Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study).
Radiofrequency ablation is an accepted treatment for non-surgical patients with liver cancer. The purpose of this study was to identify the feasibility, safety, and effectiveness of percutaneous radiofrequency ablation of malignant lung tumours. Between July 1, 2001, and Dec 10, 2005, a series of 106 patients with 183 lung tumours that were 3.5 cm in diameter or smaller (mean 1.7 cm [SD 1.3]) were enrolled in a prospective, intention-to-treat, single-arm, multicentre clinical trial from seven centres in Europe, the USA, and Australia. Proof of malignancy was obtained by biopsy in all patients. Diagnoses included non-small-cell lung cancer (NSCLC) in 33 patients, metastasis from colorectal carcinoma in 53 patients, and metastasis from other primary malignancies in 20 patients. All patients were considered by the treating physician to be unsuitable for surgery and unfit for radiotherapy or chemotherapy. Patients underwent radiofrequency ablation in accordance with standard rules for CT-guided lung biopsy and were then followed for up to 2 years. Primary endpoints were technical success (defined as correct placement of the ablation device into all tumour targets with completion of the planned ablation protocol), safety (including identification of treatment-related complications and changes in pulmonary function), and confirmed complete response of tumours (according to modified Response Evaluation Criteria in Solid Tumors). Secondary endpoints were overall survival, cancer-specific survival, and quality of life. This trial is registered with ClinicalTrials.gov, number NCT00690703. Correct placement of the ablation device into the target tumour with completion of the planned treatment protocol was feasible in 105 (99%) of 106 patients. The technical failure in one patient was caused by the inability to place the device inside a small tumour. No procedure-related deaths occurred in any of the 137 ablation procedures. Major complications consisted of pneumothorax (n=27) or pleural effusion (n=4), which needed drainage. No significant worsening of pulmonary function was noted. A confirmed complete response of target tumours lasting at least 1 year was shown in 75 (88%) of 85 assessable patients. No differences in response were noted between patients with NSCLC or lung metastases. Overall survival was 70% (95% CI 51-83%) at 1 year and 48% (30-65%) at 2 years in patients with NSCLC, 89% (76-95%) at 1 year and 66% (53-79%) at 2 years in patients with colorectal metastases, and 92% (65-99%) at 1 year and 64% (43-82%) at 2 years in patients with other metastases. Cancer-specific survival was 92% (78-98%) at 1 year and 73% (54-86%) at 2 years in patients with NSCLC, 91% (78-96%) at 1 year and 68% (54-80%) at 2 years in patients with colorectal metastases, and 93% (67-99%) at 1 year and 67% (48-84%) at 2 years in patients with other metastases. Patients with stage I NSCLC (n=13) had a 2-year overall survival of 75% (45-92%) and a 2-year cancer-specific survival of 92% (66-99%). Percutaneous radiofrequency ablation yields high proportions of sustained complete responses in properly selected patients with pulmonary malignancies, and is associated with acceptable morbidity. Randomised controlled trials comparing radiofrequency ablation with standard non-surgical treatment options are warranted.


Characterization of an NBS-LRR resistance gene homologue from soybean.
Conserved motifs such as the nucleotide-binding site (NBS) were found in many characterized plant disease resistance genes. Based on the NBS domain, resistance gene analogs have been isolated in our previous study and were used as probes to screen a soybean (Glycine max) cDNA library. A full-length cDNA, KR4, was isolated by screening the library and rapid amplification of cDNA ends method. Sequence analysis revealed that the cDNA was 3818 bp in length and the open reading frame coded for a polypeptide of 1211 amino acids with an NBS and five leucine-rich repeats domains, which were identified by Pfam protein analysis. Sequence alignment showed that KR4 was similar to 12 protein of tomato. Southern analysis indicated that the KR4 gene had low copies in soybean genome and it was mapped on the molecular linkage group E. Its expression was also investigated and it was found that KR4 was induced by exogenous salicylic acid and responded upon infection of soybean mosaic virus strain N3.


Panic and the brainstem: clues from neuroimaging studies.
One of the most influential theories has conceived unexpected panic attack (PA) as a primal defensive reaction to threat within the internal milieu of the body. This theory is based on findings suggesting the involvement of dysfunctional respiratory regulation and/or abnormally sensitive central neural network of carbon dioxide (CO2)/hydrogen ion (H+) chemoreception in PA. Thus, unexpected PA may be related to phylogenetically older brain structures, including the brainstem areas, which process basic functions related to the organism's internal milieu. The brainstem represents a crucial area for homeostatic regulation, including chemoreception and cardio-respiratory control. In addition, the midbrain dorsal periaqueductal gray may be involved in the unconditioned defense reactions to proximal threats, including internal physical stimuli. Our aim was to specifically consider the potential involvement of the brainstem in panic disorder (PD) by a comprehensive review of the available neuroimaging studies. Available data are limited and potentially affected by several limitations. However, preliminary evidence of a role of the brainstem in PD can be found and, secondly, the brainstem serotonergic system seems to be involved in panic modulation with indications of both altered serotonergic receptors and 5-HT transporter bindings. In conclusion, our review suggests that the brainstem may be involved in psychopathology of PD and supports the relevant role of subcortical serotonergic system in panic pathogenesis.


GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia.
Synchronization of neuronal activity in the neocortex may underlie the coordination of neural representations and thus is critical for optimal cognitive function. Because cognitive deficits are the major determinant of functional outcome in schizophrenia, identifying their neural basis is important for the development of new therapeutic interventions. Here we review the data suggesting that phasic synaptic inhibition mediated by specific subtypes of cortical gamma-aminobutyric acid (GABA) neurons is essential for the production of synchronized network oscillations. We also discuss evidence indicating that GABA neurotransmission is altered in schizophrenia and propose mechanisms by which such alterations can decrease the strength of inhibitory connections in a cell-type-specific manner. We suggest that some alterations observed in the neocortex of schizophrenia subjects may be compensatory responses that partially restore inhibitory synaptic efficacy. The findings of altered neural synchrony and impaired cognitive function in schizophrenia suggest that such compensatory responses are insufficient and that interventions aimed at augmenting the efficacy of GABA neurotransmission might be of therapeutic value.


Dual source-powered multifunctional Pt/FePc@Mn-MOF spindle-like Janus nanomotors for active CT imaging-guided synergistic photothermal/chemodynamic therapy.
Nanomaterials capable of dual therapeutic effects of chemodynamic therapy (CDT) and photothermal therapy (PTT) is an efficacious strategy in cancer treatment. It is still a challenge to achieve complete apoptosis of tumor tissue in CDT/PTT due to the poor permeability of nanomaterials in tumor tissue. Herein, we prepared a dual-source driven Pt/FePc@Mn-MOF spindle-like Janus nanomotor by a facile oriented connection growth method for computed tomography (CT) imaging-guided CDT and PTT. The high catalase (CAT)-like activity of nanomotors allows the generation of oxygen (O2) bubbles by catalyzing the decomposition of endogenous H2O2, which alleviates the hypoxic state of the tumor microenvironment (TME) and simultaneously drive nanomotors. Pt/FePc@Mn-MOF nanomotor with excellent photothermal conversion efficiency exhibited dual peroxidase (POD)-like and oxidase (OXD)-like activities, which can produce large amounts of ROS to obtain PTT enhanced CDT. Meanwhile, near-infrared light, as "optical brakes", can trigger Janus nanomotor to realize self-thermophoretic movement. Chemical/NIR-assisted autonomous propulsion can significantly improve the accumulation of Janus nanomotors in solid tumors and enhance their ability to penetrate tumor tissue, thus brings synergistic enhancement effect to PTT and CDT. Moreover, Mn-MOF in nanomotor can deplete the antioxidant GSH by redox reaction to release massive Mn2+, which introduce Mn2+-based CT imaging properties. This novel dual-source controlled Janus nanomotor offers great potential for multimodal therapeutic medical applications.


