Neurologic complications of bariatric surgery: involvement of central, peripheral, and enteric nervous systems.
Approximately one in three Americans is obese. Current society guidelines recommend bariatric surgery after conservative measures at weight loss have failed. The frequency of bariatric surgeries has increased significantly over the past decade. While considered both safe and effective, bariatric surgery presents a distinct set of risks. This review focuses on the neurological complications of bariatric surgery. Injuries have been reported at all levels of the nervous system, including the central, peripheral, and enteric nervous system. Injury can be classified according to time of presentation and location. The two main mechanisms of nerve injury are from mechanical injury or as a consequence of malnutrition. Encephalopathy, peripheral neuropathies, myelopathies, and radiculoneuropathies have all been reported. Mechanical injuries likely occur from mechanical compression. Malnutrition injuries result from multi-micronutrient deficiencies. The most likely candidates are vitamin B12, folate, zinc, thiamin, copper, vitamin A, and vitamin E deficiencies.


Growth substances from Veratrum tenuipetalum.
Young leaves and buds of Veratrum tenuipetalum yielded non-indolic growth accelerators and inhibitors in the acidic ether fraction. The titer of accelerators decreased while the inhibitors increased as leaves matured. This was also true when comparing extracts of immature and fruiting inflorescences. Indole 3-acetic acid was at no time detected in leaf, bud, and inflorescence extracts but indole 3-acetyl-aspartic acid was readily recovered from all of these. The alkaline ether fraction of leaf base meristems, buds, roots, and rhizomes was rich in crystalline and amorphous alkaloids and phenolic acids. Reducing the quantity of major substances through crystallization, precipitation, and filtration permitted thin film chromatographic separation of the minor alkaloids and phenolic acids in the presence of the major ones. The unchromatographed mixture, and also certain of the purified major and minor alkaloids studied, strongly inhibited growth in germinating oat and winter rye seeds. In addition, profound changes in morphology and cytology of the seminal roots resulted. DNA disappeared partially to completely from affected tissue in 2 day germinated seeds.


Comparative neuroanatomical parcellation of the human and nonhuman primate temporal pole.
The temporal pole is unique to nonhuman and human primates, although other species also present temporal cortex. A clear distinction is made between the gross anatomical, macroscopic temporal pole, located at the tip of the temporal lobe, and the temporal polar cortex, which is a general term that encompasses all reported divisions and can be applied to both nonhuman and human primates. In the 19th century early neuroanatomists identified the temporal polar cortex as a different entity, independent from the remainder of the temporal lobe. More recently, the temporal polar cortex has been subdivided into different fields. The analysis of the different portions that make up the temporal polar cortex was first described in the nonhuman primate, and later on in humans. In this review we examine the historical course of the concepts about the extension, structure, and main cytoarchitectonic areas. The different descriptions are presented in chronological order and their relevance is discussed. In general, some common features arise in nonhuman and human primates temporopolar cortex, namely, an increased thickness of this cortical area, a predominant dysgranular type of cortex, and a more restricted extension in humans relative to earlier accounts. A common pattern of cytoarchitectonic areas results from the criteria of previous authors, although the sulcal anatomy of the human temporal pole has great variability. The understanding of the extension, composition, and limits of the temporal polar cortex is crucial for identification of separate regions in neuroimaging studies. J. Comp. Neurol. 521:4163-4176, 2013. © 2013 Wiley Periodicals, Inc.


PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia.
PLA2G6-associated neurodegeneration (PLAN) and hereditary spastic paraplegia (HSP) are 2 groups of heterogeneous neurodegenerative diseases. In this study, we report PLA2G6 gene mutations in 3 families from Turkey, Morocco, and Romania. Two affected Turkish siblings presenting HSP adds the disease to PLAN phenotypes. They were homozygous for the PLA2G6 missense c.2239C>T, p.Arg747Trp variant and the ages of onset were 9 and 21. Parkinsonism, dystonia or cognitive decline were not the clinical elements in these patients contrary to the cases that has been previously reported with the same variant, however, iron accumulation was evident in their cranial magnetic resonance imaging. The Moroccan patient was homozygous for a novel missense c.1786C>T, p.Leu596Phe variant and the Romanian patient had 2 novel mutations; c.1898C>T, p.Ala633Val and c.1765_1768del, p.Ser589ThrfsTer76. Both of these patients conformed better to childhood onset PLAN with the age of onset at 4 and 7 years, respectively. Interestingly, all identified mutations were affecting the highly conserved patatin-like phospholipase domain of the PLA2G6 protein.


[Desaggregant Therapy of Patients With Ischemic Heart Disease: Unsolved Problems].
At present, choice of antiplatelet therapy in ischemic heart disease (IHD) patients depends on the IHD form, accepted treatment guidelines, contraindications, and cost of drugs. Usually, there is no regular control of the action of antiplatelet drugs. However, in many patients such therapy does not improve the long-term outcome. Increasing dosage of antiaggregants has no positive effect on prognosis. Presently attempts have been made to improve survival by introduction of double or triple drug combinations. Furthermore, although long-term treatment with combination of aspirin and clopidogrel, or both drugs plus one of the new oral anticoagulants (thrombin or a factor inhibitors) has no significant positive effect on total mortality, such therapy significantly increases risk of massive internal and particularly intracranial bleeding. In view of small decreasing effect of such therapy on the rate of reinfarction and stroke, one should search for new approaches. One of such approaches is selection of an antiplatelet drug taking into consideration its effect on the aggregative reactivity of platelets. There are considerable data proving that high residual platelet reactivity (RPR) during antiplatelet therapy is associated with elevated risk of diseases caused by arterial thrombosis. Our research demonstrates that one can overcome high RPR by substituting clopidogrel for aspirin and vice versa or by using combination of these drugs. Indeed, in patients with high RPR during aspirin or clopidogrel monotherapy this combination is associated only with slight increase of number of patients with target level of platelet reactivity. It can be supposed that in this group of patients one of oral anticoagulants (e.g. rivaroxaban) should be used in combination with clopidogrel.


Long-term dispersion stability and adhesion promotion of aqueous Cu nano-ink for flexible printed electronics.
Aqueous Cu nanoparticles are synthesized using a reducing agent and surface capping molecule which prevents the interparticular agglomeration and surface oxidation. Aqueous conductive nano ink is prepared using the resulting Cu nanoparticles and conductive Cu layers are prepared via a wet coating process. The conductive Cu layers, metalized by annealing at 300 degrees C under vacuum atmosphere, exhibit excellent electrical resistivity, showing values as low as 12 microomega cm. The long-term dispersion stability for three months is monitored through an investigation on the rheological behavior of the conductive nano ink and the resistivity variation of the conductive Cu layer. The adhesion property of the conductive Cu layer is dramatically improved when using a primer-treated polyimide film, whereas the conductive Cu layer completely peels off on a pristine polyimide film. The epoxy-contained primer plays a critical role as an intermediary between the aqueous Cu nano ink and the polyimide film.


Evidence for self-organization in determining spatial patterns of stream nutrients, despite primacy of the geomorphic template.
Nutrients in freshwater ecosystems are highly variable in space and time. Nevertheless, the variety of processes contributing to nutrient patchiness, and the wide range of spatial and temporal scales at which these processes operate, obfuscate how this spatial heterogeneity is generated. Here, we describe the spatial structure of stream nutrient concentration, quantify the relative importance of the physical template and biological processes, and detect and evaluate the role of self-organization in driving such patterns. We examined nutrient spatial patterns in Sycamore Creek, an intermittent desert stream in Arizona that experienced an ecosystem regime shift [from a gravel/algae-dominated to a vascular plant-dominated (hereafter, "wetland") system] in 2000 when cattle grazing ceased. We conducted high-resolution nutrient surveys in surface water along a 10-km stream reach over four visits spanning 18 y (1995-2013) that represent different successional stages and prewetland stage vs. postwetland state. As expected, groundwater upwelling had a major influence on nutrient spatial patterns. However, self-organization realized by the mechanism of spatial feedbacks also was significant and intensified over ecosystem succession, as a resource (nitrogen) became increasingly limiting. By late succession, the effects of internal spatial feedbacks and groundwater upwelling were approximately equal in magnitude. Wetland establishment influenced nutrient spatial patterns only indirectly, by modifying the extent of surface water/groundwater exchange. This study illustrates that multiple mechanisms interact in a dynamic way to create spatial heterogeneity in riverine ecosystems, and provides a means to detect spatial self-organization against physical template heterogeneity as a dominant driver of spatial patterns.


Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation.
The amyloidogenic processing of APP depends on two events: its phosphorylation by ROCK2 (at Thr654) and the phosphorylation of the APP-cleaving enzyme BACE1 (at Ser498). However, the mechanisms and structural details of APP-ROCK2 and BACE1-ROCK2 binding are unknown. Using direct physical methods in combination with an in silico approach, we found that BACE1 binds into the substrate-binding groove of ROCK2 with a low affinity (Kd = 18 µM), while no binding of APP to ROCK2 alone could be detected. On the other hand, a strong association (Kd = 3.5 nM) of APP to the weak ROCK2-BACE1 complex was observed, although no stable ternary complex was detected, i.e., BACE1 was displaced by APP. We constructed a sequential functional model: (1) BACE1 weakly binds to ROCK2 and induces an allosteric conformational change in ROCK2; (2) APP strongly binds to the ROCK2-BACE1 complex, and BACE1 is released; and (3) ROCK2 phosphorylates APP at Thr654 (leading to a longer stay in the early endosome during APP processing). Direct fluorescence titration experiments showed that the APP646-664 or APP665-695 fragments did not bind separately to the ROCK2-BACE1 complex. Based on these observations, we conclude that two binding sites are involved in the ROCK2-APP interaction: (1) the substrate-binding groove, where the APP646-664 sequence containing Thr654 sits and (2) the allosteric binding site, where the APP665-695 sequence binds. These results open the way to attack the allosteric site to prevent APP phosphorylation at Thr654 by ROCK2 without inhibiting the activity of ROCK2 towards its other substrates.


