Effect of staurosporine on fMet-Leu-Phe-stimulated human neutrophils: dissociated release of inositol 1,4,5-trisphosphate, diacylglycerol and intracellular calcium.
Staurosporine, a microbial alkaloid, enhances inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) production rapidly and dose-dependently in fMet-Leu-Phe (FMLP)-stimulated human neutrophils showing maximal effects at 1 microM concentration. The IP3 increase was specific for staurosporine as three other putative protein kinase C (PKC) inhibitors, H7, sphingosine and palmitoylcarnitine were unable to enhance the IP3 generation in FMLP-stimulated human neutrophils. Staurosporine, at concentrations 0.3-1.0 microM, did not affect the initial mobilization of FMLP-induced intracellular Ca2+ (Ca2+i), although a sustained elevation of cytosolic Ca2+ level was observed within 5 min. This effect could not be suppressed, even by 1 microM phorbol-myristate 12,13-acetate (PMA). Whereas lower concentrations of staurosporine (less than or equal to 100 nM) were unable to affect FMLP-induced IP3 production, DG accumulation and Ca2+i, the PMA-inhibited initial Ca2+i signal and IP3 formation triggered by FMLP were almost completely restored. At higher concentrations (greater than or equal to 300 nM) staurosporine reversed the inhibitory effect of other protein kinases, distinct from the PMA-inducible one, which may be responsible for the phosphatidyl inositol 4,5-bisphosphate (PIP2) breakdown, thus causing accumulation of IP3 and DG and an elevation of C2+i level. Whereas IP3 declined to basal level within 5 min, the DG level remained elevated during the same period. This phenomenon is attributed to phospholipase D (PLD) stimulation by staurosporine, which augments the DG synthesis, in part through PA degradation via phosphatidic acid (PA) phosphohydrolase.


Severe Delayed Drug Reactions: Role of Genetics and Viral Infections.
Adverse drug reactions (ADRs) are a significant source of patient morbidity and mortality and represent a major burden to health care systems and drug development. Up to 50% of such reactions are preventable. Although many ADRs can be predicted based on the on-target pharmacologic activity, ADRs arising from drug interactions with off-target receptors are recognized. Off-target ADRs include the immune-mediated ADRs (IM-ADRs) and pharmacologic drug effects. In this review, we discuss what is known about the immunogenetics and pathogenesis of IM-ADRs and the hypothesized role of heterologous immunity in the development of IM-ADRs.


Reactive nitrogen species as therapeutic targets for autophagy/mitophagy modulation to relieve neurodegeneration in multiple sclerosis: Potential application for drug discovery.
Multiple sclerosis (MS) is a neuroinflammatory disease with limited therapeutic effects, eventually developing into handicap. Seeking novel therapeutic strategies for MS is timely important. Active autophagy/mitophagy could mediate neurodegeneration, while its roles in MS remain controversial. To elucidate the exact roles of autophagy/mitophagy and reveal its in-depth regulatory mechanisms, we conduct a systematic literature study and analyze the factors that might be responsible for divergent results obtained. The dynamic change levels of autophagy/mitophagy appear to be a determining factor for final neuron fate during MS pathology. Excessive neuronal autophagy/mitophagy contributes to neurodegeneration after disease onset at the active MS phase. Reactive nitrogen species (RNS) serve as key regulators for redox-related modifications and participate in autophagy/mitophagy modulation in MS. Nitric oxide (•NO) and peroxynitrite (ONOO-), two representative RNS, could nitrate or nitrosate Drp1/parkin/PINK1 pathway, activating excessive mitophagy and aggravating neuronal injury. Targeting RNS-mediated excessive autophagy/mitophagy could be a promising strategy for developing novel anti-MS drugs. In this review, we highlight the important roles of RNS-mediated autophagy/mitophagy in neuronal injury and review the potential therapeutic compounds with the bioactivities of inhibiting RNS-mediated autophagy/mitophagy activation and attenuating MS progression. Overall, we conclude that reactive nitrogen species could be promising therapeutic targets to regulate autophagy/mitophagy for multiple sclerosis treatment.


The Self Care Assessment Schedule (SCAS)--I. The purpose and construction of a new assessment of self care behaviours.
The Self Care Assessment Schedule (SCAS) is a new questionnaire which measures the frequency of ten behaviours during a period of fourteen days. Data are presented for five patient samples and a group of non consulting controls and the distributions of scores between groups show expected differences. In some groups scores are significantly greater for male subjects and those with the most chronic disorders but scores are not related to age. It is tentatively suggested that the SCAS may be used to determine the severity of aspects of disability based on percentile scores.


Future expectations in the prophylaxis of intestinal bleeding.
Prophylaxis of gastrointestinal bleeding is attempted in widely varying situations. In NSAID-induced peptic ulcer, the advantage of selective cyclooxygenase 2 inhibitors with regard to gastrointestinal damage has yet to be translated into an advantage in overall morbidity. Strategies for primary and secondary prevention of variceal bleeding have been established. Therapy tailored to hepatic venous pressure gradient has the potential to achieve clinical relevance. Several methods have been developed to prevent postpolypectomy bleeding, but their optimal risk-tailored application has yet to be demonstrated. Although octreotide treatment seems to be beneficial in reducing the blood loss from angiodysplasias, controlled studies to determine its optimal use are awaited. Stress-ulcer prophylaxis is commonly applied in critically ill patients. Although data indicate that H2-receptor antagonists and omeprazole are effective in preventing clinically significant bleeding, evidence for an advantage with respect to length of hospital or intensive-care-unit stay, as well as mortality, is still lacking. Since there is misuse of acid-suppressing drugs on regular wards, in-house guidelines may offer the potential for saving costs and reducing inappropriate prescription.


Empathy, Einfühlung, and aesthetic experience: the effect of emotion contagion on appreciation of representational and abstract art using fEMG and SCR.
Since the advent of the concept of empathy in the scientific literature, it has been hypothesized, although not necessarily empirically verified, that empathic processes are essential to aesthetic experiences of visual art. We tested how the ability to "feel into" ("Einfühlung") emotional content-a central aspect of art empathy theories-affects the bodily responses to and the subjective judgments of representational and abstract paintings. The ability to feel into was measured by a standardized pre-survey on "emotional contagion"-the ability to pick up and mirror, or in short to "feel into", emotions, which often overlaps with higher general or interpersonal empathetic abilities. Participants evaluated the artworks on several aesthetic dimensions (liking, valence, moving, and interest), while their bodily reactions indicative of empathetic engagement (facial electromyography-EMG, and skin conductance responses-SCR) were recorded. High compared to low emotion contagion participants showed both more congruent and more intense bodily reactions (EMG and SCR) and aesthetic evaluations (higher being moved, valence, and interest) and also liked the art more. This was largely the case for both representational and abstract art, although stronger with the representational category. Our findings provide tentative evidence for recent arguments by art theorists for a close "empathic" mirroring of emotional content. We discuss this interpretation, as well as a potential tie between emotion contagion and a general increase in emotion intensity, both of which may impact, in tandem, the experience and evaluation of art.


The conception of community children's nursing services in Northern Ireland.
This report is an exploration of the implications of establishing a community children's nursing service in Northern Ireland. It provides a description of the backdrop to the development of the service in the United Kingdom, and the experiences of children's nurses in attempting to upgrade the quality of care offered to sick children in this province. The frustrations that have characterized this development are explored in detail within the context of broader changes in health care on the national scene. The article ends with recommendations for implementing an effective service, following our experiences in Northern Ireland.


Expermental hybridization within the genus Triturus (Urodela: Salamandridae). III. Evidence for crossing-over, true chiasmata and chomosomal homologies in the spermatogenesis of F1 species hybrids, T. cristatus carnifex female X T. marmoratus male.
Spermatogenesis in the F1 hybrid (2n=24=12 female + 12 male) between the closely related newt species T. cristatus carnifex and T. marmoratus was apparently normal up to pachytene. Many unpaired chromosomes were present at diplotene and a typical diakinesis was lacking. Primary spermatocytes at meta- and meta-anaphase contained up to 12 regular intergenomal bivalents and a corresponding number of univalents when less then 12 II. Most chiasmata were terminal or subterminal, some intercalary. Chiasmata between corresponding heterospecific chromosomes can be reported as true: real crossing over has taken place, proving the presence of primary chromosomal homologies between the 2 sets of the parental species. Evidence for recombination is based on the segregation of particular markers (i.e., subterminal C-bands and NORs) observed in certain chromosomes at metaphase II. One chromatid of single chromosomes can show the T. cristatus "pheno-type" and the other the T. marmoratus phenotype". A few primary spermatocytes contain a certain number of irregular associations (intragenomal or intrahaploid bivalents, irregular intergenomal bivalents, chromosome multivalents) joined by chiasmata which can be defined as anomalous. Other abnormalities concern the occurrence of interlocked bivalents which occasionally show an anomalous exchange between heterologous chromatids. Cytogenetic criteria useful to evaluate the taxonomic relationships between different species have been discussed as well as some possible trends in chromosome evolution and speciation within the genus Triturus.


Using text message reminders in health care services: A narrative literature review.
Despite the extensive use of mHealth behavior change interventions, questions remain about the use of technology-based reminders in delivering health care services. Text messaging, or short message service (SMS), is one reminder method that has been extensively researched. Most SMS-reminder research is distributed across a range of health care outcomes. The aim of this article is to systematically review the aggregate impact of these reminders on overall health care outcomes. A systematic literature review was conducted and yielded 2316 articles. Studies were included if they used SMS reminders to support patient health care outcomes. Study methodology was aligned with the PRISMA guidelines for systematic reviews. Following screening, 162 articles met inclusion criteria. Of these studies, 93 investigated medical compliance reminders and 56 investigated appointment reminders. The review found that nearly all the SMS-reminder studies helped improve patient medical compliance and appointment reminders. Additionally, researchers reported numerous benefits from using SMS reminders, including ease of use, relative inexpensiveness, and rapid and automated message delivery. Minimal risks were reported and most participants found the reminders to be acceptable. Text messages appear to be an effective reminder mechanism to promote improved patient appointment and medical compliance. Reminders should continue to be evaluated and improved to determine the most effective timing and frequency of messages for improving outcomes.


