How anxious were Quebec healthcare professionals during the first wave of the COVID-19 pandemic? A web-based cross-sectional survey.
The coronavirus disease 2019 (COVID-19) pandemic may cause significant anxiety among healthcare professionals (HCPs). COVID-19-related psychological impacts on HCPs in Western countries have received relatively little attention. This study aims to assess the levels of anxiety in HCPs working in the province of Quebec (Canada) during the first wave of the COVID-19 pandemic and identify factors associated with changes in anxiety scores. An exploratory online cross-sectional survey was conducted among Quebec HCPs from April to July 2020. The Spielberger's State-Trait Anxiety Inventory (STAI) was used to measure state anxiety among HCPs. Descriptive and multivariate analyses were performed. A total of 426 HCPs completed the survey. Anxiety scores ranged from 20 to 75 points, with 80 being the highest possible value on the STAI scale. Being a female HCP [B = 5.89, 95% confidence interval (CI): 2.49-9.3] and declaring having the intention to avoid caring for patients with COVID-19 (B = 3.75, 95% CI: 1.29-6.22) were associated with increased anxiety scores. Having more years of experience was associated with decreased anxiety scores [B = -0.2, 95% CI: -0.32-(-0.08)]. Organizational strategies aimed at preventing and relieving anxiety should target junior female HCPs who express the intention to avoid caring for patients with COVID-19. Seniority could become an important criterion in selecting frontline HCPs during pandemics. Further studies are needed to comprehensively examine the impacts of the COVID-19 pandemic on Canadian HCPs and identify evidence-based coping strategies.


Degenerative neurologic disease in patients formerly treated with human growth hormone. Report of the Committee on Growth Hormone Use of the Lawson Wilkins Pediatric Endocrine Society, May 1985.
One or more lots of pituitary GH supplied by the NHPP may have been contaminated with CJD pathogen. If so, it is probable that the contaminated hormone was dispensed before 1978, and there is reason to believe that it was dispensed in the late 1960s. The contamination may have been limited to one lot of GH, but this is not known with certainty. Purification methods used by the NHPP since 1978 probably exclude the CJD pathogen, but this is not yet certain. The risk to patients treated since 1978, therefore, probably is low. There is no evidence to date that GH from either of the pharmaceutical suppliers has been or is contaminated. Purification procedures used by these sources also should exclude the pathogen. To exclude the possibility that they are contaminated with the CJD pathogen, 1 1/2 to 3 years will be required to test batches of the pituitary GH used previously. The experiment needed to show that the purification method used by NHPP excludes the scrapie agent will take up to 1 year. Planning for epidemiologic studies in patients treated with pituitary GH is under way. Biosynthetic GH prepared by recombinant DNA techniques has been in clinical trial in the United States for 3 1/2 years. It has been shown to be as effective as pituitary GH in promoting growth. However, it produces a higher incidence of GH antibodies than pituitary GH preparations do. Pediatric endocrinologists support the FDA in its effort to gather the information needed to approve biosynthetic GH for treatment of GH deficiency at an early date.


GH Action in Prostate Cancer Cells Promotes Proliferation, Limits Apoptosis, and Regulates Cancer-related Gene Expression.
Previous studies investigating the effects of blocking the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in prostate cancer found no effects of the growth hormone receptor (GHR) antagonist, pegvisomant, on the growth of grafted human prostate cancer cells in vivo. However, human GHR is not activated by mouse GH, so direct actions of GH on prostate cancer cells were not evaluated in this context. The present study addresses the species specificity of GH-GHR activity by investigating GH actions in prostate cancer cell lines derived from a mouse Pten-deletion model. In vitro cell growth was stimulated by GH and reduced by pegvisomant. These in vitro GH effects were mediated at least in part by the activation of JAK2 and STAT5. When Pten-mutant cells were grown as xenografts in mice, pegvisomant treatment dramatically reduced xenograft size, and this was accompanied by decreased proliferation and increased apoptosis. RNA sequencing of xenografts identified 1765 genes upregulated and 953 genes downregulated in response to pegvisomant, including many genes previously implicated as cancer drivers. Further evaluation of a selected subset of these genes via quantitative reverse transcription-polymerase chain reaction determined that some genes exhibited similar regulation by pegvisomant in prostate cancer cells whether treatment was in vivo or in vitro, indicating direct regulation by GH via GHR activation in prostate cancer cells, whereas other genes responded to pegvisomant only in vivo, suggesting indirect regulation by pegvisomant effects on the host endocrine environment. Similar results were observed for a prostate cancer cell line derived from the mouse transgenic adenocarcinoma of the mouse prostate (TRAMP) model.


Quantitative proteomic profiling identifies global protein network dynamics in murine embryonic heart development.
Defining the mechanisms that govern heart development is essential for identifying the etiology of congenital heart disease. Here, quantitative proteomics was used to measure temporal changes in the proteome at critical stages of murine embryonic heart development. Global temporal profiles of the over 7,300 proteins uncovered signature cardiac protein interaction networks that linked protein dynamics with molecular pathways. Using this integrated dataset, we identified and demonstrated a functional role for the mevalonate pathway in regulating the cell cycle of embryonic cardiomyocytes. Overall, our proteomic datasets are a resource for studying events that regulate embryonic heart development and contribute to congenital heart disease.


Epithelial cell kinetics in the crypts of familial polyposis of colon.
Epithelial cell kinetics were examined in the uninvolved part of the rectal mucosa in nine cases of familial polyposis of colon, six cases of their first degree relatives, and six control cases. The biopsied specimen were incubated for two hours in the culture medium containing H3-thymidine. In the control cases, the proliferating zone was confined to the lower two thirds of the crypt in all except one case. Six of the nine cases of familial polyposis of colon had crypts with altered proliferating zone, i.e., incorporation of H3-thymidine was observed in the upper one third of the crypt as in the case of adenomatous polyps. Three of the six cases of the first degree relatives showed such change. There were significant differences in the incidence of such change between controls and familial polyposis of colon or their first degree relatives, whereas no significant differences between familial polyposis of colon and their first degree relatives.


Degradation of polyethoxylated nonylphenols in a sewage treatment plant. Quantitative analysis by isotopic dilution-HRGC/MS.
Polyethoxylated alkylphenols (APnEO, where n is the number of ethylene oxide molecules), are non-ionic surfactants widely used for domestic and industrial purposes. Most of APnEO are polyethoxylated nonylphenols (NPnEO). NPnEO are widespread environmental pollutants with relatively low toxicity for mammals and higher toxicity for aquatic organisms. In addition, they have been described as endocrine disrupters in recent publications. One of the main problems related to these surfactants is their uncomplete degradation, even in the most effective sewage treatment plants. Usually, the final products, more toxic and resistant to biological degradation than NPnEO, are nonylphenol (NP), monoethoxylated nonylphenol (NP1EO), diethoxylated nonylphenol (NP2EO), nonylphenoxy acetic acid (NP1EC), and nonylphenoxyethoxy acetic acid (NP2EC). In this paper, the degradation of NPnEO was studied in the different processes of a sewage treatment plant. For this purpose, NP, NP1EO and NP2EO were analysed in composite samples collected at different points along the plant (influent, pre-treatment effluent, primary effluent, plant effluent). Analyses were carried out by isotopic dilution-HRGC/MS, using available labelled nonylphenols (13C6-NP, 13C6-NP1EO, 13C6-NP2EO) as internal standards. Extraction of NPnEO from aqueous samples, previous to analysis, was performed by the Likens-Nickerson method (simultaneous steam distillation/solvent extraction, SDE).


Use of a dynamic filtration method for separation of animal cells.
For solving the problem of concentrating and washing of viable cell suspensions a dynamic filter device has been evaluated. Results show that concentrating of cells under sterile conditions can be performed. With a laboratory scale filter (Sulzer-Biodruckfilter BDF-01) a 9-fold concentration was achieved, the filtration speed was about 15 l/h. The viability did not change significantly. Details of experiments are given and advantages are discussed.


Divergent roles of superoxide and nitric oxide in reduced-size liver ischemia and reperfusion injury: Implications for partial liver transplantation.
Hepatic resection with concomitant periods of ischemia and reperfusion (I/R) are required to perform partial liver transplantation procedures such as split liver or living donor transplantation. Although great progress has been made using these types of surgeries, there remains substantial risk to both donors and recipients, with a significant number of patients developing liver injury and failure during the course these operations. Therefore, there is need to investigate the different mechanisms responsible for the tissue injury induced by ischemia and reperfusion of a reduced-size liver (RSL+I/R) with the ultimate objective of developing new therapeutic agents that may limit hepatocellular damage induced during partial liver transplantation. This review summarizes recent studies that have been performed in a mouse model of RSL+I/R. In addition, we present data demonstrating how the pathophysiological mechanisms identified in this model compare to those observed in a rat model of RSL transplantation.


Vascular chronic-fibrosing pancreatitis of the rat after 5/6-nephrectomy.
The pancreases of 77 uremic rats of a Wistar strain were investigated light-microscopically in groups of 5 animals at 11 different times between one day and ten weeks after 5/6-nephrectomy. The serum concentration of urea reached a maximum mean value of 375 mg% after three days; during the stage of chronic uremia the mean value was found to be 175 mg%. The blood pressure increased in the third week after 5/6-nephrectomy and reached in the course of the experiment values of up to 200 mm Hg and more. Histologically, after an initial acute interstitial pancreatitis with focal dystrophies of the exocrine parenchyma which was virtually cured by the 14th day of the experiment, an increasing proliferative-exudative and granulomatous vasculopathy appeared at the end of the third week. This was followed by a perivascular transmitted chronic-fibrosing pancreatitis which may be regarded as a model of vascularly induced pancreatitis. Early damage by uremia and initial pancreatitis, the rapidly developing hypertension and allergical and autoallergical reactions are discussed as aetiological complex for the vascular alterations. The typical findings of the uremic pancreatopathy, well-known in human pathology, are not reproducible.


