Effect of advance care planning video on do-not-hospitalize orders for nursing home residents with advanced illness.
The purpose of the study is to evaluate the effect of an Advance Care Planning (ACP) Video Program on documented Do-Not-Hospitalize (DNH) orders among nursing home (NH) residents with advanced illness. Secondary analysis on a subset of NHs enrolled in a cluster-randomized controlled trial (41 NHs in treatment arm implemented the ACP Video Program: 69 NHs in control arm employed usual ACP practices). Participants included long (> 100 days) and short (≤ 100 days) stay residents with advanced illness (advanced dementia or cardiopulmonary disease (chronic obstructive pulmonary disease or congestive heart failure)) in NHs from March 1, 2016 to May 31, 2018 without a documented Do-Not-Hospitalize (DNH) order at baseline. Logistic regression with covariate adjustments was used to estimate the impact of the resident being in a treatment versus control NH on: the proportion of residents with new DNH orders during follow-up; and the proportion of residents with any hospitalization during follow-up. Clustering at the facility-level was addressed using hierarchical models. The cohort included 6,117 residents with advanced illness (mean age (SD) = 82.8 (8.4) years, 65% female). Among long-stay residents (n = 3,902), 9.3% (SE, 2.2; 95% CI 5.0-13.6) and 4.2% (SE, 1.1; 95% CI 2.1-6.3) acquired a new DNH order in the treatment and control arms, respectively (average marginal effect, (AME) 5.0; SE, 2.4; 95% CI, 0.3-9.8). Among short-stay residents with advanced illness (n = 2,215), 8.0% (SE, 1.6; 95% CI 4.6-11.3) and 3.5% (SE 1.0; 95% CI 1.5-5.5) acquired a new DNH order in the treatment and control arms, respectively (AME 4.4; SE, 2.0; 95% CI, 0.5-8.3). Proportion of residents with any hospitalizations did not differ between arms in either cohort. Compared to usual care, an ACP Video Program intervention increased documented DNH orders among NH residents with advanced disease but did not significantly reduce hospitalizations. ClinicalTrials.gov Identifier: NCT02612688 .


Outcomes and Predictors of Severe Hyperoxemia in Patients Receiving Mechanical Ventilation: A Single-Center Cohort Study.
Rationale: Supplemental oxygen is among the most commonly administered therapies in intensive care units (ICUs). High supplemental oxygen exposure has been associated with harm in observational human studies and animal models, yet no consensus exists regarding which dose and duration of high oxygen constitutes harmful hyperoxemia, and little is known regarding the clinical factors that predict potentially injurious exposure. Objectives: To determine the dose and duration of the arterial partial pressure of oxygen (PaO2) associated with mortality among mechanically ventilated patients and to identify the clinical factors that predict this exposure. Methods: We performed a retrospective cohort study of patients who received invasive mechanical ventilation at a single academic institution in 2017 and 2018. We used a generalized additive model to visualize the relationship between the measured PaO2 via arterial blood gas measurements and 30-day mortality. We used multivariable logistic regression to identify patient- and hospital-level factors that predict exposure to harmful hyperoxemia. Results: We analyzed 2,133 patients with 33,310 arterial blood gas measurements obtained during mechanical ventilation. We identified a U-shaped relationship between PaO2 and mortality, in which PaO2 was positively correlated with mortality above a threshold of 200 mm Hg. A total of 1,184 patients (55.5%) had at least one PaO2 measurement above this threshold. If patients spent an entire day exposed to PaO2 > 200 mm Hg, they had 2.19 (95% confidence interval [CI], 1.33-3.60; P = 0.002) greater odds of 30-day mortality in an adjusted analysis. Any exposure to severe hyperoxemia (PaO2 > 200 mm Hg) was associated with mortality (odds ratio, 1.29; 95% CI, 1.04-1.59; P = 0.021). The strongest clinical predictor of severe hyperoxemia exposure was the identity of the ICU in which mechanical ventilation was delivered. Conclusions: Exposure to high arterial oxygen concentrations is common among mechanically ventilated patients, and the dose and duration of PaO2 ⩾ 200 mm Hg is associated with mortality. Severe hyperoxemia is highly variable across ICUs and is far more common in clinical practice than in recent randomized trials of oxygen-targeting strategies. Efforts to minimize this common and injurious exposure are needed.


The protein phosphatase inhibitor, okadaic acid, potentiates the stimulatory effect of phorbol ester on phosphatidylcholine synthesis, but not on phospholipid hydrolysis, in fibroblasts.
The potent protein phosphatase inhibitor, okadaic acid, was used to determine the possible role of protein phosphorylation reaction(s) in phorbol ester-induced synthesis and hydrolysis of phosphatidylcholine (PtdCho) in NIH 3T3 fibroblasts. Okadaic acid (2 microM) was found to enhance the stimulatory effects of lower concentrations (2.5-25 nM) of phorbol 12-myristate 13-acetate (PMA) on PtdCho synthesis, but not on PtdCho hydrolysis, after treatments for 30-60 min. These data support a view that in fibroblasts PMA stimulates only PtdCho synthesis, and not PtdCho hydrolysis, by a protein phosphorylation-dependent mechanism.


Pharmacological mechanism and clinical study of Qiming granules in treating diabetic retinopathy based on network pharmacology and literature review.
Diabetic retinopathy (DR) is a general complication of diabetes, which has become a serious threat to human health worldwide. However, the best treatment is still under development. Qiming (QM) granules are mainly composed of Astragalus membranaceus, Pueraria lobata, Rehmannia Glutinosa, Lycium barbarum, Cassiae Semen, Fructus Leonuri, Pollen Typhae, and Leech, which are beneficial to qi, nourish liver and kidney, and clear collaterals and eyes. The treatment of DR is a comprehensive application based on the above traditional Chinese medicine. In recent years, satisfactory results have been achieved for DR. Through the traditional application analysis, network pharmacology analysis and clinical research summary of QM granules, to review the effectiveness and advantages of QM granules in the treatment of DR comprehensively. Analysis of main active components of QM granules by network pharmacology and prediction of mechanism of action of QM granules on DR. Further, PubMed, Web of Science, and China National Knowledge Infrastructure were used to search literature, using the keywords of "Qiming granules", "diabetic retinopathy", "clinical research" and their combinations, mainly from 1999 to 2022. Traditional pharmacological analysis, Network pharmacological analysis, animal experiments, and clinical studies have confirmed that QM granules plays a role in the treatment of DR through multiple components, multiple targets, and multiple channels. This systematic review for the first time provides meaningful information for the further study of the pharmacodynamic material basis and pharmacological mechanism of QM granules, and also provides a basis for further study of quality markers and quality control of QM granules.


Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study (CWS).
Up to now, cardiotoxicity of epirubicin has been studied almost exclusively in adult cancer patients. The aim of this study was to investigate epirubicin in children and adolescents, in comparison with doxorubicin. About 172 soft tissue sarcoma patients (mean age at diagnosis: 8.3 years), treated with epirubicin (median cumulative dose: 450 mg/m2) or doxorubicin (median cumulative dose: 240 mg/m2) within the high-risk group of the CWS-96 study, were examined in a prospective multicentre study. Heart function was analysed by echocardiography, measuring left-ventricular fractional shortening (FS). The median follow up was 27.7 months. Incidence of clinically manifest cardiomyopathy was 0% (0/60; 95% CI: 0-6.0%) in patients treated with epirubicin, and 0.9% (1/108; 95% CI: 0-5.1%) in patients treated with doxorubicin. A further three patients showed subclinical cardiomyopathy. There was no difference in FS between the two treatment arms. Cardiotoxicity was low in our study. For the short term, cardiotoxicity seems to be only a minor problem in patients treated with epirubicin as applied in this cohort.


Distribution and pharmacology of alpha 6-containing nicotinic acetylcholine receptors analyzed with mutant mice.
The alpha6 subunit of the nicotinic acetylcholine receptor (nAChR) is expressed at very high levels in dopaminergic (DA) neurons. However, because of the lack of pharmacological tools selective for alpha6-containing nAChRs, the role of this subunit in the etiology of nicotine addiction remains unknown. To provide new tools to investigate this issue, we generated an alpha6 nAChR knock-out mouse. Homozygous null mutants (alpha6-/-) did not exhibit any gross neurological or behavioral deficits. A careful anatomic and molecular examination of alpha6-/- mouse brains demonstrated the absence of developmental alterations in these animals, especially in the visual and dopaminergic pathways, where the alpha6 subunit is normally expressed at the highest levels. On the other hand, receptor autoradiography revealed a decrease in [3H]nicotine, [3H]epibatidine, and [3H]cytisine high-affinity binding in the terminal fields of retinal ganglion cells of alpha6-/- animals, whereas high-affinity [125I]alpha-conotoxinMII (alphaCtxMII) binding completely disappeared in the brain. Moreover, inhibition of [3H]epibatidine binding on striatal membranes, using unlabeled alphaCtxMII or cytisine, revealed the absence of alphaCtxMII-sensitive and cytisine-resistant [3H]epibatidine binding sites in alpha6-/- mice, although the total amount of binding was unchanged. Because alphaCtxMII, a toxin formerly thought to be specific for alpha3beta2-containing nAChRs, is known to partially inhibit nicotine-induced dopamine release, these results support the conclusion that alpha6 rather than alpha3 is the partner of beta2 in the nicotinic modulation of DA neurons. They further show that alpha6-/- mice might be useful tools to understand the mechanisms of nicotine addiction, although some developmental compensation might occur in these mice.


Wide Complex Tachycardias.
Wide complex tachycardias (WCT) are frequently encountered in the emergency department. Causes of WCT vary from benign (eg, supraventricular with rate-related aberrancy) to life threatening (eg, atrial fibrillation with WPW, or ventricular tachycardia). It is imperative that emergency physicians are familiar with the clinical presentation, underlying causes, and electrocardiographic features of the different causes of WCT. Treatment of WCT depends on patient stability, regularity of the rhythm, and QRS morphology. When in doubt, monomorphic WCT should be presumed to be ventricular tachycardia and treated as such.