Success in mating: a coordinated approach to fitness through genotypes incorporating genes for stress resistance and heterozygous advantage under stress.
Natural populations are normally exposed to substantial environmental stress. In these circumstances, an association occurs between success in mating and extremes of sexual ornaments, rapid development, long life span, and low fluctuating morphological asymmetry. This association between important fitness traits depends on high metabolic efficiency underlain by genes for stress resistance and heterozygous advantage. In particular, the high energy demands from the development and maintenance of sexual ornaments imply that the "good genes" favored in the sexual selection process should be stress resistant. However, the generalized heterozygous advantage under stress suggests that many interacting genes are involved in promoting metabolic efficiency, so that the "good genes" approach should be replaced by a "good genotypes" approach. This "good genotype" approach has predictive power for incorporating additional fitness traits, especially where metabolic consequences can be perceived.


A level set approach to high fidelity interactive bone shaving for virtual training of surgical osteotomies.
Interactive multimodal surgical simulators are powerful tools that allow efficient and objective assessment of surgical skills. Bilateral Sagittal Split Osteotomy (BSSO) requires precise cutting of the mandible with a motorized saw that cannot afford a high margin of error. Surgeons rely on visual and haptic cues that are hard to train for through existing curricula without training directly on patients. In this paper, we present a new algorithm to achieve low-cost, precise sawing of the bone that is capable of providing realistic force feedback to the user at haptic rates (~1000Hz). Our method is centered around treating the bone surface as a level set that is evolved at interactive rates upon user's interaction with the virtual saw. The movement of the virtual saw itself is governed by a rigid body solver which is attached to the pose (6 degrees of freedom) of the haptic device via a mass-spring-damper which also supplies haptic force feedback. Our method allows parameterization of the erosion rate, saw speed, and bone density thus making it suitable to any material shaving application including dentistry (e.g., tooth milling) and a variety of surgical osteotomies.


Nurses as role models in health promotion: Piloting the acceptability of a social marketing campaign.
To pilot the acceptability to practising nurses of the concept of being healthy role models as regards obesity and weight. Nursing standards expect nurses to act as role models of professionalism, including maintaining a healthy lifestyle. Many healthcare employers wish to instigate values and social norms about professional behaviour in staff. A mixed methods study comprising two stages. In Stage One, an online survey was used to develop an intervention, which was then evaluated by a rapid intercept survey with open-ended questions. Insights from 71 obese nurses, recruited at a 2016 nursing conference, were used to develop a social marketing campaign encouraging a social norm around professional behaviour as regards healthy lifestyles and obesity, with the message that "first impressions count" in staff-patient encounters. The campaign was tested with 79 nurses at three English hospitals. In Stage One, 58% agreed that nurses should be role models and 48% that being obese made the public less likely to trust their public health messages. In Stage Two, the campaign concept of "first impressions count" was widely understood and accepted, but nurses found the introduction of a professional expectation around personal behaviours unacceptable. Nurses accept an expectation that they are healthy role models but refute its value when confronted with real-life scenarios. Other aspects of identity were privileged to avoid engaging with the healthy role model message. Personal health behaviour was seen as part of a private domain and not part of their public presentation in professional life.


[Chylothorax in a calf].
A case of chylothorax caused by fracture of thoracal vertebrae in a two-day-old Swiss Braunvieh male calf ist described. The clinical symptoms were those of a unilateral, progressive pleural effusion. This was confirmed by radiological and ultrasonographic examinations. Thoracocentesis was performed under ultrasonographic assistance. The liquid obtained from the pleural cavity was turbid and contained chylomicrons, lymphocytes and neutrophilic granulocytes as well as a high concentration of triglycerides. These qualities go together with chylus. Immunohistological examination for BVD virus turned out to be positive. An intrauterine disturbance of osteogenesis due to BVD virus must be considered a possible cause for fracture of vertebrae during delivery.


A case report of capillary leak syndrome with recurrent pericardial and pleural effusions.
Capillary leak syndrome (CLS) is a rare connective tissue disease, triggered by the leak of serous fluid into the interstitial spaces, characterized by a hallmark of oedema and effusions in confined spaces. The limiting factor in CLS management appears to be its diagnosis rather than treatment, which is usually to contain the disease progression rather than a cure. We report a case of a 51-year-old woman with recurrent life-threatening presentations of pericardial effusions, pleural effusions, and generalized swelling of face and extremities. The only notable past medical history was of Type 1 diabetes. Numerous investigations did not lead to specific disease accounting for pericardial effusions and pleural effusions. Eventually, the diagnosis of CLS was made based on hypovolaemic shock, hypoalbuminaemia, and haemoconcentration without the presence of albuminuria. She was managed with steroids to reduce system inflammation and later with immunoglobulins and tumour necrosis factor to contain the disease process. Since her diagnosis and subsequent appropriate management, she has not had further admissions with cardiac tamponade 16 months of follow-up. The diagnosis of CLS is difficult to make unless there is a high degree of suspicion and until other causes have been ruled out. It remains a challenging condition to manage as the treatment options are limited and patients recurrently present with emergencies until the correct diagnosis is made and the optimal treatment is provided.


National trends in surgical procedures for degenerative cervical spine disease: 1990-2000.
Degenerative cervical spine disease is one of the most common indications for spinal surgical intervention. The impact of the unprecedented changes in healthcare technology and delivery over the past decade is unknown. We examined this issue using the Nationwide Inpatient Sample database, a representative sample of all United States inpatient hospitalizations. All adult patients undergoing spinal procedures with a principal diagnosis of cervical spine disease were selected for analysis according to International Classification of Diseases 9th Revision clinical modification codes. Patients diagnosed with infection, neoplasia, fracture, or trauma, as well as those with noncervical or nonspecific principal diagnoses, were excluded. The total number of cervical spine procedures in the sampled population rose twofold, from 53,810 in 1990 to 112,400 in 2000. Anterior fusion procedures rose (17.8-69.5% of procedures), whereas nonfusion decompressions declined sharply (70.5-24.6%). Patient diversity increased with increasing rates of surgery among women (25.0-51.0 per 100,000) and minorities (18.4-45.7 per 100,000). Although average age (47.5-49.2 yr) and medical comorbidities (8.7-13.5% of patients) increased, mortality (0.21-0.14% of hospitalizations) and average length of stay (5.2-2.2 d) declined. Inflation-adjusted hospital charges rose by 48% to a total exceeding 2 billion dollars in 2000. Compared with one decade ago, the surgical treatment of degenerative cervical spine disease has evolved to include a higher percentage of anterior and fusion procedures performed on a more diverse, older, and comorbid patient population, with shortened hospital stay and improved morbidity and mortality, although at substantially increased cost.


Randomized Trial of Irrigation and Curetting for Cerumen Removal in Young Children.
Objectives: To gather preliminary data on the effectiveness and feasibility of cerumen removal using three irrigation methods and a metal curette in young children. Study design: Pilot study conducted as a randomized clinical trial of well and ill children age 6 months to 6 years with ≥25% cerumen occlusion in at least one ear. Children were stratified by age and randomized to one of four methods of cerumen removal: syringe with attached angiocath tubing, Elephant Ear Washer Bottle System®, OtoClear® Spray Wash Kit, or metal curette. Clinicians, blinded from treatment assignment, assessed the degree of cerumen occlusion before and after the procedure. Outcomes included reduction in cerumen occlusion, successful removal, time until completion and parental satisfaction. Rules for stopping procedures were established a priori. Results: Thirty-eight children underwent procedures (59 ears). There were no significant differences in reduction in cerumen and successful removal among the methods. Overall, 36 (61%) of 59 of procedures were successful. The syringe with angiocath tubing took the most time (P = 0.04) and resulted in the most stopped procedures (P < 0.01). Parental satisfaction scores were not significantly different. Conclusions: Irrigation methods performed comparably to cerumen removal with curette; the SA method had drawbacks. Irrigation can be performed by non-clinicians, which is potentially a significant advantage. (Clinical trial registration: http://www.isrctn.com/ISRCTN74402562).


Single nucleotide polymorphisms, gene expression and serum profile of immune and antioxidant markers associated with postpartum disorders susceptibility in Barki sheep.
The objective of this study was to explore the immunological and antioxidant alterations associated with ovine postpartum disorders. Blood samples were collected from 90 adult Barki ewes and allocated into three equal-sized groups (30 ewes each): control group (CG), inflammatory postpartum disorders group (IPG) and non-inflammatory postpartum disorders group (NIPG). PCR-DNA sequencing approach was carried out for TLR4 (256-bp) and SOD (456-bp) genes, and nucleotide sequence variations were noticed to be associated with postpartum disorders resistance/susceptibility. Gene expression profile was also evaluated and levels of IL5, IL6, IL1-ß, TNF alpha, TLR4 and Tollip were significantly up-regulated in ewes affected with postpartum disorders than resistant ones, while SOD and CAT genes pattern elicited an opposite trend. Exploring serum profile also showed a significant increase of IL-1α, IL-1β, IL-6, TNF-α, MDA and NO in IPG compared to their correspond values in NIPG and CG. However, serum levels of IL-10, CAT, GSH and GPx were significantly decreased. This study highlights that SNPs in TLR4 and SOD genes could be genetic markers for postpartum disorders resistance/susceptibility in Barki ewes. Gene expression alongside serum profiles of antioxidant markers could also be used to follow-up the immune status of ewes to build up an effective management protocol.


