Corticosteroid insensitivity is reversed by formoterol via phosphoinositide-3-kinase inhibition.
Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids, which has been linked to oxidative stress. Here we show that the long-acting β(2) -agonist formoterol (FM) reversed corticosteroid insensitivity under oxidative stress via inhibition of phosphoinositide-3-kinase (PI3K) signalling. Responsiveness to corticosteroids dexamethasone (Dex), budesonide (Bud) and fluticasone propionate (FP) was determined, as IC(50) values on TNF-α-induced interleukin 8 release, in U937 monocytic cell line treated with hydrogen peroxide (H(2) O(2) ) or peripheral blood mononuclear cells (PBMCs) from patients with COPD or severe asthma. PBMCs from severe asthma and COPD were less sensitive to Dex compared with those from healthy subjects. Both FM (10(-9) M) and salmeterol (SM, 10(-8) M) reversed Dex insensitivity in severe asthma, but only FM restored Dex sensitivity in COPD. Although H(2) O(2) exposure decreased steroid sensitivity in U937 cells, FM restored responsiveness to Bud and FP while the effects of SM were weaker. Additionally, FM, but not SM, partially inhibited H(2) O(2) -induced PI3Kδ-dependent (PKB) phosphorylation. H(2) O(2) decreased SM-induced cAMP production in U937 cells, but did not significantly affect the response to FM. The reduction of SM effects by H(2) O(2) was reversed by pretreatment with LY294002, a PI3K inhibitor, or IC87114, a PI3Kδ inhibitor. FM reversed oxidative stress-induced corticosteroid insensitivity and decreased β(2) adrenoceptor-dependent cAMP production via inhibition of PI3Kδ signalling. FM will be more effective than SM, when combined with corticosteroids, for the treatment of respiratory diseases under conditions of high oxidative stress, such as in COPD.


Fluoride incorporation in hydroxyapatite/gelatin nanocomposite.
The incorporation of fluoride ion into hydroxyapatite (HAp)/gelatin (GEL) nanocomposite was investigated. The F(-) ion incorporation into OH(- )site of HAp phase was an energetically active process, which could be confirmed from the spray solution reaction. The precursors of Ca(2+) in water and phosphates in aqueous gelatin were mixed in the humidified air chamber by air spray, and then the precipitates were aged in a reactor. The F(-) ion precursor was dissolved in the starting solution of Ca(OH)(2) in water, and the resulted Ca(OH, F)(2) complex droplets induced the formation of stable fluoroapatite (F, OH)Ap. The reaction kinetics could be assumed from TEM morphology with ED, XRD and FT-IR analysis.


Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function.
This study sought to determine whether known genetic, drug, dietary, compliance, and lifestyle factors affecting clopidogrel absorption and metabolism fully account for the variability in clopidogrel pharmacokinetics and pharmacodynamics. Platelet inhibition by clopidogrel is highly variable. Patients with reduced inhibition have increased risk for major adverse cardiovascular events. Identification of factors contributing to clopidogrel's variable response is needed to improve platelet inhibition and reduce risk for cardiovascular events. Healthy subjects (n = 160; ages 20 to 53 years; homozygous CYP2C19 extensive metabolizer genotype; no nicotine for 6 weeks, prescription drugs for 4 weeks, over-the-counter drugs for 2 weeks, and no caffeine or alcohol for 72 h; confined; restricted diet) received clopidogrel 75 mg/day for 9 days, at which time clopidogrel pharmacokinetic and pharmacodynamic endpoints were measured. At steady-state, clopidogrel active metabolite (clopidogrel(AM)) pharmacokinetics varied widely between subjects (coefficients of variation [CVs] 33.8% and 40.2% for clopidogrel(AM) area under the time-concentration curve and peak plasma concentration, respectively). On-treatment vasodilator stimulated phosphoprotein P2Y(12) platelet reactivity index (PRI), maximal platelet aggregation (MPA) to adenosine phosphate, and VerifyNow P2Y12 platelet response units (PRU) also varied widely (CVs 32% to 53%). All identified factors together accounted for only 18% of intersubject variation in pharmacokinetic parameters and 32% to 64% of intersubject variation in PRI, MPA, and PRU. High on-treatment platelet reactivity was present in 45% of subjects. Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite rigorous exclusion or control of known disease, polymorphisms (CYP2C19, CYP3A5, ABCB1, PON1), noncompliance, co-medications, diet, smoking, alcohol, demographics, and pre-treatment platelet hyperreactivity. Thus, as yet unidentified factors contribute to high on-treatment platelet reactivity with its known increased risk of major adverse cardiovascular events. (A Study of the Effects of Multiple Doses of Dexiansoprazole, Lansoprazole, Omeprazole or Esomeprazole on the Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Participants: NCT00942175).


Ultrasound-Targeted Microbubble Destruction-Mediated Inhibition of Livin Expression Accelerates Ovarian Cancer Cell Apoptosis.
Ultrasound-targeted microbubble destruction (UTMD) technique has recently been developed as a nonviral delivery of gene therapy. This study aimed at investigating the survival and apoptosis of ovarian cancer cell line OVCA-433 by inhibiting Livin expression through ultrasound-targeted microbubble destruction. We synthesized a targeted microbubble agent for UTMD-mediated shRNA against Livin gene in human ovarian cancer OVCA-433 cells. Lipid microbubbles were conjugated with a luteinizing hormone-releasing hormone analog (LHRHa) by an avidin-biotin linkage to target the ovarian cancer OVCA-433 cells expressing LHRH receptors. The microbubbles were mixed with the recombinant plasmid harboring shRNA-Livin. shRNA-Livin was transfected into OVCA-433 cells upon exposure to 1 MHz pulsed ultrasound beam (0.5 W/cm2) for 8 s. Cell survival was measured by the MTT assay, cell apoptosis by flow cytometry using annexin V/PI double staining, and cell ultrastructure by using the transmission electron microscope. The mRNA and protein expression levels of caspase-3 and caspase-8 were detected by RT-qPCR and western blotting. UTMD-mediated delivery of shRNA-Livin remarkably reduced the survival of OVCA-433 cells but promoted the apoptosis compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. It was also found that UTMD-mediated delivery of shRNA-Livin notably declined the mRNA and protein expression levels of caspase-3 and caspase-8 in OVCA-433 cells compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles can enhance the transfection efficiency of shRNA-Livin in ovarian cancer cells.


Synapse development within the spinal trigeminal nucleus.
Pars interpolaris of the spinal trigeminal nucleus of kittens has been studied with the electron microscope at birth and at several subsequent ages during the first month of life. Attention has been given to ultrastructural maturational changes that occur in this neuropil, especially events in synaptogenesis. The results of this investigation include the following observations: (1) the neuropil, even at the earliest ages studied (three-hour-old kittens), is strikingly mature, necessitating a quantitative assessment in order to determine subtle developmental changes in synaptic patterns; (2) the number of axoaxonic contacts at birth are few, and their emergence is essentially a postnatal phenomenon; (3) it appears that the immature Gray type II or symmetrical synapse possesses distinct cleft material and dense, parallel membrane specializations. Synaptic vesicle accumulation at this contact appears to occur after the membrane specializations have formed. A previous study by Kerr26 has shown a reduced potential for primary afferent reorganization with the spinal trigeminal nucleus when kittens are subjected to trigeminal rhizotomy after three days of age. Our observations on the development of axoaxonic synaptic arrangements in the neonatal period may provide an explanation for these earlier results.


Psychotherapy in combination with antidepressant drugs in patients with severe masked depressions.
Masked depressions rival overt depressions in frequency, but unfortunately an early correct diagnosis is rarely made. Psychotherapy in combination with antidepressant drugs is the treatment of choice in these patients, most of whom are severely ill by the time they are first seen by a psychiatrist. The nature of this syndrome and an overview of the treatment procedure is outlined in this paper.


Automated CT-based analysis to detect changes in the prevalence of lytic bone metastases from breast cancer.
The spinal column is the most frequent site of bone metastasis in patients with breast cancer. It is important to understand how the pattern of vertebral lesions may be affected by the introduction of modern cancer therapies. The purpose of this study was to characterize changes in the radiological appearance of spinal column metastases over the past decade using highly automated Computed Tomography (CT) based computational analysis methods. Two case series studies were performed using CT scans of patients with confirmed spinal metastases secondary to breast cancer: Cohort A with CT scans acquired between 1998 and 2001 and Cohort B with CT scans acquired between 2004 and 2007. Diseased vertebrae were classified as lytic, blastic, or mixed based on CT scan intensity through an automated 3D computer algorithm. The relative incidence of lytic vertebral metastases decreased in comparing Cohort B to Cohort A (12% vs. 49%) with a corresponding increase in mixed lesions (51% vs. 18%) Significant associations were found between the percentage of lytic lesions in number of diseased vertebrae measured per patient and lack of bisphosphonate use (RR = 2.6) and for membership in Cohort A vs. Cohort B (RR = 5.9). This work highlights a change in the CT appearance of vertebral metastases from breast cancer during the past decade toward a lower proportion of lytic disease. Observation of patient therapies suggests that differences in radiological assessment may be linked, at least in part, to bisphosphonate use. These findings have important implications for both clinical practice and research strategies involving vertebral metastases.


Presence of yeasts in southern Italian sourdoughs from Triticum aestivum flour.
Samples of sourdoughs obtained from 13 artisanal bakeries located in the Molise and Campania regions were analysed. The sourdoughs were produced with the exclusive use of Triticum aestivum wheat flour. pH values of sourdoughs from Molise were generally lower than those from Campania. The number of yeasts in the samples of sourdoughs from Molise was generally higher than in those from Campania, which in two cases evidenced counts about 2 log cfu x g(-1). By utilising and comparing traditional and biomolecular techniques of identification a complete picture of the isolates was obtained: 58 strains were identified as Saccharomyces cerevisiae, five as Candida colliculosa, four as C. lambica, three as C. krusei, three as C. valida and two as C. glabrata.