Visual attentional bias for food in adolescents with binge-eating disorder.
Evidence suggests that adults with binge-eating disorder (BED) are prone of having their attention interfered by food cues, and that food-related attentional biases are associated with calorie intake and eating disorder psychopathology. For adolescents with BED experimental evidence on attentional processing of food cues is lacking. Using eye-tracking and a visual search task, the present study examined visual orienting and disengagement processes of food in youth with BED. Eye-movement data and reaction times were recorded in 25 adolescents (12-20 years) with BED and 25 controls (CG) individually matched for sex, age, body mass index, and socio-economic status. During a free exploration paradigm, the BED group showed a greater gaze duration bias for food images than the CG. Groups did not differ in gaze direction biases. In a visual search task, the BED group showed a greater detection bias for food targets than the CG. Group differences were more pronounced for personally attractive than unattractive food images. Regarding clinical associations, only in the BED group the gaze duration bias for food was associated with increased hunger and lower body mass index, and the detection bias for food targets was associated with greater reward sensitivity. The study provided first evidence of an attentional bias to food in adolescents with BED. However, more research is needed for further specifying disengagement and orienting processes in adolescent BED, including overt and covert attention, and their prospective associations with binge-eating behaviors and associated psychopathology.


Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples.
We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the 'linker' molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC-gamma1 and PLC-gamma2). Antibodies to SLP-76 and PLC-gamma1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC-gamma2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC-gamma2 was detected in arterial endothelium). SLP-76 and PLC-gamma1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC-gamma1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples.


Mercury bioaccumulation along food webs in temperate aquatic ecosystems colonized by aquatic macrophytes in south western France.
Mercury (Hg) is considered as an important pollutant for aquatic systems as its organic form, methylmercury (MeHg), is easily bioaccumulated and bioamplified along food webs. In various ecosystems, aquatic periphyton associated with macrophyte was identified as an important place for Hg storage and methylation by microorganisms. Our study concerns temperate aquatic ecosystems (South Western France) colonized by invasive macrophytes and characterized by high mercury methylation potentials. This work establishes original data concerning Hg bioaccumulation in organisms (plants, crustaceans, molluscs and fish) from five contrasting ecosystems. For low trophic level species, total Hg (THg) concentrations were low (from 27±2ngTHgg(-1)dw in asiatic clam Corbicula fluminea to 418±114ngTHgg(-1)dw in crayfish Procambarus clarkii). THg concentrations in some carnivorous fish (high trophic level) were close to or exceeded the International Marketing Level (IML) with values ranging from 1049±220ngTHgg(-1)dw in pike perch muscle (Sander lucioperca) to 3910±1307ngTHgg(-1)dw in eel muscle (Anguilla Anguilla). Trophic levels for the individuals were also evaluated through stable isotope analysis, and linked to Hg concentrations of organisms. A significant Hg biomagnification (r(2)= 0.9) was observed in the Aureilhan lake, despite the absence of top predator fish. For this site, Ludwigia sp. periphyton, as an entry point of Hg into food webs, is a serious hypothesis which remains to be confirmed. This study provides a first investigation of Hg transfer in the ecosystems of south western France and allows the assessment of the risk associated with the presence of Hg in aquatic food webs.


The effect of 2'deoxyguanosine on human lymphocyte responses. I. 2'deoxyguanosine enhances T lymphocyte responses.
Low concentrations (40 microM) of the purine nucleoside metabolite 2'deoxyguanosine (2'dGuo), were shown to enhance both phytohaemagglutinin- and concanavalin A-induced T cell transformation. Evidence is presented which indicates that this enhancement may be due to the inhibition of suppressor T cell function resulting in the promotion of T cell growth factor production. T cell responses were only inhibited at concentrations of 2'dGuo which were toxic to the lymphocytes.


Experimental in vivo generation of intertypic recombinant strains of HSV in the mouse.
The primary replication of one strain of HSV was generally unaffected by the simultaneous inoculation of another strain either at the same site or at a different site within the same dermatome. Exceptions to this were the result of the generation of intertypic recombinants which were readily isolated only from sensory ganglia 5 and 6 days after inoculation with a mixture of HSV-1 and HSV-2 and from explant culture of the resultant latently infected ganglia. By restriction enzyme analysis the majority of the recombinant strains from primary infection were characterized as HSV 1; all those from latently infected ganglia were characterized as type 2.


A New Concept for Carotid Artery Stenting: Coating the Atherosclerotic Plaque by Covered Stent before Bare Stent Implantation.
In carotid artery stenting (CAS) procedures, distal embolism, periprocedural stent thrombosis, and 30-day stroke due to the plaque fragmentation and protrusion caused by stent implantation and balloon dilation are frequent complications. In this technical case report, a case is presented of extracranial carotid artery stenosis treated with a covered stent and subsequent implantation of a bare stent. In addition, the possibility is discussed that this new technique prevents the distal microembolic complications, periprocedural stent thrombosis, and 30-day stroke of extracranial CAS.


Developing an optimal sampling design to monitor the vehicle fuel consumption gap.
Monitoring the fuel consumption gap between official and real-world measurements is of great interest to policy makers and researchers. This study explores how sampling methods (simple random, stratified and quota sampling) can be used to supplement and validate the monitoring. Three user datasets were utilised to simulate the fuel consumption gap of the 11.6-15.5 million vehicles registered annually in the European Union (2018-2020). Results suggest that a simple random sample of 16,240 vehicles is sufficient to estimate accurately the fleets' average fuel consumption gap. Stratified sampling can reduce the sample size to less than 4,500 vehicles. To estimate accurately the fuel consumption gap of each manufacturer, the sample size increases to approximately 17,200 vehicles. The increase in sales of plug-in hybrid vehicles in 2020 led to an increase of the average fuel consumption gap by 8% and its standard deviation (variability) by 20%. This higher variability resulted in a more than double sample size, compared to previous years. It was also found that the introduction of the Worldwide Harmonized Light vehicles Test Procedure (WLTP) reduced the average gap by 20-24%. This study highlights the viability of a sampling scheme to estimate the fuel consumption gap by monitoring less than 0.05% of the fleet. Moreover the study draws attention to the need for further analysis and understanding of the real-world use and fuel consumption of plug-in hybrid vehicles.


Characterization of Spodoptera litura multicapsid nucleopolyhedrovirus 38.7 k protein, which contains a conserved BRO domain.
Homology analysis revealed that Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) 38.7 k protein has 22-83% amino acid identities with Ecotropis obliqua NPV, Mamestra configurata MNPV, Helicoverpa armigera SNPV, H. zea SNPV, S. exigua MNPV and S. littoralis MNPV 38.7 k proteins. Analysis of the relationship of these 38.7 k proteins indicated that they contain a conserved BRO-N domain, and SpltMNPV and SpliMNPV 38.7 k proteins also contain a motif found in all known viral and prokaryotic single-strand DNA binding proteins. RT-PCR results showed that SpltMNPV 38.7 k gene is transcribed actively at the late stage of infection and the mRNA start site was mapped within a consensus baculovirus late promoter motif (ATAAG). Western blot analysis revealed that the 38.7 k was expressed in infected S. litura cells as a 41 kDa form and this protein distributed in the nucleus of infected cells. Using a histone extraction protocol, SpltMNPV 38.7 k could be detected in the histone H1 fraction. Micrococcal nuclease treatment released SpltMNPV 38.7 k protein from the chromatin fraction, suggesting that its involvement in nucleosome structures. Furthermore, column chromatography using DNA-cellulose showed that SpltMNPV 38.7 k protein interacted with nucleic acids. It was proposed that SpltMNPV 38.7 k might function as a DNA-binding protein.


Phosphatidylinositol liposomes increase calcium uptake and tissue plasminogen activator secretion by fetal human lung fibroblasts.
PtdIns liposomes, at a concentration of 40 microM, induced in FLF the synthesis of t-PA-Ag, and enhanced 45Ca2+ uptake. The induction of t-PA-Ag biosynthesis by PtdIns liposomes in FLF was inhibited by 5-15 microM verapamil, an inhibitor of Ca2+ uptake via the so-called "slow channels" by 0.5-10 microM TFP, an inhibitor of Ca2+ transport ATPase, and by 10-90 microM TMB-8, an inhibitor of intracellular Ca2+ mobilization. t-PA-Ag secretion was inhibited by decreasing the Ca2+ concentration less than 1.2 mM. On the other hand, addition of 0.08 microM of calcium ionophore A23187 increased t-PA-Ag biosynthesis after 72 hr of incubation by 247% (P less than 0.01). These data support previous results and indicate that the synthesis of t-PA in FLF is Ca2+ dependent. Thus, it is suggested that PtdIns liposomes increase t-PA biosynthesis by affecting calcium metabolism.


B cell-rich niches support stem-like CD8+ T cells in cancer microenvironment.
Cytotoxic T cells are indispensable for the body's fight against most cancers. In the current issue of Cancer Cell, Gaglia et al. reveal how changes in the tumor tissue architecture creating niches of T cell-B cell interactions may support anti-tumor T cell responses.


Relevance of Coding Variation in FLG And DOCK8 in Finnish Pediatric Patients with Early-Onset Moderate-To-Severe Atopic Dermatitis.
Early-onset, persistent atopic dermatitis (AD) is proposed as a distinct subgroup that may have specific genotypic features. FLG gene loss-of-function variants are the best known genetic factors contributing to epidermal barrier impairment and eczema severity. In a cohort of 140 Finnish children with early-onset moderate-to-severe AD, we investigated the effect of coding variation in FLG and 13 other genes with epidermal barrier or immune function through the use of targeted amplicon sequencing and genotyping. A FLG loss-of-function variant (Arg501Ter, Ser761fs, Arg2447Ter, or Ser3247Ter) was identified in 20 of 140 patients showing higher transepidermal water loss values than patients without these variants. Total FLG loss-of-function variant frequency (7.14%) was significantly higher than in the general Finnish population (2.34%). When tested separately, only Arg2447Ter showed a significant association with AD (P = 0.003104). In addition, a modest association with moderate-to-severe pediatric AD was seen for rs12730241 and rs6587667 (FLG2:Gly137Glu). Loss-of-function variants, previously reported pathogenic variants, or statistically significant enrichment of nonsynonymous coding region variants were not found in the 13 candidate genes studied by amplicon sequencing. However, higher IgE and eosinophil counts were found in carriers of potentially pathogenic DOCK8 missense variants, suggesting that the role of DOCK8 variation in AD should be further investigated in larger cohorts.


