Acylamido analogs of endocannabinoids selectively inhibit cancer cell proliferation.
A series of amide derivatives of long-chain fatty acids has been studied for their effects on the proliferation of cancer cells in vitro. Fatty acids ranged from palmitic to higher polyunsaturated types containing 22 carbon atoms. The amino portions of the molecules included ammonia, ethanolamine, various amino acids and dopamine. Several cell lines were used as models and these included HTB-125 (normal human breast cells), HTB-126 (human breast cancer cells), HeLa (cervical cancer cells), WI-38 (human embryonic lung cells), RAW264.7 (mouse macrophage tumor cells) and RBL-2H3 (rat basophilic leukemia cells). The HTB lines were obtained from the same donor, so, could be considered a matched pair, that is, normal control versus cancer cells and thus, provide a model for testing specificity of action for the acylamido analogs. While many compounds were efficacious in inhibiting the proliferation of various cell lines, only two analogs showed a high degree of specificity in the matched HTB cell lines. N-palmitoyl dopamine and N-palmitoyl tyrosine each demonstrated complete specificity of action at a concentration of 10muM and were highly efficacious in both cases. No clear structure-activity pattern could be derived from these studies since the intensity of the inhibitory action seemed to depend on three factors, namely, the fatty acid, the amine group and the cell type.


Transperitoneal laparoscopic excision of primary seminal vesicle benign tumors: surgical techniques and follow-up outcomes.
To assess the feasibility, safety, and efficacy of transperitoneal laparoscopic excision of primary seminal vesicle benign tumors (SVBTs) and summarize our experience with surgical techniques and follow-up outcomes of this rare condition. This study included 6 patients who underwent transperitoneal laparoscopic excision of primary SVBTs between June 2005 and April 2011. A 5-port transperitoneal approach was used. The ipsilateral vas deferens was identified in the upper bulge of the retrovesical peritoneal reflection through a transverse approach and was dissected inwardly and used as a guide to the seminal vesicle tumor. Endoscopic Hem-o-lok clips (Teleflex Medical) were applied to control the vascular supply to the tumor base. With the contralateral vas deferens and seminal vesicle preserved, the tumor was removed together with the vas deferens and the adjoining ipsilateral seminal vesicle. The surgical procedures were successful in all 6 patients, without conversion to open surgery. The mean duration of surgery was 70 ± 16 minutes (range, 50-100 minutes), with unremarkable blood loss of less than 50 mL. The mean postoperative hospital length of stay was 5.2 ± 1.6 days (range, 4-8 days). No intra- or postoperative complications occurred. During a mean follow-up period of 42 ± 24 months (range, 12-82 months), all patients remained asymptomatic, with preserved function as reported by the patient, and there was no evidence of recurrence. Our study demonstrated that transperitoneal laparoscopic excision of primary SVBTs is a viable option for minimally invasive treatment of SVBT.


Acclimation of a marine microbial consortium for efficient Mn(II) oxidation and manganese containing particle production.
Sediment contamination with metals is a widespread concern in the marine environment. Manganese oxidizing bacteria (MOB) are extensively distributed in various environments, but a marine microbial community containing MOB is rarely reported. In this study, a consortium of marine metal-contaminated sediments was acclimated using Mn(II). The shift in community structure was determined through high-throughput sequencing. In addition, the consortium resisted several harsh conditions, such as toxic metals (1mM Cu(II) and Fe(III)), and exhibited high Mn(II) oxidation capacities even the Mn(II) concentration was up to 5mM. Meanwhile, biogenic Mn containing particles were characterized by scanning electron microscope (SEM), X-ray powder diffraction (XRD), and N2 adsorption/desorption. Dye removal performance of the Mn containing particles was assayed using methylene blue, and 20.8 mg g(-1) adsorption capacity was obtained. Overall, this study revealed several new genera associated with Mn(II) oxidation and rare biogenic Na3MnPO4CO3. Results suggested the complexity of natural microbe-mediated Mn transformation.


A controversy on the three fundamental growth determinants in selected CEE countries.
The present study is a controversy on the three fundamental growth determinants. It contributes to the literature by divulging the effects of foreign direct investment and financial development on energy consumption in Central and Eastern European countries from 1990 to 2016. In doing so, second-generation multi-econometric methodological methods are adopted to conclude this study. The Pooled Means Group (PMG) estimation approach confirms that foreign direct investment is adversely associated with energy consumption. A one-point rise in FDI in the CEE region reduces energy consumption by 0.0172 points in the long run. Congruently, the globalization index also mitigates energy consumption. Conversely, financial development and economic growth stimulate energy consumption in the CEE region. Energy consumption boosts by 0.0626 points when a one-point escalation in financial development occurs. The U-shaped link between energy consumption and economic growth is revealed. The country-wise results show that energy consumption rises due to financial development and FDI in nine countries and one country. However, reduction in energy consumption occurs due to an upsurge of financial development in seven and FDI in six countries. Moreover, the causality results suggest that energy consumption causes financial development, and FDI. The policy suggestions are included to mitigate unsustainable energy consumption and renovate the energy policy in this region.


Malignant phyllodes tumor.
The study aims to evaluate the survival and prognosis of patients with malignant phyllodes tumor. Between 1982 and 1998, 37 women with malignant phyllodes tumor were treated at the Regional Cancer Center, Trivandrum. Twelve patients were recurrent. Survival was estimated using the Kaplan-Meier method. Patient, disease, and treatment factors were compared using log-rank test. The Cox-proportional hazard model was employed to identify the prognostic factors. Thirty-six patients had surgery. Twenty-five patients received postoperative radiotherapy, and 2 received chemotherapy in addition. The median follow-up was 43 months (range 1-170 months). Eight patients failed locally, and 7 of these were successfully salvaged by surgery. The 5-year overall survival was 74.2% (95% CI, 0.44 to 0.89), whereas 5-year disease-free survival was 59.6% (95% CI, 0.39 to 0.7). The margin of surgical excision was found to be the only independent prognostic factor (p=0.003). However, patients with tumor size more than 5 cm (hazard ratio 2.9) were found to have increased hazard, whereas those receiving adjuvant radiotherapy (hazard ratio 0.6), married women (hazard ratio 0.4), and those women over the age of 35 years (hazard ratio 0.7) showed a decreased hazards. Cystosarcoma phyllodes is a rare malignancy of the female breast. Surgery with adequate margins is the primary treatment. Adjuvant radiotherapy appears to improve the disease-free survival.


Associations between oil development and sexually transmitted infections: Public health nurse perspectives.
Oil development (OD) has been associated with increased sexually transmitted infection (STI) rates, with limited focus on the North Dakota (ND) oil boom. Public health (PH) nurse experiences can provide context related to health challenges during OD-related population booms. To compare reported STI rates in ND oil-producing (OP) and non-oil-producing (NOP) counties before, during, and after the oil boom and describe PH nurse experiences during this time. We conducted secondary data analysis of oil production data and reported rates for chlamydia and gonorrhea, and conducted interviews with ND PH nurses. PH nurses within ND counties geographically located in or near OD in the state. ND county-level OD data trends were compared to similarly timed reported rates of chlamydia and gonorrhea in OP and NOP counties. PH nurse interviews were conducted addressing their STI-related experiences working in PH during the oil boom. Significant findings include a correlation between OD and gonorrhea rates. PH nurses described a limited PH infrastructure to meet the health needs of a transient, increasing population. Expanding the role of PH nurses in ND to implement STI screening and treatment would improve access to STI testing allowing for comprehensive reporting of STIs.


[Hyperventilation and inhibitory synapses].
Injection of subconvulsive doses of strychnine blocking the inhibitory synapses significantly increases the reflex activity of the respiratory muscle evoked by stimulation of the sciatic nerve as well as by inhalation of hypercapnic gas mixture. Thus the inhibitory synapses prevent the extreme hypocapnia evoked by hyperventilation.


Family cohesion is differently associated with felt stigma depending on enacted stigma in adults with epilepsy.
There have been little researches examining the role of family functioning on psychological outcomes in the field of adult epilepsy. We determined whether family functioning is correlated with felt stigma in adults with epilepsy. In this cross-sectional study, adults with epilepsy and their caregivers were recruited. Data were collected using the Family Adaptability and Cohesion Evaluation Scale (FACES) III, the Family adaptation, partnership, growth, affection, and resolve (APGAR) questionnaire, the Stigma Scale for Epilepsy (SS-E), the modified questionnaire for episodes of discrimination, and the Beck Depression Inventory. Family functioning was measured by the caregivers. A total of 273 adult patients and their primary caregivers were included. Multivariate logistic analyses showed that family cohesion and excellent family functioning were negatively correlated with felt stigma after controlling for confounding variables. Enacted stigma, depressive symptoms, and university education were also significant. Interaction between enacted stigma and family cohesion on felt stigma was significant (p = 0.049). Family cohesion was negatively correlated with felt stigma only in the patients with enacted stigma (p = 0.011). Family functioning especially family cohesion may have protective effects against development of felt stigma in adults with epilepsy. Such protecting effects against felt stigma may be different according to enacted stigma. This understanding is helpful for developing effective psychosocial interventions to reduce felt stigma in patients with epilepsy.


