Platinums sensitize human epithelial tumor cells to lymphotoxin alpha by inhibiting NFkappaB-dependent transcription.
Lymphotoxin alpha (LTalpha) was first identified as a direct anti-tumor factor, whereas increasing evidence has recently shown that in most cases the growth inhibition mediated by LTalpha requires the synergistic action of other factors, such as RNA transcription or protein synthesis inhibitor. In this study, we evaluated the combined effects of LTalpha and ten chemotherapeutic drugs on cell growth in a panel of human epithelial tumor cells, and explored the molecular mechanism of their mutual action. The results showed that platinums (cisplatin, carboplatin, oxaliplatin) are more universally effective than other chemotherapeutic drugs (doxorubicin, epi-doxorubicin, 5-flourouracil, mitomycin, cyclophosphamide, vincristine and vinorelbine) to enhance the response of six human epithelial tumor cell lines (A375, Bcap37, NCI-H157, SW480, BGC-823 and HeLa) to LTalpha. A systemic treatment with a combination of LTalpha and cisplatin in a human Bcap37 breast cancer xenograft nude mice model dramatically improved the therapeutic efficacy of LTalpha. Further analysis revealed that the sensitization of platinums was associated with platinums-induced suppression of nuclear factor-kappaB (NFkappaB) and subsequent downregulation of X-linked inhibitor of apoptosis protein (XIAP), which rescued caspase-3 from inhibition. Our results suggested that a proper combination of bio-agents such as LTalpha and conventional chemotherapeutic drugs such as platinums may be an efficient treatment strategy for human epithelial cancers.


Twenty-four-hour intravenous and oral tracer studies with L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine at a tyrosine-free, generous phenylalanine intake in adults.
The daily rates of whole-body phenylalanine oxidation and hydroxylation were determined in young men receiving [1-13C]phenylalanine and [2H2]tyrosine via primed, constant intravenous (n=3) or oral (n=5) infusion for 24 consecutive hours (12-h fast followed by 12-h fed period), and given a generous phenylalanine (100 mg.kg-1.d-1), tyrosine-free, but otherwise adequate L-amino acid-based diet for 6 d before the tracer study. Our hypothesis was that subjects would be in whole-body phenylalanine equilibrium. Estimates of the daily rates of phenylalanine oxidation (phe-ox) and hydroxylation (phe-OH) were significantly higher for the subjects receiving the oral compared with intravenous tracer (P<0.01 for both comparisons), with the estimates of phe-ox obtained with oral tracer during the 12-h fast period being close to those predicted from similar 24-h leucine kinetic studies. The precision of the agreement between the measured 24-h rates of phe-ox and phe-OH compared with the predicted daily rates by extrapolation from the last hour of the 12-h fast and fifth hour of the fed period was poor. From the 24-h data, daily phenylalanine balances were estimated to be positive for both the intravenous and oral tracer protocols, although it was less positive for the oral tracer group. These results imply that the [13C]phenylalanine probe underestimated whole-body irreversible loss of phenylalanine, and suggest that daily phenylalanine balance in earlier 24-h phenylalanine-tyrosine tracer studies at low phenylalanine intakes may have been overestimated. Studies involving [13C]tyrosine as tracer will be required to further assess whole-body aromatic amino acid balance.


[Lyme carditis presenting as acute coronary syndrome: a case report].
A case of a 26-year-old man with Lyme carditis (LC) mimicking acute coronary syndrome is presented. Considering clinical presentation, electrocardiographic findings and markedly elevated levels of cardiac biomarkers, emergency coronary angiography was performed and revealed normal coronaries. Ventricular arrhythmias of Lown grade IVb during catheterization were recorded. Echocardiography showed mild global left ventricular dysfunction with ejection fraction of 50%. The diagnosis of LC was confirmed by ELISA and Western blot serologic testing. After 21 days of continuous antibiotic therapy with ceftriaxone (2.0 g/d) the patient recovered completely. We also present the current state of knowledge on the cardiovascular aspects of Lyme borreliosis.


Safety climate in university and college laboratories: impact of organizational and individual factors.
Universities and colleges serve to be institutions of education excellence; however, problems in the areas of occupational safety may undermine such goals. Occupational safety must be the concern of every employee in the organization, regardless of job position. Safety climate surveys have been suggested as important tools for measuring the effectiveness and improvement direction of safety programs. Thus, this study aims to investigate the influence of organizational and individual factors on safety climate in university and college laboratories. Employees at 100 universities and colleges in Taiwan were mailed a self-administered questionnaire survey; the response rate was 78%. Multivariate analysis of variance revealed that organizational category of ownership, the presence of a safety manager and safety committee, gender, age, title, accident experience, and safety training significantly affected the climate. Among them, accident experience and safety training affected the climate with practical significance. The authors recommend that managers should address important factors affecting safety issues and then create a positive climate by enforcing continuous improvements.


Autophagy as an immune effector against tuberculosis.
The now well-accepted innate immunity paradigm that autophagy acts as a cell-autonomous defense against intracellular bacteria has its key origins in studies with Mycobacterium tuberculosis, an important human pathogen and a model microorganism infecting macrophages. A number of different factors have been identified that play into the anti-mycobacterial functions of autophagy, and recent in vivo studies in the mouse model of tuberculosis have uncovered additional anti-inflammatory and tissue-sparing functions of autophagy. Complementing these observations, genome wide association studies indicate a considerable overlap between autophagy, human susceptibility to mycobacterial infections and predisposition loci for inflammatory bowel disease. Finally, recent studies show that autophagy is an important regulator and effector of IL-1 responses, and that autophagy intersects with type I interferon pathology-modulating responses.


A meta-analysis of inositol for depression and anxiety disorders.
This study is a meta-analysis of inositol as a treatment for depression and anxiety disorders. PubMed, Cochrane Library database, and PsycINFO were searched up to 14 August 2013. A systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials (RCTs) were conducted comparing inositol for depressed or anxiety disorder patients. Seven RCTs in depression (two bipolar depression studies, one bipolar depression and major depressive disorder (MDD) study, two MDD studies, and two premenstrual dysphoric disorder (PMDD) studies) (n = 242) were identified. Four RCTs in anxiety disorders (two obsessive-compulsive disorder studies, one panic disorder study, and one posttraumatic stress disorder study) (n = 70) were also identified. There were no statistically significant effects of inositol on depressive, anxiety, and obsessive-compulsive symptoms and discontinuation (all-cause, side effects, and worsening psychiatric symptoms). However, inositol had marginally more responders in depression than placebo (p = 0.06), and inositol showed a trend towards superior efficacy for depressive symptoms in patients with PMDD (p = 0.07). Inositol marginally caused gastrointestinal upset compared with placebo (p = 0.06). Our results suggest that inositol may be beneficial for depressed patients, especially those with PMDD. The main limitation of this report is that a small number of studies were included in this meta-analysis.


Transverse Cracking Induced Acoustic Emission in Carbon Fiber-Epoxy Matrix Composite Laminates.
Transverse cracking induced acoustic emission in carbon fiber/epoxy matrix composite laminates is studied both experimentally and numerically. The influence of the type of sensor, specimen thickness and ply stacking sequence is investigated. The frequency content corresponding to the same damage mechanism differs significantly depending on the sensor and the stacking sequence. However, the frequency centroid does not wholly depend on the ply thickness except for the inner ply crack and a sensor located close enough to the crack. Outer ply cracking exhibits signals with a low-frequency content, not depending much on the ply thickness, contrary to inner ply cracking, for which the frequency content is higher and more dependent on the ply thickness. Frequency peaks and frequency centroids obtained experimentally are well captured by numerical simulations of the transverse cracking induced acoustic emission for different ply thicknesses.


Recent advances in understanding T cell activation and exhaustion during HBV infection.
Chronic hepatitis B virus (HBV) infection remains a major public health concern globally, and T cell responses are widely believed to play a pivotal role in mediating HBV clearance. Accordingly, research on the characteristics of HBV-specific T cell responses, from activation to exhaustion, has advanced rapidly. Here, we summarize recent developments in characterizing T cell immunity in HBV infection by reviewing basic and clinical research published in the last five years. We provide a comprehensive summary of the mechanisms that induce effective anti-HBV T cell immunity, as well as the latest developments in understanding T cell dysfunction in chronic HBV infection. Furthermore, we briefly discuss current novel treatment strategies aimed at restoring anti-HBV T cell responses.


The effect of macrocyclic chelators on the targeting properties of the 68Ga-labeled gastrin releasing peptide receptor antagonist PEG2-RM26.
Overexpression of gastrin-releasing peptide receptors (GRPR) has been reported in several cancers. Bombesin (BN) analogs are short peptides with a high affinity for GRPR. Different BN analogs were evaluated for radionuclide imaging and therapy of GRPR-expressing tumors. We have previously investigated an antagonistic analog of BN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH(2), RM26) conjugated to NOTA via a PEG(2) spacer (NOTA-PEG(2)-RM26) labeled with (68)Ga, (111)In and Al(18)F. (68)Ga-labeled NOTA-PEG(2)-RM26 showed high tumor-to-organ ratios. The influence of different macrocyclic chelators (NOTA, NODAGA, DOTA and DOTAGA) on the targeting properties of (68)Ga-labeled PEG(2)-RM26 was studied in vitro and in vivo. All conjugates were labeled with generator-produced (68)Ga with high yields and demonstrated high stability and specific binding to GRPR. The IC(50) values of (nat)Ga-X-PEG(2)-RM26 (X = NOTA, DOTA, NODAGA, DOTAGA) were 2.3 ± 0.2, 3.0 ± 0.3, 2.9 ± 0.3 and 10.0 ± 0.6 nM, respectively. The internalization of the conjugates by PC-3 cells was low. However, the DOTA-conjugated analog demonstrated a higher internalization rate compared to other analogs. GRPR-specific uptake was found in receptor-positive normal tissues and PC-3 xenografts for all conjugates. The biodistribution of the conjugates was influenced by the choice of the chelator moiety. Although all radiotracers cleared rapidly from the blood, [(68)Ga]Ga-NOTA-PEG(2)-RM26 showed significantly lower uptake in lung, muscle and bone compared to the other analogs. The uptake in tumors (5.40 ± 1.04 %ID/g at 2 h p.i.) and the tumor-to-organ ratios (25 ± 3, 157 ± 23 and 39 ± 4 for blood, muscle and bone, respectively) were significantly higher for the NOTA-conjugate than the other analogs. Chelators had a clear influence on the biodistribution and targeting properties of (68)Ga-labeled antagonistic BN analogs. Positively charged [(68)Ga]Ga-NOTA-PEG(2)-RM26 provided a low kidney radioactivity uptake, high affinity, high tumor uptake and high image contrast.


