Prospectives in cleft lip and palate repair.
A recent focus on fetal surgery has raised the possibility of fetal cleft lip and palate repairs. Because of the fetus's marked plasticity, fetal repairs may have results that more closely approximate normality. Furthermore, the impact on cost management could be dramatic with a decreased need for extensive postoperative care, orthodontia, and speech therapy. This article considers the future prospects of intrauterine cleft lip repair as the next generation of surgical advances.


Correction to "Green-Based Approach to Synthesize Silver Nanoparticles Using the Fungal Endophyte Penicillium oxalicum and Their Antimicrobial, Antioxidant, and In Vitro Anticancer Potential".
[This corrects the article DOI: 10.1021/acsomega.2c05605.].


Precise determination of photon emission probabilities for the main X- and gamma-rays of 226Ra in equilibrium with daughters.
Within the context of a joint project between VNIIM (D.I. Mendeleyev Institute for Metrology) and LNHB (Laboratoire National Henri Becquerel), special 226Ra sources were prepared by VNIIM in order to determine as accurately as possible the absolute photon emission probabilities for the main X- and gamma-rays following the decay of 226Ra and daughters. The main purpose of this work was to supplement a previous joint study by Laboratorio Nacional de Metrologia das Radiaçoes Ionizantes (LNMRI) and LNHB to determine their relative values. Some specific point sources were produced for alpha-spectrometry measurements that were undertaken at VNIIM and also for gamma-ray spectrometry studies at VNIIM and LNHB. The 226Ra activity for the gamma-spectrometric sources was measured relative to the alpha-spectrometric sources by comparing the counts of the main gamma-rays. The total uncertainty of the activity for these sources was 0.2% (k = 1). Using calibrated germanium detectors, several X- and gamma-ray spectra were analyzed to determine the absolute photon emission probabilities of 226Ra in radioactive equilibrium with daughters. The results are presented and compared to other published values.


Developmental changes in the enzymatic capacity for reduction and oxidation of alpha-ketoadipate in rat liver, heart, kidney, and brain.
alpha-Ketoadipate, an intermediate common to lysine and tryptophan metabolism, is a substrate for both alpha-ketoadipate reductase (alpha-KAR) and alpha-ketoadipate dehydrogenase (alpha-KADH). A comparison was made of the activities of these two enzymes in liver, heart, kidney, and brain of rats during the period from 5 days before birth to 56 days after birth. In general, both enzymes increased in activity during development in all tissues tested; however, different patterns of increase were observed (Figs. 1 and 2). The ratio of alpha-KADH to alpha-KAR (on the basis of activity/g tissue) did not change significantly in liver until day 10 and then increased 6.6-fold (from 0.08 to 0.53) in the period from day 10 to day 28. For other tissues the ratios increased 5.5-fold in hearts (from 0.2 to 1.1), 12-fold in kidney (from 0.2 to 2.4), and 5.3-fold in brain (from 0.3 to 1.6) during the period from day -5 to day 56. These results suggest that alpha-KAR has a major role in the metabolism of lysine and tryptophan during development.


Deconstructing the neuropathic pain phenotype to reveal neural mechanisms.
After nerve injury maladaptive changes can occur in injured sensory neurons and along the entire nociceptive pathway within the CNS, which may lead to spontaneous pain or pain hypersensitivity. The resulting neuropathic pain syndromes present as a complex combination of negative and positive symptoms, which vary enormously from individual to individual. This variation depends on a diversity of underlying pathophysiological changes resulting from the convergence of etiological, genotypic, and environmental factors. The pain phenotype can serve therefore, as a window on underlying pathophysiological neural mechanisms and as a guide for developing personalized pain medicine.


Application of analytical isotachophoresis in the study of platelet membrane proteins in patients with chronic myeloproliferative disorders.
The supernatants of dispase-treated platelets from normal persons and patients with myeloproliferative disorders were analysed by capillary isotachophoresis. The examined myeloproliferative disorders were three cases of chronic myelogeneous leukemia, one case of chronic neutrophilic leukemia, one case of essential thrombocythemia and one case of polycythemia vera. An additional peak was revealed in the samples from the patients with chronic myelogeneous leukemia. Platelets from the other three patients showed no additional bands. Isotachophoresis will be useful not only to analyse the superficial peptide on the cell membrane but also to define the peptide associated with malignant transformation.


Custom-made denture teeth and denture base material for removable partial dentures.
A method that uses Isosit material to fabricate custom-made denture teeth and denture base has been described. The advantages of this technique are the denture teeth can be made to function in harmony with dynamics of the stomatognathic system; any type of occlusal scheme can be used; the material is esthetically pleasing; it can be characterized; it can be used as a denture base material, which can also be characterized; it can be repaired, relined, or rebased with little difficulty; and laboratory procedures can be accomplished in the dental office or laboratory.


Luminescence research and its relation to ultraweak cell radiation.
The fundamental laws of photochemistry and the essential results of experimental research on ultraweak cell radiation are presented. By comparing all the facts it can be concluded that the phenomena discussed may arise from a variety of possible reactions and sources. Recombination reactions of certain radicals actually do release sufficient energy to generate UV-photons of the intensity under consideration. On the other hand, stimulated emission cannot be excluded in view of the distinct deviation of the radiation field from thermal equilibrium. There exist, however, various other candidates, such as direct emitters like flavins, indoles, porphyrins, carbonyl derivatives and aromatic compounds, and molecular oxygen and its various species, as well as collective molecular interactions, e.g. dimole or exciplex transitions, triplet-triplet annihilation, collective hydrolysis, electric field effects in membranes, etc. Careful biochemical and biophysical experiments are still necessary to find answers to all the questions that remain; not only individual problems have to be solved, but it is important to keep in mind the interrelationships between certain reactions.


Examination of psychosocial predictors of Virginia pharmacists' intention to utilize a prescription drug monitoring program using the theory of planned behavior.
Little is known about the main drivers of pharmacists' intention to utilize prescription drug monitoring programs (PDMPs) when making care decisions and the actual contribution of these factors in explaining intention and behavior. This study examined what theory of planned behavior (TPB) model constructs (i.e., attitude, subjective norm [SN], perceived behavioral control [PBC]), past utilization behavior (PUB) and perceived moral obligation (PMO) were significant predictors of Virginia community pharmacists' intention to utilize a PDMP. A cover letter with a link to a 28-item online survey was e-mailed to 600 members of the Virginia Pharmacists Association. Multiple regression analyses were used to determine the association between pharmacists' intention to utilize the PDMP database and attitude, SN, PBC, PUB and PMO. Ninety-seven usable responses were received, for a response rate of 16.2%. A majority of the respondents were Caucasian (96.4%), female (50.5%), working in independent community pharmacies (60.4%) with an average age of 49.5 ± 13.4 years. Overall, pharmacists intended to utilize a PDMP (mean = 5.3 ± 4.6; possible range: -9 to 9), had a positive attitude toward utilizing PDMP (mean = 6.3 ± 5.3; possible range: -12 to 12), perceived that others wanted them to utilize a PDMP (SN score = 3.7 ± 2.4; range: -6 to 6), and believed that they had control over utilization behavior (PBC score = 4.5 ± 4.0; range: -9 to 9). Attitude (β = 0.723, P < 0.001), SN (β = 0.230, P = 0.014) and PBC (β = -0.215, P = 0.026) significantly predicted pharmacists' intent, accounting for 56.7% of the variance in intention to utilize the PDMP database (P < 0.001). The addition of PMO (P < 0.001) significantly contributed to explaining the variance in intention but PUB did not. Members of the Virginia Pharmacists Association who responded to the survey showed a strong positive intent to utilize PDMP database. Pharmacists' attitudes, subjective norm, perceived behavioral control and perceived moral obligation were significant predictors of intention but past utilization behavior was not. The TPB is a useful theoretical framework when predicting PDMP utilization behavior of community pharmacists, accounting for 56.7% of the variance in intention.


Acute compartment syndrome following intramedullary pulse lavage and débridement for osteomyelitis of the tibia.
The implantation of gentamicin loaded polymethylmethacrylate (PMMA) beats and other local antibiotic carriers is a common practice in the treatment of chronic osteomyelitis as is the use of local jet lavage débridement. This article presents the case of a patient with chronic osteomyelitis of the tibia, who had no complication after débridement, intramedullary reaming and pulse lavage without tourniquet but sustained a compartment syndrome 2 weeks later during a second procedure in which an intraoperative tourniquet and pulse lavage were combined.


Ionizing radiation and atherosclerosis: current knowledge and future challenges.
The evaluation of the health effects of low-dose ionizing radiation has always been a focus of debate and investigation within the scientific community. During the last decade, epidemiological studies provided evidence that an excess risk of cardiovascular diseases (CVDs) can be associated with moderate and low dose radiation. The precise quantification of CVD risk in the low-dose radiation range (<500 mSv) is not well characterized, and it is unclear whether there is a threshold dose below which there is no risk. A limited number of studies with imaging surrogate endpoints and cardiovascular biomarkers in asymptomatic patients revealed early signs of cardiovascular alterations, even at a low dose. In vitro studies have shown that several mechanisms, including endothelial dysfunction, inflammation, oxidative stress, alterations of coagulation and platelet activity may have a relevant role in radiation-induced cardiovascular effects. Exposure to high-dose data in experimental models accelerates the development of atherosclerosis, predisposing to the formation of an inflammatory, thrombotic plaque phenotype, especially in animals that are genetically predisposed to this disease. On the contrary, low dose exposure produced both protective and detrimental effects, suggesting that multiple mechanisms may influence radiation-induced atherosclerosis. However, only very limited and specific information can be obtained from cell cultures and animal models. Planned studies of radiation-exposed cohorts need to be conducted to explore biological mechanisms of low-dose radiation-associated cardiovascular disease. Further investigations with functional imaging to assess vascular function and cardiovascular biomarkers have great potential for providing new insights into low-dose radiation cardiovascular risk, especially in occupational exposure and modern medicine.


Bioleaching of heavy metal from woody biochar using Acidithiobacillus ferrooxidans and activation for adsorption.
A woody biochar which was the byproduct of gasification of sawdust was treated with bioleaching by Acidithiobacillus ferrooxidans. After bioleaching, most heavy metal was removed from biochar. Leaching efficiency of heavy metal was efficient in a wide pulp density range from 1% to 10% (w/v) and decreased only a little with the increase in pulp density. It made application of biochar free of heavy metal risk. Benefitting from the improvement in functional group composition and pore structure after bioleaching, adsorption capacity of biochar to methylene blue and heavy metal was enhanced greatly. Adsorption of methylene blue could be described by pseudo-second-order model and Langmuir equation and the enhancement was mainly caused by the modification of physical character of biochar. Adsorption of heavy metal could be described by Freundlich equation and was mainly determined by chemical character of biochar.


