Highly Stable Pt-Based Oxygen Reduction Electrocatalysts toward Practical Fuel Cells: Progress and Perspectives.
The high cost and poor reliability of cathodic electrocatalysts for the oxygen reduction reaction (ORR), which requires significant amounts of expensive and scarce platinum, obstructs the broad applications of proton exchange membrane fuel cells (PEMFCs). The principles of ORR and the reasons for the poor stability of Pt-based catalysts are reviewed. Moreover, this paper discusses and categorizes the strategies for enhancing the stability of Pt-based catalysts in fuel cells. More importantly, it highlights the recent progress of Pt-based stability toward ORR, including surface-doping, intermetallic structures, 1D/2D structures, rational design of support, etc. Finally, for atomic-level in-depth information on ORR catalysts in fuel cells, potential perspectives are suggested, such as large-scale preparation, advanced interpretation techniques, and advanced simulation. This review aims to provide valuable insights into the fundamental science and technical engineering for practical Pt-based ORR electrocatalysts in fuel cells.


The effect of isradipine on theophylline pharmacokinetics in healthy volunteers.
The effects of isradipine 2.5 mg and 5 mg on the disposition of theophylline were investigated in a placebo-controlled, randomized, three-way, crossover trial. Eleven healthy, nonsmoking men each received a treatment of placebo, and isradipine 2.5 mg and 5 mg every 12 hours for 6 consecutive days. On the morning of day 6, 2 hours after the isradipine dose, theophylline (solution) 5.0 mg/kg was administered orally, and blood samples were collected over 24 hours. A 2-week washout period separated treatment sequences. Plasma samples were analyzed for theophylline using high-performance liquid chromatography. Using a two-way analysis of variance, no significant changes in apparent theophylline clearance were observed between placebo, and isradipine 2.5 and 5 mg (0.815 +/- 0.164, 0.870 +/- 0.212, and 0.827 +/- 0.164 ml/min/kg, respectively; p = 0.136). Similarly, no significant change in volume of distribution was noted. These findings suggest that isradipine at recommended dosages does not impair theophylline metabolism.


Law enforcement worker suicide: an updated national assessment.
The purpose of this paper is to update the assessment of national data on law enforcement worker suicide based on the National Occupational Mortality Surveillance database (NOMS, Centers for Disease Control and Prevention). Death certificate data for 4,441,814 decedents, age 18-90 who died in one of the 26 reporting states were the source of NOMS data. Utilizing proportionate mortality ratios (PMRs), the ratio of suicides in law enforcement occupations in those who are 18-90 years old with a designated usual occupation was calculated. Findings indicate a significantly higher proportion of deaths from suicide for law enforcement officers (PMR = 154, 95% CI = 147-162), compared to all the US decedents in the study population who were employed during their lifetime. Law enforcement personnel are 54% more likely to die of suicide than all decedents with a usual occupation. PMRs were highest for African-Americans, Hispanic males and for females. PMRs were similar for detectives, corrections officers and all law enforcement jobs, when not stratified by race, ethnicity and sex. Bias may arise because a PMR can be affected by disproportionate increased or decreased mortality from causes of death other than suicide. A better understanding of the scope of law enforcement suicide can inform policy focused on the planning and initiation of prevention programs. The use of a national database to study law enforcement worker suicide adds to other information available on law enforcement worker suicide in specific geographic areas. The discussion on prevention in this paper presents ideas for policy.


Shock-wave measurement using a calibrated interferometric fiber-tip sensor.
The results of shock-wave measurements using a calibrated fiber-tip sensor based on a Michelson interferometer are presented. A transfer function, obtained by an independent experiment that describes the properties of the sensor system, was used to correct the measured shock-wave data in the Fourier frequency domain. The phase of the transfer function was determined from its amplitude by a fitting procedure using minimum-phase terms. As an example of application, the acoustic output field of an electromagnetic lithotriptor was investigated, and the shock-wave source was reliably characterized. The measured data provide a basis for estimating the hazard to which a patient is exposed during shock-wave treatment and for optimizing a lithotriptor system to produce a sharply localized and effective acoustic field.


The effect of late-onset sepsis on mortality across different gestational ages in a neonatal intensive care unit: A historical study.
Late-onset sepsis is a frequent complication in neonatal intensive care units. This study aims to understand the effect of late-onset sepsis on mortality in hospitalised neonatal patients across different gestational ages. This is a single-centre, historical cohort study including neonates admitted to hospital during a 10-year period (2002 - 2011). Neonates were stratified by gestational age: extremely preterm (<28 weeks), very preterm (28 to 32 weeks), late preterm (33 to 36 weeks), full term (>37 weeks). Tertiary NICU in Ghent, Belgium. Logistic regression analysis was used to assess adjusted relationships between late-onset sepsis and mortality, reported as odds ratio (OR) and 95% confidence interval (CI). A total of 4928 neonates were included, of which 2071 were term (42.0%), 1425 were late preterm (28.9%), 1165 very preterm (23.6%) and 264 were extremely preterm neonates (5.4%). 40 neonates developed late-onset sepsis (8.2 episodes/1000 patient days). Overall, in-hospital mortality was 5.4%. Late-onset sepsis was an independent risk factor for mortality in the total cohort (OR = 2.41; 95% CI = 1.46-3.96). However, when gestational age groups were considered separately, late-onset sepsis was associated with mortality in very preterm neonates (OR = 2.45; 95% CI = 1.03-5.84) and in the late preterm neonates (OR = 3.92; 95% CI = 1.41-10.87), but not in other neonates. Comorbidities burdening neonatal hospital survival include acute lung disease, brain damage, periventricular leukomalacia, surgery, and broncho-pulmonary dysplasia. Late-onset sepsis is an independent risk factor for mortality in very preterm and late preterm neonates. Understanding how late-onset sepsis among other factors impact mortality enables a patient and family-centred approach to nursing care including the anticipation of realistic milestones. Late-onset sepsis is especially detrimental to preterm neonates and this could be taken into consideration by nurses when communicating with families in the perinatal period.


Virtual measurements of paracellular permeability and chronic inflammation via color coded pixel-wise T1 mapping.
To assess whether quantitative T1 relaxometry can measure permeability, chronic inflammation and mural thickening of mouse bladder wall. Adult female C57BL6 mice unexposed to radiation (controls) or 40 wk postirradiation of 10 Gy were scanned at 9.4 T before and after instillation (0.1 mL) of aqueous, novel contrast mixture (NCM) containing 4 mM gadobutrol and 5 mM ferumoxytol. Rapid acquisition with refocused echo (RARE) sequence was used with variable repetition times (TR). Pixel-wise maps of T1 relaxation times for the segmented bladder wall layers were generated from voxel-wise, nonlinear least square data fitting of TR-dependent signal intensity acquired with TR array of 0.4-10 s followed by the histology of harvested bladder. Significant differences between precontrast and postcontrast T1 (ΔT1) were noted in urothelium and lamina propria of both groups but only in detrusor of irradiated group (P < 0.001; 2-way ANOVA). Nearly twofold higher gadobutrol permeability (550 ± 73 vs. 294 ± 160 μM; P < 0.01) derived as per 1/ΔT1 = r1. [C] in urothelium of irradiated group. Inflammation and bladder wall thickening (0.75 ± 0. vs. 0.44 ± 0.08 mm; P < 0.001) predicted by MRI was subsequently confirmed by histology and altered expression of CD45 and zonula occludens-1 (ZO-1) relative to controls. NCM enhanced MRI relies on the retention of large molecular weight ferumoxytol in lumen for negative contrast, while permeation of the non-ionic, small molecular weight gadobutrol through ZO-1 generates positive contrast in bladder wall for virtual measurement of paracellular permeability and assessment of chronic inflammation in thin and distensible bladder wall, which is also defined by its variable shape and location within pelvis.


Biological Homochirality and the Search for Extraterrestrial Biosignatures.
Most amino acids and sugar molecules occur in mirror, or chiral, images of each other, knowns as enantiomers. However, life on Earth is mostly homochiral: proteins contain almost exclusively L-amino acids, while only D-sugars appear in RNA and DNA. The mechanism behind this fundamental asymmetry of life remains unknown, despite much progress in the theoretical and experimental understanding of homochirality in the past decades. We review three potential mechanisms for the emergence of biological homochirality on primal Earth and explore their implications for astrobiology: the first, that biological homochirality is a stochastic process driven by local environmental fluctuations; the second, that it is driven by circularly-polarized ultraviolet radiation in star-forming regions; and the third, that it is driven by parity violation at the elementary particle level. We argue that each of these mechanisms leads to different observational consequences for the existence of enantiomeric excesses in our solar system and in exoplanets, pointing to the possibility that the search for life elsewhere will help elucidate the origins of homochirality on Earth.


Occurrence of retained lens fragments after phacoemulsification in The Netherlands.
To determine the incidence of retained lens fragments after phacoemulsification in The Netherlands and to evaluate the effect of vitrectomy on this complication. Eleven vitreoretinal centers in The Netherlands. We performed a retrospective analysis of all patients with retained lens fragments (N = 70) who were referred for vitreoretinal surgery to 11 specialized centers. Seven patients (10%) were treated with medication alone, and 63 (90%) had pars plana vitrectomy. Minimum follow-up after vitrectomy was 3 months. The incidence of retained lens fragments in The Netherlands was calculated at 0.9/1000 cataract operations. Retained lens fragments occurred during the learning curve and with experienced surgeons. After medical or surgical treatment, visual acuity was 20/40 or better in 43 of 70 patients (61%). Uveitis disappeared in all cases. Retinal detachment occurred in 10 patients (14%). Attached retinal breaks were treated in an additional 5 patients. Corneal grafting was performed in 2 patients. Patients who had immediate vitrectomy did not have better functional results than patients in whom vitrectomy was delayed. The iris-fixated claw lens was implanted successfully when capsular support was insufficient. The introduction of phacoemulsification in The Netherlands is associated with an increase of patients with retained lens fragments. Retained lens fragments are complicated by an increased risk for retinal detachment and corneal decompensation. Vitrectomy resulted in a marked improvement of visual acuity and clearing of uveitis.