Habitual loud snoring. A study of prevalence and associations in 850 middle-aged French males.
Most studies on habitual snoring have focused on its prevalence. However, from the clinical point of view, the intensity of snoring is of upmost importance, as it suggests the existence of sleep apnoeas. The aim of the study was to assess the prevalence of loud snoring using a standard questionnaire and to evaluate the anthropometric and sleep characteristic differences between loud and light snorers in a sample of middle-aged males. The subjects were middle-aged active male employees. They completed a structured sleep questionnaire and had standard anthropometric measurements. Subjects reporting habitual snoring (> or =3 nights/week) were further classified as loud or light snorers. Of the 850 male subjects volunteering, 149 (17.5%) were habitual loud snorers. Loud snorers were older and had a greater waist-to-hip ratio as compared with light snorers. In univariate analysis, loud snoring was associated with gasping/snorting during sleep, breathing stops during sleep, waking up too early, excessive daytime sleepiness and falling asleep while watching TV. Logistic regression identified four independent associates of loud snoring: gasping during sleep, excessive daytime sleepiness, falling asleep watching TV and age. Loud snoring is present in a significant proportion of middle-aged men and is associated with central obesity and age. It disturbs sleep and elicits significant daytime sleepiness. Its association with breathing pauses (univariate) and its independent association with gasping during sleep suggests that loud snoring could be considered a clinical correlate of obstructive sleep apnoeas.


Author Correction: Identification of Exo1-Msh2 interaction motifs in DNA mismatch repair and new Msh2-binding partners.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


[Ten-year experience with Barron ligature in the Ostrava surgical clinic].
The authors aim to present the problematics of hemorrhoid treatment using the Barron ligature semiinvasive method, to healthcare professionals.


Using a Multiple-Case Study Design to Explore the Worship Experiences of Black Families Affected by Dementia.
The purpose of this multiple-case study was to report on the worship experiences of Black families affected by dementia. Data were collected through participant observations of family caregivers (n = 4) and persons living with dementia (n = 4) during worship services and semi-structured interviews with the family caregivers over six months. Data were initially analyzed case-by-case, then across-cases. Four overarching themes emerged: Welcoming church culture, Community support from the church, Engagement during worship service, and Connectedness between the caregiver and their family member living with dementia. Family caregivers reported that their family member with dementia was attentive and expressed moments of clarity during and immediately after worship services. Worship services can be tailored to support families affected by dementia and can promote engagement of the person living with dementia with church activities and family members. Health practitioners are encouraged to acknowledge the influence of religious practices within Black families affected by dementia and integrate them into interdisciplinary care plans and programs.


Comparative Analysis of Microbial Diversity in Termite Gut and Termite Nest Using Ion Sequencing.
Termite gut and termite nest possess complex microbial communities. However, only limited information is available on the comparative investigation of termite gut- and nest-associated microbial communities. In the present study, we examined and compared the bacterial diversity of termite gut and their respective nest by high-throughput sequencing of V3 hypervariable region of 16S rDNA. A total of 14 barcoded libraries were generated from seven termite gut samples and their respective nest samples, and sequenced using Ion Torrent platform. The sequences of each group were pooled, which yielded 170,644 and 132,000 reads from termite gut and termite nest samples, respectively. Phylogenetic analysis revealed significant differences in the bacterial diversity and community structure between termite gut and termite nest samples. Phyla Verrucomicrobia and Acidobacteria were observed only in termite gut, whereas Synergistetes and Chlorobi were observed only in termite nest samples. These variations in microbial structure and composition could be attributed with the differences in physiological conditions prevailing in the termite gut (anoxic and alkaline) and termite nest (oxic, slightly acidic and rich in organic matter) environment. Overall, this study unmasked the complexity of bacterial population in the respective niche. Interestingly, majority of the sequence reads could be classified only up to the domain level indicating the presence of a huge number of uncultivable or unidentified novel bacterial species in both termite gut and nest samples. Whole metagenome sequencing and assessing the metabolic potential of these samples will be useful for biotechnological applications.


Surfactant functionalization induces robust, differential adhesion of tumor cells and blood cells to charged nanotube-coated biomaterials under flow.
The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Functionalized biomaterial surfaces hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, a straightforward technique to functionalize and alter the charge of naturally occurring halloysite nanotubes using surfactants is reported to induce robust, differential adhesion of tumor cells and blood cells to nanotube-coated surfaces under flow. Negatively charged sodium dodecanoate-functionalized nanotubes simultaneously enhanced tumor cell capture while negating leukocyte adhesion, both in the presence and absence of adhesion proteins, and can be utilized to isolate circulating tumor cells regardless of biomarker expression. Conversely, diminishing nanotube charge via functionalization with decyltrimethylammonium bromide both abolished tumor cell capture while promoting leukocyte adhesion.


Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.
Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis. Clonal populations, obtained from both ovarian cancer cell lines (IGROV-1 and SKOV3) and tumor xenografts upon glucose deprivation, were defined as glucose deprivation resistant (GDR) or glucose deprivation sensitive (GDS) clones based on their in vitro behaviour. GDR and GDS clones were characterized using a multi-omics approach, including genetic, transcriptomic and metabolic analysis, and tested for their tumorigenic potential and reaction to anti-angiogenic therapy. Two clonal populations, GDR and GDS, with strikingly different viability following in vitro glucose starvation, were identified in ovarian cancer cell lines. GDR clones survived and overcame glucose starvation-induced stress by enhancing mitochondrial oxidative phosphorylation (OXPHOS) and both pyruvate and lipids uptake, whereas GDS clones were less able to adapt and died. Treatment of ovarian cancer xenografts with the anti-VEGF drug bevacizumab positively selected for GDR clones that disclosed increased tumorigenic properties in NOD/SCID mice. Remarkably, GDR clones were more sensitive than GDS clones to the mitochondrial respiratory chain complex I inhibitor metformin, thus suggesting a potential therapeutic strategy to target the OXPHOS-metabolic dependency of this subpopulation. A glucose-deprivation resistant population of ovarian cancer cells showing druggable OXPHOS-dependent metabolic traits is enriched in experimental tumors treated by anti-VEGF therapy.


Removal of 2-arachidonylglycerol by direct hemoperfusion therapy with polymyxin B immobilized fibers benefits patients with septic shock.
Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.


Perception of stress contrasts in semantic and nonsemantic contexts by children.
Using 140 subjects (20 children each from kindergarten through the sixth grade), this study followed the developmental trends of children on two tasks involving the perception of stress contrasts. Task I consisted of discriminating whether two syllables in bisyllabic nonsense words have the same or different stress patterns. Task II consisted of sentence pairs, for half of which the first sentence in each pair provided appropriate lexical as well as stress patterns for the second sentence. The first sentence in the remaining sentence pairs provided the appropriate lexical context but an inappropriate stress context for the second sentence. Subjects were to evaluate whether members of each sentence pair sound "good together' or "not good together.' Results yielded remarkable lawfulness in the developmental trends for both tasks, and were discussed in terms of children's perception of stress contrasts in semantic vs. nonsemantic conditions.


Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study.
To determine the outcome of withholding anticoagulation from patients with suspected acute pulmonary embolism in whom computed tomographic (CT) findings are interpreted as negative for pulmonary embolism. This retrospective cohort study included 1512 consecutive patients referred from August 7, 1997, to November 30, 1998, for CT because of clinically suspected acute pulmonary embolism. All patients were examined by electron beam CT, and scanning was performed in a cephalocaudad direction from the top of the aortic arch to the base of the heart with 3-mm collimation, 2-mm table incrementation, and an exposure time of 0.2 second (130 peak kV, 620 mA, and standard reconstruction algorithm). Contrast material was infused at a rate of 3 to 4 mL/s through an antecubital vein with an automated injector. Findings on CT were interpreted as either positive or negative. The main outcome measures were deep venous thrombosis, pulmonary embolism, and vital status within 3 months after the CT scan and the cause of death based on medical record review, mailed patient questionnaires, and telephone interviews. In 1010 patients (67%) CT scans were interpreted as negative for acute pulmonary embolism. Seventeen patients were excluded because they received anticoagulation. Of the remaining 993 patients, deep venous thrombosis or pulmonary embolism developed in 8; 118 patients died, 3 of pulmonary embolism. Nineteen patients were known to be alive, but additional clinical information could not be obtained. The 3-month cumulative incidence of overall deep venous thrombosis or pulmonary embolism was 0.5% (95% confidence interval, 0.1%-1.0%) and of fatal pulmonary embolism, 0.3% (95% confidence interval, 0.0%-0.7%). The incidence of (1) overall deep venous thrombosis or pulmonary embolism or (2) fatal pulmonary embolism among patients with suspected acute pulmonary embolism, negative CT results, and no other evidence of venous thromboembolism is low. Withholding anticoagulation in these patients appears to be safe.


Investigating the use of Aspergillus niger fermentation broth as a washing treatment for arsenic and antimony co-contaminated soil.
High concentrations of arsenic and antimony contamination in soil are a potential risk to the ecological environment and human health. Soil washing can effectively and permanently reduce the soil contamination. This study used Aspergillus niger fermentation broth as a washing agent to remove As and Sb from contaminated soil. Characterization of organic acids in the fermentation broth by high-performance liquid chromatographic (HPLC) and chemically simulated leaching experiments revealed that oxalic acid played a significant role in removing As and Sb from the soil. The effect of washing conditions on the metal removal rate of Aspergillus niger fermentation broth was investigated by batch experiments, and the optimal conditions were determined: no dilution, pH 1, L/S ratio 15:1, and leaching at 25 °C for 3 h. The soils were washed three times under optimal conditions, with 73.78%, 80.84%, and 85.83% removal of arsenic and 65.11%, 76.39%, and 82.06% removal of antimony, respectively. The results of metal speciation distribution in the soil showed that the fermentation broth could effectively remove As and Sb on amorphous Fe/Al hydrous oxides in soil. The analysis of X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) of soils before and after washing showed that the washing of Aspergillus niger fermentation broth had a minor effect on the structural changes of soils. After washing, soil organic matter and soil enzyme activity were increased. Thus, Aspergillus niger fermentation broth shows excellent potential as a washing agent for removing As and Sb from soils.


