Anticipatory information makes the difference: Behavioral effects and user assessments of a cyclist warning system to enhance cyclists' situation awareness.
Increasing numbers of crashes involving pedelecs, and particularly older pedelec users, induce a need to enhance cycling safety. We evaluated a prototype cyclist warning system (CWS) that aims to increase situation awareness (SA) by alerting to safety critical events (SCE) with trimodal (auditory, visual, tactile). To investigate the effects of CWS usage, we conducted a 2x2 mixed design bicycle simulator study with factors (1) CWS usage (within: rides WITH vs. WITHOUT CWS) and (2) age group (between: younger vs. older cyclists) on braking reaction time, gaze behavior, mental workload, and perceived safety. In sum, N = 64 participants (n = 32 younger, 18-40 years; n = 32 older, ≥ 55 years) took part in the study and experienced two balanced blocks of short rides including SCE of particular relevance for cycling safety. CWS usage resulted in earlier braking reactions to all investigated SCE and partly earlier fixation on the critical interaction partners (CIP) indicating increased cyclists' SA. Consistently to behavioral measures, participants' assessments regarding perceived safety further supported the safety improvements derived from CWS independently of age group. Moreover, CWS usage did not add to mental workload ratings. Age effects were selectively found for gaze data showing that across all SCE, older adults fixated longer and more frequently on street alignment, and less frequently on other road users. Taken together, the CWS evaluation showed promising results indicating the potential of the tested CWS to increase SA and enhance cyclists' safety both on a behavioral level and regarding subjective assessments. Further research should address the systems' safety potential under real-world conditions and for situations of higher complexity. Understanding the potential impact of road safety measures such as CWS is important to contribute effectively to reducing SCE.


IL-12, IL-6 and IFN-gamma production by lymphocytes of pregnant women with rheumatoid arthritis remission during pregnancy.
Rheumatoid arthritis (RA) is an autoimmune disease with progressive activity. The RA remission was observed in women during pregnancy, but the mechanism responsible for remission is hypothetical only and concerns mechanisms of immune regulation such as lymphocyte subpopulations and interleukin production. The lymphocyte subpopulations and interleukin production in vitro in a group of healthy non-pregnant women, healthy pregnant women and pregnant women suffering from RA may help towards a better understanding of regulation of the immune processes. The investigations were performed in trimester III--2 days after delivery and 6 weeks after delivery. Peripheral blood lymphocytes were isolated on Gradisol gradient and analysed immediately or after having been cultured for 72 hours in RPMI medium supplemented with 10% FCS. The cultures were terminated after 72 h, supernatants stored at -72 degrees C for interleukin evaluation. The concentrations of IFN-gamma, IL-2, IL-6, IL-12, TNF-alpha and its soluble receptors R-I, R-II were estimated in non-stimulated and PHA (Sigma, 5 microg/ml) stimulated culture supernatants using ELISA Endogen kits according to the manufacturer's instructions. The general pattern of T cell subpopulation distribution was similar in all analysed groups. Decreased IFN-gamma, IL-12 and increased IL-6 production by lymphocytes after PHA stimulation was found in trimester III in pregnant women with RA as compared to healthy pregnant woman. The obtained results suggest that in pregnant women with RA the TH1 cell response predominates, contrary to healthy pregnant women with TH2 type functional response. These phenomena were not observed after delivery.


NMR studies of the structure and dynamics of peptide E, an endogenous opioid peptide that binds with high affinity to multiple opioid receptor subtypes.
Structural and dynamic properties of opioid peptide E have been examined in an sodium dodecyl sulfate (SDS) micelle. Structural and dynamic studies both indicate that this peptide exhibits greater segmental mobility than typical structured proteins. An nmr structural analysis of adrenal peptide E in SDS micelles indicated the presence of two well-defined beta-turns, one at the N-terminus encompassing residues 3 to 6, and the second in the region between residues 15 and 18. Certain side chain dihedral angles were also remarkably well defined, such as the chi 1 angle of F4, which exhibited a trans configuration. These calculated structures were based on a set of 9.5 restraints per residue. The backbone dynamics of peptide E in SDS micelles were examined through an analysis of 15N-relaxation parameters. An extended model-free analysis was used to interpret the relaxation data. The overall rotational correlation time is 19.7 ns. the average order parameter S2 is 0.66 +/- 0.15. The N-terminal loop region residues including G3 to R6 have an average order parameter of 0.70 +/- 0.23. The average order parameter lies somewhere between that observed for a random coil (e.g., S2 = 0.3) and that of a well-defined tertiary fold (e.g., S2 = 0.86). This suggests that peptide E in SDS micelles adopts a restricted range of conformations rather than a random coil. Based on the helical structure recently obtained for the highly homologous kappa-agonist dynorphin-A(1-17) and the beta-turn in the same region of peptide E, it is reasonable to assume that these two elements of secondary structure reflect different receptor subtype binding geometries. The intermediate order parameters observed for peptide E in an SDS micelle suggest a degree of dynamic mobility that may enable facile interconversion between helical and beta-turn geometries in the N-terminal agonist domain.


Use of glazed ceramic waste as additive in mortar and the mathematical modelling of its strength.
This study investigated the reusability of waste material from the tile manufacturing industry as an alternative material to natural pozzolan trass. Yield strength values of mortar made from Portland cement (CEM 142.5), were measured by adding glazed ceramic waste and trass at various weight ratios (5 to 40%). The test results proved that the strength values at 2, 7, and 28 days gave good results for concentrations of waste materials less than 5-10% in the cement. A decrease in strength was observed at higher concentrations. Mathematical modelling results showed a logarithmic correlation between the mortar strength and weight fraction of cement.


Relation of race and sex to the use of reperfusion therapy in Medicare beneficiaries with acute myocardial infarction.
There are few reports describing the combined influence of the race and sex of a patient on the use of reperfusion therapy for acute myocardial infarction. To determine the relation of race and sex to the receipt of reperfusion therapy for myocardial infarction in the United States, we reviewed the medical records of 234,769 Medicare patients with myocardial infarction. From these records we identified 26,575 white or black patients who met strict eligibility criteria for reperfusion therapy. We then performed bivariate and multivariate analyses of prevalence ratios to determine predictors of the use of reperfusion therapy in four subgroups of patients categorized according to race and sex: white men, white women, black men, and black women. Among eligible patients, white men received reperfusion therapy with the highest frequency (59 percent), followed by white women (56 percent), black men (50 percent), and black women (44 percent). After adjustment for differences in demographic and clinical characteristics, white women were as likely as white men to receive reperfusion therapy (prevalence ratio, 1.00; 95 percent confidence interval, 0.98 to 1.03). Likewise, black women were as likely as black men to receive reperfusion therapy (prevalence ratio, 1.00; 95 percent confidence interval, 0.89 to 1.13). However, black women were significantly less likely to receive reperfusion therapy than white men (prevalence ratio, 0.90; 95 percent confidence interval, 0.82 to 0.98), as were black men (prevalence ratio, 0.85; 95 percent confidence interval, 0.78 to 0.93). After adjustment for differences in clinical and demographic characteristics and clinical presentation, differences according to sex in the use of reperfusion therapy are minimal. However, blacks, regardless of sex, are significantly less likely than whites to receive this potentially lifesaving therapy.


Using a telephone survey to acquire genetic and behavioral data related to cigarette smoking in "made-anonymous" and "registry" samples.
In the Smokers and Nonsmokers Study, the authors investigated the feasibility of using random digit dialing telephone interviews to locate adults in the continental United States who were willing to provide DNA from buccal swabs through the mail. Interviews with 3,383 adults regarding their smoking-related behaviors (response rate = 70%) were conducted in 1999-2000; swab returns continued into early 2001. Overall, 57% of interviewees agreed to receive mailed information explaining the study. Better-educated persons (odds ratio (OR) = 1.3, 95% confidence interval (CI): 1.1, 1.6), younger persons (OR = 0.988, 95% CI: 0.983, 0.992), persons with symptoms of depression (OR = 1.8, 95% CI: 1.4, 2.4), and current smokers (OR = 2.25, 95% CI: 1.8, 2.8) were likelier to agree to receive a mailing. Approximately 26% of interviewees (45% of those receiving kits) returned buccal swabs, and 18% were successfully genotyped. Older (OR = 1.02, 95% CI: 1.01, 1.03), better-educated (OR = 1.4, 95% CI: 1.1, 1.7), and White (OR = 1.8, 95% CI: 1.4, 2.5) participants were more likely to return DNA samples, but current smokers (OR = 0.6, 95% CI: 0.5, 0.8) were less likely to do so. Participants were randomly assigned to one of two forms of participation: the "registry" group (names were kept on file) or the "made-anonymous" group (names were unassociated with samples). The two groups were equally likely to return kits, but registry respondents were more likely to nominate siblings for participation in the study (OR = 1.6, 95% CI: 1.2, 2.1). The participants in this study were similar demographically to the national population. The authors conclude that random digit dialing surveys coupled with mail collection of DNA may constitute a practical method of obtaining DNA samples for biobehavioral research.


Novel Toll-Like Receptor 9 Agonist Derived from Cryptococcus neoformans Attenuates Allergic Inflammation Leading to Asthma Onset in Mice.
The enhanced type 2 helper (Th2) immune response is responsible for the pathogenesis of allergic asthma. To suppress the enhanced Th2 immune response, activation of the Th1 immune response has been an alternative strategy for anti-asthma therapy. In this context, effective Th1-inducing adjuvants that inhibit the development of allergic asthma but do not flare the side effects of the primary agent are required in clinical treatment and preventive medicine. In this study, we aimed to determine the regulation of the Th2 type immune response in asthma by a novel immunostimulatory oligodeoxynucleotide (ODN) derived from Cryptococcus neoformans, termed ODN112, which contains a cytosine-guanine (CG) sequence but not canonical CpG motifs. Using an ovalbumin-induced asthma mouse model, we assessed the effect of ODN112 on prototypical asthma-related features in the lung and on the Th1/Th2 profile in the lymph nodes and lung of mice treated with ODN112 during sensitization. ODN112 treatment attenuated asthma features in mice. In the bronchial lymph nodes of the lungs and in the spleen, ODN112 increased interferon-γ production and attenuated Th2 recall responses. In dendritic cells (DCs) after allergen sensitization, ODN112 enhanced cluster of differentiation (CD) 40 and CD80 expression but did not alter CD86 expression. Interleukin-12p40 production from DCs was also increased in a Th2-polarizing condition. Our results suggest that ODN112 is a potential Th1-inducing adjuvant during Th2 cell differentiation in the sensitization phase.