Four-Dimensional Computed Tomography Angiography Demonstrating a Ruptured Basilar Artery Aneurysm Causing Anterior Cerebral Circulation Arrest.
A 61-year-old woman suffered a pronounced subarachnoid hemorrhage. Conventional computed tomography angiography (CTA) showed no enhancement of the intracranial vasculature, whereas there was normal contrast enhancement of bilateral external carotid artery branches. Subsequent four-dimensional computed tomography angiography (4D-CTA) demonstrated active contrast leakage out of a ruptured basilar tip aneurysm, whereas there was no enhancement of the anterior circulation at any time point, consistent with intracranial anterior circulation arrest. This case illustrates that 4D-CTA is superior to conventional CTA for the evaluation of intracranial flow dynamics and delayed intracranial vascular contrast filling.


An integrated automated multispectral imaging technique that simultaneously detects and quantitates viral RNA and immune cell protein markers in fixed sections from Epstein-Barr virus-related tumours.
Epstein-Barr virus (EBV) is an oncovirus that is commonly associated with the development of lymphomas and epithelial carcinomas. In the era of immunotherapy, histological evaluation of EBV-related cancers is currently a multi-sample, multi-technique process requiring separate time-consuming detection of EBV-encoded small RNAs by in situ hybridisation (ISH), and parallel labelling of sections for cancer-associated protein markers. Using EBV-associated tumours as proof-of-concept for feasibility, here we developed an approach that allows simultaneous detection of EBV RNAs and multiple protein markers such as PD-L1, EBV-LMP, CD8, CD4, CD20, CD30 and CD15on a single tissue section based on our recently reported automated staining protocol. We successfully combined multiplex immunofluorescence (mIF) to detect 3 abovementioned protein markers involved in cancer, with ISH, and applied the protocol to f tissue samples from patients diagnosed with EBV-associated pulmonary lymphoepithelioma-like carcinoma (LELC), gastric carcinoma and Hodgkin's Lymphoma. Empowered by the Vectra 3 Automated Quantitative Pathology Imaging System, we demonstrate the utility and potential of this integrated approach to concurrently detect and quantitate viral RNA and protein biomarkers of immune and tumour cells. This study represents an important step forward in the research and diagnosis of EBV-associated cancers, and could be readily modified to include other proteins and RNA markers to apply to other malignancies. More importantly, the novel automated ISH-mIF protocol that we detailly described here could also be readily reproduced by most of the diagnostic and research lab to future projects that aim to look at both RNA and protein markers.


Combining Optical Coherence Tomography and Optical Coherence Tomography Angiography Longitudinal Data for the Detection of Visual Field Progression in Glaucoma.
To use longitudinal optical coherence tomography (OCT) and OCT angiography (OCTA) data to detect glaucomatous visual field (VF) progression with a supervised machine learning approach. Prospective cohort study. One hundred ten eyes of patients with suspected glaucoma (33.6%) and patients with glaucoma (66.4%) with a minimum of 5 24-2 VF tests and 3 optic nerve head and macula images over an average follow-up duration of 4.1 years were included. VF progression was defined using a composite measure including either a "likely progression event" on Guided Progression Analysis, a statistically significant negative slope of VF mean deviation or VF index, or a positive pointwise linear regression event. Feature-based gradient boosting classifiers were developed using different subsets of baseline and longitudinal OCT and OCTA summary parameters. The area under the receiver operating characteristic curve (AUROC) was used to compare the classification performance of different models. VF progression was detected in 28 eyes (25.5%). The model with combined baseline and longitudinal OCT and OCTA parameters at the global and hemifield levels had the best classification accuracy to detect VF progression (AUROC = 0.89). Models including combined OCT and OCTA parameters had higher classification accuracy compared with those with individual subsets of OCT or OCTA features alone. Including hemifield measurements significantly improved the models' classification accuracy compared with using global measurements alone. Including longitudinal rates of change of OCT and OCTA parameters (AUROCs = 0.80-0.89) considerably increased the classification accuracy of the models with baseline measurements alone (AUROCs = 0.60-0.63). Longitudinal OCTA measurements complement OCT-derived structural metrics for the evaluation of functional VF loss in patients with glaucoma.


Measurement of human body parameters for human postural assessment via single camera.
We present a camera-based human body parameters measurement approach and develop a human postural assessment system. The approach combines the conventional contact measurement method and the non-contact measurement method to overcome some shortcomings in terms of time, expense, and professionalism in early methods. The entire measurement system consists of a computer, a high-definition camera, and the sticky points that are applied to the participant's body before the measurement. The camera captures the triple view image of human body. Then, the human body outline and the joint points of the human skeleton are extracted to locate the bone feature points. Finally, measurements and extractions of the human parameters are made. Experimental results demonstrate that the global postural assessment system provides quantitative guidance for human postural evaluation, and it completely changes how human postural is evaluated. The postural assessment system is significant for early diagnosis of diseases and medical rehabilitation treatment.


Central nervous system effects and behavioral interactions with ethanol of centrally administered dilazep and its metabolites in mice.
Dilazep (i.p.), a coronary vasodilator and an uptake inhibitor of adenosine, dose dependently potentiated acute ethanol-induced motor incoordination in mice. In view of peripheral cardiovascular depressive effects of dilazep, the effect of i.c.v. dilazep (25, 50 and 75 micrograms), and its metabolites, 1,4-bis(3-hydroxypropyl)perhydro-1,4-diazepine (BHPD) (15, 31 and 62 micrograms) and 1-[3-(3,4,5-trimethoxybenzoyloxy)propyl]perhydro-1,4-diazepine (TBPD) (62 and 125 micrograms) on ethanol-induced motor incoordination was studied. Dose-related potentiation of ethanol-induced motor incoordination was noted with dilazep and its metabolites. Whereas dilazep (i.p.) produced no apparent central nervous system (CNS) effects, by i.c.v. route, it caused CNS excitation including tonic-clonic seizures. Adenosine uptake inhibition, Ca2+ entry blockade or direct activation of adenosine receptors was ruled out as the possible mechanism of seizures because dipyridamole, verapamil or N6-(2-phenylisopropyl)-adenosine (R-PIA) administered i.c.v., while potentiating ethanol (i.p.)-induced motor incoordination did not produce seizures. The CNS excitation was minimal with BHPD and none with TBPD. Theophylline pretreatment partially blocked potentiation of ethanol-induced motor incoordination by dilazep and BHPD and not by TBPD. The data suggest dilazep-induced potentiation of ethanol-induced motor incoordination is partially due to central adenosine receptor mechanism and partly due to other yet unknown mechanism(s) and further supported our earlier reports about adenosine involvement in the CNS effects of ethanol. The data also suggest that dilazep (i.c.v.)-induced seizures are due to mechanism(s) other than adenosine uptake inhibition, Ca2+ entry blockade or direct adenosine receptor activation.


Preparation and biological evaluation of 4-O-demethyldaunorubicin (carminomycin I) and of its 13-dihydro derivative.
A mutant strain of Streptomyces peucetius produced an anthracycline antibiotic whose structure has been established to be 4-O-demethyl-13-dihydrodaunorubicin (4), by application of spectroscopic methods and chemical degradation. A new synthesis of 4-O-demethyl-daunorubicin (carminomycin I, 2) starting from daunomycinone, together with the comparison of the antitumor activity of the anthracycline glycosides 2 and 4 are also reported.


Side-effect evaluation of a new diazepam formulation: venous sequela reduction following intravenous (i.v.) injection of a diazepam emulsion in rabbits.
Diazepam has been incorporated into a stable, submicronized injectable emulsion. Venous sequela induction in rabbits following iv administration of diazepam in a marketed hydroalcoholic solution and in the emulsion were determined and compared over a 5-day period. There was a marked difference in the local reactions induced by the iv administration of the marketed diazepam hydroalcoholic solution and the diazepam emulsion, even on the first postinjection day. This difference was confirmed by pathological analysis. The highest mean venous sequela score was reached by the rabbit group injected with the marketed diazepam solution. It should be noted that no statistical difference was observed between the saline and the diazepam emulsion rabbit groups during the 5 days of the observation period. The moderate increase in the venous sequela score values compared to that for the saline solution should be attributed to the intrinsic effect produced by diazepam itself, and not to the emulsion vehicle, which was shown not to induce any vascular reaction in the present study.


A method of human diaphorase locus 3 phenotyping in human semen by isoelectric focusing.
A rapid method for the separation of diaphorase (DIA 3) isozymes in the pH range 6-8 is presented. Isoelectric focusing (IEF) of DIA 3 on 0.2 mm thick polyacrylamide gels took 60 min at 5 degrees C. Separated bands are sharp and common phenotypes are readily distinguishable. The method combines high resolution, speed, reproducibility and reagent economy with simplicity.


Facile preparation of N-tert-butyl amides under heat-, metal- and acid-free conditions by using tert-butyl nitrite (TBN) as a practical carbon source.
tert-Butyl nitrite (TBN) is a nontoxic substance that has frequently been used as a source of nitrogen, oxygen, or nitric oxide (NO), but not as a carbon source in chemical transformations. Here, for the first time to the best of our knowledge, we introduced TBN as a source of carbon (tert-butyl group) for the synthesis of highly valuable N-tert-butyl amides from nitriles and water under very mild conditions.


Assignment of the gene for dipeptidase 2 to Mus musculus chromosome 18 by somatic cell hybridization.
Evidence is presented for the assignment of the gene for dipeptidase 2 to Mus musculus chromosome 18 by synteny testing and karyotypic analysis of Chinese hamster x mouse somatic cell hybrid clones. DIP-2 and chromosome 18 were expressed concordantly in 24/24 clones examined (ten primary clones and 14 secondary clones). Synteny testing indicated that DIP-2 was not expressed concordantly with the expression of any marker enzymes.