The natural course of elevated levels of depressive symptoms in patients with vascular disease over eight years of follow-up. The SMART-Medea study.
Patients with cardiovascular disease have an increased risk for depression, and depression predicts poor prognosis in these patients, but the long-term course of depression is not known. We studied the natural course of elevated levels of depressive symptoms in patients with cardiovascular disease over eight years follow-up. Within the Second Manifestations of ARTerial disease - Memory, depression and aging (SMART-Medea) study, depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) in 690 patients (62±10 years) at baseline and bi-annually during 8 years follow-up. Natural course was described for symptom severity and course type (never, single episode, intermittent, and chronic) based on the cut-off point of ≥6 on the PHQ-9. Using multinomial regression analysis (reference: never depressed) we estimated age- and sex-adjusted odds ratios (OR) for the associations of demographic factors and vascular disease categories with course type. Of the 690 patients, 60% was never depressed, 10% had a single episode, 19% had an intermittent and 11% a chronic course of depression. Increased risk for chronic course was observed for women (OR=3.42; 95% CI=1.98-5.90), those with younger age (OR=3.20; 95% CI=1.73-5.94), and for patients with cerebrovascular disease when compared to patients with coronary artery disease (OR=2.50; 95% CI=1.31-4.78). No information was available on clinical diagnosed major depressive disorder and/or clinical events during follow-up. In patients with cardiovascular disease, an intermittent or chronic course of elevated levels of depressive symptoms is very common. Patients with cardiovascular disease may require more careful clinical monitoring and management of depressive symptoms.


Anisotropically Aligned Cell-Laden Nanofibrous Bundle Fabricated via Cell Electrospinning to Regenerate Skeletal Muscle Tissue.
For muscle regeneration, a uniaxially arranged micropattern is important to mimic the structure of the natural extracellular matrix. Recently, cell electrospinning (CE) has been tested to fabricate cell-laden fibrous structures by embedding cells directly into micro/nanofibers. Although homogenous cell distribution and a reasonable cell viability of the cell-laden fibrous structure fabricated using the CE process are achieved, unique topographical cues formed by an aligned fibrous structure have not been applied. In this study, a CE process to achieve not only homogeneous cell distribution with a high cell viability, but also highly aligned cells, which are guided by aligned alginate fibers is employed. To attain the aligned cell-laden fibrous structure, various processing conditions are examined. The selected condition is applied using C2C12 myoblast cells to ensure the biocompatibility and guidance of cell elongation and alignment. As a control, a cell-printed scaffold using a 3D bioprinter is used to compare the efficiency of cell alignment and differentiation of myoblasts. Highly arranged, multinucleated cell morphology is confirmed in the CE scaffold, which successively facilitates myogenic differentiation. It is believed that this study will be a new platform for obtaining cell alignment and will significantly benefit the efforts on muscle regeneration.


[Health and hygienic characteristics of raw waste disposal in the Zenica-Doboj Canton].
The authors have investigated the sanitary problematics of the terminal municipal waste disposal by the methods of the field inspection and quering in the comparison with the incidence of relevant diseases among the people living in the neighbouring settlements. Ten municipal waste deponia are registered in the region with the range of distance of one hundred meters afar from the periphery of the human settlements, in Breza, to 3,500 meters afar, in Maglaj. According to the quering, only 30% of waste deponia do not affect the health seccurity of direct neighbouring area, but none of them fulfill the necessary sanitary conditions of disposition, though the waist deponium "Vila" (Tesanj) is the nearest to the wishful conditions. Half, out of all deponia, are not guarded at all, neither by human or by technical support. The incidence of the relevant diseases is evidently correlative to the nearness of wast deponia location to the human settlements; For instance, in the surrounding of main waste-deponium for Zenica (Tetovo), in the last year (1999), the incidence of the relevant diseases was 620 of cases per 100,000 of population, but on the furthest point (The village Janjići), the incidence of the relevant diseases was only 77/000.


Can virtual reality be used to measure and train surgical skills?
The quantitative literature on the use of virtual environments to measure and train a variety of surgical skills is critically reviewed. We selected works from the years 1995-2000. Theoretical perspectives, such as those of Saltzman (1979), Bernstein (1967) and Schmidt (1975) and techniques, such as hierarchical task analysis, are presented and contrasted with the largely atheoretical approach of the practitioners of virtual surgery. It is concluded that the quantitative work discussed provides few findings of value to practising surgeons. This may be due in part to the lack of consideration paid to fundamental issues in the learning of motor skills, such as whether motor skills learning is most effective with varying training conditions and the distinction between purely motoric aspects and knowledge of procedures. Possible ways forward for surgical training are outlined. It is suggested that the theoretical perspectives and techniques available in the area of motor behaviour should be incorporated into future experimental studies of surgery in virtual environments.


Lipid rescue resuscitation from local anaesthetic cardiac toxicity.
Systemic local anaesthetic toxicity is a rare but potentially fatal complication of regional anaesthesia. This toxicity is due to inhibition of ionotropic and metabotropic cell signal systems and possibly mitochondrial metabolism. It is associated with CNS excitation and, in the extreme, refractory cardiac dysfunction and circulatory collapse. Infusion of lipid emulsion has been shown in animal models to reliably reverse otherwise intractable cardiac toxicity and the mechanism of lipid rescue is probably a combination of reduced tissue binding by re-established equilibrium in a plasma lipid phase and a beneficial energetic-metabolic effect. Recent case reports have suggested the clinical efficacy of lipid infusion by the recovery of patients from intractable cardiac arrest. Future areas of investigation will focus on improved treatment regimes and better understanding of the mechanism of lipid rescue, which might allow superior alternative therapies, or treatment of other toxic events. An educational website has been established to help disseminate information about lipid emulsion therapy and to serve as a medium for physicians to share experiences or thoughts on the method and local anaesthetic toxicity.


Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma.
Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5' untranslated region (5'UTR) was fused with luciferase reporter and named as 5'Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the translation of 5'Sin1-Luc but not the control luciferase without the SIN1 5'UTR, suggesting that Sin1 5'UTR is necessary for Pdcd4 to inhibit Sin1 translation. Ectopic expression of wild-type Pdcd4 and Pdcd4(157-469), a deletion mutant that binds to translation initiation factor 4A (eIF4A), sufficiently inhibited Sin1 translation, and thus suppressed mTORC2 kinase activity and invasion in colon tumor cells. By contrast, Pdcd4(157-469)(D253A,D418A), a mutant that does not bind to eIF4A, failed to inhibit Sin1 translation, and consequently failed to repress mTORC2 activity and invasion. In addition, directly inhibiting eIF4A with silvestrol significantly suppressed Sin1 translation and attenuated invasion. These results indicate that Pdcd4-inhibited Sin1 translation is through suppressing eIF4A, and functionally important for suppression of mTORC2 activity and invasion. Moreover, in colorectal cancer tissues, the Sin1 protein but not mRNA was significantly upregulated while Pdcd4 protein was downregulated, suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not mRNA level in colorectal cancer patients. Taken together, our work reveals a novel mechanism by which Pdcd4 inhibits Sin1 translation to attenuatemTORC2 activity and thereby suppresses invasion.


Promoting Mental Health and Preventing Mental Illness in General Practice.
This paper calls for the routine integration of mental health promotion and prevention into UK General Practice in order to reduce the burden of mental and physical disorders and the ensuing pressure on General Practice. The proposals & the resulting document (https://ethicscharity.files.wordpress.com/2015/09/rcgp_keymsg_150925_v5.pdf) arise from an expert 'Think Tank' convened by the London Journal of Primary Care, Educational Trust for Health Improvement through Cognitive Strategies (ETHICS Foundation) and the Royal College of General Practitioners. It makes 12 recommendations for General Practice: (1) Mental health promotion and prevention are too important to wait. (2) Work with your community to map risk factors, resources and assets. (3) Good health care, medicine and best practice are biopsychosocial rather than purely physical. (4) Integrate mental health promotion and prevention into your daily work. (5) Boost resilience in your community through approaches such as community development. (6) Identify people at increased risk of mental disorder for support and screening. (7) Support early intervention for people of all ages with signs of illness. (8) Maintain your biopsychosocial skills. (9) Ensure good communication, interdisciplinary team working and inter-sectoral working with other staff, teams and agencies. (10) Lead by example, taking action to promote the resilience of the general practice workforce. (11) Ensure mental health is appropriately included in the strategic agenda for your 'cluster' of General Practices, at the Clinical Commissioning Groups, and the Health and Wellbeing Board. (12) Be aware of national mental health strategies and localise them, including action to destigmatise mental illness within the context of community development.


Dopamine D3 receptor-based medication development for the treatment of opioid use disorder: Rationale, progress, and challenges.
Opioid abuse and related overdose deaths continue to rise in the United States, contributing to the current national opioid crisis. Although several opioid-based pharmacotherapies are available (e.g., methadone, buprenorphine, naloxone), they show limited effectiveness in long-term relapse prevention. In response to the opioid crisis, the National Institute on Drug Abuse proposed a list of pharmacological targets of highest priority for medication development for the treatment of opioid use disorders (OUD). Among these are antagonists of dopamine D3 receptors (D3R). In this review, we first review recent progress in research of the dopamine hypothesis of opioid reward and abuse and then describe the rationale and recent development of D3R ligands for the treatment of OUD. Herein, an emphasis is placed on the effectiveness of newly developed D3R antagonists in the animal models of OUD. These new drug candidates may also potentiate the analgesic effects of clinically used opioids, making them attractive as adjunctive medications for pain management and treatment of OUD.