[Enriched-enrollment randomized-withdrawal trials].
A clinical trial's power depends on the probability of observing an effect of the tested drug in the trial population, on the size of this effect, and on the heterogeneousness of the judgment criterion in the population. Enriched-enrollment randomized-withdrawal trials are clinical trials which comprise a first period in which subjects are selected depending on whether they respond to the tested drug or not. The responding patients are subsequently randomized into 2 groups: in one of them the treatment is pursued, in the other group a placebo is substituted. These designs are very useful in pediatrics, decreasing the number of subjects needed, on condition that the effect of the treatment is only suspensive in a setting of chronic disease. Here we discuss the advantages and disadvantages of such trials.


"A vaccine that nonetheless remains apart": Papillomavirus and vaccination in France
Vaccination against the human papillomavirus (HPV) is currently not widespread in France, where the vaccination rate is one of the lowest in Europe. However, this virus is encountered by 80% of the population and causes 3000 new cases of cancer per year. This vaccination constitutes a real lever for action. Using a qualitative approach (semi-directive interviews), we documented the perceptions, reluctance, and obstacles of sixteen general practitioners in Ile de France. The objective was to understand the low vaccination rate and to propose sustainable solutions to increase adherence to this vaccine. The HPV vaccine is different from other vaccines, which makes it more difficult for the public to understand. Firstly, because it affects the privacy of patients from a very young age. Secondly, because it has long been dedicated to a female public and the opening of vaccination to boys of the same age leads to a change in discourse and a break with its gendered image. Finally, this vaccination is taking place in a context where there is a marked reluctance to vaccinate in France, with a rapid circulation of more or less reliable information that often places the medical profession in difficulty. Health professionals play a key role in convincing and encouraging patients to adhere to the vaccine, and a majority of doctors are still in favor of vaccination. Relying on a wider group of health professionals could help to increase adherence to the vaccine in France.


Cytidine 5'-diphosphocholine ameliorates hyperoxic lung injury in a neonatal rat model.
Bronchopulmonary dysplasia (BPD) is an important cause of morbidity. The aim of this study was to evaluate the preventive effect of cytidine 5'-diphosphocholine (CDP-choline) treatment on hyperoxic lung injury in a neonatal rat model. A total of 30 newborn pups were divided into control, hyperoxia, and hyperoxia + CDP-choline groups. After birth, pups in the control group were kept in room air and received saline injections, whereas those in hyperoxia and hyperoxia + CDP-choline groups were exposed to 95% O₂ and received daily injections of saline and CDP-choline throughout postnatal day 10, respectively. Histopathological scoring, radial alveolar count, lamellar body membrane protein expression, fibrosis, proinflammatory cytokine levels, lung tissue and bronchoalveolar lavage (BAL) fluid phospholipid content, and apoptosis were evaluated. Hyperoxia-induced severe lung damage was reduced significantly by CDP-choline treatment. Radial alveolar count and lamellar body membrane protein expression were significantly recovered, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells, active caspase-3 expression, and tissue proinflammatory cytokine levels were decreased by CDP-choline administration. Lung tissue and BAL phospholipid contents showed significant increases after CDP-choline administration. These data show that CDP-choline ameliorates hyperoxic lung injury in a neonatal rat model. It may therefore be suggested that CDP-choline may be a novel therapeutic option for the prevention of BPD.


Effect of weekend admission on process of care and clinical outcomes for the management of acute coronary syndromes: a retrospective analysis of three UK centres.
The effect of weekend versus weekday admission following acute coronary syndrome (ACS) on process of care and mortality remains controversial. This study aimed to investigate the 'weekend-effect' on outcomes using a multicentre dataset of patients with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction/unstable angina (NSTEMI/UA). This retrospective observational study used propensity score (PS) stratification to adjust estimates of weekend effect for observed confounding. Logistic regression was used to estimate odds ratios (ORs) for binary outcomes and time-to-event endpoints were modelled using Cox proportional hazards to estimate hazard ratios (HRs). Three tertiary cardiac centres in England and Wales that contribute to the Myocardial Ischaemia National Audit Project. Between January 2010 and March 2016, 17 705 admissions met the study inclusion criteria, 4327 of which were at a weekend. Associations were studied between weekend admissions and the following primary outcome measures: in-hospital mortality, 30-day mortality and long-term survival; secondary outcomes included several processes of care indicators, such as time to coronary angiography. After PS stratification adjustment, mortality outcomes were similar between weekend and weekday admission across patients with STEMI and NSTEMI/UA. Weekend admissions were less likely to be discharged within 1 day (HR 0.72, 95% CI 0.66 to 0.78), but after 4 days the length of stay was similar (HR 0.97, 95% CI 0.90 to 1.04). Fewer patients with NSTEMI/UA received angiography between 0 and 24 hours at a weekend (HR 0.71, 95% CI 0.65 to 0.77). Weekend patients with STEMI were less likely to undergo an angiogram within 1 hour, but there was no significant difference after this time point. Patients with ACS had similar mortality and processes of care when admitted on a weekend compared with a weekday. There was evidence of a delay to angiography for patients with NSTEMI/UA admitted at the weekend.


In-vivo administration of recombinant IL-2 increases the number of Thy-1+ dendritic epidermal cells.
The number, morphology and response of Thy-1+ dendritic epidermal cells to recombinant interleukin-2 (rIL-2) were investigated in young and aged mice. The Thy-1+ dendritic cells in the aged mice continued to express T-cell receptor (TCR) gamma/delta but differed morphologically from those of the young mice. The aged mice had 50% fewer cells than the young ones. In the rIL-2 treated mice all the Thy-1+ cells were expressed as TCR gamma/delta and exposure to rIL-2 increased the number of these cells in a time- and dose-dependent manner when given systemically and locally. In the aged mice daily injection of rIL-2 increased the number of Thy-1+ dendritic cells within 2 weeks to almost that of young mice, however they had a lower response in the earlier stage. Nude mice showed no response to rIL-2.


Smoking, drinking and colorectal cancer in Hong Kong Chinese: a case-control study.
Expert opinions differ on the causal role of cigarettes and alcohol in colorectal cancer. This study investigates such associations in Hong Kong Chinese. A hospital-based case-control study was conducted from April 1998 to March 2000. Newly diagnosed colorectal adenocarcinoma and sex- and age-matched inpatient controls without gastrointestinal and malignant conditions were included. Structured interviews were conducted using a validated questionnaire to study any association of smoking, drinking and the lifelong extent of such exposures with colorectal cancer risk. We successfully interviewed 822 cases and 926 controls. Current regular cigarette smokers had an increased rectal cancer risk (adjusted OR = 1.44; 95% CI = 1.001-2.06). Increasing tertiles of smoking duration in ever smokers was also associated with increased rectal cancer risk (p trend = 0.038). An increased risk of colorectal cancer was found in current drinkers (adjusted OR = 1.42; 95% CI = 1.09-1.85) and in those who drank > or = 4 days (current and ex-drinkers) or > 4 units (ever and ex-drinkers) weekly. Moreover, colorectal cancer risk was found to decrease with increasing duration of drinking abstention (p trend = 0.006). This is the first report of a positive association between cigarette smoking and rectal cancer risk in a Chinese population. Current drinkers and those who drank regularly and heavily had increased colorectal cancer risk. Moreover, this study is the first to show that drinking cessation could be effective in reversing such increased risk in a duration-dependent manner. These new findings are important for cancer prevention and healthcare promotion.


Higher prevalence of LAP+ (Latency TGFβ-Associated Peptide) T cells at the tissue level in patients with early gastric cancer.
The presence of cells with regulatory functions in patients with cancer is one of the mechanisms whereby the immune system cannot confront tumor growth. We sought to determine the prevalence of immunoregulatory T-cell subpopulations, expressing the latency TGFβ-associated peptide (LAP), in patients with gastric adenocarcinoma. T cells were enriched from blood or gastric tissue (tumoral, TT or tumor-free, TF) samples from 22 patients, 6 with early (EGC) and 16 with advanced gastric cancer (AGC). CD4, CD8, LAP, FoxP3 and IFN-γ were measured by cytometry. CD8 + LAP + cells were increased at tumoral sites, especially in early stages of the disease, as compared to tumor-free explants (EGC 5.28 % [4.67-6.64]*; AGC 2.90 % [1.37-4.44]; TF 3.14 % [2.33-4.16]; *p < 0.05 vs TF). Likewise, the LAP+/CD8 + LAP- ratio is increased in gastric samples from patients with early disease (EGC 0.38 [0.30-0.45]*, AGC 0.12 [0.07-0.14]; TF 0.12 [0.09-0.31]; *p < 0.05 vs AGC).Disease progression is accompanied by decreased LAP membrane expression and, probably, increased LAP secretion, therefore limiting the response to the tumor.


Transitional care programs for trauma patients: A scoping review.
Transitional care programs establish comprehensive outpatient care after hospitalization. This scoping review aimed to define participant characteristics and structure of transitional care programs for injured adults as well as associated readmission rates, cost of care, and follow-up adherence. We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews standard. Information sources searched were Medline, the Cochrane Library, CINAHL, and Scopus Plus with Full Text. Eligibility criteria were systematic reviews, clinical trials, and observational studies of transitional care programs for injured adults in the United States, published in English since 2000. Two independent reviewers screened all full texts. A data charting process extracted patient characteristics, program structure, readmission rates, cost of care, and follow-up adherence for each study. A total of 10 studies described 9 transitional care programs. Most programs (60%) were nurse/social-worker-led post-discharge phone call programs that provided follow-up reminders and inquired regarding patient concerns. The remaining 40% of programs were comprehensive interdisciplinary case-coordination transitional care programs. Readmissions were reduced by 5% and emergency department visits by 13% among participants of both types of programs compared to historic data. Both programs improved follow-up adherence by 75% compared to historic data. Transitional care programs targeted at injured patients vary in structure and may reduce overall health care use.