Clinical presentations of newly diagnosed HIV-infected patients at a university hospital in Bangkok, Thailand.
Epidemiology and clinical features of newly diagnosed HIV-infected patients vary and depend on period of time and geographical area. A retrospective review was conducted in adults with positive HIV antibody testing between January and December 2006 at a university hospital setting. Prevalence of HIV infection was 1.0%. There were 221 patients with a median age of 35.5 (range, 15.8-72.3) years, and 57% were males. The most common risk of HIV acquisition was heterosexual (63.8%). The most common reason for HIV testing was preoperative screening (41.2%). Of all, 52.9%, 37.1%, and 10% were diagnosed as AIDS, asymptomatic, and symptomatic patients, respectively. Median CD4 count at HIV diagnosis was 260 (range, 6-1284) cells/mm(3). AIDS-defining illnesses were found in 35.7%. Overall mortality rate was 1.8%. More than half of newly diagnosed HIV-infected patients have advanced HIV disease and are unaware of their HIV status. These results reflect inadequate education of HIV risks and voluntary HIV testing in Thailand.


Liquid chromatographic determination of hydralazine in human plasma with 2-hydroxy-1-naphthaldehyde pre-column derivatization.
A selective and sensitive high-performance liquid chromatographic method is described for determination of hydralazine and its metabolites in human plasma. The method involves pre-column derivatization with 2-hydroxy-1-naphthaldehyde at pH 1.2. The reaction product and Methyl Red used as internal standard are extracted into dichloromethane and chromatographed in the reversed-phase mode on an ODS-2 column using acetonitrile-aqueous triethylamine phosphate buffer (80:20, v/v) at pH 3 as eluent. The plasma calibration curve of hydralazine is linear in the concentration range 10-500 ng ml-1. The detection limit is 1 ng ml-1 and the relative standard deviation is less than 2.4. In vivo pharmacokinetics of hydralazine in two volunteers after oral administration of 50 mg of the drug is studied using the proposed LC method.


MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells.
The drug-resistance of pancreatic cancer cells results in poor therapeutic effect. To predict the therapeutic effect of the chemotherapy drugs to specific patients and to reverse the resistance of pancreatic cancer cells are critical for chemotherapy of pancreatic cancer. MicroRNAs (miRNAs) have been reported to play important roles in the genesis of drug-resistance of various cancer types. There are also many advantages of miRNAs in diagnosis and therapy of disease. Although several miRNAs regulating 5-Fluorouracil (5-FU) resistance in human pancreatic cancer have been reported, the detailed molecular mechanism remains to be determined. In this study, we found that miR-320a was significantly up-regulated in 5-FU resistant pancreatic cancer cells. Over-expression of miR-320a strongly contributed to pathogenesis of pancreatic cancer, which was represented by the increased proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition. Furthermore, we demonstrated that miR-320a was able to bind to 3'UTR of PDCD4 mRNA, and mediated its down-regulation in 5-FU resistance of human pancreatic cancer cells. Whereas restoration of PDCD4 expression could partially attenuate the function of miR-320a in pancreatic cancer. Taken together, our study demonstrated that miR-320a played important role in regulating 5-FU resistance by targeting PDCD4 and might be developed as new therapeutic target for pancreatic cancer.


Simultaneous determination of aliphatic and aromatic amines in water and sediment samples by ion-pair extraction and gas chromatography-mass spectrometry.
A gas chromatography-mass spectrometry (GC-MS) method has been proposed for the determination of aliphatic and aromatic amines in a variety of environmental samples including wastewater, river water, sea water and sediment samples. The method includes ion-pair extraction with bis-2-ethylhexylphosphate (BEHPA), derivatisation of compounds with isobutyl chloroformate (IBCF) and their GC-MS analysis. Aliphatic and aromatic amines were isolated from aqueous samples using BEHPA as ion-pair reagent and derivatised with IBCF for their chromatographic analysis. Solid-liquid extraction of aliphatic and aromatic amines in sediment samples were performed in Soxhlet apparatus with acidic MeOH and ion-pair extraction with BEHPA were carried out for the isolation of amines followed by derivatisation with IBCF. Aliphatic and aromatic amines were then analysed with GC-MS in both electron impact (EI) and positive and negative ion chemical ionisation (PNICI) mode as their isobutyloxycarbonyl (isoBOC) derivatives. The obtained recoveries ranged from 81.0 to 98.0% and the precision of this method, as indicated by the relative standard deviations (RSDs) was within the range of 0.5 and 4.3%. The detection limits obtained from calculations by using GC-MS results based on S/N = 3 were within the range from 0.07 to 0.50 ng/l.


Biomarkers of aggression in dementia.
Dementia is a clinical syndrome defined by progressive global impairment of acquired cognitive abilities. It can be caused by a number of underlying conditions. The most common types of dementia are Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular cognitive impairment (VCI) and dementia with Lewy bodies (DLB). Despite the fact that cognitive impairment is central to the dementia, noncognitive symptoms, most commonly described nowadays as neuropsychiatric symptoms (NPS) exist almost always at certain point of the illness. Aggression as one of the NPS represents danger both for patients and caregivers and the rate of aggression correlates with the loss of independence, cognitive decline and poor outcome. Therefore, biomarkers of aggression in dementia patients would be of a great importance. Studies have shown that different genetic factors, including monoamine signaling and processing, can be associated with various NPS including aggression. There have been significant and multiple neurotransmitter changes identified in the brains of patients with dementia and some of these changes have been involved in the etiology of NPS. Aggression specific changes have also been observed in neuropathological studies. The current consensus is that the best approach for development of such biomarkers may be incorporation of genetics (polymorphisms), neurobiology (neurotransmitters and neuropathology) and neuroimaging techniques.


Affordability of medicines and patients' cost-reducing behaviour: empirical evidence based on SUR estimates from Italy and the UK.
Studies have demonstrated that co-payments on medication reduce the consumption of both non-essential and essential drugs, and that the latter can lead to worse health outcomes. Far less is known about how patients cope with the cost of medication, particularly if affordability is an issue, and how this compares across two countries with different prescription charge policies. Therefore, the aim of this article is to explore empirically how, and to what extent, costs incurred by patients influence their decision-making behaviour in accessing medicines. Based on the findings from focus groups, a questionnaire was designed that addressed medication cost issues relevant to patients in both the UK and Italy. Using an econometric model, several hypotheses are tested regarding patients' decision-making behaviour and how it is influenced by health status, sociodemographic characteristics and the novel concept of a self-rated affordability measure. Quite a large percentage of patients (70.3% in the UK and 66.5% in Italy) stated they have to think about the cost of medicines at least sometimes. Respondents adopted numerous cost-reducing strategies, subdivided into (i) those initiated by patients and (ii) those involving self-medication. Their use was strongly influenced by income and drug affordability problems, but the self-rated affordability measure was a stronger predictor. Commonly used strategies were not to get prescribed drugs dispensed at all, prioritizing by not getting all prescribed items dispensed or delaying until the respondent got paid. Furthermore, respondents with affordability issues were also cost-conscious when self-medicating with over-the-counter (OTC) products for minor conditions such as dyspepsia. Despite patients in both countries using cost-reducing strategies, their use was more pronounced in the UK, where the prescription charge was significantly higher than in Italy. The results from this study provide detail on the kinds of strategies patients use to reduce the cost burden of prescription charges, and support previous research showing they may be foregoing essential medication. Because the same questionnaire was applied in two European countries, where the national health systems aim to provide healthcare services that are accessible to all citizens in need, it offers interesting insights for policy makers in other countries, where patients may have to pay a larger share of their drugs out-of-pocket, such as the US.


Large increase in a Dutch woman's lifetime risk of developing breast cancer.
A large increase in the incidence of breast cancer has been observed in many countries over the last two decades. On the other hand, however, breast cancer mortality has decreased. The prominent burden of breast cancer in the female population induces a lot of discussion about incidence and mortality rates, whereas lifetime risks are less mentioned. This study provides information on the changes in risks for Dutch women with regards to being diagnosed with breast cancer (both invasive and in situ) or dying from this disease during the screening era. We used the life table method to calculate lifetime risks for the period 1989-2003. The lifetime risk for developing breast cancer increased from 1 in 10 in 1989 to 1 in 7 in 2003; the risk of dying from breast cancer decreased respectively from 1 in 22 to 1 in 26. The increasing incidence is alarming but has to be seen in perspective; the decreasing mortality is promising and shows that, at most, one third of the breast cancer cases are fatal.


Associations of Serum Adipokines With Subclinical Interstitial Lung Disease Among Community-Dwelling Adults: The Multi-Ethnic Study of Atherosclerosis (MESA).
Adipokines have inflammatory and fibrotic properties that may be critical in interstitial lung disease (ILD). We examined associations of serum adipokine levels with CT imaging-based measures of subclinical ILD and lung function among community-dwelling adults. A subset of the original Multi-Ethnic Study of Atherosclerosis cohort (n = 1,968) had adiponectin, leptin, and resistin measured during follow-up visits (2002-2005). We used regression models to examine associations of adiponectin, leptin, and resistin levels with (1) high-attenuation areas (HAAs) from CT scans (2004-2005, n = 1,144), (2) interstitial lung abnormalities (ILAs) from CT scans (2010-2012, n = 872), and (3) FVC from spirometry (2004-2006, n = 1,446). We used -(1/HAA2), which we denoted with H, to model HAA as our outcome to meet model assumptions. Higher adiponectin was associated with lower HAA on CT imaging among adults with a BMI ≥ 25 kg/m2 (P for BMI interaction = .07). Leptin was more strongly associated with ILA among never smokers compared with ever smokers (P for smoking interaction = .004). For every 1-SD increment of log-transformed leptin, the percent predicted FVC was 3.8% lower (95% CI, -5.0 to -2.5). Higher serum resistin levels were associated with greater HAA on CT in a fully adjusted model. For every 1-SD increment of log-transformed resistin there was an increase in H of 14.8 (95% CI, 3.4-26.3). Higher adiponectin levels were associated with lower HAA on CT imaging among adults with a higher BMI. Higher leptin and resistin levels were associated with lower FVC and greater HAA, respectively.