SLIDE: automatic spine level identification system using a deep convolutional neural network.
Percutaneous spinal needle insertion procedures often require proper identification of the vertebral level to effectively and safely deliver analgesic agents. The current clinical method involves "blind" identification of the vertebral level through manual palpation of the spine, which has only 30% reported accuracy. Therefore, there is a need for better anatomical identification prior to needle insertion. A real-time system was developed to identify the vertebral level from a sequence of ultrasound images, following a clinical imaging protocol. The system uses a deep convolutional neural network (CNN) to classify transverse images of the lower spine. Several existing CNN architectures were implemented, utilizing transfer learning, and compared for adequacy in a real-time system. In the system, the CNN output is processed, using a novel state machine, to automatically identify vertebral levels as the transducer moves up the spine. Additionally, a graphical display was developed and integrated within 3D Slicer. Finally, an augmented reality display, projecting the level onto the patient's back, was also designed. A small feasibility study [Formula: see text] evaluated performance. The proposed CNN successfully discriminates ultrasound images of the sacrum, intervertebral gaps, and vertebral bones, achieving 88% 20-fold cross-validation accuracy. Seventeen of 20 test ultrasound scans had successful identification of all vertebral levels, processed at real-time speed (40 frames/s). A machine learning system is presented that successfully identifies lumbar vertebral levels. The small study on human subjects demonstrated real-time performance. A projection-based augmented reality display was used to show the vertebral level directly on the subject adjacent to the puncture site.


Ultrasound-guided genitourinary interventions: principles and techniques.
Ultrasound (US) is often used to guide various interventional procedures in the genitourinary (GU) tract because it can provide real-time imaging without any radiation hazard. Moreover, US can clearly visualize the pathway of an aspiration or biopsy needle to ensure the safety of the intervention. US guidance also helps clinicians to access lesions via the transabdominal, transhepatic, transvaginal, transrectal, and transperineal routes. Hence, US-guided procedures are useful for radiologists who wish to perform GU interventions. However, US-guided procedures and interventions are difficult for beginners because they involve a steep initial learning curve. The purpose of this review is to describe the basic principles and techniques of US-guided GU interventions.


The voices of youths in COVID-19 times: exploring young people's emotional representations.
Since the spread of the COVID-19 virus worldwide, the pandemic had psychological consequences for the entire population for various reasons including restrictions, isolation, and socioeconomic changes. Young people were particularly affected by these psychological consequences, which formed the focus of the mental health concerns voiced by the World Health Organization. This research aimed to analyze, first-hand, the primary emotions that COVID-19 evoked in young Spanish people after two years of the pandemic. Participants were recruited through a snowball sampling procedure using emails, virtual platforms of the schools, and social networks, and a google forms questionnaire was administered for data collection. A total of 479 Spanish young people (18-36 years) participated in this study. The questionnaire consisted of a free-association exercise based on the Grid Elaboration Method (GEM) to analyze the participants' emotional representations of COVID-19. In addition, lexical analysis was used to analyze the text corpus. As a result, it could be observed that sadness was the core emotion experienced among young people, followed by fear. Specifically, emotional breakdown, fear, fatigue, and anger figured centrally in their emotional representations. Moreover, the findings revealed new patterns of self- and onward blaming towards youths. It was concluded that results of this research provide important clues for managing the mental health of young people, particularly during future pandemics.


Distinctive lack of CD48 expression in subsets of human dendritic cells tunes NK cell activation.
CD48 is a glycosyl phosphatidylinositol anchor protein known to be virtually expressed by all human leukocytes. Its ligand, 2B4, is a signaling lymphocyte activation molecule-related receptor involved in NK cell activation. Because dendritic cells (DCs) are strong inducers of NK cell functions, we analyzed the expression of CD48 in different human DC subsets. We observed that monocytes differentiating in DCs promptly down-regulate CD48. Similarly, DCs isolated from inflamed lymph nodes generally do not express CD48. Plasmocytoid DCs do not express CD48 either, whereas myeloid DCs harbored in blood, bone marrow, and thymus express it. In addition, we showed that CD48 expression in DCs affects NK cell functions during NK/DC cross-talk, because NK cells obtained from normal donors and from X-linked lymphoproliferative disease patients are, respectively, triggered or inhibited by DCs expressing surface CD48. Remarkably, IFN-gamma production by lymph node NK cells, in contrast to blood NK cells, can be negatively modulated by 2B4/CD48 interactions, indicating a 2B4 inhibitory pathway in lymph node NK cells. Therefore, the CD48 deficiency of DCs harbored in inflamed lymph nodes that we report in this study might be relevant to successfully activate lymph node NK cells in the early phase of the immune response. Our results show that distinct subsets of human DCs, differently from all other mononuclear hemopoietic cells, specifically do not express CD48. Moreover, the expression of CD48 depends on the anatomic location of DCs and might be related to the tissue-specific 2B4 function (activating or inhibitory) of the NK cells with which they interact.


Emergency department utilization and risk factors for mortality in older patients: an analysis of Korean National Emergency Department Information System data.
With trends in population aging an increasing number of older patients are visiting the emergency department (ED). This study aimed to identify the characteristics of ED utilization and risk factors for in-hospital mortality in older patients who visited EDs. This nationwide observational study used National Emergency Department Information System data collected during a 2-year period from January 2016 to December 2017. The characteristics of older patients aged 70 years or older were compared with those of younger patients aged 20 to 69 years. Risk factors associated with in-hospital mortality were analyzed by multivariable logistic regression. A total of 6,596,423 younger patients and 1,737,799 older patients were included. In the medical and nonmedical older patient groups, significantly higher proportions of patients were transferred from another hospital, utilized emergency medical services, had Korean Triage and Acuity Scale scores of 1 and 2, required hospitalization, and required intensive care unit admission in the older patient group than in the younger patient group. ED and post-hospitalization mortality rates increased with age; in particular, older medical patients aged 90 or older had an in-hospital mortality rate of 9%. Older age, male sex, transfer from another hospital, emergency medical service utilization, a high Korean Triage and Acuity Scale score, systolic blood pressure <100 mmHg, respiratory rate >20/min, heart rate >100/min, body temperature <36°C, and altered mental status were associated with in-hospital mortality. Development of appropriate decision-making algorithms and treatment protocols for high risk older patients visiting the ED might facilitate appropriate allocation of medical resources to optimize outcomes.


Calsequestrinlike calcium-binding protein is expressed in calcium-accumulating cells of Pistia stratiotes.
To contend with high calcium (Ca) levels in the environment, many plant species contain crystal idioblasts, specialized cells which accumulate large amounts of Ca as oxalate crystals. The biochemical processes involved in the accumulation of Ca in crystal idioblasts are unknown, as these cells constitute only a minor proportion of the total plant tissue. To address how crystal idioblasts buffer cytosolic Ca during crystal formation, we purified these cells from water lettuce and assessed their biochemistry. We show here that crystal idioblast cells contain three Ca-binding proteins not detectable in mesophyll cells. One of the Ca-binding proteins shares antigenicity with rabbit calsequestrin, a high-capacity low-affinity Ca-binding protein, and is encoded by related nucleotide sequences. Immunocytochemical localization studies further demonstrate that a calsequestrinlike protein is present primarily in crystal idioblasts and is preferentially localized in the endoplasmic reticulum, an organelle enriched in Ca as evidenced by vital staining. We thus conclude that crystal idioblasts possess a buffering system involving calsequestrinlike proteins, a process that likely plays an essential role in the bulk control of Ca in plant cells.


Past, present, and future technologies for oral delivery of therapeutic proteins.
Biological drugs are usually complex proteins and cannot be orally delivered due to problems related to degradation in the acidic and protease-rich environment of the gastrointestinal (GI) tract. The high molecular weight of these drugs often results in poor absorption into the periphery when administered orally. The most common route of administration for these therapeutic proteins is injection. Most of these proteins have short serum half-lives and need to be administered frequently or in high doses to be effective. So, difficulties in the administration of protein-based drugs provides the motivation for developing drug delivery systems (DDSs) capable of maintaining therapeutic drug levels without side effects as well as traversing the deleterious mucosal environment. Employing a polymer as an entrapment matrix is a common feature among the different types of systems currently being pursued for protein delivery. Protein release from these matrices can occur through various mechanisms, such as diffusion through or erosion of the polymer matrix, and sometimes a combination of both. Encapsulation of proteins in liposomes has also been a widely investigated technology for protein delivery. All of these systems have merit and our worthy of pursuit.


Comparison of the effectiveness of uvulopalatopharyngoplasty and laser palatoplasty for snoring.
We present the surgical management of 51 patients with a primary diagnosis of snoring. Patients with sleep apnoea syndrome were eliminated from the study. Four procedures were used: the classical uvulopalatopharyngoplasty, a limited uvulopalatoplasty, laser palatoplasty with tonsillectomy; and laser palatoplasty alone. Fifty-one of the 67 patients (76.1%) responded to a telephone questionnaire with a mean follow-up period of 18.2 months, 78.4% of patients reported improved or absent snoring. There was almost equal patient satisfaction between the conventional technique and the laser technique. The improvement in snoring was not influenced by the type of operation performed.


Physiotherapeutic Approach for Volar Barton Fracture Left Side Without Neurological Deficits: A Case Report.
Distal radius bone fracture termed a volar Barton fracture takes place when the ventral portion of the bone is displaced. This fracture happens obliquely within the joint itself. This is the case report of a 52-year-old female, who met with a road traffic accident and injured her left wrist. After the necessary investigation, she was diagnosed with a volar Barton fracture of the left wrist without any neurological deficits. After this, she was managed with open reduction and internal fixation with plate osteosynthesis. Postoperatively, the patient complained of pain around the left wrist joint and there was also restriction in the movements of the left wrist, which caused it to be difficult to perform everyday tasks. We report that following surgery, physical therapy intervention significantly reduced the intensity of pain, improved the range of motion, and strength of the muscle, and remarkable progress in the patient's functional independence. An Upper Extremity Functional Index was used as an outcome measure.