Interventions for replacing missing teeth: management of soft tissues for dental implants.
Dental implants are usually placed by elevating a soft tissue flap, but in some instances, they can also be placed flapless reducing patient discomfort. Several flap and suturing techniques have been proposed. Soft tissues are often manipulated and augmented for aesthetic reasons. It is often recommended that implants are surrounded by a sufficient width of attached/keratinized mucosa to improve their long-term prognosis. To evaluate whether (1a) flapless procedures are beneficial for patients, and (1b) which is the ideal flap design; whether (2a) soft tissue correction/augmentation techniques are beneficial for patients, and (2b) which are the best techniques; whether (3a) techniques to increase the perimplant keratinized mucosa are beneficial for patients, and (3b) which are the best techniques; and (4) which are the best suturing techniques/materials. The Cochrane Oral Health Group's Trials Register, The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched. Handsearching included several dental journals. Authors of all identified trials, an internet discussion group and 55 dental implant manufacturers were contacted to find unpublished randomised controlled trials (RCTs). The last electronic search was conducted on 15 January 2007. All RCTs of root-form osseointegrated dental implants comparing various techniques to handle soft tissues in relation to dental implants. Outcome measures were: prosthetic and implant failures, aesthetics evaluated by patients and dentists, biological complications, postoperative pain, patient preference, ease of maintenance by patient, and width of the attached/keratinized mucosa. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Authors were contacted for missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Heterogeneity was to be investigated including both clinical and methodological factors. Eight potentially eligible RCTs were identified and five trials including 140 patients in total were included. Two trials (100 patients) compared flapless placement of dental implants with conventional flap elevation, two trials (20 patients) crestal versus vestibular incisions, and one trial (20 patients) Erbium:YAG laser versus flap elevation at the second-stage surgery for implant exposure. On a patient, rather than per implant basis, implants placed with a flapless technique and implant exposures performed with laser induced statistically significant less postoperative pain than flap elevation. There were no other statistically significant differences for any of the remaining analyses. Flapless implant placement is feasible and has been shown to reduce patient postoperative discomfort in adequately selected patients. There is insufficient reliable evidence to provide recommendations on which are the best incision/suture techniques/materials, or whether techniques to correct/augment perimplant soft tissues or to increase the width of keratinized/attached mucosa are beneficial to patients or not. Properly designed and conducted RCTs are needed to provide reliable answers to these questions.


Pseudocholinesterase deficiency associated with HELLP syndrome.
We report a case of decreased plasma pseudocholinesterase activity in a patient with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. The pseudocholinesterase activity returned to normal with concomitant recovery of HELLP syndrome. This possible association is significant when general anesthesia is provided to patients with HELLP syndrome.


Development of a non-melanoma skin cancer detection model.
The incidence and prevalence of skin cancer is rising. A detection model could support the (screening) process of diagnosing non-melanoma skin cancer. A questionnaire was developed containing potential actinic keratosis (AK) and basal cell carcinoma (BCC) characteristics. Three nurses diagnosed 204 patients with a lesion suspicious of skin (pre)malignancy and filled in the questionnaire. Logistic regression analyses generated prediction models for AK and BCC. A prediction model containing nine characteristics correctly predicted the presence or absence of AK in 83.2% of the cases. BCC was predicted correctly in 91.4% of the cases by a model containing eight characteristics. The nurses correctly diagnosed AK in 88.3% and BCC in 90.9% of the cases. Detection or screening models for AK and BCC could be made with a limited number of variables. Nurses also diagnosed skin lesions correctly in a high percentage of cases. Further research is necessary to investigate the robustness of these findings, whether the percentage of correct diagnoses can be improved and how best to implement model-based prediction in the diagnostic process.


Provider Perspectives of Battlefield Acupuncture: Advantages, Disadvantages and Its Potential Role in Reducing Opioid Use for Pain.
Nonpharmacological options to treat pain are in demand, in part to address the opioid crisis. One such option is acupuncture. Battlefield acupuncture (BFA) is an auricular needling protocol currently used to treat pain in the Veterans Health Administration. We aimed to identify the advantages and disadvantages of BFA from providers' perspectives. We rely on an inductive qualitative approach to explore provider perceptions through thematic analysis of semistructured interviews with 43 BFA providers across the nation. We identified the following themes. Disadvantages included: (1) clinical guidelines are insufficient; (2) patients often request multiple BFA visits from providers; (3) BFA can be uncomfortable; (4) BFA may not be an effective treatment option unless it can be provided "on demand"; and (5) BFA can promote euphoria, which can have deleterious consequences for patient self-care. Perceived advantages included: (1) BFA can simultaneously effectively control pain while reducing opioid use; (2) BFA may alleviate the pain that has been unsuccessfully treated by conventional methods; (3) BFA gives providers a treatment option to offer patients with substance use disorder; (4) BFA helps build a trusting patient-provider relationship; (5) BFA can create the opportunity for hope. Providers perceive BFA to have many benefits, both clinical and relational, including ways in which it may have utility in addressing the current opioid crisis. BFA is easy to deliver and has potential clinical and relational utility. Efforts to better understand effectiveness are warranted.


Parent Cultural Adaptation and Child Functioning in Culturally Diverse, Urban Families of Preschoolers.
Parent cultural adaptation and preschool behavioral and socioemotional functioning were examined in a community sample of urban families from diverse cultural backgrounds. Participants were 130 families of children (mean age = 4.1 years) attending eight public Pre-Kindergarten programs in urban communities. Parents completed a measure of cultural adaptation that taps into acculturation and enculturation, and teachers reported on children's externalizing problems, internalizing problems and adaptive behavior in the classroom. Parents' ethnic identity was a significant predictor of children's functioning. The retention of parents' culture of origin and specific aspects of acculturation are related to positive outcomes in a sample of culturally diverse families of preschoolers living in urban communities. Bicultural parents (those with high ethnic and US American identity) had children with lower levels of internalizing problems and higher levels of adaptive behavior relative to parents who were not bicultural. Implications for enhancing positive child outcomes through the promotion of parental ethnic identity are discussed.


The effect of chiropractic care on jet lag of Finnish junior elite athletes.
To determine the effect of chiropractic care on jet lag in Finnish junior elite athletes. Fifteen Finnish junior elite athletes. Through use of a table of random numbers, each athlete was assigned by sex to one of 3 groups: chiropractic adjustment, sham adjustment, or control. As needed, the chiropractic adjustment group athletes (n = 5) were adjusted on a daily basis by licensed chiropractors using a toggle/recoil procedure. The sham adjustment group athletes (n = 5) received sham adjustments on a daily basis by licensed chiropractors. The control group athletes (n = 5) were not adjusted or sham-adjusted but participated in all test protocols. Sleep, jet lag, chiropractic, and mood data (the last acquired through use of the Profile of Mood States) were collected on a daily basis for 18 consecutive days. Repeated-measures analyses of variance (3 x 2) of total mood disturbance scores and heart rate variables indicated that there were no significant (.05 level) between-group differences. Sleep data were analyzed through use of a 3 x 2, repeated-measures multivariate analysis of variance. Pillai's trace indicated that there were no between-group differences. Self-assessment of jet lag by participants after traveling to Georgia and after returning to Finland showed no between-group differences. It was concluded that chiropractic care did not reduce the effects of jet lag.


Pulp canal obliteration after extrusive and lateral luxation in young permanent teeth: A scoping review.
In the literature, no single therapeutic approach is preferred for treating dental pulp responses such as pulp canal obliteration (PCO). Some authors still recommend preventive endodontic treatment, whereas others choose not to intervene, to avoid causing possible iatrogenic complications. This review was conducted to explore, in the current scientific literature, the degree of knowledge concerning the onset and development of PCO and pulp necrosis (PN) following dental trauma (i.e. extrusive luxation and lateral luxation) in children and young adults (6-20 years). The authors also evaluated whether and to what extent the stage of dental root development at the time of traumatic dental injury (TDI) influences these pulp responses, and whether PN can arise in teeth already affected by PCO. MATERIALS AND METHODS The literature search was carried out during the period October 2019 to January 2020, using the following databases: PubMed/MEDLINE, SCOPUS and Web of Science. Articles in English reporting on young patients with PCO or PN in permanent teeth affected by trauma were included. Theresearch, whose questions were summarised according to the PICO method, considered the following aspects: patient age, type of TDI, stage of root development, initial treatment, presence of calcification or necrosis, time to onset of the two outcomes (PCO and PN), and duration of follow-up. The articles found were evaluated by two reviewers; in the event of disagreement regarding the inclusion of an article, a third reviewer was called upon to decide. The initial screening of the databases, using the selected search keywords, yielded a total of 343 articles. After exclusion of duplicates and articles not meeting the inclusion criteria, 11 articles remained. Of these, only four completely met the inclusion criteria. Closer analysis of these four publications revealed that they would not easily yield standardised sets of clinical data that might be homogenised in order to produce clear meta-analytical data. Hence the need to limit the data collected to the following seven items: number and type of injuries, type of initial intervention, duration of follow-up, main pulp responses, number and type of pulp responses. PCO is a physiological pulp response associated with a traumatic event, usually a luxation injury. It is diagnosed on the basis of combined radiographic and clinical-anamnesticdata. Signs of PCO start to appear at around one year after the traumatic event, and its development reaches completion by about five years post-trauma. PN, on the other hand, is clearly apparent within the first year. Endodontic treatment, be it carried out as a preventive measure or following detection of PCO, is inappropriate and can cause serious iatrogenic damage. Treatment is indicated only in cases of definite PN.


