Pressor responses to distension of the ureter in anaesthetised rats: characterisation of a model of acute visceral pain.
We have characterised pressor responses to stimulation of the ureter in anaesthetised rats (n = 20) as a model of acute visceral pain. The left ureter was cannulated close to the bladder and graded stimuli applied (5-90 mmHg, 30 s). The threshold was approximately 25 mmHg. Suprathreshold pressures evoked responses proportional to the stimulus intensity, which were little altered when stimulation of the kidney was prevented by ligation of the ureteric-pelvic junction. The stimulus response curve was dose-dependently attenuated by morphine (1-3 mg kg-1 i.v.), in a naloxone reversible manner. The characteristics of the responses observed correlate well with pain sensation in man and with the properties of ureteric primary afferent neurones in animals.


Quantitative Validation of MRI-Based Motion Estimation for Brain Impact Biomechanics.
Head impact can cause traumatic brain injury (TBI) through axonal overstretch or subsequent inflammation and understanding the biomechanics of the impact event is useful for TBI prevention research. Tagged magnetic resonance imaging (MRI) acquired during a mild-acceleration impact has enabled measurement and visualization of brain deformation in vivo. However, measurements using MRI are subject to error, and having independent validation while imaging in vivo is very difficult. Thus, characterizing the accuracy of these measurements needs to be done in a separate experiment using a phantom where a gold standard is available. This study describes a method for error quantification using a calibration phantom compatible with MRI and high-speed video (the gold standard). During linear acceleration, the maximum shear strain (MSS) in the phantom ranged from 0 to 12%, which is similar to in vivo brain deformation at a similar acceleration. The mean displacement error against video was 0.3±0.3 mm, and the MSS error was 1.4±0.3%. To match resolutions, video data was filtered temporally using an averaging filter. Compared to the unfiltered results, resolution matching improved the agreement between MRI and video results by 15%. In conclusion, tagged MRI analysis compares well to video data provided that resolutions are matched-a finding that is also applicable when using MRI to validate simulations.


Intra-oral trigeminal-mediated sensations influencing taste perception: A systematic review.
Food perception is a multimodal sensation which implies cross-modal interplays. Tactile, thermal, painful and kinaesthetic stimuli arising from food intake may impact on flavour perception, especially taste perception. The influence of oral somatosensory signals on food taste perception remains unclear. The aim of the present systematic review was to appraise the effects of oral mechanical, thermal, chemical and pain sensations on taste perception. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a search of the literature from 1968 to 2018 was conducted using MEDLINE via PubMed, EMBASE and clinical trials (PROSPERO registration reference: CRD42018100176). A total of 105 articles were included for analysis. The results from this review suggest that taste abilities and taste perception are frequently modified by food textural and chemical properties. Furthermore, saliva features, dental and prosthetic status and oral pain can also modulate taste perception. Biological and physiological phenomena underlying these results may be involved such as tastant release, tastant detection, taste transduction and central trigemino-gustatory interplays.


In vitro skin permeation of potassium hexachloroplatinate and a comparison with potassium tetrachloroplatinate.
Halogenated platinum salts are known respiratory sensitizers in the workplace, and occupational exposure to platinum via the respiratory system and skin has been reported. The aim of this study was to compare the permeability and skin retention of potassium hexachloroplatinate to previously published data of potassium tetrachloroplatinate. Experiments were performed using female Caucasian skin and Franz diffusion cells with the application of 0.3 mg Pt/mL in the donor solution for 24-h. After 8-h of exposure, 1.87 ng/cm2 of Pt was detected in the receptor solution with exposure to potassium hexachloroplatinate, whereas 0.47 ng/cm2 was detected with exposure to potassium tetrachloroplatinate. After 24-h of exposure the Pt retention in the skin was 1861.60 ng/cm2 and 1486.32 ng/cm2 with exposure to potassium hexa- and tetrachloroplatinate respectively. The faster rate of Pt permeation from exposure to potassium hexachloroplatinate was confirmed by the flux and permeability coefficient values. The results indicate a higher permeability and skin retention of Pt when exposed to potassium hexachloroplatinate, confirming a higher risk associated with occupational exposure to this platinum compound relative to potassium tetrachloroplatinate.


Efficacy of focused radiofrequency with ultrasound in body contouring: A study of 64 patients.
Energy-based devices are increasingly used for noninvasive body contouring. Our aim was to investigate the clinical efficacy of combined radiofrequency and ultrasound device for reduction in body circumference in various body parts. The aim of our study was to investigate the clinical efficacy of combined focused radiofrequency and ultrasound device for reduction in body circumference in various body parts. We aimed to report objective measurements in terms of circumference reduction and patient satisfaction scores. We retrospectively analyzed data of 64 patients who were treated with focused radiofrequency and ultrasound device during August 2017-December 2019. All patients had received 4 sessions at one-week interval. Body circumference measurements were done before treatment and one month after the last session. Patients were also asked to score their satisfaction with the result of treatment on a scale of 1 to 5. Abdomen was treated in 40 patients, thighs in 18 patients, and arms in 7 patients. One patient had received treatments to both abdomen and thighs. Circumference measurements in all body parts differed significantly between baseline and one month after the 4th session. Patients were satisfied with the result of treatment (score: 4.48 ± 0.66). No adverse events were noted. Focused radiofrequency and ultrasound combination is a safe and effective treatment modality for body contouring. Patients should be informed about moderate degrees of improvement.


3,3,6,6-Tetra-methyl-9-[6-(3,3,6,6-tetra-methyl-1,8-dioxo-2,3,4,5,6,7,8,9-octa-hydro-1H-xanthen-9-yl)pyridin-2-yl]-2,3,4,5,6,7,8,9-octa-hydro-1H-xanthene-1,8-dione.
In the title mol-ecule, C(39)H(45)NO(6), the two tetra-methyl-octa-hydroxanthen-1,8-dione substituents are arranged approximately parallel to each other and approximately perpendicular to the plane of the pyridine ring. The six-membered xanthene rings adopt flattened boat conformations with the O and methine C atoms deviating from the plane of the other four atoms.


Modulation of trehalase activity in Saccharomyces cerevisiae by an intrinsic protein.
The regulation of cytosolic trehalase activity in yeast has been described as cycles of activation by phosphorylation by cAMP protein kinase. In this paper, evidence is presented for another regulatory mechanism--the binding of an endogenous inhibitory protein. This negative modulator was isolated during the purification procedure of cytosolic cryptic trehalase from repressed wild-type cells of Saccharomyces cerevisiae. However, in derepressed cells the inhibitor was not found nor was it present in ras2 mutant cells submitted to a heat treatment. The trehalase inhibitory activity proved to be a calmodulin ligand protein and, therefore, involved in the modulation of trehalase activity by Ca2+ ions.


Muscle sympathetic single-unit response patterns during progressive muscle metaboreflex activation in young healthy adults.
Muscle sympathetic single units can respond differentially to stress, but whether these responses are linked to the degree of sympathoexcitation is unclear. Fifty-three muscle sympathetic single units (microneurography) were recorded in 17 participants (8 women; 24 ± 3 yr). Five 40-s bouts of 10% static handgrip were performed during a 10-min forearm ischemia to progressively increase metabolite accumulation. Each static handgrip was separated by a 75-s ischemic rest [postexercise circulatory occlusion (PECO)] to assess the isolated action of the muscle metaboreflex. During each set of PECO, individual single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. From sets 1-5 of PECO, the proportion of single units with activated (34, 45, 68, 87, and 89%), nonresponsive (43, 44, 23, 7, and 9%), or inhibited (23, 11, 9, 6, and 2%) responses changed (P < 0.001) as total muscle sympathoexcitation increased. A total of 51/53 (96%) single units were activated in at least one set of PECO, 16 (31%) initially inhibited before activation. This response pattern delayed the activation onset compared with noninhibited units (set 3 ± 1 vs. 2 ± 1, P < 0.001). Once activated, the spike-frequency rate of rise was similar (8.5 ± 6.5 vs. 7.1 ± 6.0 spikes/min per set, P = 0.48). Muscle sympathetic single-unit firing demonstrated differential control during muscle metaboreflex activation. Single units that were initially inhibited during progressive metaboreflex activation were capable of being activated in later sets. These findings reveal that single-unit activity is influenced by convergent neural inputs (i.e., both inhibitory and excitatory), which yield heterogenous single-unit activation thresholds.NEW & NOTEWORTHY Muscle sympathetic single units respond differentially to sympathoexcitatory stress such that single units can increase firing to contribute to the sympathoexcitatory response or can be nonresponsive or even inhibited. We observed a subgroup of single units that can respond bidirectionally, being first inhibited before activated by progressive increases in forearm muscle metaboreflex activation. These results suggest convergent neural inputs (i.e., inhibitory and excitatory), which yield heterogenous muscle sympathetic single-unit activation thresholds.


Physiological and biochemical effects of Ti3AlC2 nanosheets on rice (Oryza sativa L.).
MAX phase materials are a new type of nanomaterial with wide applications, but the potential effects of MAX phase materials on plants have not been reported. Herein, we selected Ti3AlC2 nanosheets as a typical MAX phase material to investigate its potential impacts on rice (Oryza sativa L.) at 0-1000 μg·mL-1. The foliar application of Ti3AlC2 at 100 and 1000 μg·mL-1 inhibited the growth of rice seedlings by producing excess reactive oxygen species (ROS). Furthermore, foliar spraying of Ti3AlC2 at 100 μg·mL-1 decreased the stomatal aperture (78.6%) and increased the number of trichomes (100%). These responses demonstrated that the application of Ti3AlC2 could interfere with the immune system of plants by changing the structure and function of leaves, disturbing the activities of antioxidant enzymes. According to the above results, we concluded that the toxicity of Ti3AlC2 nanosheets on plants was mainly caused by the release of titanium ions. This study provides a valuable reference for understanding the impact of MAX phase materials on plants.


