Psychosocial symptoms in very young children assessed for sexual abuse: A qualitative analysis from the ASAC study.
Child sexual abuse (CSA) is a worldwide problem with serious consequences. No recognizable symptom pattern for suspected CSA has yet been identified in very young children. We aim to investigate psychosocial symptoms in a sample of children with confirmed or strongly suspected CSA and the interpretations given to such symptoms by independent clinical experts. Secondly we examined whether experts were able to identify confirmed victims of severe CSA. A qualitative study including inductive content analysis of medical files and focus group discussions with independent experts on the interpretation of psychosocial symptoms was conducted. We included 125 children (76 boys, 60.8%, and 49 girls, 39.2%; median age 3.3 years; age range 0-11) who were involved in the Amsterdam sexual abuse case (ASAC) and had been examined for strongly suspected CSA. We identified four themes among the psychosocial symptoms: problems concerning emotions, behavior, toilet training, and development, whether or not associated with the daycare center or the perpetrator. Clinical experts identified signs of posttraumatic stress disorder (PTSD), regression in continence skills (not otherwise explained), and problems triggered by exposure to the perpetrator or the abuse location as concerning symptoms for CSA. Less concerning symptoms were designated as worrisome if they were numerous and there was no clear explanation for these symptoms. A clear symptom pattern was lacking and about half of the confirmed severe victims of CSA did not display any psychosocial problems. Therefore, it is difficult for experts to identify confirmed CSA victims. Thus, the assessment of suspected CSA should be over time and multidisciplinary.


A novel stable isotope labelling assisted workflow for improved untargeted LC-HRMS based metabolomics research.
Many untargeted LC-ESI-HRMS based metabolomics studies are still hampered by the large proportion of non-biological sample derived signals included in the generated raw data. Here, a novel, powerful stable isotope labelling (SIL)-based metabolomics workflow is presented, which facilitates global metabolome extraction, improved metabolite annotation and metabolome wide internal standardisation (IS). The general concept is exemplified with two different cultivation variants, (1) co-cultivation of the plant pathogenic fungi Fusarium graminearum on non-labelled and highly 13C enriched culture medium and (2) experimental cultivation under native conditions and use of globally U-13C labelled biological reference samples as exemplified with maize and wheat. Subsequent to LC-HRMS analysis of mixtures of labelled and non-labelled samples, two-dimensional data filtering of SIL specific isotopic patterns is performed to better extract truly biological derived signals together with the corresponding number of carbon atoms of each metabolite ion. Finally, feature pairs are convoluted to feature groups each representing a single metabolite. Moreover, the correction of unequal matrix effects in different sample types and the improvement of relative metabolite quantification with metabolome wide IS are demonstrated for the F. graminearum experiment. Data processing employing the presented workflow revealed about 300 SIL derived feature pairs corresponding to 87-135 metabolites in F. graminearum samples and around 800 feature pairs corresponding to roughly 350 metabolites in wheat samples. SIL assisted IS, by the use of globally U-13C labelled biological samples, reduced the median CV value from 7.1 to 3.6 % for technical replicates and from 15.1 to 10.8 % for biological replicates in the respective F. graminearum samples.


Myoclonus.
Myoclonus remains a challenging movement phenotype to characterize, evaluate, and treat. A systematic assessment of the temporal sequence, phenomenology, and distribution of movements can assist in the rational approach to diagnosis and management. Cortical forms of myoclonus are increasingly recognized as primarily cerebellar disorders. A syndrome of orthostatic myoclonus has been recognized by electrophysiology in patients with neurodegenerative disorders, mainly in Alzheimer disease, accounting for impairments in gait and balance previously mischaracterized as normal pressure hydrocephalus or orthostatic tremor. Tyrosine hydroxylase deficiency and Silver-Russell syndrome (uniparental disomy of chromosome 7) have been established as two novel causes of the myoclonus-dystonia syndrome. Mutations in the glycine receptor (GlyR) α1-subunit gene (GLRA1) explain the major expression of hyperekplexia, an inherited excessive startle disorder, butnewly identified mutations in GlyR β-subunit (GLRB) and glycine transporter 2 (GlyT2) genes (SLC6A5) account for "minor" forms of this disorder manifested as excessive startle and hypnic jerks. The entity previously known as palatal myoclonus has been reclassified as palatal tremor in recognition of its clinical and electromyographic features and no longer enters the differential diagnosis of myoclonic disorders. Increasing documentation of psychogenic features in patients previously characterized as having propriospinal myoclonus has cast doubts on the existence of this distinctive disorder. Myoclonus can be a prominent manifestation of a wide range of disorders. Electrophysiologic testing aids in distinguishing myoclonus from other mimics and classifying them according to cortical, subcortical, or spinal origin, which assists the choice of treatment. Despite the lack of randomized clinical trials, levetiracetam appears most effective in patients with cortical myoclonus, whereas clonazepam remains the only first-line therapeutic option in subcortical and spinal myoclonus.


A new method of surgical treatment of funnel chest with help of permanent magnets.
35 patients have benefited from the following procedure: After a double chondrotomy accompanied if need be by resection of the costal cartilages and a sternotomy, a magnet is placed in the retrosternal space. The wound is closed. A second magnet is placed externally on special corset. The magnetic chest expansion is achieved in between one and one and a half months. The internal magnet is removed six months after the operation. Its authors claim a series of 33 good results, without any relapses, after a follow-up of 2 1/2 years.


Fabrication and Characterization of SnO₂/Graphene Composites as High Capacity Anodes for Li-Ion Batteries.
Tin-oxide and graphene (TG) composites were fabricated using the Electrostatic Spray Deposition (ESD) technique, and tested as anode materials for Li-ion batteries. The electrochemical performance of the as-deposited TG composites were compared to heat-treated TG composites along with pure tin-oxide films. The heat-treated composites exhibited superior specific capacity and energy density than both the as-deposited TG composites and tin oxide samples. At the 70th cycle, the specific capacities of the as-deposited and post heat-treated samples were 534 and 737 mA·h/g, respectively, and the corresponding energy densities of the as-deposited and heat-treated composites were 1240 and 1760 W·h/kg, respectively. This improvement in the electrochemical performance of the TG composite anodes as compared to the pure tin oxide samples is attributed to the synergy between tin oxide and graphene, which increases the electrical conductivity of tin oxide and helps alleviate volumetric changes in tin-oxide during cycling.


Treatment Strategies for Infected Wounds.
The treatment of skin wounds is a key research domain owing to the important functional and aesthetic role of this tissue. When the skin is impaired, bacteria can soon infiltrate into underlying tissues which can lead to life-threatening infections. Consequently, effective treatments are necessary to deal with such pathological conditions. Recently, wound dressings loaded with antimicrobial agents have emerged as viable options to reduce wound bacterial colonization and infection, in order to improve the healing process. In this paper, we present an overview of the most prominent antibiotic-embedded wound dressings, as well as the limitations of their use. A promising, but still an underrated group of potential antibacterial agents that can be integrated into wound dressings are natural products, especially essential oils. Some of the most commonly used essential oils against multidrug-resistant microorganisms, such as tea tree, St. John's Wort, lavender and oregano, together with their incorporation into wound dressings are presented. In addition, another natural product that exhibits encouraging antibacterial activity is honey. We highlight recent results of several studies carried out by researchers from different regions of the world on wound dressings impregnated with honey, with a special emphasis on Manuka honey. Finally, we highlight recent advances in using nanoparticles as platforms to increase the effect of pharmaceutical formulations aimed at wound healing. Silver, gold, and zinc nanoparticles alone or functionalized with diverse antimicrobial compounds have been integrated into wound dressings and demonstrated therapeutic effects on wounds.


Miamiensis avidus (Ciliophora: Scuticociliatida) causes systemic infection of olive flounder Paralichthys olivaceus and is a senior synonym of Philasterides dicentrarchi.
The scuticociliate Miamiensis avidus was isolated from olive flounder Paralichthys olivaceus showing typical symptoms of ulceration and hemorrhages in skeletal muscle and fins. In an infection experiment, olive flounder (mean length: 14.9 cm; mean weight: 26.8 g) were immersion challenged with 2.0 x 10(3), 2.0 x 10(4) and 2.0 x 10(5) ciliates ml-1 of the cloned YS1 strain of M. avidus. Cumulative mortalities were 85% in the 2.0 x 10(3) cells ml-1 treatment group and 100% in the other 2 infection groups. Many ciliates, containing red blood cells in the cytoplasm, were observed in the gills, skeletal muscle, skin, fins and brains of infected fish, which showed accompanying hemorrhagic and necrotic lesions. Ciliates were also observed in the lamina propria of the digestive tract, pharynx and cornea. The fixed ciliates were 31.5+/-3.87 pm in length and 18.5+/-3.04 microm in width, and were ovoid and slightly elongated in shape, with a pointed anterior and a rounded posterior, presenting a caudal cilium. Other morphological characteristics were as follows: 13 to 14 somatic kineties, oral ciliature comprising membranelles M1, M2, M3, and paroral membranes PM1 and PM2, contractile vacuole at the posterior end of kinety 2, shortened last somatic kinety and a buccal field to body length ratio of 0.47+/-0.03. In addition, continuous PM1 and PM2, lack of M3 and variable kinetosome numbers in M2 and M3 were frequently observed. Specimens in the current study were compared with previous reports on M. avidus and Philasterides dicentrarchi and confirmed consistently that these 2 taxa are conspecific.


Situational assessment of empathy and compassion: Predicting prosociality using a video-based task.
Classical psychometric approaches in social science measure individuals' tendency to experience empathy and compassion. Using abstract questionnaire items, they place high demand on subjects' capacity to introspect, memorize, and generalize the corresponding emotions. We employed a Socio-affective Video Task (SoVT)-an alternative approach that measures situationally elicited emotions-and assessed its predictive power over prosocial behavior against classical questionnaires in a sample of Israeli university students. We characterized the conceptual embedding of the SoVT concerning other measures of prosocial affect and cognition, and tested group identification as an alternative precursor to prosocial behavior. Eighty participants rated their reactions to videos that presented the suffering of others or everyday scenes on scales of negative affect (providing a proxy for elicited empathy) and compassion. We then administered classical questionnaires that target empathy (the Interpersonal Reactivity Index) and compassion (the Compassionate Love Scale), as well as measures of hypothetical and real-life helping and prosocial attitudes-including conflict attitudes and intergroup bias. While compassion ratings in the SoVT failed to predict prosociality more accurately than classical questionnaires, the SoVT empathy index succeeded and correlated strongly with other precursors of prosociality. These results support video-based situational assessment as an implicit and robust alternative in the measurement of empathy-related processes.


