Coalescence-Induced Jumping for Removing the Deposited Heterogeneous Droplets: A Molecular Dynamics Simulation Study.
The removal of the deposited droplets on a solid surface is crucial to considerable practical applications that require self-cleaning properties. In this work, a strategy of cleaning a deposited droplet ("D-droplet") by coalescing with a heterogeneous and easily jumping droplet ("J-droplet") is proposed. Molecular dynamics simulation studies have shown that the coalescence of these two kinds of droplets would not guarantee the removal of D-droplet, unless the lifting ability of J-droplet is enhanced through the reduction of the solid-liquid interaction. However, this is a bad scenario with low efficiency. Further investigation suggests that by introducing two J-droplets to produce triple-coalescence dynamics, the D-droplet could be successfully jumping from the substrates due to the coalescence-induced effect, which is also verified by the free energy calculation. Moreover, the effects of the size of the droplets and the arrangement mode of these three droplets on the jumping dynamics are both considered. The studies not only help advance our understanding of coalescence-induced jumping of heterogeneous droplets, but also open up new ways to remove the deposited impure droplets, which is expected to guide the fields of self-cleaning.


The prognostic value of cardiopulmonary exercise testing in interstitial lung disease: a systematic review.
The heterogeneity of interstitial lung disease (ILD) results in prognostic uncertainty concerning end-of-life discussions and optimal timing for transplantation. Effective prognostic markers and prediction models are needed. Cardiopulmonary exercise testing (CPET) provides a comprehensive assessment of the physiological changes in the respiratory, cardiovascular and musculoskeletal systems in a controlled laboratory environment. It has shown promise as a prognostic factor for other chronic respiratory conditions. We sought to evaluate the prognostic value of CPET in predicting outcomes in longitudinal studies of ILD. MEDLINE, Embase and the Cochrane Database of Systematic Reviews were used to identify studies reporting the prognostic value of CPET in predicting outcomes in longitudinal studies of ILD. Study quality was assessed using the Quality in Prognosis Study risk of bias tool. Thirteen studies were included that reported the prognostic value of CPET in ILD. All studies reported at least one CPET parameter predicting clinical outcomes in ILD, with survival being the principal outcome assessed. Maximum oxygen consumption, reduced ventilatory efficiency and exercise-induced hypoxaemia were all reported to have prognostic value in ILD. Issues with study design (primarily due to inherent problems of retrospective studies, patient selection and presentation of numerous CPET parameters), insufficient adjustment for important confounders and inadequate statistical analyses limit the strength of the conclusions that can be drawn at this stage. There is insufficient evidence to confirm the value of CPET in facilitating "real-world" clinical decisions in ILD. Additional prospective studies are required to validate the putative prognostic associations reported in previous studies in carefully phenotyped patient populations.


Assessing sleep behaviors in Latino children and adolescents: what is known, what are we missing, and how do we move forward?
Sleep health is a commonly overlooked component of pediatric cardiometabolic risk. Disparities in sleep duration and meeting of pediatric sleep guidelines have been well documented among at-risk populations in the United States, including Latinos. However, sleep research often fails to describe or account for contextual and cultural factors impacting the ability for Latino families to meet guidelines. The current review focuses on recent findings related to measurement of sleep duration, understanding of contextual factors that impact sleep hygiene, and interventions designed to increase sleep duration and quality among U.S. Latino families with infants, young children, and adolescents. Ten studies focusing on sleep health in U.S. Latino children, using different study designs were identified. Overall, cross-sectional studies confirmed inadequate sleep among Latino children, intervention studies demonstrated promise of culturally-sensitive health behavior education for improving sleep in early childhood, and qualitative studies highlighted neighborhood and cultural factors that impact sleep quality. Rather than new prevalence studies on adherence to sleep recommendations among Latino families, research focusing on adapting clinical guidelines to accommodate the realities of many Latino families (e.g., co-sleeping and bedsharing) will advance our knowledge. A shift towards objective measurement of the 24-h period as well as evaluating specific contextual barriers that make It challenging to meet sleep guidelines for Latino children is needed.


Birth size is not associated with depressive symptoms from adolescence to middle-age: results from the Northern Swedish Cohort study.
Low birth weight has been shown to be related to increased risk of depression later in life - but the evidence is not conclusive. We examined the association of size at birth with repeatedly measured depressive symptoms in 947 individuals from the Northern Swedish Cohort, a community-based age-homogeneous cohort born in 1965, and followed with questionnaires between ages 16 and 43 (participation rate above 90% in all the surveys). Information on birth size was retrieved from archived birth records. Length of gestation was known for a subsample of 512 individuals (54%). We studied the association of birth weight and ponderal index with self-reported depressive symptoms at ages 16, 21, 30 and 43; with the life-course average of depressive symptoms score and with longitudinal trajectories of depressive symptoms retrieved by latent class growth analysis. Socioeconomic background, mental illness or alcohol problems of a parent, exposure to social adversities in adolescence and prematurity were accounted for in the analyses. We did not find any relationship between weight or ponderal index at birth and our measure of depressive symptoms between ages 16 and 43 in a series of different analyses. Adjustment for length of gestation did not alter the results. We conclude that size at birth is not associated with later-life depressive symptoms score in this cohort born in the mid-1960s in Sweden. The time and context need to be taken into consideration in future studies.


Evidence for prescribing exercise as treatment in pediatric rheumatic diseases.
There has been an increasing recognition of adverse short-, mid-, or long-term effects associated with the treatment as well as the disease itself that impair the health-related quality of life and functional capacity of children and adolescents with rheumatic diseases. Interestingly, cumulative evidence has suggested that exercise training may benefit patients with juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, juvenile dermatomyositis and juvenile fibromyalgia, attenuating several clinical symptoms related to physical disability. Remarkably, recent evidence also suggests that exercise may have direct effects on the pathogenesis of autoimmune diseases by attenuating chronic low-grade systemic inflammation. It is also important to emphasize that no exercise-related adverse effects have been reported. This short review provides the evidence for physical training as a treatment of pediatric rheumatic diseases, introducing a novel concept that exercise is a treatment for these populations.


Parental nutritional programming and a reminder during juvenile stage affect growth, lipid metabolism and utilisation in later developmental stages of a marine teleost, the gilthead sea bream (Sparus aurata).
Nutrition during periconception and early development can modulate metabolic routes to prepare the offspring for adverse conditions through a process known as nutritional programming. In gilthead sea bream, replacement of fish oil (FO) with linseed oil (LO) in broodstock diets improves growth in the 4-month-old offspring challenged with low-FO and low-fishmeal (FM) diets for 1 month. The present study further investigated the effects of broodstock feeding on the same offspring when they were 16 months old and were challenged for a second time with the low-FM and low-FO diet for 2 months. The results showed that replacement of parental moderate-FO feeding with LO, combined with juvenile feeding at 4 months old with low-FM and low-FO diets, significantly (P<0·05) improved offspring growth and feed utilisation of low-FM/FO diets even when they were 16 months old: that is, when they were on the verge of their first reproductive season. Liver fatty acid composition was significantly affected by broodstock or reminder diets as well as by their interaction. Moreover, the reduction of long-chain PUFA and increase in α-linolenic acid and linoleic acid in broodstock diets lead to a significant down-regulation of hepatic lipoprotein lipase (P<0·001) and elongation of very long-chain fatty acids protein 6 (P<0·01). Besides, fatty acid desaturase 2 values were positively correlated to hepatic levels of 18 : 4n-3, 18 : 3n-6, 20 : 5n-3, 22 : 6n-3 and 22 : 5n-6. Thus, this study demonstrated the long-term nutritional programming of gilthead sea bream through broodstock feeding, the effect of feeding a 'reminder' diet during juvenile stages to improve utilisation of low-FM/FO diets and fish growth as well as the regulation of gene expression along the fish's life-cycle.


Reliability and validity of the self-efficacy for exercise and outcome expectations for exercise scales with minority older adults.
Older African Americans and Latinos tend to exercise less than older Whites and are more likely to have chronic diseases that could benefit from exercise. Measurement of self-efficacy of exercise and exercise outcome expectations in this older population is required if exercise is to be monitored carefully and enhanced in this population. The purpose of this study was to test the reliability and validity of the Self-Efficacy for Exercise Scale (SEE) and Outcome Expectations for Exercise Scale (OEE) in a sample of African American and Latino older adults. A total of 166 individuals, 32 males (19%) and 134 females (81%) with an average age of 72.8 +/- 8.4 years participated in the study. The SEE and OEE scales were completed using face-to-face interviews. There was evidence of internal consistency for both scales with alphas of .89 and .90 for the SEE scale and .72 and .88 for the OEE scale. There was some evidence of validity for both scales based on confirmatory factor analysis and hypothesis testing, because factor loadings were greater than .50 in all but two items in the OEE, and there were significant relationships between self-efficacy and outcome expectations and exercise behavior at all testing time-points. The measurement models showed a fair fit of the data to the models. The study provided some evidence for the reliability and validity of the SEE and OEE when used with minority older adults, and it provides some guidelines for future scale revisions and use.


Three-year outcomes following 1420 ABO-incompatible living-donor kidney transplants performed after ABO antibody reduction: results from 101 centers.
Reports from experienced centers suggest that recipients of an ABO-incompatible living-donor kidney transplant after reduction of ABO antibodies experience no penalty in graft and patient survival versus ABO-compatible transplants, but confirmation that these results can be widely replicated is lacking. Living-donor kidney transplants from ABO-incompatible donors after ABO antibody reduction registered with the Collaborative Transplant Study during 2005 to 2012 were analyzed and compared with (i) a matched group of ABO-compatible transplant recipients and (ii) all ABO-compatible transplants from centers that performed at least five ABO-incompatible grafts during the study period. One thousand four hundred twenty living-donor ABO-incompatible kidney transplants were analyzed. Three-year death-censored graft survival was virtually identical for ABO-incompatible transplants versus matched and center controls (P=0.92 and P=0.60, respectively). Patient survival rates were also similar (P=0.15 and P=0.11, respectively). Early patient survival was lower in ABO-incompatible grafts (P=0.006 vs. matched controls; P=0.001 vs. center controls) because of a higher rate of early infectious death (P=0.037 and P<0.001, respectively). Death-censored graft and patient survival were not significantly affected by induction therapy and anti-CD20 treatment. ABO antibody reduction by column adsorption was associated with similar death-censored graft survival to plasmapheresis. In this analysis of prospectively collected data from a large series of ABO-incompatible living-donor kidney transplants performed at 101 centers, death-censored graft and patient survival rates were similar to those achieved in ABO-compatible control groups over the same period.