Chinese Herbal Medicine Adjusting Brain Microenvironment via Mediating Central Nervous System Lymphatic Drainage in Alzheimer's Disease.
Due to its complex pathogenesis and lack of effective therapeutic methods, Alzheimer's disease (AD) has become a severe public health problem worldwide. Recent studies have discovered the function of central nervous system lymphatic drainage, which provides a new strategy for the treatment of AD. Chinese herbal medicine (CHM) has been considered as a cure for AD for hundreds of years in China, and its effect on scavenging β-amyloid protein in the brain of AD patients has been confirmed. In this review, the mechanism of central nervous system lymphatic drainage and the regulatory functions of CHM on correlation factors were briefly summarized. The advances in our understanding regarding the treatment of AD via regulating the central lymphatic system with CHM will promote the clinical application of CHM in AD patients and the discovery of new therapeutic drugs.


Neonatal necrotizing enterocolitis adversely affects neural conduction of the rostral brainstem in preterm babies.
Necrotizing enterocolitis (NEC) is a devastating neonatal disease, often leading to long term neurodevelopmental impairment. The effect of NEC on the immature brain remains not fully understood. We test the hypothesis that NEC adversely affects functional integrity, particularly neural conduction, of the preterm brainstem. Thirty-two preterm NEC babies (30-36weeks gestation) were recruited at term age. Maximum length sequence brainstem auditory evoked response was recorded and analysed with click rates 91-910/s at term age. The results were compared with normal term babies and age-matched healthy preterm babies. Wave V latency, I-V and III-V intervals, and III-V/I-III interval ratio differed significantly among the three groups of babies at all click rates 91-910/s. Compared with normal term babies, preterm NEC babies showed significant increase in all these MLS BAER variables at all rates, with no apparent abnormalities in wave I and III latencies and I-III interval. All these abnormalities were more significant at higher than at lower click rates. No notable abnormalities were seen in wave amplitudes. Compared with age-matched healthy preterm babies, NEC babies showed similar abnormalities, although the abnormalities were relatively less significant. MLS BAER components that mainly reflect neural conduction in the more central regions of the auditory brainstem were abnormal in preterm NEC babies, although those components that mainly reflect peripheral function were generally normal. Neonatal NEC adversely affects myelination of the more rostral or central regions of the immature brainstem, resulting in delayed or impaired neural conduction, but spares the more peripheral regions.


The unusual hypertensive patient.
Many young patients with systemic hypertension have secondary causes which if identified early could lessen the cardiovascular complications associated with long standing hypertension. Coarctation of the aorta is one of those rare causes. We describe a 40 year old male with hypertension, coarctation of the aorta, bicuspid aortic valve, PDA and an adrenal mass.


Turbulent flow of red cells in dilute suspensions. Effect on kinetics of O2 uptake.
The turbulent flow properties of dilute (0.06% by volume) suspensions of human red blood cells in 4-mm-bore glass tubing were estimated by laser anemometry. The flow properties of the dilute red cell suspension were similar to those of a dilute suspension of polystyrene spheres (0.5 micron diameter) in isotonic NaCl solution. Flow was found to be laminar when the Reynolds number was below 2,000, transitional in the range of Reynolds numbers from 2,000 to 3,000, and fully turbulent above Reynolds number 3,000. These results differ from previous studies of more concentrated red cell suspensions. The length scales of the turbulence were also estimated: at a Reynolds number near 4,000 the macroscale is about 1.25 mm, the Taylor microscale is about 0.85 mm, and the Kolmogoroff scale is near 0.075 mm. The results are discussed in relation to previous measurements of the rate of oxygen uptake by dilute red cell suspensions in the flow-type rapid reaction apparatus. Our results suggest that under the conditions of most of these oxygen uptake measurements, the turbulent flow is characterized by eddies about 1 mm across, mixing with each other on a time scale of about 45 ms. Since most of the reported oxygen uptake measurements involve a similar time scale, it is possible that an effective "unstirred layer" influenced the reported rate of oxygen uptake.


Development of Serum Marker Models to Increase Diagnostic Accuracy of Advanced Fibrosis in Nonalcoholic Fatty Liver Disease: The New LINKI Algorithm Compared with Established Algorithms.
Detection of advanced fibrosis (F3-F4) in nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis. Serum markers have been proposed as alternatives to biopsy. We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms. We included 158 patients with biopsy-proven NAFLD. Of these, 38 had advanced fibrosis. The following fibrosis algorithms were calculated: NAFLD fibrosis score, BARD, NIKEI, NASH-CRN regression score, APRI, FIB-4, King´s score, GUCI, Lok index, Forns score, and ELF. Study population was randomly divided in a training and a validation group. A multiple logistic regression analysis using bootstrapping methods was applied to the training group. Among many variables analyzed age, fasting glucose, hyaluronic acid and AST were included, and a model (LINKI-1) for predicting advanced fibrosis was created. Moreover, these variables were combined with platelet count in a mathematical way exaggerating the opposing effects, and alternative models (LINKI-2) were also created. Models were compared using area under the receiver operator characteristic curves (AUROC). Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83, respectively. Higher accuracy was achieved with the novel LINKI algorithms. AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89. The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be validated in further studies including larger cohorts.


Social anxiety in the general population: introducing abbreviated versions of SIAS and SPS.
Social anxiety is characterized by the experience of stress, discomfort and fear in social situations, and is associated with substantial personal and societal burden. Two questionnaires exist that assess the aspects of social anxiety, i.e. social interaction anxiety (SIAS) and social phobia (SPS). There is no agreement in literature on the dimensionality of social anxiety. Further, the length of a questionnaire may negatively affect response rates and participation at follow-up occasions. To explore the structure of social anxiety in the general population, and to examine psychosocial and sociodemographic correlates. Our second aim was to construct abbreviated versions of SIAS and SPS that can be easily used and with minimal burden. A total of 1598 adults from the general Dutch population completed a survey asking information on social anxiety, mood and demographics. Exploratory and confirmatory factor analyses as well as reliability analysis with item-total statistics were performed. Confirmatory factor analysis revealed a 3-factor structure for social phobia, and a 2-factor structure for the SIAS, with the second factor containing both reversely scored items. The abbreviated versions of SPS (11 items) and SIAS (10 items) show excellent discriminant and construct validity (Cronbach's α=.90 and .92), while specificity analysis showed that gender, marital status and educational level (SIAS(10): p<.0005; SPS(11): p<.0005) are important determinants of social anxiety. In the general population, social interaction anxiety and social phobia are two aspects of a higher-order factor of social anxiety. Social anxiety is validly captured by the short versions of SPS and SIAS, reducing the questionnaire burden for participants in epidemiological and biobehavioral research.


Long circulation and cytotoxicity of PEGylated gemcitabine and its potential for the treatment of pancreatic cancer.
Gemcitabine [2', 2'-difluoro-2'-deoxycytidine (dFdC)] is a low molecular weight, deoxycytidine analog inhibiting cellular DNA synthesis. Currently, it is the frontline drug approved by Food and Drug Administration (FDA) for the treatment of pancreatic cancer. However, efforts to use gemcitabine as an anti-cancer agent have been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and intracellular action. Polymer-drug conjugates, in this regard have spawned an approach to improve the cytotoxicity efficiency and bioavailability of gemcitabine by chemical modification. The present study describes the synthesis of a water soluble formulation of PEGylated gemcitabine characterized by FT IR, (1)H NMR and RP-HPLC chromatography. The PEGylated gemcitabine has a prolonged circulation time in plasma as studied in an animal model. This eventually caused a marked improvement in the cytotoxicity and apoptosis-inducing activity in pancreatic cancer cell lines (MIA PaCa 2 and PANC 1). Hence, these findings demonstrate the PEGylated gemcitabine is a desirable approach for therapy by intravenous administration. Successful clinical application of this approach can significantly contribute to the treatment of pancreatic cancer.


Non-destructive detection of blueberry skin pigments and intrinsic fruit qualities based on deep learning.
This paper proposes a novel method to improve accuracy and efficiency in detecting the quality of blueberry fruit, taking advantage of deep learning in classification tasks. We first collected 'Tifblue' blueberries at seven different stages of maturity (10-70 days after full bloom) and measured the pigments of the blueberry skin and the total sugar and the total acid of the pulp. We then established a skin pigment contents prediction network (SPCPN), based on the correlation between the pigments and blueberry pictures, and also a fruit intrinsic qualities prediction network (FIQPN), based on the correlation between the pigments and fruit qualities. Finally, the SPCPN and FIQPN were consolidated into the blueberry quality parameters prediction network (BQPPN). The results showed that the anthocyanins in the blueberry skin were significantly correlated with the total sugar, total acid, and sugar / acid ratio of the fruit. After verification, the results also indicated that, for the prediction of anthocyanins, chlorophyll, and the anthocyanin / chlorophyll ratio, the SPCPN network model was found to achieve higher R2 (RMSE) values of 0.969 (0.139), 0.955 (0.005), 0.967 (15.4), respectively. The FIQPN network model was also able to evaluate the value of total sugar (R2 = 0.940, RMSE = 4.905), total acid (R2 = 0.930, RMSE = 2.034), and the sugar / acid ratio (R2 = 0.973, RMSE = 0.580). The above results indicated the potential for utilizing deep learning technology to predict the quality indicators of blueberry before harvesting. © 2020 Society of Chemical Industry.


Bowel necrosis associated with early jejunal tube feeding: A complication of postoperative enteral nutrition.
Postoperative enteral nutrition may sometimes be responsible for severe complications such as mesenteri ischemia. Studies in the English literature were identified by a computer-assisted search of the MEDLINE database using the key words "enteral feeding OR jejunostomy" AND "complications OR mesenteric ischemia." Cited references of each retrieved paper were checked for relevance. All reports of mesenteric ischemia in the setting of postoperative enteral feeding were included. In cases of multiple articles from the same institution with overlapping patients, the most exhaustive article was included. All reports were abstracted for number of patients, presence of preoperative comorbidities, development of perioperative hypotension or mesenteric occlusion, and outcome. Nine studies were retrieved in which enteral feedings were responsible for bowel ischemia; we report an additional case. The common clinical picture is that of a patient without significant risk factors for mesenteric ischemia, which during the early postoperative course develops nonspecific abdominal symptoms and then rapidly progresses to septic shock and eventually to multisystem organ failure and death. Mesenteric ischemia may present in up to 3.5% of enterally fed surgical patients; the associated mortality approaches 100%. The lack of specific symptoms requires a high index of suspicion for diagnosis; prompt abdominal exploration and bowel resection are the only chance for survival. The benefits of enteral nutrition outweigh the likelihood of severe complications; when mesenteric ischemia develops, early diagnosis is challenging and the prognosis is poor.