Social assets and mental distress among the homeless: exploring the roles of social support and other forms of social capital on depression.
This paper explores the role of social capital in mediating the effects of stressors on depression among a disadvantaged population. Utilizing a survey of 155 homeless people in a mid-sized southern U.S. city, the authors address the relevance of social capital for quality of life. The paper provides a critical test of whether social support and other forms of social capital matter when monetary and human capital is extremely limited. Under these resource-restricted circumstances does social capital add to our understanding of the distress process or does it merely restate the well established relationship between social support and quality of life outcomes? Various forms of social capital are measured: religious social capital, group participation, social trust, and bridging social capital along with a commonly used measure of social support -- perceived strong tie support. Findings suggest that social capital matters for even the most resource poor populations. In addition, social capital variables add significantly to the variance explained in depressive symptomatology over and above that traditionally explained by perceived social support.


Emergency contraception.
Emergency contraception is increasing in use and has become a universal standard of care in the United States. This article reviews available forms of emergency contraception, their indications, contraindications, adverse effects and efficacy at preventing pregnancy. This article describes the mechanism of action of different forms of emergency contraception and provides recommendations on when to start or restart an ongoing method of contraceptive after emergency contraception use. Literature on the impact of the advance provision of emergency contraception on contracepting behaviors is reviewed, and behavior change counseling related to emergency contraception is described.


Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study.
The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e' (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.


Lusutrombopag has slightly stronger effects on patients with mild thrombocytopenia compared with those with severe thrombocytopenia: A multicenter propensity score matching study.
Lusutrombopag effectively increases platelet count in patients with severe thrombocytopenia. However, no multicenter studies analyzing the effects of Lusutrombopag on patients with mild thrombocytopenia (platelet count > 50 000/µL) have been performed. In this study, we aimed to clarify the efficacy of Lusutrombopag on these patients by unifying background factors by propensity score matching. A total of 139 patients with thrombocytopenia were enrolled, and matched for age, sex, etiology, disease, treatment, liver function, renal function, peripheral blood count, and spleen index. The primary endpoint was to compare the increase in platelet count from baseline between the high-platelet group (>50 000/µL) and the low-platelet group (<50 000/µL) after Lusutrombopag treatment, using propensity score matching. The secondary endpoint was to clarify platelet transfusion avoidance rate and adverse events, moreover, to identify independent predictors associated with the increase in platelet count. The mean increase in platelet count was 67 000/μL vs 48 000/μL in all patients (high- vs low-platelet group, P = .024), and 64 000/μL vs 48 000/μL (P = .12) after propensity score matching. The increase in platelet count and the platelet transfusion avoidance rate tended to be higher in the high-platelet group. There was no significant difference between adverse events. Predictors associated with an increase in platelet count were sex, estimated glomerular filtration rate, and spleen index by multivariate analysis. Lusutrombopag has a little stronger effect in patients with mild thrombocytopenia than those with severe thrombocytopenia and showed a more substantial effect in patients with impaired renal function and small spleen.


MRSaiFE: An AI-based Approach Towards the Real-Time Prediction of Specific Absorption Rate.
The purpose of this study is to investigate feasibility of estimating the specific absorption rate (SAR) in MRI in real time. To this goal, SAR maps are predicted from 3T- and 7T-simulated magnetic resonance (MR) images in 10 realistic human body models via a convolutional neural network. Two-dimensional (2-D) U-Net architectures with varying contraction layers and different convolutional filters were designed to estimate the SAR distribution in realistic body models. Sim4Life (ZMT, Switzerland) was used to create simulated anatomical images and SAR maps at 3T and 7T imaging frequencies for Duke, Ella, Charlie, and Pregnant Women (at 3, 7, and 9 month gestational stages) body models. Mean squared error (MSE) was used as the cost function and the structural similarity index (SSIM) was reported. A 2-D U-Net with 4 contracting (and 4 expanding) layers and 64 convolutional filters at the initial stage showed the best compromise to estimate SAR distributions. Adam optimizer outperformed stochastic gradient descent (SGD) for all cases with an average SSIM of 90.5∓3.6 % and an average MSE of 0.7∓0.6% for head images at 7T, and an SSIM of >85.1∓6.2 % and an MSE of 0.4∓0.4% for 3T body imaging. Algorithms estimated the SAR maps for 224×224 slices under 30 ms. The proposed methodology shows promise to predict real-time SAR in clinical imaging settings without using extra mapping techniques or patient-specific calibrations.


Idiotype vaccines produced with a non-cytopathic alphavirus self-amplifying RNA vector induce antitumor responses in a murine model of B-cell lymphoma.
A promising therapy for patients with B-cell lymphoma is based on vaccination with idiotype monoclonal antibodies (mAbs). Since idiotypes are different in each tumor, a personalized vaccine has to be produced for each patient. Expression of immunoglobulins with appropriate post-translational modifications for human use often requires the use of stable mammalian cells that can be scaled-up to reach the desired level of production. We have used a noncytopathic self-amplifying RNA vector derived from Semliki Forest virus (ncSFV) to generate BHK cell lines expressing murine follicular lymphoma-derived idiotype A20 mAb. ncSFV/BHK cell lines expressed approximately 2 mg/L/24 h of A20 mAb with proper quaternary structure and a glycosylation pattern similar to that of A20 mAb produced by hybridoma cells. A20 mAb purified from the supernatant of a ncSFV cell line, or from the hybridoma, was conjugated to keyhole limpet hemocyanin and used to immunize Balb/c mice by administration of four weekly doses of 25 µg of mAb. Both idiotype mAbs were able to induce a similar antitumor protection and longer survival compared to non-immunized mice. These results indicate that the ncSFV RNA vector could represent a quick and efficient system to produce patient-specific idiotypes with potential application as lymphoma vaccines.


Safety of an Inactivated SARS-CoV-2 Vaccine Among Healthcare Workers in Turkey: An Online Survey
As vaccination against coronavirus disase-19 (COVID-19) evolves, hesitancy has become a problematic issue that has gradually spread worldwide. The main reason for vaccine hesitancy is uncertainties about vaccine side effects. To evaluate the safety of an inactivated COVID-19 vaccine, CoronaVac, and determine the risk factors of emergence of side effects. Cross-sectional study. An online questionnaire was administered via the internet to healthcare workers who received one or two doses of CoronaVac. The online survey consisted of three sections detailing sociodemographic data, COVID-19 history, and post-vaccine side effects. Side effects that occurred in the period starting from immediately after the first vaccination to the end of the 14th day after the second vaccination were recorded. A total of 1628 healthcare workers responded to the online survey. Of these, 24.3% had a side effect either after the first or second dose of CoronaVac. Redness and/or pain at the inoculation site, headache, muscle and joint pains, palpitations, and dizziness were the most common side effects. Female sex, age <50 years, and thyroid disorder in the pre-vaccine period were found to be risk factors for the emergence of side effects. Blood pressure control could not be achieved in 2.2% of participants despite medication use, and permanent medication was needed in 2.5% of participants for blood pressure control. Almost a quarter of healthcare workers have at least one side effect after the first or second dose of CoronaVac. Female gender, age <50 years, and thyroid disorder appear to be risk factors for the occurrence of side effects.


Management of Common Complications of Lactation: The Breast Surgeon's Role in Examining the Science and Debunking Old Myths.
Breast surgeons are well poised to promote evidence-based recommendations for lactation-related breast disorders and clarify existing misconceptions in traditional care. Surgeons can resolve lactational fluid collections and avoid milk fistula development during drainage and/or other procedures on the breast. Using principles of surgical wound management, they can provide effective care of nipple trauma. They can distinguish between inflammatory and infectious mastitis and promote delicate tissue handling to prevent breast injury and phlegmon. Finally, breast surgeons can debunk the myth of fungal infections occurring on the highly vascularized nipple and recognize common presentations of conditions such as dermatitis.


Interaction of metal oxide nanoparticles with microplastics: Impact of weathering under riverine conditions.
The ubiquitous distribution of microplastics (MPs) leads to inevitable interactions with the toxic pollutants present in the environment including metal-oxide nanoparticles. This study investigates the interaction of CeO2 nanoparticles (CeNPs) with MPs generated from a disposable plastic container. Further, rough MPs (R-MPs), generated through mechanical abrasion of MPs with sand, were used to probe the impact of roughness. To understand the sorption kinetics and underlying interaction processes, batch experiments were carried out. The results distinctly indicate that CeNPs sorption occurred on MPs surfaces and was consistent with the pseudo-second order kinetics model. For pristine MPs, the sorption capacity was as high as 12.9 mg/g while for R-MPs kinetic equilibrium was achieved faster and an enhanced sorption capacity (13.4 mg/g) was identified. A rise in sorption with an increase in salinity was noted while pH and humic acid exhibited a negative correlation. The observed interactions were attributed to the aggregation profile and surface charge of CeNPs and MPs. Surprisingly, CeNPs also got loaded onto MPs in non-agitated and undisturbed conditions. The sorption process was influenced by the type of aqueous matrix and the sorption capacity at equilibrium followed the trend: distilled water> synthetic freshwater> river water. FTIR spectra, zeta potential, SEM imaging, and elemental mapping revealed electrostatic interaction as the dominant mechanism. This work contributes towards the knowledge gap on the environmental risk of MPs.