A new abietene diterpene and other constituents from Kaempferia angustifolia Rosc.
A new abietene diterpene, kaempfolienol (5S,6S,7S,9S,10S,11R,13S-abiet-8(14)-enepenta-6,7,9,11,13-ol, 1), was isolated from a rhizome extract of Kaempferia angustifolia Rosc. along with the known compounds crotepoxide, boesenboxide, zeylenol, 2'-hydroxy-4,4',6'-trimethoxychalcone, (24S)-24-methyl-5α-lanosta-9(11),25-dien-3β-ol, β-sitosterol and β-sitosterol-3-O-β-D-glucopyranoside. The structures of all compounds were elucidated on the basis of mass spectroscopic and NMR data. Zeylenol (2), the major constituent of the plant, was derivatized into diacetate, triacetate and epoxide derivatives through standard organic reactions. The cytotoxic activity of compounds 1, 2 and the zeylenol derivatives was evaluated against the HL-60, MCF-7, HT-29 and HeLa cell lines.


[Adaptive significance of the ciradian rhythm of oviposition in Drosophilidae: comparison of eight species of the genus Zaprionus].
The circadian rhythm of oviposition under light conditions LD 12:12 was studied in eight species of Zaprionus. Interspecific differences proved to be of little importance. In all cases, the maximum of egg production took place at the beginning of the photophase and egg laying was often restricted to a few hours. Such a rhythm is highly different from that observed, in a previous work, among the Drosophila species of the melanogaster subgroup.


DrasCLR: A self-supervised framework of learning disease-related and anatomy-specific representation for 3D lung CT images.
Large-scale volumetric medical images with annotation are rare, costly, and time prohibitive to acquire. Self-supervised learning (SSL) offers a promising pre-training and feature extraction solution for many downstream tasks, as it only uses unlabeled data. Recently, SSL methods based on instance discrimination have gained popularity in the medical imaging domain. However, SSL pre-trained encoders may use many clues in the image to discriminate an instance that are not necessarily disease-related. Moreover, pathological patterns are often subtle and heterogeneous, requiring the ability of the desired method to represent anatomy-specific features that are sensitive to abnormal changes in different body parts. In this work, we present a novel SSL framework, named DrasCLR, for 3D lung CT images to overcome these challenges. We propose two domain-specific contrastive learning strategies: one aims to capture subtle disease patterns inside a local anatomical region, and the other aims to represent severe disease patterns that span larger regions. We formulate the encoder using conditional hyper-parameterized network, in which the parameters are dependant on the anatomical location, to extract anatomically sensitive features. Extensive experiments on large-scale datasets of lung CT scans show that our method improves the performance of many downstream prediction and segmentation tasks. The patient-level representation improves the performance of the patient survival prediction task. We show how our method can detect emphysema subtypes via dense prediction. We demonstrate that fine-tuning the pre-trained model can significantly reduce annotation efforts without sacrificing emphysema detection accuracy. Our ablation study highlights the importance of incorporating anatomical context into the SSL framework. Our codes are available at https://github.com/batmanlab/DrasCLR.


Pharmacological interventions for heart failure in people with chronic kidney disease.
Approximately half of people with heart failure have chronic kidney disease (CKD). Pharmacological interventions for heart failure in people with CKD have the potential to reduce death (any cause) or hospitalisations for decompensated heart failure. However, these interventions are of uncertain benefit and may increase the risk of harm, such as hypotension and electrolyte abnormalities, in those with CKD. This review aims to look at the benefits and harms of pharmacological interventions for HF (i.e., antihypertensive agents, inotropes, and agents that may improve the heart performance indirectly) in people with HF and CKD. We searched the Cochrane Kidney and Transplant Register of Studies through 12 September 2019 in consultation with an Information Specialist and using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised controlled trials of any pharmacological intervention for acute or chronic heart failure, among people of any age with chronic kidney disease of at least three months duration. Two authors independently screened the records to identify eligible studies and extracted data on the following dichotomous outcomes: death, hospitalisations, worsening heart failure, worsening kidney function, hyperkalaemia, and hypotension. We used random effects meta-analysis to estimate treatment effects, which we expressed as a risk ratio (RR) with 95% confidence intervals (CI). We assessed the risk of bias using the Cochrane tool. We applied the GRADE methodology to rate the certainty of evidence. One hundred and twelve studies met our selection criteria: 15 were studies of adults with CKD; 16 studies were conducted in the general population but provided subgroup data for people with CKD; and 81 studies included individuals with CKD, however, data for this subgroup were not provided. The risk of bias in all 112 studies was frequently high or unclear. Of the 31 studies (23,762 participants) with data on CKD patients, follow-up ranged from three months to five years, and study size ranged from 16 to 2916 participants. In total, 26 studies (19,612 participants) reported disaggregated and extractable data on at least one outcome of interest for our review and were included in our meta-analyses. In acute heart failure, the effects of adenosine A1-receptor antagonists, dopamine, nesiritide, or serelaxin on death, hospitalisations, worsening heart failure or kidney function, hyperkalaemia, hypotension or quality of life were uncertain due to sparse data or were not reported. In chronic heart failure, the effects of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) (4 studies, 5003 participants: RR 0.85, 95% CI 0.70 to 1.02; I2 = 78%; low certainty evidence), aldosterone antagonists (2 studies, 34 participants: RR 0.61 95% CI 0.06 to 6.59; very low certainty evidence), and vasopressin receptor antagonists (RR 1.26, 95% CI 0.55 to 2.89; 2 studies, 1840 participants; low certainty evidence) on death (any cause) were uncertain. Treatment with beta-blockers may reduce the risk of death (any cause) (4 studies, 3136 participants: RR 0.69, 95% CI 0.60 to 0.79; I2 = 0%; moderate certainty evidence). Treatment with ACEi or ARB (2 studies, 1368 participants: RR 0.90, 95% CI 0.43 to 1.90; I2 = 97%; very low certainty evidence) had uncertain effects on hospitalisation for heart failure, as treatment estimates were consistent with either benefit or harm. Treatment with beta-blockers may decrease hospitalisation for heart failure (3 studies, 2287 participants: RR 0.67, 95% CI 0.43 to 1.05; I2 = 87%; low certainty evidence). Aldosterone antagonists may increase the risk of hyperkalaemia compared to placebo or no treatment (3 studies, 826 participants: RR 2.91, 95% CI 2.03 to 4.17; I2 = 0%; low certainty evidence). Renin inhibitors had uncertain risks of hyperkalaemia (2 studies, 142 participants: RR 0.86, 95% CI 0.49 to 1.49; I2 = 0%; very low certainty). We were unable to estimate whether treatment with sinus node inhibitors affects the risk of hyperkalaemia, as there were few studies and meta-analysis was not possible. Hyperkalaemia was not reported for the CKD subgroup in studies investigating other therapies. The effects of ACEi or ARB, or aldosterone antagonists on worsening heart failure or kidney function, hypotension, or quality of life were uncertain due to sparse data or were not reported. Effects of anti-arrhythmic agents, digoxin, phosphodiesterase inhibitors, renin inhibitors, sinus node inhibitors, vasodilators, and vasopressin receptor antagonists were very uncertain due to the paucity of studies. The effects of pharmacological interventions for heart failure in people with CKD are uncertain and there is insufficient evidence to inform clinical practice. Study data for treatment outcomes in patients with heart failure and CKD are sparse despite the potential impact of kidney impairment on the benefits and harms of treatment. Future research aimed at analysing existing data in general population HF studies to explore the effect in subgroups of patients with CKD, considering stage of disease, may yield valuable insights for the management of people with HF and CKD.


