Electrocardiographic measures of repolarization heterogeneity are not predictive for Torsades de Pointes among undifferentiated patients with prolonged QTc: A case control study.
Torsades de Pointes (TdP) is a potentially lethal polymorphic ventricular tachydysrhythmia associated with and caused by prolonged myocardial repolarization. However, prediction of TdP is challenging. We sought to determine if electrocardiographic myocardial repolarization heterogeneity is necessary and predictive of TdP. We performed a case control study of TdP at a large urban hospital. We identified cases based on a hospital center electrocardiogram (ECG) database search for tracings from 1/2005 to 6/2019 with heart rate corrected QT (QTc) > 500, QRS < 120, and heart rate (HR) < 60, and a subsequent natural language search of electronic health records for the terms: TdP, polymorphic ventricular tachycardia, sudden cardiac death, and relevant variants. Controls were drawn in a 2:1 ratio to cases from a similar pool of ECGs, and matching for QTc, heart rate, sex, and age. We abstracted historical, laboratory, and ECG data using detailed written instructions and an electronic database. We included a second blinded data abstractor to test data abstraction and manual ECG measurement reliability. We used General Electric (GE) QT Guard software for automated repolarization measurements. We compared groups using unpaired statistics. We included 75 cases and 150 controls. The number of current QTc prolonging medications and serum electrolytes were substantially the same between the two groups. We found no significant difference in measures of QT or T wave repolarization heterogeneity. Electrocardiographic repolarization heterogeneity is not greater in otherwise unselected patients with QTc prolongation who suffer TdP and does not appear predictive of TdP. However, previous observations suggest specific repolarization characteristics may be useful for defined patient subgroups at risk for TdP.


Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: A SPECT study.
The purpose of this study was to examine the change of dopamine transporters (DAT) binding in methamphetamine (METH) abusers in a two-week period of abstinence and its association with cognitive function. Seven healthy subjects and seven METH abusers were recruited. At baseline conditions, the values of specific uptake ratio (SUR) of DAT binding measured by single photon emission computed tomography were lower in METH abusers than in controls. After a two-week period of abstinence, DAT binding was partially recovered and there were no statistic differences in SUR between METH abusers and controls. There was a borderline correlation between the changes of DAT binding in the right, but not the left, striatum and the %Error of Wisconsin Card Sorting Test. These findings indicate that DAT binding in METH abusers can be reversed in a short period of abstinence. The recovery of DAT binding was asymmetric and possibly parallel with the improvement of cognitive function.


Trapped gas at maximum lung volume in intact isolated rat lungs.
Excised rat lungs were ventilated with air in a liquid filled plethysmograph that was enclosed in a large pressure chamber, C(B). The lungs were inflated then deflated by removing or adding saline to the plethysmograph while the trachea was attached to a cannula extending through the plethysmograph base. In this system, tracheal pressure, Pao, was equal to gas pressure inside C(B). The gas pressure was held constant at either ambient pressure (Pamb), Pamb + 350 Torr, or Pamb - 350 Torr. When excised lungs were ventilated slowly from their atelectatic state for 10 inflation-deflation cycles with Pao equal to any one of the three pressures, an equivalent amount of gas was trapped in the lungs. If after 10 cycles, however, lungs containing trapped gas were inflated and held at maximum lung volume, the trapped gas spaces could be made to expand in response to rarefaction or compression of the tracheal gas. The amount of expansion and contraction of the trapped gas spaces demonstrates that trapped gas is likely trapped between menisci of a foam that occlude the alveoli or small airways.


Community-based bilingual doula support during labour and birth to improve migrant women's intrapartum care experiences and emotional well-being-Findings from a randomised controlled trial in Stockholm, Sweden [NCT03461640].
To evaluate the effectiveness of community-based bilingual doula (CBD) support for improving the intrapartum care experiences and postnatal wellbeing of migrant women giving birth in Sweden. Randomised controlled trial. Six antenatal care clinics and five hospitals in Stockholm, Sweden. 164 pregnant Somali-, Arabic-, Polish-, Russian- and Tigrinya-speaking women who could not communicate fluently in Swedish, were ≥18 years and had no contra-indications for vaginal birth. In addition to standard labour support, women were randomised to CBD support (n = 88) or no such support during labour (n = 76). Trained CBDs met with women prior to labour, provided support by telephone after labour had started, then provided emotional, physical and communication support to women throughout labour and birth in hospital, and then met again with women after the birth. Women's overall ratings of the intrapartum care experiences (key question from the Migrant Friendly Maternity Care Questionnaire) and postnatal wellbeing (mean value of Edinburgh Postnatal Depression Scale) at 6-8 weeks after birth. In total, 150 women remained to follow-up; 82 women (93.2%) randomised to receive CBD support and 68 women (89.5%) randomised to standard care (SC). Of women allocated CBD support, 60 (73.2%) received support during labour. There were no differences between the groups regarding women's intrapartum care experiences (very happy with care: CBD 80.2% (n = 65) vs SC 79.1% (n = 53); OR 1.07 CI 95% 0.48-2.40) or emotional wellbeing (EPDS mean value: CBD 4.71 (SD 4.96) vs SC 3.38 (SD 3.58); mean difference 1.33; CI 95% - 0.10-2.75). Community-based doula support during labour and birth for migrant women neither increased women's ratings of their care for labour and birth nor their emotional well-being 2 months postpartum compared with receiving standard care only. Further studies on the effectiveness of CBD powered to evaluate obstetric outcomes are needed. Trial registration at ClinicalTrial.gov NCT03461640 https://www.google.com/search?client=firefox-b-d&q=NCT03461640.


The pneumoconioses.
The pneumoconioses are by and large industrial diseases, although casual contact may be important on occasion, particularly with asbestos. The effect of dust on the lung ranges from only radiographic changes to severe functional impairment. Destruction and fibrosis of lung parenchyma may be the end result in severe disease. Great improvement has been made in recent years in the control of dust in the numerous situations where it may cause disease. We are still faced with evaluating existing standards of particle concentration in air breathed by workers and establishing safe limits and better control of the particles placed into the general environment. Undoubtedly, there are other particulates which potentially can cause lung disease of which we are not aware. Of even more concern is the realization that a latent period of 20 years or so may be necessary for physicians to become aware of the pathologic process. Every physician who sees patients with pulmonary problems must inquire regarding a history of dust exposure and be prepared to interpret that history.


[Financial and medicolegal impact of dental trauma].
Dental injuries are among the most common complications of general anesthesia. Yet few studies have assessed the costs and factors that involve the responsibility of the anesthetist. A retrospective study was conducted at the university hospital of Reims on 46 cases of dental injuries directly related to anaesthesia. Ten patients made a claim for compensation. Two of them have received compensation following a medical expertise, which revealed for the first patient a possible alternative to general anaesthesia, and the second, hardware failure of intubation. The Administrative Court was entered once in 9 years. The global insurance-cost amounts to 4476 euros for all patients. The review of all cases of anaesthesia shows clearly that the dental claims are associated with a significant under clinical evaluation of dental status and criteria for difficult intubation during the anaesthesia. The information to the patient on this risk is not obvious from reading the anaesthesia records. No mouth guard was used. This work proves that the statements of caution are the most common and a minority of dental trauma lead to a claim. Claims are due to the high cost of dental care repair. The proportion of patients receiving benefits is extremely low. Medical expertise is an essential part of the evaluation of medical responsibilities. No compensation was paid without expertise. The lack of physical examination and information are contrary to our professional obligations and may involve our responsibility. The lack of patient information is not generated for compensation to the extent that the consequences of failure are easily dental weighed against the benefits of the entire medical-surgical procedure that the patient has agreed.


Significance of placental cord insertion site in twin pregnancy.
To investigate the association between abnormal cord insertion and the development of twin-specific complications, including birth-weight discordance, selective fetal growth restriction (sFGR) and twin-to-twin transfusion syndrome (TTTS). This was a single center retrospective cohort study of twin pregnancies. Abnormal cord insertion was defined as either marginal (umbilical cord attachment site less than 2 cm to the nearest margin of the placental disc) or velamentous (cord attached to the membrane before reaching the placental disc with clear evidence of vessels traversing the membranes to connect with the placental disc), as described in placental pathology reports. Twins with major structural or chromosomal abnormalities and monochorionic monoamniotic twins were not included in the study. Information on the pregnancies, ultrasound findings, prenatal investigations and interventions was obtained from the electronic ultrasound database, while data on placental histopathological findings, pregnancy outcome, mode of delivery, birth weight, gestational age at delivery and admission to the neonatal intensive care unit were obtained from maternity records. Categorical variables were compared using the chi-square or Fisher's exact test, while continuous variables were compared using the Student's t-test, ANOVA for multiple comparisons and the Kruskal-Wallis test. Of the 497 twin pregnancies included in the analysis, 351 (70.6%) were dichorionic and 146 (29.4%) were monochorionic. The incidence of birth-weight discordance of 25% or more was significantly higher in pregnancies with velamentous and those with marginal cord insertions compared to those with normal cord insertion (24.0%, 15.3% vs 7.6%, P < 0.001 and P = 0.020, respectively). In pregnancies with birth-weight discordance of 25% or more, the smaller twins had significantly higher prevalence of velamentous (13.8%) and marginal (34.2%) cord insertions compared with the larger twins (1.8% and 18.5%, respectively, P < 0.001). The smaller twins of the monochorionic diamniotic pregnancies showed an even higher prevalence of velamentous (29.5%) and marginal (40.9%) cord insertions compared with the larger twins (2.3% and 31.5%, respectively, P < 0.001). Compared with the normal cord insertion group, only velamentous insertion was associated significantly with the risk of sFGR (odds ratio (OR), 9.24 (95% CI, 2.05-58.84), P < 0.001) and birth-weight discordance of 20% or more (OR, 4.34 (95% CI, 1.36-14.61), P = 0.007) and 25% or more (OR, 6.81 (95% CI, 1.67-34.12), P = 0.003) in monochorionic twin pregnancies. There was no significant association between velamentous cord insertion and TTTS (P = 0.591), or between marginal cord insertion and the development of sFGR (P = 0.233), birth-weight discordance of 25% or more (P = 0.114) or TTTS (P = 0.487). Subgroup analysis of dichorionic twins showed that abnormal cord insertion was not associated with the risk of birth-weight discordance (P = 0.999), sFGR (P = 0.308), composite neonatal adverse outcome (P = 0.637) or intrauterine death (P = 0.349). Monochorionic twins with velamentous cord insertion are at increased risk of birth-weight discordance and sFGR. Sonographic delineation of placental cord insertion could be of value in the antenatal stratification of twin pregnancies. Prospective studies are required to assess the value and predictive accuracy of this potential screening marker. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Direct matrix assisted laser desorption ionization mass spectrometry-based analysis of wine as a powerful tool for classification purposes.
The variables affecting the direct matrix assisted laser desorption ionization mass spectrometry-based analysis of wine for classification purposes have been studied. The type of matrix, the number of bottles of wine, the number of technical replicates and the number of spots used for the sample analysis have been carefully assessed to obtain the best classification possible. Ten different algorithms have been assessed as classification tools using the experimental data collected after the analysis of fourteen types of wine. The best matrix was found to be α-Cyano with a sample to matrix ratio of 1:0.75. To correctly classify the wines, profiling a minimum of five bottles per type of wine is suggested, with a minimum of three MALDI spot replicates for each bottle. The best algorithm to classify the wines was found to be Bayes Net.