Efficacy and safety of cold forceps biopsy for diminutive pharyngeal neoplasms: Single-center, prospective pilot study.
Management of diminutive pharyngeal neoplasms is controversial. Thus, we conducted a single-center, prospective pilot study to investigate the efficacy and safety of endoscopic excision with cold forceps biopsy (CFB) of these lesions. Thirty-nine lesions endoscopically diagnosed with narrow-band imaging as pharyngeal neoplasms of 3 mm or smaller were excised with CFB using jumbo biopsy forceps (cap diameter 2.8 mm, jaw volume 12.4 mm3 ). The primary outcome was endoscopically determined local remnant/recurrence rate 3 months after CFB. The secondary outcomes were histopathologically determined local remnant/recurrence rate; risk factors associated with the endoscopic remnant/recurrence; and incidence of intraoperative or delayed bleeding and other adverse events. Histological diagnosis of the 39 CFB-excised lesions were: 11 high-grade dysplasia (28.2%), 22 low-grade dysplasia (56.4%), two basal cell hyperplasia (5.1%) and four atypical squamous epithelium (10.3%).Twenty-seven patients (30 lesions) underwent follow-up endoscopy 3 months after CFB; the endoscopic and pathological local remnant/recurrence rate was 20% (6/30; 95% confidence interval (CI), 7.7-36.6%) and 16.7% (5/30; 95% CI, 5.6-34.7%), respectively. Location of the lesion in the hypopharynx was a significant risk factor associated with the endoscopic local remnant/recurrence (P = 0.049). No significant adverse events occurred. Cold forceps biopsy with jumbo biopsy forceps appears to be a safe and effective technique for excising diminutive pharyngeal neoplasms. Although small, the excised lesions may have a remarkably high frequency of high-grade dysplasia. (Clinical trial registration number: UMIN000037980).


Management of infertility in women with polycystic ovary syndrome : a practical guide.
The management of infertility in women with polycystic ovary syndrome (PCOS) centers around options for inducing ovulation. This is an evidence-based review of the management of PCOS, which includes a MEDLINE search of publications between 1986 and May 2005 and a search of the Cochrane Database. Weight loss, exercise, and metformin will induce ovulation in many insulin-resistant women and obese women with PCOS, and should always be the first-line treatment. Ovulation induction has been performed with clomiphene citrate (clomifene) as the first-line treatment, but the use of aromatase inhibitors has been shown to be as successful. The strategies for reducing the risks of gonadotropin therapy such as low-dose follicle-stimulating hormone (FSH) stimulation and the addition of metformin are discussed. Both gonadotropin releasing-hormone agonists and antagonists are equally effective in in vitro fertilization stimulation in conjunction with FSH therapy. Metformin may have a benefit in pregnancy in reducing the risks of miscarriage and diabetes mellitus; however, prospective trials are still lacking.


Hydroxyl radical dominated elimination of plasticizers by peroxymonosulfate on metal-free boron: Kinetics and mechanisms.
Plasticizer pollution in drinking water and aquatic systems has raised global concerns due to the lasting and chronic hazards to marine life and public health. Metal-free materials are promising as green catalysts for wastewater purification. In this study, amorphous boron was applied as a metal-free activator to decompose peroxymonosulfate (PMS) for the degradation of plasticizers in water. Integrating radical trapping and selectively quenching tests with kinetic evaluation and electrochemical analysis, hydroxyl radical was found to be the dominating reactive oxygen species (ROS). With a strong oxidative capacity, the boron/PMS system can effectively degrade both bisphenols and phthalates plasticizers. In contrast, a carbon nanotube-catalyzed PMS system mediated a nonradical pathway to oxidize the electron-rich plasticizer (bisphenol A), but ineffectively to decompose the highly recalcitrant phthalates plasticizers (diethyl phthalate). Moreover, we unveiled that the boron surface was oxidized to boron oxide during the redox reaction, and the oxide would be self-cleaned in the acidic solution to regenerate fresh boron and restore the activity during the cyclic operations. Therefore, this work not only gains new insights into the radical and nonradical oxidations by metal-free catalysis, but also provides feasible technologies for plasticizer purification in water.


Neuroinflammation in Parkinson's disease: a meta-analysis of PET imaging studies.
Increasingly, evidence implicates an important role of neuroinflammation in neurodegeneration progression. Yet, brain imaging has not reached a consistent conclusion that neuroinflammation is involved in the pathogenesis of Parkinson's disease (PD). We aimed to review the evidence to quantitatively assess the existence and spatial distribution of neuroinflammation in the brain of PD patients. We systematically searched literature databases for case-control studies which used positron emission tomography to detect neuroinflammation represented by translocator protein (TSPO) levels in PD patients compared with healthy controls (HC). Standardized mean differences (SMD) were selected as effect sizes and random-effects models were used to combine effect sizes. Subgroup analyses for separate brain regions were conducted. Fifteen studies comprising 455 (HC = 198, PD = 238) participants and 19 brain regions were included. Compared to HC, PD patients had elevated TSPO levels in midbrain, putamen, anterior cingulate, posterior cingulate, thalamus, striatum, frontal, temporal, parietal, occipital, cortex, hippocampus, substantia nigra, pons, cerebellum, and caudate when using 1st-generation ligands. TSPO levels were elevated in the midbrain of PD patients when 2nd-generation ligands were used. We discussed the possible explanations of contrasting difference between these outcomes.


Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells.
Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible cells. However, the signaling pathway of their apoptotic effects remains undefined. In this study, the cytotoxic effect of emodin on various human hepatoma cell lines was investigated. Results demonstrated that emodin exhibited strongly suppressing effect on HepG2/C3A, PLC/PRF/5, and SK-HEP-1 cells, with the IC(50) value of 42.5, 46.6, and 53.1 microM, respectively. Furthermore, emodin induced apoptosis in HepG2/C3A cells was clearly verified by the appearance of DNA fragmentation and sub-G(1) accumulation. Besides, HepG2/C3A cells were found to be arrested in G(2)/M phase after the cells were treated with 60 microM emodin for 48 h. Moreover, significant increase in the levels of apoptosis-related signals such as p53 (419.3 pg/ml), p21 (437.4 units/ml), Fas (6.6 units/ml), and caspase-3 (35.4 pmol/min) were observed in emodin treated HepG2/C3A cells. Taken together, emodin displays effective inhibitory effects on the growth of various human hepatoma cell lines and stimulates the expression of p53 and p21 that resulted in the cell cycle arrest of HepG2/C3A cells at G(2)/M phase. Results also suggest that emodin-induced apoptosis in HepG2/C3A cells were mediated through the activation of p53, p21, Fas/APO-1, and caspase-3. It implies that emodin could be a useful chemotherapeutical agent for treatment of hepatocellular carcinoma (HCC).


Outcomes after hand and upper extremity transplantation.
Hand and upper extremity transplantation (HUET) has emerged as the most frequently performed reconstructive procedure in the burgeoning field of vascularized composite allotransplantation (VCA). VCA refers to a form of transplant with multiple tissue types that represents a viable treatment option for devastating injuries where conventional reconstruction would be unable to restore form and function. As hand transplantation becomes increasingly more common, discussions on advantages and disadvantages of the procedure seem to intensify. Despite encouraging functional outcomes, current immunosuppressive regimens with their deleterious side-effect profile remain a major concern for a life-changing but not life-saving type of transplant. In addition, a growing number of recipients with progressively longer follow-up prompt the need to investigate potential long-term sequelae, such as chronic rejection. This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive treatment. The implications of these findings for VCA in terms of achievements and challenges ahead will then be discussed.


A matrix metalloproteinase inhibitor which prevents fibroblast-mediated collagen lattice contraction.
Matrix metalloproteinases (MMPs) and the specific tissue inhibitors of metalloproteinases (TIMPs) are involved in tissue turnover in normal and pathological processes including wound healing. Marimastat, a potent inhibitor of MMPs, was used to investigate the role of MMPs in an in vitro wound contraction model, the dermal equivalent, in which fibroblasts are grown in a collagen matrix. Marimastat inhibited fibroblast-mediated lattice contraction and this inhibition was reversible upon removal of the inhibitor, indicating that MMPs play an important role in fibroblast-mediated collagen lattice contraction, modelling what may happen when granulation tissue contracts in a healing wound.


Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery.
Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient's clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.


[Local Allergic Reaction to Subcutaneous Treatment with Procaine in a Patient with Shoulder Pain - a Case Study].
A 53-year-old man presented at the general practitioner's office with 2 weeks of existing shoulder pain without radiation. On physical examination, no abnormalities were found, except for left-sided tension of the shoulder muscles. Because of the expected self-limiting nature of the complaints, no further tests were conducted. Based on shoulder pain with local muscle tension, the working diagnosis cervicobrachialgia was adopted. The pain was treated with local subcutaneous administration of procaine. 4 days later, the patient presented with distinct patches of urticaria at the injection sites, which regressed spontaneously over the course of 2 weeks. Allergic reactions occuring after treatment with procaine are rare, but can be life-threatening if systemic or afflicting vital structures.Patients should be informed about the importance of the allergy in relation to medical procedures, such as dental treatment, and about cross-reactivity with other medication.


Rising Billing for Intermediate Intensive Care among Hospitalized Medicare Beneficiaries between 1996 and 2010.
Intermediate care (i.e., step-down or progressive care) is an alternative to the intensive care unit (ICU) for patients with moderate severity of illness. The adoption and current use of intermediate care is unknown. To characterize trends in intermediate care use among U.S. hospitals. We examined 135 million acute care hospitalizations among elderly individuals (≥65 yr) enrolled in fee-for-service Medicare (U.S. federal health insurance program) from 1996 to 2010. We identified patients receiving intermediate care as those with intensive care or coronary care room and board charges labeled intermediate ICU. In 1996, a total of 960 of the 3,425 hospitals providing critical care billed for intermediate care (28%), and this increased to 1,643 of 2,783 hospitals (59%) in 2010 (P < 0.01). Only 8.2% of Medicare hospitalizations in 1996 were billed for intermediate care, but billing steadily increased to 22.8% by 2010 (P < 0.01), whereas the percentage billed for ICU care and ward-only care declined. Patients billed for intermediate care had more acute organ failures diagnoses codes compared with general ward patients (22.4% vs. 15.8%). When compared with patients billed for ICU care, those billed for intermediate care had fewer organ failures (22.4% vs. 43.4%), less mechanical ventilation (0.9% vs. 16.7%), lower mean Medicare spending ($8,514 vs. $18,150), and lower 30-day mortality (5.6% vs. 16.5%) (P < 0.01 for all comparisons). Intermediate care billing increased markedly between 1996 and 2010. These findings highlight the need to better define the value, specific practices, and effective use of intermediate care for patients and hospitals.