[Calcium ion uptake by the skin fibroblast culture under normal conditions and in systemic diseases of the connective tissue].
Radioactive calcium (45Ca) uptake and the effect of adrenaline on this process was studied on the suspension of cells derived from the monolayer cultures of fibroblasts of the skin of healthy donors and of patients with systemic scleroderma and rheumatic fever. A significant increase of calcium uptake was shown in case of scleroderma in comparison with the normal and rheumatism cases. Adrenaline (2 X 10(-7)--2 X 10(-5) M) enhanced the rate of calcium uptake by fibroblasts in control and had the opposite effect in scleroderma. The data obtained indicated alteration of the fibroblast membrane function in systemic scleroderma which could underlay the change in the metabolic activity of these cells.


Clinical decision support must be useful, functional is not enough: a qualitative study of computer-based clinical decision support in primary care.
Health information technology, particularly electronic decision support systems, can reduce the existing gap between evidence-based knowledge and health care practice but professionals have to accept and use this information. Evidence is scant on which features influence the use of computer-based clinical decision support (eCDS) in primary care and how different professional groups experience it. Our aim was to describe specific reasons for using or not using eCDS among primary care professionals. The setting was a Finnish primary health care organization with 48 professionals receiving patient-specific guidance at the point of care. Multiple data (focus groups, questionnaire and spontaneous feedback) were analyzed using deductive content analysis and descriptive statistics. The content of the guidance is a significant feature of the primary care professional's intention to use eCDS. The decisive reason for using or not using the eCDS is its perceived usefulness. Functional characteristics such as speed and ease of use are important but alone these are not enough. Specific information technology, professional, patient and environment features can help or hinder the use. Primary care professionals have to perceive eCDS guidance useful for their work before they use it.


Experience-dependent plasticity of cerebellar vermis in basketball players.
The cerebellum is involved in the learning and retention of motor skills. Using animal and human models, a number of studies have shown that long-term motor skill training induces structural and functional plasticity in the cerebellum. The aim of this study was to investigate whether macroscopic alteration in the volume of cerebellum occurs in basketball players who had learned complex motor skills and practiced them intensively for a long time. Three-dimensional magnetic resonance imaging volumetry was performed in basketball players (n = 19) and healthy controls (n = 20), and the volumes of cerebellum and vermian lobules were compared between two groups. Although there was no macroscopic plasticity detected in the cerebellum as a whole, detailed parcellation of cerebellum revealed morphological enlargement in the vermian lobules VI-VII (declive, folium, and tuber) of basketball players (P < 0.0166), which might then be interpreted as evidence for plasticity. This finding suggests that the extensive practice and performance of sports-related motor skills activate structural plasticity of vermian lobules in human cerebellum and suggests that vermian VI-VII plays an important role in motor learning.


Change in weight and adiposity in college students: a systematic review and meta-analysis.
The purpose of this systematic review and meta-analysis was to assess changes in body weight and relative adiposity (%FAT) during college and identify potential moderating variables. A review of peer-reviewed articles published before June 28, 2013 identified 49 studies evaluating the effect of the first year of college on the dependent variables of body weight (137 effects from 48 studies) and %FAT (48 effects from 19 studies). Statistical analysis was conducted between July 1, 2013, and May 1, 2014. Effect sizes were calculated by subtracting the mean pre-test measurements from the mean post-test measurements. Participants' weight increased 1.55 kg (95% CI=1.3, 1.8 kg) during college, with a 1.17% increase in %FAT (95% CI=0.7, 1.6%). Meta-regression analysis concluded that changes in body weight and %FAT were positively associated with study duration, suggesting that effects measuring change over a longer duration yielded larger effects when compared to effects with shorter observations. Sex and baseline BMI were not associated with change in weight or %FAT after accounting for study duration. The increase in weight and %FAT during the college years is equal to 1.55 kg and 1.17%, respectively. Change in body weight during the first year of college is significantly less than that during the cumulative remaining years of college. By understanding the magnitude of change, appropriate prevention efforts can be designed for the college population, which may be beneficial in reducing adult overweight and obesity rates.


Effect of age on tear osmolality.
Certain aspects of tear physiology change with age (reflex secretion and stability), whereas others remain unchanged (tear volume, evaporation rate, basal tear production). To establish the variation in tear osmolality with age, 0.2 to 0.4 microliter samples were collected from 50 normal males and 50 normal females (age range 17 to 75 years). Nanoliter aliquots of the samples were analyzed by freezing point depression nanoliter osmometry. Mean tear osmolality for the whole group was 303.6 +/- 13.0 mOsm/kg and was not significantly affected by age (r2 = 0.014, p = 0.378). For males the mean was 307.1 +/- 14.4 and for females 300.1 +/- 10.4 mOsm/kg, a significant gender difference (p = 0.006). Males under age 41 had tear osmolality which was not significantly different from that of males over 41 years of age (307.7 +/- 15.6 and 305.7 +/- 11.5 mOsm/kg, respectively, p = 0.671) but the mean tear osmolality for females under age 41 years (297.6 +/- 11.2 mOsm/kg) was significantly different from that of older females (304.8 +/- 6.7 mOsm/kg, p = 0.017). There was no significant correlation between age and osmolality for males (r2 = 0.003, p = 0.699), but there was a significant correlation for females (r2 = 0.159, p = 0.004). Males under age 41 years have a significantly higher mean tear osmolality than females under 41 years of age (p = 0.003). The age and gender differences found for tear osmolality can be accounted for by the low values in young females, which may be related to the increased tear flow observed in young females. A reduction in this high flow rate to a more "normal" level in older females may account for the rise in tear osmolality to a level which is not significantly different from that of older males. Generally in normal eyes, the osmolality of tears remains within normal limits and is not affected by age.


Adverse drug events reported by rural older adults.
Adverse drug events (ADEs) impact the health and safety of older adults. ADEs may lead to unplanned medical visits that influence health and related costs. The purpose of this study was to explore ADEs reported by rural, community-dwelling older adults. Data were collected on 138 participants' demographics, physical and mental health, sleep, medications, and ADEs. One or more ADEs were reported by 48% of participants, including central nervous symptom disturbances (16%), dry mouth (12%), hoarseness, gastrointestinal irritation, and decreased libido (all 8%). Poor sleep and poor physical health were associated with higher reported ADEs (p < 0.05). Older adults (ages 79-99) and those with higher physical health were 60% less likely to report ADEs. Those with poorer sleep quality were 50% more likely to report ADEs. Viable strategies are needed to monitor and reduce ADEs in community-dwelling older adults who use multiple medications to manage poor health and poor sleep.


The effects of physiological estrogen concentration on the immune response of urothelial carcinoma cells to bacillus Calmette-Guérin.
Meta-analysis has shown that bacillus Calmette-Guérin is less effective in females undergoing treatment for urothelial carcinoma. Urothelial carcinoma cells express immune regulatory proteins as a consequence of bacillus Calmette-Guérin induced, nuclear factor κB signaling. Nuclear factor κB is influenced by estrogen receptor binding. We evaluated the effect of the physiological estradiol concentration on the expression of bacillus Calmette-Guérin induced, nuclear factor κB regulated immune proteins. We determined the estrogen receptor expression status of human urothelial carcinoma cell lines by reverse transcriptase-polymerase chain reaction. The functional status of estrogen receptor signaling was established using estrogen receptor reporter constructs. We used gene expression profiling of urothelial carcinoma cells combined with reverse transcriptase-polymerase chain reaction to identify the nuclear factor κB dependent immune regulatory proteins expressed in response to bacillus Calmette-Guérin. We determined the influence of the estradiol concentration on bacillus Calmette-Guérin dependent interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 gene expression by quantitative reverse transcriptase-polymerase chain reaction. Urothelial carcinoma cell lines expressed functional estrogen receptor. Nuclear factor κB signaling was inhibited by estradiol in a dose and estrogen receptor dependent manner. Urothelial carcinoma cell expression of interleukin-6 and 8, chemokine (c-x-c motif) ligands 1 and 2, and chemokine (c-c motif) ligand 20 was up-regulated in response to bacillus Calmette-Guérin in a nuclear factor κB dependent manner. There was a significant dose dependent effect of estradiol on the expression of these genes in bacillus Calmette-Guérin treated urothelial carcinoma cells. The physiological concentration of estrogen influences nuclear factor κB signaling and bacillus Calmette-Guérin dependent gene expression. Serum estradiol fluctuations in women may influence the response of urothelial carcinoma to intravesical bacillus Calmette-Guérin treatment.


Apricot kernel characterization, oil extraction, and its utilization: a review.
Apricot (Prunus armeniaca L.) kernels, one of the economical stone fruit kernels, are utilized worldwide for edible, cosmetic, and medicinal purposes. Oil from the apricot kernel is valued by the richness of unsaturated fatty acids, the high proportion of oleic acids, phenols, and tocopherol content. Oil yield with quality from apricot kernel varies with region, variety, and adopted method of oil extraction. This review discusses apricot kernel characterization, different conventional and novel methods of oil extraction, their merits and demerits as reported in the literature. Novel technologies such as microwave-assisted oil extraction, ultrasound-assisted oil extraction, enzyme-assisted oil extraction, and supercritical fluid oil extraction have emerged as the most promising extraction methods that allow efficient oil recovery in very environment-friendly ways. Knowledge of the extraction technique aids in giving higher oil recovery with minimal nutritional losses while retaining the original organoleptic properties.


Predictive factors for inadequate bowel cleansing in colon capsule endoscopy.
Achieving adequate bowel cleansing is of utmost importance for the efficiency of colon capsule endoscopy (CCE). However, information about predictive factors is lacking. The aim of this study was to assess the predictive factors of poor bowel cleansing in the CCE setting. In this observational study, 126 patients who underwent CCE at two tertiary care hospitals were included between June 2017 and January 2020. Participants prepared for bowel cleansing with a 1-day clear liquid diet, a 4-L split-dose polyethylene glycol regimen and boosters with sodium phosphate, sodium amidotrizoate and meglumine amidotrizoate. Domperidone tablets and bisacodyl suppositories were administered when needed. Overall and per-segment bowel cleansing was evaluated using a CCE cleansing score. Simple and multiple logistic regression analysis were carried out to assess poor bowel cleansing and excretion rate predictors. Overall bowel cleansing was optimal in 53 patients (50.5%). Optimal per-segment bowel cleansing was achieved as follows: cecum (86 patients; 74.8%), transverse colon (91 patients; 81.3%), distal colon (81 patients; 75%) and rectum (64 patients; 66.7%). In the univariate analysis, elderly (OR, 1.03; 95% CI (1.01-1.076)) and constipation (OR, 3.82; 95% CI (1.50-9.71)) were associated with poor bowel cleansing. In the logistic regression analysis, constipation (OR, 3.77; 95% CI (1.43-10.0)) was associated with poor bowel cleansing. No variables were significantly associated with the CCE device excretion rate. Our results suggest that constipation is the most powerful predictor of poor bowel cleansing in the CCE setting. Tailored cleansing protocols should be recommended for these patients.


