A novel ICG-labeled cyclic TMTP1 peptide dimer for sensitive tumor imaging and enhanced photothermal therapy in vivo.
TMTP1 is a polypeptide independently screened in our laboratory, which can target tumors in situ and metastases. In previous work, we have successfully developed a near-infrared (NIR) probe TMTP1-PEG4-ICG for tumor imaging. However, the limited ability to target tumor micrometastases hinders its further clinical application. Multimerization of peptides has been extensively demonstrated as an effective strategy to increase receptor binding affinity due to "multivalent effect" or "apparent cooperative affinity". In this study, a novel TMTP1 homodimer-directed NIR probe (TMTP1-PEG4)2-ICG was successfully constructed and synthesized. The cyclic TMTP1 peptides were bridged by two PEG4 linkers and then labeled with ICG-NHS for tumor imaging and photothermal therapy. In vivo biodistribution were assessed in normal BALB/c mice, and tumor targeting abilities of (TMTP1-PEG4)2-ICG and its monomer were evaluated and compared in 4T1-bearing subcutaneous tumor and lymph node metastasis model mice. Biodistribution analysis in vivo revealed that (TMTP1-PEG4)2-ICG was cleared mainly in both liver and kidney dependent way. Comparing with free ICG dye or TMTP1-PEG4-ICG probe, this improved (TMTP1-PEG4)2-ICG dimer showed more sensitive tumor imaging and could clearly identify tumors at a minimum volume of 10 mm3. Additionally, when compared to its monomer, lymph node (LN) metastases could also be apparently visualized and easily distinguished from normal LN by the novel dimer at 24 h post-injection. The blocking study revealed that the tumor accumulation of this probe was specifically medicated by receptor-ligand interaction. Furthermore, with the increase in stability and tumor targeting ability of ICG in vivo, the probe could also be an attractive photothermal agent to significantly inhibit tumor growth under 808 nm NIR laser irradiation. In conclusion, our work revealed that the novel (TMTP1-PEG4)2-ICG dimer could be a promising theranostic agent for sensitive tumor imaging and imaging-guided photothermal therapy, indicating its broad prospects for further clinical transformation.


Effects of nifedipine on insulin secretion and glucose metabolism in rats and in hypertensive type 2 (non-insulin dependent) diabetics.
The effects of nifedipine (Adalat) on glucose metabolism and insulin release were studied in rats and in patients with type 2 diabetes mellitus complicated with hypertension. 1. In rats, 2.5-50 micrograms/kg of intravenous nifedipine reduced glucose tolerance and insulin release after intravenous glucose in a dose related fashion, although fasting blood sugar and insulin were not affected at 50 micrograms/kg of nifedipine. 2. Daily 20 to 60 mg of oral nifedipine for 12-75 weeks to 14 type 2 diabetics with hypertension did not affect their fasting blood glucose or hemoglobin A1. Mean glucose tolerance curve after the treatment was significantly ameliorated, although insulin response during the oral glucose loading did not show any significant change. Those results suggest firstly that there may be a difference in insulinopenic effect of nifedipine between the species, and secondly that long-term administration of nifedipine produced no adverse influence on glucose metabolism in type 2 diabetics.


Feasibility, safety, and efficacy of totally endoscopic coronary artery bypass grafting: multicenter European experience.
The invention of robotic systems has begun a new era of endoscopic cardiac surgery. Reports on totally endoscopic coronary artery bypass grafting are limited, however, and data regarding feasibility, safety, and efficacy are needed to determine this technique's position in the therapeutic armamentarium. This study describes the largest multicenter experience in the literature with robotic totally endoscopic coronary artery bypass grafting specifically addressing procedural feasibility, safety, and efficacy. Between September 1998 and November 2002, a total of 228 patients with coronary artery disease were scheduled for totally endoscopic coronary artery bypass grafting with the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale, Calif.) at five European institutions. Patients underwent totally endoscopic coronary artery bypass grafting with either an on-pump (group A, n = 117) or an off-pump approach (group B, n = 111). Patients underwent postoperative angiography or stress electrocardiography and were followed up for 6 months. Procedural feasibility was demonstrated through the completion of 164 successful totally endoscopic cases. Sixty-four patients (group C, 28%) had conversion to nonrobotic procedures. Conversion rates decreased with time. The overall procedural efficacy, as defined by angiographic patency or lack of ischemic signs on stress electrocardiography, was 97%. The incidence of major adverse cardiac events within 6 months was 5%. Both on- and off-pump totally endoscopic coronary artery bypass grafting are feasible, with a conversion rate that diminishes with increasing experience. Conversion does not adversely affect outcome and thus constitutes a safe alternative. Although target vessel reintervention may be slightly higher than that reported for open coronary artery bypass grafting, graft patency and major adverse cardiac events for both approaches are comparable to those reported in the Society of Thoracic Surgeons database, demonstrating the safety and efficacy of the totally endoscopic coronary artery bypass grafting procedure.


Changes in motor cortical excitability induced by paired associative stimulation.
Changes in afferent input have been shown to be capable of inducing reorganisations of motor cortex in humans. Using TCMS we examined the efficacy of a new associative afferent stimulation paradigm in inducing motor cortical reorganisation in humans. Using TCMS, stimulus response curves were constructed before and following a 1 h period of associative stimulation of two muscles motor points. The effect of an asynchronous peripheral stimulation paradigm was investigated in a separate series of control experiments. One hour of associative stimulation of two muscles motor points resulted in a significant increase in the excitability of the corticospinal projection to those stimulated muscles. The increase in excitability peaked 1 h following the stimulation period. This increase in excitability did not generalise to either adjacent or more remote muscles. The control stimulation paradigm produced no significant change in corticospinal excitability. These results confirm the importance of associative input for the induction of plasticity in the human motor cortex. The findings reported here further elucidate the role of afferent input in motor cortical reorganisation. These findings have implications for our understanding of the mechanisms of motor learning and may also be relevant to the design of new afferent stimulation therapies.


Redefining Primum Non Nocere to Include Reproductive Autonomy: A New Paradigm in Subspecialty Medicine.
People with chronic medical illnesses are at particularly high risk for adverse pregnancy outcomes, yet current clinical approaches largely fail to identify and support their individualized reproductive and pregnancy goals. Instead, the predominant approach to pregnancy in subspecialty medicine is disease centered rather than patient centered. To better meet the individual needs and preferences of people with childbearing potential who have chronic medical conditions, we advocate in this article for a paradigm shift in subspecialty care that honors individuals' reproductive autonomy and human right of reproduction.


Association Between Neuromuscular Variables and Graft Harvest in Soft Tissue Quadriceps Tendon Versus Bone-Patellar Tendon-Bone Anterior Cruciate Ligament Autografts.
Quadriceps tendon (QT) autografts are increasingly popular for anterior cruciate ligament reconstruction (ACLR). However, no study has compared QT autografts with bone-patellar tendon-bone (BTB) autografts regarding the electromechanical delay (EMD), the peak torque (PT), and the rate of force development (RFD) in the superficial quadriceps muscles (rectus femoris [RF], vastus medialis [VM], and vastus lateralis [VL]). We hypothesized (1) there would be a significantly lower PT, lower RFD, and longer quadriceps EMD of the operative limb for the QT versus the BTB autograft; (2) the PT, the RFD, and the quadriceps EMD of the operative limb would be significantly depressed compared with those of the nonoperative limb, regardless of the surgical technique; and (3) there would be greater increases in the RF EMD than in the VM or the VL EMD. Cohort study; Level of evidence, 3. A total of 34 patients (age, 18-40 years), who had undergone ACLR (QT, n = 17; BTB, n = 17) at least 1 year before testing and performed 3 perceived maximal effort isometric tests, which were time synchronized with surface electromyography (EMG) on their operative and nonoperative limbs, were included in this study. EMD, PT, and RFD data were analyzed using a 2 (limb) × 2 (graft) × 3 (repetition) mixed repeated-measures analysis of variance. The EMD, the PT, and the RFD were not significantly affected by graft choice. For the VL, a significant repetition × graft × limb interaction was detected for the VL EMD (P = .027; ηp = 0.075), with repetition 3 having longer EMD than repetition 2 (mean difference [MD], 16 milliseconds; P = .039). For the RF EMD, there was a significant repetition × limb interaction (P = .027; ηp = 0.074), with repetition 3 being significantly longer on the operative versus the nonoperative limb (MD, 24 milliseconds; P = .004). Further, the operative limb EMD was significantly longer for repetition 3 versus repetition 2 (MD, 17 milliseconds; P = .042). For the PT, there was a significant effect for repetition (P = .003; ηp = 0.114), with repetition 1 being significantly higher than both repetitions 2 (MD, 8.52 N·m; P = .001) and 3 (MD, 7.79 N·m; P = .031). For the RFD, significant limb (P = .034; ηp = 0.092) and repetition (P = .010; ηp = 0.093) effects were seen, with the nonoperative limb being significantly faster than the operative limb (MD, 23.7 N·m/s; P = .034) and repetition 1 being significantly slower than repetitions 2 (MD, -20.46 N·m/s; P = .039) or 3 (MD, -29.85 N·m/s; P = .002). The EMD, the PT, and the RFD were not significantly affected by graft type when comparing QT and BTB autografts for ACLR; however, all neuromuscular variables were affected regardless of the QT or the BTB harvest.


An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.
A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.


Analysis of Twitter conversations in obstetric anesthesiology using the hashtag #OBAnes during the onset of the COVID-19 pandemic.
#OBAnes is the most used hashtag in obstetric anesthesiology. The primary objective of the study was to characterize #OBAnes tweets at the onset of the COVID-19 pandemic. Observational study of all tweets using #OBAnes between June 30, 2019 and October 19, 2020. A list of 19 topics was compiled to categorize each tweet. All Twitter users were manually assigned into one of 19 Symplur Healthcare Stakeholder categories. There were 12 431 tweets with #OBAnes during the study period, posted by 1704 unique users. The top user category was Doctor (n = 1211, 71%) with 9665 (78%) tweets. The top three topics identified within Twitter conversations were neuraxial anesthesia, COVID-19, and general anesthesia. Twitter facilitated thousands of obstetric anesthesia-related discussions during the onset of the COVID-19 pandemic, with most conversations centering on anesthesia type (neuraxial or general anesthesia).