TNFAIP3 may be key to TLR4-activation of the inflammasome in the retinal vasculature.
The goal of these studies were to determine whether tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) regulated toll-like receptor 4 (TLR4) actions on the NOD-like receptor protein 3 (NLRP3) inflammasome. Western blotting was done on retinal lysates from TLR4 floxed and endothelial cell specific TLR4 knockout mice for TNFAIP3, TLR4, and NLRP3 pathway proteins. Retinal endothelial cells (REC) were grown in normal (5 mM) and high glucose (25 mM) and treated with TNFAIP3 siRNA, followed by Western blotting for TLR4 and NLRP3 pathway proteins. Loss of TLR4 in endothelial cells increased TNFAIP3 levels, while decreasing NLRP3 pathway proteins. High glucose culturing conditions increased TLR4 and NLRP3 proteins, which were also increased by TNFAIP3 siRNA. Data demonstrate that TLR4 regulates NLRP3 pathway proteins. TNFAIP3 can regulate TLR4 and the NLRP3 pathway. TNFAIP3 may offer a new target for therapeutic development against retinal inflammation.


Maternal Satisfaction With Delivery Services and its Associated Factors Among Mothers Who Gave Birth at Public Health Centers in Yeka Sub City, Addis Ababa, Ethiopia.
This study aimed to assess maternal satisfaction and associated factors with delivery care services uptake among mothers who gave birth at public health centers. An institution-based cross-sectional study was conducted in the Yeka Sub-City in Addis Ababa, Ethiopia. A systematic sampling technique was used to select mothers. Bivariable and multivariable analysis was done to identify associated variables. The overall mothers' satisfaction with delivery care services uptake was 63%. The median age of the participants was 28 years. In multivariable analysis privacy measures taken at delivery care services uptake, mothers' education level, occupational status of mothers, and family income level of mothers were associated with mothers' satisfaction in delivery care services. Mother's income levels of 1501 to 5000 birr were satisfied with the service (AOR = 2.49; 95% CI: 1.3, 4.76). However, mothers whose income below1500 birr were dissatisfied. In conclusion, a mother's educational level, occupational status, and family income affect mothers' satisfaction with delivery care services uptake in public health centers, in the Yeka Sub-City. Evaluating health care services uptake from the client's point of view and targeting to identify problems is very necessary.


Efficacy of combination therapy with pembrolizumab and axitinib for metastatic renal collecting duct cell carcinoma: A report on two cases.
Immunotherapy-based combinations have become the standard first-line therapy for metastatic renal cell carcinoma. However, combined immunotherapy for renal collecting duct carcinoma had been reported, but its therapeutic efficacy had been unclear. The first case was a 62-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with multiple bone metastases. After 7 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. The second case was a 71-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with lymph node and lung metastases. After 9 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. In both cases, the tumor cell expression of programmed death ligand-1 was negative, and CD4+ and CD8+ cells were observed in the tumor. Combined immunotherapy with pembrolizumab and axitinib may be effective for metastatic renal collecting duct carcinoma.


Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes.
Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LVDP at this time. Although both BW 755C (n = 7), a dual inhibitor of CO and lipoxygenase (LO) (CF:90 +/- 4%, LVDP:99 +/- 6%) and diethylcarbamazine (DCM) (n = 8), a LO inhibitor (CF:88 +/- 11%, LVDP:87 +/- 4%), significantly inhibited the cardiodepressive effects of activated PMN. BW 755C alone abolished the CL response (431 +/- 158 counts), whereas DCM had no effect on CL (30105 +/- 1698 counts).(ABSTRACT TRUNCATED AT 250 WORDS)


Carbon accounting model for forests in Australia.
CAMFor (Carbon Accounting Model for Forests) is a sophisticated spreadsheet model developed to assist in carbon accounting and projection. This model can integrate information from a range of alternate sources including user input, default parameters and third party model outputs to calculate the carbon flows associated with a stand of trees and the wood products derived from harvests of that stand. Carbon is tracked in the following pools: * Biomass (stemwood, branches, bark, fine and coarse roots, leaves and twigs) * Soil (organic matter and inert charcoal) * Debris (coarse and fine litter, slash, below ground dead material) * Products (waste wood, sawn timber, paper, biofuel, reconstituted wood products). These pools can be tracked following thinning, fires and over multiple rotations. A sensitivity module has been developed to assist examination of the important assumptions and inputs. This paper reviews the functionality of CAMFor and reports on its use in a case study to explore the precision of estimates of carbon sequestration in a eucalypt plantation. Information on variability in unbiased models, measurement accuracy and other sources of error are combined in a sensitivity analysis to estimate the overall precision of sequestration estimates.


Cloning of usp45, a gene encoding a secreted protein from Lactococcus lactis subsp. lactis MG1363.
We have cloned usp45, a gene encoding an extracellular secretory protein of Lactococcus lactis subsp. lactis strain MG1363. Unidentified secreted 45-kDa protein (Usp45) is secreted by every mesophilic L. lactis strain we tested so far and it is chromosomally encoded. The nucleotide sequence of the usp45 gene revealed an open reading frame of 1383 bp encoding a protein of 461 amino acids (aa), composed of a 27-aa signal peptide and a mature protein initiated at Asp28. The gene contains a consensus promoter sequence and a weak ribosome-binding site; the latter is rather uncommon for Gram-positive bacteria. Expression studies in Escherichia coli showed efficient synthesis and secretion of the protein. Usp45 has an unusual aa composition and distribution, and it is predicted to be structurally homologous with P54 of Enterococcus faecium. Up to now, no biological activity could be postulated for this secreted protein.


[The diagnostic value of immunoglobulin G in the cerebrospinal fluid of brain tumor patients, particularly in malignant tumors].
The diagnostic value of immunoglobulin G in cerebrospinal fluid (CSF-IgG) has been evaluated in patients with brain tumors. The (CSF-IgG) level in patients with malignant brain tumors was found to be significantly elevated when compared to the level in control patients without a disorder of the central nerve system. Especially significant was high level of CSF-IgG found in patients whose tumor had invaded into ventricles. The CSF-IgG level was found to decrease to a normal range by a total or subtotal resection of the tumor, but not by partial resection. On the other hand, CSF which contained large amount of IgG inhibited the lymphocyte proliferative response to phytomitogen. These results suggest that CSF-IgG seems to correlate with the tumor volume, and is important as a tumor marker in patients with a malignant brain tumor.


Hydrogen ion concentration and coronary artery bypass graft surgery with and without cardiopulmonary bypass.
Acidosis during cardiopulmonary bypass (CPB) has been related to the strong ion difference (SID) and the composition of intravascular fluids that are administered. Less intravascular fluids tend to be administered during off- than on-pump CABG and should influence the degree of acidosis that develops. This study aimed to explore the role of CPB in the development of acidosis by comparing changes in hydrogen ion concentration ([H+]) and electrolytes in patients undergoing on- and off-pump coronary artery bypass graft (CABG) surgery. Eighty two patients had arterial blood gas measurements pre-operatively, following CABG and at approximately 0600 h the morning after surgery. Carbon dioxide tension (PaCO2) and concentrations of sodium, potassium, chloride, [H+], bicarbonate and haemoglobin were measured and strong ion difference calculated. Data was analysed using mixed repeated-measures analysis of variance. Intra-operatively, mean SID decreased more in the on- compared to the off-pump group (4.0 mmol/L, 95% confidence interval 2.8-5.3 mmol/L, p < 0.001). Neither [H+] or PaCO2 changed significantly and there were no significant difference between the groups. By the morning following surgery, [H+] and PaCO2 had both increased (p < 0.001) and difference in SID had disappeared (p = 0.17). Despite significant differences in changes in SID, there were no differences in [H+] between patients during or after CABG surgery whether performed on- or off-pump. This may be have been the result of greater haemodilution in the on- compared to the off-pump group, compensating for change in SID by reducing the concentration of weak acids. Although it was associated with significantly greater decrease in SID, CPB was not associated with any significant increased risk of acidosis.


Quantitative evaluation of noncovalent interactions between polyphosphate and dissolved humic acids in aqueous conditions.
As one kind of phosphorus species, polyphosphate (poly-P) is ubiquitous in natural environments, and the potential interactions between poly-P and humic substances in the sediments or natural waters would influence the fate of poly-P in the environments. However, the mechanism of the interactions has not yet been understood clearly. In this work, the characteristics and mechanisms of the interactions between humic acids (HA) and two model poly-P compounds with various chain lengths have been investigated. Results show that a stable polyphosphate-HA complex would be formed through the noncovalent interactions, and hydrogen bond might be the main driving force for the binding process, which might be formed between the proton-accepting groups of poly-P (e.g., PO and P-O(-)) and the oxygen containing functional groups in HA. Our findings implied that the presence of humic substances in natural waters, soils and sediments would influence the potential transport and/or mobility of environmental poly-P.


What information underlies correct rejections in short-term recognition memory?
We propose that correct rejections are based on information that contradicts the study set, rather than on insufficient familiarity. Using two-dimensional stimuli, we varied the featural overlap between lures and the study set so that one feature of the lure had occurred during study and the second feature of the lure had not occurred. Familiarity varied with the number of times the studied feature had occurred, whereas detectability of the extralist feature varied with the number of studied alternatives on the same dimension. Lures increased in difficulty with familiarity only when familiarity of the studied feature was confounded with the number of alternatives to the extralist feature. Hence, the difficulty in rejecting the lure was controlled by the number of alternatives to the extralist feature, not by the familiarity of the lure. Current theory requires additional representation assumptions and a new comparison process to accommodate these data.