Alternative splicing of TGF-betas and their high-affinity receptors T beta RI, T beta RII and T beta RIII (betaglycan) reveal new variants in human prostatic cells.
The transforming growth factors (TGF)-beta, TGF-beta1, TGF-beta2 and TGF-beta 3, and their receptors [T beta RI, T beta RII, T beta R III (betaglycan)] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants T beta RIB, T beta RIIB and TGF-beta 2B in human prostatic cells. Interestingly, a novel human receptor transcript T beta RIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant T beta RIB with four additional amino acids was identified also in human. Expression of the variant T beta RIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of T beta RIIC and TGF-beta 2B mainly in the epithelial cells with a preferential localization of TGF-beta 2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-beta ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-beta2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1) with a major participation of T beta RII. In general, expression of the splice variants was more heterogeneous in contrast to the well-known isoforms. The identification of the splice variants T beta RIB and the novel isoform T beta RIIC in man clearly contributes to the growing complexity of the TGF-beta family.


Dorsal approach to scaphoid nonunion.
The surgical approach for treatment of scaphoid nonunion usually involves various combinations of screws and Kirschner wires, with or without bone grafts. This article reports our results with 36 dorsal-approach bone grafting procedures for treatment of scaphoid nonunion with Kirschner wires. Union was achieved in 89%. The average follow-up was 5 years. Flexion/extension averaged 76% of the opposite wrist, and grip strength was 88% of the opposite hand. Ninety-one percent of the employed patients returned to their original jobs. The dorsal approach provides satisfactory exposure for fragment reduction and bone grafting.


The Burden of Agoraphobia in Worsening Quality of Life in a Community Survey in Italy.
Current nosology redefined agoraphobia as an autonomous diagnosis distinct from panic disorder. We investigated the lifetime prevalence of agoraphobia, its association with other mental disorders, and its impact on the health-related quality of life (HR-QoL). Community survey in 2,338 randomly selected adult subjects. Participants were interviewed with the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS), administered by clinicians. The diagnoses were based on the ICD-10 criteria. The Short-Form Health Survey (SF-12) was used to quantify HR-QoL. In the sample, 35 subjects met the criteria for agoraphobia (1.5%), with greater prevalence among women (2.0%) than men (0.9%): odds ratio (OR) 2.23; 95% CI: 1.0-5-2. Agoraphobia was more often seen among those with (n=26; 1.1%) than without (n=9; 0.4%) panic disorder: OR=8.3; 2.9-24.4. Co-morbidity with other mental disorders was substantial. The mean score of SF-12 in people with agoraphobia was 35.2±7.8, with similar levels of HR-QoL in people with (35.3±7.9) or without (34.8±7.3) panic disorder: ANOVA: F(1;33)=0.0; p=1.00. One out of seventy people may suffer from agoraphobia in their lifetime. The attributable burden in terms of HR-QoL is substantial and comparable to the one observed for chronic mental disorders such as major depression, post-traumatic stress disorder, or obsessive-compulsive disorder.


Quantitative dual-energy CT for evaluating hepatocellular carcinoma after transarterial chemoembolization.
We aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal-Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.


The growth of the dendritic trees of Purkinje cells in irradiated agranular cerebellar cortex.
The heads of noenatal Wistar rats were irradiated with 200 rads daily from birth to the 10th day post-partum. Ten litters each containing 5 animals were killed at 30 days post-partum and their brains treated by the Golgi-Cox technique. The dendritic trees of 24 Purkinje cells were analysed using the quantitative technique of network analysis, and comparisons made between parameters obtained from 20 normal Purkinje cells. All dendritic trees in agranular irradiated cortex were markedly reduced in size (as indicated by total dendritic length and total number of segments) although mean path lengths were normal. Segment lengths were normal over proximal branches, but uniformly increased over distal branches. Abnormal appendages, called 'giant spines' were observed on many dendrites. They were often some 10 mum in length and their presence effectively reduced segment lengths, increased the frequency of trichotomy and deviated growth from the normal random terminal pattern so that long collateral branching topologies were formed. Nevertheless, trichotomy was uniformly reduced in those trees without 'giant spines' and the distribution of branching patterns suggested that growth had proceeded by random terminal dichotomy. These results demonstrate that the development of dendritic trees is retarded in the agranular irradiated cerebellum, where synaptogenesis is very greatly reduced below normal. The quantitative changes in segment lengths, size of trees, and trichotomy accord with those predicted by the filopodial synaptogenic hypothesis of dendritic growth formulated by Vaughn et al. 99, whilst the results of the topological analysis suggest that branching is established by a degree of non-random interaction between growing dendrites and their substrate. 'Claw-like' dendritic complexes within some Purkinje cell trees may have been induced by aberrent fibre bundles of few surviving granule cells.


The design of macromolecular crystallography diffraction experiments.
The measurement of X-ray diffraction data from macromolecular crystals for the purpose of structure determination is the convergence of two processes: the preparation of diffraction-quality crystal samples on the one hand and the construction and optimization of an X-ray beamline and end station on the other. Like sample preparation, a macromolecular crystallography beamline is geared to obtaining the best possible diffraction measurements from crystals provided by the synchrotron user. This paper describes the thoughts behind an experiment that fully exploits both the sample and the beamline and how these map into everyday decisions that users can and should make when visiting a beamline with their most precious crystals.


Ebola Virus IgG Seroprevalence in Southern Mali.
Mali had 2 reported introductions of Ebola virus (EBOV) during the 2013-2016 West Africa epidemic. Previously, no evidence for EBOV circulation was reported in Mali. We performed an EBOV serosurvey study in southern Mali. We found low seroprevalence in the population, indicating local exposure to EBOV or closely related ebola viruses.


Immuno-protective efficiency of feed-based whole-cell inactivated bivalent vaccine against Streptococcus and Aeromonas infections in red hybrid tilapia (Oreochromis niloticus × Oreochromis mossambicus).
Streptococcosis and motile aeromonad septicemia (MAS) are well-known diseases in tilapia culture, which cause mass mortality with significant economic losses. The development of feed-based bivalent vaccines in controlling these diseases has been initiated, however, the mechanisms of immunities and cross-protection in fish remain unclear. This study was conducted to assess the immuno-protective as well as the cross-protective efficacy of a newly developed feed-based bivalent vaccine against Streptococcus and Aeromonas infections in red hybrid tilapia. A total of five groups of fish were vaccinated orally through two different techniques; bivalent vaccine (inactivated Streptococcus iniae and Aeromonas hydrophila) sprayed on feed pellets (BS group); bivalent vaccine (inactivated S. iniae and A. hydrophila) incorporated in feed (BI group); monovalent inactivated S. iniae and A. hydrophila vaccine separately incorporated into feed as monovalent S. iniae (MS group) and monovalent A. hydrophila (MA group); and control group (without vaccine). The feed-based vaccine was delivered orally at 5% of body weight for five consecutive days. The booster doses were given in the same manner on weeks 2 and 6. Serum and skin mucus samples were collected to assess the IgM responses using indirect ELISA. The first administration of the feed-based vaccine stimulated the IgM levels that lasted until week 3, while the second booster ensured that the IgM levels remained high for a period of 16 weeks in the BI, MS and MA groups. The BI group developed a strong and significantly (P < 0.05) higher systemic and mucosal IgM responses against both S. iniae and A. hydrophila and also cross-protective antigen S. agalactiae and A. veronii compared to the BS and control groups. Quantitative real-time PCR results also showed that the relative expressions of IL-8, INF-γ and IgM in the BI immunized fish spleen, head kidney and hindgut exhibited various significant (P < 0.05) rising trends following both the vaccination and the challenge phase. On weeks 10, all fish were challenged through the intraperitoneal route, where relative percent survivals (RPS) of 82.22 ± 3.85% when challenged with S. iniae, 77.78 ± 3.85% when challenged with A. hydrophila and 77.78 ± 3.85% when co-challenged with both S. iniae and A. hydrophila were observed in the BI group, which were significantly higher (P < 0.05) compared to the other groups. The BI group also showed significantly (P < 0.05) higher partial cross-protections following challenges with S. agalactiae (RPS at 60.00 ± 6.67%) and A. veronii (RPS at 57.78 ± 7.70%). This study demonstrated that immunization with feed-based BI vaccine elicited immune responses that were capable of protecting red hybrid tilapia against streptococcosis and MAS.


fRMA ST: frozen robust multiarray analysis for Affymetrix Exon and Gene ST arrays.
Frozen robust multiarray analysis (fRMA) is a single-array preprocessing algorithm that retains the advantages of multiarray algorithms and removes certain batch effects by downweighting probes that have high between-batch residual variance. Here, we extend the fRMA algorithm to two new microarray platforms--Affymetrix Human Exon and Gene 1.0 ST--by modifying the fRMA probe-level model and extending the frma package to work with oligo ExonFeatureSet and GeneFeatureSet objects. All packages are implemented in R. Source code and binaries are freely available through the Bioconductor project. Convenient links to all software and data packages can be found at http://mnmccall.com/software email@example.com.