Arabidopsis 4-COUMAROYL-COA LIGASE 8 contributes to the biosynthesis of the benzenoid ring of coenzyme Q in peroxisomes.
Plants have evolved the ability to derive the benzenoid moiety of the respiratory cofactor and antioxidant, ubiquinone (coenzyme Q), either from the β-oxidative metabolism of p-coumarate or from the peroxidative cleavage of kaempferol. Here, isotopic feeding assays, gene co-expression analysis and reverse genetics identified Arabidopsis 4-COUMARATE-COA LIGASE 8 (4-CL8; At5g38120) as a contributor to the β-oxidation of p-coumarate for ubiquinone biosynthesis. The enzyme is part of the same clade (V) of acyl-activating enzymes than At4g19010, a p-coumarate CoA ligase known to play a central role in the conversion of p-coumarate into 4-hydroxybenzoate. A 4-cl8 T-DNA knockout displayed a 20% decrease in ubiquinone content compared with wild-type plants, while 4-CL8 overexpression boosted ubiquinone content up to 150% of the control level. Similarly, the isotopic enrichment of ubiquinone's ring was decreased by 28% in the 4-cl8 knockout as compared with wild-type controls when Phe-[Ring-13C6] was fed to the plants. This metabolic blockage could be bypassed via the exogenous supply of 4-hydroxybenzoate, the product of p-coumarate β-oxidation. Arabidopsis 4-CL8 displays a canonical peroxisomal targeting sequence type 1, and confocal microscopy experiments using fused fluorescent reporters demonstrated that this enzyme is imported into peroxisomes. Time course feeding assays using Phe-[Ring-13C6] in a series of Arabidopsis single and double knockouts blocked in the β-oxidative metabolism of p-coumarate (4-cl8; at4g19010; at4g19010 × 4-cl8), flavonol biosynthesis (flavanone-3-hydroxylase), or both (at4g19010 × flavanone-3-hydroxylase) indicated that continuous high light treatments (500 µE m-2 s-1; 24 h) markedly stimulated the de novo biosynthesis of ubiquinone independently of kaempferol catabolism.


Validation of the extended ICF core set for stroke from the patient perspective using focus groups.
The extended international classification of functioning, disability and health (ICF) core set for stroke is an application of the ICF of the World Health Organisation (WHO) with the purpose to represent the typical spectrum of functioning of persons with stroke. The objective of the study was to add evidence to the validation of the extended ICF core set for stroke from the perspective of patients using focus groups to explore the aspects of functioning and health important to persons with stroke. The sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The focus groups were digitally recorded and transcribed verbatim. After qualitative data analysis, the resulting concepts were linked to ICF categories and compared to the categories included in the extended ICF core set for stroke. Sixty patients participated in 15 focus groups. The content of 131 out of 166 ICF categories contained in the extended ICF core set for stroke was reported by the persons with stroke. The content of 31 additional categories that are not covered in the extended ICF core set for stroke was raised. The existing version of the extended ICF core set for stroke could be confirmed almost entirely from patient perspective.


LONG-TERM stability of arsenic in iron amended contaminated soil.
This study aimed at elucidating the long-term efficiency of soil remediation where chemical stabilization of arsenic (As) contaminated soil using zerovalent iron (Fe) amendments was applied. A combination of chemical extraction and extended X-Ray absorption fine structure (EXAFS) spectroscopy technique was applied on soils collected from five laboratory and field experiments in Sweden and France. All soils were treated with 1 wt% of zerovalent Fe grit 2-15 years prior to the sampling. The results indicate that all studied soils, despite the elapsed time since their amendment with Fe grit, had substantial amounts of ferrihydrite and/or lepidocrocite. These metastable and the most reactive Fe (oxyhydr)oxides (mainly ferrihydrite) were still present in substantial amounts even in the soil that was treated 15 years prior to the sampling and contributed most to the As immobilisation in the amended soils. This increases confidence in the long-term efficiency of As immobilisation using zerovalent Fe amendments. Both applied methods, sequential extraction and EXAFS, were in line for most of the samples in terms of their ability to highlight As immobilisation by poorly crystalline Fe phases.


Characterization of nucleohistone and nucleoprotamine components in the mature human sperm nucleus.
To simultaneously determine the localization of histones and protamines within human sperm nuclei. Immunofluorescence of the core histones and protamines and fluorescence in situ hybridization of the telomere region of chromosome 16 was assessed in decondensed human sperm nuclei. Immunofluorescent localization of histones, protamine 1 (PRM1) and protamine 2 (PRM2) along with fluorescence in situ hybridization localization of chromosome 16 telomeric sequences revealed a discrete distribution in sperm nuclei. Histones localized to the posterior ring region (i.e. the sperm nuclear annulus), whereas PRM1 and PRM2 appeared to be dispersed throughout the entire nucleus. The co-localization of the human core sperm histones with the telomeric regions of chromosome 16 is consistent with the reorganization of specific non-protamine regions into a less compacted state.


Replacement of Asp-162 by Ala prevents the cooperative transition by the substrates while enhancing the effect of the allosteric activator ATP on E. coli aspartate transcarbamoylase.
The available crystal structures of Escherichia coli aspartate transcarbamoylase (ATCase) show that the conserved residue Asp-162 from the catalytic chain interacts with essentially the same residues in both the T- and R-states. To study the role of Asp-162 in the regulatory properties of the enzyme, this residue has been replaced by alanine. The mutant D162A shows a 7700-fold reduction in the maximal observed specific activity, a twofold decrease in the affinity for aspartate, a loss of homotropic cooperativity, and decreased activation by the nucleotide effector adenosine triphosphate (ATP) compared with the wild-type enzyme. Small-angle X-ray scattering (SAXS) measurements reveal that the unliganded mutant enzyme adopts the T-quaternary structure of the wild-type enzyme. Most strikingly, the bisubstrate analog N-phosphonacetyl-L-aspartate (PALA) is unable to induce the T to R quaternary structural transition, causing only a small alteration of the scattering pattern. In contrast, addition of the activator ATP in the presence of PALA causes a significant increase in the scattering amplitude, indicating a large quaternary structural change, although the mutant does not entirely convert to the wild-type R structure. Attempts at modeling this new conformation using rigid body movements of the catalytic trimers and regulatory dimers did not yield a satisfactory solution. This indicates that intra- and/or interchain rearrangements resulting from the mutation bring about domain movements not accounted for in the simple model. Therefore, Asp-162 appears to play a crucial role in the cooperative structural transition and the heterotropic regulatory properties of ATCase.


Evidence for distinct steps in response preparation from a delayed response paradigm.
Task parameters still affect reaction times even when all necessary information for executing an action is presented prior to a Go signal to execute the action. Hypotheses in terms of short-term memory capacity, residual activation, and a separate motor-programming stage have been suggested to explain what can and cannot be prepared prior to a delayed Go signal. To test these hypotheses, we used a delayed response task, in which participants were to initiate a movement at onset of an imperative Go signal following the target stimulus. Across Experiments 1-3 we varied task properties including stimulus type, information uncertainty and response complexity, respectively, while controlling other factors. We also varied the time available to process the response by randomly varying the interval between onset of the target and the Go signal (i.e., the stimulus onset asynchrony, or SOA). If the preparation process is completed before initiation, the examined factor should display a strong interaction with SOA, with its effect disappearing at long SOAs. Our results showed strong, weaker, and no interaction patterns for the three factors, respectively, favoring the separate stage hypothesis, according to which response preparation is separated into steps to arrange kinematic specifications into muscle-controllable terms.


[Directed modification of the structure of cytochrome P-450 substrates as a method of generating new inducers of the microsomal monooxygenase system].
Using the previously obtained data on the substrate-type induction of monooxygenase by xenobiotics of phenobarbital type, the method of conversion of typical substrates for cytochrome P-450 into inducers of biosynthesis of this enzymatic system by blocking in the substrate molecule of the position subjected to oxidative conversion in the enzyme active center was tested. The introduction of the methyl group in the omega-1 position of amobarbital, of Cl- into positions 2 and 4 of biphenyl and the substitution of methyl groups for the isopropyl groups in the 4-N(CH3)2 position of aminopyrine provides for marked induction of these derivatives of cytochrome P-450 and some monooxygenase activities.


Physical activity and health during the menopausal transition.
The benefits of regular physical activity are well established, but evidence for a protective effect against the adverse health consequences accompanying the menopausal transition is limited. This article reviews that evidence, concluding that more physical activity is generally associated with fewer somatic and mood symptoms. Physical activity seems to minimize weight gain and changes in body composition and fat distribution experienced at midlife and might attenuate the rapid bone density loss that occurs. Given these benefits, clinicians treating perimenopausal women should encourage their patients to follow guidelines for physical activity (≥150 minutes a week of moderate-intensity activity).


Predictive Value of Serum NGAL and β2 Microglobulin in Blood and Urine amongst Patients with Acute Pancreatitis and Acute Kidney Injury.
This study aimed to explore the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) and β2 microglobulin (β2-MG) in blood and urine amongst patients with acute pancreatitis (AP) and acute kidney injury (AKI). The clinical data of 80 patients with AP, who were treated in the study hospital from November 2019, to November 2022, were selected for retrospective analysis. They were divided into AKI group (n = 25) and non-AKI group (n = 55) in accordance with the presence of AKI. The levels of serum NGAL and β2-MG in blood and urine were compared in both groups. Logistic regression analysis was used to explore the influencing factors of AKI in patients with AP and the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of serum NGAL and β2-MG in the blood and urine of patients with AKI and AP. The AKI group had higher serum NGAL and β2-MG in blood and urine than the non-AKI group. Logistic regression analysis showed that the high levels of serum NGAL and β2-MG in blood and urine were risk factors for AKI in patients with AP (p < 0.05). The areas under the curve (AUC), sensitivity and specificity of the combined prediction were 0.97, 84.00% and 98.20%, respectively, showing a good prediction efficiency. The increased levels of serum NGAL and β2-MG in blood and urine have a warning significance for patients with AP and AKI and a certain predictive value. So, their combination detection provides a reliable reference for the identification of clinical AKI.