Fibrillation-prone conformations of the amyloid-β-42 peptide at the gold/water interface.
Proteins in the proximity of inorganic surfaces and nanoparticles may undergo profound adjustments that trigger biomedically relevant processes, such as protein fibrillation. The mechanisms that govern protein-surface interactions at the molecular level are still poorly understood. In this work, we investigate the adsorption onto a gold surface, in water, of an amyloid-β (Aβ) peptide, which is the amyloidogenic peptide involved in Alzheimer's disease. The entire adsorption process, from the peptide in bulk water to its conformational relaxation on the surface, is explored by large-scale atomistic molecular dynamics (MD) simulations. We start by providing a description of the conformational ensemble of Aβ in solution by a 22 μs temperature replica exchange MD simulation, which is consistent with previous results. Then, we obtain a statistical description of how the peptide approaches the gold surface by multiple MD simulations, identifying the preferential gold-binding sites and giving a kinetic picture of the association process. Finally, relaxation of the Aβ conformations at the gold/water interface is performed by a 19 μs Hamiltonian-temperature replica exchange MD simulation. We find that the conformational ensemble of Aβ is strongly perturbed by the presence of the surface. In particular, at the gold/water interface the population of the conformers akin to amyloid fibrils is significantly enriched, suggesting that this extended contact geometry may promote fibrillation.


A cytidine deaminase expressed in the post-infective L3 stage of the filarial nematode, Brugia pahangi, has a novel RNA-binding activity.
A number of genes have been identified that are highly expressed in the post-infective L3 stage of the filarial parasite, Brugia pahangi. Amongst these was a cDNA with homology to the cytidine deaminase (CDD) gene family. Phylogenetic analysis of the various cytosine nucleoside deaminases suggest that Brugia pahangi CDD evolved with significant divergence from the RNA editing family. In order to characterize its function, we have expressed Brugia pahangi CDD in bacteria as a chimera with maltose-binding protein (MBP). Biochemical analysis demonstrates the MBP-CDD fusion protein functions as an authentic cytidine deaminase with an obligate requirement for zinc. In addition to cytidine deaminase activity, however, the fusion protein demonstrates RNA binding activity with specificity for AU-rich sequences and was found to bind an RNA template spanning the edited site of mammalian apolipoprotein B (apoB) mRNA. This RNA binding activity was not found in two different recombinant bacterial CDD proteins. In vitro RNA editing assays revealed that MBP-CDD failed to mediate cytidine deamination of a mammalian apoB RNA template. Furthermore, binding of MBP-CDD to the apoB RNA did not inhibit in vitro editing of this template by apobec-1. The data suggest that the cytosine nucleoside deaminases and RNA editing deaminases have acquired different mechanisms of binding to an AU-rich RNA template, presumably with different functional implications.


Rectocutaneous fistula and nonunion after TranS1 axial lumbar interbody fusion L5-S1 fixation: case report.
The authors report a case of rectal injury, rectocutaneous fistula, and pseudarthrosis after a TranS1 axial lumbar interbody fusion (AxiaLIF) L5-S1 fixation. The TranS1 AxiaLIF procedure is a percutaneous minimally invasive approach to transsacral fusion of the L4-S1 vertebral levels. It is gaining popularity due to the ease of access to the sacrum through the presacral space, which is relatively free from intraabdominal and neurovascular structures. This 35-year-old man had undergone the procedure for the treatment of degenerative disc disease. The patient subsequently presented with fever, syncope, and foul-smelling gas and bloody drainage from the surgical site. A CT fistulagram and flexible sigmoidoscopy showed evidence of rectocutaneous fistula, which was managed with intravenous antibiotic therapy and bowel rest with total parenteral nutrition. Subsequent studies performed 6 months postoperatively revealed evidence of pseudarthrosis. The patient's rectocutaneous fistula symptoms gradually subsided, but his preoperative back pain recurred prompting a revision of his L5-S1 spinal fusion.


Selective alterations in the cellular distribution of apolipoprotein E immunoreactivity following transient cerebral ischaemia in the rat.
The aim of this study was to examine the cellular localization and alterations of apolipoprotein E (apoE) following a transient ischaemic insult using immunohistochemistry. Transient cerebral ischaemia was induced in Wistar rats by occlusion of both carotid arteries with hypotension followed by reperfusion for 4 h (n = 5), 24 h (n = 5) or 72 h (n = 6). In sham-operated animals (n = 9), the carotids were not occluded. In this model, ischaemia for 15 min results in selective neuronal damage in the caudate nucleus and neocortex (24 h after reperfusion) and the hippocampal CA1 pyramidal cells (72 h after reperfusion) while there is minimal damage in other areas such as the CA3 hippocampal region. In sham animals apoE immunoreactivity was confined to astrocytes and their processes. ApoE immunoreactivity was not altered at 4 h post-ischemic reperfusion. At 24 h reperfusion, intense apoE staining of the cytoplasm of astrocytes and neuropil within the caudate and neocortex was observed and at 72 h reperfusion apoE stained neuronal cell bodies within these regions. Within the CA1 region at 24 h reperfusion, there was increased immunoreactivity of the cytoplasm of astrocytes and the neuropil was more intensely stained compared with sham animals. At 72 h reperfusion, intense apoE staining of pyramidal cell bodies and dendrites was consistently observed in the CA1 region of the hippocampus. In contrast, at 72 h reperfusion, apoE staining of astrocytic processes was dramatically reduced in the CA1 region although GFAP staining indicated their preservation. The results demonstrate that following an ischaemic insult apoE is localized to degenerating neurons and their processes. This may indicate an inherent protective response of cells to injury. Alternatively, the results are consistent with the hypothesis that apoE is synthesized and released by astrocytes and taken up by neurons following injury.


The longitudinal associations between personal belief in a just world and teacher justice among advantaged and disadvantaged school students.
The Just World Hypothesis states that people need to believe in a just world in which they get what they deserve and deserve what they get. This study examines the longitudinal associations between personal belief in a just world (BJW), the belief that events in one's own life are just and teacher justice in different status groups. It is posited that the more individuals believe in a personal just world, the more they feel they are treated justly by others, and this should be particularly true for students with a low-status background. Longitudinal questionnaire data were obtained from students with German and Turkish/Muslim backgrounds over a period of 3-4 months. The pattern of results revealed that personal BJW was important for the Turkish/Muslim students in evaluating teachers as more just over a given period of time, but not for the German students. That is, the buffering effect of personal BJW was crucial for the disadvantaged students.


[Ability of virus SV40 T-antigen to simulate the effect of specific T lymphocyte growth factor--interleukin-2].
The entering of T-lymphocytes into the DNA-synthesizing phase was marked by three consecutive signals, i.e., antigenic influence, interleukin-2, a specific T-lymphocyte cell growth factor, and non-specific serum growth-promoting factors, in the first place, transferrin. This system was used for the study of effects of virus SV40 T-antigen on cell mitotic cycle. Purified T-antigen was injected consecutively into T-lymphocytes, using erythrocyte ghost vesicles instead of one of control signals. It was shown that T-antigen cannot simulate the antigenic response but simulates the effect of interleukin-2, a specific growth-promoting factor. However, both normally proliferating T-lymphocytes and T-antigen-induced lymphocytes showed an absolute requirement for transferrin and, apparently, for other nonspecific growth-promoting factors. It was assumed that the polymorphism of tumours induced by papovaviruses is determined by the ability of their "early" proteins to imitate the effects of their specific growth-promoting factors on the cells.


