A treatment paradigm for high-grade brain arteriovenous malformations: volume-staged radiosurgical downgrading followed by microsurgical resection.
The surgical treatment of many large arteriovenous malformations (AVMs) is associated with substantial risks, and many are considered inoperable. Furthermore, AVMs larger than 3 cm in diameter are not usually treated with conventional single-session radiosurgery encompassing the entire AVM volume. Volume-staged stereotactic radiosurgery (VS-SRS) is an option for large AVMs, but it has mixed results. The authors report on a series of patients with high-grade AVMs who underwent multiple VS-SRS sessions with resultant downgrading of the AVMs, followed by resection. A cohort of patients was retrieved from a single-institution AVM patient registry consisting of prospectively collected data. VS-SRS was performed as a planned intentional treatment. Surgery was considered as salvage therapy in select patients. Sixteen AVMs underwent VS-SRS followed by surgery. Four AVMs presented with rupture. The mean patient age was 25.3 years (range 13-54 years). The average initial Spetzler-Martin grade before any treatment was 4, while the average supplemented Spetzler-Martin grade (Spetzler-Martin plus Lawton-Young) was 7.1. The average AVM size in maximum dimension was 5.9 cm (range 3.3-10 cm). All AVMs were supratentorial in location and all except one were in eloquent areas of the brain, with 7 involving primary motor cortex. The mean number of VS-SRS sessions was 2.7 (range 2-5 sessions). The mean interval between first VS-SRS session and resection was 5.7 years. There were 4 hemorrhages that occurred after VS-SRS. The average Spetzler-Martin grade was reduced to 2.5 (downgrade, -1.5) and the average supplemented Spetzler-Martin grade was reduced to 5.6 (downgrade, -1.5). The maximum AVM size was reduced to an average of 3.0 cm (downsize=-2.9 cm). The mean modified Rankin Scale (mRS) scores were 1.2, 2.3, and 2.2 before VS-SRS, before surgery, and at last follow-up, respectively (mean follow-up, 6.9 years). Fifteen AVMs were cured after surgery. Ten patients had good outcomes at last follow-up (7 with mRS Score 0 or 1, and 3 with mRS Score 2). There were 2 deaths (both mRS Score 1 before treatment) and 4 patients with mRS Score 3 outcome (from mRS Scores 0, 1, and 2 [n=2]). Volume-staged SRS can downgrade AVMs, transforming high-grade AVMs (initially considered inoperable) into operable AVMs with acceptable surgical risks. This treatment paradigm offers an alternative to conservative observation for young patients with unruptured AVMs and long life expectancy, where the risk of hemorrhage is substantial. Difficult AVMs were cured in 15 patients. Surgical morbidity associated with downgraded AVMs is reduced to that of postradiosurgical/preoperative supplemented Spetzler-Martin grades, not their initial AVM grades.


Effects of norepinephrine and a combined norepinephrine and dobutamine infusion on systemic hemodynamics and indices of renal function in normotensive neonatal thoroughbred foals.
Norepinephrine is a potent vasopressor that increases arterial blood pressure but may have adverse effects on renal blood flow. The combination of norepinephrine and dobutamine may lead to improved renal perfusion compared to an infusion of norepinephrine alone. The effects of these drugs in the normotensive neonatal foal have not been reported. Norepinephrine increases arterial blood pressure. Adding dobutamine to a norepinephrine infusion will change the renal profile during the infusions without changing the arterial blood pressure. Eight conscious Thoroughbred foals were used in this study. Each foal received norepinephrine (0.1 microg/kg/min), combined norepinephrine (0.1 microg/kg/min) and dobutamine (5 microg/kg/min), and a control dose of saline in a masked, placebo-controlled study. Heart rate, arterial blood pressure (direct), and cardiac output (lithium dilution) were measured, and systemic vascular resistance, stroke volume, cardiac index, and stroke volume index were calculated. Urine output, creatinine clearance, and fractional excretion of sodium, potassium, and chloride were measured. Norepinephrine and a combined norepinephrine and dobutamine infusion increased arterial blood pressure and systemic vascular resistance and decreased heart rate and cardiac index as compared to saline. The combination resulted in higher arterial pressure than norepinephrine alone. There was no significant difference in urine output, creatinine clearance, or fractional excretion of electrolytes with either infusion as compared to saline. These data suggest that norepinephrine and a combined norepinephrine and dobutamine infusion cause unique hemodynamic effects without affecting indices of renal function, and this effect warrants further investigation.


Hospital costs of acute pulmonary embolism.
Pulmonary embolism places a heavy economic burden on health care systems, but the components of hospital cost have not been elucidated. We evaluated hospitalized patients with the primary diagnosis of pulmonary embolism. Our goal was to determine the total and component costs associated with their hospital care. We included patients hospitalized at Brigham and Women's Hospital from September 2003 to May 2010. Patient demographics, characteristics, comorbidities, interventions, and treatments were obtained from the electronic medical record. Costs were obtained using the hospital's accounting software and categorized into the areas providing direct patient supplies or care. We identified 991 hospitalized patients with acute pulmonary embolism. In-hospital mortality was 4.2%, and 90-day mortality after hospital discharge was 13.8%. The median length of hospital stay was 3 days, and the mean length of hospital stay was 4 days. The mean total hospitalization cost per patient was $8764. Nursing costs, which included room and board, were $5102. Pharmacy ($966) and radiology ($963) costs were similar. Pharmacy costs ($966) were dominated by the use of low-molecular-weight heparin ($232). Radiology costs ($963) were dominated by the use of diagnostic imaging examinations ($672). During the observation period, an average of 160 patients with pulmonary embolism were admitted each year, requiring an annual hospital expense ranging from $884,814 to $1,866,489. Pulmonary embolism has a high case fatality rate and remains an expensive illness to diagnose and treat. Nursing costs comprise the largest component of costs.


Increased mortality among Indigenous persons during and after release from prison in New South Wales.
To estimate the overall and cause specific mortality of Aboriginal offenders in New South Wales (NSW), Australia. The study cohort consisted of all Aboriginal men and women aged 18 years and older who had experienced full-time imprisonment in NSW between 1 January 1988 and 31 December 2002. Their data were linked probabilistically to the Australian National Death Index to obtain information on death. Standardised mortality ratios were calculated for all causes of death and adjusted for age, sex, and calendar year. The cohort comprised 7,980 men and 1,373 women with 75,801 person years of observation. During a median follow-up period of 8.3 years, 485 men and 73 women died, giving an overall mortality rate of 733 and 755 deaths per 100,000 person-years. The risk of death in men was 4.8 (95% CI: 4.4-5.3) times and among women 12.6 (95% CI: 10.0-15.8) times that of the NSW residents, with a markedly elevated risk for almost all conditions. The leading cause of death was cardiovascular disease in men (112 deaths, 23%) and mental and behavioural disorders (17 deaths, 23%) in women. The risk of death was greatest following release from prison. High mortality rates for cardiovascular disease, a preventable and treatable condition, were seen among Aboriginal offenders. Prison has an important role to play in screening marginalised populations for a range of health conditions. This is particularly true for Indigenous offenders.


Simulation of polymer--polymer interdiffusion using the dynamic lattice liquid model.
In this paper, we present computer simulation results concerning interdiffusion of fully compatible components in symmetric binary (AB) polymer mixtures in solutions. The simulation is performed in two dimensions using the algorithm based on the dynamic lattice liquid model. The solvent molecules are taken into account explicitly. The evolution of the concentration profiles in time at an interface is studied for chain lengths N=2,4,8,16 for three polymer concentrations phi=0.1,0.5,0.9. The tracer diffusion coefficients for polymer chains and for the solvent are obtained by monitoring the mean square displacements of their center of mass. The relationships between coefficients of interdiffusion and self-diffusion are tested.


Development of a ZIF-91-Porous-Liquid-Based Composite Hydrogel Dressing System for Diabetic Wound Healing.
Porous metal-organic framework (MOF) liquids with permanent porosity, good fluidity, and fine dispersion attract broad attention in catalysis, transportation, gas storage, and chemical separations. Yet, the design and synthesis of porous MOF liquids for drug delivery remain less explored. Herein, a simple and general strategy is reported to prepare ZIF-91 porous liquid (ZIF-91-PL) via surface modification and ion exchange. The cationic nature of ZIF-91-PL not only renders it antibacterial but also with high curcumin loading capacity and sustained release. More importantly, the acrylate group on the grafted side chain of ZIF-91-PL makes it feasible to crosslink with modified gelatin through light curing, and the obtained hydrogel shows a significantly improved healing effect on the wound of diabetes. This work demonstrates for the first time, a MOF-based porous liquid for drug delivery, and the further fabrication of composite hydrogel may have potential applications in biomedical science.


RNA-DNA hybrid (R-loop) immunoprecipitation mapping: an analytical workflow to evaluate inherent biases.
The impact of R-loops on the physiology and pathology of chromosomes has been demonstrated extensively by chromatin biology research. The progress in this field has been driven by technological advancement of R-loop mapping methods that largely relied on a single approach, DNA-RNA immunoprecipitation (DRIP). Most of the DRIP protocols use the experimental design that was developed by a few laboratories, without paying attention to the potential caveats that might affect the outcome of RNA-DNA hybrid mapping. To assess the accuracy and utility of this technology, we pursued an analytical approach to estimate inherent biases and errors in the DRIP protocol. By performing DRIP-sequencing, qPCR, and receiver operator characteristic (ROC) analysis, we tested the effect of formaldehyde fixation, cell lysis temperature, mode of genome fragmentation, and removal of free RNA on the efficacy of RNA-DNA hybrid detection and implemented workflows that were able to distinguish complex and weak DRIP signals in a noisy background with high confidence. We also show that some of the workflows perform poorly and generate random answers. Furthermore, we found that the most commonly used genome fragmentation method (restriction enzyme digestion) led to the overrepresentation of lengthy DRIP fragments over coding ORFs, and this bias was enhanced at the first exons. Biased genome sampling severely compromised mapping resolution and prevented the assignment of precise biological function to a significant fraction of R-loops. The revised workflow presented herein is established and optimized using objective ROC analyses and provides reproducible and highly specific RNA-DNA hybrid detection.


