Phosphate modification of fructose-1,6-bisphosphate aldolase in Escherichia coli.
When E. coli carrying multicopy plasmids for fructose-1,6-P2 aldolase or phosphoglycerate kinase was grown in the presence of 32Pi, there was label at the position of cognate high level polypeptide after SDS-PAGE. As tested for aldolase, the label was resistant to acetone, RNase, and hot TCA treatments, and was also observed by immunoprecipitation, which was competed for by purified aldolase. Incorporation of label also occurred in the presence of chloramphenicol. Immunoprecipitation revealed apparent aldolase labeling in the wild type strain as well.


Studies on closure of the ductus arteriosus. X. In vivo effect of prostaglandin.
The effect of prostaglandins F2alpha, E1 and of 7-oxa-13-prostynoic acid on the newborn rabbit ductus can be studied using the whole-body freezing technique. PGF2alpha and PGE1 were able to re-open the closing ductus arteriosus in adequately oxygenated animals. PGF2alpha administration was accompanied by a strong physical reaction in the rat but less in the rabbit. PGE1 had sedative effects in both animals. A prostaglandin antagonist, 7-oxa-13-prostynoic acid had no effect on normal ductal closure nor did it counteract the effects of PGF2alpha and PGE1. The role of prostaglandins in homeostasis during the fetal and newborn period may be to modify ductal tone.


Crowds and power - coordinated in vitro development of a benign breast lesion.
We have discovered an organoid culture approach that recapitulates morphology and coordinated development of a benign breast tumor. This system may be useful to groups investigating normal mammary gland biology and coordination of collective cell behavior in the mammary gland.


Chicken red-sensitive cone visual pigment retains a binding domain for transducin.
Iodopsin (a red-sensitive cone visual pigment) and rhodopsin (a rod pigment) were isolated from chicken retina. They were separately reconstituted into phosphatidylcholine liposomes and then mixed with rod transducin (T alpha and T beta gamma) purified from bovine retina. Iodopsin enhanced, only when irradiated, the binding of GppNHp to T alpha to a similar extent to irradiated rhodopsin. Furthermore, the binding of GppNHp to T alpha in the presence of a photobleaching intermediate of iodopsin preferably required T beta gamma-2 rather than T beta gamma-1, which is very similar in profile to that in the presence of the intermediate of rhodopsin (J. Biol. Chem., in press). These results indicate that the binding domain for transducin in iodopsin should closely resemble that in rhodopsin.


Preliminary comparison of the efficacy of several surgical treatments based on maxillomandibular advancement procedures in adult patients with obstructive sleep apnoea: a systematic review and network meta-analysis.
To evaluate the efficacy of eight different surgical treatments based on maxillomandibular advancement (MMA), which has emerged in recent years, for adult obstructive sleep apnoea (OSA) patients. The literature was searched from January 2010 to May 2020 for studies of adult OSA patients with different types of MMA procedures to perform a network meta-analysis. The outcomes were changes in the apnoea-hypopnoea index (AHI), the lowest pulse oxygen saturation (SpO2 min) and the Epworth Sleepiness Scale (ESS). Treatment hierarchy was summarized according to the rank charts. Eight studies were included and encompassed a total of 227 adult patients diagnosed with OSA. Among them, 225 patients underwent combined surgery or simple MMA surgery, including modified maxillomandibular advancement (MMMA),counterclockwise maxillomandibular advancement (CMMA), drug-induced sleep endoscopy and maxillomandibular advancement (MMA + DISE), transoral robotic surgery and maxillomandibular advancement (MMA + TORS), uvulopalatopharyngoplasty (UPPP), maxillomandibular advancement and uvulopalatopharyngoplasty (MMA + UPPP), uvulopalatopharyngoplasty with uvula preservation and maxillomandibular advancement (MMA + HUPPP); MMA consisting of Le Fort I osteotomy and bilateral inverted-L osteotomy (ILOs), genioplasty and iliac bone grafting; and MMA consisting of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty. The results showed that the most effective surgical treatment is MMA + HUPPP [- 56.79 (WMD); 95% confidence interval (CI): - 113.02 to - 3.33] (P < 0.00001), which was far superior to other approaches. MMA combined with HUPPP had the highest efficacy. The MMA consisted of Le Fort I osteotomy, bilateral sagittal split ramus osteotomies and genioplasty; CMMA and MMA + TORS are likely also great choices.


[Coat's disease treated with bevacizumab (Avastin)].
We report a case of Coats' disease in a 10-year-old-girl who presented with a profound visual deficit, exudative retinal detachment, vascular telangiectasias and subretinal lipid, who underwent treatment with an intravitreal injection of bevacizumab (AVASTIN(TM)). Serial examinations documented an involutional response with a reduction of the subretinal fluid, exudates and macular thickness. The aetiology of Coats' disease remains uncertain, as does its optimal management. Although resolution of a case depends partially on age, and can even occur spontaneously on rare occasions, intravitreal injections of bevacizumab should be considered when planning treatment.


Proteolytic activity of mycoplasmas and ureaplasmas isolated freshly from human saliva.
Mycoplasma and Ureaplasma strains freshly isolated from human saliva were examined for proteolytic activity. All the strains tested (101 strains of Mycoplasma salivarium, 97 strains of Mycoplasma orale, and 3 strains each of Mycoplasma hominis and Ureaplasma urealyticum) decomposed horse serum proteins, bovine albumin, and casein. Ten of the M. salivarium and 8 of the M. orale strains were tested for aminopeptidase activity as well, using L-leucine-p-nitroanilide as a substrate, and were shown to possess the activity. Thus proteolytic activity was suggested to be one of the biological characteristics of these two species. The level of both caseinolytic and aminopeptidase activity was significantly higher in M. salivarium than M. orale strains.


Improvement of Duchenne muscular dystrophy phenotype following obestatin treatment.
This study was performed to test the therapeutic potential of obestatin, an autocrine anabolic factor regulating skeletal muscle repair, to ameliorate the Duchenne muscular dystrophy (DMD) phenotype. Using a multidisciplinary approach, we characterized the ageing-related preproghrelin/GPR39 expression patterns in tibialis anterior (TA) muscles of 4-, 8-, and 18-week-old mdx mice (n = 3/group) and established the effects of obestatin administration at this level in 8-week-old mdx mice (n = 5/group). The findings were extended to in vitro effects on human immortalized DMD myotubes. An analysis of TAs revealed an age-related loss of preproghrelin expression, as precursor of obestatin, in mdx mice. Administration of obestatin resulted in a significant increase in tetanic specific force (33.0% ± 1.5%, P < 0.05), compared with control mdx mice. Obestatin-treated TAs were characterized by reduction of fibres with centrally located nuclei (10.0% ± 1.2%, P < 0.05) together with an increase in the number of type I fibres (25.2% ± 1.7%, P < 0.05) associated to histone deacetylases/myocyte enhancer factor-2 and peroxisome proliferator-activated receptor-gamma coactivator 1α axis, and down-regulation of ubiquitin E3-ligases by inactivation of FoxO1/4, indexes of muscle atrophy. Obestatin reduced the level of contractile damage and tissue fibrosis. These observations correlated with decline in serum creatine kinase (58.8 ± 15.2, P < 0.05). Obestatin led to stabilization of the sarcolemma by up-regulation of utrophin, α-syntrophin, β-dystroglycan, and α7β1-integrin proteins. These pathways were also operative in human DMD myotubes. These results highlight the potential of obestatin as a peptide therapeutic for preserving muscle integrity in DMD, thus allowing a better efficiency of gene or cell therapy in a combined therapeutic approach.


Antigen-specificity of antiretinal antibodies in patients with noninfectious uveitis.
Antiretinal antibodies (ARAs) have previously been described in noninfectious uveitis. However, the antigen specificity of these ARAs has not been investigated. The purpose of this study was to identify antigen-specific ARAs in noninfectious uveitis. A total of 18 patients with noninfectious uveitis were enrolled. Surface plasmon resonance was used to measure binding responses of patient and control sera against several uveitogenic proteins: recoverin, S-antigen, interphotoreceptor retinoid binding (IRBP), retinal-pigment-epithelium-specific 65-kDa protein (RPE65), tyrosinase-related protein 1 (TRYP1), and tyrosinase-related protein 2 (TRYP2). The frequency of ARA positivity against S-antigen, IRBP, RPE65, TYRP1, and TYRP2 in patients with uveitis did not differ significantly from that of normal controls. However, ARA positivity for recoverin was more frequently observed in patients with uveitis (p = 0.002). A total of 10 patients in the uveitis cohort had birdshot chorioretinopathy, and all 10 were positive for anti-recoverin ARAs. Patients with noninfectious uveitis have increased frequency of ARA positivity against recoverin. This ARA deserves further investigations as a potential biomarker and pathogenic agent in noninfectious uveitis, especially in birdshot chorioretinopathy.


Benzohydroxamic acid induces polyspermic fertilization in the sea urchin Arbacia punctulata.
Benzohydroxamic acid (BHA) is a competitive inhibitor of the sea urchin sperm peroxidase. We now report that addition of BHA to fertilization cultures of Arbacia punctulata promotes polyspermy. This effect is dose and sperm density dependent. The cortical reaction (elevation of the fertilization envelope) is not retarded by BHA. BHA must be added to the cultures before the eggs complete the cortical reaction at 60 sec post insemination in order to induce polyspermy. Since sea urchin eggs release H2O2 during the cortical reaction at fertilization, these findings support our hypothesis that the sperm peroxidase has a functional role in helping to prevent polyspermy.


Intensive case management for high-risk patients with first-episode psychosis: service model and outcomes.
The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis service showed significant improvement in key service outcomes. Further analysis is needed to determine cost savings and effects on psychosocial outcomes. Targeting intensive case management services to high-risk patients with unmet needs should reduce the distress associated with pathways to care for patients, their families, and the community. National Health & Medical Research Council and the Colonial Foundation.