Breastfeeding restored the gut microbiota in caesarean section infants and lowered the infection risk in early life.
The initialization of the neonatal gut microbiota (GM) is affected by diverse factors and is associated with infant development and health outcomes. In this study, we collected 207 faecal samples from 41 infants at 6 time points (1, 3, and 7 days and 1, 3, and 6 months after birth). The infants were assigned to four groups according to delivery mode (caesarean section (CS) or vaginal delivery (VD)) and feeding pattern (breastfeeding or formula milk). The meconium bacterial diversity was slightly higher in CS than in VD. Three GM patterns were identified, including Escherichia/Shigella-Streptococcus-dominated, Bifidobacterium-Escherichia/Shigella-dominated and Bifidobacterium-dominated patterns, and they gradually changed over time. In CS infants, Bifidobacterium was less abundant, and the delay in GM establishment could be partially restored by breastfeeding. The frequency of respiratory tract infection and diarrhoea consequently decreased. This study fills some gaps in the understanding of the restoration of the GM in CS towards that in VD.


Monitoring leaching of Cd2+ from cadmium-based quantum dots by an Cd aptamer fluorescence sensor.
Quantum Dots (QDs) have been demonstrated with outstanding optical properties and thus been widely used in many biological and biomedical studies. However, previous studies have shown that QDs can cause cell toxicity, mainly attributable to the leached Cd2+. Therefore, identifying the leaching kinetics is very important to understand QD biosafety and cytotoxicity. Toward this goal, instrumental analyses such as inductively coupled plasma mass spectrometry (ICP-MS) have been used, which are time-consuming, costly and do not provide real-time or spatial information. To overcome these limitations, we report herein a fast and cost-effective fluorescence sensor based a Cd2+-specific aptamer for real-time monitoring the rapid leaching kinetics of QDs in vitro and in living cells. The sensor shows high specificity towards Cd2+ and is able to measure the Cd2+ leached either from water-dispersed CdTe QDs or two-layered CdSe/CdS QDs. The sensor is then used to study the stability of these two types of QDs under conditions to mimic cellular pH and temperature and the results from the sensor are similar to those obtained from ICP-MS. Finally, the sensor is able to monitor the leaching of Cd2+ from QDs in HeLa cells. The fluorescence aptamer sensor described in this study may find many applications as a tool for understanding biosafety of numerous other Cd-based QDs, including leaching kinetics and toxicity mechanisms in living systems.


Comparison of chloride concentration and osmolality in proximal tubular fluid, peritubular capillary plasma and systemic plasma in the rat.
1. Chloride concentration and osmolalities were compared in consecutively collected samples of proximal tubular fluid, peritubular capillary plasma and systemic plasma. 2. Mean chloride concentrations (m-mole/l) were 141.3+/-2.6 in tubular fluid, 114.8+/-1.7 in peritubular capillary plasma and 119.4+/-1.8 in systemic plasma. 3. Mean osmolalities (m-osmole/kg H2O) were 297+/-2.2 in tubular fluid, 293+/-2.4 in peritubular capillary plasma and 299+/-1.8 in systemic plasma. 4. These differences are discussed in relation to the anatomical and functional organization of the peritubular capillaries and renal tubules.


Use of nonsteroidal anti-inflammatory drugs after radical retropubic prostatectomy: a prospective, randomized trial.
To assess the efficacy and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) administered after radical retropubic prostatectomy (RRP). One hundred patients undergoing open RRP by one surgeon were divided randomly and prospectively into two groups of 50 patients, each receiving systematically either an NSAID (lornoxicam) or paracetamol for postoperative analgesia. Opiates were administered if needed for breakthrough pain. Parameters potentially correlated with postoperative bleeding, such as preoperative and postoperative hemoglobin (Hb) differences, estimated blood loss, number of transfusions, and drain output were recorded. Furthermore, the degree of pain was assessed daily with a visual analogue scale score until discharge from hospital. After procedures with similar estimated blood loss, postoperative bleeding was not more in the NSAIDs group, as evidenced by similar transfusion rates (P <or=1), similar postoperative Hb values (P >0.05), and Hb drop after the procedure. No patient required re-exploration for bleeding; drain output when elevated was never attributed to postoperative bleeding. Pain control as evaluated by the visual analogue scale pain score was adequate with the use of NSAIDs and not statistically different from the non-NSAIDs group during postoperative days 1 and 4 and onward. Pain control with lornoxicam was even better on postoperative days 2 and 3 (P <or=0.05). Nonsteroidal anti-inflammatory drugs administered after open RRP are safe and effective. They do not increase the risk of bleeding and offer improved analgesia.


Intervention and management of congenital left heart obstructive lesions.
While congenital heart defects are typically diagnosed in early childhood, depending on the severity of the lesion, they may not be recognized until later childhood or in adulthood. Left heart pressure loading lesions, including mitral valve stenosis, subaortic stenosis, valvular aortic stenosis, supravalvular aortic stenosis, and coarctation of the aorta, may be found as an isolated lesion or as a constellation together known as Shone syndrome. This review will highlight the literature published regarding the diagnosis, intervention, and long-term management of left heart pressure loading lesions.


Tangent screen perimetry using twin test objects.
A T-shaped carrier with twin test objects is an inexpensive efficient visual field screening device which facilitated identification of a nasal steppe, a paracentral scotoma, an enlarged blind spot, an arcuate scotoma, macular sparing, or hemianopic defects.


The use of labetalol in the management of cocaine crisis.
We report a case of successful resuscitation and clinical management in a 31-year-old man who allegedly ingested 20 g of cocaine hydrochloride. The physiologic and pharmacologic mechanisms of cocaine toxicity are reviewed. The use of labetalol in resolving the cardiovascular crisis is specifically detailed.


Diagnostic yield of next generation sequencing gene panel assays for early-onset glaucoma in an ethnically diverse population.
Early-onset glaucoma is a potentially sight-threatening condition with high heritability. Next generation sequencing is a cost-effective alternative to individual gene screening that could expedite its diagnosis. However, the diagnostic yield of multigene panel assays for early-onset glaucoma varies according to the tested population. The purpose of this study was to ascertain the diagnostic yield of next generation sequencing panels in our cohort and to identify population characteristics that increase such yield. We conducted a retrospective review of the medical records of consecutive patients from November 2016 to August 2021 who were evaluated at our clinics for early-onset glaucoma and had undergone next generation sequencing panels for molecular diagnosis. A total of 118 patients were included, in 22 of whom (19%) a causative variant was identified. Diagnostic yield varied by age of onset: of 60 patients with onset at <3 years of age, 19 (32%) had such variants identified. In contrast, of 58 patients with later-onset glaucoma, 3 (5%) had said variants identified (P = 0.0003). Other metrics that increased diagnostic yield were presence of additional ocular anomalies (P = 0.0092) and identifying ethnicity as White (compared with non-White, P = 0.0001). In childhood glaucoma, earlier age of onset is correlated with higher likelihood of pathogenic variant identification. The large proportion of unsolved cases indicates a robust opportunity for gene discovery and genetic therapy targets in early-onset glaucoma patients.


Conformation of poly-L-glutamate is independent of ionic strength.
CD and UV resonance Raman measurements surprisingly find that the charge screening of even 2 M concentrations of NaCl and KCl does not alter the unfolded PPII and 2.5(1)-helix conformations of poly-L-glutamate. These salts appear to be excluded from the region between the side chain charges and the peptide backbone. Furthermore, no direct ion pairing occurs between these salts and the side chain carboxylates.


African American Women's Experiences with Birth After a Prior Cesarean Section.
Women who have had a cesarean section (C-section) and become pregnant again may choose to have a planned repeat cesarean delivery (RCD) or vaginal birth after a cesarean (VBAC). This study aimed to characterize the pregnancy and birth experiences of African American (AA) women who had a successful VBAC, failed VBAC, or RCD. Eligible participants (N = 25) self-identified as AA, had a C-section and a subsequent birth(s) in the past 12 years, and were educated past high school. Each participant was individually interviewed via phone call. The Sort and Sift, Think and Shift method was used to evaluate interview transcripts to minimize researcher bias and emphasize the voices of the participants. The resulting themes included the impact of providers on pregnancy and childbirth satisfaction, the value of autonomy in maternal health decision-making, and the role that racism plays in AA women's birth experiences. Although some participants recalled a positive experience, the presence of limited autonomy, lack of support, and negative experiences with providers indicate that birth after a prior C-section for AA women can be improved. Providers should address their own racial biases and utilize the shared decision-making approach when their patients decide between a VBAC and RCD to improve patient satisfaction.


Validation of global and segmental left ventricular contractile function using gated planar technetium-99m sestamibi myocardial perfusion imaging.
The purpose of this study was to test the hypothesis that segmental wall motion analysis determined from gated planar technetium-99m sestamibi myocardial imaging is reproducible and agrees well with echocardiographic data. Technetium-99m sestamibi is a new radiopharmaceutical recently approved for myocardial perfusion imaging. Its advantages include a dosimetry that allows use of a dose 10 to 15 times higher than that of thallium-201. As a result, myocardial counts are markedly improved and images can be collected in a gated mode to potentially allow assessment of global and segmental ventricular function. However, the reproducibility and accuracy of technetium-99m sestamibi imaging for measurement of global and segmental left ventricular function have not been evaluated or compared with those of a standard ventricular function technique, such as echocardiography. We studied 136 patients referred for clinical technetium-99m sestamibi imaging. One-day rest-stress planar technetium-99m sestamibi protocols were used, gating the stress images. After technetium-99m sestamibi imaging, all patients had standard rest two-dimensional echocardiography. Global and segmental technetium-99m sestamibi and echocardiographic left ventricular contraction was graded qualitatively as normal or abnormal using a four-point grading system. Interobserver and intraobserver agreement was extremely high for global and segmental technetium-99m sestamibi wall motion analysis, with absolute agreements ranging from 0.92 to 1.00 and corresponding kappa values of 0.74 to 1.00 (p < 0.00001). Agreement with global and segmental echocardiographic wall motion was similarly very high, with absolute agreements ranging from 0.93 to 1.00 and corresponding kappa values of 0.75 to 1.00 (p < 0.00001). Gated technetium-99m sestamibi cardiac imaging provides information with regard to rest global and segmental left ventricular systolic function that is highly reproducible and agrees very well with results of two-dimensional echocardiography.