Clinical features of pneumothorax associated with COVID-19: A retrospective analysis of two centres.
Pneumothorax is a known sequela of coronavirus disease 2019 (COVID-19). However, the clinical features of pneumothorax associated with COVID-19 have not been fully elucidated. Patients who developed pneumothorax within 6 months of being diagnosed with COVID-19 were retrospectively analysed at two institutions. We investigated the background factors, COVID-19 severity and treatment, timing of pneumothorax onset, treatment modalities, treatment duration, and prognosis of these patients. A total of 21 patients were diagnosed with pneumothorax within 6 months of COVID-19 diagnosis. The combined incidence rate of pneumothorax at two institutions was 0.89 %. The mean age of these patients was 72.5 years, and they were predominantly male (90.5 %), with a history of smoking (76.1 %). The most frequent comorbidity was hypertension, followed by type 2 diabetes mellitus, COPD, and malignancy. Approximately 76 % of the patients had moderate or severe disease requiring oxygenation. Moreover, 90.5 % of these patients were taking antiviral drugs; 52.4 %, immunosuppressant agents (baricitinib/tocilizumab); and 66.7 % were on dexamethasone. The median time to the onset of pneumothorax was 15.0 days, and 86 % of cases occurred within 1 month of COVID-19 diagnosis. Bilateral pneumothorax and pneumomediastinum were noted in one patient each. Chest drainage was performed in 71.4 % of the patients. The mean treatment duration for pneumothorax was 14.1 days, and the 30-day mortality rate was 28.6 %. Pneumothorax associated with COVID-19 was more common in patients with moderate or severe disease requiring oxygenation, and occurred within 1 month of COVID-19 diagnosis. Pneumothorax associated with COVID-19 is a serious complication with a high mortality rate and clinicians should pay attention to it.


Anesthetic and intensive care management of left main coronary artery to main pulmonary artery fistula diagnosed in postoperative case of tetralogy of fallot.
Cases of coronary to pulmonary artery fistula are seen in patients of pulmonary atresia with ventricular septal defect (VSD). These fistulas are rarely seen in patients of Tetralogy of Fallot (TOF). In this case report, we have presented ICU management of a postoperative case of TOF, with missed diagnosis of left main coronary artery (LMCA) to main pulmonary artery (MPA) fistula.


User-oriented batch reactor solutions to the homogeneous surface diffusion model for different activated carbon dosages.
This paper presents a simplified approach and user-oriented solutions to the homogeneous surface diffusion model (HSDM) equations for determining the surface diffusivity using a batch reactor system. Once the surface diffusivity is known, this model could also be used to estimate the performance of activated carbon (AC) applications as a function of contact time. In addition, fixed-bed performance can be predicted using the user-oriented solutions to the HSDM for fixed beds. The step-by-step procedure for determining surface diffusion coefficients of an activated carbon adsorber, which was initially developed by Hand, Crittenden and Thacker in 1983 for a carbon dose where C(equilibrium)/C(0)=0.5, is modified to allow calculations for different carbon dosages. This modification provides solutions to the HSDM equations for different activated carbon dosages. The solutions to the HSDM framework are provided as simplified algebraic equations suitable for quick and easy estimations of D(S). The excel spread sheet is provided in the supplemental information and a detailed example is discussed.


Role of volume and prostaglandin synthesis in the suppression of renin by saline in the rat.
To evaluate the contribution of plasma volume expansion per se on acute inhibition of renin release by sodium chloride infusion, renin responses to comparable plasma volume expansion with intravenous infusions of sodium chloride, sodium bicarbonate, or albumin were studied in separate groups of sodium chloride-depleted rats. In addition, urinary prostaglandin E2 (PGE2) excretion rate was compared in the saline- and sodium bicarbonate-infused animals to evaluate the relationship between acute changes in renin release and intrarenal PGE2 synthesis. All three groups were plasma volume-expanded by approximately 55%. Plasma renin activity (PRA) decreased in response to saline (12.3 +/- 1.0 to 6.7 +/- 0.7 ng AI/ml/hr; P less than 0.01) whereas PRA did not change with sodium bicarbonate (11.3 +/- 1.4 to 10.2 +/- 1.5) or albumin (9.9 +/- 0.7 to 8.2 +/- 1.0). The rate of PGE2 excretion was not changed by either saline (72.2 +/- 13.1 to 72.3 +/- 18.7 pg/min) or sodium bicarbonate infusion (70.7 +/- 8.8 to 64.9 +/- 7.0). These results support the hypothesis that acute suppression of PRA by infusion of saline is not dependent upon volume expansion per se. In confirmation of earlier observations, inhibition of renin release by sodium chloride was related to chloride. Finally, the results suggest that the renal tubular mechanism for inhibition of renin release by sodium chloride is not related to overall changes in renal PGE2 synthesis in the rat.


Effect of Cosmos, Crotalaria, Foeniculum, and Canavalia species, single-cropped or mixes, on the community of predatory arthropods.
Some plants can attract natural enemy by offering resources such as alternative food and refuge. However, studies need to be conducted before agricultural landscape diversification is implement. Our objective was to determine the best floristic compositions of cosmos (Cosmos sulphureus-Asteraceae), showy rattlepod (Crotalaria spectabilis-Fabaceae), fennel (Foeniculum vulgare-Apiaceae), and jack bean (Canavalia ensiformis-Fabaceae) to attract and maintain predatory arthropods, and know the potential of these treatments for future use in diversifying agricultural systems. The experimental design consisted in seven treatments of four species in single-crop, intercrops in three densities called mix1, mix2, and mix3, and the control (weeds). For the arthropod families classified as very frequent and constant, population dynamics in intercropping treatments was plotted according to the plant phenology. We conclude that all plants cultivated in single-cropping and intercropping treatments showed high predator richness and can potentially be used to diversify cultivated areas. Sulfur cosmos as a single crop and three mixes attracts higher numbers and greater family richness. Spider families-Oxyopidae, Araneidae and Thomisidae-and insects-Chrysopidae and Coccinellidae are more frequents. The dynamics of the predator populations varied according to the mixes treatment.


Receptor mobility, the cytoskeleton, and particle binding during phagocytosis.
Particle engulfment during phagocytosis has long been appreciated to be an active, actin-driven process. By contrast, the preceding stage--securing the target to the surface of the phagocyte--was thought to result from the passive diffusion of receptors along the membrane towards their ligands on the particle surface. Recent evidence, however, challenges this notion, demonstrating that receptors do not diffuse freely along the phagocyte surface and that actin polymerization and tyrosine phosphorylation are required for optimal particle binding. The interpretation and significance of these observations are the subject of this opinion piece.


Luteolin reduces zinc-induced tau phosphorylation at Ser262/356 in an ROS-dependent manner in SH-SY5Y cells.
In brain, excess zinc alters the metabolism of amyloid precursor protein, leading to β-amyloid protein deposition, one of the hallmarks of Alzheimer's disease (AD) pathology. Recently, it has been reported that zinc accelerates in vitro tau fibrillization, another hallmark of AD. In the current study, we examined the effect of high-concentration zinc on tau phosphorylation in human neuroblastoma SH-SY5Y cells. We found that incubation of cells with zinc resulted in abnormal tau phosphorylation at Ser262/356. Moreover, the current study has investigated whether luteolin (Lu), a bioflavonoid, could decrease zinc-induced tau hyperphosphorylation and its underlying mechanisms. Using Western blot and protein phosphatase activity assay, activities of tau kinases and phosphatase were investigated. Our data suggest (1) that zinc induces tau hyperphosphorylation at Ser262/356 epitope and (2) that Lu efficiently attenuates zinc-induced tau hyperphosphorylation through not only its antioxidant action but also its regulation of the phosphorylation/dephosphorylation system.


High-affinity binding of a protein-lipopolysaccharide phytotoxin from Verticillium dahliae to cotton membranes.
The presence of a specific binding site for a protein-lipopolysaccharide (PLP) phytotoxin isolated from culture filtrates of Verticillium dahliae has been demonstrated in plasma membranes from cotton seedlings. The 125I-labelled PLP was used as a ligand in binding assays with plasma membrane enriched fractions. Root tissue exhibited the highest amount of binding activity compared to hypocotyl and cotyledon tissue. Binding of the [125I]PLP was saturable, reversible, and with an affinity (Kd = 1.42 x 10(-8) M) comparable with the concentration required for biological activity. A single class of binding site was found, and the maximal number of binding sites were estimated as 5.4 x 10(-15) mol/micrograms protein.


Disturbances of the temporal organization of speech following bilateral thalamic surgery in a patient with Parkinson's disease.
This report summarizes a detailed analysis of the speech of a 45-yr-old man who had become dysarthric following bilateral thalamic surgery for the relief of symptoms of Parkinson's disease. His speech was characterized by a rapid rate and a mild-to-moderate articulatory deficit. Intelligibility was markedly reduced. The rapid rate was found to be the result of decreased syllable durations rather than to changes in pause or phrase patterns. Decreased syllable durations resulted from abnormal shortening of vowels. Consonant releases were found to be prolonged. This distorted temporal relationship among speech segments was considered to be an important factor in the patient's poor intelligibility and partially explained why uniform electronic expansion of his speech resulted in only negligible increase in intelligibility. It is hypothesized that this speech disturbance results from the interaction of central "metronomic" abnormality with a peripheral neuromotor articulatory impairment.


Experimental evolution of an essential Bacillus gene in an E. coli host.
The acquisition of foreign genes by HGT potentially greatly speeds up adaptation by allowing faster evolution of beneficial traits. The evolutionary integration of novel genes into host gene expression and physiology is critical for adaptation by HGT, but remains largely unknown. We are exploring the evolutionary consequences of gene acquisition in populations of Escherichia coli in real time. A plasmid bearing the genes necessary for sucrose catabolism was constructed and introduced into a single E. coli genotype. Wild-type E. coli is generally incapable of utilizing sucrose, but E. coli transformants were able to grow on sucrose as a sole carbon and energy source, albeit poorly. Twelve replicate populations were initiated and propagated in sucrose minimal media for 300 generations. Over this time, we observed large fitness improvements in the selected environment. These results demonstrate the potential for HGT to substantially increase microbial niche breadth.


School Shooters: Patterns of Adverse Childhood Experiences, Bullying, and Social Media.
Since 2013 there have been at least 421 recorded incidents of gunfire on school grounds METHOD: This study used a critical review of national and local media news reports of 25 American male school shooter cases from 2013 to 2019. Approximately 88% of school shooters had at least one social media account, and 76% posted disturbing content of guns and threatening messages. Over 72% of shooters had at least one reported adverse childhood experience, and 60% reported being bullied in-person or online DISCUSSION: Professionals who work with adolescents are front-line providers who routinely assess student safety. Social media use is often underassessed, demonstrating a knowledge gap that may reveal insights into the perspective and well-being of adolescents. Inclusion of questions on social media, adverse childhood experiences, and experiences of bullying by pediatric nurses and others may be proactive measures that can help identify, protect, and intervene with at-risk students.