Genetics of colon carcinogenesis in mice treated with 1,2-dimethylhydrazine.
Genetic analysis of colon tumor induction by symmetrical 1,2-dimethylhydrazine (DMH) was undertaken in F1, F2, and reciprocal backcross hybrids derived from a cross between two inbred mouse strains, the 100% susceptible ICR/Ha and completely resistant C57BL/Ha. Mice, 12 to 14 weeks old, received 22 successive weekly s.c. injections of 0.35% aqueous solution of DMH buffered to pH 6.5. A dose of 15 mg/kg/mouse/week produced invasive colon adenocarcinomas in all ICR/Ha males and females (60 of 60) within 22 weeks. None of the 90 C57BL/Ha mice developed DMH tumors during 44 weeks of observation. Susceptibility to the carcinogen was dominant, as indicated by 100% colon tumor incidence in reciprocal ICR/Ha X C57BL/HaF1 hybrids (68 of 68) and in the susceptible backcross ICR/Ha X F1 (42 of 42). Tumor yield in F2 hybrids (94 of 120) was 78%, which is in close agreement with the 3:1 ratio expected if a single dominant DMH susceptibility gene is inherited via the F1 from the ICR/Ha grandparent. Likewise, tumor yield in resistant backcross mice of genotype C57BL/Ha X F1 (46 of 117) is not out of line with the anticipated 1:1 ratio in the latter type of test hybrids. Tests with five isozyme markers and two coat color genes have tentatively ruled out linkage of DMH susceptibility on seven autosomes. The 47% tumor incidence among 57 male resistant backcross hybrids, regardless of whether their single X chromosome was inherited from the ICR/Ha or C57BL/Ha strain, provides evidence against sex linkage.


Soy protein isolate-guar gum-goose liver oil O/W Pickering emulsions that remain stable under accelerated oxidation at high temperatures.
Goose liver oil (GLO) is a solid-liquid mixture, rich in polyunsaturated fatty acids and high in nutritional value, but poor in fluidity and easily oxidized. Therefore, oil-in-water (O/W) Pickering emulsions of three polysaccharides and soy protein isolate (SPI) with GLO were prepared to improve the stability of it. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Fourier-transform infrared spectroscopy, and zeta potential revealed that the SPI and complexes with konjac glucomannan, pectin, and guar gum (GG) ranged from 17 to 75 kDa, with the site of action being the -OH stretch and the amide group, and bound by hydrogen bonding. Adding konjac glucomannan and GG significantly increased the water contact angle of the SPI to 74.1° and 59.0°, respectively. Therefore, the protein-polysaccharide complexes could enhance the emulsion stability. In addition, the O/W Pickering emulsions with GLO had near-Newtonian fluid rheological properties with a significant increase in apparent viscosity and viscoelasticity, forming a dual network structure consisting of a ductile and flexible protein network and a rigid and brittle polysaccharide network. The microstructure observation indicated that the O/W emulsions were spherical and homogeneous. The highest emulsification activity was observed for the SPI-GG-GLO emulsions, without significant delamination or flocculation and high oxidative stability after 7 days in storage. These results demonstrate that the construction of SPI-GG-GLO O/W Pickering emulsions can stabilize GLO even at high temperatures that promote oxidation. © 2023 Society of Chemical Industry.


Phase I/II study of decitabine in patients with myelodysplastic syndrome: a multi-center study in Japan.
The management of myelodysplastic syndrome (MDS) remains challenging. We performed a phase I/II study to evaluate the safety and efficacy of decitabine in patients with MDS in Japan. Patients with MDS with red cell transfusion dependence or 5-30% blasts in marrow and with an International Prognostic Scoring System score of intermediate-1 or higher were eligible. Patients received intravenous decitabine at 15 or 20 mg/m(2) daily for 5 days every 4 weeks. A total of 37 patients were enrolled. Three patients received 15 mg/m(2) and experienced no dose limiting toxicity during the first cycle. Thirty-four patients received 20 mg/m(2) . Grade 3 or greater non-hematologic toxicities included cerebral infarction (n = 1), subdural hematoma (n = 1), elevated blood glucose (n = 1), and pulmonary hypertension (n = 1). At 20 mg/m(2) , complete response, partial response, and hematologic improvement were observed in 7 (20.6%), 2 (5.9%), and 7 (20.6%) patients, respectively. Complete cytogenetic response was observed in 30% of evaluable 20 patients. The median number of cycles to clinical response was 4 (range 4-8), and duration of remission was 474+ days (range 294-598+). The 2-year rate of acute myeloid leukemia-free survival was 52%. Correlative studies revealed hypomethylation in multiple genes in peripheral blood cells after treatment. Hypomethylation was generally more profound in CD15 + peripheral blood cells, which reflects myeloid cells, than in peripheral blood mononuclear cells. In summary, decitabine was safe and demonstrated efficacy in Japanese patients with high-risk MDS. This trial was registered at ClinicalTrials.gov (NCT00796003).


Analysis of the accuracy and reliability of the Short-Form Fonseca Anamnestic Index in the diagnosis of myogenous temporomandibular disorder in women.
The Fonseca Anamnestic Index is a questionnaire used to classify individuals with temporomandibular disorders. Previous studies have shown that the Fonseca Anamnestic Index provides a multidimensional measurement of the temporomandibular disorders construct and that the main dimension presents a good fit to the model according to the item response theory. To evaluate the between-day reliability, accuracy, and best cut-off score of the Short-Form Fonseca Anamnestic Index for the diagnosis of myogenous temporomandibular disorders. The sample consisted of 123 women (57 with myogenous temporomandibular disorders and 66 asymptomatic), evaluated by the Research Diagnostic Criteria for Temporomandibular Disorders. The participants answered the Short-Form Fonseca Anamnestic Index on two occasions with a seven-day interval between tests. For the analysis of between-day reliability, the intraclass correlation coefficient, the standard error of measurement and the minimum detectable change were used. The Receiver Operating Characteristic curve was used to determine the diagnostic accuracy and the best cut-off point. The Short-Form Fonseca Anamnestic Index demonstrated excellent reliability (intraclass correlation coefficient≥0.95) for all items and for the total Short-Form Fonseca Anamnestic Index score (intraclass correlation coefficient=0.98; standard error of measurement=3.28; minimum detectable change=9.09). The level of accuracy of the Short-Form Fonseca Anamnestic Index for the diagnosis of myogenous temporomandibular disorders was high (area under the curve of 0.97), with a better cut-off score of 17.5 points. The Fonseca Anamnestic Index should be used in its short form to classify the absence of myogenous temporomandibular disorders (scores between 0 and 15 points) or presence of myogenous temporomandibular disorders (scores between 20 and 50 points) in women.


Temporal relationship between uric acid concentration and risk of diabetes in a community-based study population.
Some observational studies have identified elevated uric acid concentration as a risk factor for diabetes, while others have found an inverse relationship. We examined both the association of uric acid level with incident diabetes and the change in uric acid concentration after a diabetes diagnosis. We analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study and quantified the independent association between uric acid level and incident diabetes via Cox proportional hazards models. The association between duration of diabetes and change in uric acid level was examined via linear regression. Among 11,134 participants without diagnosed diabetes at baseline (1987-1989), there were 1,294 incident cases of diabetes during a median of 9 years of follow-up (1987-1998). Uric acid level was associated with diabetes even after adjustment for risk factors (per 1 mg/dL, hazard ratio = 1.18, 95% confidence interval: 1.13, 1.23), and the association remained significant after adjustment for fasting glucose and insulin levels. Among participants with diabetes (n = 1,510), every additional 5 years' duration of diabetes was associated with a 0.10-mg/dL (95% confidence interval: 0.04, 0.15) lower uric acid level after adjustment. We conclude that uric acid concentration rises prior to diagnosis of diabetes and then declines with diabetes duration. Future studies investigating uric acid as a risk factor for cardiovascular disease should adequately account for the impact and timing of diabetes development.


Association Between Teaching Status and Mortality in US Hospitals.
Few studies have analyzed contemporary data on outcomes at US teaching hospitals vs nonteaching hospitals. To examine risk-adjusted outcomes for patients admitted to teaching vs nonteaching hospitals across a broad range of medical and surgical conditions. Use of national Medicare data to compare mortality rates in US teaching and nonteaching hospitals for all hospitalizations and for common medical and surgical conditions among Medicare beneficiaries 65 years and older. Hospital teaching status: major teaching hospitals (members of the Council of Teaching Hospitals), minor teaching hospitals (other hospitals with medical school affiliation), and nonteaching hospitals (remaining hospitals). Primary outcome was 30-day mortality rate for all hospitalizations and for 15 common medical and 6 surgical conditions. Secondary outcomes included 30-day mortality stratified by hospital size and 7-day mortality and 90-day mortality for all hospitalizations as well as for individual medical and surgical conditions. The sample consisted of 21 451 824 total hospitalizations at 4483 hospitals, of which 250 (5.6%) were major teaching, 894 (19.9%) were minor teaching, and 3339 (74.3%) were nonteaching hospitals. Unadjusted 30-day mortality was 8.1% at major teaching hospitals, 9.2% at minor teaching hospitals, and 9.6% at nonteaching hospitals, with a 1.5% (95% CI, 1.3%-1.7%; P < .001) mortality difference between major teaching hospitals and nonteaching hospitals. After adjusting for patient and hospital characteristics, the same pattern persisted (8.3% mortality at major teaching vs 9.2% at minor teaching and 9.5% at nonteaching), but the difference in mortality between major and nonteaching hospitals was smaller (1.2% [95% CI, 1.0%-1.4%]; P < .001). After stratifying by hospital size, 187 large (≥400 beds) major teaching hospitals had lower adjusted overall 30-day mortality relative to 76 large nonteaching hospitals (8.1% vs 9.4%; 1.2% difference [95% CI, 0.9%-1.5%]; P < .001). This same pattern of lower overall 30-day mortality at teaching hospitals was observed for medium-sized (100-399 beds) hospitals (8.6% vs 9.3% and 9.4%; 0.8% difference between 61 major and 1207 nonteaching hospitals [95% CI, 0.4%-1.3%]; P = .003). Among small (≤99 beds) hospitals, 187 minor teaching hospitals had lower overall 30-day mortality relative to 2056 nonteaching hospitals (9.5% vs 9.9%; 0.4% difference [95% CI, 0.1%-0.7%]; P = .01). Among hospitalizations for US Medicare beneficiaries, major teaching hospital status was associated with lower mortality rates for common conditions compared with nonteaching hospitals. Further study is needed to understand the reasons for these differences.


