Attention cortical responses to enlarged faces are reduced in underweight subjects: an electroencephalographic study.
A previous electroencephalographic (EEG) study has shown that obese subjects are characterized by reduced attention frontal responses to food images, thus raising the hypothesis of attention deficits associated with abnormal body weight (Babiloni et al., 2009a,b). In this line, here we tested the hypothesis of reduced attention cortical responses in underweight subjects. EEG data were recorded in 16 normal-weight and 16 underweight subjects during an "oddball" paradigm. The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL), and clicked the mouse after the rare stimuli. These stimuli depicted the same frequent stimuli graphically dilated by 25% along the horizontal axis. Cortical attention responses were probed by the difference between positive event-related potentials peaking around 400-500 ms post-stimulus for the rare minus frequent stimuli (P300). Low resolution electromagnetic source tomography (LORETA) estimated P300 sources. In the FACE condition, the amplitude of prefrontal (Brodmann area: BA10 and BA11) and tempo-parietal (BA19, BA20, BA21, BA22, BA36, BA37, BA39, BA40) sources was lower in the underweight than normal-weight subjects. These results suggest that anterior-posterior cortical attention processes to face images declined in underweight subjects. The present study motivates future research evaluating if this mechanism is related to a poor judgment about body shape.


Temporal-spatial epidemiology of foot-and-mouth disease outbreaks in Mongolia, 2000 - 2002.
Prior to 2000, foot-and-mouth disease (FMD) had not been observed in Mongolia since 1973; however, between April 2000 and July 2002, Mongolia reported 44 FMD outbreaks that affected cattle, sheep, goats, and camels. The objectives of this study were to describe the distributions of the 44 reported FMD outbreaks in Mongolia and to assess their spatial clustering and directions of movement. Official reports were collected to obtain the number and species of animals both affected and at risk, and the date and geographical coordinates of each outbreak. Significant global and local spatial clusters of reported FMD outbreaks were identified. Disease spread during the second epidemic moved 76 degrees northeast and the spread of the disease during the third epidemic moved 110 degrees northwest. FMD outbreaks were clustered intensely close to other FMD-positive counties. These findings can be used in the future to help plan prevention and control measures in high risk areas.


HuR stabilizes a polyadenylated form of replication-dependent histone mRNAs under stress conditions.
All metazoan mRNAs have a poly(A) tail at the 3' end with the exception of replication-dependent histone (RDH) mRNAs, which end in a highly conserved stem-loop (SL) structure. However, a subset of RDH mRNAs are reported to be polyadenylated under physiologic conditions. The molecular details of the biogenesis of polyadenylated RDH [poly(A)+ RDH] mRNAs remain unknown. In this study, our genome-wide analyses reveal that puromycin treatment or UVC irradiation stabilizes poly(A)+ RDH mRNAs, relative to canonical RDH mRNAs, which end in an SL structure. We demonstrate that the stabilization of poly(A)+ RDH mRNAs occurs in a translation-independent manner and is regulated via human antigen R (HuR) binding to the extended 3' UTR under stress conditions. Our data suggest that HuR regulates the expression of poly(A)+ RDH mRNAs.-Ryu, I., Park, Y., Seo, J.-W., Park, O. H., Ha, H., Nam, J.-W., Kim, Y. K. HuR stabilizes a polyadenylated form of replication-dependent histone mRNAs under stress conditions.


Insights from atomic-resolution X-ray structures of chemically synthesized HIV-1 protease in complex with inhibitors.
The human immunodeficiency virus 1 (HIV-1) protease (PR) is an aspartyl protease essential for HIV-1 viral infectivity. HIV-1 PR has one catalytic site formed by the homodimeric enzyme. We chemically synthesized fully active HIV-1 PR using modern ligation methods. When complexed with the classic substrate-derived inhibitors JG-365 and MVT-101, the synthetic HIV-1 PR formed crystals that diffracted to 1.04- and 1.2-A resolution, respectively. These atomic-resolution structures revealed additional structural details of the HIV-1 PR's interactions with its active site ligands. Heptapeptide inhibitor JG-365, which has a hydroxyethylamine moiety in place of the scissile bond, binds in two equivalent antiparallel orientations within the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientation. When JG-365 was converted into the natural peptide substrate for molecular dynamic simulations, we found putative catalytically competent reactant states for both lytic water and direct nucleophilic attack mechanisms. Moreover, free energy perturbation calculations indicated that the insertion of catalytic water into the catalytic site is an energetically favorable process.


Reduced Imaging Radiation Exposure and Costs Associated with Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.
Radiation exposure from diagnostic imaging may increase cancer risk of Crohn's disease (CD) patients, who are already at increased risk of certain cancers. To compare imaging radiation exposure and associated costs in CD patients during the year pre- and post-initiation of anti-tumor necrosis factor (anti-TNF) agents or corticosteroids. Adults were identified from a large US claims database between 1/1/2005 and 12/31/2009 with ≥ 1 abdominal imaging scan and 12 months of enrollment before and after initiating therapy with anti-TNF or corticosteroids. Imaging utilization, radiation exposure, and healthcare costs pre- and post-initiation were examined. Anti-TNF-treated patients had significantly fewer imaging examinations the year prior to initiation than corticosteroid-treated patients. Cumulative radiation doses before initiation were significantly higher for corticosteroid patients compared to anti-TNF patients (22.3 vs. 17.7 millisieverts, P = 0.0083). After therapy initiation, anti-TNF-treated patients had significantly fewer imaging examinations (2.9 vs. 5.2, P < 0.0001) and less radiation exposure (7.4 vs. 15.4 millisieverts, P <0.0001) than corticosteroid-treated patients in the follow-up period. Reductions in imaging costs adjusted for 1000 patient-years after initiation of therapy were - $275,090 and - $121,960 (P = 0.0359) for anti-TNF versus corticosteroid patients, respectively. This analysis demonstrated that patients treated with anti-TNF agents have fewer imaging examinations, less radiation exposure, and lower healthcare costs associated with imaging than patients treated with corticosteroids. These benefits do not account for additional long-term benefits that may be gained from reduced radiation exposure.


April 2012 intra-oceanic seismicity off Sumatra boosted by the Banda-Aceh megathrust.
Large earthquakes nucleate at tectonic plate boundaries, and their occurrence within a plate's interior remains rare and poorly documented, especially offshore. The two large earthquakes that struck the northeastern Indian Ocean on 11 April 2012 are an exception: they are the largest strike-slip events reported in historical times and triggered large aftershocks worldwide. Yet they occurred within an intra-oceanic setting along the fossil fabric of the extinct Wharton basin, rather than on a discrete plate boundary. Here we show that the 11 April 2012 twin earthquakes are part of a continuing boost of the intraplate deformation between India and Australia that followed the Aceh 2004 and Nias 2005 megathrust earthquakes, subsequent to a stress transfer process recognized at other subduction zones. Using Coulomb stress change calculations, we show that the coseismic slips of the Aceh and Nias earthquakes can promote oceanic left-lateral strike-slip earthquakes on pre-existing meridian-aligned fault planes. We further show that persistent viscous relaxation in the asthenospheric mantle several years after the Aceh megathrust explains the time lag between the 2004 megathrust and the 2012 intraplate events. On a short timescale, the 2012 events provide new evidence for the interplay between megathrusts at the subduction interface and intraplate deformation offshore. On a longer geological timescale, the Australian plate, driven by slab-pull forces at the Sunda trench, is detaching from the Indian plate, which is subjected to resisting forces at the Himalayan front.


Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome.
To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing health-related quality of life in children with recurrent headache: reliability and validity of the PedsQLTM 4.0 in a pediatric headache sample.
To evaluate the reliability and validity of a commonly used measure of health-related quality of life (HRQOL), the Pediatric Quality of Life Inventory (PedsQL 4.0), in a sample of children with a recurrent headache syndrome. Participants were 40 children aged 7-12 who completed measures of HRQOL, headache-related disability, and headache activity during a baseline period and following a self-directed cognitive-behavioral intervention. The data are supportive of the reliability (internal consistency and test-retest) and validity (criterion related, convergent, known-groups, and responsiveness to intervention) of the PedsQL 4.0 within a pediatric headache sample. We conclude that the PedsQL 4.0 is a reliable and valid measure of HRQOL in children with recurrent headache and captures important information not routinely evaluated in chronic pain populations.


Characteristics and outcomes among lung transplant patients with respiratory syncytial virus infection.
To describe characteristics and outcomes among lung transplantation (LT) patients with respiratory syncytial virus (RSV) infection and elucidate the predictors of 1-year survival after RSV infection. This was a retrospective chart review study among LT patients with RSV infection between 2013 and 2018 (90 episodes among 87 patients; mean age 56.3 ± 13.1 years, M:F 52:35). A contemporaneous control group consisting of LT patients without RSV infection (n = 183) was included. One-year survival after the RSV infection was the primary endpoint. Median time from LT to RSV infection was 30 (1-155) months. Before RSV infection, the median decline in forced vital capacity (FVC) was 9.7 cc (-17.8 to 83 cc) or 0.29% (-1.4% to 4.6%) per month, while the forced expiratory volume (FEV1 ) decline was 7.5 cc (-8.8 to 58 cc) or 0.3% (-0.57% to 4.3%) per month with no statistically significant change after RSV infection. One-year survival among patients with RSV infection was 86.2% (75/87). Pre-infection diagnosis of chronic lung allograft dysfunction (CLAD; adjusted HR: 4.29, 1.08-17.0; P = .038) and FVC or FEV1 decline >10% during 6 months post infection (adjusted HR: 35.1, 3.26-377.1; P = .003) were independently associated with worse survival. On propensity score matched analysis, RSV infection was not associated with worse post-transplant survival (HR with 95% CI: 0.79, 0.47-1.34; P = .38). A majority of LT patients in the current cohort did not experience an alteration in the trajectory of FVC or FEV1 decline after developing RSV infection, and their post-transplant survival was not adversely impacted. Established CLAD at the time of RSV infection and post infection >10% decline in FVC or FEV1 are independently associated with worse survival after RSV infection.