A new alternative mechanism in glioblastoma vascularization: tubular vasculogenic mimicry.
Glioblastoma is one of the most angiogenic human tumours and endothelial proliferation is a hallmark of the disease. A better understanding of glioblastoma vasculature is needed to optimize anti-angiogenic therapy that has shown a high but transient efficacy. We analysed human glioblastoma tissues and found non-endothelial cell-lined blood vessels that were formed by tumour cells (vasculogenic mimicry of the tubular type). We hypothesized that CD133+ glioblastoma cells presenting stem-cell properties may express pro-vascular molecules allowing them to form blood vessels de novo. We demonstrated in vitro that glioblastoma stem-like cells were capable of vasculogenesis and endothelium-associated genes expression. Moreover, a fraction of these glioblastoma stem-like cells could transdifferentiate into vascular smooth muscle-like cells. We describe here a new mechanism of alternative glioblastoma vascularization and open a new perspective for the antivascular treatment strategy.


Built-in software in children on long-term ventilation in real life practice.
Information gathered with built-in software (BIS) on new ventilators allow clinicians to access long-term noninvasive ventilation (LTNIV) data. Nevertheless, few evidence are available in literature that highlight potential strengths and disadvantages of using BIS in pediatrics. We aim to evaluate the use of BIS in a cohort of 90 children on LTNIV in our unit, focusing mainly on adherence, air leaks, and residual sleep events. We found that caregivers' perception of ventilator use is independent from objective adherence (P = .137). Furthermore, we failed to find any predictors of adherence. As regards air leaks, we found that pre-scholars' (0-6 years old) total air leaks are lower than teenagers' (more than 12 years old) (P < .05). Multiple regressive analysis showed that age at the beginning of therapy is a predictor of total air leaks: prescholars are associated with lower values (P < .05), while scholars (6-12 years old) are associated with higher values (P < .05). Finally, we explored the validity of BIS automatic scoring of sleep events (AHIBIS ) as compared with the manual scoring of polygraphy (AHIPG ). AHIBIS is within a range of 3.98 from AHIPG in 95% of cases, with a 64% of sensitivity and a 67% of specificity in identifying a pathological state. The disagreement between the two methods seems to increase for high AHI values. In conclusion, data gathered by BIS are a useful support tool for the clinician in assessing the course of LTNIV. However, clinicians must be aware of the several limitations of built-in software, especially in pediatrics.


Distributed optimization of multi-class SVMs.
Training of one-vs.-rest SVMs can be parallelized over the number of classes in a straight forward way. Given enough computational resources, one-vs.-rest SVMs can thus be trained on data involving a large number of classes. The same cannot be stated, however, for the so-called all-in-one SVMs, which require solving a quadratic program of size quadratically in the number of classes. We develop distributed algorithms for two all-in-one SVM formulations (Lee et al. and Weston and Watkins) that parallelize the computation evenly over the number of classes. This allows us to compare these models to one-vs.-rest SVMs on unprecedented scale. The results indicate superior accuracy on text classification data.


Deep Learning Algorithms with Demographic Information Help to Detect Tuberculosis in Chest Radiographs in Annual Workers' Health Examination Data.
We aimed to use deep learning to detect tuberculosis in chest radiographs in annual workers' health examination data and compare the performances of convolutional neural networks (CNNs) based on images only (I-CNN) and CNNs including demographic variables (D-CNN). The I-CNN and D-CNN models were trained on 1000 chest X-ray images, both positive and negative, for tuberculosis. Feature extraction was conducted using VGG19, InceptionV3, ResNet50, DenseNet121, and InceptionResNetV2. Age, weight, height, and gender were recorded as demographic variables. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated for model comparison. The AUC values of the D-CNN models were greater than that of I-CNN. The AUC values for VGG19 increased by 0.0144 (0.957 to 0.9714) in the training set, and by 0.0138 (0.9075 to 0.9213) in the test set (both p < 0.05). The D-CNN models show greater sensitivity than I-CNN models (0.815 vs. 0.775, respectively) at the same cut-off point for the same specificity of 0.962. The sensitivity of D-CNN does not attenuate as much as that of I-CNN, even when specificity is increased by cut-off points. Conclusion: Our results indicate that machine learning can facilitate the detection of tuberculosis in chest X-rays, and demographic factors can improve this process.


Late Onset Ornithine Transcarbamylase Deficiency Triggered by an Acute Increase in Protein Intake: A Review of 10 Cases Reported in the Literature.
While the urea cycle disorders (UCDs) classically present in the neonatal stage, they have become increasingly recognized as a rare cause of unexplained hyperammonemic encephalopathy in adults. Many metabolic triggers for late-onset UCDs have been described in the literature including excessive protein intake. In this case series, ten such documented cases are reviewed with analysis of patient demographic, protein load, treatment course, and patient outcome. Common delays in treatment include recognition of hyperammonemia as the cause of encephalopathy and initiation of hemodialysis. In only one case was a diet history used to raise suspicion for a metabolic derangement. Metabolic disorders remain an important consideration in adults presenting with encephalopathy not explained by more common etiologies, and recent and remote dietary history may provide valuable information.


Regulator LdhR and d-Lactate Dehydrogenase LdhA of Burkholderia multivorans Play Roles in Carbon Overflow and in Planktonic Cellular Aggregate Formation.
LysR-type transcriptional regulators (LTTRs) are the most commonly found regulators in Burkholderia cepacia complex, comprising opportunistic pathogens causing chronic respiratory infections in cystic fibrosis (CF) patients. Despite LTTRs being global regulators of pathogenicity in several types of bacteria, few have been characterized in Burkholderia Here, we show that gene ldhR of B. multivorans encoding an LTTR is cotranscribed with ldhA encoding a d-lactate dehydrogenase and evaluate their implication in virulence traits such as exopolysaccharide (EPS) synthesis and biofilm formation. A comparison of the wild type (WT) and its isogenic ΔldhR mutant grown in medium with 2% d-glucose revealed a negative impact on EPS biosynthesis and on cell viability in the presence of LdhR. The loss of viability in WT cells was caused by intracellular acidification as a consequence of the cumulative secretion of organic acids, including d-lactate, which was absent from the ΔldhR mutant supernatant. Furthermore, LdhR is implicated in the formation of planktonic cellular aggregates. WT cell aggregates reached 1,000 μm in size after 24 h in liquid cultures, in contrast to ΔldhR mutant aggregates that never grew more than 60 μm. The overexpression of d-lactate dehydrogenase LdhA in the ΔldhR mutant partially restored the formed aggregate size, suggesting a role for fermentation inside aggregates. Similar results were obtained for surface-attached biofilms, with WT cells producing more biofilm. A systematic evaluation of planktonic aggregates in Burkholderia CF clinical isolates showed aggregates in 40 of 74. As CF patients' lung environments are microaerophilic and bacteria are found as free aggregates/biofilms, LdhR and LdhA might have central roles in adapting to this environment.IMPORTANCE Cystic fibrosis patients often suffer from chronic respiratory infections caused by several types of microorganisms. Among them are the Burkholderia cepacia complex bacteria, which cause progressive deterioration of lung function that, in some patients, might develop into fatal necrotizing pneumoniae with bacteremia, known as "cepacia syndrome." Burkholderia pathogenesis is multifactorial as they express several virulence factors, form biofilms, and are highly resistant to antimicrobial compounds, making their eradication from the CF patients' airways very difficult. As Burkholderia is commonly found in CF lungs in the form of cell aggregates and biofilms, the need to investigate the mechanisms of cellular aggregation is obvious. In this study, we demonstrate the importance of a d-lactate dehydrogenase and a regulator in regulating carbon overflow, cellular aggregates, and surface-attached biofilm formation. This not only enhances our understanding of Burkholderia pathogenesis but can also lead to the development of drugs against these proteins to circumvent biofilm formation.


Reduced toxicity of daunorubicin by conjugation to dextran.
Daunorubicin-dextran conjugate (dau-dex) was compared to free daunorubicin for acute and subacute toxicity and efficacy in tumor chemotherapy. LD50 and LD2 values of dau-dex are about threefold higher than those of the free drug. The therapeutic index of dau-dex is also higher, manifesting a "safe-region" in which no mortality occurs either from YAC lymphoma or from drug toxicity. Dau-dex caused almost no damage to heart tissue during the 2 months following four injections of the therapeutic dose and caused no change in the differential count of bone marrow cells. Altogether, the subacute toxicity of dau-dex is much lower than that of free daunorubicin, as expressed by negligible histologic damage to all organs examined and compared to the massive atrophy of spleen and bone marrow effected by the free drug.


Seatbelt syndrome with gastric mucosal breaks and intra-gastric wall air leakage.
As numerous reports were published regarding the so-called seatbelt syndrome involved in car crashes, most of them were mentioned about small intestine, duodenum and colon perforations and solid organ bleeding. No reports have been published regarding multiple gastric mucosal tears with intra-gastric wall air leakage with massive bleeding. A 65-year-old woman was admitted after a motor vehicle crash. She vomited massive fresh blood. Gastric mucosal breaks, approximately 5 cm in length, were observed. Computed tomography imaging revealed multiple gastric mucosal breaks. We report a rare case wherein a traffic accident caused a serious condition associated with massive digestive bleeding.


Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage.
Cerebral vasospasm secondary to aneurysmal subarachnoid hemorrhage that has become refractory to maximal medical management can be treated with selective intra-arterial papaverine infusions. Papaverine is a potent vasodilator of the proximal, intermediate, and distal cerebral arteries and can improve cerebral blood flow (CBF). When infused intra-arterially using endovascular microcatheter techniques, papaverine can effectively increase angiographic vessel diameter, decrease prolonged cerebral circulation time, and improve cerebral oxygenation. However, one of the major disadvantages of papaverine is its transient nature, which can result in recurrent and/or persistent angiographic and clinical vasospasm that may require multiple repeated infusions, despite a successful response to the initial treatment. Intra-arterial papaverine can be used alone or in combination with balloon angioplasty. This article reviews the mechanism of action, technique of administration, effects on CBF, clinical results, and complications of intra-arterial papaverine for the treatment of cerebral vasospasm.


Effect of a novel designed intensive patient care program on cognitive impairment, anxiety, depression as well as relapse free survival in acute ischemic stroke patients: a randomized controlled study.
Objective: We aimed to evaluate the influence of a novel designed intensive patient care program (IPCP) on cognitive impairment, anxiety, depression and relapse-free survival (RFS) in acute ischemic stroke (AIS) patients. Methods: Two hundred forty-two AIS patients were consecutively recruited in this randomized controlled study and randomly allocated to IPCP group or control group as 1:1 ratio. Patients received IPCP and conventional treatment in IPCP group, while received usual education, cognitive rehabilitation training and conventional treatment in control group for 12-month intervention. Cognitive impairment, anxiety and depression were assessed by Mini-Mental State Examination (MMSE), Hospital Anxiety and Depression Scale (HADS) anxiety (HADS-A), and HADS depression (HADS-D) at baseline (M0), month (M)3, M6 and M12. After intervention, patients were followed up until 2018/7/30 and RFS was calculated. Results: IPCP increased MMSE score at M12 and change of MMSE score (M12-M0), while decreased cognitive impairment rate at M12. For anxiety, decreased change of HADS-A score (M12-M0) and lower anxiety rate at M12 were observed in IPCP group compared to control group. For depression, decreased HADS-D score at M6 and M12, reduced change of HADS-D score (M12-M0) and lower depression rate at M12 were shown in IPCP group compared to control group. Besides, RFS was numerically longer in IPCP group compared to control group, but without statistical significance. Conclusions: IPCP presents with a positive influence on improving cognitive impairment and decreasing anxiety as well as depression, while a less effect on improving RFS in AIS patients. Abbreviation: IPCP: intensive patient care program; RFS: relapse free survival; AIS: acute ischemic stroke; MRA: magnetic resonance angiography; ITT: intention-to-treat; LOCF: last observation carried forward.


Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport.
19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD(2) or 1,25(OH)(2)D(3). Calcium absorption increased from 16.5% +/- 7.8% in vehicle-treated rats to 27.5% +/- 7.2% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 21.6% +/- 3.9%, 26.2% +/- 5.5%, and 27.4% +/- 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). Similar results were obtained for phosphate absorption, with an increase from 28.2% +/- 5.5% in vehicle-treated rats to 40.2% +/- 4.7% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 32.9% +/- 2.2%, 36.2% +/- 4.5%, and 36.8% +/- 3.8% in rats given 10, 50, and 100 ng/day 19-norD(2), respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.


From arteries to boreholes: steady-state response of a poroelastic cylinder to fluid injection.
The radially outward flow of fluid into a porous medium occurs in many practical problems, from transport across vascular walls to the pressurization of boreholes. As the driving pressure becomes non-negligible relative to the stiffness of the solid structure, the poromechanical coupling between the fluid and the solid has an increasingly strong impact on the flow. For very large pressures or very soft materials, as is the case for hydraulic fracturing and arterial flows, this coupling can lead to large deformations and, hence, to strong deviations from a classical, linear-poroelastic response. Here, we study this problem by analysing the steady-state response of a poroelastic cylinder to fluid injection. We consider the qualitative and quantitative impacts of kinematic and constitutive nonlinearity, highlighting the strong impact of deformation-dependent permeability. We show that the wall thickness (thick versus thin) and the outer boundary condition (free versus constrained) play a central role in controlling the mechanics.


Novel therapies for septic shock over the past 4 decades.
Infections that result in shock and organ failure are a major public health problem worldwide. Severe sepsis and septic shock affect patients of all ages and often complicate chronic diseases. They are the major causes of death in critical care units and contribute substantially to hospital inpatient costs. Translating the scientific advances of the last 4 decades into clinical practice has been challenging. Despite many attempts to develop new therapies, the basic elements of treatment have not changed since the 1960s. In this Grand Rounds, we summarize the results of the clinical trials conducted during the last 4 decades, discuss some lessons learned, and suggest possible directions for future investigation.


High frequency circular translation pin-on-disk method for accelerated wear testing of ultrahigh molecular weight polyethylene as a bearing material in total hip arthroplasty.
The temporal change of the direction of sliding relative to the ultrahigh molecular weight polyethylene (UHMWPE) component of prosthetic joints is known to be of crucial importance with respect to wear. One complete revolution of the resultant friction vector is commonly called a wear cycle. It was hypothesized that in order to accelerate the wear test, the cycle frequency may be substantially increased if the circumference of the slide track is reduced in proportion, and still the wear mechanisms remain realistic and no overheating takes place. This requires an additional slow motion mechanism with which the lubrication of the contact is maintained and wear particles are conveyed away from the contact. A three-station, dual motion high frequency circular translation pin-on-disk (HF-CTPOD) device with a relative cycle frequency of 25.3 Hz and an average sliding velocity of 27.4 mm/s was designed. The pins circularly translated at high frequency (1.0 mm per cycle, 24.8 Hz, clockwise), and the disks at low frequency (31.4mm per cycle, 0.5 Hz, counter-clockwise). In a 22 million cycle (10 day) test, the wear rate of conventional gamma-sterilized UHMWPE pins against polished CoCr disks in diluted serum was 1.8 mg per 24 h, which was six times higher than that in the established 1 Hz CTPOD device. The wear mechanisms were similar. Burnishing of the pin was the predominant feature. No overheating took place. With the dual motion HF-CTPOD method, the wear testing of UHMWPE as a bearing material in total hip arthroplasty can be substantially accelerated without concerns of the validity of the wear simulation.


Compositional bias and size of genomes of human DNA viruses.
Genomes of 144 human DNA viruses were analyzed in the aspect of their compositional asymmetry. DNA viruses were divided into two groups according to their genome sizes. The analysis revealed that the level of guanine and cytosine (GC content) in the coding sequences of small genome DNA viruses was significantly lower than that of large genome DNA viruses. Because small genome viruses replicate their genomes using cellular enzymes, while large genome viruses use their own enzymes for genome replication, the two groups of viruses may be under different mutational bias and/or selection pressure. In these viruses, GC content at the third codon position correlated with GC content at the first and second codon position. However, the relationship in small genome DNA viruses was weaker than that in large genome DNA viruses, suggesting that their genome composition may be more strongly influenced by codon usage preference or restriction on amino acid composition.


Evidence of beta-adrenergic involvement in forced swimming-induced behavioural despair of mice.
Modulation of forced swimming-induced immobility by beta-adrenoceptor activation was investigated in mice. Isoprenaline prolonged the immobility duration of mice in a dose-related manner when the animals were forced to swim for 6 min periods. On the other hand, salbutamol (a beta 2-agonist) reduced the immobility duration of mice. Pretreatment with propranolol (1,2,4,8 and 16 mg/kg, ip), atenolol (10 mg/kg, ip) and metoprolol (10 mg/kg, ip) antagonized the immobility-enhancing effect of isoprenaline. Chronic administration (10 mg/kg/day) for 8 days of propranolol and imipramine protected the animals from isoprenaline-evoked prolongation of immobility. These findings suggest that central beta 1- and beta 2-subtypes of adrenoceptors may be acting in opposite directions to modify the immobility duration of mice. Activation of central beta 1-adrenoceptors may lead to enhanced behavioural despair, whereas a reverse effect may be observed on beta 2-adrenoceptor activation.


CRISPR/Cas9-mediated Cxcr4 disease allele inactivation for gene therapy in a mouse model of WHIM syndrome.
WHIM syndrome is an autosomal dominant immunodeficiency disorder caused by gain-of-function mutations in chemokine receptor CXCR4 that promote severe panleukopenia because of retention of mature leukocytes in the bone marrow (BM). We previously reported that Cxcr4-haploinsufficient (Cxcr4+/o) hematopoietic stem cells (HSCs) have a strong selective advantage for durable hematopoietic reconstitution over wild-type (Cxcr4+/+) and WHIM (Cxcr4+/w) HSCs and that a patient with WHIM was spontaneously cured by chromothriptic deletion of the disease allele in an HSC, suggesting that WHIM allele inactivation through gene editing may be a safe genetic cure strategy for the disease. We have developed a 2-step preclinical protocol of autologous hematopoietic stem and progenitor cell (HSPC) transplantation to achieve this goal. First, 1 copy of Cxcr4 in HSPCs was inactivated in vitro by CRISPR/Cas9 editing with a single guide RNA (sgRNA) that does not discriminate between Cxcr4+/w and Cxcr4+/+ alleles. Then, through in vivo natural selection, WHIM allele-inactivated cells were enriched over wild-type allele-inactivated cells. The WHIM allele-inactivated HSCs retained long-term pluripotency and selective hematopoietic reconstitution advantages. To our knowledge, this is the first example of gene therapy for an autosomal dominant gain-of-function disease using a disease allele inactivation strategy in place of the less efficient disease allele repair approach.