Monte Carlo simulations for configuring and testing an analytical proton dose-calculation algorithm.
Contemporary treatment planning systems for proton radiotherapy typically use analytical pencil-beam algorithms - which require a comprehensive set of configuration data - to predict the absorbed dose distributions in the patient. In order to reduce the time required to prepare a new proton treatment planning system for clinical use, it was desirable to configure the planning system before measured beam data were available. However, it was not known if the Monte Carlo simulation method was a practical alternative to measuring beam profiles. The purpose of this study was to develop a model of a passively scattered proton therapy unit, to simulate the properties of the proton fields using the Monte Carlo technique and to configure an analytical treatment planning system using the simulated beam data. Additional simulations and treatment plans were calculated in order to validate the pencil-beam predictions against the Monte Carlo simulations using realistic treatment beams. Comparison of dose distributions in a water phantom revealed small dose difference and distances to agreement under the validation conditions. The total simulation time for generating the 768 beam configuration profiles was approximately 6 weeks using 30 nodes in a parallel processing cluster. The results of this study show that it is possible to configure and test a proton treatment planning system prior to the availability of measured proton beam data. The model presented here provided a means to reduce by several months the time required to prepare an analytical treatment planning system for patient treatments.


Recommendations for a Clinical Decision Support System for Work-Related Asthma in Primary Care Settings.
The aim of this study was to describe a recommended clinical decision support (CDS) approach for work-related asthma for incorporation in electronic health records (EHRs) for primary care health care providers. Subject matter experts convened by the American Thoracic Society reviewed available guidelines and published literature to develop specific recommendations. It is important to recognize possible work-related asthma among persons with new-onset or worsening asthma. The work group recommends incorporating three simple questions about temporal relations between asthma symptoms and work in EHR systems and identified specific clinical conditions to trigger this intervention. Patients with positive responses to the three questions should have the asthma diagnosis documented and have further evaluation, education, and possible referral. An effective CDS system for improving recognition of work-related asthma may help reduce morbidity and mortality of asthma in adults.


Does verbal labeling influence age differences in proactive and reactive cognitive control?
The main goal of this study was to examine whether different types of verbal labeling can influence age-related changes in the dynamic control of behavior by inducing either a proactive or reactive mode of control. Proactive control is characterized by a strong engagement in maintaining task-relevant information to be optimally prepared while reactive control is characterized by a reactivation of task-related information during responding. To investigate dynamic shifts between these control modes, we applied the AX-Continuous-Performance-Task in 2 experiments that differed in the complexity of stimuli and types of labeling in children (range = 7-10 years), younger (range = 19-33 years), and older adults (range = 69-83 years). We expected that labeling the cue information would promote a shift from a reactive to a proactive control mode primarily in children and older adults, while labeling the probe information would result in a shift from a proactive to a reactive control mode primarily in younger adults. Results of both experiments indicated that children, younger, and older adults were equally engaged in cue processing and performed the task in a proactive manner. While cue labeling did not further promote performing the task proactively, probe labeling induced a shift to a reactive control mode, especially in children. In the first experiment, including younger children than in the second experiment, children had more problems than adults to reactivate cue information to overcome a strong response tendency. These findings support the view that verbal labeling can influence the regulation of behavior by selectively attracting attention to relevant information in a given task.


Calpain-mediated cleavage of Beclin-1 and autophagy deregulation following retinal ischemic injury in vivo.
Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular stress. Although being recently implicated in neurodegeneration, it remains still unclear whether autophagy has a detrimental or protective role. In this study, we investigated the dynamics of the autophagic process in retinal tissue that has undergone transient ischemia, an experimental model that recapitulates features of ocular pathologies, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion. Retinal ischemia, induced in adult rats by increasing the intraocular pressure, was characterized by a reduction in the phosphatidylethanolamine-modified form of LC3 (LC3II) and by a significant decrease in Beclin-1. The latter event was associated with a proteolytic cleavage of Beclin-1, leading to the accumulation of a 50-kDa fragment. This event was prevented by intravitreal treatment with the non-competitive N-methyl-D-aspartate antagonist MK801 and calpain inhibitors or by calpain knockdown. Blockade of autophagy by pharmacological inhibition or Beclin-1 silencing in RGC-5 increased cell death, suggesting a pro-survival role of the autophagic process in this neuronal cell type. Altogether, our results provide original evidence for calpain-mediated cleavage of Beclin-1 and deregulation of basal autophagy in the rat retina that has undergone ocular ischemia/reperfusion injury.


Perceived control moderated the self-efficacy-enhancing effects of a chronic illness self-management intervention.
Identifying moderators of the effects of self-efficacy-enhancing interventions could improve their efficiency. We examined the effects of a home-based variant of the Chronic Disease Self-Management Program on self-efficacy, and explored the moderating effects of perceived control over self-management (PCSM). In a randomized controlled trial, patients (N= 415) aged>40 years with various chronic conditions plus basic activity impairment and/or significant depressive symptoms were randomized to one of three groups: intervention provided in homes or by telephone, v. usual care control. We used mixed effects linear models for repeated measures to examine effects on self-management self-efficacy at 6-month follow-up and explore moderation by PCSM. Only the home intervention had a significant self-efficacy-enhancing effect (Wald test, chi( 2) = 13.8, p = 0.008; effect size = 0.3). The effect was moderated by PCSM, considered as a continuous [effective in subjects with lower PCSM (Wald test, chi(2) = 13.4, p = 0.009)] or categorical (effective only for subjects in the lowest tercile) variable. People with lower PCSM appear more likely to experience enhanced self-efficacy from chronic illness self-management training than those with higher PCSM. These findings, although preliminary, suggest that office-based measurement of PCSM might identify those chronically ill patients likely to benefit most from self-management training.


Oral health program preferences among pregnant women in a managed care organization.
The purpose of the study was to understand the oral health information preferences of pregnant women and new mothers. This study was conducted at a Minnesota managed care organization. A random sample of 250 women with public program insurance and 250 privately insured women was selected from the population of pregnant women in the claims systems. The study consisted of a mailed survey and phone contact to nonresponders. The analytic sample consisted of 123 public-pay and 127 private-pay respondents. Descriptive statistics summarize the preferences for oral health care topics. Receiving information by mail was preferred by both groups. Women favored information concerning infant-specific oral health more than information on both mother and infant oral health. While public-pay respondents had more enthusiasm for many topics, the topic preference rankings within each sample were similar. Similarities in program preferences suggest that common interventions could be designed that would appeal to both groups without extensive tailoring.


Effect of twin birth calvings on milk production, reproductive performance, and survival of lactating cows.
To evaluate effect of twin birth calvings on milk production, reproductive performance, and survival of lactating cows. Retrospective observational cohort study. 33,868 cows from 20 farms. Data on age at calving for primiparous cows and mature equivalent milk yield for multiparous cows, assistance at calving, stillbirths, twin births, gestation duration, pregnancy at the end of the data collection period, and culling-death for all cows were extracted from farm computer records and used for statistical analysis. Prevalence of twin parturitions was 1.3% (159/12,050) and 6.5% (1,410/21,818) for primiparous and multiparous cows, respectively. Primiparous and multiparous cows with singletons produced more milk than cows with live twins or at least 1 dead twin (primiparous, 33.1 vs 31.9 vs 31.2; multiparous, 36.5 vs 35.7 vs 35.0). Multiparous cows with dead twins produced less milk than cows with live twins. Compared with dams with singleton birth, cows with twins were 0.78 times as likely to conceive and 1.42 times as likely to die or be culled. Cows with dead twins also had increased time to conception, compared with live twins. Twin birth was associated with decreased survival, milk production, and reproductive performance. Having at least 1 dead twin was even more detrimental than having live twins and resulted in decreased milk production and reproductive performance of lactating cows.