TNSNet: Thyroid nodule segmentation in ultrasound imaging using soft shape supervision.
Thyroid nodules are a common disorder of the endocrine system. Segmentation of thyroid nodules on ultrasound images is an important step in the evaluation and diagnosis of nodules and an initial step in computer-aided diagnostic systems. The accuracy and consistency of segmentation remain a challenge due to the low contrast, speckle noise, and low resolution of ultrasound images. Therefore, the study of deep learning-based algorithms for thyroid nodule segmentation is important. This study utilizes soft shape supervision to improve the performance of detection and segmentation of boundaries of nodules. Soft shape supervision can emphasize the boundary features and assist the network in segmenting nodules accurately. We propose a dual-path convolution neural network, including region and shape paths, which use DeepLabV3+ as the backbone. Soft shape supervision blocks are inserted between the two paths to implement cross-path attention mechanisms. The blocks enhance the representation of shape features and add them to the region path as auxiliary information. Thus, the network can accurately detect and segment thyroid nodules. We collect 3786 ultrasound images of thyroid nodules to train and test our network. Compared with the ground truth, the test results achieve an accuracy of 95.81% and a DSC of 85.33. The visualization results also suggest that the network has learned clear and accurate boundaries of the nodules. The evaluation metrics and visualization results demonstrate the superior segmentation performance of the network to other classical deep learning-based networks. The proposed dual-path network can accurately realize automatic segmentation of thyroid nodules on ultrasound images. It can also be used as an initial step in computer-aided diagnosis. It shows superior performance to other classical methods and demonstrates the potential for accurate segmentation of nodules in clinical applications.


Number of argyrophilic nucleolar organizer regions is a good indicator of lymph node metastasis in patients with esophageal carcinoma.
The number of argyrophilic nucleolar organizer regions (AgNORs) was evaluated as a predictor of lymph node metastasis in 45 patients who had undergone resection of advanced squamous cell carcinoma of the esophagus. The mean AgNOR score of carcinomas was 5.0 +/- 1.8, and it was greater than that of normal esophageal epithelium adjacent to a carcinoma (2.3 +/- 0.5, P < 0.001). The AgNOR score of tumors from 26 patients with lymph node metastasis was 6.1 +/- 1.6, and it was greater than that of tumors from 19 patients without lymph node metastasis (3.7 +/- 1.0, P < 0.001). The AgNOR scores of metastatic lymph nodes (4.9 +/- 1.5) from 26 patients with lymph node metastasis were closely related to the number of metastatic lymph nodes of individual patients (r = 0.582, P < 0.0001). The 3-year survival rate in patients with low AgNOR scores (AgNOR score < 5, n = 22) was 56.2%. By contrast, that in patients with high AgNOR scores (AgNOR score > or = 5, n = 20) was only 13.1%. There was a statistically significant difference between the two survival curves (P < 0.05). These results indicate that the AgNOR score is a good indicator of lymph node metastasis and suggest that it might also be a useful prognostic marker in patients with esophageal cancer.


Effect of placebo on meal-stimulated gastric acid secretion and serum gastrin concentration. Studies in healthy volunteers and duodenal ulcer patients.
The effect of placebos on gastric acid secretion in humans is unknown, even though placebo therapy is relatively effective in ulcer patients. Therefore, we evaluated the effect of a placebo capsule on meal-stimulated gastric acid secretion and serum gastrin concentrations in 10 healthy subjects and also in 10 patients with chronic duodenal ulcer. Each subject and patient was studied twice and in random order, once with placebo therapy prior to the meal and once without placebo. In either healthy subjects or duodenal ulcer patients, meal-stimulated acid secretion and serum gastrin concentrations were not significantly different with or without placebo administration. These studies demonstrate that a placebo capsule, administered by a physician just prior to a meal, has little, if any, effect on acid secretion or gastrin release in response to the meal. Any beneficial effects of placebos in treating patients with peptic ulcer disease are probably unrelated to inhibition of meal-stimulated gastric acid secretion.


Overexpression of superoxide dismutase in Trypanosoma cruzi results in increased sensitivity to the trypanocidal agents gentian violet and benznidazole.
The parasitic protozoan Trypanosoma cruzi is exposed to toxic oxygen metabolites which arise from drug metabolism or immune mechanisms, in addition to those produced by endogenous processes. Identification and functional analysis of parasite enzymes which confer protection against oxidative stress is therefore of importance. To investigate the role of T. cruzi superoxide dismutase (SOD) we transfected epimastigotes with an expression vector containing a putative Fe-SOD gene homologue and achieved overexpression of enzyme activity (5-8 fold). Inhibition studies carried out on the partially purified enzyme revealed azide and H2O2 sensitivity and cyanide insensitivity, the profile expected of an Fe-isoform. Phenotypic analysis of transformed parasites showed that they were more susceptible than control cells to growth inhibition by the trypanocidal drug benznidazole and by gentian violet, an agent which can be used to decontaminate blood supplies in endemic areas. These results may reflect an imbalance in the antioxidant defences of the parasite produced as a result of overexpression of Fe-SOD.


The Na+-Ca2+ exchange system in vascular smooth muscle cell membrane vesicles isolated from cultured cells and from tissue is similar.
The existence of a Na+-Ca2+ exchange system was investigated in sarcolemmal vesicles isolated from cultured cells of dog mesenteric artery. When Na+-loaded membrane vesicles were suspended in a Na+-free KCl medium to create an outwardly directed Na+ concentration gradient across the membrane, a time-dependent uptake of Ca2+ was observed. This uptake of Ca2+ was drastically reduced when the vesicles were suspended in NaCl medium to eliminate the Na+ concentration gradient across the membrane. Monensin also decreased Ca2+ uptake in Na+-loaded vesicles. The apparent Km for Ca2+ was 2.97 microM and the apparent maximum velocity was 4.27 nmol/min per mg protein. The data indicate that a Na+-Ca2+ exchange system exists in sarcolemmal membranes isolated from cultured cells and that it is similar to the system in membranes isolated from the tissue.


[The nature, diagnosis and treatment of post-concussion syndrome].
The relationship between brief loss of consciousness, subsequent cognitive and emotional complaints, and impact on daily functioning continues to be hotly debated. In this paper the strong variability about prevalence of the postconcussional syndrome found in several studies is outstanding and the main issues of this disagreement are suggested. Recent neuroimaging techniques are discussed and some neuropsychological measures are suggested. Currents models (organic/psychogenic) of postconcussional symptoms are reviewed, and a multifactorial model which integrates biological factors with the relevance of neuropsychological deficits--attention, memory, speed of information processing--and coping process is proposed. Finally, according with this model, we conclude with some suggestions to improve neuropsychological intervention and medical treatment of these patients.


An unconventional approach to chest wall pain.
Would acupuncture provide some relief while this patient waited for an x-ray to identify the source of his left lateral chest wall pain?


IMPACT OF COLLIMATION ON RADIATION EXPOSURE IN ADULT AND PAEDIATRIC DIGITAL X-RAY IMAGING.
This study aimed to evaluate the collimation practices and quantify the overexposure due to extensive X-ray field area. The study was carried out in four digital X-ray units (including one paediatric X-ray unit). A total of 749 X-ray projections (555 adult and 194 paediatric) were evaluated. In adult X-ray units, the radiation field size was two times larger than the electronically collimated field. In the paediatric unit, the radiation field was 3.7 times larger than the electronic collimated field. The average additional entrance surface dose due to the excess radiation field used in a paediatric X-ray unit varied between 9.3 (2.5%) and 201.4 $\mu $Gy (10.9%). Therefore, proper pre-patient collimation should be applied whenever feasible, which reduces the patient radiation dose considerably.


Distribution and metabolism of gastrin. An experimental study of the fate of 123 I-gastrin in the rat as studied by external detection with a gamma camera.
In anesthetized rats, the activity distribution of intravenously administered synthetic human gastrin I, labelled with 123 I, was recorded externally by a gamma camera. In intact rats activity was found to accumulate in the kidneys and later in the stomach. After bilateral nephrectomy, the gastric apperance of activity was delayed. In both cases, the gastric activity is considered to emanate not from intact 123 I-gastrin but from free iodide, split off during gastrin degradation. The renal accumulation of gastrin in intact animals as well as the delayed gastric uptade of iodide in nephrectomized animals support the hypothesis that the kidneys are important organs for gastrin metabolism.


Transfer and transformation characteristics of Zn and Cd in soil-rotation plant (Brassica napus L and Oryza sativa L) system and its influencing factors.
Rice-rape rotation is a widely practiced cropping system in China. However, changes in soil properties and management could change the bioavailability of Cd, In order to explore the occurrence state, transportation and transformation characteristics of heavy metals Cd and Zn in rice-rape rotation system in Guizhou karst area with high background value of Cd. In the karst rice-rape rotation area, the physical and chemical properties of soil, chemical specifications and activities of Cd and Zn at different soil depths and during various crop growth stages, and the bioaccumulation of Cd and Zn in different tissues of rice and rape were studied by field experiment and laboratory analysis. The bioaccumulation of Cd and Zn and the effects of physical and chemical soil properties on the activities and bioavailabilities of Cd and Zn during rice-rape rotation were explored. The findings revealed that soil particle size, composition, pH, redox potential, soil organic matter, and Cd and Zn contents varied dramatically, especially in deep soils. The physical and chemical properties of the deep and surface soils were significantly related to the bioaccumulation of Cd and Zn. Cd and Zn are activated during crop rotation. Cd was easier to be enriched in rice, while Zn was easier to be enriched in rape. The correlation between Cd and Zn contents in Brassica campestris L and their enrichment abilities were not significant, but that in Oryza sativa L were significant. During rice-rape rotation, the chemical speciations and activities of Cd and Zn changed with the changes of soil properties and waterlogging environment. This study had important basic guiding significance for the evaluation, prevention and control of heavy metal pollution, and improving soil quality in different rotation systems in karst areas, and was conducive to promoting the safe production of rape and rice.


Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10.
Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally.