Cell type- and region-specific enhancement of adult hippocampal neurogenesis by daidzein in middle-aged female mice.
Adult hippocampal neurogenesis is associated with various brain functions, such as learning, memory, and emotion. Intriguingly, reduction in new cell production in the hippocampus in middle age may underlie some of the cognitive deficits. Among several factors that may affect adult hippocampal neurogenesis, estrogens have been suggested to be critically involved in the cognitive impairment of postmenopausal women. Phytoestrogens, such as daidzein and genistein, are expected to work as estrogen substitutes. In this study, we aimed to clarify the effects of daidzein on adult hippocampal neurogenesis using middle-aged (12-month-old) female mice. Animals received daily intraperitoneal injections of daidzein or vehicle for four weeks, and the cells at specific stages of neurogenesis were presumptively defined using molecular markers. Administration of daidzein did not affect the numerical densities (NDs) of primary progenitors, early transient amplifying progenitors (TAPs), and astrocytes. In contrast, the NDs of late TAPs, neural progenitors, and immature granule cells were increased by daidzein. The NDs of proliferating cells, but not apoptotic cells, were also increased by daidzein. To examine the effects of daidzein on maturation of adult-born cells, we three-dimensionally traced their dendritic arbors: the branch number, total length, and intersection number (Sholl analysis) of immature granule cells were increased by daidzein. In general, the effects of daidzein were more dominant in the dorsal region than in the ventral region. The cell type- and region-specific enhancement of adult hippocampal neurogenesis by daidzein provides a key to understanding the actions of estrogen substitutes for the treatment of postmenopausal women.


Treatment-refractory myasthenia gravis.
Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission and is a prototypical autoimmune disorder. Most patients with MG are successfully treated with acetylcholinesterase inhibitors, corticosteroids, and/or steroid sparing agents such as azathioprine and mycophenolate mofetil. There is a small subset of patients, however, with treatment-refractory disease. In these cases, medications such as rituximab, high-dose cyclophosphamide, and eculizumab may be used. Thymectomy (in some cases repeat thymectomy) is another option in selected patients. Studies evaluating these and other forms of therapy in treatment-refractory MG are reviewed.


New trends in tinnitus management.
Tinnitus is a perception of sound in absence of sound stimulation. Tinnitus in many cases cannot be eliminated by conventional medical treatment with drugs or surgery. Some people who begin to notice tinnitus, whether spontaneous or induced by noise, trauma or other insult, will experience spontaneous resolution, but many patients will have persistent tinnitus. For some of them, tinnitus sensation will be joined by tinnitus suffering, with many adverse effects like anxiety, depression and sleep disorders. For these tinnitus sufferers the psychological and acoustic approach proposed by the Tinnitus Retraining Therapy and Acoustic Desensitization Protocol may be helpful. Periodically new treatments are suggested like low-frequency repetitive transcranial magnetic stimulation and sequential phase shift sound cancellation treatment based on the frequency and loudness matching of the tinnitus. The aim of this work is to review modern considerations for the treatment of tinnitus.


Altered lung motion is a sensitive indicator of regional lung disease.
Since lung diseases adversely affect airflow during breathing, they must also alter normal lung motion, which can be exploited to detect these diseases. However, standard imaging techniques such as CT and MRI imaging during breath-holds provide little or no information on lung motion and cannot detect diseases that cause subtle changes in lung structure. Phase-contrast X-ray imaging provides images of high contrast and spatial resolution with temporal resolutions that allow multiple images to be acquired throughout the respiratory cycle. Using X-ray phase-contrast imaging, coupled with velocimetry, we have measured lung tissue movement and determined velocity fields that define speed and direction of regional lung motion throughout a breath in normal Balb/c nude male mice and mice exposed to bleomycin. Regional maps of lung tissue motion reveal both the heterogeneity of normal lung motion, as well as abnormal motion induced by bleomycin treatment. Analysed histologically, bleomycin treatment caused pathological changes in lung structure that were heterogenous, occupying less than 12% of the lung at 6 days after treatment. Moreover, plethysmography failed to detect significant changes in compliance at either 36 h or 6 days after treatment. Detailed analysis of the vector fields demonstrated major differences (p < 0.001) in regional lung motion between control and bleomycin-treated mice at both 36 h and 6 days after treatment. The results of this study demonstrate that X-ray phase-contrast imaging, coupled with velocimetry, can detect early stage, subtle and non-uniform lung disease.


Soluble B7-H3 in Colorectal Cancer.
We present the results of comparative ELISA of the concentration of soluble form of immunity checkpoint B7-H3 (sB7-H3) in the serum of patients with colorectal cancer (CRC) at different stages before treatment and healthy control donors. The analysis revealed a statistically significant difference between the median levels of sB7-H3 in the blood serum of CRC patients (19.66 ng/ml) and healthy donors (16.76 ng/ml) (p=0.0025). ROC analysis showed 62.9% sensitivity and 56.7% specificity for CRC patients (cut-off 17.62 ng/ml; p=0.0028). An association of sB7-H3 levels with tumor progression was revealed. We demonstrated that sB7-H3 levels were significantly lower in patients with regional metastases than in patients without metastases (p=0.039) and that sB7-H3 concentration tends to decrease at the late stages of the disease. Thus, high serum level of sB7-H3 in CRC patients can be a favorable prognostic factor in future.


Osteocalcin triggers Fas/FasL-mediated necroptosis in adipocytes via activation of p300.
The uncarboxylated form of osteocalcin (GluOC) regulates glucose and lipid metabolism in mice. We previously showed that low-dose (≤10 ng/ml) GluOC induces the expression of adiponectin and peroxisome proliferator-activated receptor γ (PPARγ) via a cAMP-PKA-ERK-CREB signaling pathway in 3T3-L1 adipocytes. We also noticed that high-dose (≥20 ng/ml) GluOC inhibits the expression of adiponectin and PPARγ in these cells. We have here explored the mechanism underlying these effects of high-dose GluOC. High-dose GluOC triggered morphological changes in 3T3-L1 adipocytes suggestive of the induction of cell death. It activated the putative GluOC receptor GPRC6A and thereby induced the production of cAMP and activation of protein kinase A (PKA), similar to signaling by low-dose GluOC with the exception that the catalytic subunit of PKA also entered the nucleus. Cytosolic PKA induced phosphorylation of cAMP response element-binding protein (CREB) at serine-133 via extracellular signal-regulated kinase (ERK). Nuclear PKA appeared to mediate the inhibitory phosphorylation of salt-inducible kinase 2 (SIK2) at serine-358 and thereby to alleviate the inhibitory phosphorylation of the CREB co-activator p300 at serine-89. The activation of CREB and p300 resulted in increased expression of the transcription factor FoxO1 and consequent upregulation of Fas ligand (FasL) at the plasma membrane. The interaction of FasL with Fas on neighboring adipocytes triggered the phosphorylation at threonine-357/serine-358 and homotrimerization of mixed-lineage kinase domain-like protein (MLKL), a key regulator of necroptosis, as well as Ca2+ influx via transient receptor potential melastatin 7 (TRPM7), the generation of reactive oxygen species and lipid peroxides, and dephosphorylation of dynamin-related protein 1 (DRP1) at serine-637, resulting in mitochondrial fragmentation. Together, our results indicate that high-dose GluOC triggers necroptosis through upregulation of FasL at the plasma membrane in a manner dependent of activation of CREB-p300, followed by the activation of Fas signaling in neighboring adipocytes.


Angiotensin II decreases mortality rate in gerbils with unilateral carotid ligation.
Evidence indicates that after vascular occlusion, infusion of angiotensin II restores blood supply to ischemic tissues by stimulating the development of collateral circulation through a mechanism independent of the mechanical effects of increased blood pressure. To test this effect in focal cerebral ischemia, angiotensin II was intravenously administered for four hours to gerbils immediately after unilateral carotid ligation. Three different pressor doses, 50, 250, and 500 ng/kg/min, were used, and mortality rate was evaluated at 1 and 2 days after vascular occlusion. Two additional groups similarly prepared were infused either with saline or with the pressor agent metaraminol. There was a significant inverse relationship between the infusion dose of angiotensin II and mortality: the greater the infusion dose of angiotensin II, the lower the mortality rate. Infusion of metaraminol, at the dose chosen to mimic the pressor effect of the highest angiotensin II dose, yielded a mortality rate which was statistically indistinguishable from that obtained with saline infusion. It is concluded that the mortality rate after unilateral carotid occlusion is significantly reduced by intravenous administration of angiotensin II through mechanisms unrelated to its hypertensive action. Evidence suggests that this may occur by the enhancement of the development of collateral circulation and therefore the reduction of the severity of brain ischemia.


