Preventable burden of head and neck cancer attributable to tobacco and alcohol between 1990 and 2039 in China.
Tobacco use and heavy alcohol consumption are risk factors for head and neck cancer (HNC), including oral, pharynx, and larynx cancer. No study has investigated the preventable burden of HNC attributable to tobacco and alcohol in China. We extracted data from 1990 to 2019 from the Global Burden of Disease. The preventable burden attributable to tobacco and alcohol was estimated by subtracting the overlapping fraction derived from a literature search. Descriptive analyses were performed initially, followed by joinpoint regression and age-period-cohort (APC) analysis. The future burden was forecasted using a Bayesian APC model. The crude burden increased significantly, while the age-standardized rates showed a downward trend from 1990 to 2019 in China. Both all-age and age-standardized population attributable fractions rose significantly, potentially due to the poor prognosis of tobacco- and alcohol-associated HNC. The absolute burden would continue to climb in the next 20 years from 2019, largely due to population aging. For site-specific burden, compared with total, pharynx, and larynx cancer burden, the substantial upward trend of oral cancer burden indicated a strong interaction with risk factors such as genetic susceptibility, betel nut chewing, oral microbiota, and human papillomavirus. The burden of oral cancer attributable to tobacco and alcohol is a major concern and is anticipated to become more severe than cancer in other anatomic sites. Altogether, our study provides useful information to rethink the current restrictions on tobacco and alcohol, lean healthcare resources, and develop effective HNC prevention and control strategies.


Workers, capitalists, and the government: fiscal policy and income (re)distribution.
We propose a novel two-agent New Keynesian model to study the interaction of fiscal policy and household heterogeneity in a tractable environment. Workers can save in bonds subject to portfolio adjustment costs; firm ownership is concentrated among capitalists who do not supply labor. The model is consistent with micro data on empirical intertemporal marginal propensities to consume, and it avoids implausible profit income effects on labor supply. Relative to the traditional two-agent model, these features imply, respectively, a lower sensitivity of consumption to the composition of public financing; and smaller fiscal multipliers alongside pronounced redistributive effects.


Generation and characterisation of monoclonal antibodies against influenza virus A, subtype H5N1.
The emergence of highly pathogenic avian influenza A virus (HPAIV) subtype H5N1 in 1997 has since resulted in large outbreaks in poultry and in transmission from poultry to humans, mostly in southeast Asia, but also in several European countries. Effective diagnosis and control measures are essential for the management of HPAIV infections. To develop a rapid diagnostic test, a panel of murine monoclonal antibodies (mAbs) against influenza virus A subtype H5 was generated. Eleven mAbs were produced and characterised according to their reactivity by indirect and sandwich ELISA and western blotting against different H5 subtypes representing past and viruses currently circulating. Ten out of 11 mAbs reacted strongly with the haemagglutinin (HA) protein of H5 viruses, whereas one mAb reacted with the M1 protein. Targeted HA protein epitopes seemed to be conformational. One hybridoma clone binds to a linear epitope of the M1 protein. One specific mAb reacts with HPAIV H5 in the immunofluorescence test, and two antibodies neutralised H5 viruses. On the basis of the results, the set of seven mAbs is appropriate for developing diagnostic tests. With the generated mAbs, a sandwich ELISA was developed recognising all H5N1 strains tested but no other influenza viruses. With this ELISA, as little as 0.005 HA units or 0.1 ng/ml H5N1 was detected, surpassing other ELISA tests. The novel reagents have the potential to improve significantly available rapid antigen detection systems.


Reduction of the PaO2/FiO2 ratio in acute aortic dissection – relationship between the extent of dissection and inflammation –.
Acute aortic dissection (AAD) often accompanies acute respiratory failure. The aim of this study was to clarify the relationship between the incidence of oxygenation impairment and the extent of distal type AAD. A total of 49 patients with medically treated distal type AAD were retrospectively examined. AAD% was defined as the percentage of the volume of false lumen to that of aorta in the descending aorta. AAD% was measured by computed tomography. C-reactive protein (CRP) levels, white blood cell (WBC) counts, body temperature and arterial partial pressure of oxygen/fraction of inspired oxygen (PaO(2)/FiO(2)) ratio were measured serially. Oxygenation impairment was defined as a PaO(2)/FiO(2) ratio ≤ 200. This occurred in 19 patients (39%). In patients with oxygenation impairment, AAD% (50.8 ± 10.9% vs 28.0 ± 11.9%, P<0.001), peak CRP levels (15.2 ± 6.5 mg/dl vs 9.6 ± 4.6 mg/dl, P<0.001), peak WBC counts (13,600 ± 3,700/µl vs 10,400 ± 2,800 /µl, P=0.001) and body temperature (38.1 ± 0.5°C vs 37.8 ± 0.4°C, P=0.045) were higher than those without oxygenation impairment. It was found that there were inverse correlations between the PaO(2)/FiO(2) ratio and AAD% (r=-0.604, P<0.001), and between peak CRP levels and the PaO(2)/FiO(2) ratio (r=-0.635, P<0.001). Multivariate analysis demonstrated that the only independent predictor of oxygenation impairment was AAD% (odds ratio, 1.323; 95% confidence interval, 1.035-1.691, P=0.026). Respiratory failure in AAD appears to be closely correlated with the amount of aortic injury, possibly mediated by the magnitude of the systemic inflammatory reaction to the aortic injury.


Design and test of a Microsoft Kinect-based system for delivering adaptive visual feedback to stroke patients during training of upper limb movement.
The present paper describes the design and test of a low-cost Microsoft Kinect-based system for delivering adaptive visual feedback to stroke patients during the execution of an upper limb exercise. Eleven sub-acute stroke patients with varying degrees of upper limb function were recruited. Each subject participated in a control session (repeated twice) and a feedback session (repeated twice). In each session, the subjects were presented with a rectangular pattern displayed on a vertical mounted monitor embedded in the table in front of the patient. The subjects were asked to move a marker inside the rectangular pattern by using their most affected hand. During the feedback session, the thickness of the rectangular pattern was changed according to the performance of the subject, and the color of the marker changed according to its position, thereby guiding the subject's movements. In the control session, the thickness of the rectangular pattern and the color of the marker did not change. The results showed that the movement similarity and smoothness was higher in the feedback session than in the control session while the duration of the movement was longer. The present study showed that adaptive visual feedback delivered by use of the Kinect sensor can increase the similarity and smoothness of upper limb movement in stroke patients.


The association of serum vitamin D concentrations in paediatric migraine.
Migraine is a neurologic condition characterized by hypersensitivity to auditory, olfactory, visual, and cutaneous stimuli; vomiting and nausea; and severe headache. It is the most frequent headache syndrome in children and can be categorized in chronic and/or episodic. Multiple dietary supplements have been inaugurated for the management of migraine, the most prevalent of which is vitamin D. In recent years, vitamin D deficiency has been a global public health problem, with 30-80% of the worldwide population having vitamin D deficiency. The significant role of vitamin D in neurological disorders is underlined by its key role in the brain function of the central nervous system (CNS). Current approaches in paediatric neurology include nonsteroidal anti-inflammatory drugs (NSAID) for the treatment of paediatric migraine, among others. Vitamin D is one of the dietary factors that has been linked to migraine, however, this association has mostly been examined in the adult population. The aim of this study is to investigate the association between serum vitamin D and paediatric migraine by conducting a review of existing literature. The main question is described with the PICO format (population, intervention, control, and outcomes), while the assessment of the present research is under the PRISMA guidelines for systematic reviews. A systematic review of the literature reveals a remarkable association between vitamin D and migraine presentation in the paediatric population, affecting the frequency and duration of the episodes. That being the case, vitamin D supplementation could potentially improve the quality of life of paediatric patients suffering from migraine headaches.


Efficacy of transvaginal contrast-enhanced MRI in the early staging of cervical carcinoma.
The objective of this study was to evaluate the efficacy of transvaginal contrast for local staging of cervical carcinoma. Fifty patients diagnosed with cervical carcinoma prospectively underwent magnetic resonance (MR) imaging before and after vaginal opacification (VO) with a mixture of 25 ml saline and 25 ml barium. T2-weighted (T2W) TSE images in axial and sagittal planes were compared before and after vaginal opacification. Dynamic T1W images in sagittal and fat-suppressed T1W images in transverse planes were also evaluated after intravenous contrast administration. Involvement of vaginal wall, lumen, and fornices; parametrium; rectum; and bladder were noted. Changes in local tumor staging and in treatment planning were also assessed after vaginal opacification. MR results were later compared with surgical pathological findings. Twenty-eight patients who went through surgical staging were included in the study. VO did not change any of the MR interpretations in 14 patients (50%). Correct staging was achieved with T2W TSE images with and without VO (in sagittal and transverse planes) in 78.5% and 50% of the patients, respectively. VO correctly lowered staging in seven and increased it in three patients compared with sagittal standard T2W images. Treatment planning was also changed in four (14%) of these patients. When overall accuracy of MR staging to indicate the appropriate treatment was evaluated, patients would have received the proper treatment in 90% and 79% of the cases when only T2W sagittal images with and without VO were evaluated, respectively. Dynamic gradient-echo images in sagittal planes and postcontrast T1W images in transverse planes evaluated with T2W series after VO, accomplished correct staging in 23 (82%) of the patients. MRI staging in early cervical cancer may be difficult and overestimated, especially if the tumor is slightly extended into the proximal vagina. Use of vaginal contrast medium is an easy, well-tolerated, and effective method to better delineate the borders of the tumor. It increases the specificity and accuracy of MR staging by showing the exact relation of the tumor with the vaginal wall and beyond.