Diode array detection of low level co-eluting species in high-performance liquid chromatography.
A simple and sensitive method for detecting low levels (0.5 and 1.0%, w/w) of co-eluting species in HPLC has been developed. This method is based on the subtraction of normalized peak up-slope and down-slope spectra from that of the apex. Visual inspection of the resultant "difference spectra" allows for a qualitative judgement regarding the integrity of the peak under consideration.


Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation.
In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into the most cranial parts of the augmented region. There was no statistically significant difference in new bone formation after 3 and 6 months (24.89 ± 10.22% vs 31.29 ± 2.29%), respectively. Within the limits of the present study and according to previously published data, implant insertion in regions augmented with this bone substitute material could be considered already after 3 months. Further clinical studies with bone substitute materials are necessary to validate these findings.


Preparation and Characterization of Protein-loaded PFC Nanoemulsions for the Treatment of Heart Diseases by Pulmonary Administration.
In the treatment of heart disease, strategies for the targeted delivery of protein therapeutics to the heart by inhalation are still immature. Perfluorocarbons (PFCs) are inert chemicals with good biocompatibility, and unique physico-chemical properties that have recently led to their applications in numerous fields. In this study, we combined the advantages of protein-phospholipid complexes and PFC emulsions and then synthesized protein-loaded PFC nanoemulsions (PNEs) to test whether, after inhalation, these nanoemulsions could deliver therapeutic proteins to the heart. After preparing protein-phospholipid complexes by lyophilization, we obtained PNEs by extrusion. The particle size and surface charge of PNEs were about 140 nm and -50 mV, respectively. In vitro results showed that the PNEs had a fine particle fraction of 35% and exhibited sustained protein release. Translocation studies were done using three types of pulmonary epithelial cells, and ~7% translocation was observed in the Calu-3 cell line. Further, they were easily absorbed by cells and had therapeutic effects in culture. In vivo results showed that the PNEs successfully delivered proteins to the myocardial tissue of rats and reduced ischemic myocardial injury caused by acute myocardial infarction (AMI). This study suggests that inhalation of PNEs is a new potential strategy to deliver proteins to cardiac tissues for treating heart diseases.


Ethylene-mediated regulation of coleoptile elongation in rice seedlings.
Rice is an important food crop in the world and the study of its growth and plasticity has a profound influence on sustainable development. Ethylene modulates multiple agronomic traits of rice as well as abiotic and biotic stresses during its lifecycle. It has diverse roles, depending on the organs, developmental stages and environmental conditions. Compared to Arabidopsis (Arabidopsis thaliana), rice ethylene signalling pathway has its own unique features due to its special semiaquatic living environment and distinct plant structure. Ethylene signalling and responses are part of an intricate network in crosstalk with internal and external factors. This review will summarize the current progress in the mechanisms of ethylene-regulated coleoptile growth in rice, with a special focus on ethylene signaling and interaction with other hormones. Insights into these molecular mechanisms may shed light on ethylene biology and should be beneficial for the genetic improvement of rice and other crops.


Electrophysiological CNS-processes related to associative learning in humans.
The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli.


Oenococcus oeni allows the increase of antihypertensive and antioxidant activities in apple cider.
This study aimed to investigate the impact of the malolactic fermentation (MLF) carried out by Oenococcus oeni on antihypertensive and antioxidant activities in cider. The MLF was induced using three strains of O. oeni. The modification in phenolic compounds (PCs) and nitrogen organic compounds, antioxidant, and antihypertensive activities were determined after MLF. Among the 17 PCs analyzed caffeic acid was the most abundant compound and phloretin, (-)-epicatechin, and myricetin were detected only in malolactic ciders, however, (-)-epigallocatechin was not detected after MLF. The evaluation of nitrogen organic compounds revealed a drop in total protein concentration (from 17.58 to 14.00 mg N/L) concomitantly with a significant release of peptide nitrogen (from 0.31 to a maximum value of 0.80 mg N/L) after MLF. In addition, an extracellular proteolytic activity was evidenced in all MLF supernatants. The FRAP activity increased reaching a maximum of 120.9 μmol FeSO4/mL and the ABTS radical-scavenging activity increased until 6.8 mmol ascorbic acid/L. Moreover, the angiotensin I-converting enzyme inhibitory activity reached a maximum value of 39.8%. The MLF conducted by O. oeni in ciders enables the increase of interesting biological activities and this finding could constitute a valuable tool to add value to final product.


Sequential changes in serum thyroglobulin (Tg) and its autoantibodies (TgAb) following subtotal thyroidectomy of patients with preoperatively detectable TgAb.
The changes in serum concentrations of thyroglobulin antibodies (TgAb) were investigated in eight patients with various thyroid disorders before, during and after thyroid surgery. TgAb was measured by a radioassay using 125I-thyroglobulin. In six patients the TgAb decreased rapidly during operation. Of these patients four had low concentrations pre-operatively, and the decrease in TgAb resulted in undetectable concentrations for more than 2 days, Serum thyroglobulin (Tg), measured in the specimens with undetectable TgAb, i.e immediately following surgery, showed concentration vs time curves resembling curves from patients with no antibody present. Furthermore, two of these patients had such a high concentration of TgAb pre-operatively that the initial Tg release was not sufficient to remove the TgAb, resulting in detectable TgAb throughout the investigation period. Serum samples drawn during and after operation were chromatographed according to molecular size, showing measureable Tg corresponding to 19S Tg. TgAb was only measureable in fractions corresponding to 7S IgG. The expected presence of complexed Tg and TgAb could not be demonstrated, but the analytical methods might have been unable to reveal this. The remaining two patients with thyroiditis showed no decrease in TgAb. This was compatible with a low content of Tg in the throid measured in one of them.


Genotypic and phenotypic characteristics of juvenile/adult onset vanishing white matter: a series of 14 Chinese patients.
Vanishing white matter (VWM) is one of the most prevalent leukoencephalopathies and is caused by recessive mutations in gene eIF2B1-5. The onset may vary from an antenatal disorder that is rapidly fatal to an adult-onset disorder with chronic progressive deterioration. Based on a comprehensive study of 14 juvenile/adult patients diagnosed in our department as well as a review of 71 previously reported cases of genetically confirmed juvenile/adult-onset VWM since 2001, we attempted to delineate the clinical symptoms, disease evolution, episodic aggravation, associated symptoms, MRI findings and genotypic characteristics of adult VWM. The onset age of neuropsychiatric symptoms was 23.4 ± 10.6 years, and the mean follow-up time was 8.1 ± 4.8 years. Major clinical symptoms included headache, epilepsy, cognitive decline, cerebellar ataxia, and urinary disturbances. Episodic aggravation was found in 42.9% of the patients in our series. Molecular studies revealed fourteen novel missense mutations. Diffuse abnormal signals characterized by T1-weighted hypointensity and T2-weighted hyperintensity were observed in the supratentorial white matter. The symmetrical leukoencephalopathy must be considered in patients of any age with premature ovarian failure or optic neuropathy. The VWM disease spectrum consists of characteristic imaging findings in combination with extremely wide variability in VWM patients.


Feasibility study of preemptive withdrawal of immunosuppression based on chimerism testing in children undergoing myeloablative allogeneic transplantation for hematologic malignancies.
An increasing percentage of autologous cells (increasing chimerism) in the whole blood (WB) chimerism test following allogeneic transplant is related to a very high risk of relapse. Preemptive immunotherapy may decrease the risk of relapse in some patients. Our prospective multi-institutional study evaluated the feasibility of longitudinal chimerism testing in a central laboratory, compared WB, CD3+ and leukemia-specific lineage chimerism in patients with a variety of hematologic malignancies, and evaluated the feasibility of fast withdrawal of immunosuppression based on WB chimerism results. Centralized chimerism testing was feasible and showed low interassay variability. Increasing mixed chimerism (MC) in WB was not useful as a predictor of relapse in our study. The presence of full donor chimerism in WB, CD3+ and leukemia-specific lineages on all measurements was related to a significantly lower risk of relapse than the presence of MC in either subset (11 vs 71%, respectively; P=0.03). Increasing host chimerism in leukemia-specific lineage heralds relapse, but it was not detected early enough to allow immunotherapy. Further studies correlating lineage-specific chimerism and minimal residual disease are required. The goal of preemptive immunotherapy should be to achieve full donor chimerism in WB in CD3+ and leukemia-specific lineages.


Tracing geochemical pollutants in stream water and soil from mining activity in an alpine catchment.
This research developed a method of tracing major water chemical parameters (WCP) and soil heavy metals (HM) to identify the processes of mining pollution in topographically complex landscapes. Ninety-nine spatially distributed water samples were collected to characterise the hydrochemical characteristics of an alpine river in north-west China. Sixty river WCP and fifty-six soil HM samples from areas near mining sites were then used to analyse the mining pollution process. Geographical and mining activity characteristics were derived from topographic and mine site information. The occurrence of sulphates (SO42-) and nitrates (NO3-) in river water were highly correlated (up to 0.70), providing strong evidence of pollution from nearby mining activities. Levels of arsenic and cadmium were high in first and fifth order streams, where mining activities were most concentrated. The modelling results showed that geographical patterns and mining activity account for predicting HM distribution, and WCP can be reasonable predictors to trace soil mining pollution. This research can help improve the accuracy of predicting the mining pollution process.