OPTIMISE: a pragmatic stepped wedge cluster randomised trial of an intervention to improve primary care for refugees in Australia.
To examine whether primary care outreach facilitation improves the quality of care for general practice patients from refugee backgrounds. Pragmatic, cluster randomised controlled trial, with stepped wedge allocation to early or late intervention groups. 31 general practices in three metropolitan areas of Sydney and Melbourne with high levels of refugee resettlement, November 2017 - August 2019. Trained facilitators made three visits to practices over six months, using structured action plans to help practice teams optimise routines of refugee care. Change in proportion of patients from refugee backgrounds with documented health assessments (Medicare billing). Secondary outcomes were refugee status recording, interpreter use, and clinician-perceived difficulty in referring patients to appropriate dental, social, settlement, and mental health services. Our sample comprised 14 633 patients. The intervention was associated with an increase in the proportion of patients with Medicare-billed health assessments during the preceding six months, from 19.1% (95% CI, 18.6-19.5%) to 27.3% (95% CI, 26.7-27.9%; odds ratio, 1.88; 95% CI, 1.42-2.50). The impact of the intervention was greater in smaller practices, practices with larger proportions of patients from refugee backgrounds, recent training in refugee health care, or higher baseline provision of health assessments for such patients. There was no impact on refugee status recording, interpreter use increased modestly, and reported difficulties in refugee-specific referrals to social, settlement and dental services were reduced. Low intensity practice facilitation may improve some aspects of primary care for people from refugee backgrounds. Facilitators employed by local health services could support integrated approaches to enhancing the quality of primary care for this vulnerable population. Australian New Zealand Clinical Trials Registry, ACTRN12618001970235 (retrospective).


Sequence Analysis of 20,453 Severe Acute Respiratory Syndrome Coronavirus 2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern.
Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several variants of concern emerged globally, including the UK variant (B.1.1.7), the South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California variants of interest (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. On the basis of our extensive genome sequencing program involving 20,453 coronavirus disease 2019 patient samples collected from March 2020 to February 2021, we report identification of all six of these SARS-CoV-2 variants among Houston Methodist Hospital (Houston, TX) patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency (aggregate of 1.1%) in the population, they are geographically widespread. Houston is the first city in the United States in which active circulation of all six current variants of concern has been documented by genome sequencing. As vaccine deployment accelerates, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence, frequency, and medical impact of consequential variants and their patterns and trajectory of dissemination.


Molecular mechanism underlying transport and allosteric inhibition of bicarbonate transporter SbtA.
SbtA is a high-affinity, sodium-dependent bicarbonate transporter found in the cyanobacterial CO2-concentrating mechanism (CCM). SbtA forms a complex with SbtB, while SbtB allosterically regulates the transport activity of SbtA by binding with adenyl nucleotides. The underlying mechanism of transport and regulation of SbtA is largely unknown. In this study, we report the three-dimensional structures of the cyanobacterial Synechocystis sp. PCC 6803 SbtA-SbtB complex in both the presence and absence of HCO3- and/or AMP at 2.7 Å and 3.2 Å resolution. An analysis of the inward-facing state of the SbtA structure reveals the HCO3-/Na+ binding site, providing evidence for the functional unit as a trimer. A structural comparison found that SbtA adopts an elevator mechanism for bicarbonate transport. A structure-based analysis revealed that the allosteric inhibition of SbtA by SbtB occurs mainly through the T-loop of SbtB, which binds to both the core domain and the scaffold domain of SbtA and locks it in an inward-facing state. T-loop conformation is stabilized by the AMP molecules binding at the SbtB trimer interfaces and may be adjusted by other adenyl nucleotides. The unique regulatory mechanism of SbtA by SbtB makes it important to study inorganic carbon uptake systems in CCM, which can be used to modify photosynthesis in crops.


DNA assay based on monolayer-barcoded nanoparticles for mass spectrometry in combination with magnetic microprobes.
Mass spectrometry (MS) based methodology offers simple, fast and sensitive diagnosis. While it has become the predominate approach in biomolecular analysis, it has not been suitable for analyzing nucleic acid due to its low ionization efficiency. We report herein on a DNA assay based on monolayer-barcoded nanoparticles that were encoded with reporter mass molecules, which act as surrogate molecules for the matrix-assisted laser desorption/ionization time-of-flight MS (MALDI-TOF MS) identification of target DNA through mass spectrometry in combination with magnetic microprobes. This assay demonstrated high MS sensitivity, with the ability to detect target DNA at femtomolar (10(-15) M) levels. This inaugural effort using combined techniques is significant because it showed an extraordinary analytical capability for differentiating the single nucleotide polymorphism (SNP), which comprises the most abundant source of genetic variation in the human genome. We also report herein the feasibility of MS detection of two target DNAs that have the same mass but different nucleotide base composition, which classic MS methodology is inherently unable to differentiate.


Detection of hypoxia markers in the cerebellum after a traumatic frontal cortex injury: a human postmortem gene expression analysis.
The response to traumatic brain injury (TBI) is complex and induces various biological pathways in all brain regions that contribute to bad outcomes. The cerebellar hypoxia after a frontal cortex injury may potentiate the pathophysiological impacts of TBI. Therefore, a gene expression analysis was conducted to determine the influence of hypoxia on TBIs. Total RNA, including microRNAs, was isolated from the cerebellum of individuals who had died from severe frontal cortex injuries or due to natural causes of death (reference group). From a total of 19,596 genes, an average of 59.56% messenger RNAs (mRNAs) appeared expressed with 42 of them showing significant >2-fold differences of upregulated (n = 18) and downregulated (n = 24) genes. The validity of 14 candidate genes (with low p values and high fold differences or based on cited literature) was confirmed using qRT-PCR (Spearman correlation r(2) = 0.93). Only four genes appeared to be either upregulated (FOSB and IL6) or downregulated (HSD11B1 and HSPA12B). From a total of 667 microRNAs, altogether, 248 microRNAs appeared expressed with 13 of them showing significant differences in the mean gene expression. The combination of two mRNAs (HSPA12B/FOSB or IL6/HSD11B1) or two microRNAs (either miR-138/miR-744 or miR-195/miR-324-5p) completely discriminated both groups, a finding unaltered by potential confounders such as age at biosampling, survival time, and the postmortem interval. Cerebellar hypoxia markers are important to understand the pathophysiology of TBIs and could be used for therapeutic strategies or forensic purposes, e.g., to assess the severity of a brain injury.


The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction.
Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = -0.52 and -0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s' and e' tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e', r = -0.59 and -0.67, both P < 0.001), reduced cardiac output responses to exercise (r = -0.59 and -0.61, both P < 0.0001), and more severely impaired peak VO2 (r = -0.60 and -0.67, both P < 0.0001). Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search.


BCG vaccine: Worrying proposal for COVID-19.
Bacille Calmette-Guérin (BCG) vaccine is proven to be effective in protecting against severe tuberculosis. It has been suggested to be able to exert a non-specific beneficial effect as protection against other infectious diseases. The duration of protection against tuberculosis is estimated to be from 10 to 15 years, but the duration of the protection against other infections is not known, maybe up to 20 years, maybe much shorter than that. We don't know it for sure. BCG induced trained immunity paradigm is based on experimental models, cohort studies with low number of individuals, and some epidemiological data in which other possible interfering factors are not controlled. The titles and scopes of scientific articles should be cautiously considered as they can promote indications of getting vaccinated or revaccinated with BCG, before its effectiveness is confirmed and recommendations are published. Besides, revaccination with BCG can put at serious risk patients with primary or secondary immunodeficiency. Maybe BCG vaccine is effective in preventing COVID-19 deaths or reducing its severity, but may the effect of this vaccine be relevant even with poor health politics and assistance? It is very difficult to compare the epidemiologic data about COVID-19 in different countries. There are countless factors, mainly social and related to the healthcare system, which can be more decisive than the hypothesis of trained immunity induced by BCG. Until now, we can say that BCG's protective role is, at least, insufficient, given many other factors that corroborate SARS-CoV-2 infection and/or its severity.


Cardiac surgery in a fixed-reimbursement environment.
Hospital and physician services in Canada are funded by public (government) sources. This article will describe the practice of cardiac surgery in this setting. Federal legislation has prescribed the principles of accessibility, universality, comprehensiveness, portability, and public administration for essential healthcare services in Canada. Provincial and territorial governments are responsible for the provision of services, receiving federal tax and cash transfers that supplement provincial/territorial funds for hospital, physician, and community health services. Hospitals negotiate annually for global budgets. Physicians work as independent contractors in hospitals (and communities) and are usually paid as specified by fee-for-service contracts negotiated at intervals with governments. Cardiac surgical services have been planned conjointly with government. Forty-two centers in Canada serve a population of 28 million. All but three of these centers are located in tertiary teaching hospitals; all but one do more than 200 pumps annually. The rate of cardiac operations is 80 per 100,000 population. In Ontario, the Provincial Adult Cardiac Care Network makes recommendations to governments about the distribution of the 7,600 pumps annually (population, 11 million), rationalizing waiting lists based on an urgency rating scale. Patients requiring emergent/urgent operations are well served. The average waiting time for an elective cardiac operation is 10.5 weeks. The waiting list mortality is less than 0.5%. The Provincial Adult Cardiac Care Network also determines the placement of new programs and participates in creating hospital funding formulas developed from a combination of resource and acuity intensity weighting. Most surgeons hold full-time academic appointments but are funded largely by practice income. Surgical fees average $2,000 (Canada) per case. Overhead, including malpractice insurance, is approximately 45%. All Canadian patients enjoy reasonably timely access to good cardiac surgical care. Further constraints on physician compensation and (academic) hospital funding will compromise this balance.