A systematic review of studies using pedometers to promote physical activity among youth.
While pedometers have an important role to play in the promotion of lifestyle activity among adults, less known is regarding their impact on behavior among youth (i.e. children and adolescents). The primary aim of this review was to identify the effectiveness of pedometers in promoting physical activity among youth. Secondary aims were to assess the quality of existing studies and examine the different ways that pedometers have been used to promote activity. A systematic search of six electronic databases was conducted using combinations of the following key words 'physical activity', 'walking', 'intervention', 'promotion', 'evaluation', and 'pedometer'. The quality of the studies was assessed against predetermined criteria. Our search identified 14 studies, of which 12 resulted in increases in physical activity. Three studies used pedometers as open-loop feedback mechanisms to increase physical activity by making access to sedentary activities contingent on achieving activity targets. Ten studies used pedometers for self-monitoring and one study incorporated pedometers into an integrated school curriculum. Pedometers have been used successfully in a variety of ways to promote activity among youth. Since there are so few studies at this time, there is ample need and opportunity to contribute to the knowledge base.


Degradation of CL-20 by white-rot fungi.
In previous studies, we found that the emerging energetic chemical, CL-20 (C6H6N12O12, 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane), can be degraded following its initial denitration using both aerobic and anaerobic bacteria. The C and N mass balances were not determined due to the absence of labeled starting compounds. The present study describes the degradation of the emerging contaminant by Phanerochaete chrysosporium using ring-labeled [15N]-CL-20 and [14C]-CL-20. Ligninolytic cultures degraded CL-20 with the release of nitrous oxide (N2O) in amounts corresponding to 45% of the nitrogen content of CL-20. When ring-labeled [15N]-CL-20 was used, both 14N14NO and 15N14NO were observed, likely produced from -NO2 and N-NO2, respectively. The incubation of uniformly labeled [14C]-CL-20 with fungi led to the production of 14CO2 (> 80%). Another ligninolytic fungus, Irpex lacteus, was also able to degrade CL-20, but as for P. chrysosporium, no early intermediates were observed. When CL-20 was incubated with manganese peroxidase (MnP), we detected an intermediate with a [M-H]- mass ion at 345 Da (or 351 and 349 Da when using ring-labeled and nitro-labeled [15N]-CL-20, respectively) matching a molecular formula of C6H6N10O8. The intermediate was thus tentatively identified as a doubly denitrated CL-20 product. The concomitant release of nitrite ions (NO2-) with CL-20 degradation by MnP also supported the occurrence of an initial denitration prior to cleavage and decomposition.


MR imaging of femoroacetabular impingement.
FAI is a common cause of OA of the hip. It can be caused by decreased offset of the femoral head and neck, resulting in abutment of the femoral neck against the acetabular rim (cam impingement) and abutment of this area into the well-constrained socket (pincer impingement)within normal range of motion [15]. This repetitive mechanical trauma to the hip joint causes mechanical wear of the labrum and articular cartilage; left untreated, it causes pain, labral tears, and chondral injuries leading to progressive OA of the hip. The identification of FAI as a cause of OA allows appropriate therapy early and thus delays or prevents end-stage arthritis.MR imaging and MR arthrography are accurate noninvasive imaging modalities able to demonstrate acetabular labral disease and adjacent cartilage damage as well as the subchondral cysts and synovial herniation pits associated with impingement. In addition, MR imaging is able to detect underlying subtle anatomic variations of the femoral head-neck junction and acetabulum associated with FAI.


Synthetic approaches to the 2015-2018 new agrochemicals.
In this review, the synthesis of 33 agrochemicals that received an international standardization organization (ISO) name between January 2015 and December 2018 is described. The aim is to showcase the broad range and scope of reactions, reagents and intermediates used to discover and produce the latest active ingredients addressing the crop protection industry's needs.


(18)F-FDG PET/CT in inflammatory pseudotumor of the colon causing intussusception.
Inflammatory pseudotumor is a rare benign lesion mimicking malignancy both clinically and radiologically. An accurate diagnosis is still difficult and is based on the histological examination. Since inflammatory pseudotumor is exceptionally rare in the colon, this unexpected lesion can be mistaken for malignancy. We report the first case of inflammatory pseudotumor in the colon that showed (18)F-fluorodeoxyglucose (FDG) uptake and acted as the lead point causing colocolic intussusception.


Selective accumulation of hydroxytryptamines by frog tectal neurones.
By means of histofluorescence microscopy, 5,7-dihydroxytryptamine was shown to be taken up by selective populations of brain neurones of the frog, Rana pipiens, following both intracranial administration and in vitro incubation with isolated brain preparations. Presumptive non-aminergic cell bodies of the superficial aspect of tectal lamina 6 exhibited more avid uptake than did putative serotonin perikarya of the raphe complex. Within the tectum, 5,7-dihydroxytryptamine uptake appeared to be restricted to large piriform neurons; in the torus semicircularis, it occurred in a morphologically dissimilar group of scattered cells. The same tectal cell system accumulated 5-hydroxytryptamine and 6-hydroxytryptamine, but not N-acetylserotonin, melatonin, or noradrenaline. 5,7-Dihydroxytryptamine uptake was insensitive to cold or imipramine; however, it was blocked by ouabain at high but not low temperature. At concentrations greater than or equal to 100 microM, 5,7-dihydroxytryptamine-induced fluorescence was sufficiently intense to permit tracing of intratectal dendrites and tectofugal axonal processes projecting to a lateral diencephalic neuropil and an ipsilateral isthmic neuropil. While previous monoamine histofluorescence and immunohistologic studies have not revealed serotonin-containing perikarya in the ranid tectum, our findings demonstrate that lamina 6 piriform projection neurones, presumably lacking indolamine-synthesizing enzymes, possess a striking capability for accumulating hydroxylated tryptamines.


Intake of NOAC is associated with hematoma expansion of intracerebral hematomas after traumatic brain injury.
Novel oral anticoagulants are increasingly replacing vitamin K antagonists in the prophylaxis of thromboembolism as they are associated with lower incidence of spontaneous intracerebral hematomas and they do not require drug level monitoring. However, management dilemmas are apparent in patients on novel oral anticoagulants who have developed intracerebral hematomas after traumatic brain injury, since clinical experience with their reversal strategies is limited. We retrospectively studied 90 patients with traumatic intracerebral hematomas undergoing treatment at the surgical intensive care unit of the BG University Clinic Bergmannsheil in Bochum between 2015 and 2018. We analyzed potential prognostic factors for their radiological (expansion of intracerebral hematoma) and clinical (patients' outcome) course, in particular the role of novel oral anticoagulants. 71.1% of patients were male; mean age was 67.3 years. Hematoma's expansion occurred in 35.9% of our patients, whereas 62.2% of our cohort showed a favorable outcome, defined as Glasgow Outcome Scale 4 and 5. Intake of novel oral anticoagulants was associated with a higher rate of hematoma's expansion compared to patients on vitamin K antagonists (p = 0.05) or to patients with normal coagulation status (p = 0.002). A younger age (p < 0.001) was identified as the sole independent prognostic factor for a more favorable outcome, after excluding our cases, who underwent a cardiopulmonary resuscitation. Our data showed a higher rate of hematoma's expansion in patients with traumatic intracerebral hematomas on novel oral anticoagulants vs. vitamin K antagonists and recommend the consideration of prophylactic reversal of the novel oral anticoagulants at admission. Larger prospective trials are warranted to conclude whether the current specific reversal protocols are safe and effective.


Assessment of US Pharmacies Contracted With Health Care Institutions Under the 340B Drug Pricing Program by Neighborhood Socioeconomic Characteristics.
This cross-sectional study assesses pharmacy participation in the 340B Drug Pricing Program following the 2010 expansion and the extent to which growth has occurred in socioeconomically disadvantaged neighborhoods.


Synergy between TLR3 and IL-18 promotes IFN-γ dependent TRAIL expression in human liver NK cells.
Natural killer (NK) cells are a component of innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. However, intra-hepatic NK cells' ability to respond to virus is still mostly unknown. Our results show that the synthetic dsRNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, activates NK cells directly in the context of cytokines found in the liver, i.e.: poly I:C plus inflammatory cytokines (IL-18, IL-12, and IL-2) induced NK cell IFN-γ production and TRAIL expression, and anti-inflammatory cytokines (TGF-β and IL-10) inhibit NK cell IFN-γ production. Neutralization of IFN-γ blocks poly I:C plus inflammatory cytokines-induced NK cell TRAIL expression, suggesting that IFN-γ is an autocrine differentiation factor for these cells. A better understanding of the intra-hepatic NK cell activation against viral infection may help in the design of therapies and vaccines for the control of viral hepatitis.


First report of novel assemblages and mixed infections of Giardia duodenalis in human isolates from New Zealand.
Giardia duodenalis (syn. G. intestinalis and G. lamblia) is a protozoan parasite that cause disease (giardiasis) in humans and other animals. The pathogen is classified into eight assemblages, further divided into sub-assemblages, based on genetic divergence and host specificities. There are two zoonotic subtypes known as assemblages A and B, whilst assemblages from C to H are mainly found in domesticated animals, rodents and marine mammals. Here, we report for the first time the presence of assemblage E and sub-assemblage AIII in human isolates from the South Island in New Zealand. We identified a > 99% nucleotide similarity of assemblage E and sub-assemblage AIII with sequences of the gdh gene available in GenBank from individual human samples collected in Dunedin and Christchurch, respectively. We also performed a deep sequencing approach to assess intra-host assemblage variation. The sample from Dunedin showed evidence of mixed assemblage E and zoonotic sub-assemblage BIV. The report of two novel assemblages and mixed infections provides insights into the genetic diversity, epidemiology and transmission dynamics of Giardia duodenalis in New Zealand.