Dephospho-CoA kinase, a nuclear-encoded apicoplast protein, remains active and essential after Plasmodium falciparum apicoplast disruption.
Malaria parasites contain an essential organelle called the apicoplast that houses metabolic pathways for fatty acid, heme, isoprenoid, and iron-sulfur cluster synthesis. Surprisingly, malaria parasites can survive without the apicoplast as long as the isoprenoid precursor isopentenyl pyrophosphate (IPP) is supplemented in the growth medium, making it appear that isoprenoid synthesis is the only essential function of the organelle in blood-stage parasites. In the work described here, we localized an enzyme responsible for coenzyme A synthesis, DPCK, to the apicoplast, but we were unable to delete DPCK, even in the presence of IPP. However, once the endogenous DPCK was complemented with the E. coli DPCK (EcDPCK), we were successful in deleting it. We were then able to show that DPCK activity is required for parasite survival through knockdown of the complemented EcDPCK. Additionally, we showed that DPCK enzyme activity remains functional and essential within the vesicles present after apicoplast disruption. These results demonstrate that while the apicoplast of blood-stage P. falciparum parasites can be disrupted, the resulting vesicles remain biochemically active and are capable of fulfilling essential functions.


Prisoner's science.
Decisions involving cooperation or competition are common in science. Here, we consider three situations frequently encountered in the biomedical sciences, namely, establishing priority, sharing reagents, and selecting a journal for publication, through the lens of the prisoner's dilemma. In each situation, cooperation is the best strategy for scientists and for science.


The Neglected Role of Buddhism in the Development of Medicine in Late Imperial China Viewed through the Life and Work of Yu Chang (1585-1664).
Despite significant revisions over recent decades, the field of medicine in late imperial China continues to be defined by a number of problematic boundaries such as that between medicine and religion. In this article I challenge the validity of this boundary through a detailed examination of the life and work of the hugely influential seventeenth-century physician Yu Chang (1585-1664), whose openly Buddhist critique of literati medicine has hitherto largely escaped the attention of medical historians. I argue that Yu Chang's case, read against the more widespread revival of Buddhism at the time, the important historical role of literati-Buddhist networks, and evidence of many other late imperial physicians' interest in Buddhism, was not exceptional. A wider reevaluation of Buddhism's role in the development of medicine in late imperial China as well as its historical neglect is therefore called for.


Effects of flow scarcity on leaf-litter processing under oceanic climate conditions in calcareous streams.
Although temporary streams represent a high proportion of the total number and length of running waters, historically the study of intermittent streams has received less attention than that of perennial ones. The goal of the present study was to assess the effects of flow cessation on litter decomposition in calcareous streams under oceanic climate conditions. For this, leaf litter of alder was incubated in four streams (S1, S2, S3 and S4) with different flow regimes (S3 and S4 with zero-flow periods) from northern Spain. To distinguish the relative importance and contribution of decomposers and detritivores, fine- and coarse-mesh litter bags were used. We determined processing rates, leaf-C, -N and -P concentrations, invertebrate colonization in coarse bags and benthic invertebrates. Decomposition rates in fine bags were similar among streams. In coarse bags, only one of the intermittent streams, S4, showed a lower rate than that in the other ones as a consequence of lower invertebrate colonization. The material incubated in fine bags presented higher leaf-N and -P concentrations than those in the coarse ones, except in S4, pointing out that the decomposition in this stream was driven mainly by microorganisms. Benthic macroinvertebrate and shredder density and biomass were lower in intermittent streams than those in perennial ones. However, the bags in S3 presented a greater amount of total macroinvertebrates and shredders comparing with the benthos. The most suitable explanation is that the fauna find a food substrate in bags less affected by calcite precipitation, which is common in the streambed at this site. Decomposition rate in coarse bags was positively related to associated shredder biomass. Thus, droughts in streams under oceanic climate conditions affect mainly the macroinvertebrate detritivore activity, although macroinvertebrates may show distinct behavior imposed by the physicochemical properties of water, mainly travertine precipitation, which can override the flow intermittence effects.


Investigation of the carbohydrate metabolism of normal and neoplastic hepatocytes using 2,6-dichlorophenolindophenol as a probe for NAD(P)H production measured by voltammetry.
An electrochemical technique is described for measurement of intracellular NAD(P)H production. This technique involves an auxiliary redox system taken up by the cells which is then measured voltammetrically after reduction by NAD(P)H. The redox system used was 2, 6-dichlorophenolindophenol (DCPIP). It was shown to undergo a quasi-reversible two-electron transfer at the rotating gold disc electrode serving as an indicator electrode. The anodic wave of the reduced form of DCPIP was taken to indicate the amount of NAD(P)H produced by metabolic processes with glucose as substrate for a given number of cells. The following types of cell were investigated in suspension: Morris hepatoma 3924, a hepatocyte-derived cell line, and normal hepatocytes. Marked differences between normal and transformed cells were found under aerobic compared to anaerobic conditions. These were explained in terms of alterations in carbohydrate metabolism, e.g., Pasteur effect occurring on cell transformation.


Hematopoietic versus leukemic stem cell quiescence: Challenges and therapeutic opportunities.
Hematopoietic stem cells (HSC) are responsible for the production of mature blood cells. To ensure that the HSC pool does not get exhausted over the lifetime of an individual, most HSCs are in a state of quiescence with only a small proportion of HSCs dividing at any one time. HSC quiescence is carefully controlled by both intrinsic and extrinsic, niche-driven mechanisms. In acute myeloid leukemia (AML), the leukemic cells overtake the hematopoietic bone marrow niche where they acquire a quiescent state. These dormant AML cells are resistant to chemotherapeutics. Because they can re-establish the disease after therapy, they are often termed as quiescent leukemic stem cells (LSC) or leukemia-initiating cells. While advancements are being made to target particular driver mutations in AML, there is less focus on how to tackle the drug resistance of quiescent LSCs. This review summarises the current knowledge on the biochemical characteristics of quiescent HSCs and LSCs, the intracellular signaling pathways and the niche-driven mechanisms that control quiescence and the key differences between HSC- and LSC-quiescence that may be exploited for therapy.


Centration of intraocular lenses with circular haptics.
To evaluate two intraocular lens (IOL) models with a circular haptic configuration designed to better distribute forces within the capsular bag over 360 degrees. University and Maria Middelares hospitals, Antwerp, Belgium. Two IOLs with circular haptics were evaluated for 6 months after implantation: a one-piece, all-poly(methyl methacrylate) (PMMA), Corneal IS M 5.5 lens with a 5.5 mm biconvex optic, overall diameter of 9.8 mm, and two semicircular open haptics (n = 103); a plano-convex, all-PMMA, modified Anis lens with a 5.5 mm plano-convex optic, total diameter of 10.0 or 11.0 mm (depending on diopter), and closed-loop haptics (n = 335). All lenses were inserted through a 5.5 mm scleral incision after phacoemulsification and placed in the capsular bag through a 4.5 mm curvilinear capsulorhexis. The IOLs centered without being rotated. Six months after implantation, the IOL optics were well centered, even in eyes with an eccentric capsulorhexis (19%). In two eyes with partial zonulysis and in seven with posterior capsule rupture, decentration of less than 0.5 mm was observed. Both lenses provided uniform capsular support without causing stress lines in the posterior capsule. There were no cases of capsule contraction syndrome. Posterior capsule fibrosis reducing visual acuity occurred in 4% of eyes in both series. The Corneal IS M 5.5 and the Anis lens with circular haptics prevented late optic decentration and, therefore, would be useful in cases of eccentric capsulorhexis, partial zonulysis, anterior radial tears, and posterior capsule rupture. These IOLs may also prevent capsular contraction.


Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function.
Potent T cell responses against infections and malignancies require a rapid yet tightly regulated production of toxic effector molecules. Their production level is defined by post-transcriptional events at 3' untranslated regions (3' UTRs). RNA binding proteins (RBPs) are key regulators in this process. With an RNA aptamer-based capture assay, we identify >130 RBPs interacting with IFNG, TNF, and IL2 3' UTRs in human T cells. RBP-RNA interactions show plasticity upon T cell activation. Furthermore, we uncover the intricate and time-dependent regulation of cytokine production by RBPs: whereas HuR supports early cytokine production, ZFP36L1, ATXN2L, and ZC3HAV1 dampen and shorten the production duration, each at different time points. Strikingly, even though ZFP36L1 deletion does not rescue the dysfunctional phenotype, tumor-infiltrating T cells produce more cytokines and cytotoxic molecules, resulting in superior anti-tumoral T cell responses. Our findings thus show that identifying RBP-RNA interactions reveals key modulators of T cell responses in health and disease.


Hydrodynamics- and hydrochemistry-affected microbial selenate reduction in aquifer: Performance and mechanisms.
Selenate [Se(VI)] with higher content in groundwater will be harmful for human beings. Hence, effective treatment for Se(VI) in aquifer should be conducted reasonably. Microbial reduction of Se(VI) to elemental selenium with weak movability and toxicity has attracted significant attention due to its high efficiency and no secondary contamination. However, hydrodynamic and hydrochemical influences with corresponding mechanisms during Se(VI) bioreduction are still not clear. In this study, influences of flow rate, initial Se(VI) and organic concentrations, coexisting nitrate were evaluated. Se(VI) removal efficiency and capacity reached 96.42 ± 6.82% and 41.28 ± 3.41 (g/m3·d) with flow rate of 0.56 mL/min, initial Se(VI) and chemical organic demand concentrations of 10 mg/L and 400 mg/L. Dechloromonas and Pseudomonas were presumably contributed to Se(VI) reduction, with upregulated serA and tatC genes. Solid Se0 was identified as the final product from Se(VI) reduction. These results will be beneficial for the further comprehending of Se(VI) remediation in aquifer.