Adjuvant Topical Interferon Alpha 2b for the Treatment of Monkeypox Ocular Manifestations.
The aim of this study was to report a case of ocular Mpox that responded favorably to treatment with topical interferon and oral doxycycline. This is a case report of a previously healthy 24-year-old woman who developed a pustular rash, headache, fever, arthralgia, sore throat, and asthenia 3 weeks before attending to our clinic. Her main complaint at the moment of the visit was pain, photophobia, foreign body sensation, blurred vision, red eye, and discharge on the left eye. The slit-lamp examination of the left eye showed severe conjunctival hyperemia associated with tarsal follicles, 360 degrees ciliary injection, diffuse corneal epithelial edema with white linear epithelial infiltrates, pigmented and nonpigmented keratic precipitates, and two 1-mm peripheral corneal ulcers with white infiltrates, associated with positive fluorescein staining. Anterior chamber cellularity and flare were mildly present. Mpox with ocular manifestations diagnosis was confirmed by real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) testing; samples were taken from corneal, conjunctival, and nasopharynx swab as well as a skin scab. Topical interferon alpha 2b 1 MIU/mL every 6 hours for 1 month and oral doxycycline 100 mg BID were administered along with other medications with consequent decrease of inflammation and malaise symptoms 1 week later, associated with uncorrected visual acuity improvement. Alternative and efficacious treatment options for Mpox ocular manifestations are needed to prevent further disease progression and sequelae in countries with no access to the gold-standard therapy. Topical interferon alpha 2b and oral doxycycline have shown adequate response as shown with this patient.


Differences Across Illness Perceptions in Inflammatory Bowel Disease and Their Relationships to Psychological Distress and Quality of Life.
Patients with greater inflammatory bowel disease activity readily identify poorer psychosocial outcomes; however, the role of gender, disease type, and individual illness perceptions facets are less well known. This study aimed to characterize the role of illness perceptions, gender, and disease type on anxiety, depression, and quality of life. Eighty-one patients diagnosed with inflammatory bowel disease (39 men, mean age 35 years) attending a tertiary hospital outpatient clinic were studied. Questionnaires used included the Manitoba Index, the Brief Illness Perceptions Questionnaire, Hospital Anxiety and Depression Scale, and the World Health Organization Brief Quality of Life Scale. Female patients with active disease tended to report increased anxiety, depression, and reduced quality of life. Regarding illness perceptions, patients with Crohn disease reported significantly more concerns about its chronicity, while female patients reported being significantly more concerned about the impact of their illness on identity, chronicity, overall concern, and having a greater emotional impact. Hierarchical regression indicated that 36% of depression, 42% of anxiety, and 57% of quality of life could be accounted for by disease activity and type, gender, and illness perceptions. The findings suggest that in addition to a patient's perceived disease status, gastroenterology nurses should also be aware that patient gender and their perceptions of illness play a significant impact not only on anxiety and depression but also on quality of life. Increased disease activity is associated with more severe anxiety and depression and reduced quality of life. Female patients are also at a greater risk of reporting negative illness perceptions and increased levels of anxiety, depression, and lower quality of life.


Effectiveness of task-shifting for the detection of diabetic retinopathy in low- and middle-income countries: a rapid review protocol.
Diabetic retinopathy is the most common ocular complication of diabetes and a cause of vision loss in adults. Diabetic retinopathy screening leading to early identification of the disease followed by timely treatment, can prevent vision loss in people living with diabetes. A key barrier to the implementation of screening services in low- and middle-income countries is the low number of ophthalmologists per million population. Interventions that shift screening to non-ophthalmology cadres have been implemented in programmes in low- and middle-income countries and are routinely used in high-income countries. The aim of this rapid review is to summarise the published literature reporting the effectiveness of task-shifting interventions for the detection of diabetic retinopathy by non-ophthalmologists in low- and middle-income countries. We will search MEDLINE, Embase, Global Health and Cochrane Register of Studies for studies reporting task-shifting interventions for diabetic retinopathy detection. The review will include studies published in the last 10 years in the English language. We will include any interventional or observational comparative study measuring outcomes in terms of participation or access to diabetic retinopathy detection services (uptake) and quality of diabetic retinopathy detection services (detection, severity, diagnostic accuracy). For included studies, cost-effectiveness of the task-shifting intervention will also be presented. Two reviewers will screen search results independently. The risk of bias assessment and data extraction will be carried out by one reviewer with verification of 10% of the papers by a second reviewer. The results will be synthesised narratively. Differences in health systems organization, structure and resources will determine the need and success of task-shifting interventions for DR screening. The review will examine how these interventions have been used and/or tested in LMICs. The results will be of interest to policy makers and programme managers tasked with designing and implementing services to prevent and manage diabetes and its complications in similar settings. OSF: https://osf.io/dfhg6/ .


How Qualitative Case Study Methodology Informs Occupational Therapy Practice: A Scoping Review.
Qualitative case study methodology (QCSM) is a useful research approach that has grown in popularity within the social sciences; however, it has received less attention in the occupational therapy literature. The current scoping review aims to explore how studies utilizing a QCSM help inform occupational therapy knowledge and practice. Electronic searches were conducted in April 2017, and the resultant 388 publications were screened by three reviewers in Covidence. In all, 27 publications met the inclusion criteria and were included in the scoping review. Case studies in the occupational therapy literature have explored phenomena relating to the delivery of intervention, theoretical concepts, clinical reasoning, and education and research methods and were situated in a range of different practice areas and contexts. QCSM is a valuable approach in occupational therapy research that contributes to the body of knowledge and theory that informs occupational therapy practice.


A Phase I and pharmacokinetic study of squalamine, an aminosterol angiogenesis inhibitor.
The purpose of this study was to assess the feasibility and characterize the pharmacokinetics of squalamine administered as a continuous i.v. infusion daily for 5 days every 3 weeks. Patients with advanced solid malignancies were treated with escalating doses of squalamine as a 5-day continuous i.v. infusion every 3 weeks. Doses were initially escalated in 100% increments from a starting dose of 6 mg/m(2)/day, with a single patient treated at each dose level until moderate toxicity was observed, at which time additional patients were treated. Thirty-three patients were treated with 73 courses of squalamine at 13 dose levels ranging from 6 to 700 mg/m(2)/day. Hepatotoxicity, characterized by brief, asymptomatic elevations in transaminases and hyperbilirubinemia, was the principal dose-limiting toxicity of squalamine. At 700 mg/m(2)/day, two of three patients developed grade 4 hyperbilirubinemia, which precluded further dose escalation. At 500 mg/m(2)/day, one of seven patients experienced dose-limiting grade 4 hyperbilirubinemia and grade 3 neurosensory changes, which resolved soon after treatment. Squalamine pharmacokinetics were dose-proportional. At 500 mg/m(2)/day, the mean (percentage coefficient of variation) clearance, half-life, and volume of distribution of squalamine were 2.67 liters/h/m(2) (85%), 9.46 h (81%), and 36.84 liters/m(2) (124%), respectively, and steady-state concentrations [20.08 micro g/ml (13%)] were well above those that inhibit angiogenesis in preclinical models. At the recommended Phase II dose of 500 mg/m(2)/day, squalamine is well tolerated and results in plasma concentrations at least an order of magnitude higher than those required for prominent antiangiogenic effects in preclinical studies.


Face validation of a portable ergonomic laparoscopy skills simulator for single-incision laparoscopic surgery training.
In recent years, many efforts have been made to reduce the trauma of surgical access further by the use of single-incision laparoscopic surgery (SILS). The Ergo-Lap (ergonomic laparoscopic) simulator was taken to the 20th International Congress of the European Association for Endoscopic Surgery (EAES) in 2012 in Brussels, Belgium. During the congress, the simulator was assessed by 13 general surgeons with different SILS experience using a standardized questionnaire to determine the usability of the Ergo-Lap simulator training for basic SILS skills. Eleven of the 13 participants rated the simulator as an attractive simulator (attractive here means arousing interest of the trainees). For the aspects of training in an ergonomic way, 12 of 13 participants rated it as good to excellent because the work space and task panel location can be adjusted according to the length of instruments. Also, 92% (12 of 13) thought the Ergo-Lap simulator was useful for practicing basic SPLS skills. And 85% (11 of 13) thought it was very easy to use. For SILS skills training, this in~xpensive and portable Ergo-Lap simulator offers a feasible training opportunity to help trainees practice their SILS skills under ergonomic conditions.


The role of the spleen in regulating the plasma levels of factor VIII--von Willebrand's factor after DDAVP.
Organ transplantation and perfusion studied indicate that the spleen plays an important role in the regulation of plasma levels of factor VIII-von Willebrand's factor (FVIII-vWF). To better understand the mechanisms that regulate the FVIII-vWF increases after infusion of 1-deamino-8-D-arginine vasopressin (DDAVP), we have measured factor VIII coagulant activity (FVIII:C) and antigen (FVIII:CAg) and von Willebrand's factor antigen (vWF:Ag) and ristocetin cofactor (vWF:RCof) in 9 asplenic subjects with normal baseline concentrations, in 7 asplenic subjects with high concentrations, and in 14 normal controls with intact spleens. In "normal" aasplenics, all the FVIII-vWF-related measurements increased significantly over baseline values, indicating that responsiveness to DDAVP is not abolished by splenectomy. The maximal vWF:Ag and vWF:RCof responses were no different from those of normal controls, suggesting that DDAVP releases vWF from storage sites other than the spleen. The FVIII:C response was significantly lower than in normal controls, but FVIII:CAg did not differ, making FVIII:CAg higher than FVIII:CAg in "normal" asplenics. These findings suggest that the spleen, rather than being a storage site for FVIII, is the organ in which a partially inactive form of FVIII acquires full coagulant activity. In "high" asplenics, all the FVIII-vWF-related measurements increased less than in "normal" splenics, indicating that long-term elevations of plasma concentrations of FVIII-vWF are accompanied by decreased release from those storage pool(s) mobilized by DDAVP.


Early-life chemical exposures and risk of metabolic syndrome.
The global prevalence of obesity has been increasing at a staggering pace, with few indications of any decline, and is now one of the major public health challenges worldwide. While obesity and metabolic syndrome (MetS) have historically thought to be largely driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. There is now increasing evidence to suggest that exposure to synthetic chemicals in our environment may also play a key role in the etiology and pathophysiology of metabolic diseases. Importantly, exposures occurring in early life (in utero and early childhood) may have a more profound effect on life-long risk of obesity and MetS. This narrative review explores the evidence linking early-life exposure to a suite of chemicals that are common contaminants associated with food production (pesticides; imidacloprid, chlorpyrifos, and glyphosate) and processing (acrylamide), in addition to chemicals ubiquitously found in our household goods (brominated flame retardants) and drinking water (heavy metals) and changes in key pathways important for the development of MetS and obesity.