[Relationship between sulfur dioxide pollution and upper respiratory outpatients in Jiangbei, Ningbo].
To describe the daily average concentration of sulfur dioxide (SO2) in Ningbo, and to analysis the health impacts it caused in upper respiratory disease. With outpatients log and air pollutants monitoring data matched in 2011-2013, the distributed lag non-linear models were used to analysis the relative risk of the number of upper respiratory patients associated with SO2, and also excessive risk, and the inferred number of patients due to SO2 pollution. The daily average concentration of SO2 didn't exceed the limit value of second class area. The coefficient of upper respiratory outpatient number and daily average concentration of SO2 matched was 0.44,with the excessive risk was 10% to 18%, the lag of most SO2 concentrations was 4 to 6 days. It could be estimated that about 30% of total upper respiratory outpatients were caused by SO2 pollution. Although the daily average concentration of SO2 didn't exceed the standard in 3 years, the health impacts still be caused with lag effect.


Biomarkers and phenotypic expression in Alzheimer's disease: exploring the contribution of frailty in the Alzheimer's Disease Neuroimaging Initiative.
The present study aimed at investigating if the main biomarkers of Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual's frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants' frailty status: CSF Aβ1-42, 181P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the 18F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ1-42, hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the 18F-AV-45 PET. No significant differences were observed among the two frailty groups concerning ApoE genotype, CSF T-tau, and P-tau. Increasing frailty levels were associated with a weakened relationship between dementia and 18F-AV-45 uptake and hippocampus volume and with a stronger relationship of dementia with FDG PET. Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and dementia should increasingly be conceived as "complex diseases of aging," determined by multiple, simultaneous, and interacting pathophysiological processes.


Ischemic lesion burden and characteristics of aortic atheroma.
To investigate whether ischemic lesion burden including lesion pattern, number, and volume would vary depending on risk stratification of aortic atheroma (AA). Acute stroke patients were enrolled if they had (1) acute ischemic lesions on diffusion-weighted imaging within 5 days of symptom onset, (2) cardioembolic stroke established through extensive workup, and (3) only ascending or arch AA detected by transesophageal echocardiography as an embolic source. AA was classified as complex (protruding ≥4 mm into the aortic lumen or any mobile or ulcerative component) or simple (<4 mm). Eighty-one patients (male: 65.4% and age: 66.7 ± 11.0 years) were included in the study. Thirty-four patients (41.9%) had complex atheroma. These patients had a greater number of ischemic lesions (median: 2 lesions [range: 1-42] versus one lesion [range: 1-27], P = .017) and a larger infarct size (9.01 cc [range: 3.58-49.14] versus 4.6 cc [range: 2.3-13.28), P = .056) than the simple atheroma group. Multivariable logistic regression analysis showed that ischemic lesion volume was independently associated with complex atheroma (odds ratio: 1.03, 95% confidence interval: 1.002-2.148, P = .035), while multiple lesions were related (odds ratio: 3.03, 95% confidence interval: .88-10.42, P = .079). Ischemic lesion burden in patients with AA differed according to AA characteristics, suggesting that the morphological features of AA could reflect an embolic potential of AA.


20,23,26,29,32,35,38,41-Octa-oxa-5,9,13-triaza-penta-cyclo-[184.108.40.206.1.1]tetra-tetra-conta-1,3(42),7,9,11(44),15(43),16,18,30-nona-ene-6,12-dione acetone mono-solvate.
In the crystal structure of the title compound, C(33)H(39)N(3)O(10)·C(3)H(6)O, the acetone mol-ecule is encapsulated into the cavity of the cryptand and fixed by two N-H⋯O and one C-H⋯O hydrogen bond. C-H⋯O and C-H⋯N inter-actions link neighbouring cryptands. The dihedral angles between the pyridine ring and the benzene rings are 86.47 (17) and 85.53 (13)°.


Food microstructure and starch digestion.
Microstructural characteristics of starch-based natural foods such as parenchyma or cotyledon cell shape, cell size and composition, and cell wall composition play a key role in influencing the starch digestibility during gastrointestinal digestion. The stability of cell wall components and the arrangement of starch granules in the cells may affect the free access of amylolytic enzymes during digestion. Commonly used food processing techniques such as thermal processing, extrusion cooking, and post-cooking refrigerated storage alter the physical state of starch (gelatinization, retrogradation, etc.) and its digestibility. Rheological characteristics (viscosity) of food affect the water availability during starch hydrolysis and, consequently, the absorption of digested carbohydrates in the gastrointestinal tract. The nonstarch ingredients and other constituents present in food matrix, such as proteins and lipids interact with starch during processing, which leads to an alteration in the overall starch digestibility and physicochemical characteristics of digesta. Starch digestibility can be controlled by critically manipulating the food microstructure, processing techniques, and food composition.


Postural asymmetries following unilateral subthalomotomy for advanced Parkinson's disease.
Two cases of postural asymmetries following unilateral stereotaxic subthalamotomy were observed with head and body tilting to the side contralateral to the STN lesion, which corrected itself completely or partially with levodopa treatment. After subsequent contralateral STN surgery, the postural asymmetry disappeared in both patients. Possible mechanism is discussed.


Quantification of flunitrazepam's oxidative metabolites, 3-hydroxyflunitrazepam and desmethylflunitrazepam, in hepatic microsomal incubations by high-performance liquid chromatography.
A high-performance liquid chromatographic assay for the quantification of the oxidative metabolites of flunitrazepam, 3-hydroxyflunitrazepam and desmethylflunitrazepam, in human liver microsomal incubations was developed. Both metabolites were quantifiable in a single assay following a solvent extraction and reversed-phase high-performance liquid chromatography with UV detection. Standard curve concentrations for both metabolites ranged from 0.2 to 10 microM. Assay performance was determined using quality control samples and the intra- and inter-day accuracy and precision as determined by the coefficient of variations which were less than 15% (0.5-6 microM) for both metabolites. This method provides good precision and accuracy for use in kinetic studies of the oxidative metabolism of flunitrazepam in human liver microsomes.


The natural history of recurrence after bronchoplastic procedures for non-small cell lung cancer.
The natural course of recurrence after bronchoplastic procedures for non-small cell lung cancer (NSCLC) has not been described. Sex, age, tnm-stage, histology, neoadjuvant chemotherapy, disease-free interval (months), exact localisation of tumour recurrence, time between first and second recurrence (months), survival after first and second recurrence (months), causes of death were retrospectively recorded in 83 patients operated between December 1993 and July 2001. One patient was lost to follow-up, five resections were nonradical. Survivors' follow-up lasted 5 to 100.7 months (mean 43.3). Fourteen patients (14.4%) died tumor free. Eleven (13.2%) distant recurrences were diagnosed 1 to 42 months (mean 10.6) postoperatively, eight (9.6%) died 0 to 17 months (mean 7.55) after diagnosis. Nine local recurrences (10.8%)-5 unifocal, 4 multifocal-occurred 2 to 35 months (mean 17.3) postoperatively, eight died 0 to 8 months (mean 2.13) after diagnosis. Nine mixed recurrences (10.8%)-1 synchronous, 8 metachronous-were found (14.8%) 2 to 21 months postoperatively (mean 8.3). All died 4 to 41 months (mean 17.83) after diagnosis. Fourteen mediastinal lymph node recurrences occurred, ten as a primary recurrence and four as secondary. Lymph nodes were involved in all multifocal recurrences. Intrabronchial recurrence was observed in five patients and was always a result of progressive regional lymph node recurrence. The pattern and natural history of recurrence cannot be sufficiently explained by stage and surgical radicality and suggest different genetic characteristics of the primary tumor. In case of reoperation due to intrabronchial recurrence adjuvant mediastinal irradiation should be considered.


Bladder reconstruction after cystectomy: use of ileocecal segment and three-loop ileal reservoir.
We report on 11 patients who in 1980-1982 had bladder reconstruction, after cystectomy for bladder cancer, utilizing the ileocecal valve as an antireflux mechanism and a direct urethrocecal anastomosis. They received preoperative irradiation (2,000 rad) and had some early complications such as pelvic abscesses and temporary urinary fistulas. We have since omitted preoperative radiation on cases performed in 1984-1987 and they did not have these complications.


Pregnancy-related human leukocyte antigen sensitization leading to cardiac allograft vasculopathy and graft failure in a heart transplant recipient: a case report.
In this report, we present a heart transplant recipient who developed cross-reactive paternal and donor-specific human leukocyte antigen (HLA) class II antibodies during pregnancy, leading to accelerated cardiac allograft vasculopathy and severe allograft dysfunction 17 years after transplantation. This resulted in acute heart failure and ventricular arrhythmias requiring repeat heart transplantation.