Relationship between ABO blood groups and oral cancer.
Cancer is a unique disease characterized by abnormal growth of cells which have the ability to invade the adjacent tissues and sometimes even distant organs. Oral cancer has multifactorial etiology and is significantly associated with risk factors of the individual's lifestyle, particularly, chronic use of tobacco, spicy food, alcohol and smoking. Many studies have indicated that genetic factors also have an influence on the etiology of cancer. To evaluate if any of the ABO blood groups are associated with an increased risk for oral cancer. The present study was conducted at Kidwai Memorial Institute of Oncology (KMIO), Bangalore, after obtaining permission from the Director of the institute. The study sample comprised 235 oral cancer patients and 812 controls. For statistical analysis, Chi-square test and odds ratio were used to assess the relationship between ABO blood groups and oral cancer. Probability level was fixed at ≤0.05. It was found that people with blood group A had 1.46 times higher risk of developing oral cancer compared to people of other blood groups. By employing a simple blood grouping test during community field programs, people with blood group A in the age group of 40-59 years having tobacco chewing habits can be apprised that they are more at risk to develop oral cancer than people with other blood groups.


[Affinity modification of creatine kinase from the rabbit skeletal muscle by gamma-amide of ATP--a nitrogen mustard derivative].
A study of creatine kinase modification by ATP gamma-(N-(2-chloroethyl)-N-methyl)amide was performed. The attachment 1,7-1,8 moles of analogue per mole of functional dimer results in full inactivation of the enzyme. The substrates, ATP and ADP, protect the enzyme both against inactivation and covalent binding of analogue. The affinity modification rate depends on the reagent and magnesium ion concentrations and pH of the reaction mixture. The dissociation constants (1,0 and 1,5 mM) for the enzyme-analogue complexes and the affinity modification maximal rate constants (2,1 X 10(-3) and 1,2 X 10(-3) c-1) in the absence and presence of Mg2+ ions were estimated. Some differences in the affinity modification rates were observed for the nonidentical M and M'-subunits of creatine kinase. The data obtained are indicative of a histidine residue alkylation by the ATP analogue. This histidine (pK 7,7) may function as a general acid-base catalyst in deprotonation of the guanidinium group of creatine as the latter is phosphorylated by ATP.


Feline plasma adrenocorticotropic hormone: validation of a chemiluminescent assay and concentrations in cats with hypercortisolism, primary hypoadrenocorticism and other diseases.
The aims of this study were to validate a commercially available chemiluminescent assay for measurement of feline plasma adrenocorticotropic hormone concentration (ACTH), to determine the normal reference interval (RI) of plasma ACTH in healthy cats, to assess plasma ACTH in cats with naturally occurring hypercortisolism (HC), primary hypoadrenocorticism (PH) and other diseases (OD), and to evaluate the effect of aprotinin on plasma ACTH degradation. Forty healthy cats, 10 with HC, 11 with PH and 30 with OD, were included. The chemiluminescent enzyme immunometric assay was evaluated by measurement of intra-assay precision, interassay precision and linearity. The RI for plasma ACTH in healthy cats was established using robust methods. Plasma ACTH of samples collected with and without aprotinin, stored at 4°C and assayed over a 6-day period, was measured. The intra-assay coefficients of variance (CVs) ranged from 2.7% to 4.3% and interassay CVs from 3.3% to 10.7%. Dilution studies showed excellent accuracy (R2 >0.99). The RI for plasma ACTH in healthy cats was 32-370 pg/ml. Plasma ACTH was not significantly different between healthy cats and the OD group. Cats with pituitary-dependent hypercortisolism (PDH) and PH had significantly higher plasma ACTH than the other groups. Plasma ACTH did not show significant differences when samples collected with and without aprotinin were compared. The Immulite chemiluminescent assay is a valid technique for measuring plasma ACTH in cats and the RI of plasma ACTH is quite wide. Owing to the low overlap between healthy or OD cats and cats with HC or PH, the measurement of plasma ACTH appears to be useful and should be included in the diagnostic work-up when HC or PH are suspected. Furthermore, the measurement of plasma ACTH may be an accurate test for differentiating PDH from adrenal-dependent hypercortisolism.


[B-type natriuretic peptide and clinical judgement in the diagnosis of heart failure in patients presenting with acute dyspnoea].
B-type natriuretic peptide (BNP) is increased in left ventricular dysfunction and congestive heart failure e. The aim of the study was to determine the diagnostic accuracy of BNP and the degree to which BNP adds to clinical judgement in the diagnosis of heart failure. The BNP Multinational Study was a seven-centre prospective study of 1586 patients presenting to emergency departments with acute dyspnoea who had BNP levels measured with a rapid, point-of-care device on arrival. 1538 (97%) had pre-test probability of congestive heart failure determined from 0-100% by the attending physician in the emergency department who was blinded to the BNP levels. The final diagnosis was adjudicated by two independent cardiologists, also blinded to BNP results, who reviewed all clinical data and standardised congestive heart failure scores. The final diagnosis was congestive heart failure in 722 (47%) patients. Pre-test probability of this condition > or = 80% as determined by the attending physician had a sensitivity of 49% and specificity of 96 % for correct diagnosis. BNP > or = 100 pg/ml had a sensitivity of 90% and a specificity of 73% for correct diagnosis. In determining the correct diagnosis (congestive heart failure or not), adding BNP to clinical judgement would have enhanced diagnostic accuracy from 74% to 81%. Measurement of BNP adds to the clinical information in the diagnosis of congestive heart failure in patients presenting with acute dyspnoea.


Effect of pulmonary rehabilitation on balance in persons with chronic obstructive pulmonary disease.
To describe within-subject effects of pulmonary rehabilitation (PR) on balance in persons with chronic obstructive pulmonary disease (COPD) and to determine whether any observed changes in balance were associated with change in exercise tolerance or health-related quality of life. Single-arm longitudinal study. Inpatient PR center. Subjects with COPD (N=29; mean +/- SD age, 69.8+/-10.3y; forced expiratory volume in 1 second, 46.3%+/-22.3% predicted; 59% men [n=17]). A standardized 6-week multidisciplinary PR program (exercise training, breathing exercises, education, and psychologic support). Balance was assessed using the Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and the Activities-Specific Balance Confidence (ABC) scale. Exercise tolerance was determined from the 6-minute walk test (6MWT), and health-related quality of life from the Chronic Respiratory Questionnaire (CRQ). Subjects showed small improvements in BBS (2.8+/-2.8 points; P<.001) and TUG (-1.5+/-2.4s; P=.003) scores, but not in ABC scores (4.8+/-15.4 points; P>.05). There was a weak relationship between change in BBS and change in CRQ scores (r=.40; P=.045) and no relationship with change in 6MWT. PR contributed to minor improvements in balance and had no effect on balance confidence in subjects with COPD. Further work is warranted to determine the optimal intervention for improving balance in this population.


Medicare in interventional pain management: A critical analysis.
Recent years have been quite eventful for interventional pain physicians with numerous changes in the Medicare payment system with a view for the future and what it holds for interventional pain management for 2006 and beyond. On February 8, 2006, President Bush signed the Deficit Reduction Act of 2005, which cuts the federal budget by 39 billion dollars and Medicare and Medicaid by almost 11 billion dollars over five years. The Act contains a number of important provisions that effect physicians in general and interventional pain physicians in particular. This Act provides one year, 0% conversion factor update in payments for physicians services in 2006. Medicare has four programs or parts, namely Medicare Parts A, B, C, and D, and two funds to pay providers for serving beneficiaries in each of these program. Part B helps pay for physician, outpatient hospital, home health, and other services for the aged and disabled who have voluntarily enrolled. Before 1922, the fees that Medicare paid for those services were largely based on physician's historical charges. Despite Congress's actions of freezing or limiting the fee increases, spending continued to rise because of increases in the volume and intensity of physician services. Medicare spending per beneficiary for physician services grew at an average annual rate of 11.6% from 1980 through 1991. Consequently Congress was forced to reform the way that Medicare sets physician fees, due to ineffectiveness of the fee controls and reductions. The sustained growth rate (SGR) system was established because of the concern that the fee schedule itself would not adequately constrain increases in spending for physicians' services. The law specifies a formula for calculating the SGR, based on changes in four factors: (1) estimated changes in fees; (2) estimated change in the average number of Part B enrollees (excluding Medicare Advantage beneficiaries); (3) estimated projected growth in real gross domestic product (GDP) growth per capita; and (4) estimated change in expenditures due to changes in law or regulation. Overall, the frequency of utilization of interventional procedures has increased substantially since 1998. In 2006 and beyond, interventionalists will face a number of evolving economic and policy-related issues, including reimbursement discrepancies, issues related to CPT coding, issues related to utilization, fraud, and abuse.


A population study of the incidence of fibromyalgia among women aged 26-55 yr.
In a population survey, we assessed the incidence of fibromyalgia (FM) among females. A screening questionnaire about pain was distributed twice (in 1990 and 1995) to 2498 females aged 20-49 yr, living in South Norway. A positive answer classified the responder as positive, merely negative answers as negative. One hundred females converting from negative to positive responders and 100 females remaining negative responders (controls) underwent a structural interview and examination for tender points (TP). Of the 870 negative responders in 1990, 717 answered the questionnaire in 1995. Of these, 523 were still negative responders, while 194 were positive converters. Twelve of the converters developed FM and none of the controls. The calculated annual incidence of FM in females was 583/100,000. This rather high incidence is most likely explained by the design of the study, also detecting cases usually not seen in hospital settings.


