3D-Printable Denture Base Resin Containing SiO2 Nanoparticles: An In Vitro Analysis of Mechanical and Surface Properties.
To evaluate the flexural strength (FS), impact strength (IS), surface roughness (Ra), and hardness of 3D-printed resin incorporating silicon dioxide nanoparticles (SNPs). A total of 320 acrylic specimens were fabricated with different dimensions according to test specifications and divided into a control group of heat denture base resin, and 3 test groups (80/test (n = 10) of unmodified, 0.25 wt%, and 0.5 wt% SNPs modified 3D-printed resin. 10,000 thermal cycles were performed to half of the fabricated specimens. FS, IS (Charpy impact), Ra, and hardness were evaluated and the collected data was analyzed with ANOVA followed by Tukey's post hoc test (α = 0.05). Incorporating SNPs into 3D-printed resin significantly increased the FS, IS (at 0.5%) and hardness compared to unmodified 3D-printed resin (p < 0.001). However, the FS of pure 3D-printed and 3D/SNP-0.50% resin and IS of all 3D-printed resin groups were significantly lower than the control group (p < 0.0001). Hardness of 3D/SNP-0.25% and 3D/SNP-0.50% was significantly higher than control and unmodified 3D-printed resin (p < 0.0001), with insignificant differences between them. The Ra of all 3D-printed resin groups were significantly higher than control group (p < 0.001), while insignificant difference was found between 3D-printed groups. Thermal cycling significantly reduced FS and hardness for all tested groups, while for IS the reduction was significant only in the control and 3D/SNP-0.50% groups. Thermal cycling significantly increased Ra of the control group and unmodified 3D-printed resin (p < 0.001). The addition of SNPs to 3D-printed denture base resin improved its mechanical properties while Ra was not significantly altered. Thermal cycling adversely affected tested properties, except IS of unmodified 3D-printed resin and 3D/SNP-0.25%, and Ra of modified 3D-printed resin.


Perineural Spread of Tumor in the Skull Base and Head and Neck.
Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.


Dependence of hepatocyte-specific gene expression on cell-cell interactions in primary culture.
In co-culture with non-parenchymal liver epithelial cells, rat hepatocytes show a marked increase in albumin and total protein synthesis when compared with cells maintained as pure populations in which an early decline in albumin secretion takes place. Analysis of the relative amounts of different mRNA sequences, determined by hybridization, indicated that the increase in protein synthesis resulted essentially from an increased level of the corresponding mRNAs. In addition, when cell-cell contacts were established between the two cell types several days after the seeding of hepatocytes, the stimulation of albumin secretion was similarly observed with a significant increase of the corresponding mRNA on days 10-14 of culture. Transcriptional assays, in which isolated nuclei were used for the study of RNA synthesis, showed that liver-specific gene transcription was significantly increased and maintained for at least 2 weeks. These results demonstrate for the first time long-term stabilization and reversibility of various specific mRNAs at high levels by adult hepatocytes in primary culture. They suggest that establishment of cell-cell contacts between hepatocytes and liver epithelial cells are essential for the maintenance of a high rate of transcription of the liver-specific genes.


[Proliferation and transdetermination in blastemas of the female genital disc of drosophila melanogaster after culture in vivo].
1. Genital-imaginal discs of femaleDrosophila melanogaster were fragmented or locally damaged and then culturedin vivo in the abdomens of adult flies (technqiue:HADORN, 1963). The proliferation rate of the autotypic anlagen, as well as the frequency and the quality of allotypic differentiation after transplantation in larvae undergoing metamorphosis, were studied. 2. Only the anlagen of the anal plates can he extensively cultured. Blastemas of soft parts and of vaginal plates have a low proliferation capacity. 3. The rate of transdetermination is very high for the anlage of the anal plates. The blastemas of other autotypic elements rarely transdetermine and they only form small allotypic areas. 4. Transdeterminations originating from anlagen of anal plates are correlated with an enlargement of the autotypic blastemas. In contrast, the occurence of transdetermination in anlagen of the vaginal plates is correlated with a multiplication of the entire genitalia. 5. Twenty-four different allotypic structures which are normally derived from the antennae-, leg-, wing- or clypeo-labrum primordia have been observed. 6. After a first transdetermination step (initial cases) the anlagen of the anal plates form new anlagen, namely of the praefrons, the basis of the maxillary palpus (Rostralhaut), femur and tarsus. From these "primary formation centers" successive steps are possible as in normogenesis. The anlagen of the allotypic third antenna segment behaves as a "secondary formation center", which will differentiate leg, wing and possibly palpus after it has passed further secondary transdetermination steps. 7. According to the observed frequencies, the segments of the allotypic antennae are formed one after another. 8. The organisation and the typical pattern of the allotypic organs are identical to those formed in normal development. 9. The daughter cells of a single cell of a determined blastema are able to produce normal anlagen which are competent to form an integrated pattern. Such a cell can form qualitatively different allotypic blastemas which each correspond to a different imaginai disc.


3D in silico study of magnetic fluid hyperthermia of breast tumor using Fe3O4 magnetic nanoparticles.
Modeling and simulation of the temperature distribution, the mass concentration, and the heat transfer in the breast tissue are hot issues in magnetic fluid hyperthermia treatment of cancer. The breast tissue can be visualized as a porous matrix with saturated blood. In this paper, 3D in silico study of breast cancer hyperthermia using magnetic nanoparticles (MNPs) is conducted. The 3D FEM models are incorporated to investigate the infusion and backflow of nanofluid in the breast tumor, the diffusion of nanofluid, temperature distribution during the treatment, and prediction of the fraction of tumor necrosis while dealing with the thermal therapy. All the hyperthermia procedures are simulated and analyzed on COMSOL Multiphysics. The sensitivity of frequency and amplitude of the applied magnetic field (AMF) is investigated on the heating effect of the tumor. The mesh dependent solution of Penne's bioheat model is also analyzed. The simulated results demonstrate successful breast cancer treatment using MNPs with minimum side effects. Validation of current simulations results with experimental studies existing in literature advocates the success of our therapy. The increase in the amplitude and frequency of the AMF increases of the temperature in the tumor. The variation of mesh from coarser to finer increased the temperature through small fractions. We have also simulated the magnetic induction problem where the magnetic field is generated by current-carrying coil conductors induce heat in nearby breast tumors due to excitation of MNPs by magnetic flux. This research will aid treatment protocols and real-time clinical breast cancer treatments.


Mental health services for mood disorder outpatients in Milan during COVID-19 outbreak: The experience of the health care providers at San Raffaele hospital.
The spread of COVID-19 throughout Italy, particularly Lombardy, led to adopt quarantine measures, known to exacerbate pre-existing psychiatric conditions. We described a telephone-based surveillance on 101 euthymic Mood Disorder outpatients in Milan by a non-standardized survey to evaluate reactions to lockdown measures and the presence of quarantine stressors. Frustration was the most represented quarantine stressor. Being jobless was significantly related to the presence of frustration, somatization, increased alertness, psychic anxiety and low mood; younger age to the presence of psychic anxiety, alertness and financial concerns. No recurrences were observed at the time of writing.


St. Jude Medical cardiac valves in small aortic roots: follow-up to sixteen years.
Prosthetic aortic valve replacement in the small aortic root raises concerns of its long-term effects. Between 1978 and 1994, 270 patients received only small aortic prostheses (< or = 21 mm). There were 117 men (43.3%) and 153 women (56.7%) with a mean age of 64.3 +/- 11.6 years (range 19 to 87 years). The body surface areas ranged from 1.2 to 2.26 m2 (mean 1.71 +/- 0.27 m2). Ninety-one percent of patients had New York Heart Association class III or IV symptoms and 33% underwent concomitant coronary artery bypass grafting. The operative mortality rate was 3.3% (9 deaths) and follow-up (100%) extended from 1 to 16 years (mean 6.2 +/- 3.9 years) with cumulative survival of 1676 patient-years. There were 55 late deaths (3.28% per patient-year). The linearized rates of morbidity reported as percent per patient-year were as follows: structural failure, 0%; paravalvular leak, 0.12%; prosthetic endocarditis, 0.24%; anticoagulant-related morbidity, 1.24%; and thromboembolism, 1.10%. In 89% of the survivors New York Heart Association functional performance had improved to class II or I. The actuarial survival with 95% confidence intervals at 5, 10, and 16 years was 86.9% (82.5%, 91.3%), 68.6% (60.6%, 76.6%), and 53.6% (36.6%, 70.6%), respectively. Freedom from late valve-related events (95% confidence intervals) at 10 and 16 years was as follows: thromboembolism, 91.2% (86.6%, 95.8%) and 78.3% (62.6%, 94%); anticoagulant-related morbidity, 89.1% (83.8%, 94.4%) and 81.0% (65.1%, 96.9%); and prosthetic endocarditis, 98.8% (97.5%, 100%) and 98.8% (97.5%, 100%), respectively. Multivariate analysis revealed age at operation, myocardial infarction, and endocarditis affected the long-term survival. The risk of sudden death irrespective of body surface area and valve size was not statistically different. Thus the long-term performance of the St. Jude Medical valve in small aortic roots is satisfactory.


Randomised phase II trial of gemcitabine plus vinorelbine vs gemcitabine plus cisplatin vs gemcitabine plus capecitabine in patients with pretreated metastatic breast cancer.
An increasing proportion of patients are exposed to anthracyclines and/or taxanes in the adjuvant or neoadjuvant setting. Re-exposure in the metastatic stage is limited by drug resistance, thus evaluation of non-cross-resistant regimens is mandatory. Anthracycline-pretreated patients were randomly assigned to three gemcitabine-based regimens. Chemotherapy consisted of gemcitabine 1.000 mg m(-2) plus vinorelbin 25 mg m(-2) on days 1+8 (GemVin), or plus cisplatin 30 mg m(-2) on days 1+8 (GemCis), or plus capecitabine 650 mg m(-2) b.i.d. orally days 1-14 (GemCap), q3w. The primary end point was response rate. A total of 141 patients were recruited on the trial. The overall response rates were 39.0% (GemVin), 47.7% (GemCis) and 34.7% (GemCap). Median progression-free survival was estimated with 5.7, 6.9 and 8.3 months, respectively. Corresponding median survival times were 17.5 (GemVin), 13.0 (GemCis) and 19.4 months (GemCap). Neutropenia ≥grade 3 occurred in 16.7% (Gem/Vin), 4.4% (GemCis) and 0% (Gem/Cap), whereas non-haematological toxicities were rarely severe except grade 3 hand-foot syndrome in 2.0% of the GemCap patients (per patient analysis). This randomised phase II trial has revealed comparable results for three gemcitabine-based regimens regarding treatment efficacy and toxicity. Gemcitabine-based chemotherapy appears to be a worthwhile treatment option for pretreated patients with metastatic breast cancer.