Anxiety-Related Frontocortical Activity Is Associated With Dampened Stressor Reactivity in the Real World.
Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes, from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys have begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here, we used a combination of approaches-including neuroimaging assays of threat anticipation and emotional-face perception and more than 10,000 momentary assessments of emotional experience-to demonstrate that individuals who showed greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experienced lower levels of stressor-dependent distress in their daily lives (ns = 202-208 university students). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.


[GENE THERAPY: HISTORY OF DEVELOPMENT AND CURRENT STATE (LITERATURE REVIEW)].
The article provides a brief overview of the history of gene therapy from its inception to the present. It describes the main events that characterize the periods of history of the formation of this therapeutic direction in medicine; the basis achievements and problems of each periods. It lists the main gene therapy drugs that licensed at different times listed; innovative gene therapy technologies, which are now use in clinical practice or are still at the stage of approbation. The article is a review of publications from the Scopus and PubMed and official information from public Internet sources.


Modified method for effective primary vascular smooth muscle progenitor cell culture from peripheral blood.
In previous studies, vascular smooth muscle progenitor cells (vSMPCs) isolated from peripheral blood mononuclear cells (PBMCs) were cultured using medium containing platelet-derived growth factor-BB (PDGF-BB) for 4 weeks. However, this method requires long culture periods of up to 4 weeks and yields low cell counts. Therefore, we proposed the modified method to improve the cell yield and purity and to reduce the cell culture period. PBMCs were isolated from human peripheral blood and cultured by the conventional method using medium containing PDGF-BB alone or the modified method using medium containing PDGF-BB, basic fibroblast growth factor (bFGF), and insulin-transferrin-selenium ITS for 4 weeks. The purity of vSMPCs was analyzed for the expression of a- smooth muscle actin (SMA) by flow cytometry and significantly higher in the modified method than conventional methods at the 1st and 2nd weeks. Also, mRNA expression of a-SMA by real-time PCR was significantly higher in the modified method than conventional method at the 2 weeks. The yield of vSMPCs by trypan blue exclusion assay was significantly higher in the modified method than conventional method at the 1st, 2nd and 3rd weeks. The primary culture using the modified method with PDGF-BB, bFGF, and ITS not only improved cell purity and yield, but also shortened the culture period, compared to the conventional culture method for vSMPCs. The modified method will be a time-saving and useful tool in various studies related to vascular pathology.


Cyclohexylmethylpiperidinyltriphenylpropioamide: a selective muscarinic M(3) antagonist discriminating against the other receptor subtypes.
To discover a highly selective M(3) antagonist, a combinatorial library was prepared. The library was designed to identify a novel structural class of M(3) antagonists by exploring the spatial arrangement of the pharmacophores in known M(3) antagonists. After the evaluation of 1000 library members, a potent M(3) antagonist, 14a (K(i) = 0.31 nM), with novel structural features was identified. Compound 14a showed high selectivity for M(3) receptors over the other muscarinic receptor subtypes (M(1)/M(3) = 380-fold, M(2)/M(3) = 98-fold, M(4)/M(3) = 45-fold, M(5)/M(3) = 120-fold).


Prognostic and clinic-pathological significances of HOXB8, ILK and FAT4 expression in colorectal cancer.
HOXB8 is a protein that was found to promote cancer proliferation and invasion. ILK is a protein kinase which has a role in carcinogenesis. FAT4 is a tumor homologue that has a role in EMT and autophagy regulation. To identify expression of Human HOXB8, Integrin-linked kinase (ILK1) and FAT homolog 4 (FAT4) in colorectal cancer (CRC) correlating their expression with pathological, prognostic and clinical parameters of CRC. We assessed the expression of HOXB8, ILK and FAT4 in fifty CRC patients and ten samples from nearby non-neoplastic colonic mucosa using immunohistochemistry. The expression of HOXB8 and ILK in CRC was positively associated with high tumor grade, advanced tumor stage, lymph node involvement (p < 0.001), occurrence of distant metastases (p = 0.003 and 0.024 respectively), higher incidence of tumor recurrence (p = 0.03, p < 0.001 respectively), worse survival rates (p = 0.038 and 0.003 respectively). The expression of FAT4 in CRC was correlated with lower grade, early stage of the tumor, absence of lymph node involvement (p < 0.001) and lack of distant metastases (p = 0.011). High FAT4 expression was associated with absence of tumor recurrence (p < 0.001) and favorable survival rates (p < 0.001 and 0.003). High immunohistochemical expression of HOXB8 and ILK in addition to low immunohistochemical expression of FAT4 was associated with unfavorable prognostic and pathological parameters of CRC.


Antibodies from patients and mice with autoimmune diseases react with recombinant hnRNP core protein A1.
Sera from autoimmune patients and normal volunteers were tested for antibodies to the A1 core protein of heteronuclear ribonucleoprotein (hnRNP) particles by ELISA and Western blot assays. The A1 protein used in these studies was produced by recombinant DNA technology. Thirty-seven per cent of patients with systemic lupus erythematosus produced anti-A1 antibodies, compared to 7% of normal controls. Several strains of autoimmune mice were also analysed. They spontaneously made high-titered responses to A1. Normal strains showed very low anti-A1 response unless they were specifically immunized with the antigen. Following immunization, normal mice also made high-titered responses to the A1 protein. These studies demonstrated that the A1 protein itself is an autoantigenic component of hnRNP particles. Our studies uncovered no evidence of linkage between the production of anti-A1 and of anti-DNA antibodies.


Research on the coupling and coordination of green finance, higher education, and green economic growth.
Green finance is the main way to solve financing problems and support green technology innovation. The development of higher education is the source of innovative human capital and a key factor in promoting green economic growth. Studying the relationship between the three is an important realistic meaning for achieving green economic growth. Based on the idea of system coupling, this paper adopts the analysis method of the three-system coupling coordination model. This paper constructs a three-system coupling model, which incorporates green finance, higher education, and green economic growth into a unified framework, and based on a comprehensive review of the interaction and mechanism, the degree of system coupling is analyzed from the regional and provincial levels. Conclusions of the study are as follows: (1) the composite indexes of green finance, higher education, and green economic growth are all on the rise. The highest increase has been found in the index of higher education. In addition, the green finance index has also shown an accelerated upward trend in recent years, and green economic growth index has also shown a steady rise in recent years. (2) The upward trend of the coupling degree is relatively observable, but the overall coupling degree is still at low level. The coupling state has jumped from the low-degree coupling stage to the primary coupling stage, and the coupling degrees of the three major regions all show a fluctuating rising trends, but there are apparent regional differences. The degree of coupling between the eastern region and the other two regions is quite different. (3) During the sample period, the degree of coordination between green finance, higher education, and green economic growth in each province has increased to varying degrees. The degree of coordination in the eastern region is the best, the western region is the worst, and the central region is somewhere in between. The study concludes with implications for the protection of the environment. Finally, based on the empirical analysis results, this paper puts forward corresponding countermeasures and suggestions from the perspectives of improving the ability of green technology innovation, promoting the development of green finance and the high-quality development of higher education, and hoping to provide theoretical reference for the coordinated development of China's regional economy.


Cs2CO3 as a source of carbonyl and ethereal oxygen in a Cu-catalysed cascade synthesis of benzofuran [3,2-c] quinolin-6[5-H]ones.
The simultaneous construction of C-C, C-O, and C-N bonds utilizing Cs2CO3 as a source of both carbonyl (CO) and ethereal oxygen and a cascade synthesis of benzofuro[3,2-c]quinolin-6(5H)-one have been achieved using a combination of Cu(OAc)2 and Ag2CO3. A plausible mechanism has been proposed for this unprecedented transformation.


Dietetics students' low knowledge, attitudes, and work preferences toward older adults indicate need for improved education about aging.
This study examined students' knowledge and attitudes about aging and their interest in working with the older adult population in the United States. A 97-item questionnaire included demographic items, a ranking section on work preferences by age groups, and two validated scales: the Palmore Facts on Aging Quiz, and the Oberleder Attitude Scale. Those surveyed were enrolled in the 10 largest universities in the 5 states with the largest population of older adults: California, Florida, New York, Texas, and Pennsylvania. Of 555 questionnaires that program directors requested for their class(es), 299 completed questionnaires were returned. This 54% return rate was affected by program directors requesting more questionnaires than needed. Of the 299 dietetics/nutrition students who completed the survey, 65% were in the 18 to 22 year age range, 91% were women, 81% were non-Hispanic white, and 81% were seniors in college. Pearson's correlation was applied to test for relationships between knowledge and attitudes; t tests for differences in knowledge, attitudes, and work preferences by age, gender, and experience with older adults; and Tukey's multiple comparison test for differences in knowledge, attitudes, and work preferences by state. Students had low knowledge about aging (Palmore, mean percent correct +/- standard deviation = 40.1%+/-13.0%) and neutral attitudes toward older adults (Oberleder, mean score = 69.1+/-8.2). When asked which of 10 age groups they preferred to work with, respondents ranked the 3 oldest age groups (65 to 74, 75 to 84, 85 and older) lowest on average (6.0, 7.3, 8.6, respectively). More didactic instruction about aging and more positive experiences with older adults through fieldwork may be needed to prepare future practitioners to provide nutrition services to this increasing population segment.


Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT3 receptors.
1. Angiotensin (Ang) II modulates cardiovascular baroreflexes; whether or not the peptide influences chemosensitive cardiovascular reflexes is not known. We tested the hypothesis that Ang II modulates the reflex control of sympathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT3) cardiopulmonary receptors. 2. The 5HT3 receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained reflex decrease of renal sympathetic nerve activity (RSNA) but only transient (<3 min) changes of arterial blood pressure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3. Infusion of Ang II at a dose that did not affect baseline BP, HR and RSNA enhanced the PBG-evoked reflex decrease of RSNA (-54+/-5% in Ang II treated versus -33+/-6% in control rats after 15 min PBG, P<0.05, n = 6 each) in methohexital-anaesthetized rats. 4. The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the reflex responses to PBG in anaesthetized as well as conscious animals. The effect of the ACE inhibitor was abolished by concomitant infusion of Ang II. 5. The reflex response to stimulation of cardiopulmonary 5HT3 afferents was also impaired by the Ang II type 1 receptor (AT1) blocker ZD7155 but not by the type 2 (AT2) blocker PD 123319. 6. Infusion of a volume load to stimulate cardiopulmonary baroreceptors induced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA -26+/-6% in Ang II treated versus -47+/-6% in control rats after volume load, P<0.05, n = 6 each) but unaffected by ACE inhibition. 7. The reflex control of RSNA by cardiopulmonary 5HT3 receptors is enhanced by Ang II via AT1 receptors. Thus, Ang II facilitates a chemosensitive cardiovascular reflex, in contrast to its inhibitory influences on mechanosensitive reflexes.