Differentiation of Takotsubo Cardiomyopathy from ST Elevation Myocardial Infarction in Patients Activated for Fast-Track Coronary Angiography.
To compare clinical and electrocardiographic (ECG) features between Takotsubo cardiomyopathy (TC) and ST-elevation myocardial infarction (STEMI). We retrospectively reviewed clinical, electrocardiographic, and laboratory features of 20 consecutive TC patients and 155 consecutive STEMI patients who were activated for fast-track coronary angiography and were ultimately diagnosed with either TC or STEMI and compared these data between the two groups. Patients with TC were older (p = 0.001), more often female (p = 0.001), had more often been triggered by intense emotional or physical stress (p = 0.001) or illness (p = 0.001), and had a lower rate of smoking (p = 0.005) than STEMI patients. Compared with patients who presented with anterior wall STEMI, those with TC less commonly had Q waves (30.0% vs. 62.9%, p = 0.007) and reciprocal change (0.0% vs. 37.1%, p = 0.001), and had a lower rate of ST-segment elevation in lead V1 (5.0% vs. 59.8%, p = 0.001). ST-segment depression was also more common in TC in lead aVR (20.0% vs. 2.1%, p = 0.008). Previously proposed ECG criteria had low sensitivity, but high specificity in our patients. Our proposed point scoring model includes the use of both clinical and ECG findings. According to our proposed model, a score ≥4 had 90% sensitivity and 98% specificity in differentiating TC from acute anterior STEMI (AUC = 0.976, p<0.001). In patients activated for fast-track coronary angiography because of acute coronary ST-segment elevation syndrome, a number of clinical and ECG features differ between TC patients and patients with true STEMI. Our proposed point scoring model that uses clinical and ECG findings demonstrated improved diagnostic accuracy in differentiating TC from acute anterior STEMI.


Localization of [3H]nitrobenzylthioinosine binding sites in rat spinal cord and primary afferent neurons.
The distribution of [3H]nitrobenzylthioinosine ([3H]NBI) binding to nucleoside transport sites in rat spinal cord and spinal roots was examined using membrane binding and autoradiographic techniques. A single class of high affinity binding sites having dissociation constants (KD) between 0.42 +/- 0.05 and 0.088 +/- 0.012 nM was observed in dorsal and ventral spinal cord and their associated roots. The maximal number of binding sites (Bmax) in dorsal and ventral spinal cord was 110.1 +/- 7.1 and 73.6 +/- 7.5 fmol/mg protein, respectively. The highest levels of [3H]NBI binding were found in the dorsal grey matter of the cervical and lumbar enlargements. Autoradiographic studies showed that [3H]NBI sites were especially concentrated in the substantia gelatinosa of the dorsal spinal cord and the nucleus caudalis of the spinal trigeminal nucleus. The level of these binding sites in dorsal roots was nearly 4 times that observed in ventral roots; 98.5 and 23.0 fmol/mg protein, respectively. Adult animals depleted of unmyelinated sensory fibers by neonatal capsaicin treatment showed significantly reduced numbers of [3H]NBI sites (35%) in dorsal roots but not ventral roots, while KD values were unaffected. These results indicate that [3H]NBI sites are enriched in areas of the spinal cord and brainstem which subserve sensory functions and that these sites are located, in part, on unmyelinated primary afferent fibers.


Tetrahydroalstonine possesses protective potentials on palmitic acid stimulated SK-N-MC cells by suppression of Aβ1-42 and tau through regulation of PI3K/Akt signaling pathway.
Alzheimer's disease (AD) is the most common neurodegenerative disease. The morbidity of Alzheimer's disease is currently on the rise worldwide, but no effective treatment is available. Cornus officinalis is an herb and edible plant used in traditional Chinese medicine, whose extract has neuroprotective properties. In this investigation, we endeavored to refine a systems pharmacology strategy combining bioinformatics analysis, drug prediction, network pharmacology, and molecular docking to screen tetrahydroalstonine (THA) from Cornus officinalis as a therapeutic component for AD. Subsequent in vitro experiments were validated using MTT assay, Annexin V-PI flow cytometry, Western blotting, and immunofluorescence analysis. In Palmitate acid-induced SK-N-MC cells, THA restored the impaired PI3K/AKT signaling pathway, regulated insulin resistance, and attenuated BACE1 and GSK3β activity. In addition, THA significantly reduced cell apoptosis rate, down-regulated relative levels of p-JNK/JNK, Bax/Bcl-2, cytochrome C, active caspase-3 and caspase-3, and attenuated Palmitate acid-induced Aβ1-42 and Tau generation. THA may regulate the phenotype of AD and reduce cell apoptosis by modulating the PI3K/AKT signaling pathway. This systematic analysis provides new ramifications concerning the therapeutic utility of tetrahydroalstonine for AD.


A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.
RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.


Induction of labour versus expectant management for nulliparous women over 35 years of age: a multi-centre prospective, randomised controlled trial.
British women are increasingly delaying childbirth. The proportion giving birth over the age of 35 rose from 12% in 1996 to 20% in 2006. Women over this age are at a higher risk of perinatal death, and antepartum stillbirth accounts for 61% of all such deaths. Women over 40 years old have a similar stillbirth risk at 39 weeks as women who are between 25 and 29 years old have at 41 weeks.Many obstetricians respond to this by suggesting labour induction at term to forestall some of the risk. In a national survey of obstetricians 37% already induce women aged 40-44 years. A substantial minority of parents support such a policy, but others do not on the grounds that it might increase the risk of Caesarean section. However trials of induction in other high-risk scenarios have not shown any increase in Caesarean sections, rather the reverse. If induction for women over 35 did not increase Caesareans, or even reduced them, it would plausibly improve perinatal outcome and be an acceptable intervention. We therefore plan to perform a trial to test the effect of such an induction policy on Caesarean section rates.This trial is funded by the NHS Research for Patient Benefit (RfPB) Programme. The 35/39 trial is a multi-centre, prospective, randomised controlled trial. It is being run in twenty UK centres and we aim to recruit 630 nulliparous women (315 per group) aged over 35 years of age, over two years. Women will be randomly allocated to one of two groups: Induction of labour between 39⁰/⁷ and 39⁶/⁷ weeks gestation. Expectant management i.e. awaiting spontaneous onset of labour unless a situation develops necessitating either induction of labour or Caesarean Section.The primary purpose of this trial is to establish what effect a policy of induction of labour at 39 weeks for nulliparous women of advanced maternal age has on the rate of Caesarean section deliveries. The secondary aim is to act as a pilot study for a trial to answer the question, does induction of labour in this group of women improve perinatal outcomes? Randomisation will occur at 36⁰/⁷-39⁶/⁷ weeks gestation via a computerised randomisation programme at the Clinical Trials Unit, University of Nottingham. There will be no blinding to treatment allocation. The 35/39 trial is powered to detect an effect of induction of labour on the risk of caesarean section, it is underpowered to determine whether it improves perinatal outcome. The current study will also act as a pilot for a larger study to address this question. ISRCTN11517275.


Hospitalfoodie: an interprofessional case study of the redesign of the nutritional management and monitoring system for vulnerable older hospital patients.
To date, a solution to the problem of hospital malnutrition in older patients in the UK has not been found through previous approaches using isolated interventions. To identify opportunities for, and to develop and prototype a new food and nutritional management system able to meet individual patients' daily requirements. Using an interprofessional team approach, design researchers worked alongside food scientists, dieticians, medical sociologists, ergonomists, computer scientists, technologists, key stakeholders and a 'food family' (those concerned with nutrition management, and food supply and delivery in hospital, i.e. food producers, caterers, ward staff, nurses dieticians, physicians, speech and occupational therapists), as well as with older people representatives. Through ethnography and workshop-based methods, major opportunities for service improvement were identified. An iterative design and development process was deployed using mixed methods including ethnography, mapping, personas, storyboarding, role-playing, enactment and narratives. Prototypes of interactive interfaces were developed to test the workability of an electronic nutritional management and monitoring system linked to a nutrition composition database. In parallel, new food products were developed, led by food scientists, and a catering supply and delivery system for ward-based food provision was also developed. The methods used to facilitate interprofessional collaboration, the engagement of the food family, and to develop the food and nutrition service concept are described. A demonstration prototype was displayed in exhibition format at a series of conferences to gather further feedback. Early responses to the 'hospitalfoodie' demonstration prototype were favourable and indicate that, with further development, the prototype may offer the means for improving nutritional care standards in hospitals and be adaptable for use across other patient groups.


Analysis of translesion replication across an abasic site by DNA polymerase IV of Escherichia coli.
Unrepaired replication-blocking DNA lesions are bypassed by specialized DNA polymerases, members of the Y super-family. In Escherichia coli the major lesion bypass DNA polymerase is pol V, whereas the function of its homologue, pol IV, is not fully understood. In vivo analysis showed that pol V has a major role in bypass across an abasic site analog, with little or no involvement of pol IV. This can result from the inability of pol IV to bypass the abasic site, or from in vivo regulation of its activity. In vitro analysis revealed that purified pol IV, in the presence of the beta subunit DNA sliding clamp, and the gamma complex clamp loader, bypassed a synthetic abasic site with very high efficiency, reaching 73% in 2 min. Bypass was observed also in the absence of the processivity proteins, albeit at a 10- to 20-fold lower rate. DNA sequence analysis revealed that pol IV skips over the abasic site, producing primarily small deletions. The RecA protein inhibited bypass by pol IV, but this inhibition was alleviated by single-strand binding protein (SSB). The fact that the in vitro bypass ability of pol IV is not manifested under in vivo conditions suggests the presence of a regulatory factor, which might be involved in controlling the access of the bypass polymerases to the damaged site in DNA.