Temperature and place associations with Inuit mental health in the context of climate change.
Climate change has important implications for mental health globally. Yet, few studies have quantified the magnitude and direction of associations between weather and mental health-related factors, or assessed the geographical distribution of associations, particularly in areas experiencing rapid climatic change. This study examined the associations between air temperature variables and mental health-related community clinic visits across Nunatsiavut, Labrador, Canada, and the place-specific attributes of these associations. Daily de-identified community clinic visit data were collected from the provincial electronic health recording system and linked to historical weather data (2012-2018). A multilevel, multivariable negative binomial regression model was fit to investigate associations between temperature variables and mental health-related community clinic visits across the region, adjusting for seasonality as a fixed effect and community as a random effect. A multivariable negative binomial model was then fit for each Nunatsiavut community, adjusting for seasonality. Mental health-related visits contributed to 2.4% of all 228,104 visit types across the study period; this proportion ranged from 0.6% to 11.3% based on community and year. Regionally, the incidence rate of mental health-related community clinic visits was greater after two weeks of warm average (i.e. above -5ᵒC) temperatures compared to temperatures below -5ᵒC (IRR-5≤5ᵒC = 1.47, 95% CI = 1.21-1.78; IRR6≤15ᵒC = 2.24, 95% CI = 1.66-3.03; IRR>15ᵒC = 1.73, 95% CI = 1.02-2.94), and the incidence rate of mental health-related clinic visits was lower when the number of consecutive days within -5 to 5ᵒC ranges (i.e. temperatures considered to be critical to land use) increased (IRR = 0.96; 95% CI = 0.94-0.99), adjusting for seasonal and community effects. Community-specific models, however, revealed that no two communities had the same association between meteorological conditions and the incidence rate of daily mental health-related visits. Regionally, longer periods of warm temperatures may burden existing healthcare resources and shorter periods of temperatures critical to land use (i.e. -5 to 5ᵒC) may present enjoyable or opportunistic conditions to access community and land-based resources. The heterogeneity found in temperature and mental health-related clinic visits associations across Nunatsiavut communities demonstrates that place quantitatively matters in the context of Inuit mental health and climate change. This evidence underscores the importance of place-based approaches to health policy, planning, adaptation, and research related to climate change, particularly in circumpolar regions such as Nunatsiavut where the rate of warming is one of the fastest on the planet.


Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients With Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach.
In the era of artificial intelligence and precision medicine, the use of quantitative imaging methodological approaches could improve the cancer patient's therapeutic approaches. Specifically, our pilot study aims to explore whether CT texture features on both baseline and first post-treatment contrast-enhanced CT may act as a predictor of overall survival (OS) and progression-free survival (PFS) in metastatic melanoma (MM) patients treated with the PD-1 inhibitor Nivolumab. Ninety-four lesions from 32 patients treated with Nivolumab were analyzed. Manual segmentation was performed using a free-hand polygon approach by drawing a region of interest (ROI) around each target lesion (up to five lesions were selected per patient according to RECIST 1.1). Filtration-histogram-based texture analysis was employed using a commercially available research software called TexRAD (Feedback Medical Ltd, London, UK; https://fbkmed.com/texrad-landing-2/) Percentage changes in texture features were calculated to perform delta-radiomics analysis. Texture feature kurtosis at fine and medium filter scale predicted OS and PFS. A higher kurtosis is correlated with good prognosis; kurtosis values greater than 1.11 for SSF = 2 and 1.20 for SSF = 3 were indicators of higher OS (fine texture: 192 HR = 0.56, 95% CI = 0.32-0.96, p = 0.03; medium texture: HR = 0.54, 95% CI = 0.29-0.99, p = 0.04) and PFS (fine texture: HR = 0.53, 95% CI = 0.29-0.95, p = 0.03; medium texture: HR = 0.49, 209 95% CI = 0.25-0.96, p = 0.03). In delta-radiomics analysis, the entropy percentage variation correlated with OS and PFS. Increasing entropy indicates a worse outcome. An entropy variation greater than 5% was an indicator of bad prognosis. CT delta-texture analysis quantified as entropy predicted OS and PFS. Baseline CT texture quantified as kurtosis also predicted survival baseline. Further studies with larger cohorts are mandatory to confirm these promising exploratory results.


Decrease in MAP3Ks expression enhances the cell death caused by hyperthermia.
Hyperthermia is a promising anticancer treatment modality. However, the molecular mechanism underlying the thermal sensitivity of tumor cells is largely unknown. The aim of this study was to clarify how biochemical changes triggered by heat stimulate antitumor activity. The expression levels of various MAPK members in HeLa cells with or without hyperthermia were evaluated by western blotting and RT-PCR. The intracellular Ca2+ concentration [Ca2+]i was monitored by digital imaging using CaTM-2 AM. An in vitro cleavage assay was used to determine whether calcium-dependent protease calpain cleaves MAPK components. Cell proliferation and clonogenicity were assessed in the absence or presence of siRNAs targeting MAPK members. Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2 but not of the downstream MAP2K and MAPK members. The hyperthermia-induced degradation of TAK1 and MEKK2 was rescued by either the proteasome inhibitor MG132 or the calpain inhibitor ALLN; however, RAF1 was not affected by the inhibitors. Heat induced down regulation of RAF1. Hyperthermia increased [Ca2+]i and calpain I expression. The calcium ionophore A23187 decreased TAK1 and MEKK2 levels. An in vitro cleavage assay demonstrated that TAK1 and MEKK2 are calpain I substrates. Knockdown of TAK1, RAF1 and MEKK2 suppressed cell proliferation and clonogenicity. Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2, without reduction of the downstream components in the MAP3K-MAP2K-MAPK cascade, by a calpain-dependent degradation pathway or transcriptional regulation. TAK1, RAF1 and/or MEKK2 play crucial roles in cell proliferation and clonogenicity and are potential molecular targets for hyperthermia.


Evaluation of VEGF-A in platelet and microRNA-126 in serum after coronary artery bypass grafting.
Platelet functions are thought to contribute to clinical outcomes after heart surgery. This study was conducted to assess the pivotal roles of vascular endothelial growth factor-A (VEGF-A) and microRNA-126 (miR-126) during coronary artery bypass grafting (CABG). Whole blood was collected for platelet isolation from 67 patients who underwent CABG surgery between July 2013 and March 2014. VEGF-A and miR-126 levels in serum, plasma, and platelets were measured at various time points and compared with clinical characteristics. The platelet count was decreased at 3 days after CABG. This dynamic change in platelet count was larger after conventional coronary artery bypass (CCAB) than off-pump coronary artery bypass (OPCAB). VEGF-A in the same number of platelets (IP-VEGF-A) was increased at 3 days after CABG, followed by an increase of VEGF-A in serum (S-VEGF-A) at 7 days after surgery. The miR-126-3p level in serum (S-miR-126-3p) increased rapidly after CABG and then decreased below preoperative levels. The IP-VEGF-A level on day 7 after CABG in patients with peripheral artery disease (PAD), who suffered from endothelial dysfunction, was higher compared with patients without PAD. Conversely, S-miR-126-3p on day 7 after surgery was lower in patients with PAD than in patients without PAD. Low levels of S-miR-126-3p due to endothelial dysfunction may lead to high IP-VEGF-A, which is closely related to complications after CABG.


Batch operation of biofilter--free-water surface wetland series for enhancing nitritation and anammox.
This study compared two series of ecologically engineered treatment systems for nitrogen removal by enhancing nitritation and anammox. Each treatment series had two biofilters followed by one free-water surface (FWS) wetland. The first series included biofilters packed with marble chips and demonstrated a development process in nitrogen removal through the first 26 cycles of weekly batch operation. The series then stabilized at an average ammonium removal rate of 19.2 g N/m3 x d and total nitrogen removal rate of 10.6 g N/m3 x d during the latest 22 cycles. The second series, which consisted of biofilters packed with pea pebbles, experienced decreasing nitrogen removal rates. Anammox and heterotrophic denitrification accounted for 77% and 23%, respectively, of the total nitrogen removal in the marble biofilters. Nitrogen removal rates in the FWS wetlands increased significantly with ammonium loading rates increasing up to approximately 30 g N/m3.d. Ammonium and total nitrogen removal followed zero-order reaction kinetics. The marble biofilter-wetland series reached an ammonium removal rate of 30.3 g N/m3 x d and total nitrogen removal rate of 23.0 g N/m3 x d through the latest 22 cycles of batch operation at the average ammonium loading rate of 56.4 g N/m3 x d.