Evaluation of Rofenaid and a commercial bacterin for prevention of cranial form of fowl cholera in turkeys.
Rofenaid, a potentiated sulfadimethoxine at drug concentrations of 0.04, 0.02, and 0.01% in feed, a combination of vaccination with a commercial bacterin and 0.01% potentiated sulfadimethoxine (Rofenaid), and vaccination separately, significantly (P less than 0.05) increased livability of turkeys experimentally induced with the cranial form of fowl cholera as compared to that of the nonmedicated nonvaccinated exposed turkeys. Turkeys were exposed by the administration of Pasteurella multocida (isolate 8579) in the drinking water.


Ab initio solution of macromolecular crystal structures without direct methods.
The majority of macromolecular crystal structures are determined using the method of molecular replacement, in which known related structures are rotated and translated to provide an initial atomic model for the new structure. A theoretical understanding of the signal-to-noise ratio in likelihood-based molecular replacement searches has been developed to account for the influence of model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, molecular replacement need not be restricted to the use of models comprising a substantial fraction of the unknown structure. Instead, likelihood-based methods allow a continuum of applications depending predictably on the quality of the model and the resolution of the data. Unexpectedly, our understanding of the signal-to-noise ratio in molecular replacement leads to the finding that, with data to sufficiently high resolution, fragments as small as single atoms of elements usually found in proteins can yield ab initio solutions of macromolecular structures, including some that elude traditional direct methods.


What do we know about the cytological features of pure intraductal carcinomas of the salivary glands?
Intraductal carcinomas (IDCs) are rare, poorly characterised salivary gland tumours. The cytological features of IDCs are even less known. In this paper, a systematic literature review of pure IDCs (without stromal invasion, not associated with other histotypes) of low-grade (LG-IDCs) and high-grade (HG-IDCs) was performed. The bibliographic research included multiple databases (PubMed, Scopus, Web of Science). Mild-moderate nuclear atypia favoured LG-IDCs, severe atypia favoured HG-IDCs. Preoperative fine-needle aspiration cytology (FNAC) was performed in 13/94 published cases (14%): 10 parotid; two oral; one submandibular. All the cases were histologically LG-IDCs, except two parotid IDCs. FNAC results included: negative for malignancy (three of 13 cases, 23%); tumour of uncertain malignant potential (seven of 13, 54%); malignancy (three of 13, 23%). The ductal component was identified in two cases; mucoepidermoid carcinoma was suggested in two additional cases. The grade was underestimated on FNAC evaluation in one HG-IDC as focal high-grade features were present on subsequent histological examination. The cases diagnosed as malignant tumours or describing intermediate atypia resulted in LG-IDCs on subsequent histology. Occasional mitoses were described only in one HG-IDC; this feature may have not been considered in the remaining published cases. FNAC and clinico-pathological correlation are important aids for clinicians and pathologists. FNAC could assist surgery even if an accurate diagnosis is sometimes impossible. Discrepancy in grading the nuclear atypia between the FNAC material and the resected specimen can occur, sometimes being unavoidable. Further studies are needed to better characterise this rare tumour.


The role of neuropathology in the management of newly diagnosed glioblastoma: a systematic review and evidence-based clinical practice guideline.
These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma (GBM) QUESTION : For adult patients with newly diagnosed GBM does testing for Isocitrate Dehydrogenase 1 or 2 (IDH 1/2) mutations afford benefit beyond standard histopathology in providing accurate classification and outcome prognostication? Level III IDH 1/2 mutational status by immunohistochemistry (IHC) and/or sequencing is suggested for classification and prognostic information. Level III Non-canonical IDH 1/2 mutations are very rare in patients aged 55 or older and universal testing of variant mutations by sequence analysis is not suggested for this age range. For adult patients with lower grade infiltrating astrocytomas (WHO grades II and III) can the IDH-wildtype status designation supersede histopathology to predict prognosis and biologic relevance to eventual behavior as a GBM? Level III The designation of infiltrating astrocytomas (WHO grades II and III) as IDH-wildtype is not suggested as sufficient for a higher grade designation alone. Level III It is suggested that IDH-wildtype WHO grades II and III astrocytomas be tested for molecular-genetic alterations typical of IDH-wildtype GBM such as EGFR amplification, gain of chromosome 7/loss of chromosome 10 and TERT-p mutation to substantiate prediction of behavior similar to IDH-wildtype glioblastoma. Level III It is suggested that a diagnosis of diffuse astrocytic glioma, IDH-wildtype, with molecular features of GBM, WHO grade IV be rendered for infiltrating astrocytomas that lack histologic criteria of GBM but harbors molecular-genetic alterations of IDH-wildtype glioblastoma. For adult patients with newly diagnosed infiltrating glioma arising in the midline does testing for H3-K27M mutations provide information beyond that gained by histopathology for accurate classification and outcome prognostication? Level III It is suggested that infiltrating gliomas arising in midline anatomic locations be tested for the H3-K27M mutation as they tend to exhibit WHO grade IV behavior even if they lack histologic criteria for glioblastoma.


Iron status in Danish women aged 35-65 years. Relation to menstruation and method of contraception.
Iron status was assessed by serum (S-) ferritin and hemoglobin (Hb) in a population survey comprising 883 non-gravid Danish women in age cohorts of 35, 45, 55, and 65 years. Premenopausal women (n = 676) had lower S-ferritin, median 42 micrograms/l, than postmenopausal women (n = 207), median 80 micrograms/l (p < 0.0001). Of premenopausal women, 12.1% had S-ferritin < or = 20 micrograms/l (i.e. depleted iron stores), and 35.6% S-ferritin of 21-40 micrograms/l (i.e. small iron stores). Corresponding figures in postmenopausal women were 0.5% and 13.2%. Premenopausal blood donors (n = 88) had lower S-ferritin than non-donors (p < 0.001). In premenopausal women, S-ferritin levels were strongly dependent on the duration of menstrual bleeding (p < 0.0001), which in turn was related to the method of contraception. Women (n = 64) using hormonal contraceptives (the pill) had menstrual bleeding of shorter duration than those (n = 511) not using pills or intrauterine devices (IUD), who in turn had bleeding of shorter duration than those (n = 101) using IUD. Median S-ferritin in pill users was 62 micrograms/l, in those not using pills or IUD 42 micrograms/l, and in IUD users 36 micrograms/l. S-ferritin values < 40 micrograms/l (i.e. small and depleted iron stores) were seen in 25% of pill users, in 48% of those not using pills or IUD, and in 61% of IUD users.(ABSTRACT TRUNCATED AT 250 WORDS)


T1 Relaxation Time in Lungs of Asymptomatic Smokers.
Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers. Lung T1 measurements from 35 subjects, 23 never smokers and 12 current smokers were retrospectively analyzed from an institutional review board approved study. All 35 subjects underwent pulmonary function test (PFT) measurements and lung T1, with similar T1 measurement protocols. A backward linear model of T1 as a function of FEV1, FVC, weight, height, age and PY was tested. A significant correlation between lung T1 and PY was found with a negative slope of -3.2 ms/year (95% confidence interval [CI] [-5.8, -0.6], p = 0.02), when adjusted for age and height. Lung T1 shortens with ageing among all subjects, -4.0 ms/year (95%CI [-6.3, -1.7], p = 0.001), and among the never smokers, -3.7 ms/year (95%CI [-6.0, -1.3], p = 0.003). A correlation between lung T1 and PY when adjusted for both age and height was found, and T1 of the lung shortens with ageing. Accordingly, PY and age can be significant confounding factors when T1 is used as a biomarker in lung MRI studies that must be taken into account to detect underlying patterns of disease.


Impact of woodland agri-environment management on woodland structure and target bird species.
Agri-environment incentives form a central mechanism supporting changes to land management to provide public benefits. This study assesses the medium-term effects of woodland management on 13 target, specialist woodland bird species, as well as other woodland birds in a single region of the UK. The abundance of breeding birds (using two methods: point counts and territory mapping) and metrics of woodland structure were recorded on sites with Woodland Improvement Grants (improvement sites) and nearby comparison sites (control sites). Initial measurements were made prior to management and repeated 7-9 years later. A separate comparison of changes in bird abundance was made between the managed woodland sites and woodland from similar landscapes surveyed as part of the national Breeding Bird Survey (BBS). There was an increase in abundance of target species on improvement sites compared to a decrease on both control sites and BBS sites, although this was only evident from point count data. The effects on target species were stronger than for other woodland specialists and there was no apparent effect on woodland generalists, suggesting that the management interventions were appropriate for the target species. Changes in woodland structure were generally consistent with the expected effect of management, with lower tree density and greater Bramble (Rubus sp.) cover. However, contrary to the aim of increasing understorey cover, a reduction was recorded within the 2-10 m height category in improvement sites. This contrast is due to the removal of young trees during thinning affecting this height band and the short time period since management to allow regrowth. Our findings show that bespoke management supported through government agri-environment incentives can have a positive impact on target woodland birds. For managed forests, identifying species requirements and how management can be adapted to improve their habitats can be an effective way of delivering biodiversity gains when financial incentives are provided to achieve policy goals.


Intravascular ultrasound-guided high-pressure balloon predilatation for optimal drug-eluting stent deployment in restenosis of a stent implanted 7 years earlier. Do we know the right technique for in-stent restenosis restenting?
Although off-label, drug-eluting stent (DES) implantation is a preferred intervention for in-bare metal stent restenosis (BMS ISR). Off-label DES implantation appears to be associated with a higher risk of stent thrombosis and lesion recurrence. Accordingly, routine BMS ISR restenting with DES is associated with more frequent subsequent thrombosis. Intravascular ultrasound (IVUS) studies point to stent underexpansion as the major mechanism of late DES failure. We report a case of a patient with BMS ISR in whom IVUS clarified initial BMS expansion; consequently, high-pressure predilatation with an angiographically oversized conventional balloon was applied prior to DES deployment; and finally, IVUS verified the stent expansion.