Physical activity is related to lower levels of pain, fatigue and depression in individuals with spinal-cord injury: a correlational study.
This was a prospective cross-sectional study for people with chronic spinal cord injury (SCI). To (1) evaluate the intensity level and nature of physical activity in community-dwelling individuals living with SCI, and (2) explore the relation between descriptive individual variables (for example, lesion level), secondary complications and participation in physical activity. Urban community setting. A total of 49 subjects with SCI who used a manual wheelchair for primary mode of mobility (mean years since injury, 11.8; mean age, 43.7 years; 67% paraplegia) completed the physical activity recall assessment for people with SCI (PARA-SCI). Approximately 50% of reported physical activity among individuals with SCI is due to activities of daily living. The amount of physical activity was not related to lesion level, age, body mass index or waistline size. Greater heavy-intensity activity was related to lower levels of pain and fatigue and higher levels of self-efficacy, whereas higher amounts of mild-intensity activity and total activity were related to less depressive symptoms. Activities of daily living are a large component for physical activity among individuals with SCI. It appears that greater physical activity is associated with less secondary complications (pain, fatigue and depression) in individuals with SCI.


Using GO-WAR for mining cross-ontology weighted association rules.
The Gene Ontology (GO) is a structured repository of concepts (GO terms) that are associated to one or more gene products. The process of association is referred to as annotation. The relevance and the specificity of both GO terms and annotations are evaluated by a measure defined as information content (IC). The analysis of annotated data is thus an important challenge for bioinformatics. There exist different approaches of analysis. From those, the use of association rules (AR) may provide useful knowledge, and it has been used in some applications, e.g. improving the quality of annotations. Nevertheless classical association rules algorithms do not take into account the source of annotation nor the importance yielding to the generation of candidate rules with low IC. This paper presents GO-WAR (Gene Ontology-based Weighted Association Rules) a methodology for extracting weighted association rules. GO-WAR can extract association rules with a high level of IC without loss of support and confidence from a dataset of annotated data. A case study on using of GO-WAR on publicly available GO annotation datasets is used to demonstrate that our method outperforms current state of the art approaches.


Contemporaneous symptom networks of multidimensional symptom experiences in cancer survivors: A network analysis.
Symptom networks can provide empirical evidence for the development of personalized and precise symptom management strategies. However, few studies have explored the symptom networks of multidimensional symptom experiences in cancer survivors. The objectives of this study were to generate symptom networks of multidimensional symptom experiences in cancer survivors and explore the centrality indices and density in these symptom networks METHODS: Data from 1065 cancer survivors were obtained from the Shanghai CANcer Survivor (SCANS) Report. The MD Anderson Symptom Inventory was used to assess the prevalence and severity of 13 cancer-related symptoms. We constructed contemporaneous networks with all 13 symptoms after controlling for covariates. Distress (rs = 9.18, rc = 0.06), sadness (rs = 9.05, rc = 0.06), and lack of appetite (rs = 9.04, rc = 0.06) had the largest values for strength and closeness. The density of the "less than 5 years" network was significantly different from that of the "5-10 years" and "over 10 years" networks (p < 0.001). We found that while fatigue was the most severe symptom in cancer survivorship, the centrality of fatigue was lower than that of the majority of other symptoms. Our study demonstrates the need for the assessment of centrality indices and network density as an essential component of cancer care, especially for survivors with <5 years of survivorship. Future studies are warranted to develop dynamic symptom networks and trajectories of centrality indices in longitudinal data to explore causality among symptoms and markers of interventions.


Permanent daylight saving time would reduce deer-vehicle collisions.
Overlap between wildlife and human activity is key to causing wildlife-vehicle collisions, a globally pervasive and growing source of wildlife mortality.1,2 Policies regarding clock time often involve abrupt seasonal shifts in human activity, potentially influencing rates of human-wildlife conflict. Here, we harness the biannual shift between standard and daylight saving time as a natural experiment to reveal how the timing of human activity influences deer-vehicle collisions. Based on 1,012,465 deer-vehicle collisions and 96 million hourly traffic observations across the United States, we show that collisions are 14 times more frequent 2 hours after sunset than before sunset, highlighting the importance of traffic during dark hours as a key determinant of deer-vehicle collision risk. The switch from daylight saving to standard time in autumn causes peak traffic volumes to shift from before sunset to after sunset, leading to a 16% spike in deer-vehicle collisions. By reducing traffic after dark, our model predicts that year-round daylight saving time would prevent 36,550 deer (Odocoileus sp.) deaths, 33 human deaths, 2,054 human injuries, and US$1.19 billion in collision costs annually. In contrast, permanent standard time is predicted to increase collisions by an even larger magnitude, incurring an additional US$2.39 billion in costs. By targeting the temporal dimension of wildlife-vehicle collisions, strategies such as year-round daylight saving time that reduce traffic during dark hours, especially during the breeding season of abundant ungulates, would yield substantial benefits for wildlife conservation and reduce the social and economic costs of deer-vehicle collisions.


Magnitude-dependent response of osteoblasts regulated by compressive stress.
The present study aimed to investigate the role of magnitude in adaptive response of osteoblasts exposed to compressive stress. Murine primary osteoblasts and MC3T3-E1 cells were exposed to compressive stress (0, 1, 2, 3, 4, and 5 g/cm2) in 3D culture. Cell viability was evaluated, and expression levels of Runx2, Alp, Ocn, Rankl, and Opg were examined. ALP activity in osteoblasts and TRAP activity in RAW264.7 cells co-cultured with MC3T3-E1 cells were assayed. Results showed that compressive stress within 5.0 g/cm2 did not influence cell viability. Both osteoblastic and osteoblast-regulated osteoclastic differentiation were enhanced at 2 g/cm2. An increase in stress above 2 g/cm2 did not enhance osteoblastic differentiation further but significantly inhibited osteoblast-regualted osteoclastic differentiation. This study suggested that compressive stress regulates osteoblastic and osteoclastic differentiation through osteoblasts in a magnitude-dependent manner.


Clinical prediction versus ultrasound measurement of IOL power.
1. Clinical prediction was better than ultrasound prediction for the first 20 cases. It was approximately equal for the next 20 cases, but after this ultrasound was the more accurate. 2. There was no significant difference in ability of either clinical prediction of ultrasound to predict the power of various types of lenses, namely, 4-loop intracapsular lenses, 2-loop extracapsular lenses and Choyce-style anterior chamber lenses. 3. There was no clinically significant difference in accuracy of prediction regardless of the source (manufacturer) studied in this series. 4. Two major factors affecting results which ultrasound is totally helpless in predicting are surgically induced astigmatism and accuracy of stated lens power supplied.


Effect of protein supplementation on plasma sodium levels in the syndrome of inappropriate antidiuresis: a monocentric, open-label, proof-of-concept study-the TREASURE study.
The syndrome of inappropriate antidiuresis (SIAD) can be treated with oral urea; however, compliance is impaired by its poor palatability. To investigate whether dietary proteins could increase plasma sodium levels through urea-induced osmotic diuresis. An open-label, proof-of-concept trial. University Hospital of Basel, Switzerland, between October 2021 and February 2023. Outpatients with chronic SIAD. Ninety grams of protein daily for 7 days in the form of protein powder, followed by 30 g of oral urea daily for 7 days after a wash-out period of ≥1 week. The increase in sodium levels from baseline to the end of the 7-day protein supplementation. Seventeen patients were included. After 7 days of 90 g daily protein supplementation (n = 17), plasma sodium levels increased from 131 (129-133) to 133 (132-137), that is, by a median of 3 mmol L-1 (0-5) (P = .01). Plasma urea levels increased by 3 mmol L-1 (1.7-4.9) (P < .01), and urine urea to creatinine ratio increased by 21.2 mmol mmol-1 (6.2-29.1) (P < .01). After 7 days of 30 g oral urea (n = 10), plasma sodium levels increased from 132 (130-133) to 134 (131-136), that is, by a median of 2 mmol L-1 (1-3) (P = .06). Plasma urea levels increased by 5.8 mmol L-1 (2.7-9.2) (P < .01), and urine urea to creatinine ratio increased by 31.0 mmol mmol-1 (18.7-45.1) (P < .01). Our findings suggest that protein powder increases plasma sodium levels in patients with chronic SIAD through protein-induced ureagenesis and osmotic diuresis. The effects are comparable with oral urea.


Hypotonic medium increases calcium permeant channels activity in human normal and dystrophic myotubes.
Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin and an elevated intracellular calcium level. Single-channel recordings were performed with the cell-attached configuration of the patch-clamp technique. The present study shows, on human co-cultured normal and dystrophic muscle cells, the evidence for an increased activity of calcium permeant cationic mechano-sensitive channels under hypotonic medium stimulation. This activity was particularly enhanced in DMD cells. The hypotonic medium induced drastic changes in the single-channel activity characteristics, which are: a large increase of the calcium over potassium permeability ratio; and a great enhancement of the quantity of current crossing through these channels. These channels could contribute to a significant calcium entry, which could participate in the abnormal calcium homeostasis observed in DMD muscle.


Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells.
Human bone marrow-derived mesenchymal cells (MSCs) are precursors of nonhematopoietic mesenchymal cells of the bone marrow microenvironment. MSCs were shown to inhibit alloreactive T lymphocytes, but the mechanism and mediators of this effect are not fully understood. Here we describe a novel interaction between blood monocytes and bone marrow-derived, culture-expanded MSCs, which results in inhibition of T-lymphocyte activation. We found that CD14+ monocytes from blood activate MSCs to secrete inhibitory molecules that lead to inhibition of alloreactive T cells. This cellular communication is not contact-dependent, but rather is mediated by soluble factors that include interleukin (IL)-1beta. MSC-mediated inhibition of alloreactive T lymphocytes is associated with downregulation of activation markers CD25, CD38, and CD69 detected both in CD4+ and CD8+ T lymphocytes. The cytokines secreted by MSCs that mediate T-cell inhibition include transforming growth factor-beta1, but not IL-10. The interaction between blood monocytes and the MSCs represents a unique immune regulatory paradigm that can potentially be exploited in clinic.


A Comparison of Approach and Avoidance Sexual Goals in Couples With Vulvodynia and Community Controls.
Provoked vestibulodynia (PVD) is a prevalent form of vulvodynia that interferes with the sexual and relational functioning of affected couples. Approach and avoidance sexual goals are associated with the sexual and relationship well-being of women with PVD and their partners. However, whether sexual goals differ in couples coping with PVD compared with community couples is unknown. To compare the approach and avoidance sexual goals of women with PVD and their partners with a control sample of community women and their partners to build on an established motivational model and to compare the sexual goals of women with PVD with those of their partners. Women diagnosed with PVD and their partners (n = 161) and control couples (n = 172) completed measures of approach and avoidance sexual goals. Approach and Avoidance Sexual Goals Questionnaire. Women with PVD reported lower approach and higher avoidance sexual goals than control women, whereas partners of women with PVD did not differ from control partners in their sexual goals. Women with PVD also reported lower approach and higher avoidance sexual goals compared with their partners, whereas there were no differences between partners in the control sample. Given that avoidance sexual goals have been linked to negative sexual and relational outcomes, clinicians could strive to help couples with PVD become aware of their sexual motives, with the aim of weakening avoidance sexual goals and bolstering approach sexual goals. This is the first study to empirically document differences in sexual goals between couples affected by PVD and community couples. Limitations include the study's correlational design, differences in demographic characteristics between samples, and the homogeneity of participants' sexual orientation. Findings suggest that the sexual goals of women affected by PVD differ from those of community women and from their partners and support sexual goals as targets for psychological interventions to help couples coping with PVD. Dubé JP, Bergeron S, Muise A, et al. A Comparison of Approach and Avoidance Sexual Goals in Couples With Vulvodynia and Community Controls. J Sex Med 2017;14:1412-1420.


Biventricular repair in children with atrioventricular septal defects and a small right ventricle: anatomic and surgical considerations.
We sought to characterize morphology and to evaluate a strategy of using biventricular repair in patients with a small right ventricle and an unbalanced atrioventricular septal defect. Thirty-eight children with a small right ventricle and an atrioventricular septal defect underwent operative therapy. Thirty-two had biventricular repair, and 6 had single-ventricle palliation. A small right ventricle was defined on the basis of echocardiographic measurements expressed as the atrioventricular valve index (ie, right atrioventricular valve/left atrioventricular valve area) and as the ratio of right ventricular to left ventricular length. Validation of measurements in patients with a small right ventricle and an atrioventricular septal defect was achieved by comparison with balanced case-matched control subjects with atrioventricular septal defects. Children with a small right ventricle and an atrioventricular septal defect had a lower atrioventricular valve index (mean, 0.41 +/- 0.1 vs 0.52 +/- 0.1 [control], P < .0001) and lower right ventricular/left ventricular length ratio (0.78 +/- 0.1 vs 0.99 +/- 0.17 [control], P < .0001). Children with a small right ventricle undergoing single-ventricle palliation had the smallest right ventricular dimensions. There were 4 operative deaths. Three patients with a small right ventricle and an atrioventricular septal defect who underwent biventricular repair and had an atrioventricular valve index of less than 0.50 required early reoperation for right ventricular inadequacy. A restrictive atrial fenestration was created in 11 infants. Survival at 10 years was 87% for patients undergoing biventricular repair versus 100% for control subjects (P = .042). Extending the use of biventricular repair in properly selected patients with a small right ventricle and an atrioventricular septal defect is feasible. An atrial fenestration improves the physiologic tolerance to repair in selected patients. The use of biventricular repair in children with atrioventricular valve indexes of less than 0.50 requires caution.


Wrist arthroscopy.
Understanding of wrist biomechanics and pathology is enhanced by wrist arthroscopy. The procedure does indeed provide an alternative to arthrotomy in selected situations, greatly decreasing patient morbidity. It is a difficult skill to acquire; however, wrist arthroscopy presents diagnostic and therapeutic benefits that far outweigh this short-lived drawback.


V Flow technology in measurement of wall shear stress of common carotid arteries in healthy adults: Feasibility and normal values.
To evaluate the feasibility of vector flow imaging technique (V Flow) in measurement of wall shear stress (WSS) of common carotid arteries (CCA) in healthy adults and to provide the normal WSS values assessed by V Flow. This prospective study was approved by the Ethics Committee of our University. Eighty healthy adult volunteers were included (mean age 43.3 y, 47 females, 33 males). The volunteers were classified into three groups according to their age: group I (age 20 - 39 y), group II (age 40 - 59 y) and group III (age 60 - 80 y). Mindray Resona 8 ultrasound machine and a linear array transducer (3-9 MHz) was used, equipped with the updated V Flow function. Common carotid arteries of both sides were evaluated in three segments (initial segment, middle segment and near bifurcation segment). The WSS values of CCA were measured by two independent radiologists. The intraclass correlation coefficient (ICC) of observer reliability in WSS measurement was calculated. Inter-observer reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). V Flow measurements were performed successfully in 79 volunteers (98.8 %, 79/80). The mean value of WSS in right CCA was (0.66±0.24) Pa, in left CCA was (0.66±0.18) Pa (P > 0.05). Mean WSS value had a moderately negative correlation with age group (P < 0.05). The mean WSS value of group I(mean±SD, 0.75±0.25 Pa) is larger than group II (mean±SD, 0.62±0.13 Pa) and group III (mean±SD, 0.49±0.11 Pa) (P < 0.05). The ICC of observer reliability of group I, II and III was 0.96 (95% confidence interval (95% CI) 0.92-0.98), 0.94 (95% CI 0.88-0.97), 0.93 (95% CI 0.76-0.98) respectively. The Bland-Altman plots showed that the 95% LOA were -0.17-0.12 (Pa) for group I, -0.09-0.13 (Pa) for group II and -0.08-0.10 (Pa) for group III. V Flow measurement is a simple, rapid and feasible imaging method for the WSS assessment of CCA in healthy volunteers, which will probably be an important tool for assessing CCA function.


Mid-Term Outcomes of the All-Soft Quadriceps Tendon Autograft Are Noninferior to Hamstring Autograft in Primary Anterior Cruciate Ligament Reconstruction: Comparison With Minimum 5-Year Follow-Up.
To compare the 5-year clinical and functional outcomes of the soft-tissue quadriceps tendon (QT) with those of the hamstring tendon (HT) autograft. A retrospective review of patients undergoing anterior cruciate ligament reconstruction using either soft-tissue QT or double-tendon HT autograft with at least 5 years of follow-up was conducted. Surgical technique included anteromedial portal creation for the femoral tunnel and transtibial technique for the tibia. Graft fixation was achieved with interference composite screws for the QT and combination of interference composite screw and suture button for the HT cohort. The 2 groups were compared for differences in outcomes, including International Knee Documentation Committee (IKDC) score, Lysholm score, return to sport, and complications. A total of 37 patients with QT autograft and 46 HT autografts were included in the study, with a mean follow up of 69.9 months and 70.9 months, respectively. The QT group demonstrated a larger graft size on average (9.64 mm vs 7.90 mm, P < .001). The IKDC and Lysholm scores were similar between the 2 groups at 2-years' postoperatively. At 5 years' postoperatively, the QT group demonstrated significantly greater IKDC (P = .018) and Lysholm (P = .007) scores. The cohorts demonstrated similar rates of achieving minimal clinically important difference thresholds at both 2 and 5 years' postoperatively. The 2 groups also demonstrated comparable rates of return to sport, time to return, and postoperative complications. Although the QT autograft demonstrated increased patient-reported outcome scores when compared with the HT at 5 years' postoperatively, there was no clinically significant difference between the cohorts at 2 or 5 years' postoperatively. The QT autograft is an effective alternative to HT autograft with noninferior results to the HT autograft at mid-term follow-up. III, retrospective comparison study.


5-Methoxypsoralen (Bergapten) for photochemotherapy. Bioavailability, phototoxicity, and clinical efficacy in psoriasis of a new drug preparation.
In a previous study we evaluated a microcrystalline preparation of 5-methoxypsoralen (5-MOP; Bergapten) for its photochemotherapeutic properties. Preliminary data indicated that the clinical efficacy of 5-MOP is comparable to that of 8-methoxypsoralen. 5-MOP appeared as a promising alternative photosensitizer for the management of psoriasis because of the almost complete lack of phototoxic and drug intolerance reactions that are frequently encountered in patients undergoing 8-MOP photochemotherapy. With a new liquid preparation of 5-MOP we have now extended our earlier investigation on a larger clinical scale and have correlated the clinical response with the bioavailability of the drug. Serum level determinations showed an absorption rate of only approximately 25% that of 8-MOP. When administered in the same dosage as 8-MOP, 5-MOP turned out to be significantly less effective; however, by doubling the oral dosage, comparable results in terms of clearing of psoriasis were obtained. Also with this high-dose 5-MOP regimen, no drug intolerance was noted and other side effects, such as severe erythema, pruritus, and nausea, occurred only rarely. We propose 5-MOP as a valuable alternative for photochemotherapy (PUVA) of PUVA-responsive diseases.