Influencing factors on the tendency of general practitioners to join in urban family physician program: a cross-sectional survey on Iranian physicians.
Urban family physician program (UFPP) is initiated as pilot by policy makers as a main reform in future of primary health care in Iran. Despite an ongoing pilot implementation of this program from 2012, it remains a main question about providing sufficient number of general practitioners (GPs). This study aimed to investigate the factors which affect GPs' decision to join in the UFPP. In this national cross-sectional study a sample of 666 GPs, using convenience sampling, filled a self-report questionnaire. The multivariate logistic regression was applied to explore the demographic, practice and views determinants of the tendency of GPs to join in the UFPP. More than half of GPs (58.6%) participated in the study had a positive tendency to join in the UFPP. Older GPs (adjusted OR = 3.72; 95%CI 1.05-13.09), working in public sector (adjusted OR = 2.26; 95%CI 1.43-3.58), lower income level (adjusted OR = 6.69; 95%CI 2.95-15.16), higher economic expectations (adjusted OR = 2.08; 95%CI 1.19-3.63), and higher satisfaction from medicine profession (adjusted OR = 2.00; 95%CI 1.14-3.51) were the main factors which increased the GPs tendency to enter in UFPP. Decision for joining in the program is mainly affected by GPs' economic status. This clarifies that if the program can make them closer to their target income, they would be more likely to decide for joining in the program.


Comparative chemical studies on the quail (Coturnix coturnix japonica) egg ovalbumin.
1. Three components of quail ovalbumin were fractionated by gel filtration and ion exchange chromatography. 2. These were A1, A2, and A3, of which the major is A2. They contained phosphorus of 3, 2 and 1 residues, respectively. 3. The amino acid composition were higher in Lys, Asp, Ser, Thr and Gly, and lower in Arg, Glu and Ile than chicken ovalbumin. 4. The carbohydrate compositions were slightly higher in hexose and lower in hexosamine than chicken ovalbumin. 5. The molecular weight was determined to be 43,000, and the isoelectric point was pI 4.70.


Ultrastructural changes in neurons of medullary giant-cell nucleus in growing rat exposed to acute stress.
Ultrastructural transformations in neurons of the medullary giant-cell reticular nucleus of young rats during exposure to acute emotional and painful stress attest to activation of the protein synthesis system (nucleolar hypertrophy, well-developed elements of the granular endoplasmic reticulum, increased content of free ribosomes and polysomes) in the majority of cells and the appearance of organelle injuries in some these cells.


Force-dependent remodeling of cytoplasmic ZO-1 condensates contributes to cell-cell adhesion through enhancing tight junctions.
The physiological importance of biomolecular condensates is widely recognized, but how it is controlled in time and space during development is largely unknown. Here, we show that a tight junction protein ZO-1 forms cytoplasmic condensates in the trophectoderm (TE) of the mouse embryo before E4.0. These disappear via dissolution, and ZO-1 accumulates at the cell junction as the blastocyst cavity grows and internal pressure on TE cells increases. In contrast, this dissolution was less evident in TE cells attached to the inner cell mass because they receive weaker tensile forces. Furthermore, analyses using MDCK cells demonstrated that the ZO-1 condensates are generated and maintained by liquid-liquid phase separation. Our study also highlights that the dynamics of these condensates depends on the physical environment via an interaction between ZO-1 and F-actin. We propose that the force-dependent regulation of ZO-1 condensation contributes to the establishment of robust cell-cell adhesion during early development.


Non-polarizable collagen in dermatofibrosarcoma protuberans: a useful diagnostic aid.
The stroma in dermatofibrosarcoma protuberans (DFSP) stains with trichrome, but is not polarizable (birefringent, doubly refractile). The usefulness of polarizing neoplastic stroma as a diagnostic aid in distinguishing DFSP from dermatofibroma and fibromatosis was evaluated. Forty cases of dermatofibroma of all types, 12 cases of dermal fibromatosis, and 15 cases of DFSP were examined. None of DFSPs contained polarizable collagen, whereas 11 of the 12 (92%) fibromatoses and 35 of the 40 (88%) dermatofibromas did. Of the 5 dermatofibromas that did not polarize, all were composed primarily of round to polyhedral histiocytic cells, including foam cells, frequently surrounding small obliterated capillaries. Although not pathognomonic, the presence of nonpolarizable collagen appears to be an additional histological marker useful in differentiating DFSP from dermatofibroma and fibromatosis.


Extinction of the Edinburgh lineage of the allopolyploid neospecies, Senecio cambrensis Rosser (Asteraceae).
Senecio cambrensis is a new allopolyploid species, which originated independently in North Wales and in Edinburgh, Scotland. Despite extensive searches, the species has not been found growing at any of its previously recorded sites in Edinburgh or at other potential sites in the area since 1993. We have concluded that the Edinburgh lineage of S. cambrensis is now extinct and discuss possible causes of its extinction. The lineage was present in Edinburgh from at least 1974 and therefore survived in the wild for a minimum of 19 years. The species remains well established in parts of North Wales.


Health-related quality of life in men with osteoporosis: a systematic review and meta-analysis.
The increased social and economic burdens make osteoporosis in men an emerging public health issue. However, the quality of life among men with osteoporosis is still unclear. This systematic review and meta-analysis aimed to evaluate the health-related quality of life (HRQoL) among men with osteoporosis or osteoporotic fracture. PubMed, EMBASE, and the Cochrane Library database were systematically searched from inception to May 2021. Studies were included if they used validated questionnaires to measure HRQoL among osteoporotic men. A meta-analysis was performed using a random-effects model or fixed-effects model to calculate the standard mean difference (SMD) or mean difference (MD) with 95% confidential interval (95% CI). 14 studies involving 6338 male participants were chosen for systematic review, of which 10 were included in the meta-analysis. Men with osteoporosis had poorer global HRQoL and multiple dimensions of HRQoL than men without osteoporosis. Hip fracture, vertebral fractures, or wrist fractures dramatically impaired HRQoL of men, and physical function was declined even before hip fracture (SMD = -0.60, 95% CI, -0.82 to -0.39). Femoral and lumbar BMD was positively correlated with HRQoL, and a number of fragility fractures and time since fracture had negative effects on HRQoL. Effective anti-osteoporotic drugs could improve HRQoL of men. The health-related life quality of men was significantly impaired by osteoporosis and fracture of the hip, vertebral, or wrist. We should pay more attention to the diagnosis and treatment of male osteoporosis to improve the life quality of men.


Actin marker lines in grapevine reveal a gatekeeper function of guard cells.
Resistance to abiotic and biotic stress is a central topic for sustainable agriculture, especially in grapevine, one of the field crops with the highest economic output per acreage. As early cellular factors for plant defense, actin microfilaments (AF) are of high relevance. We therefore generated a transgenic actin marker line for grapevine by expressing a fusion protein between green fluorescent protein and the second actin-binding domain of Arabidopsis (Arabidopsis thaliana) fimbrin, AtFIM1. Based on this first cytoskeletal-marker line in grapevine, the response of AFs to phytopathogenic microorganisms could be followed in vivo. Upon inoculation with fluorescently labeled strains of phytopathogenic bacteria, actin responses were confined to the guard cells. In contrast, upon contact with zoospores of Plasmopara viticola, not only the guard cells, but also epidermal pavement cells, where no zoospores had attached responded with the formation of a perinuclear actin basket. Our data support the hypothesis that guard cells act as pacemakers of defense, dominating the responses of the remaining epidermal cells.


Metallococcus carri gen. nov., sp. nov., a novel member of the family Dermacoccaceae isolated from an automotive air conditioning system.
Strain designated DB0510T was isolated from an automobile evaporator core collected in Korea. Cells are gram-stain-positive, aerobic, and coccoid. The strain grew at 15-45 ℃, pH 5.0-8.5 and 0-8.0% (w/v) NaCl. Growth occurs on R2A, trypticase soy agar, Luria-Bertani agar, and nutrient agar. Phylogenetic analysis showed that the strain belongs to the family Dermacoccaceae and strain DB0510T was distinctly separated from validly named genera of this family. Signature nucleotides in 16S rRNA gene sequence revealed that the strain contained the Dermacoccaceae family-specific 16S rRNA signature nucleotides patterns. The major fatty acids were C17:0 and C17:1 cis-9. The only menaquinone was MK-8 (H4). The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, and two unidentified lipids. The diagnostic cell-wall amino acid at position 3 of the peptide subunit was found to be lysine. The cell-wall peptidoglycan contained alanine, aspartic acid, glutamic acid, glycine, lysine, and serine and thus the peptidoglycan type was concluded to be of A4α type with Lys-Gly-Ser-Asp interpeptide bridge. The genome size was 3.49 Mbp and G + C content of the genome DNA was 69.4 mol%. On the basis of the phenotypic, genomic, and chemotaxonomic characteristics, strain DB0510T is considered to represent a novel genus and species within the family Dermacoccaceae, for which the name Metallococcus carri gen. nov., sp. nov. is proposed. The type strain of Metallococcus carri is DB0510T (= KACC 19663 T = NBRC 113349 T).


Right atrial thrombus in constrictive pericarditis.
We describe right atrial thrombus complicated by tricuspid valve obstruction in a patient with constrictive pericarditis. This report highlights the role of surgical thrombectomy, and the investigation of constrictive pericarditis to exclude intra-cardiac thrombus.


RPB5-Mediating Protein Promotes Cholangiocarcinoma Tumorigenesis and Drug Resistance by Competing With NRF2 for KEAP1 Binding.
Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. RMP-overexpressing tumor cells exhibited enhanced tolerance to oxidative stress and apoptosis. Mechanistically, RMP competes with NRF2 for binding to the Kelch domain of KEAP1 (Kelch-like ECH-associated protein 1) through the E**E motif, leading to decreased NRF2 degradation via ubiquitination, thus increasing NRF2 nuclear translocation and downstream transactivation of antioxidant genes. This RMP-KEAP1-NRF2 axis promotes ICC tumorigenesis, metastasis, and drug resistance. Consistent with these findings, the RMP level in human ICC is positively correlated with the protein level of NRF2 and is associated with poor prognosis. These findings reveal that RMP is involved in the oxidative stress defense program and could be exploited for targeted cancer therapies.