Defining difficult intravenous access (DIVA): A systematic review.
The term "difficult intravenous access" (DIVA) is commonly used but not clearly defined. Repeated attempts at peripheral intravenous catheter (PIVC) insertion can be a traumatic experience for patients, leading to sub-optimal clinical and economic outcomes. We conducted a systematic literature review (SLR) to collate literature definitions of DIVA, with the aim of arriving at an evidence-driven definition. The SLR was designed to identify clinical, cost, and quality of life publications in patients requiring the insertion of a PIVC in any setting, including studies on US-guidance and/or guidewire, and studies with no specific intervention. The search was restricted to English language studies published between 1st January 2010 and 30th July 2020, and the Ovid platform was used to search several electronic databases, in addition to hand searching of clinical trial registries. About 121 studies were included in the SLR, of which 64 reported on the objectives relevant to this manuscript. Prevalence estimates varied widely from 6% to 87.7% across 19 publications, reflecting differences in definitions used. Of 43 publications which provided a definition of DIVA, six key themes emerged. Of these, themes 1-3 (failed attempts at PIV access using traditional technique; based on physical examination findings for example no visible or palpable veins; and personal history of DIVA) were covered by all but one publication. Following a failed insertion attempt, the most common number of subsequent attempts was 3, and it was frequently reported that a more experienced clinician would attempt to gain access after multiple failed attempts. Considering the themes identified, an evidence-driven definition of DIVA is proposed: "when a clinician has two or more failed attempts at PIV access using traditional techniques, physical examination findings are suggestive of DIVA (e.g. no visible or palpable veins) or the patient has a stated or documented history of DIVA."


Combining proton and silaborane-based superhalogen anions - an effective route to new superacids as verified via systematic DFT calculations.
Based on systematic DFT calculations, silaborane-based superhalogen anions, which obey the Wade-Mingos rule, are shown to be capable of giving rise to superacids via their combination with protons. Compared to previous carborane-based systems, the acidities of the composites here are stronger in both the gas phase and solution phase. Thus, the potential of candidates based on silaborane could be greater than those based on carborane in the search for ultra-strong acidic systems. Within a given group, a higher superhalogen anion vertical electron detachment energy (VDE) generally leads to stronger acidity. This consistency arises from the dominant role of the VDE, as established through the decomposition of the gas-phase acidity into different contributions. Thus, constructing superacids from superhalogens is a rational route whose future should be positive. Besides the VDE, other effects, i.e., the deformation energy (DE) and bond dissociation energy (BDE), could also be crucial, especially in terms of the differences between the acidities of composites belonging to different groups. A comparison between the results in the gas phase and solution phase indicates that complete calculations of both gas-phase ΔGacid and solution-phase pKa values are necessary to obtain an unbiased description of the acidity. The solvation free energies of the participants in the deprotonation process, especially the conjugate acid, are responsible for the discrepancies between gas phase and solution phase behavior.


Evaluating the Adjuvant Effect of Dexamethasone to Ropivacaine in Transversus Abdominis Plane Block for Inguinal Hernia Repair and Spermatocelectomy: A Randomized Controlled Trial.
The transversus abdominis plane (TAP) block is a relatively straightforward regional technique used for postoperative analgesia in patients undergoing abdominal surgeries. Various adjuvants have been used in past to prolong the duration of action of analgesia in peripheral nerve blocks. Several studies investigating the analgesic efficacy of dexamethasone added to local anesthetic agents, such as bupivacaine, have shown promising results. However, there are few studies comparing the efficacy of dexamethasone with ropivacaine. To determine if the addition of dexamethasone 8 mg to ropivacaine 0.2% in a TAP block would prolong the analgesic effect when compared with ropivacaine 0.2% alone after inguinal hernia repair and spermatocelectomy. A randomized, double blinded, placebo-controlled, prospective study. Teaching hospital. A total of 82 patients undergoing inguinal hernia repair or spermatocelectomy were enrolled in the study, of which 41 patients received TAP block with ropivacaine with saline, and the other 41 received ropivacaine with dexamethasone immediately following surgery. Both the proceduralist (resident) and the patient were blinded to the solution used. Visual analog pain scores (0 - 10) were obtained pre-block and immediately post block. Our primary endpoint was visual analog pain score at 12 hours, with 24 and 48-hour pain scores as the secondary endpoints. The averaged pre-block pain score was 7.6 ± 1.7 in the saline group and 7.7 ± 2.2 in the dexamethasone group. There was an improvement in the pain scores from the baseline, at 12 hours after the administration of the block in both the groups. Although the dexamethasone group had a greater change in pain score (-3.2) than the saline group (-2.2), the difference between the 2 groups was not statistically significant (0.08). We did not observe significant differences in change from baseline at 24 hours and 48 hours between the 2 groups (P value = 0.74 and 0.44, respectively). We did not assess the total dose of analgesics used during the surgery with the assumption that the effect of intraoperative analgesics should wear off by the time we collect the 12-hour pain score. We did not control for the expertise of the provider that performed the block, as some of the providers may have been junior residents with limited experience and expertise in the area. Additionally, we were unable to include postoperative opioid consumption due to concerns of inconsistencies during patient reporting and data quality. In conclusion, we could not show a statistically significant prolongation of analgesia for TAP blocks with ropivacaine when dexamethasone was added, though there was a one point drop in pain score at 12 hours post block when dexamethasone was added to the block solution. This decrease in pain scores at 12 hours may still be beneficial to patient satisfaction given the low side effect profile of dexamethasone. As ropivacaine has a lower pH than other local anesthetic agents, further well designed studies are needed to investigate the combination of this drug with more alkaline drugs like corticosteroids. Regional anesthesia, transversus abdominis plane, dexamethasone, ropivacaine.


Progress in the generation of spinal cord organoids over the past decade and future perspectives.
Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo. As emerging bioengineering methods have led to the optimization of cell culture protocols, spinal cord organoids technology has made remarkable advancements in the past decade. Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes. Moreover, fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment. These qualities make spinal cord organoids valuable tools for disease modeling, drug screening, and tissue regeneration. By utilizing this emergent technology, researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases. However, at present, spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine. Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.


Correlation of light-induced changes in retinal extracellular potassium concentration with c-wave of the electroretinogram.
1. Double-barrel, potassium-specific microelectrodes have been used to measure light-induced transient changes in [K+]o in the frog eye cup preparation. These changes in [K+]o have been termed the potassioretinogram (KRG). 2. The KRG consists of two components: a rapid increase in [K+]o in the proximal retina and a slow decrease in [K+]o in the distal retina. 3. The KRG decrease has the rhodopsin action spectrum, is maximal in the photoreceptor layer, persists after aspartate treatment, and has an increment threshold curve which saturates at moderate background intensities. The rhodopsin rods are, therefore, most likely the only neurons which generate this ionic change, although the Müller (glial) cells may also be involved in this process. 4. The KRG decrease has the same time course as the c-wave of the electroretinogram for all variations in the stimulus parameters, including intensity, duration, and chromaticity. 5. It is suggested that the c-wave may be produced by the pigment epithelial cells as they hyperpolarize in response to the decrease in [K+]o around the photoreceptors.


Calcinosis cutis arising in morphea: a case series.
Calcinosis cutis, although common in systemic sclerosis, has been rarely reported in patients with morphea. We describe four patients with calcinosis cutis arising within morphea plaques, discuss their treatments and outcomes, and review previously published cases. Current management recommendations for concomitant morphea and dystrophic calcinosis cutis are based on limited data and expert opinion, which has primarily focused on reduction of active inflammation and reduction of symptoms related to calcinosis or ulceration. In most cases, no improvement of calcinosis was noted. The use of intralesional corticosteroids to active lesions in conjunction with systemic treatment, including methotrexate when indicated, appear promising treatments to halt progression of the disease. Surgical excision seems to be the most definitive treatment for calcinosis affecting morphea plaques, but the current literature lacks details regarding disease recurrence following operative management.


The first 9 years of kidney paired donation through the National Kidney Registry: Characteristics of donors and recipients compared with National Live Donor Transplant Registries.
The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR. Compared with all United Network for Organ Sharing (UNOS) live donor transplant patients (49 610), all UNOS living unrelated transplant patients (23 319), and all other KPD transplant patients (4236), the demographic and clinical characteristics of NKR transplant patients (2037) appear similar to contemporary national trends. In particular, among the NKR patients, there were a significantly (P < .001) greater number of retransplants (25.6% vs 11.5%), hyperimmunized recipients (22.7% vs 4.3% were cPRA >80%), female recipients (45.9% vs 37.6%), black recipients (18.2% vs 13%), and those on public insurance (49.7% vs 41.8%) compared with controls. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible pairs and even chains initiated by deceased donors, to unlock more opportunities for those harder-to-match pairs.


Contractile force of canine tracheal smooth muscle during continuous stretch.
Canine tracheal smooth muscle strips were mounted horizontally in a tissue bath between a force transducer and a motor-driven movable steel rod, which was used to change muscle length. Muscle length and force were continuously measured during stretch and simultaneously plotted on an X-Y recorder. Active force during stretch was investigated as follows: an initial length was set with the muscle relaxed, where it was contracted isometrically with acetylcholine. After active force reached a steady state, muscle length was decreased until the total tension was equal to zero. The muscle was then stretched slowly to obtain a continuous length-force curve. Results show that force during stretch increases as the length at which the initial isometric contraction is elicited, is decreased. A possible interpretation is that during tonic muscle contraction, the contractile element is able to shorten very slowly relative to the rate at which the muscle was retracted. Thus, the contractile element length established during isometric contraction would affect the muscle force obtained during subsequent stretch of the muscle.