Feminizing adrenocortical tumor. Histological and ultrastructural study.
A case of a feminizing adrenocortical tumor associated with Cushing's syndrome in a 29 year old male is presented. The ultrastructural features are compared with adrenal tumors secreting aldosterone, glucocorticoids of androgens. As in adrenal carcinomas, this tumor demonstrates nuclear pleomorphism with enlarged nucleoli and nuclear pseudoinclusions. The cytoplasmic organelles show some parallels between feminizing and androgen-secreting adrenal tumors. Different types of mitochondria occur with varying amounts of smooth endoplasmic reticulum. Numerous microbodies are present. Histological and ultrastructural signs indicating probably malignancy are discussed and it is noted that most of the feminizing adrenal tumors are carcinomata. Neither local recurrence nor distant metastases have yet been detected in this case, two years after excision of the tumor.


Implant and patient survival rates using Exeter Trauma Stem hemiarthroplasty in fracture neck of femur patients: The largest study to date.
Exeter Trauma Stems (ETS) femoral hemiarthroplasties are based on Exeter THR stems with a few design changes. Little has been published on ETS survival rates to justify their high cost compared to other cheaper implants. This is the largest prospective study to assess ETS implant failure-free survival rates in fracture neck of femur patients (NOF). This non-developing-centre study examined whether these design differences have altered implant survival (compared with Exeter THR's published survival data). Data were prospectively collected by independent audit officers. Dislocation, periprosthetic fracture, re-admission with severe hip pain, deep infection and revision surgery were considered events of interest in implant failure-free survival. This study assessed 1,123 ETS stems (36 patients received bilateral ETS) in NOF patients. The mean patient age at the time of operation was 83 years (range; 49 - 102 years). The mean observation period was 2.5 years (range; 0 days - 8 years). Only 29 implants failed. All failure events were reported within the first year. Stem failure-free survival was 97.2% at eight years (CI 95.9% - 98%). Dislocation occurred in 10 patients (1%), periprosthetic femoral fracture in 4 (0.4%), and deep infection in 11 patients (1.2%). Patient survival rates were 75% and 48% at one and five years respectively. ETS has high implant failure-free survival rates when used in hip fractures. ETS design changes have not altered ETS survival when used in hip fractures compared with the published literature of Exeter THR stem when used as a treatment for OA. Exeter Trauma Stems in NOF patients might last these elderly patients their entire short lifetime.


Synthesis of organic compounds from carbon monoxide and water by UV photolysis.
The photolysis of water vapor with carbon monoxide at 1849 A yields alcohols, aldehydes and organic acids, with an overall quantum yield of 3.3 x 10(-2). This rather high quantum yield could have led to a contribution of approximately 10(11) organic molecules cm-2 sec-1 to the pool of organic material on the primitive Earth. The reactions are initiated by the photolysis of water molecules and the resulting hydrogen atoms reduce the carbon monoxide to a variety of one and two carbon compounds. The organic molecules are dissolved in water and thus escape destruction by photolysis. Photolysis of water vapor with carbon dioxide did not yield organic compounds under these conditions.


Ginsenoside compound K acts via LRP1 to alleviate Amyloid β42-induced neuroinflammation in microglia by suppressing NF-κB.
Alzheimer's disease (AD), has caused a mass of disability and mortality in elder populations, which increases global health burden. There are still limited effective disease-modifying drugs. Alleviating microglia-evoked neuroinflammation has become a promising treatment strategy for AD. Ginsenoside Compound K has been demonstrated to exhibit anti-inflammatory and neuroprotective benefits. Here we measured the effects of Ginsenoside Compound K in inhibiting amyloid-induced microglia inflammation and the possible molecular mechanisms and target of action in vitro. The cytotoxicity of all chemical reagents on BV2 cells were evaluated using the MTT assay. qRT-PCR and ELISA were carried out to detect the inflammatory cytokines levels. Western blot was utilized to determine the effect of Ginsenoside Compound K on the nuclear factor-κB (NF-κB) p65 nuclear translocation. Antagonist Receptor Associated Protein (RAP) was used to verify the engagement of low-density lipoprotein receptor-related protein 1(LRP1). Ginsenoside Compound K diminished inflammatory cytokine production and reversed NF-κB p65 nuclear translocation induced by Aβ42 oligomers. LRP1 expression was up-regulated by Ginsenoside Compound K. When LRP1 was blocked by antagonist RAP, the protective effect of Ginsenoside Compound K was massively eliminated. These observations provide evidence for anti-inflammatory effect of Ginsenoside Compound K through NF-κB pathway via LRP1 activation, and support further evaluation of Ginsenoside Compound K as a potential effective modulator for AD.


Direct observation of single DNA structural alterations at low forces with surface-enhanced Raman scattering.
DNA experiences numerous mechanical events, necessitating single-molecule force spectroscopy techniques to provide insight into DNA mechanics as a whole system. Inherent Brownian motion limits current force spectroscopy methods from observing possible bond level structural changes. We combine optical trapping and surface-enhanced Raman scattering to establish a direct relationship between DNA's extension and structure in the low force, entropic regime. A DNA molecule is trapped close to a surface-enhanced Raman scattering substrate to facilitate a detectable Raman signal. DNA Raman modes shift in response to applied force, indicating phosphodiester mechanical alterations. Molecular dynamic simulations confirm the local structural alterations and the Raman sensitive band identified experimentally. The combined Raman and force spectroscopy technique, to our knowledge, is a novel methodology that can be generalized to all single-molecule studies.


Nuclear reactivity indices within regional density functional theory.
Regional chemical potential values-mu(R) have been obtained with the use of nuclear reactivity indices. Perturbational formulae use values of reactivity indices of isolated molecular fragments. The changes of the parameters (DeltaN(R),{ DeltaQ(i)}i epsilonR) within each fragment determine the value of the regional chemical potential after a chemical reaction. The computational scheme has been tested numerically along the chemical reaction path. We have studied a set of chemical reactions to obtain regional chemical potentials (mu(ts)R) and regional transfer potentials (T(ts)R) for transition states of the following chemical reactions: HF+CO=HFCO, HCl+CO=HClCO, HF+SiO=HFSiO and HF+GeO=HFGeO. The results are reasonable and encouraging. Values of these indices show the possible reactivity directions of the transition states examined.


[Work schedule and accidents among subjects digging tunnels for the new high speed railway network in Toscana].
We analysed the temporal distribution of all the accidents occurred in the last 4 years among the workers engaged in tunnel digging for the new high speed railway network. The frequency and severity rates show significant differences according to work shifts and time of occurrence, with particular reference to hour of the day, hour of duty, day of the week, day of duty, and month of the year).


Transforming acidic coiled-coil containing protein 3 suppresses influenza A virus replication by impeding viral endosomal trafficking and nuclear import.
Transforming acidic coiled-coil containing protein 3 (TACC3) is a motor spindle protein that plays an essential role in stabilization of the mitotic spindle. In this study, we show that the overexpression of TACC3 reduces the viral titers of multiple influenza A viruses (IAVs). In contrast, the downregulation of TACC3 increases IAVs propagation. Next, we map the target steps of TACC3 requirement to the early stages of viral replication. By confocal microscopy and nuclear plasma separation experiment, we reveal that overexpression of TACC3 results in a substantial decrease of IAV NP accumulation in the nuclei of infected cells. We further show that viral attachment and internalization are not affected by TACC3 overexpression and detect that the early and late endosomal trafficking of IAV in TACC3 overexpression cells is slower than negative control cells. These results suggest that TACC3 exerts an impaired effect on the endosomal trafficking and nuclear import of vRNP, thereby negatively regulating IAV replication. Moreover, the infection of different IAV subtypes decreases the expression level of TACC3 in turn. Consequently, we speculate that IAV ensures the generation of offspring virions by antagonizing the expression of inhibitory factor TACC3. Collectively, our results establish TACC3 as an important inhibitory factor for replication of the IAV, suggesting that TACC3 could be a potential target for the development of future antiviral compounds.


Triheptanoin in acute mouse seizure models.
Triheptanoin, the triglyceride of heptanoate, is used to treat certain hereditary metabolic diseases in USA because of its anaplerotic potential. In two chronic mouse seizure models this clear tasteless oil was found to be reproducibly anticonvulsant. Here we investigated the effects of triheptanoin feeding in C3H and CD1 mice using standard acute seizure models. Feeding 30-40% triheptanoin (caloric intake) consistently elevated blood propionyl-carnitines, but inconsistent anticonvulsant effects were observed in the fluorothyl, pentylenetetrazole and 6Hz seizure models. A 2mA consistent increase in the maximal electroshock threshold was found after 3 weeks of 35% triheptanoin feeding (p=0.018). In summary, triheptanoin shows a unique anticonvulsant profile in seizure models, compared to other treatments that are in the clinic. Therefore, despite small and/or inconsistent effects of triheptanoin in acute seizure models, triheptanoin remains of interest as a potential add-on treatment for patients with medically refractory epilepsy.


Variables related to long-term smoking status following cardiac events.
Abstinence rates for smokers following a myocardial infarction (MI) or coronary by-pass surgery (CABG) are far superior to those for persons attending formal cessation programs. However, only two studies have used any biochemical verification of self-report in this population, and it is unclear what variables are associated with successful cessation post-MI or -CABG. The present study used alveolar carbon monoxide levels to verify self-report of post-MI and -CABG veterans and obtained only a 29% abstinence rate. Most abstinent veterans quit immediately after their first cardiac event, and only the belief that smoking contributed to their cardiac problems predicted long-term smoking status.


Biological and serological comparison of two embryo-lethal mycoplasmas isolated from turkeys.
Two uncharacterised, independently isolated, embryo-lethal mycoplasmas obtained from turkeys and designated W8 and CT were compared with each other and with a third, culturally similar, embryo-lethal turkey mycoplasma, Iowa 695, by cultural and serological methods. The three mycoplasma isolates were serologically distinct and CT could be differentiated from W8 by its ability to reduce 2,3,5-triphenyltetrazolium chloride under aerobic conditions.