Exploring machine learning methods for absolute configuration determination with vibrational circular dichroism.
The added value of supervised Machine Learning (ML) methods to determine the Absolute Configuration (AC) of compounds from their Vibrational Circular Dichroism (VCD) spectra was explored. Among all ML methods considered, Random Forest (RF) and Feedforward Neural Network (FNN) yield the best performance for identification of the AC. At its best, FNN allows near-perfect AC determination, with accuracy of prediction up to 0.995, while RF combines good predictive accuracy (up to 0.940) with the ability to identify the spectral areas important for the identification of the AC. No loss in performance of either model is observed as long as the spectral sampling interval used does not exceed the spectral bandwidth. Increasing the sampling interval proves to be the best method to lower the dimensionality of the input data, thereby decreasing the computational cost associated with the training of the models.


How Nurses in Johannesburg Address Intimate Partner Violence in Female Patients: Understanding IPV Responses in Low- and Middle-Income Country Health Systems.
One in three women, globally, experiences intimate partner violence (IPV). Although 80% of the world's population resides in the low- and middle-income countries (LMICs), health system responses to IPV are poorly understood. In 2013, the World Health Organization released new guidelines for IPV but universal screening was not recommended in LMICs due to perceived lack of capacity and insufficient evidence. South Africa, with IPV prevalence estimated at 31% to 55%, offers a window into LMIC health systems. South African women seek health care for partner abuse, yet no guidelines exist to direct providers. This research aimed to understand how and why nurses respond to IPV. Using a descriptive design, 25 nurses from five health facilities were interviewed, generating rich narratives of provider actions. Themes were coded and analyzed. An iterative process of constant comparison of emergent data was undertaken to verify and confirm final themes. In the absence of IPV guidelines, nurses employed interventions characterized as counseling, ascertaining abuse, and referral. Nurses' actions were motivated by fear for patients' survival, perceived professional obligations, patients' expectations of receiving treatment, personal experiences of IPV, and weak police responses to IPV. Findings indicated nurses were responding to IPV in a routine manner, yet comprehensive guidelines remain essential to govern and locate their actions within the framework of a public health response. South Africa yields lessons for enhancing understanding of IPV responses in LMICs, while contributing to a slim evidence base of the "how" and "why" of provider actions toward IPV in patients.


A new scheme for fuzzy rule-based system identification and its application to self-tuning fuzzy controllers.
There are many important issues that need to be resolved for identification of a fuzzy rule-based system using clustering. We address three such important issues: 1) deciding on the proper domain(s) of clustering; 2) deciding on the number of rules; and 3) getting an initial estimate of parameters of the fuzzy systems. We justify that one should start with separate clustering of X (input) and Y (output). We propose a scheme to establish correspondence between the clusters obtained in X and Y. The correspondence dictates whether further splitting/merging of clusters is needed or not. If X and Y do not exhibit strong cluster substructures, then again clustering of X* (input data augmented by the output data) exploiting the results of separate clustering of X and Y, and of the correspondence scheme is recommended. We justify that usual cluster validity indices are not suitable for finding the number of rules, and the proposed scheme does not use any cluster validity index. Three methods are suggested to get the initial estimate of membership functions (MFs). The proposed scheme is used to identify the rule base needed to realize a self-tuning fuzzy PI-type controller and its performance is found to be quite satisfactory.


Assessing the relationship between adverse pregnancy outcomes and area-level deprivation in Wales 2014-2019: a national population-based cross-sectional study.
The aim of this study was to assess the relationship between deciles of area-level deprivation and seven adverse pregnancy outcomes in Wales. Cross-sectional analysis. 64 699 live births in Wales from 31 March 2014 to 16 September 2019. We examined each of the following seven adverse pregnancy outcomes: (1) small for gestational age (SGA); (2) large for gestational age; (3) preterm birth; (4) third-degree or fourth-degree perineal tear; (5) major postpartum haemorrhage (MPPH); (6) a lower Apgar score at 5 min and (7) emergency caesarean section. There was no significant association between increasing aggregate measures of area-level deprivation and the adverse pregnancy outcomes we studied. Women living in an area with greater access to services are more likely to have a baby that is SGA (1.27, 95% CI 1.11 to 1.49), have a greater likelihood of a perineal tear (1.74, 95% CI 1.15 to 2.61), are significantly less likely to have MPPH (0.79, 95% CI 0.64 to 0.96), have a baby with an Apgar score of 0.26 higher (95% CI 0.22 to 0.29) and are significantly less likely to have an emergency caesarean section (0.81, 95% CI 0.73 to 0.88). Women living in areas with higher employment (0.26, 95% CI 0.19 to 0.36) and better health (0.26, 95% CI 0.19 to 0.35) were less likely to experience perineal tear. There was no clear social-spatial gradient in area-level deprivation and adverse pregnancy outcomes. We found a stronger association for individual-level behavioural risk factors than area-level factors. These findings support the benefits that accessible and holistic person-centred care may bring through addressing individual behavioural risk factors. There is a need for improved data completeness and further individual-level data on risk factors such as employment and income to better understand the role which may be played by population-level policies and their pathways to affecting outcomes.


Effects of glycine 64 substitutions in RNA-dependent RNA polymerase on ribavirin sensitivity and pathogenicity of coxsackievirus A6.
Hand, foot, and mouth disease (HFMD) caused by a group of enteroviruses is a global public health problem. In recent years, coxsackievirus A6 (CVA6) has emerged as an important HFMD agent. Previous studies have shown that mutations of glycine 64 in RNA-dependent RNA polymerase (3D polymerase), which is central to viral replication, cause phenotypic changes such as ribavirin resistance, increased replication fidelity, and virulence attenuation in poliovirus and enterovirus A71. In this study, we constructed CVA6 mutants with G64R, G64S, and G64T substitutions by site-directed mutagenesis in full-length cDNA of an infectious CVA6 strain cloned in pcDNA3.1. Viral RNA was obtained by in vitro transcription, and the rescued virus strains were propagated in RD cells. Sequencing after six passages revealed that G64S and G64T mutations were stably inherited, whereas G64R was genetically unstable and reversed to the wild type. Comparison of the biological characteristics of the wild-type and mutant CVA6 strains in an in vivo model (one-day-old ICR mice) revealed that the pathogenicity of CVA6-G64S and CVA6-G64T was significantly reduced compared to wild-type CVA6. In vitro experiments indicated the mutant CVA6-G64S and CVA6-G64T strains had increased resistance to 0.8 mM ribavirin and a decreased replication rate in the presence of 0.8 mM guanidine hydrochloride. Our results show that mutation of residue 64 reduces CVA6 susceptibility to ribavirin and increases CVA6 susceptibility to guanidine hydrochloride, together with increased replication fidelity and attenuated viral pathogenicity, thus laying a foundation for the development of safe and effective live attenuated CVA6 vaccine.


Further evidence for non-pancreatic insulin immunoreactivity in guinea pig brain.
The existence of large amounts of insulin in rat brain and of a porcine- or rat-like insulin in guinea pig brain have been disputed on the basis of differing results from standard (Method I) and hydrophobic adsorption techniques (Method II) for concentrating insulin from acid ethanol extracts. To try to resolve these differences, acid ethanol extracts of rat and guinea pig brains were divided into equal aliquots and concentrated for insulin radioimmunoassay (RIA) by both techniques. The RIA used guinea pig anti-porcine insulin serum, with 50% B0 for purified pancreatic porcine, rat and guinea pig insulin standards being 1.35, 2.38 and greater than 1,000 ng/ml, respectively. Oral glucose (4 g/kg) produced plasma glucose of 377 mg/dl in a guinea pig by 20 min but was not associated with any porcine- or rat-like immunoreactive insulin. Dilutions of guinea pig and rat brain extracts had parallel cross-reactivity with insulin standard curves. Insulin contents of rat brain (uncorrected for recovery) against porcine and rat insulin standards, respectively, were 1.33 and 1.93 ng/g (Method I) and 5.93 and 11.67 ng/g (Method II). Rat plasma was 0.85 and 1.42 ng/ml, respectively. Guinea pig contained 1.35 and 1.89 ng/g (uncorrected), respectively (Method I), and 2.99 and 5.62 ng/g, respectively (Method II). Guinea pig plasma was below the sensitivity of the RIA (less than 0.15 ng/ml). These results suggest that a porcine- or rat-like insulin may exist in guinea pig brain.


Full-Length P2X7 Structures Reveal How Palmitoylation Prevents Channel Desensitization.
P2X receptors are trimeric, non-selective cation channels activated by extracellular ATP. The P2X7 receptor subtype is a pharmacological target because of involvement in apoptotic, inflammatory, and tumor progression pathways. It is the most structurally and functionally distinct P2X subtype, containing a unique cytoplasmic domain critical for the receptor to initiate apoptosis and not undergo desensitization. However, lack of structural information about the cytoplasmic domain has hindered understanding of the molecular mechanisms underlying these processes. We report cryoelectron microscopy structures of full-length rat P2X7 receptor in apo and ATP-bound states. These structures reveal how one cytoplasmic element, the C-cys anchor, prevents desensitization by anchoring the pore-lining helix to the membrane with palmitoyl groups. They show a second cytoplasmic element with a unique fold, the cytoplasmic ballast, which unexpectedly contains a zinc ion complex and a guanosine nucleotide binding site. Our structures provide first insights into the architecture and function of a P2X receptor cytoplasmic domain.


[Age and changes in the structure of the walls of the intrinsic arteries of the uterus].
By means of common histological, histochemical and morphometrical methods age changes in the cushion-like intimal protrusions of the intraorganic arteries have been studied in 176 uteri of women at all ages that died from trauma and other diseases which do not produce any changes in the uterus. Beginning from two years of age, in the uterus segmentary artery wall certain intimal thickenings are revealed; at this age they consist of immature fibrillar and cellular elements of the connective tissue and single myocytes. At the pubertal age an intensive development of the cushion-like protrusions is observed. The amount of myocytes in them increases at the expense of migration from muscular tunic of the vessel; they arrange chaotically. Then the structure of the elastic and collagenous carcass of the protrusions becomes more complex, the myocytes in them are oriented along the course of the artery, or along the sloping spiral. During adolescence and mature age, cyclic changes in the wall structure of the uterus intraorganic arteries are observed, depending on the phase of the menstrual cycle. During the second part of the proliferative phase, certain retruction of the protrusions is observed, and at the end of the secretion phase--maximal increase in their height. The intimal protrusions are specialized structures, playing an important role in ensuring an optimal blood circulation in the uterus during ovulation and in performing menstruation. Reverse development of these structures takes place in elderly and old age.


