic disease was not apparent on histopathology in 113 of 300 (38%) rabbits. Gross post mortem examination by veterinary practitioners did not always reflect reported histopathological changes. No macroscopic abnormalities were seen in 78/185 (42%) of rabbit haemorrhagic disease cases. Rapid death and death of other rabbits in the household were common features of rabbit haemorrhagic disease. Ante mortem clinical signs included anorexia, collapse, lethargy, seizures, icterus, bleeding from the mouth, dyspnoea, hypothermia, pyrexia, bradycardia or poor blood clotting. Clinical importance Rabbit haemorrhagic disease can be suspected from a history of sudden death, especially if multiple rabbits are affected. There is not always macroscopic evidence of the disease but histopathology is useful to support or refute a diagnosis of rabbit haemorrhagic disease and provide information about other causes of death.

Pregnancy increases the risk of pulmonary embolism. Computed tomography pulmonary angiography (CTPA) is used for diagnosis. CT generates ionising radiation, and thus, abdominal shielding may be used. This phantom study investigated the effects of patient shielding and scan length reduction on the fetal and maternal ionising radiation dose from CTPA. The absorbed dose to the fetus was measured using thermoluminescent dosemeters. Estimated effective doses to the pregnant patient were based on the dose-length products. Shielding increased both the effective dose to the patient by 47% and the mean absorbed dose to the fetus (0.10 vs. 0.12 mGy; p

Objective This study aimed to assess psychological functioning, quality of life, and regret about screening after a positive fecal immunochemical test (FIT) and subsequent colonoscopy, and to evaluate changes over time. Methods This is a prospective cohort study. Individuals aged 55 to 75 with a positive FIT that were referred for colonoscopy between July 2017 and November 2018, were invited to complete questionnaires related to psychological distress and health‐related quality of life at three predefined time points: before colonoscopy, after histopathology result notification, and after 6 months. Four questionnaires were used: the Psychological Consequences Questionnaire (PCQ), the six‐item Cancer Worry Scale (CWS), the Decision Regret Scale (DRS), and the 36‐item Short‐Form (SF‐36). Results A total of 1066 participants out of 2151 eligible individuals were included. Patients with cancer showed a significant increase in psychological dysfunction (P = .01) and cancer worry (P = .008) after colonoscopy result notification, and a decline to pre‐colonoscopy measurements after 6 months. In the no‐cancer groups, psychological dysfunction and cancer worry significantly decreased over time (P 25). A good global quality of life was reported in participants with no cancer. Conclusion Some psychological distress remains up to 6 months after colonoscopy in participants who tested false‐positive in the Dutch bowel cancer screening program.

The use of iodine-131 S values based on reference computational phantoms with fixed thyroid model may lead to significant dosimetric errors in patients who may have different thyroid location from the reference phantoms. In the present study, we investigated individual thyroid location variation by examining the computed tomography image sets of 40 adult male and female patients. Subsequently, the thyroid location of the adult male and female mesh-type reference phantoms of the International Commission on Radiological Protection (ICRP) was adjusted to match each the highest, mean and the lowest locations of the thyroid observed in this dataset. The thyroid-adjusted phantoms were implemented into the Geant4 Monte Carlo code to calculate thyroid location-dependent iodine-131 S values (rT ← thyroid) for a total of 30 target regions. The maximum variation among the observed thyroid locations was 39 mm and 36 mm for male and female patients, respectively. The mean thyroid locations of both male and female patients showed a good agreement with the ICRP reference phantoms. The thyroid location-dependent Iodine-131 S values were significantly different from the reference phantoms for most target regions by up to a factor of 3. The use of thyroid location-dependent S values in dose reconstructions should help quantify the dosimetric uncertainty in epidemiologic investigations of patients receiving iodine-131 therapy for hyperthyroidism and thyroid cancer.

Background Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. Methods Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. Results A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4–20] vs. 7(3–13] vs. 7(3–14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous ( p = 0.025), musculoskeletal ( p = 0.029), renal ( p = 0.027) and cardiorespiratory ( p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive ( p = 0.034) and exhibited higher anti-dsDNA titres ( p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia ( p = 0.002), thrombocytopenia ( p = 0.004) or low complement ( p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. Conclusions Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Objective: Clinical options for managing nonmetastatic prostate cancer (PCa) vary. Each option has side effects associated with it, leading to difficulty in decision‐making. This study aimed to assess the relationship between patient involvement in treatment decision‐making and subsequent decision regret (DR), and quantify the impact of health‐related quality of life (HRQL) outcomes on DR. Methods: Men living in the United Kingdom, 18 to 42 months after diagnosis of PCa, were identified from cancer registration data and sent a questionnaire. Measures included the Decision Regret Scale (DRS), Expanded Prostate cancer Index Composite short form (EPIC‐26), EQ‐5D‐5L, and an item on involvement in treatment decision‐making. Multivariable ordinal regression was utilized, with DR categorized as none, mild, or moderate/severe regret. Results: A total of 17 193 men with stage I‐III PCa completed the DRS: 36.6% reported no regret, 43.3% mild regret, and 20.0% moderate/severe regret. The odds of reporting DR were greater if men indicated their views were not taken into account odds ratio ([OR] = 6.42, 95% CI: 5.39‐7.64) or were involved “to some extent” in decision‐making (OR = 4.63, 95% CI: 4.27‐5.02), compared with men who were “definitely” involved. After adjustment, including for involvement, men reporting moderate/big problems with urinary, bowel, or sexual function were more likely to experience regret compared with men with no/small problems. Better HRQL scores were associated with lower levels of DR. Conclusions: This large‐scale study demonstrates the benefit of patient involvement in treatment decision‐making for nonmetastatic PCa. However, men experiencing side effects and poorer HRQL report greater DR. Promoting engagement in clinical decision‐making represents good practice and may reduce the risk of subsequent regret.