Evaluating the utility of hydrothermolysis pretreatment approaches in enhancing lignocellulosic biomass degradation by the anaerobic fungus Orpinomyces sp. strain C1A.
Members of the anaerobic fungi (Phylum Neocallimastigomycota) are efficient biomass degraders and represent promising agents for fuel and chemical production from lignocellulosic biomass. Pretreatment of lignocellulosic biomass is considered an unavoidable first step in enzyme-based saccharification schemes, but its necessity in any proposed anaerobic fungi-based schemes is still unclear. Here, we evaluated the effect of hydrothermal pretreatments on the extent of corn stover and switchgrass degradation by an anaerobic fungal isolate, Orpinomyces sp. strain C1A. Using a factorial experimental design, we evaluated the effect of three different temperatures (180, 190, and 200°C) and three hold times (5, 10, and 15min). Pretreated corn stover and switchgrass were more amenable to degradation by strain C1A when compared to untreated biomass, as evident by the higher proportion of plant biomass degraded compared to untreated controls. However, when factoring in the proportion of biomass lost during the pretreatment process (ranging between 25.78 and 58.92% in corn stover and 28.34 and 38.22% in switchgrass), hydrothermolysis provided negligible or negative improvements to the extent of corn stover and switchgrass degradation by strain C1A. Product analysis demonstrated a shift towards higher ethanol and lactate production and lower acetate production associated with increase in pretreatment severity, especially in switchgrass incubations. The results are in stark contrast to the requirement of pretreatment in enzyme-based schemes for biomass saccharification, and their implications on the potential utility of anaerobic fungi in biofuel and biochemical production are discussed.


Hyperpigmentation of an Atherosclerotic Carotid Artery Plaque in a Patient on Chronic Suppressive Minocycline Therapy.
Minocycline is an oral tetracycline antibiotic that has been used to treat a variety of medical conditions. A recognized side effect of minocycline is hyperpigmentation, most commonly a cutaneous phenomenon affecting the lower extremities. In our case report, we present a patient on chronic suppressive minocycline therapy identified intraoperatively with hyperpigmentation involving an atherosclerotic carotid plaque.


Enabling Nucleophilic Reactivity in High-Spin Fe(II) Imido Complexes: From Elementary Steps to Cooperative Catalysis.
ConspectusTransition metal complexes featuring an M═NR bond have received great attention as critical intermediates in the synthesis of nitrogen-containing compounds. In general, the properties of the imido ligand in these complexes are dependent on the nature of the metal center. Thus, the imido ligand tends to be nucleophilic in early transition metal complexes and electrophilic in late transition metal complexes. Nonetheless, the supporting ligand can have a dramatic effect on its reactivity. For example, there are sporadic examples of nucleophilic late transition metal imido complexes, often based on strongly donating supporting ligands. Building on these earlier works, in this Article, we show that the imido ligand in a low-coordinate high-spin bis(carbene)borate Fe(II) complex is able to access previously unknown reaction pathways, ultimately leading to new catalytic transformations. We first focus on the synthesis, characterization, and stoichiometric reactivity of a highly nucleophilic Fe(II) imido complex. The entry point for this system is the intermediate-spin three-coordinate Fe(III) imido complex, which is generated from the reaction of an Fe(I) synthon with an organic azide. Alkali metal reduction leads to a series of M+ (M = Li, Na, K) coordinated and charge-separated (M = K(18-C-6)) high-spin Fe(II) imido complexes, all of which have been isolated and fully characterized. Combined with the electronic structure calculations, these results reveal that the alkali ions moderately polarize the Fe═N bond according to K+ ≈ Na+ < Li+. As a result, the basicity of the imido ligand increases from the charged separated complex to K+, Na+, and Li+ coordinated complexes, as validated by intermolecular proton transfer equilibria. The impact of the counterion on imido ligand reactivity is demonstrated through protonation, alkylation, and hydrogen atom abstraction reactions. The counterion also directs the outcome of [2 + 2] reactions with benzophenone, where alkali coordination facilitates double bond metathesis. Building from here, we describe how the unusual nucleophilicity of the high-spin Fe(II) imido complex revealed in stoichiometric reactions can be extended to new catalytic transformations. For example, a [2 + 2] cycloaddition reaction serves as the basis for the catalytic guanylation of carbodiimides under mild conditions. More interestingly, this complex also exhibits the first ene-like reactivity of an M═NR bond in reactions with alkynes, nitriles, and alkenes. These transformations form the basis of catalytic alkyne and nitrile α-deuteration and pKa-dictated alkene transposition reactions, respectively. Mechanistic studies reveal the critical role of metal-ligand cooperativity in facilitating these catalytic transformations and suggest the new avenues for transition metal imido complexes in catalysis that extend beyond classical nitrene transfer chemistry.


Effect of platelet-activating factor on hepatic capillary pressure in isolated dog liver.
We determined the effects of platelet-activating factor (PAF), a potent vasoactive autacoid phospholipid, on the capillary pressure and liver weight (Wt) in isolated canine livers perfused with blood bivascularly via the portal vein and hepatic artery. PAF (0.01-33 microg) administered intraportally produced dose-dependent increases in the hepatic capillary pressure, as assessed by triple vascular occlusion pressure (Pto), and Wt. An intraportal injection of 10 microg PAF produced increases in Pto by 10 mmHg and Wt by 35 g/100 g liver weight. This hepatic vasoconstriction was attributed to a threefold increase in the portal vein resistance and a fourfold increase in the hepatic vein resistance. The hepatic arterial resistance was not changed when PAF was arterially or intraportally injected. In conclusion, in isolated perfused dog livers, PAF increases the hepatic capillary pressure and liver weight due to contraction of both the portal vein and hepatic vein, but not the hepatic artery.


State-of-the-art myocardial strain by CMR feature tracking: clinical applications and future perspectives.
Based on conventional cine sequences of cardiac magnetic resonance (CMR), feature tracking (FT) is an emerging tissue tracking technique that evaluates myocardial motion and deformation quantitatively by strain, strain rate, torsion, and dyssynchrony. It has been widely accepted in modern literature that strain analysis can offer incremental information in addition to classic global and segmental functional analysis. Furthermore, CMR-FT facilitates measurement of all cardiac chambers, including the relatively thin-walled atria and the right ventricle, which has been a difficult measurement to obtain with the reference standard technique of myocardial tagging. CMR-FT objectively quantifies cardiovascular impairment and characterizes myocardial function in a novel way through direct assessment of myocardial fiber deformation. The purpose of this review is to discuss the current status of clinical applications of myocardial strain by CMR-FT in a variety of cardiovascular diseases. KEY POINTS: • CMR-FT is of great value for differential diagnosis and provides incremental value for evaluating the progression and severity of diseases. • CMR-FT guides the early diagnosis of various cardiovascular diseases and provides the possibility for the early detection of myocardial impairment and additional information regarding subclinical cardiac abnormalities. • Direct assessment of myocardial fiber deformation using CMR-FT has the potential to provide prognostic information incremental to common clinical and CMR risk factors.


Prognostic value of left atrial strain in patients with wild-type transthyretin amyloid cardiomyopathy.
This study was performed to investigate whether left atrial (LA) strain by echocardiography provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 113 patients who had enough information for two-dimensional speckle tracking echocardiography were enrolled in this study. During a median follow-up of 668 days, 28 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.5 ± 7.4 vs. 78.1 ± 6.1 years, P < 0.01), had a lower incidence of carpal tunnel syndrome (21% vs. 47%, P < 0.05), and had a higher high-sensitivity cardiac troponin T [0.085 (0.063-0.105) vs. 0.049 (0.036-0.079) ng/mL, P < 0.01] and B-type natriuretic peptide concentrations [419 (239-541) vs. 271 (155-462) pg/mL, P < 0.01] and lower estimated glomerular filtration rate (41.8 ± 15.4 vs. 53.4 ± 14.6 mL/min/1.73 m2 , P < 0.01). Electrocardiography showed higher rate of a V1-V3 QS pattern (52% vs. 24%, P < 0.01) and complete left bundle branch block (27% vs. 6%, P < 0.01), and echocardiography showed a significantly lower peak LA strain rate during the contraction phase (0.16 ± 0.13 vs. 0.28 ± 0.27 S-1 , P < 0.05), LA strain during the reservoir phase (LASr) (5.84 ± 2.41 vs. 8.22 ± 4.05%, P < 0.01), and peak LA strain rate during the reservoir phase (0.26 ± 0.09 vs. 0.33 ± 0.15 S-1 , P < 0.05) in the cardiovascular death group than in non-event group. By contrast, conventional echocardiographic findings were not significantly different between these two groups. After adjusting for conventional predictive factors of ATTRwt-CM (age, high-sensitivity cardiac troponin T and B-type natriuretic peptide concentrations, and estimated glomerular filtration rate), multivariable Cox proportional hazard analyses showed that LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 0.84; 95% confidence interval, 0.72-0.98; P < 0.05). After adjusting for age and echocardiographic findings associated with cardiovascular death (LA volume index and peak LA strain rate during the contraction phase), LASr was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (odds ratio, 0.83; 95% confidence interval, 0.70-0.98; P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve of LASr for cardiovascular death was 0.686 and that the best cut-off value of LASr was 6.69% (sensitivity, 62.4%; specificity, 64.3%). In the Kaplan-Meier analysis, patients with low LASr (<6.69%) had a significantly higher probability of total cardiovascular death (P < 0.05) and heart failure-related hospitalization (P < 0.05). Left atrial strain during the reservoir phase provides significant prognostic value in patients with ATTRwt-CM even after adjusting for conventional predictive factors.


Short term cadmium administration dose dependently elicits immediate biochemical, neurochemical and neurobehavioral dysfunction in male rats.
Cadmium is a toxic environmental and industrial pollutant. Cadmium toxicity has been reported to produce biochemical and behavioral dysfunction that may cause adverse effects on several organs including the central nervous system. The present study was designed to investigate the neurotoxic effects of Cadmium Chloride (CdCl2) at three different doses by using different behavioral models. Lipid peroxidation (LPO), superoxide dismutase (SOD) and acetylcholinesterase (AChE) activities were also monitored following acute intraperitoneal injection of cadmium. Twenty four adult locally bred Albino Wistar rats were divided into control and 3 test groups (n = 6). Control rats were injected intraperitoneally with saline (0.9% NaCl) and test groups were injected with CdCl2 (1 mg/kg, 2 mg/kg and 3 mg/kg) dissolved in physiological solution. Behavioral activities of rats were monitored after 1 h of cadmium injection. Locomotor activity and depression-like symptoms were measured by Open Field Test (OFT) and Forced Swimming Test (FST) respectively. Anxiety like behavior was monitored using Light-dark Transition (LDT) test and memory functions of rats were assessed by Morris Water Maze test (MWM). In the present study acute cadmium administration dose dependently increased anxiety in rats as compared to control rats. A significant increase in depression-like symptoms was also exhibited by cadmium treated rats. These behavioral dysfunctions may be attributed to the decreased superoxide dismutase (SOD) activity and simultaneously increased brain lipid peroxidation (LPO). Moreover learning and memory assessed by MWM showed dose dependent impairment in memory function in cadmium treated rats as compared to control rats. Acetylcholinesterase (AChE) activity was also decreased in brains of cadmium administered rats. It is suggested in this study that behavioral, biochemical and neurochemical dysfunctions caused by acute cadmium administration occur in a dose dependent manner.