[Liver albumin dialysis (MARS)--treatment of choice in Amanita phalloides poisoning?].
Amanita phalloides is a direct life-threatening poisoning because of acute multiorgan failure. Urgent liver transplantation (LTx) is the last chance to save patient's life in severe cases. In many cases of mushroom poisoning the patient dies because of unavailability of a liver graft. Liver albumin dialysis (MARS) is a promising treatment to bridge the patient to LTx or stabilize his or her condition until spontaneous liver regeneration occurs. Four family members (father, mother and two sons) were eating self-collected mushrooms (Russula vesca). Typically for the Amanita phalloides poisoning, the first symptoms appeared in all persons more than 12 hours after mushroom ingestion. Because they did not improve, the whole family was admitted to the Regional Hospital in Ketrzyn (24 hours after mushroom ingestion). Mycological examination of gastric washings was positive only in the mother, in whom the Amanita phalloides spores were found. During the first 48 hours of poisoning the biochemical indexes of liver injury were observed in all persons. The whole family members were sent to centers where liver albumin dialysis could be performed: the mother was admitted to the Department of Nephrology and Dialysis Therapy in Olsztyn, the father and the first son were admitted to the Clinical Toxicology Department in Krak6w, and the second son was admitted to the Department of Internal Medicine and Acute Poisonings in Gdańsk. Three albumin dialysis procedures were performed in the case of mother with complete liver recovery. After the first liver albumin dialysis, the father of the family was disqualified from the following procedures because of severe coagulation disturbances (GI bleeding), and died the fourth day after mushroom ingestion. The first son fulfilled the King's College criteria and was accepted for high urgency liver transplantation. After two albumin dialysis procedures had been able and the patient was urgently sent to the Department of General and Transplantation Surgery in Szczecin, where liver transplantation was successfully performed. The second son was treated conservatively with improvement of general condition and biochemical indexes and no albumin dialysis procedure was necessary. Liver albumin dialysis may be effective in severe Amanita phalloides poisoning to stabilize the condition of a patient until spontaneous liver regeneration occurs or as a bridge to LTx. In cases of a family poisoning, proper coordination and cooperation among toxicology departments and transplant centers is required.


Abortion and conscientious objection.
In this article I do not seek to discuss when, if ever, abortion is morally permissible. Rather I seek to analyse the precise legal status of the exemptions afforded under British law to those with a conscientious objection to abortion. I then argue that the legal status quo in Britain is not morally satisfactory, and that the law urgently needs to be changed.


Physical Activity and Emotional Regulation in Physical Education in Children Aged 12-14 Years and Its Relation with Practice Motives.
This study aimed to analyze the different types of emotional regulation in first and second year high school students according to sex and age. Many adolescents do not meet the minimum WHO recommendations, at a critical stage in which habits that will later be maintained are established. For this reason, physical education is an important means to promote these habits and an understanding of the reasons for their participation in physical education. For this purpose, PLOC-2 was used. The Kolmogorov-Smirnov test was used to determine the characteristics of the data, the ANOVA test to explore the differences between sexes, and the Spearman test for correlations between the type of regulation and age. The results showed significant differences in several items and emotional regulation by sex and an inverse correlation between age and demotivation. There are differences between the reasons why both sexes perform physical activity, and we have determined that boys have more intrinsic regulation than girls do.


Development of a preliminary in vitro drug screening assay based on a newly established culturing system for pre-adult fifth-stage Onchocerca volvulus worms.
The human filarial parasite Onchocerca volvulus is the causative agent of onchocerciasis (river blindness). It causes blindness in 270,000 individuals with an additional 6.5 million suffering from severe skin pathologies. Current international control programs focus on the reduction of microfilaridermia by annually administering ivermectin for more than 20 years with the ultimate goal of blocking of transmission. The adult worms of O. volvulus can live within nodules for over 15 years and actively release microfilariae for the majority of their lifespan. Therefore, protracted treatment courses of ivermectin are required to block transmission and eventually eliminate the disease. To shorten the time to elimination of this disease, drugs that successfully target macrofilariae (adult parasites) are needed. Unfortunately, there is no small animal model for the infection that could be used for discovery and screening of drugs against adult O. volvulus parasites. Here, we present an in vitro culturing system that supports the growth and development of O. volvulus young adult worms from the third-stage (L3) infective stage. In this study we optimized the culturing system by testing several monolayer cell lines to support worm growth and development. We have shown that the optimized culturing system allows for the growth of the L3 worms to L5 and that the L5 mature into young adult worms. Moreover, these young O. volvulus worms were used in preliminary assays to test putative macrofilaricidal drugs and FDA-approved repurposed drugs. The culture system we have established for O. volvulus young adult worms offers a promising new platform to advance drug discovery against the human filarial parasite, O. volvulus and thus supports the continuous pursuit for effective macrofilaricidal drugs. However, this in vitro culturing system will have to be further validated for reproducibility before it can be rolled out as a drug screen for decision making in macrofilaricide drug development programs.


Autosomal dominant aniridia: probable linkage to acid phosphatase-1 locus on chromosome 2.
Maximum likelihood analysis for linkage between autosomal dominant aniridia and 12 biochemical and serological markers in a single large family showed a probable linkage between autosomal dominant aniridia and the enzyme acid phosphatase-1. The presence of an autosomal dominant aniridia gene linked to acid phosphatase-1 on chromosome arm 2p and the existence of an aniridia syndrome resulting from deletion of band 13 of the short arm of chromosome 11 establishes a chromosome basis for genetic heterogeneity of aniridia phenotypes.


Investigation the electroplating behavior of self formed CuMn barrier.
The electrical and material properties of Copper (Cu) mixed with [0-10 atomic% manganese (Mn)] and pure Cu films deposited on silicon oxide (SiO2)/silicon (Si) are explored. Cu electroplating on self formed CuMn barrier was investigated with different Mn content. The electrochemical deposition of the Cu thin film onto the electrode using CuMn barrier was investigated. Scanning electron microscopic (SEM) micrographs of copper electroplating on CuMn films were examined, and the copper nucleation behaviors changed with the Mn content. Since the electrochemical impedance spectroscopy (EIS) is widely recognized as a powerful tool for the investigation of electrochemical behaviors, the tool was also used to verify the phenomena during plating. It was found that the charge-trasfer impedance decrease with the rise in the Mn content below 5%, but increase with the rise in the Mn content higher than 5%. The result was corresponded to the surface energy, the surface morphology, the corrosion and the oxidation of the substrate.


[Evaluation of bone mass density after extensive resections within the alimentary tract].
The authors have examined a group of 30 patients at 24-36 months after extensive resections within the alimentary tract. The bone density assessment has been done. The results were compared to those obtained from another group of 30 patients awaiting sinister operations. Bone loss was found in all postoperative patients. However, it was statistically significant only in patients after pancreatoduodenectomy.


Periodontal disease and oral hygiene in Arussi province, Ethiopia.
A dental health survey was conducted in the Arussi province in Ethiopia. The survey comprised 1,700 persons between 6 and 54 years of age in five age groups from four regions of the province. Findings concerning periodontal disease and oral hygiene are reported in the present paper. The onset of periodontal disease was early, with 60% of the children in the 6-7 year group having gingivitis. In general, periodontal disease was found in a majority of the surveyed population (83%). Severe periodontal destruction was, however, unusual before the age of 30, but at the age of 45-54 years 52% of the sample exhibited pocket formation. The level of periodontal disease in Ethiopia was judged as low to moderate. A close relationship was observed between oral cleanliness and periodontal condition. A possible favorable influence of the diet and traditional oral cleaning methods is conceivable.


Anticoagulant proteases from western diamondback rattlesnake (Crotalus atrox) venom.
Crotalus atrox venom contains agents that render human fibrinogen and plasma incoagulable by thrombin. To elucidate the mechanism of alteration of fibrinogen clotting function by the venom, four immunochemically different proteases, I, II, III, and IV, were purified from the venom by anion-exchange chromatography and column gel filtration. All four proteases had anticoagulant activity rendering purified fibrinogen incoagulable. Proteases I and IV do not affect fibrinogen in plasma but in purified fibrinogen cleave the A alpha chain first and then the B beta and gamma chains. Both enzymes are metalloproteases containing a single polypeptide chain with 1 mol of zinc, are inhibited by (ethylenedinitrilo)tetraacetate and human alpha 2-macroglobulin, and have an optimal temperature of 37 degrees C and an optimal pH of 7. Protease I has a molecular weight (Mr) of 20 000 and is the most cationic. Protease IV has an Mr of 46 000 and is the most anionic glycoprotein with one free sulfhydryl group. Proteases II and III degrade both purified fibrinogen and fibrinogen in plasma, cleaving only the B beta chain and leaving the A alpha and gamma chains intact. Both enzymes are alkaline serine proteases, cleave chromogenic substrates at the COOH terminal of arginine or lysine, are inhibited by diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride, and have an optimal temperature of 50-65 degrees C. Protease II is a single polypeptide chain glycoprotein with an Mr of 31 000. Protease III is a two polypeptide chain protein with an Mr of 24 000, each of the two chains having an Mr of 13 000; its activity is not affected by major protease inhibitors of human plasma. Proteases II and III are enzymes with unique and limited substrate specificity by cleaving only the B beta chain, releasing a peptide of Mr 5000 and generating a fibrinogen derivative of Mr 325 000, with intact A alpha and gamma chains and poor coagulability. Since the two enzymes are active in human plasma and serum, it is postulated that proteases II and III can mediate anticoagulant effects in vivo after envenomation.


[Bulinus truncatus, Planorbarius metidjensis and endemic bilharziosis in the southwestern Morocco].
Since Planorbarius metidjensis was recently found to be an experimental intermediate host of Schistosoma haematobium in the South-West of Morocco, a study on planorbid and B. truncatus was carried out from 1997 to 2005. Eleven planorbid populations were identified in 1997 in the Agadir province, all living at high altitude (from 340 to 1380 m). In contrast, most of the seven bulinid populations inhabited low-lying zones. Three annual generations of P. metidjensis (April-July June-September, and August-March) were noted in two populations (living in perennial bodies of water) in Imouzzer so that juvenile snails were present throughout the year. The dissection of numerous snails collected from these 18 populations between 1999 and 2005 revealed the absence of natural infections with S. haematobium. As most cases of human bilharziosis detected in the Agadir region between 1993 and 1997 are located in highlands, P. metidjensis might be the principal intermediate host of S. haematobium in districts at 500 m above sea level.