Does a single bolus thrombolytic reduce door to needle time in a district general hospital?
To answer the question "In patients presenting with ST elevation acute myocardial infarction (STEMI) and no contraindication to thrombolysis, does the introduction of Tenecteplase reduce door to needle times?" Firstly, an observational study was performed to compare the time taken to prepare standard thrombolytic therapy with Tenecteplase. Secondly, door to needle times were compared before and after the introduction of Tenecteplase. The study was powered to be 80% sure of finding a change of 10% in the number of patients meeting the national service framework standard of a 30 minute door to needle time. Tenecteplase takes 10.5 minutes less time to prepare than standard treatment (p value <0.001). After the introduction of Tenecteplase the percentage of patients receiving thrombolysis in 30 minutes increased from 58% to 76% (p value <0.01) Tenecteplase is quicker to prepare than standard therapy, resulting in a significant improvement in performance against the national service framework target.


Cloning and sequence analysis of coat protein gene for characterization of sugarcane mosaic virus isolated from sugarcane and maize in Thailand.
Three isolates of sugarcane mosaic virus (SCMV) from sugarcane and maize in Thailand, were selected and used as viral sources for coat protein (CP) genes cloning by immunocapture reverse transcription polymerase chain reaction (IC-RT-PCR). The CP gene sequences and their deduced amino acids were determined. The sequences of three cloned CP genes, UT6TH-sgc and UD7TH-sgc from sugarcane, and SBC2TH-mz from maize were compared with other previously reported sequences of SCMV-CP gene and their phylogeny were studied. The analysis revealed that Thai SCMV CP gene contained 942 nucleotides encoded for coat protein MW of 33.65 kDa. The nucleotide sequence identity among cloned CPs from three isolates were 98-99% to each other. The N-terminus of the Thai SCMV CP contained a distinctive sequence, especially at nucleotide positions 28-46 of the N-terminal variable 70 amino acid residues which discriminated Thai SCMV from all previously reported SCMV isolates. Thai SCMV were placed in a separate branch of SCMV-MDB cluster which is closely related to most of SCMV isolates from maize, and distinct from the other cluster containing sugarcane-SCMV strains.


Effects of orally administered glandular kallikrein on urinary kallikrein and prostaglandin excretion, plasma immunoreactive prostanoids and platelet aggregation in essential hypertension.
The effects of orally administered glandular kallikrein on urinary kallikrein, aldosterone and prostaglandin E (PGE) excretion, plasma renin activity (PRA), immunoreactive 6-keto PGF1 alpha and thromboxane B2 concentrations and platelet aggregation were studied in 12 patients with essential hypertension (EH). After a 2-week control period, each patient was given orally 450 KU/day of hog glandular kallikrein for 8 weeks. Urinary kallikrein, aldosterone and PGE excretion, and plasma 6-keto PGF1 alpha and thromboxane B2 concentrations were measured by radioimmunoassay. Platelet aggregation was measured by the addition of ADP, collagen or ristocetin with an aggregometer. Urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration were significantly decreased in patients with EH. There were no significant differences in PRA, urinary aldosterone excretion and plasma thromboxane B2 concentrations between control subjects and patients with EH. There was a significant decrease in blood pressure in patients with EH coinciding with significant increases of urinary kallikrein and PGE excretion and plasma immunoreactive 6-keto PGF1 alpha concentration after administration of glandular kallikrein. There was also a significant inhibition of platelet aggregation induced by collagen in these patients. Thus, a suppression of the kallikrein-kinin-prostaglandin system in patients with EH was found, and a decrease in blood pressure with an increment of urinary kallikrein, PGE excretion, plasma immunoreactive 6-keto PGF1 alpha and inhibition of platelet aggregation in vivo by the administration of glandular kallikrein.


Influence of succinylation of bovine serum albumin on its conformation and bilirubin binding.
In order to investigate the role of lysine residues in the interaction of bilirubin with bovine serum albumin, five succinylated preparations of albumin, namely: 23%, 39%, 49%, 55% and 87%, were prepared, and their conformational and bilirubin-binding properties were studied by the techniques of gel filtration, ultraviolet and visible spectroscopy, and fluorescence quenching. Gel filtration experiments performed at pH 7.0 and ionic strengths 0.15 and 1.0 suggested that the albumin molecule undergoes gradual disorganization with increase in succinylation. The Stokes radius and frictional ratio at ionic strength 0.15 increased from 3.7 nm and 1.36, respectively, for the native protein to 6.3 nm and 2.26 for maximally (87%) succinylated albumin. Interestingly, increase in ionic strength to 1.0 caused significant refolding in succinylated preparations as evidenced by a decrease in Stokes radius and frictional ratio (5.3 nm and 1.90 for 87% succinylated albumin). Progressive succinylation produced a steady decline in the intensity of bilirubin-induced fluorescence quenching, and in the visible spectral changes of the bilirubin-albumin complex at 480 nm. Both of these changes had a good correlation with increase in Stokes radius. Increase in ionic strength to 1.0 produced a significant reversal in these properties. From these results we conclude that probably none of the surface lysine residues is involved in bilirubin-albumin interaction, and that if lysine residues are involved in this interaction they must be buried in the protein interior.


Vitreomacular interface in patients with familial exudative vitreoretinopathy.
Familial exudative vitreoretinopathy (FEVR) is a rare hereditary vitreoretinal disease that occurs in young patients and results in an avascular peripheral retina, retinal neovascularization, and tractinal retinal detachment. Patients occasionally have concurrent macular diseases. However, the vitreomacular relationship in FEVR remains unclear. We report two cases, a 22-year-old woman (case 1) and a 14-year-old boy (case 2) with FEVR who have the characteristic findings of the disease in the vitreomacular interface and the macular morphology, observed using spectral-domain optical coherence tomography (SD-OCT). In case 1, the best-corrected visual acuity (BCVA) was 20/20 bilaterally. SD-OCT showed a perifoveal posterior vitreous detachment (PVD) with vitreofoveal adhesion in the left eye. In case 2, SD-OCT showed a perifoveal PVD in the right eye (BCVA, 20/30) with numerous small deposits that appeared as rod-shaped attachments perpendicular to the parafoveal face without intraretinal and subretinal materials beneath the posterior hyaloid face that corresponded to white material on the fundus examination. Fluorescein angiography showed a circumferential peripheral avascular area and peripheral neovascularization in both cases. These SD-OCT findings suggested that a perifoveal PVD and small deposits, which appeared as rod-shaped attachments perpendicular to the parafoveal face in patients with FEVR, may carry the risk of macular disease and decreased visual acuity.


Pulmonary aspiration during unsuccessful cardiopulmonary resuscitation.
The incidence of pulmonary aspiration in a group of patients who did not respond to cardiopulmonary resuscitation (CPR) was assessed at autopsy and found to be 29%. This figure is undoubtedly an underestimate of the total problem, and some indication of the potential for aspiration during CPR is revealed by the fact that 46% of the patients studied had full stomaches at autopsy. Clearly this fact has implications for CPR methods as suggested by Cummings and Eisenberg. The problem could be reduced by incorporating the use of cricoid pressure into the techniques of Basic CPR but this will require modification of current teaching.


[The 20-minute iodine uptake in Graves' disease. 2. Natural course during medical treatment (author's transl)].
The early (20 min) radioiodine uptake has been used to monitor the fluctuations in disease activity among 35 Graves' disease patients treated for 18 months with carbimazole and T3. A wide variety of behaviour was observed. Although as a group the uptake tended to fall progressively with time, in some it fell only to rise again and in others it fluctuated erratically. The initial fall in uptake in a substantial minority of patients was sufficient to suggest that carbimazole may exert a fundamental and beneficial influence of the immunological disturbance in Graves' disease.


Fabrication of p-type 2D single-crystalline transistor arrays with Fermi-level-tuned van der Waals semimetal electrodes.
High-performance p-type two-dimensional (2D) transistors are fundamental for 2D nanoelectronics. However, the lack of a reliable method for creating high-quality, large-scale p-type 2D semiconductors and a suitable metallization process represents important challenges that need to be addressed for future developments of the field. Here, we report the fabrication of scalable p-type 2D single-crystalline 2H-MoTe2 transistor arrays with Fermi-level-tuned 1T'-phase semimetal contact electrodes. By transforming polycrystalline 1T'-MoTe2 to 2H polymorph via abnormal grain growth, we fabricated 4-inch 2H-MoTe2 wafers with ultra-large single-crystalline domains and spatially-controlled single-crystalline arrays at a low temperature (~500 °C). Furthermore, we demonstrate on-chip transistors by lithographic patterning and layer-by-layer integration of 1T' semimetals and 2H semiconductors. Work function modulation of 1T'-MoTe2 electrodes was achieved by depositing 3D metal (Au) pads, resulting in minimal contact resistance (~0.7 kΩ·μm) and near-zero Schottky barrier height (~14 meV) of the junction interface, and leading to high on-state current (~7.8 μA/μm) and on/off current ratio (~105) in the 2H-MoTe2 transistors.


SparkGIS: Efficient Comparison and Evaluation of Algorithm Results in Tissue Image Analysis Studies.
Algorithm evaluation provides a means to characterize variability across image analysis algorithms, validate algorithms by comparison of multiple results, and facilitate algorithm sensitivity studies. The sizes of images and analysis results in pathology image analysis pose significant challenges in algorithm evaluation. We present SparkGIS, a distributed, in-memory spatial data processing framework to query, retrieve, and compare large volumes of analytical image result data for algorithm evaluation. Our approach combines the in-memory distributed processing capabilities of Apache Spark and the efficient spatial query processing of Hadoop-GIS. The experimental evaluation of SparkGIS for heatmap computations used to compare nucleus segmentation results from multiple images and analysis runs shows that SparkGIS is efficient and scalable, enabling algorithm evaluation and algorithm sensitivity studies on large datasets.