[Inhibitory effect of iguratimod on TNFalpha production and NF-kappaB activity in LPS-stimulated rat alveolar macrophage cell line].
To investigate the effect of iguratimod (T-614), a non-steroidal anti-inflammatory drug, on TNFalpha mRNA expression and TNFalpha production, and on the activity of nuclear factor-kappaB (NF-kappaB) in the rat alveolar macrophage cell line (NR8383) activated by LPS. NR8383 cells were pretreated with T-614 (13.4, 26.7, 53.4 micromol x L(-1)), then were stimulated with LPS. The production of TNFalpha in the supernatant of NR8383 was assayed by enzyme-linked immunosorbent assay (ELISA). The TNFalpha mRNA level was determined by a semi-quantitative PCR assay. Assessment of the NF-kappaB DNA binding activity was performed by an ELISA kit. T-614 inhibited LPS-stimulated mRNA expression and production of TNFalpha in a concentration-dependent manner, as well as the activity of NF-kappaB. The IC50 value of effect of T-614 on TNFalpha level was 26.2 micromol x L(-1). The inhibitory effect of T-614 on the production of TNFalpha in LPS-stimulated NR8383 cells may be mediated by suppression of NF-kappaB activity.


Using the Specialization Framework to Determine Degree of Dietary Specialization in a Herbivorous Woodrat.
To be considered a dietary specialist, mammalian herbivores must consume large quantities of a plant species considered "difficult" with respect to nutrient or toxin content, and possess specialized adaptations to deal with plant defensive compounds or low nutritional content. Populations of Neotoma lepida in the Great Basin consume Juniperus osteosperma, a plant heavily defended by terpenes, but a detailed dietary analysis of this population is lacking. Therefore, we investigated the extent of dietary specialization in this species in comparison with the better-studied specialist species, N. stephensi. Microhistological analysis of feces from N. lepida revealed that greater than 90% of their diet in nature was comprised of juniper. In laboratory tolerance trials, N. lepida tolerated a diet of 80% J. osteosperma, similar to that observed for N. stephensi. There was no difference in the abilities of N. lepida and N. stephensi to metabolize hexobarbital, a proxy compound for terpene metabolism. In preference tests of native and non-native juniper species, N. lepida did not exhibit a preference for its native or co-occurring juniper, J. osteosperma, over the non-native species, J. monosperma, whereas N. stephensi preferred its native or co-occurring juniper J. monosperma over non-native J. osteosperma. Behavioral and habitat differences between these woodrat species lead to the categorization of N. stephensi as an obligate juniper specialist with a small range that overlaps that of its preferred food, J. monosperma, and N. lepida as a facultative juniper specialist with a large range, and only a portion of its distribution containing populations that feed extensively on J. osteosperma.


Functionally similar species of ciliates have similar dynamics: A biennial survey study in a large eutrophic lake.
The spatial and temporal planktonic ciliate community structure of a large shallow eutrophic lake was described in detail based on a monthly monitoring campaign over 2 years using the quantitative protargol stain approach. We found that there was a large variety and low constancy of ciliate plankton and a clear advantage of several small species. Balanion planctonicum, Rimostrombidium brachykinetum, and Urotricha farcta contributed 19.7%, 13.4%, and 10.7% to the total abundance, respectively. The ciliate community was significantly varied in different lake regions of different eutrophication levels, and the distribution of some of the main species, especially prostomatids and scuticociliatids, might be closely related to the nutrient level of the lake regions. The seasonal dynamics of ciliate taxa with similar functional feeding habits across regions at different trophic levels are more convergent than those of species with very different functions, and the top-down effect (cladocerans, rotifers), nutrition, and water temperature were the key factors shaping ciliate community structure. The results of this study accentuate the important effects of species functional diversity on community differences and may improve our knowledge of ciliate diversity and functional ecology in shallow eutrophic lakes.


Heterogeneous nuclear ribonucleoprotein K modulates angiotensinogen gene expression in kidney cells.
The present studies aimed to identify the 70-kDa nuclear protein that binds to an insulin-responsive element in the rat angiotensinogen gene promoter and to define its action on angiotensinogen gene expression. Nuclear proteins were isolated from rat kidney proximal tubular cells and subjected to two-dimensional electrophoresis. The 70-kDa nuclear protein was detected by Southwestern blotting and subsequently identified by mass spectrometry, which revealed that it was identical to 65-kDa heterogeneous nuclear ribonucleoprotein K (hnRNP K). hnRNP K bound to the insulin-responsive element of the rat angiotensinogen gene was revealed by a gel mobility shift assay and chromatin immunoprecipitation assay. hnRNP K inhibited angiotensinogen mRNA expression and promoter activity. In contrast, hnRNP K down-expression by small interference RNA enhanced angiotensinogen mRNA expression. Moreover, hnRNP K interacted with hnRNP F in pulldown and co-immunoprecipitation assays. Co-transfection of hnRNP K and hnRNP F further suppressed angiotensinogen mRNA expression. Finally, in vitro and in vivo studies demonstrated that high glucose increases and insulin inhibits hnRNP K expression in rat kidney proximal tubular cells. In conclusion, our experiments revealed that hnRNP K is a nuclear protein that binds to the insulin-responsive element of the rat angiotensinogen gene promoter and modulates angiotensinogen gene transcription in the kidney.


Structural and Functional Progression in the Early Manifest Glaucoma Trial.
To elucidate the temporal relationship between detection of glaucomatous optic disc progression, as assessed by fundus photography, and visual field progression. Prospective, randomized, longitudinal trial. Three hundred six study eyes with manifest glaucoma with field loss and 192 fellow eyes without any field defect at the start of the trial, from a total of 249 subjects included in the Early Manifest Glaucoma Trial (EMGT), were assessed. Evaluation of visual field progression and optic disc progression during an 8-year follow-up period. Three graders independently assessed optic disc progression in optic disc photographs. Visual field progression was assessed using glaucoma change probability maps and the EMGT progression criterion. Time to detection of visual field progression and optic disc progression. Among study eyes with manifest glaucoma, progression was detected in the visual field first in 163 eyes (52%) and in the optic disc first in 39 eyes (12%); in 1 eye (0%), it was found simultaneously with both methods. Among fellow eyes with normal fields, progression was detected in the visual field first in 28 eyes (15%) and in the optic disc first in 34 eyes (18%); in 1 eye (1%), it occurred simultaneously. In eyes with manifest glaucoma, progression in the visual field was detected first more than 4 times as often as progression in the optic disc. Among fellow eyes without visual field loss at baseline, progression was detected first as frequently in the optic disc as in the visual field.


Awareness Levels of the Link Between Oropharyngeal Cancer and HPV Infection Among Spanish Women: a Hospital-Based Cross-sectional Study.
Several observational studies have demonstrated the increased awareness of human papillomavirus (HPV) as an etiological factor of oropharyngeal cancers (OPCs). The incidence of OPCs has increased in recent times, particularly among younger women, and the efficacy of the HPV vaccine in preventing these cancers has gained attention among the medical community. The aim of this study was to explore the health literacy of Spanish adult women regarding factors associated with HPV and its link to OPCs, as well as their awareness of the HPV vaccination. A survey was distributed to 508 women, and 409 (70.5%) were considered as valid participants. The majority of the participants were Caucasian (97.8%) with a mean age of 44.1 ± 11.6. Out of all the participants, only 48.9% women identified HPV as a possible etiology of OPC. The most common sources of information regarding this association were the internet (31.3%), video media (28.9%), and healthcare professionals (28.9%), whereas 16.1% of the participants reported that they had obtained information from three or more sources. The average number of correct answers in the 16-item survey which was used to determine the participants' knowledge of HPV-related diseases was 8.7 ± 4.2, and the average number of correct answers in the 6-item survey regarding the usefulness of the HPV vaccination was 3.3 ± 1.6. According to bivariate models, the variables associated with a poorer level of awareness were related mainly to education (p < 0.001), sexual behavior (p < 0.001), and employment status (p < 0.001). This study contributes toward the discovery of the previously unforeseen psychosocial burden of HPV and its related diseases among Spanish women.


Acute liver failure with thyrotoxicosis treated with liver transplantation.
We describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF). We present a case report and review the relevant literature. An extensive evaluation excluded possible causes of ALF other than thyrotoxicosis. The management of thyrotoxicosis posed several unique challenges in the setting of ALF, particularly because we did not want to use potentially hepatotoxic thionamides. The patient was treated with prednisone and propranolol and was started on potassium iodide when she was listed for liver transplantation. She underwent an uncomplicated liver transplant and subsequent thyroidectomy and is doing well. This well-characterized case describes thyrotoxicosis as a possible cause of ALF after thoroughly excluding other possible causes and illustrates the challenges of simultaneously managing both disorders. To our knowledge, this is the first report of ALF possibly resulting from untreated thyrotoxicosis that was successfully treated with liver transplantation.


Particle assembly and genome packaging.
Foamy virus (FV) replication is distinct from that of all other retroviruses in many respects, including viral assembly. In fact, the viral assembly pathway is rather similar to that of hepadnaviruses such as hepatitis B virus. Foamy virus Gag does not contain landmark retroviral assembly domains such as the major homology region, Cys-His boxes, or a defined M domain. Like hepadnaviruses, the FV Gag protein is not cleaved and contains arginine-rich regions at the carboxyl terminus. In addition, egress of FV particles requires presence of the envelope glycoproteins. Finally, the cis-acting sequences in the FV genome required for genome incorporation, although poorly defined, differ in location from other retroviruses.


Ultrasound-guided insertion of pulmonary artery catheter: Case report.
This is a case report of a 17-year old girl, who presented with aortic valve regurgitation and patent ductus arteriosus, and she underwent aortic valve replacement (AVR) and (PDA) ligation. Because of the extensive thrill and pulsation in the neck due to carotid artery dilatation, pulmonary artery catheter (PAC) was inserted under ultrasound guidance. This case report is to encourage the use of ultrasound for the safe puncture of internal jugular vein for the insertion of central line and PAC, particularly in the case of aortic valve regurge patients where carotid artery dilatation expected.


The effect of notchplasty on tunnel widening in anterior cruciate ligament reconstruction.
To investigate changes in femoral tunnel diameter, dimension, and volume after anterior cruciate ligament reconstruction with notchplasty. Porcine knee specimens were divided into 2 groups of 10 specimens each. Group A did not receive notchplasty. A 2-mm notchplasty was conducted in group B. Seven-millimeter-diameter femoral tunnels were drilled and a doubled flexor digitorum profundus tendon was inserted and fixed with an EndoButton (Smith & Nephew, Andover, MA) in each knee specimen. Samples were mounted on a materials testing machine. Each group was preloaded at 10 N and subjected to 20 loading cycles (between 0 and 40 N), followed by 1,000 loading cycles in the elastic region (between 10 and 150 N). High-resolution computed tomography with 1.0-mm slices was conducted with all samples before and after testing. A 3-dimensional model was constructed to evaluate the degree of the tunnel change. In group B the mean longest diameter and dimension of the femoral tunnel significantly increased after the test (P = .005 and P = .001, respectively). The volumetric loss of bony structure after the test in group B was significantly greater than that in group A (P = .039). Meanwhile, no significant difference was found before and after the test in terms of tunnel diameter, dimension, and volumetric loss around the tunnel in group A. The intra-articular orifice of the femoral tunnel was enlarged after the uniaxial cyclic loading test after notchplasty. An enlarged tunnel orifice may lead to a discrepancy between the tunnel and the graft at the tunnel aperture. The data may have an implication that suspensory fixation with a notchplasty has a negative effect on the full graft accommodation at the tunnel aperture. Aperture widening may affect graft positioning, leading to subtle changes in graft biomechanics and laxity.