A comparative analysis of symmetric diketopyrrolopyrrole-cored small conjugated molecules with aromatic flanks: From geometry to charge transport.
Diketopyrrolopyrrole (DPP) derivatives are promising compounds for application in organic electronics. Here, we investigate several symmetrical N-unsubstituted and N-methyl substituted DPPs which differ in the heteroatom in the aromatic flanks. The conformational, electronic, and optical properties are characterized for single molecules in vacuum or a solvent. The intermolecular interactions are evaluated for interacting dimers. Here, a number of stacking geometries is tested, and dimers with mutual orientation of the molecules corresponding to the minimal binding energies are determined. The predicted charge carrier mobilities for stacks having minimal binding energies corroborate experimentally measured values. We conclude that DFT prediction of such stacks is a promising and computationally inexpensive approach to a rough estimation of transport properties. Additionally, the super-cell of the experimentally resolved crystal structure is used to study the dynamics and to compute the charge transport along the hopping pathways. We discuss obtained high mobilities and relate them to the symmetry of DPP core. © 2018 Wiley Periodicals, Inc.


Desmosterolosis: an illustration of diagnostic ambiguity of cholesterol synthesis disorders.
Desmosterolosis is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic mutations of DHCR24 (homozygous or compound heterozygous), which encodes 3-β-hydroxysterol Δ-24-reductase. We report two sisters homozygous for the 571G>A (E191K) DHCR24 mutation. Comparison of the propositae to other reported individuals shows that psychomotor developmental delay, failure to thrive, dysgenesis of the corpus callosum, cerebral white matter atrophy and spasticity likely constitute the minimal desmosterolosis phenotype. The nonspecific features of desmosterolosis make it difficult to suspect clinically and therefore screening for it should be entertained early in the diagnostic evaluation.


Support for Alcohol Policies in Marginalized Populations.
Kingdon [(2014) Agendas, Alternatives, and Public Policies. Essex. United Kingdom: Pearson Education Limited] argues that windows of opportunity to pass policies emerge when problems, solutions and policy support co-occur. This study aims to identify a set of alcohol policies with the potential to reduce alcohol-related disparities given high levels of support from marginalized groups, such as racial/ethnic minorities and lower-income groups. This study used data from five US National Alcohol Surveys, which were based on household probability samples of adults in 1995 (n = 4243), 2000 (n = 5736), 2005 (n = 1445), 2010 (n = 4164) and 2015 (n = 4041). We used multiple logistic regression to determine the odds of policy support by racial/ethnic group and income level, considering price, place and marketing policies as well as individual-level interventions. Overall a majority of Americans supported banning alcohol sales in corner stores (59.4%), banning alcohol advertisements on television (55.5%), and establishing universal health coverage for alcohol treatment (80.0%). Support was particularly high among Blacks, Hispanics/Latinos and lower-income persons. Multivariate models showed that compared with White people, foreign-born Hispanics/Latinos had the most robust levels of support, including raising alcohol taxes (aOR = 2.40, 95% CI: 2.00, 2.88, P < 0.0001), banning alcohol sales in corner stores (aOR = 2.85, 95% CI: 2.22, 3.65, P < 0.0001) and reducing retail sales hours (aOR = 2.91, 95% CI: 2.38, 3.55, P < 0.0001). Of the policies examined, banning alcohol sales at corner stores is most likely to be in a "window of opportunity" for reducing alcohol-related disparities. By simultaneously reducing population-level consumption and harms from others' drinking, place-based policies have the potential to reduce harms experienced by marginalized groups.


[Characteristics of mitochondrial DNA from Candida spec. EH15].
The restriction endonucleases EcoRI, PstI and BglII were used to digest the mitochondrial DNA from Candida spec. EH 15. Molecular masses of single digested DNA fragments were calculated. The mitochondrial DNA size (28-30 x 10(6) D) comprises 2/3 of the mitochondrial DNA from Saccharomyces cerevisiae.


Effects of endocrine disrupting chemicals on myelin development and diseases.
In the central and peripheral nervous systems, myelin is essential for efficient conduction of action potentials. During development, oligodendrocytes and Schwann cells differentiate and ensure axon myelination, and disruption of these processes can contribute to neurodevelopmental disorders. In adults, demyelination can lead to important disabilities, and recovery capacities by remyelination often decrease with disease progression. Among environmental chemical pollutants, endocrine disrupting chemicals (EDCs) are of major concern for human health and are notably suspected to participate in neurodevelopmental and neurodegenerative diseases. In this review, we have combined the current knowledge on EDCs impacts on myelin including several persistent organic pollutants, bisphenol A, triclosan, heavy metals, pesticides, and nicotine. Besides, we presented several other endocrine modulators, including pharmaceuticals and the phytoestrogen genistein, some of which are candidates for treating demyelinating conditions but could also be deleterious as contaminants. The direct impacts of EDCs on myelinating cells were considered as well as their indirect consequences on myelin, particularly on immune mechanisms associated with demyelinating conditions. More studies are needed to describe the effects of these compounds and to further understand the underlying mechanisms in relation to the potential for endocrine disruption.


Cell size and shape changes in the myoepithelium of the mammary gland during differentiation.
We have studied changes in myoepithelial cell size and shape during different stages of mouse mammary gland differentiation by using the fluorescent probe for actin NBD-phallacidin. Pieces of mammary tissue were fixed, mounted on slides, permeabilized with cold acetone (-20 degrees C), and then treated with nitrobenzoxadiazole-phallacidin. Myoepithelial cells lining ducts of glands at all stages of development are spindle-shaped structures oriented parallel to the long axis of the duct at the base of the luminal epithelium. In virgin animals, myoepithelial cells also occur as linear tracts oriented parallel to the long axis of small projections along the sides of ducts and terminal end buds. In early pregnancy, small stellate-shaped cells begin to appear around presumptive secretory units. By late pregnancy, larger star-shaped units of intense fluorescence appear at the base of alveoli. During lactation, both cell bodies and cell processes further enlarge as these interlacing stellate-shaped cells encompass the expanded alveoli. In regressing glands, cell size decreases and the processes appear to retract. Although alveoli are virtually absent in the multipartate resting gland, myoepithelial cells remain around lateral buds of ducts. These myoepithelial cells have two distinct shapes: small star-shaped cells capping the buds and spindle-shaped cells oriented parallel to the long axis of the buds. A comparison of myoepithelial cell shape in virgin mice and nulliparous women indicates a more developed cell in the human gland at this stage of development. Intact segments of mammary gland combined with NBD-phallacidin as a probe for actin provide an ideal system for future studies of the control of myoepithelial cell size and shape and their influence on cell functions.


Obstructive sleep apnea and white matter hyperintensities: correlation or causation?
Obstructive sleep apnea (apnea) is thought to cause small vessel ischemic episodes in the brain from hypoxic events, postulated as white matter hyperintensities (hyperintensities) identified on MRI which are implicated in cognitive decline. This study sought to evaluate these correlations. A retrospective evaluation of adults who underwent polysomnography (4/1/2016 to 4/30/2017) and a brain MRI prior to apnea diagnosis or within a year post-diagnosis was completed. MRI visual evaluation of hyperintensities using Fazekas scores were collected blind to clinical data. Collated clinical/MRI data were stratified and analyzed using chi-square, fishers t-tests, ANOVA/ANCOVA and linear regression. Stratification by apnea category revealed no significant differences in any variables including hyperintensity measures (Fazekas p=0.1584; periventricular p=0.3238; deep p=0.4618; deep total p=0.1770). Stratification by Fazekas category, periventricular and deep hyperintensities revealed increasing prevalence with age (p=0.0001); however, apnea categories were not significantly associated (Fazekas p=0.1479; periventricular p=0.3188; deep p=0.4503), nor were any individual apnea indicators. Continuous apnea measurements werre not associated with any hyperintensity factor; total deep hyperintensities were not associated with any apnea factors. Continuous BMI was not found to be associated with any apnea or hyperintensity factors. Only hypertension was noted to be associated with Fazekas (p=0.0045), deep (p=0.0010) and total deep (p=0.0021) hyperintensities; however, hypertension was not associated with apnea category (p=0.3038) or any associated factors. These data suggest apneas alone from OSA are insufficient to cause WMH, but other factors appear to contribute to the complex development of small vessel ischemic injury associated with age and cognitive decline.


Insulin ameliorates hypoxia-induced autophagy, endoplasmic reticular stress and apoptosis of myocardial cells: In vitro and ex vivo models.
Whether and how insulin counteracts the cytotoxic effects of hypoxia and improves cardiomyocyte viability remains unclear. To achieve this aim, cultured neonatal rat cardiomyocytes pretreated with vehicle or 1 μM insulin were exposed to either normoxic or hypoxia environment for up to 24 h. Cell viability was monitored and cellular apoptosis as well as necrosis, indexes of autophagy, endoplasmic reticular (ER) stress, and expressions of specific relevant mediators of the signaling pathways of autophagy were also assessed. Hypoxia impaired cell viability, induced autophagy, triggered apoptosis, activated ER stress pathway-associated apoptotic responses along with downstream pro-apoptotic transcriptional factor C/EBP homologous protein (CHOP), and increased apoptosis of myocardial cells. On the other hand, insulin pretreatment effectively ameliorated autophagy via PI3-K/Akt signaling pathway, suppressed ER stress, and prevented hypoxia-induced cellular apoptosis. In an ex vivo study, isolated rat hearts were pre-treated in some cases with insulin and subjected to proximal left coronary artery ligation to induce acute myocardial ischemia. Coronary ligation-induced acute ischemia upregulated glucose-related protein 78 (GRP78) and triggered cellular apoptosis in the jeopardized myocardium. Conversely, insulin pretreatment suppressed these hypoxia-related cytotoxic events and reduced myocardial infarct size by up to 15.2%. In conclusion, hypoxia impedes cell viability through triggering autophagy, ER stress and apoptosis, whereas insulin pretreatment effectively prevents these cytotoxic actions of hypoxia, preserves myocardial cell viability and reduces myocardial infarct size. These results indicated the cytoprotective mechanism of insulin against the insult of hypoxia may justify insulin as a therapeutic option for patients with acute myocardial infarction.