Photography and radical psychiatry in Italy in the 1960s. The case of the photobook Morire di Classe (1969).
In the 1960s Franco Basaglia, the Director of a Psychiatric Hospital in a small city on the edge of Italy (Gorizia), began to transform that institution from the inside. He introduced patient meetings and set up a kind of Therapeutic Community. In 1968 he asked two photographers - Carla Cerati and Gianni Berengo Gardin - to take photos inside Gorizia and other asylums. These images were then used in a photobook called Morire di Classe (To Die Because of your Class) (1969). This article re-examines in detail the content of this celebrated book and its history, and its impact on the struggle to reform and abolish large-scale psychiatric institutions. It also places the book in its social and political context and as a key text of the anti-psychiatry movement of the 1960s.


Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study.
Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively. In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatinib.


Skeletal muscle mass in acute coronary syndrome prognosis: Gender-based analysis from Hellenic Heart Failure cohort.
Predictive and prognostic ability of muscle mass in CVD settings is increasingly discussed. The gender-specific effect of skeletal muscle mass index (SMI) on 10-year recurrent fatal/non fatal cardiovascular disease (CVD) event of acute coronary syndrome (ACS) patients was evaluated. In 2006-2009, n = 1000 consecutive patients (n = 222 women), hospitalized at the First Cardiology Clinic of Athens with ACS diagnosis and with symptoms and left ventricular function indicative of heart failure were selected. SMI was created to reflect skeletal muscle mass through appendicular skeletal muscle mass (indirectly calculated through population formulas) divided by body mass index (BMI). In the 10-year follow-up (2016), 55% of ACS patients experienced recurrent fatal/non fatal CVD events (53% in women vs.62% in men, p = 0.04). Patients in the 2nd SMI tertile (mostly overweight) had 10% lower risk for CVD recurrence (women:men rate ratio = 0.87) over their counterparts in the 1st (mostly normalweight) and 3rd tertile (mostly obese). Multivariate analysis revealed that ACS patients in the 2nd SMI tertile presented 46% and 85% lower CVD event risk over their counterparts in the 1st tertile (Hazard Ratio (HR) = 0.54, 95% Confidence Interval (95% CI) 0.30, 0.96, p = 0.002) and 3rd tertile (HR = 1.85, 95%CI 1.05, 2.94, p = 0.03). Gender-based analysis revealed that this trend remained significant only in women. Inflammatory markers had strong confounding effect. A U-shape association between SMI and 10-year CVD event especially in women was highlighted. This work reveals gender-specific remarks for "obesity-lean paradox" in secondary prevention, implying that high muscle mass accompanied by obesity and excess adiposity may not guarantee better prognosis.


Different strategies of retrograde approach in coronary angioplasty for chronic total occlusion.
Retrograde approach through the collateral channels has been recently proposed and has the potential to improve the success rate of percutaneous coronary intervention (PCI) in chronic total occlusion (CTO) lesions of the coronary arteries. The author performed retrograde approach for CTO lesions in 45 patients from January 2006 to January 2007 at different medical institutions worldwide. The details of the techniques were examined retrospectively. The septal branch route was used in 93% of the cases. The author classified the strategies into six types after the successful crossing of a guidewire into the target artery distal to the CTO lesion through the collateral channels. Among them, "Just landmark," "Controlled antegrade and retrograde subintimal tracking," and "Proximal true lumen puncture" strategies were used most frequently (32, 27, and 30%, respectively). The retrograde guidewires could be successfully passed distal to the CTO lesion in 37 patients (82%), among them the final PCI success was achieved in 31 patients, yielding the PCI success by pure retrograde approach of 69%. The final success rate among 45 patients including 42 patients with previous failed attempts was 84% (38 patients). There were no serious complications related to the retrograde approach. Retrograde approach with different strategies, mainly through septal arteries, can provide a high success rate with PCI, as shown in 83% of patients with previous failed attempts at traditional PCI for CTO lesions, with there being no serious complications. More experience of this technique and its refinement are required for further improvement of PCI techniques for CTO lesions.


Prevalence of methicillin-resistant staphylococcus aureus as an etiology of community-acquired pneumonia.
Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of skin infections. Recent case series describe severe community-acquired pneumonia (CAP) caused by MRSA, but the prevalence and risk factors are unknown. We prospectively enrolled adults hospitalized with CAP from 12 university-affiliated emergency departments during the winter-spring of 2006 and 2007. Clinical information and culture results were collected, and factors associated with MRSA were assessed. Of 627 patients, 595 (95%) had respiratory (50%) and/or blood cultures (92%) performed. A pathogen was identified in 102 (17%); MRSA was identified in 14 (2.4%; range by site, 0%-5%) patients and in 5% of patients admitted to the intensive care unit. Two (14%) MRSA pneumonia patients died. All 9 MRSA isolates tested were pulsed-field type USA300. Features significantly associated with isolation of MRSA (as compared with any other or no pathogen) included patient history of MRSA; nursing home admission in the previous year; close contact in the previous month with someone with a skin infection; multiple infiltrates or cavities on chest radiograph; and comatose state, intubation, receipt of pressors, or death in the emergency department. Methicillin-resistant Staphylococcus aureus remains an uncommon cause of CAP. Detection of MRSA was associated with more severe clinical presentation.


Wolbachia's role in mediating its flea's reproductive success differs according to flea origin.
Endosymbionts-microbes that live within and engage in prolonged and intimate associations with their hosts-are gaining recognition for their direct impact on plant and animal reproduction. Here we used the overlooked Wolbachia-flea system to explore the possibility that endosymbionts may also play a role as mediators in shaping the reproductive success of their hosts. We simultaneously quantified the Wolbachia density in field- and laboratory-originated fleas that fed and mated on rodents for either 5 or 10 days and assessed their body size and current reproductive success. By combining multigroup analysis and model selection approaches, we teased apart the contribution of the direct effects of the flea's physiological age and body size and the mediation effect of its Wolbachia endosymbionts on flea reproductive success, and we showed that the latter was stronger than the former. However, interestingly, the mediation effect was manifested only in laboratory-originated fleas, for which the increase in Wolbachia with age translated into lower reproductive success. These results suggest that some well-supported phenomena, such as aging effects, may be driven by endosymbionts and show once again that the role of endosymbionts in shaping the reproductive success of their host depends on their selective environment.


Cernilton for benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH), nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH has been growing steadily. Cernilton, prepared from the rye-grass pollen Secale cereale, is one of the several phytotherapeutic agents available for the treatment of BPH. This systematic review aims to assess the effects of Cernilton on urinary symptoms and flow measures in men with benign prostatic hyperplasia (BPH). Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. Trials were eligible if they were: (1) randomized controlled trials or controlled clinical trials comparing Cernilton with placebo or other BPH medications in men with BPH; and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. Main outcome measure for comparing the effects of Cernilton with placebo and standard BPH medications were the change in urologic symptoms scales. Secondary outcomes included changes in nocturia as well as urodynamic measures (peak and mean urine flow, residual volume, prostate size). Main outcome measure for side effects was the number of men reporting side effects. 444 men were enrolled in 2 placebo-controlled and 2 comparative trials lasting from 12 to 24 weeks. Three studies used a double-blind method although treatment allocation concealment was unclear in all. Cernilton improved "self rated urinary symptoms" (percent reporting satisfactory or improving symptoms) versus placebo and Tadenan. The weighted risk ratio (RR) for self-rated improvement versus placebo was 2.40 [95% CI = 1.21, 4. 75], and the weighted RR versus Tadenan was 1.42 [95% CI = 1.21, 4. 75]. Cernilton reduced nocturia compared with placebo and Paraprost. Versus placebo, the weighted RR was 2.05 [95% CI = 1.41, 3.00], and versus Paraprost, the WMD was -0.40 times per evening [95% CI = -0. 73, -0.07]. Cernilton did not improve urinary flow rates, residual volume or prostate size compared to placebo or the comparative study agents. Adverse events were rare and mild. The withdrawal rate for Cernilton was 4.8% compared to 2.7% for placebo and 5.2% for Paraprost. The Cernilton trials analyzed were limited by short duration, limited number of enrollees, gaps in reported outcomes, and unknown quality of the preparations utilized. The comparative trials lacked a proven active control. The available evidence suggests Cernilton is well tolerated and modestly improves overall urologic symptoms including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.


Dipeptidyl peptidase III is a zinc metallo-exopeptidase. Molecular cloning and expression.
We have purified dipeptidyl peptidase III (EC 126.96.36.199) from human placenta. It had a pH optimum of 8.8 and readily hydrolysed Arg-Arg-beta-naphthylamide. Monoamino acid-, Gly-Phe-, Gly-Pro- and Bz-Arg-beta-naphthylamides were not hydrolysed at all. The enzyme was inhibited by p-chloromercuriphenylsulphonic acid, metal chelators and 3,4-dichloroisocoumarin and contained 1 mol of zinc per mol of enzyme. The zinc dissociation constant was 250 fM at pH 7. 4 as determined by the zinc binding study. We isolated, by immunological screening of a Uni-ZAP XR cDNA library constructed from rat liver mRNA species, a cDNA clone with 2633 bp encoding the rat enzyme. The longest open reading frame encodes a 827-residue protein with a theoretical molecular mass of 92790 Da. Escherichia coli SOLR cells were infected with the pBluescript phagemid containing the cloned cDNA and established the overexpression of a protein that hydrolysed Arg-Arg-beta-naphthylamide. The recombinant protein was purified and the amino acid sequence of the protein was confirmed. We presumed that the putative zinc-binding domain involved in catalysis was present in the recombinant enzyme. It was a novel zinc-binding motif in that one amino acid residue was inserted into the conserved HEXXH motif characteristic of the metalloproteinases.