The fusion site of envelope fragments from each serotype of Dengue virus in the P64k protein, influence some parameters of the resulting chimeric constructs.
To characterize the effect of the envelope fragment fusion site in the P64k protein from Neisseria meningitidis several chimeric constructs were obtained. One variant consisted in the insertion of the E fragment from each Dengue serotype within the lipoil binding domain of the P64k, whereas the other was based on the fusion of the envelope fragment at the C-terminus of the same meningoccocal protein. The results of the expression study revealed the majoritary levels with the C-terminus fusion variants of each serotype. In contrast, the highest proportion of soluble protein was reached with the insertion variants independently of the viral serotype. On the other hand, a significant level of degradation was detected for the semipurified forms of the insertion variants being remarkable in the Dengue 2 construct. Finally, the recognition by Dengue murine antibodies was similar independently of the fusion site. Regarding these results, we can affirm the suitability of the C-terminus fusion variants for further vaccine development as well as for a diagnostic system.


Comorbidity and polypharmacy impact neurobehavioral symptoms and symptom validity failure among post-9/11 veterans with mild traumatic brain injury.
The study aimed to examine the association between post-concussive comorbidity burdens [post-traumatic stress disorder (PTSD), depression, and/or headache] and central nervous system (CNS) polypharmacy (five or more concurrent medications) with reported neurobehavioral symptoms and symptom validity screening among post-9/11 veterans with a history of mild traumatic brain injury (mTBI). Administrative medical record data from the Department of Veterans Affairs (VA) were used in the study. Post-9/11 veterans with mTBI and at least 2 years of VA care between 2001 and 2019 who had completed the comprehensive traumatic brain injury evaluation (CTBIE) were included in the study. Retrospective cross-sectional design was used in the study. Neurobehavioral Symptom Inventory (NSI), International Classification of Diseases, Ninth Revision, and Clinical Modification diagnosis codes were included in the study. Of the 92,495 veterans with a history of TBI, 90% had diagnoses of at least one identified comorbidity (PTSD, depression, and/or headache) and 28% had evidence of CNS polypharmacy. Neurobehavioral symptom reporting and symptom validity failure was associated with comorbidity burden and polypharmacy after adjusting for sociodemographic characteristics. Veterans with concurrent diagnoses of PTSD, depression, and headache were more than six times more likely [Adjusted odds ratio = 6.55 (99% CI: 5.41, 7.92)]. to fail the embedded symptom validity measure (Validity-10) in the NSI. TBI-related multimorbidity and CNS polypharmacy had the strongest association with neurobehavioral symptom distress, even after accounting for injury and sociodemographic characteristics. Given the regular use of the NSI in clinical and research settings, these findings emphasize the need for comprehensive neuropsychological evaluation for individuals who screen positively for potential symptom overreporting, the importance of multidisciplinary rehabilitation to restore functioning following mTBI, and the conscientious utilization of symptom validity measures in research efforts.


Anaerobic susceptibility tests. Evaluation of the stability of antimicrobials in Wilkens-Chalgren broth and the effect of media prereduction.
The stability of eight antimicrobial agents in WILKENS-CHALGREN broth was evaluated. The activities of only carbenicillin and benzyl penicillin were significantly decreased after storage for eight weeks at--20 degrees C. Anaerobic reduction of the susceptibility testing broth prior to inoculation was found to be unnecessary.


Impact of a patient safety leadership program on head nurses and clinical nurses: a quasi-experimental study.
to evaluate the impact of a patient safety leadership program on head nurses and clinical nurses in the same nursing unit. a pre-post quasi-experimental study that included 60 head nurses and 240 clinical nurses was conducted. Only the head nurses received patient safety leadership program training for 12 months. Before and after the training, the General Self-Efficacy Scale was completed by the head nurses, and the General Self-Efficacy Scale, the Hospital Leadership Behavior Assessment Scale, the Safety Behavior Scale and the Maslach Burnout Inventory were completed by the clinical nurses. Descriptive and inferential analyses of the data were performed using absolute and relative frequencies, means and standard deviations, and paired t-tests to assess the effect of the training. both the head nurses' and the clinical nurses' self-efficacy increased significantly (p <0.01) after the training. The leadership behavior of the head nurses and the safety behavior of the clinical nurses also improved significantly (p<0.05). We observed a statistically significant reduction in "emotional exhaustion" and an increase in "personal accomplishment" among the clinical nurses (P<0.001). the patient safety leadership program had a positive impact on the head nurses' self-efficacy and leadership behavior and the clinical nurses' self-efficacy, safety behavior and job burnout.


Dimensions of stereotypical attitudes among older adults: Analysis of two countries.
Much research on attitudes towards older adults has used younger adults as participants and identified a range of negative attitudes towards older persons. Comparatively little literature has explored the attitudes of older adults themselves towards their own age cohort. The present study explicitly compared attitudes towards other older adults from samples of 195 older adults in Australia and 172 older Canadians. Attitudinal measures included the Aging Attitudes Questionnaire (assesses older adults' attitudes toward other older adults), Fraboni Scale of Ageism (assesses younger adults' attitudes toward older adults) and the Reactions to Aging Questionnaire (assesses attitudes toward one's own aging), as well as a scale measuring knowledge of aging, the Facts on Aging Quiz, adapted for Australia and Canada. Responses on the three attitudinal measures were subjected to principal components analysis. Two components emerged in both samples, one defined by the Reactions to Aging Questionnaire and Aging Attitudes Questionnaire scales and the second by the Fraboni Scale of Ageism scales. Regression analyses to ascertain prediction of scores on the Facts on Aging Quiz, adapted for Australia and Facts on Aging Quiz, adapted for Canada showed that only the Aging Attitudes Questionnaire scale for Physical Changes predicted scores on the Facts on Aging Quiz, adapted for Australia and no attitudes predicted Facts on Aging Quiz, adapted for Canada scores. It appears that older adults distinguish between their own aging and aging in others. Knowledge of aging appears to be predicted only by attitudes toward physical changes. Given increasing proportions of older adults in the population, as well as increasing access to aging information available to older cohorts, continued research on how older adults view themselves and the aging process is important, and will almost certainly continue to evolve over time. Geriatr Gerontol Int 2016; 16: 1226-1230.


Surface engineering of carbon selenide nanofilms on carbon cloth: An advanced and ultrasensitive self-supporting binder-free electrode for nitrite sensing.
Large uptakes of nitrite have been proven to be detrimental to human health, therefore, the development of high-performance nitrite sensors is highly emergent. Herein, a carbon selenide nanofilms modified carbon fiber cloth (CSe2 NF/CC) electrode was obtained via in-situ synthesis to detect nitrite. The electrode integrates the collective merits of macroporous CC and pleated carbon selenide nanofilms, possessing a low overpotential of 0.83 V, a high electrochemical active surface area (EASA) of 5.39 cm2, great electrical conductivity, and fast charge transport as well as ion diffusion. The proposed electrode achieved a low limit of detection of 0.04 μmol L-1 (S/N = 3), a high sensitivity of 2048.56 μA mmol L-1 cm-2, excellent selectivity, and long-term stability. Additionally, the CSe2 NF/CC was successfully used for nitrite detection in different food samples such as pickled vegetables and sausage samples.


Hippocalcin: a calcium-binding protein of the EF-hand superfamily dominantly expressed in the hippocampus.
Hippocalcin is a recently identified Ca(2+)-binding protein with three EF-hand structures, dominantly expressed in the hippocampal pyramidal layer. The complete amino acid sequence of hippocalcin deduced from the cDNA is composed of 195 residues, has a calculated molecular mass of 22,574 daltons, and has a striking sequence homology to those of visinin, recoverin, S-modulin, neurocalcins and neural visinin-like proteins. Hippocalcin binds 3 mol of Ca2+ per mol of protein at submicromolar Ca2+ levels, and associates the plasma membrane in a Ca(2+)-dependent manner. Hippocalcin is myristoylated at its NH2-terminal glycine residue, and this modification is a key event in terms of its membrane-association property.


Effect of ultraviolet-C light disinfection at terminal patient discharge on hospital-acquired infections in bone marrow transplant and oncology units.
We employed an interrupted time series analysis to assess the impact of ultraviolet-C light disinfection at terminal discharge in an oncology unit and a bone marrow transplant unit on the incidence of hospital-acquired infections. The deployment of ultraviolet-C light disinfection was associated with a significant decrease in the rate of Clostridioides difficile infections and a significant decrease in the rate of central line-associated blood stream infections in the bone marrow transplant unit.


Ligation of an unusually large vessel during maxillary sinus floor augmentation. A case report.
The purpose of the present case report was to document a maxillary sinus floor augmentation procedure involving ligation of a blood vessel with a nearly 3-mm diameter in the lateral wall of the maxillary sinus. A bilateral maxillary sinus floor augmentation procedure was performed in a 51-year-old healthy man. The preoperative computed tomography scan revealed a bony canal within the lateral maxillary sinus wall of the right as well as the left side close to the alveolar ridge. A vessel with a diameter of nearly 3 mm was identified during the sinus floor augmentation on the left side. The vessel was exposed and ligated. A vessel with a diameter of approximately 1 mm was identified on the right side and the sinus floor augmentation was performed without ligation. No complications were observed and the postoperative healing was uneventful. Although accidental laceration of vessels with an unusually large diameter during maxillary sinus floor augmentation is not life-threatening, impaired visualisation may compromise the augmentation procedure, including the elevation of the Schneiderian membrane. Moreover, postoperative bleeding and formation of a haematoma may occur. Therefore, ligation of vessels with an unusually large diameter is recommended during maxillary sinus floor augmentation to minimise intra- and postoperative complications.