The impact of gender on the long-term morbidity and mortality of patients with type 2 diabetes receiving structured personal care: a 13 year follow-up study.
The aim of this study was to assess gender differences in mortality and morbidity during 13 follow-up years after 6 years of structured personal care in patients with type 2 diabetes mellitus. In the Diabetes Care in General Practice (DCGP) multicentre, cluster-randomised, controlled trial (ClinicalTrials.gov registration no. NCT01074762), 1,381 patients newly diagnosed with type 2 diabetes were randomised to receive 6 years of either structured personal care or routine care. The intervention included regular follow-up, individualised goal setting and continuing medical education of general practitioners participating in the intervention. Patients were re-examined at the end of intervention. This observational analysis followed 970 patients for 13 years thereafter using national registries. Outcomes were all-cause mortality, incidence of diabetes-related death, any diabetes-related endpoint, myocardial infarction, stroke, peripheral vascular disease and microvascular disease. In women, but not men, a lower HR for structured personal care vs routine care emerged for any diabetes-related endpoint (0.65, p = 0.004, adjusted; 73.4 vs 107.7 events per 1,000 patient-years), diabetes-related death (0.70, p = 0.031; 34.6 vs 45.7), all-cause mortality (0.74, p = 0.028; 55.5 vs 68.5) and stroke (0.59, p = 0.038; 15.6 vs 28.9). This effect was different between men and women for diabetes-related death (interaction p = 0.015) and all-cause mortality (interaction p = 0.005). Compared with routine care, structured personal diabetes care reduced all-cause mortality and diabetes-related death in women but not in men. This gender difference was also observed for any diabetes-related outcome and stroke but was not statistically significant after extensive multivariate adjustment. These observational results from a post hoc analysis of a randomised controlled trial cannot be explained by intermediate outcomes like HbA1c alone, but involves complex social and cultural issues of gender. There is a need to rethink treatment schemes for both men and women to gain benefit from intensified treatment efforts.


Cytotoxicity reduction by O-nicotinoylation of antiviral 6-benzylaminopurine ribonucleosides.
One of the promising approaches in the development of nucleoside prodrugs is to use the nucleoside analogs containing lipophilic biodegradable residues, which are cleaved to biologically active forms after metabolic transformations in the cell. The introduction of such fragments makes it possible to reduce the general toxicity of the drug candidate and increase its stability in the cell. In order to study the influence of biodegradable lipophilic groups on antiviral activity and cytotoxicity, in this work we synthesized N6-benzyl-2',3',5'-tri-O-nicotinoyl adenosine and N6-(3-fluorobenzyl)-2',3',5'-tri-O-nicotinoyl adenosine, derivatives of N6-benzyladenosine (BAR) and N6-(3-fluorobenzyl)adenosine (FBAR), which had previously shown prominent antiviral activity against human enterovirus EV-A71 but appeared to be cytotoxic. The obtained fully-O-nicotinoylated BAR and FBAR inhibited reproduction of EV-A71 strains BrCr and 46973 and manifested significantly lower cytotoxicity compared to non-protected compounds. In addition, we performed enzymatic hydrolysis of the fully-O-nicotinoylated FBAR in the presence of esterases (CalB and PLE) to investigate metabolic degradation of O-nicotinoylated compounds in cells. Both enzymes hydrolyzed the tested substrate to form the corresponding O-deprotected nucleoside that may suggest the role of hydrolase-type enzymes as general participants of metabolic activation of O-nicotinoylated prodrugs in different cells.


Senescence and apoptosis in yeast mother cell-specific aging and in higher cells: a short review.
It is our intention to give the reader a short overview of the relationship between apoptosis and senescence in yeast mother cell-specific aging. We are studying yeast as an aging model because we want to learn something of the basic biology of senescence and apoptosis even from a unicellular eukaryotic model system, using its unrivalled ease of genetic analysis. Consequently, we will discuss also some aspects of apoptosis in metazoa and the relevance of yeast apoptosis and aging research for cellular (Hayflick type) and organismic aging of multicellular higher organisms. In particular, we will discuss the occurrence and relevance of apoptotic phenotypes for the aging process. We want to ask the question whether apoptosis (or parts of the apoptotic process) are a possible cause of aging or vice versa and want to investigate the role of the cellular stress response system in both of these processes. Studying the current literature, it appears that little is known for sure in this field and our review will therefore be, for a large part, more like a memorandum or a program for future research.


Experiences of Canadian mental health providers in identifying and responding to online and in-person sexual abuse and exploitation of their child and adolescent clients.
Sex offenders often use the internet to communicate with children to facilitate in-person sexual abuse or to create and distribute sexual images of children. Mental healthcare providers are a major source of referrals to child welfare authorities and are well-positioned to identify sexual exploitation. This study investigated the perceived ability of mental healthcare workers to recognize and respond to concerns about online and in-person sexual exploitation of their pediatric clients. The authors administered a cross-sectional survey to 209 mental healthcare providers within the public health system of Alberta, Canada. The survey contained four sections related to sexual exploitation: two of which can take place online or in-person (grooming and sexual abuse) and two of which require the internet or a digital device (luring and sexual image distribution). Each section asked whether the mental healthcare provider had experience working with clients affected by these concerns, what barriers they encounter, how confident they are in their abilities and whether they have formal training in a topic. The vast majority of participants (83%) worked with a client impacted by grooming, luring, sexual abuse or sexual image distribution in the last year. Participants reported more training, more confidence and fewer barriers when identifying and responding to sexual abuse as compared to grooming, luring or sexual image distribution. There is a need to improve mental health providers understanding of how technology is being utilized to exploit children, so that they can respond effectively to protect their clients.


Extracorporeal shock wave therapy versus local corticosteroid injection for the treatment of carpal tunnel syndrome: a meta-analysis.
Many studies have demonstrated the effectiveness of extracorporeal shock wave therapy (ESWT) and local corticosteroid injection (LCI) for the treatment of carpal tunnel syndrome (CTS), and some studies showed that the effect of ESWT was superior to LCI. We performed this meta-analysis to compare the clinical effects across the two therapies. Relevant randomized controlled trials (RCTs) comparing ESWT and LCI for the treatment of CTS were searched in electronic database. The Cochrane risk bias tool was used for quality assessment. After data extraction and quality assessment of the included studies, a meta-analysis was performed using RevMan 5.3 software. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were analyzed. The protocol for this systematic review was registered on INPLASY (202080025) and is available in full on the inplasy.com ( https://doi.org/10.37766/inplasy2020.8.0025 ) RESULTS: A total of 5 RCT studies with 204 patients were included from the electronic database. The meta-analysis results showed that two therapies were not significantly different in terms of visual analog scale (VAS) score (P = 0.65), Boston Carpal Tunnel Questionnaire (BQ) score (P = 0.14), sensory distal latency (P = 0.66), and nerve conduction velocity (NCV) of the sensory nerve (P = 0.06). There were significant differences between the results of motor distal latency (P < 0.0001), compound muscle action potential (CMAP) amplitude (P < 0.00001), and sensory nerve action potential (SNAP) amplitude (P = 0.004). In terms of pain relief and function improvement, the effects of ESWT and LCI are not significantly different. In terms of electrophysiological parameters, LCI has a stronger effect on shortening motor distal latency; ESWT is superior to LCI in improving action potential amplitude. ESWT is a noninvasive treatment with fewer complications and greater patient safety. In light of the heterogeneity and limitations, these conclusions require further research for definitive conclusions to be drawn.


Treatment retention of infliximab and etanercept originators versus their corresponding biosimilars: Nordic collaborative observational study of 2334 biologics naïve patients with spondyloarthritis.
Although clinical trials support equivalence of originator products and biosimilars for etanercept and infliximab, real-world studies among biologics-naïve patients with spondyloarthritis (SpA) are lacking. The objectives were to compare treatment retention in biologics-naïve patients with SpA starting either the originator product or a biosimilar of infliximab and etanercept, and to explore the baseline characteristics of these patients. Patients with SpA (ankylosing spondylitis/non-radiographical axial SpA/undifferentiated SpA), starting infliximab or etanercept as their first-ever biological disease-modifying antirheumatic drug during January 2014-June 2017 were identified in five Nordic biologics-rheumatology registers. Baseline characteristics were retrieved from each registry; comorbidity data were identified through linkage to national health registers. Country-specific data were pooled, and data on infliximab and etanercept were analysed separately. Comparisons of treatment retention between originators and biosimilars were assessed through survival probability curves, retention rates (2 years for infliximab/1 year for etanercept) and Hazard Ratios (HR). We included 1319 patients starting infliximab (24% originator/76% biosimilar), and 1015 patients starting etanercept (49% originator/51% biosimilar). Baseline characteristics were largely similar for the patients treated with the originators compared with the corresponding biosimilars. Survival probability curves were highly similar for the originator and its biosimilar, as were retention rates: infliximab 2-year retention originator, 44% (95% CI 38% to 50%)/biosimilar, 46% (95% CI: 42% to 51%); and etanercept 1-year retention originator, 66% (95% CI 61% to 70%)/biosimilar, 73% (95% CI 68% to 78%). HRs were not statistically significant. This observational study of biologics-naïve patients with SpA from five Nordic countries showed similar baseline characteristics and very similar retention rates in patients treated with originators versus biosimilars, for both infliximab and etanercept, indicating comparable effectiveness in clinical practice.