Quality of nursing doctoral education in seven countries: survey of faculty and students/graduates.
This study aimed to compare the findings of the quality of nursing doctoral education survey across seven countries and discuss the strategic directions for improving quality. No comparative evaluation of global quality of nursing doctoral education has been reported to date despite the rapid increase in the number of nursing doctoral programmes. A descriptive, cross-country, comparative design was employed. Data were collected from 2007-2010 from nursing schools in seven countries: Australia, Japan, Korea, South Africa, Thailand, UK and USA. An online questionnaire was used to evaluate quality of nursing doctoral education except for Japan, where a paper version was used. Korea and South Africa used e-mails quality of nursing doctoral education was evaluated using four domains: Programme, Faculty (referring to academic staff), Resource and Evaluation. Descriptive statistics, correlational and ordinal logistic regression were employed. A total of 105 deans/schools, 414 faculty and 1149 students/graduates participated. The perceptions of faculty and students/graduates about the quality of nursing doctoral education across the seven countries were mostly favourable on all four domains. The faculty domain score had the largest estimated coefficient for relative importance. As the overall quality level of doctoral education rose from fair to good, the resource domain showed an increased effect. Both faculty and students/graduates groups rated the overall quality of nursing doctoral education favourably. The faculty domain had the greatest importance for quality, followed by the programme domain. However, the importance of the resource domain gained significance as the overall quality of nursing doctoral education increased, indicating the needs for more attention to resources if the quality of nursing doctoral education is to improve.


First trimester coffee and tea intake and risk of gestational diabetes mellitus: a study within a national birth cohort.
Coffee and tea consumption is associated with a decreased type 2 diabetes risk in non-pregnant adults. We examined the relation between first trimester coffee and tea consumption and gestational diabetes mellitus (GDM) risk. Population-based cohort study. Denmark 1996-2002. Non-diabetic women with singleton pregnancies in the Danish National Birth Cohort (n = 71,239). Estimated adjusted relative risks (RR) and 95% confidence intervals (95%CI) for the association between first trimester coffee and tea or estimated total caffeine and GDM. GDM ascertained from the National Hospital Discharge Register or maternal interview. Coffee or tea intake was reported in 81.2% (n = 57,882) and 1.3% (n = 912) of pregnancies were complicated by GDM. Among non-consumers, 1.5% of pregnancies were complicated by GDM. Among coffee drinkers, GDM was highest among women who drank ≥8 cups/day (1.8%) with no significant difference across intake levels (P = 0.10). Among tea drinkers, there was no difference in GDM across intake levels (1.2%; P = 0.98). After adjustment for age, socio-occupational status, parity, pre-pregnancy body mass index, smoking, and cola, there was suggestion of a protective, but non-significant association with increasing coffee (RR ≥8 versus 0 cups/day = 0.89 [95%CI 0.64-1.25]) and tea (RR ≥8 versus 0 cups/day = 0.77 [95%CI 0.55-1.08]). Results were similar by smoking status, except a non-significant 1.45-fold increased risk with ≥8 coffee cups/day for non-smokers. There was a non-significant reduced GDM risk with increasing total caffeine. Our results suggest that moderate first trimester coffee and tea intake were not associated with GDM increased risk and possibly may have a protective effect.


Tachyarrhythmias During Hospitalization for COVID-19 or Multisystem Inflammatory Syndrome in Children and Adolescents.
Background Cardiac complications related to COVID-19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID-19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID-19-related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID-19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 [range, 10.4-17.4] versus 10.0 [range, 5.4-14.8] years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID-19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.


[Isolation of the tritium labeled subunit II of cytochrome oxidase].
Radioactively labelled subunit II of cytochrome oxidase is isolated after irradiation of molecular crystals of the enzyme with thermally activated tritium.


Neuropsychological and neuropsychiatric prediction of global cognitive status among older Spanish-speaking Hispanics and English-speaking whites.
Neuropsychological and depression measures have been found to predict cognitive functioning. We compared these associations among whites and Spanish-speaking Hispanics. Fifty-two pairs of whites and Hispanics were matched demographically and clinically in a cross-sectional study. Hierarchical regression analyses predicted Global Deterioration Scale (GDS) rating by baseline neuropsychological tests and depression symptoms. Neuropsychological tests predicted GDS better in whites; depression symptoms--specifically retardation--predicted well in Hispanics but not whites. Immediate recall of the New York University (NYU)-Paragraph Test and the Retardation item of the Hamilton Depression Rating Scale were associated with GDS in Hispanics and delayed recall of the NYU-Paragraph Test and Wechsler Adult Intelligence Scale-Digit Symbol in whites. Neuropsychological tests and depression symptoms predicted GDS differently in Hispanics and whites. These results suggest that other measures should be considered to increase the predictive accuracy of neuropsychological tests when assessing cognitive status in Spanish-speaking Hispanics. Additional studies of specific ethnic/racial and sociodemographic subgroups are warranted.


Concise Total Synthesis of (+)-Gliocladins B and C.
The first total synthesis of (+)-gliocladin B is described. Our concise and enantioselective synthesis takes advantage of a new regioselective Friedel-Crafts-based strategy to provide an efficient multigram-scale access to the C3-(3'-indolyl)hexahydropyrroloindole substructure, a molecular foundation present in a significant subset of epipolythiodiketopiperazine natural alkaloids. Our first-generation solution to (+)-gliocladin B involved the stereoselective formation of (+)-12-deoxybionectin A, a plausible biosynthetic precursor. Our synthesis clarified the C15 stereochemistry of (+)-gliocladin B and allowed its full structure confirmation. Further studies of a versatile dihydroxylated diketopiperazine provided a concise and efficient synthesis of (+)-gliocladin B as well as access to (+)-gliocladin C.


Spontaneous behavioral responses in the orofacial region: a model of trigeminal pain in mouse.
To develop a translational mouse model for the study and measurement of non-evoked pain in the orofacial region by establishing markers of nociceptive-specific grooming behaviors in the mouse. Some of the most prevalent and debilitating conditions involve pain in the trigeminal distribution. Although there are current therapies for these pain conditions, for many patients, they are far from optimal. Understanding the pathophysiology of pain disorders arising from structures innervated by the trigeminal nerve is still limited, and most animal behavioral models focus on the measurement of evoked pain. In patients, spontaneous (non-evoked) pain responses provide a more accurate representation of the pain experience than do responses that are evoked by an artificial stimulus. Therefore, the development of animal models that measure spontaneous nociceptive behaviors may provide a significant translational tool for a better understanding of pain neurobiology. C57BL/6 mice received either an injection of 0.9% saline solution or complete Freund's adjuvant into the right masseter muscle. Animals were video-recorded and then analyzed by an observer blind to the experiment group. The duration of different facial grooming patterns performed in the area of injection were measured. After 2 hours, mice were euthanized and perfused, and the brainstem was removed. Fos protein expression in the trigeminal nucleus caudalis was quantified using immunohistochemistry to investigate nociceptive-specific neuronal activation. A separate group of animals was treated with morphine sulfate to determine the nociceptive-specific nature of their behaviors. We characterized and quantified 3 distinct patterns of acute grooming behaviors: forepaw rubbing, lower lip skin/cheek rubbing against enclosure floor, and hindpaw scratching. These behaviors occurred with a reproducible frequency and time course, and were inhibited by the analgesic morphine. Complete Freund's adjuvant-injected animals also showed Fos labeling consistent with neuronal activation in nociceptive-specific pathways of the trigeminal nucleus after 2 hours. These behaviors and their correlated cellular responses represent a model of trigeminal pain that can be used to better understand basic mechanisms of orofacial pain and identify new therapeutic approaches to this common and challenging condition.


Altered in vitro functions of platelets prepared by the Haemonetics blood processor.
The function and ultrastructure of platelets collected by the Haemonetics blood processor were investigated. Aggregability, release ability, and morphology of these platelets were compared with platelets of the same donors before plateletpheresis was instiuted. Data of a group of 15 normal donors were pooled and analyzed. Our results showed that Haemonetics-isolated platelets had the following altered in vitro functions. Adenosine diphosphate-induced aggregation was markedly reduce, and epinephrine-induced aggregation was often absent. Collagen-induced aggregation was characterized by prolongation of the aggregation time and, sometimes, also by reduction of aggregation. Increase of adenosine diphosphate or collagen concentration resulted in improvement of aggregation of Haemonetics-collected platelets; increase of epinephrine concentration had no effect. Exogenous CaCL2, pre-Haemonetics platelet-rich or platelet-poor plasma failed to correct the abnormal aggregation of post-Haemonetics platelets. Release of labeled serotonin induced by spinephrine and collagen was reduced. However, the ultrastructure of post-Haemonetics platelets was normal.


Electrophoresis in microfabricated devices using photopolymerized polyacrylamide gels and electrode-defined sample injection.
Microfabrication techniques have become increasingly popular in the development of the next generation of DNA analysis systems. While significant progress has been reported by many researchers, complete microfabricated integrated DNA analysis devices are still in the earliest stages of development. Most miniaturized analysis systems have incorporated noncross-linked polymer solutions as the separation medium of choice and the operation of these systems necessitates the use of high electric fields and long separation lengths. In this paper, we present two techniques that may help alleviate this problem and accelerate the development of the so-called 'lab-on-a-chip' systems. We present the use of photodefinable polyacrylamide gels as a sieving medium for DNA electrophoresis. These gels offer the significant advantages of faster curing times, locally controlled gel interface, and simpler handling over chemically polymerized gels. We also introduce an electrode-defined sample compaction and injection technique. This technique helps achieve sample compaction without migration into the gel and offers significant control over the size and application of the sample plug. The use of these technologies for double-stranded DNA separations in microfabricated separation systems is demonstrated.