Down-regulation of AUXIN RESPONSE FACTORS 6 and 8 by microRNA 167 leads to floral development defects and female sterility in tomato.
Auxin regulates the expression of diverse genes that affect plant growth and development. This regulation requires AUXIN RESPONSE FACTORS (ARFs) that bind to the promoter regions of these genes. ARF6 and ARF8 in Arabidopsis thaliana are required to promote inflorescence stem elongation and late stages of petal, stamen, and gynoecium development. All seed plants studied thus far have ARF6 and ARF8 orthologues as well as the microRNA miR167, which targets ARF6 and ARF8. Whether these genes have broadly conserved roles in flower development is not known. To address this question, the effects of down-regulation of ARF6 and ARF8 were investigated through transgenic expression of Arabidopsis MIR167a in tomato, which diverged from Arabidopsis before the radiation of dicotyledonous plants approximately 90-112 million years ago. The transgenic tomato plants overexpressing MIR167a exhibited reductions in leaf size and internode length as well as shortened petals, stamens, and styles. More significantly, the transgenic plants were female-sterile as a result of failure of wild-type pollen to germinate on the stigma surface and/or to grow through the style. RNA-Seq analysis identified many genes with significantly altered expression patterns, including those encoding products with functions in 'transcription regulation', 'cell wall' and 'lipid metabolism' categories. Putative orthologues of a subset of these genes were also differentially expressed in Arabidopsis arf6 arf8 mutant flowers. These results thus suggest that ARF6 and ARF8 have conserved roles in controlling growth and development of vegetative and flower organs in dicots.


Approaches to inferring multi-regional interactions from simultaneous population recordings: Inferring multi-regional interactions from simultaneous population recordings.
Most past studies of neural representations and dynamics have focused on recordings from single brain areas. However, growing evidence of brain-wide, parallel representations of cognitive variables suggests that analyzing neural representations and dynamics in individual brain areas can benefit from understanding the context of multi-regional interactions that support them. Moreover, perturbation experiments revealed that the manner in which these parallel representations interact with each other can differ dramatically across different pairs of brain areas. Recent advances in recording technology offer a potentially powerful substrate to study how multi-regional interactions coordinate neural representations in individual brain areas and dictate behavior on a single-trial basis through simultaneous recordings of multiple brain areas. We review pragmatic approaches to studying multi-regional interactions and illustrate them in the concrete context of a rodent delayed response task paradigm.


The modified fluorescence based vesicle fluctuation spectroscopy technique for determination of lipid bilayer bending properties.
Lipid bilayer is the main constitutive element of biological membrane, which confines intracellular space. The mechanical properties of biological membranes may be characterized by various parameters including membrane stiffness or membrane bending rigidity, which can be measured using flicker noise spectroscopy. The flicker noise spectroscopy exploits the spontaneous thermal undulations of the membrane. The method is based on the quantitative analysis of a series of microscopic images captured during thermal membrane fluctuations. Thus, measured bending rigidity coefficient depends on the image quality as well as the selection of computational tools for image processing and mathematical model used. In this work scanning and spinning disc confocal microscopies were used to visualize fluctuating membranes of giant unilamellar vesicles. The bending rigidity coefficient was calculated for different acquisition modes, using different fluorescent probes and different image processing methods. It was shown that both imaging approaches gave similar bending coefficient values regardless of acquisition time. Using the developed methodology the effect of fluorescent probe type and aqueous phase composition on the value of the membrane bending rigidity coefficient was measured. Specifically it was found that the bending rigidity coefficient of DOPC bilayer in water is smaller than that determined for POPC membrane. It has been found that the POPC and DOPC bending rigidities coefficient in sucrose solution was lower than that in water. Fluorescence imaging makes possible the quantitative analysis of membrane mechanical properties of inhomogeneous membrane.


A new stable epithelial cell line (RK-L) from normal rat kidney.
A stable epithelial cell line has been established from the kidneys of a normal Sprague-Dawley rat. This line, termed RK-L, has a high proliferative capacity (minimal doubling time 12.3 h) and can be grown in medium containing 1% fetal bovine serum. Thus far, the line has been carried through more than 60 serial passages. The RK-L cells were found to display similarities with kidney tubule cells. Using light microscopy, confluent cultures were seen as pavement-like monolayers forming domes, which are thought to result from transepithelial fluid transport. Electron microscopy revealed polarized cells that had microvilli on the apical surface, junction complexes in the apical part of the lateral cell membrane, and a basal lamina-like layer. Pinocytotic activity was indicated by infoldings of the apical plasma membrane and the formation of vesicles. The RK-L line should prove useful for investigations of kidney tubule transport mechanisms.


Erratum to: Prevalence of resistant hypertension and associated factors for blood pressure control status using Korean ambulatory blood pressure monitoring registry data.
[This corrects the article DOI: 10.1186/s40885-016-0045-x.].


Gammadelta T-cell large granular lymphocyte (LGL) leukemia with spontaneous remission.
T-cell large granular lymphocyte (LGL) leukemia is a clonal disorder with an indolent clinical course. In July 1995, a 46-year-old Japanese man was admitted to our hospital because his anemia had progressed. He had a white blood cell count of 3.9 x 10(9)/L with 75% lymphocytes, which were intermediate to large and had almost round nuclei and azurophilic granules, and anemia with a red blood cell count (RBC) of 2.69 x 10(12)/L, hemoglobin (Hb) of 9.5 g/dL, and hematocrit (Hct) of 28.3%. Electron microscopic examination showed that most of the lymphocytes had a parallel tubular array and dense core granules in their cytoplasm. Flow cytometry and Southern blotting of the T-cell antigen receptor (TCR) genes using the peripheral blood species showed monoclonal proliferation of LGLs with a CD3+, TCRgammadelta+, CD4-, CD8-, CD16+, CD56-, CD57-, HLA-DR+ phenotype, and a TCR gamma gene rearrangement, respectively, suggesting that the patient was diagnosed as having gammadelta T-cell LGL leukemia. He had no symptoms, organomegaly, or skin lesions. About 1.5 years after diagnosis, the anemia gradually improved with disappearance and appearance of a rearranged band in the TCR-gamma gene and TCR-beta gene, respectively. About 7 years after diagnosis, the anemia improved completely with a RBC of 5.01 x 10(12)/L, Hb of 14.8 g/dL, and Hct of 44.3%, and he was in complete remission without TCR-beta and -gamma gene rearrangements. He had received no therapy. This is the first report of spontaneous remission of gammadelta T-cell LGL leukemia.


Continuous infusion vincristine and bleomycin with high dose methotrexate for resistant non-Hodgkin's lymphoma.
Sixteen patients with resistant non-Hodgkin's lymphoma were treated with continuous infusions of vincristine (1-2 mg/m2 daily X 2 days) and bleomycin (0.25 mg/kg bolus dose, then 0.25 mg/kg/daily X 5 days). Responding patients received high dose methotrexate (1500 mg/m2) with citrovorum rescue on days 15, 22, 29, 36. Treatment cycles were repeated every six weeks in responding patients. The response frequency was 50% (three complete and five partial responses). Median response duration was 29 weeks. Major toxicity included stomatitis (63%) and leukopenia (44%). One episode each of possible hypersensitivity pneumonitis and paralytic ileus occurred. Continuous infusions of vincristine and bleomycin should be studied further in less critically ill patients.


Origin and molecular specification of oligodendrocytes in the telencephalon.
Previous studies have demonstrated that oligodendrocytes in the spinal cord and brainstem originate from restricted domains of ventral neuroepithelium under the influence of sonic hedgehog protein (SHH). However, the origin of oligodendrocytes in the telencephalon, the most anterior part of the CNS, has not been established. A recent study has precisely mapped the origin of telencephalic oligodendrocytes to a small region of the ventral telencephalon in rodents, and has presented evidence that telencephalic oligodendrogenesis is, like that of the spinal cord, under the influence of SHH signaling.


Stereoselective S-oxygenation of an aryl-trifluoromethyl sulfoxide to the corresponding sulfone by rat liver cytochromes P450.
Toltrazuril sulfoxide (TZR.SO) is the metabolite of the antiparasitic drug toltrazuril (TZR; 1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl- 1,3,5-triazine-2,4,6(1H,3H,5H)-trione). The results of the present paper demonstrate that TZR.SO was metabolized by rat liver microsomes to the corresponding sulfone (TZR.SO2). The reaction was mediated almost exclusively by different cytochromes P450, the most active being cytochromes P450 3A. TZR.SO exists as a racemic mixture; when each enantiomer was incubated separately in the presence of untreated rat liver microsomes, a 7.3-fold difference in the rate of S-oxygenation was found, indicating a marked substrate enantioselectivity for the reaction.


Models of the bis-histidine-coordinated ferricytochromes: Mössbauer and EPR spectroscopic studies of low-spin iron(III) tetrapyrroles of various electronic ground states and axial ligand orientations.
The EPR and magnetic Mössbauer spectra of a series of axial ligand complexes of tetrakis(2,6-dimethoxyphenyl)porphyrinatoiron(III), [(2,6-(OMe)(2))(4)TPPFeL(2)](+), where L= N-methylimidazole, 2-methylimidazole, or 4-(dimethylamino)pyridine, of one axial ligand complex of tetraphenylporphyrin, the bis(4-cyanopyridine) complex [TPPFe(4-CNPy)(2)](+), and of one axial ligand complex of tetraphenylchlorin, [TPCFe(ImH)(2)](+), where ImH=imidazole, have been investigated and compared to those of low-spin Fe(III) porphyrinates and ferriheme proteins reported in the literature. On the basis of this and previous complementary spectroscopic investigations, three types of complexes have been identified: those having (d(xy))(2)(d(xz),d(yz))(3) electronic ground states with axial ligands aligned in perpendicular planes (Type I), those having (d(xy))(2)(d(xz),d(yz))(3) electronic ground states with axial ligands aligned in parallel planes (Type II), and those having the novel (d(xz),d(yz))(4)(d(xy))(1) electronic ground state (Type III). A subset of the latter type, with planar axial ligands aligned parallel to each other or strong macrocycle asymmetry that yield rhombic EPR spectra, cannot be created using the porphyrinate ligand. Type I centers are characterized by "large g(max)" EPR spectra with g>3.2 and well-resolved, widely spread magnetic Mössbauer spectra having A(zz)/ g(N)mu(N)>680 kG, with A(xx) negative in sign but much smaller in magnitude than A(zz), while Type II centers have well-resolved rhombic EPR spectra with g(zz)=2.4-3.1 and also less-resolved magnetic Mössbauer spectra, and usually have A(zz)/ g(Nmu(N) in the range of 440-660 kG (but in certain cases as small as 180 kG) and A(xx) again negative in sign but only somewhat smaller (but occasionally larger in magnitude) than A(zz), and Type III centers have axial EPR spectra with g( upper left and right quadrants ) approximately 2.6 or smaller and g( vertical line )<1.0-1.95, but often not resolved, and less-resolved magnetic Mössbauer spectra having A(zz)/ g(N)mu(N) in the range of 270-400 kG, and A(xx) again negative in sign but much smaller in magnitude than A(zz). An exception to this rule is [TPPFe(4-CNPy)(2)](+), which has A(xx)/ g(N)mu(N)=-565 kG, A(yy)/ g(N)mu(N)=629 kG, and A(zz)/ g(N)mu(N)=4 kG. A subset of Type II complexes (Type II') have rhombicities ( V/Delta) much greater than 0.67 and A(zz)/ g(N)mu(N) ranging from 320 to 170 kG, with A(xx) also negative but with the magnitude of A(xx) significantly larger than that of A(zz). These classifications are also observed for a variety of ferriheme proteins, and they lead to linear correlations between A(zz) and either A(xx), g(zz), or V/Delta for Types I and II (but not for A(zz) versus V/Delta for Type II'). Not enough data are yet available on Type III complexes to determine what, if any, correlations may be observed.