A satellite-based hybrid model for trophic state evaluation in inland waters across China.
Eutrophication is one of the major threats to the inland water ecosystem. Satellite remote sensing provides a promising way to monitor trophic state at large spatial scale in an efficient manner. Currently, most satellite-based trophic state evaluation approaches have focused on water quality parameters retrieval (e.g., transparency, chlorophyll-a), based on which trophic state was evaluated. However, the retrieval accuracies of individual parameter do not meet the demand for accurate trophic state evaluation, especially for the turbid inland waters. In this study, we proposed a novel hybrid model to estimate trophic state index (TSI) by integrating multiple spectral indices associated with different eutrophication level based on Sentinel-2 imagery. The TSI estimated by the proposed method agreed well with the in-situ TSI observations, with root mean square error (RMSE) of 6.93 and mean absolute percentage error (MAPE) of 13.77%. Compared with the independent observations from Ministry of Ecology and Environment, the estimated monthly TSI also showed good consistency (RMSE=5.91,MAPE=10.66%). Furthermore, the congruent performance of the proposed method in the 11 sample lakes (RMSE=5.91,MAPE=10.66%) and the 51 ungauged lakes (RMSE=7.16,MAPE=11.56%) indicated the favorable model generalization. The proposed method was then applied to assess the trophic state of 352 permanent lakes and reservoirs across China during the summers of 2016-2021. It showed that 10%, 60%, 28%, and 2% of the lakes/reservoirs are in oligotrophic, mesotrophic, light eutrophic, and middle eutrophic states respectively. Eutrophic waters are concentrated in the Middle-and-Lower Yangtze Plain, the Northeast Plain, and the Yunnan-Guizhou Plateau. Overall, this study improved the trophic state representativeness and revealed trophic state spatial distribution of Chinese inland waters, which has the significant meanings for aquatic environment protection and water resource management.


Pediatric esthetic otoplasty.
Pediatric otoplasty is generally considered to be a "simple" procedure, but an astute surgeon recognizes the challenges of this operation and is mindful of the degree of detail involved in its planning and execution. The vast number of described otoplasty methods, which are ever evolving, is a testament to the complexity of this procedure. In this article, the authors' methodology with respect to preoperative analysis and planning, surgical technique, and postoperative care, including management of complications and potential pitfalls, are highlighted.


A meta-analysis of cohort studies including dose-response relationship between shift work and the risk of diabetes mellitus.
Previous reviews have suggested that shift work is associated with an increased risk of diabetes mellitus (DM); however, the results should be interpreted with caution due to differences in study designs and non-comprehensive literature searches. In addition, the quantitative dose-response relationship between years of shift work and DM risk is still unknown. We aimed to conduct an updated meta-analysis with cohort studies and to evaluate the relationship between the duration of shift work and the risk of DM in a dose-dependent manner. The PubMed and Web of Science databases were searched through 15 August 2019, and multivariate-adjusted relative risks (RRs) were pooled using random-effects models. Restricted cubic spline analysis with three knots was used to explore the relationship of years of shift work and risk of DM. Twelve cohort studies with 28 independent reports involving 244,266 participants and 15,906 DM cases were included. The summarized adjusted RR for the relationship between shift work and DM risk was 1.14 (95% CI 1.10 to 1.19; I2 = 38.9%, P = 0.028). The summary RR of a 5-year increase in shift work was 1.07 (95% CI 1.04 to 1.09), without heterogeneity (I2= 0.0%, P = 0.829) for the female population. Shift work is associated with an increased risk of DM, and a strong and highly significant linear dose-response relationship between the duration of shift work and the risk of DM in women was observed. Further studies are needed to confirm the results, establish causality and elucidate the underlying mechanisms.


Paclitaxel-loaded sodium deoxycholate-stabilized zein nanoparticles: characterization and in vitro cytotoxicity.
Paclitaxel (PTX) is one of the most successful antineoplastic drugs and is widely used for the treatment of many forms of advanced and refractory cancer. Unfortunately, various drawbacks including non-selective cytotoxicity, poor water solubility and low bioavailability limit its clinical use. The aim of this study was to characterize a novel colloidal system made up of the natural protein zein, that would be able to efficiently retain the anticancer compound and increase its in vitro pharmacological effects. In fact, zein has promising characteristics that render it a potential material to be used in drug delivery application. The influences of temperature, pH and serum incubation on the stability of these particles, entrapment efficiency of PTX and in vitro toxicity on different cancer cell lines were evaluated. The nanosystems containing PTX demonstrated suitable storage stability, and were not destabilized by temperatures of up to 50 °C, pH alterations, the freeze-drying process or serum proteins. The encapsulation of PTX did not destabilize the structure of the zein nanoparticles and a suitable drug entrapment efficiency resulted. PTX-loaded zein nanoparticles showed an increased toxicity on different cancer cell lines with respect to the free drug, confirming its potential application in preclinical and clinical investigations.


The 2018 adult heart allocation policy change benefits low-volume transplant centers.
The effect of the 2018 adult heart allocation policy change at an institution-level remains unclear. The present study assessed the impact of the policy change by transplant center volume. The United Network for Organ Sharing database was queried for all adults undergoing isolated heart transplantation from November 2016 to September 2020. Era 1 was defined as the period before the policy change and Era 2 afterwards. Hospitals were divided into low-(LVC) medium-(MVC) and high-volume (HVC) tertiles based on annual transplant center volume. Competing-risks regressions were used to determine changes in waitlist death/deterioration, while post-transplant mortality was assessed using multivariable Cox proportional-hazards models. A total of 3531 (47.0%) patients underwent heart transplantation in Era 1 and 3988 (53.0%) in Era 2. At LVC, Era 2 patients were less likely to experience death/deterioration on the waitlist (subhazard ratio .74, 95% CI .63-.88), while MVC and HVC patients experienced similar waitlist death/deterioration across eras. After adjustment, transplantation in Era 2 was associated with worse 1-year mortality at MVC (hazard ratio, HR, 1.42 95% CI 1.02-1.96) and HVC (HR 1.42, 95% CI 1.02-1.98) but not at LVC. Early analysis shows that LVC may be benefitting under the new allocation scheme.


Evaluation of sample treatments in a safe and straightforward procedure for the detection of SARS-CoV-2 in saliva.
To evaluate four sample treatments in a safe and straightforward procedure to detect SARS-CoV-2 in saliva. Four sample treatments were evaluated in a 3-step procedure to detect SARS-CoV-2 in saliva: 1) heating at 95 °C for 5 min for sample inactivation; 2) sample treatment; 3) analysis by reverse-transcription loop-mediated isothermal amplification (LAMP). Saliva samples used were from infected individuals or were spiked with known quantities of viral particles. Three treatments had a limit of detection (LOD) of 500.000 viral particles per ml of saliva and could be used to detect individuals with potential to transmit the disease. The treatment of phosphate buffer, dithiothreitol, ethylenediaminetetraacetic acid and proteinase K, with an additional 95 °C heating step, yielded a lower LOD of 95; its sensitivity ranged from 100% in patients with nasopharyngeal swab reverse-transcriptase polymerase chain reaction cycle threshold values <20 to 47.8% for values >30. This report highlights the importance of an adequate sample treatment for saliva to detect SARS-CoV-2 and describes a flexible procedure that can be adapted to point-of-care. Although its sensitivity when LAMP is used is lower than reverse-transcriptase polymerase chain reaction, this procedure can contribute to COVID-19 control by detecting individuals able to transmit the disease.


Meso-diacylated calix[4]pyrrole: structural diversities and enhanced binding towards dihydrogenphosphate ion.
Meso-diacylated calix[4]pyrrole was obtained via acid catalysed condensation of meso-acylated dipyrromethane with acetone. Selective presence of flexible substituents at the calix[4]pyrrole periphery led to interesting structural motifs in the solid state along with enhanced binding towards anions, especially dihydrogenphosphate ion via anchoring.


Counting knowledge and skill in cognitive addition: a comparison of normal and mathematically disabled children.
The relationship between counting knowledge and computational skills (i.e., skill at counting to solve addition problems) was assessed for groups of first-grade normal and mathematically disabled (MD) children. Twenty-four normal and 13 MD children were administered a series of counting tasks and solved 40 computer-administered addition problems. For the addition task, problem-solving strategies were recorded on a trial-by-trial basis. Performance on the counting tasks suggested that the MD children were developmentally delayed in the understanding of essential and unessential features of counting and were relatively unskilled in the detection of certain forms of counting error. On the addition task, the MD children committed many more computational errors and tended to use developmentally immature counting procedures. The immature counting knowledge of the MD children, combined with their relatively poor skills at detecting counting errors, appeared to underlie their poor computational skills on the addition task. Suggestions for future research are presented.


Alternative splicing: combinatorial output from the genome.
Alternative splicing has emerged as a mechanism that can account for a large proportion of the disparity between the modest number of genes in the human genome and the much higher complexity of the expressed proteome. At least a third, and probably the majority, of human genes are alternatively spliced, and some genes can generate thousands of protein isoforms by complex alternative splicing events. Analysis of the transcriptome will therefore require the development of massively parallel technologies that are able to encompass the complexity arising from alternative splicing.


Monounsaturated fatty acids might be key factors in the Mediterranean diet that suppress rheumatoid arthritis disease activity: The TOMORROW study.
The Mediterranean diet is reportedly effective in suppressing disease activity in rheumatoid arthritis (RA), but the key elements responsible for this effect remain unknown. The presented study therefore aimed to identify such elements. This study included 208 consecutive patients with RA (RA group) and 205 age- and sex-matched healthy volunteers (controls) from the prospective "TOMORROW" cohort study that has been ongoing since 2010 were included in this study. Food and nutrient intake was assessed using the brief self-administered diet history questionnaire (BDHQ), Mediterranean diet scores were calculated based on intake by controls and disease activity was determined from disease activity scores in 28 joints and erythrocyte sedimentation rates (DAS28-ESR). Intake of monounsaturated fatty acids (MUFA) was significantly lower in the RA, than in the control group (P = 0.003) and the ratio of consumed monounsaturated to saturated fatty acid (MUFA/SFA) significantly differed within the RA group after being sub-classified according to DAS28-ESR. Moreover, DAS28-ESR significantly correlated with MUFA/SFA intake after age adjustment (R = -0.228, P < 0.01). Logistic regression analysis selected high MUFA intake as an independent predictor of remission in the RA group with borderline boundary significance (odds ratio, 1.97; 95% CI, 0.98-3.98; P = 0.057). Changes in DAS28-ESR between 2010 and 2011 significantly correlated with MUFA/SFA intake after age adjustment (R = 0.180, P = 0.01). Daily MUFA intake, a component of the Mediterranean diet score, might suppress disease activity in RA patients.