Evaluating techniques of myocardial preservation for aortic valve replacement: operative risk.
In a two-year period 105 patients underwent isolated aortic valve replacement without hospital death. Eighty-three patients were operated on using hypothermic ischemic arrest; 22 patients had coronary perfusion. The early postoperative cardiac performance and incidence of complications did not differ between groups, although cardiopulmonary bypass time was shorter in the ischemic arrest group. These data suggest that ischemic arrest is a satisfactory method for myocardial preservation. However, because of the low hospital mortality rate with either method, these results and those of others cannot be taken to indicate the superiority of any method of myocardial preservation.


Studies on interrelations between eosinophilia, serum IgE and tissue mast cells.
In an examination of a variety of diseases associated with a peripheral blood eosinophilia it is evident that the eosinophilia is not necessarily accompanied by increased amounts of serum IgE. Tissue eosinophilia occurring with mast cell hyperplasia and usually increased amounts of IgE, indicate atopic allergy. It is considered that the eosinophilic granuloma of soft tissue (Kimura's disease) is an atopic disease and quite different from histiocytosis X.


Extreme Lateral Supracerebellar Infratentorial Approach: Surgical Anatomy and Review of the Literature.
The extreme lateral supracerebellar infratentorial (ELSI) approach has the potential to access several distinct anatomical regions that are otherwise difficult to reach. We have illustrated the surgical anatomy through cadaveric dissections and provided an extensive review of the literature to highlight the versatility of this approach, its limits, and comparisons with alternative approaches. The surgical anatomy of the ELSI has been described using 1 adult-injected cadaveric head. Formalized noninjected brain specimens were also dissected to describe the brain parenchymal anatomy of the region. An extensive review of the literature was performed according to each targeted anatomical region. Illustrative cases are also presented. The ELSI approach allows for wide exposure of the middle and posterolateral incisural spaces with direct access to centrally located intra-axial structures such as the splenium, pulvinar, brainstem, and mesial temporal lobe. In addition, for skull base extra-axial tumors such as petroclival meningiomas, the ELSI approach represents a rapid and adequate method of access without the use of extensive skull base approaches. The ELSI approach represents one of the most versatile approaches with respect to its ability to address several anatomical regions centered at the posterior and middle incisural spaces. For intra-axial pathologies, the approach allows for access to the central core of the brain with several advantages compared with alternate approaches that frequently involve significant brain retraction and cortical incisions. In specific cases of skull base lesions, the ELSI approach is an elegant alternative to traditionally used skull base approaches, thereby avoiding approach-related morbidity.


Clinical utility of high-resolution portal films.
We have evaluated the film quality and overall clinical utility of a unique high-resolution portal film system which utilizes high contrast graphics art film. A total of 127 unselected patients had their conventional portal films and high-resolution films of the same site, compared and graded subjectively for a variety of parameters by an independent panel of radiotherapists and radiographers. Although consistent improvements in most aspects of image quality were noted, improved overall clinical usefulness of the high-resolution portal film system in comparison to the conventional films, when subjected to multiple regression analysis, was confined to lateral neck views only. High-resolution portal film utility was also found to depend significantly on field size with areas less than 110 cm2 having a markedly worse clinical utility score.


Elderly cancer survivorship: an integrative review and conceptual framework.
The intersection of ageing and cancer in the phase of post-treatment survivorship represents a large and growing population with unique needs. The goal of this work is to review and integrate the current gerontology and oncology literature relevant to elderly cancer survivorship, to identify knowledge gaps and research opportunities and to propose a conceptual model to guide future research. The long-term, global goal is the prevention of morbidity and mortality in elderly cancer survivors by identification of vulnerable elders, maintenance of independence, tailoring of treatment, establishing intervention guidelines and planning for necessary resources within the entire trajectory of cancer survival for older survivors. Targeted and integrative review of selected literature from multiple disciplines. Search engines included PubMed, article reference lists and internet searches for epidemiological data (US Census, World Health Organization, American Cancer Society, Canadian Cancer Cancer Society, etc). A conceptual model that incorporates the gerontologic, oncologic and personal characteristics of older cancer survivors is proposed that may provide a comprehensive approach by which to frame elderly survivorship research. Cancer survivorship among the elderly is quantitatively and qualitatively different from cancer survivorship among other age groups. The current large numbers and predicted increase in elderly cancer survivors in the near future mandate attention to this population. Future research must consider the complexity of intersecting needs in the gero-oncology population.


Neonatal lupus erythematosus in four successive siblings born to a mother with discoid lupus erythematosus.
A young woman with inactive discoid lupus erythematosus (LE) gave birth in three successive pregnancies to four male infants who showed cutaneous, and in one case cardiac, signs of neonatal LE. The mother had Ro and La antibodies although the anti-nuclear factor (ANF) was not consistently detectable. Three of the infants received phototherapy for neonatal jaundice. Maternal discoid LE may give rise to neonatal LE, and successive siblings can be affected.


Nociceptin Increases Antioxidant Expression in the Kidney, Liver and Brain of Diabetic Rats.
Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1-17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.


Current management of the hepatorenal syndrome.
Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease. Historically, the development of HRS was considered a pre-terminal event due to a lack of efficacious therapy. Although liver transplantation remains the optimum therapy for HRS, many patients may be unsuitable for liver grafting. In addition, organ shortage may necessitate the institution of alternative pharmacological therapies to bridge patients to transplantation or to maintain renal function. This article reviews the definitions of Types-1 and -2 HRS, and addresses strategies for the prevention of the syndrome. It will also discuss management approaches to the cirrhotic patient with renal failure, specifically, assessment of novel vasoconstrictor therapies, such as vasopressin analogues, alpha-adrenoreceptor agonists, and the use of transjugular intra-hepatic shunts either alone or in combination with other therapeutic agents.


Interleukin-10 and Transforming Growth Factor-β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver.
Normothermic ex vivo liver perfusion (NEVLP) is a novel system for organ preservation that may improve over static cold storage clinically and offers the chance for graft modification prior to transplantation. Although recent studies have shown the presence of inflammatory molecules during perfusion, none have yet shown the effects of NEVLP on liver-resident immune cell activation. We investigated the effects of NEVLP on liver-resident immune cell activation and assessed the ability of anti-inflammatory cytokines interleukin 10 (IL10) and transforming growth factor β (TGF-β) to improve organ function and reduce immune activation during perfusion. Rat livers were perfused for 4 hours at 37°C with or without the addition of 20 ng/mL of each IL10 and TGF-β (n = 7). Naïve and cold storage (4 hours at 4°C) livers served as controls (n = 4). Following preservation, gene expression profiles were assessed through single-cell RNA sequencing; dendritic cell and macrophage activation was measured by flow cytometry; and cytokine production was assessed by enzyme-linked immunosorbent assay. NEVLP induced a global inflammatory gene expression signature, most notably in liver-resident macrophages and dendritic cells, which was accompanied by an increase in cell-surface levels of major histocompatibility complex (MHC) II, CD40, and CD86. Immune activation was partially ameliorated by IL10 and TGF-β treatment, but no changes were observed in inflammatory cytokine production. Overall levels of liver damage and cellular apoptosis from perfusion were low, and liver function was improved with IL10 and TGF-β treatment. This is the first study to demonstrate that liver-resident immune cells gain an activated phenotype during NEVLP on both the gene and protein level and that this activation can be reduced through therapeutic intervention with IL10 and TGF-β.


Integration of micro-filtration into osmotic membrane bioreactors to prevent salinity build-up.
The high salinity remains as one of major obstacles of the osmotic membrane bioreactor (OMBR). In this study, a new pathway was explored to prevent the salinity build-up by integrating the micro-filtration (MF) membrane to the OMBR (MF-OMBR). The results indicated that the salinity characterized by conductivity in the MF-OMBR was effectively alleviated and controlled at a lower value of about 5 mS/cm, and the stable flux of forward osmosis (FO) membrane correspondingly increased to approximately 5.5L/(m(2)h). Besides, the addition of MF membrane in the OMBR could increase the total organic carbon (TOC) and ammonium nitrogen (NH3-N) removals due to the activated sludge by improving the microbial activity. The membrane fouling especially the reversible fouling in the MF-OMBR was severer compared to that in the conventional OMBR, which resulted in a lower water flux than the expectation due to the increase of filtration resistance and external concentration polarization.


Financial risk protection and universal health coverage: evidence and measurement challenges.
Financial risk protection is a key component of universal health coverage (UHC), which is defined as access to all needed quality health services without financial hardship. As part of the PLOS Medicine Collection on measurement of UHC, the aim of this paper is to examine and to compare and contrast existing measures of financial risk protection. The paper presents the rationale behind the methodologies for measuring financial risk protection and how this relates to UHC as well as some empirical examples of the types of measures. Additionally, the specific challenges related to monitoring inequalities in financial risk protection are discussed. The paper then goes on to examine and document the practical challenges associated with measurement of financial risk protection. This paper summarizes current thinking on the area of financial risk protection, provides novel insights, and suggests future developments that could be valuable in the context of monitoring progress towards UHC.


Both splicing variants of the dopamine D2 receptor mRNA are up-regulated by antipsychotic drugs.
We have investigated the effects of antipsychotic drugs on the expression of the two dopamine D2 receptor splicing variants using multiprobe oligonucleotide solution hybridisation. Both long and short mRNA variants were increased in abundance by approximately 2-fold by both haloperidol and loxapine after 32 days drug administration.