Pharmacology and pharmacokinetics of estrogens.
The primary source of estrogen, ovarian 17 beta-estradiol, is normally converted to estrone and estriol, both of which are metabolized to their sulfate and glucuronide forms, as well as oxidated to nonestrogens. In postmenopausal women, the primary sources of estrogen are nonovarian, including the production of androstenedione from the adrenal cortex and its metabolism to estrone by the liver, adipose tissue, skeletal muscle, kidney, brain, and hair follicles. Estrogen circulates bound to sex hormone-binding globulin and albumin. The sulfate form may be a storage form of this hormone and is freely converted back to estrone and estriol. The glucuronide and sulfate forms have limited cell penetration; they are excreted mainly in the kidney, with little tubular reabsorption. Several theories have been advanced to explain the effects of estrogens on the basis of their receptors. A consideration of pharmacologic and pharmacokinetic characteristics reveals specific advantages and disadvantages of the preparations currently available for estrogen replacement therapy. Oral agents have the disadvantage of being subject to a considerable first-pass hepatic effect, resulting in their conversion to estriol, oxidation to nonestrogens, and conjugation to sulfate and glucuronide salts. These preparations can also be associated with poor patient compliance, as can injectable, topical, or suppository preparations. On the other hand, transdermal patches are not subject to a first-pass hepatic effect, provide relatively uniform serum levels, and may help alleviate the problem of noncompliance.


The interaction of adriamycin with small unilamellar vesicle liposomes. A fluorescence study.
The interaction of the antineoplastic agent adriamycin with sonicated liposomes composed of phosphatidylcholine alone and with small amounts (1-6%) of cardiolipin has been studied by fluorescence techniques. Equilibrium binding data show that the presence of cardiolipin increases the amount of drug bound to liposomes when the bilayer is below its phase transition temperature and when the ionic strength is relatively low (0.01 M). At higher ionic strength (0.15 M) and above the Tm (i.e. conditions which are closer to the physiological state) the binding of the drug to the two liposome types is nearly the same. Thus the differences in the interactions of adriamycin with cardiolipin-containing membranes, as opposed to those composed of phosphatidylcholine alone, are not due simply to increased binding but rather to an altered membrane structure when this lipid is present. Quenching of adriamycin fluorescence by iodide shows that bound drug is partially, but not completely, buried in the liposomal membrane. Both in the presence and absence of cardiolipin the bulk of the adriamycin is more accessible to the quencher below the Tm than above it; that is, a solid membrane tends to exclude the drug from deep penetration. Above the Tm, the presence of cardiolipin alters the nature of liposome-adriamycin interaction. Here the fluorescence quenching data suggest that the presence of small amounts of cardiolipin (3%) in a phosphatidylcholine matrix creates two types of binding environments for drug, one relatively exposed and the other more deeply buried in the membrane. The temperature dependence of the adriamycin fluorescence and the liposome light scattering reveal that cardiolipin alters the thermal properties of the bilayer as well as its interaction with adriamycin. At low ionic strength lateral phase separations may occur with both pure phosphatidylcholine and when 3% cardiolipin is present; under these conditions the bound adriamycin exists in two kinds of environment. It is notable that only adriamycin fluorescence reveals this phenomenon; thebulk property of liposome light scattering reports only on the overall membrane phase change. These data suggest that under certain conditions the drug binding sites in the membranes are decoupled from the bulk of the lipid bilayer.


Spatial Proliferation of Epithelial Cells Is Regulated by E-Cadherin Force.
Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-cadherin force-dependent manner. In this study, the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers. To determine if high levels of E-cadherin force were necessary to induce proliferation at the center of the colony, a lower-force mutant of E-cadherin was developed. Cells with lower E-cadherin force had significantly reduced proliferation for cells at the center of the colony but minimal differences for cells at the edges of the colony. Similarly, increasing substrate stiffness was found to increase E-cadherin force and increase the proliferation rate across the colony. Taken together, these results show that forces through cell-cell junctions regulate proliferation across large groups of epithelial cells. In addition, an important finding of this study is that junction forces are dynamic and modulate cellular function even in the absence of externally applied loads.


Acuity Comparison Methods via Timed Test-Retest Precision of Matching-Card e-ETDRS Compared to PDI Check in Treated Amblyopes and Superb Normals.
Existing and emerging visual acuity methods like dynamic and dichoptic presentation, preferential looking and eye tracking promise to afford better and earlier assessment in children with and without amblyopia so we propose methods needed to easily evaluate and compare their metrics. Patients older than 8 years with treated amblyopia and superb vision (logMAR -0.1 to -0.3) normals performed timed, patched eETDRS with Sloan matching card at 3.00 m and PDI Check dichoptic near rivalry dynamic test to demonstrate test re-Test and compared disparate acuity with intraclass correlation (ICC) and Bland Altman 95% limits of agreement (LOA) to generate a simple method of qualifying acuity test matching. 26 amblyopic patients and 11 superb-vision normals performed eETDRS retest, PDI Check retest and combined ICC of 0.98, 0.60 and 0.27, respectively, and Bland Altman LOA of 0.24, 2.06 and 2.28 logMAR. The time to test one eye with eETDRS had median (interquartile range; IQR) duration of 280 (205 to 346) seconds, while the PDI Check autostereoscopic dichoptic for both eyes only took 39 (30 to 47) seconds. Optimum ICC and LOA for visual acuity comparison should be >0.95 and <0.3 logMAR, whereas "good" ICC and should be 0.75-0.89 ICC and 1.0-1.49 logMAR LOA. Superb vision subjects (logMAR < -0.1) and treated amblyopic patients confirmed optimum comparable eETDRS, and fair test re-Test PDI Check but suppression on near dichoptic testing confirmed disparity compared to optimized eETDRS distance acuity.


High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice.
Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.


Using item response theory in the development and validation of the College-Oriented Eating Disorders Screen.
The current study examined the psychometric characteristics of the College-Oriented Eating Disorders Screen (COEDS), a college-student-focused screening measure to assess and identify individuals at-risk for the development of eating disordered pathology. By screening a large pool of pilot questions and using methods based in item response theory (IRT), seven items were identified with well-targeted contents that discriminated well across the continuum of eating disorder severity. The resulting measure evidenced a unidimensional factor structure and correlated highly with the original COEDS, standard measures of eating disorders pathology, and a measure of associated symptomatology (e.g., depressive symptoms). Based on these results, we discuss the utility of the COEDS as a prognostic indicator for risk of eating disordered pathology among college students.


The rise of neuroskepticism.
The increasing popularity of functional neuroimaging technologies in multiple disciplines has gained attention from within and outside the field of neuroscience. As the scope of research employing functional neuroimaging technologies broadens, there appears to also be a growing concern about the use of these technologies and the related social, ethical and legal issues. These concerns have been coined 'neuroskepticism'. First, we review how the term neuroskepticism has been previously used and defined. Second, we examine review and commentary articles published in journals with top impact factors, probing the presence and evolution of neuroskepticism within these articles. Results demonstrate a wide, but expected, range of issues associated with functional neuroimaging. It also appears that neuroskepticism is increasing as functional neuroimaging technologies gain popularity, which may indicate the presence of a classic Gartner Hype Cycle.


Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens.
Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor selectively expressed in thyroid, lung and diencephalon. It has been shown to label pulmonary adenocarcinoma, thyroid tumors, and small cell carcinoma (pulmonary and extrapulmonary) with relatively high sensitivity and specificity. The usefulness of this immunostain in cytology specimens has not been thoroughly discussed in the literature. The authors evaluated 36 effusion cytology cases (17 pleural effusion, 18 ascitic fluid, and 1 pericardial effusion) diagnosed as metastatic adenocarcinoma and with cell blocks prepared from the file of Pamela Youde Nethersole Eastern Hospital, Hong Kong, during a three-year period from 1998 to early 2001. The clinical, radiologic, cytologic, and histologic (if any) findings were reviewed. A provisional diagnosis of the primary site was deduced for each of the 36 cases by clinical, radiologic, and/or histologic correlation. Immunohistochemical study was performed on the cell block sections of the effusion cytology specimens using mouse monoclonal antibody against TTF-1, after microwave heat-antigen retrieval. The results were correlated with the primary origin of the metastatic adenocarcinoma. Among the 17 cases of metastatic pulmonary adenocarcinoma, 15 cases showed nuclear staining for TTF-1 in most of the tumor cells (sensitivity, 88.2%). None of the 19 cases of metastatic extrapulmonary adenocarcinoma expressed TTF-1 (specificity, 100%). The current study validates TTF-1 as a highly sensitive and specific immunomarker for distinguishing between metastatic pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens, which are known to be associated with intrinsic artifact due to less than ideal cellular preservation.


The evolutionary relationships of zebrafish genes tbx6, tbx16/spadetail and mga.
The T-box (Tbx) genes encode a family of transcription factors required for development of vertebrate embryos. In an attempt to discover human orthologues of the zebrafish (Danio rerio) tbx6 and tbx16/spadetail genes, we found that the most similar human (Homo sapiens) gene is the orthologue of mouse (Mus musculus) Mga (MAX gene associated). We have identified the zebrafish orthologue of Mga using analyses of sequence similarity and the orthologies of syntenic genes. Zebrafish mga maps close to dtk (developmental receptor tyrosine kinase), the orthologue of human TYRO3 (TYRO3 protein tyrosine kinase). Like its human and mouse orthologues, zebrafish mga lacks the three conserved introns within the T-box coding sequences that are characteristic of the vertebrate T-box gene family. This suggests that these genes are derived from an ancient reverse transcription event. The human genome does not appear to possess orthologues of zebrafish tbx6 or tbx16/spadetail.


Comparison of the M RNA genome segments of two human isolates of La Crosse virus.
The M genomic RNA segments of La Crosse (LAC) virus isolates from the brains of two children autopsied 18 years apart in Wisconsin were molecularly cloned using a reverse transcriptase-PCR assay and the nucleotide sequences of the cDNAs determined. The M RNA of each virus contains 4526 nucleotides, similar to that reported previously for a New York mosquito isolate of LAC. There were 20 nucleotide differences between the two human isolates, which results in the prediction of 7 amino acid changes in the proteins encoded in the single, long open reading frame of the M segment. One of these predicted differences occurs in the G2 glycoprotein and six in the G1 glycoprotein. The two viruses were identical in terms of predicted amino acid sequence in the region believed to represent a nonstructural protein. These data have been further compared to those available for two other California serogroup isolates.