Emerging Evidence of Macrophage Contribution to Hyperinnervation and Nociceptor Sensitization in Vulvodynia.
Vulvodynia is an idiopathic chronic pain disorder and a leading cause of dyspareunia, or pain associated with sexual intercourse, for women. The key pathophysiological features of vulvodynia are vaginal hyperinnervation and nociceptor sensitization. These features have been described consistently by research groups over the past 30 years, but currently there is no first-line recommended treatment that targets this pathophysiology. Instead, psychological interventions, pelvic floor physiotherapy and surgery to remove painful tissue are recommended, as these are the few interventions that have shown some benefit in clinical trials. Recurrence of vulvodynia is frequent, even after vestibulectomy and questions regarding etiology remain. Vestibular biopsies from women with vulvodynia contain increased abundance of immune cells including macrophages as well as increased numbers of nerve fibers. Macrophages have multiple roles in the induction and resolution of inflammation and their function can be broadly described as pro-inflammatory or anti-inflammatory depending on their polarization state. This state is not fixed and can alter rapidly in response to the microenvironment. Essentially, M1, or classically activated macrophages, produce pro-inflammatory cytokines and promote nociceptor sensitization and mechanical allodynia, whereas M2, or alternatively activated macrophages produce anti-inflammatory cytokines and promote functions such as wound healing. Signaling between macrophages and neurons has been shown to promote axonal sprouting and nociceptor sensitization. This mini review considers emerging evidence that macrophages may play a role in nociceptor sensitization and hyperinnervation relevant to vulvodynia and considers the implications for development of new therapeutic strategies.


Is resilience trainable? An initial study comparing mindfulness and relaxation training in firefighters.
Motivated by the growing interest in promoting resilience in first responders and other professionals who face threatening professional circumstances, the current study investigated the effectiveness of offering a short-form mindfulness training (MT) program to firefighters. The overarching question was to determine if psychological and cognitive markers of resilience are bolstered via MT. Firefighters (n = 121) were assigned to an MT program (n = 42), an active-comparison relaxation training program (RT, n = 31), or served as no-training controls (NTC, n = 48). Both the MT and RT programs were contextualized for firefighters and consisted of 4, 2-h training sessions delivered over 4 weeks by the same expert trainer, as well as 10-15 min of daily out-of-class practice. Intent-to-treat analyses revealed a significantly greater increase in psychological resilience from baseline (T1) to post-training (T2) in firefighters who received MT vs. RT or no training. In addition, positive affect and objective attentional task performance demonstrated a greater increase over time (from T1 to T2) with more days per week of out-of-class practice for the MT group but not for the RT group. These results suggest that MT moreso than RT bolsters markers of resilience in firefighters.


Video-microscopic analysis of dye coupling in the salamander olfactory bulb.
Cells in the mitral cell (MCL) and granule cell (GCL) layers of the olfactory bulb shape the representation of odor information in the brain. After intracellular Lucifer Yellow (LY) injections into lightly fixed olfactory bulb slices, clusters of dye coupled cells were previously observed in the MCL and GCL, but the relative extent of coupling in the two layers was unknown in adults. In the present study, the time course of LY coupling in the adult salamander olfactory bulb was quantified using video-microscopic methods. Analysis of fluorescent cell body counts showed that the incidence and the extent of LY coupling are greater in the GCL than in the MCL. With optimal low-current injection procedures, 97% of the injections into the GCL exhibited at least one coupled cell, and on average groups of six to eight cells were counted. Fewer injections into the MCL exhibited only one to three coupled cells. Some of these coupled cells were clearly mitral cells. No staining of cells was observed after extracellular LY injections, and intracellular injections of dextran dyes stained single cells, providing evidence that the LY coupled cells were stained through an intercellular route, presumably gap junctions. In live intact preparations, rapid LY staining of cell clusters was also observed using patch pipettes. Together, these results provide evidence that robust coupling occurs among olfactory bulb neurons in adults, which could have functional significance.


Suppression of major histocompatibility complex class I and class II gene expression in Listeria monocytogenes-infected murine macrophages.
Macrophage cells play a central role during infection with Listeria monocytogenes by both providing a major habitat for bacterial multiplication and presenting bacterial antigens to the immune system. In this study, we investigated the influence of L. monocytogenes infection on the expression of MHC class I and class II genes in two murine macrophage cell lines. Steady-state levels of I-Abeta chain mRNA were decreased in both resting J774A.1 and P388D1 macrophages infected with L. monocytogenes whereas reduction of H-2K mRNA was only observed in P388D1 cells. In addition, L. monocytogenes suppressed induction of MHC class I and class II mRNAs in response to gamma-interferon as well as the maintenance of the induced state in activated P388D1 macrophages. Exposure to the non-pathogenic species L. innocua or a deletion mutant of L. monocytogenes, which lacks the lecithinase operon, did not cause a reduction in H-2K and I-Abeta mRNA levels nor suppress expression of Ia antigens. Inhibition of MHC gene expression may represent an important part of the cross-talk between L. monocytogenes and the macrophage that probably influences the efficiency of a T cell-mediated immune response and thus the outcome of a listerial infection.


Mapping the contributions of dyadic approaches to couples' psychosocial adaptation to prostate cancer: a scoping review.
Prostate cancer is the second-most prevalent cancer diagnosis worldwide among males. Although prostate cancer affects the physical, sexual, and mental health of patients, the impact of prostate cancer on partners has also been increasingly recognized. Hence, taking a dyadic approach is of relevance. Moreover, there is evidence of the utility of dyadic approaches to the study of relational stress that chronic diseases such as prostate cancer can bring to couples, even though knowledge is sparse about prostate cancer. This scoping review aimed to map existing dyadic studies on the psychosocial adaptation of couples to prostate cancer. A systematic search of studies published from 2005 to November 2022 was conducted on electronic databases (PubMed, Cochrane Library, EBSCOHost, Scopus, and Web of Science) following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses-Extension for Scoping Reviews). The review included 25 eligible studies from the initial 2514 articles retrieved. Overall, the results emphasized the interdependency between couple members and suggested how partners' adaptation influences patients' adaptation to prostate cancer and vice versa, regarding several psychosocial dimensions (eg, intimacy, quality of life). This work can bring awareness to health care professionals to adopt a couples approach when managing prostate cancer whenever there is a partner, due to these interdependent influences. For researchers and future studies, this work can strengthen the relevance of dyadic approaches on how couples adapt to prostate cancer and explore which other dimensions influence these complex dynamics.


Effect of initial product temperature and initial pH on foaming time during vacuum evaporation of liquid whole eggs.
During earlier studies on vacuum concentration of liquid egg white, the phenomena of foaming during the initial stages of the process were reported. In these studies, it was also shown that no concentration took place during the foaming period that varied from test to test. To minimize the total process time, this present study was undertaken to investigate what variables contributed to foaming, how they could be controlled, and what effect they had on product quality and functional properties. This study investigated the relationships among initial product temperature, initial pH, and foaming of liquid whole eggs. Two temperatures (9 and 20 C) and three pH levels (6.5, 7.3, and 8.5) were studied using a vacuum evaporation system with a maximum vacuum of 5 kPa. Tests showed that higher initial pH levels had decreased foaming times. At the end of foaming experiments, the liquid whole egg was evaluated to determine the extent of functional property change during foaming. A decrease in foaming time resulted in a decrease in whip time. The cakes made from the processed liquid whole egg had larger volumes than those from the unprocessed control. Furthermore, the liquid whole egg, which foamed the longest, had higher (P < 0.05) cake volumes. Our current experiments also verified our earlier findings that no product concentration takes place during the foaming process.


Correlation of single time-point damage scores with observed progression of radiographic damage during the first 6 years of rheumatoid arthritis.
Aggressive treatment of early rheumatoid arthritis (RA) is recommended to prevent irreversible joint damage. We evaluated the usefulness of single time-point joint radiographs for deciding whether early RA is erosive or nonerosive. In an observational study, 179 patients with recent onset of RA symptoms (median 5.1 mo), positive rheumatoid factor, and active polyarthritis had 2 to 8 radiographic observations of hands, wrists, and forefeet during 6 to 60 months of followup. Linear regression lines for all available radiographs were used to determine progression rates of total Sharp score (TSS), erosion score (ES), and joint space narrowing score (JSNS) of each patient. Using the average of 2 readers' scores, intraclass correlation coefficient was 0.97 and smallest detectable difference was 3.07 for ES, 0.93 and 7.52 for JSNS, and 0.90 and 12.71 for TSS. Mean progression rates per year were 1.20 (ES), 0.67 (JSNS), and 1.85 (TSS). Single time-point radiographs taken within 6 months of symptom onset did not correlate with progression rates (r = 0.01 to 0.07); between 7 and 18 months correlations were weak (r = 0.23 to 0.35), but were better for ES between 19 and 72 months (r = 0.60 to 0.81). Among 53 patients (31%) with no progression of TSS, only 10 of them had zero scores at baseline. Among all 630 radiographs with TSS > or = 1, 25% were associated with progression rates < or = 0. Erosion scores of single radiographic examinations done > 18 months after onset of RA symptoms correlated with progression rates, but earlier radiographs did not sufficiently predict erosive or nonerosive status to guide disease modifying antirheumatic drug treatment decisions.