Metabolic responses to lipid infusions in patients with liver cirrhosis.
Energy expenditure, whole body substrate oxidation rates and arterial substrate concentrations were measured in 14 patients with liver cirrhosis and 13 control subjects before and during sequential infusions of a long chain (LCT) or a medium chain triglyceride emulsion (MCT) without and with concomitant insulin plus glucose infusions. Resting energy expenditure, basal substrate oxidation rates and the arterial concentrations of glucose, lactate, triglycerides and ketones were normal, whereas plasma free fatty acids and glycerol were both increased in patients with liver cirrhosis. The arterial plasma triglyceride and free fatty acid concentrations as well as whole body lipid oxidation rate rose in response to LCT in both groups and the maximum lipid oxidation rate was 1.1 or 1.3 mg/kg fat free mass x min in controls and in cirrhotics, respectively (n.s.). Concomitantly, glucose oxidation rate fell to 65% of basal values in controls (p < 0.01), but remained nearly unchanged in the cirrhotic group (89% of the basal value; n.s.). The increase in plasma ketones was reduced to 67% of control values in liver cirrhosis (p < 0.01). Only a slight effect on energy expenditure was observed in both groups. When compared to controls, liver cirrhosis impaired insulin-induced increases in glucose disposal (-30%, p < 0.01) and in non oxidative glucose metabolism (-93%, p < 0.01). Concomitantly, normal increases in energy expenditure, glucose oxidation rate and the arterial plasma lactate concentrations and normal decreases in lipolysis, lipid oxidation and ketogenesis were observed in patients with liver cirrhosis. When lipids were given together with glucose, energy expenditure and lipid oxidation increased in controls, but glucose was the preferred fuel oxidised and lipid-induced thermogenesis was reduced in the cirrhotic group. Using a 50% MCT-emulsion, plasma free fatty acid concentrations further increased, but energy expenditure and lipid oxidation remained unchanged in both groups and further increases in plasma ketones were only observed in controls. Infusing glycerol in a subgroup of patients showed no thermogenic effect and a reduced glycerol clearance in liver cirrhosis.


Food deprivation decreases the exertion-induced acid hydrolase response in mouse skeletal muscle.
Strenuous prolonged running causes muscle fibre necrosis in skeletal muscles. The muscle injury is associated with inflammation and a strong increase in the total activities of certain acid hydrolases a few days after exertion. The activity changes of acid hydrolases quantitatively well reflect the severity of histopathological changes during the myopathy (for review see Salminen, Acta Physiol Scand [Suppl 539] 1985). In this study male NMRI-mice were exposed to a protocol of fasting and refeeding together with or without a 6 h run on a treadmill at 13.5 m.min-1. The animals were killed 4 days after the exercise and samples from the red part of quadriceps femoris were analyzed for arylsulfatase (ASase) and beta-glucuronidase (GUase) activities. Starvation protocols did not affect ASase or GUase. Running caused a 3.2-fold increase in ASase and a 5.1-fold increase in GUase. If mice were exercised in the fasted condition a normal exercise response occurred in both activities, but when mice were exercised 2 days after the finish of fasting the exercise response was greatly diminished. Thus food deprivation followed by 2 days refeeding induces a protection against exercise myopathy in mice. The protection greatly resembles that induced by regular endurance training preceding strenuous prolonged exertion.


Syncope and intermittent Brugada ECG pattern.
Brugada syndrome is a rare syndrome, with an estimated prevalence in Europe of 1-5/10 000 population, whose initial clinical presentation can be sudden death. Although it has a characteristic electrocardiographic pattern, this can be intermittent. The authors present the case of a 32-year-old man, with no family history of syncope or sudden death, who went to the emergency department for syncope without prodromes. The initial electrocardiogram (ECG) in sinus rhythm documented an isolated and non-specific ST-segment elevation in V2. During further diagnostic studies, a repeat ECG revealed type 1 Brugada pattern. This pattern was later seen in a more marked form during a respiratory infection. The patient subsequently underwent electrophysiological study, followed by implantation of an implantable cardioverter-defibrillator (ICD), with an episode of ventricular fibrillation converted via ICD shock two months after implantation.


Phacoemulsification devices: a consumer's update.
This report extends a previous paper on the various characteristics of the most popular phacoemulsification devices. An evaluation of 11 devices by ten different manufacturers was attempted. Only five manufacturers of six devices agreed to critical evaluation or reevaluation. As in the previous report, the devices were compared for level of patient safety, dependability, efficiency, ease of usage, and operating cost for the first 1,000 cases. At the completion of this study, we ranked the nine devices evaluated over the past 17 months as follows: (1) United Surgical (Optikon) Systems Plus, (2) Optical Micro Systems (OMS), (3) United Surgical (Optikon) Phacotron, (4) CooperVision 10,000, (5) Site XTR, (6) CooperVision KCP, (7) CooperVision 9001, (8) Phakosystems CES 4000 and (9) United Sonics. To enhance the usefulness of this consumer's guide, we asked 40 experienced cataract surgeons what they wanted in the "ideal" phacoemulsification device. The opinions of 27 who responded are included.


Natural variation in stress response is related to post-stress parental effort in male house sparrows.
The central life-history trade-off between current and future reproductive effort seems to be mediated by corticosterone in birds. However, still little is known about how naturally occurring corticosterone levels during an acute stress may influence subsequent parental behavior. In this study we observed the parental behavior of free-living male house sparrows (Passer domesticus) both before and after they were subjected to a standard capture-handling stress. We investigated the relationships between corticosterone levels, pre- and post-stress parental behavior, while we statistically controlled for a number of other variables using a multivariate regression method, the path analysis. We found that males' baseline feeding rate predicted the body mass of the nestlings, indicating that male parental care is directly linked to fitness. Corticosterone levels were not explained by baseline feeding rate, but both baseline and stress-induced corticosterone levels had a negative influence on the males' post-stress feeding behavior. Moreover, males with large bib size had a stronger stress response and lower post-stress feeding rate than small bibbed males. These results indicate that naturally occurring variation in baseline and stress-induced corticosterone levels may influence subsequent parental decisions: individuals mounting a robust stress response are likely to reduce their parental commitment. Parental effort may be regulated in a complex manner, with corticosterone mediating the life-history trade-off between current reproduction and survival. However, different resolutions of this trade-off were apparent only following the stress, therefore the ability to modulate the stress response and maintain parental care in stressful situations may be important in life-history evolution.


An update in treating transformed lymphoma.
Indolent lymphomas typically have a prolonged course and favorable prognosis. Recent data support survival times that can reach several decades, even if periodic treatment is needed to manage symptoms or stabilize disease. However, all indolent lymphomas have the potential to undergo transformation to an aggressive phenotype, clinically characterized by a rapid progression of adenopathy, new-onset constitutional symptoms, or laboratory abnormalities, and the immediate need for therapeutic intervention. The most common scenario is transformation of follicular lymphoma to either diffuse large B-cell lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations; however, other indolent subtypes such as marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma/chronic lymphocytic leukemia, or even nodular lymphocyte predominant Hodgkin lymphoma, can undergo similar histologic transformation. The prognosis of transformed lymphomas has historically been quite poor, but there is ample evidence this is changing in the rituximab era. This article will provide a review of transformed lymphomas with an emphasis on treatment and the nuances of diagnosis and clinical management. Unless otherwise specified, all discussion in this review pertains to transformed follicular lymphoma which is the more common scenario and the subtype with the most robust data. In many cases, this information can be extrapolated and applied to other indolent histologies (i.e. transformed marginal zone lymphoma); however, several other clinical scenarios, such as Richter's transformation and "double hit" transformations, warrant a distinct discussion and will be reviewed separately.


Virus-mediated inhibition of natural cytotoxicity receptor recognition.
Natural killer (NK) cells are a part of the innate immune system that functions mainly to kill transformed and infected cells. Their activity is controlled by signals derived from a panel of activating and inhibitory receptors. The natural cytotoxicity receptors (NCRs): NKp30, NKp44, and NKp46 (NCR1 in mice) are prominent among the activating NK cell receptors and they are, notably, the only NK-activating receptors that are able to recognize pathogen-derived ligands. In addition, the NCRs also recognize cellular ligands, the identity of which remains largely unknown. In this review, we summarize the current knowledge regarding viruses that are recognized by the NCRs, focusing on the diverse immune-evasion mechanisms employed by viruses to escape this detection. We also discuss the unique role the NCRs have in regulating NK cell activity with particular emphasis on the in vivo function of NKp46/NCR1.


Insulin Modulates Myogenesis and Muscle Atrophy Resulting From Skin Scald Burn in Young Male Rats.
Burn injuries (BIs) due to scalding are one of the most common accidents among children. BIs greater than 40% of total body surface area are considered extensive and result in local and systemic response. We sought to assess morphological and myogenic mechanisms through both short- and long-term intensive insulin therapies that affect the skeletal muscle after extensive skin BI in young rats. Wistar rats aged 21 d were distributed into four groups: control (C), control with insulin (C + I), scald burn injury (SI), and SI with insulin (SI + I). The SI groups were submitted to a 45% total body surface area burn, and the C + I and SI + I groups received insulin (5 UI/Kg/d) for 4 or 14 d. Glucose tolerance and the homeostatic model assessment of insulin resistance index were determined. Gastrocnemius muscles were analyzed for histopathological, morphometric, and immunohistochemical myogenic parameters (Pax7, MyoD, and MyoG); in addition, the expression of genes related to muscle atrophy (MuRF1 and MAFbx) and its regulation (IGF-1) were also assessed. Short-term treatment with insulin favored muscle regeneration by primary myogenesis and decreased muscle atrophy in animals with BIs, whereas the long-term treatment modulated myogenesis by increasing the MyoD protein. Both treatments improved histopathological parameters and secondary myogenesis by increasing the MyoG protein. Treatment with insulin benefits myogenic parameters during regeneration and modulates MuRF1, an important mediator of muscle atrophy.