Malignant Superior Vena Cava Syndrome: A Scoping Review.
Malignant superior vena cava syndrome (SVCS) is a clinical problem that results from the obstruction of blood flow in the superior vena cava by an underlying malignancy. This may occur due to external compression, neoplastic invasion of the vessel wall, or internal obstruction with bland or tumor thrombus. Although symptoms are typically mild, SVCS can cause neurologic, hemodynamic, and respiratory compromise. Classic management options include supportive measures, chemotherapy, radiation therapy, surgery, and endovascular stenting. New targeted therapeutics and techniques have also recently been developed, which may have a role in management. Nevertheless, few evidence-based guidelines exist to guide treatment of malignant SVCS, and these recommendations are typically restricted to individual disease sites. Furthermore, there are no recent systematic literature reviews that address this question. Here, we present a theoretical case to frame this clinical problem and synthesize updated evidence published in the past decade relating to the management of malignant SVCS through a comprehensive literature review.


Measurement of epidermal moisture content by magnetic resonance imaging: assessment of a hydration cream.
The moisture content of the epidermis was measured by magnetic resonance imaging (MRI), using transverse relaxation time. The spatial resolution was 86 microns, allowing a quantitative, accurate and localized determination of variations in epidermal hydration. The wrists of 15 volunteers were studied before and after application of a hydration cream. Results showed an increase of 15% of epidermal T2 after application of the cream. Moisture content curves varied according to different degrees of skin dryness. This study demonstrates that MRI is a useful tool in evaluation of epidermal hydration.


Cortical processing of distracting speech in noisy auditory scenes depends on perceptual demand.
Selective attention is essential for the processing of multi-speaker auditory scenes because they require the perceptual segregation of the relevant speech ("target") from irrelevant speech ("distractors"). For simple sounds, it has been suggested that the processing of multiple distractor sounds depends on bottom-up factors affecting task performance. However, it remains unclear whether such dependency applies to naturalistic multi-speaker auditory scenes. In this study, we tested the hypothesis that increased perceptual demand (the processing requirement posed by the scene to separate the target speech) reduces the cortical processing of distractor speech thus decreasing their perceptual segregation. Human participants were presented with auditory scenes including three speakers and asked to selectively attend to one speaker while their EEG was acquired. The perceptual demand of this selective listening task was varied by introducing an auditory cue (interaural time differences, ITDs) for segregating the target from the distractor speakers, while acoustic differences between the distractors were matched in ITD and loudness. We obtained a quantitative measure of the cortical segregation of distractor speakers by assessing the difference in how accurately speech-envelope following EEG responses could be predicted by models of averaged distractor speech versus models of individual distractor speech. In agreement with our hypothesis, results show that interaural segregation cues led to improved behavioral word-recognition performance and stronger cortical segregation of the distractor speakers. The neural effect was strongest in the δ-band and at early delays (0 - 200 ms). Our results indicate that during low perceptual demand, the human cortex represents individual distractor speech signals as more segregated. This suggests that, in addition to purely acoustical properties, the cortical processing of distractor speakers depends on factors like perceptual demand.


A cross-reacting human idiotype (B17) associated with antibodies to N-acetyl-D-glucosamine. Specificity, immunoglobulin class association, and distribution in the population.
This report describes the study of the expression of an idiotype in the human population which is associated with antibodies to N-acetyl-D-glucosamine (GlcNAc) present in most human sera presumably due to streptococcal infections. The idiotype is identified with antisera and monoclonal antibodies prepared against the IgM (kappa) antibody secreted by the Epstein-Barr virus-transformed human B cell line B17. At least 90% of 207 individuals tested had immunoglobulin with B17 idiotypic determinants in their sera, as demonstrated with conventional and one monoclonal anti-idiotypic antibody. Another monoclonal anti-idiotypic antibody reacted with antibodies in only a few of the sera. No correlation was found between the level of expression of different idiotopes in individual human sera, suggesting molecular heterogeneity of the B17-positive antibody population. B17-positive immunoglobulins are to a large extent specific for GlcNAc but represent only a minor population of all GlcNAc-specific antibodies in human sera. B17 determinants are on IgM (kappa) in all human sera and on IgG and IgA in some. In addition, some lambda-bearing Ig was found to react with anti-B17 antisera, suggesting the detection of VH-associated idiotypic determinants in this experimental system.


Single-crystalline Sb-doped SnO2 nanowires: synthesis and gas sensor application.
The synthesis of semiconducting Sb-doped SnO2 nanowires in mass production by an in situ doping approach are reported, and the ethanol sensing results demonstrated that Sb-doped SnO2 nanowires have a promising application for the fabrication of gas sensors with low resistance, and quick response and recovery times.


Dual Single-Atomic Ni-N4 and Fe-N4 Sites Constructing Janus Hollow Graphene for Selective Oxygen Electrocatalysis.
Nitrogen-coordinated metal single atoms in carbon have aroused extensive interest recently and have been growing as an active research frontier in a wide range of key renewable energy reactions and devices. Herein, a step-by-step self-assembly strategy is developed to allocate nickel (Ni) and iron (Fe) single atoms respectively on the inner and outer walls of graphene hollow nanospheres (GHSs), realizing separate-sided different single-atom functionalization of hollow graphene. The Ni or Fe single atom is demonstrated to be coordinated with four N atoms via the formation of a Ni-N4 or Fe-N4 planar configuration. The developed Ni-N4 /GHSs/Fe-N4 Janus material exhibits excellent bifunctional electrocatalytic performance, in which the outer Fe-N4 clusters dominantly contribute to high activity toward the oxygen reduction reaction (ORR), while the inner Ni-N4 clusters are responsible for excellent activity toward the oxygen evolution reaction (OER). Density functional theory calculations demonstrate the structures and reactivities of Fe-N4 and Ni-N4 for the ORR and OER. The Ni-N4 /GHSs/Fe-N4 endows a rechargeable Zn-air battery with excellent energy efficiency and cycling stability as an air-cathode, outperforming that of the benchmark Pt/C+RuO2 air-cathode. The current work paves a new avenue for precise control of single-atom sites on carbon surface for the high-performance and selective electrocatalysts.


IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy.
The goal of this study was to test the hypothesis that IL-6 mediates the increases in superoxide, vascular hypertrophy, and endothelial dysfunction in response to angiotensin II (Ang II). Responses of carotid arteries from control and IL-6-deficient mice were examined after acute (22-hour) incubation with Ang II (10 nmol/L) or chronic infusion of Ang II (1.4 mg/kg/d for 14 days). The hypertrophic response and endothelial dysfunction produced by Ang II infusion was markedly less in carotid arteries from IL-6-deficient mice than that in control mice. IL-6 deficiency also protected against endothelial dysfunction in response to acute (local) Ang II treatment (eg, 100 mumol/L acetylcholine produced 100+/-4 and 98+/-4% relaxation in vehicle-treated and 51+/-4 and 99+/-4% relaxation in Ang II-treated, control, and IL-6-deficient vessels, respectively). Endothelial dysfunction could be reproduced in vessels from IL-6-deficient mice with combined Ang II plus IL-6 (0.1 nmol/L) treatment. Increases in vascular superoxide and IL-6, as well as reductions in endothelial nitric oxide synthase mRNA expression, produced by Ang II were absent in IL-6-deficient mice. These data demonstrate that IL-6 is essential for Ang II-induced increases in superoxide, endothelial dysfunction, and vascular hypertrophy.


Nonspecific immunity and head and neck cancer: blastogenesis reviewed and revisited.
The present study suggests a correlation between concanavalin A-driven blastogenesis and the clinical course of head and neck cancer. Blastogenesis assays were conducted on peripheral blood lymphocytes from controls and from patients with squamous cell carcinoma (SCC) of the head and neck. Our results indicated that 3H-thymidine incorporation in response to concanavalin A and phytohemagglutinin stimulation were significantly lower for patients' than for controls' lymphocytes, whereas PWM stimulation was not statistically different in these two groups. Differences between patients and controls were most notable with concanavalin A stimulation. Five of seventeen patients had a response to concanavalin A stimulation that was in the normal range when expressed as relative to control values. The clinical course of these five patients seems to point to a better prognosis than that of the remaining patients who had below-normal mitogenic responses.


Neutrophil-lymphocyte ratio is associated with all-cause mortality among critically ill patients with acute kidney injury.
Inflammation plays a critical role in the development of acute kidney injury (AKI). Neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation used to predict the prognostic outcome of several diseases. We conducted a retrospective cohort study to investigate if NLR can be used as a biomarker to predict the mortality of AKI. Records of critically ill patients with AKI were extracted from the Medical Information Mart for Intensive Care Database III version 1.3 (MIMIC-III v1.3). The primary outcome was 30-day mortality and the two secondary outcomes were in hospital and 90-day mortality. We used the Cox proportional hazards models to assess the association between different categories of NLR and outcomes. This analysis included data for 13,678 eligible subjects, with a total of 2,588 30-day, 2,224 in-hospital and 3,545 90-day deaths during the follow-up period. For 30-day mortality, an increased risk of mortality was associated with a higher level of NLR. The HR (95% confidence interval [CI]) of upper tertile (NLR > 12.14) was 1.37 (1.17-1.60) in a multivariate model when compared with that of the lower tertile (NLR < 5.55). In the quintile analysis, we confirmed the upward trend with HR (95% CI) of the fifth quintile (NLR > 17.4) of 1.35 (1.08, 1.69) in a multivariate model compared to the first quintile (NLR < 3.82). A similar tendency was observed for 90-day mortality. In the analysis of in-hospital mortality, the HR of fifth quintile (NLR > 17.4) showed a slight decrease. Our analysis indicates that a higher level of NLR is associated with increased risk of 30-day and 90-day mortality in AKI patients. The similar upward trend is not detected in analysis of in-hospital mortality.


No association between bronchial asthma and HLA-DRB1, -DQB1 alleles in the Slovak population.
109 patients (62 boys/men and 47 girls/women) suffering from bronchial asthma induced by pollen allergens were typed for HLA-DRB1 and -DQBl alleles, respectively, by a low resolution SSP technique. Frequencies of DRB1 alleles varied from 0.5 % to 16.1 %. The most frequent was HLA-DRB1*11 (16.1 %), the least frequent HLA-DRB1*09 (0.4 %). Occurrence rates of HLA-DQB1 alleles ranged from 2.3 % to 37.2 %, HLA-DQB1*03 being the most frequent (37.2 %) and DQB1*04 stood on the opposite pole (2.3 %). By comparing to occurrence rates in the healthy population, no statistically significant differences were disclosed (Tab. 2, Ref. 16).


