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001) and was preferred by 33 of 53 residents (62%); 45 of 53 (85%) wished to see the flipped classroom used at least 25% of the time. The exotropia flipped classroom scored higher than traditional classroom on the pretest (3.71/5 [74%] vs 2.87/5 [57%]; P<0.001) and post-test (4.53/5 [91%] vs 4.13/5 [83%]; P=0.01) but not the 3-month retention test (3.53/5 [71%] vs 3.37/5 [67%]; P=0.48). The esotropia classroom styles did not differ on pre- or post-test but demonstrated higher scores for the traditional classroom at 3-month retention (3.43/5 [69%] vs 2.92/5 [58%]; P=0.03). Advantages cited for flipped classroom include being interactive and engaging while incentivizing better classroom preparation.

The flipped classroom method was received favorably by trainees and may complement traditional methods of teaching.

The flipped classroom method was received favorably by trainees and may complement traditional methods of teaching.

To report the prevalence of subclinical markers of strabismus from a community-based screening of children.

A family history and ophthalmic examination (including six markers of strabismus oblique muscle dysfunction, stereopsis <60 arcsec, monofixation, nasal-temporal pursuit asymmetry, dissociated strabismus, and anisometropia) were obtained from consecutive children, aged 5-18years, in the local school system and the pediatric outpatient clinic of Mayo Clinic, Rochester, Minnesota.

A total of 1,000 children (498 males [49.8%]) were examined at a mean age of 10.6years (range, 5-18.98). Of the 1,000, 57 (5.7%) had strabismus, and 130 (13%) had some form of phoria. Of the 943 children without strabismus, 103 (10.9%) had one or more of the six subclinical markers, including 43 (4.5%) with inferior oblique dysfunction, 37 (3.9%) with anisometropia, 34 (3.6%) with subnormal stereopsis, 6 (0.6%) with nasal-temporal pursuit asymmetry, 3 (0.3%) with monofixation, and none with dissociated strabismus. A subclinical marker of strabismus occurred in 20 (12.7%) of the 157 nontropic subjects who had a family history of either strabismus, amblyopia, or both and in 83 (10.6%) of the 786 nontropic children without a family history.

In this community-based screening of children, subclinical disorders of binocular vision occurred in 10%-13% of children without strabismus, of which inferior oblique muscle dysfunction, anisometropia, and subnormal stereopsis were most prevalent. Identifying these disorders among strabismic families may be useful in elucidating the genetic puzzle of childhood strabismus.

In this community-based screening of children, subclinical disorders of binocular vision occurred in 10%-13% of children without strabismus, of which inferior oblique muscle dysfunction, anisometropia, and subnormal stereopsis were most prevalent. Identifying these disorders among strabismic families may be useful in elucidating the genetic puzzle of childhood strabismus.

Aryl hydrocarbon receptor (AhR) is a liver-enriched xenobiotic receptor that plays important role in detoxification response in liver. This study aimed to investigate how AhR signaling may impact the pathogenesis of alcohol-related liver disease (ALD).

Chronic alcohol feeding animal studies were conducted with mouse models of hepatocyte-specific AhR knockout (AhR

) and NAD(P)H quinone dehydrogenase 1 (NQO1) overexpression, and dietary supplementation of the AhR ligand indole-3-carbinol. Cell studies were conducted to define the causal role of AhR and NQO1 in regulation of redox balance and apoptosis.

Chronic alcohol consumption induced AhR activation and nuclear enrichment of NQO1 in hepatocytes of both alcoholic hepatitis patients and ALD mice. AhR deficiency exacerbated alcohol-induced liver injury, along with reduction of NQO1. Consistently, invitro studies demonstrated that NQO1 expression was dependent on AhR. However, alcohol-induced NQO1 nuclear translocation was triggered by decreased cellular oxidized nicotinamide adenine dinucleotide (NAD

)-to-NADH ratio, rather than by AhR activation. Furthermore, both invitro and invivo overexpression NQO1 prevented alcohol-induced hepatic NAD

depletion, thereby enhancing activities of NAD

-dependent enzymes and reversing alcohol-induced liver injury. In addition, therapeutic targeting of AhR in the liver with dietary indole-3-carbinol supplementation efficiently reversed alcoholic liver injury by AhR-NQO1 signaling activation.

This study demonstrated that AhR activation is a protective response to counteract alcohol-induced hepatic NAD

depletion through induction of NQO1, and targeting the hepatic AhR-NQO1 pathway may serve as a novel therapeutic approach for ALD.