Conversion of rice husk ash to zeolite beta.
White rice husk ash (RHA), an agriculture waste containing crystalline tridymite and alpha-cristobalite, was used as a silica source for zeolite Beta synthesis. The crystallization of zeolite Beta from RHA at 150 degrees C in the presence of tetraethylammonium hydroxide was monitored by XRD, FTIR and (29)Si MAS NMR techniques. It was found that zeolite Beta started to form after 12h and the complete crystallization of zeolite Beta phase was achieved after 2d. XRD, (29)Si MAS NMR and solid yield studies indicate that the transformation mechanism of silica present in RHA to zeolite Beta involves dissolution of the ash, formation of an amorphous aluminosilicate after 6h of crystallization, followed by dissolution in the mother liquor and final transformation to pure zeolite Beta crystals.


Projections of calcitonin gene-related peptide immunoreactive neurons in the vagal ganglia of the rat.
We have studied the connections of calcitonin gene-related peptide immunoreactive (CGRP-ir) sensory neurons in the ganglia of the vagus nerve. Many CGRP-ir neurons were identified in the jugular ganglion located in the cranial cavity, while fewer CGRP-ir neurons were found in the nodose ganglion located at the level of the jugular foramen. Application of Fluorogold to the cut end of the cervical vagus nerve resulted in many Fluorogold-labeled neurons in both the jugular and the nodose ganglia. Application of Fluorogold to the cut end of the subdiaphragmatic vagus nerve resulted in Fluorogold-labeled neurons mostly in the nodose ganglion with only a few labeled neurons in the jugular ganglion. Injection of Fluorogold into the heart resulted in Fluorogold-labeled neurons in both the jugular and the nodose ganglia. Double labeling combining CGRP immunohistochemistry and Fluorogold retrograde tracing showed that in cases of both the application of Fluorogold to the cut end of the cervical vagus nerve and the injection of Fluorogold into the heart, about 40% of the Fluorogold-labeled neurons in the jugular ganglion expressed CGRP-like immunoreactivity. These results indicate that many CGRP-ir neurons in the jugular ganglion innervate the cervical and thoracic visceral organs, including the heart, but only a few CGRP-ir neurons project to the abdominal visceral organs.


Effects of pulsed electromagnetic fields on cartilage apoptosis signalling pathways in ovariectomised rats.
The purpose of this study was to determine the effect of exposure to pulsed electromagnetic fields (PEMF) on modulation of the cartilage apoptosis signalling pathway in ovariectomised rats by monitoring the expression of mRNA of X-linked inhibitor of apoptosis protein (XIAP) and Bax. Forty-eight female Sprague-Dawley rats (250 ± 50 g) were randomly assigned to one of four groups: ovariectomy with PEMF treatment (PEMF group), ovariectomy with oestradiol (E2) treatment (oestrogen group), ovariectomy control (OVX group) and sham group. The ovariectomy model was prepared by surgical resection of the ovaries. After a three-month intermission, animals in the PEMF and oestrogen groups received treatment for 30 days; then serum 17β-oestradiol levels, chondrocyte morphology, and XIAP and Bax mRNA expression in knee joint cartilage were analysed. The results showed different chondrocyte formation in each group. Serum E2 content in the PEMF and oestrogen groups was significantly higher than in the OVX group (p < 0.05). The expression of XIAP mRNA in the PEMF and oestrogen groups was significantly up-regulated compared to the OVX group, while that of Bax mRNA was significantly down-regulated (p < 0.05). The correlation between E2 level and expression of Bax mRNA was positive (0.506) and statistically significant (p < 0.001). These data demonstrate that PEMF can up-regulate XIAP mRNA expression and down-regulate Bax mRNA expression in ovariectomised rats. Changes in XIAP and Bax mRNA expression may be the mechanism by which PEMF therapy affects postmenopausal osteoarthritis.


Tracheal intubation using the Airtraq video laryngoscope vs. Macintosh laryngoscope in patients with anticipated difficult intubation.
Various types of laryngoscopes have been invented to ameliorate the laryngoscopic view of the glottis, in normal and difficult airway, which helps anaesthesiologists to secure the airway during anaesthesia. In this prospective study, we aimed to compare the efficacy of the Airtraq video laryngoscope (AVL) and the Macintosh curved-blade laryngoscope (MBL), by using a common clinical assessment tool in patients with modified Mallampati class III and IV. A total of 60 patients [group A (AVL) and group M (MBL)] with modified Mallampati class III and IV listed for general anaesthesia were included. Each patient was intubated with either of the laryngoscope based on the group allotted. Time taken for tracheal intubation, grade of visualisation of glottis and need for manoeuvres to optimise the glottic view were compared. The degree of the glottic view during successful intubation attempt was easily appreciated in group A (p < 0.0001). Difference in the requirement of manoeuvres for optimising the laryngeal view/assisting in intubation as assessed by manoeuvre score was easily appreciated in group A (p < 0.010). Rise in heart rate and mean arterial pressure 1 and 2 min after intubation was more in group M than in group A (p < 0.0001). No event of any airway trauma, as evidenced by visible trauma to lips or oral mucosa or blood on laryngoscope, was observed with either of the laryngoscope. The novel AVL provides better intubation conditions with greater ease of intubation, better glottic view and lesser haemodynamic alterations during laryngoscopy than MBL.


Effect of a formative assessment intervention on nursing skills laboratory learning in a resource-constrained country.
Following a global trend, nursing education institutions in Malawi adopted the skills laboratory approach for the teaching and learning of essential nursing skills in the bachelor degree in nursing. Students and faculty expressed concern about the lack of regular and planned formative assessments that build the competencies required in the middle and senior years of study. The aim was to investigate the effect of a Formative Assessment Framework (FAF) on students learning in skills laboratories. A sequential, mixed methods design was chosen, starting with qualitative approach followed by a quantitative approach using a quasi-experimental design. Formative Assessment Framework (FAF) was developed after phase 1, validated and tested on the teaching of eight nursing procedures in phase 2. Quantitative data were collected from students (n = 160) for 6 weeks. Data were analysed using STATA software packages. Significant mean differences occurred between the pretest and posttest mean scores for seven procedures with a p-value of <0.05. The use of a Formative Assessment Framework had a significant effect on clinical teaching and learning. The findings indicate that the FAF has the capacity to improve the students' clinical preparation for competencies in the OSCE, which takes place in the skills laboratories.


Will the glass be half full or half empty? Brain potentials and emotional expectations.
Brainwave responses to words in context depend on semantic and world-knowledge expectations. Using the N400 component of event-related potentials as an index of word expectation, we explored brain responses to negatively and positively biased sentence frames randomly presented with their emotionally matched highly expected outcome or with violations that included switches to unexpected emotionally opposite outcomes or nonsense. Nonsense elicited large N400 responses regardless of the bias of the preceding sentence frame. Unexpected emotionally opposite outcomes elicited smaller than nonsense N400 responses and subsequent post-N400 frontal positivities, both unaffected by sentence frame bias. Over a midline-posterior scalp region, expected positive outcomes elicited larger N400 responses than negative ones, despite a high and matched word probability. Our study reveals that brains respond to unexpected emotional outcomes regardless of the direction of the emotional switch and hints at the possibility that the strength of positive and negative expectations may be adjusted before experiencing unexpected events.


Coordination and optimization of FDG PET/CT and COVID-19 vaccination; Lessons learned in the early stages of mass vaccination.
As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.


Innovation and new trends in critical trauma disease.
The management of critical trauma disease (CTD) has always trends the trends in military war experiences. These conflicts have historically revolutionized clinical concepts, clinical practice guidelines and medical devices, and have marked future lines of research and aspects of training and learning in severe trauma care. Moreover, in the civil setting, the development of intensive care, technological advances and the testing of our healthcare systems in the management of multiple victims, hasve also led to a need for innovation in our trauma care systems.


The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement.
Operative correction of ischemic mitral regurgitation (IMR) is associated with high risk approach. The objective of this retrospective study was to examine the interaction between the various underlying pathophysiologic mechanisms, the operative procedure, and their influence on short- and long-term outcomes. Over a 10-year period starting January 1984, mitral valve repair or replacement was performed on 150 patients with IMR. The age range was 42-86, mean 67, years; 71 (47%) were females; 139 (93%) were in NYHA functional class III or IV; 23 (15%) were reoperations; and 30 (20%) were in atrial fibrillation. Functional IMR due to annular dilatation or restrictive leaflet motion was present in 106 (71%), and structural IMR due to ruptured chordae or papillary muscle in 44 (29%). Mitral valve repair was performed in 94 (63%) with an annuloplasty ring employed in 80 (85%) patients. Mitral valve replacement was performed in 56 (37%), with 40 (71%) receiving a bioprosthesis (32 Hancock and 8 Carpentier-Edwards valves) and 16 (29%) a St. Jude valve. Coronary artery bypass graft surgery was performed in 139 (93%) patients. The overall operative mortality (OM) was 14/150 (9.3%). The OM for repair was 9.5% compared to 8.9% for replacement (P = NS). There was higher OM in the elderly, particularly in the repair group (P = 0.053), and a trend towards reduced OM in the recent years of the study (P = NS). No predictors of OM were identified by multivariate logistic regression analysis. Long-term follow-up was 98% complete and ranged from 2-120, mean 31.2, months for a total of 935 patient-years. The overall 5-year survival rate was 71 +/- 6%, with 91 +/- 5% for the replacement group compared to 56% +/- 10% for the repair group (P = 0.01). The functional subset of IMR who had a repair had the worse long-term survival (43 +/- 13%) compared to the structural/repair (76 +/- 13%) and structural/replacement groups (89 +/- 8%), and 92 +/- 7% for the functional/replacement group ((P = 0.0049). Multivariate logistic regression analysis identified the functional/repair group (hazards ratio 4.4; +/- 95%, confidence interval 1.6, 11, (P = 0.0031); and earlier years of surgery (hazards ratio 4.7; +/- 95% confidence interval 1.021; (P = 0.046) to be predictors of worse long-term survival. These results suggest that, in IMR, the underlying responsible pathophysiologic mechanisms appear to be the major determinants of survival, rather than the choice of the operative procedure.