Optimization of scanning parameters for CT colonography.
To determine the optimal collimation, pitch and reconstruction interval for CT colonography, 10 spherical polyps between 1 mm and 10 mm diameter and made of tissue equivalent material with a CT number of 40 Hounsfield units (HU) were placed in the colon of an anthropomorphic phantom. The phantom was scanned at slice thicknesses of 3 mm, 5 mm and 7 mm and pitches of 1.0, 1.3, 1.5, 1.7 and 2.0 on an IGE Hispeed advantage system. Images were reconstructed for each scanning parameter at the minimum intervals allowed along the z-axis. The optimum scanning protocol was assessed by measuring maximum contrast between the polyp and air, sensitivity for detection of each polyp along the z-axis, and relative radiation dose. In addition, images were reviewed separately by two radiologists who graded polyp conspicuity as: 0, not seen; 1, faintly seen; 2, well seen. It was found that varying the scanning parameters caused a marked alteration in the maximum contrast between each polyp and air. For example, for the 5 mm polyp, the range of contrasts from best to worst case was 910-490 HU. It was noted that with contrasts of less than 500 HU, polyps were only faintly seen. A slice thickness of 3 mm with a pitch of 2 offers optimal polyp conspicuity with a relatively low radiation dose, we conclude that scanning parameters can be optimized for threshold contrast, radiation dose and subjective conspicuity. We propose an optimal parameter of 3 mm slice thickness and pitch 2.


Fluoxetine's spectrum of action in premenstrual syndrome.
This study extends our previous report of the efficacy and tolerability of fluoxetine in severe premenstrual syndrome (PMS), describes which aspects of the disorder are responsive to such treatment, and assesses the relationship between steady-state drug level and clinical outcome. Twenty-one women with documented PMS satisfied criteria for late luteal phase dysphoric disorder (DSM-III-R) and accepted the offer of a double-blind, randomized crossover trial of fluoxetine hydrochloride 20 mg/day vs placebo. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews after 3 months each of baseline, placebo and fluoxetine treatment. Compared with an inconsistent placebo response, fluoxetine produced marked improvement in 15 of 16 women completing the trial, eight showing virtually complete remission of PMS symptoms. Fluoxetine's efficacy extended over a range of affective, physical and behavioural symptoms; its superiority obtained whether it preceded or followed placebo. Three women withdrew due to adverse effects of fluoxetine, and 10 of 16 completing the trial reported at least one adverse effect of this agent. Compared with placebo, fluoxetine produced more (but usually transient) insomnia, sweating, gastrointestinal and menstrual disturbance. Plasma levels of fluoxetine and its active metabolite were not reliably associated with efficacy nor with side effects. Serotonergic agents appear to have considerable promise in treating a range of symptoms in women with severe PMS.


Pharmacokinetic study and limited sampling strategy of cyclosporine in Japanese heart transplant recipients.
The purpose of this study was to characterize the pharmacokinetics of cyclosporine (CsA) in Japanese heart transplant patients, and to optimise the monitoring strategy based on measurements of the area under the curve of plasma concentration absorption phase or 2 h post-dose concentrations (C(2)). At defined time periods during the first year after transplantation, the area under the curve for the CsA serum concentration from 0 to 4 h (AUC(0-4 h)) was evaluated. Pharmacokinetic parameters and renal function at 1 month and 12 months after transplantation were compared in 7 Japanese patients. The highest coefficient of determination between CsA AUC(0-4 h) and a single concentration was observed using C2 (r2 =0.838). For CsA pharmacokinetics, the mean measurement of whole blood trough levels value at 12 months was significantly lower than at 1 month after transplantation (p=0.026). The mean serum creatinine level at 12 months was significantly higher than at 1 month (1.00 mg/dl vs 0.73 p=0.0194). A single-time-point model that includes C2 is useful for predicting CsA AUC(0-4 h) in Japanese heart transplant patients. Mean C2 values >1,000 ng/ml were obtained in patients with no rejection at 1 month and 12 months after transplantation; however, renal impairment may occur.


Voluntary euthanasia, physician-assisted suicide, and the right to do wrong.
It has been argued that voluntary euthanasia (VE) and physician-assisted suicide (PAS) are morally wrong. Yet, a gravely suffering patient might insist that he has a moral right to the procedures even if they were morally wrong. There are also philosophers who maintain that an agent can have a moral right to do something that is morally wrong. In this article, I assess the view that a suffering patient can have a moral right to VE and PAS despite the moral wrongness of the procedures in light of the main argument for a moral right to do wrong found in recent philosophical literature. I maintain that the argument does not provide adequate support for such a right to VE and PAS.


[Effectiveness and safety of levetiracetam in 133 children with medication resistant epileptic seizures].
Levetiracetam (LEV) is the latest drug approved in the European Union for use in polytherapy in children over 4 years of age with partial epileptic seizures that are resistant to other antiepileptic drugs. AIM. To report our experience of associating LEV in children with medication resistant epileptic seizures. We conducted an open, observational, respective study involving 133 children with refractory epilepsies: 106 with focal seizures and 27 with other types of seizures. LEV was associated over a period of more than 6 months and we evaluated its repercussion on the frequency of the seizures and the side effects related to the drug. With average doses of LEV of 1,192 +/- 749 mg/day the frequency of the seizures was reduced by over 50% in 58.6% of cases and seizures were quelled in 15.8% of patients. Side effects were produced in 27.8% of cases, and were usually transient or tolerable; these effects led to withdrawal of LEV in only eight cases (6.02%). In 37 children (27.8%), their relatives noted an improvement in their social behaviour and cognitive abilities. a) LEV is an effective drug that is well tolerated in children with refractory epilepsy; b) Its effectiveness in different types of seizures indicates a broad therapeutic spectrum; and c) LEV can even condition favourable secondary effects, a circumstance that has been reported only exceptionally in the case of other antiepileptic drugs.


Hydrogen bond induced HF elimination from photoionized fluorophenol dimers in the gas phase.
In this paper, we report finding of a remarkable chemical effect of hydrogen bonding, elimination of hydrogen fluoride (HF) from the hydrogen bonded dimers of 2-fluorophenol (2-FP) and 3-fluorophenol (3-FP), in a supersonic jet expansion upon multi-photon ionization using 4th harmonic wavelength (266 nm) of a Q-switched Nd:YAG laser, and the reaction has been probed by time-of-flight mass spectrometry. No HF elimination is observed to occur by such means from the monomer of 3-FP, but it occurs with a small yield from the monomer of 2-FP. On the other hand, upon dimerization the reaction is triggered on for 3-FP, and for 2-FP it becomes so facile that no intact dimer cation survives and only the HF eliminated product ion appears in the mass spectra. Electronic structure calculation shows that in the cationic ground (D0) state, although the reaction for 2-FP dimer is exothermic, the associated barrier is significantly high (2.75 eV) and for its occurrence, absorption of three photons (2+1 type) is required. However, the reaction is predicted barrierless in the intermediate S1 state of this dimer, and HF loss dimer cation mass peak could appear in the mass spectrum due to an effective two-photon (1+1) ionization process. In the case of 3-FP dimer, the energy barriers both in S1 (neutral) and D0 (ionic) states are high, and it is suggested that for occurrence of HF elimination, dimer cation needs to absorb an additional photon. For facilitation of HF loss from this dimer cation, a rearrangement of the geometry and formation of an intermediate adduct have been suggested, and it is argued that the latter could be produced by nucleophilic attack of the neutral moiety at the ortho site of the cationic counterpart.


Enhanced hydrogen production on porous TiO2 nanotube arrays.
Well aligned TiO2 nanotube arrays have been synthesized via anodization in an NH4F and ethylene glycol electrolyte; the resulting carbon-entrained films were treated by oxygen and argon microwave plasma. It was found that as-prepared amorphous TiO2 nanotubes can be easily crystallized into anatase at temperature lower than 150 degrees C. Carbon can be effectively eliminated in oxygen plasma and a new secondary porosity was emerged. It was found such a porous film has obvious photovoltaic and hydrogen production enhancement under simulated solar irradiation compared with that crystallized in inert argon plasma. This phenomenon may be attributed to the improvement of light adsorption and its excellent capability of hole-electron separation derives from highly ordered nanoporous configurations.


Wolff-Parkinson-White syndrome associated with a coronary sinus diverticulum: ablative surgical approach.
This report concerns a patient with drug refractory supraventricular tachycardia due to the Wolff-Parkinson-White syndrome in association with a coronary sinus diverticulum. Division of the anomalous bypass tract was initially performed by an endocardial approach together with circumferential dissection of the neck of the diverticulum. This procedure failed to ablate the bypass tract that was only successfully divided when the superficial wall of the diverticulum was excised. This case illustrates the close association that exists between an anomalous atrioventricular bypass tract and a coronary sinus diverticulum, and the importance of dividing the superficial wall of the diverticulum as an integral part of the ablative procedure.


Decades-scale degradation of commercial, side-chain, fluorotelomer-based polymers in soils and water.
Fluorotelomer-based polymers (FTPs) are the primary product of the fluorotelomer industry. Here we report on a 376-day study of the degradability of two commercial acrylate-linked FTPs in four saturated soils and in water. Using an exhaustive serial extraction, we report GC/MS and LC/MS/MS results for 50 species including fluorotelomer alcohols and acids, and perfluorocarboxylates. Modeling of seven sampling rounds, each consisting of ≥5 replicate microcosm treatments, for one commercial FTP in one soil yielded half-life estimates of 65–112 years and, when the other commercial FTP and soils were evaluated, the estimated half-lives ranged from 33 to 112 years. Experimental controls, consisting of commercial FTP in water, degraded roughly at the same rate as in soil. A follow-up experiment, with commercial FTP in pH 10 water, degraded roughly 10-fold faster than the circum-neutral control suggesting that commercial FTPs can undergo OH–-mediated hydrolysis. 8:2Fluorotelomer alcohol generated from FTP degradation in soil was more stable than without FTP present suggesting a clathrate guest–host association with the FTP. To our knowledge, these are the only degradability-test results for commercial FTPs that have been generated using exhaustive extraction procedures. They unambiguously show that commercial FTPs, the primary product of the fluorotelomer industry, are a source of fluorotelomer and perfluorinated compounds to the environment.