An evaluation of the rearfoot posture in individuals with patellofemoral pain syndrome.
Structural abnormalities of the foot may cause abnormal subtalar joint compensatory motion in order to attain normal function of the lower extremity during gait although studies have not been conclusive. Current conflict in the literature may be related to the differing measures focused on the varying protocols and also the absence of a control group in some studies. This study investigated the rearfoot posture including Subtalar Joint Neutral Position (STJN) and Relaxed Calcaneal Standing (RCS) measurements in patellofemoral pain syndrome (PFPS) and healthy subjects. The angle of STJN during non-weight bearing position and the two dimensional (2D) rearfoot RCS posture was measured using a goniometer in 14 healthy females and 13 females with PFPS. The RCS posture was also measured three dimensionally (3D) by attaching external markers to a tibia shell and the calcaneus and videoing with a four-camera three-dimensional motion analysis system. A one way ANOVA was used to assess the differences between the groups. The 2D and 3D RCS were significantly different between the groups (p ≤ 0.001) with mean -0.23° ± 1.35° , 2.52° ± 3.11° for the control group and 2.35° ± 1.4°, 7.02° ± 3.33° for the clinical group respectively. STJN showed a slight rearfoot varus (although significant p = 0.04) in PFPS (-2.20° ± 1.51° ) compared to the control group (-1.00° ± 1.36°). Negative values indicated inversion and positive values indicated eversion. The 2D and 3D RCS showed a significantly more everted posture of the rearfoot for the PFPS group. Subtalar joint varus may contribute to the increased eversion during relaxed standing in the PFPS group. Rearfoot measurements may be an important addition to other clinical measurements taken to explore the underlying aetiology of subjects with PFPS. Key PointsRearfoot posture of PFPS subjects showed a small varus position of Subtalar Joint Neutral and a rearfoot valgus in relaxed standing posture.Relaxed Calcaneal Standing and Subtalar Joint Neutral Position measurements may be an important addition to other clinical measurements taken to explore the underlying aetiology of subjects with PFPS.


Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: a prospective observational cohort study.
High weight gain in pregnancy is associated with greater postpartum weight retention, yet long-term implications remain unknown. We aimed to assess whether gestational weight change was associated with mortality more than 50 years later. The Collaborative Perinatal Project (CPP) was a prospective US pregnancy cohort (1959-65). The CPP Mortality Linkage Study linked CPP participants to the National Death Index and Social Security Death Master File for vital status to 2016. Adjusted hazard ratios (HRs) with 95% CIs estimated associations between gestational weight gain and loss according to the 2009 National Academy of Medicine recommendations and mortality by pre-pregnancy BMI. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular and diabetes underlying causes of mortality. Among 46 042 participants, 20 839 (45·3%) self-identified as Black and 21 287 (46·2%) as White. Median follow-up time was 52 years (IQR 45-54) and 17 901 (38·9%) participants died. For those who were underweight before pregnancy (BMI <18·5 kg/m2; 3809 [9·4%] of 40 689 before imputation for missing data]), weight change above recommendations was associated with increased cardiovascular mortality (HR 1·84 [95% CI 1·08-3·12]) but not all-cause mortality (1·14 [0·86-1·51]) or diabetes-related mortality (0·90 [0·13-6·35]). For those with a normal pre-pregnancy weight (BMI 18·5-24·9 kg/m2; 27 921 [68·6%]), weight change above recommendations was associated with increased all-cause (HR 1·09 [1·01-1·18]) and cardiovascular (1·20 [1·04-1·37]) mortality, but not diabetes-related mortality (0·95 [0·61-1·47]). For those who were overweight pre-pregnancy (BMI 25·0-29·9 kg/m2; 6251 [15·4%]), weight change above recommendations was associated with elevated all-cause (1·12 [1·01-1·24]) and diabetes-related (1·77 [1·23-2·54]) mortality, but not cardiovascular (1·12 [0·94-1·33]) mortality. For those with pre-pregnancy obesity (≥30·0 kg/m2; 2708 [6·7%]), all associations between gestational weight change and mortality had wide CIs and no meaningful relationships could be drawn. Weight change below recommended levels was associated only with a reduced diabetes-related mortality (0·62 [0·48-0·79]) in people with normal pre-pregnancy weight. This study's novel findings support the importance of achieving healthy gestational weight gain within recommendations, adding that the implications might extend beyond the pregnancy window to long-term health, including cardiovascular and diabetes-related mortality. National Institutes of Health.


Preparation of graphene oxide (GO)/lanthanum coordination polymers for enhancement of bactericidal activity.
In this study, graphene oxide/lanthanum coordination polymer (GLCP) nanocomposites are prepared and their bactericidal activities against seven typical Pathogenic bacteria are evaluated. The GLCPs are fabricated through the electrostatic self-assembly of La ions on negatively charged graphene oxide (GO), followed by the stabilization of π-π stacking to ensure the formation of lanthanum coordination polymers on the GO surface. The morphologies and structures of the synthesized GLCPs are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Moreover, the bactericidal effects of the well-coordinated GLCPs are investigated using the zone of inhibition and flat colony counting methods, as well as by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The five GLCPs synthesized in this study exhibit broad-spectrum antibacterial activities against seven typical Pathogenic bacteria. We believe that our study could serve as a starting point to prepare bactericidal materials for further applications.


Sex on a slide: Antoine Lacassagne and the search for a microscopic definition of masculinity and femininity.
In 1919, the French pathologist and pioneer of radiotherapy of cancer, Antoine Lacassagne, studied the case of a young man of indeterminate sexuality (a condition later named "intersex," and recently renamed, "disorders of sexual development"). Lacassagne's argument that the patient was a "true" hermaphrodite, that is, an individual who possesses at the same time male and female sexual glands, was grounded exclusively in his study of microscopic preparations. Such preparations were seen as the definitive proof of the "true biological sex" of a given person, seen as a fixed entity. On the other hand, Lacassagne's definition of biological, or rather histological sex, was dissociated from sexuality, sexual orientation and sex/gender identity. In the 1930s, the isolation of sex hormones made it possible to modulate specific sexual traits, thus destabilizing the concept of a fixed biological sex. It did not undermine, however, the central role of histological proofs. Sex on a slide continued to be seen as definitive evidence of the "true" sexual identity of an individual, but from the 1930s this proof was valid only for the time when a given microscopic preparation had been manufactured.


Perception study of perceived value and social influence of digital health services in Indonesia.
Healthtech has become a nascent sector of the internet economy since the emergence of the COVID-19 pandemic in 2020. Telemedicine features are facilitated, such as teleconsultation, e-diagnosis, e-prescribing, and e-pharmacy. However, the intention to use digital health services in Indonesia is still underdeveloped though the sales of other risk-free e-commerce products are high enough. This study aims to assess the human perception of perceived value and social influences regarding the intention to use digital health services. Google Forms web link is employed to disseminate a set of 4-Point Likert scale questionnaires. In total, 364 complete responses are collected. A descriptive approach is employed to process the data using Microsoft Excel and SPSS software. Validity and reliability are quantified using the item total-correlation method and Cronbach's Alpha coefficient. Only 87 respondents (24%) ever used digital health services, of which Halodoc (92%) is the most preferred application, and teleconsultation became the most popular service to access. Out of four, the average score is 3.16 for perceived value and 2.86 for the social influence dimension. Most respondents, not dependent on user experience, perceive more values obtained using digital health services, such as time and money savings, convenience, flexible order time, undiscovered identity, adventurous experience, and enjoyment. Another finding of this research proves that some social influences from family, friends, and mass media also bring effect to amplify the intention to use. A low level of trust is assumed to be the cause of a small number of users.


Autoimmune hepatitis type 2 following anti-papillomavirus vaccination in a 11-year-old girl.
In the last years numerous reports describing a possible association between administration of vaccines and development of autoimmune phenomena and overt autoimmune disease were published. Possible mechanisms of induction of autoimmune phenomena by vaccines and their excipients are probably similar to those implicated in induction by infectious agents. Here we report the case of an 11-year-old girl who developed autoimmune hepatitis type II after four weeks from vaccination against human papillomavirus. The possible relationships between the use of adjuvated vaccine against papillomavirus and autoimmune hepatitis are discussed. Although we do not provide evidence for a causal link, we suggest that the occurrence of the autoimmune hepatitis may be related to the stimulation of immune system by adjuvated-vaccine, that could have triggered the disease in a genetically predisposed individual. Therefore a monitoring of liver function test following administration of vaccine against papillomavirus may be useful in adolescent girl with signs of hepatopathy, as jaundice, dark urine or hepatomegaly, to early identify and to promptly treat autoimmune liver disorders.


[A multi-center prospective study for antibiotic prophylaxis to prevent perioperative infections in urologic surgery].
In order to assess the ability of our protocol for antibiotic prophylaxis to prevent perioperative infections in urologic surgery, 1,353 operations of open and laparoscopic urologic surgery conducted in 21 hospitals between September 2002 and August 2003 were subjected to analyses. We classified surgical procedures into four categories by invasiveness and contamination levels: Category A; clean less invasive surgery, Category B; clean invasive or clean-contaminated surgery, Category C; surgery with urinary tract diversion using the intestine. Prophylactic antibiotics were administrated intravenously according to our protocol, such as Category A; first or second generation cephems or penicillins on the operative day only, Category B; first and second generation cephems or penicillins for 3 days, and Category C; first, second or third generation cephems or penicillins for 4 days. The wound conditions and general conditions were evaluated in terms of the surgical site infection (SSI) as well as remote infection (RI) up to postoperative day (POD) 30. The SSI rate highest (23.3%) for surgery with intestinal urinary diversion, followed by 10.0% for surgery for lower urinary tract, 8.9% for nephroureterctomy, and 6.0% for radical prostatectomy. The SSI rates in clean surgery including open and laparoscopic nephrectomy/adrenalectomy were 0.7 and 1.4%, respectively. In SSIs, gram-positive cocci such as methicillin-resistant Staphylococcus aureus (58.8%) or Enterobacter faecalis (26.5%) were the most common pathogen. Similarly, the RI rate was the highest (35.2%) for surgery using intestinal urinary diversion, followed by 16.7% for surgery for lower urinary tract, 11.4% for nephroureterctomy, and 7.6% for radical prostatectomy, while RI rates for clean surgery were less than 5%. RIs most frequently reported were urinary tract infections (2.6%) where Pseudomonas aeruginosa (20.3%) and Enterobacter faecalis (15.3%) were the major causative microorganisms. Parameters such as age, obesity, nutritional status (low proteinemia), diabetes mellitus, lung disease, duration of operation, and blood loss volume were recognized as risk factors for SSI or RI in several operative procedures. Postoperative body temperatures, peripheral white blood counts, C reactive protein (CRP) levels in POD 3 were much higher than those in POD 2 in cases suffering from perioperative infections, especially suggesting that CRP could be a predictable marker for perioperative infections.