The Larsson frequency/volume chart is not a substitute for cystometry in the investigation of women with urinary incontinence.
The aim of the study was to assess the ability of the Larsson chart nomogram to predict the presence of detrusor instability or genuine stress incontinence without recourse to cystometry. The Larsson chart provides a probability of detrusor instability by plotting 24-hour urinary frequency against the range of void volumes. Frequency/volume chart data were obtained from the records of 216 patients who had undergone subtraction cystometry. The Larsson chart was assessed by comparing the probability of detrusor instability or of genuine stress incontinence obtained with the cystometric diagnosis. The maximum sensitivity of the Larsson chart was 52%, with a specificity of 70% for detrusor instability. For genuine stress incontinence these figures were 66% and 65% respectively. The Larsson chart provides no diagnostic information and does not remove the need for formal cystometric evaluation of patients with urinary incontinence.


A robust molecular phylogeny of the Tricladida (Platyhelminthes: Seriata) with a discussion on morphological synapomorphies.
The suborder Tricladida (Platyhelminthes: Turbellaria, Seriata) comprises most well-known species of free-living flatworms. Four infraorders are recognized: (i) the Maricola (marine planarians); (ii) the Cavernicola (a group of primarily cavernicolan planarians); (iii) the Paludicola (freshwater planarians); and (iv) the Terricola (land planarians). The phylogenetic relationships among these infraorders have been analysed using morphological characters, but they remain uncertain. Here we analyse the phylogeny and classification of the Tricladida, with additional, independent, molecular data from complete sequences of 18S rDNA and 18S rRNA. We use maximum parsimony and neighbour-joining methods and the characterization of a unique gene duplication event involving the Terricola and the dugesiids to reconstruct the phylogeny. The results show that the Maricola is monophyletic and is the primitive sister group to the rest of the Tricladida (the Paludicola plus the Terricola). The Paludicola are paraphyletic since the Terricola and one paludicolan family, the Dugesiidae, share a more recent common ancestor than the dugesiids with other paludicolans (dendrocoelids and planariids). A reassessment of morphological evidence may confirm the apparent redundancy of the existing infraorders Paludicola and Terricola. In the meantime, we suggest replacing the Paludicola and Terricola with a new clade, the Continenticola, which comprises the families Dugesiidae, Planariidae, Dendrocoelidae and the Terricola.


2,3-Dimethyl-1H-imidazol-3-ium benzene-sulfonate-1,2-dimethyl-1H-imidazole co-crystal.
In the title co-crystal, C5H9N2 +·C6H5O3S-·C5H8N2, the two 1,2-di-methyl-imidazole rings exist as partially protonated moieties in the asymmetric unit as a two-part disordered unit wherein the acidic hydrogen atom is bound to each ring. The two imidazolium cations share a strong hydrogen bond via the acidic hydrogen atom, which is disordered between two positions, being bonded to the first versus second imidazole ring in a 0.33 (2) to 0.67 (2) ratio. A benzene sulfonate anion is present for charge balance and inter-acts with the aromatic H atoms on both imidazole rings as well as with the methyl groups on the rings.


Topological barriers to defect nucleation generate large mechanical forces in an ordered fluid.
Common fluids cannot sustain static mechanical stresses at the macroscopic scale because they lack molecular order. Conversely, crystalline solids exhibit long-range order and mechanical strength at the macroscopic scale. Combining the properties of fluids and solids, liquid crystal films respond to mechanical confinement by both flowing and generating static forces. The elastic response, however, is very weak for film thicknesses exceeding 10 nm. In this study, the mechanical strength of a fluid film was enhanced by introducing topological defects in a cholesteric liquid crystal, producing unique viscoelastic and optomechanical properties. The cholesteric was confined under strong planar anchoring conditions between two curved surfaces with sphere-sphere contact geometry similar to that of large colloidal particles, creating concentric dislocation loops. During surface retraction, the loops shrank and periodically disappeared at the surface contact point, where the cholesteric helix underwent discontinuous twist transitions, producing weak oscillatory surface forces. On the other hand, new loop nucleation was frustrated by a topological barrier during fluid compression, creating a metastable state. This generated exceptionally large forces with a range exceeding 100 nm as well as extended blueshifts of the photonic bandgap. The metastable cholesteric helix eventually collapsed under a high compressive load, triggering a stick-slip-like cascade of defect nucleation and twist reconstruction events. These findings were explained using a simple theoretical model and suggest a general approach to enhance the mechanical strength of one-dimensional periodic materials, particularly cholesteric colloid mixtures.


Chest radiography in the ICU: Part 1, Evaluation of airway, enteric, and pleural tubes.
In this pictorial essay, we discuss and illustrate normal and aberrant positioning of nonvascular support and monitoring devices frequently used in critically ill patients, including endotracheal and tracheostomy tubes, chest tubes, and nasogastric and nasoenteric tubes, as well as their inherent complications. The radiographic evaluation of the support and monitoring devices used in patients in the ICU is important because the potentially serious complications arising from their introduction and use are often not clinically apparent. Familiarity with normal and abnormal radiographic findings is critical for the detection of these complications.


Genetic Control of Serum Marinobufagenin in the Spontaneously Hypertensive Rat and the Relationship to Blood Pressure.
We have investigated serum levels of immunoreactive marinobufagenin (MBG) in 16- to 20-week-old spontaneously hypertensive rats (SHRs)-A3 and in the normotensive Wistar-Kyoto (WKY) rat strain in the absence of salt loading, and we have investigated the genetic control of serum MBG. We genotyped the F2 progeny of an SHR-A3×WKY intercross using a genome-wide panel of 253 single-nucleotide polymorphism markers that were dimorphic between SHR-A3 and WKY and measured serum MBG by ELISA. Serum MBG levels were lower in SHR-A3 than WKY rats (0.39±0.07 and 1.27±0.40 nmol/L, respectively), suggesting that MBG may not play a role in the markedly divergent blood pressure measured by telemetry in rats of these 2 strains (SHR-A3 and WKY, 198.3±4.43 and 116.8±1.51 mm Hg, respectively). The strain difference in serum MBG was investigated to determine whether genomic regions influencing MBG might be identified by genetic mapping. Quantitative trait locus mapping indicated a single locus influencing serum MBG in the region of chromosome 6q12. Homozygosity of WKY alleles at this locus was associated with increased serum MBG levels. We surveyed whole genome sequences from our SHR-A3 and WKY lines, seeking coding sequence variation between SHR-A3 and WKY within the mapped locus that might explain the inherited strain difference in serum MBG. We identified amino acid substitution in the sterol transport protein Abcg5, present in SHR-A3, but absent in WKY, that is a potential mechanism influencing MBG levels.


Expanded indications for lung transplantation for pulmonary complications after hematopoietic stem cell transplantation.
Pulmonary complications after hematopoietic stem cell transplantation (HSCT) are associated with poor survival and can be treated by lung transplantation (LT). However, the indications for LT in patients with pulmonary complications after HSCT remain unclear due to low number of cases. HSCT is frequently conducted for hematologic malignancies, which have different recurrence patterns from solid-organ malignancies. Some patients also experience ABO blood type changes post-HSCT. This study aimed to reassess the indication of LT for pulmonary complications post-HSCT, focusing on disease-free interval (DFI) and ABO-incompatibility. Retrospective chart reviews were performed in patients who underwent LT for post-HSCT pulmonary complications. In patients with previous hematologic malignancy, indication was based on estimated recurrence rate instead of DFI. Donors were selected based on the recipient anti-A/B antibody profile rather than ABO type. Post-LT survival and complication rates were examined. Forty consecutive patients undergoing LT after HSCT (including 31 with previous hematologic malignancy) were analyzed. The median DFI between HSCT and LT was 64.5 months. Thirteen patients with previous hematologic malignancy had DFI <5 years but none experienced recurrence. There was no significant difference in 5-year post-LT survival between patients undergoing (74.7%) and not undergoing HSCT (68.4%). There was no significant difference in survival between patients with DFI ≥5 years (63.8%) and patients with DFI <5 years (83.3%). Five patients underwent LTs from major ABO-incompatible donors, but none developed incompatibility-related complications. Indications based on estimated recurrence rates and recipients' anti-A/B antibody profiles may increase the use of LT for patients after HSCT.


Calcium supplementation with and without hormone replacement therapy to prevent postmenopausal bone loss.
To determine whether augmentation of dietary calcium is effective in the prevention of early postmenopausal bone loss. Three-arm, placebo-controlled, randomized parallel trial. The study duration was 2.9 +/- 1.1 (SD) years. General community. 118 healthy, white women 3 to 6 years after spontaneous menopause, recruited by community announcement. Random allocation to daily intake of 1700 mg of calcium (calcium carbonate given in divided doses with meals); placebo; or conjugated equine estrogens (0.625 mg; days 1 to 25), progesterone (10 mg; days 16 to 25), and 1700 mg of elemental calcium daily. Each participant received 400 IU of vitamin D daily. Total body calcium measured by delayed gamma neutron activation analysis and whole-body counting; bone mineral density of the spine, femur, and radius measured by photon absorptiometry. Bone mineral density declined in the placebo group for the lumbar spine (-2.1%/y; 95% Cl, -3.3 to -0.9), femoral neck (-2.0%/y; Cl, -2.6 to -1.2), trochanter (-1.6%/y; Cl, -2.4 to -0.8), Ward triangle (-2.7%/y; Cl, -3.7 to -1.7), and total body calcium (-2.0%/y; Cl, -2.2 to -1.8). Rates of change were intermediate for calcium augmentation compared with placebo and estrogen-progesterone-calcium but statistically significant compared with placebo for total body calcium (-0.5%/y; Cl, -0.9 to -0.1; P = 0.006) and the femoral neck (-0.8%/y; Cl, -1.4 to -0.2; P = 0.03). Although less effective than estrogen-progesterone-calcium, calcium augmentation alone significantly retards bone loss from the femoral neck and improves calcium balance in recently postmenopausal women. Dietary calcium augmentation should be recommended as a strategic option in helping to prevent early postmenopausal bone loss.