Effectiveness and safety of diclofenac epolamine topical patch 1.3% for the treatment of acute pain due to back strain: an open-label, uncontrolled study.
The diclofenac epolamine topical patch 1.3% (DETP) is indicated for topical treatment of acute pain due to minor strains, sprains, and contusions. This exploratory, multicenter, open-label study evaluated effectiveness and safety of DETP in patients with acute pain due to back strain. Patients aged ≥ 18 years with acute pain due to nonradicular back strain with an average pain intensity of ≥ 4 (0 = no pain, 10 = pain as bad as you can imagine) entered a 3-day observation/washout period and completed daily diary modified Brief Pain Inventory assessments. At baseline, patients with an average pain intensity of ≥ 4 started DETP treatment (q12h). Patients were treated for 7 or 14 days, depending on investigator and patient assessment of pain resolution. Primary endpoint was mean change from baseline to end of treatment in average pain intensity. Key secondary endpoints included changes from baseline in least, worst, and current pain scores and Beck Depression Inventory(®) II scores. Patients and investigators assessed patch satisfaction and global pain relief. In 123 enrolled patients, baseline mean ± standard deviation average pain score was 6.5 ± 1.3, which decreased to 2.5 ± 2.4 (P < 0.0001) at end of treatment. Similarly, least, worst, and current pain scores were also reduced (P < 0.0001). Sixty-three percent of patients achieved ≥ 50% pain reduction from baseline. At the end of treatment, most patients (88%) were satisfied or very satisfied with DETP. For 85% of patients, investigators also reported being satisfied or very satisfied with DETP. Most patients (87%) and investigators (88%, rating the patient's response) rated global pain relief as moderate to complete. Fifteen patients experienced a total of 19 adverse events (AEs), 17 of which were mild to moderate, and 2 of which were severe. Three AEs were treatment related (application site rash, nausea, and tachycardia); 1 patient had a serious AE (noncardiac chest pain) considered unrelated to DETP. In this exploratory study, patients experienced well-tolerated relief for acute pain due to back strain, with ≥ 85% of patients and their investigators expressing satisfaction with DETP treatment.


Interaction of corneal nociceptive stimulation and lacrimal secretion.
To investigate the interaction between corneal stimuli at different positions and tear secretion and to establish relationships between nociceptive stimuli detection thresholds and stimulated tearing. Using a computerized Belmonte-esthesiometer, mechanical and chemical stimuli, from 0% to 200% of the threshold in 50% steps, were delivered (in random order) to the central and peripheral (approximately 2-mm inside the limbus) cornea during four separate sessions to 15 subjects. Immediately after each stimulus, tear meniscus height (TMH) was measured using optical coherence tomography to quantify the amount of lacrimal secretion, and subjects reported whether they felt tears starting to accumulate in their eyes. Thresholds (50% detection) for detection of tearing were estimated. TMH increased with increasing stimulus intensity (P < 0.05), and the overall increase was higher with central stimulation than with peripheral stimulation (P < 0.05). The changes in TMH with threshold-scaled stimulus intensity depended on test location (P < 0.05) and stimulus modality (P < 0.05). The maximum intensity of mechanical stimulation of the central cornea induced the greatest TMH (all P < 0.05). For chemical stimulation, the stimulus intensity required to induce detectable tearing was higher than that required to detect a stimulus and higher in the periphery than at the center (all P < 0.05). Noxious mechanical and chemical stimuli evoked measurable tear secretion, with central corneal mechanical stimulation evoking the strongest lacrimation reflex. Central mechanical corneal stimulation is the most effective stimulus-position pairing and appears to be the major sensory driving force for reflex tear secretion by the lacrimal functional unit.


Xenophyophores (Rhizaria, Foraminifera), including four new species and two new genera, from the western Clarion-Clipperton Zone (abyssal equatorial Pacific).
The Clarion-Clipperton Zone (CCZ) occupies a vast swathe of the Pacific with extensive polymetallic nodule deposits. Eastern and central parts host diverse assemblages of xenophyophores (megafaunal agglutinated foraminifera). Here we describe xenophyophores obtained using a Remotely Operated Vehicle from the western CCZ. Eleven distinct forms include two known species, Stannophyllum zonarium Haeckel, 1888 and Aschemonella monile Gooday and Holzmann in Gooday et al., 2017b. Another four are described as new species based on morphological and genetic data. In Abyssalia foliformis gen. nov., sp. nov. and Abyssalia sphaerica sp. nov. the flattened or spherical test comprises a homogeneous framework of sponge spicules. Psammina tenuis sp. nov. has a delicate, thin, plate-like test. Moanammina semicircularis gen. nov., sp. nov. has a stalked, fan-shaped test and is genetically identical to 'Galatheammina sp. 6' of Gooday and co-workers from the eastern CCZ. Sequence data revealed a spherical 'mudball', which disintegrated and cannot be formally described, to be a novel xenophyophore. Finally, four morphospecies are represented by dead tests: Psammina spp., Reticulammina sp., and an unknown genus with a unique test structure. This collection enhances our knowledge of Pacific xenophyophore diversity and provides the first genetic confirmation of wide geographic ranges for abyssal species.


Socio-cultural agents and their impact on body image and body change strategies among adolescents in Fiji, Tonga, Tongans in New Zealand and Australia.
This paper reports on the findings of studies that were conducted as part of the Pacific Obesity Prevention in Communities project. The studies evaluated the types of messages that adolescents received in relation to body image, physical activity and eating. The participants were male and female adolescents from Fiji (two cultural groups), Tonga, New Zealand (Tongans) and Australia (European Australians). Three studies were conducted: interviews with 48 adolescents (24 male, 24 female) from each cultural group, questionnaires with 600 adolescents (300 male, 300 female) from each cultural group and the perceptual distortion study with 100 adolescents (50 male, 50 female) from the two cultural groups in Fiji and European Australians. The results demonstrate that parents, peers, the media, as well as religious influences impact on the type of body valued by adolescents in each of the cultural groups, as well as their levels of body satisfaction. These influences also shape the type and volume of food consumed, and the type and frequency of physical activity. The results of these studies highlight the major role played by the broader societal values in shaping the nature of the messages that adolescents receive in relation to their body size, eating and physical activity.


Information content of individual genetic sequences.
Related genetic sequences having a common function can be described by Shannon's information measure and depicted graphically by a sequence logo. Though useful for many purposes, sequence logos only show the average sequence conservation, and inferring the conservation for individual sequences is difficult. This limitation is overcome by the individual information ( R i) technique described here. The method begins by generating a weight matrix from the frequencies of each nucleotide or amino acid at each position of the aligned sequences. This matrix is then applied to the sequences themselves to determine the sequence conservation of each individual sequence. The matrix is unique because the average of these assignments is the total sequence conservation, ad there is only one way to construct such a matrix. For binding sites on polynucleotides, the weight matrix has a natural cut off that distinguishes functional sequences from other sequences. R i values are on an absolute scale measured in bits of information so the conservation of different biological functions can be compared with one another. The matrix can be used to rank-order the sequences, to search for new sequences, to compare sequences to other quantitative data such as binding energy or distance between binding sites, to distinguish mutations from polymorphisms, to design sequences of a given strength, and to detect errors in databases. The R i method has been used to identify previously undescribed but experimentally verified DNA binding sites. The individual information distribution was determined for E. coli ribosome binding sites, bacterial Fis binding sites, and human donor and acceptor splice junctions, among others. The distributions demonstrate clearly that the consensus sequence is highly unusual, and hence is a poor method to describe naturally occurring binding sites.


Purification of endopeptidase-24.11 ('enkephalinase') from pig brain by immunoadsorbent chromatography.
Membrane preparations from striatum of pig brain contain endopeptidase activity towards iodoinsulin B-chain. Only 50% of the hydrolysis of insulin B-chain is inhibitable by phosphoramidon, and DEAE-cellulose chromatography can resolve the phosphoramidon-sensitive and -insensitive activities. The former activity (now designated 'endopeptidase-24.11') is responsible for hydrolysis of [D-Ala2,Leu5]enkephalin and is identical with an enzyme in brain that has previously been referred to as 'enkephalinase'. Pig striatal endopeptidase-24.11 has now been purified to homogeneity in a single step by immunoadsorbent chromatography using a monoclonal antibody. The overall purification was 23 000-fold, with a yield of 30%. The brain enzyme appears to be identical with kidney endopeptidase-24.11 in amino acid composition as well as by immunological and kinetic criteria. However, it differs slightly in apparent subunit size (Mr = 87 000), attributable to differences in glycosylation.


Ferroptosis plays a novel role in nonalcoholic steatohepatitis pathogenesis.
Ferroptosis relies on iron, and ferroptotic cell death is triggered when the balance of the oxidation-reduction system is disrupted by excessive lipid peroxide accumulation. A close relationship between ferroptosis and nonalcoholic steatohepatitis (NASH) is formed by phospholipid peroxidation substrates, bioactive iron, and reactive oxygen species (ROS) neutralization systems. Recent studies into ferroptosis during NASH development might reveal NASH pathogenesis and drug targets. Our review summarizes NASH pathogenesis from the perspective of ferroptosis mechanisms. Further, we discuss the relationship between mitochondrial dysfunction, ferroptosis, and NASH. Finally, potential pharmacological therapies directed to ferroptosis in NASH are hypothesized.


Images of infertility.
A key purpose of this article is to focus on the major role of the nurse practitioner in providing the necessary support to couples as they cope with infertility and its many manifestations. The connection between the losses and stresses of infertility and its treatment, the emotional reactions, and the appropriate interventions are discussed and visually presented in this paper.


Comparative gene mapping in the domestic cat (Felis catus).
The genetic map of the domestic cat has been developed as a model for studying both feline analogues of human genetic disease and comparative genome organization of mammals. We present here the results of syntenic mapping of 35 genes based upon concordant occurrence of feline gene homologues with feline chromosomes and previously mapped loci in a panel of 41 rodent x cat somatic cell hybrids. These somatic cell hybrids retain rodent chromosomes and segregate feline chromosomes, but in different combinations in each hybrid cell line. Thirty-three of the 35 new locus assignments extend and reaffirm conserved chromosome segment homologies between the human and cat genomes previously recognized by comparative mapping and zoo-FISH. These results demonstrate the extensive syntenic conservation between the human and feline genomes and extend the feline gene map to include 105 assigned loci.