Sleep stability in isolated rapid eye movement sleep behavior disorder, Parkinson's disease, and dementia with Lewy bodies.
Non-REM sleep symptoms remain poorly understood in alpha-synucleinopathies. The aims of the study were to compare sleep stability and transitions, arousals, and sleep cycle structure between isolated rapid eye movement (REM) sleep behavior disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy Bodies (DLB). Sleep transition and stability measures were assessed in one-night video-polysomnography records. Transition measures were the number of shifts between Wake and REM, Wake and NREM, and REM and NREM. Stability measures were the number of passages within the same sleep stage. We assessed arousals, the number/duration of sleep cycles (defined as a sequence of any NREM stage to REM), and the duration of N3 and REM sleep in each cycle. These variables were compared between two sets of groups (PD vs. DLB vs. iRBD and RDB+ vs. RBD-). We assessed 54 PD, 24 DLB, and 21 iRBD patients (54 RBD+, 22 RBD-). There were no significant differences regarding sleep stability measures. Arousal indices in N1 and N2 stages were significantly higher in PD compared with iRBD. 24% of the sample did not have any sleep cycle. PD had significantly fewer cycles than iRBD. Differences became non-significant when adjusting for medication. There was no effect of group or time of night in REM or N3 duration. There were no significant differences between RBD+ and RBD-. There were no significant differences in stability/transition measures. Arousals and disturbance in sleep cycling were higher in PD, but the difference was no longer significant after adjusting for medication. Different alpha-synucleinopathies have a similar degree of non-REM sleep instability, but medication could worsen symptoms in PD.


Accuracy of digital impressions for implant-supported complete-arch prosthesis, using an auxiliary geometry part-An in vitro study.
The aim of this study was to evaluate the accuracy of complete-arch digital impressions for fabrication of an implant-supported prosthesis in the edentulous maxilla using an auxiliary geometry part. A replica of the upper jaw of an edentulous patient with four scannable impression copings was fabricated in stainless steel. This model was scanned with an industrial non-contact 3D structured blue light 3D scanner, and the measurements of three reference distances were established as reference values. Subsequently, the model was scanned in two different scenarios (with or without an auxiliary geometry part put in place and fixed to the model) using three intraoral scanners. Measurements were taken with 3D inspection software, and a digital impression of the complete arch was built with mesh processing software by combining 2 STL files obtained with an intraoral scanner. All measurements with the auxiliary geometry part gave significantly more accurate results (p < .05). Trueness improved in the three reference distances, reaching values of 8 ± 6 µm at D12 reference distance, 20 ± 11 µm at D13 and 35 ± 22 µm at D14. Precision also improved significantly with the use of the auxiliary geometry part placed on the model (p < .05). The best precision results at reference distances D13 and D14 were obtained with the True Definition Scanner. The proposed methodology significantly improves the accuracy of complete-arch digital impressions in edentulous patients obtained in vitro, regardless of which scanner is used.


Application of isoelectric focusing for studies of major histocompatibility complex class I antigen expression on human carcinomas and sarcomas.
By one-dimension isoelectric focusing we analysed the major histocompatibility complex class I antigen expression on human tumours. Blood lymphocytes of the patients, processed in parallel, served as a basis for comparison. The prerequisite for the analysis is the preparation of metabolically active tumour cell suspensions devoid of significant leucocyte contamination. The method was found to be suitable for study of the expression of HLA alleles on ex vivo tumour cells and allowed the detection of changes imposed by in vitro treatment with interferon gamma and tumour necrosis factor alpha.


Are Dried and Powdered Moringa oleifera Lam. Leaves Susceptible to Moths That Feed on Stored Products?
The leaves of Moringa oleifera are increasingly used as a food supplement in several countries due to their nutritional composition, which is rich in protein, vitamins, and mineral salts. Foodstuffs can be damaged by several pests when stored in environments with temperatures that are favorable to insect development; therefore, the susceptibility of M. oleifera leaves to attacks of moths that feed on stored products was tested. Tests were carried out on Pyralid Cadra cautella, Corcyra cephalonica, and Plodia interpunctella, as well as Geometrid Idaea inquinata, which were reared on dried whole or powdered M. oleifera leaves, an artificial diet, or an artificial diet supplemented with dried or powdered leaves. The numbers of adults and the development periods with the different diets were recorded. M. oleifera leaves were unsuitable as a rearing medium for all of the species except I. inquinata, although only a few individuals of this species reached the adult stage. The use of an artificial diet of which one-quarter consisted of dried and powdered leaves did not affect the number of progeny or on the biological cycle, showing that the effect was due to the nutritional composition, as well as to the toxic effect. The storage of M. oleifera as powdered leaves is recommended in order to preserve the nutritional characteristics and avoid damage caused by moth larvae.


Protonated Imine-Linked Covalent Organic Frameworks for Photocatalytic Hydrogen Evolution.
Covalent organic frameworks (COFs) have emerged as an important class of organic semiconductors and photocatalysts for the hydrogen evolution reaction (HER)from water. To optimize their photocatalytic activity, typically the organic moieties constituting the frameworks are considered and the most suitable combinations of them are searched for. However, the effect of the covalent linkage between these moieties on the photocatalytic performance has rarely been studied. Herein, we demonstrate that donor-acceptor (D-A) type imine-linked COFs can produce hydrogen with a rate as high as 20.7 mmol g-1 h-1 under visible light irradiation, upon protonation of their imine linkages. A significant red-shift in light absorbance, largely improved charge separation efficiency, and an increase in hydrophilicity triggered by protonation of the Schiff-base moieties in the imine-linked COFs, are responsible for the improved photocatalytic performance.


Scale-invariant Mexican Hat wavelet descriptor for non-rigid shape similarity measurement.
The Mexican Hat wavelet (MHW) is strictly derived from the heat kernel by taking its negative first-order derivative with respect to time t. As a solution to the heat equation that the heat kernel has a clear initial condition, the Laplace-Beltrami operator. Although the MHW descriptor can effectively characterize the model information, but it has poor robustness to the model with scale transformation, and the feature description performance is affected to some extent. Following a popular mathematical method, in this paper, we bases on the MHW to study scaling invariance and proposes a new shape descriptor, the scale-invariant Mexican Hat wavelet (SIMHW), which by logarithmic sampling and Fourier transform that obtains the expression of SIMHW in Fourier domain. The experimental results show that SIMHW has finer information description ability and stronger recognition ability, and has better robustness to various non-rigid transformations. It can correctly calculate the similarity between 3D shapes and realize the effective shape retrieval.


Assessment of osteoporosis at autopsy: mechanical methods compared to radiological and histological techniques.
Osteoporosis is a common problem in the elderly female population and pathological fractures are a frequent complication, but how should the pathologist assess the severity of the disease at autopsy? In this study we have compared subjective, semi-quantitative assessments of rib fracturability, vertebral compressibility, Singh index and histomorphometric methods against a 'gold standard' assessment, namely the force required to fracture the femoral neck. We have shown good correlations between rib fracturability. Singh index and the standard chosen. Poor correlation was shown between histomorphometric techniques and the standard. Our findings suggest that gross rib fracturability is a good indicator of osteoporosis in as far as bone fragility is an indicator of the severity of osteoporosis. However, as the population under examination was small, further studies in this area are clearly warranted in order to extend these findings.


Distinct roles of carbohydrate-binding modules in multidomain β-1,3-1,4-glucanase on polysaccharide degradation.
Lam16A is a novel GH16 β-1,3-1,4-lichenase isolated from the genus Caldicellulosiruptor which can utilize untreated carbohydrate components of plant cell walls. Its catalytic module has been characterized that the six carbohydrate-binding modules (CBMs) were queued in the C-terminus, but their roles were still unclear. Here, full-length and CBM-truncated mutants of Lam16A were purified and characterized through heterologous expression in Escherichia coli. The profiles of these proteins, including the enzyme activity, degrading efficiency, substrate-binding affinity, and thermostability, were explored. Full-length Lam16A with six CBMs showed excellent thermostability and the highest activity against barley β-glucan and laminarin with optimum pH of 6.5. The CBMs stimulated degrading ability of the catalytic module, especially against β-1,3(4)-glucan-based polysaccharides. The released products from β-1,3-1,4-glucan by Lam16A or its truncated mutants revealed an endo-type glycoside hydrolase. Lam16As exhibited strong binding affinities to the insoluble polysaccharides, especially Lam16A-1CBM. The degradation of yeast cell walls by Lam16A enzyme solution relative to the control reduced the absorbance values at OD800 by ~ 85% ± 1.2, enabling the release of up to ~ 0.057 ± 0.0039 µg/mL of the cytoplasmic protein into the supernatant, lowering the viability of the cells by ~ 70.3% ± 6.9, thus causing significant damage in the cell wall structure. Taken together, CBMs could influence the substrate specificity, thermal stability, and binding affinity of β-1,3-1,4-glucanase. These results demonstrate the great potential of these enzymes to promote the bioavailability of β-1,3-glucan oligosaccharides for health benefits. KEY POINTS: • Carbohydrate-binding modules strongly influenced the enzyme activity and binding affinity, and further impacted glycoside hydrolase activity. • Lam16A enzymes have sufficient ability to hydrolyze β-1,3-1,4-glucan-based polysaccharides. • Lam16As provide a powerful tool to promote the bioavailability of β-1,3-glucan oligosaccharides.


[Liquid-crystal thermography in the diagnosis and assessment of treatment efficacy in patients with chronic lymphedema of the lips].
Thermographic examination of 80 patients with chronic labial lymphedema (CLL) in various stages of the condition has revealed a clear-cut correlation between the process stage and thermal topography manifestations. This helped plan a differentiated approach to the choice of the treatment strategy in various CLL phases. Changed thermography data in the course of treatment evidence the possibility of applying this method to the assessment of the treatment efficacy in CLL.