[Oral lupus erythematosus. Description and analysis of 11 cases].
The aim of this study is to evaluate all the cases of lupus erythematosus with oral involvement coming to the Department of Oral Medicine in the last 15 years (1984-1998). The files of the Oral Medicine Department of the University of Turin have been reviewed to search oral manifestations of lupus erythematosus according to international accepted diagnostic criteria. A total of eleven patients 7 women (64%) and 4 men (36%) with a mean age of 46 years were included. Three patients (27%) had discoid lupus erythematosus (LED) whereas 8 (73%) had systemic lupus erythematosus (LES). In four patients the diagnosis of lupus was made after oral diagnosis, whereas 7 patients (64%) had a previous diagnosis of lupus. Clinical aspect was typical in 8 cases (73%) while one patient had leukoplakia-like white patches and two patients (18%) had lichen-like oral lesion. This study suggest that primitive oral lesion of lupus are quite rare but frequently may have atypical features often difficult to differentiate from lichen planus.


[Muscle invasive bladder cancer after radical cystectomy. Prognostic factors of adjuvant chemotherapy].
The indications to administer adjuvant systemic chemotherapy to patients with urothelial carcinoma of the bladder who underwent radical cystectomy is discussed controversially and all international guidelines are very restrictive with regard to its recommendation for routine daily practice due to the low scientific evidence concerning its therapeutic benefit. Currently, adjuvant systemic chemotherapy should be preferably administered within clinical trials. In the daily routine adjuvant treatment might be given in patients with lymph node positive disease. Clinical, pathohistological and molecular biomarkers which might be associated with a positive or negative treatment response have been evaluated sparsely in the past. The presence of hemangiosis/lymphangiosis carcinomatosa and/or extranodal expansion in patients with lymph node metastases appears to be associated with a poor outcome. The markers ERCC-1, XAF and anti-apoptotic proteins of the Bcl-2 family seem to represent the most promising biomarkers associated with response to adjuvant cisplatin-based chemotherapy.


Relationship between oral health impacts and personality profiles among orthodontic patients treated with Invisalign clear aligners.
This within subject clinical experiment assessed oral health impacts before and after Invisalign orthodontic treatment and their relationships with personality characteristics. 50 patients (26 females and 24 males; mean age = 27.62 ± 8.25 years, SE = 1.17, 95% CI = 24.71-29.89 years) were assessed before and after treatment with Invisalign orthodontic treatment. Treatment clinical success was evaluated according defined clinical guidelines. Oral health impacts before and after Invisalign orthodontic treatment were measured via the Oral Health Impact Profile (OHIP). Personality features were measured via the NEO Five-Factor Inventory (NEO-FFI). Probability of α = .05 was utilized to identify significant findings. Females scored less OHIP scores after treatment (had less negative impacts) in comparison to baseline OHIP scores (t = 3.782, df = 25, P = .001, 95% CI of mean difference = 2.750-9.327). Among males, openness scores (R2 = .911, B = 5.235, 95% CI for B = 0.062-10.407, t = 2.601, P = .048) were able to predict OHIP scores before treatment; meanwhile, extraversion (R2 = .959, B = - 8.224, 95% CI for B = - 14.605-1.843, t = - 3.313, P = .021), openness (R2 = .959, B = 21.795, 95% CI for B = 10.737-32.853, t = 5.067, P = .004), and conscientiousness (R2 = .959, B = 10.293, 95% CI for B = 4.796-15.790, t = 4.813, P = .005) scores were useful to predict OHIP scores after treatment (R2 = .959, P < .05). NEO-FFI scores were not useful to predict OHIP scores before or after treatment among females (P > .05). These findings demonstrate that oral health impacts of Invisalign orthodontic treatment and personality profiles contribution to oral health impacts were different between genders.


Spontaneous rupture of a bladder diverticulum.
A case of spontaneous rupture of an acquired bladder diverticulum is presented. Diagnosis was made preoperatively and full recovery followed surgical treatment. A review of the literature revealed 9 other cases of spontaneous rupture. Bladder outlet obstruction and urinary tract infection were present in the majority of cases. In the past misdiagnosis and delayed treatment led to significant mortality. However, the prognosis currently is better due to the use of broad-spectrum antibiotics, better radiological imaging studies, and earlier diagnosis and treatment.


No reliable evidence that ozone gas stops or reverses tooth decay.
The Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, Medline and Premedline, Embase, CINAHL (Cumulative Index to nursing and Allied Health Literature)l and the Allied and Complementary Medicine Database were searched. The journal Quintessence was searched by hand and KaVo Dental (Biberach, Germany) manufacturers of HealOzone apparatus were contacted for any additional published or unpublished trials. Inclusion was assessed independently by at least two reviewers. Trials were only included if they met the following criteria: randomisation in a controlled trial; single surface in vivo carious lesion accessible to ozone application; clear allocation concealment; ozone application to the lesions in the intervention group; no such application of ozone in the control group; and outcomes measured after at least 6 months. Reviewers independently extracted information in duplicate. A paucity of comparable data did not allow meta-analytic pooling of the included studies. Three trials were included, with a combined total of 432 randomised lesions (137 participants). Forty-two conference papers, abstracts and posters were excluded (from an unknown number of studies). The risk of bias in all studies appeared high. The analyses of all three studies were conducted at the level of the lesion, which is not independent of the person. For this reason, pooling of data was not appropriate or attempted. Individual studies showed inconsistent effects of ozone on caries, across different measures of caries progression or regression. Few secondary outcomes were reported, but one trial reported an absence of adverse events. Given the high risk of bias in the available studies and lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care or can be considered a viable alternative to current methods for the management and treatment of dental caries.


Incidence and Clinical Significance of Hyperkalemia Following Heart Transplantation.
Hyperkalemia (HK) is a life-threatening complication following solid organ transplantation, and patients often need potassium-chelating agents and deviations from standard posttransplant protocols. This is the first study to report the incidence and clinical impact of hyperkalemia following heart transplantation. We retrospectively included patients who underwent heart transplantation at our institution between April 2014 and December 2018. Patients with multiorgan transplantation were excluded. Clinical outcomes of patients who had serum potassium >5.5 mEq/L in the first year posttransplant (HK group) were compared to patients who did not have serum potassium >5.5 mEq/L in the first year posttransplant (non-HK group). A total of 143 patients were included in this study. During the first year posttransplant, cumulative incidence of serum potassium >5.0, >5.5, and >6.0 mEq/L was 96%, 63%, and 24%, respectively. Fifty-five percent of patients required treatment with potassium-chelating agents. Sulfamethoxazole-trimethoprim was discontinued because of HK in 39% of patients. Overall survival of patients in the HK group (n = 89) was comparable to that of patients in the non-HK group (n = 54, 91% vs 98% at 1 year, P = .19), whereas infection-free survival was significantly lower in the HK group (34% vs 53% at 1 year, P = .010). Multivariate analysis revealed pretransplant renal dysfunction (odds ratio = 2.62; 95% confidence interval, 1.18-5.80; P = .018) and use of mechanical circulatory support (odds ratio = 2.90; 95% confidence interval, 1.08-7.76; P = .035) as significant predictors of posttransplant hyperkalemia. The incidence of HK following heart transplantation was high, with more than half of patients requiring any therapeutic interventions, and HK was related to an increase in infection events.


Greenhouse gas emission and microbial community dynamics during simultaneous nitrification and denitrification process.
This study evaluates greenhouse gas emission and the microbial community dynamics during simultaneous nitrification and denitrification (SND) process. Based on CO2 equivalents, the SND reactor released 4.28g of greenhouse gases each cycle. 2.91% of the incoming nitrogen load was emitted as N2O. The CO2 and N2O emissions mainly occurred in the aerobic stage and CH4 emissions were consistently near zero. Extracellular polymeric substance (EPS) contents in activated sludge increased during start-up the SND process. High-throughput sequencing showed increases in bacterial species richness, leading to changes in EPS content and composition observed using 3D-EEM fluorescence spectra. For denitrifying bacteria, the relative abundance of Pseudomonas significantly increased during the SND process, while Paracoccus decreased significantly. For phosphorus-accumulating bacteria, the relative abundance of Rhodocyclaceae also significantly increased. The relative abundance of other functional microbes, such as Nitrosomonadaceae (ammonia oxidizer), Nitrospirales (nitrite oxidizer) and Planctomyces (anammox) decreased significantly during the SND process.


A New Approach of Mitigating CYP3A4 Induction Led to the Discovery of Potent Hepatitis B Virus (HBV) Capsid Inhibitor with Optimal ADMET Profiles.
Described herein is a new approach to mitigate CYP3A4 induction. In this unconventional approach, a fine-tuning of the dihedral angle between the C4 phenyl and the dihydropyrimidine core of the heteroaryldihydropyrimidine (HAP) class of capsid inhibitors successfully altered the structure-activity-relationships (SARs) of the unwanted CYP3A4 induction and the desired HBV capsid inhibition to more favorable values. This eventually led to the discovery of a new capsid inhibitor with significantly reduced CYP3A4 induction, excellent anti-HBV activity, favorable preclinical PK/PD profiles, and no early safety flags.


Enhancement of memory consolidation by an avoidance conditioned stimulus: Modulation by the D3 receptor.
Conditioned stimuli (CS) paired with foot-shock can enhance memory consolidation. Because the dopamine D3 receptor (D3R) has been implicated in mediating various responses to CSs, the current study explored its potential role in modulation of memory consolidation by an avoidance CS. Male Sprague-Dawley rats trained to avoid foot-shocks in a two-way signalled active avoidance task (8 sessions, 30 trials per session, 0.8 mA foot-shock) were pre-treated with the D3R antagonist NGB-2904 (Vehicle, 0.1 or 5 mg/kg) and exposed to the CS immediately after the sample phase of an object recognition memory task. Discrimination ratios were assessed 72 h later. Immediate, but not delayed (6 h), post-sample exposure to the CS enhanced object recognition memory and this effect was blocked by NGB-2904. Control experiments with the beta-noradrenergic receptor antagonist propranolol (10 or 20 mg/kg) and D2R antagonist pimozide (0.2 or 0.6 mg/kg) indicated that NGB-2904 targeted post-training memory consolidation. Exploring the pharmacological selectivity of the NGB-2904 effect, it was found that: 1) 5 mg/kg NGB-2904 blocked conditioned memory modulation produced by post-sample exposure to a "weak" CS (one day of avoidance training) and concurrent stimulation of catecholamine activity by 10 mg/kg bupropion; and 2) post-sample exposure to a "weak" CS and concurrent administration of the D3R agonist 7-OH-DPAT (1 mg/kg) enhanced consolidation of object memory. Finally, because 5 mg/kg NGB-2904 had no effect on modulation by avoidance training in the presence of foot-shocks, the findings herein support the hypothesis that the D3R plays an important role in modulation of memory consolidation by CSs.