Cardiovascular effects produced by nitric oxide-related drugs in the caudal ventrolateral medulla.
The role of nitric oxide in the central control of blood pressure was evaluated by interfering with its local formation in the caudal region of the ventrolateral medulla (CVLM). Urethane anesthetized male Wistar rats were used. Microinjection of L-arginine (L-Arg, 25-100 nmol) produced a hypertensive effect without significant changes in heart rate (HR). Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME, 7.4 nmol) produced a significant hypotensive effect. Microinjection of L-Arg (50 nmol) combined with L-NAME (7.4 nmol) did not significantly change mean arterial pressure or HR. A similar finding was obtained with microinjection of L-Arg (50 nmol) 5 min after microinjection of methylene blue (5 nmol) into the CVLM. The pressor effect of L-Arg was also abolished by prior i.v. injection of a vasopressin V1 receptor antagonist, but not by prior i.v. injection of prazosin. These results suggest an inhibitory role for local NO in the CVLM and that nitrergic pathways at the CVLM participate in the central regulation of AVP release.


[A practical guide for the management of gliomas].
The management of gliomas in daily clinical practice is challenging. It requires a multidisciplinary and coordinated approach involving neurosurgery, radiotherapy and, finally, chemotherapy. Important progress has been made during the last years with the introduction of a combined treatment associating standard radiotherapy with concomitant chemotherapy using temozolomide, a novel alkylating agent. For the first time in many years a new treatment strategy translated into a significant prolongation of survival. In parallel, molecular markers (e.g. loss of heterozygosity on chromosomes 1p and 19q or methylation of the methyl-guanine methyl transferase [MGMT] gene promoter) allowed for identification of distinct subtypes of glioma or prediction of treatment response. In this "Practical Guide", we describe the daily practice and aim at answering some common questions in the management of patients suffering from glioblastoma, astrocytoma, oligodendroglioma and low grade glioma. The therapeutic options presented here are based on evidences from the literature. In the absence of documented evidence, the empirical choices from our local practice are explained and justified.


[Alimentary iodine deficiency in the Federal Republic of Germany (author's transl)].
Urinary iodine excretion of 1945 schoolchildren aged 13 to 15-years from 24 cities throughout the Federal Republic of Germany (FRG) was measured. For comparison, urinary excretion of 5678 adults from 20 cities was calculated from the 24-hour radio-iodine uptake (RIU) by the method of Oddie. On the average the schoolchildren excreted 25.1 mug iodine per g creatinine: by WHO criteria this can be classified as a grade II iodine deficiency. There was a significant decline of urinary iodine excretion from North to South of the FRG. Urinary iodine excretion of children with thyroid enlargement (21.9 mug/g) was significantly less than that of normal children (26.1 mug/g creatinine; P less th that 0.0005). Urinary iodine excretion of adults averaged 25 to 35 mug/g creatinine, values calculated from RIU agreeing well with those determined chemically. Alimentary iodine intake was found to vary between 30 and 70 mug/d throughout the FRG, which is less than 30% of WHO recommended figures for optimal goitre prevention (150-200 mug iodine per day). Alimentary iodine deficiency has been demonstrated throughout the FRG, increasing from North to South in parallel with an increase in goitre rate. Goitre prevention through compulsory iodinization of salt is recommended.


Retarded tempo of physiological development in childhood delays the onset of the metabolic syndrome in adulthood.
Using serial data from the Fels Longitudinal Study, we investigated the effects of early and late attainment of the peak height velocity (PHV) in childhood on the timing of the appearance of the metabolic syndrome later in life. We aimed to show if early attainment of PHV engenders greater risks for chronic diseases in boys than in girls. Therefore, we defined those boys and girls in sex-specific quartiles of the study population that were slowest to attain PHV as having a slow tempo of development, and those in the growth that most rapidly attained PHV as having a rapid tempo of development. Boys who experienced an early onset of PHV tended to have a higher risk for the metabolic syndrome, dyslipidemia and impaired fasting glucose than those who had late onset of PHV. Girls who had an early onset of PHV tended to develop more abdominal obesity than females who had a late onset of PHV.


Case Report: Takotsubo Syndrome Induced by Severe Anaphylactic Reaction During Anesthesia Induction and Subsequent High-Dose Epinephrine Resuscitation.
Takotsubo syndrome (TTS) is a type of non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete recovery. Early diagnosis and prompt treatment are of great essence. Herein, we described a case of TTS of a patient who was scheduled initially for laparoscopic endometrial cancer staging. The 69-year-old woman presented with cardiogenic shock induced by the severe anaphylactic reaction to the antibiotics during anesthesia induction. Cardiopulmonary resuscitation (CPR) was implemented while several boluses of 1 mg epinephrine were injected. After the return of spontaneous circulation, a large number of orange peel-like rash appeared on the head, face, neck, and trunk of the patient. Transesophageal echocardiography (TEE) revealed diffused decreased left ventricular systolic function. Therefore, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) were applied in the intensive care unit. Biomarkers like cardiac troponin I (cTnI) subsequently decreased with improved cardiac insufficiency. Finally, the patient was discharged in good condition. This case demonstrated that TTS could be secondary to severe anaphylactic shock and exogenous catecholamines. With the consideration of the reversible condition and predictable recovery of TTS, early vigilance and advanced life support devices should be necessary.


Overweight and obesity prevalence among adult Pacific peoples and Europeans in the Diabetes Heart and Health Study (DHAHS) 2002-2003, Auckland New Zealand.
This paper describes and compares proportions of overweight, obese, and average BMI and their relationship with physical activity for Pacific ethnic groups (Samoan, Tongan, Niue, Cook Islands) and European New Zealanders by gender who participated in the 2002-03 Diabetes Heart and Health Study (DHAHS). The DHAHS was a cross-sectional population based study of people age 35-74 years carried out in Auckland between 2002-03. A total of 1011 Pacific people comprising of 484 Samoan, 252 Tongan, 109 Niuean, 116 Cook Islanders and 47 'Other Pacific' (mainly Fijian) and 1745 European participants took part in the survey. Participants answered a self-administered questionnaire to assess their participation in physical activity, perceived weight, and their perception of their current weight. Following this participant's height and weight was measured for calculation of BMI. Ethnic-specific cut offs were used for classification of overweight (Pacific > or = 26.0-<32.0, European > or = 25.0-<30.0) and obesity (Pacific > or = 26.0, European > or = 32.0). Approximately 95% of Pacific men and 100% Pacific women were 'overweight or obese'. Proportions of obesity were for men: all Pacific 53%, Samoan 58%, Cook Island 23%, Tongan 60%, and Niuean 49%; and for women: all Pacific 74%, Samoan 75%, Cook Island 69%, Tongan 78%, and Niuean 76%. Pacific people were as accurate at estimating their body weight as Europeans, and included similar proportions who under-estimated their weight. The Cook Islands group were most likely to accurately report their weight and were significantly less likely to underestimate their weight. A significantly higher proportion of Pacific people reported that they were heavier than a year ago (22.7%) compared to Europeans (17.2%), but significantly fewer Pacific people (55.6%) reported thinking that they were overweight compared to Europeans (64.9%). After adjustment for possible confounding variables, older Pacific adults were over 11 times more likely to be obese than their Europeans counterparts. The continued rise in overweight and obesity in older Pacific adults means that almost all are now overweight or obese. This raises concerns about interventions focussed on overweight and obesity, and will require the adoption of a total Pacific population 'environmental change' approach rather than dietary or physical activity interventions targeted to overweight individuals.


Homoleptic Transition Metal Carbonyl Cations: Synthetic Approaches, Characterization and Follow-Up Chemistry.
ConspectusCarbon monoxide, CO, is one of the most important ligands in organometallic chemistry. It is an excellent π-acceptor and a moderate σ-donor. Therefore, most of the known transition metal carbonyls (TMCs) exhibit a zerovalent or even negative metal oxidation state (OS) of up to -4. However, given the right conditions, the carbonyl ligand also forms homoleptic cationic complexes with one or more transition metal atoms, the transition metal carbonyl cations (TMCCs), known with an OS of up to +3. Despite their long-standing history upon discovery of the first [M(CO)6]+ examples (M = Mn, Tc, Re) by E. O. Fischer in 1962 as well as their very fundamental nature, it took until the 1990s for the scope to be widened by Aubke, Strauss and Willner. Yet, many potential TMCC entries known from gas-phase mass spectrometry work remained unknown on preparative grounds. This is due to their high reactivity, which puts scientists to new challenges and encourages the development of suitable solvents, anions and oxidants, to cope with the demands of these fundamental salts─later referred to as pseudo-gas-phase conditions and innocent deelectronators and solvents.Hence, the utilization of extremely weakly coordinating perfluorinated alkoxyaluminates [Al(ORF)4]- and [F{Al(ORF)3}2]- (ORF = -OC(CF3)3) in combination with the polar but non- or weakly coordinating innocent solvents 1,2-difluorobenzene (oDFB) and 1,2,3,4-tetrafluorobenzene (TFB) yielded the first TMCC salts containing heptacoordinate [M(CO)7]+ (M = Nb, Ta) as well as paramagnetic [M(CO)6]+· (M = Cr, Mo, W) or [Ni(CO)4]+·. However, the use of typical inorganic oxidants Ag+, [NO]+ and Ag+/0.5 I2 regularly led to unwanted side reactions. For example, the Lewis acidic silver(I) cations form Lewis pairs with various Lewis basic TMCs yielding partly clustered [Agx{TMC}y]x+ complex salts, while nitrosonium cations may substitute for carbonyl ligands, forming [M(CO)x-1(NO)]+ complexes. The synergistic oxidizing reagent Ag+/0.5 X2 can add halonium ions X+ to the TMCs (X = Cl, Br, I). This prevented the synthesis of univalent group 8 TMCC salts. Yet, the application of radical cation salts of perfluorinated arenes as innocent deelectronators finally yielded salts of [Fe(CO)5]+· and [M3(CO)14]2+ (M = Ru, Os).TMCC salts are excellent starting materials, and the reaction of [Co(CO)5]+ and [Ni(CO)4]+· with benzene led to the previously unknown bis(benzene) sandwich complexes [Co(benzene)2]+ and [Ni(benzene)2]+·. Under the right conditions, even the very weakly bound oDFB-complex salts with [M(oDFB)2]+ (M = Co, Ni) cations form, useful as naked metal(I) synthons and for small-molecule activation.