Interferon-gamma Stimulates Monocyte Chemotactic Protein-1 Expression by Monocytes.
Monocyte chemotactic protein (MCP-1) is a specific monocyte chemoattractant and activating factor produced by both immune cells (mononuclear phagocytes and lymphocytes) and non-immune cells (parenchymal and stromal cells). In order to define the conditions under which human monocytes express MCP-1, monocytes were exposed to IFN-gamma, IL- lbeta, TNF-alpha, IL-4 or PHA under serum free conditions. There was no significant MCP-1 production by monocytes following exposure to IL-lbeta, TNF-alpha or IL-4. In contrast, stimulation with IFN-gamma resulted in a dose dependent increase in MCP-1 protein and mRNA expression. Simultaneous stimulation with IFN-gamma and IL-1beta or TNF-alpha resulted in no further increase in MCP-1 production. It is concluded that IFN-gamma, primarily a product of T(H)1 T lymphocytes, stimulates the expression of MCP-1 by monocytes.


Tractography of Meyer's Loop asymmetries.
The purpose of the current study was to use diffusion tensor imaging (DTI) to conduct tractography of the optic radiations (OR) and its component bundles and to assess both the degree of hemispheric asymmetry and the inter-subject variability of Meyer's Loop (ML). We hypothesized that there are significant left versus right differences in the anterior extent of ML to the temporal pole (TP) in healthy subjects. DTI data were acquired on a 3T Siemens MRI system using a single-shot Spin Echo EPI sequence. The dorsal, central and ML bundles of the OR were tracked and visualized in forty hemispheres of twenty healthy volunteers. The uncinate fasciculus (UF) was also tracked in these subjects so that it could be used as a distinct anatomical reference. Measurements were derived for the distance between ML-TP, ML and the temporal horn (ML-TH) and ML and the uncinate fasciculus (ML-UF). Paired difference t-tests were carried out with SPSS 14.0. ML and the UF were successfully tracked and visualized in all 20 volunteers. Significant hemispheric asymmetries were found for all measurements with left distances shorter than the right (P<0.005). In 50% of the subjects the left ML-UF distance was ≤1.9 mm. The results support our hypothesis and demonstrate that left ML-TP distances are significantly shorter than right ML-TP distances. These asymmetries are also reflected in shorter left distances between ML-TH and ML-UF. Moreover, these results are of interest to left-sided temporal lobe epilepsy surgery because it is not only more likely to disturb the anterior extent of ML but also renders the often closely located posterior aspect of the left UF more vulnerable to potential surgical impact.


Enzymatic Pre-treatment of Wastewater to Minimize Recovery by Reverse Transcriptase PCR of RNA from Inactive Bacteriophages.
Quantitative viral risk assessments for wastewaters are notoriously difficult. The often considered quantitative reverse transcriptase PCR reflects poorly on virus infectivity rates leading to inaccurate risk interpretations. Various techniques focused on the degradation of the nucleic acids of non-infective viruses were previously employed. We comparatively assessed the effectiveness of such enzymatic treatments for MS2 bacteriophage in treated wastewaters. The single use of RNase A at an appropriate concentration may be as effective as the combination of RNase followed by Proteinase K and more rapid. While all tested enzymatic treatments minimized recovery of RNA (>95 %) in the absence of infective MS2, none completely eliminated the signal recovery. Selection of any enzymatic protocol for minimizing recovery of RNA from degraded, non-infective viruses should balance the methods efficacy with its expediency.


Mass Spectrometry Analysis of the Human Brain Sphingolipidome.
In recent decades, mass spectrometry-based lipidomics has provided a fertile environment for scientific investigations of biochemical and mechanistic processes in biological systems. Notably, this approach has been used to characterize physiological and pathological processes relevant to the central nervous system by identifying changes in the sphingolipid content in the brain, cerebral spinal fluid, and blood plasma. However, despite a preponderance of studies identifying correlations between specific lipids and disease progression, this powerful resource has not yet substantively translated into clinically useful diagnostic assays. Part of this gap may be explained by insufficient depth of the lipidomic profiles in many studies, by lab-to-lab inconsistencies in methodology, and a lack of absolute quantification. These issues limit the identification of specific molecular species and the harmonization of results across independent studies. In this chapter, we contextualize these issues with recent reports identifying correlations between brain lipids and neurological diseases, and we describe the workflow our group has optimized for analysis of the blood plasma sphingolipidome, adapted to the characterization of the human brain tissue.


3D Microfluidic System for Evaluating Inhibitory Effect of Chinese Herbal Medicine Oldenlandia diffusa on Human Malignant Glioma Invasion Combined with Network Pharmacology Analysis.
To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.


Characterization of thyrotropin binding to specific receptors in human fat tissue.
Specific receptors for thyrotropin were found to exist in membranes from whole human subcutaneous fat tissue. The characteristics of the interaction of 125I-labelled thyrotropin with such receptors were determined and compared with the stable, high-affinity thyrotropin receptor shown previously to exist in guinea pig fat membranes. Specific binding was readily detectable using low concentrations of membranes (up to 80 microgram/ml), though specific binding was reduced at higher membrane concentrations. Increasing concentrations of unlabelled thyrotropin reduced fractional binding, revealing saturation of a population of mixed affinity sites (highest Ka of the order of 0.3 X 10(9) M-1). Little cross-reactivity was observed with other lipolytic or structurally related hormones, though some cross-reactivity was observed in the presence of human chorionic gonadotropin. Association was temperature-dependent and rapid at 37 degrees C, though prolonged incubation revealed some instability of binding at this temperature. Binding was reversible with a high dissociation rate constant, and was particularly sensitive to the presence of low concentrations of sodium or calcium ions. Using membranes prepared from isolated human fat cells, binding of thyrotropin was equally sensitive to the addition of cations.


Neural systems for guilt from actions affecting self versus others.
Guilt is a core emotion governing social behavior by promoting compliance with social norms or self-imposed standards. The goal of this study was to contrast guilty responses to actions that affect self versus others, since actions with social consequences are hypothesized to yield greater guilty feelings due to adopting the perspective and subjective emotional experience of others. Sixteen participants were presented with brief hypothetical scenarios in which the participant's actions resulted in harmful consequences to self (guilt-self) or to others (guilt-other) during functional MRI. Participants felt more intense guilt for guilt-other than guilt-self and guilt-neutral scenarios. Guilt scenarios revealed distinct regions of activity correlated with intensity of guilt, social consequences of actions, and the interaction of guilt by social consequence. Guilt intensity was associated with activation of the dorsomedial PFC, superior frontal gyrus, supramarginal gyrus, and anterior inferior frontal gyrus. Guilt accompanied by social consequences was associated with greater activation than without social consequences in the ventromedial and dorsomedial PFC, precuneus, posterior cingulate, and posterior superior temporal sulcus. Finally, the interaction analysis highlighted select regions that were more strongly correlated with guilt intensity as a function of social consequence, including the left anterior inferior frontal gyrus, left ventromedial PFC, and left anterior inferior parietal cortex. Our results suggest these regions intensify guilt where harm to others may incur a greater social cost.


A semi-Markov model for the average length of stay in transient states and its application.
The purpose of this paper is to develop a methodology that can be used to study the length of stay distribution of the patient in various states of the disease. The treatment data on cancer of cervix patients are used to illustrate its application.


Response inhibition and attention processing in 5- to 7-year-old children with and without symptoms of ADHD: An ERP study.
Response inhibition and attention processing in 5- to 7-year-old children with or without symptoms of attention-deficit hyperactivity disorder (ADHD) were examined. Twelve children with ADHD symptoms and 15 control children performed a CPT-AX task. Behavioral measures of inattention and impulsivity and ERP measures of conflict monitoring and inhibition (Nogo-N2 and Nogo-P3), cue-orientation and prestimulus target expectation (Cue-P2 and P3) and response preparation (CNV) were collected. ADHD children detected fewer targets and had higher Inattention scores accompanied by reduced centro-parietal Cue- and Go-P3 activity. Occipital CNV amplitude was larger in ADHD children. At fronto-central leads, strong and comparable fronto-parietal Nogo-N2 effects were found in both groups, whereas the Nogo-P3 was only marginally significant in both groups. The attenuated Cue- and Go-P3 effects in the ADHD-symptom group are interpreted as early signs of delayed attention development, resulting in less preparation and less alertness to detect significant events. Whereas the Nogo-N2 effects were interpreted as signs of comparable levels of conflict processing in both groups, the small Nogo-P3 suggests that inhibitory processing is still immature at this age. The present study shows that specific attention problems can already be detected in the behavior and brain activity of 5- to 7-year-old children with symptoms of ADHD performing a CPT-AX task, and might be better indicators for the risk of developing ADHD than impulsivity measures.


Fine-needle aspiration biopsy diagnosis of follicular variant of papillary thyroid cancer: therapeutic implications.
Frozen-section analysis of follicular lesions is often inconclusive because capsular or vascular invasions are the hallmarks of malignancy with this technique and may not be seen in the particular field studied. Using preoperative fine-needle aspiration biopsy specimens, we attempted to identify malignant follicular lesions and compare these results against frozen-section analysis. A retrospective study of 1000 consecutive thyroid fine-needle aspiration biopsy specimens was performed. Surgical pathologic correlation was available in 179 cases. Fine-needle aspiration biopsy yielded a suspicious or positive rate of 23%. Surgical pathology was available in 179 patients, of which 95% had thyroid cancer. The follicular variant of papillary cancer was identified in 26 cases, or 15% of the positive cases. Frozen-section analysis yielded false-negative results in 7 of these 26 cases (27%). Preoperative recognition of the follicular variant of papillary cancer by fine-needle aspiration biopsy may reduce the overall incidence of false-negative frozen-section findings.