Intra-Liver Allograft C3d-Binding Donor-Specific Anti-HLA Antibodies Predict Rejection After Liver Transplantation.
There is no doubt that antibody-mediated rejection (AMR) due to donor-specific anti-HLA antibodies (DSA) brings a poor outcome for liver transplant recipients. However, the relationship between intragraft DSA (g-DSA), complement-binding abilities, and AMR remains unknown. We enrolled a total of 20 liver transplant recipients who underwent protocol or episode graft biopsies in the mid to long term after liver transplant (median 48.5, range 6-198 months), and their status of g-DSA and complement 3d (C3d)-binding abilities was assessed with the graft immunocomplex capture fluorescence analysis (ICFA) technique. The prevalence of g-DSA was 15.0 % in liver transplant recipients (3/20), and serum DSA (s-DSA) also existed in 15.0% of recipients. The number of g-DSA+/s-DSA+, g-DSA+/s-DSA-, g-DSA-/s-DSA+, and g-DSA-/s-DSA- cases are 1, 2, 2, and 15, respectively. The g-DSA+ group demonstrated a significant high rejection activity index: 3.67 ± 1.53, compared with the g-DSA- group: 1.24 ± 1.15 (P = .0045). Moreover, C3d-binding reaction was notably higher in the g-DSA+ group (C3d index: 1.87 ± 0.38 vs 0.76 ± 0.35) (P < .0001). Overall, the g-DSA+ group was more associated with liver allograft rejection-not only AMR, but also T cell-mediated rejection (P = .031). These results suggest that the existence of g-DSA and intragraft C3d-binding reaction had a negative impact on the liver allografts, but in contrast s-DSA did not have any significant impact.


Pluripotency network in embryonic stem cells: maybe Leibniz was right all along.
The transcription factors Tcf3 and Nanog regulate many genes in embryonic stem cells, but according to two reports in this issue of Cell Stem Cell (Festuccia et al., 2012, Martello et al., 2012), only one, Esrrb, encoding an orphan nuclear hormone receptor, truly matters in the maintenance of self-renewal.


Evaluation of CPS compliance with legally required review of investigations by CAPs.
There is significant variability in Child Protective Services (CPS) utilization of medical-forensic experts. In 2016, Missouri legislation (HB 1877) mandated that CPS investigators submit screening forms to a Child Abuse Pediatrician (CAP) to review children < 4 years investigated for abuse. Compliance with this mandate is unknown. To measure compliance with HB 1877, hypothesizing that urban counties would have better compliance than rural counties. This retrospective study included evaluation of screening forms completed by Missouri CPS and submitted to Missouri CAPs during February, July and September of 2017. Compliance was measured in three ways. Compliance Measure 1 (CM1) was the number of screening forms versus the number of eligible CPS investigations. Compliance Measure 2 (CM2) was the average number of days from an abuse report until form submission, and Compliance Measure 3 (CM3) was the percentage of forms with complete information. Urban and rural counties were classified by 2010 census data. t-Tests were used to compare compliance measures between urban and rural counties. Overall compliance with CM1 was 69% with 1496 screening forms submitted and 2170 child maltreatment investigations for children less than 4 years of age. For CM2, mean days from abuse report to form submission was 30 days. For CM3, 60.5% of statewide forms were complete. There was no significant difference between rural and urban county compliance. Limited compliance with HB 1877 demonstrates the necessity of continued monitoring and improvement for optimal efficacy of legal mandates.


[Antidepressive agents and suicidal tendencies].
In the last 2 years the discussions on the question whether antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) can lead to suicidality, aggression and violence, flared up again. The available data on the problem, which has been discussed since the introduction of this substance group in the late 1980s, is presented in this article. A systematic literature search showed that a scientific consensus exists that the benefits of antidepressant pharmacotherapy in general, and of treatment with SSRIs and selective serotonin/norepinephrine reuptake inhibitors (SSNRIs) in particular, outweigh the risks of their use. This also applies to the treatment of children, adolescents and young adults. The agitation occasionally occurring at the beginning of treatment, which can be experienced as aversive in susceptible patients, can intensify or even trigger suicidal thoughts or impulses. This has to be paid particular attention to especially at the beginning of treatment. It is recommended that the indications for antidepressant pharmacotherapy of children, adolescents and young adults are assessed by a specialist.


Engineering FRET constructs using CFP and YFP.
Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Here we discuss how to engineer constructs for FRET between the cyan- and yellow-emitting variants of green fluorescent protein (GFP) from Aequorea victoria (CFP and YFP, respectively). Throughout this chapter, we stress the fact that FRET is highly sensitive to the relative orientation and distance between the donor and the acceptor. The chapter consists of two parts. First, we discuss FRET-based indicators encoded by single genes, which were developed in our laboratory. In this approach, a number of different constructs can be made for a comparative assessment of their FRET efficiencies. For example, the length and sequence of the linker between the fluorescent protein and the host protein should be optimized for each specific application. In the second part, we describe the use of long and flexible linkers for engineering FRET constructs, including an introduction to a general and efficient tool for making successful fusion proteins with long and flexible linkers. When CFP and YFP are fused through floppy linkers to two protein domains that interact with each other, the two fluorescent proteins will associate due to the weak dimerization propensity of Aequorea GFP, which results in moderate FRET. This approach has become even more powerful due to the construction of a new pair of fluorescent proteins for FRET: CyPet and YPet.


Patterns of Practice and Improvements in Survival Among Patients With Stage 2/3 Rectal Cancer Treated With Trimodality Therapy.
This study quantifies the trends in trimodality therapy use and its association with pathologic stage and overall survival of patients with rectal cancer at the population level. To describe changes between 2006 and 2016 in the sequence and use of chemotherapy/radiation therapy (C/RT), multiagent (MA) chemotherapy, and total neoadjuvant therapy (TNT) for patients with stage 2/3 rectal cancer and identify associations with pathologic stage and survival over time. This retrospective cohort analysis included patient records from the National Cancer Database between 2006 and 2016. Of 110 372 patient records, 77 905 were excluded owing to not receiving trimodality therapy and other predefined exclusion criteria. The final analytic cohort comprised 32 467 patients records treated with trimodality therapy, with 24 297 considered in the survival analysis. Data analysis was performed between June 2020 and December 2021. Trimodality therapy was defined as including all of the following: definitive surgery; radiation therapy (RT), alone or in combination with chemotherapy; and neoadjuvant/adjuvant single-agent (SA) or multiagent (MA) chemotherapy independent of RT. Using Cox multivariable survival analyses across demographics, surgery type, stage, year of diagnosis, and facility type, treatment groups were allocated as the following: group A: TNT (n = 8883 [27%]); group B: preoperative C/RT plus postoperative SA chemotherapy (n = 5967 [18%]); group C: preoperative C/RT plus postoperative MA chemotherapy (n = 12 926 [40%]); and group D: postoperative C/RT plus MA chemotherapy (n = 4689 [14%]). The final analytic cohort comprised 32 467 patients (mean [SD] age at diagnosis, 57.6 [11.6] years; 12 549 [38.7%] women and 19 918 [61.3%] men). Comparing 2016 with 2006, treatment shifted to fewer patients receiving postoperative C/RT (group D) (28% vs 8%; P < .001), and more preoperative C/RT and postoperative MA chemotherapy (group C) (24% vs 45%; P < .001) being used. While clinical stage 2 and 3 distribution remained unchanged, pathologic downstaging was observed to stages 0, 1, 2, and 3: 0.60%, 10%, 31%, and 57% vs 2.8%, 22%, 29%, and 45%, from 2006 to 2015, respectively (P < .001). More recent year of diagnosis was associated with an adjusted hazard ratio of 0.77 (95% CI, 0.67-0.87) for mortality within 36 months after diagnosis (2015 vs 2006). In this cohort study, the shift toward preoperative C/RT and lower pathologic stage was associated with improved overall survival in stage 2/3 rectal cancers.


Regulation by thyroid hormone of the synthesis of a cytosolic thyroid hormone binding protein during liver regeneration.
To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58-M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver.


Protein metabolism during germination of Bacillus megaterium spores. I. Protein synthesis and amino acid metabolism.
Protein synthesis during germination of Bacillus megayerium spores can be divided into two stages. During the first 75 min of germination (Stage I) endogenous nitrogen reserves are sufficient to support protein synthesis, and most amino acids are generated by proteolysis of dormant spore protein. The amino acids produced are excreted initially from the spore, but then reabsorbed and partially utilized for protein synthesis. Significant amino acid metabolism also occurs during Stage I, utilizing enzymes already present in the dormant spore. The biosynthesis of a number of amino acids is low or absent during Stage I due to the absence of biosynthetic enzymes. Subsequently, at defined times in Stage I, these missing enzymes are synthesized and amino acid biosynthesis is initiated. By the beginning of Stage II (from 75 min on) the developing spore has regained the capacity for synthesis of all amino acids and requires an exogenous nitrogen source for rapid protein synthesis.