What has changed in pediatric kidney transplantation in Turkey? Experience of an evolving center.
Reluctance to perform kidney transplantations on children is an ongoing problem in Turkey. Moreover, urological pathologies still constitute the largest portion of the underlying etiologies in chronic renal failure patients. Herein, we retrospective analyzed the data acquired from our pediatric renal transplantation patients and reviewed the registry of dialysis and transplantation data prepared by the Turkish Society of Nephrology. Forty-six living donor kidney transplantations were performed in children between 2008 and 2012. Seventeen of 46 (37%) transplantations were preemptive. The mean age at operation time was 10.8 ± 5 years. The mean patient weight was 31.3 ± 15.8 kg (range, 9.4 to 66.4 kg). A detailed urologic evaluation was performed for every child with an underlying lower urinary tract disease. One enterocystoplasty and 2 ureterocystoplasties were performed for augmentation of the bladder, simultaneously. One-year death-censored graft survival and patient survival rates were 100% and 97.8%, respectively. The mean serum creatinine level was 0.86 ± 0.32 mg/dL (range, 0.3 to 1.8 mg/dL). None of the patients had vascular complications or acute tubular necrosis. One patient suffered graft-versus-host disease during the second month after renal transplantation and died with a functioning graft. In one patient with massive proteinuria detected after transplantation, recurrence of primary disease (focal segmental glomerulosclerosis) was considered and the patient was treated successfully with plasmapheresis. One child had an acute cellular rejection and was administered pulse steroid treatment. Although challenging, all patients in all pediatric age groups can successfully be operated and managed. With careful surgical technique, close postoperative follow-up, and efforts by the experienced and respectful surgical teams in this country, we could change the negative trends toward perform kidney transplantation in the Turkish pediatric population.


Perioperative Management of Anticoagulation.
Antiplatelet and anticoagulant drugs (antithrombotics) predispose to acute and chronic subdural hematomas. Patients on these drugs are at higher likelihood of presenting with larger hematomas and more severe neurologic deficits. Standard neurosurgical and neurocritical care of subdural hematomas involves reversal of antithrombosis preoperatively, whereas reversing antiplatelet drugs is less clear. This article highlights the spectrum of antithrombotic agents in common use, their mechanisms of action, and strategies for reversal.


Spectrum-dose conversion operator of NaI(Tl) and CsI(Tl) scintillation detectors for air dose rate measurement in contaminated environments.
Spectrum-dose conversion operators, the G(E) functions, for common NaI(Tl) scintillation survey meters and CsI(Tl) detectors are obtained for measurements in a semi-infinite plane of contaminated ground field by photon-emitting radionuclides (ground source). The calculated doses at a height of 100 cm from the ground in 137Cs-contaminated environments by the Monte Carlo simulation technique are compared with those obtained using the G(E) functions by assuming idealized irradiation geometries such as anterior-posterior or isotropic. The simulation reveals that one could overestimate air dose rates in the environment by a maximum of 20-30% for NaI(Tl) detectors and 40-50% for CsI(Tl) detectors depending on photon energy when using the G(E) functions assuming idealized irradiation geometries for ground source measurements. Measurements obtained after the nuclear accident in Fukushima reveal that the doses calculated using a G(E) function for a unidirectional irradiation geometry are 1.17 times higher than those calculated using a G(E) function for the ground source in the case of a CsI(Tl) scintillation detector, which has a rectangular parallelepiped crystal (13 × 13 × 20 mm3). However, if a G(E) function is used assuming irradiation to a surface of the detector, the doses agree with those of the ground source within 2%. These results indicate that in contaminated environments, the commonly used scintillation-based detectors overestimate doses within the acceptable limit. In addition, the degree of overestimation depends on the irradiation direction of each detector assumed for developing the G(E) function. With regard to directional dependence of the detectors, reliable air dose rates in the environment can be obtained using the G(E) function determined in unidirectional irradiation geometry, provided that the irradiation surface of the crystal is determined properly.


The last piece in the vitamin B1 biosynthesis puzzle: structural and functional insight into yeast 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase.
Vitamin B(1) is essential for all organisms being well recognized as a necessary cofactor for key metabolic pathways such as glycolysis, and was more recently implicated in DNA damage responses. Little is known about the enzyme responsible for the formation of the pyrimidine moiety (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P) synthase). We report a structure-function study of the HMP-P synthase from yeast, THI5p. Our crystallographic structure shows that THI5p is a mix between periplasmic binding proteins and pyridoxal 5'-phosphate-dependent enzymes. Mutational and yeast complementation studies identify the key residues for HMP-P biosynthesis as well as the use of pyridoxal 5'-phosphate as a substrate rather than as a cofactor. Furthermore, we could show that iron binding to HMP-P synthase is essential for the reaction.


Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.
The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.


Selective photocrosslinking of functional ligands to antibodies via the conserved nucleotide binding site.
The conserved nucleotide binding site (NBS), found in the Fab variable domain of all antibody isotypes, remains a not-so-widely known and under-utilized site. Here, we describe a UV photocrosslinking method (UV-NBS) that utilizes the NBS for site-specific covalent functionalization of antibodies, while preserving antibody activity. We identified a small molecule, indole-3-butyric acid (IBA), which has affinity for the NBS (K(d) = 1-8 μM) and can be photocrosslinked to antibodies upon UV energy exposure. By synthesizing their IBA conjugated versions, we have successfully photocrosslinked various types of functional ligands to antibodies at the NBS, including affinity tags (biotin), fluorescent molecules (FITC), peptides (iRGD), and chemotherapeutics (paclitaxel). An optimal UV exposure of 1-2 J/cm(2) yielded the most efficient photocrosslinking and resulted in 1-2 conjugations per antibody, while preserving the antigen binding activity and Fc related functions. Analysis of the photocrosslinked conjugates using western blotting, mass spectrometry, and computational docking simulations demonstrated that the photocrosslinking specifically takes place at the Y/F42 residue in framework region 2 of the antibody light chain. Taken together, the UV-NBS method provides a practical, site-specific, and chemically efficient method to functionalize antibodies with significant implications in diagnostic and therapeutic settings.


Cardiac blood biomarkers in patients receiving thoracic (chemo)radiation.
Cardiotoxicity is a known consequence of thoracic irradiation and there are multiple overlapping risk factors for cardiac disease and thoracic malignancies. In this study, we quantified the impact of thoracic (chemo)radiation on cardiac troponin T (TnT), creatine kinase-myocardial band (CK-MB) and aminoterminal pro-brain natriuretic peptide (NT-proBNP). Thirty patients receiving radiation therapy to the thorax with or without concurrent chemotherapy were evaluated. Serum was collected at baseline, 2 weeks into treatment and at the completion of radiation therapy. TnT, CK-MB and NT-proBNP were quantified using commercially available immunoassays. Cardiac dosimetric parameters and clinical risk factors were examined. In 29 of 30 patients, serum TnT remained undetectable (<0.01ng/mL) throughout (chemo)radiation. In the one patient with detectable serum TnT, levels did not change significantly with treatment. Similarly, thoracic (chemo)radiation did not cause statistically significant elevations in serum CK-MB and NT-proBNP. Thus, contemporary thoracic (chemo)radiation does not commonly result in elevations of serum TnT, CK-MB or NT-proBNP. Elevations in these markers during treatment merit further evaluation.


A cohort study of incident hypertension in relation to changes in vigorous physical activity in men and women.
To assess the dose-response relationship between changes in vigorous exercise (running distance, Deltakm per week) and physician-diagnosed hypertension. Twenty-four thousand, five hundred and fifty men and 10 113 women were followed prospectively for (mean +/- SD) 7.8 +/- 1.8 and 7.5 +/- 2.0 years, respectively. Among those who maintained their running distance within +/-5 km per week (5841 men), logistic regression showed that the log odds for hypertension was significantly lower for those who ran longer distances (coefficient+/-SE:-0.019 +/- 0.003 per km per week; P < 0.0001) even when adjusted for body mass index (-0.010 +/- 0.003 per km per week; P = 0.002). Analyses of all 24 550 male and 10,113 female runners showed that the log odds for hypertension declined significantly in relation to Deltakm per week in men (-0.009 +/- 0.001; P < 0.0001) and women (-0.006 +/- 0.003; P = 0.03), which remained significant when adjusted for body mass index in men (-0.005 +/- 0.001; P < 0.0001) but not in women (-0.004 +/- 0.003; P = 0.13). In both sexes, the decline was related to the distance run at the end of follow-up but not at baseline. Compared with men who ran less than 8 km per week, the age-specific rate for incident hypertension in those who ran more than 40 km per week at the end of follow-up was 80% lower in those aged between 35 and 44 years, 66% lower in those between 45 and 54 years, 69% lower in those aged between 55 and 64 years (all P < 0.0001), and 57% lower in those older than 65 years (P = 0.08). The odds of developing hypertension are reduced in those who remain vigorously active and increased in those whose vigorous activity declined. These effects are dependent on the exercise dose and are due in part to metabolic processes associated with body weight.


UVA irradiation-induced activation of activator protein-1 is correlated with induced expression of AP-1 family members in the human keratinocyte cell line HaCaT.
To determine whether the transcription factor activator protein-1 (AP-1) could be modulated by ultraviolet A (UVA) exposure, we examined AP-1 DNA-binding activity and transactivation after exposure to UVA in the human immortalized keratinocyte cell line HaCaT. Maximal AP-1 transactivation was observed with 250 kJ/m2 UVA between 3 and 4 h after irradiation. DNA binding of AP-1 to the target 12-O-tetradecanoylphorbol-13-acetate response element sequence was maximally induced 1-3 h after irradiation. Both de novo transcription and translation contributed to the UVA-induced AP-1 DNA binding. c-Fos was implicated as a primary component of the AP-1 DNA-binding complex. Other components of the complex included Fra-2, c-Jun, JunB and JunD. UVA irradiation induced protein expression of c-Fos, c-Jun, Fra-1 and Fra-2. Phosphorylated forms of these induced proteins were determined at specific time points. A strong correlation existed between UVA-induced AP-1 activity and accumulation of c-Fos, c-Jun and Fra-1 proteins. UVA irradiation also induced c-fos and c-jun mRNA expression and transcriptional activation of the c-fos gene promoter. These results demonstrate that UVA irradiation activates AP-1 and that c-fos induction may play a critical role in the response of these human keratinocytes to UVA irradiation.