Associations of outdoor activity and screen time with adiposity: findings from rural Chinese adolescents with relatively low adiposity risks.
Whether and to what extent outdoor activity and screen time are relevant to adiposity among rural adolescents remain largely unknown as most of relevant evidence was generated from high-income countries and urban areas. This study aimed to investigate associations of outdoor activity and screen time with adiposity among early adolescents living in rural southwest China. In this cross-sectional study, seventh graders (n = 2264) were recruited from 10 middle schools of a rural county. Overweight and obesity was assessed using adolescents' body mass index and waist circumference. Adolescents' outdoor activity and screen time were measured using self-reported daily time spending on outdoor activity, watching TV, playing video games, and computers on weekdays and weekends, respectively. The prevalence of overweight/obesity and high waist circumferences were 8.0 and 4.9% and were higher among those from one-child families and with parents having high school or higher education and whose fathers were not farmers. Adolescents who did not have ≥1 h outdoor activity on weekdays were more likely to be overweight/obese (OR: 1.86, 95% CI: 1.30, 2.66) and have high waist circumferences (OR: 2.22, 95%CI: 1.39, 3.57). Adolescents who had > 2 h screen time on weekends were more likely to have high waist circumferences (OR: 2.08, 95% CI: 1.14, 3.80). Lack of outdoor activity and excessive screen time also showed synergistic effects on overweight/obesity (OR: 1.93. 95% CI: 1.15, 3.24) and high waist circumferences (OR: 3.02, 95% CI: 1.54, 5.94). Lack of outdoor activity and excessive screen time were relevant to adiposity among rural Chinese adolescents even when the obesity prevalence was low. Efforts to promote active lifestyles may help prevent rural adolescents from losing their advantage in the era of the global obesity epidemic.


Furosemide-sensitive K+ (Rb+) transport in human erythrocytes: modes of operation, dependence on extracellular and intracellular Na+, kinetics, pH dependency and the effect of cell volume and N-ethylmaleimide.
The effect of extracellular and intracellular Na+ (Nao+, Nai+) on ouabain-resistant, furosemide-sensitive (FS) Rb+ transport was studied in human erythrocytes under varying experimental conditions. The results obtained are consistent with the view that a (1 Na+ + 1 K+ + 2 Cl-) cotransport system operates in two different modes: mode i) promoting bidirectional 1:1 (Na+-K+) cotransport, and mode ii) a Nao+-independent 1:1 ki+ exchange requiring Nai+ which, however, is not extruded. The activities of the two modes of operation vary strictly in parallel to each other among erythrocytes of different donors and in cell fractions of individual donors separated according to density. Rb+ uptake through Rbo+/Ki+ exchange contributes about 25% to total Rb+ uptake in 145 mM NaCl media containing 5 mM RbCl at normal Nai+ (pH 7.4). Na+-K+ cotransport into the cells occurs largely additive to K+/K+ exchange. Inward Na+-Rb+ cotransport exhibits a substrate inhibition at high Rbo+. With increasing pH, the maximum rate of cotransport is accelerated at the expense of K+/K+ exchange (apparent pK close to pH 7.4). The apparent KmRbo+ of Na+-K+ cotransport is low (2 mM) and almost independent of pH, and high for K+/K+ exchange (10 to 15 mM), the affinity increasing with pH. The two modes are discussed in terms of a partial reaction scheme of (1 Na+ + 1 K+ + 2 Cl-) cotransport with ordered binding and debinding, exhibiting a glide symmetry (first on outside = first off inside) as proposed by McManus for duck erythrocytes (McManus, T.J., 1987, Fed. Proc., in press). N-ethylmaleimide (NEM) chemically induces a Cl--dependent K+ transport pathway that is independent of both Nao+ and Nai+. This pathway differs in many properties from the basal, Nao+-independent K+/K+ exchange active in untreated human erythrocytes at normal cell volume. Cell swelling accelerates a Nao+-independent FS K+ transport pathway which most probably is not identical to basal K+/K+ exchange. Ko+ less than Nao+ less than Lio+ less than Mgo2+ reduce furosemide-resistant Rb+ inward leakage relative to cholineo+.


Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A2 activity with varespladib.
Protobothrops mucrosquamatus, also known as the brown spotted pit viper or Taiwanese habu, is a medically significant venomous snake in Taiwan, especially in the northern area. To more fully understand the proteome profile of P. mucrosquamatus, we characterized its venom composition using a bottom-up proteomic approach. Whole venom components were fractionated by RP-HPLC and then analyzed by SDS-PAGE. Each protein band in gels was excised and subjected to protein identification by LC-MS/MS. A subsequent proteomic analysis revealed the presence of 61 distinct proteins belonging to 19 families in P. mucrosquamatus venom. Snake venom metalloproteinase (SVMP; 29.4%), C-type lectin (CLEC; 21.1%), snake venom serine protease (SVSP; 17.6%) and phospholipase A2 (PLA2; 15.9%) were the most abundant protein families, whereas several low-abundance proteins, categorized into eight protein families, were demonstrated in P. mucrosquamatus venom for the first time. Because PLA2 is known to make a major contribution to venom lethality, we evaluated whether the known PLA2 inhibitor, varespladib, was capable of preventing the toxic effects of P. mucrosquamatus venom. This small-molecule drug demonstrated the ability to inhibit PLA2 activity in vitro (IC50 = 101.3 nM). It also blunted lethality in vivo, prolonging survival following venom injection in a mouse model, but it showed limited potency against venom-induced local hemorrhage in this model. Our findings provide essential biological and pathophysiological insights into the composition of P. mucrosquamatus venom and suggest PLA2 inhibition as an adjunctive or alternative therapeutic strategy in the clinical management of P. mucrosquamatus envenoming in emergency medicine. SIGNIFICANCE: P. mucrosquamatus envenomation is a significant medical concern in Taiwan, especially in the northern region. Although antivenom is commonly used for rescuing P. mucrosquamatus envenoming, severe clinical events still occur, with more than 20% of cases requiring surgical intervention. Small-molecule therapy offers several advantages as a potential adjunctive, or even alternative, to antivenom treatment, such as heat stability, low antigenicity and ease of administration, among others. A deeper understanding of the venom proteome of P. mucrosquamatus would aid in the discovery of small-molecule drugs that could be repurposed to target specific venom proteins. Here, we applied a bottom-up proteomic approach to characterize the protein profile of P. mucrosquamatus venom. Varespladib, a small-molecule drug used to treat inflammatory disease, was repurposed to inhibit the toxicity of P. mucrosquamatus venom, and was shown to reduce the lethal effects of P. mucrosquamatus envenomation in a rodent model. Varespladib might be used as a first-aid therapeutic against P. mucrosquamatus envenoming in the pre-referral period and/or as an adjunctive agent administered together with anti-P. mucrosquamatus antivenom.


Functionally defined therapeutic targets in diffuse intrinsic pontine glioma.
Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi-histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.


Easy fabrication of aligned PLLA nanofibers-based 2D scaffolds suitable for cell contact guidance studies.
An easy, low-cost and fast wet processing-based method named ASB-SANS (Auxiliary Solvent-Based Sublimation-Aided NanoStructuring) has been used to fabricate poly(l-lactic acid) (PLLA) highly ordered and hierarchically organized 2D fibrillar patterns, with fiber widths between 40 and 500 nm and lengths exceeding tens of microns. A clear contact guidance effect of these nanofibrillar scaffolds with respect to HeLa and NIH-3T3 cells growth has been observed, on top of an overall good viability. For NIH-3T3 pronounced elongation of the cells was observed, as well as a remarkable ability of the patterns to guide the extension of pseudopodia. Moreover, SEM imaging revealed filopodia stemming from both sides of the pseudopodia and aligned with the secondary PLLA nanofibrous structures created by the ASB-SANS procedure. These results validate ASB-SANS as a technique capable to provide biocompatible 2D nanofibrillar patterns suitable for studying phenomena of contact guidance (and, more in general, the behavior of cells onto nanofibrous scaffolds), at very low costs and in an extremely easy way, accessible to virtually any laboratory.


Atypical American visceral leishmaniasis caused by disseminated Leishmania amazonensis infection presenting with hepatitis and adenopathy.
Leishmania amazonensis is widely recognised as a cause of cutaneous leishmaniasis in Latin America, but it can also disseminate to produce atypical visceral leishmaniasis with hepatitis and lymphadenopathy. The patient, an 8-year-old Brazilian boy, presented with a febrile illness and hepatosplenomegaly, elevated liver enzymes and generalised adenopathy. Serological tests using antigens of L. chagasi, the typical cause of visceral leishmaniasis in Latin America, were inconclusive. Leishmania amazonensis was eventually isolated in a culture of a lymph node. The patient recovered fully after treatment with meglumine antimoniate. As this case illustrates, L. amazonensis produces a spectrum of disease that includes atypical American visceral leishmaniasis with evidence of hepatocellular injury and generalised lymphadenopathy.


Preparation and cupric ion release behavior of Cu/LDPE porous composites with tunable pore morphology for intrauterine devices.
Copper/low-density polyethylene (Cu/LDPE) porous composites are novel materials for copper-containing intrauterine devices (Cu-IUDs). Here we report a method, i.e., by changing the mass ratio of two kinds of porogens that have different melting points through the combined techniques of injection molding and particulate leaching, to prepare the Cu/LDPE porous composites with tunable pore morphology. After these Cu/LDPE porous composites with different pore morphologies were obtained, the influences of pore morphologies on their cupric ion release behaviors were studied. The results show that the pore morphology has great influence on the cupric ion release behavior of Cu/LDPE porous composites. This phenomenon is caused by the different influences of different pore morphologies on the effective porosity and the surface hydrophilicity. And those results can be applied to guide the fabrication of Cu/LDPE porous composite Cu-IUDs with minimal weight at an appropriate cupric ion release rate.


Neuroimaging of isolated and non-isolated third nerve palsies.
A variety of aetiologies may cause third nerve palsy (TNP), and some manifestations may herald neurological emergencies. This article describes and illustrates various diseases that lead to TNP.