The widespread crucifer species Cardamine flexuosa is an allotetraploid with a conserved subgenomic structure.
The origin of Cardamine flexuosa (Wavy Bittercress) has been a conundrum for more than six decades. Here we identify its parental species, analyse its genome structure in comparison to parental genomes and describe intergenomic structural variations in C. flexuosa. Genomic in situ hybridization (GISH) and comparative chromosome painting (CCP) uncovered the parental genomes and the chromosome composition of C. flexuosa and its presumed diploid progenitors. Cardamine flexuosa is an allotetraploid (2n = 4x = 32), originating from two diploid species, Cardamine amara and Cardamine hirsuta (2n = 2x = 16). The two parental species display almost perfectly conserved chromosomal collinearity for seven out of the eight chromosomes. A 13 Mb pericentric inversion distinguishes chromosome CA1 from CH1. A comparative cytomolecular map was established for C. flexuosa by CCP/GISH. Whereas conserved chromosome collinearity between the C. amara and C. hirsuta subgenomes might have promoted intergenomic rearrangements through homeologous recombination, only one reciprocal translocation between two homeologues has occurred since the origin of C. flexuosa. The genome of C. flexuosa demonstrates that allopolyploids can maintain remarkably stable subgenomes over 10(4) -10(5) yr throughout a wide distribution range. By contrast, the rRNA genes underwent genome-specific elimination towards a diploid-like number of loci.


Assessing the mobility of Bronze Age societies in East-Central Europe. A strontium and oxygen isotope perspective on two archaeological sites.
European Bronze Age societies are generally characterised by increased mobility and the application of isotopic methods to archaeology has allowed the rate and range of human travels to be quantified. However, little is known about the mobility of the people inhabiting East-Central Europe in the late Early and Middle Bronze Age (1950-1250 BC) whose primary subsistence strategy was herding supported by crop cultivation. This paper presents the results of strontium (87Sr/86Sr) and oxygen (δ18O) isotope analyses in the enamel of people buried in collective graves at the cemeteries in Gustorzyn and Żerniki Górne. These sites are located in Kujawy and the Nida Basin, a lowland and an upland region with clearly different environmental conditions, respectively. Both sites are classified as belonging to the Trzciniec cultural circle and were used between 16th and 13th centuries BC. Among the 34 examined individuals only an adult female from Gustorzyn can be assessed as non-local based on both 87Sr/86Sr and δ18O signatures in her first molar. This may indicate the practice of exogamy in the studied population but more generally corresponds with the hypothesis of limited mobility within these societies, as has previously been inferred from archaeological evidence, anthropological analysis, and stable isotope-based diet reconstruction. New and existing data evaluated in this paper show that the 87Sr/86Sr variability in the natural environment of both regions is relatively high, allowing the tracking of short-range human mobility. A series of oxygen isotope analyses (conducted for all but one individuals studied with strontium isotopes) indicates that δ18O ratios measured in phosphate are in agreement with the predicted modern oxygen isotope precipitation values, and that this method is useful in detecting travels over larger distances. The challenges of using both 87Sr/86Sr and δ18O isotopic systems in provenance studies in the glacial landscapes of temperate Europe are also discussed.


Effect of ejaculation on Serum Prostate-Specific Antigen concentration.
To evaluate the effect of ejaculation on serum prostate-specific antigen (PSA) concentrations in patients with lower urinary tract symptom (LUTS). Our study includes 98 men (62 study and 36 control). After three days of sexual abstinence, blood samples were drawn for the measurement of baseline PSA levels. Then the patients were told to ejaculate. One, 5, 24 and 72 hours after ejaculation, serum total (tPSA), free (fPSA) and complexed PSA (cPSA) levels were measured. Serum PSA sampling was performed at the same intervals in the control group without ejaculation. The mean age in study and control groups patients were 59.03±0.99 years, 61.14±1.30 years, respectively. In the study group, changes in tPSA and fPSA levels after ejaculation were found statistically significant while changes in cPSA levels and f/tPSA ratios were not significant (p=0.016, p=0.0003, p=0.176, and p=0.173, respectively). Baseline values showed significant differences with 1st and 5th hours. No significant changes in tPSA, fPSA, cPSA levels and f/tPSA values were found in control group (p=0.223, p=0.224, p=0.444, and p=0.718, respectively). The changes in the number of patients exceeding the cutoff values after ejaculation were not statistically significant for tPSA, cPSA, and f/tPSA ratio. In this study, ejaculation increased tPSA and fPSA concentrations but it didn't have a significant effect on serum cPSA levels and f/tPSA ratios. However, recent ejaculation may affect the biopsy indication at least near cut off PSA values. Further studies are needed to explain the mechanisms of alterations in the concentration of PSA.


[Study, by the double diffusion in gel method, of the antigenic constituents of various strains of halophilic Vibrio].
The antigenic relationships among 18 strains of halophilic Vibrio (5 V. para-haemolyticus, 5 V. alginolyticus, 3 V. anguillarum and 5 Vibrio sp.) have been studied by a gel double diffusion test, either within the same species or with the others. Some halophilic Vibrio, named Vibrio sp. and having a uncertain taxonomic position, have been found close related with V. parahaemolyticus or with V. alginolyticus, whereas others are, as well as V. angiullarum, less related to those species.


Bispecific antibodies targeting EGFR/Notch enhance the response to talazoparib by decreasing tumour-initiating cell frequency.
Poly ADP ribose polymerase (PARP) inhibitors are mainly used in treating BRCA-mutant cancers, and their application in novel therapies to expand their benefit is of interest in personalized medicine. A recent report showed that pharmacological targeting of PARP increases the sensitivity of cancer cells to EGFR inhibition, but the therapeutic value of this combination has not been fully determined. We propose a strategy of combining PARP inhibitors with bispecific antibodies that target both EGFR and Notch signalling, highlighting the difficulties posed by deregulation of Notch signalling and the enrichment of cancer stem cells (CSCs) during therapy. In the present study, we showed that although PARP plus EGFR targeting led to more penetrant and durable responses in the non-small cell lung cancer (NSCLC) PDX model, it influenced the enrichment of stem-like cells and their relative proportion. Stem-like cells were significantly inhibited in vitro and in vivo by EGFR/Notch-targeting bispecific antibodies. These bispecific antibodies were effective in PDX models and showed promise in cell line models of NSCLC, where they delayed the development of acquired resistance to cetuximab and talazoparib. Moreover, combining EGFR/Notch-targeting bispecific antibodies and talazoparib had a more substantial antitumour effect than the combination of talazoparib and cetuximab in a broad spectrum of epithelial tumours. EGFR/Notch bispecific antibodies decrease the subpopulation of stem-like cells, reduce the frequency of tumour-initiating cells, and downregulate mesenchymal gene expression. These findings suggest that combining EGFR and Notch signalling blockade can potentially increase the response to PARP blockade.


Induction of monokine production by tumor cells.
Cells of the proerythromyeloid cell line K562 and of the T cell line Jurkat were able to induce an increase in TNF-, IL1 alpha-, and IL1 beta-mRNA expression in human peripheral blood derived monocytes in vitro. The activating principle of these tumor cells was associated with fractions of membrane preparations of distinct molecular mass, 32-38 kD for Jurkat cells and 46-54 kD for K562 cells, respectively. At least part of the activating constituent seemed to be protein in nature. Isolated membrane preparations of both cell types induced production and secretion of TNF. Stimulation of monocytes with the viable tumor cells led to TNF release only when Jurkat cells were used. Viable K562 cells induced enhanced TNFmRNA expression but seemed to absorb soluble TNF from the supernatant.


[Chronic T-cell lymphocytic leukemia: clinical and laboratory aspects of 5 patients].
T-cell chronic lymphocytic leukemia: clinical aspects and laboratory findings of five patients. This study illustrates the main clinical aspects and laboratory findings for five patients suffering from T-cell chronic lymphocytic leukemia. They make up 5% of our observations in the Department of Oncology-Hematology at the Busto Arsizio Hospital. Three patients with phenotype CD3+/CD4+ showed a fast course with skin involvement and poor response to chemotherapy (mean survival: 12 months). The course of a patient with unusual phenotype CD3-/CD4+ associated with autoimmune hemolytic anemia and end-stage prolymphocytic transformation was better (survival: 58 months). For 12 years we have been observing a woman suffering from the recently defined CD3+/CD8+/HNK1+ large granular lymphocytes chronic lymphocytosis with associated neutropenia. The disease has good prognosis, with poor symptomatology even without therapy. This study supports the immunological classification of the chronic lymphoproliferative diseases of leukemia and lymphoma with different clinical aspects and prognoses. This method of classification may be important in the consideration of some therapeutical approaches.


Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.
Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.


The mediated excitation energy transfer: Effects of bridge polarizability.
The observation of bridge-mediated excitation energy transfer (EET) has raised questions on the physical origin of such an effect. In this work, we studied the effect of bridge fragments in the Coulomb coupling, the major contribution to the electronic coupling in an EET process. For a series of ortho-phenyleneethynylene oligomers spaced donor-acceptors, we found that a large influence of the bridge fragment in EET coupling is through changes in the Coulomb couplings. Both enhancement and screening effects of the bridge were observed as the EET rates were modified by a factor of 0.3-23 with an intervening bridge in our calculations. The dependency of EET couplings on the orientation of transition dipoles of the donor and acceptor from quantum mechanical computations is very similar to that of a simple classical dielectric model. Our work shows that the bridge fragments can modify the Coulomb coupling with their polarizability by providing an optical dielectric medium between the donor and acceptor. In particular, when the transition dipoles of the donor and acceptor were longitudinal to a polarizable bridge, the EET rates were enhanced by one order of magnitude, as compared to the values of through-space models. Our results offer important insights into the design of efficient energy transfer systems.


Comparative study of 2 surgical techniques for castration of guinea pigs (Cavia porcellus).
The objective of this study was to compare 2 surgical approaches (scrotal or abdominal) for castration of guinea pigs and to investigate post-operative infection rates with either technique. Forty-eight guinea pigs were castrated by scrotal or abdominal technique after being randomly assigned to 1 of 2 groups (n = 24). Individuals were either castrated by an experienced exotic animal surgeon (n = 12) or by an experienced small animal surgeon (n = 12). Surgical wounds were evaluated daily before euthanasia for histological evaluation 2 wks after surgery. Post-operative infection rate was significantly higher in the scrotal group than in the abdominal group, with a higher rate for the experienced small animal surgeon. Castration of guinea pigs with the abdominal technique is significantly faster and has a significantly lower post-operative infection rate than the scrotal technique.


Acquired hearing loss in adolescents.
Studies on prevalence of acquired hearing loss across the life span have shown a trend of increase in hearing loss with age. A parallel decline in age of recreational use of loud music and cigarette smoking suggests that these early listening and recreational habits may be major contributing factors to the chronic hearing disability seen in later years. In recognition of these new recreational patterns of adolescents and young adults, Healthy People 2010 has issued a list of objectives for prevention of noise-induced hearing loss and smoking in adolescents and young adults through early education and intervention. In this article, the authors describe the effects of noise- and music-induced and smoking-induced hearing loss and provide guidelines for early identification and hearing conservation. Such an early approach to identification and conservation should ultimately help reduce hearing loss prevalence rates in adults.


Li intercalation in TiO2 anatase: Raman spectroscopy and lattice dynamic studies.
Raman spectra of the electrochemically lithiated TiO2 anatase are reported. They evidence spectral features induced by Li intercalation in the high-frequency region. Emergence of these lines supports recent hypothesis [M. Wagemaker et al., J. Am. Chem. Sec. 125, 840 (2003)] for formation of short Li-O valence bonds. This suggestion is verified by the lattice dynamics simulation based on the potential model with Li-O force constants extrapolated from known studies of the lithium oxide compounds. The obtained results confirm assumption of multiple Li positions and provide assignment of all the observed spectral features.


Antigens of the human syncytiotrophoblast microvillus plasma membrane.
Further data are presented on the isolation and biochemical analysis of syncytiotrophoblast microvillus plasma membrane preparations from normal full-term human placentas. No evidence has been obtained that IgG associated with these membranes is maternal antibody to trophoblast antigen. An oncotrophoblast plasma membrane antigen was previously identified by immunofluorescence, and an indirect radioisotopic antibody assay has now been used to confirm the detection of a cell surface antigen common to breast carcinoma cells and normal trophoblast. The relation of trophoblast plasma membrane antigens to possible maternal immunization in pregnancy is discussed.


Nanowormlike Li2FeSiO4-C composites as lithium-ion battery cathodes with superior high-rate capability.
Nanoworm-like Li2FeSiO4-C composites are synthesized using triblock copolymer Pluronic P123 (poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), EO20PO70EO20) as the structure directing agent (SDA) and under the effects of ethanol. As a polar nonaqueous cosolvent, ethanol has effects on the self-organization behavior of Pluronic P123 in water, which determines the final morphologies of the Li2FeSiO4-C composites synthesized. Li2FeSiO4-C composite nanoparticles are obtained if no ethanol is added into the system during the synthesis process. When tested as lithium-ion battery cathodes, the Li2FeSiO4-C nanoworms show superior electrochemical performances. At the rate of 1 C (1 C=166 mA g(-1)) the discharge capacity of the Li2FeSiO4-C nanoworms can reach 166 mAh g(-1) in the voltage window of 1.5-4.8 V at room temperature. At the rates of 5, 10, and 20 C, the discharge capacities of the Li2FeSiO4-C nanoworms can stabilize at 120, 110, and 90 mAh g(-1), respectively, and do not show obvious declines after hundreds of cycles. This performance of the Li2FeSiO4-C nanoworms at high rates is better than that of the Li2FeSiO4-C nanoparticles synthesized and many other Li2FeSiO4/C composites reported in the literature. The excellent electrochemical performances of the Li2FeSiO4-C nanoworms are believed to be related to the small sizes of the Li2FeSiO4 nanocrystals inside the nanoworms and the carbon that coats and embeds the nanocrystals.


Comparative Transcriptome Analysis of Two Ipomoea aquatica Forsk. Cultivars Targeted To Explore Possible Mechanism of Genotype-Dependent Accumulation of Cadmium.
A low-shoot-Cd (QLQ) and a high-shoot-Cd cultivar (T308) of water spinach (Ipomoea aquatica Forsk.) were used to investigate molecular mechanism of the genotype difference in cadmium (Cd) accumulation. RNA-Seq under 9 and 72 h cadmium exposures (5 mg L(-1)) were undertaken to explore Cd induced genotype differences in molecular processes. In total, 253 747 540 clean reads were assembled into 57 524 unigenes. Among them, 6136 and 10 064 unigenes were differentially expressed in QLQ and T308, respectively. Cell wall biosynthesis genes, such as GAUT and laccase, and three Cd efflux genes (Nramp5, MATE9, and YSL7) had higher expression levels in QLQ, while the genes in sulfur and glutathione metabolism pathway, e.g., sulfate transporter and cysteine synthase, showed higher expression levels in T308. These findings would be useful for further understanding of the mechanisms related to genotype-dependent Cd accumulation and developing the molecular assisted screening and breeding of low-shoot-Cd cultivars for water spinach.


Effectiveness of staff training programs for behavioral problems among older people with dementia.
This paper reviewed studies on staff training programs to address the behavioral problems associated with dementia among older people in residential care. The papers were classified according to whether or not the studies included a control group in the research design. The results of the review demonstrate that there has been a wide range of psychosocial and educational interventions to reduce behavioral problems among older people with dementia, with inconsistent results being obtained. However, many of these studies suffer from problems in their research design that make it difficult to evaluate their effectiveness. Problems in conducting research in the nursing home setting are highlighted, and suggestions for future research in this area are discussed.


Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan.
The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1microg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2microg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-beta1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative - again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the determination of the maximum dose, are adequately considered. The application of this two-stage assay for screening the initiating and promoting potential of chemicals is recommended for consideration by other research groups and regulatory authorities.


Conditional gene knockout and reconstitution in human iPSCs with an inducible Cas9 system.
Precise genome editing in human induced pluripotent stem cells (iPSCs) significantly enhances our capability to use human iPSCs for disease modeling, drug testing and screening as well as investigation of human cell biology. In this study, we seek to achieve conditional expression of the CD55 gene in order to interrogate its functions. We used two human iPSC lines that have unique genotypes, and constructed an inducible Cas9 gene expression system that is integrated at the AAVS1 safe harbor site in the human genome. Using paired guide RNAs, we observed efficient knock-out with an intended deletion in the coding region of several genes including CD55 and ETV6 genes. This paired guide RNA approach enabled us to efficiently identify homozygous iPSC clones with an intended deletion. Once an iPSC clone lacking CD55 expression was identified and characterized, we were able to use the same doxycycline system to induce expression of a CD55 transgene from a piggyBac vector, in both undifferentiated and differentiated iPSCs. This single cell line of gene knock-out complemented with an inducible transgene is sufficient to achieve conditional expression of the CD55 gene. The methodology described here is broadly applicable to other genes in order to interrogate their functions.


The genetic basis of thyroid autoimmunity.
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are prevalent autoimmune diseases, affecting up to 5% of the general population. AITDs arise due to interplay between environmental and genetic factors. In the past decade, significant progress has been made in our understanding of the genetic contribution to the etiology of AITDs. Excitingly, several AITD susceptibility genes have been identified and characterized. Some of these susceptibility genes are specific to either GD or HT, while others confer susceptibility to both conditions. The first AITD susceptibility gene locus identified was the Human-Leukocyte-Antigen DR (HLA-DR) gene locus. Subsequently, a quintet of non-HLA genes, including the cytotoxic T lymphocyte antigen (CTLA-4), CD40, protein tyrosine phosphatase-22 (PTPN22), thyroglobulin, and thyroid-stimulating hormone receptor (TSHR) gene, has been shown to contribute to the susceptibility to AITDs. Recently, the mechanisms by which these new AITD genes predispose to AITDs have been dissected. In this review, we overview and highlight the recent data on the genes predisposing to AITDs and the putative mechanisms by which they confer susceptibility to disease.