Rapid Aqueous Synthesis of Large-Size and Edge/Defect-Rich Porous Pd and Pd-Alloyed Nanomesh for Electrocatalytic Ethanol Oxidation.
In this work, a facile aqueous synthesis strategy was used (complete in 5 min at room temperature) to produce large-size Pd, PdCu, and PdPtCu nanomeshes without additional organic ligands or solvent and the volume restriction of reaction solution. The obtained metallic nanomeshes possess graphene-like morphology and a large size of dozens of microns. Abundant edges (coordinatively unsaturated sites, steps, and corners), defects (twins), and mesopores are seen in the metallic ultrathin structures. The formation mechanism for porous Pd nanomeshes disclosed that they undergo oriented attachment growth along the ⟨111⟩ direction. Owing to structural and compositional advantages, PdCu porous nanomeshes with certain elemental ratios (e. g., Pd87 Cu13 ) presented enhanced electrocatalytic performance (larger mass activity, better CO tolerance and stability) toward ethanol oxidation.


Cardiac Autonomic Alteration and Metabolic Syndrome: An Ambulatory ECG-based Study in A General Population.
Metabolic syndrome (MetS) has been associated with chronic damage to the cardiovascular system. This study aimed to evaluate early stage cardiac autonomic dysfunction with electrocardiography (ECG)-based measures in MetS subjects. During 2012-2013, 175 subjects with MetS and 226 healthy controls underwent ECG recordings of at least 4 hours starting in the morning with ambulatory one-lead ECG monitors. MetS was diagnosed using the criteria defined in the Adult Treatment Panel III, with a modification of waist circumference for Asians. Conventional heart rate variability (HRV) analysis, and complexity index (CI1-20) calculated from 20 scales of entropy (multiscale entropy, MSE), were compared between subjects with MetS and controls. Compared with the healthy controls, subjects with MetS had significantly reduced HRV, including SDNN and pNN20 in time domain, VLF, LF and HF in frequency domain, as well as SD2 in Poincaré analysis. MetS subjects have significantly lower complexity index (CI1-20) than healthy subjects (1.69 ± 0.18 vs. 1.77 ± 0.12, p < 0.001). MetS severity was inversely associated with the CI1-20 (r = -0.27, p < 0.001). MetS is associated with significant alterations in heart rate dynamics, including HRV and complexity.


Palliative Chemotherapy and the Surgical Oncologist.
Outcomes are improving for patients with advanced cancer, in part because of increasing diversity and efficacy of systemic therapy, often described as "palliative chemotherapy." Patients with advanced cancer receiving systemic treatment sometimes require surgical interventions, and their cancer care teams must collaborate to optimally manage medical and surgical challenges while also considering patients' goals and values. Structured communication can overcome the inherent ambiguity of the term "palliative chemotherapy" and facilitate optimal quality of care and quality of life for patients with advanced cancer who require surgical interventions.


Regulatory Roles of the Notch Signaling Pathway in Liver Repair and Regeneration: A Novel Therapeutic Target.
The liver is one of the significant regenerative organs in the body. Nevertheless, underlying molecular mechanisms regulating liver repair and regeneration following resection or damage remain largely unknown. The Notch signaling pathway is a profoundly evolutionarily well-conserved cell signaling system that mostly involves developing multicellular organisms. Malfunctions in this pathway lead to the progression of several liver disorders, including hepatoblastoma (HB), cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). The Notch pathway plays a fundamental role in cell fate during the embryonic stage's progression to the adult stage in liver tissue. Modulation of Notch signaling may be used in many patients who succumb to cirrhosis due to chronic hepatitis by virus infection. This review describes the underlying mechanisms of the Notch signaling pathway in liver development and regeneration briefly and discusses how this pathway leads to the betterment of liver disorders in the clinic.


Salivary flow and composition in elderly patients referred to an acute care geriatric ward.
The purpose of this investigation was to study oral health and salivary aspects of the frail elderly. The study hypothesis was that elderly patients with many concomitant diseases and drugs would have different salivary secretion rates and biochemical constituents than healthier patients. The stimulated flow, pH buffering capacity, and biochemical constituents were analyzed from salivas of 169 elderly subjects (51 men and 118 women, mean age 81.2 years, range 69 to 96 years) admitted to an acute geriatric ward because of sudden worsening of their health. Common statistical methods were used to analyze the differences among patient groups. The patients were grouped according to the number of concomitant diseases and daily used drugs and on the basis of salivary flow rate values. Reduced salivary flow (< 0.7 ml/min) was found in 48% of the men and 62.5% of the women, and a low buffering capacity was found in 31.9% of the men and 36.7% of the women. Age did not significantly affect the salivary flow rate. The factors that showed the strongest influence on salivary flow were endocrinologic diseases, ophthalmologic and respiratory drugs, and potassium chloride. Salivary immunoglobulin A and immunoglobulin M concentrations were significantly higher in older patients. Immunoglobulin A, lysozyme, and amylase concentrations were significantly higher in older patients taking many drugs. Patients with many concomitant diseases had significantly higher salivary urea concentrations than healthier patients. Edentulous patients had significantly higher salivary immunoglobulin A, immunoglobulin M, lysozyme, and amylase concentrations. In this study, hyposalivation was a frequent observation, and the elderly who took many drugs and had several systemic diseases had higher concentrations of most of the analyzed biochemical constituents.


Unusually sulfated and oxygenated steroids from Withania somnifera.
Four (1, 8-10) and six known (2-7) withanolides were isolated from the leaves of Withania somnifera. Among the new compounds, 10 possessed the rare 3-O-sulfate group with the saturation in A ring and 9 contained unusual 1,4-dien-3-one group. Compound 8 did not have usual 2,3 unsaturation in A ring while 1 had the rare C-16 double bond. The structures of all the compounds were elucidated by spectroscopic methods and chemical transformation.


Groundwater arsenic contamination: impacts on human health and agriculture, ex situ treatment techniques and alleviation.
Groundwater is consumed by a large number of people as their primary source of drinking water globally. Among all the countries worldwide, nations in South Asia, particularly India and Bangladesh, have severe problem of groundwater arsenic (As) contamination so are on our primary focus in this study. The objective of this review study is to provide a viewpoint about the source of As, the effect of As on human health and agriculture, and available treatment technologies for the removal of As from water. The source of As can be either natural or anthropogenic and exposure mediums can either be air, drinking water, or food. As-polluted groundwater may lead to a reduction in crop yield and quality as As enters the food chain and disrupts it. Chronic As exposure through drinking water is highly associated with the disruption of many internal systems and organs in the human body including cardiovascular, respiratory, nervous, and endocrine systems, soft organs, and skin. We have critically reviewed a complete spectrum of the available ex situ technologies for As removal including oxidation, coagulation-flocculation, adsorption, ion exchange, and membrane process. Along with that, pros and cons of different techniques have also been scrutinized on the basis of past literatures reported. Among all the conventional techniques, coagulation is the most efficient technique, and considering the advanced and emerging techniques, electrocoagulation is the most prominent option to be adopted. At last, we have proposed some mitigation strategies to be followed with few long and short-term ideas which can be adopted to overcome this epidemic.


Uterine transplantation and IVF for congenital or acquired uterine factor infertility: A systematic review of safety and efficacy outcomes in the first 52 recipients.
Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.


Early grey crescent formation experimentally induced by cycloheximide in the axolotl oocyte.
The effects of cycloheximide (CH) on grey crescent formation in artificially maturedAmbystoma mexicanum oocytes were determined. CH induced grey crescent formation after a few hours, especially after a 45° to 90° rotation from the vertical animal-vegetal axis. With low concentrations of CH (about 0.5 ng/oocyte), meiosis was still able to proceed normally to the stable second metaphase stage, but higher concentrations blocked it after 1st polar body extrusion and an interphasic nucleus appeared. Such effects were compared to those of inactone, an analogue of cycloheximide, which as a pure substance does not inhibit protein synthesis, but still contained a small amount of CH in the available samples. It is concluded that grey crescent formation can occur in non-activated oocytes. The effects of cycloheximide might be due to partial inhibition of protein synthesis and the presence of a proteinic inhibitor of the symmetry reaction in the normal oocyte is suggested.


Preparation and evaluation of various banana-based biochars together with ultra-high performance liquid chromatography-tandem mass spectrometry for determination of diverse pesticides in fruiting vegetables.
Biomass, originates from plant- or animal-based materials with a huge potential to be reused. Here we report a simple, rapid and inexpensive method for preparation of modified biochars derived from the banana peel followed by their applications in pipette-tip micro solid-phase extraction (PT-µSPE). Due to the contribution of various effective parameters on modification of banana peel biochars (BPBs), Taguchi design was used to optimize activation temperature, activation repetition, treatment material and impregnation ratio. Efficiency of the prepared BPBs were studied by extraction of twelve various pesticides, as model analytes with an extended range of log P values (1.4-5.7), followed by their determination using ultra-high performance liquid chromatography-tandem mass spectrometry. After finding the most suitable BPB, the affecting parameters on the PT-µSPE performance were optimized. Accordingly, the LOD values of 0.03-10 µg L-1, linear dynamic range of 0.1-200 µg L-1 and a range of RSD values of 5.3-19% were obtained. Eventually, five fruiting vegetables were analyzed and screened for their possible contaminations. Among the tested pesticides, chlorpyrifos, diazinon, malathion, phosalone, propargite and thiophanate-methyl were detected in eggplant, sweet pepper, zucchini and tomato.