[The dorsoventral inversion: An attempt of synthesis].
The invertebrates, with known exception of echinoderms, are hyponeurian and protostomian. By contrast, echinoderms, chordates and vertebrate are epineurian and deuterostomian. Convinced of the uniqueness origin of all species, Etienne Geoffroy Saint Hilaire (1772-1844), had postulated a complete inversion of body plan to explain this difference. He had to face up to the hostility of the fixist Georges Cuvier (1763-1832). Much later, famous embryologists such as Maurice Caullery still believed that this idea was erroneous. However, the progress of comparative embryology and of developmental biology gradually contributed to validate this idea. Based upon ancient and recent literature review, and re-examination of arthropods (Acanthoscelides obtectus Say), amphibians (Discoglossus), echinoderms (sea urchin) and mammals (rodents) embryos, we can raise up difference and common points of the gastrulation processes. The dorsoventral gradient is ensured by the couple Dpp (dorsal in arthropods)/SOG/chordin (ventral in arthropods), which appears as "inverted" in epineurians. Blastopore invagination occurs in arthopods in the ventral region, opposite to the vitellus mass (initially diffuse, then predominant on the dorsal side), whereas it occurs at the vegetative side in other hyponeurians and epineurians. It has been accepted that the BMP inhibits oral development in protostomian, whereas it activates it in Chordates. Therefore we assume, as Lowe does, that the oral cavity of deuterostomians might constitute a new structure related to the branchial system. The comparative analysis of the blastopore' orientation, the sperm penetration site, and the polarity axes of various embryos species allows to follow the different modifications and to hypothesize their relative chronology during evolution.


Zoledronic acid-induced severe lymphopenia.
Although anemia, thrombocytopenia, and mild lymphopenia have been reported in the acute phase response after zoledronic acid, severe lymphopenia has not been reported. This article describes a case of severe lymphopenia following a 5 mg zoledronic acid infusion administered to treat osteoporosis. Zoledronic acid is used to treat osteoporosis, hypercalcemia, Paget's disease, and solid malignancies, including multiple myeloma, breast cancer, and prostate cancer. An acute phase response can be seen in 42% of patients after zoledronic acid treatment. Acute phase response may be accompanied by short-term spontaneously recovered anemia, thrombocytopenia, and severe lymphopenia.


CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone.
Chemokines and their receptors function in migration and homing of cells to target tissues. Recent evidence suggests that cancer cells use a chemokine receptor axis for metastasis formation at secondary sites. Previously, we showed that binding of the chemokine CXCL12 to its receptor CXCR4 mediated signaling events resulting in matrix metalloproteinase-9 expression in prostate cancer bone metastasis. A variety of methods, including lipid raft isolation, stable overexpression of CXCR4, cellular adhesion, invasion assays, and the severe combined immunodeficient-human bone tumor growth model were used. We found that (a) CXCR4 and HER2 coexist in lipid rafts of prostate cancer cells; (b) the CXCL12/CXCR4 axis results in transactivation of the HER2 receptor in lipid rafts of prostate cancer cells; (c) Src kinase mediates CXCL12/CXCR4 transactivation of HER2 in prostate cancer cells; (d) a pan-HER inhibitor desensitizes CXCR4-induced transactivation and subsequent matrix metalloproteinase-9 secretion and invasion; (e) lipid raft-disrupting agents inhibited raft-associated CXCL12/CXCR4 transactivation of the HER2 and cellular invasion; (f) overexpression of CXCR4 in prostate cancer cells leads to increased HER2 phosphorylation and migratory properties of prostate cancer cells; and (g) CXCR4 overexpression enhances bone tumor growth and osteolysis. These data suggest that lipid rafts on the cell membrane are the key site for CXCL12/CXCR4-induced HER2 receptor transactivation. This transactivation contributes to enhanced invasive signals and metastatic growth in the bone microenvironment.


Salivary microflora and mode of delivery: a prospective case control study.
Previous cross-sectional studies have suggested that the mode of delivery can influence the composition of oral microflora. The aim of this prospective study was to compare the salivary colonization in vaginally delivered children with children delivered by Caesarian section (C-section) during their first 6 months of life. The study group consisted of 149 consecutively enrolled infants, delivered either vaginally (n = 96) or by C-section (n = 53) that volunteered after consent of their parents. Saliva samples were collected within 2 days after birth and then after 1, 3, and 6 months. A saliva sample from the mothers was obtained 6 months after delivery. The parents were asked to complete a questionnaire on socioeconomic factors, lifestyle, and hygiene at baseline and throughout the study period. All samples were analyzed with 13 pre-determined bacterial probes using checkerboard DNA-DNA hybridization. The groups were balanced at baseline concerning all relevant background factors. Gram-positive streptococci (S. mitis, S. salivarius) displayed the highest counts in both groups but a greater diversity was observed in the vaginally delivered group. A. naeslundi, A. odontolytics, F. nucleatum and L. salivarius were only detected among the vaginally delivered infants. The prevalence of S. sanguinis, S. gordoni, R. denticariosa, and B. dentinum increased by age in both groups but the prevalence was significantly lower in the C-section group (p < 0.05). There was a link between the mothers and their offspring's concerning the salivary microbial profile. The microbial composition in saliva differs by the mode of delivery during the first six months of life.


Effects of novel 17β-hydroxysteroid dehydrogenase type 10 inhibitors on mitochondrial respiration.
Mitochondrial enzymes are targets of newly synthesized drugs being tested for the treatment of neurodegenerative disorders, such as Alzheimer's disease (AD). The enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a multifunctional mitochondrial protein that is thought to play a role in the pathophysiology of AD and is one of the targets of new potential AD drugs. The in vitro effects of frentizole, riluzole, AG18051, and 42 novel modulators of HSD10 (potential AD drugs) on citrate synthase (CS) activity, monoamine oxidase (MAO) activity, complex I- or complex II-linked mitochondrial respiratory rate, and complex I activity were measured in isolated pig brain mitochondria. Based on their minimal inhibitory effects on the respiratory rate of mitochondria and CS and complex I activity, six novel compounds were selected for further testing. Assuming that inhibition of MAO-B could be a desirable effect of AD drugs, only AG18051 and one new compound met the criteria for MAO-B inhibition with minimal drug-induced effects on mitochondrial respiration. In conclusion, our in vitro screening of mitochondrial effect of novel potential AD drugs has enabled the selection of the most promising molecules for further testing that are relatively safe in terms of drug-induced mitochondrial toxicity.


Evaluation of facial artery course variations, diameters, and depth by Doppler ultrasonography.
The facial artery (FA) is the main blood vessel supplying blood to the face. It is essential to understand the anatomy of FA around the nasolabial fold (NLF). This study aimed to provide the detailed anatomy and relative positioning of FA to help avoid unexpected complications in plastic surgery. FA was observed from the inferior border of the mandible to the end of its terminal branch in 66 hemifaces of 33 patients with Doppler ultrasonography. The evaluation parameters were: (1) location, (2) diameter, (3) FA-skin depth, (4) relationship between the NLF and FA, (5) distance between the FA and significant surgical landmarks, and (6) the running layer. The FA course is classified based on the terminal branch. The most common FA course was Type 1, which had an angular branch as the final branch (59.1%). The most common FA-NLF relationship was that the FA was situated inferior to the NLF (50.0%). The mean FA diameter was 1.56 ± 0.36 mm at the mandibular origin, 1.40 ± 0.37 mm at the cheilion, and 1.32 ± 0.34 mm at the nasal ala. The FA diameter on the right hemiface was thicker than that on the left hemiface (p < 0.05). The FA mainly terminates in the angular branch, running in the medial NLF and in dermis and subcutaneous tissue, with a blood supply advantage in the right hemisphere. We suppose that a deep injection into periosteum around the NLF may be safer than an injection into the superficial musculoaponeurotic system (SMAS) layer.


In Vivo Linking of Membrane Lipids and the Anion Transporter Band 3 with Thiourea-modified Amphiphilic Lipid Probes.
Membrane proteins interact with membrane lipids for their structural stability and proper function. However, lipid-protein interactions are poorly understood at a molecular level especially in the live cell membrane, due to current limitations in methodology. Here, we report that amphiphilic lipid probes can be used to link membrane lipids and membrane proteins in vivo. Cholesterol and a phospholipid were both conjugated to a fluorescent tag through a linker containing thiourea. In the erythrocyte, the cholesterol probe fluorescently tagged the anion transporter band 3 via thiourea. Tagging by the cholesterol probe, but not by the phospholipid probe, was competitive with an anion transporter inhibitor, implying the presence of a specific binding pocket for cholesterol in this ~100 kDa protein. This method could prove an effective strategy for analyzing lipid-protein interactions in vivo in the live cell membrane.


Attenuation model of tunnel blast vibration velocity based on the influence of free surface.
In tunnel blasting excavation, it is important to clarify the attenuation law of blast wave propagation and predict the blast vibration velocity effectively to ensure safe tunnel construction and protection design. The effects of the free surface area its quantity on the blast vibration velocity are considered, and free surface parameters are introduced to improve the existing blast vibration velocity prediction formula. Based on the Tianhuan railway Daqianshiling tunnel project, field blast vibration monitoring tests are performed to determine changes in the peak blasting vibration velocity based on the blast distance and free surface area. LS-DYNA is used to establish tunnel blasting excavation models under three operating conditions; subsequently, the attenuation law of blast vibration velocity and changes in the vibration response spectrum are analysed. Results show that the free surface area and number of free surfaces enable the blast vibration velocity to be predicted under various operating conditions: a smaller free surface area results in a narrower frequency band range, whereas more free surfaces result in a narrower frequency band range. The improved blast vibration velocity prediction formula is validated using field and numerical test data. It is indicated that the improved formula is applicable to various tunnelling conditions.