Identifying self-disclosed anxiety on Twitter: A natural language processing approach.
Text analyses of social media posts are a promising source of mental health information. This study used natural language processing to explore distinct language patterns on Twitter related to self-reported anxiety diagnosis. A total of 233.000 tweets made by 605 users (300 reporting anxiety diagnosis and 305 not) over six months were comparatively analysed, considering user behavior, Linguistic Inquiry Word Count (LIWC), and sentiment analysis. Twitter users with a self-disclosed diagnosis of anxiety were classified as 'anxious' to facilitate group comparisons. Supervised machine learning models showed a high prediction accuracy (Naïve Bayes 81.1 %, Random Forests 79.8 %, and LASSO-regression 79.4 %) in identifying Twitter users' self-disclosed diagnosis of anxiety. Additionally, a Latent Profile Analysis (LPA) identified four profiles characterized by high sentiment (31 % anxious participants), low sentiment (68 % anxious), self-immersed (80 % anxious), and normative behavior (38 % anxious). The digital footprint of self-disclosed anxiety on Twitter posts presented a high frequency of words conveying either negative sentiment, a low frequency of positive sentiment, a reduced frequency of posting, and lengthier texts. These distinct patterns enabled highly accurate prediction of anxiety diagnosis. On this basis, appropriately resourced, awareness raising, online mental health campaigns are advocated.


Vascular endothelial growth factor serum concentrations in hypercholesterolemic patients.
Vascular endothelial growth factor (VEGF) promotes normal and pathological angiogenesis. VEGF is a chemotactic factor for macrophages and vascular smooth muscle cells, and induces synthesis of metalloproteinases and adhesion molecules. VEGF expression is regulated by hypoxia, cytokines, oncogenes, and oxidized low-density lipoprotein (LDL). The purpose of this study was to determine the relationship between levels of lipid parameters and VEGF, to investigate whether pravastatin treatment influences VEGF serum concentrations, and to examine the relationship between VEGF and the variations in post-treatment lipid and inflammatory parameters. Eighteen patients aged 48+/-6.8 years with total cholesterol (TC) >6.1 mmol/L comprised the hypercholesterolemic group. The controls included 12 individuals aged 50+/-7.4 years with TC <5.1 mmol/L. TC, high-density lipoprotein cholesterol (HDLC), triglycerides, LDLC, C-reactive protein (CRP), and VEGF were determined in both groups at baseline, and in the hypercholesterolemic group after 4 months of treatment with 20 mg/day pravastatin. A significant correlation was observed between concentrations of VEGF and TC, LDLC and TG, and a significant difference in VEGF concentration was observed between the control group (mean 142 ng/L) and the hypercholesterolemic group (mean 272.9 ng/L). A significant decrease was observed in TC (14.7 %), LDLC (21.5 %), CRP (22.7 %), and VEGF (14.8 %) after 4 months of treatment with pravastatin. A relationship was found between serum levels of VEGF and most atherogenic lipoproteins. In patients with hypercholesterolemia treated with pravastatin, a reduction in VEGF and CRP was seen in addition to lipid decreases.


Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the outbreak of coronavirus disease 2019 (COVID-19), has shown a vast range of clinical manifestations from asymptomatic to life-threatening symptoms. To figure out the cause of this heterogeneity, studies demonstrated the trace of genetic diversities whether in the hosts or the virus itself. With this regard, this review provides a comprehensive overview of how host genetic such as those related to the entry of the virus, the immune-related genes, gender-related genes, disease-related genes, and also host epigenetic could influence the severity of COVID-19. Besides, the mutations in the genome of SARS-CoV-2 __leading to emerging of new variants__ per se affect the affinity of the virus to the host cells and enhance the immune escape capacity. The current review discusses these variants and also the latest data about vaccination effectiveness facing the most important variants.


Effects of combined test dose and therapeutic drug monitoring strategy in exposure-directed busulfan.
Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).


Mannitol but not dantrolene prevents myocardial dysfunction following intra-cranial hypertension in rats.
Cardiac complications stemming from intra-cranial hypertension may result from impaired intra-cellular Ca(2+) homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+) release, on myocardial dysfunction associated with intra-cranial hypertension in rats. Dantrolene (10 mg) with and without 15% mannitol was administered to halothane-anesthetized rats prior to induction of intra-cranial hypertension by subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and 5% Pentaspan. Dantrolene with mannitol or 15% mannitol alone prevented the transient intra-cranial hypertension-induced hyperdynamic response and ensuing circulatory collapse that was found in animals pre-treated with 3% mannitol solution or pentaspan. Moreover, hemodynamic function was preserved irrespective of TnI cleavage. However, only animals treated with high dose 15% mannitol exhibited lower lipid peroxidation content in the heart. In contrast, pre-treatment with dantrolene alone did not prevent the cardiac complications associated with intra-cranial hypertension. In conclusion, 15% mannitol attenuated the cardiopulmonary complications associated with intra-cranial hypertension. Dantrolene without mannitol was without effect. Since mannitol exhibits free radical scavenging properties, protection could be the result of a decrease in oxidative stress after intra-cranial hypertension.


Peptide Toxins Targeting KV Channels.
A number of peptide toxins isolated from animals target potassium ion (K+) channels. Many of them are particularly known to inhibit voltage-gated K+ (KV) channels and are mainly classified into pore-blocking toxins or gating-modifier toxins. Pore-blocking toxins directly bind to the ion permeation pores of KV channels, thereby physically occluding them. In contrast, gating-modifier toxins bind to the voltage-sensor domains of KV channels, modulating their voltage-dependent conformational changes. These peptide toxins are useful molecular tools in revealing the structure-function relationship of KV channels and have potential for novel treatments for diseases related to KV channels. This review focuses on the inhibition mechanism of pore-blocking and gating-modifier toxins that target KV channels.


In situ hydrogel capturing nitric oxide microbubbles accelerates the healing of diabetic foot.
Diabetic foot ulcer (DFU) is a devastating complication in diabetes patients, imposing a high risk of amputation and economic burden on patients. Sustained inflammation and angiogenesis hindrance are thought to be two key drivers of the pathogenesis of such ulcers. Nitric oxide (NO) has been proven to accelerate the healing of acute or chronic wounds by modulating inflammation and angiogenesis. However, the use of gas-based therapeutics is difficult for skin wounds. Herein, therapeutic NO gas was first prepared as stable microbubbles, followed by incorporation into a cold Poloxamer-407 (P407) solution. Exposed to the DFU wound, the cold P407 solution would rapidly be transformed into a semisolid hydrogel under body temperature and accordingly capture NO microbubbles. The NO microbubble-captured hydrogel (PNO) was expected to accelerate wound healing in diabetic feet. The NO microbubbles had an average diameter of 0.8 ± 0.4 μm, and most of which were captured by the in situ P407 hydrogel. Moreover, the NO microbubbles were evenly distributed inside the hydrogel and kept for a longer time. In addition, the gelling temperature of 30% (w/v) P407 polymer (21 °C) was adjusted to 31 °C for the PNO gel, which was near the temperature of the skin surface. Rheologic studies showed that the PNO gel had mechanical strength comparable with that of the P407 hydrogel. The cold PNO solution was conveniently sprayed or smeared on the wound of DFU and rapidly gelled. In vivo studies showed that PNO remarkably accelerated wound healing in rats with DFU. Moreover, the sustained inflammation at the DFU wound was largely reversed by PNO, as reflected by the decreased levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the increased levels of anti-inflammatory cytokines (IL-10, IL-22 and IL-13). Meanwhile, angiogenesis was significantly promoted by PNO, resulting in rich blood perfusion at the DFU wounds. The therapeutic mechanism of PNO was highly associated with polarizing macrophages and maintaining the homeostasis of the extracellular matrix. Collectively, PNO gel may be a promising vehicle of therapeutic NO gas for DFU treatment.


Characterization and perturbation of CTCF-mediated chromatin interactions for enhancing myogenic transdifferentiation.
Expression of key transcription factors can induce transdifferentiation in somatic cells; however, this conversion is usually incomplete due to undefined intrinsic barriers. Here, we employ MyoD-induced transdifferentiation of fibroblasts as a model to illustrate the chromatin structures that impede the cell-fate transition. Focusing on the three-dimensional (3D) chromatin interactions, we show that MyoD directly establishes chromatin loops to activate myogenic transcriptional program. Similarly, dynamic changes of CTCF-mediated chromatin interactions are favorable for fibroblast-to-myoblast conversion. However, a substantial portion of CTCF-mediated chromatin interactions remain stable, and the associated genes are steady in expression and enriched for fibroblast function that may restrict cell-identity transformation. Temporal CTCF depletion can interrupt the resistant chromatin loops to enhance myogenic transdifferentiation in mice, pig, and chicken fibroblasts. Therefore, during induced transdifferentiation, the transcription factor can directly reorganize the 3D chromatin interactions, and perturbation of CTCF-mediated genome topology may resolve the limitations of cell fate transitions.