Terahertz technology and its applications in head and neck diseases.
The terahertz (THz) radiation refers to electromagnetic waves between infrared and millimeter waves. THz technology has shown a significant potential for medical diagnosis and biomedical applications over the past three decades. Therefore, exploring the biological effects of THz waves has become an important new field in life sciences. Specifically, THz radiation has been proved to be able to diagnose and treat several head and neck diseases. In this review, we primarily discuss the biological characteristics of THz waves and clinical applications of THz technology, focusing on the research progress of THz technology in head and neck diseases (brain cancer, hypopharyngeal cancer, oral diseases, thyroid nodules, Alzheimer's disease, eyes diseases, and otitis). The future application perspectives of THz technologies in head and neck diseases are also highlighted and proposed.


Extraversion and fronto-posterior EEG spectral power gradient: an independent component analysis.
Several studies show that the fronto-posterior EEG spectral power gradient is a stable individual characteristic related to personality. Whether this characteristic is specifically related to agentic extraversion and theta band of frequencies or is associated with a broader set of personality traits and frequency bands is a matter of debate, as well as the specific cortical regions contributing to this effect. To clarify these questions, we used group independent component analysis (ICA) and source localization techniques. Agentic extraversion was associated with higher theta activity in the default mode network's (DMN) posterior hub and lower theta activity in the orbitofrontal cortex (OFC). Regression analyses showed that theta activity predicted agentic extraversion better than other frequency bands and agentic extraversion predicted posterior versus frontal activity better than other personality dimensions. These results are taken to indicate higher tonic activity in OFC and lower activity in DMN in extraverts as compared to introverts.


Cloning of the MspI modification enzyme. The site of modification and its effects on cleavage by MspI and HpaII.
The gene for the MspI modification enzyme from Moraxella was cloned in Escherichia coli using the plasmid vector pBR322. Selection of transformants carrying the gene was based on the resistance of the modified plasmid encoding the enzyme to cleavage by MspI. Both chromosomal and plasmid DNA were modified in the selected clones. None of the clones obtained produced the cognate restriction enzyme which suggests that in this system the genes for the restriction enzyme and methylase are not closely linked. Crude cell extracts prepared from the recombinant strains, but not the host (E. coli HB101), contain an S-adenosylmethionine-dependent methyltransferase specific for the MspI recognition site, CCGG. Production of the enzyme is 3-4-fold greater in the transformants than in the original Moraxella strain. 5-Methylcytosine was identified as the product of the reaction chromatographically. The outer cytosine of the recognition sequence, *CCGG, was shown to be the site of methylation by DNA-sequencing methods. This modification blocks cleavage by both MspI and its isoschizomer HpaII. HpaII, but not MspI, is able to cleave the unmethylated strand of a hemimethylated substrate. The relevance of these results to the use of MspI and HpaII to analyze patterns of methylation in genomic DNA is discussed.


Assessing the Aggregation Propensity of Single-Domain Antibodies upon Heat-Denaturation Employing the ΔTm Shift.
Nano differential scanning fluorimetry is used to quantify protein thermostability and has substantially expanded the spectrum of convenient biophysical parameters used to characterize proteins. Here, this technique is used to measure the ΔTm shift for single-domain antibodies (sdAbs), which represents a comprehensive metric for the aggregation propensity of sdAbs upon heat-denaturation. By relating two melting curves at different protein concentrations, the ΔTm shift described in this protocol is ideally suited for high-throughput measurements to guide protein engineering, formulation development, and developability assessment of sdAbs.


A micro solid-phase radioimmunoassay for detection of herpesvirus type-specific antibody: parameters involved in standardization.
A micro solid-phase radioimmunoassay (micro-SPRIA) was developed to demonstrate type-specific antibodies to herpes simplex virus types 1 and 2 (HSV1 and HSV2). Glycoproteins from the 123,000 dalton region of HSV1 (VP123) and the 119,000 dalton region of HSV2 (VP119) were isolated on preparative polyacrylamide gels for use as antigens in the micro-SPRIA. Human sera selected from clinical samples by virological history and appropriate microneutralization data were used to standardize the micro-SPRIA. Optimization of the assay required the use of siliconized microtiter wells for adsorption of antigen. Maximized results were highly dependent on the concentrations of antigen, primary antibody, and secondary antibody as well as the diluents used for these principal test reagents. Incorporation of HSV glycoproteins of each respective type with the optimal condition established in this study facilitates the direct detection of type-specific antibody in human sera.


Quantitative determination of redox-active carbonyls of natural dissolved organic matter.
Natural dissolved organic matter (DOM) is ubiquitous in environment and plays an important role in numerous environmental processes. Although the molecular basis of the reactivity of DOM remains poorly understood due to its extreme complexity, redox-active carbonyls (aromatic ketones/aldehydes and quinones) within DOM are believed vitally important. Except the rough determination of total carbonyls (including non-redox active -COOR) based on inflexible 13C chemical shift range by expensive and time-consuming solid-state nuclear magnetic resonance (NMR), there is no ready method to quantify redox-active carbonyls in DOM. Here we show that after treatment with sodium borohydride (NaBH4) by selectively eliminating redox-active carbonyls, quenched fluorescence of carbon quantum dots (CD) by DOM recovered dramatically, and displayed a good linear relationship between redox-active carbonyls detected and DOM concentration (R2 ≥ 0.977), thus allowing first quantitative determination of the redox-active carbonyls of DOM. Eight DOM isolates present 0.59%-0.90% redox-active carbonyls by the current method. And this method is robust from coexisting proteins and salts. This method could provide better or equal instructive results compared with solid-state NMR for total carbonyls or electrochemical method for electron-accepting capacities (EAC). Our results provide the underlying structural basis of many important geochemical processes that mediated by DOM. We posit that this method could apply to other complex molecular systems such as the atmospheric aerosols and extracellular polymeric substances (EPS), too.


Optimization of ribosomal binding site sequences for gene expression and 4-hydroxyisoleucine biosynthesis in recombinant corynebacterium glutamicum.
4-Hydroxyisoleucine (4-HIL) has potential value for treating diabetes. α-Ketoglutarate (α-KG)-dependent l-isoleucine dioxygenase (IDO) can convert l-isoleucine (Ile) into 4-HIL. In our previous study, 4-HIL was de novo synthesized from glucose by expressing the ido gene in Corynebacterium glutamicum strain SN01, an Ile producer, and neither Ile nor α-KG was added. In this study, ribosomal binding site (RBS) engineering was applied for gene expression and 4-HIL biosynthesis in C. glutamicum. The 18 tested RBS sequences showed greatly differing strengths for expressing ido, and 8.10-104.22 mM 4-HIL was produced. To supply the cosubstrate α-KG at different levels, the odhI gene was then expressed using the RBS sequences of high, medium, and low strength in the above mentioned optimal strain SF01 carrying R8-ido. However, 4-HIL production decreased to varying amounts, and in some strains, the α-KG was redirected into l-glutamate synthesis. Next, the O2 supply was further enhanced in three ido-odhI coexpressing strains by overexpressing the vgb gene, and 4-HIL production changed dramatically. 4-HIL (up to 119.27 ± 5.03 mM) was produced in the best strain, SF08, suggesting that the synchronic supply of cosubstrates α-KG and O2 is critical for the high-yield production of 4-HIL. Finally, the avtA gene and the ldhA-pyk2 cluster were deleted separately in SF08 to reduce pyruvate-derived byproducts, and 4-HIL production increased to 122.16 ± 5.18 and 139.82 ± 1.56 mM, respectively, indicating that both strains were promising candidates for producing 4-HIL. Therefore, fine-tuning ido expression and the cosubstrates supply through RBS engineering is a useful strategy for improving 4-HIL biosynthesis in C. glutamicum.


Parent education after newborn congenital heart surgery.
The moment an infant is diagnosed with a congenital heart defect, parents experience a mixture of shock, disbelief, fear, anger, and often a profound sense of sadness. In the midst of these emotions they must learn to provide for the special needs of their infant. Providing parents with the knowledge and skills to care for their infant during this stressful time requires the concerted effort of a multidisciplinary team who can provide clear, concise, and consistent communication. This article provides a step-by-step guide to the information needs of families who are preparing to take their infants home after cardiac surgery. Parents must understand the underlying cardiac defect and the goals and objectives of the surgical repair. In addition to normal newborn care, parents need to learn about care of the incision, nutritional support, and how to safely administer prescribed medications. Potential complications and when to call their health care provider or seek emergency care are an important focus of teaching. Information about infant development, challenges specific to their infant, and pragmatic strategies to support normal development are of prime interest to parents. Written reference materials, a Web resource list, and a family discharge teaching tool provide tangible resources for the family after discharge.


Crowning Lithium Ions in Hole-Transport Layer toward Stable Perovskite Solar Cells.
State-of-the-art perovskite solar cells (PSCs) exhibit comparable power conversion efficiency (PCE) to that of silicon photovoltaic devices. However, the device stability remains a major obstacle that restricts widespread application. Doping-induced hygroscopicity, ion diffusion, and use of polar solvents in the hole-transport layer are detrimental factors for performance degradation of PSCs. Here, phase-transfer-catalyzed LiTFSI doping in Spiro-OMeTAD is developed to address these negative impacts. 12-Crown-4 as an efficient phase-transfer catalyst promotes the dissolution of LiTFSI without requiring acetonitrile. A combined experimental and theoretical study demonstrates the host-guest interaction between Li+ ions and 12-crown-4. Crowning Li+ ions by forming more stable and less diffusive crown-ether-Li+ complexes retards the generation of hygroscopic lithium oxides and mitigates Li+ -ion migration. Optimized PSCs deliver enhanced PCE and significantly improved stability under humid and thermal conditions compared with a control device. This method can also be applied to dope π-conjugated polymer. The findings provide a facile avenue to improve the long-term stability of PSCs.