Cold responses in rice: From physiology to molecular biology.
As rice originated in tropical or subtropical areas, it is generally sensitive to cold stress. Understanding the physiological and molecular mechanisms underlying rice responses to cold stress can provide new power for engineering cold-tolerant and high-yielding rice varieties.


Trends in psychotropic drug prescribing in Australia.
In 1983-1984, 9.8 million prescriptions were written for the 12 most common psychotropic drugs that are available under the Pharmaceutical Benefits Scheme. Our analysis shows that, of these prescriptions, 59% (374 per 1000 persons) were for the four most commonly prescribed benzodiazepine agents; 34% (216 per 1000 persons) were for the five main antidepressant agents; and 7% (41 per 1000 persons) were for the three main phenothiazine agents. In the period from 1977-1978 to 1983-1984, prescription volumes were relatively stable for antidepressant and phenothiazine drugs. Fluctuations in the prescribing of individual benzodiazepine agents are discussed. Older patients and women of all ages receive the majority of the psychotropic drug prescriptions that are written by Australian general practitioners.


Changes in immunologic parameters of humoral immunity and adipocytokines in obese persons are gender dependent.
The aim of this study was to investigate several immunologic parameters using of immunonephelometry and adipocytokines by the enzyme immunoassay and their changes in different states of obesity. Obesity is considered to involve a state of chronic low-grade inflammation, with links between adipose cells and the immune system. We found significantly higher complement C3 levels in all obese subjects. Levels of the complement C4 were significantly higher in obese women, but not in men, when compared with the corresponding group of normal weight subjects. The increase in C-reactive protein concentrations was significant in both obese and morbidly obese women, but only in morbidly obese men. No significant differences in tumor necrosis factor-α, interleukin-6, interleukin-10, and soluble intercellular adhesion molecule-1 were found. sE-selectin levels were higher in both overweight and obese women but only in morbidly obese men. We found decreased adiponectin concentrations in obese and morbidly obese women. Concentrations of leptin were significantly higher only in obese men (p < 0.05), whereas in women the increase in leptin levels was significant in overweight, obese, and morbidly obese subjects. In conclusion, our results demonstrate elevated levels of C3, C-reactive protein, sE-selectin, and leptin in obese women and men. In obese women, we also observed increased concentrations of C4 and decreased levels of adiponectin.


Characterization of the acetate-producing pathways in Escherichia coli.
Although the bacterium E. coli is chosen as the host in many bioprocesses, the accumulation of a common byproduct, acetate, is often problematic. Acetate, when present at high levels, will inhibit both cell growth and recombinant protein productivity. In addition, products derived from the central aerobic metabolic pathway often compete with the acetate-producing pathways poxB and ackA-pta for glucose as the substrate. As such, a significant portion of the glucose may be excreted as acetate, wasting substrate that otherwise could have been used for the desired product. We have created mutant E. coli strains with a deletion of either the poxB or the ackA-pta pathway. These two strains, along with the wild-type strain, have been studied in batch reactors over a 12 h time period, at pH 7.0 and 6.0. The wild-type strain has also been studied using glucose as the carbon source. Data were collected to correlate cellular growth, extracellular metabolite production, enzyme activity, and gene expression. Results show that the ackA-pta pathway dominates in exponential phase, and the poxB pathway dominates in stationary phase. The ackA-pta pathway is repressed in acidic environments, whereas the poxB pathway is activated.


Genus Tetrastemma Ehrenberg, 1831 (Phylum Nemertea)--a natural group? Phylogenetic relationships inferred from partial 18S rRNA sequences.
We investigated the monophyletic status of the hoplonemertean taxon Tetrastemma by reconstructing the phylogeny for 22 specimens assigned to this genus, together with another 25 specimens from closely related hoplonemertean genera. The phylogeny was based on partial 18S rRNA sequences using Bayesian and maximum likelihood analyses. The included Tetrastemma-species formed a well-supported clade, although the within-taxon relationships were unsettled. We conclude that the name Tetrastemma refers to a monophyletic taxon, but that it cannot be defined by morphological synapomorphies, and our results do not imply that all the over 100 species assigned to this genus belong to it. The results furthermore indicate that the genera Amphiporus and Emplectonema are non-monophyletic.


Melatonin influences methyl jasmonate-induced protection of photosynthetic activity in wheat plants against heat stress by regulating ethylene-synthesis genes and antioxidant metabolism.
Melatonin (MT) and methyl jasmonate (MeJA) play important roles in the adaptation of plants to different stress factors by modulating stress tolerance mechanisms. The present study reports the involvement of MT (100 µM) in MeJA (10 µM)-induced photosynthetic performance and heat stress acclimation through regulation of the antioxidant metabolism and ethylene production in wheat (Triticum aestivum L.) plants. Plants exposed to 40 °C for 6 h per day for 15 days and allowed to retrieve at 28 °C showed enhanced oxidative stress and antioxidant metabolism, increased 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) activity and ethylene production, and decreased photosynthetic performance. In contrast, the exogenously applied MT and MeJA reduced oxidative stress through improved S-assimilation (+ 73.6% S content), antioxidant defense system (+ 70.9% SOD, + 115.8% APX and + 104.2% GR, and + 49.5% GSH), optimized ethylene level to 58.4% resulting in improved photosynthesis by 75%. The use of p-chlorophenyl alanine, a MT biosynthesis inhibitor along with MeJA in the presence of heat stress reduced the photosynthetic performance, ATP-S activity and GSH content, substantiated the requirement of MT in the MeJA-induced photosynthetic response of plants under heat stress. These findings suggest that MeJA evoked the plant's ability to withstand heat stress by regulating the S-assimilation, antioxidant defense system, and ethylene production, and improving photosynthetic performance was dependent on MT.


Editorial: Black Adolescent Suicide in America: Insights From a Large Epidemiological Study.
As we sat down to review Sheftall et al.,1 we came across a chilling report in the venerable New York Times: "US suicides declined overall in 2020 but may have risen among people of color." The synchronicity would have been noteworthy, had the 2 reports not been so tragic. The pathos of the newspaper story was how painfully familiar it was, how heartbreakingly unsurprising, how sadly it rang true. This issue of the Journal includes the largest epidemiological study on Black adolescent suicide published to date. The article by Sheftall et al.1 provides reliable, granular, and actionable information about this major public health challenge.


Membrane antigens in chronic active hepatitis: physicochemical and immunological studies of soluble liver homogenate fractions.
Since the liver membrane components termed liver-specific protein (LSP) and liver membrane antigen (LM-Ag) have been implicated as target antigens in chronic active hepatitis (CAH), we performed physicochemical and immunological analyses of these and other fractions obtained from liver homogenates. Supernatants were prepared from homogenates of human and rabbit liver by centrifugation at 105,000 g for 1 hr; after gel filtration on Sepharose 6B, the LSP fraction was obtained as the excluded peak I and LM-Ag as an included fraction, peak IIB. Comparison by immunodiffusion with reference LSP and guinea pig antisera to LSP confirmed the similarity of our fractions to reference preparations. Upon SDS-polyacrylamide gel electrophoresis (SDS-PAGE), human and rabbit peak I were found to contain at least 25 distinct protein bands with a wide range of molecular weights (14,000- greater than 100,000) and the other peaks were found to be equally heterogeneous. Thin-layer polyacrylamide gel isoelectric focusing (PAGIF) revealed 35-40 separate bands in both peaks I and IIB with a wide range of isoelectric points (3.5-10.0). These results indicate that liver homogenate fractions such as LSP and LM-Ag can no longer be considered as single protein preparations, and are in fact highly complex mixtures of multiple proteins. Further separation and characterization of such fractions will facilitate identification of liver antigens for use in in vitro immunological assays.


Epidemiologic features of children with Epstein-Barr virus associated diseases in Hangzhou, China.
Epstein-Barr virus (EBV) infection is the causative agent of multiple diseases. EBV DNA in blood is a useful diagnostic marker of primary EBV infection and reactivation. This study aimed to provide epidemiological information on children with EBV-associated diseases identified by positive EBV DNA in Hangzhou, a city in East China. All children admitted to the Children's Hospital of Zhejiang University School of Medicine from 2010 to 2015 with suspected EBV-related diseases and serum EBV DNA tested by quantitative real-time polymerase chain reaction were included. Of the 10 470 children, 1205 were determined to have positive EBV DNA, and the positive rate was 11.5%. 15.8% (973 of 6162) of the illnesses of patients aged 1 to 7 years were caused by EBV as compared to that of 6.6% (179 of 2708) of children older than 7 years (P < .01) and 3.3% (53 of 1600) of of that of infants <1 year of age (P < .01). Among positive EBV DNA patients, 80.7% of EBV infections occurred in children at the age stage of 1 to 7 years. IM was the most common EBV-related disease, accounting for 75.7% of 581 hospitalized patients. Children aged 1 to 3 years were the age group most commonly hospitalized with EBV-IM (32.7% of the cohort) and EBV-hemophagocytic lymphohistiocytosis (HLH) (52.6%), while EBV-lymphoma was more common in children over 9-year old (58.3% of the cohort). The serum EBV-DNA load was much higher in patients with EBV-HLH than in patients with IM (P < .05). This is a large sample study, which revealed the epidemiological characteristics of children with EBV-associated diseases, including age, monthly and disease distribution.