This study demonstrated that AhR activation is a protective response to counteract alcohol-induced hepatic NAD+ depletion through induction of NQO1, and targeting the hepatic AhR-NQO1 pathway may serve as a novel therapeutic approach for ALD.High latitude insect populations must cope with extreme conditions, particularly low temperatures. Insects use a variety of cold hardiness mechanisms to withstand this temperature stress, and these can drive geographic distributions through overwintering mortality. The degree of cold hardiness can be altered by two evolved responses phenotypic plasticity and local adaptation. Phenotypic plasticity can occur within or between generations (transgenerational plasticity; TGP), and local adaptation can evolve through directional selection in response to regional climatic differences. We used the eastern spruce budworm, Choristoneura fumiferana (Lepidoptera Tortricidae) as a model to explore the role that variable winter temperatures play in inducing two aspects of plasticity in cold hardiness TGP and local adaptation in phenotypic plasticity. This species is one of the most destructive boreal forest pests in North America, therefore accurately predicting overwintering survival is essential for effective management. While we found no evidence of TGP in cold hardiness, there was a long term fitness cost to larvae that experienced repeated cold exposures. We also found evidence of local adaptation in both seasonal and short-term plasticity of cold hardiness, as our more northerly populations that would experience lower overwintering temperatures had more plastic responses to cold exposure. These findings provide evidence for the importance of phenotypic plasticity and local adaptation when modelling species distributions.Antizyme inhibitors 2 (AZIN2) was found to be associated with poor prognosis of patients with rectal cancer. However, no studies have reported whether AZIN2 functions in non-small cell lung cancer (NSCLC). This study aimed to investigate the role of AZIN2 in cisplatin (DDP) resistance in NSCLC. We established DDP resistant A549 and H1299 cell lines. The transcriptional and translational expression levels were examined using quantitative real-time polymerase chain reaction and western blot. Cell apoptosis was evaluated by caspase-3 activity and nucleosome ELISA assays. Luciferase reporter assay was employed to evaluate the impact of hypoxia-inducible factor (HIF-1α) on AZIN2 transcription. AZIN2 expression was found to be associated with DDP resistance and poor prognosis in patients with NSCLC. AZIN2 overexpression promoted cell viability, colony formation, and reduced cell apoptosis in H1299 cells and A549 upon DDP treatment. Correspondingly, AZIN2 knockdown significantly inhibited cell viability and colony formation, and increased cell apoptosis upon DDP treatment. Interestingly, AZIN2 expression in NSCLC cells was significantly induced by hypoxia condition. The occupancy of HIF-1α, an important regulator of the hypoxia response, remarkably enriched at the promoter region of AZIN2 under hypoxia condition. In addition, AZIN2 overexpression resulted in epithelial-mesenchymal transition (EMT). The results suggested that hypoxia-induced AZIN2 high expression may contribute to DDP resistance development by promoting the EMT.

Studies with Cannabis Sativa plant extracts and endogenous agonists of cannabinoid receptors have demonstrated anti-inflammatory, bronchodilator, and antitussive properties in the airways of allergic and non-allergic animals. However, the potential therapeutic use of cannabis and cannabinoids for the treatment of respiratory diseases has not been widely investigated, in part because of local irritation of airways by needing to smoke the cannabis, poor bioavailability when administered orally due to the lipophilic nature of cannabinoids, and the psychoactive effects of Δ9-Tetrahydrocannabinol (Δ9-THC) found in cannabis. The primary purpose of this study was to investigate the anti-inflammatory effects of two of the non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG) alone and in combination, in a model of pulmonary inflammation induced by bacterial lipopolysaccharide (LPS). The second purpose was to explore the effects of two different cannabinoid formulations administered orally (PO) andeating diseases characterised by airway inflammation.Malignant mesothelioma is an aggressive cancer type linked to asbestos exposure. Because of several intrinsic challenges, mesothelioma is often diagnosed in an advanced disease stage. Therefore, there is a need for diagnostic biomarkers that may contribute to early detection. Recently, the epigenome of tumors is being extensively investigated to identify biomarkers. This manuscript is a systematic review summarizing the state-of-the-art research investigating DNA methylation in mesothelioma. Four literature databases (PubMed, Scopus, Web of Science, MEDLINE) were systematically searched for studies investigating DNA methylation in mesothelioma up to October 16, 2020. A meta-analysis was performed per gene investigated in at least two independent studies. A total of 53 studies investigated DNA methylation of 97 genes in mesothelioma and are described in a qualitative overview. Furthermore, ten studies investigating 13 genes (APC, CDH1, CDKN2A, DAPK, ESR1, MGMT, miR-34b/c, PGR, RARβ, RASSF1, SFRP1, SFRP4, WIF1) were included in the quantitative meta-analysis. In this meta-analysis, the APC gene is significantly hypomethylated in mesothelioma, whereas CDH1, ESR1, miR-34b/c, PGR, RARβ, SFRP1, and WIF1 are significantly hypermethylated in mesothelioma. The three genes that are the most appropriate candidate biomarkers from this meta-analysis are APC, miR-34b/c, and WIF1. Nevertheless, both study number and study objects comprised in this meta-analysis are too low to draw final conclusions on their clinical applications. check details The elucidation of the genome-wide DNA methylation profile of mesothelioma is desirable in the future, using a standardized genome-wide methylation analysis approach. The most informative CpG sites from this signature could then form the basis of a panel of highly sensitive and specific biomarkers that can be used for the diagnosis of mesothelioma and even for the screening of an at high-risk population of asbestos-exposed individuals.The shallow penetration depth of photothermal agents in the first near-infrared (NIR-I) window significantly limits their therapeutic efficiency. Multifunctional nanotheranostic agents in the second near-infrared (NIR-II) window have drawn extensive attention for their combined treatment of tumors. Here, for the first time, we created oxygen-deficient black SnO2-x with strong NIR (700-1200 nm) light absorption with NaBH4 reduction from white SnO2. Hyaluronic acid (HA) could selectively target cancer cells overexpressed CD44 protein. After modification with HA, the obtained nanotheranostic SnO2-x@SiO2-HA showed high dispersity in aqueous solution and good biocompatibility. SnO2-x@SiO2-HA was confirmed to simultaneously generate enough hyperthermia and reactive oxygen species with single NIR-II (1064 nm) light irradiation. Because HA is highly affined to CD44 protein, SnO2-x@SiO2-HA has specific uptake by overexpressed CD44 cells and can be accurately transferred to the tumor site. Furthermore, tumor growth was significantly inhibited following synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) with targeted specificity under the guidance of photoacoustic (PA) imaging using 1064 nm laser irradiation in vivo.