Study of the fragmentation mechanism of novel functionalized macrocycles by Fourier transform ion cyclotron resonance mass spectrometry.
Liquid secondary ion mass spectrometry (L-SIMS) of six new functionalized macrocycles was investigated. All six compounds yielded abundant fragment ions and protonation molecular ions [M + H](+) under L-SIMS conditions. The proposed fragmentation mechanisms were supported by high-resolution accurate mass data from Fourier transform ion cyclotron resonance mass spectrometric and MS(n) experiments on using sustained off-resonance irradiation collision-induced dissociation.


Positive Selection at the Polyhomeotic Locus Led to Decreased Thermosensitivity of Gene Expression in Temperate Drosophila melanogaster.
Drosophila melanogaster as a cosmopolitan species has successfully adapted to a wide range of different environments. Variation in temperature is one important environmental factor that influences the distribution of species in nature. In particular for insects, which are mostly ectotherms, ambient temperature plays a major role in their ability to colonize new habitats. Chromatin-based gene regulation is known to be sensitive to temperature. Ambient temperature leads to changes in the activation of genes regulated in this manner. One such regulatory system is the Polycomb group (PcG) whose target genes are more expressed at lower temperatures than at higher ones. Therefore, a greater range in ambient temperature in temperate environments may lead to greater variability (plasticity) in the expression of these genes. This might have detrimental effects, such that positive selection acts to lower the degree of the expression plasticity. We provide evidence for this process in a genomic region that harbors two PcG-regulated genes, polyhomeotic proximal (ph-p) and CG3835. We found a signature of positive selection in this gene region in European populations of D. melanogaster and investigated the region by means of reporter gene assays. The target of selection is located in the intergenic fragment between the two genes. It overlaps with the promoters of both genes and an experimentally validated Polycomb response element (PRE). This fragment harbors five sequence variants that are highly differentiated between European and African populations. The African alleles confer a temperature-induced plasticity in gene expression, which is typical for PcG-mediated gene regulation, whereas thermosensitivity is reduced for the European alleles.


G-protein inactivator RGS6 mediates myocardial cell apoptosis and cardiomyopathy caused by doxorubicin.
Clinical use of the widely used chemotherapeutic agent doxorubicin is limited by life-threatening cardiotoxicity. The mechanisms underlying doxorubicin-induced cardiomyopathy and heart failure remain unclear but are thought to involve p53-mediated myocardial cell apoptosis. The tripartite G-protein inactivating protein RGS6 has been implicated in reactive oxygen species (ROS) generation, ATM/p53 activation, and apoptosis in doxorubicin-treated cells. Thus, we hypothesized that RGS6, the expression of which is enriched in cardiac tissue, might also be responsible for the pathologic effects of doxorubicin treatment in heart. In this study, we show that RGS6 expression is induced strongly by doxorubicin in the ventricles of mice and isolated ventricular myocytes via a posttranscriptional mechanism. While doxorubicin-treated wild-type (WT) mice manifested severe left ventricular dysfunction, loss of heart and body mass, along with decreased survival 5 days after doxorubicin administration, mice lacking RGS6 were completely protected against these pathogenic responses. Activation of ATM/p53 apoptosis signaling by doxorubicin in ventricles of WT mice was also absent in their RGS6(-/-) counterparts. Doxorubicin-induced ROS generation was dramatically impaired in both the ventricles and ventricular myocytes isolated from RGS6(-/-) mice, and the apoptotic response to doxorubicin in ventricular myocytes required RGS6-dependent ROS production. These results identify RGS6 as an essential mediator of the pathogenic responses to doxorubicin in heart, and they argue that RGS6 inhibition offers a rational means to circumvent doxorubicin cardiotoxicity in human patients with cancer.


Congenital inclusion cyst of the subgaleal space.
An unusual type of congenital subgaleal cyst, either dermoid or epidermoid, was found in 21 Nigerian infants. This entity was located in the midline of the scalp, anywhere from above the nasion to the inion, and occupied the subgaleal space. These cysts were noted soon after birth and gradually enlarged. They had no intracranial extension and were easily excised intact. Clinically, radiologically, and histologically they were similar to congenital inclusion dermoid cysts of the anterior fontanel. The histology and some of the peculiarities of these cysts are described. Although most of these cysts occur at the anterior fontanel, they can occur anywhere in the midline, and the subgaleal space of the anterior fontanel is not the exclusive site, as has been claimed by previous authors.


Conditional fuzzy clustering in the design of radial basis function neural networks.
This paper is concerned with the use of radial basis function (RBF) neural networks aimed at an approximation of nonlinear mappings from R(n) to R. The study is devoted to the design of these networks, especially their layer composed of RBF's, using the techniques of fuzzy clustering. Proposed is an idea of conditional clustering whose main objective is to develop clusters (receptive fields) preserving homogeneity of the clustered patterns with regard to their similarity in the input space as well as their respective values assumed in the output space. The detailed clustering algorithm is accompanied by extensive simulation studies.


Genome comparison and phylogenetic analysis of Orientia tsutsugamushi strains.
Orientia tsutsugamushi (OT) is an obligate intracellular bacterium belonging to the family Rickettsiaceae and is the causative agent of scrub typhus, or Tsutsugamushi disease. The complete genome sequences of two OT strains (Boryong and Ikeda) have recently been determined. In the present study, we performed a fine genome sequence comparison of these strains. Our results indicate that although the core gene set of the family Rickettsiaceae is highly conserved between the two strains, a common set of repetitive sequences have been explosively amplified in both genomes. These amplified repetitive sequences have induced extensive genome shuffling and duplications and deletions of many genes. On the basis of the results of the genome sequence comparison, we selected 11 housekeeping genes and carried out multilocus sequence analysis of OT strains using the nucleotide sequences of these genes. This analysis revealed for the first time the phylogenetic relationships of representative OT strains. Furthermore, the results suggest the presence of an OT lineage with higher potential for virulence, which may explain the clinical and epidemiological differences between 'classic' and 'new' types of Tsutsugamushi disease in Japan.


Actin immunoreactivity localizes with segregated microtubules and membraneous organelles and in the subaxolemmal region in the beta,beta'-iminodipropionitrile axon.
Using the peroxidase-antiperoxidase staining technique with monoclonal and polyclonal antibodies against actin, we found that, in beta,beta'-iminodipropionitrile (IDPN)-treated axons, actin immunoreactivity was codistributed with segregated microtubules and membranous organelles in the central region and excluded from the peripheral axoplasm occupied by neurofilaments. Actin immunoreactivity was also present in the subaxolemmal region. Fast axonal transport is localized in the central region of the IDPN axon (Papasozomenos et al., 1982a). As both microtubules and actin are present in the central region of IDPN axons, a possible role of actin in fast axonal transport warrants further investigation.