Ecological and individual predictors of maternal smoking behaviour. Looking beyond individual socioeconomic predictors at the community setting.
The aim of this study is to examine the prevalence of smoking during pregnancy by the individual mother's sociodemographic characteristics and ecological factors at the community level (suburbs). This analysis combined 1996 Australia Census and data on 3424 women attending Well-Baby-Clinics (WBC) between January 1996 and February 1998 within a region in South Western Sydney (SWS), Australia. The prevalence of maternal smoking was 31%. Maternal factors such as marital status, country of birth, education, occupation, socioeconomic status (SES), and types of antenatal care (ANC) were independent risk factors for maternal smoking. Small area analysis revealed suburbs within SWS with high rates of maternal smoking (47-57%). Community level characteristics such as low income, low educational level, young mothers, and unemployment can explain 85.7% of the variation in maternal smoking in SWS. Smoking during pregnancy is recognised as a serious risk factor to the unborn child. The present study draws attention to local community level factors, other than individual SES, which may be important when developing strategies for maternal smoking prevention programs.


A review of PD-1/PD-L1 siRNA delivery systems in immune T cells and cancer cells.
Programmed cell death 1 (PD-1) is a member of the CD28/CTLA-4 family of inhibitory immunological checkpoint receptors that's also widely produced by exhausted T lymphocytes in an immunosuppressive tumor microenvironment. PD-1 binds to programmed death ligand (PD-L1) and suppresses anti-cancer activity of T lymphocytes. We examined the current literature on how siRNA delivery systems can be used to target PD-1 and PD-L1, as well as the anti-cancer mechanisms and challenges associated with siRNA molecules. We look at studies that use program death 1 siRNA or program death 1 ligand siRNA to treat cancer. Several databases have been used for this purpose, including NCBI, Scopus, and Google Scholar. This study looked at several methods for delivering siRNA to immune cells and cancer cells. According to these findings, suppressing PD-1 in T cells increases T lymphocyte activity. PD-L1 suppression in DCs improves antigen presentation and co-stimulatory signals on their surface, resulting in T cell activation. Chemotherapy resistance and cancer cell suppression of T cells are reduced when PD-L1/2 is suppressed in cancer cells. The findings of this study indicated that several strategies for siRNA transfection to immune and cancer cells have been evaluated in recent decades, some of which effectively transfect siRNA to target cells, and defined PD-1 siRNA as a promising strategy for cancer treatment.


The effect of uterine contractions on fetal oxygen saturation.
To find out what happens to fetal arteriolar oxygen saturation during a uterine contraction. Prospective observational study. Labour ward, St James's University Hospital, Leeds. Eighteen women in normal labour monitored with a fetal scalp surface pulse oximetry sensor, an intrauterine pressure catheter, and a head to cervix force transducer. The effect of intrauterine pressure and head to cervix force on fetal arteriolar oxygen saturation was examined using time series analysis and a regression model of 159 contractions. Fetal oxygen saturation during a contraction. The average oxygen saturation drops after a contraction. The greatest drop in oxygen saturation is reached 92 s after the peak of a contraction and takes approximately 1 min 30 s to recover (P = 0.036). Uterine contractions during normal labour affect fetal oxygen saturation.


Successful transfemoral aortic valve replacement in a bicuspid aortic stenotic valve: requirements for a safe implant.
Although transcatheter aortic valve replacement (TAVR) has been accepted as an attractive alternative for high-risk patients with severe symptomatic aortic stenosis (AS), patients with congenital bicuspid AS has been typically disqualified for this indication due to an implied risk of device dislocation, distortion, or device malfunctioning. Nonetheless, bicuspid AS is not uncommon and frequently missed by transthoracic echocardiography. We reported an interesting case of a high-risk patient with severe symptomatic bicuspid AS who underwent successful TAVR and discussed the anatomic requirements for a safe implant in patients with bicuspid AS considered candidates for TAVR.


Perforation of the rectum and sigmoid colon during barium-enema examination. Management and prevention.
Perforation of the rectum or sigmoid colon complicated 5 of 2200 barium-enema examinations performed during a 4-year period. Three patients with rectal perforations manifested by air extravasation were successfully treated with intravenous antibiotics and complete bowel rest. Two patients with barium extravasation were treated with immediate operation and colostomy. All five patients recovered. Perforation was found to be associated with a rectal stricture due to ulcerative colitis, a rectal cancer, an incarcerated inguinal hernia, fulminant ulcerative colitis, and a normal colon in an elderly patient. To determine the pressure in the rectum that could potentially be generated during a barium-enema examination, the pressures created by a standard barium delivery set were measured, using 1-meter columns of water, 25 percent diatrizoate sodium (Hypaque), 20 percent barium, and 80 percent barium. The columns generated pressures of 70, 85, 95, and 120 mm Hg respectively. Squeezing the delivery bag increased the pressure 21 to 79 percent or a maximum of 55 mm Hg. Colorectal perforation during barium-enema examination that was not accompanied by barium extravasation could be successfully treated nonoperatively. The associated pathology and our studies of pressures generated during a barium-enema examination allow us to suggest that the incidence of colorectal perforation during barium-enema radiography can be reduced by 1) performing proctoscopy prior to barium enema, 2) avoiding the use of the rectal balloon in patients with known rectal lesions, 3) avoiding barium studies in patients with active colitis, 4) avoiding generation of pressure greater than that created by a column of barium suspension of one meter, and 5) using a lower concentration of barium when possible.


Enhanced DOC removal using anion and cation ion exchange resins.
Hardness and DOC removal in a single ion exchange unit operation allows for less infrastructure, is advantageous for process operation and depending on the water source, could enhance anion exchange resin removal of dissolved organic carbon (DOC). Simultaneous application of cationic (Plus) and anionic (MIEX) ion exchange resin in a single contact vessel was tested at pilot and bench scales, under multiple regeneration cycles. Hardness removal correlated with theoretical predictions; where measured hardness was between 88 and 98% of the predicted value. Comparing bench scale DOC removal of solely treating water with MIEX compared to Plus and MIEX treated water showed an enhanced DOC removal, where removal was increased from 0.5 to 1.25 mg/L for the simultaneous resin application compared to solely applying MIEX resin. A full scale MIEX treatment plant (14.5 MGD) reduced raw water DOC from 13.7 mg/L to 4.90 mg/L in the treated effluent at a bed volume (BV) treatment rate of 800, where a parallel operation of a simultaneous MIEX and Plus resin pilot (10 gpm) measured effluent DOC concentrations of no greater than 3.4 mg/L, even at bed volumes of treatment 37.5% greater than the full scale plant. MIEX effluent compared to simultaneous Plus and MIEX effluent resulted in differences in fluorescence intensity that correlated to decreases in DOC concentration. The simultaneous treatment of Plus and MIEX resin produced water with predominantly microbial character, indicating the enhanced DOC removal was principally due to increased removal of terrestrially derived organic matter. The addition of Plus resin to a process train with MIEX resin allows for one treatment process to remove both DOC and hardness, where a single brine waste stream can be sent to sewer at a full-scale plant, completely removing lime chemical addition and sludge waste disposal for precipitative softening processes.


Epinephrine Autoinjector Prescribing Trends: An Outpatient Population-Based Study in Olmsted County, Minnesota.
The prescribing pattern of epinephrine over time is an indicator of the secular trend of anaphylaxis. However, it is not well known in a population level in the United States. To evaluate the trend of prescriptions for epinephrine autoinjectors in Olmsted County, Minn, residents. Outpatient prescriptions for epinephrine were identified among residents of Olmsted County, Minn, between January 1, 2004, and December 31, 2010. We used the first prescription per patient per year, and the first prescription per patient during the study period to calculate incidence rates. Incidence rates per 100,000 person-years were calculated using patients prescribed epinephrine per year as the numerator and age- and sex-specific counts of the population of Olmsted County as the denominator. The relationships of age group, sex, and year of prescription with incidence rates were assessed by fitting Poisson regression models using the SAS procedure GENMOD. The overall incidence rate of epinephrine autoinjector prescriptions during the study period was 757 per 100,000 person-years (95% confidence interval: 740-774). The prescription rates per patient per year increased over time, with an annual rate of increase of 8% (P < .001), but the rates per patient remained stable (P = .077). For each year, incidence rates overall were higher in women compared with men (P < .001). From ages 0 to 19, incidence rates were higher in boys compared with girls. At age 20 and above, incidence rates were higher in women compared with men. The overall rate of epinephrine autoinjector prescriptions increased, but the rate of first-time prescriptions was stable from 2005 to 2010. In childhood, boys were more likely to receive a prescription than girls, but this reversed in later ages.


Selective Neuronal Vulnerability in Alzheimer's Disease: A Modern Holy Grail.
In this issue of Neuron, through an elegant progression of computational and bio-informatic experiments centered on transcriptomic comparison of vulnerable and resistant neurons across species, Roussarie et al. (2020) predict and provide experimental support for specific genes and molecular pathways driving Alzheimer's disease, including the splicing factor PTBP1.