Carcinogenic effect of a quanidine pesticide administered with sodium nitrite on adult mice and on the offspring after prenatal exposure.
Adult Swiss mice were treated intragastrically during the last week of pregnancy with the fungicide dodecylquanidine acetate (dodine, DGA) together with 0.05% sodium nitrite. The incidence of malignant lymphomas, lung adenomas and hepatomas was 30--70% in females. The first tumors appeared 4 months after delivery in the FO generation and at 6--7 months in the F1 generation. Among the untreated control mice the frequency of spontaneous tumors was 6%, and lymphomas developed, if at all, only after 10 months. The oncogenic activity of DGA with sodium nitrite in the offspring was dependent on the dose of DGA.A and C type RNA virus particles were demonstrated in lymphomas by electronmicroscopy. DGA alone had no effect on the cancer incidence.


Activity-stress ulcers in rats: the role of preentrainment to meal time.
Rats housed in activity wheels (A-W) or hanging cages (H-C) received food restriction to 4 h/day for 15 days. Food was given at fixed times to entrain the feeding entrainable oscillator or at irregular times to prevent entrainment. One half of the rats received food in the light phase, the other half in the dark phase of the light-dark cycle. Food was then reduced to 6 g/day for 4 days for A-W rats or 7 days for H-C rats. Stomachs were removed 24 h after the last meal and the ulcerated area was quantified. Twenty one of 32 A-W rats and 19 of 32 H-C rats had ulcers in the glandular stomach. Ulcers were significantly larger in A-W rats (p < 0.01). Activity levels (in A-W rats), % body weight loss and terminal body weight (in both groups) were significantly correlated with the area of ulcers. There was no significant time of day effect on the ulcer severity. However, an unexpected finding was that for A-W rats, those fed at fixed times had larger ulcers than those fed at irregular times (p < 0.01) while H-C rats showed an expected trend in the opposite direction. One possible explanation for this result is that for A-W rats, the reduced food supply at an expected time of day generated a greater stress response than in rats whose feeding time was unpredictable.


Humans and ecosystems over the coming millennia: overview of a biosphere assessment of radioactive waste disposal in Sweden.
This is an overview of the strategy used to describe the effects of a potential release from a radioactive waste repository on human exposure and future environments. It introduces a special issue of AMBIO, in which 13 articles show ways of understanding and characterizing the future. The study relies mainly on research performed in the context of a recent safety report concerning a repository for spent nuclear fuel in Sweden (the so-called SR-Site project). The development of a good understanding of on-site processes and acquisition of site-specific data facilitated the development of new approaches for assessment of surface ecosystems. A systematic and scientifically coherent methodology utilizes the understanding of the current spatial and temporal dynamics as an analog for future conditions. We conclude that future ecosystem can be inferred from a few variables and that this multidisciplinary approach is relevant in a much wider context than radioactive waste.


Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.
The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.


Overexpression of the ER-membrane protein P-450 CYP52A3 mimics sec mutant characteristics in Saccharomyces cerevisiae.
High expression of microsomal cytochrome P-450 CYP52A3 from Candida maltosa induces the formation of membrane stacks in Saccharomyces cerevisiae. Membrane proliferation is accompanied by coinduction of the ER proteins KAR2p and SEC61p and accumulation of precursor forms of proteins that have to translocate across the ER membrane (KAR2p, alpha factor). Cytosolic proteins (SSA1p and 2p) and mitochondrial proteins (CYT c1p and F1 beta p) are not affected. N-terminal truncated P-450 proteins remain in the cytoplasm and fail to induce membrane proliferation, KAR2p/SEC61p expression, and precursor accumulation. Membrane and precursor protein accumulation are typical features of sec mutants. We assume that the high amounts of P-450p block one or more factor(s) of the transport machinery and thereby cause the observed phenomena.


Cardiopulmonary needle embolization: a complication of central venous drug abuse.
A great variety of complications secondary to drug abuse have been reported in the literature. We report a case of multiple cardiopulmonary needle embolization. A drug addict who had resorted to central venous drug abuse was found on chest roentgenograms to have multiple asymptomatic needle fragments within her chest. In this instance chest roentgenograms and tomographs were more helpful in needle localization than computed tomography. Complications of intracardiac foreign bodies are also briefly reviewed. In attempts to diagnose this complication, a high index of suspicion is necessary as central venous drug abuse becomes increasingly more prevalent.


Disseminated vegetating infantile bromoderma: A dramatic response to systemic steroids.
Bromoderma is a rare hypersensitivity reaction caused by bromide intake. It was relatively frequent in the early years of the previous century because of the common use of bromide-containing solutions in pediatrics due to their antispasmodic, expectorant, sedative, and anticonvulsant effects. Although recently prohibited in many countries, bromides are still used as an adjuvant anticonvulsant drug and still present in some over the counter antispasmodics and analgesics. Bromoderma usually present with pustular and vegetating lesions that may represent a diagnostic challenge for dermatologists. We describe a severe case of vegetating bromoderma that showed an excellent response to the withdrawal of the bromide-containing medication associated with systemic steroid administration.


Metabolic and transcriptional response of central metabolism affected by root endophytic fungus Piriformospora indica under salinity in barley.
The root endophytic fungus Piriformospora indica enhances plant adaptation to environmental stress based on general and non-specific plant species mechanisms. In the present study, we integrated the ionomics, metabolomics, and transcriptomics data to identify the genes and metabolic regulatory networks conferring salt tolerance in P. indica-colonized barley plants. To this end, leaf samples were harvested at control (0 mM NaCl) and severe salt stress (300 mM NaCl) in P. indica-colonized and non-inoculated barley plants 4 weeks after fungal inoculation. The metabolome analysis resulted in an identification of a signature containing 14 metabolites and ions conferring tolerance to salt stress. Gene expression analysis has led to the identification of 254 differentially expressed genes at 0 mM NaCl and 391 genes at 300 mM NaCl in P. indica-colonized compared to non-inoculated samples. The integration of metabolome and transcriptome analysis indicated that the major and minor carbohydrate metabolism, nitrogen metabolism, and ethylene biosynthesis pathway might play a role in systemic salt-tolerance in leaf tissue induced by the root-colonized fungus.


Erratum to "Effects of Angiotensin-Converting Enzyme Inhibition on Circulating Endothelial Progenitor Cells in Patients with Acute Ischemic Stroke".
[This corrects the article DOI: 10.1155/2018/2827580.].


From BPA to its analogues: Is it a safe journey?
Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful?


Scalable analysis of Big pathology image data cohorts using efficient methods and high-performance computing strategies.
We describe a suite of tools and methods that form a core set of capabilities for researchers and clinical investigators to evaluate multiple analytical pipelines and quantify sensitivity and variability of the results while conducting large-scale studies in investigative pathology and oncology. The overarching objective of the current investigation is to address the challenges of large data sizes and high computational demands. The proposed tools and methods take advantage of state-of-the-art parallel machines and efficient content-based image searching strategies. The content based image retrieval (CBIR) algorithms can quickly detect and retrieve image patches similar to a query patch using a hierarchical analysis approach. The analysis component based on high performance computing can carry out consensus clustering on 500,000 data points using a large shared memory system. Our work demonstrates efficient CBIR algorithms and high performance computing can be leveraged for efficient analysis of large microscopy images to meet the challenges of clinically salient applications in pathology. These technologies enable researchers and clinical investigators to make more effective use of the rich informational content contained within digitized microscopy specimens.


Validating the positivity thresholds of drug-tolerant anti-infliximab and anti-adalimumab antibody assays.
When used proactively, drug-tolerant anti-tumour necrosis factor (TNF) antibody assays provide early opportunity to suppress immunogenicity. To validate positivity thresholds of IDKmonitor drug-tolerant anti-infliximab and -adalimumab antibody assays. We applied positivity thresholds, defined by testing sera from 498 anti-TNF naive healthy adults, from the Exeter Ten Thousand study to data from our therapeutic drug monitoring (TDM) service and Personalised Anti-TNF Therapy in Crohn's disease (PANTS) cohort to explore associations with drug level and treatment outcomes. The 80% one-sided lower confidence interval of the 99th centile concentration for anti-infliximab and -adalimumab antibodies were lower than the manufacturers threshold of 10 arbitrary units (AU)/mL; 9 and 6 AU/mL, respectively. Using these new thresholds in the TDM cohort, more adalimumab- than infliximab- (11.2% [814/7272] vs 3.1% [390/12 683] P < 0.0001) treated patients were reclassified as antibody-positive. Adalimumab drug concentrations in this reclassified group (median 8.1, interquartile range [IQR] 5.5-11.0 mg/L) were lower than those below the new threshold (<5AU/mL) (median 9.9, IQR 7.1-13.0 mg/L; P < 0.0001), but higher than at the manufacturer's threshold (10-29 AU/mL) (median 5.9 mg/L, IQR 3.5-8.7; P < 0.0001). No difference in infliximab drug concentration was observed using the new or manufacturer's positivity threshold (P = 0.11). In the PANTS cohort, patients with anti-adalimumab antibody concentrations at or above the new threshold were more likely to be in primary non-response (25/68 [37%] vs. 64/332 [19%], P = 0.0035), and non-remission at week 54 (51/62 [82%] vs. 168/279 [60%], P = 0.0011), than patients with anti-drug antibody concentrations in the group below the new threshold (0-5 AU/mL); this was not seen for anti-infliximab antibodies. Laboratories should derive antibody positivity thresholds for assays they use. For adalimumab, low-concentration anti-drug antibodies were associated with lower drug levels and treatment failure.