Predictors for adherent behavior in the COVID-19 pandemic: A cross-sectional telephone survey.
During the COVID-19 pandemic, protective measures have been prescribed to prevent or slow down the spread of the SARS-CoV-2 virus and protect the population. Individuals follow these measures to varying degrees. We aimed to identify factors influencing the extent to which protective measures are adhered to. A cross-sectional survey (telephone interviews) was undertaken between April and June 2021 to identify factors influencing the degree to which individuals adhere to protective measures. A representative sample of 1,003 people (age >16 years) in two Austrian states (Carinthia, Vorarlberg) was interviewed. The questionnaire was based on the Health Belief Model, but also included potential response-modifying factors. Predictors for adherent behavior were identified using multiple regression analysis. All predictors were standardized so that regression coefficients (β) could be compared. Overall median adherence was 0.75 (IQR: 0.5-1.0). Based on a regression model, the following variables were identified as significant in raising adherence: higher age (β = 0.43, 95%CI: 0.33-0.54), social standards of acceptable behavior (β = 0.33, 95%CI: 0.27-0.40), subjective/individual assessment of an increased personal health risk (β = 0.12, 95%CI: 0.05-0.18), self-efficacy (β = 0.06, 95%CI: 0.02-0.10), female gender (β = 0.05, 95%CI: 0.01-0.08), and low corona fatigue (behavioral fatigue: β = -0.11, 95%CI: -0.18 to -0.03). The model showed that such aspects as personal trust in institutions, perceived difficulties in adopting health-promoting measures, and individual assessments of the risk of infection, had no significant influence. This study reveals that several factors significantly influence adherence to measures aimed at controlling the COVID-19 pandemic. To enhance adherence, the government, media, and other relevant stakeholders should take the findings into consideration when formulating policy. By developing social standards and promoting self-efficacy, individuals can influence the behavior of others and contribute toward coping with the pandemic.


Correction to: Deconstructing the Dogma: Systematic Literature Review and Meta-analysis of Adjunctive Gentamicin and Rifampin in Staphylococcal Prosthetic Valve Endocarditis.
[This corrects the article DOI: 10.1093/ofid/ofac583.].


Bacterial flora in relation to cataract extraction. II. Peroperative flora.
The peroperative flora of 499 patients undergoing cataract extraction was studied with local bacterial cultures taken at the beginning and end of surgery and compared with the preoperative flora examined previously (Fahmy et al. 1975 b) on admission the day prior to surgery. The local application of a single dose of oxytetracycline - polymyxin B, approximately 18 hours before surgery, significantly reduced the incidence of bacteria at the time of surgery. However, 92% of the conjunctivas examined immediately before operation proved to harbour one or more kinds of microorganisms. Futhermore, 61% of the wound sites were found to be contaminated with bacteria at the conclusion of surgery. The reasons are discussed. The origin of Staphylococcus aureus isolated peroperatively from the conjunctiva and wound site was studied. The great majority of strains could be traced to the patient's own conjunctiva preoperatively. In a few cases S. aureus was traced to the patient's own nose, skin of face or to the surgeon's nose. The air of the wards and operating theatre as well as the hands and gloves of surgeons and assistant nurses apparently did not play any role as a source of S. aureus infection.


Conductive materials as fantastic toolkits to stimulate direct interspecies electron transfer in anaerobic digestion: new insights into methanogenesis contribution, characterization technology, and downstream treatment.
Direct interspecies electron transfer (DIET) stimulated by conductive materials (CMs) enables intercellular metabolic coupling that can address the unfavorable thermodynamical dilemma inherent in anaerobic digestion (AD). Although the DIET mechanism and stimulation have been extensively summarized, the methanogenesis contribution, characterization techniques, and downstream processes of CMs-led DIET in AD are surprisingly under-reviewed. Therefore, this review aimed to address these gaps. First, the contribution of CMs-led DIET to methanogenesis was re-evaluated by comparing the effect of various factors, including volatile fatty acids, free ammonia, and functional enzymes. It was revealed that AD systems are usually intricate and cannot allow the methanogenesis stimulation to be singularly attributed to the establishment of DIET. Additionally, considerable attention has been attached to the characterization of DIET occurrence, involving species identification, gene expression, electrical properties, cellular features, and syntrophic metabolism, suggesting the significance of accurate characterization methods for identifying the syntrophic metabolism interactions. Moreover, the type of CMs has a significant impact on AD downstream processes involving biogas purity, sludge dewaterability, and biosolids management. Finally, the central bottleneck consists in building a mathematical model of DIET to explain the mechanism of DIET in a deeper level from kinetics and thermodynamics.


Effect of cycloleucine on amino acid accumulation by human diploid fibroblasts.
Cycloleucine is a synthetic amino acid which produces, in vivo, biochemical abnoramlities comparable to those seen in human cystinuria-lysinuria. The effect of cycloleucine on intracellular accumulation of amino acids overlapping separate transport systems was studied using human diploid fibroblasts subcultures on glass coverslips. The data indicated that alpha-alanine, serine and proline accumulation was inhibited significantly by cycloleucine. The percentage of inhibition was approximately the same. Lysine was less affected by cycloleucine, but this amino acid accumulation proceeded at a rate slower than for neutral amino acids. In vitro, this inhibitory effect seems to be a generalized phenomenon affecting substrates. These results confirm in human fibroblasts data reported for human and rat kidney slices.


Application of near-infrared spectroscopy for frozen-thawed characterization of cuttlefish (Sepia officinalis).
Few works to date have reported the application of near-infrared spectroscopy (NIRS) for the characterization and authentication of cephalopods. This study investigated the feasibility of a portable NIRS instrument for the non-destructive freshness evaluation of fresh (F) and frozen-thawed (FT) cuttlefish (Sepia officinalis). Samples were examined by chemical, microbiological and sensorial analyses, during 13 days of conservation at 3 °C. The spectral data were collected on lateral mantle of cuttlefish, and different partial least squares discriminant analyses (PLS-DA) were applied for classification purposes. The interpretation of spectra was also investigated by applying the specific water coordinates, using aquaphotomics. Few significant differences in the wet chemistry and microbiological data were detected between F and FT during storage. The quality index method and microbiological analyses suggested similar behavior between F and FT samples until to near 9 days of shelf life. PLS-DA models with the spectral range 900-1650 nm achieved a classification precision of 0.91 between F and FT, while the performances for the prediction of storage days were less effective. The results of aquaphotomics plotted in aquagrams were suitable for the interpretation of the main physicochemical changes of cuttlefish throughout the shelf life. The water coordinates suggested a different molecular conformation of water species in the FT than F samples, with more free water molecules and a lower amount of bound species and the water solvation shell, respectively.


Road traffic injuries in Lazio, Italy: a descriptive analysis from an emergency department-based surveillance system.
Road crashes are the leading cause of death for young adults in industrialized countries. In most countries, the only data available are the police-based statistics, which report the number of deaths and injuries, without any information about severity or diagnosis. We describe the results of an emergency department (ED)--based integrated surveillance system of road-crash health consequences in the Lazio region (5.3 million inhabitants) for 2000. We identified all ED visits in the emergency database and then linked them with hospital discharges and mortality registry. Deaths that occurred at the site of the crash were identified in the mortality registry. Cases are classified according to body region affected, nature of the injury, and severity. We found 146,600 cases, for an overall incidence of 2,700 per 100,000 and a peak of 8,000 per 100,000 in 20- to 24-year-old men. There were 597 fatalities for men and 205 female fatalities, with an overall mortality of 15.9 per 100.000 and a hospitalization rate of 224 per 100,000. Our surveillance system reported a 6-times-higher incidence of road-traffic injuries, with 139 more fatalities than the national statistics of the same year. The underreporting in police reports and the absence of diagnostic information reveal the need for health-based surveillance systems of road-traffic injuries.


Changes to gait speed and the walk ratio with rhythmic auditory cuing.
Step length and cadence (i.e., step frequency or steps/minute) maintain an invariant proportion across a range of walking speeds, known as the walk ratio (WR = step length/cadence). While step length is a difficult parameter to manipulate, cadence is readily modifiable using rhythmic auditory cuing (RAC; e.g., synchronizing step timing to a metronome or music tempo). The purpose of this study was to determine the effects of RAC-guided cadences on enacted cadence, step length, WR, and gait speed during overground walking. Sixteen healthy young adults repeatedly crossed a GAITRite electronic walkway while attempting to synchronize step timing to RAC-guided (metronome) tempos of 80 to 140 beats per minute. Mean absolute percent error (MAPE) was used to compare RAC tempos to enacted cadence. Repeated-measures analyses of variance were performed to test for the effects of RAC on cadence, step length, WR, and gait speed. Moreover, simple linear regressions were used to determine the precise stepwise relationship between RAC conditions and each variable. Participants successfully matched their cadence to RAC beats (MAPE < 1.1%). Cadence increased proportionally to RAC (linear regression slope = 1.02), while step length also increased but at a slower rate (slope = 0.40). These dissimilar slopes resulted in a modified WR that systematically decreased with increasing cadence, although ultimately gait speed increased with increasing cadence (slope = 1.41). This relationship indicates that every 10 steps/minute incremental increase in cadence corresponded with a 14 cm/s increase in gait speed. Gait speed appears to increase in a predictable manner when cadence is guided by RAC during overground walking irrespective of apparent changes to the WR.


Predictive value of PWI for blood supply and T1-spin echo MRI for consistency of pituitary adenoma.
It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal-Wallis rank test (K-W test). A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma.