Culturally enhancing a group-based motivational interviewing substance use prevention program for Latine youth.
Group Motivational Interviewing for Teens (GMIT) has been effective in reducing youth substance use in diverse communities, yet more research is needed to determine its efficacy in reducing tobacco and alternative tobacco products (ATP) use among Latine adolescents. This study modified GMIT to include a focus on ATPs (GMIT-ATP). GMIT was also linguistically translated so it could be offered in English and Spanish, culturally enhanced, and parent sessions were added (GMIT-ATP + P). The study's aims were to 1) Develop a model of how cultural context, family relationships, and adolescent tobacco-related skills/beliefs are associated with smoking and ATP use; 2) Examine the impact of the GMIT-ATP intervention on adolescent tobacco use; 3) Examine whether the GMIT-ATP + P intervention improves family/parenting factors associated with reduced adolescent tobacco use; 4) Examine whether GMIT-ATP + P is more effective than GMIT-ATP in improving adolescent tobacco use; 5) Explore whether essential components of our behavior change model mediate the impact on tobacco use, and 6) Explore whether cultural factors influence the impacts of our intervention. Latine adolescents (ages 10-16) and their parents/guardians were recruited throughout Virginia. Parents and adolescents completed three surveys: before and immediately after the program ends and at 3-months post-intervention. Families attended 3 GMIT-ATP or GMIT-ATP + P sessions. Findings from this study will be disseminated in Latine communities and with providers working with Latine youth and can serve as a community-based model to reduce substance and tobacco use (e.g., ATP) in these Latine communities.


The persistence of Chinese medicine: adjustment and diversity.
Chinese medicine persists in many parts of East and Southeast Asia. This persistence has meant the re-organisation of traditional Chinese medical practice. Institutional developments and adjustments observed among the traditional Chinese medical practitioners, the chung-i, have created diversity. Such diversity among the chung-i is evident by comparing not only the practices which are based in shops and those which are clinic-based but also the newer and older practices.


Identifying depression and anxiety disorders in people presenting for substance use treatment.
To identify the type and proportion of depressive and related mental health disorders in a group of individuals seeking outpatient treatment at an alcohol and other drug (AOD) service. A cross-sectional study using diagnostic interviews with 95 participants (56 men, 39 women) seeking treatment from an AOD service. Mental health and substance disorders were measured using the Composite International Diagnostic Interview, Posttraumatic Stress Disorder Checklist, Beck Depression Inventory, and State-Trait Anxiety Inventory (Trait Version). This was a complex group with addiction, mental health and physical health conditions; 76% had a depressive disorder and 71% had an anxiety disorder. Most were diagnosed with at least two mental health disorders and 25% were diagnosed with four or more different disorders. Alcohol and cannabis use were the most commonly diagnosed AOD disorders. Further, those diagnosed with a drug use disorder reported significantly higher levels of depression compared with those with an alcohol-only disorder. Finally, 60% of the sample reported chronic health conditions, with over one-third taking medication for a physical condition on a regular basis. Primary care providers such as general practitioners are likely to be increasingly called on to assess, treat and/or coordinate care of patients with AOD disorders. We show that this group will likely present to their GP with more than one mental health disorder in addition to acute and chronic physical health conditions.


Clinical significance of post-liver transplant hepatitis E seropositivity in high prevalence area of hepatitis E genotype 3: a prospective study.
High hepatitis E (HEV) seroprevalence has been reported in the general population and in post-liver transplant (LT) cases in several regions, including Thailand, with genotype 3 being a predominant genotype. We hypothesized that HEV might persist at a subclinical level and might pose clinical risks in the post-LT period. We performed a cross-sectional study with 108 post-LT patients and found an IgG seroprevalence of 55.6%. Subsequently, 91 cases without clinical evidence of HEV-related hepatitis were enrolled in 1 year of prospective follow-up to determine clinical status, serologies and serum/feces HEV RNA every 4 months. HEV RNA was detected, indicating subclinical infections in patients with or without seropositivity, with an annual incidence of 7.7%. Our results suggest that subclinical HEV infection exists among LT patients in this high-prevalence area. Thus, clinicians should be aware of the possibility of disease reemergence and HEV viral transmission in LT patients.


Systemic artery-pulmonary vein fistula without sequestration.
Fistulae between an artery arising from the aorta and a pulmonary vein associated with absence of a branch of the pulmonary artery, but without anomalies of the bronchial tree, are exceedingly rare. We report a case in a child who presented with a continuous vascular murmur and developed heart failure due to the left-left shunt. Left lobectomy was performed and showed that the entire left lower lobe was occupied by a huge arteriovenous fistula between an artery stemming from the aorta and the pulmonary veins.


[Different regulation of mitochondrial apoptosis and Bcl-2 gene expression in quescent and proliferative human fibroblasts infected with cytomegalovirus].
The aim of the study was to compare the dynamics ofmitochondrial apoptosis (MA) in cells at different stages of proliferation and with different susceptibility to cytomegalovirus (CMV). It has been found that in quiescent human fibroblasts (HF) CMV regulates MA at the level of bcl-2 gene transcription, exerting both pro- and anti-apoptotic effects. Suppression of bcl-2 transcription is greater in HF-977 line, which is highly susceptible to CMV in comparison with HF-1068 line. The effect of proliferative activity on MA was studied using CMV-infected HF-110044 line at the G0- or S-phase. A direct correlation was established between accumulation of cytochrome c and caspase 3 (MA markers) and production of IE72, pp65 and gB (CMV proteins). In G0-fibrob-lasts, viral replication was highly productive and bcl-2 expression was 10-fold as high as in S-phase cells, in which viral protein production and cell death were much lower. The increased gene transcription and accumulation of Bcl-2 protein enhanced cell viability and provided synthesis of viral proteins. Impaired structure of actin microfilaments, a caspase 3 target, coincided with pronounced suppression of gamma-actin gene in S-phase HF-110044. Our findings provide an insight into CMV-induced mechanisms of MA which lead to rapid death of infected quiescent fibroblasts and to slow death of cells infected at the stage of DNA synthesis.


The case of a newspaper phobia in a 9-year-old child.
The case of E, a 9-year-old, male, with a newspaper phobia, is presented. The phobia developed over a 4-year period and gradually spread until it included many significant areas of E's life. Treatment took place over a 4-month period. It involved use of a token economy administered by E's parents. Cognitively, the treatment involved the concepts of the acquisition of perceived self-control as a consequence of the token economy agreement. This included volition, attention, and self-control by E as well as parental reinforcement.


Modality specific roles for metabotropic GABAergic signaling and calcium induced calcium release mechanisms in regulating cold nociception.
Calcium (Ca2+) plays a pivotal role in modulating neuronal-mediated responses to modality-specific sensory stimuli. Recent studies in Drosophila reveal class III (CIII) multidendritic (md) sensory neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Functional analyses revealed CIII-mediated multimodal behavioral output is dependent upon activation levels with stimulus-evoked Ca2+ displaying relatively low vs. high intracellular levels in response to gentle touch vs. noxious cold, respectively. However, the mechanistic bases underlying modality-specific differential Ca2+ responses in CIII neurons remain incompletely understood. We hypothesized that noxious cold-evoked high intracellular Ca2+ responses in CIII neurons may rely upon Ca2+ induced Ca2+ release (CICR) mechanisms involving transient receptor potential (TRP) channels and/or metabotropic G protein coupled receptor (GPCR) activation to promote cold nociceptive behaviors. Mutant and/or CIII-specific knockdown of GPCR and CICR signaling molecules [GABA B -R2, Gαq, phospholipase C, ryanodine receptor (RyR) and Inositol trisphosphate receptor (IP3R)] led to impaired cold-evoked nociceptive behavior. GPCR mediated signaling, through GABA B -R2 and IP3R, is not required in CIII neurons for innocuous touch evoked behaviors. However, CICR via RyR is required for innocuous touch-evoked behaviors. Disruptions in GABA B -R2, IP3R, and RyR in CIII neurons leads to significantly lower levels of cold-evoked Ca2+ responses indicating GPCR and CICR signaling mechanisms function in regulating Ca2+ release. CIII neurons exhibit bipartite cold-evoked firing patterns, where CIII neurons burst during rapid temperature change and tonically fire during steady state cold temperatures. GABA B -R2 knockdown in CIII neurons resulted in disorganized firing patterns during cold exposure. We further demonstrate that application of GABA or the GABA B specific agonist baclofen potentiates cold-evoked CIII neuron activity. Upon ryanodine application, CIII neurons exhibit increased bursting activity and with CIII-specific RyR knockdown, there is an increase in cold-evoked tonic firing and decrease in bursting. Lastly, our previous studies implicated the TRPP channel Pkd2 in cold nociception, and here, we show that Pkd2 and IP3R genetically interact to specifically regulate cold-evoked behavior, but not innocuous mechanosensation. Collectively, these analyses support novel, modality-specific roles for metabotropic GABAergic signaling and CICR mechanisms in regulating intracellular Ca2+ levels and cold-evoked behavioral output from multimodal CIII neurons.


Effects of Cerebral Ischemia on Levels of Vascular Endothelial Growth Factor (VEGF) and Its Soluble Receptors: A Possible Link to Angiogenesis in Arteriovenous Malformations.
To investigate the levels of vascular endothelial growth factor (VEGF) in the brain, and its soluble forms, namely sVEGFR1 and sVEGFR2, levels in the plasma of rats after cerebral ischemia. Rats were divided into three groups as follows: Group 1: Sham-operated group, Group 2: Complete occlusion of the right carotid artery, Group 3: Complete occlusion of the right carotid artery and temporary occlusion of the left carotid artery for 10 min. Blood samples were collected on days 0 and 10 prior to the sacrification to measure the sVEGFR1 and sVEGFR2 levels. On day 10, animals were sacrificed, and brain tissue was collected to analyze VEGF expression. Postoperative sVEGFR1 levels reduced significantly in Group 3, while it remained stable in other groups. sVEGFR2 levels did not change in any group. Although VEGF staining scores in the groups that underwent ischemia procedures increased compared to group 1, no significant differences were observed. Decreased levels of sVEGFR1 can be a mechanism contributing to angiogenesis in arteriovenous malformations by increasing the levels of VEGF available to bind membrane-bound VEGFRs.


Percutaneous balloon mitral valvotomy in pregnant patients with tight pliable mitral stenosis.
Percutaneous balloon mitral valvotomy was attempted in severely symptomatic (New York Heart Association class III or IV) pregnant patients (mean age 30 years) with tight mitral stenosis. Nineteen patients were pregnant (mean gestation 30 weeks, range 26 to 34) and one patient was in the immediate postpartum period. All patients had undergone a trial of diuretic therapy and 16 were also taking atenolol. Percutaneous valvotomy was performed with the Inoue catheter (18 patients) or the Schneider-Medintag bifoil (2 x 19 mm) balloon catheter (2 patients). The fluoroscopy time was 9.2 +/- 3.4 minutes. After percutaneous valvotomy the mean mitral gradient decreased from 17.9 +/- 6.2 to 5.9 +/- 2.4 mm Hg (p < 0.001). The mitral valve area (pressure half time) increased from 0.8 +/- 0.2 to 1.7 +/- 0.2 cm2 (p < 0.001). These hemodynamic changes were accompanied by immediate symptomatic improvement by at least one New York Heart Association functional grade in all patients. Moderate (3+) mitral regurgitation developed in one patient. Eighteen patients had normal infants delivered vaginally at term without assistance, and one patient had a normal infant delivered by cesarean section at 35 weeks' gestation. We conclude that percutaneous balloon mitral valvotomy for pliable mitral stenosis in pregnancy is safe for both the mother and fetus. We recommend that it be performed in symptomatic patients with tight mitral stenosis so as to avoid hemodynamic complications in the latter stages of pregnancy.