Does mediator use contribute to the spacing effect for cued recall? Critical tests of the mediator hypothesis.
When study is spaced across sessions (versus massed within a single session), final performance is greater after spacing. This spacing effect may have multiple causes, and according to the mediator hypothesis, part of the effect can be explained by the use of mediator-based strategies. This hypothesis proposes that when study is spaced across sessions, rather than massed within a session, more mediators will be generated that are longer lasting and hence more mediators will be available to support criterion recall. In two experiments, participants were randomly assigned to study paired associates using either a spaced or massed schedule. They reported strategy use for each item during study trials and during the final test. Consistent with the mediator hypothesis, participants who had spaced (as compared to massed) practice reported using more mediators on the final test. This use of effective mediators also statistically accounted for some - but not all of - the spacing effect on final performance.


Comparing results of digital photoplethysmography in two groups of chronic obstructive pulmonary disease patients with and without high pulmonary artery pressure.
Digital photoplethysmography (D-PPG) is a newly introduced method of optical screening of deep vein thrombosis (DVT) by recording changes in the size of limb due to tissue fluid. The objective of this study is to assess the effect of high pulmonary artery pressure (PAP) and consequently increased venous system pressure on D-PPG test results. Forty-five patients with and 45 patients without PAP pressure were enrolled in the study and divided into two groups. All the patients had a history of chronic obstructive pulmonary disease (COPD). D-PPG test was performed for both legs of all the patients and the results of the two groups were compared. Also, all patients underwent duplex sonography for ruling out DVT. Using venous refilling time (RT) of <22 s as the optimal cut-off point, it was found that 32 (35%) legs of patients with and 39 (43%) legs of patients without high PAP had positive D-PPG test. Although the rate of positive D-PPG test was higher in patients with high PAP, this was not statistically significant (P = 0.28). Moreover, overall correlation between RT and venous pump detected by D-PPG and PAP was r = -0.11 (P = 0.2) and r = -0.01 (P = 0.6), respectively. Our results showed that the rate of positive D-PPG test results is slightly higher in patients with pulmonary hypertension, but this difference is not statistically significant. Therefore, increased PAP could be excluded as a confounding factor of D-PPG test.


Surface water disinfection by chlorination and advanced oxidation processes: Inactivation of an antibiotic resistant E. coli strain and cytotoxicity evaluation.
The release of antibiotics into the environment can result in antibiotic resistance (AR) spread, which in turn can seriously affect human health. Antibiotic resistant bacteria have been detected in different aquatic environments used as drinking water source. Water disinfection may be a possible solution to minimize AR spread but conventional processes, such as chlorination, result in the formation of dangerous disinfection by-products. In this study advanced oxidation processes (AOPs), namely H2O2/UV, TiO2/UV and N-TiO2/UV, have been compared with chlorination in the inactivation of an AR Escherichia coli (E. coli) strain in surface water. TiO2 P25 and nitrogen doped TiO2 (N-TiO2), prepared by sol-gel method at two different synthesis temperatures (0 and -20°C), were investigated in heterogeneous photocatalysis experiments. Under the investigated conditions, chlorination (1.0 mg L(-1)) was the faster process (2.5 min) to achieve total inactivation (6 Log). Among AOPs, H2O2/UV resulted in the best inactivation rate: total inactivation (6 Log) was achieved in 45 min treatment. Total inactivation was not observed (4.5 Log), also after 120 min treatment, only for N-doped TiO2 synthesized at 0°C. Moreover, H2O2/UV and chlorination processes were evaluated in terms of cytotoxicity potential by means of 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenylte-trazolium colorimetric test on a human-derived cell line and they similarly affected HepG2 cells viability.


Calmodulin modulates hepatic membrane polarity by protein kinase C-sensitive steps in the basolateral endocytic pathway.
Membrane polarity is maintained by a complex intermingling of various trafficking pathways, including basolateral and apical endocytosis. The present work was undertaken to better define the role of basolateral endocytic transport in apical membrane homeostasis. When polarized HepG2 hepatoma cells were incubated with calmodulin antagonists, the cells lost their polarity, as reflected by an inhibition of lipid transport of a fluorescent sphingomyelin to the apical membrane and an impediment of its recycling to the basolateral membrane. Instead, an accumulation of the lipid in dilated early endosomal compartments was observed, presumably due to a frustration of vesiculation. Interestingly, lipid transport to the apical pole, lipid recycling to the basolateral membrane and cell polarity were reestablished, while dilated compartments disappeared, when the cells were simultaneously treated with specific inhibitors of protein kinase C (PKC). Consistently, following activation of PKC, extensive dilation/vacuolation of early sorting endosomes was observed, very similar as seen upon treatment with calmodulin antagonists. Thus, the results indicate that membrane trafficking at early steps of the basolateral endocytic pathway in HepG2 cells is regulated by an intricate interplay between calmodulin and PKC. This interference, although not affecting endocytosis as such, compromises cell polarity by impeding membrane trafficking from early endosomes to the apical membrane.


Findings on the efficacy and safety of thrombolytic therapy. An analysis of key clinical trials.
This past decade has seen remarkable progress in the use of thrombolytic agents to increase survival after AMI. Early IC strategies and several reperfusion trials of thrombolytic therapy visually demonstrated the efficacy of these agents. The life-saving benefits of thrombolysis have been illustrated by the large multicenter mortality trials with decreases in mortality from 15% to 8%. Mortality rates in AMI treated with rt-PA has been shown to be much lower in studies using full-dose IV heparin: TIMI IIB 4.9% (6 weeks), ASSET 7.2% (1 month), ECSG 3.7% (21 days). SK and APSAC are most effective at achieving thrombolysis when administered early in the course of AMI; rt-PA retains its superior efficacy on the older thrombus. When patients are properly screened for contraindications, IV-thrombolytic therapy is a safe and highly effective treatment for AMI. The choice of agent remains that of personal or institutional preference. Only when definitive results of ongoing and future head-to-head clinical trials are published can the effectiveness of the agents be compared accurately. Until these data are available, the most important lesson is to treat and treat quickly.


Peptic ulcers in the elderly is a surgical disease.
Operative management for peptic ulcer disease (PUD) has changed significantly over the last 30 years. For a 15-year period, records of patients undergoing operative management for peptic ulcer disease were stratified into age groups and examined with respect to presentation, type of operation, and risk factors. In all, 154 patients underwent surgery for PUD during the 1990s. Elderly patients were more likely to require an emergent operation (91%, P = 0.005), present with hemodynamic instability (25%, P = 0.025), and have a longer hospital stay (21 days, P = 0.012). Among the elderly in the 1990s as compared with the 1980s, there was increased use of nonsteroidal anti-inflammatory drugs ([NSAIDs] (49%, P = 0.005), decreased tobacco use (22%, P = 0.014), and less likelihood of postoperative renal failure (6%, P = 0.014). Elderly patients in the 1990s comprise the majority of cases presenting in a more unstable condition as compared with patients <60 years old, but show similar rates of morbidity and mortality. Elderly patients undergoing surgery for PUD have shown an increase in use of NSAIDs over the last 15 years. The types of procedures have not changed, but operations are more likely to be an emergent basis.


Transcranial Magnetic Stimulation and Diffusion Tensor Tractography for Evaluating Ambulation after Stroke.
We aimed to investigate the usefulness of combining transcranial magnetic stimulation (TMS) and diffusion tensor tractography (DTT) to evaluate corticospinal tract (CST) integrity and subsequently predict ambulatory function after middle cerebral artery (MCA) stroke. Forty-three patients with first MCA stroke underwent TMS and DTT to evaluate CST integrity. Patients were classified into four groups according to the presence of motor-evoked potentials (MEPs) obtained from the tibialis anterior muscle and CST integrity. Motor impairment and functional status were assessed using the Fugl-Meyer Assessment, Functional Ambulation Category, and Korean modified Barthel Index, both at the time of admission and after 4 weeks of rehabilitation. Patients with the presence of both measurable MEPs and a preserved CST showed better motor recovery and ambulatory function than other groups at the 4-week follow-up. Intact CSTs were not visualized in patients without detectable MEPs. Among the patients displaying MEPs, those with preserved CSTs showed better recovery of paretic lower extremities. Combined assessment using TMS and DTT to evaluate CST integrity confers advantages in predicting motor and ambulation recovery in patients with MCA stroke.