An Arabidopsis pex10 null mutant is embryo lethal, implicating peroxisomes in an essential role during plant embryogenesis.
Peroxisomes participate in many important functions in plants, including seed reserve mobilization, photorespiration, defense against oxidative stress, and auxin and jasmonate signaling. In mammals, defects in peroxisome biogenesis result in multiple system abnormalities, severe developmental delay, and death, whereas in unicellular yeasts, peroxisomes are dispensable unless required for growth of specific substrates. PEX10 encodes an integral membrane protein required for peroxisome biogenesis in mammals and yeast. To investigate the importance of PEX10 in plants, we characterized a Ds insertion mutant in the PEX10 gene of Arabidopsis (AtPEX10). Heterozygous AtPEX10::dissociation element mutants show normal vegetative phenotypes under optimal growth conditions, but produce about 20% abnormal seeds. The embryos in the abnormal seeds are predominantly homozygous for the disruption allele. They show retarded development and some morphological abnormalities. No viable homozygous mutant plants were obtained. AtPEX10 fused to yellow fluorescent protein colocalized with green fluorescent protein-serine-lysine-leucine, a well-documented peroxisomal marker, suggesting that AtPEX10 encodes a peroxisomal protein that is essential for normal embryo development and viability.


Effect of non-specifically adsorbed ions on the surface oxidation of Pt(111).
The oxidation processes of a Pt(111) electrode in alkaline electrolytes depend on non-specifically adsorbed ions according to in situ X-ray diffraction and infrared spectroscopic measurements. In an aqueous solution of LiOH, an OHad adlayer is formed in the first oxidation step of the Pt(111) electrode as a result of the strong interaction between Li(+) and OHad , whereas Pt oxidation proceeds without OHad formation in CsOH solution. Structural analysis by X-ray diffraction indicates that Li(+) is strongly protective against surface roughening caused by subsurface oxidation. Although Cs(+) is situated near the Pt surface, the weak protective effect of Cs(+) results in irreversible surface roughening due to subsurface oxidation.


Rhabdosynochus Spp. (Monogenoidea: Diplectanidae) infecting the gill lamellae of snooks, Centropomus spp. (Perciformes: Centropomidae), in Florida, and redescription of the type species, R. rhabdosynochus.
Examination of the gill lamellae of 3 species of Centropomus spp. (Centropomidae) from 9 localities around the southern coast of Florida revealed 3 species of Rhabdosynochus (Monogenoidea, Diplectanidae). The common snook, Centropomus undecimalis, was infected with Rhabdosynochus rhabdosynochus (30 of 37 infected; prevalence 81%), Rhabdosynochus hargisi (9 of 37; 24%), and Rhabdosynochus hudsoni (20 of 37; 46%); the fat snook, Centropomus parallelus, with R. rhabdosynochus (12 of 22; 55%) and R. hudsoni (8 of 22; 36%) (new host records for both); and the tarpon snook, Centropomus pectinatus, with R. hudsoni (3 of 4; 75%) (new host record). Snooks infected with R. rhabdosynochus were collected only from tidal waters of salinity ≤10.4 ppt, where the parasite dominated the monogenoidean community. Rhabdosynochus hargisi and R. hudsoni showed greater salinity tolerance; the former dominated where salinity was ≥28.8 ppt. Thus, salinity appears to be a determinate factor in partitioning the monogenoidean community, while water depth and temperature and host population (as defined by collection locality) did not appear to affect occurrence of Rhabdosynochus spp. on snooks in Florida. With the exception of Tampa Bay for R. hargisi , each locality represented a new geographic record for the respective diplectanid. The type species, R. rhabdosynochus, is redescribed based on specimens collected from its type host, C. undecimalis.


Two new species of Eimeria (Apicomplexa: Eimeriidae) from the mountain beaver, Aplodontia rufa (Rodentia: Aplodontiidae), from Oregon.
Two mountain beavers, Aplodontia rufa , were collected in Lincoln County, Oregon, and examined for coccidia. Both were infected with 2 new species of Eimeria. Oocysts of Eimeria chitkoae n. sp. were ellipsoidal with a bilayered wall and measured (L × W) 24.5 × 20.2 μm, with a shape index (SI) of 1.2. Both micropyle and oocyst residuum were absent, but a polar granule of several fragments was present. Sporocysts were ovoidal, 12.5 × 7.9 μm, SI was 1.6. Stieda and substieda bodies were present, but a parastieda body was absent; a sporocyst residuum was present, composed of a cluster of moderately coarse granules with many scattered fine granules. Stout sporozoites were 14.7 × 2.9 μm in situ, with spheroidal anterior and posterior refractile bodies. Oocysts of Eimeria lewisi n. sp. were ovoidal, with a smooth single-layered wall, and measured 13.7 × 7.8 μm, SI was 1.7. A micropyle and oocyst residuum were absent, but 1-2 polar granule(s) were present. Sporocysts were 6.6 × 4.2 μm, with SI of 1.6. A Stieda body was present, but substieda and parastieda bodies were absent; a sporocyst residuum was present, composed of a small cluster of several granules. Sporozoites were granular, 8.2 × 1.8 μm in situ, with a posterior refractile body. These are the first coccidians reported from the mountain beaver.


MicrobiomeAnalyst: a web-based tool for comprehensive statistical, visual and meta-analysis of microbiome data.
The widespread application of next-generation sequencing technologies has revolutionized microbiome research by enabling high-throughput profiling of the genetic contents of microbial communities. How to analyze the resulting large complex datasets remains a key challenge in current microbiome studies. Over the past decade, powerful computational pipelines and robust protocols have been established to enable efficient raw data processing and annotation. The focus has shifted toward downstream statistical analysis and functional interpretation. Here, we introduce MicrobiomeAnalyst, a user-friendly tool that integrates recent progress in statistics and visualization techniques, coupled with novel knowledge bases, to enable comprehensive analysis of common data outputs produced from microbiome studies. MicrobiomeAnalyst contains four modules - the Marker Data Profiling module offers various options for community profiling, comparative analysis and functional prediction based on 16S rRNA marker gene data; the Shotgun Data Profiling module supports exploratory data analysis, functional profiling and metabolic network visualization of shotgun metagenomics or metatranscriptomics data; the Taxon Set Enrichment Analysis module helps interpret taxonomic signatures via enrichment analysis against >300 taxon sets manually curated from literature and public databases; finally, the Projection with Public Data module allows users to visually explore their data with a public reference data for pattern discovery and biological insights. MicrobiomeAnalyst is freely available at http://www.microbiomeanalyst.ca.


Role of thyroxine in coordinate control of corticosterone and CBG in postnatal development.
The role of thyroxine (T4) in the ontogeny of serum corticosteroid-binding globulin (CBG) and corticosterone has been studied in the rat. Daily injection of T4 (0.1 micrograms/g body wt) resulted in the precocious appearance of both CBG and corticosterone. A dose-response study revealed an increase in both CBG and corticosterone at thyroxine doses greater than 0.02 micrograms/g body wt. In propylthiouracil-induced hypothyroid pups, the developmental rise of both CBG and corticosterone was suppressed. To determine whether T4 elevation of CBG was mediated by corticosterone, serum CBG was measured in corticosterone-injected pups (10 micrograms/g body wt). No increase in CBG was detected on days 8 and 10. A slight increase, only one-eighth that elicited by T4, occurred on day 12. There was also no synergistic effect between T4 and corticosterone. We conclude that the postnatal increase in serum T4 concentrations cues the developmental rise of both CBG and corticosterone in the rat.


Current debates in antiphospholipid syndrome: the acquired antibody-mediated thrombophilia.
Antiphospholipid (APL) syndrome is the most common form of acquired thrombophilia. It can cause significant morbidity and even mortality. The term "APL antibodies" represents a heterogeneous group of antibodies associated with this disorder. Currently no single assay can identify every APL antibody. Clinically relevant APL antibodies are mainly anticardiolipin antibodies (ACA) detected by solid phase enzyme-linked immunosorbent assay (ELISA) and lupus anticoagulants (LA) demonstrated by in vitro coagulation assay. However, there are some other antibodies associated with the APL syndrome (i.e., subgroup APL antibodies). ACAs, LAs, and subgroup APL antibodies represent intersecting, but non-identical, subsets of autoantibodies. Thus, those autoantibodies may coexist or may occur independently. Any organ system and any size of vessel can be affected during the clinical course of the disease. Therefore, the APL syndrome can manifest itself in a wide variety of clinical thrombotic features. Fetal loss and pregnancy morbidity represent a specific challenge. Despite tremendous advances in the understanding of the pathogenesis of APL syndrome during the past decade, the mainstay of management is still anticoagulation. However, there is no general agreement regarding the duration and intensity of anti-coagulant therapy. In this review, we focused on the current dilemmas and their present clarifications in the wide clinicopathologic spectrum of APL syndrome and APL antibody-related distinct pathologic conditions.


Complex regulation of GH autofeedback under dual-peptide drive: studies under a pharmacological GH and sex steroid clamp.
To test the postulate that sex difference, sex steroids, and peptidyl secretagogues control GH autofeedback, 11 healthy postmenopausal women and 14 older men were each given 1) a single iv pulse of GH to enforce negative feedback and 2) continuous iv infusion of saline vs. combined GHRH/GHRP-2 to drive feedback escape during pharmacological estradiol (E(2); women) or testosterone (T; men) supplementation vs. placebo in a double-blind, prospectively randomized crossover design. By three-way ANCOVA, sex difference, sex hormone treatment, peptide stimulation, and placebo/saline responses (covariate) controlled total (integrated) GH recovery during feedback (each P < 0.001). Both sex steroid milieu (P = 0.019) and dual-peptide stimulation (P < 0.001) determined nadir (maximally feedback-suppressed) GH concentrations. E(2)/T exposure elevated nadir GH concentrations during saline infusion (P = 0.003), whereas dual-peptide infusion did so independently of T/E(2) and sex difference (P = 0.001). All three of sex difference (P = 0.001), sex steroid treatment (P = 0.005), and double-peptide stimulation (P < 0.001) augmented recovery of peak (maximally feedback-escaped) GH concentrations. Peak GH responses to dual-peptidyl agonists were greater in women than in men (P = 0.016). E(2)/T augmented peak GH recovery during saline infusion (P < 0.001). Approximate entropy analysis corroborated independent effects of sex steroid treatment (P = 0.012) and peptide infusion (P < 0.001) on GH regularity. In summary, sex difference, sex steroid supplementation, and combined peptide drive influence nadir, peak, and entropic measurements of GH release under controlled negative feedback. To the degree that the pharmacological sex steroid, GH, and dual-peptide clamps provide prephysiological regulatory insights, these outcomes suggest major determinants of pulsatile GH secretion in the feedback domain.