Circ-BNIP3L knockdown alleviates LPS-induced renal tubular epithelial cell injury during sepsis-associated acute kidney injury by miR-370-3p/MYD88 axis.
Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of the critically ill patient with high morbidity and mortality. Thus, the goal of this study was to investigate the role of circular RNA BCL2 Interacting Protein 3 Like (circ-BNIP3L) in the pathophysiological mechanism of SA-AKI. The SA-AKI cell model was established by using lipopolysaccharide (LPS)-induced HK-2 cells in vitro. Cell survival was analyzed using cell counting kit-8 (CCK-8) assay, EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry and Western blot, respectively. Levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected using ELISA analysis. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were examined using commercial kits. Levels of genes and proteins were detected by qRT-PCR and Western blot. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to identify the target relationship between miR-370-3p and circ-BNIP3L or MYD88 (myeloid differentiation primary response 88). Circ-BNIP3L was highly expressed in SA-AKI patients and LPS-induced HK-2 cells. Silencing of circ-BNIP3L attenuated LPS-induced growth inhibition, inflammation, and oxidative stress in HK-2 cells. Mechanistically, circ-BNIP3L competitively bound to miR-370-3p to up-regulate the expression of its target MYD88. Moreover, miR-370-3p inhibition reversed the beneficial effects of circ-BNIP3L knockdown on LPS-stimulated HK-2 cells. Meanwhile, miR-370-3p overexpression abolished LPS-induced injury in HK-2 cells, which was counteracted by MYD88 up-regulation. Circ-BNIP3L knockdown alleviated LPS-induced renal tubular epithelial cell injury by miR-370-3p/MYD88 axis, opening up a completely new avenue for the treatment of sepsis-associated AKI.


Clinical features of complications from transesophageal echocardiography: a single-center case series of 10,000 consecutive examinations.
Transesophageal echocardiography (TEE) is an essential diagnostic tool that has gained widespread use in clinical cardiology. It is considered reasonably noninvasive and safe; however, insertion and operation of the TEE probe may cause hypopharyngeal, esophageal, or gastric trauma. The current study reports a single-center experience of esophagogastric trauma in 10,000 consecutive TEE examinations. TEE examinations were performed by 9 attending physicians who were trained in endoscopic procedures and had been performing TEE studies for at least 1 year. One case of hypopharyngeal perforation (0.01%), 2 cases of cervical esophageal perforation (0.02%), and no cases of gastric perforation (0%) occurred after TEE examination. No fatalities (0%) occurred. We describe the clinical characteristics of individuals who experienced esophageal perforation during this 10-year period. This single-center study demonstrates that TEE examinations are associated with a very low risk of esophagogastric trauma when performed in a safe setting by experienced operators.


[Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): a review].
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), also known as hypersensitivity syndrome (HSS), is a severe and potentially life-threatening drug reaction. The worldwide rate of mortality is about 10 %, its incidence is increasing. Drugs that most frequently induce DRESS are aromatic anticonvulsive drugs (carbamazepine, lamotrigine, phenobarbital), and more recently new retroviral therapies. The pathogenesis of DRESS is not yet fully understood, but is certainly multifactorial involving a combination of immune reactions, ethnic predisposition, genetically determined enzyme deficiencies and reactivation of herpes viruses (HHV-6, HHV-7, EBV, CMV). Because of the involvement of the skin and internal organs, the clinical picture can be very variable. No specific clinical, histologic or laboratory parameter is available, so the diagnosis has to rely on the clinical appearance. The long latency period between start of drug intake and the initial manifestation of DRESS and the successive onset of skin and organ involvement complicates the early diagnosis. Although or even because DRESS represents a diagnostic challenge, detailed knowledge about this disease is of utmost importance to enable early therapeutic actions.


[Acute renal insufficiency and cerebral infarction during high-dose intravenous immunoglobulin therapy].
Side-effects of immunoglobulins administered via the intravenous route are usually minor. However, acute renal failure and more rarely thrombotic events, including ischemic stroke, have been reported in association with immunoglobulin infusion. To our knowledge, no case of both acute failure and stroke following immunoglobulin has been described until now. Two days after immunoglobulin infusion (2 g/kg), a patient who presented with autoimmune thrombocytopenia suffered severe acute renal failure associated with an ischemic stroke in the right anterior choroid artery territory. Moreover, the stroke worsened immediately following a second infusion (1 g/kg). Clinical and neuroradiological examinations were conducted. Results indicate the need for both close monitoring of serum creatinine and diuresis before starting immunoglobulin therapy, and limiting the total dose to prevent thrombotic events such as stroke.


Comparing decision making between cancer patients and the general population: thoughts, emotions, or social influence?
This study extends a risk information seeking and processing model to explore the relative effect of cognitive processing strategies, positive and negative emotions, and normative beliefs on individuals' decision making about potential health risks. Most previous research based on this theoretical framework has examined environmental risks. Applying this risk communication model to study health decision making presents an opportunity to explore theoretical boundaries of the model, while also bringing this research to bear on a pressing medical issue: low enrollment in clinical trials. Comparative analysis of data gathered from 2 telephone surveys of a representative national sample (n = 500) and a random sample of cancer patients (n = 411) indicated that emotions played a more substantive role in cancer patients' decisions to enroll in a potential trial, whereas cognitive processing strategies and normative beliefs had greater influences on the decisions of respondents from the national sample.


Intra corneal ring segment implantation with lenticule assisted stromal augmentation for crosslinking in thin corneas.
To evaluate the safety and efficacy of intra corneal ring segment (ICRS) implantation combined with crosslinking (CXL) using a Small Incision Lenticule Extraction (SMILE) lenticule for intraoperative stromal augmentation in thin corneas. The procedure was performed in three eyes of progressive keratoconus or post refractive surgery corneal ectasia, with a preoperative mean thinnest pachymetry of 389.34 ± 5.5 μm. Keratometry flattening (preoperative mean maximum keratometry of 63.17 ± 9.31D to postoperative mean maximum keratometry of 54.77 ± 9.47D) and improvement in spectacle corrected distance visual acuity (mean preoperative LogMAR 0.43 ± 0.19 to mean postoperative LogMAR 0.71 ± 0.26) was noted at three months, with stability at one-year postoperative visit. Demarcation line was demonstrated at a depth of 220.67 ± 8.32 μm. No significant endothelial cell loss was noted. Intraoperative stromal thickness augmentation using a lenticule obtained from SMILE allows safe and effective CXL in combination with ICRS in ultrathin corneas. This allows an alternative to lamellar keratoplasty for visual rehabilitation in such eyes.


Mouse models for the study of fungal pneumonia: a collection of detailed experimental protocols for the study of Coccidioides, Cryptococcus, Fusarium, Histoplasma and combined infection due to Aspergillus-Rhizopus.
Mouse models have facilitated the study of fungal pneumonia. In this report, we present the working protocols of groups that are working on the following pathogens: Aspergillus, Coccidioides, Cryptococcus, Fusarium, Histoplasma and Rhizopus. We describe the experimental procedures and the detailed methods that have been followed in the experienced laboratories to study pulmonary fungal infection; we also discuss the anticipated results and technical notes, and provide the practical advices that will help the users of these models.


[Tertiary lymphoid structures in cancer: From biology to therapeutic guides].
Tertiary lymphoid structures (TLS) are inducible ectopic lymphoid aggregates, which form in response to various inflammatory situations, including cancer. TLS are notably composed of B lymphocytes, T lymphocytes, mature dendritic cells and other key players such as high endothelial venules. Furthermore, TLS can present different levels of organization and maturation, from simple T/B lymphocyte aggregates to authentic mature B cell follicles with germinal centers adjacent to T cell rich areas. While over the past decade, TLS may have been associated with a favorable prognosis in various cancers, the year 2022 was marked by the first prospective trial (PEMBROSARC) that reported the interest of TLS as predictive biomarkers of pembrolizumab efficacy for the treatment of soft-tissue sarcomas. All along this review, we will first address the molecular and cellular bases of TLS as well as the different strategies for identifying them in clinical practice, then discuss the prognostic/predictive impact of their presence and finally, we will elaborate on the current limitations and perspectives in translational research.


Thyroid function in preterm infants 27-29 weeks of gestational age during the first four months of life: results from a prospective study comprising 80 preterm infants.
Assessment of thyroid function in preterm neonates (PTN) 27-29 weeks of gestational age. 80 PTN, gestational age 27 weeks in 24, 28 weeks in 28, and 29 weeks in 28. Neonates were classified as healthy (n=17) or sick (n=63). Measurement of serum TSH, free T4, T4, T3 and rT3 in the mother and in the cord at the time of delivery, and in the infant at 1 hour, 24 hours, 1 week, 3 weeks, and 2 and 4 months of postnatal age. In healthy and sick preterms, TSH values peaked at 1 hour and decreased thereafter. Healthy PTN presented a peak in free T4 values at 24 hours that was not observed in sick neonates. Sick PTN had a lower TSH peak and lower free T4 values at 24 hours and 1 week than healthy ones (p < 0.05). Healthy PTN 27-29 weeks had lower TSH peak at 1 hour and lower free T4, T3 and T4 values during the first 2 months than healthy PTN 30-35 weeks (PTN30-35w) previously evaluated (p < 0.05). However, at all postnatal times healthy preterms had free T4 values above -2 SD of the mean values of healthy PTN30-35w. A wide range of free T4 values was observed in the sick group. Free T4 values above -2 SD of the mean values of healthy PTN30-35w were detected in a high proportion of sick PTN (58.3% at 24 hours, 73.5% at 1 week, 93.9% at 3 weeks, 85.1% at 2 months and 100% at 4 months). Prematurity and disease influence thyroid function, and consequently thyroid function should be individually assessed in preterms 27-29 weeks of gestation during the first 2 months of life.