Rapid, non-destructive selection of peanuts for high aflatoxin content by soaking and tandem mass spectrometry.
Peanut lots are subject to aflatoxin levels high enough to cause concern to health agencies and trade channels. A possible solution would be to mechanically sort out high aflatoxin nuts from the process stream. Only highly contaminated nuts would need to be removed. However, there exists at present no sorting mechanism which meets commercial needs of adequate reduction and product preservation. To build such a sorter requires knowledge of the properties that can be used for sorting. The first step in the design is to select on the order of one hundred undamaged contaminated nuts which can be compared with noncontaminated ones. Because contaminated nuts are rare, a very large number of nuts needs to be examined nondestructively. We present a method to rapidly carry out such a selection. The method is based on dipping nuts into extraction fluid and examining the resulting fluid by tandem MS without preliminary cleanup. This method has been applied to examine over 65,000 nuts, yielding approximately 120 nuts, each containing more than 250-43000 ng/g aflatoxin (depending on process stream).


A review of bismuth-based sorptive materials for the removal of major contaminants from drinking water.
In recent years, bismuth has gained attention of many researchers because of its sorptive properties. Sorptive properties of bismuth compounds are used for removal of ionic contaminants from aqueous solution. In this paper, an attempt is made to review the recent developments in the area of contaminant removal from aqueous solutions using bismuth-based media. List of various bismuth-based adsorbents are collected from published literature and their adsorption capacities are also compared. The methods of characterization of some of the synthesized bismuth-based materials have also been discussed. Hydrous bismuth oxides (HBOs) have sorptive potential for nitrate and fluoride removal from aqueous solution with maximum capacity of 0.508-0.512 mg/g and 0.60-1.93 mg/g respectively. Thus, it can be beneficially used for treatment of drinking water treatment, particularly in small scale household applications.


Glomus Tumor of the Kidney in a Child With Tuberous Sclerosis.
Primary glomus tumors of the kidney are rare and have never been reported in children under 16 years of age. Tuberous sclerosis complex (TSC) is an extremely variable genetic condition that can affect virtually any organ in the body. Only a single case of glomus tumor associated with TSC was reported in 1964. In this article, we describe the clinical, radiologic, and pathological features of a primary renal glomus tumor in an 8-year-old girl with TSC. This tumor is large, has a deep location, and has infiltrative margins and numerous mitoses. However, there was no disease progression in a 16-month period of follow-up. To our knowledge, this is the second report of primary renal glomus tumor in childhood, the youngest one in the literature.


War, terrorism and the public's health.
War and terrorism, which are inseparable, cause death and disability, profound psychological damage, environmental destruction, disruption of the health infrastructure, refugee crises, and increased interpersonal, self-directed and collective violence. Weapons systems such as weapons of mass destruction and landmines have their own specific devastating effects. Preparation for war and preparedness for terrorism bring constraints on civil liberties and human rights, increase militarism, and divert resources from health care and from other needed services. War and terrorism may be best prevented through addressing their causes, which include limited resources, injustice, poverty and ethnic and religious enmity, and through strengthening the United Nations and the treaties controlling specific weapons systems, particularly weapons of mass destruction. In particular, the United States should cease its interference in the internal affairs of other nations and its advocacy of unilateral pre-emptive war.


Integrated simulation approach for laser-driven fast ignition.
An integrated simulation approach fully based on the particle-in-cell (PIC) model is proposed, which involves both fast-particle generation via laser solid-density plasma interaction and transport and energy deposition of the particles in extremely high-density plasma. It is realized by introducing two independent systems in a simulation, where the fast-particle generation is simulated by a full PIC system and the transport and energy deposition computed by a second PIC system with a reduced field solver. Data of the fast particles generated in the full PIC system are copied to the reduced PIC system in real time as the fast-particle source. Unlike a two-region approach, which takes a single PIC system and two field solvers in two plasma density regions, respectively, the present one need not match the field solvers since the reduced field solver and the full solver adopted respectively in the two systems are independent. A simulation case is presented, which demonstrates that this approach can be applied to integrated simulation of fast ignition with real target densities, e.g., 300 g/cm(3).


Altered regulation of negative affect in patients with fibromyalgia: A diary study.
Fibromyalgia is characterized by widespread musculoskeletal pain and often accompanied by cognitive and emotional problems. Adaptation to fibromyalgia may therefore also rely on one's ability to regulate emotional problems. In this study, we examined two indices of emotion regulation, that is, (a) affective instability, involving frequent large fluctuations in self-reported affect, and (b) resting heart rate variability (HRV). Participants were 46 patients with fibromyalgia (Mage = 45.4 years; 39 females) and 46 matched healthy controls (Mage = 44.9 years; 37 females). Heart rate was monitored under resting conditions to derive HRV. Subsequently, participants completed an electronic end-of-day diary for 14 consecutive days assessing daily levels of pain, disability, negative affect (NA) and positive affect (PA). Affective instability was operationalized as the mean square of successive differences in daily mood. Results indicate increased levels of NA instability and reduced levels of HRV in patients with fibromyalgia in comparison with healthy controls. Furthermore, HRV and NA instability were inversely related. Finally, in patients, higher NA instability was related to increased pain disability. Current findings support the idea that patients with fibromyalgia are confronted with fluctuating emotions. These results may have important implications for treatment as they provide support for the use of emotion regulation skills training in patients with fibromyalgia to impact upon NA instability. This study provides novel insight in the link between emotion regulation indices,that is, heart-rate variability and negative affective (NA) instability, in patients with fibromyalgia, and presents evidence for differences in both emotion regulation indices between patients with fibromyalgia and healthy people. Furthermore, results link increased NA instability with increased levels of daily disability in patients with fibromyalgia. Together, these findings offer support for a key role of emotion regulation in fibromyalgia outcomes, providing pathways for clinical practice.


Oxidative red blood cell membrane injury in the pathophysiology of severe mouse beta-thalassemia.
In severe human beta-thalassemia, the pathophysiology relates to accumulation of excess alpha-globin chains at the membrane. One hypothesis is that membrane-associated alpha-globin by virtue of it's iron or hemichromes produces oxidation of adjacent membrane proteins. The availability of a mouse model of severe beta-thalassemia, as well as a transgenic (thalassemic-sickle) mouse that expresses 12% of human beta s-chain, has allowed us to study the effect of graded accumulation of alpha-chains at the red blood cell (RBC) membrane on the clinical status of the animal and on the material properties of its RBCs. Proteins from control, beta-thalassemic, and transgenic mouse RBC membranes were analyzed for evidence of oxidation, as measured by thiol-disulfide exchange chromatography, which detects intramolecular sulfhydryl oxidation. Ratios of oxidized globin to protein 7 were calculated and increased amounts were seen in thalassemic mice as compared with control mice and transgenic mice. Furthermore, there were increased amounts of thiol-free protein 4.1 in the thalassemic mice, compared with very small amounts in the control mice and intermediate amounts in the transgenic mice. Membrane mechanical stability as assessed by ektacytometry showed that the thalassemic mouse RBCs were markedly unstable. Transgenic mouse RBCs showed intermediate levels of membrane instability compared with the controls. We propose that this oxidized globin, in conjunction with oxidized protein 4.1, accounts (at least in part) for membrane instability. A 12% increase in beta s-globin chain synthesis (by decreasing excess globin available) confers considerable protection against both oxidative damage and the consequent membrane instability.


Mechanisms of action of free arachidonic acid on ovarian steroid production in the goldfish.
This study explores the mechanisms by which free arachidonic acid (AA) affects ovarian steroidogenesis by full-grown prematurational follicles of the goldfish in vitro. AA (6-400 microM) stimulated testosterone production and this action was mediated by prostaglandin E2 (PGE2). The steroidogenic actions of AA and the corresponding increase in the production of PGE2 were blocked by inhibitors of the cyclooxygenase pathway (indomethacin, ETYA). Exogenous PGE2 (20-2000 ng/ml) also stimulated steroid production. In the presence of human chorionic gonadotropin (hCG), AA had differential effects. AA potentiated the steroidogenic actions of low dosages of hCG (0.1 IU/ml), while with maximal gonadotropin (1-10 IU/ml) stimulation a high concentration of AA (400 microM) attenuated steroid production in spite of elevated PGE2 synthesis, nor did it affect the PGE2 production obtained with AA-treated follicles. The steroidogenic induction by AA via PGE2 was mediated in part by Ca2+ since the calcium channel blocker nifedipine (25 microM) inhibited stimulated steroid production by both AA and PGE2. The conversion of AA to PGE2 does not require Ca2+ since PGE2 production by AA-treated follicles was not affected by nifedipine. However, treatment with the calcium ionophore A23187 (1 microM) potentiated the stimulatory actions of AA on steroid and prostaglandin production. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (1 mM) potentiated the stimulatory actions of AA on testosterone production but had no effect on the conversion of AA to PGE2. The steroidogenic actions of AA and PGE2 involve both transcription and translation since stimulated steroidogenesis was inhibited by actinomycin D and and cycloheximide (1-10 micrograms/ml). The conversion of AA to PGE2 was also blocked by these inhibitors. These results underscore the importance of AA and PGE2 in the regulation of ovarian steroidogenesis in the goldfish.


The Afya Bora Fellowship: An Innovative Program Focused on Creating an Interprofessional Network of Leaders in Global Health.
Most current health professions education programs are focused on the development of clinical skills. As a result, they may not address the complex and interconnected nature of global health. Trainees require relevant clinical, programmatic, and leadership skills to meet the challenges of practicing in an increasingly globalized environment. To develop health care leaders within sub-Saharan Africa, the Afya Bora Consortium developed a one-year fellowship for medical doctors and nurses. Fellows from nine institutions in the United States and sub-Saharan Africa participate in 12 learning modules focused on leadership development and program management. Classroom-based training is augmented with an experiential apprenticeship component. Since 2011, 100 fellows have graduated from the program. During their apprenticeships, fellows developed projects beneficial to their development and to host organizations. The program has developed fellows' skills in leadership, lent expertise to local organizations, and built knowledge in local contexts. Most fellows have returned to their countries of origin, thus building local capacity. U.S.-based fellows examine global health challenges from regional perspectives and learn from sub-Saharan African experts and peers. The Consortium provides ongoing support to alumni through career development awards and alumni network engagement with current and past fellow cohorts. The Consortium expanded from its initial network of five countries to six and continues to seek opportunities for geographical and institutional expansion.