The impact of the evaluations made by Mini-CEX on the clinical competency of nursing students.
Clinical competency is defined as one's capabilities in terms of knowledge, attitude and practice, and is a necessity for nursing practice. Evaluation is the inseparable part of the education process, without which the quality of education could not be measured. Considering the characteristics of clinical education and its impact on the clinical competency of students, as well as the importance of making precise evaluations of them using scientific, modern and efficient approaches, this study aims to investigate the impact of the evaluation made using Mini-Clinical Evaluation Exercise on the clinical competency of the nursing students of the School of Nursing and Midwifery Shahid Behesti University. This is a quasi-experimental study with a control group conducted on students who were taking courses "Nursing care for a sick child". The students were classified into the intervention and control groups using complete enumeration. The evaluations were made using Mini-Clinical Evaluation Exercise in the intervention group and the portfolio approach in the control group. The skills regarding patient (mother-child) education, IV therapy and medication were evaluated by checklists. The results showed that the mean score of clinical competency in the intervention group was significantly higher than that of the control group. Considering the improvement of clinical competency in the intervention group, it is recommended to use Mini-Clinical Evaluation Exercise for the evaluation of students.


Immunogenicity and safety of concomitant administration of meningococcal serogroup B (4CMenB) and serogroup C (MenC-CRM) vaccines in infants: A phase 3b, randomized controlled trial.
After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB). Infants (N=251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5months (M3, M5) and a booster at 12months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres ≥1:8 was >-10%. Sufficiency of MenB response was achieved if LL95%CI of the percentage of infants with hSBA titres ≥1:4 against fHbp, NadA and PorA strains was ≥70% at M6 or ≥75% at M13. Adverse events (AEs) were collected for 7days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study. Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%CI -6.4% [M6]; -5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%CI 92%, 90%, 89% [M6]; 97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups. Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified.


Successful conservative management of benign gastro-bronchial fistula after intrathoracic esophagogastrostomy.
Benign gastro-bronchial fistula is a rare and devastating complication of esophagectomy with gastric replacement. The most likely cause is a leak from the esophagogastric anastomosis with subsequent mediastinal abscess and rupture into the posterior wall of the tracheobronchial tree. The clinical presentation includes cough upon swallowing, fever, and recurrent pneumonia. Early surgical treatment is the standard of care. A unique case of chronic gastro-bronchial fistula is reported in this article. The patient, a 57-year-old woman, was referred from another hospital after 6 months of symptomatic therapy and total enteral nutrition. A self-expanding esophageal metal stent allowed exclusion of the fistula with symptom relief and return to oral alimentation.


The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation.
Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb) protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.


Ag-Catalyzed or Ag/PPh3-Catalyzed Chemoselective Switchable Cascade Reactions of N-Propargyl Thiocarbamoyl Fluorides and Malonate Esters.
The divergent chemoselective synthesis of 2-methylene-2,3-dihydrothiazoles and 4-benzylidene pyrrolidine-2-thiones (most with E stereoselectivity) from N-propargyl thiocarbamoyl fluorides and malonate esters in moderate to excellent yields with a broad substrate scope and functional group tolerance has been accomplished. AgNTf2 catalyst at 60 °C in dichloroethane provided 4-benzylidene pyrrolidine-2-thiones. AgOTf catalyst and PPh3 ligand in refluxing acetonitrile resulted in a complete switch in the reactivity of formed α,α-diester thioamide intermediates followed by isomerization to access 2-methylene-2,3-dihydrothiazoles.


Documentation of Evidence-Based Psychotherapy and Care Quality for PTSD in the Department of Veterans Affairs.
This study measured the prevalence of evidence-based psychotherapy (EBP) templated notes in VA and tested the hypothesis that template use would be associated with care quality for posttraumatic stress disorder (PTSD). Across 130 facilities, an average of 3.6% of patients with a PTSD diagnosis received at least one EBP template in 2015. Among patients receiving psychotherapy for PTSD, an average of 8.5% received an EBP template. In adjusted models, facility-level EBP template use was associated with a greater proportion of PTSD-diagnosed patients treated in specialty clinics, greater facility-level rates of diagnostic assessment, and greater facility-level rates of psychotherapy adequacy.


Prenylation is not necessary for endogenous Ras activation in non-malignant cells.
Ras monomeric GTPases are pivotal to many core cellular processes such as proliferation and differentiation. The post-translational prenylation of Ras with a farnesyl or a geranylgeranyl moiety is thought to be critical for its membrane binding and consequent signaling activity. Inhibitors of Ras prenylation have an anti-proliferative effect in some Ras-transformed cells. We present a study of the effects of prenylation inhibitors on endogenous, wild-type Ras in three renal cell types, namely primary adult human renal fibroblasts, primary adult human mesangial cells, and a primate renal fibroblast cell line (Vero cells). We have previously demonstrated that Ras is necessary for normal proliferation in these cells. Here we show that Ras is farnesylated and not geranylgeranylated in all three cell types. Furthermore, inhibiting Ras farnesylation has no effect on cell proliferation or Ras activation. Although inhibiting geranylgeranylation in these cells does inhibit proliferation, this is through an Ras-independent mechanism. Non-prenylated Ras is able to localize to the plasma membrane, bind Raf when cells are stimulated by epidermal growth factor or platelet-derived growth factor, and activate the Ras downstream effectors mitogen-activated protein kinase and phosphotidylinositol 3-kinase. We conclude that in wild-type cells, endogenous Ras does not need to be prenylated to be active.


Comprehensive analysis of predictive factors for upstaging in intraprostatic cancer after radical prostatectomy: Different patterns of spread exist in lesions at different locations.
Accurate assessment of the clinical staging is crucial for determining the need for radical prostatectomy (RP) in prostate cancer (PCa). However, the current methods for PCa staging may yield incorrect results. This study aimed to comprehensively analyze independent predictors of postoperative upstaging of intraprostatic cancer. We conducted a retrospective analysis of data from intraprostatic cancer patients who underwent radical surgery between March 2019 and December 2022. Intraprostatic cancer was defined as a lesion confined to the prostate, excluding cases where multiparameter magnetic resonance imaging (mpMRI) showed the lesion in contact with the prostatic capsule. We assessed independent predictors of extraprostatic extension (EPE) and analyzed their association with positive surgical margin (PSM) status. In addition, based on the distance of the lesion from the capsule on mpMRI, we divided the patients into non-transition zone and transition zone groups for further analysis. A total of 500 patients were included in our study. Logistic regression analysis revealed that biopsy Gleason grade group (GG) (odds ratio, OR: 1.370, 95% confidence interval, CI: 1.093-1.718) and perineural invasion (PNI) (OR: 2.746, 95% CI: 1.420-5.309) were predictive factors for postoperative EPE. Both biopsy GG and PNI were associated with lateral (GG: OR: 1.270, 95% CI: 1.074-1.501; PNI: OR: 2.733, 95% CI: 1.521-4.911) and basal (GG: OR: 1.491, 95% CI: 1.194-1.862; PNI: OR: 3.730, 95% CI: 1.929-7.214) PSM but not with apex PSM (GG: OR: 1.176, 95% CI: 0.989-1.399; PNI: OR: 1.204, 95% CI: 0.609-2.381) after RP. Finally, PNI was an independent predictor of EPE in the transition zone (OR: 11.235, 95% CI: 2.779-45.428) but not in the non-transition zone (OR: 1.942, 95% CI: 0.920-4.098). PNI and higher GG may indicate upstaging of tumors in patients with intraprostatic carcinoma. These two factors are associated with PSM in locations other than the apex of the prostate. Importantly, cancer in the transition zone of the prostate is more likely to spread externally through nerve invasion than cancer in the non-transition zone.


Catalytically inactive heme oxygenase-2 mutant is cytoprotective.
Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation, producing iron, carbon monoxide, and bilirubin/biliverdin. HO consists of two isozymes: HO-1, which is an oxidative stress-response protein, and HO-2, which is constitutively expressed. HO-2 accounts for most HO activity within the nervous system. Its posttranslational modifications and/or interactions with other proteins make HO-2 a unique regulator of cellular homeostasis. Our previous results revealed that brain infarct volume was enlarged in HO-2 knockout mice. A similar neuroprotective role of HO-2 was shown using primary cortical neurons. To better understand the neuroprotective mechanism of HO-2, we used a catalytically inactive mutant, HO-2H45A, and investigated its cellular effects in response to hemin and hydrogen peroxide-induced cytotoxicity. We observed that HO-2WT overexpression in the HEK293 cell lines became less sensitive to hemin, whereas the inactive mutant HO-2H45A was more sensitive to hemin as compared to control. Interestingly, HO-2WT- and HO-2H45A-overexpressing cells were both protected against H2O2-induced oxidative stress and had less oxidatively modified proteins as compared to control cells. These data indicate that when HO-2 cannot metabolize the prooxidant heme, more cytotoxicity is found, whereas, interestingly, the catalytically inactive HO-2H45A was also able to protect cells against oxidative stress injury. These results suggest the multiplicity of action of the HO-2 protein itself.


Corrigendum to "Image fusion of multi-vision system with one high resolution image for the measurement of long distance" [Heliyon 9(3) (March 2023) e14433].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14433.].


Age-related changes in different steps of protein synthesis of liver and kidney of rats.
Protein synthesis in cell-free systems of rat liver and kidney decreases markedly with age. Examination of activity changes of the different steps revealed for both types of organs that reduced binding of aminoacyl-tRNA to ribosomes and reduced peptidyl transfer might be of major importance for the decrease in overall protein synthesis whereas ageing has only little effect on translocation as well as on initiation and termination.