Performance of biomarkers FibroTest, ActiTest, SteatoTest, and NashTest in patients with severe obesity: meta analysis of individual patient data.
Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions in patients with severe obesity. The aim of this study was to perform an overview of 3 studies which assessed the performance of non-invasive markers of fibrosis (FibroTest), steatosis (SteatoTest) and steato-hepatitis (NashTest, ActiTest) in these patients. 494 patients with interpretable biopsy and biomarkers using of three prospective cohorts of patients with severe obesity (BMI >35 kg/m2) were included. Histology (NAS score) and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity, specificity, positive and negative predictive values were assessed. Weighted AUROC (wAUROC Obuchowski method) was used to prevent multiple testing and spectrum effect. Two meta-analyses were performed; one used the individual patient, and the other a classical meta-analysis. Prevalence of advanced fibrosis (bridging) was 9.9%, advanced steatosis (>33%) 54.2%, and steato-hepatitis (NAS score >4) 17.2%. The mean wAUROCs were: FibroTest for advanced fibrosis (95%CI; significance) = 0.85 (0.83-0.87; P<0.0001); SteatoTest for advanced steatosis = 0.80 (0.79-0.83); and ActiTest for steato-hepatitis = 0.84 (0.82-0.86; P<0.0001). Using the classical meta-analysis (random effect model) the mean AUROCs were: FibroTest = 0.72 (0.63-0.79; P<0.0001); SteatoTest = 0.71 (0.66-0.75; P<0.0001); and ActiTest = 0.74 (0.68-0.79; P<0.0001). Despite more metabolic risk factors in one cohort, results were similar according to gender, presence of diabetes and between the 3 cohorts. In patients with severe obesity, a significant diagnostic performance of FibroTest, SteatoTest and ActiTest was observed for liver lesions.


Integrated regional services: are working process changes desirable and achievable?
In the hospital district of Helsinki and Uusimaa, 32 municipalities with one or more health centres provide primary care to their residents. Legal and organizational barriers between primary care and hospital care impede the continuity of patient care. Integrating primary and secondary care with the aid of information technology may facilitate a virtual electronic patient record, in which the viewing of images and other patient data is possible regardless of the organization that produced them. For example, in one trial, diabetic patients sent their home blood glucose measurements by modem to their health centre. Preliminary observations suggest that they could increase their glucose testing largely because they were able to transmit the results to the database and receive teleconsultations. Also, a picture archiving and communication system (PACS) has been in operation in two clinics of the Helsinki University Central Hospital for over two years and seven hospitals had become filmless by the end of 2001. A regional PACS is planned to be completed by the year 2004.


TNF-α production and apoptosis in hepatocytes after Listeria monocytogenes and Salmonella Typhimurium invasion.
Invasion of hepatocytes by Listeria monocytogenes (LM) and Salmonella Typhimurium (ST) can stimulate tumor necrosis factor alpha (TNF-α) release and induce apoptosis. In this study, we compared the behavior of hepatocytes invaded by three L. monocytogenes serotypes (LM-4a, LM-4b and LM-1/2a) and by ST to understand which bacterium is more effective in the infectious process. We quantified TNF-α release by ELISA, apoptosis rates by annexin V (early apoptosis) and TUNEL (late apoptosis) techniques. The cell morphology was studied too. TNF-α release rate was highest in ST-invaded hepatocytes. ST and LM-1/2a induced the highest apoptosis production rates evaluated by TUNEL. LM-4b produced the highest apoptosis rate measured by annexin. Invaded hepatocytes presented various morphological alterations. Overall, LM-4b and LM-1/2a proved to be the most efficient at cell invasion, although ST adapted faster to the environment and induced earlier hepatocyte TNF-α release.


Cellular interactions and control of collagenase secretion in the synovium.
Monocyte/macrophages release a factor, mononuclear cell factor (MCF), homologous with interleukin 1 (IL-1), which augments synthesis and release of collagenase and prostaglandins by connective tissue cells such as synovial cells and chondrocytes. The production of MCF is increased by interactions with immunoglobulins, collagens, and T lymphocytes. Human U937 cells, which behave as immature monocytes, do not produce MCF unless induced by a soluble product of activated T lymphocytes. Induction of MCF is augmented by 1,25-dihydroxyvitamin D. This cell culture system serves as a model for aspects of joint inflammation.


The Novel Link between Gene Expression Profiles of Adult T-Cell Leukemia/Lymphoma Patients' Peripheral Blood Lymphocytes and Ferroptosis Susceptibility.
Ferroptosis, a regulated cell death dependent on iron, has garnered attention as a potential broad-spectrum anticancer approach in leukemia research. However, there has been limited ferroptosis research on ATL, an aggressive T-cell malignancy caused by HTLV-1 infection. Our study employs bioinformatic analysis, utilizing dataset GSE33615, to identify 46 ferroptosis-related DEGs and 26 autophagy-related DEGs in ATL cells. These DEGs are associated with various cellular responses, chemical stress, and iron-related pathways. Autophagy-related DEGs are linked to autophagy, apoptosis, NOD-like receptor signaling, TNF signaling, and the insulin resistance pathway. PPI network analysis revealed 10 hub genes and related biomolecules. Moreover, we predicted crucial miRNAs, transcription factors, and potential pharmacological compounds. We also screened the top 20 medications based on upregulated DEGs. In summary, our study establishes an innovative link between ATL treatment and ferroptosis, offering promising avenues for novel therapeutic strategies in ATL.


Prognosis of incidental left bundle branch block.
Incidental left bundle branch block (iLBBB) is a frequent cause for cardiology referrals. In such instances, there is uncertainty as to its prognosis. We sought to determine the utility of cardiovascular magnetic resonance (CMR) in the risk stratification of patients with iLBBB. Clinical events were collected in patients with iLBBB who had CMR. Controls had no cardiac symptoms or cardiac disease, a normal CMR scan and electrocardiogram. Amongst patients with iLBBB [n = 193, aged 62.7 ± 12.6 years (mean ± SD)], 110/193 (56.9%) had an abnormal phenotype (iLBBBCMR+) and 83/110 (43.0%) had a normal phenotype (iLBBBCMR-). Over 3.75 years (median; inter-quartile range: 2.7-5.5), iLBBBCMR+ had a higher total mortality [adjusted hazard ratio (aHR) 6.49, 95% confidence interval (CI) 1.91-22.0] and total mortality or major adverse cardiac events (MACEs; aHR 9.15, 95% CI 2.56-32.6) than controls (n = 107). In contrast, iLBBBCMR- had a similar risk of total mortality compared with controls, but total mortality or MACEs was higher (aHR 4.24, 95% CI 1.17-15.4; P = 0.028). Amongst iLBBB patients, both myocardial fibrosis (aHR 5.15, 95% CI 1.53-17.4) and left ventricular ejection fraction (LVEF) ≤ 50% (aHR 3.88, 95% CI 1.67-9.06) predicted total mortality. Myocardial fibrosis plus LVEF ≤50% was associated with the highest risk of total mortality (aHR: 9.87, 95% CI 2.99-32.6) and total mortality or MACEs (aHR 3.98, 95% CI 1.73-9.11). Outcomes in iLBBBCMR+ were poor whereas survival in iLBBBCMR- was comparable with controls. Myocardial fibrosis and LVEF <50% had an additive effect on the risk of clinical outcomes. A CMR scan is pivotal in risk-stratifying patients with iLBBB.


Apparent intrachromosomal exchange on the human Y chromosome explained by population history.
The human Y chromosome displays an unusual content of repetitive sequences. Y-chromosomal repeats are potential targets for intrachromosomal recombination, which is thought to be involved in a number of Y-associated defects, such as male infertility. Such rearrangements could potentially be investigated by the use of highly polymorphic DNA markers located within the repeat units, such as microsatellites. Here we analyse the two copies of the Y-chromosomal microsatellite DYS385, which we identified and localized to an approximately 190 kb duplicated and inverted fragment at Yq11.223. We found a highly significant correlation (r=0.853, P&<0.001) and a nonsignificant difference in a chi(2)-test (chi(2)=15.45, P>0.05) between the allele frequency distributions at both copies of the Y-STR in a German population sample (n=70). Such nearly identical allele frequency distribution between two copies of a duplicated highly polymorphic microsatellite cannot be explained by the independent mutational process that creates microsatellite alleles. Instead, this might be interpreted as evidence for a reciprocal intrachromosomal exchange process between the duplicated fragments. However, more detailed analyses using additional human populations as well as additional Y chromosome markers revealed that this phenomenon is highly population-specific and disappears completely when Y-STR diversity is analysed in association with two Y-SNP haplogroups. We found that the diversity of the two DYS385 loci (and other Y-STRs) is highly depending on the haplogroup background, and that equal proportions of both haplogroups in the German sample explains the nearly identical allele frequency distributions at the two DYS385 loci. Thus, we demonstrate here that allele frequency distributions at duplicate loci that are suggestive of intrachromosomal recombination can be explained solely by population history.