In-hospital ventricular arrhythmia in heart failure patients: 7 year follow-up of the multi-centric HEARTS registry.
The aim of this study was to determine the incidence, predictors, and short-term and long-term outcomes associated with in-hospital sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) collectively termed ventricular arrhythmia (VA) in the heart failure (HF) patients. The HEart function Assessment Registry Trial in Saudi Arabia (HEARTS registry) is a prospective national registry of patients with chronic HF from18 tertiary care hospitals across Saudi Arabia. Diagnosis of HF was in accordance with American Heart Association/European Society of Cardiology definition criteria. The registry had enrolled 2610 HF patients during the 14 month recruitment period between October 2009 and December 2010. Occurrence of in-hospital cardiac events, prognosis, and outcome were monitored during the 7 year follow-up period. The incidence of in-hospital VA in HF was 4.2%. VA was more common among men, and mean age was lesser than non-VA patients (58.5 ± 16: 61.5 ± 15 years; P = 0.042). Smoking and family history of cardiomyopathy were significant risk factors of VA. Previous history of arrhythmia, ST elevated myocardial infarction, infections, and hypotension remained significant predictors of in-hospital VA associated with three to seven times more risk. Patients with VA had higher rates of in-hospital events like recurrent HF, haemodialysis, shock, sepsis, major bleeding, intra-aortic balloon pump, and stroke compared with those without VA, all being highly significant (P < 0.001). After adjustment for age, gender, and co-morbidities, in-hospital VA increased the risk of cardiogenic shock by 24 times, dialysis and major bleeding by 10 times, and recurrent congestive HF and pacing by five times. Survival analysis showed that all-cause mortality was significantly higher in the VA patients (P < 0.001). Presence of VA increased in-hospital and 1 month mortality to 23 and 17 times, respectively. Lower mean age of VA complicated HF patients is a matter of concern in the Saudi population. HF associated with VA increased in-hospital events and all-cause mortality indicating poor prognosis and survival. These findings enable risk stratification and reflect on the importance of early recognition of the clinical markers and predictors of VA prompting immediate management.


The plasma free fraction of 25-hydroxyvitamin D3 is not strongly associated with 25-hydroxyvitamin D3 clearance in kidney disease patients and controls.
Circulating 25-hydroxyvitamin D [25(OH)D] concentration is used to monitor vitamin D status. Plasma protein binding may influence the 25(OH)D dose-response to vitamin D treatment through a direct relationship between the plasma unbound ("free") fraction and clearance of 25(OH)D. We previously evaluated 25(OH)D3 clearance in relation to kidney function using intravenous administration of deuterium labeled 25(OH)D3. In this follow up study, we determined the free fraction of 25(OH)D3 in plasma (i.e., percent free 25(OH)D3) and the serum concentration and haplotype of vitamin D binding protein in these participants. We hypothesized that the percent free 25(OH)D3 would be positively associated with 25(OH)D3 clearance and would mediate associations between clearance and vitamin D binding protein (GC) haplotypes. Participants were mean (SD) age 64 (10) years and included 42 individuals with normal kidney function (controls), 24 individuals with chronic kidney disease, and 19 individuals with kidney failure on hemodialysis. Free plasma 25(OH)D2 and 25(OH)D3 concentrations were quantified with a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Because there is no reference measurement procedure for free 25(OH)D, we compared the new method with a widely-used predictive equation and a commercial immunoassay. The percent free 25(OH)D3 determined by predictive equation was weakly associated with 25(OH)D3 clearance (R = 0.27; P = 0.01). However, this association was absent when percent free 25(OH)D3 was determined using LC-MS/MS-measured free and total 25(OH)D3 concentrations. Method comparison uncovered a negative bias in immunoassay-measured free 25(OH)D concentrations among participants with kidney failure, so immunoassay results were not used to evaluate the association between percent free 25(OH)D3 and clearance. GC2 haplotype carriage was associated with 25(OH)D3 clearance. Among individuals with 2 relative to no GC2 alleles, clearance was 87 (95% CI: 15-158) mL/d greater. However, in contrast with the literature, GC2 carriage was not significantly related to DBP concentration or the percent free 25(OH)D3 (either predicted or measured). In conclusion, the free fraction of 25(OH)D3 is not strongly associated with 25(OH)D3 clearance but may explain small differences in clearance according to GC haplotype.


The resistance of peanut to soil-borne pathogens improved by rhizosphere probiotics under calcium treatment.
Peanut (Arachis hypogaea L.) is an important oil and economic crop. Calcium modulates plants in response to abiotic stresses and improves plant resistance to pathogens. Enrichment of beneficial microorganisms in the rhizosphere is associated with plant disease resistance and soil development. The purpose of this study was to analyze the differences in peanut rhizosphere microbial community structure between the calcium treatment and the control during two growth stages and to explain why calcium application could improve the resistance of peanuts to soil-borne pathogens. The 16S rDNA amplicon sequencing of rhizosphere microbiome showed that calcium application significantly enriched Serratia marcescens and other three dominant strains at the seedling stage. At the pod filling stage, ten dominant stains such as Sphingomonas changbaiensis and Novosphingobium panipatense were enriched by calcium. Serratia marcescens aseptic fermentation filtrate was mixed with PDA medium and inoculated with the main soil-borne pathogens in the seedling stage, which could inhibit the growth of Fusarium solani and Aspergillus flavus. The aseptic fermentation filtrate of Novosphingobium panipatense was mixed with PDA medium and inoculated with the main soil-borne pathogens in the pod filling stage, which could inhibit the growth of Sclerotium rolfsii and Leptosphaerulina arachidicola. Calcium application increases the resistance of peanuts to soil-borne pathogens by enriching them with specific dominant bacteria.


Multivariate prediction of long COVID headache in adolescents using gray matter structural MRI features.
Headache is among the most frequent symptoms after coronavirus disease 2019 (COVID-19), so-called long COVID syndrome. Although distinct brain changes have been reported in patients with long COVID, such reported brain changes have not been used for predictions and interpretations in a multivariate manner. In this study, we applied machine learning to assess whether individual adolescents with long COVID can be accurately distinguished from those with primary headaches. Twenty-three adolescents with long COVID headaches with the persistence of headache for at least 3 months and 23 age- and sex-matched adolescents with primary headaches (migraine, new daily persistent headache, and tension-type headache) were enrolled. Multivoxel pattern analysis (MVPA) was applied for disorder-specific predictions of headache etiology based on individual brain structural MRI. In addition, connectome-based predictive modeling (CPM) was also performed using a structural covariance network. MVPA correctly classified long COVID patients from primary headache patients, with an area under the curve of 0.73 (accuracy = 63.4%; permutation p = 0.001). The discriminating GM patterns exhibited lower classification weights for long COVID in the orbitofrontal and medial temporal lobes. The CPM using the structural covariance network achieved an area under the curve of 0.81 (accuracy = 69.5%; permutation p = 0.005). The edges that classified long COVID patients from primary headache were mainly comprising thalamic connections. The results suggest the potential value of structural MRI-based features for classifying long COVID headaches from primary headaches. The identified features suggest that the distinct gray matter changes in the orbitofrontal and medial temporal lobes occurring after COVID, as well as altered thalamic connectivity, are predictive of headache etiology.


Perception of first- and second-order motion: separable neurological mechanisms?
An unresolved issue in visual motion perception is how distinct are the processes underlying "first-order" and "second-order" motion. The former is defined by spatiotemporal variations of luminance and the latter by spatiotemporal variations in other image attributes, such as contrast or depth. Here we describe two neurological patients with focal unilateral lesions whose contrasting perceptual deficits on psychophysical tasks of "first-order" and "second-order" motion are related to the maps of the human brain established by functional neuroimaging and gross anatomical features. We used a relatively fine-grained neocortical parcellation method applied to high-resolution MRI scans of the patients' brains to illustrate a subtle, yet highly specific dissociation in the visual motion system in humans. Our results suggest that the two motion systems are mediated by regionally separate mechanisms from an early stage of cortical processing.


Disulfiram loaded calcium phosphate nanoparticles for enhanced cancer immunotherapy.
Considering the huge cost and long test periods required for new drug development, repurposing drugs that have already been applied in the clinic as new cancer treatment candidates represents an attractive alternative. Disulfiram (DSF) was originally used to treat alcoholism and has proven to have anticancer effects with the coadministration of copper ions (Cu2+). However, the limited water-solubility of DSF and systemic toxicity induced by exogenous Cu2+ hinder its practical application. Herein, we constructed pH-responsive lipid-coated calcium phosphate nanoparticles (LCP NPs) co-loaded with Cu2+ and DSF. After intravenous injection, those nanoparticles with long blood half-life preferentially accumulate in tumors, followed by the degradation of nanoparticles in response to the acidic tumor microenvironment, subsequently releasing Cu2+ and DSF to generate cytotoxic metabolite DTC-Copper complex, bis(diethyldithiocarbamate)-copper (CuET) for tumor treatment. In addition to direct cytotoxicity, the active metabolite CuET could effectively induce immunogenic cell death (ICD) of cancer cells to regulate the immunosuppressive tumor microenvironment, contributing to enhanced immune checkpoint blockade (ICB) therapy in triggering systemic immune responses. This work thus demonstrates the great promises of repurposing the old drug DSF as a new ICD inducer with nano-formulation, to achieve improved synergetic tumor-responsive therapy with low side effects.


Comparative analysis of the antennae of three amphipod species with different lifestyles.
Crustaceans detect chemical stimuli in the environment with aesthetasc sensilla, which are located on their 1st antennae. With the transition to other environments, chemoreception faces physical challenges. To provide a deeper understanding of the relation between the morphology of olfactory organs and different lifestyles, we studied the peripheral olfactory system of three amphipod species, the marine Gammarus salinus, the blind subterranean freshwater species Niphargus puteanus, and the terrestrial Cryptorchestia garbinii. We compared the 1st and 2nd antennae of these species with respect to length and presence of aesthetascs and other sensilla. The females of N. puteanus reveal the longest 1st antennae in relation to body size. G. salinus shows the largest aesthetascs and the same relative length of the 1st antennae as male N. puteanus. C. garbinii has very short 1st antennae and reduced (putative) aesthetascs. Our findings show that the compensation of vision loss by olfaction cannot be generally assumed in animals from dark environments. Furthermore, the behaviour of C. garbinii indicates a chemosensory ability, despite the reduction of the 1st antennae. A comparison with other terrestrial crustaceans suggests that the loss of the olfactory sense on the 1st antennae in C. garbinii might be compensated with chemoreception by the 2nd antennae.