Hydroxyl radical formation by sickle erythrocyte membranes: role of pathologic iron deposits and cytoplasmic reducing agents.
Sickle erythrocyte (RBC) membranes were previously shown to manifest increased Fenton activity (iron-dependent, peroxide-driven formation of hydroxyl radical [.OH]) compared with normal RBC membranes, but the nature of the catalytic iron was not defined. We now find that sickle membranes exposed to superoxide (.O2-) and hydrogen peroxide (H2O2) have three distinct iron compartments able to act as Fenton catalysts: preexisting free iron, free iron released during oxidant stress, and a component that cannot be chelated with deferoxamine (DF). In a model system, addition of iron compounds to normal ghosts showed that free heme, hemoglobin, Fe/adenosine diphosphate (ADP), and ferritin all catalyze .OH production; concurrent inhibition studies using DF documented that the unchelatable Fenton component is free heme or hemoglobin. During exposure to peroxide only, the iron in sickle membranes was unable to act as a Fenton catalyst without addition of a reducing agent. At physiologic concentrations, both ascorbate and glutathione restored Fenton activity. Lipid peroxidation studies showed that at physiologic levels ascorbate acts primarily as an antioxidant; however, as pharmacologic levels are reached, its pro-oxidant effects predominate. This study elucidates the catalytic ability of the iron compartments in the sickle cell membrane, the importance of which relates to the potential role of .OH in membrane damage. It also illustrates the potential participation of cytoplasmic reducing agents in this process, which may be especially relevant in the context of administration of supraphysiologic doses of ascorbate to sickle cell patients.


PET of EGFR antibody distribution in head and neck squamous cell carcinoma models.
Epidermal growth factor receptor (EGFR) is a well-characterized protooncogene that has been shown to promote tumor progression in solid cancers. Clinical results for EGFR targeting with specific monoclonal antibodies (mAbs) such as cetuximab and panitumumab are promising; however, most studies indicate that only a subgroup of patients receiving the mAbs benefit from the immunotherapy, independent of EGFR expression level. To understand the in vivo kinetics of antibody delivery and localization, we performed small-animal PET studies with (64)Cu-labeled panitumumab in xenografts derived from 3 cell lines of human head and neck squamous cell carcinoma (HNSCC). Nude mice bearing HNSCC tumors with different levels of EGFR expression were imaged with small-animal PET using (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-panitumumab. Antibody distribution in the tumors was confirmed by ex vivo immunostaining using panitumumab and fluorescein 5(6)-isothiocyanate (FITC) panitumumab. CD31 immunostaining and Evans blue assay were also performed to assess the tumor vascular density and permeability. Among these 3 tumor models, UM-SCC-22B tumors with the lowest EGFR protein expression showed the highest (64)Cu-DOTA-panitumumab accumulation, whereas SQB20 tumors with the highest EGFR expression showed the lowest (64)Cu-DOTA-panitumumab accumulation. Ex vivo staining demonstrated that SQB20 cells still had extremely high EGFR expression after forming tumors in nude mice, indicating that the low uptake of (64)Cu-DOTA-panitumumab in SQB20 tumors was not due to the loss of EGFR expression. The results from CD31 immunostaining and Evans blue permeability assay suggest that the low vessel density, poor vascular permeability, and binding site barrier are likely responsible for the overall low tumor uptake of the highly EGFR-expressing SQB20 tumors. The results from this study provide a possible explanation for the lack of an observed correlation between therapeutic efficacy of cetuximab and panitumumab and EGFR expression level as determined by immunohistochemistry or fluorescent in situ hybridization and may shed new light on the complications of anti-EGFR mAb therapy for HNSCC and other malignancies.


Insights into the prevalence and underlying causes of clonal variation through transcriptomic analysis in Pichia pastoris.
Clonal variation, wherein a range of specific productivities of secreted proteins are observed from supposedly identical transformants, is an accepted aspect of working with Pichia pastoris. It means that a significant number of transformants need to be tested to obtain a representative sample, and in commercial protein production, companies regularly screen thousands of transformants to select for the highest secretor. Here, we have undertaken a detailed investigation of this phenomenon by characterising clones transformed with the human serum albumin gene. The titers of nine clones, each containing a single copy of the human serum albumin gene (identified by qPCR), were measured and the clones grouped into three categories, namely, high-, mid- and low-level secretors. Transcriptomic analysis, using microarrays, showed that no regulatory patterns consistently correlated with titer, suggesting that the causes of clonal variation are varied. However, a number of physiological changes appeared to underlie the differences in titer, suggesting there is more than one biochemical signature for a high-secreting strain. An anomalous low-secreting strain displaying high transcript levels that appeared to be nutritionally starved further emphasises the complicated nature of clonal variation.


Investigation of 'borderline' dementia, particularly of Alzheimer's type, compared with non-demented patients with similar neuropsychological profiles.
The aim of the study was to test the fine ability of the Cambridge Cognitive Examination (CAMCOG) to differentiate between subjects with mild dementia and non-demented subjects. Ninety-four subjects took part in the study (56 non-demented and 38 mildly demented). Diagnosis was reached according to DSM-IV and NINCDS-ADRDA criteria. Items 160, 146, 171 and 178 seemed to be particularly useful for the diagnosis for subjects under 75 years of age, and items 139, 143, 146, 148, 159, 175, 177, 181, 183 and 186 for the diagnosis for subjects over 74. Further study of these items may increase ability to detect dementia in epidemiological surveys and advance knowledge about the role of factors like education or culture in interaction with advanced age. Currently, it is not possible to identify dementia at an early stage by neuropsychological methods alone. ( Int J Psych Clin Pract 2001; 5:55-61).


[Use and misuse of steroids to newborn].
A growing number of extremely preterm neonates survive; a high percentage develop chronic lung disease/bronchopulmonal dysplasia. The short-term effect of glucocorticoids in prevention or treatment is beneficial, but short- and long-term side effects are of concern. Based on non-systematic searches in the Medline and Cochrane databases, this article provides an overview of beneficial and detrimental effects (emphasis on long-term side effects) of glucocorticoids in the neonatal period. Steroids have a beneficial short-term effect on bronchopulmonal dysplasia, with reduced duration of ventilator treatment and decreased needs for oxygen supplementation at 36 weeks gestational age (odds ratio 0.62-0.76). However, survival at 40 weeks is not improved due to severe side effects. Long-term effects on neurodevelopmental outcome show a significant increase in the risk for cerebral palsy (odds ratio 1.69) and a significant increase in the risk for abnormal neurological development and cognitive impairment of equal size. No significant effects on lung function, growth and metabolic outcome later in childhood have been proven so far. Given that glucocorticoids do not increase survival of neonates, their serious side effects indicate that they should only be considered with severe ventilator-dependent lung disease after 2-3 weeks.


Evaluation of irreversible protein thermal inactivation caused by breakage of disulphide bonds using methanethiosulphonate.
Many extracellular globular proteins have evolved to possess disulphide bonds in their native conformations, which aids in thermodynamic stabilisation. However, disulphide bond breakage by heating leads to irreversible protein denaturation through disulphide-thiol exchange reactions. In this study, we demonstrate that methanethiosulphonate (MTS) specifically suppresses the heat-induced disulphide-thiol exchange reaction, thus improving the heat-resistance of proteins. In the presence of MTS, small globular proteins that contain disulphides can spontaneously refold from heat-denatured states, maintaining wild-type disulphide pairing. Because the disulphide-thiol exchange reaction is triggered by the generation of catalytic amounts of perthiol or thiol, rapid and specific perthiol/thiol protection by MTS reagents prevents irreversible denaturation. Combining MTS reagents with another additive that suppresses chemical modifications, glycinamide, further enhanced protein stabilisation. In the presence of these additives, reliable remnant activities were observed even after autoclaving. However, immunoglobulin G and biotin-binding protein, which are both composed of tetrameric quaternary structures, failed to refold from heat-denatured states, presumably due to chaperon requirements. Elucidation of the chemical modifications involved in irreversible thermoinactivation is useful for the development of preservation buffers with optimum constitutions for specific proteins. In addition, the impact of disulphide bond breakage on the thermoinactivation of proteins can be evaluated using MTS reagents.


Role of prostaglandin H synthase-2-mediated conversion of arachidonic acid in controlling 3T6 fibroblast growth.
The specific role(s) of arachidonic acid (AA) and its metabolites in the signaling pathways that regulated fibroblast growth was studied. A Western blot analysis demonstrated that prostaglandin H synthase-2 (PGHS-2) was expressed by 3T6 fibroblast cultures in RPMI 1640 supplemented with fetal calf serum (10%). Dexamethasone, which inhibits AA release and PGHS-2 expression, significantly reduced cell proliferation. Ketoprofen, a dual cyclooxygenase inhibitor, and CGP-28238, a specific PGHS-2 inhibitor, reduced fibroblast proliferation in a dose-dependent manner. These drugs also reduced [3H]thymidine incorporation into the DNA of fibroblasts. These effects were correlated with a decrease in prostaglandin (PG) E2 levels in the cell medium. However, piroxicam at doses that selectively inhibit PGHS-1 did not have a significant effect on fibroblast proliferation. Finally, we showed that the antiproliferative effect of dexamethasone and PGHS-2 inhibitors was significantly antagonized when PGE2 was added to the culture medium. Our results suggest that PGHS-2 and prostaglandins such as PGE2 might play an important role in the regulation of 3T6 fibroblast growth stimulated by growth factors of serum.