The use of recombinant gilthead sea bream (Sparus aurata) growth hormone for radioiodination and standard preparation in radioimmunoassay.
A gilthead sea bream growth hormone (sbGH) obtained by cloning and expression of sbGH cDNA was used to develop a sensitive and specific radioimmunoassay (RIA). Iodination of recombinant sbGH (rsbGH) was performed by the classical Chloramine-T method. Specific antiserum, raised in rabbits, was added in a final dilution of 1/36,000. The minimum detectable dose was 30 pg, and the midrange of the assay (ED50) was 275 pg. Intra- and inter-assay coefficients of variation (CV) were 3.3 and 5.8% at ED50 levels. Human GH (hGH), ovine GH (oGH), carp gonadotropin (cGtH), chinook salmon gonadotropin (sGtH), ovine prolactin (oPRL) and recombinant tilapia prolactin (rtiPRL) did not show cross-reactivity. Serial dilutions of chinook salmon GH (sGH) and recombinant rainbow trout GH (rtGH) showed a low but significant cross-reactivity. A good parallelism between rsbGH standard and serial dilutions of native sbGH, plasma and pituitary extracts was observed. In addition, when plasma and pituitary samples were analyzed for GH quantification, non-significant differences were observed within this and previous RIA for native sbGH. Therefore, it appears conclusive that our rsbGH can be used successfully as a standard and radioiodinated hormone in GH assays for gilthead sea bream, which is extensively cultured in the Mediterranean area.


Relationship between the retinal thickness analyzer and the GDx VCC scanning laser polarimeter, Stratus OCT optical coherence tomograph, and Heidelberg retina tomograph II confocal scanning laser ophthalmoscopy.
To assess the relationship between the retinal thickness analyzer (RTA) parameters, and those of the GDx VCC scanning laser polarimeter (GDx VCC), Stratus OCT optical coherence tomography (Stratus OCT), and Heidelberg retinal tomograph II confocal scanning laser ophthalmoscopy (HRT II). Twenty-nine primary open-angle glaucoma patients were retrospectively included in this study. Measurements were obtained using the RTA, GDx VCC, Stratus OCT, and HRT II. We calculated the correlation coefficients between the parameters of RTA and those of the other studies. Among the optic disc parameters of RTA, the cup volume was best correlated with Stratus OCT (R=0.780, p<0.001) and HRT II (R=0.896, p<0.001). Among the posterior pole retinal thickness parameters, the posterior pole abnormally thin area (PPAT) of the RTA and the inferior average of the GDx VCC were best correlated (R=-0.596, p=0.001). The PPAT of the RTA and the inferior maximum of the Stratus OCT were best correlated (R=-0.489, p=0.006). The perifoveal minimum thickness (PFMT) of the RTA and the cup shape measurement of the HRT II were best correlated (R=-0.565, p=0.004). Many RTA optic disc parameters were significantly correlated with those of the Stratus OCT and HRT II. The RTA posterior pole retinal thickness parameters were significantly correlated with those of the GDx VCC, Stratus OCT and HRT II. The RTA optic disc and posterior pole retinal thickness parameters may be valuable in the diagnosis of glaucoma.


Classification of newly-onset IDDIM and NIDDIM in subjects aged 25-45 years in Sudan.
To investigate the ability of classifying diabetes mellitus with clinical and biochemical characteristics at diagnosis in 25-45 years old patients. We determined age, body mass index (BMI), ICA, fasting C-peptide and HbA1c at diagnosis, and after 4-27 months follow up, these variables were related to the type of treatment. Omdurman Teaching Hospital, Sudan. Eighty-six consecutive newly diagnosed diabetic patients, according to WHO criteria, were included. At diagnosis, 27 patients (31.4%) were treated with insulin and 59 (68.6%) with diet and/or oral hypoglycaemic agents (OHA). Insulin-treated patients at diagnosis were younger, had lower BMI and higher HbA1c. In the non-insulin treated group at diagnosis, ICA-negative patients (n = 54) had higher fasting C-peptide (P < 0.05) than ICA-positive. The treatment was changed from insulin to diet and/or OHA in 17 patients, and to insulin in six patients. Patients who discontinued insulin had already at diagnosis higher BMI and higher fasting C-peptide concentration (P < 0.005 and P < 0.05, respectively) than patients remained on insulin. The positive predictive values for insulin treatment of ICA positivity, low fasting C- peptide, and low BMI were 90, 78 and 73%, respectively. The sensitivity, specificity and positive predictive values for these variables in concurrence were, respectively, 85, 92 and 69%. The clinical classification of newly- diagnosed young Sudanese patients was satisfactory. With regular follow up and early commencement of appropriate treatment, good glycaemic control is certainly attainable. BMI is potentially valuable for the clinical classification in such patients. ICA and fasting serum C-peptide facilitate the choice of insulin treatment, but cost is a limit to large-scale use of these tests.


Motor control during sleep and wakefulness: clarifying controversies and resolving paradoxes.
Data accumulated during the last 40 years, since the discovery that there is a loss of muscle tone during REM sleep, have delineated many of the neurotransmitter systems, synaptic mechanisms and neuronal circuitries involved in the control of somatic motoneurons during sleep and waking states. Nevertheless, there are still a number of extant controversies as well as paradoxical and conflicting data. For example, the paradoxical modulation of motor activity that occurs in individuals with cataplexy during wakefulness compared to REM sleep is unresolved as are the mechanisms that are responsible for the control of hypoglossal motoneurons during normal states and those that are operative during sleep disorders such as obstructive sleep apnea. In addition, the circuitry whereby the hypocretinergic system promotes motor activation during wakefulness, and motor inhibition during REM sleep, has yet to be clarified. The use of new techniques, such those involving optogenetics and nanoparticles, will help to clarify the preceding issues and provide as a foundation for addressing a number of current critical unanswered questions such as those dealing with the differential control of motor activity in newborns and the aged. The resulting data will strengthen the foundation for the development of efficacious therapeutics to treat disorders of motor control that occur during sleep as well as wakefulness.


Clogging of microchannels by nano-particles due to hetero-coagulation in elongational flow.
We have investigated the phenomenon of flow-induced aggregation in highly concentrated colloidal dispersions exposed to strongly converging flow fields. This phenomenon is relevant not only for classical technical operations like coating, pumping or filtration, but also for the application of concentrated suspensions in upcoming processing technologies based on microfluidic devices. A ring-slit device (gap height 10-25 μm), which allows for a variation of flow kinematics in a wide range, has been developed in order to investigate this phenomenon. Various polymer dispersions with different particle surface properties have been used as model systems. Our experiments exclude, that channel clogging is due to retention of pre-existing aggregates, fouling or hydrodynamic bridging. Instead, we demonstrate that clogging of the microchannel is induced by hetero-coagulation between primary colloidal particles and micron-sized impurities present at concentrations on the order of 100-1000 ppm. Clogging can occur even if the diameter of these impurities is less than a tenth of the gap height. Aggregation takes place in the converging flow field at the channel entrance, but not in the shear field within the slit. It can be suppressed by appropriate stabilization of the primary particles.


Long-term observation of HCV-positive patients with normal ALT values: persistence of a clinically healthy state.
The purpose of our investigation was to ascertain the presence of viral replication in subjects positive for antibodies to hepatitis C virus (anti-HCV) with persistently normal values of liver tests, to define their natural history, and to determine whether the immunoglobulin M (IgM) response could be a useful parameter to distinguish viraemic from non-viraemic patients. Twenty-seven subjects were selected based on their anti-HCV positivity and sustained normality (for at least 18 months) of alanine-aminotransferase (ALT) values. They were enrolled into the study and observed for another 1-4 years (mean 2.6). Fifteen out of 27 subjects were positive for hepatitis C virus ribonucleic acid (HCV RNA) and 12/15 were also positive for IgM. The remaining 12/27 patients were negative for both assessments. ALT levels remained in the norm throughout the investigation for all 27 subjects studied; the 15 viraemic patients showed persistent positivity for HCV RNA and the 12 positive for IgM anti-core also maintained their positivity. Patients shown to be negative for HCV RNA and IgM sustained their negativity throughout the study. Our results indicates that some patients remain viraemic while not having and/or developing clinical and biochemical signs of liver damage. IgM anti-HCV seems to be a specific index of viraemia in HCV-positives and could be useful for monitoring these patients.


Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease.
Although the ApoE epsilon4 allele is well-established as the most important genetic risk factor for Alzheimer's disease (AD), the effects of this allele on regional brain atrophy in AD patients remain controversial. We performed MRI-based volumetric measurements of the hippocampus and amygdala (normalized to intracranial volume) in 32 epsilon4+ AD patients, 23 epsilon4- AD patients, and 42 cognitively normal elderly control subjects. Analysis of covariance revealed that amygdaloid volume was significantly smaller (19.2%) in ApoE epsilon4+ than epsilon4- AD patients, controlling for disease severity (F = 10.62; d.f. = 1,52; p = 0.002; ANCOVA). Alternatively, when ApoE epsilon4 dose was considered, this effect appeared to accrue from a difference between the 0epsilon4 and each of the other two AD groups, with no significant difference between the 1epsilon4 and 2epsilon4 AD groups. Hippocampal volumes and asymmetry indices for hippocampus and amygdala did not differ between epsilon4 carriers and noncarriers. These results suggest accelerated atrophy of the amygdala in AD in association with ApoE epsilon4 and provide further evidence for regionally specific effects of this allele.


Genetic screening of ANXA11 revealed novel mutations linked to amyotrophic lateral sclerosis.
ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.


Methods of assessment of respiratory muscle fatigue (RMF).
Methods to assess fatigue of respiratory muscles, technical conditions and possibilities of practical application are discussed.


Integrating micro- and macroevolution of development through the study of horned beetles.
A major challenge in evolutionary developmental biology is to understand how developmental evolution on the level of populations and closely related species relates to macroevolutionary transitions and the origin of evolutionary novelty. Here, I review the genetic, developmental, endocrine, and ecological basis of beetle horns, a morphological novelty that exhibits remarkable diversity both below and above the species level. Integrating from a variety of approaches three major insights emerge: the origin of beetle horns relied at least in part on the redeployment of already existing genetic, developmental and endocrine mechanisms. At the same time little to no phylogenetic distance appeared to have been necessary for the evolution of diverse modifier mechanisms that permit substantial modulation of trait expression at different time points during development in different species, sexes, alternative male morphs or even different tissue regions of the same individual. Lastly, at least a subset of these modifier mechanisms can evolve rapidly in geographically isolated populations, apparently driven by relatively simple, and probably ubiquitous, changes in ecological conditions. I discuss the implications of these results for our understanding of the genesis of morphological novelty and diversity.