Early switch in tyrosine kinase inhibitor therapy for patients with chronic myeloid leukemia: An emerging clinical question.
Response to frontline BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) therapy is associated with an improved prognosis for patients with chronic myeloid leukemia (CML). Accordingly, the National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) recommend the use of specific response milestones (eg, BCR-ABL1≤10% on the International Scale at 3 months) to assess treatment success and inform follow-up care, including potentially switching to another TKI therapy. However, prior to any treatment change, the potential benefits and risks of each TKI and the goals of the patient must be considered. Here we review current NCCN and ELN response recommendations for patients with CML, highlight the impact of early responses on long-term prognosis, and discuss several reasons patients may consider a switch in TKI therapy. We also review completed and ongoing clinical studies involving a switch in frontline therapy for patients with CML, including those with a treatment-free remission phase.


Physiologic profile associated with severe multisystem inflammatory syndrome in children: a retrospective study.
The purpose of this study was to describe the clinical presentation and physiologic profile of individuals with varying degrees of severity of multisystem inflammatory syndrome in children (MIS-C). We performed a retrospective study of children diagnosed with MIS-C admitted to a single quaternary children's hospital from May 2020 to April 2021. We created an MIS-C severity score using the following parameters: hospital admission status (e.g., floor vs intensive care unit), need for inotropic or vasoactive medications, and need for mechanical ventilation. Univariate and multivariate analyses were performed to associate risk factors corresponding to the MIS-C severity score. The study included 152 children who were followed for 14 days post hospital admission. A stepwise forward selection process identified seven physiologic variables associated with "severe" MIS-C according to a logistic regression. Specifically, a combination of elevated creatinine (p = 0.013), international normalized ratio (p = 0.002), brain natriuretic peptide (p = 0.001), white blood cell count (p = 0.009), ferritin (p = 0.041), respiratory rate (p = 0.047), and decreased albumin (p = 0.047) led to an excellent discrimination between mild versus severe MIS-C (AUC = 0.915). This study derived a physiologic profile associated with the stratification of MIS-C severity. Based on a cohort of 152 individuals diagnosed with MIS-C, this study derived a nomenclature that stratifies the severity of MIS-C. Investigated demographic, presentational vital signs, and blood analytes associated with severity of illness. Identification of a multivariate physiologic profile that strongly associates with MIS-C severity. This model allows the care team to recognize patients likely to require a higher level of intensive care.


The influence of prolonged treatment with D-penicillamine on the immune response in Wilson's disease.
Humoral and cell-mediated immunity were studied in a group of patients with Wilson's disease not previously treated with D-penicillamine, and in a group of patients treated with the drug for more than two years. The previously untreated patients showed an exaggerated humoral immune response, i. e. increased levels of IgG and, IgM, higher titer of antibodies to Kunin's antigen, and depression of cell-mediated immunity, namely a decreased response to DNCB, decreased lymphocyte transformation after stimulation with Con A, PPD, Candida and streptokinase and a reduced response to streptokinase in the MIF test. After treatment the humoral response returned to normal, and in the case of IgA and antibodies to S. typhi O antigen, it even dropped below normal values. The cell-mediated immune response returned to normal with the exception of lymphocyte transformation by PHA and Candida albicans. In in vitro studies it was found that D-penicillamine had no influence on lymphocyte transformation when PHA and Con A were used as mitogens. With PPD as antigen, lymphocyte stimulation and migration inhibition were inhibited by concentrations of penicillamine ranging from 6 to 1000 microgram/ml.


Diagnostic accuracy of a rapid fecal test to confirm H pylori eradication after therapy: prospective comparison with a laboratory stool test.
To investigate the clinical performances of rapid stool test (ImmunoCard STAT HpSA, Meridian Diagnostic Inc.) in the evaluation of eradication therapy of H pylori and to compare it with a well-known and validated laboratory stool test (Amplified IDEA Hp StAR, Dako). Stool samples of 122 patients were evaluated after eradication therapy of H pylori. H pylori status was assessed by 13C-urea breath test (UBT). Stool specimens were tested using either the rapid immunoassay kit or the laboratory immunoassay kit. Forty-three patients were infected and 79 non-infected. Sensitivity and specificity of ImmunoCard STAT and Hp StAR were 58.14% and 76.4%, and 97.47% and 98.73%, respectively (P > 0.05). Overall agreement between the two tests was 92.6% (113 of 122 cases). ImmunoCard STAT seems to have rather low performances, and it cannot be regarded as a reliable tool in the post-treatment setting. Also Hp StAR cannot be recommended to confirm H pylori eradication after treatment.


Willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Meru District, Arusha Region, Northern Tanzania.
The ability for women to self-collect human papillomavirus (HPV) samples can potentially reduce the risk of cervical cancer and increase screening coverage. To assess the willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Arusha region, northern Tanzania. A hospital-based cross-sectional study was conducted among 706 women aged 18-55 years in Meru District Hospital and Usa River Health Centre from March to April 2019. Face-to-face intervies were conducted using a questionnaire. Data analysis was performed using Stata version 14.0. The log-binomial regression was used to determine factors associated with willingness to self-collection of HPV samples. Majority (70%) of the women were willing to self-collection of HPV samples for cervical cancer screening and was associated with attending Meru District hospital (PR=2.02, 95%CI 1.77-2.31); good knowledge about cervical cancer warning signs (PR=1.11, 95%CI 1.01-1.22), prevention (PR=1.13, 95%CI 1.04-1.20), and symptoms (PR=1.61, 95%CI 1.33-1.93); and having formal employment (PR=1.22, 95%CI 1.07-1.37). The majority of women were willing to self-collect HPV samples for cervical cancer screening. Self-collection is, therefore, an acceptable and viable means of screening for cervical cancer, which has great implications for Tanzania from a health policy perspective.


Demystifying biomedical signals: a student centred approach to learning signal processing.
The processing and analysis of physiological signals has become firmly established in clinical medicine and biomedical research. Many of the users of this technology however do not come from an engineering or science background, and traditional approaches in teaching signal processing are thus not appropriate for them. We have therefore developed a series of modular courses that are aimed specifically at an audience with a background in medicine, health-care or the life-sciences. In these courses, we focus on the concepts, principles and rationale of applying signal processing methods, rather than the mathematical foundations of the techniques. Thus, we aim to remove some of the perceived 'mystery' often surrounding this subject. The very practical approach, with hands-on experience using the MATLAB software, has been well received, with strong evidence that students have learnt to apply their knowledge. This paper describes the learning and teaching approach taken, and some of the experience acquired.


Effect of testosterone and oestradiol on erythropoietin production in vitro.
The effects of testosterone and oestradiol on erythropoietin production by mouse fetal liver in primary culture was studied. No stimulatory effect on in vitro erythropoietin production was observed by any of the oestradiol concentrations employed [10(-10)M to 10(-6)M]: whereas testosterone, only over a dose range of 10(-12)M to 10(-10)M, stimulated erythropoietin production by mouse fetal liver in culture. In addition, a stimulatory effect of testosterone on fetal liver tissue was obtained by injecting testosterone (20 mg/mouse) intramuscularly into pregnant mice 4 d prior to obtaining the fetal liver tissue for culture. Therefore, it is concluded that testosterone can exert a direct stimulatory effect on erythropoietin production by mouse fetal liver.


Blunt Isolated Small Bowel Perforation Intervention: Does a Delay in Management Matter?
Blunt small bowel injury is rare, and its timely diagnosis may be difficult. The effects of a delayed intervention on prognosis are unclear. We aimed to determine whether the time to surgical intervention affects outcomes in patients with blunt small bowel perforation. The study was performed between March 2010 and December 2018 in adults (age >18 years) who initially underwent computed tomography and small bowel surgery only and survived more than one day postoperatively. They were categorized into three groups based on injury-to-surgery time intervals: ≤8, 8-24, and >24 h; similarly, they were also categorized into two groups of ≤24 and >24 h. Bowel resection, length of stay (LOS), intensive care unit (ICU) LOS, morbidity, and mortality were analyzed as outcomes in 52 patients. The number of patients in the three groups (≤8, 8-24, and >24 h) based on the time-to-surgery was 33, 13, and 6, respectively. On comparing the three groups, there were no significant differences in LOS (24 [18-35], 21 [10-40], and 28 [20-98] days, respectively; p=0.321), ICU LOS (2 [1-12], 4 [2-26], and 11 [7-14] days; respectively, p=0.153), mortality (3% (n = 1), 15% (n = 2), and 0%, respectively; p=0.291), and morbidity (46% (n = 15), 39% (n = 5), and 50% (n = 3), respectively; p=0.871). However, there was a significant difference between the groups in bowel resection (67% (n = 22), 31% (n = 4), and 83% (n = 5), respectively; p=0.037). Additionally, there was no significant difference in outcomes between the two groups (≤24 and >24 h) with small bowel perforation. Delay in surgical intervention following blunt abdominal trauma may not affect the outcomes of patients with small bowel injuries, such as LOS, ICU LOS, morbidity, and mortality, except bowel resection.


Differences in Expressivity Based on Attractiveness: Target or Perceiver Effects?
A significant association exists between adults' expressivity and facial attractiveness, but it is unclear whether the association is linear or significant only at the extremes of attractiveness. It is also unclear whether attractive persons actually display more positive expressivity than unattractive persons (target effects) or whether high and low attractiveness influences expressivity valence judgments (perceiver effects). Experiment 1 demonstrated adult ratings of attractiveness were predictive of expressivity valence only for high and low attractive females and medium attractive males. Experiment 2 showed that low attractive females actually display more negative expressivity than medium and high attractive females, but there were no target effects for males. Also, attractiveness influenced expressivity valence judgments (perceiver effects) for both females and males. Our findings demonstrate that low attractive females are at a particular disadvantage during social interactions due to their low attractiveness, actual displays of negative expressivity, and perceptions of their negative expressivity.


Rapid detection of respiratory syncytial virus by a biotin-enhanced immunoassay: test performance by laboratory technologists and housestaff.
A biotin-enhanced enzyme immunoassay (EIA) for respiratory syncytial virus (RSV) antigen detection (TESTPACK RSV) was prospectively compared with virus isolation in cell culture and immunofluorescence. Of 156 nasopharyngeal swab specimens from infants with respiratory symptoms, 81 (52%) yielded RSV in culture. Compared with culture the sensitivity of the EIA was 95% and specificity was 92%; the specificity increased to 97% with a blocking assay. Compared with immunofluorescence the sensitivity of EIA was 92% and specificity was 93%. In order to assess the performance of TESTPACK RSV as a bedside test, nasopharyngeal swabs from 49 children were tested by EIA at the bedside by housestaff and by immunofluorescence in the laboratory; the sensitivity of the EIA was lower (78%) while specificity remained high (95%). Inclusion of older children may have resulted in diminished sensitivity. The TESTPACK RSV is a simple, rapid test that performs well and is easily adaptable to an office setting. Further evaluation of the test in older children may be required.