Tourniquet-less arthroscopic anterior cruciate ligament reconstruction: a technical guide & narrative review of the evidence.
Arthroscopic anterior cruciate ligament reconstruction (ACLR) is often performed with the use of a thigh tourniquet. Surgeons believe this helps improve visualisation and reduce operative time. However, tourniquet use has been associated with many complications including increased pain, neurovascular injury, venous thromboembolism, haematoma formation, and others. In this article, we describe a method allowing comparable arthroscopic visualisation to be achieved without the aid of a tourniquet for ACLR procedures. The literature evidence relating to this technique as well as tourniquet use for ACLR is also reviewed. Tourniquet-less ACLR can be achieved through the combined application of hypotensive anaesthesia, intravenous tranexamic acid, and use of adrenaline-supplemented irrigation fluid and local anaesthetic. Performing ACLR without a tourniquet avoids the risks associated with its use and reduces the severity of post-operative haemarthrosis which may contribute to the patient's pain and limit their ability to perform their rehabilitation exercises.


Elevated levels of apolipoprotein E in the high density lipoproteins of human cord blood plasma.
The concentrations and lipoprotein distributions of apolipoprotein E (apoE) in normal human umbilical cord blood plasma were determined. The mean plasma apoE level of 95 neonates was considerably higher than that of 49 normal adults (58.1 vs 35.8 micrograms/ml). This elevation of apoE levels was in striking contrast to the lower than adult levels of cholesterol (72 mg/dl vs 185 mg/dl), triglyceride (37.8 mg/dl vs 97.6 mg/dl), and LDL cholesterol (25 mg/dl vs 110 mg/dl) in neonatal plasma. For the group of 95 neonates, the plasma apoE concentration correlated significantly with total plasma cholesterol concentration (r = 0.60), with LDL cholesterol concentration (r = 0.27) and with HDL cholesterol concentration (r = 0.50). Among the neonates, 87% of plasma apoE was associated with a less dense subfraction of high density lipoprotein compared to a mean of 58% for 30 normal adults. Thus, for neonates, despite hypolipidemia, the absolute concentration of apoE in HDL (50 micrograms/ml) was 2.5 times that of adults (20 micrograms/ml). We speculate that the very low level of neonatal VLDL, providing limited substrate for lipolysis, may result in retarded removal of apoE from plasma and the observed high level of apoE in neonatal HDL. We hypothesize that in the fetus and neonate, as has been demonstrated in abetalipoproteinemia, apoE-rich HDL may functionally substitute for LDL in delivering cholesterol to cells.


Automated inhaled nitric oxide alerts for adult extracorporeal membrane oxygenation patient identification.
Recently, automated alerts have been used to identify patients with respiratory failure based on set criteria, which can be gleaned from the electronic medical record (EMR). Such an approach may also be useful for identifying patients with severe adult respiratory distress syndrome (ARDS) who may benefit from extracorporeal membrane oxygenation (ECMO). Inhaled nitric oxide (iNO) is a common rescue therapy for severe ARDS which can be easily tracked in the EMR, and some patients started on iNO may have indications for initiating ECMO. This case series summarizes our experience with using automated electronic alerts for ECMO team activation focused particularly on an alert triggered by the initiation of iNO. After a brief trial evaluation, our Smart Alert system generated an automated page and e-mail alert to ECMO team members whenever a nonzero value for iNO appeared in the respiratory care section of our EMR. If iNO was initiated for severe respiratory failure, a detailed evaluation by the ECMO team determined if ECMO was indicated. For those patients managed with ECMO, we tabulated baseline characteristics, indication for ECMO, and outcomes. From September 2012 to July 2013, 45 iNO alerts were generated on 42 unique patients. Six patients (14%) met criteria for ECMO. Of these, four were identified exclusively by the iNO alert. At the time of the alert, the median PaO₂-to-FIO₂ ratio was 64 mm Hg (range, 55-107 mm Hg), the median age-adjusted oxygenation index was 73 (range, 51-96), and the median Murray score was 3.4 (range, 3-3.75), indicating severe respiratory failure. Median time from iNO alert to ECMO initiation was 81 hours (range, -2-292 hours). Survival to hospital discharge was 83% in those managed with ECMO. Automated alerts may be useful for identifying patients with severe ARDS who may be ECMO candidates. Diagnostic test, level V.


Comparison of the state of Lithium-Sulphur and lithium-ion batteries applied to electromobility.
The market share in electric vehicles (EV) is increasing. This trend is likely to continue due to the increased interest in reducing CO2 emissions. The electric vehicle market evolution depends principally on the evolution of batteries capacity. As a consequence, automobile manufacturers focus their efforts on launching in the market EVs capable to compete with internal combustion engine vehicles (ICEV) in both performance and economic aspects. Although EVs are suitable for the day-to-day needs of the typical urban driver, their range is still lower than ICEV, because batteries are not able to store and supply enough energy to the vehicle and provide the same autonomy as ICEV. EV use mostly Lithium-ion (Li-ion) batteries but this technology is reaching its theoretical limit (200-250 Wh/kg). Although the research to improve Li-ion batteries is very active, other researches began to investigate alternative electrochemical energy storage systems with higher energy density. At present, the most promising technology is the Lithium-Sulphur (Li-S) battery. This paper presents a review of the state of art of Li-Sulphur battery on EVs compared to Li-ion ones, considering technical, modelling, environmental and economic aspects with the aim of depicting the challenges this technology has to overcome to substitute Li-ion in the near future. This study shows how the main drawbacks for Li-S concern are durability, self-discharge and battery modelling. However, from an environmental and economic point of view, Li-S technology presents many advantages over Li-ion.


LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.
A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.


Chromoendoscopic surveillance in hereditary diffuse gastric cancer: an alternative to prophylactic gastrectomy?
Hereditary diffuse gastric cancer (HDGC) is defined by germline mutations in the E-cadherin gene, CDH-1. The first family in which CDH-1 mutations were identified was a large Maori kindred, where lifetime penetrance is 70%. Prophylactic gastrectomy is an unacceptable option for many mutation carriers. The results of annual chromoendoscopic surveillance using the methylene blue/congo red technique in 33 mutation carriers over a five year period are described. Thirty three confirmed CDH-1 mutation carriers (18 males, 15 females), median age 32 years (range 14-69), were enrolled in 1999-2003. Medical records, endoscopy, and pathology were reviewed retrospectively. Over five years, 99 surveillance endoscopies were performed, of which 93 were chromo-dye enhanced. Sixty nine chromoendoscopies were normal. In 24 procedures, 1-6 pale areas/stomach (size 2-10 mm) were detected post chromo-dye application (totalling 56 pale lesions). One biopsy was taken from each pale lesion: 23 lesions (41%) showed signet ring cell carcinoma (10 patients), 10 lesions (18%) gastritis (four patients), and 23 (41%) normal mucosa (10 patients). No chromo-dyes were used in six procedures with macroscopic lesions (two HDGC, four ulceration). Total gastrectomies from patients with carcinoma were macroscopically normal but pathological mapping showed multiple microscopic foci of early signet ring cell carcinoma. Correlation of chromoendoscopic and gastrectomy findings showed that congo red/methylene blue detected carcinoma foci 4-10 mm in size but not foci <4 mm. The use of chromoendoscopy following normal white light gastroscopy facilitated detection of early gastric carcinoma foci not visible with white light gastroscopy. If these findings are validated in other HDGC kindred, chromogastroscopy represents an improved surveillance technique that can be safely considered alongside prophylactic gastrectomy.


Error analysis and performance optimization of fast hierarchical backprojection algorithms.
We recently proposed a novel fast backprojection algorithm for reconstruction of an N x N pixel object from O(N) projections in O(N(2)log(2)N) operations. In this paper, we analyze a simplified version of that algorithm, to determine the effects of various parameter choices on the algorithm's theoretical performance. We derive a bound on the variance of the per-pixel error introduced by using hierarchical backprojection. This bound is with respect to an ensemble of input sinograms, and allows us to construct confidence intervals (for any specified level) for the per-pixel errors. The bound has a simple form, and we show how to use it to select algorithm parameters for different cost versus error tradeoffs. Simulation results show that the bound accurately predicts the performance of the algorithm over a wide range of parameter choices. These results are verified for different images, including a tomographic reconstruction from the visual human dataset (VHD). The analysis therefore provides an effective tool for the selection of parameters and operating point for the fast hierarchical backprojection algorithm.


Research Techniques Made Simple: Experimental Methodology for Single-Cell Mass Cytometry.
Growing recognition of the complexity of interactions within cellular systems has fueled the development of mass cytometry. The precision of time-of-flight mass spectrometry combined with the labeling of specific ligands with mass tags enables detection and quantification of more than 40 markers at a single-cell resolution. The 135 available detection channels allow simultaneous study of additional characteristics of complex biological systems across millions of cells. Cutting-edge mass cytometry by time-of-flight (CyTOF) can profoundly affect our knowledge of cell population heterogeneity and hierarchy, cellular state, multiplexed signaling pathways, proteolysis products, and mRNA transcripts. Although CyTOF is currently scarcely used within the field of investigative dermatology, we aim to highlight CyTOF's utility and demystify the technique. CyTOF may, for example, uncover the immunological heterogeneity and differentiation of Langerhans cells, delineate the signaling pathways responsible for each phase of the hair cycle, or elucidate which proteolysis products from keratinocytes promote skin inflammation. However, the success of mass cytometry experiments depends on fully understanding the methods and how to control for variations when making comparisons between samples. Here, we review key experimental methods for CyTOF that enable accurate data acquisition by optimizing signal detection and minimizing background noise and sample-to-sample variation.


[Retrasplante cardiaco electivo. Primer caso en México].
Orthotopic cardiac retransplantation is used to treat transplanted cardiac graft end-stage failure. We present the first case of successful elective cardiac retransplantation in Mexico. It was a 25-year old male with heart transplantation who developed graft-resistant chronic vasculopathy. He underwent elective retransplantation in September 2017; complications during postoperative evolution were treated with favorable response. He was discharged owing to improvement at four weeks postoperatively. It is concluded that in adequately selected cases and comprehensively assessed, cardiac retransplantation is an appropriate option to treat cardiac graft failure.