Towards a streamlined synthesis of peptides containing α,β-dehydroamino acids.
Investigation of a strategy to streamline the synthesis of peptides containing α,β-dehydroamino acids (ΔAAs) is reported. The key step involves generating the alkene moiety via elimination of a suitable precursor after it has been inserted into a peptide chain. This process obviates the need to prepare ΔAA-containing azlactone dipeptides to facilitate coupling of these residues. Z-dehydroaminobutyric acid (Z-ΔAbu) could be constructed most efficiently via EDC/CuCl-mediated dehydration of Thr. Formation of Z-ΔPhe by this or other dehydration methods was unsuccessful. Production of the bulky ΔVal residue could be accomplished by DAST-promoted dehydrations of β-OHVal or by DBU-triggered eliminations of sulfonium ions derived from penicillamine derivatives. However, competitive formation of an oxazoline byproduct remains problematic.


Investigations on the formation of Maillard reaction products in sweet cookies made of different cereals.
In this study, the content of Maillard reaction products from its initial, intermediate and final stage (5-hydroxymethylfurfural, α-dicarbonyl compounds, furosine, N-ε-carboxymethyllysine and N-ε-carboxyethyllysine) was measured in sweet cookies made of wholegrain flour of eight genotypes of small-grain cereals (bread wheat, durum wheat, soft wheat, hard wheat, triticale, rye, hulless barley and hulless oat) and four corn genotypes (white-, yellow- and red-colored standard seeded corn and blue-colored popping corn). Furthermore, the effect of the initial content of sugars, total proteins, free and total lysine in flour on the formation of Maillard reaction products was investigated using the principle component analysis. 3-deoxyglucosone was the predominant α-dicarbonyl compound in all cereal cookies and the highest content was measured in those made from flour of different colored corn genotypes (on average, 98.35, 151.28 and 172.85 mg/kg after baking for 7, 10 and 13 min, respectively). Heating dough at 180 °C for 7, 10 and 13 min differently affected the content of 5-hydroxymethylfurfural and α-dicarbonyl compounds in the cereal cookies. The 5-hydroxymethylfurfural content gradually increased, while a reduction in 3-deoxyglucosone content was observed in the cookies baked for 13 min except for those made from soft wheat, hulless oat, red- and blue-colored corn. After 7 min of heating, the content of furosine measured in the cereal cookies reached its maximum (from 320.9 mg/kg in yellow-colored corn-based cookies to 585.7 mg/kg in hulless oat-based cookies), while N-ε-carboxymethyllysine and N-ε-carboxyethyllysine showed the opposite trend. The highest content of advanced glycation end products was detected in cookies also made from hulless oat flour rich in proteins (16.80%) and total lysine (10670.3 mg/kg). The interrelationship analysis showed that the initial content of sugars in flour of cereals affected 5-hydroxymethylfurfural and 3-deoxyglucosone formation in the cookies. In addition, a high correlation between protein-bound Maillard reaction products in the cookies and the total proteins and the total lysine content in the flours was found.


Antiphospholipid antibodies and pregnancy outcome of assisted reproductive treatment: A systematic review and meta-analysis.
Antiphospholipid antibodies (aPLs) are a group of autoantibodies associated with a variety of pregnancy complications, but the impact of aPL on the outcomes of assisted fertility treatment (ART) is controversial. This systematic review and meta-analysis were designed to explore the association between aPL and ART outcomes and to explore in which stages does aPL play a role. PubMed and Cochrane database were systematically retrieved, and odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effect model or fixed-effect model according to the heterogenicity assessed by the Cochran Q and I2 statistic test. Of 246 records identified by the search, 10 case-control studies and 13 cohort studies that explored the association between aPL and in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were analyzed. The results showed that aPL positive rate was higher in females who failed in IVF/ICSI than those who succeeded in IVF/ICSI (OR: 3.62, 95% CI: 1.95-6.74). This study also indicated that females positive for aPL have a higher miscarriage rate (RR: 1.68, 95% CI: 1.24-2.28) than those negative for aPL, but live birth rate, biochemical pregnancy rate, and clinical pregnancy rate were similar between two groups (RR: 1.01, 95% CI: 0.91-1.12; RR: 1.18, 95% CI: 0.57-2.43 and RR: 0.95, 95% CI: 0.80-1.13). There was higher aPL prevalence in females with adverse IVF/ICSI outcomes. It seems that aPL mainly affects the miscarriage rate, but has little effect on live birth rate, biochemical pregnancy rate, and clinical pregnancy rate. Routine detection of aPL before IVF/ICSI treatment is meaningful.


Rapid ED access reduces patients leaving without being seen.
Implementing a brief sign-in process for emergency department patients, and completing full registration later at the bedside, has allowed the University of California, San Diego Medical Center to eliminate a major patient flow bottleneck.


Ventricular pump performance during hypocalcemia: clinical and experimental studies.
We have compared indices of ventricular function during rapid transfusion of citrated (1.5 ml/kg/min) or heparinized (1.5 ml/kg/min) autologous blood in six patients following discontinuation of cardiopulmonary bypass. Infusion of citrated blood was associated with a lowering of plasma ionized calcium concentration ([Ca++], from 0.90 +/- 0.04 to 0.71 +/- 0.4 mM, p less than 0.001) and an increase in pulmonary artery balloon-occluded pressure (PA0, from 9.4 +/- 2.6 to 15.5 +/- 1.7 mm Hg, p less than 0.u1), without a change in left ventricular stroke work index, stroke index, or cardiac index. Transfusion of heparinized blood caused no change in plasma [Ca++]. A rise in PA0, which was similar in magnitude to that observed during citrated blood transfusion, was associated with increased left ventricular stroke work index, stroke index, cardiac index, and mean arterial pressure. Although data obtained during citrated blood transfusion suggest the presence of transient left ventricular dysfunction, its magnitude is not readily expressed in terms of ventricular function curves when accompanied by a simultaneous change in [Cized closed-chest dog by volume loading during hypocalcemia, when mean arterial pressure, heart rate, and [Ca++] were in a steady state, both prior to and following beta blockade with propranolol. Function curves obtained during severe hypocalcemia ([Ca++] = 0.43 +/- 0.02 mM) were shifted significantly to the right and downward, when compared to those obtained during normocalcemia ([Ca++] = 1.06 +/- 0.03 mM). Hypocalcemia combined with beta blockade resulted in severe left ventricular failure, as demonstrated by a flat ventricular function curve.


Allele and haplotype frequency at human leucocyte antigen class I/II and immunomodulatory cytokine loci in patients with myelodysplasia and acute myeloid leukaemia: in search of an autoimmune aetiology.
An autoimmune mechanism in the pathogenesis of myelodysplastic syndrome (MDS) is suggested by response to immunosuppression, with CD8+ T-lymphocytes implicated in the haematopoietic suppression. We therefore sought evidence for human leucocyte antigen (HLA) restriction and variant frequency differences in selected polymorphisms at the loci for the immunomodulatory cytokines, tumour necrosis factor alpha (TNF-alpha), lymphotoxin-alpha (LT-alpha) and interleukin 10 (IL-10) in patients with MDS and acute myeloid leukaemia (AML) compared with normal controls. DNA from 150 MDS/AML patients [24 AML, 53 refractory anaemia (RA), 25 RA with excess blasts (RAEB), four RAEB in transformation (RAEBt), 21 sideroblastic leukaemia, 22 chronic myelomonocytic leukaemia] was screened. Control data was from Scottish blood donors (HLA class I/II), healthy General Practitioner-based subjects (TNF-alpha/LT-alpha) and published values (IL-10). HLA class I/II haplotypes were determined using sequence-specific primers. Polymorphisms were assayed at TNF-alpha -308, LT-alpha +252 and IL10 -824, -597 and -1082 loci. Variant frequencies of common haplotypes at HLA class I and II, high-/low-producer TNF-alpha/LT-alpha and IL-10 loci were not different between patients and controls or within the French-American-British, International Prognostic Scoring System or cytogenetic subgroups and were not associated with altered survival for MDS/AML patients. TNF2 allele frequency was greater in the MDS/AML cohort (chi2 = 6.593, P < 0.05) but the biological significance was uncertain in the absence of an increased high-producer TNF-alpha/LT-alpha haplotype frequency. We can find no genetic influence for these polymorphisms in HLA class I/II, TNF-alpha/LT-alpha and IL-10 loci on either predisposition or disease progression in MDS/AML.


Prognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic Colorectal Cancer.
The prognostic value and molecular landscape of human epidermal growth factor receptor 2 (HER2) low-expressing (HER2-L) metastatic colorectal cancer (mCRC) remain unclear. This study enrolled patients with mCRC who had undergone surgical resection of primary tumor. Using the specimen, we evaluated HER2 expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positivity was defined as follows: HER2 positivity (HER2-Pos) as IHC 3 + or IHC 2+/FISH positive, HER2-L as IHC 2+/FISH negative or IHC 1+, and HER2 negativity (HER2-Neg) as IHC 0+. Gene alterations were determined by next-generation sequencing. Between 2005 and 2015, a total of 370 patients were analyzed, comprising 15 patients (4%) with HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg disease. The clinicopathologic characteristics among groups had no differences. HER2-L had a significantly higher proportion of coaltered RAS mutation than HER2-Pos (P = .037). With a median follow-up of 101.8 months, HER2-L had a significantly better median overall survival than HER2-Pos (P = .029) (18.2 months in HER2-Pos vs. 33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 patients harboring wild-type RAS and receiving anti-EGFR antibody therapy, HER2-L had a better median progression-free survival tendency than HER2-Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 5.1 in HER2-Neg (P = .036). HER2-L mCRC showed a better prognosis than HER2-Pos mCRC, and it is similar to HER2-Neg mCRC. Hence, HER2-L mCRC might have different biologic behavior in terms of prognostic value and molecular landscape of mCRC, suggesting the possibility of implementation of HER2-guided clinical development against HER2-expressing mCRC.