Methanolic extract of Origanum vulgare ameliorates type 1 diabetes through antioxidant, anti-inflammatory and anti-apoptotic activity.
Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as a consequence of pancreatic β-cell destruction and results in hyperglycaemia. Since current T1D therapy mainly involves insulin replacement, the aim of the present study was to evaluate the therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano) leaf extract rich in biophenols for the treatment of T1D. The phytochemical profile of methanolic oregano extract (MOE) and aqueous oregano extract (AOE) was determined by liquid chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while their main compounds were quantified by HPLC with diode array detection. After establishing their potent in vitro antioxidant activity, the extracts were administered to C57BL/6 mice treated with multiple low doses of streptozotocin for diabetes induction. While prophylactic AOE therapy had no impact on diabetes induction, MOE reduced diabetes incidence and preserved normal insulin secretion. In addition, MOE scavenged reactive oxygen and nitrogen species and, therefore, alleviated the need for the up-regulation of antioxidant enzymes. MOE treatment specifically attenuated the pro-inflammatory response mediated by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T regulatory cells through the impact on specific signalling pathways and transcription factors. Importantly, MOE preserved β-cells from in vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a predominant compound in MOE, exhibited only partial protection from diabetes induction. In conclusion, acting as an antioxidant, immunomodulator and in an anti-apoptotic manner, MOE protected mice from diabetes development. Seemingly, there is more than one compound responsible for the beneficial effect of MOE.


[The history of the decree on the Department of ambulatory care and community medicine].
In 1957 the Grand Council of Vaud adopted a decree aiming to clarify the administrative situation of the Department of ambulatory care and community medicine created in 1887 under the name of central dispensary. The new decree confirms the special status of the Department of ambulatory care and community medicine, which becomes a public-law institution. This article reviews the context and the stakes of this legal evolution.


Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer.
Vaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell lymphoma-extra Large) remain elusive. Bcl-xL regulates cell death by interacting with BAX (B-cell lymphoma-2 Associated X-protein), controlling its cellular localization and influencing BAX-associated processes and signaling pathways. As VRK2A interacts with the Bcl-xL-BAX complex, comprehending its regulatory engagement with Bcl-xL presents potential avenues for intervening in diseases. Using a multi-disciplinary approach, this study provides information on the cellular localization of VRK2A and establishes its interaction with Bcl-xL in the cellular milieu, pinpointing the interacting site and elucidating its anti-apoptotic property within the complex. Furthermore, this study also put forth a model that highlights the importance of VRK2A in stabilizing the ternary complex, formed with Bcl-xL and BAX, thereby impeding BAX dissociation and hence apoptosis. Therefore, further investigations associated with this important revelation will provide cues for designing cancer therapeutics in the future.


Determinants of left atrial reservoir and pump strain and use of atrial strain for evaluation of left ventricular filling pressure.
The aim of this study is to investigate determinants of left atrial (LA) reservoir and pump strain and if these parameters may serve as non-invasive markers of left ventricular (LV) filling pressure. In a multicentre study of 322 patients with cardiovascular disease of different aetiologies, LA strain and other echocardiographic parameters were compared with invasively measured LV filling pressure. The strongest determinants of LA reservoir and pump strain were LV global longitudinal strain (GLS) (r-values 0.64 and 0.51, respectively) and LV filling pressure (r-values -0.52 and -0.57, respectively). Left atrial volume was another independent, but weaker determinant of both LA strains. For both LA strains, association with LV filling pressure was strongest in patients with reduced LV ejection fraction. Left atrial reservoir strain <18% and LA pump strain <8% predicted elevated LV filling pressure better (P < 0.05) than LA volume and conventional Doppler parameters. Accuracy to identify elevated LV filling pressure was 75% for LA reservoir strain alone and 72% for pump strain alone. When combined with conventional parameters, accuracy was 82% for both LA strains. In patients with normal LV systolic function by GLS, LA pump strain >14% identified normal LV filling pressure with 92% accuracy. Left atrial reservoir and pump strain are determined predominantly by LV GLS and filling pressure. Accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function.


To live until you die.
Oncology nurses are expected to be knowledgeable in dealing with palliative care and end-of-life issues. However, patients with advanced cancer often are not offered palliative care until they are approaching the very end of their lives. Oncology nurses need to step up as patient advocates. They need to educate patients, families, physicians, and the public that aggressive cancer care can coexist with aggressive palliative care. This article discusses how to introduce palliative care much earlier in the cancer experience. Oncology nurses can become empowered and then help other nurses to improve quality of life for their patients with advanced cancer as they approach the end of their lives.


Projection-based ensemble learning for ordinal regression.
The classification of patterns into naturally ordered labels is referred to as ordinal regression. This paper proposes an ensemble methodology specifically adapted to this type of problem, which is based on computing different classification tasks through the formulation of different order hypotheses. Every single model is trained in order to distinguish between one given class (k) and all the remaining ones, while grouping them in those classes with a rank lower than k , and those with a rank higher than k. Therefore, it can be considered as a reformulation of the well-known one-versus-all scheme. The base algorithm for the ensemble could be any threshold (or even probabilistic) method, such as the ones selected in this paper: kernel discriminant analysis, support vector machines and logistic regression (LR) (all reformulated to deal with ordinal regression problems). The method is seen to be competitive when compared with other state-of-the-art methodologies (both ordinal and nominal), by using six measures and a total of 15 ordinal datasets. Furthermore, an additional set of experiments is used to study the potential scalability and interpretability of the proposed method when using LR as base methodology for the ensemble.


Super-Resolution Exciton Imaging of Nanobubbles in 2D Semiconductors with Near-Field Nanophotoluminescence Microscopy.
Two-dimensional (2D) semiconductors, such as transition metal dichalcogenides, have emerged as important candidate materials for next-generation chip-scale optoelectronic devices with the development of large-scale production techniques, such as chemical vapor deposition (CVD). However, 2D materials need to be transferred to other target substrates after growth, during which various micro- and nanoscale defects, such as nanobubbles, are inevitably generated. These nanodefects not only influence the uniformity of 2D semiconductors but also may significantly alter the local optoelectronic properties of the composed devices. Hence, super-resolution discrimination and characterization of nanodefects are highly demanded. Here, we report a near-field nanophotoluminescence (nano-PL) microscope that can quickly screen nanobubbles and investigate their impact on local excitonic properties of 2D semiconductors by directly visualize the PL emission distribution with a very high spatial resolution of ∼10 nm, far below the optical diffraction limit, and a high speed of 10 ms/point under ambient conditions. By using nano-PL microscopy to map the exciton and trion emission intensity distributions in transferred CVD-grown monolayer tungsten disulfide (1L-WS2) flakes, it is found that the PL intensity decreases by 13.4% as the height of the nanobubble increases by every nanometer, which is mainly caused by the suppression of trion emission due to the strong doping effect from the substrate. In addition to the nanobubbles, other types of nanodefects, such as cracks, stacks, and grain boundaries, can also be characterized. The nano-PL method is proven to be a powerful tool for the nondestructive quality inspection of nanodefects as well as the super-resolution exploration of local optoelectronic properties of 2D materials.


Health status, mental health and air quality: evidence from pensioners in Europe.
Environmental quality is an important determinant of individuals' well-being and one of the main concerns of the governments is the improvement on air quality and the protection of public health. This is especially the case of sensitive demographic groups, such as the old aged people. However, the question this study attempts to answer is how do individuals value the effects on the environment. The study explores the effects of old and early public pension schemes, as well as the impact of air pollution on health status of retired citizens. The empirical analysis relies on detailed micro-level data derived from the Survey of Health, Ageing and Retirement in Europe (SHARE). As proxies for health, we use the general health status and the Eurod mental health indicator. We examine two air pollutants: the sulphur dioxide (SO2) and ground-level ozone (O3). Next, we calculate the marginal willingness-to-pay (MWTP) which shows how much the people are willing to pay for improvement in air quality. We apply various quantitative techniques and approaches, including the fixed effects ordinary least squares (OLS) and the fixed effects instrumental variables (IV) approach. The last approach is applied to reduce the endogeneity problem coming from possible reverse causality between the air pollution, pensions and the health outcomes. For robustness check, we apply also a structural equation modelling (SEM) which is proper when the outcomes are latent variables. Based on our favoured IV estimates and the health status, we find that the MWTP values for one unit decrease in SO2 and O3 are respectively €221 and €88 per year. The respective MWTP values using the Eurod measure are €155 and €68. Overall, improvement of health status implies reduction in health expenditures, and in previous literature, ageing has been traditionally considered the most important determinant. However, this study shows that health lifestyle and socio-economic status, such as education and marital status, are more important, and furthermore, air pollution cannot be ignored in the agenda of policy makers.


The evolution of modern endoscopic photography.
Most of the problems of endoscopic photography through rigid and flexible instruments have been overcome. Within the not-too-distant future, it should be possible to take good endoscopic photographs through a standard 4-mm telescope using 200-ASA film, light being provided by a high-powered external flash unit transmitting light to the telescope through a liquid-filled light guide. It may, however, be better to suggest a compromise in which operative procedures and urethral photography can be carried out through the 30 degrees, 4-mm diameter telescope, but bladder inspection and photography performed through a 5.5- or 6-mm telescope. The standard set would then become a 0 degrees and 30 degrees, 4-mm diameter telescope, and a 70 degrees larger instrument for bladder photography and inspection.


Experience of advanced chronic obstructive pulmonary disease: metasynthesis of qualitative research.
Chronic obstructive pulmonary disease (COPD) is a life-limiting illness. Despite best available treatments, individuals continue to experience symptom burden and have high health care utilization. To increase understanding of the experience and ongoing needs of individuals living with COPD. Medline, PsycINFO, CINAHL, and Sociological Abstracts were searched for articles published between January 1990 and June 2013. Metasynthesis of qualitative data followed the principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Metasyntheses are increasingly used to gain understandings of complex research questions through synthesizing data from individual qualitative studies. Descriptive and analytical themes were developed through thematic synthesis and expert panel discussion of extracted primary quotes, not the primary data themselves. Twenty-two studies were included. Four hundred twenty-two free codes were condensed into seven descriptive themes: better understanding of condition, breathlessness, fatigue, frailty, anxiety, social isolation, and loss of hope and maintaining meaning. These seven themes were condensed further into three analytical themes that described the experience and ongoing needs of individuals with COPD: the need for better understanding of condition, sustained symptom burden, and the unrelenting psychological impact of living with COPD. Combining discrete qualitative studies provided a useful perspective of the experience of living with COPD over the past two decades. Further studies into the ongoing needs of individuals with COPD are unlikely to add to this well-established picture. Future research should focus on solutions through the development of interventions that address patients' ongoing needs.