Complete genome sequence of bellflower vein chlorosis virus, a novel putative member of the genus Waikavirus.
The complete genome sequence of a new virus isolated from a bellflower (Campanula takesimana) plant was determined. The genome of this virus is composed of monopartite single-stranded RNA of 11,649 nucleotides in length. BLAST searches of protein databases showed that the encoded polyprotein has a maximum amino acid sequence identity of 42% (with 99% coverage) to the polyprotein of the isolate Orissa of rice tungro spherical virus (RTSV; genus Waikavirus). Phylogenetic analysis strongly supports that the identified virus is a member of a new species of the genus Waikavirus. The name bellflower vein chlorosis virus (BVCV) is proposed for this new virus.


Peptidylarginine Deiminases as Drug Targets in Neonatal Hypoxic-Ischemic Encephalopathy.
Oxygen deprivation and infection are major causes of perinatal brain injury leading to cerebral palsy and other neurological disabilities. The identification of novel key factors mediating white and gray matter damage are crucial to allow better understanding of the specific contribution of different cell types to the injury processes and pathways for clinical intervention. Recent studies in the Rice-Vannucci mouse model of neonatal hypoxic ischemia (HI) have highlighted novel roles for calcium-regulated peptidylarginine deiminases (PADs) and demonstrated neuroprotective effects of pharmacological PAD inhibition following HI and synergistic infection mimicked by lipopolysaccharide stimulation.


Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.
The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.


Importance of glutathione in the acquisition and maintenance of sperm nuclear decondensing activity in maturing hamster oocytes.
Sperm nuclear decondensing activity in mammalian oocytes is dependent upon the maturational state of the oocyte. It is maximal in mature, metaphase II oocytes and minimal or absent in immature germinal vesicle (GV) and fertilized pronuclear oocytes. Previous studies suggested that this difference may be due to the relative ability of an oocyte to reduce the protamine disulfide bonds in the sperm nucleus. The results of this study show that mature hamster oocytes contain significantly more glutathione (GSH), about 8 mM, and hence more disulfide reducing power, as compared with GV (4 mM) or pronuclear (6 mM) oocytes. Furthermore, the acquisition of sperm nuclear decondensing activity by maturing oocytes can be prevented or delayed by blocking GSH synthesis with L-buthionine-S,R-sulfoximine during the early stages of oocyte maturation. This is the first evidence that modulation of GSH levels during oocyte maturation and fertilization may be a mechanism by which sperm nuclear decondensing activity is regulated.


Mechanisms of trophoblast invasiveness and their control: the role of proteases and protease inhibitors.
Implantation and subsequent placental development in many species including the human are dependent on trophoblast invasion of the uterine epithelium, the underlying basement membrane, connective tissue and blood vessels. However, trophoblast invasion in situ is strictly controlled by the microenvironment provided by the pregnant uterus. Key mechanisms underlying various steps in trophoblast invasion of basement membrane and stroma are similar to those identified in the case of invasive tumor cells: (a) attachment to basement membrane by binding to laminin and possibly other basement membrane components; (b) detachment from the basement membrane matrix prior to its penetration, a process that requires the presence of complex-type oligosaccharides on the cell surface; (c) breakdown of basement membrane components by trophoblast-derived metalloproteases (type IV and interstitial collagenase) and serine proteases (plasminogen activator). Type IV collagenase activity is stimulated by binding to laminin, a molecule also secreted by the trophoblast. Activation of trophoblast-derived metalloproteases appears to be plasmin-dependent. Plasmin results from the cleavage of plasminogen by trophoblast-derived plasminogen activator. Control of trophoblast invasion in situ is mediated by decidua-derived transforming growth factor beta (TGF beta) which in turn induces tissue inhibitor of metalloproteases (TIMP) both in the decidua and the trophoblast. We suggest that this control of trophoblast invasiveness is regulated both spatially as well as temporally during gestation. A preprogrammed decline in trophoblast invasiveness with increasing gestational age remains an additional possibility. The nature of the loss of control of trophoblast invasiveness in choriocarcinoma remains to be identified. Refractoriness to TGF beta action remains to strong possibility.


Processing of electrical activity in human muscle during a gradual increase in force.
The integrated electrical activity, the number of zero crossings and the number of turns, the mean amplitude and the ratio between them, of the electrical activity were compared in the brachial biceps muscle and the anterior tibial muscle of 20 controls. The electrical activity and force were analysed every 100 msec during a gradual increase in force from zero to maximum within 10 sec. The square root of integrated electrical activity increased linearly with increasing force. The slope of this relation was inversely related to maximum force when the increasing force was expressed in kilograms. The number of zero crossings per unit time increased with increasing force up to 40-60% of maximum force after which it remained constant. Comparison of 100 microV and 50 microV level detections suggested that there is a cancellation of small spike components in the electrical activity during higher force. The square root of integrated electrical activity was linearly related to mean amplitude between turns and the number of zero crossings was linearly related to the number of turns. In conclusion the information obtained by analysis of integrated activity and number of zero crossings is probably also obtained by number of turns and mean amplitude analysis.


Effectiveness of cognitive behavioral therapy supported by virtual reality in the treatment of body image in eating disorders: one year follow-up.
Body image disturbance is a significant maintenance and prognosis factor in eating disorders. Hence, existing eating disorder treatments can benefit from direct intervention in patients' body image. No controlled studies have yet compared eating disorder treatments with and without a treatment component centered on body image. This paper includes a controlled study comparing Cognitive Behavioral Treatment (CBT) for eating disorders with and without a component for body image treatment using Virtual Reality techniques. Thirty-four participants diagnosed with eating disorders were evaluated and treated. The clinical improvement was analyzed from statistical and clinical points of view. Results showed that the patients who received the component for body image treatment improved more than the group without this component. Furthermore, improvement was maintained in post-treatment and at one year follow-up. The results reveal the advantage of including a treatment component addressing body image disturbances in the protocol for general treatment of eating disorders. The implications and limitations of these results are discussed below.


Effect of perioperative complications after endovascular therapy in patients with peripheral artery disease due to femoropopliteal lesions.
Despite wide use, high initial success, and acceptable durability of endovascular therapy (EVT) for femoropopliteal (FP) lesions, the frequency of 30-day perioperative complications (POCs) and their effect on clinical outcomes have not been systematically evaluated, which is the subject of this study. We used a multicenter database of 2145 consecutive patients (70% male; overall mean age, 73 ± 9 years) who successfully underwent EVT for FP lesions to investigate independent predictors of POCs (logistic regression analysis) and effect of POCs on prognostic outcomes (Cox proportional regression). POCs were observed in 209 patients (10%). In multivariate logistic regression analysis, body mass index <18.5 kg/m(2), critical limb ischemia, and TransAtlanic Inter-Society Consensus for the Management of Peripheral Arterial Disease class D lesions were independently associated with POCs (adjusted odds ratios [95% confidence intervals], 2.0 [1.3-2.9], 2.5 [1.9-3.3], and 1.6 [1.2-2.1], respectively). After risk stratification of POCs according to the number of these risk factors, the incidence of POCs was higher in the groups with higher scores. Follow-up for >30 days (mean, 2.3 ± 1.8 years) was available for 2079 of 2145 patients. A Cox hazard regression model adjusted for baseline clinical characteristics showed POCs were negatively and independently associated with future occurrence of major adverse limb events (defined as major amputation and major reintervention) or death (hazard ratio [95% confidence interval], 1.6 [1.2-2.1]; P < .05). Body mass index <18.5 kg/m(2), critical limb ischemia, and TransAtlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease class D lesion were positively associated with POCs after EVT for FP lesions. The occurrence of POCs may adversely affect clinical outcomes in the chronic phase.


Discovery of NM23-H2 as an estrogen receptor beta-associated protein: role in estrogen-induced gene transcription and cell migration.
The regulation of the estrogenic responses may be influenced by the proteins that associate with estrogen receptors (ERs) rather than solely with the receptors themselves. ERbeta is expressed in blood vessels and may play an important role in vascular disease. We hypothesized that specific proteins interact with ERbeta to modulate its response to estrogens. By means of a yeast two hybrid screen, we discovered that NM23-H2, a multi-faceted protein associates specifically with ERbeta. NM23-H2 and ERbeta consistently co-localize in a variety of human tissues (e.g. breast tissue), whereas ERalpha and NM23-H2 did not co-localize. Estrogen response element-mediated transcription increased by 97% when NM23-H2 and ERbeta were over-expressed in MCF-7 cells (p< or =0.001). Moreover, there was a synergistic effect of NM23-H2 over-expression with estrogen treatment on the reduction of MCF-7 cell migration (p< or =0.001). These results suggest that NM23-H2 associates with ERbeta and is capable of modulating estrogen-induced gene transcription, as well as cell migration. Hence, NM23-H2 may play an important role in modulating the response to endogenous and exogenous estrogens, perhaps even within the context of vascular disease.


Recovery from milk allergy in early childhood: antibody studies.
We assessed the relationships of clinical symptoms and serum antibody levels during follow-up of 47 patients, aged 3 to 66 months, who were shown by formal milk challenge to have cow milk allergy. Three groups of patients were identified. Group 1 patients (n = 15) were sensitized to IgE and responded rapidly to small volumes of milk with urticaria, an exacerbation of eczema, wheeze, or vomiting. In the second group (n = 24), symptoms of milk enteropathy (vomiting and diarrhea) developed between 1 and 20 hours after milk ingestion. In the group 3 patients (n = 8), coughing, diarrhea, eczematoid rashes, or a combination of these developed more than 20 hours after normal volumes of milk were given. Serum levels of IgG, IgA, IgM, and IgE and of milk-specific anti-cow milk antibodies of these isotypes were measured initially and then at a median follow-up time of 16 months (range 6 to 39 months). In this investigation, changes in these immunologic measures during the study period were related to whether or not clinical tolerance to cow milk was achieved. At follow-up, six patients from group 1, ten from group 2, and two from group 3 were milk tolerant. No consistent change in any of the immunologic measurements was associated with remission of the disease. These findings raise the question of whether acquisition of clinical tolerance to cow milk in cow milk allergy can be attributed solely to immunologic events.


Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry.
The optimal use of diuretics in decompensated heart failure remains uncertain. We analyzed data from the ADHERE registry to look at the impact of diuretic dosing. 62,866 patients receiving <160 mg and 19,674 patients > or =160 mg of furosemide were analyzed. The patients receiving the lower doses had a lower risk for in-hospital mortality, ICU stay, prolonged hospitalization, or adverse renal effects. These findings suggest that future studies should evaluate strategies for minimizing exposure to high doses of diuretics.


Behavioural aspects of terrorism.
Behavioural and social sciences are useful in collecting and analysing intelligence data, understanding terrorism, and developing strategies to combat terrorism. This article aims to examine the psychopathological concepts of terrorism and discusses the developing roles for behavioural scientists. A systematic review was conducted of studies investigating behavioural aspects of terrorism. These studies were identified by a systematic search of databases, textbooks, and a supplementary manual search of references. Several fundamental concepts were identified that continue to influence the motives and the majority of the behaviours of those who support or engage in this kind of specific violence. Regardless of the psychological aspects and new roles for psychiatrists, the behavioural sciences will continue to be called upon to assist in developing better methods to gather and analyse intelligence, to understand terrorism, and perhaps to stem the radicalisation process.


Serologic cross-reactions among streptococcal group A, A-variant, and C polysaccharides.
Serologic cross-reactions among streptococcal groups A, A-variant (A-V), and C cell wall polysaccharides were found previously in studies employing capillary or quantitative precipitin techniques. Similar cross-reactions occur with radioimmune precipitation using extrinsically labeled 125I-streptococcal antigens. This study was performed to determine the degree of cross-reactivity when intrinsically labeled 14C-polysaccharide antigens were used in the radioimmune precipitin assay. Unadsorbed antisera from rabbits immunized with group A streptococci bound 3-5% as much 14C-A-V antigen as homologous A carbohydrate but undetectable amounts of C polysaccharide. Similarly, A-V antisera bound 3-5% as much 14C-A or 14C-C carbohydrate as A-V antigen. Group C antiserum bound 1-2% as much A and A-V antigens as C carbohydrate. Thus, less than 3% of intrinsically labelled 14C-A or 14C-C carbohydrate represents exposed A-V antigenic sites, i.e., exposed polyrhamnose backbone. Otherwise, group A, C, or A-V carbohydrates failed to exhibit heterologous determinants. Anti-peptidoglycan antibodies in antisera did not result in serologic cross-reactivity. These data suggest that formamide-extracted streptococcal group-specific polysaccharides, intrinsically labeled with 14C, may possess greater group specificity than 125I-carbohydrates and yield only negligible cross-reactivity with heterologous antisera. This degree of cross-reactivity does not appear to be sufficient to account for the persistently elevated serum levels of antibody to group A carbohydrate in patients with rheumatic heart disease.


ATP-induced axial movement of myosin heads in living thick filaments recorded with a gas environmental chamber attached to the electron microscope.
Using a gas environmental (hydration) chamber, in which biological specimens can be kept in wet state, we succeeded in recording images of 'living' muscle thick filaments with gold position markers attached to the myosin heads. The position of individual myosin heads did not change appreciably with time in the absence of ATP, indicating stability of the myosin head mean position. On application of ATP, the position of individual myosin heads was found to move by approximately 20 nm along the filament axis, while no appreciable movement of the filaments was detected. The ATP-induced myosin head movement was not observed in filaments in which ATPase activity of the myosin heads was eliminated. Application of ADP produced no appreciable myosin head movement. These results show that the ATP-induced myosin head movement takes place in the absence of the thin filaments. Since ATP reacts rapidly with the myosin head (M) to form the complex (M.ADP.Pi) having average lifetime of > 10 s, the observed myosin head movement may be mostly associated with reaction, M + ATP-->M.ADP.Pi. This work will open a new research field to study dynamic structural changes of individual biomolecules which are kept in 'living' state in an electron microscope.


Reducing instruments in a vitrectomy surgical tray: cost savings and results from a major academic hospital.
Unused or rarely used instruments in standard surgical trays can unnecessarily increase costs. Prior studies have demonstrated the practicality and cost savings of reduced instrument tray sizes in various subspecialties. This study describes results and estimated cost savings from a reduced instrument tray used for vitrectomy surgery at a large, tertiary academic medical center. Common usage patterns of vitrectomy instruments by one retina surgeon were reviewed and a reduced instrument vitrectomy tray was created and implemented in successive vitrectomy surgeries. Need for opening the previously utilized larger tray was recorded. Estimated cost savings of the new trays were calculated based upon per instrument sterilization, processing, and instrument replacement costs. New vitrectomy trays including just 7 instruments (89% reduction compared to original trays) were created and implemented in 189 successive cases. The original tray was never opened. Estimated cost savings from saved sterilization and processing resources is approximately $9588 per year. Assuming 5- and 10-year lifespan per instrument, annual cost avoidance is projected at $7886 and $15,772, respectively. Other indirect benefits relevant to healthcare quality were also noted. A reduced instrument tray can be successfully implemented for vitrectomy surgery and can result in significant indirect benefits as well as direct cost savings from reduced sterilization costs. Our study highlights the substantial impact made by evaluating the usage pattern and making appropriate instrument tray changes for just one retina surgeon. Applying these same methods to other surgeons and specialties can have significant implications on healthcare costs and quality.


Zileuton improves memory deficits, amyloid and tau pathology in a mouse model of Alzheimer's disease with plaques and tangles.
The 5-lipoxygenase (5LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD), and plays an active role in the development of brain amyloidosis in the APP transgenic mice. In the present paper, we studied the effect of its pharmacological inhibition on the entire AD-like phenotype of a mouse model with plaques and tangles, the 3 × Tg mice. Compared with mice receiving placebo, the group treated with zileuton, a specific 5LO inhibitor, manifested a significant improvement of their memory impairments. The same animals had a significant reduction in Aβ levels and deposition, which was secondary to a down-regulation of the γ-secretase pathway. Additionally, while total tau levels were unchanged for both groups, zileuton-treated mice had a significant reduction in its phosphorylation state and insoluble forms, secondary to a decreased activation of the cdk5 kinase. These data establish a functional role for 5LO in the pathogenesis of the full spectrum of the AD-like phenotype and represent the successful completion of the initial step for the preclinical development of 5LO inhibitors as viable therapeutic agents for AD.


A Narrowing Mortality Gap: Temporal Trends of Cause-Specific Mortality in a National Matched Cohort Study in US Veterans With Rheumatoid Arthritis.
To examine temporal trends in all-cause and cause-specific mortality in patients with rheumatoid arthritis (RA) in the Veterans Health Administration (VHA). We conducted a matched cohort study in the VHA from January 1, 2000 to December 31, 2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non-RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA-related risk of all-cause and cause-specific mortality. Among 29,779 incident RA patients (matched to 245,226 non-RA patients), 9,565 deaths occurred. RA patients were at increased risk of all-cause (adjusted hazard ratio [HRadj ] 1.23 [95% confidence interval (95% CI) 1.20-1.26]), cardiovascular (HRadj 1.19 [95% CI 1.14-1.23]), cancer (HRadj 1.19 [95% CI 1.14-1.24]), respiratory (HRadj 1.46 [95% CI 1.38-1.55]), and infection-related mortality (HRadj 1.59 [95% CI 1.41-1.80]). Interstitial lung disease was the cause of death most strongly associated with RA (HRadj 3.39 [95% CI 2.88-3.99]). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All-cause mortality risk related to RA was lower among those diagnosed during 2012-2017 (HRadj 1.10 [95% CI 1.05-1.15]) compared to 2000-2005 (HRadj 1.31 [95% CI 1.26-1.36]), but still higher than for non-RA controls (P < 0.001). Cause-specific mortality trends were similar. Excess RA-related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Although our findings support that RA-related mortality risk is decreasing over time, a mortality gap remains for all-cause and cause-specific mortality in RA.


Bounded stability of the quiet standing posture: an intermittent control model.
The paper presents a control model of body sway in quiet standing, which aims at achieving bounded stability by means of an intermittent control mechanism. Control bursts are generated when the current state vector exits an area of uncertainty around the reference point in the phase plane. This area is determined by the limited resolution of proprioceptive signals and the burst generation mechanism is predictive in the sense that it incorporates a rough, but working knowledge (internal model) of the biomechanics of the human inverted pendulum. We show that such a model, in spite of its simplicity and of the fact that it relies on very noisy measurements, is robust and can explain in a detailed way the measured sway patterns.


Patch marking in the aphid hyperparasitoid, Dendrocerus carpenteri: the information contained in patch marks.
The aim of this study was to test if females of the aphid hyperparasitoid Dendrocerus carpenteri (Curtis produce patch marks. We tested if these marks inform a foraging female of the identity of the producer of the mark (the female herself or a conspecific female) and on the producer's success or failure in finding hosts in the marked area. We also tested if the responses to patch marks differ depending on the size and/or egg load of the female. On average, females walked shorter paths and spent less time in previously explored areas in comparison to control areas only if the area had first been explored successfully (host found) by a conspecific female. If no host had been found or if the area had been explored by the same female previously, no differences between average values were recoreded. However, egg load also seemed to influence foraging decisions in those experiments where average values were not different between previously explored and control areas. Females with a low egg load tended to spend less time in previously explored areas than females with a high egg load. Average values therefore somehow obscured the individual responses to pathc marks. The results suggest that at least D. carpenteri females with a low egg load continuously apply a marking pheromone while walking. This pheromone seems to contain information on the identity of the producer. In addition, different pheromones seem to be applied depending on whether or not hosts are present in the area.