Adansonia digitata L. fruit shell extract alleviates lead-induced neurotoxicity in mice via modulation of oxidative stress and a possible chelating activity.
Lead is a ubiquitous environmental heavy metal known to induce neurotoxicity. It has been postulated that substance with high antioxidant capacity could alleviate lead-induced neurotoxicity. Adansonia digitata fruit shell extract (ADFS) has been reported to have high phenolic contents and exerts antioxidant activity. This study investigated the effects of Adansonia digitata fruit shell extract on lead-induced neurotoxicity in mice. Male balb/c mice (n = 7) were administered with Pb-acetate (50 mg/kg) 30 mins before ADFS (250 mg/kg and 500 mg/kg) or succimer (50 mg/kg) per orally for 28 days. Motor activities were evaluated on days 29 and 30 through horizontal bar and open field tests respectively. Further, spectrophotometry, atomic absorption spectrophotometry and haematoxylin and eosin staining were carried-out to determine the expression of oxidative stress biomarkers, level of lead concentration in the brain and histology of the cerebellum respectively. Lead acetate exposure significantly (p < 0.05) induced motor deficits in horizontal bar test and open field test, caused oxidative stress, high concentration of lead in the brain as well as histological aberration in the cerebellum. ADFS significantly (p < 0.05) reversed the motor deficits evident by increased muscle strength and number of lines crossed. Further, ADFS significantly reversed oxidative stress evident by increased levels of SOD, CAT and GSH and decreased level of MDA. There was also significant (p < 0.05) decrease in brain lead concentration as well as reduced cerebellar cells death. Findings suggest that ADFS attenuated motor deficits via inhibition of oxidative stress and chelating activity which is comparable to succimer. Hence, ADFS should be explored for possible development of chelating agent against lead and other heavy metals toxicity.


Associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing maintenance hemodialysis.
Previous clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD. This retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression. Baseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022-1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612-0.900, p = 0.002) levels were independent predictors of all-cause mortality. Sclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.


Dynamic assessment and system dynamics simulation of safety risk in whole life cycle of coal mine.
Based on the accident causation theory, the mechanism and inducement of construction safety risk in mining enterprises are clarified. The safety risk system of mining enterprises is divided into five subsystems: personnel, material equipment, technology, environment, and management by rough set theory. The comprehensive weight of each risk factor is calculated by network analytic hierarchy process and fuzzy comprehensive evaluation method. Taking a mine in Shanxi Province as the research object, the causal traceability diagram and stock flow diagram of the risk system of mining enterprises are constructed by means of system dynamics model. The influence of various risk factors of the mine on the overall safety risk management level of the enterprise is simulated, and the numerical value of key personnel influence factors is adjusted. The sensitivity changes of safety productivity and safety risk management level of mining enterprises in different situations are analyzed. The results show that: (1) the management and personnel subsystem has the greatest impact on the safety risk management of mining enterprises, followed by the technology, material equipment, and environment subsystem. (2) Increasing safety input can improve the safety level and reduce the expected safety value time, otherwise it will reduce the safety level and delay the expected safety value time. (3) Further simulation of the personnel subsystem, it is found that the factors affecting the safety level of mining enterprises contain six factors, namely, the technical level of construction personnel, the management level of manager, the conduct code of construction personnel, the safety consciousness of practitioners, the basic quality of construction personnel, and the physical and mental state of construction personnel. (4) The conversion rate of personnel safety input to manager's management level and the safety consciousness of practitioners presents a steep decline-slow rise-gradually steady development trend, which mainly because the benefits of safety input have certain time delay and lag.


Simulating the multicausality of Alzheimer's disease with system dynamics.
In Alzheimer's disease (AD), cognitive decline is driven by various interlinking causal factors. Systems thinking could help elucidate this multicausality and identify opportune intervention targets. We developed a system dynamics model (SDM) of sporadic AD with 33 factors and 148 causal links calibrated with empirical data from two studies. We tested the SDM's validity by ranking intervention outcomes on 15 modifiable risk factors to two sets of 44 and 9 validation statements based on meta-analyses of observational data and randomized controlled trials, respectively. The SDM answered 77% and 78% of the validation statements correctly. Sleep quality and depressive symptoms yielded the largest effects on cognitive decline with which they were connected through strong reinforcing feedback loops, including via phosphorylated tau burden. SDMs can be constructed and validated to simulate interventions and gain insight into the relative contribution of mechanistic pathways.


Engineered Axonal Tracts as "Living Electrodes" for Synaptic-Based Modulation of Neural Circuitry.
Brain-computer interface and neuromodulation strategies relying on penetrating non-organic electrodes/optrodes are limited by an inflammatory foreign body response that ultimately diminishes performance. A novel "biohybrid" strategy is advanced, whereby living neurons, biomaterials, and microelectrode/optical technology are used together to provide a biologically-based vehicle to probe and modulate nervous-system activity. Microtissue engineering techniques are employed to create axon-based "living electrodes", which are columnar microstructures comprised of neuronal population(s) projecting long axonal tracts within the lumen of a hydrogel designed to chaperone delivery into the brain. Upon microinjection, the axonal segment penetrates to prescribed depth for synaptic integration with local host neurons, with the perikaryal segment remaining externalized below conforming electrical-optical arrays. In this paradigm, only the biological component ultimately remains in the brain, potentially attenuating a chronic foreign-body response. Axon-based living electrodes are constructed using multiple neuronal subtypes, each with differential capacity to stimulate, inhibit, and/or modulate neural circuitry based on specificity uniquely afforded by synaptic integration, yet ultimately computer controlled by optical/electrical components on the brain surface. Current efforts are assessing the efficacy of this biohybrid interface for targeted, synaptic-based neuromodulation, and the specificity, spatial density and long-term fidelity versus conventional microelectronic or optical substrates alone.


Response of adrenal sympathetic efferent nerve activity to mechanical and thermal stimulations of the facial skin area in anesthetized rats.
The effect of mechanical and thermal stimulations to the forehead or cheek innervated by the trigeminal nerve on adrenal sympathetic efferent nerve activity was studied in alpha-chloralose-urethane anesthetized rats. Innoxious mechanical stimulations to the forehead or cheek caused a reflex decrease of nerve activity, while noxious mechanical stimulations to the forehead or cheek caused a reflex increase in activity. Thermal stimulation of the forehead and bilateral cheeks at below 15 degrees C or above 45 degrees C increased activity though it failed to do so between 20 and 40 degrees C. These excitatory responses lasted only as long as the period of the stimulation. These results suggest that excitatory reflex responses mediated by supraspinal circuit to adrenal nerve activity are not, characteristically, of an enduring nature.


Advances in the management of bile duct obstruction: percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography.
Jaundice can be diagnosed anatomically and frequently histopathologically without laparotomy by radiologic and endoscopic techniques, combined with biopsy or cytology. Benign and malignant causes of bile duct obstruction can be managed by endoscopic and radiologic methods with reduced morbidity and mortality, displacing abdominal operation for many entities. Even unresectable or inoperable lesions can be effectively palliated by these new techniques.


Laparoscopic colectomy significantly decreases length of stay compared with open operation.
Current literature tends not to adjust for biases in patient selection attributable to comorbidities that could provide alternate explanations for length of stay differences in laparoscopic versus open colectomy. We hypothesized that utilizing the National Surgical Quality Improvement Program (NSQIP) dataset and acuity adjustment methods would demonstrate an independent improvement in length of stay for laparoscopic colectomy. We used CPT coding to select all colectomies in NSQIP public use files from 2005-2009. Outlier status for surgical length of stay (SLOS) was defined as >75th percentile. Logistic regression analysis was used to predict this outlier status and linear regression to directly predict SLOS. Acuity adjustment was performed by using the most prevalent variables from multiple NSQIP annual reports. This work was done under the approval of our institutional review board and the data use agreement of the American College of Surgeons. Data were analyzed by using SPSS(®). A total of 45,645 colectomies were reviewed, of which 12,455 (27.3%) were laparoscopic. The 75th percentile for SLOS was 11 days. This implied that 9,249 (27.9%) of the open colectomies were outliers, whereas only 1,152 (9.2%) of laparoscopic colectomies were outliers (p < 0.001). When optimizing a simple linear regression to predict SLOS, using common acuity adjustors (i.e., age, functional status, wound category, etc.), the variable marking open procedures consistently had a coefficient of 1.8, implying that open procedures increased SLOS by 1.8 days (p < 0.001). Utilizing logistic regression to predict outlier status, open colectomies were associated with an odds ratio of 3.79 for outlier status (p < 0.001), thus implying an independent effect on SLOS. These results indicate that laparoscopic colectomy independently decreases SLOS compared with open colectomy. This study is unique in using statistical methods to control for selection bias of patients who might be more "surgically fit."


An exploratory study of the role of trust in medication management within mental health services.
To develop understandings of the nature and influence of trust in the safe management of medication within mental health services. Mental health services in the UK. Qualitative methods were applied through focus groups across three different categories of service user--older adult, adults living in the community and forensic services. An inductive thematic analysis was carried out, using the method of constant comparison derived from grounded theory. Participants' views on the key factors influencing trust and the role of trust in safe medication management. The salient factors impacting trust were: the therapeutic relationship; uncertainty and vulnerability; and social control. Users of mental health services may be particularly vulnerable to adverse events and these can damage trust. Safe management of medication is facilitated by trust. However, this trust may be difficult to develop and maintain, exposing service users to adverse events and worsening adherence. Practice and policy should be oriented towards developing trust.


Extracellular phospholipase A2 activity in cell free peritoneal lavage fluid from mice with zymosan peritonitis.
The kinetics and appearance of extracellular phospholipase A2 (PLA2) activity and its relationship to the appearance of arachidonic acid (AA) metabolites in the peritoneal cavity of mice injected with zymosan is described. AA metabolites levels including leukotriene C4 (LTC4) were maximum 15-30 min after zymosan. Peak PLA2 activity was also found 15-30 min after zymosan and was significantly increased above levels found in saline control exudates (3.83 +/- 0.89 and 0.35 +/- 0.11, respectively, p less than or equal to 0.05). Results show that an extracellular PLA2 is present in zymosan peritonitis.