Yeast and bacteria cell hydrophobicity and hydrocarbon biodegradation in the presence of natural surfactants: rhamnolipides and saponins.
This study concerns the relation between hydrocarbon biodegradation in the presence of natural surfactants and cell hydrophobicity resulting from the use of these surfactants. The relative capabilities of two bacterial strains (Pseudomonas aeruginosa and Bacillus subtilis) and two yeast strains (Candida maltosa, Yarrowia lipolytica) were investigated. The selected microorganisms were tested separately and in combination in order to achieve the optimal degrading performance. The surface cell hydrophobicity of microorganisms and the degree of hydrocarbon biodegradation were measured. The microbial adhesion to the hydrocarbon (MATH) test was used to denote the surface cell hydrophobicity of the microbial species. The results indicate the correlation between the modification of the surface cell and the degree of hydrocarbon biodegradation; however results for bacteria differ from that obtained for yeast strains. Saponins, as the surfactant, was more effective than rhamnolipides during hydrocarbon biodegradation, though the concentration of this surfactant has no significant influence on the surface cell hydrophobicity.


Evaluating the Uptake and Acceptability of Standardized Postoperative Rehabilitation Guidelines Using an Online Knowledge Translation Approach.
Providing physical therapists with evidence-based and consensus-derived guidelines to manage postoperative shoulder patients is essential; these guidelines should be readily available and provide clinically applicable information. Knowledge translation (KT) initiatives that encourage interaction between clinicians and researchers, that have multifaceted components and use a variety of strategies, can significantly change practice. The objective of this study was to determine the uptake and acceptability of standardized postoperative shoulder guidelines with an accompanying online KT resource through evaluation of website analytics and a quantitative survey. A multi-pronged approach was used to assess uptake and acceptability of the guidelines and online KT resource. Website analytics of usage and geographical location of users was measured as were physical therapist survey responses. Website analytics revealed that 5406 individuals used the online resource between October 2012 and September 2013 with the average visit lasting 8 minutes; only 47% of users were within the guideline developers' surgical referral region. Physical therapists who used the new shoulder guidelines were very satisfied or satisfied (96%) with the guidelines, reporting they promoted patient-specific clinical decision-making extremely or very well (68%). They viewed the online KT resource positively, with 79% rating it as "very useful" or "quite useful." Physical therapists from regions beyond those expected to use the new shoulder guidelines were also aware of the website and also rated it as very useful. The survey sample was relatively small and did not directly assess patient outcomes. An online KT web resource developed in conjunction with standardized postoperative shoulder guidelines was perceived as useful based on website analytics and survey responses. Active KT strategies such as this can improve uptake and dissemination of best practice in physical therapy.


Relationship between airflow limitation in response to upper airway negative pressure during wakefulness and obstructive sleep apnea severity.
The objective was to determine if alteration in airflow induced by negative pressure (NP) applied to participants' upper airways during wakefulness, is related to obstructive sleep apnea (OSA) severity as determined by the apnea-hypopnea index (AHI). Adults 18 years of age or greater were recruited. All participants underwent overnight polysomnography to assess their apnea-hypopnea index (AHI). While awake, participants were twice exposed, orally, to -3 cm H2O of NP for five full breaths. The ratio of the breathing volumes of the last two breaths during NP exposure to the last two breaths prior to NP exposure was deemed the NP ratio (NPR). Eighteen participants were enrolled. A strong relationship between the AHI and the exponentially transformed NPR (ExpNPR) for all participants was observed (R2 = 0.55, p < 0.001). A multivariable model using the independent variable ExpNPR, age, body mass index and sex accounted for 81% of variability in AHI (p = 0.0006). A leave-one-subject-out cross-validation analysis revealed that predicted AHI using the multivariable model, and actual AHI from participants' polysomnograms, were strongly related (R2 = 0.72, p < 0.001). We conclude that ExpNPR, was strongly related to the AHI, independently of demographic factors known to be related to the AHI.


Comparison of physical and psychological health outcomes for motorcyclists and other road users after land transport crashes: an inception cohort study.
Serious injuries and fatalities among vulnerable road users on two wheeled motorised vehicles have increased across Australia and internationally in the past decade yet fallen for motor vehicle occupants. Almost half of all reported motorcycle injury crashes cause serious injury or death, nearly double that of motor vehicle police-reported crashes. This study explores associations with sociodemographic and pre-injury health characteristics and health outcomes after a road traffic injury; aiming to compare motorcyclists with other road users and inform recovery care. An inception cohort study recruited 1854 individuals aged > 17 years, injured following land-transport crashes in New South Wales, Australia (July 2013-November 2016). Interviews conducted at baseline, 6-and 12-months post-injury elicited demographic, socioeconomic, and self-reported health conditions. Primary analysis involved 1854 participants who were recruited at baseline as three distinct road user groups; 628 (33.9%) motorcyclists, 927 (50%) vehicle occupants and 299 (16.1%) bicyclists. At baseline, injury patterns differed significantly between road user groups; motorcyclists were more than twice as likely to sustain lower extremity injury (p < 0.001); to have more severe injury severity scores (p < 0.001) and longer hospital stays versus vs vehicle occupants and bicyclists (< 0.001) across these measures. Injured motorcyclists were predominantly male (88.1%, p < 0.001), were younger on average (38 years) than bicyclists (41.5 years), had lower income and education levels, and poorer pre-injury physical health than other road user groups. Despite these differences, at 12 months post-injury motorcyclists had better physical health (SF12-PCS 2.07 (0.77, 3.36), p = 0.002) and reported lower pain scores (- 0.51 (- 0.83, - 0.2), p < 0.001) than vehicle occupants. Motorcyclists displayed less evidence of psychological distress than vehicle occupants, but more than bicyclists across several measures used. Road user types differ in important characteristics, including pre-injury health status and recovery after injury. As vulnerable road users experiencing transport crash and considering their higher initial injury severity, the degree of recovery among motorcyclists compared with other user types is remarkable and unexplained. Health and recovery outcomes after land-transport crashes is least favourable among vehicle occupants despite their higher levels of protection in a crash. This information is valuable for targeting early intervention strategies by road user type during the post-crash care phase, to improve long-term recovery.


Taurine regulates corticotropin secretion at the level of the supraoptic nucleus during stress in rats.
We studied the consequence of taurine release within the supraoptic nucleus (SON) for the hormonal stress response. Rats were chronically implanted with both microdialysis probes in the SON and jugular venous catheters. Three days later the animals received either Ringer's solution or a specific taurine antagonist via retrodialysis directly into the SON during a 10-min forced swimming session, while simultaneously blood samples were collected. Compared to the Ringer's control, treatment with the taurine antagonist significantly attenuated the increase in plasma corticotropin concentration caused by the stressor exposure (P < 0.05, analysis of variance). This finding supports the hypothesis that the hypothalamic-neurohypophysial system is a potent regulator of the hormonal stress response and suggests an important role for taurine in this context.


Prophylactic migraine therapy: mechanisms and evidence.
This article focuses on the scientific evidence for pharmacotherapy for migraine prevention. Non-pharmacologic approaches are not discussed. However, it is important to remember the complementary value of some of these strategies (eg, biofeedback) to migraine treatment.


An ontology-based approach for modelling and querying Alzheimer's disease data.
The recent advances in biotechnology and computer science have led to an ever-increasing availability of public biomedical data distributed in large databases worldwide. However, these data collections are far from being "standardized" so to be harmonized or even integrated, making it impossible to fully exploit the latest machine learning technologies for the analysis of data themselves. Hence, facing this huge flow of biomedical data is a challenging task for researchers and clinicians due to their complexity and high heterogeneity. This is the case of neurodegenerative diseases and the Alzheimer's Disease (AD) in whose context specialized data collections such as the one by the Alzheimer's Disease Neuroimaging Initiative (ADNI) are maintained. Ontologies are controlled vocabularies that allow the semantics of data and their relationships in a given domain to be represented. They are often exploited to aid knowledge and data management in healthcare research. Computational Ontologies are the result of the combination of data management systems and traditional ontologies. Our approach is i) to define a computational ontology representing a logic-based formal conceptual model of the ADNI data collection and ii) to provide a means for populating the ontology with the actual data in the Alzheimer Disease Neuroimaging Initiative (ADNI). These two components make it possible to semantically query the ADNI database in order to support data extraction in a more intuitive manner. We developed: i) a detailed computational ontology for clinical multimodal datasets from the ADNI repository in order to simplify the access to these data; ii) a means for populating this ontology with the actual ADNI data. Such computational ontology immediately makes it possible to facilitate complex queries to the ADNI files, obtaining new diagnostic knowledge about Alzheimer's disease. The proposed ontology will improve the access to the ADNI dataset, allowing queries to extract multivariate datasets to perform multidimensional and longitudinal statistical analyses. Moreover, the proposed ontology can be a candidate for supporting the design and implementation of new information systems for the collection and management of AD data and metadata, and for being a reference point for harmonizing or integrating data residing in different sources.


Development of approaches to improve the healing following muscle contusion.
Muscle injuries are a challenging problem in traumatology, and the most frequent occurrence in sports medicine. Muscle contusions are among the most common muscle injuries. Although this injury is capable of healing, an incomplete functional recovery often occurs, depending on the severity of the blunt trauma. We have developed an animal model of muscle contusion in mice (high energy blunt trauma) and characterized the muscle's ability to heal following this injury using histology and immunohistochemistry to determine the level of muscle regeneration and the development of scar tissue. We have observed a massive muscle regeneration occurring in the first 2 wk postinjury that is subsequently followed by the development of muscle fibrosis. Based on these observations, we propose that the enhancement of muscle growth and regeneration, as well as the prevention of fibrotic development, could be used as approach(es) to improve the healing of muscle injuries. In fact, we have identified three growth factors (bFGF, IGF-1, and NGF) capable of enhancing myoblast proliferation and differentiation in vitro and improving the healing of the injured muscle in vivo. Furthermore, the ability of adenovirus to mediate direct and ex vivo gene transfer of beta-galactosidase into the injured site opens possibilities of delivering an efficient and persistent expression of these growth factors in the injured muscle. These studies should help in the development of strategies to promote efficient muscle healing with complete functional recovery following muscle contusion.