Differences in the inhibition of coagulation factor XIII-A from animal species revealed by Michael Acceptor- and thioimidazol based blockers.
The A-subunit of blood coagulation factor XIII is a pro-transglutaminase, which cross-links α- and γ-fibrin-chains in its activated form. Selective inhibitors against FXIII-A may be desirable drugs to prevent the development of thromboses. Animal models are generally used for proof of principle and for toxicological studies in drug development. The aim of the study was to investigate the specificity of a set of FXIII-A-blockers against FXIII-A from different species, i.e. human, dog, mouse, rat and pig. Thus the usefulness of different animal species for FXIII-A-blocker drug development should be evaluated. FXIII-A proteins were recombinantly produced in insect cells and purified to homogeneity. They were characterized by SDS- and native PAGE, a transamidase assay and isopeptidase assay. The inhibition second-order rate constants of different irreversible inhibitors were determined using the isopeptidase assay. All FXIII-A species were able to assemble with recombinant human FXIII-B into a heterotetrameric complex. Kinetic parameters of FXIII-A species were determined. Second-order rate constants for FXIII-A inhibition by two irreversible inhibitors were determined and differed considerably. FXIII-A species of dog, mouse and rat were inhibited in a manner similar to human FXIII-A. Pig FXIII-A however was resistant to a previously described non-peptidic inhibitor. Furthermore, the results showed considerably better inhibition with the novel peptide-based inhibitor compared to the non-peptidic compound. Our data shows that biochemical interspecies comparison studies are a prerequisite for animal studies. Peptide-derived inhibitors carrying a Michael Acceptor Pharmacophore (MAP) are a promising new class of FXIII-A-inhibitors.


Systemic lupus erythematosus and varicella-like rash following COVID-19 in a previously healthy patient.
Emerging reports show that coronavirus disease 2019 (COVID-19) may lead to autoimmune and autoinflammatory diseases. However, COVID-19 triggered systemic lupus erythematosus (SLE) has never been reported to our knowledge. COVID-19 also has associated cutaneous manifestations. Here we present a case of SLE with antiphospholipid antibody syndrome in a previously healthy patient with COVID-19, who subsequently developped a varicella-like exanthem on the trunk. The disease resulted in death of the patient. The pathophysiological mechanisms resulting in overlapping disorders in our patient remain unknown, adding to the growing mystery of this virus and raising questions about the nature of its link with cutaneous, autoimmune, and autoinflammatory manifestations. Sharing the images of this case may benefit physicians dealing with similar patients during this pandemic.


Early versus late surfactant replacement therapy in severe respiratory distress syndrome.
26 preterm infants with severe respiratory distress syndrome (RDS) have been treated at different ages with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). Criteria for treatment included clinical and radiological signs of severe RDS (grade III-IV), requirement of artificial ventilation and an FiO2 greater than or equal to 0.6. Nineteen neonates have been subjected to early treatment (2-15 h of age, mean birth weight SD: 1201 +/- 387 g) and 7 patients to late treatment (greater than 15 h to 48 h of age, birth weight SD 1624 +/- 649 g). Average FiO2 before treatment was 0.88 in early-treated patients and 0.8 in late-treated patients, age at treatment was 4.6 h and 36 h, respectively (median). Both early- and late-treated infants exhibited an improvement in oxygenation (more than twofold increase of the PaO2/FiO2 ratio) within 5 minutes after initiation of therapy. Average duration of intermittent pressure ventilation was 15 days in the early treatment group and 19 days in the late treatment group. Total exposition to greater than 21% oxygen was 21 days in early-treated and 48 days in late-treated infants. Pneumothorax occurred in none of the patients. All early treated infants survived without signs of severe bronchopulmonary dysplasia (BPD greater than 21% O2, greater than 90 days plus radiological changes). However, two out of seven late-treated infants developed severe BPD; one patient died as a consequence of cardiopulmonary deterioration. Two patients in the early treatment group died of nonpulmonary complications. We conclude that surfactant replacement therapy should probably be initiated as soon as possible after manifestation of severe RDS.


Fifth-order asymptotic geometric aberrations of electron lenses.
In this article the analytical expressions of the fifth-order asymptotic geometric aberrations of electron lenses are derived by Mathematica. The process of the derivation is analogous to the method described in "Principles of Electron Optics" by P.W. Hawkes and E. Kasper. All the analytical formulae for asymptotic aberration coefficients in polynomials in the reciprocal magnification are numerically cross-validated with the differential algebraic (DA) method. The results indicate that the derived formulae are doubtless correct.


A content analysis of the aims, strategies, and effects of food and nonalcoholic drink advertising based on advertising industry case studies.
Placing limitations on advertising of food and nonalcoholic drinks to children is an effective strategy in addressing childhood obesity. The industry maintains that further restrictions are unnecessary. To ascertain whether the advertising campaigns were successful according to the industry evaluations and more specifically the effects of marketing on children. A total of 117 case studies (1980-2016) published by the advertising industry which evaluate the effects of advertising campaigns were reviewed. This industry data source had been previously used to analyze the effects of alcohol advertising campaigns. The nutrition profile of the products was assessed by applying the World Health Organisation Nutrition Profile model designed to restrict the marketing of foods and beverages to children. The food and drink industry advertising campaigns target specific consumers including children, use several persuasive marketing techniques (utilizing celebrities and gamification), often position unhealthy products as healthy, and lead to increased sales of the advertised product with good returns on investment. The health-related claims made, and aspects of the campaigns related to the marketing of the products to children are summarized. Our analysis of food and non-alcoholic drinks case studies aligns with similar analyses of tobacco and alcohol advertising. This analysis, based on internal industry data, presents important evidence on the effects of advertising on consumption-related outcomes and the mechanisms by which they are achieved.


The effects of dialysis on brain water and EEG in stable chronic uremia.
Cerebral edema in uremic animals and humans, as well as an EEG deterioration in humans, has been reported after dialysis. Both are manifestations of the dialysis disequilibrium syndrome (DDS). This study was designed to analyze the changes induced by dialysis in the EEG pattern (spectral analysis), in the cerebral hydration, and ventricular size (computed tomography [CT] of the brain) in a group of 11 stable uremic patients. They volunteered for a randomized crossover study of 4 months each of standard hemodialysis (HD) and hypertonic hemodiafiltration (H HDF). H HDF is a dialysis technique that is shorter and more efficient than HD. An EEG recording, a CT scan of the brain, and blood biochemistry were performed before and after a HD (four hours, blood flow rate 250 mL/min) and a H HDF run (three hours, blood flow rate 400 mL/min). Approximately 6 weeks of stabilization on each treatment were allowed before these studies. No difference was found in the density of seven specific brain structures (base and apical cuts), when comparing pre- v post-HD, pre- v post-H HDF, pre- HD v pre-H HDF, and post-HD v post-H HDF. Furthermore, no difference was evident either in the bicaudate diameter of the lateral ventricles or in the transverse diameter of the third ventricle. In addition, no significant in-between- and within-treatment difference was observed when analyzing the EEG% power (3-7/7-13 Hz) data. In conclusion, this study shows neither a postdialysis change in brain density and ventricular size nor a postdialysis EEG deterioration in a group of stable uremic patients undergoing both a rapid and a standard dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Immediate early response 3 gene promotes aggressive progression and autophagy of AML by negatively regulating AKT/mTOR.
Immediate early response 3 (IER3) plays a vital role in many tumors. This study aims to explore the function and mechanism of IER3 in Acute myeloid leukemia (AML). The expression of IER3 in AML was performed by bioinformatics analysis. CCK-8 proliferation assay, flow cytometry cycle assay, clone formation assay, and tumorigenic ability were used to investigate the effect of IER3 on AML cells. Unbiased label-free quantitative proteomics and label-free quantitative phosphoproteomics analysis were performed. The regulatory relationship between SATB1(Special AT-rich sequence binding protein 1) and IER3 was investigated by Real time-PCR, Western blot, Chromatin immunoprecipitation (CHIP), and PCR. The result indicated that the prognosis of the high IER3 expression group was significantly worse than that of the low expression group. CCK-8 assay showed that IER3 enhanced the proliferation ability. Cell cycle analysis showed IER3 could promote HL60 cells to enter the S phase of DNA synthesis from the quiescent phase. IER3 could stimulate HEL cells to enter mitosis. Clone-formation experiments suggested that IER3 enhanced clonogenic ability.IER3 promoted the tumorigenesis of AML. Further experimental investigation revealed that IER3 promoted autophagy and induced the occurrence and development of AML by negatively regulating the phosphorylation activation of AKT/mTOR pathway. SATB1 was found to bind to the promoter region of IER3 gene and negatively regulate its transcription. IER3 could promote the development of AML and induce autophagy of AML cells by negatively regulating the phosphorylation and activation of AKT/mTOR. By the way, SATB1 may negatively target regulates IER3 transcription.


Activation of c-Src and Fyn kinases by protein-tyrosine phosphatase RPTPalpha is substrate-specific and compatible with lipid raft localization.
Src family tyrosine kinases (SFKs) function in multiple signaling pathways, raising the question of how appropriate regulation and substrate choice are achieved. SFK activity is modulated by several protein-tyrosine phosphatases, among which RPTPalpha and SHP2 are the best established. We studied how RPTPalpha affects substrate specificity and regulation of c-Src and Fyn in response to epidermal growth factor and platelet-derived growth factor. We find that RPTPalpha, in a growth factor-specific manner, directs the specificity of these kinases toward a specific subset of SFK substrates, particularly the focal adhesion protein Paxillin and the lipid raft scaffolding protein Cbp/PAG. A significant fraction of RPTPalpha is present in lipid rafts, where its targets Fyn and Cbp/PAG reside, and growth factor-mediated SFK activation within this compartment is strictly dependent on RPTPalpha. Forced concentration of RPTPalpha into lipid rafts is compatible with activation of Fyn. Finally, RPTPalpha-induced phosphorylation of Paxillin and Cbp/PAG induces recruitment of the SFK inhibitory kinase Csk, indicative of negative feedback loops limiting SFK activation by RPTPalpha. Our findings indicate that individual SFK-controlling PTPs play important and specific roles in dictating SFK substrate specificity and regulatory mechanism.