Parasitic and fungal disease of bones and joints.
Among the musculoskeletal infections, fungal and parasitic diseases are infrequent and may have a nonspecific imaging factor. The incidences of fungal and parasitic bone infections are related to geographic distribution, ethnic and nutritional factors, and occupation. Immunocompromise and ease of travel can lead to increased incidence. These are a group of chronic disorders, and delayed diagnosis is common because radiographs, computed tomography, isotope studies, and magnetic resonance imaging are useful but often do not have specific signs for determination of the causative infective fungal or parasitic organism. Definitive diagnosis is possible with a high index of clinical suspicion and aspiration.


Depth-dose evaluation and optimisation of the irradiation facility for boron neutron capture therapy of brain tumours.
Boron neutron capture therapy (BNCT) of brain tumours was investigated using thermal neutrons generated by a middle-power research reactor such as the TRIGA-II. The spatial distributions of neutrons and gamma rays were measured using a head phantom at different collimator apertures. Total depth-dose distributions were deduced from these results and were evaluated. We also obtained an optimum condition in terms of the collimator aperture, the 10B concentration in the tumour and the ratio of 10B concentration in the tumour to that in normal tissue. We found that, under this condition, BNCT using thermal neutrons from the TRIGA-II could be successfully used to treat a deep tumour.


Emergency relief during Europe's famine of 1817 anticipated crisis-response mechanisms of today.
Humanitarian professionals continue to seek best practice guidelines for famine relief. Many emergency interventions in developing countries draw on recent lessons from the 20th century, although attention has also been paid to historical experiences such as the 19th century evolution of India's Famine Codes and responses to Ireland's famine of the 1840s. This presentation goes further back in time to examine public responses to the pan-European famine of 1816-1817. It finds that many of the experimental actions set in place at that time contributed to a growing public acceptance of the role of government action in times of crisis, while establishing a variety of viable approaches that continue to be used today.


Selective vulnerability of ARID1A deficient colon cancer cells to combined radiation and ATR-inhibitor therapy.
ARID1A is frequently mutated in colorectal cancer (CRC) cells. Loss of ARID1A function compromises DNA damage repair and increases the reliance of tumor cells on ATR-dependent DNA repair pathways. Here, we investigated the effect of ionizing radiation (IR), in combination with ATR inhibitors (ATRi) in CRC cell lines with proficient and deficient ARID1A. The concept of selective vulnerability of ARID1A deficient CRC cells to ATRi was further tested in an ex vivo system by using the ATP-tumor chemosensitivity assay (ATP-TCA) in cells from untreated CRC patients, with and without ARID1A expression. We found selective sensitization upon ATRi treatment as well as after combined treatment with IR (P<0.001), especially in ARID1A deficient CRC cells (P <0.01). Knock-down of ARID1B further increased the selective radiosensitivity effect of ATRi in ARID1A negative cells (P<0.01). Mechanistically, ATRi abrogates the G2 checkpoint (P<0.01) and homologous recombination repair (P<0.01) in ARID1A deficient cells. Most importantly, ex-vivo experiments showed that ATRi had the highest radiosensitizing effect in ARID1A negative cells from CRC patients. Collectively, our results generate pre-clinical and clinical mechanistic rationale for assessing ARID1A defects as a biomarker for ATR inhibitor response as a single agent, or in a synthetic lethal approach in combination with IR.


Further characterization of the membrane anchor found on the tissue-specific class I molecule Qa2.
Previous studies have determined that various Qa2 serologic determinants can be removed from the surface of spleen cells by treatment with a phospholipase C. Our studies have determined that the class I molecule Qa2, expressed on the surface of spleen cells and activated T cells, behaves as an integral membrane protein based on its ability to associate with detergent micelles. Studies utilizing two purified phospholipase C have revealed that although most (90 to 95%) of the Qa2 molecules expressed on the surface of resting spleen cells are released as intact 40-kDa polypeptides associated with beta 2-microglobulin, activated T cells contain a major cell subpopulation expressing lipase-resistant Qa2 molecules. Flow cytometric analysis revealed that L3T4+-activated T cells expressed lipase-sensitive Qa2 molecules, whereas Lyt-2+ cells express lipase-resistant forms of the Qa2 molecule. The relationship between the secreted form of the Qa2 molecule and the lipase-generated soluble Qa2 molecule was investigated. Based on SDS-PAGE analysis, the secreted Qa2 molecules has a Mr of 39 kDa whereas the cell surface form released from either resting spleen or activated T cells by phosphatidylinositol-specific phospholipase C has a Mr of approximately equal to 40 kDa. Furthermore, the secreted Qa2 molecule lacks an epitope, cross-reacting determinant, often present on lipase-solubilized cell surface molecules. Thus, based on serologic and biochemical criteria, the soluble Qa2 molecules generated by an exogenous phospholipase C and the secreted Qa2 molecule are structurally distinct.


Is the perceived impact of disciplinary procedures on medical doctors' professional practice associated with working in an open culture and feeling supported? A questionnaire among medical doctors in the Netherlands who have been disciplined.
Disciplinary procedures can have a negative impact on the professional functioning of medical doctors. In this questionnaire study, doctors' experience with open culture and support during a disciplinary procedure is studied to determine whether open culture and support are associated with perceived changes in the professional practice of doctors. All doctors who received a warning or a reprimand from the Dutch Medical Disciplinary Board between July 2012 and August 2016 were invited to fill in a 60-item questionnaire concerning open culture, perceived support during the disciplinary procedure and the impact of the procedure on professional functioning as reported by doctors themselves. The response rate was 43% (n=294). A majority of doctors perceive their work environment as a safe environment in which to talk about and report incidents (71.2% agreed). Respondents felt supported by a lawyer or legal representative and colleagues (92.8% and 89.2%, respectively). The disciplinary procedure had effects on professional practice. Legal support and support from a professional confidant and a professional association were associated with fewer perceived changes to professional practice. Our study shows that doctors who had been disciplined perceive their working environment as open. Doctors felt supported by lawyers and/or legal representatives and colleagues. Legal support was associated with less of a perceived impact on doctors' professional practice.


Human Wharton's Jelly-Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials.
Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton's jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton's jelly, is a promising source of mesenchymal stem cells.


Conservative surgery and radiation therapy for macroscopically multiple ipsilateral invasive breast cancers.
The presence of macroscopically multiple ipsilateral invasive breast cancer (MMIIBC) has been considered a contraindication for breast conservation. Early series reported high rates of local recurrence. A treatment regimen was developed to accommodate patient requests for breast conservation in MMIIBC. We reviewed medical records of the 15 MMIIBC patients who underwent partial mastectomy followed by radiation between 1989 and 1997. All patients had 2 or more separate macroscopic tumors greater than 2 mm in diameter. After tumor excision, all specimens were evaluated; the protocol required surgical margins of at least 2 mm. As of June 2000 (median follow-up 76 months), 14 patients (93%) were alive without evidence of disease. One patient died of systemic disease without local recurrence. In selected cases, the combination of breast conservative surgery and radiation therapy with systemic therapy results in acceptable local-regional control. Patients who present with MMIIBC with clear surgical margins should be considered for breast conservation.


Enhancement of growth and paramylon production of Euglena gracilis by co-cultivation with Pseudoalteromonas sp. MEBiC 03485.
This study investigated the putative effects of co-cultivation of Euglena gracilis with Pseudoalteromonas sp. MEBiC 03485 on the growth of E. gracilis and its paramylon production. The strain MEBiC 03485 had beneficial effects on the growth and paramylon contents of E. gracilis. To determine the optimal conditions for co-cultivation, the effects of algal to bacterial inoculum ratios and E. gracilis growth stages were examined. Under optimal conditions, the biomass productivity and paramylon production were increased by more than 23% and 34%, respectively. These effects were attributed to the extracellular polymeric substances (EPS) from the strain MEBiC 03485. GC-MS and HPAEC were carried out to analyze the composition of EPS. It was found that the EPS consisted of rhamnose, galactose, glucose, and mannose. These results suggest a novel approach for potentially enhancing the growth of E. gracilis as well as its paramylon production, via co-culturing with the symbiotic strain MEBiC 03485.


Assessment of Cerebral and Cerebellar White Matter Microstructure in Spinocerebellar Ataxias 1, 2, 3, and 6 Using Diffusion MRI.
Development of imaging biomarkers for rare neurodegenerative diseases such as spinocerebellar ataxia (SCA) is important to non-invasively track progression of disease pathology and monitor response to interventions. Diffusion MRI (dMRI) has been shown to identify cross-sectional degeneration of white matter (WM) microstructure and connectivity between healthy controls and patients with SCAs, using various analysis methods. In this paper, we present dMRI data in SCAs type 1, 2, 3, and 6 and matched controls, including longitudinal acquisitions at 12-24-month intervals in a subset of the cohort, with up to 5 visits. The SCA1 cohort also contained 3 premanifest patients at baseline, with 2 showing ataxia symptoms at the time of the follow-up scans. We focused on two aspects: first, multimodal evaluation of the dMRI data in a cross-sectional approach, and second, longitudinal trends in dMRI data in SCAs. Three different pipelines were used to perform cross-sectional analyses in WM: region of interest (ROI), tract-based spatial statistics (TBSS), and fixel-based analysis (FBA). We further analyzed longitudinal changes in dMRI metrics throughout the brain using ROI-based analysis. Both ROI and TBSS analyses identified higher mean (MD), axial (AD), and radial (RD) diffusivity and lower fractional anisotropy (FA) in the cerebellum for all SCAs compared to controls, as well as some cerebral alterations in SCA1, 2, and 3. FBA showed lower fiber density (FD) and fiber crossing (FC) regions similar to those identified by ROI and TBSS analyses. FBA also highlighted corticospinal tract (CST) abnormalities, which was not detected by the other two pipelines. Longitudinal ROI-based analysis showed significant increase in AD in the middle cerebellar peduncle (MCP) for patients with SCA1, suggesting that the MCP may be a good candidate region to monitor disease progression. The patient who remained symptom-free throughout the study displayed no microstructural abnormalities. On the other hand, the two patients who were at the premanifest stage at baseline, and showed ataxia symptoms in their follow-up visits, displayed AD values in the MCP that were already in the range of symptomatic patients with SCA1 at their baseline visit, demonstrating that microstructural abnormalities are detectable prior to the onset of ataxia.