Emergency use authorization of medicines: History and ethical dilemma.
The regulatory approval process of the United States Food and Drug Administration and European Union is the most demanding and challenging worldwide. They have the provision of the expedited approval pathways, i.e., "Emergency use authorizations" and "Conditional marketing authorizations," respectively, to give approval to novel therapeutics agents during emergency situations. India, firstly formalized the accelerated pathway named "Accelerated Approval Process" as per the New Drugs and Clinical Trials rule 2019 to address unmet medical needs that was implemented by the Central Drug Standard Control Organization to approve the novel therapeutics agents during COVID-19. Hence, our aim is to understand and compare the different emergency approval processes in the world, their underlined claims and conditions with the list of approved products under this concept. All the information collected and analyzed from different official websites of regulatory bodies. In this review, we have enlightened on all these processes with their few approved products.


Phosphatases maintain low catalytic activity of SGK1: DNA damage resets the balance in favor of phosphorylation.
The serum- and glucocorticoid-induced kinase 1 (SGK1) promotes cell survival under stress conditions and facilitates the emergence of drug resistance in cancer. The underlying mechanisms of these observations are not fully understood. In this study, we found that SGK1 activity is suppressed by the action of the S/T phosphatases PP5 and PP2A, which constantly dephosphorylate SGK1. Using newly developed anti-phospho SGK1 antibodies and inhibitors of phosphatases, we determined that the high degree of dephosphorylation is caused by two factors: the tendency of SGK1 to unfold, which makes it dependent on Hsp90 chaperone complexes composed of four proteins, Hsp90/CDC37/PP5/SGK1, and where the phosphatase PP5 persistently dephosphorylates SGK1 within the complex. SGK1 binding to PP2A regulatory subunits B55γ and B55δ brings PP2A catalytic subunit close to exposed SGK1 phosphoresidues. A further association of phosphorylated pS37-FAM122A-an endogenous inhibitor of PP2A-to the holoenzyme diminishes dephosphorylation of SGK1 mediated by PP2A. Our study also reveals that genotoxic stress can reverse the dominant impact of phosphatases over kinases by activating the DNA-dependent protein kinase, which enhances mTORC2 activity directed to SGK1. Thus, our results provide insight into a molecular pathway that enables SGK1 to gain phosphorylation and catalytic activity and promote cell survival, potentially diminishing the efficacy of cancer treatments. As the DNA damage response operates in many cancer cells and is further induced by chemotherapies, the findings of this study could have significant implications for the development of novel cancer therapies targeting SGK1.


Cubic phase-forming dry powders for controlled drug delivery on mucosal surfaces.
The purpose of this study was to prepare and physicochemically characterize protein-loaded, glycerol monooleate (GMO)-based dry powder systems, which can be used for the controlled mucosal delivery of macromolecules (e.g., nasal, buccal, pulmonary). Bovine serum albumin (BSA)-loaded powders were prepared by spray-drying, freeze-drying and/or spray-freezing using different types of carrier materials, including mannitol, polyvinyl pyrrolidone (PVP 25) and polyethylene glycols (PEGs). The systems were characterized by optical and polarized light microscopy, X-ray powder diffraction, gel electrophoresis and diffusion studies. The type of carrier material strongly affected the resulting particle size and shape. The presence of GMO effectively slowed down BSA release. Importantly, broad ranges of release patterns could be achieved by varying the type of preparation method and composition of the dry powders. In all cases, the primary structure of the BSA remained intact. GMO, which is a wax solid at room temperature, has been successfully converted into dry powder formulations that offer potential for the controlled mucosal delivery of proteins.


Fibroblast growth factors promote the survival of adult rat retinal ganglion cells after transection of the optic nerve.
Basic and acidic fibroblast growth factors (FGF) were implanted next to the proximal stump of the transected optic nerve of adult rats, in order to assess whether these molecules have neurotrophic activity in vivo. Of the 119,973 +/- 2484 (S.E.M.) retinal ganglion cells present in retinae of unoperated control rats, 11,375 +/- 2413 (S.E.M.) remained at 30 days after transection of the optic nerve in control operated rats. After implantation of gel foam soaked in basic FGF, the number of retinal ganglion cells surviving at 30 days after axotomy tripled (36,387 +/- 3270 (S.E.M.], after acidic FGF, it increased almost 4-fold (40,916 +/- 5405 (S.E.M.]. These results indicate that FGF has neurotrophic activity in the adult central nervous system, and that this molecule is able to rescue adult retinal ganglion cells from axotomy induced cell death. It remains to be shown whether FGF acts directly on retinal ganglion cells or indirectly via glial cells or other cells.


Helicobacter hepaticus promotes liver fibrosis through oxidative stress induced by hydrogenase in BALB/c mice.
It has been documented that Helicobacter hepaticus produces a nickel-containing hydrogen-oxidizing hydrogenase enzyme, which is necessary for hydrogen-supported amino acid uptake. Although H. hepaticus infection has been shown to promote liver inflammation and fibrosis in BALB/c mice, the impact of hydrogenase on the progression of liver fibrosis induced by H. hepaticus has not been explored. BALB/c mice were inoculated with hydrogenase mutant (ΔHyaB) or wild type (WT) H. hepaticus 3B1 for 12 and 24 weeks. H. hepaticus colonization, hepatic histopathology, serum biochemistry, expression of inflammatory cytokines, and oxidative stress signaling pathways were detected. We found that ΔHyaB had no influence on the colonization of H. hepaticus in the liver of mice at 12 and 24 weeks post infection (WPI). However, mice infected by ΔHyaB strains developed significantly alleviated liver inflammation and fibrosis compared with WT infection. Moreover, ΔHyaB infection remarkably increased the expression of hepatic GSH, SOD, and GSH-Px, and decreased the liver levels of MDA, ALT, and AST compared to WT H. hepaticus infected group from 12 to 24 WPI. Furthermore, mRNA levels of Il-6, Tnf-α, iNos, Hmox-1, and α-SMA were significantly decreased with an increase of Nfe2l2 in the liver of mice infected by ΔHyaB strains. In addition, ΔHyaB H. hepaticus restored the activation of the Nrf2/HO-1 signaling pathway, which is inhibited by H. hepaticus infection. These data demonstrated that H. hepaticus hydrogenase promoted liver inflammation and fibrosis development mediated by oxidative stress in male BALB/c mice.


Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.
Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD.


Biomechanical Assessment of Tilted Mandibular Second Molars with Full-Crown Adjacent to Implant-Supported Restoration: 3D Finite Element Analysis.
The aim of this study was to investigate the effects of tooth root inclination and crown preparation angulation on the stress distribution of tilted second molars, supporting structures and adjacent implant by using the finite element analysis method. 3D finite element models of tilted second molar and tooth-supporting structures, including the two designs with three different angles of root inclination and crown preparation angulations, were constructed for full-crown restoration. For all models, the stress distribution was analyzed under vertical and oblique loading conditions. The maximum equivalent stress (MES) increased as root inclination increased, and the highest stress value occurred in the tooth root furcation of the model with 30° root inclination under oblique loading. When root inclination was the same, the MES of each structure was approximate under the same direction load regardless of crown preparation angulation. Higher stress values were found on the tooth root, periodontal ligament, and cortical bone of all models under oblique load compared with vertical load. The highest stress value occurred in the distal adjacent area of implant. Tooth roots with less than 30° inclination, occlusal preparation parallel to the bite plane and small oblique force loading are recommended as significant considerations for full-crown restoration of a mesial inclined mandibular second molar.


Cyclic dipeptides and the human microbiome: Opportunities and challenges.
Research into the human microbiome has implicated its constituents in a variety of non-communicable diseases, with certain microbes found to promote health and others leading to dysbiosis and pathogenesis.Microbes communicate and coordinate their behaviour through the secretion of small molecules, such as cyclic dipeptides (CDPs), into their surrounding environment. CDPs are ubiquitous signalling molecules thatexhibit a wide range of biological activities, with particular relevance to human health due to their potential to act as microbiome modulators.


Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging Combined with T1 Mapping Identifies Dysplastic Module and Hepatocellular Carcinoma: A Retrospective Study.
Hepatocellular carcinoma (HCC) is the leading type of liver cancer in adults, often resulting in fatal outcomes for those with cirrhosis. Dysplastic nodule (DN) is a liver nodule that is substantial in size, ranging from 1-2 cm. However, accurately distinguishing between DN and HCC on imaging has posed a challenge. The aim of this study is to assess the usefulness of Gd-EOB-DTPA-enhanced MRI T1 mapping in distinguishing between DN and HCC. This study analyzed 66 patients with confirmed HCC or DN who underwent Gd-EOB-DTPA-enhanced MRI T1 mapping before surgery or puncture at the Army Medical Center in China. The T1 values of each lesion were measured before and after Gd-EOB-DTPA administration, and various calculations were made, including absolute and percentage reduction in T1 value and coefficient of variation. The t-test was used to compare these values between the two groups, and the efficacy of T1 mapping values for differential diagnosis of HCC and DN was evaluated using the receiver operating characteristic curve (ROC). The study found that T1pre, T1hp, ΔT1, ΔT1%, and CV in the HCC group were significantly higher than in the DN group (p < 0.01). The accuracy of T1hp, ΔT1, and CVT1-hp in identifying HCC from DN was high, with AUCs of 0.955, 0.910, and 0.932, respectively. ΔT1% also had some accuracy, with an AUC of 0.818. Our results provide preliminary evidence that Gd-EOB-DTPA-enhanced MRI T1, CVT1-hp mapping, can be a valuable tool in diagnosing and differentiating between HCC and DN.