Preoperative quadriceps muscle strength deficit severity predicts knee function one year after anterior cruciate ligament reconstruction.
Quadriceps strength is critical for patients with anterior cruciate ligament (ACL) reconstruction; however, little is known about the relationship between preoperative quadriceps strength deficit and postoperative subjective knee functions. The study aimed to investigate the relationship between preoperative quadriceps strength and postoperative knee function in patients after ACL reconstruction. Seventy-five male patients with primary ACL reconstruction surgery with hamstring autografts between 2014 and 2017 were included. An isokinetic dynamometer assessed quadriceps strength while self-reported knee functions were measured by the International Knee Documentation Committee (IKDC) and Lysholm scores at baseline and 1 year after surgery. The three identified groups (Q1-Q3) were classified according to the preoperative quadriceps muscle strength deficit. Q1 were patients with < 25% quadriceps muscle strength deficit, Q2 showed a 25-45% deficit, and Q3 included those with a deficit > 45%. We compared knee functions between the three groups and examined the associations between preoperative variables and functional knee outcomes. The preoperative quadriceps muscle strength deficit had a negative association with the knee functional scores at 1 year follow-up including the IKDC score (rs = - 0.397, p = 0.005) and the Lysholm score (rs = - 0.454, p < 0.001), but not other factors. Furthermore, only the Q1 group, with < 25% deficit in preoperative quadriceps muscle strength, showed a significant correlation in postoperative IKDC score (r = - 0.462, p = 0.030), and Lysholm score (r = - 0.446, p = 0.038). Preoperative quadriceps muscle strength deficit had a significant negative relationship with postoperative function at 1 year following ACL reconstruction.


Demonstrating the feasibility of collecting secondary, de-identified data on Australian patients receiving treatment as part of a Medicine Access Programme.
In Australia, data generated from the carefully selected, treated and monitored patients enrolled in clinical trials largely inform routine care and funding approvals. Medicine Access Programmes (MAP) enable drug access and while potentially a rich source of data, historically have not collected data beyond a participant list. To explore the feasibility of using MAP to identify patient populations for inclusion in non-interventional studies. Clinicians affiliated with the Walter and Eliza Hall Institute engaged with Roche to implement PeRSIA, a secondary data use non-interventional study of patients receiving neoadjuvant pertuzumab for non-metastatic HER2+ breast cancer. The study utilised a pre-existing Roche-sponsored MAP to identify clinicians as data contributors. Data security, ownership and reporting issues were addressed utilising the BioGrid platform and standards developed for existing Walter and Eliza Hall Institute registries. Disease experts developed project-specific Case Report Forms documenting treatment, surgical and cancer-specific outcomes, and adverse events. To date, 12 of 16 (75%) clinicians approached to participate in PeRSIA are contributing de-identified data. From February through September 2018, data on 41 patients from seven centres were collected. Median patient age is 56 years (range 36-81), 36 (88%) had Stage 2 to 3 disease and 27 (66%) were node positive. The median number of cycles of neoadjuvant pertuzumab planned was 4. This initial report is, to our knowledge, the first description of a secondary data use non-interventional study collecting comprehensive data on patients enrolled, independently, in a MAP. This effort continues and opportunities with other industry partners are being pursued.


Occupational dose from natural radionuclides in phosphate fertilizers.
In this investigation the occupational exposure of single persons due to the gamma radiation of the natural radionuclides in rock phosphates and phosphate fertilizers and their contribution to the population dose in the FRG has been determined. The exposure rates in the working fields production, transport, loading and storage or rock phosphates and phosphate fertilizers and due to their application in agriculture have been measured by means of scintillation dose rate meters or LiF-thermoluminescence dosemeters or have been estimated from specific activities. Mean additional exposure rates of 2--26 muR/h, with local maximum values up to 190 muR/h, were observed. From these values, together with statistical data for the number of occupied persons and annual working times in the various working fields, the mean and maximum annual dose of individuals and the contribution to the mean population dose have been estimated. The results show that a maximum annual dose to individuals from 0.4 mrem/y (agriculture) up to 45 mrem/y (production plants or storehouses) can occur. The corresponding mean annual doses are 0.05--20 mrem/y. The contribution of the occupational radiation exposure due to rock phosphates and phosphate fertilizers to the mean population dose is 174 man . rem/y related to whole body. To this, fertilizer production contributes 40 man . rem/y, transport and loading 45 man . rem/y, agricultural storehouses 31 man . rem/y, and agriculture 58 man . rem/y. Altogether, this investigation shows that an occupational radiation exposure of individuals may occur which corresponds to the mean terrestrial radiation exposure in the FRG. The contribution of the occupational collective doses due to phosphates to the population dose, however, is negligibly small.


Tensile bond strength of polyvinyl siloxane impressions bonded to a custom tray as a function of drying time: Part I.
Time-dependent bond strength studies of two polyvinyl siloxane impression materials to acrylic resin disks with their respective adhesives were studied to determine the optimal time for maximum bond strength. Six groups were tested with varying adhesive dry times of 0, 7, 15, and 60 minutes and 8 and 24 hours before testing. The results indicated that the bond strength of the adhesive increased at least twofold from time zero to 7 minutes adhesive dry time and peaked at 60 minutes for one of the materials and at 8 hours for the other. Bond strengths increased rapidly to the 15-minute test interval and then seemed to plateau. Both materials exhibited decreased adhesive bond strengths at 24 hours.


Effect of a relative pricing intervention and active merchandising on snack purchases: interrupted time series analysis of a hospital retailer-led strategy.
Pricing policies have been shown to be an effective lever for promoting healthier dietary choices in consumer food environments. It is not yet well understood how pricing can be used to encourage healthier substitute purchases. The aim of the study was to assess the effect of a retailer-led relative pricing intervention on weekly purchases of targeted snack foods and beverages. This was an ecological analysis in a real-world large tertiary hospital consumer food environment setting in urban Canada, comprised of four retail outlets: two large cafeterias, one smaller cafeteria, and one grab-and-go café. An interrupted time series analysis was designed to evaluate the effect of Snacking Made Simple, a retailer-led relative pricing intervention applied to 10 popular snack foods and beverages (n = 87 weeks, 66 weeks baseline and 21 weeks intervention, April 2018 to December 2019), on weekly purchase differences between healthier and less healthy targeted items, adjusted for weekly sales volume. Five healthier items were price discounted, alongside a price increase for five less healthy items. The intervention was actively merchandised in keeping with behaviour change theory. Weekly purchases of targeted snacks became healthier during the intervention period (β = 21.41, p = 0.0024). This followed a baseline period during which weekly purchases of less healthy targeted snacks had outpaced over time those of healthier targeted snacks (β = -11.02, p = 3.68E-14). We estimated that, all else being equal, a hypothetical 9.43 additional weeks of the intervention would be required to transition to net-healthier targeted snack purchases in this environment. The effects of the intervention varied by retail outlet, and the outcome appears driven by specific food items; further, examining merchandising implementation, we posited whether direct versus indirect substitution may have affected purchasing outcomes. Relative pricing may be a promising way to incentivize healthier substitute purchasing in the consumer food environment. Added attention to merchandising strategy as well as value-add factors within food categories and their effects on price salience may be an important factor in effective intervention design.


Reduction in sudden late death by concomitant revascularization with aortic valve replacement.
To determine the impact of coronary atherosclerosis and myocardial revascularization on survival after aortic valve replacement, we reviewed our experience with single aortic valve replacement between 1969 and 1984. Of 474 patients (mean age 62 +/- 13 years), 185 (39%) had no associated coronary artery disease, 233 (49%) had coronary artery bypass grafting, and 56 (12%) had unbypassed coronary artery disease. Early (30-day) mortality rates were 2.2%, 8.2%, and 7.1%, respectively (p less than 0.01, coronary disease absent versus present). Actuarial survival rates at 10 years were 77% +/- 4%, 41% +/- 6%, and 26% +/- 11% (p less than 0.001, coronary disease absent versus present), with 1 to 177 months of follow-up (mean 56 +/- 40). Preoperative angina (39%) did not predict the presence of coronary artery disease (61%). Multivariate logistic regression analysis showed that early deaths were associated with advanced preoperative New York Heart Association functional class (p less than 0.001), advanced age (p less than 0.05), more extensive coronary artery disease (p less than 0.05), and lack of cardioplegic myocardial protection (p less than 0.05). Complete revascularization did not increase operative risk when coronary artery disease was present (early mortality 6.8%, p = not significant). Late deaths were strongly associated with the presence of coronary artery disease (p less than 0.001) and reduced left ventricular ejection fraction (less than or equal to 55%, p less than 0.01). Late cardiac mortality was most commonly attributable to sudden death (30/71, 42%), especially in the unbypassed coronary disease cohort (9/14, 64%). The actuarial rate of freedom from sudden death at 10 years was 52% +/- 17% in the unbypassed coronary artery disease group (p = 0.009), compared with 90% +/- 3% and 91% +/- 3% in the revascularized and no coronary disease patients, respectively. Thus, coexistent coronary atherosclerosis has a detrimental impact on early and late survival after aortic valve replacement. Revascularization does not increase operative risk when associated coronary artery disease is present and significantly reduces the occurrence of late sudden death. Strategies that minimize operative risk when associated coronary artery disease is present include use of cardioplegia and complete revascularization.


Analytical methods for determining ascorbic acid in biological samples, food products, and pharmaceuticals.
Over the last decade, numerous publications have appeared describing analyses for ascorbic acid in food products, pharmaceuticals, and biological samples. This review focuses on the chemistry associated with many of these procedures. The papers discussed have historical importance, are important to understanding the method, or have significantly advanced ascorbic acid analysis. The review has 4 major sections: spectroscopic, electrochemical, enzymatic, and chromatographic methods of analysis.