Lung mass density analysis using deep neural network and lung ultrasound surface wave elastography.
Lung mass density is directly associated with lung pathology. Computed Tomography (CT) evaluates lung pathology using the Hounsfield unit (HU) but not lung density directly. We have developed a lung ultrasound surface wave elastography (LUSWE) technique to measure the surface wave speed of superficial lung tissue. The objective of this study was to develop a method for analyzing lung mass density of superficial lung tissue using a deep neural network (DNN) and synthetic data of wave speed measurements with LUSWE. The synthetic training dataset of surface wave speed, excitation frequency, lung mass density, and viscoelasticity from LUSWE (788,000 in total) was used to train the DNN model. The DNN was composed of 3 hidden layers of 1024 neurons for each layer and trained for 10 epochs with a batch size of 4096 and a learning rate of 0.001 with three types of optimizers. The test dataset (4000) of wave speeds at three excitation frequencies (100, 150, and 200 Hz) and shear elasticity of superficial lung tissue was used to predict the lung density and evaluate its accuracy compared with predefined lung mass densities. This technique was then validated on a sponge phantom experiment. The obtained results showed that predictions matched well with test dataset (validation accuracy is 0.992) and experimental data in the sponge phantom experiment. This method may be useful to analyze lung mass density by using the DNN model together with the surface wave speed and lung stiffness measurements.


Diabetes improvement and resolution following laparoscopic vertical sleeve gastrectomy (LVSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures: a systematic review of randomized controlled trials.
The prevalence of type 2 diabetes is growing in both developed and developing countries and is strongly linked with the prevalence of obesity. Bariatric surgical procedures such as laparoscopic vertical sleeve gastrectomy (LVSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are increasingly being utilized to manage related comorbid chronic conditions, including type 2 diabetes. A systematic review of randomized controlled trials (RCTs) was undertaken using the PRISMA guidelines to investigate the postoperative impact on diabetes resolution following LVSG versus LRYGB. Seven RCTs involving a total of 732 patients (LVSG n = 365, LRYGB n = 367) met inclusion criteria. Significant diabetes resolution or improvement was reported with both procedures across all time points. Similarly, measures of glycemic control (HbA1C and fasting blood glucose levels) improved with both procedures, with earlier improvements noted in LRYGB that stabilized and did not differ from LVSG at 12 months postoperatively. Early improvements in measures of insulin resistance in both procedures were also noted in the studies that investigated this. This systematic review of RCTs suggests that both LVSG and LRYGB are effective in resolving or improving preoperative type 2 diabetes in obese patients during the reported 3- to 5-year follow-up periods. However, further studies are required before longer-term outcomes can be elucidated. Areas identified that need to be addressed for future studies on this topic include longer follow-up periods, standardized definitions and time point for reporting, and financial analysis of outcomes obtained between surgical procedures to better inform procedure selection.


Prescription information leaflets: a pilot study in general practice.
Leaflets containing information about medicines were issued to 56 patients prescribed penicillins and 43 patients prescribed non-steroidal anti-inflammatory drugs. The patients were interviewed between four and 10 days later and their responses compared with those of 65 patients prescribed penicillin and 33 prescribed nonsteroidal anti-inflammatory drugs who did not receive a leaflet. Patients who received a leaflet were more likely to be completely satisfied with their treatment and with the information they had been given. They were also more likely to know the name of their medicine and much more aware of potential unwanted effects. Although there was no evidence that knowledge increased the incidence of adverse effects, when these did occur they were more likely to be recognised as being due to the medicine. Further studies of other leaflets are warranted, including leaflets for drugs that are taken long term.


Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma.
Scirrhous hepatocellular carcinoma is a rare ill-defined morphological subtype of hepatocellular carcinoma characterized by marked stromal fibrosis. This variant can be difficult to distinguish from intrahepatic cholangiocarcinoma and metastatic adenocarcinoma, especially on needle biopsies. We performed immunohistochemistry for hepatocellular and adenocarcinoma-associated markers on 20 scirrhous hepatocellular carcinoma cases and compared the results with classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Scirrhous hepatocellular carcinomas were significantly less likely to be HepPar-1 positive than classical hepatocellular carcinomas (26% and 74%, respectively; P<0.001) and were significantly more likely to express adenocarcinoma-associated markers such as epithelial cell adhesion molecule (63 vs 11%; P<0.001), cytokeratin 19 (26 vs 2%; P<0.001), and cytokeratin 7 (53 vs 2%; P<0.001). At least one of these adenocarcinoma-related markers was positive in 80% of scirrhous hepatocellular carcinoma cases. Glypican 3 and arginase were positive in 79% and 85% of cases of scirrhous hepatocellular carcinoma, respectively; the combined use of these two markers yielded 100% sensitivity for scirrhous hepatocellular carcinoma. In conclusion, the scirrhous morphology, absence of HepPar-1 staining, and frequent positivity with adenocarcinoma-related markers in scirrhous hepatocellular carcinoma can lead to an erroneous diagnosis of adenocarcinoma. Glypican 3 and arginase are the most reliable markers for identifying hepatocellular differentiation in this setting.


Gastrointestinal Manifestations of Lead Poisoning: A Brief Report.
Gastrointestinal (GI) manifestations of lead poisoning include abdominal pain, constipation, and diarrhea. Depending on the severity of a symptom, surgical consultation is required. The present study aimed to make a comparison between the mean blood lead levels of patients hospitalized for lead toxicity and the various Gl symptoms. A retrospective cross-sectional study was performed in 2020 at Khorshid Hospital, the main regional referral center for poisoned patients (Isfahan, Iran). A total of 82 patients aged ≥18 years who were hospitalized for lead poisoning during 2017-2018 were included in the study. Patients' information was extracted from hospital medical records, including demographic information, clinical manifestations, blood lead levels, and treatment outcome. The mean age of the patients was 48.18±11.9 years, 91.5% were men, and 62.2% suffered from multiple GI symptoms, with abdominal pain being predominant (31.7%). Blood lead levels in patients with multiple GI symptoms were higher than those with only one symptom (P=0.01). Surgical consultation was required in 14.6% of the patients. Multiple GI symptoms were the main predictive factor for blood lead levels above 70 mg/dL (P=0.03, Odds ratio=3.06, 95% CI=1.09-8.61). Given the prevalence of abdominal pain and its association with elevated blood lead levels, differential diagnosis of abdominal pain should include lead toxicity.


Duplication of the inferior vena cava in a patient presenting for IVC filter placement.
Given the complex embryogenesis of the inferior vena cava (IVC), anatomic variations are commonly encountered. Duplication of the IVC occurs in up to 2.8% of the population. Though asymptomatic, a duplicated IVC has important clinical implications when attempting caval filtration. We present the case of a 45- year-old male with factor V leiden and protein C deficiency, who required cessation of warfarin anticoagulation in preparation for cervical laminectomy. The patient had a duplicated IVC and required placement of a caval filter in each IVC.


Multimodal assessment of early tumor response to chemotherapy: comparison between diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles targeted at cell death.
The aim of this study was to determine the value of different magnetic resonance (MR) protocols to assess early tumor response to chemotherapy. We used a murine tumor model (TLT) presenting different degrees of response to three different cytotoxic agents. As shown in survival curves, cyclophosphamide (CP) was the most efficient drug followed by 5-fluorouracil (5-FU), whereas the etoposide treatment had little impact on TLT tumors. Three different MR protocols were used at 9.4 Tesla 24 h post-treatment: diffusion-weighted (DW)-MRI, choline measurement by (1) H MRS, and contrast-enhanced MRI using ultrasmall iron oxide nanoparticles (USPIO) targeted at phosphatidylserine. Accumulation of contrast agent in apoptotic tumors was monitored by T(2) -weighted images and quantified by EPR spectroscopy. Necrosis and apoptosis were assessed by histology. Large variations were observed in the measurement of choline peak areas and could not be directly correlated to tumor response. Although the targeted USPIO particles were able to significantly differentiate between the efficiency of each cytotoxic agent and best correlated with survival endpoint, they present the main disadvantage of non-specific tumor accumulation, which could be problematic when transferring the method to the clinic. DW-MRI presents a better compromise by combining longitudinal studies with a high dynamic range; however, DW-MRI was unable to show any significant effect for 5-FU. This study illustrates the need for multimodal imaging in assessing tumor response to treatment to compensate for individual limitations.