Comment on: "A novel approach to peatlands as archives of total cumulative spatial pollution loads from atmospheric deposition of airborne elements complementary to EMEP data: Priority pollutants (Pb, Cd, Hg)" by Ewa Miszczak, Sebastian Stefaniak, Adam Michczyński, Eiliv Steinnes and Irena Twardowska.
A recent paper by Miszczak et al. (2020) examines metal contamination of mires in Poland and Norway. The authors conclude that lead (Pb) records in ombrotrophic peatlands cannot be used to reconstruct the chronological history of anthropogenic activities due to post-depositional mobility of the metal. We contest this general conclusion which stands in contrast with a significant body of literature demonstrating that Pb is largely immobile in the vast majority of ombrotrophic peatlands. Our aim is to reaffirm the crucial contribution that peat records have made to our knowledge of atmospheric Pb contamination. In addition, we reiterate the necessity of following established protocols to produce reliable records of anthropogenic Pb contamination in environmental archives.


Privacy considerations in the context of an Australian observational database.
Observational databases are increasingly acknowledged for their value in clinical investigation. Australian general practice in particular presents an exciting opportunity to examine treatment in a natural setting. The paper explores issues such as privacy and confidentiality--foremost considerations when conducting this form of pharmacoepidemiological research. Australian legislation is currently addressing these exact issues in order to establish clear directives regarding ethical concerns. The development of a pharmacoepidemiological database arising from the integration of computerized Australian general practice records is described in addition, to the challenges associated with creating a database which considers patient privacy. The database known as 'Medic-GP', presently contains more than 950,000 clinical notes (including consultations, pathology, diagnostic imaging and adverse reactions) over a 5-year time period and relates to 55,000 patients. The paper then details a retrospective study which utilized the database to examine the interaction between antibiotic prescribing and patient outcomes from a community perspective, following a policy intervention. This study illustrates the application of computerized general practice records in research.


An interdisciplinary team approach to providing dysphagia treatment in the schools.
The diagnosis and treatment of pediatric dysphagia in school systems are still in the infancy stages. They are being addressed in a variety of ways and by a variety of personnel. Speech-language pathologists (SLPs) in school systems throughout the country are faced with students who exhibit the signs and symptoms of dysphagia; however, there is a lack of organized procedures for the diagnosis and treatment of dysphagia in the schools. In some cases, SLPs are asked to treat a disorder for which they have no training. In both scenarios there are concerns about the services that students are receiving as well as professional liability. The purpose of this article is to address some of the more pressing issues related to the diagnosis and treatment of dysphagia in the schools and to provide the school-based SLP with some solutions to these problems. The question to be answered is, What is the best way to address dysphagia in the schools?


Pseudodominant Inheritance of Retinitis Pigmentosa Due to Mutations in the Phosphodiesterase 6B Gene: A Case Report.
Mutations in the phosphodiesterase 6B (PDE6B) gene are a rare cause of autosomal recessive retinitis pigmentosa (arRP). We report on a non-consanguineous family with a pseudodominant inheritance of RP due to PDE6B mutations. We conducted a chart review of four members of a Puerto Rican family who underwent a comprehensive ophthalmic evaluation by at least one of the authors. The mutational screening was done using a genotyping microarray provided by Invitae Corporation, using next-generation sequencing (NGS) technology. Genomic DNA obtained from saliva samples is enriched for targeted regions using a hybridization-based protocol and sequenced using Illumina technology. A descriptive analysis was done. Patient 1A had a normal ophthalmic examination and a heterozygous pathogenic variant in the PDE6B gene c.1540del PLeu514Trpfs*61. Patients 1B, 2A, and 2B had mid-peripheral retinitis pigmentosa, concentric visual field ring scotomata in both eyes (OU), extinguished electroretinogram (ERG), and homozygous pathogenic variants in the PDE6B gene c.1540del PLeu514Trpfs*61. Even though mutations in the PDE6B gene usually lead to arRP, they may be inherited in a pseudodominant pattern in geographically isolated populations. Genotyping studies in patients with RP are warranted to classify inheritance mode correctly.


Mood patterns based on momentary assessment of positive and negative moods over a day and coronary artery calcification in the CARDIA study.
Retrospective assessments of negative mood have predicted coronary artery disease development and progression. Using momentary assessment, we evaluated associations between average positive and negative mood states and diurnal mood patterns, with prevalent and incident coronary artery calcification (CAC), a measure of calcified atherosclerosis. In a prospective cohort study of 669 white and African American men and women, aged 33 to 45 years, from the Coronary Artery Risk Development in Young Adults Study, mood was assessed at Year 15 examination, six times over a weekday. Prevalent, progressive, and 5-year incident CAC (any detectable CAC [score >0]) and substantial CAC (CAC score ≥ 20) were assessed at examinations at Years 15 and 20 by electron-beam tomographic scans. We employed a modified Poisson regression approach for binary data with robust error estimation to quantify relative risk. In multivariate-adjusted analyses, those with high-average positive mood that improved over a day had a lower risk of prevalent CAC higher than 0 (relative risk [RR] = 0.17 [95% confidence interval {CI} = 0.04-0.67]) and substantial CAC (RR = 0.25 [95% CI = 0.06-0.95]). In contrast, those with high-average, increasingly negative mood over a day had a higher risk of prevalent CAC (RR = 1.85 [95% CI = 0.86-3.99]) and substantial CAC (RR = 3.11 [95% CI = 1.29-7.49]). Findings were similar for progressive CAC at Year 20. This pattern of high/worsening negative mood (not positive mood) during the day was also predictive of 5-year incident CAC (RR = 2.99 [95% CI = 1.00-8.93]). Diurnal mood patterns were associated with the progression of calcified atherosclerosis, with negative mood predicting greater progression and positive mood predicting lower progression.


Challenges of current treatment and exploring the future prospects of nanoformulations for treatment of atopic dermatitis.
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by a burning sensation and eczematous lesions in diverse portions of the body. The treatment of AD is exclusively focused to limit the itching, reduce inflammation, and repair the breached barrier of the skin. Several therapeutic agents for the treatment and management of AD have been reported and are in use in clinics. However, the topical treatment of AD has been an unswerving challenge for the medical fraternity owing to the impaired skin barrier function in this chronic skin condition. To surmount the problems of conventional drug delivery systems, numerous nanotechnology-based formulations are emerging as alternative new modalities for AD. Latter enhances the bioavailability and delivery to the target disease site, improves drug permeation and therapeutic efficacy with reduced systemic and off-target side effects, and thus improves patient health and promotes compliance. This review aims to describe the various pathophysiological events involved in the occurrence of AD, current challenges in treatment, evidence of molecular markers of AD and its management, combinatorial treatment options, and the intervention of nanotechnology-based formulations for AD therapeutics.


Establishing dental recall interval for Pakistani children: A longitudinal study.
To determine the caries increment rate in children to establish appropriate dental recall interval. The prospective longitudinal study was conducted from May 2016 to October 2017 in Bhakkar city of Punjab, Pakistan, and comprised schoolchildren aged 12 years. The caries progression rate was measured using the Modified Beck's method or adjusted caries increment. The response rate at baseline and at each follow-up was compared. Bonferroni correction was used to compare baseline mean caries increment with caries increment at 6, 12 and 18 months. Data was analysed using SPSS 17 and Stata 14. Of the 226 subjects enrolled, 183(81%) were present at the last follow-up. However, only 147(65%) subjects were available for all the four measurements. Significantly high caries increment among cavitated lesions was observed at all the three follow-ups compared to the baseline (p=0.0001). The caries increment rate was low in cavitated lesions, but when non-cavitated and cavitated lesions were merged, they showed high caries increment.


Histone Lactylation Boosts Reparative Gene Activation Post-Myocardial Infarction.
Inflammation resolution and cardiac repair initiation after myocardial infarction (MI) require timely activation of reparative signals. Histone lactylation confers macrophage homeostatic gene expression signatures via transcriptional regulation. However, the role of histone lactylation in the repair response post-MI remains unclear. We aimed to investigate whether histone lactylation induces reparative gene expression in monocytes early and remotely post-MI. Single-cell transcriptome data indicated that reparative genes were activated early and remotely in bone marrow and circulating monocytes before cardiac recruitment. Western blotting and immunofluorescence staining revealed increases in histone lactylation levels, including the previously identified histone H3K18 lactylation in monocyte-macrophages early post-MI. Through joint CUT&Tag and RNA-sequencing analyses, we identified Lrg1, Vegf-a, and IL-10 as histone H3K18 lactylation target genes. The increased modification and expression levels of these target genes post-MI were verified by chromatin immunoprecipitation-qPCR and reverse transcription-qPCR. We demonstrated that histone lactylation regulates the anti-inflammatory and pro-angiogenic dual activities of monocyte-macrophages by facilitating reparative gene transcription and confirmed that histone lactylation favors a reparative environment and improves cardiac function post-MI. Furthermore, we explored the potential positive role of monocyte histone lactylation in reperfused MI. Mechanistically, we provided new evidence that monocytes undergo metabolic reprogramming in the early stage of MI and demonstrated that dysregulated glycolysis and MCT1 (monocarboxylate transporter 1)-mediated lactate transport promote histone lactylation. Finally, we revealed the catalytic effect of IL (interleukin)-1β-dependent GCN5 (general control non-depressible 5) recruitment on histone H3K18 lactylation and elucidated its potential role as an upstream regulatory element in the regulation of monocyte histone lactylation and downstream reparative gene expression post-MI. Histone lactylation promotes early remote activation of the reparative transcriptional response in monocytes, which is essential for the establishment of immune homeostasis and timely activation of the cardiac repair process post-MI.