Inertial cues do not enhance knowledge of environmental layout.
Several sensory modalities besides vision are available to people as they move through an environment, learning where things are. For example, sensory information about linear and angular acceleration (i.e., inertial information) has been shown to be useful for maintaining orientation in a room-sized space. Because noise in inertial systems can compound over time and over extended travel, it is an open question whether inertial information is important for acquiring knowledge about large-scale environments. We addressed this issue in an experiment in which people learned the spatial layout of a large environment under conditions that varied in the degree to which valid inertial cues were available. The presence of valid inertial cues did not facilitate the acquisition of an accurate memory of the environment. Moreover, the presence of invalid inertial cues did not interfere with such acquisition. We conclude that the effect of inertial information on the acquisition of environmental knowledge is minimal.


Gastric motility in conscious rats given oxytocin and an oxytocin antagonist centrally.
Previous experiments have shown that gastric motility is inhibited by microinjection of oxytocin (OT) into the dorsal motor nucleus of the vagus (DMN) in anesthetized rats, and that the inhibition of gastric motility after electrical stimulation of the hypothalamic paraventricular nucleus (PVN) is blocked by microinjection of an OT receptor antagonist directly into the DMN. As an extension of these observations, the present series of studies demonstrate that gastric motility in unanesthetized, freely moving rats was reduced both by intracerebroventricular (i.c.v.) administration of OT and by electrical stimulation of the PVN, and that both of these inhibitory effects were blocked by i.c.v. administration of an OT antagonist. Moreover, an OT antagonist administered i.c.v. alone caused an increase in baseline gastric motility. However, pretreatment with the same OT antagonist i.c.v. did not block the inhibitory effects of systemic LiCl or cholecystokinin on gastric motility in conscious rats. These results suggest that oxytocinergic neurons exert a tonic inhibitory effect on gastric motility in rats, but that the inhibitory effects of LiCl and cholecystokinin on gastric motility are not primarily mediated by parvocellular OT-containing neurons projecting from the PVN to the DMN.


The efficacy of cibenzoline for reducing the left ventricular pressure gradient of hypertrophic obstructive cardiomyopathy: A case report.
A 46 year-old man with hypertrophic obstructive cardiomyopathy (HOCM) was referred to this clinic complaining of shortness of breath. His symptoms remained even after he had been treated with bisoprolol, lisinopril, and verapamil. We started treating him with cibenzoline, instead of verapamil. Continuous-wave Doppler examination revealed a marked decrease from 95.9 mm Hg to 8.8 mmHg in the left ventricular outflow tract pressure gradient after administration of cibenzoline, and the symptom disappeared. The electrical axis of the electrocardiogram deviated from +53 to +95 degrees, and the QRS interval was increased from 0.095 to 0.114 seconds. By the M-mode echocardiogram, the interventricular septum was observed moved paradoxically in the early, systolic phase. We suggest the possibility that cibenzoline modifies intraventricular conduction and causes asynchronous contraction of the left ventricle, resulting in decrease in the left ventricular outflow tract pressure gradient.


Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER): a cost-effectiveness analysis.
In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. The randomised, controlled, non-inferiority Stratall trial was done in a decentralised setting in Cameroon. Between May 23, 2006, and Jan 31, 2008, ART-naive adults were randomly assigned (1:1) to clinical monitoring (CLIN) or viral load and CD4 cell count plus clinical monitoring (LAB) and followed up for 24 months. We calculated costs, number of life-years saved (LYS), and incremental cost-effectiveness ratios (ICERs) with data from patients who had been followed up for at least 6 months. We considered two cost scenarios in which viral load plus CD4 cell count tests cost either US$95 (scenario 1; Abbott RealTime HIV-1 assay) or $63 (scenario 2; generic assay). We compared ICERs with a WHO-recommended threshold of three times the per-person gross domestic product (GDP) for Cameroon ($3670-3800) and an alternative lower threshold of $2385 to determine cost-effectiveness. We assessed uncertainty with one-way sensitivity analyses and cost-effectiveness acceptability curves. 188 participants who underwent LAB and 197 who underwent CLIN were followed up for at least 6 months. In scenario 1, LAB increased costs by a mean of $489 (SD 430) per patient and saved 0·103 life-years compared with CLIN (ICER of $4768 [95% CI 3926-5613] per LYS). In scenario 2, the incremental mean cost of LAB was $343 (SD 425) -ie, an ICER of $3339 (2507-4173) per LYS. A combined strategy in which LAB would only be used in patients starting ART with a CD4 count of 200 cells per μL or fewer suggests that 0·120 life-years would be saved at an additional cost of $259 per patient in scenario 1 (ICER of $2167 [95% CI 1314-3020] per LYS) and $181 in scenario 2 (ICER of $1510 [692-2329] per LYS) when compared with CLIN. Laboratory monitoring was not cost effective in 2006-10 compared with clinical monitoring when the Abbott RealTime HIV-1 assay was used according to the $3670 cost-effectiveness threshold (three times per-person GDP in Cameroon), but it might be cost effective if a generic in-house assay is used. French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER).


The first report of the occurrence of cilium in fat-storing cells in the reptilian liver (Eumeces algeriensis, Daudin 1802).
Fat-storing cells in the liver of an adult Schneider's skink were investigated by means of transmission electron microscopy. The fat-storing cells were localized in the perisinusoidal space or in the hepatic "recessus". They revealed a single cilium originating from one of the paired centrioles and projecting into the perisinusoidal space. The functional significance of a single cilium in the fat-storing cell is still unclear.


Age-dependent response of lactate dehydrogenase of pituitary of rat to testosterone.
The effects of time and various doses of testosterone on the responsiveness of lactate dehydrogenase of pituitary of 7-, 38- and 78-week-old rats were studied. The activity of the enzyme increases in 78-week-old rats. Castration decreases the enzyme activity at all ages. Maximum increase in the enzyme activity is seen with 50 and 100 microgram of testosterone 4 h after administration of hormone to castrated rats. No further time and dose-dependent effect is observed. The magnitude of increase for the enzyme is higher at the age of 38 weeks and decreases in 78-week-old rats.


Stable sulfur isotope analysis of SO2 pollution impact on vegetation.
The δ34S value of SO2 emitted by natural gas refineries is about +25, which is higher than that for non-industrial sulfur sources in our study areas. Terrestrial mosses absorb SO2 from the atmosphere and have a δ34S value which is directly related to the degree of SO2 stress to which they are subjected. The δ34S values for conifer needles are lower than for mosses at the same collection site, which indicates that trees obtain sulfur from both atmospheric and soil sources.Potted conifers were transferred to sites differing in their degree of SO2 stress. This difference is reflected by the change of δ34S values of their needles. SO2 absorbant pot covers, such as charcoal and moss, reduce the amount of airborne sulfur which is available to tress. Moss also may reduce SO2 absorbed by soils in forest stands. We have used analysis of δ34S values to (1) help define SO2 dispersion patterns; (2) reveal the rates at which plants accumulate this pollutant; and (3) associate suspected SO2 injury more closely to an emission source.


The response of regional well-being to place-based policy interventions.
Enhancing the well-being of its citizens is the central remit of the EU's regional policy, but as yet, there is no analysis of the effects of EU regional policy on local well-being. The aim of this paper is to examine this relationship. To do this, we define a novel regionalised well-being measure and we exploit a dataset on regional expenditure in a continuous treatment framework. Based on both parametric and semi-parametric approaches, our analysis demonstrates that the EU regional development policy does influence regional well-being differently from GDP. We find evidence of a linear monotonic response of well-being growth to total transfers, although this effect varies according to the time lag considered and the level of development of the region.


One-minute time interval estimation as a novel ultrashort tool for distress screening.
Our study explores the potential relationship between time estimation and level of distress in cancer patients prior to starting chemotherapy. Time estimation was assessed in 262 chemonaïve patients with solid tumors by evaluating each subject's prospective estimation of how fast 1 min passed compared to the actual time. The median value (40 s) of time estimation was used to stratify the patients into two categories of fast and slow time estimation. The National Comprehensive Cancer Network Distress Thermometer was used at the beginning of treatment to evaluate levels of distress. Patients scoring 4 or above (51.9%) were regarded as having high levels of distress. The pattern of the time estimation distributions significantly changed according to the level of distress. Patients with a fast time estimation had significantly higher levels of distress (4.55 ± 3.1) than patients with a slow time estimation (3.3 ± 2.9) (p = 0.001). ROC analysis revealed that at the optimal cutoff value of time estimation, patients with low and high distress levels can be discriminated with an AUC = 0.60 (95% CI: 0.53-0.67, p = 0.005) and with a sensitivity of 62.5% and specificity of 53.2%. Moreover, in a multivariate logistic regression model, fast time estimation was an independent predictor of high levels of distress. Time estimation is a novel potent indicator of high levels of distress in cancer patients. This test is an easily performed, time-saving, and nonintrusive ultrashort screening tool that is even suitable for patients who are not willing to reveal their level of distress via direct questionnaires.


Using DNA-barcoded Malaise trap samples to measure impact of a geothermal energy project on the biodiversity of a Costa Rican old-growth rain forest.
We report one year (2013-2014) of biomonitoring an insect community in a tropical old-growth rain forest, during construction of an industrial-level geothermal electricity project. This is the first-year reaction by the species-rich insect biodiversity; six subsequent years are being analyzed now. The site is on the margin of a UNESCO Natural World Heritage Site, Área de Conservación Guanacaste (ACG), in northwestern Costa Rica. This biomonitoring is part of Costa Rica's ongoing efforts to sustainably retain its wild biodiversity through biodevelopmental integration with its societies. Essential tools are geothermal engineering needs, entomological knowledge, insect species-rich forest, government-NGO integration, common sense, DNA barcoding for species-level identification, and Malaise traps. This research is tailored for integration with its society at the product level. We combine an academic view with on-site engineering decisions. This biomonitoring requires alpha-level DNA barcoding combined with centuries of morphology-based entomological taxonomy and ecology. Not all desired insect community analyses are performed; they are for data from subsequent years combined with this year. We provide enough analysis to be used by both guilds now. This biomonitoring has shown, for the first year, that the geothermal project impacts only the biodiversity within a zone less than 50 m from the project margin.