Selective immobilization of iodide onto a novel bismuth-impregnated layered mixed metal oxide: Batch and EXAFS studies.
A novel Mg/Al/Bi ternary mixed metal oxide (MMO) was successfully prepared by a simple coprecipitation and calcination process. The Mg/Al/Bi MMO (molar ratio = 3:0.4:0.6) presented synergistically enhanced adsorption efficiency for iodide in water with porous structure. Kinetic adsorption results indicated good agreement with pseudo first-order-kinetic model (R = 0.998) and the maximum adsorption capacity calculated by Langmuir isotherm of Mg/Al/Bi MMO was 202.2 mg/g, which is higher than that of Mg/Al layered double oxide (LDO) (161.0 mg/g) and bismuth oxide (57.5 mg/g). In addition, the Mg/Al/Bi MMO showed good adsorption efficiency under neutral condition (pH 7), by which the material exhibits relatively strong resistance to the presence of co-existing anions in water due to the ion selectivity. Extended X-ray absorption fine structure (EXAFS) spectra revealed that the enhanced adsorption of iodide by Mg/Al/Bi MMO can be induced by selective Bi-O-IBformation, which is stable waste form for its treatment. Consequently, it is clear that the novel Mg/Al/Bi MMO is a potentially attractive material in terms of selective uptake of iodide with forming stable chemical complex in radioactive contaminants.


Enzyme-Inspired Room-Temperature Lithium-Oxygen Chemistry via Reversible Cleavage and Formation of Dioxygen Bonds.
Li-O2 batteries are promising energy storage systems due to their ultra-high theoretical capacity. However, most Li-O2 batteries are based on the reduction/oxidation of Li2 O2 and involve highly reactive superoxide and peroxide species that would cause serious degradation of cathodes, especially carbon-based materials. It is important to explore lithium-oxygen reactions and find new Li-O2 chemistry which can restrict or even avoid the negative influence of superoxide/peroxide species. Here, inspired by enzyme-catalyzed oxygen reduction/oxidation reactions, we introduce a copper(I) complex 3 N-CuI (3 N=1,4,7-trimethyl-1,4,7-triazacyclononane) to Li-O2 batteries and successfully modulate the reaction pathway to a moderate one on reversible cleavage/formation of O-O bonds. This work demonstrates that the reaction pathways of Li-O2 batteries could be modulated by introducing an appropriate soluble catalyst, which is another powerful choice to construct better Li-O2 batteries.


Purification and cloning of two high molecular mass isoforms of peanut seed oleosin encoded by cDNAs of equal sizes.
Oleosins are small plant proteins characterized by a long hydrophobic core flanked by amphipathic N- and C-terminal domains, which act as emulsifiers for the storage of lipids in seeds. They have been sequenced in a number of oilseeds important for the food industry but not in peanuts. We purified the major isoform of peanut oleosin by preparative electrophoresis with continuous elution, in sufficient amounts to raise specific antibodies, perform circular dichroism and N-sequence tryptic fragments. The structure of the purified oleosin was dominated by alpha-helix that may be assigned to the SDS-resistant central hydrophobic stretch. A two-step RT-PCR strategy was developed to determine the cDNA sequence of this oleosin. Two cDNA variants of equal sizes encoding for isoforms of 176 amino acids each were identified. The isoforms differed by seven amino acids mainly located in the N- and C-terminal domains. The corresponding mRNAs were estimated at 0.9 kb by Northern blot and were transcribed from genes without introns. Immunoprecipitation of the in vitro-translated peanut oleosin labeled with [14C]leucine or [35S]methionine produced the full-length protein (17 kDa) and a 6-kDa peptide corresponding to the N/C-terminal domains. This peptide was able to form SDS-PAGE stable oligomers by interacting with the full-length protein. A similar peptide was released after [125I]iodination of the purified oleosin that generated intermediate-sized oligomers also visible by Western blot on a crude oleosin extract. Oligomers reflect the natural ability of oleosins to strongly interact with each other via not only their central domains but also their N- and C-terminal domains.


Electron Spin Relaxation of Tb3+ and Tm3+ Ions.
Electron spin relaxation times T1 and Tm of Tb3+ and Tm3+ in 1:1 water:ethanol and of Tb3+ doped (2%) in crystalline La2(oxalate)3 decahydrate were measured between about 4.2 and 10 K. Both cations are non-Kramers ions and have J = 6 ground states. Echo-detected spectra are compared with CW spectra and with field-stepped direct-detected EPR spectra. Due to the strong temperature dependence of T1, measurements were not made above 10 K. Between about 4.2 and 6 K T1 is strongly concentration dependent between 1 and ~50 mM. T1 values at 4.2 K are in the μs range which is orders of magnitude faster than for 3d transition metals. Phase memory times, Tm, are less than 500 ns, which is short relative to values observed for 3d transition metals and organic radicals at 4 K. Tm is longer in the oxalate lattice which is attributed to the lower proton concentration in oxalate than in the organic solvent, which decreases nuclear spin diffusion. The rigidity of the crystalline lattice also may contribute to longer Tm.


The vibration perception threshold in gastrectomized patients with low serum B12. A clinical and biothesiometric follow-up after intensive B12 therapy.
In 42 gastrectomized patients with low serum B12 the vibration perception threshold (VPT) was significantly elevated as compared with a control group. Forty patients were followed up after 6-12 months of intensive vitamin B12 therapy. Within an adequately treated group (25 patients) remission of symptoms and signs of peripheral neuropathy was observed, including a statistically significant reduction of the VPT measured on the medial malleolus and big toe. Such a reduction was not observed in the adequately treated group of patients with myclopathy. Findings in the inadequately treated group were less definite, both as regards remission of clinical findings and VPT. In four untreated patients the neurological symptoms and signs progressed during the follow-up period. On the basis of these findings intensive and long-lasting treatment with vitamin B12 is recommended for gastrectomized patients showing signs of neuropathy.


Clinical, sociodemographic profile and stressors in patients with conversion disorders: An exploratory study from southern India.
Patients present with "conversion disorder" as a response to any underlying stressful situation. It is clinically important to evaluate the presence, type, and temporal relation of the stressors, resulting in conversion. Further, knowing the sociodemographic and psychological profile of the conversion patient helps in better management. The aim of the study was to study the clinical presentations, sociodemographic characteristics, and underlying stressors associated with conversion disorder. Fifty patients admitted to the Department of Psychiatry, NRI Medical College and Hospital, Guntur, Andhra Pradesh, from January 2013 to December 2014, who fulfilled the inclusion criteria of the study were evaluated for sociodemographic characteristics, clinical presentations, and stressor on a semi-structured pro forma. Majority of the patients with conversion symptoms were children and young adults (74.0%), females (62.0%), students (46.0%), married (54.0%), and those from nuclear families (78.0%) and rural background (62.0%). Socioeconomic status wise, majority (66.0%) of the patients belonged to middle class. Majority of the patients (92.0%) had a recognizable precipitating factor, of which family-related/marital (36.0%) and education/school-related (18.0%) problems accounted for the major types. Purely motor symptoms were the predominant presentation (84.0%) with unresponsiveness/syncopal attack and pseudo seizure being the commonest. Conversion disorders are commonly seen in females, children and young adults, students, and in those belonged to middle class in socioeconomic status and rural areas. They are mostly preceded by identifiable psychosocial stressors.


Use of the Diels-Alder adduct of pyrrole in organic synthesis. Formal racemic synthesis of Tamiflu.
A new synthetic route to Tamiflu was developed via the Diels-Alder reaction of pyrrole and bromoacetylene.


Lack of effects of low frequency repetitive transcranial magnetic stimulation on alpha rhythm phase synchronization in migraine patients.
The study aimed to test the modulation induced by 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) of the occipital cortex on the alpha phase synchronization under repetitive flash stimuli in 15 migraine without aura patients compared to 10 controls. The EEG was recorded by 7 channels, while flash stimuli were delivered at 9, 18, 21 and 24 Hz in basal, rTMS (15 min of 1 Hz stimulation of the occipital cortex) and sham conditions. Migraine patients displayed increased alpha-band phase synchronization under visual stimulation, while an overall desynchronizing effect was evident in controls. The rTMS resulted in a slight increase of synchronization index in migraine patients, which did not cause significant differences in respect to the basal and sham conditions. The synchronizing-desynchronizing changes of alpha rhythm under repetitive flash stimulation, seem independent from the state of occipital cortex excitability. Other mechanisms beyond cortical excitability may contribute to explain migraine pathogenesis.


Influence of particle characteristics, heating temperature and time on the pyrolysis product distributions of polystyrene micro- and nano-plastics.
Pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) has been widely used for the detection of micro- and nanoplastics (MNPs) in the environment. However, there is a lack of thorough investigation on the effects of pyrolysis temperature and time, as well as the particle source, size and mass of MNPs on the pyrolysis efficiency and pyrolysis product distribution of MNPs. Herein, taking the common plastics polystyrene (PS) as a model, we systematically evaluated the influences of the above factors on the pyrolysis of PS MNPs. Results showed that pyrolysis temperature and time significantly affect the pyrolysis efficiency. By measuring the relative response values of the indicator compound styrene trimers to styrene monomer, the optimum condition was determined as the temperature of 510 ℃ and pyrolysis time longer than 18 s. Meanwhile, the mass of MNPs also affected the distribution of PS pyrolysis products. The proportions of styrene dimers and trimers increased slightly with PS MNP mass, while the source, particle size of MNPs have little effect on the pyrolysis product distribution. This work proposed a suitable pyrolysis temperature and time for the determination of PS by Py-GC/MS, which would contribute to the accurate analysis of PS MNPs in the environment.


Thiazolidinedione: A Privileged Scaffold for the Development of Anticancer Agents.
Thiazolidinedione, an important heterocyclic ring system, is a pharmacophore and a privileged scaffold in medicinal chemistry. Researchers have shown its potential application as a backbone for inhibitors, as it is involved in anticancer development strategies, cancer progression and metastasis. In this paper, the anticancer activities of thiazolidinedione derivatives were reviewed for the first time with respect to different substituents and their positions. This work may imitate a stirring wheel to guide further advanced development of new anticancer molecules with high efficacy.