Epidemiology of adult rib fracture and factors associated with surgical fixation: Analysis of a chest wall injury dataset from England and Wales.
Chest wall trauma is commonly seen in patients admitted with both high and low-energy transfer injury. Whilst often associated with other injuries, it is also seen in isolation following simple falls in the older patient. Fixation of the chest wall grows in popularity as part of optimising patient care, particularly in terms of critical care stay. There is currently no description of the epidemiology of these injuries at a national level; nor has there been identification of factors that predict which of these patients undergoes surgery. The United Kingdom Trauma Audit & Research Network (TARN) database was analysed for the period April 2016 to 30th May 2017 for all adult patients presenting with a rib or sternal fracture. Characteristics of the population were described and a binary logistic regression model constructed to explore the influences of several explanatory variables on whether fixation was performed. Of 16,638 patients with chest wall trauma, 402 underwent fixation. Most chest wall injury patients were admitted under three specialties (orthopaedics (19.1%), emergency medicine (16.6%) and general surgery (17.7%)). The odds of fixation in unilateral flail chest was 107.51 (p <0.0001), in bilateral flail or combined complexsternal fracture 47.63 (p = 0.007) and in 3 or more non-flail ribs 15.62 (p<0.0001) when compared to less than three non-flail rib fractures. The odds of fixation was higher in an MTC (p<0.0001) compared to a non-specialist hospital. The odds of fixation was higher in older patients (1.02, p<0.0001) and the more severely injured (1.02, p<0.0001). There is considerable variation nationally in the management of chest wall trauma. Injury type, patient age and care setting contribute to decision making in fracture fixation. This unique national dataset characterises for the first time the nature of contemporary chest wall trauma management and should help inform the design of future research on this topic.


Complete atrioventricular block decreases left ventricular assist device flow rate.
A 52-year-old man, living at home, had been on left ventricular assistance for 15 months with a Novacor pump (Worldheart, Ottawa, ON, Canada). Following the onset of effort dyspnea that had recently become worse, he was admitted to the hospital. A review of the pump showed that its flow rate had significantly decreased. An electrocardiogram showed a third-degree atrioventricular block. A pacemaker was implanted and the patient became asymptomatic immediately afterwards. This clinical case report shows the importance of satisfactory right ventricle filling in these patients. Right ventricle filling can be impaired by conduction disorders.


State-level seat belt use in the United States, 2011-2016: Comparison of self-reported with observed use and use by fatally injured occupants.
Despite 49 states and the District of Columbia having seat belt laws that permit either primary or secondary enforcement, nearly half of persons who die in passenger vehicle crashes in the United States are unbelted. Monitoring seat belt use is important for measuring the effectiveness of strategies to increase belt use. Document self-reported seat belt use by state seat belt enforcement type and compare 2016 self-reported belt use with observed use and use among passenger vehicle occupant (PVO) fatalities. We analyzed the Behavioral Risk Factor Surveillance System (BRFSS) self-reported seat belt use data during 2011-2016. The Pearson correlation coefficient (r) was used to compare the 2016 BRFSS state estimates with observed seat belt use from state-based surveys and with unrestrained PVO fatalities from the Fatality Analysis Reporting System. During 2011-2016, national self-reported seat belt use ranged from 86-88%. In 2016, national self-reported use (87%) lagged observed use (90%) by 3 percentage points. By state, the 2016 self-reported use ranged from 64% in South Dakota to 93% in California, Hawaii, and Oregon. Seat belt use averaged 7 percentage points higher in primary enforcement states (89%) than in secondary states (82%). Self-reported state estimates were strongly positively correlated with state observational estimates (r = 0.80) and strongly negatively correlated with the proportion of unrestrained PVO fatalities (r = -0.77). National self-reported seat belt use remained essentially stable during 2011-2016 at around 87%, but large variations existed across states. Practical Applications: If seat belt use in secondary enforcement states matched use in primary enforcement states for 2016, an additional 3.98 million adults would have been belted. Renewed attention to increasing seat belt use will be needed to reduce motor-vehicle fatalities. Self-reported and observational seat belt data complement one another and can aid in designing targeted and multifaceted interventions.


EHMT2 methyltransferase governs cell identity in the lung and is required for KRAS G12D tumor development and propagation.
Lung development, integrity and repair rely on precise Wnt signaling, which is corrupted in diverse diseases, including cancer. Here, we discover that EHMT2 methyltransferase regulates Wnt signaling in the lung by controlling the transcriptional activity of chromatin-bound β-catenin, through a non-histone substrate in mouse lung. Inhibition of EHMT2 induces transcriptional, morphologic, and molecular changes consistent with alveolar type 2 (AT2) lineage commitment. Mechanistically, EHMT2 activity functions to support regenerative properties of KrasG12D tumors and normal AT2 cells-the predominant cell of origin of this cancer. Consequently, EHMT2 inhibition prevents KrasG12D lung adenocarcinoma (LUAD) tumor formation and propagation and disrupts normal AT2 cell differentiation. Consistent with these findings, low gene EHMT2 expression in human LUAD correlates with enhanced AT2 gene expression and improved prognosis. These data reveal EHMT2 as a critical regulator of Wnt signaling, implicating Ehmt2 as a potential target in lung cancer and other AT2-mediated lung pathologies.


Effects of isoflurane on electrophysiological measurements in children with the Wolff-Parkinson-White syndrome.
This study was designed to assess the effects of isoflurane (ISO) on the electrophysiological properties of the accessory pathway, atrium, ventricle, and AV node in children with the Wolff-Parkinson-White (WPW) syndrome. The results of programmed electrical stimulation were analyzed in 51 patients (4 months to 17 years of age) with WPW. The study population was divided into two groups. Twenty-seven patients received local anesthesia and intramuscular injection of meperidine, promethazine, and chlorpromazine (MPC group). Twenty-four patients received general anesthesia with ISO inhalation (ISO group). We compared the antegrade effective refractory period of the accessory pathway (antegrade APERP), ventricular effective refractory period (VERP), atrial effective refractory period (AERP), AH interval, and cycle length of circus movement tachycardia (CMT-CL) in 12 pairs of age and sex matched patients selected from the MPC and ISO groups. Of the 12 pairs of age and sex matched patients, antegrade APERP in patients who received ISO (299 +/- 17 ms, mean +/- SEM) was significantly longer as compared with matched patients in the MPC group (262 +/- 5 ms, P < 0.025). The VERP and AERP in patients from the ISO group were significantly prolonged compared with the MPC patients (239 +/- 7 vs 210 +/- 8 ms, P < 0.025, and 228 +/- 11 vs 180 +/- 6 ms, P < 0.01, respectively). There was no significant difference in the AH interval or CMT-CL between the two subgroups. Thus, ISO prolongs the antegrade APERPs as well as the effective refractory periods of atrial and ventricular muscle in children with WPW, while the AH interval and CMT-CL appear to be unaffected. Care must be taken in interpreting measurements of the antegrade APERP made in patients under general anesthesia for RF ablation of accessory pathways.


Streptokinase is a flexible multi-domain protein.
The structure of streptokinase in solution has been studied by dynamic light scattering, small-angle X-ray scattering and circular dichroism spectroscopy. The Stokes' radius and radius of gyration of the protein monomer are 3.58 nm and 4.03 nm, respectively. The maximum intraparticle distance of the molecule is 14 nm. More than half of the amino acids of the molecule are organized in regular secondary structures. The X-ray scattering curve, the results from dynamic light scattering, and the finding that at least 50% of the amino acid residues are organized in regularly folded secondary structures are consistent with the following structural model. Streptokinase consists of four compact, separately folded, domains linked by mobile segments of the protein chain. The molecule exhibits the conformation of a flexible string-of-beads in solution.


Tauritermes bandeirai: A new drywood termite (Isoptera, Kalotermitidae) from the Caatinga and Atlantic Forest of Brazil.
The imago and soldier castes of a new Tauritermes Krishna, 1961 species, Tauritermes bandeirai sp. nov. are described. It is the fourth species of Tauritermes and occurs from the Caatinga and Atlantic Forest of Brazil. Unlike its congeners, the soldier of T. bandeirai has prominent frontal horns.


[Bullous ichthyosis. A particular form of epidermolytic hyperkeratosis].
We report three familial cases of a particular type of ichthyosis bullosa. The clinical picture is different from bullous congenital ichthyosiform erythroderma, but the histologic and ultrastructural features are those of epidermolytic hyperkeratosis.


Detection of circulatory disturbance after pulmonary vein division during a living donor lobectomy.
Indocyanine green (ICG) is widely used during thoracic surgery to enhance visualization, allowing assessment of the intersegmental plane based on intrapulmonary blood flow (Travis et al. in Ann Thorac Surg 108(2):363-369, 2019; Seshiru et al. in Gen Thorac Cardiovasc Surg 66(2):81-90, 2018). Using ICG to detect blood flow disruption after lung resection, however, has not been addressed. We therefore report a case in which the left lingular pulmonary vein was incidentally divided during left lower lobectomy in a living-lung donor. Intraoperative ICG-enhanced near-infrared fluoroscopic imaging to assess intrapulmonary blood flow detected the problem. We thus avoided potential postoperative residual lung complications in this patient.


Counting difficulties: retained instruments, sponges, and needles.
Patients in whom a sponge or instruments is left after surgery may suffer complications including pain, infection, abscess, or intestinal obstruction. Consequences or retained items for surgical team members may include malpractice lawsuits and adverse actions from the National Practitioner Data Bank and state licensing board. Adherence to AORN recommended practices for counting and facility counting policies can protect both patients and practitioners.


Cryptorchidism as a potential source of misinterpretation in ¹⁸FDG-PET imaging in restaging lymphoma patients.
The estimated prevalence of cryptorchidism in young males is close to 2%. In oncological PET/CT studies, it might be difficult to recognize false-positive ¹⁸FDG uptake due to an ectopic testis. In this pilot study, we report on three patients with lymphoma referred for assessment of response to treatment and in whom cryptorchidism was not known at the time of ¹⁸FDG-PET/CT imaging. In each of these patients, moderate ¹⁸FDG uptake corresponding to an ovoid mass in the inguinal canal was (or could has been) misinterpreted as a lymphoma-involved inguinal lymph node. Clues to avoid misinterpretation are discussed. Moderate ¹⁸FDG uptake in ectopic testes represents a potential source of false-positive at initial staging or evaluation of therapeutic response of lymphomas and other malignancies that needs to be recognized.