[Laparoscopic radical cystectomy. The new gold standard for bladder carcinoma?].
The experience of a renowned Latin American laparoscopic center is reported and the differences with the open technique are thoroughly discussed. During a 7 year period a total of 85 laparoscopic cystectomies were performed; in 92%of the cases urinary diversion was performed extracorporeally. This accounted for: 14 anterior exanterations, 50 radical cystoprostatectomies, 7 radical cystectomies and 14 simple cystectomies. Male to female ratio was 3:1. Mean patient age was 63 years (range 29 to 83). Mean Body Mass Index (BMI) was 28 kg/m2(range 20 to 47). Operative data and long term results are analyzed. All 85 procedures were completed laparoscopically without need for conversion to open surgery. Orthotopic neobladder, Santiago pouch, Studer, Fontana and Le Bag were performed in 42, 13, 16, 12 and 1 case respectively. Ileal conduit, Indiana pouch and Mainz II were employed in 24, 10 and 9 cases respectively. All Mainz II were performed intracorporeally. Mean operative time and blood loss were 279 minutes (range 180 to 375) and 436 ml (range 50 to 1.500) respectively. A total of 8 patients (11%) presented perioperative complications: 5 vascular lesions, 2 eviscerations and 2 septicemias. Delayed complications were observed in 7 cases (9%); 3 urinary sepsis, 1 ureteral stenosis, 2 spontaneous ruptures and 1 mesenteric ischemia. Mean hospital stay was 8.8 days (range de 4 to 28). There was no operative mortality. Mean follow-up was 18 months (range 2 to 68 months). Ten patients (13%) presented disease progression and death. Laparoscopic radical cystectomy is associated with diminished operative bleeding, time to oral intake and hospital stay. Though this is a reproducible technique it demands a very long learning curve.


The influence of food on food intake: methodological problems and mechanisms of action.
Emphasis has been placed on the understanding of the regulation of food intake in the hope of aiding the battle against obesity and of helping to ameliorate the anorexia of cancer and eating disorders. Available data suggest that the regulatory system is multifaceted and complex. This review focuses on current research on the regulation of appetite and satiety by carbohydrates, fats, and proteins as well as by artificial sweeteners. Some methodological problems and potential mechanisms of action at the biochemical level are discussed. Evidence suggests that organisms are more successful in defending against calorie dilution than in adjusting to increases in calories. The implications of that defense relative to the use of ersatz nutrients are explored.


A Gulf Stream frontal eddy harbors a distinct microbiome compared to adjacent waters.
Mesoscale oceanographic features, including eddies, have the potential to alter productivity and other biogeochemical rates in the ocean. Here, we examine the microbiome of a cyclonic, Gulf Stream frontal eddy, with a distinct origin and environmental parameters compared to surrounding waters, in order to better understand the processes dominating microbial community assembly in the dynamic coastal ocean. Our microbiome-based approach identified the eddy as distinct from the surround Gulf Stream waters. The eddy-associated microbial community occupied a larger area than identified by temperature and salinity alone, increasing the predicted extent of eddy-associated biogeochemical processes. While the eddy formed on the continental shelf, after two weeks both environmental parameters and microbiome composition of the eddy were most similar to the Gulf Stream, suggesting the effect of environmental filtering on community assembly or physical mixing with adjacent Gulf Stream waters. In spite of the potential for eddy-driven upwelling to introduce nutrients and stimulate primary production, eddy surface waters exhibit lower chlorophyll a along with a distinct and less even microbial community, compared to the Gulf Stream. At the population level, the eddy microbiome exhibited differences among the cyanobacteria (e.g. lower Trichodesmium and higher Prochlorococcus) and in the heterotrophic alpha Proteobacteria (e.g. lower relative abundances of specific SAR11 phylotypes) versus the Gulf Stream. However, better delineation of the relative roles of processes driving eddy community assembly will likely require following the eddy and surrounding waters since inception. Additionally, sampling throughout the water column could better clarify the contribution of these mesoscale features to primary production and carbon export in the oceans.


Human and Zoonotic Dermatophytoses: Epidemiological Aspects.
Dermatophytes are a group of molds characterized by the ability to produce keratinases, thereby carving out for themselves specific ecological niches. Their traditional division into three genera, Trichophyton, Microsporum, and Epidermophyton has been expanded to nine and the species in each genus were modified. Dermatophytes are among the most prevalent causes of human and animal mycoses. Their epidemiology is influenced by various factors. These factors may be evolutive such as the predilected environment of the fungus, namely, humans (anthropophilic), animals (zoophilic), or environment (geophilic), is evolutionary and thus may require centuries to develop. Many other factors, however, result from a variety of causes, affecting the epidemiology of dermatophytoses within a shorter time frame. This review aims at summarizing the factors that have modified the epidemiology of dermatophytoses during the last decades. Geographic and climatic conditions, demography such as age and gender, migration, socio-economic conditions, lifestyle, and the environment have had an impact on changes in the epidemiology of dermatophytoses, as have changes in the pattern of human interaction with animals, including pets, farm, and wild animals. A typical example of such changes is the increased prevalence of Trichophyton tonsurans, which spread from Latin America to the United States and subsequently becoming a frequent etiological agent of tinea capitis in Africa, Middle East, and other areas. The comprehension of the epidemiology of dermatophytoses has a major bearing on their prevention and treatment. Since it is undergoing continuous changes, periodic assessments of the most recent developments of this topic are required. This article aims at providing such an overview.


P-glycoprotein-mediated multidrug resistance: experimental and clinical strategies for its reversal.
The study of the cellular, biochemical, and molecular biology and pharmacology of MDR has provided one of the most active and exciting areas within cancer research and one that holds great promise for translation into clinical benefit. While convincing evidence for the functional role of P-gp in mediating clinical drug resistance in humans remains elusive, studies of the clinical expression of P-gp and trials of chemosensitizers with cancer chemotherapy suggest "resistance modification" strategies may be effective in some tumors with intrinsic or acquired drug resistance. However, even if P-gp-associated MDR proves to be a relevant and reversible cause of clinical drug resistance, numerous problems remain to be solved before effective clinical chemosensitization may be achieved. Such factors as absorption, distribution, and metabolism; the effect of chemosensitizers on chemotherapeutic drug clearance; toxicity to normal tissues expressing P-gp; and the most efficacious modulator regimens all remain to be defined in vivo. Clearly, the identification of more specific, potent, and less clinically toxic chemosensitizers for clinical use remains critical to the possible success of this approach. Nonetheless, the finding that a number of pharmacological agents can antagonize a well-characterized form of experimental drug resistance provides promise for potential clinical applications. Further study of chemosensitizers in humans and the rational design of novel chemosensitizers with improved activity should define the importance of MDR in clinically resistant cancer.