GH response to GH-releasing factor in dementia and its relation with TSH response to TSH-releasing factor.
We have studied the GH response to GH-releasing factor (GRF) and the TSH response to TSH-releasing factor (TRH) in two groups or patients with dementia. A group of 28 patients with Alzheimer's disease (AD) and another group of 28 patients with dementia of vascular origin (VD). The GH response to GRF exhibited no difference between AD and VD patients (12.2 +/- 10.85 micrograms/L vs. 9.96 +/- 9.9) and there was no correlation with GH response to GRF and sex, stage of the disease and cerebral atrophy. The number of cases with exaggerated, normal or without response were similar in AD or VD patients. The TSH response to TRH exhibited no difference between AD and VD patients (9.18 +/- 4.93 mU/ml vs. 10.35 +/- 8.81). There was no correlation with TSH response to TRH and sex, stage of the disease, cerebral atrophy and response of GH to GRF. The number of cases with exaggerated, normal or without response was similar in AD or VD patients.


Natural killer clones derived from fetal (25 wk) blood. Probing the human T cell receptor with WT31 monoclonal antibody.
We have conducted a phenotypic and functional analysis of 19 cloned cell lines generated after allogeneic stimulation of circulating lymphocytes from a normal human fetus aged 25 wk. Using a limited series of mAbs (Anti-T3, WT31, T4, T8, and NKH1A), cloned cells were found to fall in three groups. Three clones have a conventional "inducer" phenotype. Three clones have a phenotype (T3+, WT31+, T8+, and NKH1A+) similar to that of certain NK active mature T lymphocytes present in adult peripheral blood. In contrast, 13 cell lines display surface characteristics that have not been described previously. Indeed, they express T3 proteins but not the WT31 determinant. In light of previous studies, these results show that WT31 mAb is a unique reagent directed at an invariant epitope of the human T cell receptor that is not present on all circulating T3+ fetal lymphocytes. Functionally the T3+, WT31+, and NKH1A+ clones were found to kill immunizing LAZ 388 cells, as well as K562, while T3+, WT31- and NKH1A+ clones display NK-like function exclusively. Moreover, only WT31+ lymphocytes present in the cell line used for cloning experiments have the capacity to recognize alloantigen-bearing cells. Together, these data suggest that expression of WT31 may be necessary for recognition of alloantigens, while NK reactions mediated by T3+ lymphocytes are WT31-independent.


Monotherapy of stable angina pectoris with bopindolol in comparison with diltiazem.
The efficiency of bopindolol (B) in the treatment of moderate stable angina pectoris was compared with that of diltiazem (D) by clinical evaluation and exercise tolerance. Following washout of previous treatment, patients were randomly assigned to either medication: 16 to D and 15 to B. The initial dose of B was 1 mg once daily, increased after 4 weeks to 2 mg once daily; the respective doses of D were 120 and 240 mg, given in 4 divided doses. Therapy resulted in an average decrease of 22 pain episodes and 256 min of pain time per month in the B group, whereas the respective reductions in the D group were 1.65 episodes and 129 min. Improvement in the exercise test indices following 8 weeks of treatment was more marked in the B group than in the D group. The average double product at peak exercise decreased markedly in the B group and more moderately in the D group. Thus, 2 mg B given once daily effectively blocked B receptors and relieved angina more efficiently than 240 mg D given in 4 divided doses.


Patients' openness to discussing implantable cardioverter defibrillator deactivation at end of life: a cross-sectional study.
It is recommended that patients and clinicians discuss end-of-life deactivation of their implantable cardioverter defibrillator (ICD) prior to device implantation and throughout the illness trajectory to facilitate shared decision-making. However, such discussions rarely occur, and little is known about patients' openness to this discussion. The purpose of this study was to explore factors associated with patients' openness to discussing end-of-life ICD deactivation with clinicians. This cross-sectional study recruited 293 patients with an ICD from outpatient clinics in the USA, Australia, and South Korea. Patients were classified into an open or resistant group based on their desire to discuss device deactivation at end of life with clinicians. Multivariable logistic regression was used to explore factors related to patients' openness to this discussion.About half of the participants (57.7%) were open to discussing such issues with their clinicians. Factors related to patients' openness to discussing device deactivation at end of life were living with someone, not having severe comorbid conditions (cancer and/or chronic kidney disease), greater ICD knowledge, and more experience discussing end-of-life issues with clinicians (odds ratio: 0.479, 0.382, 1.172, 1.332, respectively). Approximately half of the ICD recipients were reluctant to discuss device deactivation at end of life with clinicians. Unmodifiable factors were their living arrangement and severe comorbidity. ICD knowledge and prior experience discussing end-of-life issues were potentially modifiable factors in the future. These factors should be addressed when assessing patients' readiness for a shared discussion about device deactivation at end of life.


Improving Pathologists' Communication Skills.
The 2015 Institute of Medicine report on diagnostic error has placed a national spotlight on the importance of improving communication among clinicians and between clinicians and patients [1]. The report emphasizes the critical role that communication plays in patient safety and outlines ways that pathologists can support this process. Despite recognition of communication as an essential element in patient care, pathologists currently undergo limited (if any) formal training in communication skills. To address this gap, we at the University of Washington Medical Center developed communication training with the goal of establishing best practice procedures for effective pathology communication. The course includes lectures, role playing, and simulated clinician-pathologist interactions for training and evaluation of pathology communication performance. Providing communication training can help create reliable communication pathways that anticipate and address potential barriers and errors before they happen.


Molecular mechanisms of go signaling.
Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane protein in mammalian brains. It functions to couple cell surface receptors to intercellular effectors, which is a critical process for cells to receive, interpret and respond to extracellular signals. Go protein belongs to the pertussis toxin-sensitive Gi/Go subfamily of G proteins. A number of G-protein-coupled receptors transmit stimuli to intercellular effectors through Go. Go regulates several cellular effectors, including ion channels, enzymes, and even small GTPases to modulate cellular function. This review summarizes some of the advances in Go research and proposes areas to be further addressed in exploring the functional role of Go.


Bioactive compounds of Shuang-Huang-Lian prescription and an insight into its binding mechanism by β2 -adrenoceptor chromatography coupled with site-directed molecular docking.
Owing to the promising clinical efficacy and relatively simple composition, Shuang-Huang-Lian prescription is widely prescribed for the treatment of acute upper respiratory tract infection and acute bronchitis in practice. This necessitates the understanding of the bioactive compounds of the prescription and their binding mechanism to β2 -adrenoceptor, which mediates the aforementioned ailments. In this work, a column containing immobilized β2 -adrenoceptor was prepared using a diazonium salt reaction. The bioactive compound collected from the β2 -adrenoceptor column was identified as chlorogenic acid by using high-performance liquid chromatography coupled with ion trap mass spectrometry. Using an injection amount dependent method, chlorogenic acid proved the binding to β2 -adrenoceptor through two kinds of sites. The numbers of the sites were (1.42 ± 0.03) × 10-8 and (9.06 ± 0.49) × 10-8 M. The association constants were (2.72 ± 0.01) × 105 and (2.80 ± 0.01) × 104 M-1 , respectively. Molecular docking analysis of the interaction between chlorogenic acid and β2 -adrenoceptor indicated that the binding mainly occurred on Ser169 , Ser173 , and Phe287 of β2 -adrenoceptor. These results paved the way to screen bioactive compounds of other traditional medicines by receptor chromatography.


A comprehensive review of the psychological effects of brainwave entrainment.
Brainwave entrainment (BWE), which uses rhythmic stimuli to alter brainwave frequency and thus brain states, has been investigated and used since the late 1800s, yet many clinicians and scientists are unaware of its existence. We aim to raise awareness and discuss its potential by presenting a systematic review of the literature from peer-reviewed journals on the psychological effects of BWE. Terms used to describe BWE and psychological outcomes were used to search English language studies from OVID Medline (1950-2007), PsychInfo (1806-2007), and Scopus. Twenty studies selected satisfied the following criterion: studies needed to use rhythmic stimuli with the aim ofaffecting psychological outcomes. Peer-reviewed experimental and quasi-experimental studies were accepted. Case studies and review articles were excluded. Psychological outcomes were measured using standard assessment methods or as deemed appropriate by peer review. Other clinical measurements, including electroencephalogram response, galvanic skin response, and neurotransmitter levels were not included. Psychological outcomes addressed cognition, stress and anxiety, pain relief, headaches or migraines, mood, behavior, and premenstrual syndrome (PMS). Protocols included the use of single, alternating, ascending, or descending frequencies or were determined by the subject, using auditory and/or photic stimulation. Studies examined single session effects and/or longer-term multiple session effects. Findings to date suggest that BWE is an effective therapeutic tool. People suffering from cognitive functioning deficits, stress, pain, headache/migraines, PMS, and behavioral problems benefited from BWE. However, more controlled trials are needed to test additional protocols with outcomes.


Regulation of c-myc and c-fos mRNA levels by polyomavirus: distinct roles for the capsid protein VP1 and the viral early proteins.
The levels of c-myc, c-fos, and JE mRNAs accumulate in a biphasic pattern following infection of quiescent BALB/c 3T3 mouse cells with polyomavirus. Maximal levels of c-myc and c-fos mRNAs were seen within 1 hr and were nearly undetectable at 6 hr after infection. At 12 hr after infection mRNA levels were again maximal and remained elevated thereafter. Empty virions (capsids) and recombinant VP1 protein, purified from Escherichia coli, induced the early but not the late phase of mRNA accumulation. Virions, capsids, and recombinant VP1 protein stimulated [3H]thymidine nuclear labeling and c-myc mRNA accumulation in a dose-responsive manner paralleling their affinity for the cell receptor for polyoma. The second phase of mRNA accumulation is regulated by the viral early gene products, as shown by polyomavirus early gene mutants and by a transfected cell line (336a) expressing middle tumor antigen upon glucocorticoid addition. These results suggest that polyomavirus interacts with the cell membrane at the onset of infection to increase the levels of mRNA for cellular genes associated with cell competence for DNA replication, and subsequently these levels are maintained by the action of the early viral proteins.