State of the Art and Advances in Peripheral Nerve Surgery.
This review is intended to describe and actualize the basic knowledge of the three basic entities that affect the peripheral nerve system and can be treated by surgery: nerve trauma, chronic nerve compressions, and tumors.Regarding trauma, emphasis is given on the timing of surgery, given the fact that the moment in which the surgery is performed and the employed microsurgical reconstruction technique are the most important factors in the final result. Open lesions with associated nerve injury should be managed with an early exploration carried out before 7 days. Closed injuries are usually deferred, with few exceptions, from 3 to 6 months after the trauma.In turn, chronic compressions require an appropriate clinical, neurophysiological, and imaging diagnosis. Isolated sensory symptoms can be treated actively though without surgery: motor signs like atrophy should be regarded as a sign for immediate surgery, as a deferred treatment might cause an irreversible nerve and muscular damage. Endoscopic approaches are a valuable tool for treatment in selected neuropathies.Finally, nerve tumors demand a thorough preoperative evaluation, as benign tumors are treated in a very different way when compared to malignant lesions. Benign tumors can usually be safely and completely resected without sacrificing the nerve of origin. When malignancy is confirmed, extensive resection to optimize patient survival is the main objective, potentially at the expense of neurological function. This may then be followed by adjuvant radiation and/or chemotherapy, depending on the nature of the tumor and the completeness of resection attained. The role of nerve biopsy remains controversial, and several modern diagnostic techniques might be helpful.


Evaluation of the Frequency and Anatomy of Radix Entomolaris and Paramolaris in Lower Molars by Cone Beam Computed Tomography (CBCT) in Northern Iran, 2020-2021: A Retrospective Study.
The presence of an additional root, known as a radix, in the lower molars is of significant importance in the context of root canal therapy since it has the potential to contribute to treatment failure. Furthermore, it is imperative to take this circumstance into consideration when doing tooth extraction using a radix. The present study investigated the anatomical characteristics and prevalence rates of radix entomolaris and paramolaris in mandibular molars using cone beam computed tomography. Cone beam computed tomography scans of the lower molars of 376 patients were processed through Newtom's NNT viewer software. Radix type, radix root canal length, radix root curvature, Vertucci's classification of the canal, and gender of patients were recorded. The results of the research were analyzed with chi-squared. The prevalence of radix was found to be 0.74%, with entomolaris and paramolaris present in 54.54% and 45.46% of cases, respectively. There was no statistically significant difference between the two variables of radix type and gender, as indicated by a p-value of 0.08. The mean curvature and length of the radix root were measured to be 56.63° and 15.09 mm, respectively. The average root curvature in individuals diagnosed with radix entomolaris and paramolaris was found to be 62.33° and 49.80°, respectively. The study found that the root curvature of entomolaris exhibited a statistically significant difference compared to paramolaris (P=0.031). The mean length of the radix entomolaris and paramolaris roots was found to be 15.50 and 14.60 mm, respectively. There was no statistically significant difference observed in the mean root lengths of the various radix types (P=0.37). According to Vertucci's classification, all radixes were classified as type 1. The investigated population had a low incidence of radix. The curvature of radix entomolaris exhibited a statistically significant increase compared to radix paramolaris. There was no observed correlation between gender and the length of radix roots in relation to the type of radix root.


Glomerular Classification Using Convolutional Neural Networks Based on Defined Annotation Criteria and Concordance Evaluation Among Clinicians.
Diagnosing renal pathologies is important for performing treatments. However, classifying every glomerulus is difficult for clinicians; thus, a support system, such as a computer, is required. This paper describes the automatic classification of glomerular images using a convolutional neural network (CNN). To generate appropriate labeled data, annotation criteria including 12 features (e.g., "fibrous crescent") were defined. The concordance among 5 clinicians was evaluated for 100 images using the kappa (κ) coefficient for each feature. Using the annotation criteria, 1 clinician annotated 10,102 images. We trained the CNNs to classify the features with an average κ ≥0.4 and evaluated their performance using the receiver operating characteristic-area under the curve (ROC-AUC). An error analysis was conducted and the gradient-weighted class activation mapping (Grad-CAM) was also applied; it expresses the CNN's focusing point with a heat map when the CNN classifies the glomerular image for a feature. The average κ coefficient of the features ranged from 0.28 to 0.50. The ROC-AUC of the CNNs for test data varied from 0.65 to 0.98. Among the features, "capillary collapse" and "fibrous crescent" had high ROC-AUC values of 0.98 and 0.91, respectively. The error analysis and the Grad-CAM visually showed that the CNN could not distinguish between 2 different features that had similar visual structures or that occurred simultaneously. The differences in the texture or frequency of the co-occurrence between the different features affected the CNN performance; thus, to improve the classification accuracy, methods such as segmentation are required.


Impact of advanced maternal age on adverse infant outcomes: A Japanese population-based study.
The number of births among women of higher age has been rapidly increasing in many countries for several decades. While recent epidemiological studies on the impact of maternal age on infant outcomes in developed countries have evaluated the outcomes of singleton infants, few population-based studies have investigated all deliveries including multiple births. Thus, we aimed to assess the impact of maternal age on adverse infant outcomes using data from all birth certificates, including multiple births, in Shiga prefecture, Japan. The data from all birth certificates in Shiga Prefecture from 2013 to 2014 (23,294 births from 23,048 mothers) were obtained. We evaluated the impact of maternal age on adverse infant outcomes, including small for gestational age (SGA), low birth weight (LBW), and preterm birth (PTB). A multivariable logistic regression analysis was performed to determine adjusted odds ratios (aORs) for infant outcomes with various maternal factors, including multiple pregnancies. Statistical analysis for trend was performed using the Jonckheere-Terpstra test. The incidence rates of adverse infant outcomes began to increase at a maternal age of 30 years. A maternal age of ≥35 years was associated with significantly increased risks of adverse infant outcomes, including SGA (adjusted odds ratio [aOR]: 1.15, 95% confidence interval [95% CI]: 1.03-1.29), LBW (aOR: 1.29, 95% CI: 1.16-1.43), and PTB (aOR: 1.17, 95%CI: 1.04-1.33). The risk of adverse infant outcomes was significantly increased in women older than 35 years of age. These data would be useful for younger women to decide family-planning in advance.


Detection of hepatoma in liver cirrhosis.
The analogic liver scintigram using 99mTc sulfur colloid in cirrhotic patients does not permit determination of the nature of the areas of decreased uptake. Scintigrams with 67Ga citrate generally show increased activity in cases of hepatoma. In some cases, however, 67Ga citrate is less concentrated in neoplasic tissue, and it is not possible to detect a tumoral lesion in a cirrhotic liver. This is why we used double isotope scintigraphies with 67Ga citrate and 99mTc sulfur colloid, with digital subtraction, after simultaneous recording of 99mTc and 67Ga data on magnetic tape by means of an interface. In our series of 22 patients, the comparison of the results obtained by this double isotope technique with histology showed no false positive in substraction scintigrams. There was one false negative because of the lack of significance in the subtracted image for one of the six patients with cancer of the liver. For three of the six patients with hepatoma, the gallium scintigram showed an increased uptake in the tumor area. For the three other cases, the gallium uptake was equilibrated throughout the liver scintigraphy. It was therefore in cases where the gallium scintigram showed no increased activity that the subtraction technique was of greatest value, for it permitted the diagnosis of hepatoma in two cases.


Urine metabolite profiling of Indian Antarctic Expedition members: NMR spectroscopy-based metabolomic investigation.
The southernmost region of earth, Antarctica, has world's most challenging environments. Those who live for long time and work in Antarctic stations are subjected to environmental stresses such as cold weather, photoperiod variations leading to disrupted sleep cycles, constrained living spaces, dry air, non-availability of fresh food items, and high electromagnetic radiations, psychological factors, such as geographical and social isolation, etc. All these factors have a significant impact on the human body. The present study investigated the impact of Antarctica harsh environment on human physiology and its metabolic processes by evaluating urine metabolome, using 1H NMR spectroscopy and analyzing certain physiological and clinical parameters for correlation with physiological expression data and metabolite results. Two study groups - before Antarctic exposure (B) and after Antarctic exposure (E), consisting of 11 subjects, exposed to one-month summer expedition, were compared. 35 metabolites in urine samples were identified from the 700 MHz 1H NMR spectra from where integral intensity of 22 important metabolites was determined. Univariate analysis indicated significant decrease in the levels of citrate and creatinine in samples collected post-expedition. Multivariate analysis was also performed using 1H NMR spectroscopy, because independent metabolite abundances may complement each other in predicting the dependent variables. 10 metabolites were identified among the groups; the OPLS-DA and VIP score indicated variation in appearance of metabolites over different time periods with insignificant change in the intensities. Metabolite results illustrate the impact of environmental stress or altered life style including the diet with absence of fresh fruits and vegetables, on the pathophysiology of the human health. Metabolic adaptation to Antarctic environmental stressors may help to highlight the effect of short-term physiological status and provide important information during Antarctic expeditions to formulate management programmes.


Impact of silk biomaterial structure on proteolysis.
The goal of this study was to determine the impact of silk biomaterial structure (e.g. solution, hydrogel, film) on proteolytic susceptibility. In vitro enzymatic degradation of silk fibroin hydrogels and films was studied using a variety of proteases, including proteinase K, protease XIV, α-chymotrypsin, collagenase, matrix metalloproteinase-1 (MMP-1) and MMP-2. Hydrogels were used to assess bulk degradation while films were used to assess surface degradation. Weight loss, secondary structure determined by Fourier transform infrared spectroscopy and degradation products analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis were used to evaluate degradation over 5 days. Silk films were significantly degraded by proteinase K, while silk hydrogels were degraded more extensively by protease XIV and proteinase K. Collagenase preferentially degraded the β-sheet content in hydrogels while protease XIV and α-chymotrypsin degraded the amorphous structures. MMP-1 and MMP-2 degraded silk fibroin in solution, resulting in a decrease in peptide fragment sizes over time. The link between primary sequence mapping with protease susceptibility provides insight into the role of secondary structure in impacting proteolytic access by comparing solution vs. solid state proteolytic susceptibility.