Older first-time mothers and early postpartum depression: a prospective cohort study of women conceiving spontaneously or with assisted reproductive technologies.
To evaluate whether older first-time mothers (≥37 years) have higher rates of postpartum depression compared with younger first-time mothers, controlling for mode of conception and known risk factors for postpartum depression. Prospective cohort study. Assisted reproductive technology (ART) clinics in two large Australian cities and public and private antenatal clinics and/or classes in the vicinity of ART clinics. Nulliparous women who had conceived spontaneously (n = 295) or through ART (n = 297) in three age-groups: younger, 20 to 30 years (n = 173); middle, 31 to 36 years (n = 214); and older, ≥37 years (n = 189). Semistructured interviews and questionnaires. Major depressive disorder in the first 4 months after birth as assessed by structured diagnostic interview. The study performed 592 complete pregnancy assessments and 541 postpartum assessments. The prevalence of major depressive disorder was 7.9%, at the lower end of community rates. Neither maternal age-group nor mode of conception was statistically significantly related to depression. Older first-time mothers, whether conceiving through ART or spontaneously, do not show increased vulnerability to postnatal depression.


Molecular simulations of retention in chromatographic systems: use of biased Monte Carlo techniques to access multiple time and length scales.
The use of configurational-bias Monte Carlo simulations in the Gibbs ensemble allows for the sampling of phenomena that occur on vastly different time and length scales. In this review, applications of this simulation approach to probe retention in gas and reversed-phase liquid chromatographic systems are discussed. These simulations provide an unprecedented view of the retention processes at the molecular-level and show excellent agreement with experimental retention data.


The development of a sensitive methodology to characterise hard shell capsule puncture by dry powder inhaler pins.
In order for hard-shell capsules to function effectively as drug reservoirs in dry powder inhalers, the capsule must be punctured with sharpened pins to release the powdered medicament upon inspiration. Capsule performance in this setting is poorly understood. This study aims to develop a methodology to characterise hard shell capsule penetration by needles from commercial dry powder inhalers, to determine whether changes to capsule materials impact on their performance. Two pin types from two commercial dry powder inhalers were mounted in a material-testing machine, equipped with a 500 N load cell. A stainless steel bush was used to secure a capsule directly below the steel pin. Hypromellose (n=10) and gelatin capsules (n=10) were conditioned in 'normal' or low humidity conditions and were subsequently punctured with both types of pin. Each puncture event was recorded on a load-displacement curve. The force required for puncture was 2.82±0.26 N for hypromellose capsules and 4.54±0.26 N for gelatin capsules, stored in normal humidity. Different capsule materials possessed distinguishable signature profiles but repeated force-displacement profiles were highly reproducible i.e. intra-individual variability was minimal. A rapid, robust yet sensitive methodology has therefore been developed that is able to characterise hard shell capsule materials based on the puncture performance.


Tick control: thoughts on a research agenda.
Tick control is critical to the control of tick borne disease, while the direct impact of ticks on livestock productivity is also well known. For livestock, tick control today rests overwhelmingly on the twin approaches of genetics and chemical acaricides, although the disadvantages and limitations of both are recognized. The achievement of the full potential of vaccination, the application of biocontrol agents and the coordinated management of the existing technologies all pose challenging research problems. Progress in many areas has been steady over the last decade, while the acquisition of molecular information has now reached a revolutionary stage. This is likely to have immediate impact on the identification of potential antigens for improved vaccines and novel targets for acaricide action. In many circumstances, the rate limiting step in making scientific progress will remain unchanged, namely the resource constraint on evaluating these appropriately in large animals. For other approaches, such as the use of biocontrol agents, the limitation is likely to be less in the identification of suitable agents than in their delivery in an efficient and cost effective way. Our scientific understanding of the molecular basis for the tick vector-tick borne disease interaction is in its infancy but the area is both challenging and, in the long term, likely to be of great practical importance. What is arguably the most difficult problem of all remains: the translation of laboratory research into the extremely diverse parasite control requirements of farming systems in a way that is practically useful.


PCSK9 inhibitors revisited: Effectiveness and safety of PCSK9 inhibitors in a real-life Spanish cohort.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have emerged as a therapeutic option for patients with hypercholesterolemia who do not attain low-density lipoprotein cholesterol (LDL-C) goals and/or are intolerant to other lipid-lowering drugs. Our aim was to analyze the effectiveness and safety of PCSK9i in routine clinical practice and factors related to poor outcomes. We conducted an ambispective study in 115 patients who recieved alirocumab or evolocumab, in a tertiary level hospital. From February 2017 to April 2020, patients were recruited and followed up for a median of 20.4 months. The main outcomes were relative reduction in LDL-C, percentage of patients achieving the therapeutic goals established by 2016 ESC/EAS guidelines, incidence of major cardiovascular events (MACEs) and drug-related adverse events (ADRs). The median LDL-C achieved was 57.0 mg/dL (relative reduction of 59.9% from baseline, p< 0.001). After adjusting for confounders, smaller LDL-C reductions were related to female sex, absence of concomitant lipid-lowering therapy and treatment with alirocumab. Overall, 84.6% of the patients achieved the therapeutic goals. During follow-up, 7 MACEs were detected. ADRs, generally considered mild, affected 38.1% of the participants (mainly mialgias and arthralgias) and triggered discontinuations in 8.7% of cases. PCSK9i are effective and safe, although certain factors may influence their effectiveness. Interestingly, our results suggest that alirocumab and evolocumab may not be therapeutic equivalents, as initially suggested.


Nursing operations automation and health care technology innovations: 2025 and beyond.
This article reviews why nursing operations automation is important, reviews the impact of computer technology on nursing from a historical perspective, and considers the future of nursing operations automation and health care technology innovations in 2025 and beyond. The increasing automation in health care organizations will benefit patient care, staffing and scheduling systems and central staffing offices, census control, and measurement of patient acuity.


Impact of High-Flow Nasal Cannula Oxygenation on the Prevention of Hypoxia During Endoscopic Retrograde Cholangiopancreatography in Elderly Patients: A Randomized Clinical Trial.
Hypoxia is the most frequently occurring adverse effect during endoscopic retrograde cholangiopancreatography (ERCP) under sedation; thus, oxygen must be properly supplied to prevent a reduction of oxygen saturation. In this study, we intend to verify the preventive effect for hypoxia during ERCP, using a high-flow nasal cannula (HFNC), in elderly patients. As a multicenter prospective randomized trial, patients who underwent ERCP with propofol-based sedation were randomly assigned into two groups: Patients in the HFNC group were supplied with oxygen via an HFNC, and those in the standard nasal cannula group were supplied with oxygen via a low-flow nasal cannula. The co-primary end points were the lowest oxygen saturation rate and hypoxia during the overall procedure. A total of 187 patients (HFNC group: 95; standard nasal cannula group: 92) were included in the analysis. Unexpected hypoxia events were more frequently observed among patients in the standard nasal cannula group than among patients in the HFNC group (13% vs. 4%, odds ratio 3.41, 95% confidence interval 1.06-11.00, p = 0.031). The mean of the lowest oxygen saturation rate during ERCP was significantly lower in the standard nasal cannula group than in the HFNC group (95% vs. 97%, p = 0.002). Oxygen supplementation with an HFNC can prevent oxygen desaturation and hypoxia events in patients undergoing ERCP under sedation. Trial registration Clinical Research Information Service (CRIS; KCT0004960).


Dirty engineering data-driven inverse prediction machine learning model.
Most data-driven machine learning (ML) approaches established in metallurgy research fields are focused on a build-up of reliable quantitative models that predict a material property from a given set of material conditions. In general, the input feature dimension (the number of material condition variables) is much higher than the output feature dimension (the number of material properties of concern). Rather than such a forward-prediction ML model, it is necessary to develop so-called inverse-design modeling, wherein required material conditions could be deduced from a set of desired material properties. Here we report a novel inverse design strategy that employs two independent approaches: a metaheuristics-assisted inverse reading of conventional forward ML models and an atypical inverse ML model based on a modified variational autoencoder. These two unprecedented approaches were successful and led to overlapped results, from which we pinpointed several novel thermo-mechanically controlled processed (TMCP) steel alloy candidates that were validated by a rule-based thermodynamic calculation tool (Thermo-Calc.). We also suggested a practical protocol to elucidate how to treat engineering data collected from industry, which is not prepared as independent and identically distributed (IID) random data.


The effect of 3β, 6β, 16β-trihydroxylup-20(29)-ene lupane compound isolated from Combretum leprosum Mart. on peripheral blood mononuclear cells.
The Combretum leprosum Mart. plant, popularly known as mofumbo, is used in folk medicine for inflammation, pain and treatment of wounds. From this species, it is possible to isolate three triterpenes: (3β, 6β, 16β-trihydroxylup-20(29)-ene) called lupane, arjunolic acid and molic acid. In this study, through preclinical tests, the effect of lupane was evaluated on the cytotoxicity and on the ability to activate cellular function by the production of TNF-α, an inflammatory cytokine, and IL-10, an immuno regulatory cytokine was assessed. The effect of lupane on the enzymes topoisomerase I and II was also evaluated. For this reason, peripheral blood mononuclear cells (PBMCs) were obtained and cytotoxicity was assessed by the MTT method at three different times (1, 15 and 24 h), and different concentrations of lupane (0.3, 0.7, 1.5, 6, 3 and 12 μg/mL). The cell function was assessed by the production of TNF-α and IL-10 by PBMCs quantified by specific enzyme immunoassay (ELISA). The activity of topoisomerases was assayed by in vitro biological assays and in silico molecular docking. The results obtained showed that lupane at concentrations below 1.5 μg/mL was not toxic to the cells. Moreover, lupane was not able to activate cellular functions and did not alter the production of IL-10 and TNF-α. Furthermore, the data showed that lupane has neither interfered in the action of topoisomerase I nor in the action of topoisomerase II. Based on preclinical results obtained in this study, we highlight that the compound studied (lupane) has moderate cytotoxicity, does not induce the production of TNF-α and IL-10, and does not act on human topoisomerases. Based on the results of this study and taking into consideration the reports about the anti-inflammatory and leishmanicidal activity of 3β, 6β, 16β-trihydroxylup-20(29)-ene, we suggest that this compound may serve as a biotechnological tool for the treatment of leishmaniasis in the future.