Intracellular third loop-C-terminal tail interaction in prostaglandin EP3beta receptor.
The secondary structures of and the interactions between the intracellular domains (the three loops and the C-terminal tail) of the mouse-derived prostaglandin E2 receptor EP3beta subtype were investigated using peptides mimicking the domains. The N-termini of the peptides were palmitoylated to anchor on unilamellar vesicles composed of phosphatidylserine, enriched in the cytoplasmic leaflet of mammalian plasma membranes. Circular dichroism spectroscopy revealed that the peptides corresponding to the intracellular third loop (i3) and the C-terminus (C-term) assumed beta-sheet and associated alpha-helical structures, respectively. A structural change was observed when i3 was mixed with C-term, indicating an interaction between them. Fluorescence experiments showed that i3 suppressed the self-association of C-term, confirming the interaction. These results demonstrate for the first time specific interaction between the intracellular third loop and the C-terminus. A model is proposed for the activation of the receptor.


Peripheral blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1 beta.
The objective of this study was to characterize interleukin-1 receptor antagonist (IL-1ra) and interleukin-1 beta (IL-1 beta) production by human peripheral blood neutrophils (polymorphonuclear leukocytes; PMN). Unstimulated PMN contained IL-1ra protein in the absence of IL-1ra mRNA; IL-1 beta mRNA and protein were undetectable. Lipopolysaccharide (LPS), granulocyte/macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha), individually, transiently increased IL-1ra steady-state mRNA levels in PMN, with associated increases in IL-1ra protein synthesis. LPS, GM-CSF, and TNF-alpha generated similar increases in IL-1 beta mRNA, yet only LPS resulted in detectable synthesis of IL-1 beta protein. IL-4 enhanced LPS-induced IL-1ra production by PMN and inhibited LPS-induced IL-1 beta production. by PMN and inhibited LPS-induced IL-1 beta production. IL-1ra protein present within stimulated PMN supernatants existed in the 22- to 25-kD glycosylated form. Polymerase chain reaction amplification determined that only sIL-1ra mRNA was present within stimulated PMN; icIL-1ra mRNA was undetectable. These results indicate that freshly isolated PMN possess a small amount of IL-1ra protein and that these cells can respond to stimuli with a low level of sIL-1ra transcription and translation. PMN may be a major source of IL-1ra in inflammatory exudates where these cells predominate.


Patient and family engagement in patient care and research in Canadian intensive care units: a national survey.
While patient and family engagement may improve clinical care and research, current practices for engagement in Canadian intensive care units (ICUs) are unknown. We developed and administered a cross-sectional questionnaire to ICU leaders of current engagement practices, facilitators, and barriers to engagement, and whether engagement was a priority, using to an ordinal Likert scale from 1 to 10. The response rate was 53.4% (124/232). Respondents were from 11 provinces and territories, mainly from medical surgical ICUs (76%) and community hospitals (70%). Engagement in patient care included bedside care (84%) and bedside rounds (66%), presence during procedures/crises (65%), and survey completion (77%). Research engagement included ethics committees (36%), protocol review (31%), and knowledge translation (30%). Facilitators of engagement in patient care included family meetings (87%), open visitation policies (81%), and engagement as an institutional priority (74%). Support from departmental (43%) and hospital (33%) leadership was facilitator of research engagement. Time was the main barrier to engagement in any capacity. Engagement was a higher priority in patient care vs research (median [interquartile range], 8 [7-9] vs 3 [1-7]; P < 0.001) and in pediatric vs adult ICUs (10 [9-10] vs 8 [7-9]; P = 0.003). Research engagement was significantly higher in academic vs other ICUs (7 [5-8] vs 2 [1-4]; P < 0.001), and pediatric vs adult ICUs (7 [5-8] vs 3 [1-6]; P = 0.01). Organizational strategies and institutional support were key facilitators of engagement. Engagement in patient care was a higher priority than engagement in research.


Primary structure of the variable regions encoding antibody to NG2, a tumour-specific antigen on the rat chondrosarcoma HSN. Correlation of idiotypic specificities with amino acid sequences.
Eight syngeneic rat monoclonal antibodies that recognize structurally overlapping epitopes on the chondroitin proteoglycan NG2, a tumour-specific antigen on the chemically induced rat chondrosarcoma HSN, have been analysed for the sequence of their immunoglobulin heavy (H) and light (L) chain variable (V) regions. This analysis defined five groups of antibodies which are very similar for both the H and L chains and revealed that a wide range of different V regions are capable of binding to the same antigenic determinant. However, three mAbs, 11/160, ALN/12/17 and ALN/9/94, which recognize a sequential epitope, were found to use almost identical heavy (V-D-J) and light (V-J) chains in regions demonstrating an exclusivity in specific protein-protein interaction for this particular epitope. Two other mAbs, ALN/11/53 and AL/3/12, used similar V and J segments but totally different D regions. With the exception of the pair ALN/11/53 and AL/3/12, this grouping of antibodies matches that derived from the idiotypic specificity study we have reported previously. The reactivity pattern of Ab1 11/160, ALN/12/17 and ALN/9/94 with six anti-idiotopic mAbs raised against 11/160 demonstrated that the idiotope recognized by Ab2 HIM/3/41 was defined by a single amino acid, Asn, at position 52 within the CDR2 loop of the VH region; whereas the D region of Ab1 ALN/11/53 was implicated as the structural correlate of idiotypy. The substitution of AsnH52 influenced the Id recognition but Ag binding was not affected suggesting that Ab2 HIM/3/41 did not mimic the NG2 Ag.


Retrieval of aerosol optical properties from GOCI-II observations: Continuation of long-term geostationary aerosol monitoring over East Asia.
Since the Geostationary Ocean Color Imager (GOCI) was successfully launched in 2010, the GOCI Yonsei aerosol retrieval (YAER) algorithm has been continuously updated to retrieve hourly aerosol optical properties. GOCI-II has 4 more channels including UV, finer spatial resolution (250 m), and daily full disk coverage as compared to GOCI, and was launched in February 2020, onboard the GEO-KOMPSAT-2B (GK-2B) satellite. In this study, we extended the YAER algorithm to GOCI-II data based on its improved performance in many aspects and present the first results of aerosol optical properties retrieved from GOCI-II data. Utilizing the overlapping period between the GOCI-II and GOCI in geostationary Earth orbit, we present GOCI-II aerosol retrievals for high aerosol-loading cases over East Asia and show that these have a consistent spatial distribution with those from GOCI. Furthermore, GOCI-II provides AOD at an even higher spatial resolution, revealing finer changes in aerosol concentrations. Validation results for one year data show that the GOCI-II AOD has a correlation coefficient of 0.83 and a ratio within the expected error (EE) of 59.4 % when compared with the aerosol robotic network (AERONET) data. We compared statistical metrics for the GOCI and GOCI-II AODs to assess the consistency between the two datasets. In addition, it was found that there is a strong correlation between the two datasets from the comparison of gridded GOCI and GOCI-II AOD products. It is expected that data from GOCI-II will continue long-term aerosol records with high accuracy that can be used to address air-quality issues over East Asia.


Expanding the spectrum of SOX1-antibodies in neuropathy: the coexistence of anti-SOX1 and Guillain-Barré syndrome-a case report.
Antibodies against SOX1 (or anti-glial nuclear antibody, AGNA) are partially characterized onconeural antibodies, firstly described in association with small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome is the most frequent paraneoplastic syndrome (PNS) found in patients with anti-SOX1-antibody positivity. Other associations are chronic axonal polyneuropathy, paraneoplastic limbic encephalitis, and paraneoplastic cerebellar degeneration. We describe a case of Guillain-Barré syndrome (GBS) with classical demyelinating phenotype associated with a positivity for anti-SOX1-antibodies. A therapy with intravenous immunoglobulin led to progressive clinical improvement. After 12 months, clinical and neurophysiological pictures showed complete recovery. A thorough paraneoplastic screening was negative for underlying tumors. This is the first case of GBS associated with anti-SOX1-antibodies described in literature. Although the concept of paraneoplastic GBS is controversial, different cases have been reported and GBS is considered a non-classical paraneoplastic syndrome. Our case expands the anti-SOX1-antibody clinical spectrum with relevant implications for the clinical practice.


Urinary incontinence and its functional anatomy in frontotemporal lobar degenerations.
The frontal lobes play a crucial role in micturition control. However, no reports exist on the functional role of distinct frontal brain regions in urinary incontinence (UIC) in patients with a neurodegenerative damage of the frontal lobe. The aim of the present study was therefore to explore if functional brain lesions were associated with UIC in patients suffering from frontotemporal lobar degenerations (FTLD). Forty-four patients, including eight incontinent subjects, underwent cranial positron emission tomography scanning with (18)F-fluoro-2-deoxy-glucose ((18)F-FDG PET) to assess the relative metabolic rate of glucose (rCMRglc). Group comparisons of rCMRglc were conducted in SPM2 to identify brain regions where the group of incontinent patients (FTLD+UIC) had significant alterations compared with the group without UIC (FTLD-UIC). At the stringent statistical threshold of p < 0.05, corrected for multiple comparisons according to the family-wise error rate, the statistical analysis revealed two significant right-hemispheric hypometabolic clusters located in the premotor/anterior cingulate cortex and the putamen/claustrum/insula. No hypermetabolic regions were found. The present study is the first to provide evidence for brain functional alterations involved in the occurrence of UIC in FTLD. These results provide an important piece of evidence to the understanding of a particularly distressing autonomic nervous system symptom of dementia.