De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain.
Mosquito- and tick-borne pathogens including Chikungunya, Dengue, Japanese encephalitis, West Nile, Yellow fever and Zika virus, represent a new economic and public health challenge. In the absence of effective vaccines and specific therapies, only supportive regimens are administrated for most of these infections. Thus, the development of a targeted therapy is mandatory to stop the rapid progression of these pathogens and preoccupant associated burdens such as Guillain-Barre syndrome, microcephaly. For this, it is essential to develop biochemical tools to help study and target key viral enzymes involved in replication such as helicase complexes, methyl-transferases and RNA-dependent RNA polymerases. Here, we show that a highly purified ZIKV polymerase domain is active in vitro. Importantly, we show that this isolated domain is capable of de novo synthesis of the viral genome and efficient elongation without terminal nucleotide transferase activity. Altogether, this isolated polymerase domain will be a precious tool to screen and optimize specific nucleoside and non-nucleoside inhibitors to fight against Zika infections.


MMP-9 Mediates Cross-Talk between Neutrophils and Endothelial Cells in Psoriasis.
In their report, Chen et al. provide new insights into psoriasis pathogenesis, showing that neutrophil infiltration of skin lesions increases vascular endothelial cell (VEC) activation, leading to cutaneous vasodilation and enhanced vascular permeability. In patients with psoriasis, neutrophil-derived matrix metalloproteinase 9 (MMP-9) plays a pivotal role in VEC barrier dysfunction, via extracellular signal-regulated kinase-1/2 and p38 pathways. Pharmacologic inhibition of MMP-9 in two different models confers reduced cutaneous vasodilation, vascular permeability, and inflammation, suggesting MMP-9 as a target in psoriasis pathogenesis.


Postoperative complications of spinal vs general anesthesia in elderly patients undergoing hip hemiarthroplasty.
Elderly patients with hip fractures are at high risk for mortality due to postsurgical complications. Hip hemiarthroplasty is a routine procedure done in elderly patients for surgical repair of femoral neck fractures. Both general and spinal anesthesia can be used in elderly patients undergoing hemiarthroplasty. Rates of postoperative complications among the two anesthetic choices have not been directly compared. In this study, we compare the rates of postoperative complications in elderly patients (age greater than 70) undergoing hip hemiarthroplasty for femoral neck fractures using a national database. Data for the years 2015-2020 from the National Surgical Quality Improvement Program (NSQIP) were used for the study. Patients greater than 70 years of age who received a hip hemiarthroplasty with general anesthesia or spinal anesthesia were identified using CPT procedure codes. Pertinent preoperative variables and rates of postoperative complications were characterized and analyzed. Our study found that elderly patients who received spinal anesthesia had, on average, longer length of stays but shorter operative times compared to patients who received general anesthesia. Furthermore, we found that patients who received spinal anesthesia had lower rates of systemic sepsis, cardiac arrests, and blood transfusions when compared to patients who received general anesthesia. Finally, we found that overall rates of mortality were significantly lower in the spinal anesthesia cohort compared to the general anesthesia cohort. Our work suggests that patients who underwent spinal anesthesia for hip arthroplasty may have lower rates of postoperative complications. This work further highlights the role of anesthetic choice in preventing complications following hip hemiarthroplasty procedures.


Sentencing and mental disorder: the evolution of the Verdins Principles, strategic interdisciplinary advocacy and evidence-based reform.
In DPP v O'Neill, the Victorian Court of Appeal excluded personality disorders from the scope of the sentencing principles that apply to offenders with mental health problems around Australia (the 'Verdins principles'). This decision was based on a fundamental misunderstanding of the nature of personality disorders and had the potential to create serious injustice for many marginalised people. To redress this problem, the authors engaged in a unique process of strategic advocacy, which resulted in the Victorian Court of Appeal overturning O'Neill in the recent case of Brown v The Queen. This article examines the evolution of the Verdins principles, the problems that arose in O'Neill, the collaborative strategy used to address those problems and the successful outcome of that interdisciplinary strategy.


[Use of positron emission tomography in assessing hidden extrathoracic metastasis in non small cell lung cancer].
Positron emission tomography combined with computed axial tomography (PET/CT) is used for staging non small cell lung cancer (NSCLC). This study aims to describe PET/CT findings of unsuspected extrathoracic metastasis when used in mediastinal evaluation of patients with apparently resectable NSCLC. Prospective and concurrent study including all NSCLC patients between June 2004 and November 2006 who underwent PET/CT after considering them as candidates for surgery, with resectable disease after bronchoscopy, thorax and abdominal CT, brain CT and bone gammagraphy evaluation, if metastasis at these locations were suspected. Metastasis were confirmed histopathologically or assumed when they had a compatible evolution. A total of 91 patients with NSCLC underwent PET/CT. In 24 of them (26%) at least one suspicious extrathoracic uptake was seen. In 7 patients (7.7%) those uptakes were NSCLC extrathoracic metastasis hidden from conventional staging. In 3 of these cases (13.1%) extrathoracic uptakes corresponded to metacrhonous tumours or pre-malignant conditions. Benign lesions were found in 12 patients (13.1%), and in 2 cases (2.2%) the uptake origins were undetermined. PET/CT is a complementary diagnosis method for assessing hidden metastases which could modify the therapeutical approach in patients otherwise suitable for surgery.


Influence of pancreatic status, CFTR mutations, Staphylococcus aureus and/or Pseudomonas aeruginosa infection/colonization on lung function in cystic fibrosis during a 2-year follow-up period.
Cystic fibrosis (CF) presents with progressive and chronic deterioration of lung function due to inflammation and colonization/infection of the lungs. This study evaluated spirometry and colonization/infection with Staphylococcus aureus and/or Pseudomonas aeruginosa over a 24-month follow-up period. A total of 52 CF patients were studied with spirometry: forced vital capacity (FVC), forced expiratory volume in one second of FVC (FEV1), FEV1/FVC and forced expiratory flow between 25% and 75% of FVC (FEF25-75%). Colonization/infection was evaluated as predominantly S. aureus, predominantly P. aeruginosa or concomitance of these microorganisms. In CF, there was a higher prevalence of p.Phe508del/p.Phe508del genotype (16/52; 30.8%) and female gender (33/52; 63.5%). Spirometry (% predicted) markers worsened for the following groups over the 24-month period: (i) male: FVC, FEV1, FEV1/FVC, FEF25-75%; (ii) female: FVC%, FEV1, (iii) predominantly S. aureus: FVC, FEV1, FEV1/FVC, FEF25-75%; (iv) predominantly P aeruginosa: FEV1/FVC; (v) concomitant S. aureus and P. aeruginosa: FVC, FEV1. Age correlated with reduction of FVC(Liter) (Rho = -0.50) and FEV1(Liter) (Rho = -0.46). Pancreatic insufficiency and severe cystic fibrosis transmembrane regultador (CFTR) mutations were associated with deteriorating lung function. In CF, deterioration of lung function as evaluated by spirometry was continuous and varied according to sex, pancreatic insufficiency, and severe CFTR mutations. No differences were observed between groups in terms of predominant type of bacteria, but the reduction of spirometry parameters was significant in the predominantly S. aureus and concomitant infection groups.


Acute care utilisation towards the end of life and the place of death for patients with serious mental disorders: a register-based cohort study in South London.
The aim of the study was to explore acute care utilisation towards end of life by and the place of death for patients with serious mental disorders and to demonstrate any inequalities in end-of-life care faced by this patient group. This is a retrospective cohort study using linked, routinely collected data. This study used linked data extracted from mental health records, Hospital Episode Statistics and mortality data. Adult cases (≥18 years old) were included if they had a serious mental disorder and died between 2007 and 2015. Multiple imputation was used to manage missing data, and generalised linear models were used to assess multiple adjusted associations between sociodemographic and clinical explanatory variables and acute service use at the end of life and in-hospital deaths. A cohort of 1350 adults was analysed. More than half visited the accident and emergency (A&E) department in the last 90 days of life, and a third had a burdensome transition (multiple hospital admissions in the last 90 days of life or at least one in the last three days); the median number of days spent in the hospital was 4 (range: 0-86). Having more comorbidities was a strong correlate of more A&E visits (adjusted odds ratio [OR] = 1.03 [95% confidence interval = 1.02-1.04]), burdensome transitions (adjusted OR = 1.06 [1.04-1.08]) and days spent in the hospital (adjusted OR = 1.04 [1.03-1.05]). Having a diagnosis of schizophrenia spectrum disorder, compared with other serious mental disorder diagnoses, was associated with fewer A&E visits (adjusted OR = 0.78 [0.71-0.88]) and fewer days in the hospital (adjusted OR = 0.77 [0.66-0.89]). Younger age was associated with more A&E visits (adjusted OR = 1.28 [1.07-1.53]) and fewer days spent in the hospital (adjusted OR = 0.70 [0.52-0.95]). Hospital deaths were high (51%), and in a fully adjusted model, they were associated with having more comorbidities (adjusted OR = 1.02 [1.01-1.03]) and accessing acute care at the end of life (including more A&E visits; adjusted OR = 1.07 [1.05-1.10]), burdensome transitions (adjusted OR = 1.53 [1.37-1.71]) and days spent in the hospital (adjusted OR = 2.05 [1.70-247]). People with comorbidities are more likely to use more burdensome acute health care at the end of life and are more likely to die in the hospital. Hospital deaths could be reduced, and end-of-life care could be improved by targeting patients with comorbidities and who are accessing more acute healthcare services.


Substrate specificity of the galactokinase from the human gut symbiont Akkermansia muciniphila ATCC BAA-835.
Galactokinases, which catalyze the phosphorylation of galactose and possible other monosaccharides, can provide an activated sugar donor to synthesize sugar-containing molecules. In this study, a novel galactokinase from human gut symbiont Akkermansia muciniphila ATCC BAA-835 (GalKAmu) was expressed and characterized. GalKAmu displayed broad substrate tolerance, with catalytic activity towards Gal (100 %), GalN (100 %), GalA (20.2 %), Glc (52.5 %), GlcNAc (15.5 %), Xyl (<5%), ManNAc (58 %), ManF (37.4 %) and l-Glc (80 %). Most interestingly, this was the first GalK isoform which can tolerate ManNAc. Thus, our characterization of GalKAmu broadens the substrate selection of galactokinases.