Alarm system management: evidence-based guidance encouraging direct measurement of informativeness to improve alarm response.
Although there are powerful incentives for creating alarm management programmes to reduce 'alarm fatigue', they do not provide guidance on how to reduce the likelihood that clinicians will disregard critical alarms. The literature cites numerous phenomena that contribute to alarm fatigue, although many of these, including total rate of alarms, are not supported in the literature as factors that directly impact alarm response. The contributor that is most frequently associated with alarm response is informativeness, which is defined as the proportion of total alarms that successfully conveys a specific event, and the extent to which it is a hazard. Informativeness is low across all healthcare applications, consistently ranging from 1% to 20%. Because of its likelihood and strong evidential support, informativeness should be evaluated before other contributors are considered. Methods for measuring informativeness and alarm response are discussed. Design directions for potential interventions, as well as design alternatives to traditional alarms, are also discussed. With the increased attention and investment in alarm system management that alarm interventions are currently receiving, initiatives that focus on informativeness and the other evidence-based measures identified will allow us to more effectively, efficiently and reliably redirect clinician attention, ultimately improving alarm response.


Mitral repair in complete atrioventricular canal. Ease of correction in early infancy.
During the past 5 years all patients with complete atrioventricular (AV) were subjected to surgical correction regardless of age. Thus we were able to assess the ease and reliability of mitral repair in early infancy. Key features of operation include division of bridging leaflets when indicated, selection of a patch sufficiently small to prevent postoperative annular dilation, attachment of the leaflets to the patch with continuous nonpledget-supported sutures at a level determined by the chordal structure, and, based on the size of the mural leaflet, construction of a bicuspid or tricuspid mitral valve. Operative mortality and postoperative morbidity were no greater in patients under 6 months of age than in older patients. Reoperation for mitral regurgitation was required in three patients. In all of them, the primary reason for the failure of repair was that the mitral valve had been left tricuspid; in two of them, the mitral anulus was dilated, as well. Repair was uniformly accomplished by bicuspidization, combined in two instances with a Wooler-type annuloplasty and shortening of the free margin of the aortic leaflet. The absence of secondary scarring of the leaflets in the patients under 6 months of age facilitated repair in this age group. Early repair is possible, and preferable, provided that meticulous attention is paid to the technical features of the repair and a proper decision is made with regard to treatment of the mitral "cleft."


Mental disorders, suicidal ideation, plans and attempts among Canadian police.
Recent investigations have demonstrated a significant prevalence of mental health disorders, including post-traumatic stress disorder (PTSD), and suicidal ideation, plans and attempts among Canadian public safety personnel, including police officers. What remains unknown is the relationship between mental disorders and suicide among sworn police officers, and the prevalence of both among civilian police workers. To examine the relationship between suicidal ideation, plans and attempts and positive mental health screens for depression, anxiety, panic disorder, alcohol abuse and PTSD among Canadian sworn and civilian police employees. Participants completed an online survey that included self-report screening tools for depression, anxiety, panic disorder, alcohol abuse and PTSD. Respondents were also asked if they ever contemplated, planned or attempted suicide. Between-group (Royal Canadian Mounted Police [RCMP], provincial/municipal police and civilians) differences on mental health screening tools were calculated using Kruskal-Wallis analyses. The relationship between mental disorders and suicidal ideation, plans and attempts was evaluated with a series of logistic regressions. There were 4236 civilian and sworn officer participants in the study. RCMP officers reported more suicidal ideation than other police and scored highest on measures of PTSD, depression, anxiety, stress and panic disorder, which were significantly associated with suicidal ideation and plans but not attempts. Relative to provincial and municipal police, civilians reported more suicide attempts and scored higher on measures of anxiety. The results identify a strong relationship between mental health disorders and increased risk for suicidal ideation, plans and attempts among sworn and civilian Canadian police employees.


Accuracy of continuous central venous oxygen saturation monitoring in patients undergoing cardiac surgery.
Continuous assessment of central venous oxygen saturation (S(cevox)O(2)) with the CeVOX device (Pulsion Medical Systems, Munich, Germany) was evaluated against central venous oxygen saturation (S(cv)O(2)) determined by co-oximetry. In 20 cardiac surgical patients, a CeVOX fiberoptic probe was introduced into a standard central venous catheter placed in the right internal jugular vein and advanced 2-3 cm beyond the catheter tip. After in vivo calibration of the probe, S(cevox)O(2), S(cv)O(2), mixed venous oxygen saturation (S(mv)O(2)) haemoglobin (Hb), body temperature, heart rate, central venous and mean arterial pressure, and cardiac index were assessed simultaneously at 30 min intervals during surgery and at 60 min intervals during recovery in the intensive care unit. Agreement between S(cevox)O(2), and S(cv)O(2) was determined by Bland-Altman analysis. Simple regression analysis was used to assess the correlation of S(cevox)O(2), and S(cv)O(2) to Hb, body temperature and haemodynamic parameters. Values of S(cevox)O(2) and S(cv)O(2) (84 data pairs during surgery and 106 in the intensive care unit) ranged between 45-89% and 43-90%, respectively. Mean bias and limits of agreement of S(cevox)O(2) and S(cv)O(2) were -0.9 (-7.9/+6.1)% during surgery and -1.2 (-10.5/+8.1)% in the intensive care unit. In 37.9% of all measured data pairs, the difference between S(cevox)O(2) and S(cv)O(2) was beyond clinically acceptable limits (> or =1 s.d.). Mean bias was significantly influenced by cardiac index. Sensitivity and specificity of S(cevox)O(2) to detect substantial (> or =1 s.d.) changes in S(cv)O(2) were 89 and 82%, respectively. In adult patients during and after cardiac surgery, the current version of the CeVOX device might not be the tool to replace S(cv)O(2) determined by co-oxymetry, although sensitivity and specificity of S(cevox)O(2 )to predict substantial changes in S(cv)O(2) were acceptable.


NT-proBNP and Risk of Dementia in a General Japanese Elderly Population: The Hisayama Study.
Background Epidemiological evidence implies a link between heart disease and dementia. However, few prospective studies have assessed the association between serum NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels and dementia. Methods and Results A total of 1635 community-dwelling Japanese elderly aged ≥60 years without dementia (57% women, mean age±SD 70.8±7.7 years) were followed up for 10 years. Serum NT-proBNP levels were divided into 4 categories (≤54, 55-124, 125-299, and ≥300 pg/mL). The hazard ratios were estimated using a Cox proportional hazards model. During the follow-up period, 377 subjects developed all-cause dementia, 247 Alzheimer disease, and 102 vascular dementia. The age- and sex-adjusted incidence of all-cause dementia was 31.5 per 1000 person-years and increased significantly with higher serum NT-proBNP levels, being 16.4, 32.0, 35.7, and 45.5, respectively (P for trend <0.01). Subjects with serum NT-proBNP levels of ≥300 pg/mL had a significantly higher risk of all-cause dementia (hazard ratio=2.46, 95% CI 1.63-3.71) than those with serum NT-proBNP levels of ≤54 pg/mL after adjusting for confounders. Similar risks were observed for Alzheimer disease and vascular dementia. Incorporation of the serum NT-proBNP level into a model with known risk factors for dementia significantly improved the predictive ability for incident dementia (c-statistics 0.780-0.787, P=0.02; net reclassification improvement 0.189, P=0.001; integrated discrimination improvement 0.011, P=0.003). Conclusions Higher serum NT-proBNP levels were significantly associated with an increased risk of dementia. Serum NT-proBNP could be a novel biomarker for predicting future risk of dementia in the general elderly population.


Gendering family composition: sex preferences for children and childbearing behavior in the Nordic countries.
It has been argued that a society's gender system may influence parents' sex preferences for children. If this is true, one should expect to find no evidence of such preferences in countries with a high level of gender equality. In this article, we exploit data from population registers from Denmark, Finland, Norway, and Sweden to examine continuities and changes in parental sex preferences in the Nordic countries during the past three to four decades. First, we do not observe an effect of the sex of the first born child on second-birth risks. Second, we detect a distinct preference for at least one child of each sex among parents of two children. For third births, Danish, Norwegian, and Swedish parents seem to develop a preference for having a daughter, while Finns exhibit a significant preference for having a son. These findings show that modernization and more equal opportunities for women and men do not necessarily lead to parental gender indifference. On the contrary, they may even result in new sex preferences.


Epidemiology of cervical spondylotic myelopathy and its risk of causing spinal cord injury: a national cohort study.
This study aimed to determine the age- and sex-specific incidence of cervical spondylotic myelopathy (CSM) and its associated risk of causing subsequent spinal cord injury (SCI). Using the National Health Insurance Research Database (NHIRD), a 12-year nationwide database in Taiwan, this retrospective cohort study analyzed the incidence of hospitalization caused by CSM. All patients diagnosed with and admitted for CSM were identified during the study period. The CSM patients were divided into 2 groups, a control group and an operated group. An incidence density method was used to estimate age- and sex-specific incidence rates of CSM. The Kaplan-Meier method and Cox regression analyses were performed to compare the risk of SCI between the 2 groups. From 1998 to 2009, covering 349.5 million person-years, 14,140 patients were hospitalized for CSM. The overall incidence of CSM-related hospitalization was 4.04 per 100,000 person-years. Specifically, males and older persons had a higher incidence rate of CSM. During the follow-up of these patients for 13,461 person-years, a total of 166 patients were diagnosed with SCI. The incidence of SCI was higher in the control group than the operated group (13.9 vs 9.4 per 1000 person-years, respectively). During the follow-up, SCI was more likely to occur in CSM patients who were treated conservatively (crude HR 1.48, p = 0.023; adjusted HR 1.57, p = 0.011) than in those who underwent surgery for CSM. In a national cohort of eastern Asia, the incidence of CSM-caused hospitalization was 4.04 per 100,000 person-years, with higher incidences observed in older and male patients. Subsequent SCI was more likely to develop in patients who received nonoperative management than in those who underwent surgery. Therefore, patients with CSM managed without surgery should be cautioned about SCI. However, further investigations are still required to clarify the risks and complications associated with surgery for CSM.