Greater knowledge and appreciation of commonly-used research study designs.
In this article we provide an overview of the different study designs commonly utilized in carrying out clinical and public health research and of the points to consider in reviewing these study designs. The design and conduct of cross-sectional health surveys, case-control, prospective, and case-crossover observational studies, and randomized controlled trials, are discussed in this review article. It is hoped that careful attention to the concerns we have raised will lead to the design and conduct of high-quality research projects and their write-up.


Conditions of contact, common in-group identity, and in-group bias toward contingent workers.
In a survey-based field study of 111 permanent Finnish restaurant employees, the authors investigated intergroup relations between permanent and contingent workers. On the basis of the common in-group identity model, the authors hypothesized that the conditions of contact (supportive norms and perceived intergroup competition) would be related to common in-group identity, which in turn would be negatively related to intergroup bias. The present results indicated that perceived competition and institutional support were related to in-group bias only through their influence on the common in-group identity, as the model predicted.


Modulating effect of hesperetin on the molecular expression pattern of apoptotic and cell proliferative markers in 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis.
Oral squamous cell carcinoma (OSCC) is widespread malignant neoplasm and refractory cancers in worldwide. Here, we studied the chemopreventive potential of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs). Oral tumours were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA three times a week for 10 weeks. This causes sequentially hyperplasia, dysplasia and well differentiates squamous cell carcinoma (SCC) with up-regulation of molecular markers like mutant-p53, Caspase-3 and caspase-9 and cyclin-D1. Histology, immunohistochemistry (IHC), real time PCR (qRT-PCR) and western blot analysis of hesperetin treated animals shows a reversal in the above expression pattern to near normal in buccal mucosal tissue. Therefore, hesperetin exhibits the potential protective effect against DMBA-induced oral cancer through apoptotic and anti-proliferative properties. However, a long-term observation would be needed to confirm the possibility of malignant change of the resulted dysplastic lesions upon hesperetin pretreatment.


Comparison of two rapid automated analysis tools for large FTIR microplastic datasets.
One of the biggest issues in microplastic (MP, plastic items <5 mm) research is the lack of standardisation and harmonisation in all fields, reaching from sampling methodology to sample purification, analytical methods and data analysis. This hampers comparability as well as reproducibility among studies. Concerning chemical analysis of MPs, Fourier-transform infrared (FTIR) spectroscocopy is one of the most powerful tools. Here, focal plane array (FPA) based micro-FTIR (µFTIR) imaging allows for rapid measurement and identification without manual preselection of putative MP and therefore enables large sample throughputs with high spatial resolution. The resulting huge datasets necessitate automated algorithms for data analysis in a reasonable time frame. Although solutions are available, little is known about the comparability or the level of reliability of their output. For the first time, within our study, we compare two well-established and frequently applied data analysis algorithms in regard to results in abundance, polymer composition and size distributions of MP (11-500 µm) derived from selected environmental water samples: (a) the siMPle analysis tool (systematic identification of MicroPlastics in the environment) in combination with MPAPP (MicroPlastic Automated Particle/fibre analysis Pipeline) and (b) the BPF (Bayreuth Particle Finder). The results of our comparison show an overall good accordance but also indicate discrepancies concerning certain polymer types/clusters as well as the smallest MP size classes. Our study further demonstrates that a detailed comparison of MP algorithms is an essential prerequisite for a better comparability of MP data.


Alternating direction method of multiplier for tomography with nonlocal regularizers.
The ordered subset expectation maximization (OSEM) algorithm approximates the gradient of a likelihood function using a subset of projections instead of using all projections so that fast image reconstruction is possible for emission and transmission tomography such as SPECT, PET, and CT. However, OSEM does not significantly accelerate reconstruction with computationally expensive regularizers such as patch-based nonlocal (NL) regularizers, because the regularizer gradient is evaluated for every subset. We propose to use variable splitting to separate the likelihood term and the regularizer term for penalized emission tomographic image reconstruction problem and to optimize it using the alternating direction method of multiplier (ADMM). We also propose a fast algorithm to optimize the ADMM parameter based on convergence rate analysis. This new scheme enables more sub-iterations related to the likelihood term. We evaluated our ADMM for 3-D SPECT image reconstruction with a patch-based NL regularizer that uses the Fair potential function. Our proposed ADMM improved the speed of convergence substantially compared to other existing methods such as gradient descent, EM, and OSEM using De Pierro's approach, and the limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm.


Evaluation and extension of the cusum technique with an application to Salmonella surveillance.
The cumulative sum (cusum) technique was examined for its use in a disease surveillance system for detecting temporal clusters of events. Optimal technique parameters were derived for scenarios not previously considered. Simulation modeling produced results that evaluated deviations from predefined rate increases. The cusum technique was less prone to false alarms and more efficient at detecting large rate increases than previously reported. As demonstrated using data obtained from a Salmonella surveillance system operated by a state animal diagnostic laboratory system, the cusum technique could provide early warning of an epidemic problem.


The Essential Role of ClpXP in Caulobacter crescentus Requires Species Constrained Substrate Specificity.
The ClpXP protease is a highly conserved AAA+ degradation machine that is present throughout bacteria and in eukaryotic organelles. ClpXP is essential in some bacteria, such as Caulobacter crescentus, but dispensible in others, such as Escherichia coli. In Caulobacter, ClpXP normally degrades the SocB toxin and increased levels of SocB result in cell death. ClpX can be deleted in cells lacking this toxin, but these ΔclpX strains are still profoundly deficient in morphology and growth supporting the existence of additional important functions for ClpXP. In this work, we characterize aspects of ClpX crucial for its cellular function. Specifically, we show that although the E. coli ClpX functions with the Caulobacter ClpP in vitro, this variant cannot complement wildtype activity in vivo. Chimeric studies suggest that the N-terminal domain of ClpX plays a crucial, species-specific role in maintaining normal growth. We find that one defect of Caulobacter lacking the proper species of ClpX is the failure to properly proteolytically process the replication clamp loader subunit DnaX. Consistent with this, growth of ΔclpX cells is improved upon expression of a shortened form of DnaX in trans. This work reveals that a broadly conserved protease can acquire highly specific functions in different species and further reinforces the critical nature of the N-domain of ClpX in substrate choice.


Breakfast consumption frequency is associated with dyslipidemia: a retrospective cohort study of a working population.
Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China. This retrospective cohort study used data from the physical examinations and questionnaire survey of working participants at Nanfang Hospital from January 20, 2015 to October 16, 2020. Univariate and multivariate analyses were conducted to explore the relationship between breakfast consumption frequency and dyslipidemia in this working population (n = 7644). The prevalence of dyslipidemia among the participants was 26.4%. The univariate logistic regression test showed that the breakfast consumption frequency was inversely correlated with dyslipidemia. After adjusting for multiple factors, such as sex, age, body mass index, hypertension, hyperuricaemia, diabetes, smoking status, alcohol consumption, education level, marital status, long-term exposure to kitchen oil fumes, attending business dinners, and sleep time, it was found that breakfast consumption remained inversely associated with dyslipidaemia. The odds ratio for daily breakfast consumption was 0.466 (95% confidence interval 0.283-0.770, P = 0.003). After adjusting for confounding factors, we found that the higher the frequency of breakfast consumption, the lower the odds ratios for hypertriglyceridaemia. This study demonstrated that breakfast consumption frequency was inversely correlated with dyslipidemia. The higher the frequency of breakfast, the lower the risk of hypertriglyceridaemia. This study provides a basis on which dietary suggestions for the working population and lifestyle guidance for patients with a clinical need to prevent dyslipidemia can be made.


"Pick up anything that moves": a qualitative analysis of a police crackdown against people who use drugs in Tijuana, Mexico.
Homeless people who use drugs (PWUD) are often displaced, detained, and/or forced into drug treatment during police crackdowns. Such operations follow a zero-tolerance approach to law enforcement and have a deleterious impact on the health of PWUD. In Mexico, municipal police officers (MPOs) conducted the largest crackdown documented at the Tijuana River Canal (Tijuana Mejora) to dismantle an open drug market. We analyzed active-duty MPOs' attitudes on the rationale, implementation, and outcomes of the crackdown. We also included the involvement of non-governmental allies in the disguised imprisonment as drug treatment referral and potential legal consequences of having illegally detained PWUD. Between February-June 2016, 20 semi-structured interviews were conducted with MPOs in Tijuana. Interviews were transcribed, translated and coded using a consensus-based approach. Emergent themes, trends and frameworks were analyzed through a hermeneutic grounded theory protocol. Participants recognized the limitations of Tijuana Mejora in effectively controlling crime and addressing drug treatment solutions. MPOs perceived that the intent of the operation was to displace and detain homeless PWUD, not to assist or rehabilitate them. The police operation was largely justified as a public safety measure to reduce the risk of injury due to flooding, decrease drug consumption among PWUD and protect local tourism from PWUD. Some participants perceived the crackdown as a successful public health and safety measure while others highlighted occupational risks to MPOs and potential human rights violations of PWUD. Tijuana Mejora illustrated why public and private actors align in enforcing zero-tolerance drug policy. Perceptions of care are often based on captivity of the diseased, not in health and well-being of PWUD. Officer perceptions shed light on the many limitations of this punitive policing tool in this context. A shift towards evidence-based municipal strategies to address drug use, wherein police are perceived as partners in harm reduction rather than antagonists, is warranted.