Room for improvement: a randomised controlled trial with nested qualitative interviews on space, place and treatment delivery.
Healthcare-oriented design in hospitals can promote better clinical outcomes. Creating optimal facilities may increase treatment effects. We investigated the influence of the treatment room on effects of exercise therapy. In a mixed-method randomised controlled double-blind trial, middle-aged individuals reporting knee or hip pain performed 8 weeks of exercise therapy in (1) a newly built physically enhanced environment, (2) a standard environment or (3) were waitlisted, receiving no intervention. Participants and therapists were blind to study aim. Primary outcome was participants' Global Perceived Effect (GPE; seven-point Likert scale). Six nested focus group interviews with participants (n=25) and individual interviews with therapists (n=2) explored experiences of the environments. 42 people exercised in the physically enhanced environment, 40 in the standard environment, 21 were waitlisted. Contrary to our hypothesis, the treatment response seemed greater in the standard environment for GPE (0.98, 95% CI0.5 to 1.4) than for the physically enhanced environment (0.37, 95% CI -0.2 to 0.9), between-group difference (0.61, 95% CI -0.1 to 1.3) did not reach statistical significance (p=0.07). Waitlist group reported no improvement (-0.05 95% CI -0.5 to 0.4). In interviews, participants from the standard environment expressed greater social cohesion and feeling at home. Qualitative themes identified; reflection, sense of fellowship and transition. Secondary patient-reported outcomes and qualitative findings supported the primary finding, while improvements in muscle strength and aerobic capacity did not differ between exercise groups. Results suggest that the physical environment contributes to treatment response. Matching patients' preferences to treatment rooms may improve patient-reported outcomes. ClinicalTrials.gov identifier: NCT02043613.


Inadvertent Arterial Peripherally Inserted Central Catheter Insertion With Corresponding Electrocardiographic Tracings: A Case Report.
Electrocardiographic (ECG) tip confirmation is a validated technique to place the distal tip of a peripherally inserted central catheter (PICC) in the distal superior vena cava at or near the cavoatrial junction during point-of-care insertions. This case report discusses an inadvertent arterial PICC placement despite navigation technology demonstrating similar confirmatory ECG changes seen in standard venous insertions. The findings demonstrate that ECG navigation technology should not be used to rule out arterial PICC placement.


[Effect of pyridoxine, riboflavin, potassium orotate, folic and glutamic acids on the recovery of work capacity in sexually immature rats].
It has been shown in experiments on 3-4-week-old rats that the use of pyridoxine, riboflavin, potassium orotate, folic and glutamic acids for 30 days accelerates the recovery of the working capacity after maximal exercise, increases the content of ATP in the muscles, and reduces the blood urea content.


Two-dimensional self-assembly of benzotriazole on an inert substrate.
The ultra-high vacuum (UHV) room temperature adsorption of benzotriazole (BTAH), a well-known corrosion inhibitor for copper, has been investigated on the pristine Au(111) surface using a combination of surface sensitive techniques. The dimensionality of the molecule is reduced from the 3D crystal structure to a 2-dimensional surface confinement, which induces the formation of hydrogen bonded 1-dimensional molecular chains consisting of alternating pro-S and pro-R enantiomers mainly. The 0-dimensional system is characteristic of gas-phase BTAH, which undergoes a tautomeric equilibrium, with consequences for the resulting adsorbed species. The balance between hydrogen bonding, inter-chain van der Waals interactions and surface-molecule interactions, and the correlation with the dimensionality of the system, are discussed in light of the experimental results and a computational description of the observed features.


Changes in childhood pneumonia and infant mortality rates following introduction of the 13-valent pneumococcal conjugate vaccine in Nicaragua.
In 2010, Nicaragua became the first developing nation to add 13-valent pneumococcal conjugate vaccine (PCV-13) to its national immunization schedule, using a "3+0" dosing schedule. We assessed changes in incidence rates of health facility visits for childhood pneumonia and infant mortality after PCV-13 introduction in the Department of León, Nicaragua. We collected visit diagnoses from all 107 public health facilities in León between 2008 and 2012. We compared rates of pneumonia hospitalizations, ambulatory visits for pneumonia and infant mortality during the prevaccine (2008-2010) and vaccine (2011-2012) periods among different age groups of children using generalized estimating equations, accounting for clustering by municipality. Exposure time was estimated by official municipality population estimates. The adjusted incidence rate ratio for pneumonia hospitalization in the vaccine versus prevaccine period was 0.67 (0.59-0.75) among infants and 0.74 (0.67-0.81) among 1-year olds. The adjusted incidence rate ratio for ambulatory visits for pneumonia was 0.87 (0.75-1.01) among infants, and 0.84 (0.74, 0.95) among 1-year olds. The adjusted incidence rate ratio for infant mortality was 0.67 (0.57-0.80). We also observed lower rates of health facility visits for pneumonia among age groups (2- to 4-year old and 5- to 14-year old) not eligible to receive PCV-13. Within the first 2 years of a PCV-13 immunization program in Nicaragua, we observed lower rates of hospitalizations and ambulatory visits for pneumonia among children of all ages and a lower infant mortality rate. Lower rates of pneumonia among age groups not eligible to receive PCV-13 suggest an indirect effect of the vaccine.


Risky behaviors and educational attainment among young Mexican-origin mothers: The role of acculturative stress and the educational aspiration-expectation gap.
The current longitudinal study examined how Mexican-origin adolescent mothers' (N = 204) reports of acculturative stress during late adolescence were associated with their educational attainment and engagement in risky behaviors in young adulthood, 4 years post-partum; we also examined whether this association was mediated by discrepancies between adolescents' educational aspirations and expectations. Findings revealed that mothers' greater reports of stress regarding English competency pressures and pressures to assimilate were associated with a larger gap between their aspirations and expectations. Mothers' reports of greater stress from pressures against assimilation, however, were associated with a smaller gap between aspirations and expectations. As expected, a larger gap between aspirations and expectations was associated with lower educational attainment and increased engagement in risky behaviors. Finally, significant mediation emerged, suggesting that the influence of stress from English competency pressures and pressures to assimilate on young mothers' educational attainment and engagement in risky behaviors was mediated through the aspiration-expectation gap. Findings are discussed with respect to understanding discrepancies between young mothers' aspirations and expectations in the context of acculturative stress.


Competitive effect of vitamin D2 and Ca2+ on phospholipid model membranes: an FTIR study.
The interaction of Ca(2+), with dipalmitoyl phosphatidylcholine (DPPC) model membranes was studied in the presence and absence of vitamin D(2) by using Fourier transform infrared spectroscopy. Addition of vitamin D(2) and/or Ca(2+) into pure DPPC liposomes shifts the phase transition to higher temperature, orders and decreases the dynamics of the acyl chains in both phases and does not induce hydrogen bond formation in the interfacial region. Moreover, the dynamics of the head group of the phospholipid decreases in both phases. The addition of vitamin D(2) into DPPC liposomes containing Ca(2+), decreases the effect of Ca(2+) at all the functional groups under investigation. Similarly, the effect of vitamin D(2) also decreases in the presence of Ca(2+). This behavior is dominant at high Ca(2+) concentrations. Our results show how simultaneous presence of vitamin D(2) and Ca(2+) alter the behavior of each other, which is reflected as a decrease in the interactions between the ions and vitamin D(2) within the membrane.


Requirements for a quality dashboard: Lessons from National Clinical Audits.
Healthcare organizations worldwide use quality dashboards to provide feedback to clinical teams and managers, in order to monitor care quality and stimulate quality improvement. However, there is limited evidence regarding the impact of quality dashboards and audit and feedback research focuses on feedback to individual clinicians, rather than to clinical and managerial teams. Consequently, we know little about what features a quality dashboard needs in order to provide benefit. We conducted 54 interviews across five healthcare organizations in the National Health Service in England, interviewing personnel at different levels of the organization, to understand how national (UK) clinical audit data are used for quality improvement and factors that support or constrain use of these data. The findings, organized around the themes of choosing performance indicators, assessing performance, identifying causes, communicating from ward to board, and data quality, have implications for the design of quality dashboards, which we have translated into a series of requirements.


spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk.
Drosophila has eight Hox proteins, and they require factors acting in parallel to regulate different segmental morphologies. Here we find that the Drosophila gene split ends (spen), has a homeotic mutant phenotype, and appears to encode such a parallel factor. Our results indicate that spen plays two important segment identity roles. One is to promote sclerite development in the head region, in parallel with Hox genes; the other is to cooperate with Antennapedia and teashirt to suppress head-like sclerite development in the thorax. Our results also indicate that without spen and teashirt functions, Antennapedia loses its ability to specify thoracic identity in the epidermis. spen transcripts encode extraordinarily large protein isoforms (approx. 5,500 amino acids), which are concentrated in embryonic nuclei. Both Spen protein isoforms and Spen-like proteins in other animals possess a clustered repeat of three RNP (or RRM) domains, as well as a conserved motif of 165 amino acids (SPOC domain) at their C-termini. Spen is the only known homeotic protein with RNP binding motifs, which indicates that splicing, transport, or other RNA regulatory steps are involved in the diversification of segmental morphology. Previous studies by Dickson and others (Dickson, B. J., Van Der Straten, A., Dominguez, M. and Hafen, E. (1996). Genetics 142, 163-171) identified spen as a gene that acts downstream of Raf to suppress Raf signaling in a manner similar to the ETS transcription factor Aop/Yan. This raises the intriguing possibility that the Spen RNP protein might integrate signals from both the Raf and Hox pathways.