Analytical expressions for the shape of axisymmetric membranes with multiple domains.
Based on the Canham-Helfrich free energy, we derive analytical expressions for the shapes of axisymmetric membranes consisting of multiple domains. We give explicit equations for both closed vesicles and almost cylindrical tubes. Using these expressions, we also find the shape of a tube attached to a spherical vesicle. The resulting shapes compare well to numerical data, and our expressions can be used to easily determine membrane parameters from experimentally obtained shapes.


Vitamin D and Vitamin D3 Supplementation during Photodynamic Therapy: A Review.
Photodynamic therapy is an unconventional yet increasingly common method of treating dermatological diseases and cancer that is implemented more often in adults than in children. Current clinical uses include treatment of actinic keratosis, superficial basal cell carcinomas, and acne. Despite its high efficiency, photodynamic therapy support supplements have recently been reported in the literature, including calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, and vitamin D3 cholecalciferol. In clinical trials, photodynamic therapy enhanced with vitamin D or D3 supplementation has been reported for treatment of squamous cell skin cancers, actinic keratosis, and psoriasis. Experimental research on the effect of photodynamic therapy with vitamin D or D3 has also been carried out in breast cancer cell lines and in animal models. The aim of this review is to evaluate the usefulness and effectiveness of vitamin D and D3 as supports for photodynamic therapy. For this purpose, the Pubmed and Scopus literature databases were searched. The search keyword was: "vitamin D in photodynamic therapy". In the analyzed articles (1979-2022), the authors found experimental evidence of a positive effect of vitamin D and D3 when used in conjunction with photodynamic therapy. An average of 6-30% (in one case, up to 10 times) increased response to photodynamic therapy was reported in combination with vitamin D and D3 as compared to photodynamic therapy alone. Implementing vitamin D and D3 as a supplement to photodynamic therapy is promising and may lead to further clinical trials and new clinical methodologies.


Cortical signature of clock drawing performance in Alzheimer's disease and mild cognitive impairment.
It is unclear whether clock drawing test (CDT) performance relies on a widely distributed cortical network, or whether this test predominantly taps into parietal cortex function. So far, associations between cortical integrity and CDT impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) largely stem from cortical volume analyses. Given that volume is a product of thickness and surface area, investigation of the relationship between CDT and these two cortical measures might contribute to better understanding of this cognitive screening tool for AD. 38 patients with AD, 38 individuals with MCI and 31 healthy controls (HC) underwent CDT assessment and MRI at 3 Tesla. The surface-based analysis via Freesurfer enabled calculation of cortical thickness and surface area. CDT was scored according to the method proposed by Shulman and related to the two distinct cortical measurements. Higher CDT scores across the entire sample were associated with cortical thickness in bilateral temporal gyrus, the right supramarginal gyrus, and the bilateral parietal gyrus, respectively (p < 0.001 CWP corr.). Significant associations between CDT and cortical thickness reduction in the parietal lobe remained significant when analyses were restricted to AD individuals. There was no statistically significant association between CDT scores and surface area (p < 0.001 CWP corr.). In conclusion, CDT performance may be driven by cortical thickness alterations in regions previously identified as "AD vulnerable", i.e. regions predominantly including temporal and parietal lobes. Our results suggest that cortical features of distinct evolutionary and genetic origin differently contribute to CDT performance.


Excess risk of subsequent malignant neoplasms in adolescent and young adult cancer survivors: Results from the first Italian population-based cohort.
Evidence about late effects in adolescent and young adult (AYA) cancer survivors is scarce. This study assessed the risk of subsequent malignant neoplasms (SMNs) to identify the most common SMNs to be considered in follow-up care. Population-based cancer registries retrospectively identified first primary tumors (between 1976 and 2013) and SMNs in AYAs (15-39 years old at their cancer diagnosis). AYA cancer survivors were those alive at least 5 years after their first cancer diagnosis. The excess risk of SMNs was measured as standardized incidence ratios (SIRs) and absolute excess risk together with the cumulative incidence of SMNs. The cohort included 67,692 AYA cancer survivors. The excess risk of developing any SMN (SIR, 1.6; 95% confidence interval, 1.5-1.7) was 60%. The excess risk of SMNs was significantly high for survivors of lymphomas; cancers of the breast, thyroid, female genital tract, digestive organs, gonads, and urinary tract; and melanomas. The cumulative incidence of all SMNs in AYA cancer survivors within 25 years of their first cancer diagnosis was approximately 10%. Subsequent tumors contributing to approximately 60% of all SMNs were breast cancer, colorectal cancer, corpus uteri cancer, and ovarian cancer in females and colorectal cancer, bladder cancer, prostate cancer, lung cancer, and lymphomas in males. These results highlight the need to personalize follow-up strategies for AYA cancer survivors.


Quantifying the contribution of grape hexoses to wine volatiles by high-precision [U¹³C]-glucose tracer studies.
Many fermentation volatiles important to wine aroma potentially arise from yeast metabolism of hexose sugars, but assessing the relative importance of these pathways is challenging due to high endogenous hexose substrate concentrations. To overcome this problem, gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) was used to measure high-precision (13)C/(12)C isotope ratios of volatiles in wines produced from juices spiked with tracer levels (0.01-1 APE) of uniformly labeled [U-(13)C]-glucose. The contribution of hexose to individual volatiles was determined from the degree of (13)C enrichment. As expected, straight-chain fatty acids and their corresponding ethyl esters were derived almost exclusively from hexoses. Most fusel alcohols and their acetate esters were also majority hexose-derived, indicating the importance of anabolic pathways for their formation. Only two compounds were not derived primarily from hexoses (hexanol and isobutyric acid). This approach can be extended to other food systems or substrates for studying precursor-product relationships.


Analysis of chest wall elevation after the Nuss procedure using 3D body scanning technique in patients with pectus excavatum.
For the evaluation of the chest wall deformity, we adopted a non-invasive 3D body scanning system. The objective of this study is to evaluate surgical effect on the whole thorax using 3D scanning technique before and after Nuss procedure. We performed 3D body scanning using Structure Sensor (Occipital Inc, USA) in 11 symmetric patients (average age 13 ± 3.2) under general anesthesia before and after Nuss procedure. Using the scanned data, the improved chest wall was analyzed using 3D-Rugle (Medic Engineering, Japan) imaging software. Preoperative and postoperative 3D data were super-imposed and a thoracic elevating distance in the line of the axial and sagittal section through the deepest point was calculated. Pre- and postoperative external sternal angle (ESA) were calculated from the scanned data. Mean thoracic elevation distance at the deepest point was 38.6 ± 6.1 mm and it was 28.4 ± 5.1 mm and 19.4 ± 4.9 mm at 4 cm and 8 cm cranial side, respectively. Average ESA improved from 3.9 ± 1.6 degrees to 15.0 ± 1.1 degrees after the operation. Chest depression was effectively elevated 39 mm at the deepest point after Nuss procedure. An indirect elevation effect by pectus bars was found on the wide area of the anterior chest.


Patient-specific Monte Carlo-based dose-kernel approach for inverse planning in afterloading brachytherapy.
Brachytherapy planning software relies on the Task Group report 43 dosimetry formalism. This formalism, based on a water approximation, neglects various heterogeneous materials present during treatment. Various studies have suggested that these heterogeneities should be taken into account to improve the treatment quality. The present study sought to demonstrate the feasibility of incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to improve the dose conformity and increase the treatment quality. The method was based on precalculated dose kernels in full patient geometries, representing the dose distribution of a brachytherapy source at a single dwell position using MC simulations and the Geant4 toolkit. These dose kernels are used by the inverse planning by simulated annealing tool to produce a fast MC-based plan. A test was performed for an interstitial brachytherapy breast treatment using two different high-dose-rate brachytherapy sources: the microSelectron iridium-192 source and the electronic brachytherapy source Axxent operating at 50 kVp. A research version of the inverse planning by simulated annealing algorithm was combined with MC to provide a method to fully account for the heterogeneities in dose optimization, using the MC method. The effect of the water approximation was found to depend on photon energy, with greater dose attenuation for the lower energies of the Axxent source compared with iridium-192. For the latter, an underdosage of 5.1% for the dose received by 90% of the clinical target volume was found. A new method to optimize afterloading brachytherapy plans that uses MC dosimetric information was developed. Including computed tomography-based information in MC dosimetry in the inverse planning process was shown to take into account the full range of scatter and heterogeneity conditions. This led to significant dose differences compared with the Task Group report 43 approach for the Axxent source.


Cellular Senescence and the Senescence-Associated Secretory Phenotype as Drivers of Skin Photoaging.
Chronic exposure to UVR is known to disrupt tissue homeostasis, accelerate the onset of age-related phenotypes, and increase the risk for skin cancer-a phenomenon defined as photoaging. In this paper, we review the current knowledge on how UV exposure causes cells to prematurely enter cellular senescence. We describe the mechanisms contributing to the accumulation of senescent cells in the skin and how the persistence of cellular senescence can promote impaired regenerative capacity, chronic inflammation, and tumorigenesis associated with photoaging. We conclude by highlighting the potential of senolytic drugs in delaying the onset and progression of age-associated phenotypes in the skin.


Estimation of the concordance correlation coefficient for repeated measures using SAS and R.
The concordance correlation coefficient is one of the most common approaches used to assess agreement among different observers or instruments when the outcome of interest is a continuous variable. A SAS macro and R package are provided here to estimate the concordance correlation coefficient (CCC) where the design of the data involves repeated measurements by subject and observer. The CCC is estimated using U-statistics (UST) and variance components (VC) approaches. Confidence intervals and standard errors are reported along with the point estimate of the CCC. In the case of the VC approach, the linear mixed model output and variance components estimates are also provided. The performance of each function is shown by means of some examples with real data sets.