Insights into the structure and function of the RNA ligase RtcB.
To be functional, some RNAs require a processing step involving splicing events. Each splicing event necessitates an RNA ligation step. RNA ligation is a process that can be achieved with various intermediaries such as self-catalysing RNAs, 5'-3' and 3'-5' RNA ligases. While several types of RNA ligation mechanisms occur in human, RtcB is the only 3'-5' RNA ligase identified in human cells to date. RtcB RNA ligation activity is well known to be essential for the splicing of XBP1, an essential transcription factor of the unfolded protein response; as well as for the maturation of specific intron-containing tRNAs. As such, RtcB is a core factor in protein synthesis and homeostasis. Taking advantage of the high homology between RtcB orthologues in archaea, bacteria and eukaryotes, this review will provide an introduction to the structure of RtcB and the mechanism of 3'-5' RNA ligation. This analysis is followed by a description of the mechanisms regulating RtcB activity and localisation, its known partners and its various functions from bacteria to human with a specific focus on human cancer.


Jiawei guomin decoction regulates the degranulation of mast cells in atopic dermatitis mice via the HIS/PAR-2 pathway.
Guomin decoction (GMD) is a traditional Chinese medicine commonly used in clinical practice. It has traditionally been used to treat all allergic diseases. Currently, Jiawei Guomin Decoction (JWGMD) is used to treat sensitive skin after initial therapy. Although it has a significant clinical therapeutic effect, the exact role of mast cell degranulation in treating atopic dermatitis (AD) is still unclear. GMD and JWGMD can both treat allergic diseases, while JWGMD focuses on skin allergies. This study aims to explore the potential effect of JWGMD on the degranulation of mast cells in an AD mouse model induced by 2,4-dinitrofluorobenzene (DNFB) and investigate the effectiveness of JWGMD in alleviating disease progression to further provide specific therapeutic targets for treating AD. The scratching times and skin lesions of model mice induced by DNFB were observed, and skin tissues were collected for subsequent measurement. Histopathological changes in the back skin of mice were observed by haematoxylin eosin (H&E) staining, Toluidine blue staining was used to detect the degranulation of mouse skin mast cells, and the relationship between the expression of histamine (HIS), mast cell tryptase (MCT) and mast cell degranulation was analysed by enzyme-linked immunosorbent assay (ELISA). The expression of protease-activated receptor-2 (PAR-2), histamine 1 receptor (H1R), H2R, H4R and MCT proteins in AD mice was detected by Western blot (WB). Immunofluorescence assay (IFA) further confirmed the localization of PAR-2, H1R, H2R, H4R, and MCT proteins in the skin. Quantitative real-time PCR (qPCR) was used to determine PAR-2, H1R, H2R and H4R mRNA levels in skin lesions to further clarify the mechanism by which JWGMD amplifies mast cell degranulation in AD. In addition, a reliable ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry (UPLC-QE-MS) nontargeted metabolomics analysis was performed to analyse the differences in metabolite abundance between GMD and JWGMD, and these results were used to identify the active components in JWGMD that may have antipruritic and anti-inflammatory properties and inhibit mast cell degranulation. After intermittent stimulation with DNFB, the skin lesions showed extensive desquamation, dryness, scabbing, skin thickening, and slight bleeding. Both treatments alleviated this phenomenon and reduced the number of scratches, with JWGMD being the most effective. JWGMD can significantly reduce inflammatory cell infiltration, oedema, and some capillary neogenesis in mice and reduce the degranulation of mast cells. The ELISA results showed that JWGMD can increase the levels of MCT and HIS proteins. The WB and IFA results demonstrated that JWGMD reduced the expression levels of PAR-2, H1R, H4R, and MCT proteins in skin lesions, with protein localization mainly in the epidermal layer, while H2R protein levels were increased and mainly localized in the dermis. In addition, JWGMD downregulates the mRNA expression of PAR-2, H1R, H2R, and H4R. Interestingly, through UPLC-QE-MS nontargeted metabolomic analysis, we detected the anti-inflammatory and antiallergy active substances in JWGMD, such as methyl eugenol, dictamnine and sinapine. JWGMD may alleviate itching through methyl syringol, dictamnine, sinapine and other substances, and its mechanism may be related to inhibiting the HIS/PAR-2 pathway in AD model mice and further regulating the self-amplification of mast cell degranulation. JWGMD is a potential drug for treating AD. Therefore, it deserves continuous attention and research.


Characterization of the E506Q and H537A dysfunctional mutants in the E. coli ABC transporter MsbA.
MsbA is a member of the ABC transporter superfamily that is specifically found in Gram-negative bacteria and is homologous to proteins involved in both bacterial and human drug resistance. The E506Q and H537A mutations have been introduced and used for crystallization of other members of the ABC transporter protein family, including BmrA and the ATPase domains MalK, HlyB-NBD, and MJ0796, but have not been previously studied in detail or investigated in the MsbA lipid A exporter. We utilized an array of biochemical and EPR spectroscopy approaches to characterize the local and global effects of these nucleotide binding domain mutations on the E. coli MsbA homodimer. The lack of cell viability in an in vivo growth assay confirms that the presence of the E506Q or H537A mutations within MsbA creates a dysfunctional protein. To further investigate the mode of dysfunction, a fluorescent ATP binding assay was used and showed that both mutant proteins maintain their ability to bind ATP, but ATPase assays indicate hydrolysis is severely inhibited by each mutation. EPR spectroscopy data using previously identified and characterized reporter sites within the nucleotide binding domain along with ATP detection assays show that hydrolysis does occur over time in both mutants, though more readily in the H537A protein. DEER spectroscopy demonstrates that both proteins studied are purified in a closed dimer conformation, indicating that events within the cell can induce a stable, closed conformation of the MsbA homodimer that does not reopen even in the absence of nucleotide.


Quit in general practice: a cluster randomised trial of enhanced in-practice support for smoking cessation.
This study will test the uptake and effectiveness of a flexible package of smoking cessation support provided primarily by the practice nurse (PN) and tailored to meet the needs of a diversity of patients. This study is a cluster randomised trial, with practices allocated to one of three groups 1) Quit with Practice Nurse 2) Quitline referral 3) GP usual care. PNs from practices randomised to the intervention group will receive a training course in smoking cessation followed by access to mentoring. GPs from practices randomised to the Quitline referral group will receive information about the study and the process of written referral and GPs in the usual care group will receive information about the study. Eligible patients are those aged 18 and over presenting to their GP who are daily or weekly smokers and who are able to give informed consent. Patients on low incomes in all three groups will be able to access free nicotine patches.Primary outcomes are sustained abstinence and point prevalence abstinence at the three month and 12 month follow-up points; and incremental cost effectiveness ratios at 12 months. Process evaluation on the reach and acceptability of the intervention approached will be collected through Computer Assisted Telephone Interviews (CATI) with patients and semi-structured interviews with PNs and GPs.The primary analysis will be by intention to treat. Cessation outcomes will be compared between the three arms at three months and 12 month follow-up using multiple logistic regression. The incremental cost effectiveness ratios will be estimated for the 12 month quit rate for the intervention groups compared to usual care and to each other. Analysis of qualitative data on process outcomes will be based on thematic analysis. High quality evidence on effectiveness of practice nurse interventions is needed to inform health policy on development of practice nurse roles. If effective, flexible support from the PN in partnership with the GP and the Quitline could become the preferred model for providing smoking cessation advice in Australian general practice. ACTRN12609001040257.


Robust automated tumour segmentation on histological and immunohistochemical tissue images.
Tissue microarray (TMA) is a high throughput analysis tool to identify new diagnostic and prognostic markers in human cancers. However, standard automated method in tumour detection on both routine histochemical and immunohistochemistry (IHC) images is under developed. This paper presents a robust automated tumour cell segmentation model which can be applied to both routine histochemical tissue slides and IHC slides and deal with finer pixel-based segmentation in comparison with blob or area based segmentation by existing approaches. The presented technique greatly improves the process of TMA construction and plays an important role in automated IHC quantification in biomarker analysis where excluding stroma areas is critical. With the finest pixel-based evaluation (instead of area-based or object-based), the experimental results show that the proposed method is able to achieve 80% accuracy and 78% accuracy in two different types of pathological virtual slides, i.e., routine histochemical H&E and IHC images, respectively. The presented technique greatly reduces labor-intensive workloads for pathologists and highly speeds up the process of TMA construction and provides a possibility for fully automated IHC quantification.


Outbreak of hepatitis A among homosexual men in Sydney.
This study examined an outbreak of hepatitis A in eastern Sydney during 1991-1992. Data were based on cases of hepatitis A in eastern Sydney residents reported from January 1991 to October 1992. Five hundred seventy cases of hepatitis A were reported. Of these, 515 (90%) occurred in male patients, of whom 330 were reported to be homosexual or bisexual. The highest attack rate (71/10,000) occurred in men aged 20 to 29 years of age. This outbreak affected large numbers of young homosexual men living in the inner eastern suburbs of Sydney. Hepatitis A vaccination should be considered for all susceptible homosexual men. Further research into the use of hepatitis A vaccine as an outbreak control measure is also recommended.


Vietnamese American Dementia Caregivers' Perceptions and Experiences of a Culturally Tailored, Evidence-Based Program to Reduce Stress and Depression.
Vietnamese American dementia caregivers are at increased risk for adverse mental health compared to the general U.S. population given their sociodemographic and immigration experiences, yet programs that address their needs are lacking. The current article describes Vietnamese American dementia caregivers' perceptions and experiences of a culturally tailored, evidence-based intervention to reduce stress and depression. A convenience sample of caregivers was recruited from the San Francisco Bay area and randomly assigned to intervention ("Our Family Journey"; OFJ) (n = 30) or control (written dementia caregiving information) (n = 30) groups. All intervention and 76.7% of control caregivers reported that the OFJ or educational materials, respectively, were very/somewhat helpful. Three or more skills were refined/learned by 96.7% of OFJ and 36.6% of control participants. Qualitative findings indicated that the intervention had positive effects on well-being and taught new caregiving skills. This first U.S. study to address the mental health needs of Vietnamese American dementia caregivers shows positive perceptions/experiences and demonstrates a model to address a significant need in the community. [Journal of Gerontological Nursing, 45(9), 39-50.].