No show is a major problem in planning appointments for infertility patients.
We examined the pattern of bookings for and actual visits undertaken by patients attending the Infertility Clinics at the Rotunda Hospital Dublin as well as the accuracy of systems in place for recording such events. The data provided by the Hospital Patient Administration System (PAS), clinic worksheets and clinic record chart of first visit couples attending initially over a 12 month period 1995/1996 and their subsequent records to February 1998 was analysed. Comparable figures were provided from the corresponding private clinic over the same time frame. Sixty-nine percent had already had investigations and treatment elsewhere. Discrepancies were noted between the PAS and manual systems as confirmed by the patient records. The manual proved more accurate. We found 32% (88 of 276) patients failed to turn up for a first appointment compared with 17% of private patients. Un-notified no-show provides great logistic difficulties in planning clinic management. Waiting lists grow, staff and patients alike are greatly inconvenienced. This apparent recklessness makes the Charter of Rights for Hospital Patients difficult to comply with. A possible answer is to demand reconfirmation near to the clinic date and in it's absence reassign the appointment to another. Population education is clearly needed.


Characteristics of good mentors.
Physician executives who have advanced in their careers have had people who helped them. Six successful physician executives were interviewed about how mentors encouraged, taught, and helped them grow. Most agreed the term role model was more comfortable to them than the word mentor and that they only recognized these people as mentors when they looked back on their career paths--not at the time the interactions were happening. Sometimes they were role models and sometimes they were just the right person with the right information at the right time. Most were located in the person's city and organization and seen daily, but some were in another part of the country and seen on occasional visits but regularly talked to each other on the phone. Generally they were friends who created safe environments for learning, were protectors, gave specific feedback, viewed problems from a different angle, and stretched the thinking of those who sought their advice.


Differing effects of N-methyl-D-aspartate receptor subtype selective antagonists on dyskinesias in levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine monkeys.
The antiparkinsonian and antidyskinetic profile of two N-methyl-D-aspartate (NMDA) receptor antagonists, a competitive antagonist, (R)-4-oxo-5-phosphononorvaline (MDL 100,453), and a novel noncompetitive allosteric site antagonist, 4-hydroxy-N-[2-(4-hydroxyphenoxy)ethyl]-4-(4-methylbenzyl)piper idi ne (Co 101244/PD 174494), was assessed in six levodopa-treated 1-methyl-4-phenyl-tetrahydropyridine-lesioned parkinsonian monkeys. The effects on motor function of these two drugs, alone and in combination with levodopa, were then correlated with NMDA subtype selectivity and apparent affinity for four diheteromeric NMDA receptor subunit combinations expressed in Xenopus oocytes. MDL 100, 453 (300 mg/kg s.c.) by itself increased global motor activity (p =. 0005 versus vehicle) and administered 15 min after a low dose of levodopa/benserazide s.c., MDL 100,453 (50, 300 mg/kg s.c.) showed dose-dependent potentiation of antiparkinsonian responses and also produced dyskinesias. Following injection of a fully effective dose of levodopa, MDL 100,453 (300 mg/kg s.c.) also produced a 25% increase in mean dyskinesia score (p =.04). In contrast, Co 101244 did not change motor activity by itself and only showed a tendency to potentiate the antiparkinsonian response when given in combination with a low dose of levodopa, which did not attain statistical significance. However, with a high dose of levodopa, Co 101244 (0.1, 1 mg/kg s.c.) displayed antidyskinetic effects (67 and 71% reduction, respectively) while sparing levodopa motor benefit. In vitro, MDL 100,453 was an NMDA glutamate-site antagonist, with approximately 5- to 10-fold selectivity for the NR1A/NR2A subtype combination (K(b) = 0.6 microM) versus NR1A in combination with 2B, 2C, or 2D. In contrast, the allosteric site antagonist Co 101244 showed approximately 10,000-fold selectivity for the NR1A/NR2B (IC(50) = 0.026 microM) versus the other three subunit combinations tested. Taken together, the data suggest that the NR2 subunit selectivity profile of NMDA receptor antagonists can play an important role in predicting behavioral outcome and offer more evidence that NR2B-selective NMDA receptor antagonists may be useful agents in the treatment of Parkinson's disease.


IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide.
Alkylating agents, such as temozolomide, are among the most effective cytotoxic agents used for malignant gliomas, but responses remain very poor. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) plays an important role in cellular resistance to alkylating agents. IFN-beta can act as a drug sensitizer, enhancing toxicity against a variety of neoplasias, and is widely used in combination with other antitumor agents such as nitrosoureas. Here, we show that IFN-beta sensitizes glioma cells that harbor the unmethylated MGMT promoter and are resistant to temozolomide. By means of oligonucleotide microarray and RNA interference, we reveal that the sensitizing effect of IFN-beta was possibly due to attenuation of MGMT expression via induction of the protein p53. Our study suggests that clinical efficacy of temozolomide might be improved by combination with IFN-beta using appropriate doses and schedules of administration.


[Echographic measurement of extraocular muscles in vivo].
Thickness of the extraocular rectus muscles can be displayed and measured by non-standardized A-scan echography. To establish a norm for the thickness of the rectus muscles, 100 eyes of 50 subjects were examined, with the result that the four recti ranged from 3 mm to 5 mm in thickness. The methodology and the normal range derived may be helpful in the diagnosis and differentiation of diseases affecting the extraocular muscles, such as Graves' disease and myositis.


Nutlin-3 induces BCL2A1 expression by activating ELK1 through the mitochondrial p53-ROS-ERK1/2 pathway.
Nutlin-3 which occupies the p53 binding pocket in HDM2, has been reported to activate apoptosis through both the transcriptional activity-dependent and -independent programs of p53. Transcription-independent apoptosis by nutlin-3 is triggered by p53 which is translocated to mitochondria. However, we previously demonstrated that the nutlin-3-induced mitochondrial translocation of p53 stimulates ERK1/2 activation, an anti-apoptosis signal, via mitochondrial ROS generation. We report on how nutlin-3-stimulated ERK1/2 activity inhibits p53-induced apoptosis. Among the anti-apoptotic BCL2 family proteins, BCL2A1 expression was increased by nutlin-3 at both the mRNA and protein levels, and this increase was prevented by the inhibition of ERK1/2. TEMPO, a ROS scavenger, and PFT-μ , a blocker of the mitochondrial translocation of p53, also inhibited BCL2A1 expression as well as ERK1/2 phosphorylation. In addition, nutlin-3 stimulated phosphorylation of ELK1, which was prevented by all compounds that inhibited nutlin-3-induced ERK1/2 such as U0126, PFT-μ and TEMPO. Moreover, an increase in BCL2A1 expression was weakened by the knockdown of ELK1. Finally, nutlin-3-induced apoptosis was found to be potentiated by the knockdown of BCL2A1, as demonstrated by an increase of in hypo-diploidic cells and Annexin V-positive cells. Parallel to the increase in apoptotic cells, the knockdown of BCL2A1 augmented the cleavage of poly(ADP-ribose) polymerase-1. It is noteworthy that the augmented levels of apoptosis induced by the knockdown of BCL2A1 were comparable to those of apoptosis induced by U0126. Collectively, these results suggest that nutlin-3-activated ERK1/2 may stimulate the transcription of BCL2A1 via the activation of ELK1, and BCL2A1 expression may contribute to the inhibitory effect of ERK1/2 on nutlin-3-induced apoptosis, thereby constituting a negative feedback loop of p53-induced apoptosis.


Agomelatine in the treatment of mild-to-moderate depression in patients with cardiovascular disease: results of the national multicenter observational study PULSE.
PULSE was a large, observational, multicenter study designed to evaluate the efficacy and safety of agomelatine in the treatment of major depression in patients with cardiovascular disease (CVD). Patients with mild-to-moderate major depressive episodes, without psychotic symptoms, were treated as outpatients or in cardiac facilities in 46 regions of Russia. The patients received antidepressant monotherapy with agomelatine 25 or 50 mg, once daily, for 12 weeks. The mean age of the patients (N=896) was 51.4±9.9 years, and 68.5% were women. A progressive improvement in the total score on both the anxiety and depression subscales of the Hospital Anxiety and Depression Scale (HADS), from 13.1±3.8 and 13.9±3.1 at baseline to 3.7±2.8 and 3.9±3.0, respectively, was observed by 12 weeks. All individual HADS scores improved rapidly; the change between visits was also significant (P<0.0001). The majority (84.6%) were remitters (HADS total score <7) by 12 weeks. The Clinical Global Impression - Severity and Improvement scores also improved quickly. The mean hypochondria index (Whiteley Index) decreased significantly from 48.0±11.8 at baseline to 25.2±9.2 at 12 weeks (P<0.0001). The main hemodynamic indices improved or remained stable, and biochemical parameters reflecting liver function (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, total bilirubin) did not exceed three times the upper limits of established norms. Agomelatine resulted in statistically significant improvements in depressive symptoms, anxiety, and hypochondria in depressed patients with CVD, and had good tolerability. Our data suggest that agomelatine is safe to treat depression in patients with CVD.


Incubation temperature alters thermal preference and response to heat stress of broiler chickens along the rearing phase.
The current study aimed to investigate whether embryonic temperature manipulation may alter thermal preference throughout the rearing phase of broiler chickens and how this manipulation may affect response to thermal challenge, metabolism, growth rate and feed intake rate. Eggs were exposed to a constant incubation temperature [machine temperatures: 36°C (Low), 37.5°C (Control), and 39°C (High); eggshell temperature of 37.4 ± 0.08°C, 37.8 ± 0.15°C, and 38.8 ± 0.33°C, respectively] from d 13 till hatching. Low treatment chickens showed lower plasma T3 and GH levels at d 1 of age and lower T3 level at d 42 of age compared to the Control treatment. Preferred ambient, rectal temperature, T4 level, growth rate, food intake rate, and response to thermal challenge were not altered in these chickens. On the other hand, High-treatment chickens exhibited high preferred ambient temperature and rectal temperature during the first 2 wk post-hatch, lower plasma T3 level at d 21 and 42 and a delayed increase in respiratory movement in response to thermal challenge compared to the Control treatment. However, chickens subjected to the Control and High treatments did not differ in T4 and GH level and performance. We conclude that exposure to high temperature during late embryonic development has long-lasting effects on the thermoregulatory system of broiler chickens by affecting the heat tolerance of these chickens. Moreover, the preferred ambient temperature of the chickens from heat-treated eggs correspond to those recommended for the strain under study, whereas for the cold-treated and control-chickens it was 1°C below, indicating that incubation temperature might have consequences on the ambient temperature chickens require during the rearing phase.