High yield of protein-rich forage rice achieved by soil amendment with composted sewage sludge and topdressing with treated wastewater.
Aiming to promote low-cost production of protein-rich forage rice and resource recycling from wastewater treatment plants, a pot experiment was conducted to assess the possibility to substitute mineral fertilizers with composted sewage sludge (CSS) with/without top-dressing with treated municipal wastewater (TWW). Results indicated that a basal application of CSS at 2.6 g N pot-1 replaced conventional mineral fertilization of 1.3 g N pot-1 to produce comparable yields with the same rice protein content, although there might be a risk of increased As concentration in rice grains. Interestingly, CSS application at a reasonable dose of 1.3 g N pot-1, followed by a topdressing with TWW resulted in 27% higher yield and 25% superior rice protein content relative to the mineral fertilization, with no risk of heavy metal(loid) accumulation in grains and in paddy soils. Here we demonstrated an appealing fertilization practice with zero use of mineral fertilizers in paddy rice cultivation, expectedly contributing towards sustainable rice farming and animal husbandry in Japan.


Important considerations when assessing the effect of essential fatty acids on cognitive performance.
Over the past decade, there have been many studies determining the effect of dietary ω-3 and ω-6 fatty acids intake on cognitive performance; however, they have largely been inconsistent in their conclusions. In this letter, we provide context to the article by Dong et al., titled "Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and nutrition examination Survey (NHANES) 2011-2014" and provide methodological considerations with regards to covariate measurement and inclusion that can be generalized to future cross-sectional studies. In particular, delineating 1) the type and source of fatty acid, in context of an individual's overall dietary patterns, 2) sociobehavioral risk factors and physical & mental comorbidities, 3) and daily cognitive activity are important to adequately control for covariates.


Bone Health in Glomerular Kidney Disease.
To summarize the literature regarding alterations in bone health in patients with glomerular kidney disease and highlight areas in need of additional investigation. There is mounting evidence that children and adults with glomerular conditions, with or without compromised kidney function, comprise a distinct subgroup of patients with unique risk factors for altered bone health. Patients with glomerular kidney disease are exposed to both disease-related and treatment-related factors that affect bone structure and function. In addition to chronic kidney disease-related risk factors for impaired bone health, high rates of exposure to osteotoxic medications, varying degrees of systemic inflammation, and altered vitamin D metabolism may contribute to compromised bone health in individuals with glomerular disease. Further study is needed to better understand these risk factors and the complex interaction between the immune system and bone cells in glomerular disease.


The Demands of Surgery Residency: More Than Just Duty Hours?
Efforts to improve surgical resident well-being could be accelerated with an improved understanding of resident job demands and resources. In this study, we sought to obtain a clearer picture of surgery resident job demands by assessing how residents distribute their time both inside and outside of the hospital. Furthermore, we aimed to elucidate residents' perceptions about current duty hour regulations. A cross-sectional survey was sent to 1098 surgical residents at 27 US programs. Responses regarding work hours, demographics, well-being (utilizing the physician well-being index), and perceptions of duty hours in relation to education and rest, were collected. Data were evaluated using descriptive statistics and content analysis. A total of 163 residents (14.8% response rate) were included in the study. Residents reported a median total patient care hours per week of 78.0 h. Trainees spent 12.5 h on other professional activities. Greater than 40% of residents were "at risk" for depression and suicide based on physician well-being index scores. Four major themes associated with education and rest were identified: 1) duty hour definitions and reporting mechanisms do not completely reflect the amount of work residents perform, 2) quality patient care and educational opportunities do not fit neatly within the duty hour framework, 3) resident perceptions of duty hours are impacted the educational environment, and 4) long work hours and lack of adequate rest negatively affect well-being. The breadth and depth of trainee job demands are not accurately captured by current duty hour reporting mechanisms, and residents do not believe that their current work hours allow for adequate rest or even completion of other clinical or academic tasks outside of the hospital. Many residents are unwell. Duty hour policies and resident well-being may be improved with a more holistic accounting of resident job demands and greater attention to the resources that residents have to offset those demands.


Comparison of gamma index based on dosimetric error and clinically relevant dose-volume index based on three-dimensional dose prediction in breast intensity-modulated radiation therapy.
Measurement-guided dose reconstruction has lately attracted significant attention because it can predict the delivered patient dose distribution. Although the treatment planning system (TPS) uses sophisticated algorithm to calculate the dose distribution, the calculation accuracy depends on the particular TPS used. This study aimed to investigate the relationship between the gamma passing rate (GPR) and the clinically relevant dose-volume index based on the predicted 3D patient dose distribution derived from two TPSs (XiO, RayStation). Twenty-one breast intensity-modulated radiation therapy plans were inversely optimized using XiO. With the same plans, both TPSs calculated the planned dose distribution. We conducted per-beam measurements on the coronal plane using a 2D array detector and analyzed the difference in 2D GPRs between the measured and planned doses by commercial software. Using in-house software, we calculated the predicted 3D patient dose distribution and derived the predicted 3D GPR, the predicted per-organ 3D GPR, and the predicted clinically relevant dose-volume indices [dose-volume histogram metrics and the value of the tumor-control probability/normal tissue complication probability of the planning target volume and organs at risk]. The results derived from XiO were compared with those from RayStation. While the mean 2D GPRs derived from both TPSs were 98.1% (XiO) and 100% (RayStation), the mean predicted 3D GPRs of ipsilateral lung (73.3% [XiO] and 85.9% [RayStation]; p < 0.001) had no correlation with 2D GPRs under the 3% global/3 mm criterion. Besides, this significant difference in terms of referenced TPS between XiO and RayStation could be explained by the fact that the error of predicted V5Gy of ipsilateral lung derived from XiO (29.6%) was significantly larger than that derived from RayStation (- 0.2%; p < 0.001). GPR is useful as a patient quality assurance to detect dosimetric errors; however, it does not necessarily contain detailed information on errors. Using the predicted clinically relevant dose-volume indices, the clinical interpretation of dosimetric errors can be obtained. We conclude that a clinically relevant dose-volume index based on the predicted 3D patient dose distribution could add to the clinical and biological considerations in the GPR, if we can guarantee the dose calculation accuracy of referenced TPS.


A dynamic landscape of allergen associations in delayed-type cutaneous hypersensitivity.
Delayed-type hypersensitivity represents a significant clinical and public health challenge. Patients undergoing patch testing may exhibit positive reactions to more than one allergen. It is recognized that reactions to specific pairs of allergens are associated, reflecting a combination of exposure patterns and structural similarity. To explore the influence of time of testing, age, sex and atopy status on allergen pair associations in a series of 45 110 consecutive patients tested over 30 years. Patch test records of all patients undergoing testing with a modified European baseline series between 1985 and 2014 were retrieved from a database at St John's Institute of Dermatology. Reactions were read on days 2 and 4. For each allergen it was recorded whether the allergen was tested and whether the result was positive or negative. This is the largest reported study of patch test allergen pair relationships. Our analysis shows a high degree of variability in allergen pair associations. Rigorous statistical analysis reveals a large number of differences between groups, including a significant increase in the association between formaldehyde and multiple formaldehyde-releasing preservatives over the study period, in addition to pair associations with cobalt and formaldehyde-releasing preservatives. These were present to a significantly greater extent in men than in women. These observations extend our understanding of cutaneous allergy, with implications for both clinical practice and mechanisms of cutaneous hypersensitivity.


New potentiometric PVC membrane electrode for Ferric Reduction Antioxidant Power assay.
In this study, a fast, reproducible and simple-to-apply a new potentiometric determination method was developed for the evaluation of iron (III) reducing power (FRAP), one of the antioxidant capacity tests. For this purpose, an all-solid-state contact iron (III)-selective poly vinyl chloride (PVC) membrane electrode (FRAP-PME) has been developed. In the structure of the developed polymeric membrane electrode (PME), Fe(II)-quercetin compound was used as the active ingredient. It was obtained that PME exhibits a linear potentiometric behavior against the concentration change of Fe(III) ion between 1.0 × 10-1-1.0 × 10-5 mol L-1 and the detection limit is 8.0 × 10-6 molL-1. PME showed a very rapid potential response (40-45 s) and was found to have a very high selectivity towards Fe(III) ion in the presence of other species that might interfere. The proposed potentiometric method has been successfully applied to evaluate the iron (III) reducing power of plant extracts.


Distinct CpG methylation profiles characterize different clinical groups of neuroblastic tumors.
The hypermethylation of CpG islands within gene promoter regions is an epigenetic phenomenon that is often, but not always, associated with the transcriptional silencing of downstream genes and contributes to carcinogenesis. We have determined the pattern of methylation of several genes involved in distinct biological pathways, including cell proliferation and apoptosis, in neuroblastoma and in the nonmalignant ganglioneuroma. The purpose of this work was to search for epigenetic signatures that could be associated with defined clinical and biological parameters and that, in prospective, could identify specific risk categories among the patients. We have analysed 31 malignant neuroblastoma with or without MYCN amplification and 13 benign ganglioneuroma and we have observed dramatic differences in the methylation pattern of five genes (CASP8, 14.3.3sigma, DeltaN-p73, RASSF1A and DCR2) between these tumors indicating that this phenomenon is not tissue-specific and can be considered as cancer-dependent. Furthermore, the methylation pattern of 14.3.3sigma, RASSF1A and of an intragenic segment of CASP8 was significantly different between MYCN amplified and single copy neuroblastoma suggesting a specific role of epigenetic alterations in aggressive neuroblastoma.


Purification and inhibition by neuropeptides of angiotensin-converting enzyme from rat brain.
Angiotensin-converting enzyme was solubilized with papain from a particulate fraction of rat brain and purified to apparent homogeneity by a procedure including DEAE-cellulose, hydroxylapatite, Sephadex G-200, Cys(Bzl)-Pro-Sepharose, and ricin-Sepharose chromatography. Bradykinin potentiators, SQ 14,225, and Arg-Pro-Pro strongly inhibited the activity of the purified enzyme, whereas Phe-Ala, phosphoramidon, and pentobarbital exerted little inhibitory effect on the activity. Among neuropeptides investigated, substance P, bradykinin, and Leu-enkephalin (Arg6) exerted strong inhibitory actions on the enzyme. Furthermore, the latter two peptides were shown to be good substrates for the enzyme. Thus, angiotensin-converting enzyme of rat brain is distinct from endogenous enkephalinase and may interact with various neuropeptides located in the brain.