Three-point Method to Guide the Tibial Resection and Component Placing in Total Knee Arthroplasty.
To introduce a three-point method combining the midpoint of the posterior cruciate ligament (PCL), the midsulcus of the tibial spines, and the midpoint of the anterior cruciate ligament (ACL) to determine appropriate tibial resection and component placing during TKA and to compare this method with Insall's 1/3 method. A consecutive series of 128 knees that underwent TKA from January 2015 to August 2018 were analyzed. In one group (64 knees), the medial 1/3 of tibial tubercle (the Insall's traditional method) was used for tibial component alignment. In the other group (64 knees), the three-point line connecting the midpoint of the PCL, the midpoint of the tibial spines, and the midpoint of the ACL was used for tibial component alignment. Both groups used the anterior tibial tendon as the distal reference for tibial resection. The coronal alignment error of the tibial component was determined by the angle between the line parallel to the tibial component platform and the tibial mechanical axis measured on postoperative radiograph. The axial rotation error of the femoral or tibial component was the intersection angle between the transepicondylar axis (TEA) and a line tangent to the posterior edge of the femoral or tibial component measured on CT. The coronal and axial alignment errors were compared between the two groups. The average coronal alignment error of the tibial component in the three-point method group was 0.2° ± 1.4° versus - 0.9° ± 1.8°in the Insall's 1/3 method group (P < 0.001), and the mean absolute value in the three-point method group reduced by 37.3% compared to Insall's traditional method group. The average axial rotation error of the femoral component was 0.2° ± 1.2° in the three-point method group versus - 1.1° ± 1.7° in the Insall's 1/3 method group (P < 0.001), and the mean absolute value in three-point method group decreased by 43.9% compared to Insall's traditional method group. The average axial rotation error of the tibial component was 0.4° ± 1.4° versus - 1.4° ± 1.8° in the Insall's 1/3 method group (P < 0.001), and the mean absolute value in the three-point method group reduced by 35.5% compared to the Insall's traditional method group. The rates of rotation outliers were significantly lower in the three-point method group (P < 0.05). The line connecting the midpoint of the PCL, the midsulcus of the tibial spines, and the midpoint of the ACL could be used as the reference for the tibial resection and component placing. This method appears to be more accurate than Insall's 1/3 method. The results of this study provide a candidate method for component orientation with little error.


Removal of arsenic(v) from aqueous solutions using sulfur-doped Fe3O4 nanoparticles.
In this study, magnetic sulfur-doped Fe3O4 nanoparticles (Fe3O4:S NPs) were applied as adsorbents for the removal of As(v). Fe3O4:S NPs were fabricated by a two-step route, which included low-temperature mixing and high-temperature sintering. The as-prepared Fe3O4:S NPs could effectively remove As(v) under a wide pH range of 2-10 and presented a high As(v) adsorption capacity of 58.38 mg g-1, which was much better than undoped Fe3O4 nanoparticles (20.24 mg g-1). Adsorption experiments exhibited a pseudo-second-order model of adsorption kinetics and a Langmuir isotherm model of adsorption isotherms. Additionally, the coexisting ions such as NO3 -, SO4 2-, and CO3 2- had no significant effect on As(v) adsorption and the adsorbent worked well in actual smelting wastewater. XPS and FTIR spectra of Fe3O4:S NPs before and after As(v) adsorption showed that Fe-OH groups played a significant role in the adsorption mechanisms. Moreover, the magnetic Fe3O4:S NPs adsorbents after adsorption could be rapidly separated from wastewater with an external magnetic field. Therefore, Fe3O4:S NPs could be an ideal candidate for the removal of As(v) from water.


Central Toxic Keratopathy in Siblings After Laser-Assisted Keratomileusis: Case Report and Literature Review.
The purpose of this study was to report an isolated case of 2 siblings who developed central toxic keratopathy (CTK) after undergoing laser-assisted keratomileusis (LASIK) on the same day. This was a case report and literature review. Two sisters with no significant medical history underwent uncomplicated LASIK on the same day. Postoperative day 1 slitlamp examination findings were unremarkable. One week later, both patients returned for routine examination and were found to have a reduction in visual acuity, hyperopic shift, bilateral central opacification at the interface, and characteristic posterior stromal "mud cracks" or macrostriae most consistent with the entity CTK. The patients reported only mild ocular discomfort with minimal signs of inflammation. None of the other LASIK patients from the same surgery day nor any previous or following days thereafter developed any complications. The siblings were closely followed and treated with a short course of prophylactic topical antibiotics and rapid steroid taper, along with aggressive lubrication and long-term systemic treatment including oral doxycycline, vitamin C, and coenzyme Q10. Three months later, both patients had resolution of CTK with an uncorrected visual acuity of 20/20 or better in both eyes. CTK is a rare, noninflammatory but potentially sight-threatening entity most commonly associated with excimer laser ablation procedures. Its pathophysiology is poorly understood but likely multifactorial. Its isolated presentation in this case of 2 siblings suggests a possible underlying genetic predisposition, which has not been previously described. With careful monitoring and early supportive treatment, patients can have a complete and rapid resolution.


Hip screening in newborns in the UK: what are the latest guidelines?
The Newborn and Infant Physical Examination screening is a national screening programme which aims to identify infants with congenital abnormalities to minimise the risk of long-term complications. It involves a top to toe examination with special focus on the heart, eyes, testes and hips. The hip component of the Newborn and Infant Physical Examination screen aims to pick up infants with developmental dysplasia of the hips and refer them for appropriate treatment in a timely manner. Guidelines for the hip section of have recently changed. This article reviews these changes, the timings of the follow up and investigations, and the diagnosis and management of developmental dysplasia of the hips.


Assessment of the Effects of Age, Gender, and Exercise Training on the Cardiac Sympathetic Nervous System Using Positron Emission Tomography Imaging.
Using positron emission tomography (PET) imaging, we sought to determine whether normal age or exercise training cause changes in the cardiac sympathetic nervous system function in male or female healthy volunteers. Healthy sedentary participants underwent PET studies before and after 6 months of supervised exercise training. Presynaptic uptake by the norepinephrine transporter-1 function was measured using PET imaging of [(11)C]-meta-hydroxyephedrine, a norepinephrine analog, and expressed as a permeability-surface area product (PSnt in mL/min/mL). Postsynaptic function was measured as β-adrenergic receptor density (β'max in pmol/mL tissue) by imaging the β-receptor antagonist [(11)C]-CGP12177. Myocardial blood flow (MBF in mL/min/mL tissue) was measured by imaging [(15)O]-water. At baseline, there was no age difference in β'max or MBF but PSnt declined with age (1.12±0.11 young vs 0.87±0.06 old, p = .036). Before training, women had significantly greater MBF (0.87±0.03 vs 0.69±0.03, p < .0001) and PSnt (1.14±0.08 vs 0.75±0.07, p < .001) than men. Training increased VO2 max by 13% (p < .0001), but there were no training effects on β'max, PSnt, or MBF. Greater MBF in females and a trend to increased PSnt post-training persisted. With age, presynaptic uptake as measured by PSnt declines, but there were no differences in β'max. Endurance training significantly increased VO2 max but did not cause any changes in the measures of cardiac sympathetic nervous system function. These findings suggest that significant changes do not occur or that current PET imaging methods may be inadequate to measure small serial differences in a highly reproducible manner.


The Benefits and Challenges of Implementing Motivational Features to Boost Cognitive Training Outcome.
In the current literature, there are a number of cognitive training studies that use N-back tasks as their training vehicle; however, the interventions are often bland, and many studies suffer from considerable attrition rates. An increasingly common approach to increase participant engagement has been the implementation of motivational features in training tasks; yet, the effects of such "gamification" on learning have been inconsistent. To shed more light on those issues, here, we report the results of a training study conducted at two Universities in Southern California. A total of 115 participants completed 4 weeks (20 sessions) of N-back training in the laboratory. We varied the amount of "gamification" and the motivational features that might make the training more engaging and, potentially, more effective. Thus, 47 participants trained on a basic color/identity N-back version with no motivational features, whereas 68 participants trained on a gamified version that translated the basic mechanics of the N-back task into an engaging 3D space-themed "collection" game (Deveau et al. Frontiers in Systems Neuroscience, 8, 243, 2015). Both versions used similar adaptive algorithms to increase the difficulty level as participants became more proficient. Participants' self-reports indicated that the group who trained on the gamified version enjoyed the intervention more than the group who trained on the non-gamified version. Furthermore, the participants who trained on the gamified version exerted more effort and also improved more during training. However, despite the differential training effects, there were no significant group differences in any of the outcome measures at post-test, suggesting that the inclusion of motivational features neither substantially benefited nor hurt broader learning. Overall, our findings provide guidelines for task implementation to optimally target participants' interest and engagement to promote learning, which may lead to broader adoption and adherence of cognitive training.


Parents' emotion dysregulation and children's emotional overeating: The role of emotion regulation feeding.
Parents' use of food to regulate children's emotions (i.e., emotion regulation feeding) has been associated with children's emotional overeating. However, less is known about how parents' emotion regulation feeding acts as a moderator between parents' emotion dysregulation and children's emotional overeating. A total of 216 parents (Mage = 35.84 years, SD = 6.11) of 3- to 5-year-old children were recruited to complete an online survey. Analyses revealed that emotion regulation feeding moderated the association between parents' emotion dysregulation and children's emotional overeating, such that parents with high emotion dysregulation and high emotion regulation feeding had children who engaged in more emotional overeating compared to parents with low emotion regulation feeding. This finding suggests that less adaptive feeding aggravates the association between parents' emotion dysregulation and children's emotional overeating.


Molnupiravir: A new candidate for COVID-19 treatment.
The novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in china and has rapidly spread to many countries around the world. The effective pharmacotherapy can reduce the mortality of COVID-19. Antiviral medications are the candidate therapies for the management of COVID-19. Molnupiravir is an antiviral drug with anti-RNA polymerase activity and currently is under investigation for the treatment of patients with COVID-19. This review focuses on summarizing published literature for the mechanism of action, safety, efficacy, and clinical trials of molnupiravir in the treatment of COVID-19 patients.


The association between food diversity and serum antioxidant indices in cataract patients compared to healthy subjects.
Cataract is a chronic disorder that is related to antioxidant-oxidant imbalance situation. We aimed to investigate the association between food diversity and serum antioxidant and oxidant indices in cataract patients compared to healthy subjects. In this case-control study, ninety volunteers (aged > 50 years) were divided into the cataract (n = 45) and healthy control (n = 45) groups. Anthropometric variables, physical activity and stress levels, food diversity score, serum total oxidant capacity (TOC), and total antioxidant capacity (TAC) measurements were done for all participants. Serum TAC, even after adjustment for stress level, was significantly higher in healthy people compared to cataract patients (P < 0.001). In addition, serum TOC was significantly lower in healthy controls compared to cataract patients (P < 0.002). In healthy group, there was a weak significant positive association between serum TAC and meats group diversity (r = 0.149, P = 0.047). In addition, there was a moderate negative association between meats group diversity and TOC in the healthy controls (r = -0.712, P = 0.041). In the cataract group, there was a significant negative association between serum TOC and diversity score of fruits (r = -0.811, P = 0.017) and meats group (r = -0.926, P = 0.046) as well as total score of food diversity (r = -0.466, P = 0.003). It seems that increase in total dietary diversity and food groups' diversity can have a beneficial effect on oxidant situation among cataract patients.