Magnetic resonance spectroscopy and its application in colorectal cancer diagnosis and screening: A narrative review.
There are several slightly invasive methods to detect colorectal carcinoma (CRC) including colonoscopy and sigmoidoscopy; but there is no noninvasive, accurate screening test. It is recommended to initiate screening at the age of 50 for non-familial CRC. Laboratory tests are routinely suggested if internal observation and imaging are recommended for further evaluation. Spectroscopic-based imaging, such as magnetic resonance spectroscopy (MRS) is an interesting and promising tool with the potential to be an alternative to some minimally invasive procedures, such as biopsy. Accordingly, MRS might be a suitable substitution for invasive methods, such as colonoscopy. This article aimed to review the studies that have evaluated the MRS technique as a screening tool in CRC.


Hellebrigenin induces cell cycle arrest and apoptosis in human hepatocellular carcinoma HepG2 cells through inhibition of Akt.
Hellebrigenin, one of bufadienolides belonging to cardioactive steroids, was found in skin secretions of toads and plants of Helleborus and Kalanchoe genera. In searching for natural constituents with anti-hepatoma activities, we found that hellebrigenin, isolated from traditional Chinese medicine Venenum Bufonis, potently reduced the viability and colony formation of human hepatocellular carcinoma cells HepG2, and went on to explore the underlying molecular mechanisms. Our results demonstrated that hellebrigenin triggered DNA damage through DNA double-stranded breaks and subsequently induced cell cycle G2/M arrest associated with up-regulation of p-ATM (Ser(1981)), p-Chk2 (Tyr(68)), p-CDK1 (Tyr(15)) and Cyclin B1, and down-regulation of p-CDC25C (Ser(216)). It was also found that hellebrigenin induced mitochondrial apoptosis, characterized by Bax translocation to mitochondria, disruption of mitochondrial membrane potential, release of cytochrome c into cytosol and sequential activation of caspases and PARP. In addition, Akt expression and phosphorylation were inhibited by hellebrigenin, whereas Akt silencing with siRNA significantly blocked cell cycle arrest but enhanced apoptosis induced by hellebrigenin. Activation of Akt by human insulin-like growth factor I (hIGF-I) could obviously attenuate hellebrigenin-induced cell death. In summary, our study is the first to report the efficacy of hellebrigenin against HepG2 and elucidated its molecular mechanisms including DNA damage, mitochondria collapse, cell cycle arrest and apoptosis, which will contribute to the development of hellebrigenin into a chemotherapeutic agent in the treatment of liver cancer.


Investigation of low-temperature selective catalytic reduction of NOx with ammonia over Cr-promoted Fe/AC catalysts.
Fe/activated coke (AC) and Cr-Fe/AC catalysts with AC as a supporter and Cr and Fe as active components were prepared by an impregnation method for low-temperature selective catalytic reduction (SCR) of NO with NH3. The effects of Cr addition and its concentrations on the deNOx performance of Fe/AC catalysts were studied at low temperature. The Cr addition promotes the low-temperature SCR activity of the 8Fe/AC catalyst and the 8Fe6Cr/AC catalyst has the best low-temperature SCR deNOx performance, which the NOx conversions are greater than 90% at 160-240 °C. The 8Fe6Cr/AC catalyst has good water resistance. However, when 100 ppm SO2 was introduced into the reaction gas, its deNOx efficiency drops to 45% at 180 °C. To clarify the specific effects of Cr addition on the NOx conversions and sulfur poisoning, the Cr-Fe/AC catalysts were characterized by X-ray diffraction, BET, H2 temperature-programmed reduction, NH3 temperature-programmed desorption, X-ray photoelectron spectroscopy, and Fourier infrared spectroscopy. The addition of Cr into Fe/AC catalysts greatly increases the BET surface area and the number of weak and medium-strong acid sites on the catalyst surface and improves the ratio of Fe3+/Fe2+. These factors enhance the NOx conversion of 8Fe/AC catalyst. The formed sulfates and hydrogen sulfates cover the active sites on the catalyst surface, which lead to the sulfur poisoning of the 8Fe6Cr/AC catalyst. Graphical abstract.


Proof of concept for a syndromic surveillance system based on routine ambulance records in the South West of England, for the influenza season 2016/2017.
The introduction of electronic patient records in the ambulance service provides new opportunities to monitor the population. Approximately 36% of patients presenting to English ambulance services are discharged at scene. Ambulance records are therefore an ideal data source for syndromic early event detection systems to monitor infectious disease in the pre-hospital population. It has been previously found that tympanic temperature records can be used to detect influenza outbreaks in emergency departments. This study aimed to determine whether routine tympanic temperature readings collected by ambulance crews can be used to detect seasonal influenza. Here we show that temperature readings do allow the detection of seasonal influenza before methods applied to conventional data sources. The counts of pyretic patients were used to calculate a sliding case ratio as a measurement to detect seasonal influenza outbreaks. This method does not rely on conventional thresholds and can be adapted to the data. The data collected correlated with seasonal influenza. The 2016/2017 outbreak was detected up to nine weeks before other surveillance programmes. The results show that ambulance records can be a useful data source for biosurveillance systems. Temperature readings from routinely collected ambulance patient records can be used as a surveillance tool for febrile diseases.


Cancer mutations rewire the RNA methylation specificity of METTL3-METTL14.
Chemical modification of RNAs is important for post-transcriptional gene regulation. The METTL3-METTL14 complex generates most N 6 -methyladenosine (m 6 A) modifications in mRNAs, and dysregulated methyltransferase expression has been linked to numerous cancers. Here we show that changes in m 6 A modification location can impact oncogenesis. A gain-of-function missense mutation found in cancer patients, METTL14 R298P , promotes malignant cell growth in culture and in transgenic mice. The mutant methyltransferase preferentially modifies noncanonical sites containing a GGAU motif and transforms gene expression without increasing global m 6 A levels in mRNAs. The altered substrate specificity is intrinsic to METTL3-METTL14, helping us to propose a structural model for how the METTL3-METTL14 complex selects the cognate RNA sequences for modification. Together, our work highlights that sequence-specific m 6 A deposition is important for proper function of the modification and that noncanonical methylation events can impact aberrant gene expression and oncogenesis.


Diagnostic significance of levels of immunoglobulin A in seminal fluid of patients with prostatic disease.
Immunoglobulin A (IgA) levels in semen and in prostatic fluid of 48 patients with benign and malignant diseases of the prostate were estimated. It is speculated from this small study that the IgA levels rise in benign prostatic hyperplasia; in early adenocarcinoma of the prostate (Stages A and B) the rise if furthered, while in the late stages (Stages C and D) the levels fall.


SAR and QSAR of COVID-19 Main Protease-Inhibitor Interactions of Recently X-ray Crystalized Complexes.
COVID-19 is still widespread worldwide and up to now there is no established antiviral able to control the disease. Main protease is responsible for the viral replication and transcription; thus, its inhibition is a promising route to control virus proliferation. The present study aims to examine detail interactions between main protease and recently reported ninety-seven inhibitors with available X-ray crystallography to define factors enhance inhibition activity; thirty-two of most potent inhibitors were examined to identify sites and types of interaction. The study showed formation of covalent bond, H-bond and hydrophobic interaction with key residues in the active side. Covalent bond is observed in seventeen complexes, all of them by attack of the 145Cys thiol group on Michael acceptor, aldehyde or its hydrate, α-ketoamide, double bond or acetamide methyl group; the latter type requires H-bonding between acetamide carbonyl oxygen and at least one of 143Gly, 144Ser or 145Cys. Potent inhibitors, disulfiram and ebselen docked in the same binding site. Accordingly, factors identify inhibition include forming covalent bond and existing terminal hydrophobic groups and amidic or peptidomimetic structure. Binding affinity was found correlated with topological diameter up to 24 bond, molecular size, branching, polar surface area up to 199 Å2 and hydrophilicity. The online version contains supplementary material available at 10.1007/s40011-021-01338-8.


Anti-inflammatory effect of leaves of Vernonia zeylanica in lipopolysaccharide-stimulated RAW 264.7 macrophages and carrageenan-induced rat paw-edema model.
Vernonia zeylanica (L.) Less (Family: Compositae) is a medicinal plant used as external applications for boils, bone fractures, eczema and internally for asthma in traditional medicine in Sri Lanka. Anti-nociceptive, anti-bacterial and anti-proliferative activities have been reported previously. To investigate the anti-inflammatory activity of methanol/dichloromethane extract (MDE) of leaves of V. zeylanica by assessing in vivo inhibition of rat paw-edema, in vitro inhibition of the production of nitric oxide (NO) and superoxide and inhibitory effect on inducible nitric oxide synthase (iNOS) gene expression. In vivo anti-inflammatory activity of MDE was tested at the dose of 1500 mg/kg using rat paw-edema model. Indomethacin and Gum acacia was used as the positive and vehicle control respectively. In vitro NO inhibitory activity of 7.8-250 μg/ml MDE was tested using lipopolysaccharide (LPS)-stimulated (1 μg/ml) mouse macrophages (RAW264.7 cells) and rat peritoneal cells (RPC) obtained following carrageenan-induction (5 mg/Kg). Griess method was used to quantify the nitrite levels in culture supernatants. In vitro inhibition of superoxide production of Phorbal 12-myristate 13-acetate (PMA)-stimulated RAW cells was determined by quantitative Nitroblue Tetrazolium (NBT) assay. N-monomethyl-L-arginine acetate (NMMA) (1 mM) and Diphenyleneiodonium chloride (DPI) (10 μM) were used as the positive controls for inhibitory activity of NO and superoxide production respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was carried out to test the inhibitory effect on mRNA expression of iNOS gene. Treatment with MDE of V. zeylanica at 1500 mg/kg showed significant inhibition of paw-edema from 1st-5th hour (P < 0.01) compared with the control. The reference drug, indomethacin showed a biphasic pattern and its highest inhibition was (98.3 ± 7.1%) at 4th h (P < 0.01). MDE of V. zeylanica showed similar inhibition of paw-edema with highest inhibition recorded as 94.5 ± 5.28%, at 5th h (P < 0.01). The inhibitory concentration (IC50) of MDE for in vitro NO inhibitory activity was 105 μg/ml for RAW cells and 80 μg/ml for RPCs. Both NO inhibitory activities showed significant dose-dependency (r = 0.998 and r = 0.915 respectively; p < 0.05). MDE concentration of 250 μg/ml showed 55% inhibition of ROS production in RAW cells. NMMA showed 78% and 70.1% inhibition of NO production with RAW cells and RPCs whereas DPI showed 61% superoxide inhibitory activity with RAW cells. NO inhibitory activity of MDE on RAW cells was confirmed by the significant reduction (99.1%) in iNOS gene expression. These results demonstrated potent anti-inflammatory activity of MDE of V. zeylanica reflected by its significant in vivo inhibition of rat paw-edema, in vitro inhibition of NO and superoxide production, and the reduction of iNOS gene expression. Thus, further purification and isolation of bioactive compounds from V. zeylanica are emphasized.