Development of a 3-Dimensional Model to Study Right Heart Dysfunction in Pulmonary Arterial Hypertension: First Observations.
Pulmonary arterial hypertension (PAH) patients eventually die of right heart failure (RHF). Currently, there is no suitable pre-clinical model to study PAH. Therefore, we aim to develop a right heart dysfunction (RHD) model using the 3-dimensional engineered heart tissue (EHT) approach and cardiomyocytes derived from patient-induced pluripotent stem cells (iPSCs) to unravel the mechanisms that determine the fate of a pressure-overloaded right ventricle. iPSCs from PAH and healthy control subjects were differentiated into cardiomyocytes (iPSC-CMs), incorporated into the EHT, and maintained for 28 days. In comparison with control iPSC-CMs, PAH-derived iPSC-CMs exhibited decreased beating frequency and increased contraction and relaxation times. iPSC-CM alignment within the EHT was observed. PAH-derived EHTs exhibited higher force, and contraction and relaxation times compared with control EHTs. Increased afterload was induced using 2× stiffer posts from day 0. Due to high variability, there were no functional differences between normal and stiffer EHTs, and no differences in the hypertrophic gene expression. In conclusion, under baseline spontaneous conditions, PAH-derived iPSC-CMs and EHTs show prolonged contraction compared with controls, as observed clinically in PAH patients. Further optimization of the hypertrophic model and profound characterization may provide a platform for disease modelling and drug screening.


Endobronchial T-cell lymphoma in a patient with chronic pyothorax.
We report a very rare case of primary endobronchial peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS), which presented as an endobronchial tumor obstructing the main airway. An 81-year-old man was referred to our hospital for a 1-month history of productive cough and wheeze. Computed tomography revealed chronic pyothorax with calcified foci in the right lung and a mass inside the bronchus intermedius. Flexible bronchoscopy identified an endobronchial tumor obstructing the bronchus intermedius. The biopsy specimen showed an infiltration composed predominantly of small atypical lymphocytes. Immunohistochemical analyses demonstrated that the proliferating cells were positive for CD3, CD4, and CD5 and negative for CD8 and CD20. Pathological tests confirmed that the case was PTCL-NOS. PTCL-NOS should be considered in the differential diagnosis of endobronchial tumors.


Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states.
We demonstrate that single interneurons can toggle the output neurons of the cerebellar cortex (the Purkinje cells) between their two states. The firing of Purkinje cells has previously been shown to alternate between an "up" state in which the cell fires spontaneous action potentials and a silent "down" state. We show here that small hyperpolarizing currents in Purkinje cells can bidirectionally toggle Purkinje cells between down and up states and that blockade of the hyperpolarization-activated cation channels (H channels) with the specific antagonist ZD7288 (10 microM) blocks the transitions from down to up states. Likewise, hyperpolarizing inhibitory postsnyaptic potentials (IPSPs) produced by small bursts of action potentials (10 action potentials at 50 Hz) in molecular-layer interneurons induce these bidirectional transitions in Purkinje cells. Furthermore, single interneurons in paired interneuron --> Purkinje cell recordings, produce bidirectional switches between the two states of Purkinje cells. The ability of molecular-layer interneurons to toggle Purkinje cells occurs when Purkinje cells are recorded under whole-cell patch-clamp conditions as well as when action potentials are recorded in an extracellular loose cell-attached configuration. The mode switch demonstrated here indicates that a single presynaptic interneuron can have opposite effects on the output of a given Purkinje cell, which introduces a unique type of synaptic interaction that may play an important role in cerebellar signaling.


Panic attack semiology in right temporal lobe epilepsy.
Panic attack semiology as a manifestation of epileptic seizures may lead to difficulties and delay in diagnosis. We present a case series to demonstrate the association of ictal panic and anxiety symptoms with partial seizures lateralized to the right temporal lobe. From 112 consecutive patients with intractable temporal lobe epilepsy (59 right, 53 left) referred for video-EEG monitoring, five patients were identified whose seizures had been diagnosed as panic attacks in the past. Their ictal symptomatology included feelings of panic and impending doom, hyper-ventilation, palpitation, diaphoresis, shortness of breath and generalized paresthesiae. Ictal panic was not identified in 72 patients with extra temporal epilepsy investigated during the same period. EEG documented a right anterior to mid-temporal focus in all five patients. Brain MRI or pathology showed right mesial temporal sclerosis in four and a right temporal ganglioglioma in one. Ictal tachycardia was documented with EEG-EKG recording in the latter patient, prior to right anterior temporal lobectomy and amygdalohippocampectomy. Reinvestigation of this patient five years later for recurrent seizures, no longer associated with panic symptomatology, showed right temporal ictal onsets with seizure spread to the left temporal lobe, now associated with ictal bradycardia. Our case series provides further evidence to support a relationship between panic attack symptomatology and ictal involvement of the right mesial temporal region [Published with video sequences].


Role of Australian primary healthcare organisations (PHCOs) in primary healthcare (PHC) workforce planning: lessons from abroad.
To review international experience in order to inform Australian PHC workforce policy on the role of primary healthcare organisations (PHCOs/Medicare Locals) in PHC workforce planning. A NZ and UK study tour was conducted by the lead author, involving 29 key informant interviews with regard to PHCOs roles and the effect on PHC workforce planning. Interviews were audio-taped with consent, transcribed and analysed thematically. Emerging themes included: workforce planning is a complex, dynamic, iterative process and key criteria exist for doing workforce planning well; PHCOs lacked a PHC workforce policy framework to do workforce planning; PHCOs lacked authority, power and appropriate funding to do workforce planning; there is a need to align workforce planning with service planning; and a PHC Workforce Planning and Development Benchmarking Database is essential for local planning and evaluating workforce reforms. With the Australian government promoting the role of PHCOs in health system reform, reflections from abroad highlight the key action within PHC and PHCOs required to optimise PHC workforce planning.


Analyzing false memories in children with associative lists specific for their age.
Two experiments attempted to resolve previous contradictory findings concerning developmental trends in false memories within the Deese-Roediger-McDermott (DRM) paradigm by using an improved methodology--constructing age-appropriate associative lists. The research also extended the DRM paradigm to preschoolers. Experiment 1 (N=320) included children in three age groups (preschoolers of 3-4 years, second-graders of 7-8 years, and preadolescents of 11-12 years) and adults, and Experiment 2 (N=64) examined preschoolers and preadolescents. Age-appropriate lists increased false recall. Although preschoolers had fewer false memories than the other age groups, they showed considerable levels of false recall when tested with age-appropriate materials. Results were discussed in terms of fuzzy-trace, source-monitoring, and activation frameworks.


[Development, science, and politics: the debate surrounding creation of the Instituto Internacional da Hiléia Amazônica].
The article uses the debate surrounding creation of the Instituto Internacional da Hiléia Amazônica (International Institute of the Hylean Amazon--IIHA) as a point of departure for analyzing the topic of development. We first address post-World War II relations between science and development. Next, we examine the Brazilian government's initiatives in the Amazon during the 1940s and how the IIHA project was received. Lastly, we analyze the controversies ignited in Brazil by Unesco's plan. The IIHA project was a catalyst of the development debate in post-World War II Brazil. The discussions then sparked in Brazil and the project's denouement solidified a development model for the Amazon that even today underpins initiatives taken in the region.


Data on oxidants and antioxidants.
The monovalent reduction of O2 gives rise to highly reactive O2 intermediates, such as superoxide radical (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (OH.), as well as to singlet O2 (1O2). These O2 metabolites are capable of acting on several groups of substances: enzymes to inactivate them, polyunsaturated fatty acids to form lipid peroxides and DNA to cause single strand breaks and mutations. There are, however, several lines of antioxidant defences, which can be enzymatic (superoxide dismutase, catalase, glutathione peroxidase) or non-enzymatic (glutathione, vitamins C and E, beta-carotene, etc.). These defences are necessary to protect the cell against the intracellular or extracellular generation of O2 metabolites. Since O2 intermediates can affect the general cellular metabolism and inhibit cell replication or reduce protein synthesis, all the biological effects of O2 and its metabolites should therefore be considered in the pathogenesis of emphysematous lesions in the lung.


[Three-dimensional analysis of human chorioamniotic membranes structure in term pregnancy].
Physical and structural chorioamniotic membranes integrity is due to a precise process of synthesis and degradation of collagen; surrounding collagenolitic activity raises during labor, what leads to a structural loss and mechanical resistance weakening, the main cause of its rupture under physiological and pathological conditions. Understanding of its three-dimensional structure is essential to characterize normal and pathological labor. To analyze three-dimensional structure of human chorioamniotic membranes at gestational term. Descriptive study to analyze the distribution of collagens type I, II and IV in human chorioamniotic membranes at term (37 to 40 gestational weeks) without labor by means of confocal and electronic scan microscopy. Cells' amnios shapes a homogeneous epithelium without a close intercellular contact (classic epithelium) what may contribute to transmembranal diffusion molecules' transport. Amnios connective tissue is too a complex fibrilar net of type I collagen, structurally supported by type IV collagen. On the contrary, corion has a great amount of cells in close contact, with a few fibers of type I and II collagen, and almost none of type IV collagen cells. Three-dimensional analysis of chorioamniotic membranes connective tissue, particularly amnios, allows to understand the main role of type IV collagen on supporting its structure, as well as collagenolitic enzymes in its degradation and rupture under normal and pathological conditions.