Nanopore sequencing of microbial communities reveals the potential role of sea lice as a reservoir for fish pathogens.
Caligus rogercresseyi is a copepod ectoparasite with a high prevalence in salmon farms in Chile, causing severe welfare and economic concerns to the sector. Information on the parasite's underpinning mechanisms to support its life strategy is recently being investigated. Due to the critical role of microbiota, this study aimed to characterize the microbiota community associated with C. rogercresseyi from different regions with salmon aquaculture in Chile. Using third-generation sequencing with Nanopore technology (MinION) the full 16S rRNA gene from sea lice obtained from 8 areas distributed over the three main aquaculture regions were sequenced. Microbiota of the parasite is mainly comprised of members of phyla Proteobacteria and Bacteroidetes, and a core microbiota community with 147 taxonomical features was identified, and it was present in sea lice from the three regions. This community accounted for 19% of total identified taxa but more than 70% of the total taxonomical abundance, indicating a strong presence in the parasite. Several taxa with bioactive compound secretory capacity were identified, such as members of genus Pseudoalteromonas and Dokdonia, suggesting a possible role of the lice microbiota during the host infestation processes. Furthermore, the microbiota community was differentially associated with the salmon production, where several potential pathogens such as Vibrio, Tenacibaculum, and Aeromonas in Los Lagos, Aysén, and Magallanes region were identified. Notably, the Chilean salmon industry was initially established in the Los Lagos region but it's currently moving to the south, where different oceanographic conditions coexist with lice populations. The results originated by this study will serve as foundation to investigate putative role of sea lice as vectors for fish pathogens and also as reservoirs for antibiotic-resistant genes.


Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus.
Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced dose- and time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression.


An interactive eye-tracking system for measuring radiologists' visual fixations in volumetric CT images: Implementation and initial eye-tracking accuracy validation.
Eye-tracking approaches have been used to understand the visual search process in radiology. However, previous eye-tracking work in computer tomography (CT) has been limited largely to single cross-sectional images or video playback of the reconstructed volume, which do not accurately reflect radiologists' visual search activities and their interactivity with three-dimensional image data at a computer workstation (e.g., scroll, pan, and zoom) for visual evaluation of diagnostic imaging targets. We have developed a platform that integrates eye-tracking hardware with in-house-developed reader workstation software to allow monitoring of the visual search process and reader-image interactions in clinically relevant reader tasks. The purpose of this work is to validate the spatial accuracy of eye-tracking data using this platform for different eye-tracking data acquisition modes. An eye-tracker was integrated with a previously developed workstation designed for reader performance studies. The integrated system captured real-time eye movement and workstation events at 1000 Hz sampling frequency. The eye-tracker was operated either in head-stabilized mode or in free-movement mode. In head-stabilized mode, the reader positioned their head on a manufacturer-provided chinrest. In free-movement mode, a biofeedback tool emitted an audio cue when the head position was outside the data collection range (general biofeedback) or outside a narrower range of positions near the calibration position (strict biofeedback). Four radiologists and one resident were invited to participate in three studies to determine eye-tracking spatial accuracy under three constraint conditions: head-stabilized mode (i.e., with use of a chin rest), free movement with general biofeedback, and free movement with strict biofeedback. Study 1 evaluated the impact of head stabilization versus general or strict biofeedback using a cross-hair target prior to the integration of the eye-tracker with the image viewing workstation. In Study 2, after integration of the eye-tracker and reader workstation, readers were asked to fixate on targets that were randomly distributed within a volumetric digital phantom. In Study 3, readers used the integrated system to scroll through volumetric patient CT angiographic images while fixating on the centerline of designated blood vessels (from the left coronary artery to dorsalis pedis artery). Spatial accuracy was quantified as the offset between the center of the intended target and the detected fixation using units of image pixels and the degree of visual angle. The three head position constraint conditions yielded comparable accuracy in the studies using digital phantoms. For Study 1 involving the digital crosshairs, the median ± the standard deviation of offset values among readers were 15.2 ± 7.0 image pixels with the chinrest, 14.2 ± 3.6 image pixels with strict biofeedback, and 19.1 ± 6.5 image pixels with general biofeedback. For Study 2 using the random dot phantom, the median ± standard deviation offset values were 16.7 ± 28.8 pixels with use of a chinrest, 16.5 ± 24.6 pixels using strict biofeedback, and 18.0 ± 22.4 pixels using general biofeedback, which translated to a visual angle of about 0.8° for all three conditions. We found no obvious association between eye-tracking accuracy and target size or view time. In Study 3 viewing patient images, use of the chinrest and strict biofeedback demonstrated comparable accuracy, while the use of general biofeedback demonstrated a slightly worse accuracy. The median ± standard deviation of offset values were 14.8 ± 11.4 pixels with use of a chinrest, 21.0 ± 16.2 pixels using strict biofeedback, and 29.7 ± 20.9 image pixels using general biofeedback. These corresponded to visual angles ranging from 0.7° to 1.3°. An integrated eye-tracker system to assess reader eye movement and interactive viewing in relation to imaging targets demonstrated reasonable spatial accuracy for assessment of visual fixation. The head-free movement condition with audio biofeedback performed similarly to head-stabilized mode.


Comparison of thrombin and ristocetin in the interaction between von Willebrand factor and platelets.
It is known that the antibiotic ristocetin exposes the platelet membrane receptor for factor VIII/von Willebrand glycoprotein (FVIII/vWF). Recent reports suggest that low concentrations of thrombin also cause platelet membrane receptors to become available for FVIII/vWF. As a consequence, the suspicion has been raised that thrombin provides similar or equivalent activity in vivo to that observed for ristocetin under in vitro conditions. In this study, we quantitated the extent to which thrombin promotes the binding of FVII/vWF to platelets and determined whether or not this interaction initiates or complements platelet aggregation. With ristocetin present, the amount of 125I-FVIII/vWF that became platelet-bound correlated closely with the onset, rate, and extent of platelet aggregation. In contrast, at every thrombin concentration tested, the amount of 125I-FVIII/vWF that specifically bound to platelets was about 6% of that observed with ristocetin. Significantly, FVIII/vWF did not augment the rate of aggregation of platelets in response to thrombin or initiate platelet aggregation when subaggregating doses of thrombin were used. These observations indicate that the minimal association that occurs between FVIII/vWF and the platelet membrane in the presence of thrombin does not correlate with platelet aggregation and therefore is not analogous to the effects of ristocetin. Whether the low level of binding relates to another process, such as platelet-endothelial interactions, remains unknown.


Interferon-induced vitiligo in a patient with chronic viral hepatitis C infection.
Vitiligo is an autoimmune disease characterized by depigmentation of the skin due to destruction of melanocytes. Interferons have been used for the treatment of chronic hepatitis C and some malignancies. We report interferon alpha-2a-induced vitiligo in a male patient with chronic active hepatitis C. All skin lesions disappeared completely without requiring therapy after discontinuation of interferon. This case suggests that vitiligo may be developed during interferon therapy as a side effect.


Checking the Pulse of PitCon '88.
At PitCon '88-otherwise known as the Pittsburgh Conference and Exposition on Analytical Chemistry and Applied Spectroscopy-exhibited instruments capitalized on improvements in existing technology rather than novel concepts or design. This year's models feature increasing automation, particularly for aspects of sample presentation. The 1988 generation of so-called hyphenated systems emphasize a combination of techniques within the same work station-gas chromatography to detect and separate organic contaminants combined with mass spectrometry to identify them, for example. And in keeping with strict environmental standards, many companies are stressing the ability of their latest instruments to detect levels of environmental pollutants in the parts per billion, rather than parts per million, range. PitCon '88 lured more than 25,000 participants to New Orleans for the week of 22 to 26 February. Approximately 830 companies displayed their wares at 2400 booths, and it took two separate facilities to house them. Specialized symposia on advances in spectroscopic, chromatographic, and electrochemical techniques increased in number as did the number of individual talks and posters. And new this year were three general interest symposia-identifying antiques by spectrochemical techniques, cholesterol, and drug testing in the workplace.


Observed size distribution changes in American lobsters over a 12-year period in southwestern Nova Scotia, Canada.
Size distribution and size frequency information of American lobsters (Homarus americanus) are often used to help estimate the age distributions, and reproductive output for the species and to guide the determination of appropriate minimum legal sizes for the fishery. This study used truncated linear regression models to estimate the effects of sampling year, sampling month, lobster sex and water depth on the lobster size. A dataset of almost 130,000 trap-caught lobsters from the two most important lobster fishing areas of Atlantic Canada collected over a 12-year period (2004-2015) was analyzed. It was shown that truncated models can help to account for biases due to the trap sampling method from vessels and from wharf samplings. There were significant annual and seasonal changes in size distribution, and data collected outside the fishing season showed a significant increase in carapace length in 2014 and 2015, potentially reflecting a northward shift of the range of lobster populations due to more favourable settlement and recruitment habitats. Size also increased in late summer, likely due to moult. Our results demonstrated that landed lobsters, especially females, were smaller than the predicted size-at-maturity in the region (96.5 mm carapace length), which could have long-term repercussions for the stock's reproductive potential.


Surface Immobilization of a Re(I) Tricarbonyl Phenanthroline Complex to Si(111) through Sonochemical Hydrosilylation.
A sonochemical-based hydrosilylation method was employed to covalently attach a rhenium tricarbonyl phenanthroline complex to silicon(111). fac-Re(5-(p-Styrene)-phen)(CO)3Cl (5-(p-styrene)-phen = 5-(4-vinylphenyl)-1,10-phenanthroline) was reacted with hydrogen-terminated silicon(111) in an ultrasonic bath to generate a hybrid photoelectrode. Subsequent reaction with 1-hexene enabled functionalization of remaining atop Si sites. Attenuated total reflectance-Fourier transform infrared spectroscopy confirms attachment of the organometallic complex to silicon without degradation of the organometallic core, supporting hydrosilylation as a strategy for installing coordination complexes that retain their molecular integrity. Detection of Re(I) and nitrogen by X-ray photoelectron spectroscopy (XPS) further support immobilization of fac-Re(5-(p-styrene)-phen)(CO)3Cl. Cyclic voltammetry and electrochemical impedance spectroscopy under white light illumination indicate that fac-Re(5-(p-styrene)-phen)(CO)3Cl undergoes two electron reductions. Mott-Schottky analysis indicates that the flat band potential is 239 mV more positive for p-Si(111) co-functionalized with both fac-Re(5-(p-styrene)-phen)(CO)3Cl and 1-hexene than when functionalized with 1-hexene alone. XPS, ultraviolet photoelectron spectroscopy, and Mott-Schottky analysis show that functionalization with fac-Re(5-(p-styrene)-phen)(CO)3Cl and 1-hexene introduces a negative interfacial dipole, facilitating reductive photoelectrochemistry.