Progranulin genetic screening in frontotemporal lobar degeneration patients from central Italy.
Recently, mutations in the progranulin gene (GRN) were reported to account for the vast majority of Frontotemporal lobar Degeneration (FTLD) and a growing number of reports describe the implication of this gene in the development of the FTLD pathology with a significant variation in clinical features. To better clarify the contribution of GRN mutations to Italian FTLD, we screened 381 subjects: 171 cases and 210 healthy subjects, all from Central Italy, particularly of Tuscan origins. GRN gene was analyzed using High Resolution Melting Analysis and automated Genetic Analyzer. Human Progranulin ELISA Kit was employed to determine the plasma progranulin levels. The screening showed a total of six genetic variants in the GRN gene: 3 pathogenic and 3 non pathogenic in 13 out of 171 patients. The rare intronic variant IVS2 +7 G > A was found in one patient. The pathogenetic mutation, p.T272SfsX10, is confirmed as the most common GRN mutation in Italian FTLD patients with a frequency in our study of 2.32%. Moreover, we identified the first Italian patient with the p.R493X mutation, to date described in 43 families worldwide. Our data report, for the first time, the occurrence of GRN mutations in Tuscany, Central Italy, confirming that genetic variations in this gene could be a considerable genetic cause of FTLD and that genetic screening might be useful both in familial and sporadic FTLD patients.


Orientation discrimination for bars defined by orientation texture.
A texture pattern consisting of short (0.2 deg) lines contained a 5.0 deg x 1.4 deg texture-defined bar. The bar was rendered visible by the difference in orientation (2 theta) between the lines inside the bar and outside the bar. Orientation-discrimination threshold for the texture-defined bar was a U-shaped function of 2 theta over the range 2 theta = 0 degree to 2 theta = 180 degrees. The lowest threshold was at 2 theta = 90 degrees, and was 0.57 degrees for both subjects tested. This threshold was little different from the lowest values of threshold for motion-defined bars, disparity-defined bars, and colour-defined gratings reported elsewhere. A luminance-defined bar was created by switching off all texture lines outside the texture-defined bar. Orientation-discrimination threshold fell to a limiting value as the luminance contrast of this bar was progressively increased. The lowest value of orientation discrimination for the luminance-defined bar (0.42 degrees and 0.35 degrees for the two subjects) was not greatly less than the lowest value for the texture-defined bar.


Barriers to cancer screening.
Many barriers to cancer screening have been summarized and discussed. Barriers have been documented in all patient populations, but some groups such as ethnic minorities and the elderly face unique barriers. The barriers to cancer screening, are multifactorial, but much of the responsibility for change must lie with health care providers and the health care delivery industry. This is not to free the patient of all responsibility, but some significant barriers are beyond their direct control. Take, for example, socioeconomic status, disease knowledge, and culturally related perceptions and myths about cancer detection and treatment. The health care industry must do a better job identifying and overcoming these barriers. The significant effects of provider counseling and advice must not be underestimated. Patients must first be advised, and then further actions must be taken if they reject the screening advice. Did they refuse adherence to recommendations because they do not view themselves as susceptible, because of overwhelming personal barriers, or because of a fatalistic attitude toward cancer detection and treatment? If that is the case, physicians and health care institutions must attempt to change perceptions, educate, and personalize the message so that patients accept their disease susceptibility [table: see text]. Multiple patient and provider risk factors have been identified that can be used to target patients particularly at high risk for inadequate cancer screening and providers at high risk for performing inadequate screening. Research has clearly demonstrated the effectiveness of interventions to improve tracking of patient and physician compliance with screening recommendations. Further research is needed to show the impact of managed-care penetration and payer status on screening efforts, and incentive schemes need to be tested that reward institutions and third-party payers who develop uniform standards and procedures for cancer screening. The greatest responsibility lies with medical and health care institutions and those who determine the priorities of these institutions. Patient and physician barriers to mass cancer screening can be addressed by institutional support. If the quality of care delivered by providers, group practices, managed-care organizations, and HMOs is assessed with priority given to the regularity and consistency with which basic screening procedures are performed, cancer screening will undoubtedly receive greater attention in the clinic. Medical institutions must collaborate to develop standards for cancer screening with attention to the cost-effectiveness of various screening techniques to determine how limited resources can best be spent in cancer control. Such efforts should keep in mind "that a very small change implemented over a broad population may have a greater effect in absolute numbers than a large level of change applied in a small segment of the population."


Is coeliac disease screening in risk groups justified? A fourteen-year follow-up with special focus on compliance and quality of life.
The benefits of serologic screening for coeliac disease in asymptomatic individuals are debatable. To investigate dietary compliance, quality of life and bone mineral density after long-term treatment in coeliac disease patients found by screening in risk groups. The study comprised 53 consecutive screen-detected coeliac patients diagnosed 14 years (median) ago. Dietary compliance was assessed by interview, 4-day food record and serology. Quality of life was evaluated by the Psychological General Well-Being and SF-36 questionnaires, gastrointestinal symptoms by the Gastrointestinal Symptom Rating Scale and bone mineral density by dual-energy x-ray absorptiometry. Comparisons were made to 44 symptom-detected-treated coeliac patients, 110 non-coeliac subjects and the general population. A total of 96% of screen-detected and 93% of symptom-detected coeliac patients adhered to a strict or fairly strict gluten-free diet. In screen-detected patients, quality of life and gastrointestinal symptoms were similar to those in symptom-detected patients or non-coeliac controls and bone mineral density was similar to that in the general population. Long-term dietary compliance in screen-detected patients was good. Quality of life and bone mineral density were comparable with those in non-coeliac subjects and the general population. Active screening in coeliac disease risk groups seems to be reasonable rather than harmful.


Contact sensitization of children: a two-decade years history in Naples.
Contact sensitization (CS) and allergic contact dermatitis (ACD) were once thought to be rare in children. The aim of our study was to assess CS and ACD in children affected by eczematous conditions referring to our contact and occupational dermatoses service, and to compare the obtained data to the results of a similar study performed in our Department in late Eighties. A retrospective analysis of Patch Test data from the Database of Contact Allergy of the Department of Dermatology, University Federico II of Naples, was performed. Moreover results were compared to previous data recorded and analyzed in our center. Of the 416 examined patients, tested during 2005-2010 with the pediatric series, 37.5% developed at least one positive reaction, 15.4% was diagnosed with ACD. The most common allergen was nickel sulphate (16.8%) and the most frequently involved body sites were head and neck (16.3%). Compared to the 1989 study data, our current results highlighted an increase of CS (P<0.001) and ACD diagnosis (P<0.01). ACD and CS are significantly increased during the last 20 years in our young patients population. The widespread chemical use and premature adult-like attitude may be responsible for earlier and extended exposure to sensitizers.


Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: relation to pulmonary hemodynamics.
In 12 patients who underwent the Fontan procedure for complex cardiac anomalies, lung scanning with xenon-133 was performed to assess the intrapulmonary ventilation-perfusion distribution, and comparison was made with a control group. All data were then analyzed in relation to either pre- or postoperative pulmonary hemodynamic data. In ventilation scans, the intrapulmonary distribution in the right lung was almost normal. In perfusion scans, an abnormal increased upper to lower lobe perfusion ratio greater than the normal value found in the control group was noted in seven patients (58.3%). There was a significant correlation (p less than 0.02) between the upper to lower lobe perfusion ratio and postoperative pulmonary vascular resistance. Furthermore, this perfusion ratio correlated inversely with the preoperative (p less than 0.005) and postoperative (p less than 0.02) right pulmonary artery area index, defined as the ratio of cross-sectional area to the normal value. Of five patients with less than 90% arterial oxygen saturation, four showed an abnormal distribution of pulmonary blood flow greater than the normal perfusion ratio. No patient had evidence of a pulmonary arteriovenous fistula by the echocardiographic contrast study. These results suggest that abnormal distribution of pulmonary blood flow to the upper lung segment may develop in patients after the Fontan procedure, and that insufficient size of the pulmonary artery before operation and the consequent postoperative elevation of pulmonary vascular resistance may be responsible for this perfusion abnormality.


Dynamic associations between temporal behavior changes caused by the COVID-19 pandemic and subjective assessments of policymaking: A case study in Japan.
To design effective policies against COVID-19, there is a need for more evidence-based research. However, associations between actual policies and temporal behavior changes have remained underexplored. To fill this important research gap, a nationwide retrospective life-oriented panel survey on individuals' behavior changes from April to September 2020 was implemented in Japan. Reliability of information sources, risk perceptions, and attitudes toward policymaking were also investigated. Valid data were collected from 2643 respondents residing in different parts of the country. Risks were reported about general infections and public transport use. Attitudes toward policymaking were mainly about policymaking capacity and PASS-LASTING based policy measures. A dynamic structural equation model (DSEM) was developed to quantify dynamic associations between individuals' behavior changes over time and subjective assessments (i.e., attitudes) of policymaking. Survey results revealed that behavior changes are mostly characterized by avoidance behaviors. Modeling estimation results showed a statistically-significant sequential cause-effect relationship between accumulated behavior changes in the past, subjective factors, and the most recent behavior changes. The most recent behavior changes are mostly affected by accumulated behavior changes in the past. Effects of subjective assessments of policymaking on the most recent behavior changes are significant but moderate. Among attitudes toward policymaking, attitudes toward policymaking capacity are more influential than willingness to follow PASS-LASTING based policy measures. High risks of using public transport are found to significantly influence the most recent behavior changes, together with other risk perception factors. Insights into effective COVID-19 policymaking are summarized.