Cardiovascular reactions from hypothalamic self-stimulation in the rat.
Arterial blood pressure (BP) and heart rate (HR) were continuously recorded during lateral hypothalamic self-stimulation with optimal stimulus parameters in rats. Hyper-hypotensive, hypertensive and hypotensive reactions were observed during separate self-stimulation, and the biphasic type considerably prevailed over other types of reactions. During the single cycles of self-stimulation hyper-hypotensive and hypertensive reactions with different heart rate reactions also occurred. In this case the biphasic type was seen in 75% of all reactions, whereas the hypotensive type occurred in 25% of the cases. The main type of BP reaction (92%) during continuous self-stimulation for 60-240 min was a gradual increase of the mean BP level from 15 to 40 mm Hg against initial values (p less than 0.001), that depended on the duration of self-stimulation. Changes of HR were more variable: tachycardia and bradycardia were seen approximately with the same frequency. Comparative analysis of cardiovascular reactions during hypothalamic SS and escape reactions provoked by ventromedial hypothalamus stimulation revealed some peculiarities of autonomic manifestations during positive and negative emotional reactions. The results of this comparison raises the question of a stress-reaction during self-stimulation behaviour.


Oncological problems in AIDS--a review of the clinical features and management.
Since the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic in the early 1980s, several malignant conditions have been recognised to be associated with this syndrome which affect up to 40% of AIDS patients at some stage of their illness. They include Kaposi's sarcoma, systemic non-Hodgkin's lymphoma, primary central nervous system lymphoma and invasive cervical cancer. Kaposi's sarcoma and primary central nervous system lymphoma were tumours rarely seen below the age of 50 prior to the epidemic and therefore were recognised early to be AIDS-related conditions. However, systemic non-Hodgkin's lymphoma and invasive cervical cancer were only recognised when sufficient epidemiological evidence became available to indicate an increased incidence of these conditions amongst the HIV-infected population. In the presence of immunosuppression, the biological behaviour of these conditions are significantly altered with a more advanced stage at presentation, a more aggressive disease course and poorer responses to treatment. There is evidence that in each of these malignant conditions, an additional viral infection may be responsible for their pathogenesis. Kaposi's sarcoma-associated herpes virus is implicated in the development of Kaposi's sarcoma, Epstein-Barr virus in systemic non-Hodgkin's lymphoma as well as primary central nervous system lymphoma and human papilloma virus in invasive cervical cancer. Developing effective treatment strategies with minimal toxicity for these patients remains the greatest challenge as they often have serious coexisting illnesses and tolerate chemotherapy poorly because of insufficient bone marrow function reserve.


Estrogenic Potentials of Traditional Chinese Medicine.
Estrogen, a steroid hormone, is associated with several human activities, including environmental, industrial, agricultural, pharmaceutical and medical fields. In this review paper, estrogenic activity associated with traditional Chinese medicines (TCMs) is discussed first by focusing on the assays needed to detect estrogenic activity (animal test, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay and yeast two-hybrid assay), and then, their sources, the nature of activities (estrogenic or anti-estrogenic, or other types), and pathways/functions, along with the assay used to detect the activity, which is followed by a summary of effective chemicals found in or associated with TCM. Applications of estrogens in TCM are then discussed by a comprehensive search of the literature, which include basic study/pathway analysis, cell functions, diseases/symptoms and medicine/supplements. Discrepancies and conflicting cases about estrogenicity of TCM among assays or between TCM and their effective chemicals, are focused on to enlarge estrogenic potentials of TCM by referring to omic knowledge such as transcriptome, proteome, glycome, chemome, cellome, ligandome, interactome and effectome.


Diagnosis and repair of perineal injuries: knowledge before and after expert training-a multicentre observational study among Palestinian physicians and midwives.
To assess whether a 2 days training with experts teaching on diagnosis and repair of perineal injuries among Palestinian midwives and physicians could change their level of knowledge towards the correct diagnosis and treatment. Multicentre observational study. Obstetric departments in 6 government Palestinian hospitals. All physicians and midwives who attended the training. A questionnaire comprising of 14 questions on the diagnosis and repair of perineal tears was distributed to all participants before the training (n=150; 64 physicians and 86 midwives) and 3 months after the training (n=124, 53 and 71, respectively). Characteristics, differences of the study population and level of knowledge before and after the training were presented as frequencies and percentages. Consistency in responses was tested by estimating the p value of McNemar test. Among physicians only 11.4% had accurate knowledge on perineal anatomy before the training compared with 78.85% after the training (p<0.001). For midwives, the corresponding numbers were 9.8% and 54.2%, respectively (p<0.001). Before the training, 5.8% of the physicians were aware that rectal examination is mandatory before and after suturing of episiotomies compared with 45.8% after the training (p<0.001). The corresponding numbers for midwives were 0% and 18% (p<0.001), respectively. Physicians knowledge of best practice of skin repair following episiotomy improved from 36.5% to 64.5% (p=0.008) and among midwives from 26.1% to 50.7% (p<0.001). Physicians knowledge of the overlap technique in the repair of full thickness external anal sphincter tears improved from 28.5% to 42.8% (p=0.05), whereas knowledge of repairing torn internal anal sphincter separately improved from 12.8% to 86.8% (p<0.001). Improvement in the level of knowledge on diagnosis and repair of perineal tears was observed for all physicians and midwives who attended the 2 days' expert training. Regular ongoing training will serve to maintain the newly acquired knowledge.


Capsaicin in the treatment of dermatologic disease.
Capsaicin cream is the first of a class of neuropeptide active agents to be introduced into dermatologic therapy. Capsaicin's effects appear primarily related to its ability to deplete the neuropeptide substance P from local sensory terminals in the skin. The use of capsaicin cream in the treatment of postherpetic neuralgia and psoriasis is discussed. I believe that capsaicin and other neuropeptide active agents may become important therapeutic modalities for the dermatologist in the near future.


Further considerations for placebo controls in surgical trials.
The use of invasive placebo controls in surgical trials can be challenging. The ASPIRE guidance, published in the Lancet in 2020, provided advice for the design and conduct of surgical trials with an invasive placebo control. Based on a more recent international expert workshop in June 2022, we now provide further insights into this topic. These include the purpose and design of invasive placebo controls, patient information provision and how findings from these trials may be used to inform decision-making.


Sensitivity maps and system requirements for magnetic induction tomography using a planar gradiometer.
We evaluated analytically and experimentally the performance of a planar gradiometer as a sensing element in a system for magnetic induction tomography. A system using an excitation coil and a planar gradiometer was compared against a system with two coils. We constructed one excitation coil, two different sensing elements and a high-resolution phase detector. The first sensor was a PCB square spiral coil with seven turns. The second sensor was a PCB planar gradiometer with two opposite square spirals of seven turns, with a distance between centres of 8 cm. Theoretical sensitivity maps were derived from basic equations and compared with experimental data obtained at 150 kHz. The experimental sensitivity maps were obtained measuring the perturbation produced by a brass sphere of 12 mm in empty space. The advantage of using a gradiometer is that it can be adjusted to give a minimum signal for homogeneous objects, while increasing the sensitivity to local perturbations of the conductivity. Results show that a system using a planar gradiometer as detector has less demanding requirements for the electronic system than a system using simple coils.


Laparoscopic Varicocelectomy with Single Incision in Children.
Single port laparoscopic varicocelectomy had been introduced to treat varicocele. As the special instrument with three ports was a bit larger for children, a modified technique of single incision with two trocars was attempted in our department. The study was designed to compare it with the traditional laparoscopic method via three ports. Twelve boys of 14 varicoceles were admitted to accept laparoscopic varicocelectomy of single incision with two trocars. Thirty-two patients of 33 varicoceles with traditional three-port laparoscopy were reviewed as control. Data were collected to compare within the two groups. All procedures were completed successfully in both groups. No significant difference in terms of patient's age, operative time, blood loss, analgesic requirement, hospital stay or complication. The technique of laparoscopic varicocelectomy through a single incision with two trocars is safe, effective, and cosmetically acceptable.


Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section.
To assess neurotrophic factor upregulation in the retina after damage to the optic nerve and relate that regulation to changes in photoreceptor stability and function. Retinas of adult pigmented (Long-Evans) rats were examined at successive times (1-60 days) after unilateral optic nerve section. The distribution and expression of ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (FGF-2) and their receptor elements FGFR1 and CNTFRalpha were studied with immunohistochemistry and Western blot analysis. FGF-2 and CNTF mRNA levels were also assessed, with semiquantitative reverse transcription-PCR. Levels and localization of the intracellular signaling molecule ERK and its activated, phosphorylated form pERK, were examined by immunohistochemistry. To assess the correlation between neurotrophic factor levels and their protective effect against light damage, albino (Sprague-Dawley) rats were exposed to bright continuous light (1000 lux) for 24 or 48 hours at successive times after nerve section. The TUNEL technique was used to visualize neuronal cell death in the retina. CNTF upregulation was detected 1 week after optic nerve section, peaked at 2 weeks, and fell to control levels at 4 weeks. CNTF appeared first in the inner retina in the ganglion cells, then in the Muller cells in which it became prominent at the outer limiting membrane (OLM) and in the outer segment (OS) region of photoreceptors. FGF-2 upregulation became prominent, particularly in photoreceptors, 21 to 28 days after surgery, continued to 2 months, and slowly declined thereafter. Double labeling with antibodies to ligand and the receptor showed colocalization of CNTF to its receptor at the OS region, whereas FGF-2-to-FGFR1 binding was found in the outer nuclear (ONL) and outer plexiform (OPL) layers. Optic nerve section provided a significant protective effect against light-induced damage in the first 2 weeks. There was no protection when animals were exposed to damaging light 1 month after nerve section. The upregulation of CNTF 7 to 14 days after nerve section correlates with a reduction in the a-wave described previously. Colocalization of CNTF and CNTFRalpha on the outer segments suggests that CNTF acts at the photoreceptor membrane. The slower upregulation of FGF-2 correlates with a reduction of the b-wave. FGF-2/FGFR1 colocalization in the OPL suggests that this factor acts at the synaptic terminals of photoreceptors, modulating the release of neurotransmitters. The time course of pERK upregulation suggests that the successive upregulation of CNTF and FGF-2 activates the ERK pathway. Based on the time course of protection against bright continuous light, it seems that CNTF plays a major role in this effect, and FGF-2 has a less important role in the protection against light-induced damage.