Residual factor VII activity and different hemorrhagic phenotypes in CRM(+) factor VII deficiencies (Gly331Ser and Gly283Ser).
Two cross-reacting material-positive (CRM(+)) factor VII (FVII) mutations, associated with similar reductions in coagulant activity (2.5%) but with mild to asymptomatic (Gly331Ser, c184 [in chymotrypsin numbering]) or severe (Gly283Ser, c140) hemorrhagic phenotypes, were investigated. The affected glycines belong to structurally conserved regions in the c184 through c193 and c140s activation domain loops, respectively. The natural mutants 331Ser-FVII and 283Ser-FVII were expressed, and in addition 331Ala-FVII and 283Ala-FVII were expressed because 3 functional serine-proteases bear alanine at these positions. The 331Ser-FVII, present in several asymptomatic subjects, showed detectable factor Xa generation activity in patient plasma (0.7% +/- 0.2%) and in reconstituted system with the recombinant molecules (2.7% +/- 1.1%). The reduced activity of recombinant 283Ala-FVII (7.2% +/- 2.2%) indicates that the full function of FVII requires glycine at this position, and the undetectable activity of 283Ser-FVII suggests that the oxydrile group of Ser283 participates in causing severe CRM(+) deficiency. Furthermore, in a plasma system with limiting thromboplastin concentration, 283Ser-FVII inhibited wild-type FVIIa activity in a dose-dependent manner.


Coronary vasospastic action of thromboxane A2 in isolated, working guinea pig hearts.
The effects of thromboxane A2 (TXA2) on isolated, working guinea pig heart and left ventricular papillary muscle preparations were investigated. TXA2 was generated by the enzymatic conversion of prostaglandin H2 (PGH2) with indomethacin-treated horse platelet microsomes (IPM). TXA2 caused dose-dependently a considerable decrease in the coronary flow, left ventricular systolic pressure and left ventricular dp/dt in the perfused heart, while the similar effects of PGH2 were transient and weaker than those of TXA2. These effects of TXA2 disappeared after the TXA2-generating system was left standing at 37 degree C for 3 min. When IPM in the TXA2-generating system was pretreated with a TXA2 synthetase inhibitor, L-8027, the enhanced cardiac responses induced by the mixture of IPM and PGH2 disappeared. TXA2 had no direct effect on the contractile force of the papillary muscle. These results suggest that TXA2 has a specific coronary vasopastic action without a direct inotropic effect.


Response of mouse plantaris muscle to functional overload: comparison with rat and cat.
Functional overload (FO) of a muscle by removing its synergists results in a compensatory hypertrophy of the muscle. However, the extent of the response appears to be dependent, at least in part, on the activity and/or loading levels of the muscle following surgery. Thus, differences in the inherent physical activity levels across species may be an important factor to consider. In the present study, the effects of 8 weeks of FO on the isometric mechanical properties of the plantaris of mice (highly active) were determined and the findings compared with the results from previous studies performed on the plantaris of rats (highly active) and cats (less active). FO resulted in approximately a doubling of the mass, the physiological cross-sectional area and the maximum tetanic tension per unit cross-sectional area, was similar in the plantaris of control and FO mice. Isometric twitch speed properties were unaffected, but the tension enhancement in response to an increase in the rate of stimulation showed the pattern of a "faster" muscle following FO. The fatigue resistance of the plantaris in FO mice was significantly higher than in control mice. Although the degree of hypertrophy that occurred in the mouse plantaris was similar to that observed after FO in rats and in cats that are exercised intermittently at high intensities, there were differences in the mechanical properties that may be related to the adaptability of species and/or the behavioral responses to the overload.


Expression in Escherichia coli and in vitro refolding of the human protein pLG72.
Recently, genes coding for pLG72 and d-amino acid oxidase have been related to schizophrenia, a widespread psychiatric disorder that affects about 1% of population. pLG72 is a puzzling, novel protein present only in primates and proposed to be an activator of d-amino acid oxidase. Here we report on the overexpression of wild-type and His-tagged pLG72 in Escherichia coli. Both variants form inclusion bodies and have been refolded and purified to homogeneity: the acquisition of secondary and tertiary structure was demonstrated by CD spectroscopy. A figure of approximately 70 mg of pure protein per liter of fermentation broth was achieved.


Estimating visitors' willingness to pay for a conservation fund: sustainable financing approach in protected areas in Ethiopia.
An increasing number of protected areas (PAs) are being established in many countries to conserve and preserve the wildlife species and to maintain earth's ecological balance, but in emerging economies such as Ethiopia, PAs are currently confronted with inadequate conservation funding that makes it tough to protect the remaining biodiversity. PAs, therefore try to use other financial means such as ecotourism to subsidize their financial shortage and nourishes the nexus between conservation and development. Estimation of visitors' willingness to pay (WTP) would be useful to craft strategies to strengthen the self-financing capability of PAs and hence realizing environmental and livelihood goals. In this study, the visitors' WTP for the proposed conservation fund in the context of Bale Mountains National Park (BMNP) was estimated using a contingent valuation method. The finding indicated that 75% of visitors were willing to pay a conservation fee. The mean WTP was estimated to be US$7.40 for foreign visitors and US$1.00 for domestic visitors. The finding suggests that the implementation of conservation fee in addition to the existing entry fee helps to improve the long-term sustainable financing of PAs.


Chinese medicine single-walled carbon nanotube targeting compound for antitumor therapy: a feasible way?
Malignant cancer is the leading cause of death in man, exceeding cerebrovascular disease and heart disease. More than half of the total mortality due to malignant cancer is from lung, liver, intestinal and gastric cancer. Chemotherapy is one of the effective treatments for cancer. However, the great majority of Western anticancer medicines have considerable side effects. Herbal medicines offer many more advantages than synthesized compounds because they are made from purely natural compounds and have less adverse effects. However, the single administration methods used as standard in herbal medicine, and deficient drug targeting, severely limit their anticancer activity. Single-walled carbon nanotubes (SWNTs) can be used as drug carriers. They have been modified to form Chinese anticancer medicine-SWNT compounds which can specifically target tumors, thereby significantly increasing the therapeutic effectiveness of these medicines. Water-soluble SWNTs have high stability. As a drug carrier, SWNTs functional modification of the anticancer medicine may improve the targeting and killing of tumor cells. SWNTs have been attached to the Chinese antitumor medicines paclitaxel and plumbagin and have achieved excellent therapeutic effects. Furthermore, choosing the best administration methods such as internal iliac arterial infusion, intravesical infusion and embedment of a hypodermic chemotherapeutic pump, may also improve the anticancer effects of Chinese medicine.


Characterization and modeling of Bragg gratings written in polymer fiber for use as filters in the THz region.
We demonstrate fiber Bragg gratings written in polymer fiber for use in the THz window for the first time. A KrF excimer laser operating at 248 nm was used to inscribe notch-type gratings in single component Topas subwavelength fiber. A transmission loss at the centre wavelength of the grating of 60 dB is observed in short gratings containing only 192 notches. Experimental results and modeling are presented. The gratings are expected to find use in THz signal filtering and chemical or biosensing applications.


Hyperuricemia Inhibition Protects SD Rats Against Fructose-Induced Obesity Hypertension Via Modulation of Inflammation and Renin-Angiotensin System in Adipose Tissue.
The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms. A rat model with obesity hypertension was induced by a high-fructose diet. In the experiment I, the rats were fed with fructose for 8 wks along with allopurinol or benzbromarone at the beginning. In the experiment II, the rats were fed with fructose for 8 wks firstly. And then, these rats were treated with allopurinol or benzbromarone for additional 6 wks. Fructose-fed rats showed hyperuricemia, abdominal obesity hypertension and an activation in adipose renin-angiotensin system (RAS). Also, fructose-fed rats had higher levels of proinflammatory cytokines and more macrophages infiltrating in adipose tissue. In the experiment I, allopurinol and benzbromarone significantly reduced serum uric acid at 8 wk. Adipose RAS overactivation, adipose inflammatory responses and the development of obesity hypertension were all effectively prevented by hyperuricemia inhibition. In the experiment II, 6-wk treatment with allopurinol and benzbromarone significantly decreased serum uric acid, downregulated adipose RAS, abolished adipose inflammation and improved obesity hypertension. In conclusion, urate-lowering therapy protects rats against fructose-induced obesity hypertension. The mechanisms appear to be via downregulated adipose RAS and reduced inflammation in adipose tissue.


The UV fading of hydrocarbon fluorescence and its prevention for observations in single living cells.
Excitation intensities used for standard microspectrofluorometric observations of natural cell fluorescence, i.e. NAD(P)H, lead to fading of hydrocarbon (polycyclic aromatic, heterocyclic) fluorescence in EL2 cells incubated with such compounds. The disappearance of hydrocarbon fluorescence under excitation at 366 nm seems to be an exponential function of time. The fading prevents studies on hydrocarbon metabolization in correlation with intracellular microelectrophoretic injection of substrate, e.g. glucose-6-P. A return to 8-10 times less intense excitation conditions used in an earlier prototype microspectrofluorometer, has allowed the observation of sequential changes in the difference spectra (after glucose-6-P minus before) of hydrocarbon-treated cells (e.g. benzo(a)pyrene, dibenzocarbazols). The possible relative contributions of NAD(P)H and hydrocarbon metabolites (or alterations) to such sequential spectra are still under consideration, but the main obstacle to their observation, fading, is removed by less intense excitation.