Sleep driving: sleepwalking variant or misuse of z-drugs?
Sleep driving is most often classified as a variant of sleepwalking, but should be distinguished from impaired driving due to misuse or abuse of sedative/hypnotic drugs. Z-drugs; zolpidem and zopiclone in particular, have been associated with the majority of reported cases of impaired driving. Numerous studies have found z-drugs in driving under influence (DUI) related police stops, arrests and accidents. Impaired drivers are reported to have 1) blood levels of z-drugs that exceed therapeutic ranges 2) failed to take the medication at the correct time or remain in bed for sufficient time and/or 3) combined z-drugs with other central nervous system (CNS) depressants and/or alcohol. Consistent with CNS depression, z-drug-impaired drivers may demonstrate cognitive function at low levels with drivers still able to understand and respond to questions while sleepwalkers are completely unable to understand or interact with police. Z-drug-impaired drivers are often severely physically impaired, unable to stand up or maintain balance while sleepwalkers are able to stand and walk unaided. Sleep driving and impaired driving due to z-drugs may overlap. Sleep driving and drug-impaired driving are statistically rare events, but due to the billions of doses prescribed each year may still result in numerous DUI related arrests and accidents.


Phosphoinositide 3-kinase-mediated activation of cofilin phosphatase Slingshot and its role for insulin-induced membrane protrusion.
Cofilin plays an essential role in actin filament dynamics and membrane protrusion in motile cells. Cofilin is inactivated by phosphorylation at Ser-3 by LIM kinase and reactivated by dephosphorylation by cofilin-phosphatase Slingshot (SSH). Although cofilin is dephosphorylated in response to various extracellular stimuli, signaling pathways regulating SSH activation and cofilin dephosphorylation have remained to be elucidated. Here we show that insulin stimulates the phosphatase activity of Slingshot-1L (SSH1L) and cofilin dephosphorylation in cultured cells, in a manner dependent on phosphoinositide 3-kinase (PI3K) activity. Consistent with this, the level of Ser-3-phosphorylated cofilin is increased in PTEN (phosphatase and tensin homolog deleted in chromosome 10)-overexpressing cells and decreased in PTEN-deficient cells. Insulin induced the accumulation of SSH1L and active Akt (a downstream effector of PI3K), together with a PI3K product phosphatidylinositol 3,4,5-trisphosphate, onto membrane protrusions. Cofilin, but not Ser-3-phosphorylated cofilin, accumulated in membrane protrusions in insulin-stimulated cells, indicating that cofilin is dephosphorylated in these areas. Finally, suppression of SSH1L expression by RNA interference abolished insulin-induced cofilin dephosphorylation and the membrane protrusion. These findings suggest that SSH1L is activated downstream of PI3K and plays a critical role in insulin-induced membrane protrusion by dephosphorylating and activating cofilin.


How older men live with stress urinary incontinence: Patient experience and navigation to treatment.
To explore the context in which older men navigate treatment for stress urinary incontinence (SUI) following prostate surgery by characterizing lived experience of men with symptomatic SUI. Mixed method study using surveys and semistructured interviews to examine a cohort of men who underwent evaluation for treatment of postprostatectomy SUI. Thirty-six men were interviewed after consultation for SUI and 31 had complete quantitative clinical data. Twenty-six underwent surgery and 10 chose no surgical intervention. In qualitative interviews, respondents experienced substantial decline in quality of life due to incontinence citing concerns associated with use of pads and worrying about incontinence. Most patients reported "workarounds"-efforts to mitigate or manage incontinence including Kegels, physical therapy, and garments. Participants also reported lifestyle changes including less strenuous physical activity, less sexual activity, and/or fewer social gatherings. Patients then described a "breaking point" where incontinence workarounds were no longer sufficient. After seeking evaluation, men described challenges in exploring treatment for SUI, including access to care and provider knowledge of treatment options. In a novel study of patients living with SUI a predictable lived experience was observed that culminated in a desire for change or "breaking point." In all men, this led to treatment-seeking behaviors and for many it led to SUI intervention. Despite effective treatments, patients continue to meet barriers gaining access to SUI evaluation and treatment.


Functional genetic screen of human diversity reveals that a methionine salvage enzyme regulates inflammatory cell death.
Genome-wide association studies can identify common differences that contribute to human phenotypic diversity and disease. When genome-wide association studies are combined with approaches that test how variants alter physiology, biological insights can emerge. Here, we used such an approach to reveal regulation of cell death by the methionine salvage pathway. A common SNP associated with reduced expression of a putative methionine salvage pathway dehydratase, apoptotic protease activating factor 1 (APAF1)-interacting protein (APIP), was associated with increased caspase-1-mediated cell death in response to Salmonella. The role of APIP in methionine salvage was confirmed by growth assays with methionine-deficient media and quantitation of the methionine salvage substrate, 5'-methylthioadenosine. Reducing expression of APIP or exogenous addition of 5'-methylthioadenosine increased Salmonellae-induced cell death. Consistent with APIP originally being identified as an inhibitor of caspase-9-dependent apoptosis, the same allele was also associated with increased sensitivity to the chemotherapeutic agent carboplatin. Our results show that common human variation affecting expression of a single gene can alter susceptibility to two distinct cell death programs. Furthermore, the same allele that promotes cell death is associated with improved survival of individuals with systemic inflammatory response syndrome, suggesting a possible evolutionary pressure that may explain the geographic pattern observed for the frequency of this SNP. Our study shows that in vitro association screens of disease-related traits can not only reveal human genetic differences that contribute to disease but also provide unexpected insights into cell biology.


[The influence of the combined treatment on the energy metabolism in patients with the uterine cancer].
The experience of management of the patients with cancer of the uterus body was summarized to improve the results of combined (surgical and radiation) treatment. The essential initial disorders of the power supply metabolism, keeping worsening after the operation, were revealed. The conduction of the immune correction therapy in complex of preoperative preparation with individual selection of the immune preparations using the tests in vitro had promoted the postoperative period course improvement, the frequency of complications reduction, the stabilization and tendency for the power supply metabolism restoration after the operation and further during the radiation therapy conduction.


Mechanically activated catalyst mixing for high-yield boron nitride nanotube growth.
Boron nitride nanotubes (BNNTs) have many fascinating properties and a wide range of applications. An improved ball milling method has been developed for high-yield BNNT synthesis, in which metal nitrate, such as Fe(NO3)3, and amorphous boron powder are milled together to prepare a more effective precursor. The heating of the precursor in nitrogen-containing gas produces a high density of BNNTs with controlled structures. The chemical bonding and structure of the synthesized BNNTs are precisely probed by near-edge X-ray absorption fine structure spectroscopy. The higher efficiency of the precursor containing milling-activated catalyst is revealed by thermogravimetric analyses. Detailed X-ray diffraction and X-ray photoelectron spectroscopy investigations disclose that during ball milling the Fe(NO3)3 decomposes to Fe which greatly accelerates the nitriding reaction and therefore increases the yield of BNNTs. This improved synthesis method brings the large-scale production and application of BNNTs one step closer.


An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities.
Phenolics are widespread dietary antioxidants. Among these, chlorogenic acids (CGAs) received considerable attention for their wide distribution and part of human diet with potential biological effects. CGAs (71 compounds), being esters of derivatives of cinnamic acids with quinic acid are widely distributed in plant materials. Coffee is among the highest found in plants, ranging from 4 to 14%. Besides, these are reported in plant foods such as apples, pears, carrot, tomato, sweet potato, Phyllostachys edulis, oilseeds, Prunus domestica L, cherries, and eggplant. The traditional Chinese medicinal plants such as flowers and buds of Lonicera japonica Thunb and the leaves of Eucommia ulmodies contained CGAs as bioactive compound. These play an important role in the formation of roasted coffee flavor and have a marked influence on coffee cup quality. CGAs are considered as main precursors of coffee flavor and pigments. Recent technological advancements in the separation and purification of CGAs such as molecular-imprinted polymer technique; microwave-assisted extraction; pH gradient counter current chromatography has also been described. The consumption of coffee correlated to several health benefits such as reducing the risk of human chronic diseases such as inflammation, diabetes, and cardiovascular disease owing to its antioxidant potential.


Agreement of invasive and non-invasive blood pressure measurements in anaesthetised pigs using the Surgivet V9203.
The automated oscillometric method is a common method for measuring blood pressure non-invasively and is broadly and confidently used in the veterinary setting. Twenty-one pigs undergoing anesthesia for exploratory laparotomy were enrolled in a study to evaluate the performance of the Surgivet V9203 non-invasive blood pressure (NIBP) monitor. The aim was to compare measurements of arterial blood pressure obtained simultaneously using the Surgivet V9203 oscillometric system and an intra-arterial catheter-transducer system, both at the level of the metatarsus. Invasive blood pressure (IBP) was consistently underestimated by the non-invasive method. Bland-Altman analysis showed poor agreement between the two modalities based on evaluation of mean bias and 95% limits of agreement. The Surgivet V9203 cannot therefore be recommended as a reliable alternative to invasive blood pressure monitoring in anaesthetised pigs. As pulse detection is one of the most important factors affecting NIBP accuracy it is likely that our findings may reflect an anatomical or physiological difference in the species that alters the detection of wall movement by the oscillometric technique and additionally, makes the algorithm used by the Surgivet to determine blood pressure parameters unsuitable for use in pigs.


Polo-like kinases and the microtubule organization center: targets for cancer therapies.
Studies from eukaryotic model systems, ranging from yeast to human, indicate that Polo and Polo-like kinases (Plks) are essential for the activity of the microtubule organization center. Polo/Plks localize to centrosomes or spindle pole bodies and undergo dramatic subcellular relocation during the cell cycle. Deregulated activities of Plks often result in abnormalities in centrosome duplication, maturation, and/or microtubule dynamics. Genetic and biochemical approaches have identified several candidate genes that either lie in the same pathway as POLO/PLKs or whose products are direct targets of Polo/Plks during the centrosome cycle. Recent studies have demonstrated that mammalian Plks also regulate the function of the Golgi complex, a cellular organelle closely associated with the centrosome and also having microtubule organization activity. Furthermore, deregulated expression of human PLK1 and PLK3 is strongly correlated with the development of many types of malignancies, and ectopic expression of kinase-active Plk3 or Plk1 dominant negative protein leads to rapid cell death. Given that several effective anti-tumor drugs directly interfere with microtubule dynamics, mammalian Plks are excellent targets for the development of anticancer drugs.