Foxp3+-inducible regulatory T cells suppress endothelial activation and leukocyte recruitment.
The ability of regulatory T cells (Treg) to traffic to sites of inflammation supports their role in controlling immune responses. This feature supports the idea that adoptive transfer of in vitro expanded human Treg could be used for treatment of immune/inflammatory diseases. However, the migratory behavior of Treg, as well as their direct influence at the site of inflammation, remains poorly understood. To explore the possibility that Treg may have direct anti-inflammatory influences on tissues, independent of their well-established suppressive effects on lymphocytes, we studied the adhesive interactions between mouse Treg and endothelial cells, as well as their influence on endothelial function during acute inflammation. We show that Foxp3(+) adaptive/inducible Treg (iTreg), but not naturally occurring Treg, efficiently interact with endothelial selectins and transmigrate through endothelial monolayers in vitro. In response to activation by endothelial Ag presentation or immobilized anti-CD3ε, Foxp3(+) iTreg suppressed TNF-α- and IL-1β-mediated endothelial selectin expression and adhesiveness to effector T cells. This suppression was contact independent, rapid acting, and mediated by TGF-β-induced activin receptor-like kinase 5 signaling in endothelial cells. In addition, Foxp3(+) iTreg adhered to inflamed endothelium in vivo, and their secretion products blocked acute inflammation in a model of peritonitis. These data support the concept that Foxp3(+) iTreg help to regulate inflammation independently of their influence on effector T cells by direct suppression of endothelial activation and leukocyte recruitment.


Micropatterning neuronal networks.
Spatially organised neuronal networks have wide reaching applications, including fundamental research, toxicology testing, pharmaceutical screening and the realisation of neuronal implant interfaces. Despite the large number of methods catalogued in the literature there remains the need to identify a method that delivers high pattern compliance, long-term stability and is widely accessible to neuroscientists. In this comparative study, aminated (polylysine/polyornithine and aminosilanes) and cytophobic (poly(ethylene glycol) (PEG) and methylated) material contrasts were evaluated. Backfilling plasma stencilled PEGylated substrates with polylysine does not produce good material contrasts, whereas polylysine patterned on methylated substrates becomes mobilised by agents in the cell culture media which results in rapid pattern decay. Aminosilanes, polylysine substitutes, are prone to hydrolysis and the chemistries prove challenging to master. Instead, the stable coupling between polylysine and PLL-g-PEG can be exploited: Microcontact printing polylysine onto a PLL-g-PEG coated glass substrate provides a simple means to produce microstructured networks of primary neurons that have superior pattern compliance during long term (>1 month) culture.


Anesthesia with nontracheal intubation in thoracic surgery.
To study one-lung respiration during VATS wedge resection of bullae and pulmonary nodules with nontracheal intubation, and to explore the changes of vital signs when patients return to two-lung ventilation. Twenty-two patients with normal cardiopulmonary function and absence of contraindications to epidural anesthesia were included in this study. VATS wedge resection of bullae or pulmonary nodules was performed. 0.5% Ropivacain was administrated for epidural anesthesia (T8-9), and 2 mL of 2% lidocaine was used for local anesthetic block of the intrathoracic vagus nerves. The BIS value was maintained between 50 and 70 by target-controlled infusion of propofol and remifentanil. Electrocardiogram (ECG), heart rate (HR), blood pressure (Bp), pulse oxygen saturation (SpO(2)), respiratory rate (RR), bispectral index (BIS) and urine volume were monitored. None patients were converted to endotracheal intubation during anesthesia. MAP and SpO(2) after wound disclosure were stable (P>0.05), level of CVP significantly elevated, HR and RR increased (P<0.05), PaCO(2) increased gradually while PaO(2) remained stable. Fifteen minutes after wound closure, MAP, RR and SpO(2) returned to their pre-anesthesia levels, PH value gradually recovered, PaCO(2) tended to decrease and returned to normal one hour after wound closure. Physical agitation occurred in one case due to inadequate epidural anesthesia during skin incision. Cough before intrathoracic vagal blockade was noted in two cases (9.1%) because of lobe traction. Nontracheal intubation is feasible in VATS wedge resection of bullae and pulmonary nodules. The patients are with stable intraoperative vital signs and none experiences hypoxemia; intraoperative hypercapnia is tolerable and transient, which can be improved quickly when bilateral lungs resume spontaneous respiration.


Thermal properties of capacitively coupled electrodes in interstitial hyperthermia.
The multi-electrode current source (MECS) interstitial hyperthermia system which is used for treatment of cancer, employs segmented electrodes inserted in plastic tubes implanted in the treatment volume. The mean power deposition of the individual electrodes is controlled by varying the duty cycle of the RF signal applied to the electrodes, using thermocouples inside the electrodes for thermometry. A non-zero loss angle results in self-heating of the catheter. The thermal influence of self-heating was investigated and an analysis of the measurement of temperatures inside the catheter during and after heating is presented. Analytical models and a high-resolution numerical model were used for the calculation of steady state and transient distributions, respectively. The model results are compared with experimental data obtained in a muscle equivalent phantom. Results indicate that there is no difference between temperature inside and outside the catheter when using lossless catheter materials (e.g. PE and PTFE). Self-heating in the catheter wall has an adverse effect on the uniformity of the stationary temperature distribution and the reliability of temperature measurement with internal thermometry. These problems remain within acceptable limits for mildly lossy materials; the difference between the temperature inside and outside is only 6% when using low-loss Nylon. Analysis of the thermal decay after power-off shows that low-loss materials allow more time to obtain an accurate estimate of the tissue temperature at the catheter wall during power-on. This effect is enhanced by the presence of minute air layers in the applicator. Distortion of temperature gradients along the catheter was also investigated. Key factors are the thermal conduction across the catheter wall, and especially the presence of minute layers of air between consecutive layers of the probe. The distortion extends less than two millimetres, which is acceptable. The simulation results are compatible with measurements in phantoms and show that, if the proper choice of materials is made, the MECS applicator answers our expectations and that the temperature measurement inside the catheter can be used for direct feedback treatment control.


Dose Effects of Recombinant Adenovirus Immunization in Rodents.
Recombinant adenovirus type 5 (rAd) has been used as a vaccine platform against many infectious diseases and has been shown to be an effective vaccine vector. The dose of the vaccine varies significantly from study to study, making it very difficult to compare immune responses and vaccine efficacy. This study determined the immune correlates induced by serial dilutions of rAd vaccines delivered intramuscularly (IM) and intranasally (IN) to mice and rats. When immunized IM, mice had substantially higher antibody responses at the higher vaccine doses, whereas, the IN immunized mice showed a lower response to the higher rAd vaccine doses. Rats did not show dose-dependent antibody responses to increasing vaccine doses. The IM immunized mice and rats also showed significant dose-dependent T cell responses to the rAd vaccine. However, the T cell immunity plateaued in both mice and rats at 109 and 1010 vp/animal, respectively. Additionally, the highest dose of vaccine in mice and rats did not improve the T cell responses. A final vaccine analysis using a lethal influenza virus challenge showed that despite the differences in the immune responses observed in the mice, the mice had very similar patterns of protection. This indicates that rAd vaccines induced dose-dependent immune responses, especially in IM immunized animals, and that immune correlates are not as predictive of protection as initially thought.


Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster.
Animals bear communities of gut microorganisms with substantial effects on animal nutrition, but the host genetic basis of these effects is unknown. Here we use Drosophila to demonstrate substantial among-genotype variation in the effects of eliminating the gut microbiota on five host nutritional indices (weight, protein, lipid, glucose and glycogen contents); this includes variation in both the magnitude and direction of microbiota-dependent effects. Genome-wide association studies to identify the genetic basis of the microbiota-dependent variation reveal polymorphisms in largely non-overlapping sets of genes associated with variation in the nutritional traits, including strong representation of conserved genes functioning in signalling. Key genes identified by the GWA study are validated by loss-of-function mutations that altered microbiota-dependent nutritional effects. We conclude that the microbiota interacts with the animal at multiple points in the signalling and regulatory networks that determine animal nutrition. These interactions with the microbiota are probably conserved across animals, including humans.


Two Dimensions of Nutritional Value: Nutri-Score and NOVA.
Front-of-pack labels can improve the ability of consumers to identify which foods are healthier, making them a useful public health tool. Nutri-Score is a front-of-pack labelling system adopted by several European countries. This system ranks foods according to their nutritional quality, but does not consider other dimensions such as the degree of food processing. The aim of this study is to compare the nutritional quality (as assessed by Nutri-Score) and the ultra-processing (as assessed by the NOVA classification) of foods in the Open Food Facts database. A simple correspondence analysis was carried out to study the relationship between the two systems. Ultra-processed foods (NOVA 4) were found in all Nutri-Score categories, ranging from 26.08% in nutritional category A, 51.48% in category B, 59.09% in category C, 67.39% in category D to up to 83.69% in nutritional category E. Given the negative effect that the consumption of ultra-processed foods has on different aspects of health, front-of-pack labelling with Nutri-Score should at least be accompanied by complementary labelling indicating the level of processing, such as the NOVA classification.