Regional environmental controllers influence continental scale soil carbon stocks and future carbon dynamics.
Understanding the influence of environmental factors on soil organic carbon (SOC) is critical for quantifying and reducing the uncertainty in carbon climate feedback projections under changing environmental conditions. We explored the effect of climatic variables, land cover types, topographic attributes, soil types and bedrock geology on SOC stocks of top 1 m depth across conterminous United States (US) ecoregions. Using 4559 soil profile observations and high-resolution data of environmental factors, we identified dominant environmental controllers of SOC stocks in 21 US ecoregions using geographically weighted regression. We used projected climatic data of SSP126 and SSP585 scenarios from GFDL-ESM 4 Earth System Model of Coupled Model Intercomparison Project phase 6 to predict SOC stock changes across continental US between 2030 and 2100. Both baseline and predicted changes in SOC stocks were compared with SOC stocks represented in GFDL-ESM4 projections. Among 56 environmental predictors, we found 12 as dominant controllers across all ecoregions. The adjusted geospatial model with the 12 environmental controllers showed an R2 of 0.48 in testing dataset. Higher precipitation and lower temperatures were associated with higher levels of SOC stocks in majority of ecoregions. Changes in land cover types (vegetation properties) was important in drier ecosystem as North American deserts, whereas soil types and topography were more important in American prairies. Wetlands of the Everglades was highly sensitive to projected temperature changes. The SOC stocks did not change under SSP126 until 2100, however SOC stocks decreased up to 21% under SSP585. Our results, based on environmental controllers of SOC stocks, help to predict impacts of changing environmental conditions on SOC stocks more reliably and may reduce uncertainties found in both, geospatial and Earth System Models. In addition, the description of different environmental controllers for US ecoregions can help to describe the scope and importance of global and local models.


Distal renal tubular acidosis in children with chronic hydronephrosis.
The difference between the PCO2 of alkalinized urine and the PCO2 of blood has been proposed as an indirect means of assessing distal nephron H+ secretion. Following oral bicarbonate loading and alkalinization of the urine to pH greater than or equal to 7.2, eight of nine children with chronic hydronephrosis and four children with idiopathic distal RTA had low (U-B)PCO2 values when compared with seven normal subjects. This findings leads us to conclude that chronic hydronephrosis may cause a form of distal RTA which persists many years after surgical diversion procedures have been carried out.


Use and Outcomes of Hepatitis B Virus-Positive Grafts for Kidney or Heart Transplantation in the United States From 1999 to 2021.
The gap between demand and supply for solid organ transplants requires strategies to expand the donor pool. Successful use of hepatitis B virus (HBV)-positive grafts has been reported in liver transplantation. In this United Network for Organ Sharing database (January 1999 to June 2021) retrospective cohort study, outcomes of kidney transplant (KT) or heart transplant (HT) recipients with HBV donor grafts (hepatitis B surface antigen and/or for HBV nucleic acid test-positive) were examined. Propensity score matching was performed for HBV-positive to negative graft recipients (1:5 for renal transplantation and 1:10 for HT). Of 448 HBV-positive donors with 896 kidneys, 352 kidneys (39.3%) and 56 hearts (12.5%) were transplanted. Of these, 312 kidneys (88.6%) and 45 hearts (80.3%) were transplanted in hepatitis B surface antigen-negative recipients. Ten-year graft survival was 47.1% and 49% (log-rank P = 0.353), and patient survival was 58% and 59% (P = 0.999) for KT recipients. Similar figures among HT recipients were 41.9% and 38.9% for graft survival (P = 0.471), and 54.3% and 61.2% for patient survival (P = 0.277). Subgroup analyses in recipients with HBV nucleic acid test-positive grafts irrespective of antibodies to HBV core antigen-positive status, and recipients negative for anti-HBs (548 renal transplantation and 209 HT) were similar. Although we are limited by lack of available data on posttransplant anti-HBV treatment, the study observations suggest that using HBV-positive grafts is a reasonable strategy to expand the donor pool among candidates waiting for KT or HT.


Preservative chemicals as a new health risk related to traditional medicine markets in western Africa.
Health risks associated to the use of tropical wildlife have so far been envisioned through the lens of zoonotic pathogens spread by the bushmeat trade, putting aside the equally vibrant network of traditional medicine markets (TMMs). We collected information on the preservative techniques used for animal body parts from TMMs in Benin through a semi-structured questionnaire addressed to 45 sellers. We show that a recent shift from traditional preservative techniques using harmless treatments towards modern techniques -involving the recurrent use of hazardous chemicals (such as Sniper)- is likely to pose a serious health risk to practitioners and consumers of animal parts from TMMs in Benin. We conclude that the non-regulation of the TMM activities represents a critical risk to both biodiversity conservation and human health in western Africa.


Detection, quantification and confirmation of anabolic steroids in equine plasma by liquid chromatography and tandem mass spectrometry.
Anabolic androgenic steroids are related to the male sex hormones and are abused in equine sports. In an effort to deter the abuse of anabolic steroids, a sensitive LC-MS/MS method was developed for detection, quantification and confirmation of eight major anabolic steroids (testosterone, normethandrolone, nandrolone, boldenone, methandrostenolone, tetrahydrogestrinone (THG), trenbolone, and stanozolol) in equine plasma. Formation of solvent adduct ions of the analytes was observed under electrospray ionization (ESI) conditions, and desolvation of the solvent adduct ions by source collision-induced decomposition (CID) increased the abundance of the [M+H]+ ions as well as the multiple-reaction monitoring (MRM) signals. ESI (+) and APCI (+) were compared with respect to sensitivity for the analytes and the former provided better sensitivity. The matrix effect on ion suppression or enhancement was evaluated, and was negligible. Confirmation of the analytes was performed using criteria of three ion transitions and LC retention time of each analyte. The limit of detection (LOD) and quantification (LOQ) was 25 pg/mL. The limit of confirmation (LOC) was 25 pg/mL for boldenone; 50 pg/mL for normethandrolone, nandrolone, and methandrostenolone; and 100 pg/mL for testosterone, THG, trenbolone, and stanozolol. The analytes were evaluated for stability and found to be stable in plasma for 24h at room temperature, 13 days at 4 degrees C, and 34 days at -20 and -70 degrees C. The method was successfully applied to analyses of equine plasma samples for pharmacokinetics study. This method is sensitive and useful for detection, quantification and confirmation of these anabolic steroids in equine plasma.


Clinical benefit of surveillance after resection of pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
The value of routine surveillance after resection of pancreatic ductal adenocarcinoma (PDAC) is unclear, and expert guidelines offer conflicting recommendations. This study is a systematic review of evidence for surveillance programs. A systematic review of studies evaluating different surveillance methods was undertaken. A meta-analysis was performed for those studies reporting rates of asymptomatic recurrence, treatment of recurrence and overall survival, according to different surveillance methods. Ten studies were included in the literature review, with five studies appropriate for meta-analysis (1596 patients). Patients within active surveillance programs were more likely to have recurrence detected at an asymptomatic stage (Pooled Rate: 49.3% vs. 19.1%, p = 0.043). Within studies reporting these outcomes, patients with asymptomatic recurrence were more likely to receive treatment for recurrence (Odds Ratio 3.49; 95% CI: 1.73-7.07; p < 0.001) and had longer overall survival (Mean Difference: 9.5 months; 95% CI: 4.1-14.8; p < 0.001) than those with symptoms at time of recurrence. Routine surveillance after surgery for PDAC appears to detect more patients at an asymptomatic stage. Data from these non-randomised trials also suggest that treatment rates and survival may be superior in patients were recurrence is detected when asymptomatic. As such, these data suggest that routine surveillance may improve patient outcomes, although an appropriately conducted trial would be required to address concerns that various sources of bias may be affecting these results.


Low back pain and comorbidity clusters at 17 years of age: a cross-sectional examination of health-related quality of life and specific low back pain impacts.
Comorbidities in adults negatively affect the course of low back pain (LBP). Little is known of the presence and/or impact of LBP comorbidities in adolescents. Subjects from the Raine Study cohort at age 17 years (n = 1,391) provided self-report of diagnosed medical conditions/health complaints, health-related quality of life (36-Item Short Form Health Survey [SF-36]), lifetime experience of LBP, and specific LBP impacts (taking medication, missing school/work, interference with normal/physical activities). Latent class analysis was used to estimate clusters of comorbidities based on diagnosed disorders. Profiles of SF-36 and impact were examined between clusters. Four distinct comorbidity clusters were identified: cluster 1: Low probability of diagnosed LBP or any other medical condition (79.7%); cluster 2: High probability of diagnosed LBP and neck/shoulder pain, but a low probability of other diagnosed health conditions (9.6%); cluster 3: Moderate probability of diagnosed LBP and high probability of diagnosed anxiety and depression (6.9%); cluster 4: Moderate probability of diagnosed LBP and high probability of diagnosed behavioral and attention disorders (3.8%). The clusters had different SF-36 and LBP impact profiles, with clusters 3 and 4 having poorer SF-36 scores, and clusters 2 to 4 having greater risk for specific LBP impacts, than cluster 1. Identified comorbidity clusters support adolescent and adult studies reporting associations between LBP, other pain areas, psychological disorders, and disability. Tracking these clusters into adulthood may provide insight into health care utilization in later life, whereas identification of these individuals early in the life span may help optimize intervention opportunities.


Effects of chronic exposure to low doses of Δ9- tetrahydrocannabinol in adolescence and adulthood on serotonin/norepinephrine neurotransmission and emotional behaviors.
Chronic exposure to the Δ9-tetrahydrocannabinol (THC), the main cannabis pharmacological component, during adolescence has been shown to be associated with an increased risk of depression and suicidality in humans. Little is known about the impact of the long-term effects of chronic exposure to low doses of THC in adolescent compared to adult rodents. THC (1mg/kg i.p., once a day) or vehicle was administered for 20 days in both adolescent (post-natal day, PND 30-50) and young adult rats (PND 50-70). After a long washout period (20 days), several behavioral paradigms and electrophysiological recordings of serotonin (5-HT) and norepinephrine (NE) neurons were carried out. Adolescent THC exposure resulted in depressive lbehaviors: a significant decrease in latency to first immobility in the forced swim test, increased anhedonia in the sucrose preference test. Decrease entries in the open arm were observed in the elevated plus maze after adolescent and adult exposure, indicating anxiousphenotype. A significant reduction in dorsal raphe serotonergic neural activity without changing locus coeruleus noradrenergic neural activity was found in THC adolescent and adult exposure. Altogether, these findings suggest that low doses of chronic THC exposure during the developmental period and adulthood could result in increased vulnerability of the 5-HT system and anxiety symptoms; however, depressive phenotypes occur only after adolescent, but not adult exposure, underscoring the higher vulnerability of young ages to the mental effects of cannabis.