Wnt5a is necessary for normal kidney development in zebrafish and mice.
Wnt5a is important for the development of various organs and postnatal cellular function. Little is known, however, about the role of Wnt5a in kidney development, although WNT5A mutations were identified in patients with Robinow syndrome, a genetic disease which includes developmental defects in kidneys. Our goal in this study was to determine the role of Wnt5a in kidney development. Whole-mount in situ hybridization was used to establish the expression pattern of Wnt5a during kidney development. Zebrafish with wnt5a knockdown and Wnt5a global knockout mice were used to identify kidney phenotypes. In zebrafish, wnt5a knockdown resulted in glomerular cyst formation and dilated renal tubules. In mice, Wnt5a global knockout resulted in pleiotropic, but severe, kidney phenotypes, including agenesis, fused kidney, hydronephrosis and duplex kidney/ureter. Our data demonstrated the important role of Wnt5a in kidney development. Disrupted Wnt5a resulted in kidney cysts in zebrafish and pleiotropic abnormal kidney development in mice.


Ab initio studies on the optical effects in the deep ultraviolet nonlinear optical crystals of the KBe2BO3F2 family.
Electronic structures of the deep ultraviolet nonlinear optical crystals of the KBe(2)BO(3)F(2) (KBBF) family, including KBBF, RbBe(2)BO(3)F(2) and CsBe(2)BO(3)F(2), have been investigated based on a plane-wave pseudopotential method. Their linear and nonlinear optical coefficients are also calculated, and are in good agreement with the experimental results. A real-space atom-cutting method is adopted to analyze the respective contributions of the alkali metal cations and anionic groups to optical response. The results show that the contributions of anionic groups to the nonlinear optical anisotropic responses are dominant, but the influence of the A-site alkali metal cations becomes slightly more pronounced with the increase of their radius. Moreover, the birefringence difference among these crystals strongly depends on the volume effect, i.e., the spatial density of the (BO(3))(3-) anionic groups.


Obesity Does Not Affect Outcomes in Hybrid Versus Cemented Total Knee Arthroplasty in Asians.
This study aims to evaluate patient reported and functional outcomes following hybrid versus cemented total knee arthroplasty (TKA) in patients, stratified by body mass index (BMI). Registry data of patients undergoing primary TKA between January 2004 and January 2013 were collected. Baseline interviews were conducted preoperatively to assess sociodemographic characteristics, BMI, and knee arthritis severity, using the Knee Society Score which consists of the Knee Society Knee Score and the Knee Society Function Score (KSFS) and Oxford Knee Score (OKS). These scores were collected prospectively, preoperatively, and postoperatively up to 2 years. Two-year outcomes and 5-year revision rates were then compared between (1) hybrid and cemented TKA groups and (2) BMI subclasses within the hybrid and cemented TKA groups. Patients who underwent cemented TKA had marginally better flexion range, KSFS, and OKS at 2 years postoperatively. In the overweight category, flexion range, KSFS, and OKS were marginally lower for hybrid TKAs. There were no differences in outcomes between the 2 groups in Class I and II obesity. Within the cemented TKA group, there were no differences in the outcomes between BMI subclasses. There were significant differences in the KSFS (0.023) and OKS (0.030) between the BMI subclasses within the hybrid TKA group, with patients in Class II obesity faring the worst. There was no statistically significant difference in the revision rates. We conclude that obesity does not affect outcomes in hybrid versus cemented TKA.


One-Pot Synthesis and Purification of Ultralong Silver Nanowires for Flexible Transparent Conductive Electrodes.
Metal nanowires (NWs) have become the most promising candidates for the next generation of flexible transparent conductive electrodes (FTCEs), with high transmittance and low sheet resistance. In this work, ultralong silver NWs (Ag NWs), ∼220 μm (even larger than 400 μm) in length and ∼55 nm in diameter (aspect ratio: ∼4000), were synthesized via a one-pot polyol process using high molecular weight poly(vinylpyrrolidone) (Mw = 1 300 000) and an appropriate concentration of FeCl3 (12.5 μM) through hydrothermal reaction. The prepared Ag NWs were purified by a filter cloth (pore size: about 30 × 50 μm2) to remove the Ag nanoparticles and short-length Ag NWs. The FTCE based on the ultralong Ag NWs without any post-treatments exhibits low sheet resistance of 155.0 Ω sq-1 and transmittance of 97.70% at 550 nm. The outstanding performance of FTECs demonstrated that the ultralong Ag NWs are ideal materials for applications in flexible transparent optical devices.


Sublingual targeting of STING with 3'3'-cGAMP promotes systemic and mucosal immunity against anthrax toxins.
Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity. We found that sublingual immunization of mice with Bacillus anthracis protective antigen (PA) and the STING ligand 3'3'-cGAMP promotes PA-specific serum IgG Ab responses of the same magnitude as those induced after immunization with PA and the experimental adjuvant cholera toxin (CT). Interestingly, this STING ligand also promoted serum anti-PA IgA and IgA-producing cells in the bone marrow. Furthermore, the saliva of mice immunized with the STING ligand exhibited similar levels of PA-specific IgA Abs as groups immunized with CT as adjuvant. The adjuvant activity of 3'3'-cGAMP was associated with mixed Th1, Th2, and Th17 responses. This STING ligand also induced rapid IFN-β and IL-10 responses in sublingual tissues and cervical lymph nodes, and TGF-β responses in the cervical lymph nodes, which could contribute to promoting IgA responses after sublingual immunization.


Developmental control of IFN-alpha expression in murine embryos.
The expression of IFN-alpha transcripts was investigated in murine embryos, fetuses, and fetal annexes in mid and late pregnancy. We have shown by Northern blot analysis, reverse transcription-polymerase chain reaction, and in situ hybridization the presence of IFN-alpha transcripts in mouse placenta, fetus, and newborn. From the 14th day of gestation until birth, a typical IFN-alpha transcript (1.2 kb) is found in the fetus. A transcript of larger size (2.2 kb) appears near birth and is present in the newborn mouse. Fetal annexes between the 10th and 21st days of gestation also express IFN-alpha. From the 10th day until birth, the 1.2-kb IFN-alpha mRNA species is present, as well as unusually large transcripts: 4 and 7 kb. To localize IFN-alpha transcripts, in situ hybridization was performed, using 35S-IFN-alpha antisense RNA probe in comparison with the sense RNA probe. The tissue pattern of IFN-alpha transcription in fetuses shows a clear labeling of many epithelia, such as skin, ependyme, and intestine glandular epithelium. A possible relation with cellular differentiation is discussed.


Signaling from the Golgi: mechanisms and models for Golgi phosphoprotein 3-mediated oncogenesis.
Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention.


Health promotion activities in annual reports of local governments: 'Health for All' targets as a tool for content analysis.
This article presents an instrument to study the annual reporting of health promotion activities in local governments within the three intervention municipalities of the Stockholm Diabetes Prevention Program (SDPP). The content of health promotion activities are described and the strengths, weaknesses and relevance of the method to health promotion discussed. A content analysis of local governmental reports from 1995-2000 in three Swedish municipalities. A matrix with WHO's 38 'Health for All' (HFA) targets from 1991 was used when coding the local health promotion activities. There are many public health initiatives within the local governmental structure even if they are not always addressed as health promotion. The main focuses in the local governmental reports were environmental issues, unemployment, social care and welfare. Local governmental reports were found to be a useful source of information that could provide knowledge about the priorities and organizational capacities for health promotion within local authorities. Additionally the HFA targets were an effective tool to identify and categorize systematically local health promotion activities in the annual reports of local governments. Identifying local health promotion initiatives by local authorities may ease the development of a health perspective and joint actions within the existing political and administrative structure. This paper provides a complementary method of attaining and structuring information about the local community for developments in health promotion.


A Bit of Fit: Minimalist Intervention in Adolescents Based on a Physical Activity Tracker.
Only 5% of Canadian youth meet the recommended 60 minutes of moderate to vigorous physical activity (MVPA) per day, with leisure time being increasingly allocated to technology usage. Direct-to-consumer mHealth devices that promote physical activity, such as wrist-worn physical activity trackers, have features with potential appeal to youth. The primary purpose of this study was to determine whether a minimalist physical activity tracker-based intervention would lead to an increase in physical activity in young adolescents. A secondary aim of this study was to assess change in physical activity across a 7-week intervention, as measured by the tracker. Using a quasi-experimental crossover design, two groups of 23 young adolescents (aged 13-14 years) were randomly assigned to immediate intervention or delayed intervention. The intervention consisted of wearing a Fitbit-Charge-HR physical activity tracker over a 7-week period. Actical accelerometers were used to measure participants' levels of MVPA before and at the end of intervention periods for each group. Covariates such as age, sex, stage of change for physical activity behavior, and goal commitment were also measured. There was an increase in physical activity over the course of the study period, though it was not related to overall physical activity tracker use. An intervention response did, however, occur in a subset of participants. Specifically, exposure to the physical activity tracker was associated with an average daily increase in MVPA by more than 15 minutes (P=.01) among participants who reported being in the action and maintenance stages of behavior change in relation to participation in physical activity. Participants in the precontemplation, contemplation, and preparation stages of behavior change had no change in their level of MVPA (P=.81). These results suggest that physical activity trackers may elicit improved physical activity related behavior in young adolescents demonstrating a readiness to be active. Future studies should seek to investigate if integrating physical activity trackers as part of more intensive interventions leads to greater increases in physical activity across different levels of stages of behavior change and if these changes can be sustained over longer periods of time.


Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells through induction of apoptosis and G2/M cell cycle arrest.
The plant Euphorbia helioscopia L. has been used in traditional Chinese medicine for treating various disorders such as tuberculosis and edema. The aim of this study was to investigate the effect of euphornin, a bioactive compound isolated from E. helioscopia, on proliferation of human cervical adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and cell cycle progression. The sulforhodamine B assay was used to study the effect of euphornin on the proliferation of HeLa cells. Morphological changes to cell nuclei were identified after Hoechst 33342 staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting was applied to investigate the influence of euphornin on cell cycle progression. Proteins were obtained from HeLa cells and analyzed by Western blots. A cell viability assay showed that euphornin inhibited proliferation of HeLa cells in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis in a concentration-dependent manner, with the rates of apoptosis ranging from 25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also markedly increased by euphornin treatment. Analysis of cell cycles indicated that euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein. The various assays demonstrated that euphornin treatment resulted in a significant suppression of cell growth accompanied by G2/M cell cycle arrest and increased rate of apoptosis via mitochondrial and caspase pathways. Our findings suggest that euphornin has the potential to be used as a cancer therapeutic agent against human cervical adenocarcinoma.