Skin Reactions to Immune Checkpoint Inhibitors.
Due to the novelty of immune checkpoint inhibitors, their cutaneous adverse events (AEs) have only been recently characterized. This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat cutaneous AEs. Pruritus and rash are among the top five immune-related AEs reported in clinical trials for this class of therapy. Incidence varies between 35 and 60% for cutaneous AEs among the seven FDA-approved drugs used as monotherapy or combination therapy. Although only 2% are reported as grade 3 or 4 events with monotherapy, the incidence can be as high as 6-9% for combination therapy and the impact on quality of life can be significant for these patients. Of ipilimumab patients, 43.5% have a cutaneous AE, and, at our institution, 20% of them had a dose interruption as a result. This means potentially 9% of patients have dose interruption of ipilimumab because of their cutaneous AEs. In the following chapter, we review the categories of these drugs, common cutaneous effects, their grading, and management options.


The effect of colorectal cancer screening on health status in a survey study.
Colorectal cancer (CRC) screening has been found to reduce mortality from CRC but it may have adverse effects on other aspects of health. Our aim was to evaluate the effect of CRC screening on overall health status among men and women within a randomized health-services study in Finland. A random sample of 10,648 men and women born in 1951 received a questionnaire on health and lifestyle. They were randomized for CRC screening or controls (1:1) in 2011 (N = 10,271). The current study population consisted of those who responded to the questionnaire both before and after screening (n = 4895). Self-rated health (SRH), perceived healthiness of diet and perceived physical fitness were used to determine health status, and assessed with logistic and ordered logistic models using calendar time (2010, 2012), screening randomization and demographic characteristics as covariates. SRH, healthiness of diet and physical fitness improved over time (OR 1.32, CI 1.17-1.48, OR 1.23, CI 1.08-1.41 and OR 1.44, CI 1.28-1.60, respectively). Compared to non-invited controls, CRC screening invitation had no effect on these measures (OR 0.91, CI 0.74-1.12, OR 0.95, CI 0.75-1.20, and OR 1.09, CI 0.87-1.37, respectively). Women reported better health status than men. However, among those who attended screening, women reported weaker, and men better health status than the respective controls. CRC screening did not have any effect on health status measured using self-rated health, healthiness of diet, and physical fitness. Thus, screening for colorectal cancer can be recommended as a health policy.


Ammonia as an indicator of exercise stress implications of recent findings to sports medicine.
The role of ammonia in exercise-induced fatigue is reviewed. Implications for integrated activity of developing hyperammoneic states, caused by various precipitating conditions such as exercise, liver dysfunction, hypoxia, hyperoxia, and chemical poisoning are described. The central role of ammonia in diverse important metabolic pathways indicates its ubiquitous role in a spectrum of activity ranging from elite exhaustive performance of sportsmen and -women to life-threatening organ dysfunction. The action of ammonia and metabolites from associated pathways in producing seemingly dangerous short term conditions, but inducing possible long term protection against degenerative processes associated with ageing (free radical-induced cellular damage) indicate the paradoxical position of ammonia and its associated metabolic pathways for health and disease processes.


The Brain Health Platform: Combining Resilience, Vulnerability, and Performance to Assess Brain Health and Risk of Alzheimer's Disease and Related Disorders.
It is difficult to assess brain health status and risk of cognitive impairment, particularly at the initial evaluation. To address this, we developed the Brain Health Platform to quantify brain health and identify Alzheimer's disease and related disorders (ADRD) risk factors by combining a measure of brain health: the Resilience Index (RI), a measure of risk of ADRD; the Vulnerability Index (VI); and the Number-Symbol Coding Task (NSCT), a measure of brain performance. The Brain Health Platform is intended to be easily and quickly administered, providing an overview of a patient's risk of developing future impairment based on modifiable and non-modifiable factors as well as current cognitive performance. This cross-sectional study comprehensively evaluated 230 participants (71 controls, 71 mild cognitive impairment, 88 ADRD). VI and RI scores were derived from physical assessments, lifestyle questionnaires, demographics, medical history, and neuropsychological examination including the NSCT. Individuals with abnormal scores were 95.7% likely to be impaired, with a misclassification rate of 9.7%. The combined model had excellent discrimination (AUC:0.923±0.053; p < 0.001), performing better than the Montreal Cognitive Assessment. The Brain Health Platform combines measures of resilience, vulnerability, and performance to provide a cross-sectional snapshot of overall brain health. The Brain Health Platform can effectively and accurately identify even the very mildest impairments due to ADRD, leveraging brief yet powerful and actionable indices of brain health and risk that could be used to develop personalized, precision medicine-like interventions.


Evaluation of the Gen-Probe PACE 2 assay for the detection of asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in male arrestees.
The LET and Gen-Probe PACE 2 assay are used to screen male arrestees for evidence of infection with chlamydia and gonorrhea in the intake/booking area of the Jefferson Parish Correctional Center. To determine the accuracy of the Gen-Probe PACE 2 assay for the detection of asymptomatic infection with Chlamydia trachomatis and Neisseria gonorrhoeae infections in male arrestees. From December 1993 to March 1994, 196 arrestees younger than 22 years were screened with the Gen-Probe PACE 2 assay and McCoy shell vial culture for Chlamydia trachomatis. From April to October 1994, 444 arrestees of all ages were screened with the Gen-Probe PACE 2 assay and standard culture for Neisseria gonorrhoeae. The sensitivity, specificity, and predictive values of the Gen-Probe PACE 2 assay, compared with culture, were calculated with 95% confidence intervals. The Gen-Probe PACE 2 assay compared with culture had a sensitivity, specificity, and positive predictive value for Chlamydia trachomatis of 84%, 99%, and 93% and for Neisseria gonorrhoeae of 54%, 99.5%, and 78%. The Gen-Probe PACE 2 assay is useful for screening young males in this jail setting and is more accurate for detecting Chlamydia trachomatis compared with Neisseria gonorrhoeae.


Downstream or upstream administration of P2Y12 receptor blockers in non-ST elevated acute coronary syndromes: study protocol for a randomized controlled trial.
The optimal timing to administer a P2Y12 inhibitor in patients presenting with a non-ST elevation acute coronary syndrome remains a topic of debate. Pretreatment with ticagrelor before coronary anatomy is known as a widely adopted strategy. However, there is poor evidence on how this compares with administration of a P2Y12 inhibitor after defining coronary anatomy (i.e., downstream administration). Moreover, there are limited head-to-head comparisons of the two P2Y12 inhibitors-ticagrelor and prasugrel-currently recommended by the guidelines. DUBIUS is a phase 4, multicenter, parallel-group, double randomized study conducted in NSTE-ACS patients designed to compare a pretreatment strategy (including only ticagrelor) versus a downstream strategy (including prasugrel or ticagrelor) and to compare downstream prasugrel with downstream ticagrelor. A total of 2520 patients will be randomly assigned to pretreatment with ticagrelor or to no pretreatment. The PCI group of the downstream arm will be further randomized to receive prasugrel or ticagrelor. The two primary hypotheses are that the downstream strategy is superior to the upstream strategy and that downstream ticagrelor is non-inferior to downstream prasugrel, both measured by the incidence of a composite efficacy and safety endpoint of death from vascular causes, non-fatal MI, or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4, and 5 bleedings. The DUBIUS study will provide important evidence related to the benefits and risks of pretreatment with ticagrelor compared with a strategy of no pretreatment. Moreover, the clinical impact of using downstream ticagrelor compared with downstream prasugrel will be assessed. ClinicalTrials.gov NCT02618837 . Registered on 1 December 2015.


Dietary modification as adjunct treatment in Ménière's disease: patient willingness and ability to comply.
To evaluate ease of use and compliance with dietary modification in the treatment of vertigo in patients with Ménière's disease. Mailed patient retrospective questionnaire and chart review. Tertiary referral neurotologic private practice. 136 patients with Ménière's who returned a mailed questionnaire. Mean age at first clinic visit was 53 years, and at questionnaire was 62 years, with 54.4% female subjects. Median initial hearing was AAO-HNS Stage 1. Most patients also received diuretics and/or other treatments. Reduced sodium and caffeine-free diet. Ratings of diet difficulty, length of use, compliance level and nutritional understanding, and AAO-HNS vertigo class and functional rating before and with nutritional intervention. 46.3% of the respondents received written diet guidelines; only 3.2% were referred for nutritional counseling, and another 7.8% sought counseling independently. 77.8% and 84.7% rated a low sodium and a caffeine-free diet, respectively, as manageable or easy to follow; 77.9% followed the diet for 1 year or greater, but only 10.3% could list 5 "correct" foods to eat and 26% 5 foods to avoid. Those who followed the diet greater than 6 months had larger improvement in number of spells and functional rating and a higher rate of Class A/B vertigo outcome (p ≤ 0.01, p = 0.012, and p = 0.038, respectively). Knowledge of foods to eat and avoid correlated with vertigo class (rho = -0.21, p ≤ 0.029 and rho = -0.26, p ≤ 0.01, respectively); the more foods correctly listed, the better the AAO-HNS class). Nutrition education by referral to a registered dietitian may improve outcomes in the medical treatment of Ménière's disease.


The MHC influences acute graft versus host disease in MHC matched adults undergoing allogeneic bone marrow transplantation.
To determine whether the MHC plays an antigen non-specific role in the development of acute GVHD, the prevalence of acute GVHD in relation to MHC genotype was examined in 51 adult patients undergoing allogeneic BM grafting. The majority of patients received grafts from HLA-identical siblings. HLA-B7 haplotypes were associated with a decreased risk of acute GVHD (2 of 15, p = 0.005) whereas HLA-B44 haplotypes were associated with a higher risk of acute GVHD (11 of 14, p = 0.02). As these alleles have been reported previously as having opposite effects in relation to inflammatory mediators, these findings may have important implications with respect to donor selection and patient management.