[Prevalence of Borrelia burgdorferi sensu lato in ticks, Ixodes ricinus in Tarnowskie Góry district].
Borrelia burgdorferi is an aetiological factor of borreliosis (Lyme disease). The main vectors of Borrelia burgdorferi are larvae, nymphs, and females of Ixodes ricinus. The aim of this paper was to analyse infection parameters of Borrelia burgdorferi in a selected populations of Ixodes ricinus. The study was conducted in Tarnowskie Góry administrative district (Krupski Młyn, Zielona, Lubliniec, Tarnowskie Góry, Swierklaniec, Tworóg, and Zbrosławice). A total of 85 ticks were collected with a piece of cloth dragged over the vegetation. The Borrelia burgdorferi infection was confirmed with a PCR method, using flagellin protein gene DNA amplification. DNA of Borrelia burgderferi sensu lato was present in 14 ticks, which constituted 16.5% of the population studied. The percentage of infected females and nymphs was 26.8%, 22.2%, and 5.6%, respectively. A high prevalence of the pathogen (50%) was in ticks revealed in the recreation areas and the community forest in Swierklaniec.


Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial.
Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects. To test whether selepressin improves outcome in septic shock. An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 μg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018. Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters. Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days. Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, -1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, -6.5% to 8.8%]; P = .77; kidney replacement therapy-free days: 18.5 vs 18.2; difference, 0.3 [95% CI, -2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, -1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%). Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock. ClinicalTrials.gov Identifier: NCT02508649.


Noncovalent Shiga-like toxin assemblies: characterization by means of mass spectrometry and tandem mass spectrometry.
Shiga-like toxin 1 (SLTx), produced by enterohemorrhagic strains of Escherichia coli (EHEC), belongs to a family of structurally and functionally related AB(5) protein toxins that are associated with human disease. EHEC infection often gives rise to hemolytic colitis, while toxin-induced kidney damage is one of the major causes of hemolytic uremic syndrome (HUS) and acute renal failure in children. As such, an understanding and analysis of the noncovalent interactions that maintain the quaternary structure of this toxin are fundamentally important since such interactions have significant biochemical and medical implications. This paper reports on the analysis of the noncovalent homopentameric complex of Shiga-like toxin B chain (SLTx-B(5)) using electrospray ionization (ESI) triple-quadrupole (QqQ) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) and the analysis of the noncovalent hexameric holotoxin (SLTx-AB(5)) using ESI time-of-flight (TOF) MS. The triple-quadrupole analysis revealed highly charged monomer ions dissociate from the multiprotein complex to form dimer, trimer, and tetramer product ions, which were also seen to further dissociate. The ESI-TOFMS analysis of SLTx-AB(5) revealed the complex remained intact and was observed in the gas phase over a range of pHs. Theses findings demonstrate that the gas-phase structure observed for both the holotoxin and the isoloated B chains correlates well with the structures reported to exist in the solution phase for these proteins. Such analysis provides a rapid screening technique for assessing the noncovalent structure of this family of proteins and other structurally related toxins.


Antimicrobial resistance control activities at a tertiary hospital in a low-resource setting: an example of Queen Elizabeth Central Hospital in Malawi.
Addressing AMR has been most problematic in low- and middle-income countries, which lack infrastructure, diagnostic capacity, and robust data management systems, among other factors. The implementation of locally-led efforts in a low-income country to develop sustainability and build capacity for AMR control within the existing infrastructure has not been well documented. We detail current AMR control initiatives at Queen Elizabeth Central Hospital, a tertiary referral government hospital in Malawi with limited resources, and present the activities accomplished to date, lessons learned, and challenges ahead. The key areas of AMR control initiatives that the group focused on included laboratory diagnostics and surveillance, antimicrobial stewardship, infection prevention and control, pharmacy, leadership, education, and funding. The hospital AMR Control Working Group increased awareness, built capacity, and implemented activities around AMR control throughout the hospital, in spite of the resource limitations in this setting. Our results are based on the substantial leadership provided by the working group and committed stakeholders who have taken ownership of this process. Limited resources pose a challenge to the implementation of AMR control activities in low- and middle-income countries. Leadership is central to implementation. Future efforts will need to transition the initiative from an almost fully personal commitment to one with wider engagement to ensure sustainability.


The Seed Coat Extract of Black Soybean Decreases Nicotine-Induced Vascular Fiber Degradation by Suppressing Matrix Metalloproteinase 2 Expression.
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of vascular walls and progressive dilation of the abdominal aorta. Nicotine, the main component of tobacco, is reportedly associated with the development and rupture of AAA. It is desirable to attenuate the destructive effect of nicotine on vascular walls, using dietary food components. However, effective methods for preventing AAA progression using dietary food components remain unestablished. This study focuses on proanthocyanidins, well known for their potent antioxidant activity. We speculated that proanthocyanidins can suppress nicotine-induced weakening of vascular walls. To estimate the effect of black soybean seed coat extract (BSSCE), rich in proanthocyanidins, on nicotine-induced weakening of the aortic wall, mice were divided into four groups: the control diet and distilled water group (named C), BSSCE solution diet and distilled water group (named B), control diet and 0.5 mg/mL nicotine solution group (named CN), and BSSCE solution diet and 0.5 mg/mL nicotine solution group (named BN). Nicotine-induced degradation of elastin and collagen fibers were significantly suppressed in BN group. The positive areas for matrix metalloproteinase (MMP)-2 and oxidative stress in BN group were significantly decreased compared to those in CN group. These results suggest that proanthocyanidins-rich BSSCE can prevent the weakening of the aortic wall via inhibiting MMP-2 upregulation.


Induction of tibial dyschondroplasia by carbamate and thiocarbamate pesticides.
Tibial dyschondroplasia (TD) is a major poultry leg problem, the natural etiology of which is unknown. Certain dithiocarbamate pesticides such as tetramethyl thiuram disulfide (thiram) have been shown to induce the disease in chickens. Because many different carbamate and thiocarbamate chemicals are used in a number of agricultural, industrial, and household applications, the objective of this study was to determine whether all chemicals of these categories induce TD and whether there is a concentration-dependent relationship between the ingestion of these chemicals and the incidences and the severity of the disease. Week-old broiler chicks were fed diets containing thiram or other assorted carbamate and thiocarbamate pesticides mixed in feed for 24-48 hr between ages 8 and 10 days. The birds were killed on day 15 and the proximal tibial and tarsometatarsal growth plates were evaluated for the presence and severity of TD lesions. TD was distinguished by broadening of growth plates; upon histologic exam chondrocytes appeared to be shrunken and dead. When compared by including equimolar concentrations of these chemicals in the feed, the dithiocarbamates with more than two sulfide groups, such as disulfiram, ferbam, thiram, and ziram were potent inducers of TD, whereas those with two sulfides to no sulfide group appeared ineffective at inducing TD. Both thiram and ferbam also reduced the bird's body weights. Thiram increased the incidence and the severity of the disease, denoted by TD index, in a dose-dependent manner. These results suggest that inadvertent contamination of feed or litter with some of these or similar chemicals may cause leg problems in poultry.


Self treatment of eye diseases in Malawi.
Self-treatment for eye diseases is very common in most developing countries yet there has been little investigation of such attitudes and practices. In many settings, people do not proceed beyond self-treatment and do not receive care from either traditional healers or Western eye care providers. Visual impairment and blindness can be the result. We conducted population-based survey of use of eye care services and self-treatment in two districts of Malawi. Adults were administered a detailed interview regarding their use of eye care services (Western and traditional as well as self-treatment) and their knowledge and use of traditional eye medicines. Self-treatment was defined as use of either Western or traditional medicines by the individual for their most recent eye condition. Only eye conditions that were considered severe by the study subjects were correlated with treatment options. Interviews were carried out among 800 adults in the study areas. Self-treatment was reported for the last episode of eye disease by 39.8% of the study population. Factors associated with self-treatment included sex, religion and socioeconomic status. Even though 76.8% of the respondents reported treatment from the health center or hospital to be the least expensive option, many opted for self-treatment first. Among those opting for self-treatment 72% used traditional eye medicines. Even among cases that individuals considered to be quite severe (these included cataract, trachoma and conjunctivitis), self-treatment was the option of choice in 22.2% of cases.


An Online Calculator for the Prediction of Survival in Glioblastoma Patients Using Classical Statistics and Machine Learning.
Although survival statistics in patients with glioblastoma multiforme (GBM) are well-defined at the group level, predicting individual patient survival remains challenging because of significant variation within strata. To compare statistical and machine learning algorithms in their ability to predict survival in GBM patients and deploy the best performing model as an online survival calculator. Patients undergoing an operation for a histopathologically confirmed GBM were extracted from the Surveillance Epidemiology and End Results (SEER) database (2005-2015) and split into a training and hold-out test set in an 80/20 ratio. Fifteen statistical and machine learning algorithms were trained based on 13 demographic, socioeconomic, clinical, and radiographic features to predict overall survival, 1-yr survival status, and compute personalized survival curves. In total, 20 821 patients met our inclusion criteria. The accelerated failure time model demonstrated superior performance in terms of discrimination (concordance index = 0.70), calibration, interpretability, predictive applicability, and computational efficiency compared to Cox proportional hazards regression and other machine learning algorithms. This model was deployed through a free, publicly available software interface (https://cnoc-bwh.shinyapps.io/gbmsurvivalpredictor/). The development and deployment of survival prediction tools require a multimodal assessment rather than a single metric comparison. This study provides a framework for the development of prediction tools in cancer patients, as well as an online survival calculator for patients with GBM. Future efforts should improve the interpretability, predictive applicability, and computational efficiency of existing machine learning algorithms, increase the granularity of population-based registries, and externally validate the proposed prediction tool.