Using SHRP2 naturalistic driving data to examine driver speeding behavior.
Speeding-related crashes continue to be a serious problem in the United States. According to the National Highway Traffic Safety Administration, 26% of all fatal crashes in 2017 had speeding as a contributing factor. Vehicle speed data recorded during the Strategic Highway Research Program 2 (SHRP 2) Naturalistic Driving Study were analyzed to identify the frequency of speeding episodes. Up to 100 trips were sampled from 2,910 individual drivers aged 16-64. Vehicle speed data from individual trips were parsed into continuous speeding episodes (SEs) and Free-Flow Episodes (FFEs), which approximated opportunities to speed. Driving 10 mph above the posted speed limit (PSL) was common, and 99.8% of drivers had at least one occurrence SE within their trip sample, yielding an average of 2.75 SEs per trip (623,202 SEs in total). The analysis focused on a subset of higher-speed SEs in which the vehicle reached speeds of at least 15 mph above the PSL during the SE (71,113 SEs in total). Average maximum speeds for most higher-speed SEs ranged between 12 mph to 15 mph above the PSL, and most also lasted less than 2 min. Most drivers spent less than 5% of the FFE time speeding, and only a small number of drivers spent more than 10% of the time speeding. There was also a clear trend towards the younger group having higher overall percentages of SE time relative to FFE time. Practical Applications: The methods and measures developed in this study provide the foundation for future analyses to determine if there are different types of speeding that vary in terms of risky characteristics, and further, if certain drivers are more likely to engage in riskier speeding behavior. Identifying higher-risk speeders is an important step for developing countermeasures and strategies targeting drivers that are at greatest risk of speed-related crashes.


An observational study of the potential for human exposures to pet-borne diazinon residues following lawn applications.
This study examined the potential for pet dogs to be an important pathway for transporting diazinon residues into homes and onto its occupants following residential lawn applications. The primary objectives were to investigate the potential exposures of occupants and their pet dogs to diazinon after an application to turf at their residences and to determine if personal contacts between occupants and their pet dogs resulted in measurable exposures. It was conducted from April to August 2001 before the Agency phased out all residential uses of diazinon in December 2004. Six families and their pet dogs were recruited into the study. Monitoring was conducted at pre-, 1, 2, 4, and 8 days post-application of a commercial, granular formulation of diazinon to the lawn by the homeowner. Environmental samples collected included soil, indoor air, carpet dust, and transferable residues from lawns and floors. Samples collected from the pet dogs consisted of paw wipes, fur clippings, and transferable residues from the fur by a technician or child wearing a cotton glove(s). First morning void (FMV) urine samples were collected from each child and his/her parent on each sampling day. Diazinon was analyzed in all samples, except urine, by GC-MS. The metabolite 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy) was analyzed in the urine samples by HPLC-MS/MS. Mean airborne residues of diazinon on day 1 post-application were at least six times higher in both the living rooms (235+/-267 ng/m(3)) and children's bedrooms (179+/-246 ng/m(3)) than at pre-application. Mean loadings of diazinon in carpet dust samples were at least 20 times greater on days 2, 4, and 8 post-application than mean loadings (0.03+/-0.04 ng/cm(2)) at pre-application. The pet dogs had over 900 times higher mean loadings of diazinon residues on their paws on day 1 post-application (88.1+/-100.1 ng/cm(2)) compared to mean loadings (<0.09 ng/cm(2)) at pre-application. The mean diazinon loadings on the fur clippings were at least 14 times higher on days 1, 2, 4, and 8 post-application than mean loadings (0.8+/-0.4 ng/cm(2)) at pre-application. For transferable residues from dog fur, the mean loadings of diazinon on the technician's cotton glove samples were the lowest before application (0.04+/-0.08 ng/cm(2)) and the highest on day 1 post-application (10.4+/-23.9 ng/cm(2)) of diazinon to turf. Urinary IMPy concentrations for the participants ranged from <0.3 to 5.5 ng/mL before application and <0.3-12.5 ng/mL after application of diazinon. The mean urinary IMPy concentrations for children or adults were not statistically different (p>0.05) at pre-application compared to post-application of diazinon to turf. The results showed that the participants and their pet dogs were likely exposed to low levels of diazinon residues from several sources (i.e., air, dust, and soil), through several pathways and routes, after lawn applications at these residences. Lastly, the pet dog appears to be an important pathway for the transfer and translocation of diazinon residues inside the homes and likely exposed occupants through personal contacts (i.e., petting).


Beyond Empathy to System Change: Four Poems on Health by Bertolt Brecht.
Bertolt Brecht's poem "A Worker's Speech to a Doctor" is frequently cited as a means to raise awareness among health workers of the health effects of living and working conditions. Less cited is his Call to Arms trilogy of poems, which calls for class-based action to transform the capitalist economic system that sickens and kills so many. In this article, we show how "A Worker's Speech to a Doctor," with its plea for empathy for the ill, contrasts with the more activist and often militant tone of the Call to Arms trilogy: "Call to a Sick Communist," "The Sick Communist's Answer to the Comrades," and "Call to the Doctors and Nurses." We also show that, while "A Worker's Speech to a Doctor" has been applied in the training of health workers, its accusatorial tone towards health workers' complicity in the system the poem is critiquing risks alienating such workers. In contrast, the Call to Arms trilogy seeks common ground, inviting these same workers into the broader political and social fight against injustice. While we contend that the description of the sick worker as a "Communist" risks estranging these health workers, our analysis of the Call to Arms poems nevertheless indicates that their use can contribute to moving health workers' educational discourse beyond a laudable but fleeting elicitation of empathy for the ill towards a structural critique and deeper systemic understanding in order to prompt action by health workers to reform or even replace the capitalist economic system that sickens and kills so many.


Effects of insulin and glucose concentrations on glucose utilization in fetal sheep.
Glucose and insulin clamp experiments were performed in vivo in chronically catheterized, late-gestation fetal lambs to quantify the effects of glucose and insulin on fetal glucose metabolism. Fetal glucose uptake from the placenta via the umbilical circulation (umbilical glucose uptake) was measured by application of the Fick principle, and fetal glucose utilization rate (GUR) was measured using [U-14C]glucose tracer. Fetal plasma insulin concentrations ranged from 2 to 119 microU.ml-1 and fetal blood glucose concentrations ranged from 7.3 to 62.6 mg.dl-1. GUR varied from 2.82 to 15.12 mg/min/kg and the exogenous glucose entry rate (umbilical glucose uptake + glucose infusion) varied from 2.46 to 13.95 mg/min/kg. The mean GUR [6.53 +/- 0.28 (SEM) mg/kg/min] was not different from the mean exogenous glucose entry rate [6.29 +/- 0.30 (SEM) mg/kg/min]. Multiple linear regression analysis on a glucose-by-insulin surface demonstrated a best-fit model of fetal glucose utilization following the quadratic equation: GUR = -0.322 + [0.289 (glucose)] + [0.108 (insulin)] - [0.00319 (glucose)2] - [0.000673 (insulin)2], r = 0.883 (all terms significant at p less than 0.02). This model predicted a GURmax of 10.56 mg/min/kg at blood glucose concentration = 45.3 mg/dl and plasma insulin concentration = 80 microU/ml and Km values for blood glucose concentration and plasma insulin concentration of 20.6 mg/dl and 10 microU/ml, respectively. According to this model, the glucose and insulin effects were additive. Furthermore, change in GUR was not proportionate to change in glucose concentration, accounting for a decreasing metabolic clearance rate at higher glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)


Perturbation-evoked electrodermal responses are sensitive to stimulus and context-dependent manipulations of task challenge.
Recent work has demonstrated that postural instability evokes an electrodermal response (EDR) that is temporally coupled to perturbation onset. The purpose of this study was to determine whether arousal linked to balance recovery is associated with the size of the perturbation (stimulus-dependent variations); and/or the challenge of executing a motor response to recover stability (context-dependent task variations). Twelve healthy subjects received whole-body perturbations while seated in a tilting chair that required a compensatory upper limb reaction to regain balance following instability. The influence of perturbation amplitude (stimulus-dependent challenge- slow vs. fast perturbations) and task condition (context-dependent challenge- unrestricted vs. restricted movement) on EDR timing and magnitude parameters were examined. While EDR latency was consistent across conditions with onset occurring approximately 2s after the perturbation, peak-to-peak EDR amplitude was influenced by both stimulus-dependent and context-dependent challenges and also mirrored postural response amplitude. Compared to the Slow condition, EDR amplitude was 27 ± 6% larger in the Fast condition (p=0.0004). Similarly, EDR amplitude was 244 ± 86% larger in the Restricted task condition relative to the Unrestricted task condition (p=0.006). Context-dependent EDR modulation suggests that autonomic reactivity is associated with some higher level of processing independent of the degree of challenge related to stimulus characteristics. This work has potential implications for understanding determinants of central nervous system reactivity among individuals with impaired limb control where the recovery challenge is uniquely linked to the context.


Biosurfactant-affected mobility of oxytetracycline and its variations with surface chemical heterogeneity in saturated porous media.
Herein, the influences of rhamnolipid (a typical biosurfactant) on oxytetracycline (OTC) transport in the porous media and their variations with the surface heterogeneities of the media (uncoated sand, goethite (Goe)-, and humic acid (HA)-coated sands) were explored. Compared to uncoated sand, goethite and HA coatings suppressed OTC mobility by increasing deposition sites. Interestingly, rhamnolipid-affected OTC transport strongly depended on the chemical heterogeneities of aquifers and biosurfactant concentrations. Concretely, adding rhamnolipid (1-3 mg/L) inhibited OTC mobility through sand columns because of the bridging effect of biosurfactant between sand and OTC. Unexpectedly, rhamnolipid of 10 mg/L did not further improve the inhibition of OTC transport owing to the fact that the deposition capacity of rhamnolipid reached its maximum. OTC mobility in Goe-coated sand columns was inhibited by 1 mg/L rhamnolipid. However, the inhibitory effect decreased with the increasing rhamnolipid concentration (3 mg/L) and exhibited a promoted effect at 10 mg/L rhamnolipid. This surprising observation was that the increased rhamnolipid molecules gradually occupied the favorable deposition sites (i.e., the positively charged sites). In comparison, rhamnolipid facilitated OTC transport in the HA-coated sand column. The promotion effects positively correlated with rhamnolipid concentrations because of the high electrostatic repulsion and deposition site competition induced by the deposited rhamnolipid. Another interesting phenomenon was that rhamnolipid's enhanced or inhibitory effects on OTC transport declined with the increasing solution pH because of the decreased rhamnolipid deposition on porous media surfaces. These findings benefit our understanding of the environmental behaviors of antibiotics in complex soil-water systems containing biosurfactants.