Two-way AIC: detection of differentially expressed genes from large scale microarray meta-dataset.
Detection of significant differentially expressed genes (DEGs) from DNA microarray datasets is a common routine task conducted in biomedical research. For the detection of DEGs, numerous methods are proposed. By such conventional methods, generally, DEGs are detected from one dataset consisting of group of control and treatment. However, some DEGs are easily to be detected in any experimental condition. For the detection of much experiment condition specific DEGs, each measurement value of gene expression levels should be compared in two dimensional ways, or both with other genes and other datasets simultaneously. For this purpose, we retrieve the gene expression data from public database as possible and construct "meta-dataset" which summarize expression change of all genes in various experimental condition. Herein, we propose "two-way AIC" (Akaike Information Criteria), method for simultaneous detection of significance genes and experiments on meta-dataset. As a case study of the Pseudomonas aeruginosa, we evaluate whether two-way AIC method can detect test data which is the experiment condition specific DEGs. Operon genes are used as test data. Compared with other commonly used statistical methods (t-rank/F-test, RankProducts and SAM), two-way AIC shows the highest specificity of detection of operon genes. The two-way AIC performs high specificity for operon gene detection on the microarray meta-dataset. This method can also be applied to estimation of mutual gene interactions.


Co-Promoted CoNi Bimetallic Nanocatalyst for the Highly Efficient Catalytic Hydrogenation of Olefins.
Bimetallic catalysts, especially non-noble metals, hold great potential for substituting for noble metals in catalytic hydrogenation. In present study, a series of CoxNiy (x + y = 6) bimetallic catalysts were prepared through the impregnation-reduction method and cyclohexene was chosen as probe-molecule to study the promotion effect of Co on the catalytic olefin hydrogenation reactions. Meanwhile, density functional theory (DFT) was utilized to investigate the formation energies and the charge distribution of CoNi bimetals, as well as the transition state (TS) searches for hydrogen dissociation and migration. The results suggest that bimetals tend to have superior catalytic performance than pure metals, and Co3Ni3 shows the highest catalytic activity on the cyclohexene hydrogenation. It was found that the charge transfer from Co to Ni and the alloying give rise to the refinement of CoNi grains and the improvement of its catalytic activity and stability. Thus, it may be possible to obtain better catalytic performance by tuning the metal/metal atomic ratio of bimetals.


Allotypy of the rabbit kappa 2 light chain: evidence that the kappa 2 isotype is expressed by all members of the rabbit species.
The rabbit kappa 2 light chain subtype was described after isolation of the Basilea mutant strain, which does not express the kappa 1 subtype; antibodies raised in domestic rabbits against the Basilea kappa 2 chain recognized antigenic determinants present in Basilea strain rabbits and in some wild Oryctolagus cuniculus individuals. Some authors have proposed that the kappa 2 isotype is expressed in some individuals and is silent in others. The results presented here provide immunochemical and genetic evidence that the kappa 2 isotype presents at least two allotypic forms, bas 1 (equivalent to bas+) and bas 2 (equivalent to the so-called bas-), which are expressed in low levels in all members of the rabbit species. In addition, preliminary data on the expression of the bas 2 allotype in some hares (Lepus capensis) are reported. On the basis of these results, the rules guiding the selection of kappa 1 and kappa 2 isotypic light chain expression in this species may now be approached.


Efficacy of resorbable plates for reduction and stabilization of laryngeal fractures.
We evaluated the efficacy of resorbable reconstruction plates (polylactic acid copolymer) for the open reduction and stabilization of displaced laryngeal fractures. Both MacroPore and Leibinger reconstruction plates were used with equal ease of application in 3 adult male patients. We found the plating system to be especially effective for the reduction of comminuted cricoid fractures. Adequate skeletal stabilization allowed early resumption of phonatory and respiratory function without long-term intraluminal stenting for skeletal support. No complications of hematoma, seroma, or infection were experienced. Resorbable plates appear to be relatively safe and useful for internal fixation of both cartilaginous and ossified parts of the larynx, allowing rapid rehabilitation and return of function.


Peptides mimicking the flap of human renin: synthesis, conformation, and antibody recognition.
Four peptides related to human renin flap region have been synthesized. Two of them are ring closed through appropriately designed disulfide bridges. Structure analysis involving IR and NMR techniques and recognition by polyclonal human renin antibodies provides support for a beta-hairpin secondary structure of the cyclized peptides identical with that presented by the flap section in the speculative human renin model [Blundell, T., Sibanda, B. L., & Pearl, L. (1983) Nature (London) 304, 273-275; Sibanda, B. L., Blundell, T., Hobart, P. M., Fogliano, M., Bindra, J. S., Dominy, B. W., & Chirgwin, J. M. (1984) FEBS Lett. 174, 102-111].


Posture in dentists: Sitting vs. standing positions during dentistry work--An EMG study.
Adequate working posture is important for overall health. Inappropriate posture may increase fatigue, decrease efficiency, and eventually lead to injuries. The purpose was to examine posture positions used during dentistry work. In order to quantify different posture positions, we recorded muscle activity and positions of body segments. The position (inclination) data of the back was used to assess two postures: sitting and standing during standard dental interventions. During standard interventions, whether sitting or standing, a tilt of less than 20 degrees was most prevalent in the forward and lateral flexion directions. Amplitude of electromyography signals corresponding to the level of muscle activity were higher in sitting compared with the electromyography in standing position for all muscle groups on the left and right side of the body. Significant difference between muscle activity in two working postures was evident in splenius capitis muscle on the left (p = 0.032), on the right side of the body (p = 0.049) and in muscle activity of mastoid muscle on the left side (p = 0.029). These findings show that risk for increased fatigue and possible injures can be reduced by combining the sitting and standing occupational postures.


Prevalence of Arthritis and Arthritis-Attributable Activity Limitation by Urban-Rural County Classification - United States, 2015.
Rural populations in the United States have well documented health disparities, including higher prevalences of chronic health conditions (1,2). Doctor-diagnosed arthritis is one of the most prevalent health conditions (22.7%) in the United States, affecting approximately 54.4 million adults (3). The impact of arthritis is considerable: an estimated 23.7 million adults have arthritis-attributable activity limitation (AAAL). The age-standardized prevalence of AAAL increased nearly 20% from 2002 to 2015 (3). Arthritis prevalence varies widely by state (range = 19%-36%) and county (range = 16%-39%) (4). Despite what is known about arthritis prevalence at the national, state, and county levels and the substantial impact of arthritis, little is known about the prevalence of arthritis and AAAL across urban-rural areas overall and among selected subgroups. To estimate the prevalence of arthritis and AAAL by urban-rural categories CDC analyzed data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS). The unadjusted prevalence of arthritis in the most rural areas was 31.8% (95% confidence intervals [CI] = 31.0%-32.5%) and in the most urban, was 20.5% (95% CI = 20.1%-21.0%). The unadjusted AAAL prevalence among adults with arthritis was 55.3% in the most rural areas and 49.7% in the most urban. Approximately 1 in 3 adults in the most rural areas have arthritis and over half of these adults have AAAL. Wider use of evidence-based interventions including physical activity and self-management education in rural areas might help reduce the impact of arthritis and AAAL.


Untreated congenital and posttraumatic high dislocation of the hip treated by replacement in adult age: 22 hips in 16 patients followed for 1-8 years.
Between 1993 and 2001, we replaced 22 hips in 16 patients with high dislocation of the hip. All but 1 case was due to congenital dislocation. In all cases the femur was osteotomized below the lesser trochanter and a straight uncemented stem inserted in the medullary canal. The acetabular prostheses were inserted at the site of the original acetabulum, usually after augmenting the acetabular rim by using the medial half of the resected proximal femur. The lateral part of the proximal femur with the intact attachment of the gluteus medius muscle was transposed and fixed to the femoral diaphysis thereby restoring direction of muscle pull. The HHS score increased from a median value of 42 points preoperatively to a median of 86 points after median 25 months of follow-up. Limp, which before surgery was severe in all cases, was less marked or had disappeared at follow-up. The legs had been lengthened median 2.5 (1.0-4.5) cm. No postoperative infections occurred. Palsy or loss of sensory function was not observed in any patient. Dislocation was the commonest complication. It occurred in 3 hips, 2 of which had to be revised to ensure stability.


Persistently elevated soluble MHC class I polypeptide-related sequence A and transforming growth factor-β1 levels are poor prognostic factors in head and neck squamous cell carcinoma after definitive chemoradiotherapy.
We evaluated the prognostic significance of immunologic inhibitory biomarkers in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma levels of soluble MHC class I polypeptide-related sequence A (sMICA) and transforming growth factor-β1 (TGF-β1) were measured before and 2 weeks after CRT. The median follow-up was 32.9 months (range: 12.4-40.6 months). The pre-treatment sMICA (p < 0.001) and TGF-β1 (p < 0.001) levels were significantly increased in HNSCC patients, compared to healthy controls. In HNSCC patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3 pg/mL, respectively, while the median pre-CRT and post-CRT TGF-β1 levels were 57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated TGF-β1, and five patients (16.7%) exhibited persistently elevated sMICA and TGF-β1. Patients with persistently elevated sMICA and TGF-β1 after CRT experienced an earlier tumor progression (p = 0.030), and poor overall survival (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently elevated sMICA and TGF-β1 levels after CRT are at higher risk of tumor progression or death.