Calcineurin homologous protein: a multifunctional Ca2+-binding protein family.
The calcineurin homologous protein (CHP) belongs to an evolutionarily conserved Ca(2+)-binding protein subfamily. The CHP subfamily is composed of CHP1, CHP2, and CHP3, which in vertebrates share significant homology at the protein level with each other and between other Ca(2+)-binding proteins. The CHP structure consists of two globular domains containing from one to four EF-hand structural motifs (calcium-binding regions composed of two helixes, E and F, joined by a loop), the myristoylation, and nuclear export signals. These structural features are essential for the function of the three members of the CHP subfamily. Indeed, CHP1-CHP3 have multiple and diverse essential functions, ranging from the regulation of the plasma membrane Na(+)/H(+) exchanger protein function, to carrier vesicle trafficking and gene transcription. The diverse functions attributed to the CHP subfamily rendered an understanding of its action highly complex and often controversial. This review provides a comprehensive and organized examination of the properties and physiological roles of the CHP subfamily with a view to revealing a link between CHP diverse functions.


Tracheobronchial resection and reconstruction.
To assess the indications and results of airway resection and how frequently airway reconstructive options changed proposed therapy. A retrospective survey of patients undergoing major airway resection. University of Washington-affiliated hospitals, Seattle, May 1992 through December 1996. Fifty consecutive patients with resectable benign and malignant tracheal or main bronchial disease undergoing tracheobronchial resections. Patients underwent major airway resection as follows: tracheal or laryngotracheal resection, 23 patients; carinal resection, 6; and bronchial sleeve resection with or without pulmonary resection, 21. Indications for surgery were non-small cell lung cancer in 19 patients, primary airway tumor in 12, thyroid carcinoma in 1, and tracheal or bronchial stenosis in 18. Change in prereferral planned therapy from palliative to definitive or to pulmonary-sparing procedure, morbidity and mortality, relief of symptoms, and survival. Mortality was 0%, and morbidity, 32% (15/50). Airway reconstruction changed the proposed therapy in 42 patients (84%). Functional results were good to excellent in 17 (94%) of 18 patients with benign disease. Patients with malignant disease had a 1-year survival of 93% (27/29) and a 2-year survival of 67% (12/18). Airway resection and reconstruction provide reliable relief of benign and malignant tracheobronchial disease with minimal morbidity and mortality. Airway reconstruction frequently changed prereferral planned therapy and provided definitive and parenchymal-sparing procedures to patients with complex airway lesions.


Fatigue in systemic lupus erythematosus: contributions of disease activity, pain, depression, and perceived social support.
Pain and psychological distress are associated with fatigue, and social support may play a buffering role in the adjustment to a chronic disease. Investigations of the relationship between fatigue and disease activity in chronic diseases have provided inconclusive findings. The influence of medications on perceived fatigue remains unclear. We investigated the relationship between pain, depression, fatigue, and disease activity in patients with systemic lupus erythematosus (SLE). Participants (n = 127) completed a psychosocial questionnaire during routine clinic visits. Hierarchical multiple regression analysis was conducted to predict the contribution of disease activity, pain, depression (Beck Depression Inventory), and perceived social support to fatigue. Disease activity as measured by SLE Disease Activity Index (SLEDAI) did not significantly predict self-reported levels of fatigue. Medication usage did not predict fatigue levels. Pain and depression were both unique positive predictors of fatigue. Controlling for pain and depression, perceived social support contributed negatively to the variance in fatigue scores, suggesting a buffering effect. This model reliably explained 42% of the variance in fatigue scores. Our results emphasize the importance of depression, pain, and perceived social support in predicting reported fatigue levels in patients with SLE. In contrast, disease activity measured by SLEDAI does not appear to account for fatigue in SLE. Understanding the effect of psychosocial factors on fatigue in SLE may improve patient outcomes through psychosocial interventions aimed at reducing pain and increasing coping skills and social support.


Paraoxonase 1 as a major bioactivating hydrolase for olmesartan medoxomil in human blood circulation: molecular identification and contribution to plasma metabolism.
Olmesartan medoxomil (OM) is a prodrug-type angiotensin II type 1 receptor antagonist. The OM-hydrolyzing enzyme responsible for prodrug bioactivation was purified from human plasma through successive column chromatography and was molecularly identified through N-terminal amino acid sequencing, which resulted in a sequence of 20 amino acids identical to that of human paraoxonase 1 (PON1). Two recombinant allozymes of human PON1 (PON1(192QQ) and PON1(192RR)) were constructed and were clearly demonstrated to hydrolyze OM; hydrolysis by the latter allozyme was slightly faster than that by the former. In addition, we evaluated the contribution of PON1 to OM bioactivation in human plasma. Enzyme kinetic studies demonstrated that OM was hydrolyzed more effectively by the recombinant PON1 proteins than by purified albumin. The OM-hydrolyzing activities of the recombinant PON1 proteins and diluted plasma were greatly reduced in the absence of calcium ions. Immunoprecipitation with anti-PON1 IgG completely abolished the OM-hydrolyzing activity in human plasma, whereas the activity was partially inhibited with anti-albumin IgG. The distribution pattern of the OM-hydrolyzing activity in human serum lipoprotein fractions and lipoprotein-deficient serum was examined and showed that most of the OM-hydrolyzing activity was located in the high-density lipoprotein fraction, with which PON1 is closely associated. In conclusion, we identified PON1 as the OM-bioactivating hydrolase in human plasma on a molecular basis and demonstrated that PON1, but not albumin, plays a major role in OM bioactivation in human plasma.


Debutant iOS app and gene-disease complexities in clinical genomics and precision medicine.
The last decade has seen a dramatic increase in the availability of scientific data, where human-related biological databases have grown not only in count but also in volume, posing unprecedented challenges in data storage, processing, analysis, exchange, and curation. Next generation sequencing (NGS) advancements have facilitated and accelerated the process of identifying genetic variations. Adopting NGS with Whole-Genome and RNA sequencing in a diagnostic context has the potential to improve disease-risk detection in support of precision medicine and drug discovery. Several bioinformatics pipelines have been developed to strengthen variant interpretation by efficiently processing and analyzing sequence data, whereas many published results show how genomics data can be proactively incorporated into medical practices and improve utilization of clinical information. To utilize the wealth of genomics and health, there is a crucial need to generate appropriate gene-disease annotation repositories accessed through modern technology. Our focus here is to create a comprehensive database with mobile access to actionable genes and classified diseases, considered the foundation for clinical genomics and precision medicine. We present a publicly available iOS app, PAS-Gen, which invites global users to freely download it on iPhone and iPad devices, quickly adopt its easy to use interface, and search for genes and related diseases. PAS-Gen was developed using Swift, XCODE, and PHP scripting that uses Web and MySQL database servers, which includes over 59,000 protein-coding and non-coding genes, and over 90,000 classified gene-disease associations. PAS-Gen is founded on the clinical and scientific premise that easier healthcare and genomics data sharing will accelerate future medical discoveries. We present a cutting-edge gene-disease database with a smart phone application, integrating information on classified diseases and related genes. The PAS-Gen app will assist researchers, medical practitioners, and pharmacists by providing a broad and view of genes that may be implicated in the likelihood of developing certain diseases. This tool with accelerate users' abilities to understand the genetic basis of human complex diseases and by assimilating genomic and phenotypic data will support future work to identify gene-specific designer drugs, target precise molecular fingerprints for tumors, suggest appropriate drug therapies, predict individual susceptibility to disease, and diagnose and treat rare illnesses.


Some notes on cellular logic operators.
Cellular logic machines used for feature extraction in pattern recognition have increased in speed to the point of making it possible to execute programs equivalent to 1 billion general-purpose computer instructions in 1 TV frame time. Unfortunately, most cellular logic operators (CLO's) are designed ad hoc. It is important, therefore, to begin to systematize the generation of algorithms using CLO sequences for pattern analysis. These notes systematically analyze some aspects of CLO's which are used in shape discrimination and idealization and in object counting and sizing. New extensions of subfield numbering schemes in the hexagonal tessellation are introduced.


Histological features of carotid plaque in patients with ocular ischemia versus cerebral events.
Patients with carotid artery stenosis and ocular ischemic events have a much lower risk of future ipsilateral ischemic stroke on medical treatment and lower procedural risks for endarterectomy and stenting than patients with cerebral ischemic events, and are closer in risk to patients with asymptomatic stenosis. The reasons for this difference in prognosis are not fully understood, but may reflect differences in carotid plaque pathology. In consecutive patients undergoing carotid endarterectomy for recently symptomatic stenosis (Oxford Plaque Study, Athero-Express Study), we compared carotid plaque histology (using validated semiquantitative scales) in those who had cerebral events within the last 6 months (n=1317) versus those with ocular events only (n=323). Compared with plaques from patients with ocular events only, those from patients with cerebral events had significantly more large lipid core (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.05-1.82; P=0.02), inflammation (OR, 1.32; 95% CI, 1.02-1.72; P=0.04) and overall plaque instability (OR, 1.37; 95% CI, 1.05-1.80; P=0.02), and less fibrous content (OR, 0.71; 95% CI, 0.54-0.92; P=0.01), and calcification (OR, 0.70; 95% CI, 0.54-0.91; P=0.008). The overall number of histological features known to be associated with vulnerable plaque was greater in patients with cerebral events than in those with ocular events (P=0.002). Carotid plaques from patients undergoing endarterectomy for previous ocular ischemic events have fewer vulnerable plaque features than those from patients with recent cerebral ischemic events, possibly explaining some of the differences in risk of stroke between these groups.


Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.
Lyme disease, due to infection with the tick-borne spirochete Borrelia burgdorferi, is a multisystem disorder that can lead to chronic disabling symptoms. Abs to the outer surface protein A (OspA) of B. burgdorferi provide protection against infection, and OspA is now the basis of a first generation recombinant vaccine undergoing phase III efficacy studies. Recent studies have suggested that T cells reactive with N-terminal epitopes in OspA could contribute to the development of treatment-resistant Lyme arthritis. In the present studies, we use the murine model of Lyme borreliosis to define an OspA T cell epitope located in the carboxyl terminus that accelerates anti-OspA IgG production after infection. In addition, we show that this T cell epitope is elicited by immunization with rOspA or with a truncated form of OspA that contains the B cell epitope targeted by protective OspA mAb. Polyclonal antisera to the truncated OspA fragment can protect mice from challenge infection. These results are the first demonstration of a B. burgdorferi-specific peptide that elicits a biologically important T cell response in vivo and have implications for the design of a second generation OspA-based subunit vaccine.


Older Adolescents' Understanding of Participant Rights in the BlackBerry Project, a Longitudinal Ambulatory Assessment Study.
For a long-term, longitudinal study that used BlackBerry smartphones for passive ambulatory assessment among older adolescents, this study focused on three areas of ethical concern: (1) adolescents' competence to give assent; (2) understanding of confidentiality, the protection of information, and project goals; and (3) awareness of procedures and benefits, and comfort with the research design. One hundred and seventy-eight participants were 17 and 18 years old (84 girls). Results suggested that participants freely gave consent and understood most, but not all of the informed consent information. Participants reported a high level of satisfaction. Participants showed less understanding of when their confidentiality would be broken and how data would be protected.


Functionalized Multiwalled Carbon Nanotubes for Highly Stable Room Temperature and Humidity-Tolerant Triethylamine Sensing.
Triethylamine (TEA) poses a significant threat to our health and is extremely difficult to detect at the parts-per-billion (ppb) level at room temperature. Carbon nanotubes (CNTs) are versatile materials used in chemiresistive vapor sensing. However, achieving high sensitivity and selectivity with a low detection limit remains a challenge for pristine CNTs, hindering their widespread commercial application. To address these issues, we propose functionalized multiwalled CNTs (MWCNTs) with carboxylic acid (COOH)-based sensing channels for ultrasensitive TEA detection under ambient conditions. Advanced structural analyses confirmed the necessary modification of MWCNTs after functionalization. The sensor exhibited excellent sensitivity to TEA in air, with a superior noise-free signal (10 ppb), an extremely low limit of detection (LOD ≈ 0.8 ppb), excellent repeatability, and long-term stability under ambient conditions. Moreover, the response values became more stable, demonstrating excellent humidity resistance (40-80% RH). Notably, the functionalized MWCNT sensor exhibited improved response and recovery kinetics (200 and 400 s) to 10 ppm of TEA compared to the pristine MWCNT sensor (400 and 1300 s), and the selectivity coefficient for TEA gas was improved by approximately three times against various interferants, including ammonia, formaldehyde, nitrogen dioxide, and carbon monoxide. The remarkable improvements in TEA detection were mainly associated with the large specific surface area, abundant active sites, adsorbed oxygen, and other defects. The sensing mechanism was thoroughly explained by using Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and gas chromatography-mass spectrometry (GC-MS). This study provides a new platform for CNT-based chemiresistive sensors with high selectivity, low detection limits, and enhanced precision with universal potential for applications in food safety and environmental monitoring.


The ultrastructure of bone as revealed in electron microscopy of ion-milled sections.
Mineral makes up more than half the volume of bone, but its spatial and structural relationship to collagen and other proteins is still a matter of debate. Due to the nanometer-size of bone crystals this matter can be resolved only with transmission electron microscope (TEM) images. Using sections cut with an ultramicrotome, previous investigators determined most mineral lies in the 40nm wide gap zone in collagen fibrils. Using less invasive sectioning methods (ion milling and focused ion beam [FIB]) reveals that most mineral is extrafibrillar, occurring in the form of mineral lamellae, polycrystalline plates 300nm or more long, packed around collagen fibrils in stacks of four or more lamellae <1nm apart. While Ca and P also occur in the gap zone, they do not appear to be in the form of well-crystallized apatite. This new model for bone ultrastructure resolves outstanding problems presented by the previous model.


Alternative drying processes for the industrial preservation of lactic acid starter cultures.
The preservation of lactic acid starter cultures by alternative drying processes has attracted increasing attention due to the high costs and energy consumption of freezing and freeze drying. This review thus aims to provide a survey regarding the state of knowledge of starter culture production at high levels of viability. The results from numerous studies on various drying processes and lactic acid bacteria are summarized. The alternative drying processes considered, such as spray drying, fluidized bed drying, and vacuum drying, are mainly of industrial interest. The features, advantages, and disadvantages of these drying processes are described. In conclusion, the important factors that need to be considered, standardized, or optimized to achieve high levels of viability include intrinsic tolerance of cultures, growth media and conditions, stress induction, cell harvesting conditions, protective agents, rehydration conditions, enumeration of cells, and storage conditions.


Management of lymphoma recurrence after allogeneic transplantation: the relevance of graft-versus-lymphoma effect.
Donor lymphocyte infusions, by virtue of a graft-versus-tumor effect, have been shown to induce remissions in leukemia that recurs after allogeneic bone marrow transplantation. Similar effects have been postulated to contribute to the decreased recurrence rate observed after allogeneic transplantation in non-Hodgkin's lymphoma. This lower recurrence rate may be due to a variety of other mechanisms. We aimed to evaluate the role of graft-versus-lymphoma effects in patients in whom lymphomas recur after allogeneic transplantation. At the time of recurrence, immunosuppressive therapy was withheld. Patients with non-responding disease received an infusion of donor lymphocytes. Patients were observed for response and graft-versus-host disease. Disease in four of nine patients responded to withdrawal of immunosuppressive therapy. A minor response was observed in one of three recipients of donor lymphocyte infusions. Responses were observed among two patients with follicular lymphoma, one with large cell lymphoma and one with lymphoblastic lymphoma. A minor response was observed in a patient with prolymphocytic leukemia/lymphoma. We conclude that withdrawal of immunosuppressive therapy and donor lymphocyte infusion can induce durable remissions in patients with recurrent lymphoma after allogeneic transplantation.


Organogermanium reactive intermediates. The direct detection and characterization of transient germylenes and digermenes in solution.
Diphenylgermylene (Ph2Ge) and its Ge=Ge doubly bonded dimer, tetraphenyldigermene (6a), have been characterized directly in solution for the first time by laser flash photolysis methods. The germylene is formed via (formal) cheletropic photocycloreversion of 3,4-dimethyl-1,1-diphenylgermacyclopent-3-ene (4a), which is shown to proceed in high chemical (>95%) and quantum yield (phi = 0.62) by steady-state trapping experiments with methanol, acetic acid, isoprene, and triethylsilane. Flash photolysis of 4a in dry deoxygenated hexane at 23 degrees C leads to the prompt formation of a transient assigned to Ph2Ge (lambda(max) = 500 nm; epsilon(max) = 1650 M(-1) cm(-1)), which decays with second-order kinetics (tau approximately 3 micros), with the concomitant growth of a second transient species that is assigned to digermene 6a (tau approximately 40 micros; lambda(max) = 440 nm). Analogous results are obtained from 1,1-dimesityl- and 1,1-dimethyl-3,4-dimethylgermacyclopent-3-ene (4b and 4c, respectively), which afford Mes2Ge (tau approximately 20 micros; lambda(max) = 560 nm) and Me2Ge (tau approximately 2 micros; lambda(max) = 480 nm), respectively, as well as the corresponding digermenes, tetramesityl- (6b; lambda(max) = 410 nm) and tetramethyldigermene (6c; lambda(max) = 370 nm). The results for the mesityl compound are compared to the analogous ones from laser flash photolysis of the known Mes2Ge/6b precursor, hexamesitylcyclotrigermane. The spectra of the three germylenes and two of the digermenes are in excellent agreement with calculated spectra, derived from time-dependent DFT calculations. Absolute rate constants for dimerization of Ph2Ge and Mes2Ge and for their reaction with n-butylamine and acetic acid in hexane at 23 degrees C are also reported.


Supercritical Carbon Dioxide-Assisted Decellularization of Aorta and Cornea.
Tissue engineering approaches utilize both natural and synthetic materials in the repair and regeneration processes. A naturally sourced material for this purpose is required to be free from any antigenic matter such as cells or cellular components. Decellularization of tissues may be achieved through chemical or physical removal agents. Supercritical carbon dioxide (sc-CO2) has been used on the purpose of removing bioburden from tissues and offers an alternative to the traditionally used treatment methods. In addition to many advantages it offers with regard to the successful decellularization of tissues, it is known to have a sterilization effect. This study provides an insight into sc-CO2-assisted decellularization trials of corneal and aortic tissues. Results showed that high pressure of the fluid bursts the cells during the treatment and rapid depressurization was found to be effective in the removal of the cells from the tissues. sc-CO2 decellularization offers significantly reduced treatment times, complete decellularization, and preserved extracellular matrix structure.


On ugliness.
Ugliness results from the emergence into consciousness of certain fantasies that alter the person's aesthetic sense in such a way that the formal qualities of the experience, the shape, texture, and color, appear to become the sources of our most disturbing and repulsive feelings. This paper reviews the psychoanalytic writings concerning the problem of ugliness and offers a psychoanalytic model of this universal phenomenon. Clinical vignettes illustrate key points. The paper closes with a discussion of how ugliness can be an opportunity for both the analyst and the artist--he or she confronts ugliness, and through the analytic and creative process, brings form and perfection to disintegration and disorder.