Nanosized MoSe2@Carbon Matrix: A Stable Host Material for the Highly Reversible Storage of Potassium and Aluminum Ions.
Owing to their low cost and abundant reserves relative to conventional lithium-ion batteries (LIBs), potassium-ion batteries (PIBs), and aluminum-ion batteries (AIBs) have shown appealing potential for electrochemical energy storage, but progress so far has been limited by the lack of suitable electrode materials. In this work, we demonstrated a facile strategy to achieve highly reversible potassium and aluminum ions storage in strongly coupled nanosized MoSe2@carbon matrix, induced through an ion complexation strategy. We present a broad range of electrochemical characterization of the synthesized product that exhibits high specific capacities, good rate capability, and excellent cycling stability toward PIBs and AIBs. Through a series of systematic ex situ X-ray photoelectron spectroscopy (XPS) characterizations and density functional theory (DFT) calculations, the Al3+ intercalation mechanism of MoSe2-based AIBs are elucidated. Moreover, both the assembled PIBs and AIBs worked well when exposed to low and high temperatures within the range of -10 to 50 °C, showing promise for energy storage devices in harsh environment. The present study provides new insights into the exploration of MoSe2 as high-performance electrode materials for PIBs and AIBs.


Enhanced production of phenazine-like metabolite produced by Streptomyces aurantiogriseus VSMGT1014 against rice pathogen, Rhizoctonia solani.
The efficacy of a rhizobacterium Streptomyces aurantiogriseus VSMGT1014 for the production of bioactive metabolites with antifungal properties was evaluated under in vitro conditions. The production of bioactive metabolites by S. aurantiogriseus VSMGT1014 in International Streptomyces Project-2 (ISP-2) broth, supplemented with glucose and ammonium acetate was found to be the most suitable carbon and nitrogen sources for the maximum production of bioactive metabolites against rice pathogen, Rhizoctonia solani. The zone of inhibition range from 23.5 to 28.5 mm and 10.3 to 18.3 mm for glucose and ammonium acetate supplemented media, respectively. The culture filtrate of S. aurantiogriseus VSMGT1014 at pH 7.5, 37 °C at 120 rpm in 6 days of incubation showed the maximum production of bioactive metabolites with antagonistic potential. The crude metabolite was characterized by different spectral studies such as Ultraviolet spectrum, infrared-spectrum and based on the different analytical techniques, including thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) with the retention time 29.4 and the bioactive metabolite was identified as phenazine, which was confirmed by pure phenazine compound as positive control.


Is hypnotic assessment relevant to neurology?
Studies conducted in healthy subjects have clearly shown that different hypnotic susceptibility, which is measured by scales, is associated with different functional equivalence between imagery and perception/action (FE), cortical excitability, and information processing. Of note, physiological differences among individuals with high (highs), medium (mediums), and low hypnotizability scores (lows) have been observed in the ordinary state of consciousness, thus independently from the induction of the hypnotic state, and in the absence of specific suggestions. The potential role of hypnotic assessment and its relevance to neurological diseases have not been fully explored. While current knowledge and therapies allow a better survival rate, there is a constant need to optimize rehabilitation treatments and quality of life. The aim of this paper is to provide an overview of hypnotizability-related features and, specifically, to discuss the hypothesis that the stronger FE, the different mode of information processing, and the greater proneness to control pain and the activity of the immune system observed in individuals with medium-to-high hypnotizability scores have potential applications to neurology. Current evidence of the outcome of treatments based on hypnotic induction and suggestions administration is not consistent, mainly owing to the small sample size in clinical trials and inadequate control groups. We propose that hypnotic assessment may be feasible in clinical routine and give additional cues into the treatment and rehabilitation of neurological diseases.


Effects of short term exposure of eggs to magnetic field before incubation on hatchability and post-hatch performance of meat chickens.
The effects of exposing meat-type breeder eggs to magnetic field (MF) before incubation on hatchability traits (percents of hatchability and hatchability failures of eggs), chick weight at hatch, and post-hatch performance (weight gain, feed intake, and feed conversion ratio (FCR)) from 1 to 39 d of age were investigated. Eggs from a Ross flock at 38 weeks of age were exposed to MF of 18 Gauss (1.8 mT) at 50 Hz for 0, 15, 30, 45, 60, and 75 min (MF0, MF15, MF30, MF45, MF60, and MF75) before incubation. Exposing eggs to MF did not influence hatchability of eggs and chick weight at hatch. However, chickens of MF60 and MF75 treatments had lower weight gain and feed intake than those of the non-exposed treatment at 39 d of age. MF exposure of eggs did not influence FCR of chickens between 1 and 21 d of age, but tended to increase FCR, albeit non-significantly, between 22 and 39 d of age. It is concluded that exposing meat-type breeder eggs to MF of 18 Gauss (1.8 mT) at 50 Hz for up to 75 min did not influence hatchability traits and chick weight at hatch. However, MF exposure of eggs for 60 and 75 min reduced body weight gain and feed intake of chickens over the 39-d experimental period.


Plasma levels of hydroxy-flutamide in patients with prostatic cancer receiving the combined hormonal therapy: an LHRH agonist and flutamide.
The present study describes a method for the measurement of the plasma levels of hydroxy-flutamide (Flu-OH), the biologically active and main circulating metabolite of flutamide. We have observed that two to four hours after oral administration of 250 mg of flutamide to healthy young men, as well as to patients with prostate cancer, the plasma concentration of Flu-OH reaches a peak at approximately 1.7 microM. The plasma concentration of Flu-OH measured at months 6, 12, and 18 of treatment shows a minimal basal level of 3.4 microM with a maximal increase at 6.8 to 8.5 microM at 2 to 4 hours. Since the serum levels of testosterone in these patients are approximately 1 nM, the levels of the active antiandrogen are at a 5000- to 10000-fold excess. However, due to the low affinity of the antiandrogen for the androgen receptor, it is extremely important to maintain this concentration of the antiandrogen in plasma constant.


Peptidomic analysis of the neurolysin-knockout mouse brain.
A large number of intracellular peptides are constantly produced following protein degradation by the proteasome. A few of these peptides function in cell signaling and regulate protein-protein interactions. Neurolysin (Nln) is a structurally defined and biochemically well-characterized endooligopeptidase, and its subcellular distribution and biological activity in the vertebrate brain have been previously investigated. However, the contribution of Nln to peptide metabolism in vivo is poorly understood. In this study, we used quantitative mass spectrometry to investigate the brain peptidome of Nln-knockout mice. An additional in vitro digestion assay with recombinant Nln was also performed to confirm the identification of the substrates and/or products of Nln. Altogether, the data presented suggest that Nln is a key enzyme in the in vivo degradation of only a few peptides derived from proenkephalin, such as Met-enkephalin and octapeptide. Nln was found to have only a minor contribution to the intracellular peptide metabolism in the entire mouse brain. However, further studies appear necessary to investigate the contribution of Nln to the peptide metabolism in specific areas of the murine brain. Neurolysin was first identified in the synaptic membranes of the rat brain in the middle 80's by Frederic Checler and colleagues. Neurolysin was well characterized biochemically, and its brain distribution has been confirmed by immunohistochemical methods. The neurolysin contribution to the central and peripheral neurotensin-mediated functions in vivo has been delineated through inhibitor-based pharmacological approaches, but its genuine contribution to the physiological inactivation of neuropeptides remains to be firmly established. As a result, the main significance of this work is the first characterization of the brain peptidome of the neurolysin-knockout mouse. This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: César López-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.


Self-motion perception without sensory motion.
Various studies have demonstrated a role for cognition on self-motion perception. Those studies all concerned modulations of the perception of a physical or visual motion stimulus. In our study, however, we investigated whether cognitive cues could elicit a percept of oscillatory self-motion in the absence of sensory motion. If so, we could use this percept to investigate if the resulting mismatch between estimated self-motion and a lack of corresponding sensory signals is motion sickening. To that end, we seated blindfolded participants on a swing that remained motionless during two conditions, apart from a deliberate perturbation at the start of each condition. The conditions only differed regarding instructions, a secondary task and a demonstration, which suggested either a quick halt ("Distraction") or continuing oscillations of the swing ("Focus"). Participants reported that the swing oscillated with larger peak-to-peak displacements and for a longer period of time in the Focus condition. That increase was not reflected in the reported motion sickness scores, which did not differ between the two conditions. As the reported motion was rather small, the lack of an effect on the motion sickness response can be explained by assuming a subthreshold neural conflict. Our results support the existence of internal models relevant to sensorimotor processing and the potential of cognitive (behavioral) therapies to alleviate undesirable perceptual issues to some extent. We conclude that oscillatory self-motion can be perceived in the absence of related sensory stimulation, which advocates for the acknowledgement of cognitive cues in studies on self-motion perception.


On High-Dimensional Covariate Adjustment for Estimating Causal Effects in Randomized Trials with Survival Outcomes.
The purpose of this work is to improve the efficiency in estimating the average causal effect (ACE) on the survival scale where right-censoring exists and high-dimensional covariate information is available. We propose new estimators using regularized survival regression and survival Random Forest (RF) to adjust for the high-dimensional covariate to improve efficiency. We study the behavior of the adjusted estimators under mild assumptions and show theoretical guarantees that the proposed estimators are more efficient than the unadjusted ones asymptotically when using RF for the adjustment. In addition, these adjusted estimators are n - consistent and asymptotically normally distributed. The finite sample behavior of our methods is studied by simulation. The simulation results are in agreement with the theoretical results. We also illustrate our methods by analyzing the real data from transplant research to identify the relative effectiveness of identical sibling donors compared to unrelated donors with the adjustment of cytogenetic abnormalities.