The Financial and Emotional Impact of Atopic Dermatitis on Children and Their Families.
To examine the personal financial impact of atopic dermatitis (AD) and attempt to correlate cost of AD with emotional impact. Between March 2011 and December 2013, 82 caretakers of children 6 months to 12 years of age with moderate-to-severe AD were recruited at the time of dermatology clinic visits in Cleveland, Ohio, to complete surveys. The response rate was >95%. Participants were asked questions about direct expenses (medical visits, medications, and other products) and indirect expenses (time missed from work, childcare costs) related to AD in the past 4 weeks. Emotional impact was measured by the Childhood Atopic Dermatitis Impact Scale. The mean monthly personal cost of AD in the month before the office visit was $274 (median $114; IQR $29, $276), with $75 from direct costs (median $45; IQR $20, $110) and $199 from indirect costs (median $0; IQR $0, $208). An average of 34.8% of available monthly money was spent on AD care in the month before the office visit. For patients with Medicaid, there was a significant correlation between monthly adjusted personal cost and Childhood Atopic Dermatitis Impact Scale score (r = 0.548; P < .001); however, this correlation did not exist for patients who had commercial insurance (r = 0.269; P = .166). Our results illustrate the high emotional and financial burden of childhood AD and provide insight into spending patterns. In addition, our study correlate costs with emotional burden of AD for lower-income patients.


Tobacco-free campuses - a pipe dream? A survey of current smoking cessation practice in mental health units in Ireland.
Smoking and vaping are prohibited on Ireland's Health Service Executive (HSE) campuses. The HSE states that there is no evidence to suggest vaping is less damaging than cigarettes. Recent meta-analyses have shown that e-cigarettes are in fact less dangerous and can help smokers quit. Our study analyses the current smoking policies in place in mental health 'approved centres' in Ireland, what is being done to help smokers quit while in-patients and the level of support among staff for the introduction of e-cigarettes as a harm reduction tool. Clinical nurse managers from each mental health approved centre were surveyed to assess adherence to smoking policies. Only 5% of surveyed units enforce the HSE's Tobacco Free Campus Policy; 55% of units supported the idea of using e-cigarettes to help patients quit cigarettes. Ireland's hospital campuses are not tobacco free. Changes need to be made to our smoking policies and their enforcement.


Can Comprehensive Imaging Analysis with Analytic Morphomics and Geriatric Assessment Predict Serious Complications in Patients Undergoing Pancreatic Surgery?
We aimed to determine whether comprehensive imaging analysis with analytic morphomics (AM) enhances or replaces geriatric assessment (GA) in risk-stratifying pancreatic surgery patients. One hundred thirty-four pancreatic surgery patients were identified from a prospective cohort. Sixty-three patients in the cohort had preoperative CT scans in addition to comprehensive geriatric assessments. CT scans were processed using AM. Associations with National Surgical Quality Improvement Program (NSQIP) serious complications were evaluated using univariate analysis and robust elastic net modeling to obtain AUROC curves by adding AM and GA measures to our previously defined clinical base risk model (age, body mass index, American Society of Anesthesiologists classification, and Charlson comorbidity index). NSQIP serious complications were associated with low psoas Hounsfield units (HUs) (p = 0.002), low-density (0 to 30 HU) psoas area (p = 0.01), visceral fat HU (p ≤ 0.001), visceral fat area (p = 0.009), subcutaneous fat HU (p = 0.023), and total body area (p = 0.012) on univariate analysis. Elastic net models incorporating the base model with geriatric assessment and psoas HU (AUC = 0.751), and AM alone (AUC = 0.739) have greater predictive value than the base model alone (AUC = 0.601). The model utilizing AM and GA in combination had the highest predictive value (AUC = 0.841). When combined, AM and GA improve prediction of NSQIP serious complications compared to either technique alone. The additive nature of these two modalities suggests they likely capture unique aspects of a patient's fitness for surgery.


Head and neck teratomas in children--A series of 23 cases at Great Ormond Street Hospital.
Head and neck teratomas are rare and malignant change is rarer still. This is a report detailing all of the teratomas treated by the ear, nose and throat or craniofacial teams over the last 28 years at our institution. Examining the common presenting and radiological features as well as our success rates compared to the current literature. A retrospective review of all cases presenting to our institution with a head and neck teratoma were analysed. Data regarding the following characteristics were collected: antenatal history, clinical features, biological serum makers, radiological and pathological characteristics. Surgical treatment, rates of reoccurrence and the degree of post-operative follow up were also analysed. 23 cases in total were included: 8 cervical, 6 nasopharyngeal, 5 thyroid, 2 thymus, 2 temporal. One had malignant change. The majority of children presented at birth with respiratory distress, 5 cases were picked up antenatally and one case presented at 10 years of age. All were treated surgically; with complete excision in 20 patients. No clinical recurrence occurred but further surgery was performed for radiologically suspected residual disease in one case. This is the largest detailed case series in literature in regard to head and neck teratomas. Illustrating that this is frequently a benign disease process disease in the head and neck region and has an excellent long term prognosis following surgery. In the situation of incomplete resection careful meticulous follow up with radiological imaging and a multidisciplinary team approach is a safe and viable alternative.


Cognitive dysfunction in patients with pituitary tumour who have been treated with transfrontal or transsphenoidal surgery or medication.
This study was carried out to examine the neuropsychological status of patients treated for pituitary tumour by transfrontal surgery, transphenoidal surgery or medical treatment only, with or without radiotherapy. Three groups of 23 patients who had been treated for pituitary tumour were compared with 23 healthy controls on a range of neuropsychological measures. The surgical patients were also subdivided into two groups and compared. The neuropsychological measures were standardized psychological tests designed to assess aspects of attention, memory and executive function. The patients were those who had been treated with transfrontal surgery (n = 23), transsphenoidal surgery (n = 23) and medication only (n = 23). The groups did not differ with respect to age, education or premorbid ability level as assessed by the National Adult Reading Test. All participants were free of known sources of cognitive impairment other than pituitary tumour. Comparison of the four groups revealed that nearly half of the transfrontal, one-third of the transsphenoidal and one-quarter of the non-surgical group had three or more neuropsychological tests scores below the 10th percentile compared to less than 5% of the controls. Impairments in memory and executive function were found in both surgical groups. The non-surgical patients appeared to have problems only on tasks requiring high levels of cognitive processing. Differences were found between the two surgical groups with respect to the severity of the cognitive impairment, the transfrontal patients having more severe impairment than the transsphenoidal. No significant negative effects on cognitive functioning were associated with radiotherapy; however, transfrontal surgery patients who had not been treated with radiotherapy were found to be more impaired than other patients. This was thought to be related to radical surgery. Many patients with treated pituitary tumour suffer significant cognitive impairment. The severity and nature of impairment differs between treatment groups, although the cause of this could not be addressed by this study. Recommendations are made for future research and clinical practice.


Diagnostic and Therapeutic Outcomes Following Systematic Assessment of Patients with Concurrent Suspected Vocal Cord Dysfunction and Asthma.
Vocal cord dysfunction (VCD) is present in 25% to 50% of patients with asthma. When both diagnoses are suspected, accurate diagnosis and targeted management represent a clinical challenge. To evaluate diagnostic and therapeutic outcomes following systematic assessment for patients with concurrent suspected VCD and asthma. Patients underwent systematic evaluation by clinical assessment and validated questionnaires, followed by multidisciplinary management. VCD was confirmed by visualization of paradoxical vocal fold motion at baseline or following provocation. Asthma was confirmed by demonstrating variable airflow obstruction. Asthma medications were deescalated in those with low clinical probability of asthma and no variable airflow obstruction. Response to 2 or more sessions of speech pathology was assessed by subjective report and standardized questionnaires. Among 212 consecutive patients, 62 (29%) patients had both VCD and asthma, 54 (26%) had VCD alone, 51 (24%) had asthma alone, and 45 (21%) had neither. Clinician assessment and the Laryngeal Hypersensitivity Questionnaire both predicted laryngoscopy-confirmed VCD. Deescalation or discontinuation of asthma therapy was possible in 37 of 59 (63%) patients without variable airflow obstruction, and was most successful (odds ratio, 5.5) in the presence of laryngoscopy-confirmed VCD (25 of 31, or 81%) Patients with VCD responded subjectively to 2 or more sessions of speech pathology, but laryngeal questionnaire scores did not improve. Expert clinician assessment and the Laryngeal Hypersensitivity Questionnaire predict the presence of laryngoscopy-confirmed VCD. Systematic assessment for both VCD and asthma facilitates deescalation or discontinuation of unnecessary asthma medications. Subjective symptom improvement following speech pathology was not paralleled by laryngeal questionnaire scores in this cohort.


Focal non granulomatous orchitis in a patient with Crohn's disease.
Crohn's disease is a systemic disease and sometimes involves the testicle, usually leading to granulomatous lesions. We report herein a case of focal non-granulomatous orchitis in a 21-year-old patient with active Crohn's disease treated by an anti-tumor necrosis factor monoclonal antibody. This circumscribed testicular lesion mimicked a tumor, leading to orchiectomy. Pre-operative blood tests (i.e. alpha-fetoprotein, lactate dehydrogenase and human chorionic gonadotrophin) were strictly normal Pathological examination of the testicle revealed a focal inflammatory infiltrate predominantly composed of lymphocytes accompanied by few plasma cells, lacking giant cells or granulomas. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed.After discussing and excluding other plausible causes (burnt-out /regressed germ cell tumor, infection, vascular or traumatic lesions, iatrogenic effects), we concluded that this particular case of orchitis was most likely an extra-digestive manifestation of inflammatory bowel disease. To our knowledge, this is the first described case of focal non-granulomatous orchitis associated with Crohn's disease. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2117747284160112.