First Atmospheric Science Results from the Mars Exploration Rovers Mini-TES.
Thermal infrared spectra of the martian atmosphere taken by the Miniature Thermal Emission Spectrometer (Mini-TES) were used to determine the atmospheric temperatures in the planetary boundary layer and the column-integrated optical depth of aerosols. Mini-TES observations show the diurnal variation of the martian boundary layer thermal structure, including a near-surface superadiabatic layer during the afternoon and an inversion layer at night. Upward-looking Mini-TES observations show warm and cool parcels of air moving through the Mini-TES field of view on a time scale of 30 seconds. The retrieved dust optical depth shows a downward trend at both sites.


[Intranasal opioids for acute pain].
Intranasal drug administration is an easy, well-tolerated, noninvasive transmucosal route that avoids first-pass metabolism in the liver. The nasal mucosa provides an extensive, highly vascularized surface of pseudostratified ciliated epithelium. It secretes mucus that is subjected to mucociliary movement that can affect the time of contact between the drug and the surface. Absorption is influenced by anatomical and physiological factors as well as by properties of the drug and the delivery system. We review the literature on intranasal administration of fentanyl, meperidine, diamorphine, and butorphanol to treat acute pain. The adverse systemic effects are similar to those described for intravenous administration, the most common being drowsiness, nausea, and vomiting. Local effects reported are a burning sensation with meperidine and a bad taste.


Metabolic compartmentation of plastid prenyllipid biosynthesis--evidence for the involvement of a multifunctional geranylgeranyl reductase.
The addition of phytyl side chain to chlorophylls, tocopherols and phylloquinone is prerequisite to their integration into plastid membranes. We have cloned a cDNA encoding a pre-geranylgeranyl reductase from Arabidopsis thaliana. The deduced primary structure predicts a mature size with a molecular mass of 47 kDa and displays a characteristic dinucleotide binding domain. Geranylgeranyl reductase expressed in Escherichia coli sequentially catalyzes the reduction of geranylgeranyl-chlorophyll a into phytyl-chlorophyll a as well as the reduction of free geranylgeranyl diphosphate into phytyl diphosphate. Due to its multifunctionality and weak hydrophobicity, we suggest that in plastid the same geranylgeranyl reductase is recruited into the chlorophyll, the tocopherol and the phylloquinone pathways. The geranylgeranyl reductase gene is up-regulated during etioplast to chloroplast and chloroplast to chromoplast development.


Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.
Folate and vitamin B12 are needed for the proper embryo-fetal development possibly through their interacting role in the 1-carbon metabolism. Folate fortification reduces the prevalence of complex birth defects, and more specifically neural tube defects (NTDs). GIF and FUT2 are 2 genes associated with the uptake and blood level of vitamin B12. We evaluated GIF and FUT2 as predictors of severe birth defects, in 183 aborted fetuses compared with 375 healthy newborns. The GIF290C allele frequency was estimated to 0.4% in healthy newborns and to 8.1% in NTD fetuses (odds ratio 17.8 [95% confidence interval CI: 4.0-77.6]). The frequency of FUT2 rs601338 secretor variant was not different among groups. The GIF 290C heterozygous/FUT2 rs601338 secretor variant combined genotype was reported in 6 of the 37 NTD fetuses, but not in other fetuses and healthy newborns (P < .0001). This GIF/FUT2 combined genotype has been previously reported in children with congenital gastric intrinsic factor (GIF) deficiency, with respective consequences on B12 binding activity and GIF secretion. In conclusion, a genotype reported in congenital GIF deficiency produces also severe forms of NTD. This suggests that vitamin B12 delivery to neural tissue by the CUBN/GIF pathway could play a role in the neural tube closure mechanisms.


A deletion mutation in the SH2-N domain of Shp-2 severely suppresses hematopoietic cell development.
Shp-1 and Shp-2 are cytoplasmic protein tyrosine phosphatases that contain two Src homology 2 (SH2) domains. A negative regulatory role of Shp-1 in hematopoiesis has been strongly implicated by the phenotype of motheaten mice with a mutation in the Shp-1 locus, which is characterized by leukocyte hypersensitivity, deregulated mast cell function, and excessive erythropoiesis. A targeted deletion of 65 amino acids in the N-terminal SH2 (SH2-N) domain of Shp-2 leads to an embryonic lethality at midgestation in homozygous mutant mice. To further dissect the Shp-2 function in hematopoietic development, we have isolated homozygous Shp-2 mutant embryonic stem (ES) cells. Significantly reduced hematopoietic activity was observed when the mutant ES cells were allowed to differentiate into embryoid bodies (EBs), compared to the wild-type and heterozygous ES cells. Further analysis of ES cell differentiation in vitro showed that mutation in the Shp-2 locus severely suppressed the development of primitive and definitive erythroid progenitors and completely blocked the production of progenitor cells for granulocytes-macrophages and mast cells. Reverse transcriptase PCR analysis of the mutant EBs revealed reduced expression of several specific marker genes that are induced during blood cell differentiation. Stem cell factor induction of mitogen-activated protein kinase activity was also blocked in Shp-2 mutant cells. Taken together, these results indicate that Shp-2 is an essential component and primarily plays a positive role in signaling pathways that mediate hematopoiesis in mammals. Furthermore, stimulation of its catalytic activity is not sufficient, while interaction via the SH2 domains with the targets or regulators is necessary for its biological functions in cells. The in vitro ES cell differentiation assay can be used as a biological tool in dissecting cytoplasmic signaling pathways.


[Administration of diprivan during urological surgery in children].
In 56 children, aged from 6 to 14 years, while performing urological operations the narcosis using ketamine was applied and in 43--basing on diprivan and anesthesy with phentanyl. In all the children premedication was conducted using atropine, dimedrol and sibazone. Pain in the vein while diprivan was injected occurred in 6 (14%) of children, involuntary movements--in 16 (37%). While application of diprivan in all the children the mild arterial hypertension was observed, bradycardia was absent on all stages of anesthesy period. The waking up period duration after conduction of anesthesy using ketamine had constituted at average (86.9 +/- 13.1) min, and using diprivan--(35.2 +/- 11.3) min (P < 0.01). Anesthesy basing on diprivan owes significant advantages in comparison with narcosis using ketamine during performance of urological operation in a child.


Authentication and banking of human pluripotent stem cells.
Pluripotent human stem cell lines from embryos or reprogrammed adult cells are not all alike. Cell lines differ widely in their propensity for differentiation, their chromosomal integrity and epigenetic state, immunological profiles, and their availability for research. It is important that all pluripotent cell lines be protected from loss by being properly banked and authenticated, which will also protect current experimental data by enabling its future reproducibility. This unit considers basic guidelines for banking and authentication of pluripotent stem cells that should be easily implementable within any laboratory. Cell Banking is the disciplined preservation of a cell stock in the originally obtained state, as well as stocks representing the baseline state for experimental efforts. Each of these stocks must be authenticated appropriately. Authentication of pluripotent lines verifies five properties: the unique identity of the line, its sterility or freedom from contaminating microorganisms and pathogens, the integrity and stability of its genome, its expression of typical markers of the stem cell phenotype, and its pluripotency upon differentiation. This unit lists and compares several assays to verify each of these stem cell line properties. Thanks to recent advances in molecular biology and the availability of state-of-the-art assays from service providers, the time and material costs of banking and authentication are not excessive for the typical research laboratory.


Development of a live attenuated dengue virus vaccine using reverse genetics.
There are four serotypes of dengue (DEN1-DEN4) virus that are endemic in most areas of Southeast Asia, Central and South America, and other subtropical regions. The number of cases of severe disease associated with DEN virus infection is growing because of the continued spread of the mosquito vector, Aedes aegypti, which transmits the virus to humans. Infection with DEN virus can result in an asymptomatic infection, a febrile illness called dengue fever (DF), and the very severe disease called dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Currently, a licensed vaccine is not available. However, a tetravalent vaccine is urgently needed to prevent DF and DHF/DSS, the latter of which occurs predominantly in partially immune individuals. A live attenuated, tetravalent DEN virus vaccine candidate has been generated using reverse genetics that is able to provide immunity to each of the four serotypes of DEN. Attenuation has been achieved by generating recombinant DEN (rDEN) viruses which are modified by deletion or, alternatively, by antigenic chimerization between two related DEN viruses using the following two strategies: 1) introduction of an attenuating 30 nucleotide deletion (Delta30) mutation into the 3' untranslated region of DEN1 and DEN4; and 2) replacement of structural proteins of the attenuated rDEN4Delta30 vaccine candidate with those from DEN2 or DEN3. Attenuation of the four monovalent vaccine candidates has been achieved for rhesus monkeys or humans and an immunogenic tetravalent vaccine candidate has been formulated. The level of attenuation of each dengue vaccine component can be increased, if needed, by introduction of additional attenuating mutations that have been well characterized.


Temperature effects on the scattering of polarons and bipolarons in organic conductors.
The scattering process between an electron-polaron and a hole-bipolaron has been simulated using a version of the Su-Schrieffer-Heeger (SSH) model modified to include an external electric field, Coulomb interactions, and temperature effects in the scope of nonadiabatic molecular dynamics. The simulations reveal remarkable details concerning the polaron-bipolaron recombination reaction. It is found that there exists a critical temperature regime below which a hole-bipolaron and a mixed state composed by an electron-polaron and an exciton are formed and a hole-bipolaron and a free electron are the resulting products of the collisional process, if the temperature is higher than the critical value. In addition, it is obtained that both channels depend sensitively on the strength of the applied electric field. These significant results may provide guidance to understand processes regarding electroluminescence in polymer diodes.