The effect of redox potential on the kinetics of fluorescence induction in pea chloroplasts. I. Removal of the slow phase.
The effect of alteration of redox potential on the kinetics of fluorescence induction in pea chloroplasts has been investigated. Potentiometric titration of the initial (Fi) level of fluorescence recorded upon shutter opening gave a two component curve, with Em(*7) at -20 mV and -275 mV, almost, identical to results obtained using continuous low intensity illumination (Horton, P. and Croze, E. (1979) Biochim. Biophys. Acta 545, 188--201). The slow or tail phase of induction observed in the presence of DCMU can be eliminated by poising the redox potential at approx. 0 to +50 mV. At this potential Fi was increased by less than 10% and the higher potential quencher described above was only marginally reduced. The disappearance of the slow phase titrated as an n = 1 component with an Em(7) of +120 mV. Therefore it seems unlikely that the slow phase of fluorescence induction is due to photoreduction of the -20 mV quencher. These results are discussed with reference to current ideas concerning heterogeneity on the acceptor side of Photosystem II.


[Passage of ceftriaxone in the aqueous humor and tears. Comparison with other beta-lactams].
The intraocular distribution of ceftriaxone (a new cephalosporin of the third generation) was studied in 33 patients undergoing cataract surgery. The mean level of antibiotic in the aqueous humor was of 0,53 micrograms/ml (1.25% of the serum level), in the tears show an average rate of 5.75 micrograms/ml (13% of the serum level) was found. A study of the kinetics in the tears shows increasing levels for the first 18th hours.


Facets of adult attachment style in patients with obsessive-compulsive disorder.
Literature data did not show univocal evidence in discriminating which form of attachment insecurity is involved in obsessive-compulsive disorder (OCD): both anxiety and avoidance was related to OCD symptomatology. No study used the Attachment Style Questionnaire (ASQ) that allows for investigation of differentiated facets of attachment anxiety and of avoidance. We investigated: (1) whether individuals with OCD differed from controls in the facets of attachment security (anxiety and avoidance), (2) which attachment facets predicted a diagnosis of OCD, controlling for socio-demographics and obsessive beliefs, (3) which attachment facets predicted specific OCD symptoms, controlling for socio-demographics and obsessive beliefs. Two hundred seventy participants (135 OCD patients and 135 matched controls) completed the Obsessive-Compulsive Inventory-Revised, Obsessive Beliefs Questionnaire-46 and ASQ. OCD patients reported respectively lower and higher levels on confidence and attachment anxiety than controls. Higher need of approval was the most important predictor of OCD diagnosis beyond the other attachment facets, and even of the obsessive beliefs. Using multivariate generalised linear models, the two facets of attachment anxiety, the need for approval (that predicted higher levels of obsessing and ordering symptoms), and preoccupation with relationships (that predicted higher hoarding symptoms) seemed to explain variance over and above OCD-related beliefs and socio-demographics. Discomfort with closeness contributed to the predictions of ordering symptoms. In conclusion, the interpersonal dynamics related to attachment in OCD patients should be carefully considered during assessment and treatment of OCD patients in clinical practice.


Atomistic modeling of apatite-collagen composites from molecular dynamics simulations extended to hyperspace.
The preparation of atomistic models of apatite-collagen composite mimicking enamel at length scales in the range of 1-10 nanometers is outlined. This bio-composite is characterized by a peculiar interplay of the collagen triplehelix and the apatite crystal structure. Structural coherence is however only obtained after drastic rearrangements, namely the depletion of protein-protein hydrogen bonds and the incorporation of calcium triangles which are stabilized by salt-bridges with the collagen molecule. Starting from an isolated collagen triple helix and a single-crystalline apatite structure, a composite model is obtained by gradually merging the two components via an additional (hyperspace) coordinate. This approach allows smooth structural relaxation of both components whilst avoiding singularities in potential energy due to atomic overlap.


Orally active aminopyridines as inhibitors of tetrameric fructose-1,6-bisphosphatase.
A novel sulfonylureido pyridine series exemplified by compound 19 yielded potent inhibitors of FBPase showing significant glucose reduction and modest glycogen lowering in the acute db/db mouse model for Type-2 diabetes. Our inhibitors occupy the allosteric binding site and also extend into the dyad interface region of tetrameric FBPase.


The effectiveness of an educational intervention to enhance undergraduate nursing students' competence with interprofessional collaboration.
Interprofessional collaboration and teamwork have been identified as priorities for delivering quality client care. Improved teamwork, communication, and collaboration among healthcare professionals improve client outcomes. Nurse professionals are challenged to be equally engaged with other healthcare professionals to develop a culturally competent client-centered plan of care. The purpose of the current project was to examine the effectiveness of a multifaceted educational intervention on prelicensure nursing students' development of interprofessional competencies with teams and teamwork, communication, roles and responsibility, values, and ethics. Metrics used included the Interprofessional Collaboration Competency Attainment (ICCAS) and the Assessment of Collaborative Environments (ACE-15) surveys. The results support practical and statistical significance in the students' self-reported collaborative competence across all items of the ICCAS at p < 0.000 level, and across each individual item. The multifaceted educational strategy effectively engaged prelicensure nursing students with other healthcare disciplines to develop a client-centered plan of care and achieve interprofessional competencies.


Direct analysis in real time-mass spectrometry for the rapid detection of metabolites of aconite alkaloids in intestinal bacteria.
In the present work, direct analysis of real time ionization combined with multi-stage tandem mass spectrometry (DART-MS(n)) was used to investigate the metabolic profile of aconite alkaloids in rat intestinal bacteria. A total of 36 metabolites from three aconite alkaloids were identified by using DART-MS(n), and the feasibility of quantitative analysis of these analytes was examined. Key parameters of the DART ion source, such as helium gas temperature and pressure, the source-to-MS distance, and the speed of the autosampler, were optimized to achieve high sensitivity, enhance reproducibility, and reduce the occurrence of fragmentation. The instrument analysis time for one sample can be less than 10 s for this method. Compared with ESI-MS and UPLC-MS, the DART-MS is more efficient for directly detecting metabolic samples, and has the advantage of being a simple, high-speed, high-throughput method.


Trace anesthetic exposure. Consequences and control.
Epidemiologic and animal studies indicate that chronic exposure to anesthetic gases may consitute a potential health hazard. This is suggested by a higher incidence of spontaneous abortion among female operating room personnel, congenital anomalies in the offspring of operating room personnel, and neoplasia of the reticuloendothelial system. Human data show that performance can be compromised during exposure to anesthetic traces. A direct cause and effect relationship between anesthetic exposure and the alleged hazards will require further prospective studies. Such a study is being planned by the Ad Hoc Committee of the American Society of Anesthesiologists. In the interim, monitoring programs should be established to define adequate clearances of the anesthetic agents. Minimum standards and recommended procedures should be established regarding operating room ventilation and design. The use of effective scavengers and anesthetic techniques not requiring the use of inhalational agents should be encouraged. In this way a clear distinction may be defined by the prosepective study planned by the American Society of Anesthesiologists in 1978.


Innate lymphoid cell composition associates with COVID-19 disease severity.
The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unknown. Understanding the immune response in COVID-19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID-19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID-19. Blood samples collected from moderately (n = 11) and severely ill (n = 12) COVID-19 patients, as well as healthy control donors (n = 16), were analysed with 18-parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID-19 patients, and serum biomarkers were analysed with multiplex immunoassays. Innate lymphoid cells were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID-19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID-19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. This study provides insights into the potential role of ILCs in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.


Comparison of long-term effect of thymoglobulin treatment in patients with a high risk of delayed graft function.
T-lymphocyte depletion is a strategy to reverse the impact of ischemia-reperfusion injury (IRI) in progression to chronic allograft dysfunction, especially among patients at high risk for delayed graft function (DGF). The present work assessed the effect of thymoglobulin among a population with a high incidence of DGF. We analyzed 209 transplanted patients: 97 in the thymoglobulin and 112 in the control group. The main complication was DGF (59.3%), with a similar incidence in both groups (63.9% vs. 55.3%; P = .36). Acute rejection episodes (ARE) were decreased with thymoglobulin (8.2% vs. 28.5%; P < .001), but cytomegalovirus viremia was 3.4-fold more frequent (58.3% vs. 17.1%; P < .001). One-year graft function was significantly better in the thymoglobulin group (59.2 ± 17.2 vs. 51.8 ± 15.3 mL/min; P = .004), even when censored by ARE (59.7 ± 17.5 vs. 53.3 ± 14.4; P = .023). The same difference was observed at the 2-year follow-up (P = .024), even when censored for ARE (P = .045). A multivariate analysis showed thymoglobulin to be a factor strongly associated with protection of graft function (P = .039). Despite not reducing the incidence of DGF, thymoglobulin induction significantly reduced the incidence of ARE and showed a long-term profile of protection of renal graft function, independent of the reduction in ARE.


Genome-wide characterization of peptidyl-prolyl cis-trans isomerases in Penicillium and their regulation by salt stress in a halotolerant P. oxalicum.
Peptidyl-prolyl cis-trans isomerases (PPIases) are the only class of enzymes capable of cis-trans isomerization of the prolyl peptide bond. The PPIases, comprising of different families viz., cyclophilins, FK506-binding proteins (FKBPs), parvulins and protein phosphatase 2A phosphatase activators (PTPAs), play essential roles in different cellular processes. Though PPIase gene families have been characterized in different organisms, information regarding these proteins is lacking in Penicillium species, which are commercially an important fungi group. In this study, we carried out genome-wide analysis of PPIases in different Penicillium spp. and investigated their regulation by salt stress in a halotolerant strain of Penicillium oxalicum. These analyses revealed that the number of genes encoding cyclophilins, FKBPs, parvulins and PTPAs in Penicillium spp. varies between 7-11, 2-5, 1-2, and 1-2, respectively. The halotolerant P. oxalicum depicted significant enhancement in the mycelial PPIase activity in the presence of 15% NaCl, thus, highlighting the role of these enzymes in salt stress adaptation. The stress-induced increase in PPIase activity at 4 and 10 DAI in P. oxalicum was associated with higher expression of PoxCYP18. Characterization of PPIases in Penicillium spp. will provide an important database for understanding their cellular functions and might facilitate their applications in industrial processes through biotechnological interventions.