Thallium-201 for cardiac stress tests: residual radioactivity worries patients and security.
A 47-year-old man presented to the Emergency Department (ED) in duress and stated he was "highly radioactive." There were no reports of nuclear disasters, spills, or mishaps in the local area. This report discusses the potential for thallium-201 (Tl-201) patients to activate passive radiation alarms days to weeks after nuclear stress tests, even while shielded inside industrial vehicles away from sensors. Characteristics of Tl-201, as used for medical imaging, are described. This patient was twice detained by Homeland Security Agents and searched after he activated radiation detectors at a seaport security checkpoint. Security agents deemed him not to be a threat, but they expressed concern regarding his health and level of personal radioactivity. The patient was subsequently barred from his job and sent to the hospital. Tl-201 is a widely used radioisotope for medical imaging. The radioactive half-life of Tl-201 is 73.1h, however, reported periods of extended personal radiation have been seen as far out as 61 days post-administration. This case describes an anxious, but otherwise asymptomatic patient presenting to the ED with detection of low-level personal radiation. Documentation should be provided to and carried by individuals receiving radionuclides for a minimum of five to six half-lives of the longest-lasting isotope provided. Patients receiving Tl-201 should understand the potential for security issues; reducing probable tense moments, confusion, and anxiety to themselves, their employers, security officials, and ED staff.


Prostacyclin improves glucose utilization in patients with sepsis.
In patients with sepsis, impaired glucose metabolism and altered microcirculatory blood flow are common findings. Prostacyclin (PGI2) improves tissue oxygenation, indicated by enhanced oxygen delivery (DO2) and oxygen uptake (VO2). The purpose of this study was to explore whether these effects are associated with improved glucose utilization. In 7 patients with sepsis, glucose metabolism was analyzed using dideuterated and 13C-labeled glucose and isotope dilution mass spectrometry. All patients received total parenteral nutrition with glucose covering 60% to 70% of the predicted energy expenditure and needed continuous intravenous insulin (40 microU.kg-1.min-1) to keep blood glucose concentrations below 10 mmol.l-1.VO2 and carbon dioxide production (VCO2) were continuously measured directly from the respiratory gases via indirect calorimetry. After equilibration of the infused labeled glucose with body glucose pool, baseline variables of glucose metabolism were assessed: glucose oxidation rate was determined from the enrichment of 13CO2 in the expired gas during primed constant infusion of [U-13C]glucose, glucose turnover rate (Ra) from the plasma enrichment of simultaneously infused [6,6-2H2]glucose. Endogenous glucose production rate was calculated as the difference between Ra and glucose infusion rate. Then, we examined the effect of PGI2 infusion (5 to 12.5 ng.kg-1.min-1) on glucose metabolism and gaseous exchange. The PGI2-induced increase in DO2 (from 15.8 to 17.7 ml.kg-1.min-1; P < .05) resulted in an increase in directly measured VO2 from 5.0 to 5.3 ml.kg-1.min-1 (P < .01) whereas VCO2 remained unchanged. Although glucose turnover and production rates remained constant, glucose oxidation rate increased significantly from 1.21 to 1.38 mg.kg-1.min-1 (P < .02). Improving tissue perfusion and oxygenation with PGI2 may also modify the impaired glucose metabolism by increasing glucose oxidation rate in patients with sepsis, suggesting enhanced adenosine triphosphate production.


Genotype-specific effects of ericoid mycorrhizae on floral traits and reproduction in Vaccinium corymbosum.
Most plants interact with mycorrhizal fungi and animal pollinators simultaneously. Yet, whether mycorrhizae affect traits important to pollination remains poorly understood and may depend on the match between host and fungal genotypes. Here, we examined how ericoid mycorrhizal fungi affected flowering phenology, floral traits, and reproductive success, among eight genotypes of highbush blueberry, Vaccinium corymbosum (Ericaceae). We asked three overarching questions: (1) Do genotypes differ in response to inoculation? (2) How does inoculation affect floral and flowering traits? (3) Are inoculated plants more attractive to pollinators and less pollen limited than non-inoculated plants of the same genotype? To examine these questions, we experimentally inoculated plants with ericoid mycorrhizal fungi, grew the plants in the field, and measured flowering and floral traits over 2 years. In year 2, we conducted a hand-pollination experiment to test whether plants differed in pollen limitation. Inoculated plants had significantly higher levels of colonization for some genotypes, and there were significant floral trait changes in inoculated plants for some genotypes as well. On average, inoculated plants produced significantly larger floral displays, more fruits per inflorescence, and heavier fruits with lower sugar content, than non-inoculated, control plants. Hand pollination enhanced the production of fruits, and fruit mass, for non-inoculated plants but not for those that were inoculated. Our results demonstrate that inoculation with ericoid mycorrhizal fungi enhanced flowering and altered investment in reproduction in genotype-specific ways. These findings underscore the importance of examining belowground symbionts and genotype-specific responses in their hosts to fully understand the drivers of aboveground interactions.


Creating a priority list of non-communicable diseases to support health research funding decision-making.
To develop and pilot a framework based on multi-criteria decision analysis (MCDA) to prioritize non-communicable diseases (NCDs) to support health research funding decision-making. The framework involves identifying NCDs to be prioritized, specifying prioritization criteria and determining their weights from a survey of stakeholders. The mean weights from the survey are applied to the NCDs' ratings on the criteria to generate a 'total score' for each NCD, by which the NCDs are prioritized. Nineteen NCDs and five criteria were included. The criteria, in decreasing order of importance (mean weights in parentheses), are: deaths across the population (27.7 %), loss of quality-of-life across the population (23.0 %), cost to patients and families (18.6 %), cost to the health system (17.2 %), and whether vulnerable groups are disproportionately affected (13.4 %). The priority list of NCDs, stratified into four tiers of importance, is: 'Very critical' priority: coronary heart disease, back and neck pain, diabetes mellitus; 'Critical' priority: dementia and Alzheimer's disease, stroke; 'High' priority: colon and rectum cancer, depressive disorders, chronic obstructive pulmonary disease, chronic kidney disease, breast cancer, prostate cancer, arthritis, lung cancer; and 'Medium' priority: asthma, hearing loss, melanoma skin cancer, addictive disorders, non-melanoma skin cancer, headaches. The results indicate the framework for prioritizing NCDs for research funding is feasible and effective. The framework could also be used for other health conditions.


Effect of different teaching/learning approaches using virtual patients on student's situational interest and cognitive load: a comparative study.
Virtual Patients (VPs) have been receiving considerable attention in medical education as an authentic learning and teaching approach. The study aimed to evaluate the effect of using different approaches of conduction of virtual patients (VPs) on students' cognitive load and situational interest. The study is an experimental study. Two different cohorts have participated during the academic year 2019/2020 and 2020/2021. The first cohort (Group 1) was exposed to a lecture followed by an independent VPs session, and the second cohort (Group 2) was exposed to a collaborative VPs session. The situational interest and Cognitive load were compared between the two groups. All sessions are about one topic related to maxillofacial trauma. Findings showed that there was no significant difference between the median score of the situational interest at repeated time points during the Collaborative VPs (Group 2). However, in group 1, there was a significant difference between the median score of situational interest at repeated time points during independent VPs where the lowest score was found to be at the end of the session. Also, results showed that the collaborative VPs (Group 2) showed a high median score of situational interest than both lecture and independent VPs (Group 1). Furthermore, the study showed that there is no significant difference in the intrinsic cognitive load among the three sessions. However, the extraneous cognitive load was low in collaborative VPs (Group 2) than in both lecture and independent VPs sessions (Group 1). The use of VPs in a collaborative interactive learning activity is more effective than its use as an independent learning activity in enhancing students' situational interest and reducing cognitive load. However, giving independent VPs after the lecture with the same topic is considered a limitation of the study as this can affect the situational interest of the students by filling their gab of knowledge.


Coherent control in the extreme ultraviolet and attosecond regime by synchrotron radiation.
Quantum manipulation of populations and pathways in matter by light pulses, so-called coherent control, is currently one of the hottest research areas in optical physics and photochemistry. The forefront of coherent control research is moving rapidly into the regime of extreme ultraviolet wavelength and attosecond temporal resolution. This advance has been enabled by the development of high harmonic generation light sources driven by intense femtosecond laser pulses and by the advent of seeded free electron laser sources. Synchrotron radiation, which is usually illustrated as being of poor temporal coherence, hitherto has not been considered as a tool for coherent control. Here we show an approach based on synchrotron radiation to study coherent control in the extreme ultraviolet and attosecond regime. We demonstrate this capability by achieving wave-packet interferometry on Rydberg wave packets generated in helium atoms.


Chitinase family genes in grape differentially expressed in a manner specific to fruit species in response to Botrytis cinerea.
Chitinases (Chi), an important resistance-related protein, act against fungal pathogens by catalyzing the fungal cell wall, whereas are involved in different biological pathways in grape. In this study, we found 42 Chi family genes in Vitis vinifera L. (VvChis) and evaluated their expression levels after Botrytis infection, stress hormones like ethylene (ETH) and methyl-jasmonate (MeJA), and abiotic stresses like salinity and temperature changes in ripened fruits. VvChis were categorized into five groups including A, B, C, D, and E belonged to glycoside hydrolase family 18 and 19 (GH18 and GH19) according to genes structure, which expression analysis showed distinct temporal and spatial expression patterns changed in different tissues and various development stages. Different responsive elements to biotic and abiotic stresses were determined in the promoter regions of VvChis, specially elicitor-responsive element that was conserved among all VvChis genes. The expression levels of VvChis in groups A, B, and E increased after Botrytis cinerea infection in leaves and berries. Meanwhile, VvChis in glycoside hydrolase family 18 (GH18) were up-regulated under MeJA and ETH treatment, although the induction of VvChis by low temperature was more significant than high temperature. The expression of VvChis was also positively correlated with the concentration of NaCl treatment. Furthermore, differential gene-overexpression of VvChi5, VvChi17, VvChi22, VvChi26, and VvChi31 in strawberry and tomato fruits demonstrated the involvement of various isoforms in resistance to Botrytis infection through antioxidant system and lignin accumulation, which led to a reduction of damage. Among different isoforms of VvChis, we confirmed the interaction of Chi17 with Metallothionein (MTL) as oxidative stress protection, which suggests VvChis can modulate oxidative stress during postharvest storage in ripened fruits.


Shiwei Qingwen decoction regulates TLR4/NF-κB signaling pathway and NLRP3 inflammasome to reduce inflammatory response in lipopolysaccharide-induced acute lung injury.
Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear. To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia. First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model. HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1β, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1β) in vivo and vitro. The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.