Measuring satisfaction and anesthesia related outcomes in a surgical day care centre: A three-year single-centre observational study.
To evaluate patient satisfaction and patient reported anaesthesia related outcome parameters after outpatient surgery. A three-year (2013-2016) observational study. A surgical day care centre embedded in a tertiary care, university hospital. Adult Dutch-speaking patients who underwent surgery under general or regional anaesthesia on an outpatient basis (n=5424). A questionnaire was developed to evaluate patients' satisfaction with care during their hospitalisation in the surgical day centre, as well as to assess their reports of anaesthesia related outcomes. Various aspects of care were measured, including care by nurses, care by doctors, organisational and safety items. Variation in satisfaction and surgery and anaesthesia related outcomes as a function of different categories (gender, age, education, type of anaesthesia, discipline and era) were also investigated. Confirmatory factor analysis showed an excellent fit to the hypothesized factors of the survey. Satisfaction scores were very high for different aspects of care, resulting in 98% of patients being (very) satisfied (59.1% very satisfied, 38.9% satisfied). Male (p=0.0003), higher educated (p<0.0001) and older patients (p<0.0001) were more likely to be very satisfied. Postoperative nausea and vomiting (PONV) were frequent (nausea: 13.9%, vomiting: 3.3%), and more present in female than in male patients (p<0.0001). Pain scores at the PACU differed among disciplines (p<0.0001) were higher in female patients compared to male patients (3.41% versus 2.54%, p<0.0001) and after general anaesthesia compared to regional anaesthesia (3.25% versus 0.39%, p<0.0001) and decreased with higher age (p=0.0001) and education level (p=0.0033). Whereas satisfaction with all aspects of care is generally high, the results regarding pain and PONV should inspire quality improvement initiatives. The questionnaire developed in this study can be a vehicle to assess and improve the quality of care in surgical day care centres.


Young Women Subjected to Nonconsensual Condom Removal: Prevalence, Risk Factors, and Sexual Self-Perceptions.
The purpose of this study was to investigate nonconsensual condom removal (NCCR), also termed "stealthing," which involves a male partner removing a condom during sex without knowledge or consent. Young women (N = 364) provided self-report data on sociodemographic characteristics, NCCR experiences, and sexual self-perceptions. Almost 10% of the participants reported experiencing NCCR, with increased risk linked to nonheterosexuality, nonexclusive relationship status, and more sexual partners. Women with NCCR histories reported less confidence to refuse unwanted sexual advances and felt less in control of themselves as sexual beings. Together, the findings suggested NCCR is a somewhat common sexual risk behavior which may pose acute and sustained psychosexual harm to victims.


Making the unconscious conscious: Developing maladaptive scripts into conviction narratives.
In his 'script theory,' Tomkins first proposed that people unconsciously organize their life experiences in terms of narrative structures he termed "scripts." I use a clinical vignette to illustrate how the psychotherapeutic process of "making the unconscious conscious" involves becoming aware of the maladaptive scripts that people unwittingly live by, and developing them into the "conviction narratives" proposed by the authors.


[Effect of hypothalamic electrostimulation on the 11-hydroxy-corticosteroid content in the blood and on the immunological indices in rabbits with Brown-Pearce carcinoma].
In animals with Brown--Pearce carcinoma electric stimulation of the hypothalamus makes it possible to model an increased corticosterone level in blood at early stages of the tumor growth, which conditions more active development of antitumor reactions and consequently an enhanced tumor resorption. The increased level of free corticosterone seems to be essential for "triggering" and an active mode of proceeding of antitumor immune reactions.


The use of breast-conserving surgery for women treated for breast cancer in the Department of Veterans Affairs.
Previous non-stage-adjusted research described a lower use of breast-conserving surgery (BCS) for the treatment of breast cancer in the Veterans Health Administration (VHA) facilities than in the private sector. We combined data from the VHA Centralized Cancer Registry with administrative datasets to describe surgical treatment for locoregional breast cancer in VHA facilities from 2000 to 2006. When considering only procedures performed in VHA facilities, BCS rates decreased from 50.5% (53/105) in 2000 to 42.3% (n = 58/137) in 2006; however, after accounting for procedures conducted in the private sector and paid for by the VHA, BCS rates approached those experienced in breast cancer patients cared for outside the VHA. Based solely on procedures performed in the VHA, rates of BCS use are much lower in the VHA than in the private sector. We were able to show similar rates of BCS use when we accounted for procedures paid for by the VHA but performed at an outside facility. Further exploration and prospective analyses to examine these findings are needed.


Optimization of aeromedical base locations in New Mexico using a model that considers crash nodes and paths.
In a recent paper, Tokar Erdemir et al. (2008) introduce models for service systems with service requests originating from both nodes and paths. We demonstrate how to apply and extend their approach to an aeromedical base location application, with specific focus on the state of New Mexico (NM). The current aeromedical base locations of NM are selected without considering motor vehicle crash paths. Crash paths are the roads on which crashes occur, where each road segment has a weight signifying relative crash occurrence. We analyze the loss in accident coverage and location error for current aeromedical base locations. We also provide insights on the relevance of considering crash paths when selecting aeromedical base locations. Additionally, we look briefly at some of the tradeoff issues in locating additional trauma centers vs. additional aeromedical bases in the current aeromedical system of NM. Not surprisingly, tradeoff analysis shows that by locating additional aeromedical bases, we always attain the required coverage level with a lower cost than with locating additional trauma centers.


R-phycocyanin II, a new phycocyanin occurring in marine Synechococcus species. Identification of the terminal energy acceptor bilin in phycocyanins.
A new member of the phycocyanin family of phycobiliproteins, R-phycocyanin II (R-PC II) has been discovered in several strains of marine Synechococcus sp. R-PC II has absorption maxima at 533 and 554 nm, a subsidiary maximum at 615 nm, and a fluorescence emission maximum at 646 nm. It is the first phycoerythrobilin (PEB)-containing phycocyanin of cyanobacterial origin. The purified protein is made up of alpha and beta subunits in equal amounts and is in an (alpha beta)2 aggregation state. The alpha and beta subunits of this protein are homologous to the corresponding subunits of previously described C- and R-phycocyanins as assessed by amino-terminal sequence determination and analyses of sequences about sites of bilin attachment. R-PC II carries phycocyanobilin (PCB) at beta-84 and PEB at alpha-84 and beta-155 (residue numbering is that for C-phycocyanin), whereas in C-phycocyanin PCB is present at all three positions. In R-phycocyanin, the bilin distribution is alpha-84 (PCB), beta-84 (PCB), beta-155 (PEB). In both R-phycocyanin and R-phycocyanin II excitation at 550 nm, absorbed primarily by PEB groups, leads to emission at 625 nm from PCB. These comparative data support the conclusion that the invariant beta-84 PCB serves as the terminal energy acceptor in phycocyanins.


Pycnogenol, a compound isolated from the bark of pinus maritime mill, attenuates ventilator-induced lung injury through inhibiting NF-κB-mediated inflammatory response.
During mechanical ventilation, high end-inspiratory lung volume results in a permeability type pulmonary oedema, called ventilator-induced lung injury (VILI). The pathophysiology of ventilator-induced lung injury involves multiple mechanisms, such as excessive inflammation. And pycnogenol is a mixture of flavonoid compounds extracted from pine tree bark that have anti-inflammatory activity. We investigated the effects of pyncogenol on ventilator-induced lung injury in rats. Rats were orally administrated with pycnogenol once (30 mg/kg) 2 days before lung injury induction with mechanical ventilation, then the rats were divided into three groups: lung-protective ventilation (LV group, n = 20), injurious ventilation (HV group, n = 20), HV + pycnogenol group (HV + Pyc group, n = 20). Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses. Pretreatment with pycnogenol could markedly decrease lung wet/dry ratio, lower myeloperoxidase (MPO) activity and total protein concentration and reduce the production of TNF-α, IL-6, IL-1β and MIP-2 in the BALF in ventilator-induced lung injury rats. Additionally, pycnogenol improved the histology of the lung and significantly inhibited the phosphorylation of NF-κB p65 and the degradation of IκB-α. Pycnogenol treatment could attenuate ventilator-induced lung injury in rats, at least in part, through its ability to reduce the production of inflammatory cytokines via inhibiting the activation of NF-κB, indicating it as a potential therapeutic candidate for ventilator-induced lung injury.


Choline and methionine regulate lipid metabolism via the AMPK signaling pathway in hepatocytes exposed to high concentrations of nonesterified fatty acids.
High concentrations of nonesterified fatty acids (NEFAs) and β-hydroxybutyric acid (BHBA) induce lipid peroxidation, resulting in liver damage. Choline and methionine (Met) can promote energy balance and benefit liver health in transition dairy cows; however, the regulating mechanism remains unclear. In the present study, we established the hepatocyte damage model by 1.5 mM NEFAs or BHBA treatment, and examined lipid metabolism in hepatocytes. The results showed that 1.5 mM NEFAs and 1.5 mM BHBA significantly decreased the messenger RNA (mRNA) expression of AMP-activated protein kinase (AMPK)-α as well as its target genes carnitine palmitoyltransferase-1α (CPT-1α), acetyl-CoA carboxylase, fatty acid synthetase, and Apolipoprotein B100 (ApoB100). Choline and Met upregulated the phosphorylation level of AMPK-α, which was blocked by BML (an AMPK-α inhibitor). The mRNA expression level of peroxisome proliferator-activated receptor-α (PPAR-α), CPT-1α, and ApoB100 showed a similar trend. The expressions of liver X recptoer α (LXR-α) and sterol regulatory element-binding protein 1c (SREBP-1c) were decreased by choline and Met, while only the decrease of LXR-α was blocked by BML. These findings indicate that the high-level NEFAs and BHBA weaken the lipid metabolism by impairing the fatty acid oxidation, synthesis, and transport proteins. Choline and Met regulate PPAR-α and LXR-α transcriptional activity through AMPK-α phosphorylation and regulate SREBP-1c independently of AMPK-α to promote lipid oxidation and transport in NEFAs-treated hepatocytes.