Turkish reference ranges for the left fetal modified myocardial performance index.
This study aimed to assess fetal cardiac left ventricular function in healthy pregnant women by calculating the modified myocardial performance index (Mod-MPI) and to construct reference ranges for the Turkish population. One-hundred-two randomly selected healthy singleton pregnant women ranging between 25 and 39 gestational weeks were included in the study. Left fetal Mod-MPI was measured for each pregnant woman. Women with chronic systemic diseases or fetuses with chromosomal or structural abnormalities were excluded from the study. Mitral valve (MV) and aortic valve (AoV) clicks were used as landmarks to define the following time periods that were used to calculate the Mod-MPI: isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET). The mean Mod-MPI was 0.42±0.10. The mean IRT, ICT, and ET were 43.5±10.2, 27.27±8.1, and 170.5±16.9, respectively. A significant correlation was found between Mod-MPI and gestational age, umbilical artery systolic/diastolic (UA S/D) ratio and the middle cerebral artery pulsatility index (MCA PI) values (r=0.199, p=0.047, r=-0.328, p=0.001, and r=-0.0349, p=0.001, respectively) Conclusions. The current study`s results will be a reference for future studies, especially studies investigating pathological conditions that impact fetal cardiac function.


Observing crossover between quantum speed limits.
Quantum mechanics sets fundamental limits on how fast quantum states can be transformed in time. Two well-known quantum speed limits are the Mandelstam-Tamm and the Margolus-Levitin bounds, which relate the maximum speed of evolution to the system's energy uncertainty and mean energy, respectively. Here, we test concurrently both limits in a multilevel system by following the motion of a single atom in an optical trap using fast matter wave interferometry. We find two different regimes: one where the Mandelstam-Tamm limit constrains the evolution at all times, and a second where a crossover to the Margolus-Levitin limit occurs at longer times. We take a geometric approach to quantify the deviation from the speed limit, measuring how much the quantum evolution deviates from the geodesic path in the Hilbert space of the multilevel system. Our results are important to understand the ultimate performance of quantum computing devices and related advanced quantum technologies.


Ambivalence over emotional expressiveness in intimate relationships: a shift from an individual characteristic to dyadic attribute.
This study investigates how ambivalence over emotional expressiveness (AEE) relates to various aspects of intimate relationships, including perception of the relationship, marital satisfaction, and dyadic closeness. Whereas most commonly AEE has been treated as an individual attribute, we suggest looking at a combined measure of the AEE of both spouses as a dyadic attribute. We examine the contribution of each spouse's level of AEE as well as joint couple AEE to explain variations in the marital relationship. Data were collected from both spouses of 226 Israeli couples. Findings indicated that the AEE of individuals was more predictive of lower relationship quality than neuroticism and that dyadic AEE explains relationship quality more than the AEE of individual partners. Implications for future research and practice are discussed.


Motion Planning and Iterative Learning Control of a Modular Soft Robotic Snake.
Snake robotics is an important research topic with a wide range of applications, including inspection in confined spaces, search-and-rescue, and disaster response. Snake robots are well-suited to these applications because of their versatility and adaptability to unstructured and constrained environments. In this paper, we introduce a soft pneumatic robotic snake that can imitate the capabilities of biological snakes, its soft body can provide flexibility and adaptability to the environment. This paper combines soft mobile robot modeling, proprioceptive feedback control, and motion planning to pave the way for functional soft robotic snake autonomy. We propose a pressure-operated soft robotic snake with a high degree of modularity that makes use of customized embedded flexible curvature sensing. On this platform, we introduce the use of iterative learning control using feedback from the on-board curvature sensors to enable the snake to automatically correct its gait for superior locomotion. We also present a motion planning and trajectory tracking algorithm using an adaptive bounding box, which allows for efficient motion planning that still takes into account the kinematic state of the soft robotic snake. We test this algorithm experimentally, and demonstrate its performance in obstacle avoidance scenarios.


An Orientational Harvesting Occipital Artery Technique via far Lateral Approach: A Cadaveric Study.
To provide further information on the identification of the occipital artery (OA) and suggest an improved approach to its anterograde dissection technique for harvesting. Six cadaveric specimens were prepared for surgical simulation, and the anterograde approach was used to harvest the OA; a hockey stick incision was made from the C2 spinous process through the nuchal ligament to the mastoid tip. By retracting the scalp flap from the posterior arch of C2 to the transverse process, the suboccipital triangle was reflected by a single myocutaneous flap from the inferior nuchal line. In addition, 70 head computed tomography angiography scans were assessed bilaterally (n = 140) to study the running pattern of the OA. The mean total length of the mobilized OA was 11.8 ± 0.7 cm, with a diameter of 1.5 ± 0.1-2.1 ± 0.2 mm at the suboccipital segment and 1.3 ± 0.1 mm at the upper edge of the surgical incision. The average distance of OA at the inferior nuchal line to the midline was 2.9 ± 0.3 cm, the average distance of OA at the superior nuchal line to midline was 4.1 ± 0.2 cm, the average distance of OA at incision edge to midline was 5.2 ± 0.3 cm. Orientational anterograde technique for OA harvesting is a fast and easy approach. This approach avoids critical neurovascular structures. The most important step is to identify the OA near the lateral edge of the superior oblique muscle. Subsequently, in conjunction with preoperative computed tomography angiography, an imaginary line that crosses the inferior and superior nuchal lines may be established to assist in the separation of the OA.


Severe Corneal Disorders Developed After Brimonidine Tartrate Ophthalmic Solution Use.
The primary side effects associated with 0.1% brimonidine tartrate (BT) ophthalmic solution with sodium chlorite are allergic conjunctivitis, blepharitis, and conjunctival hyperemia. However, cornea-related side effects are rare. In this study, we report 2 similar cases in which corneal neovascularization, corneal infiltration, and corneal opacity developed after BT eye-drop use. Retrospective report of 2 cases of corneal infiltration after BT eye-drop use. Case 1 involved a 78-year-old woman with follicular conjunctivitis, corneal neovascularization, and infiltration in her left eye after unilateral instillation of BT eye drops in that eye. Case 2 involved a 75-year-old woman with bilateral corneal neovascularization and infiltration after instillation of BT eye drops. In both cases, the corneal complications were deemed to be side effects of BT, so those eye drops were replaced with 0.1% fluorometholone eye drops. After replacement, blepharitis and corneal neovascularization successfully resolved; however, a layer of opacity remained across the transparent layer of the cornea in both cases. We encountered 2 cases of corneal and conjunctival complications that developed as side effects after BT eye-drop use, thus indicating that strict attention should be paid to the possibility of side effects after initiation of antiglaucoma eye-drop use.


Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.
Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 Å resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a zbetter model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease-associated mutants.


Evaluation of geriatric patients with special reference to clinical trials of so-called nootropic drugs. I. General considerations and screening.
This article, the first in a series, reviews some well-known difficulties involved in the assessment and evaluation of elderly patients. The various aims of assessment proper and of evaluation are delineated and a clear description of the specific purposes of assessment of the elderly is presented. These can differ considerably from the assessment aims for younger persons, for whom the tests were developed, thereby placing the use of traditional psychometric devices with the elderly in a doubtful position. An individualized, ecologically relevant approach is therefore suggested as an alternative. This position is further supported by the evidence that few of the standard psychometric criteria - validity, reliability, and representative reference groups - are met when standardized psychometric instruments are used with an older population. Evaluation of treatment effects, particularly drug effects, is elaborated with this evidence in mind, and the screening process is analyzed in terms of the special demands the characteristics of elderly subjects make on it. Later articles will also address the evaluation of treatment effects, concentrating on the selection of specific procedures and the assessment of baseline behavior and behavior change.


Factors affecting prognosis with penetrating wounds of the heart.
To determine factors affecting prognosis for patients with penetrating wounds of the heart. A retrospective review of 302 patients with penetrating heart wounds undergoing emergency thoracotomy (August of 1980 through June of 1997) in a Level I trauma center. There were 148 patients with gunshot wounds (GSW) and 154 patients with stab wounds with 23% and 58% survival rates, respectively. Of 43 patients having no signs of life at the scene, 5 patients (12%) achieved some cardiac activity and were brought to the operating room (OR), but none survived. Of 67 patients "arresting" in the ambulance, 23 got to the OR, but only 3 patients (4%) survived. Of 27 patients "arresting" in the emergency department (ED), 18 patients reached the OR, but only 5 patients (19%) survived. Of 15 patients having an ED thoracotomy because of rapid deterioration there, 4 patients (27%) survived. Thus, of the 152 patients with an ED thoracotomy, 93 patients had gunshot wounds and none survived; of the 59 with stab wounds, 12 (20%) survived (p < 0.001). Of 150 patients having an OR thoracotomy, 111 (74%) survived. Single-chamber injuries had a survival rate of 51% (112 of 219 patients), but multiple chamber and/or intrapericardial great vessel injuries had only a 13% survival rate (11 of 83 patients) (p < 0.001). Intrapericardial aortic injuries were uniformly fatal in 15 patients. In patients with stab wounds, pericardial tamponade was associated with a higher survival rate (66%; 56 of 84 patients) than in those without tamponade (47%; 33 of 70 patients). The physiologic status of the patient at presentation, mechanism of injury, and presence of a tamponade were significant prognostic factors in this series of penetrating cardiac injuries. Multiple-chamber injuries, especially with great vessel involvement, were associated with a high mortality rate. ED thoracotomies for gunshot wounds of the heart were uniformly fatal.