[Rational combinations of hormonal and cytostatic agents in disseminated forms of breast cancer].
The report deals with the results of chemotherapy of 25 cases of advanced breast cancer. The patients had received tamoxifen + diethylstilbestrol (or chlorotrianizen) to stimulate a short-term proliferation in tumor and to potentiate the effect of cytostatic drugs. Complete regression of tumor was observed in I case and partial regression--in 12 cases (overall response--52%). Tumor growth stimulation effect was assessed on the basis of changes in DNA synthesis rate and proliferative pool as evidenced by repeated biopsy of tumor.


Controlling the fractal dimension in self-assembly of terpyridine modified insulin by Fe2+ and Eu3+ to direct in vivo effects.
Metal ion-induced self-assembly (SA) of proteins into higher-order structures can provide new, dynamic nano-assemblies. Here, the synthesis and characterization of a human insulin (HI) analog modified at LysB29 with the tridentate chelator 2,2':6',2''-terpyridine (Tpy) is described. SA of this new insulin analog (LysB29Tpy-HI) in the presence of the metal ions Fe2+ and Eu3+ at different concentrations was studied in solution by fluorescence luminescence and CD spectroscopy, dynamic light scattering, and small-angle X-ray scattering, while surface assembly was probed by AFM. Unique oligomerization was observed in solution, as Fe2+ yielded small magenta-colored discrete non-native assemblies, while Eu3+ caused the formation of large fractal assemblies. Binding of both metal ions to Tpy was demonstrated spectroscopically, and emission lifetime experiments revealed a distinct Eu3+ coordination geometry that included two water molecules. SAXS suggested that LysB29Tpy-HI with Fe2+ oligomerized to a discrete, roughly octameric species, while LysB29Tpy-HI with Eu3+ gave very large assemblies that could be modelled as fractals. The fractal dimensionality increased with the Eu3+ concentration. We propose that this is a consequence of Eu3+ binding to both Tpy and to free carboxylic acid groups on the insulin surface. LysB29Tpy-HI maintained insulin receptor affinity, and showed extended blood glucose lowering and plasma concentration after subcutaneous injection in rats. The combination of metal ion directed SA and native SA provides control of nano-scale fractal dimensionality and points towards use in therapeutics.


Ultrastructure of endocrine-like cells in lamina propria of human gastric mucosa.
Endocrine cells of gastric and gut mucosa are commonly thought to be present only within mucosal glands. In a previous report, we described argyrophilic cells in the lamina propria in 40% of surgical gastric specimens, using light microscopy. All these patients had chronic gastritis. Argyrophilia, however, is a non-specific reaction which could occur in other than endocrine cells. The present study was undertaken to describe the ultrastructure of argyrophil cells in the lamina propria. In five patients with chronic gastritis, endoscopic biopsies were taken from the fundic, intermediate, and pyloric areas of the stomach. Single and/or clustered argyophil cells were seen by light microscopy in the lamina propria of the intermediate and pyloric areas. On electron-microscopy, these cells had the following characteristics of endocrine-like cells: they were characterised by numerous electron dense granules in the cytoplasm, 100-300 nm in diameter; the cytoplasm contained poorly-developed rough endoplasmic reticulum and well-developed smooth endoplasmic reticulum with occasional vesicles. Immunostaining gave negative results for various gastrointestinal hormones. These ultrastructural characteristics of lamina propria cells are similar to endocrine cells of the APUD series. We conclude that endocrine-like cells occur in the lamina propria of the human stomach in the presence of chronic gastritis.


Metabolic acidosis in dextran-induced anaphylactic reactions.
Results of arterial blood gas and acid-base balance analyses were analyzed in 50 patients suffering from dextran-induced anaphylactic reactions. Metabolic acidosis was always present in severe cases, leading to cardiac arrest, and also frequently found in those with less severe reactions with only slightly impaired circulation. Bronchospastic respiratory signs were frequently encountered but acidosis was noted to develop even without these symptoms. The severity of the acidosis was generally underestimated during treatment. Arterial PO2 and PCO2 were not significantly affected during these reactions.


Antimicrobial Resistance in Typhoidal Salmonella: Surveillance for Enteric Fever in Asia Project, 2016-2019.
Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan. From September 2016-September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric fever. Antimicrobial resistance of isolates was determined by disc diffusion using Clinical and Laboratory Standard Institute cut-off points. We reported the frequency of multidrug resistance (MDR)(resistance to ampicillin, cotrimoxazole, and chloramphenicol), extensive drug resistance (XDR) (MDR plus non-susceptible to fluoroquinolone and any 3rd generation cephalosporins), and fluoroquinolone (FQ) and azithromycin non-susceptibility. We enrolled 8,705 blood culture confirmed enteric fever cases: 4,873 (56%) from Bangladesh, 1,602 (18%) from Nepal and 2,230 (26%) from Pakistan. Of these, 7,591 (87%) were Salmonella Typhi and 1114 (13%) were S. Paratyphi. MDR S. Typhi was identified in 17% (701/4065) of isolates in Bangladesh, and 1% (19/1342) in Nepal. In Pakistan, 16 % (331/2084) of S. Typhi isolates were MDR, and 64% (1319/2074) were XDR. FQ nonsusceptibility among S. Typhi isolates was 98% in Bangladesh, 87% in Nepal, and 95% in Pakistan. Azithromycin non-susceptibility was detected in 77 (2%) in Bangladesh, 9 (.67%) in Nepal and 9 (.59%) isolates in Pakistan. In Pakistan, three (2%) S. Paratyphi isolates were MDR; no MDR S. Paratyphi was reported from Bangladesh or Nepal. Although AMR against S. Paratyphi was low across the three countries, there was widespread drug resistance among S. Typhi, including FQ non-susceptibility and the emergence of XDR S. Typhi in Pakistan, limiting treatment options. As typhoid conjugate vaccine (TCV) is rolled out, surveillance should continue to monitor changes in AMR to inform policies and to monitor drug resistance in S. Paratyphi, for which there is no vaccine.


DNA structure, nucleosome placement and chromatin remodelling: a perspective.
A major question in chromatin biology is to what extent the sequence of DNA directly determines the genetic and chromatin organization of a eukaryotic genome? We consider two aspects to this question: the DNA sequence-specified positioning of nucleosomes and the determination of NDRs (nucleosome-depleted regions) or barriers. We argue that, in budding yeast, while DNA sequence-specified nucleosome positioning may contribute to positions flanking the regions lacking nucleosomes, DNA thermodynamic stability is a major component determinant of the genetic organization of this organism.


Dissection of estrogen receptor alpha signaling pathways in osteoblasts using RNA-sequencing.
The effects of 17-β-estradiol in osteoblasts are primarily mediated by the nuclear transcription factors, estrogen receptor (ER)α and ERβ. ERs function through three general modes of action: DNA-binding dependent through estrogen response elements (EREs; designated nuclear ERE signaling); nuclear signaling via protein-protein interactions to other transcription factors (nuclear non-ERE signaling); and extra-nuclear signaling (membrane-bound functions of ERs). Identification of the specific transcriptional signatures regulated by each of these modes of action should contribute to an enhanced understanding of estrogen signaling in osteoblasts. To achieve this goal, we utilized specific mutations of ERα that eliminate the ability of the receptor to signal through a specific mode of action. The non-classical ERα knock-in (NERKI) mutation is incapable of signaling through direct DNA binding to EREs and the nuclear only ERα (NOER) mutation eliminates all membrane-localized signaling. Comparison of the gene expression patterns elicited by these mutations with the wild-type ERα (WT) pattern provides mode-specific data concerning transcriptional regulation by ERα. We expressed these constructs in the ER-negative osteoblastic cell line hFOB (-/+ estrogen) and performed global RNA-sequencing. Using a series of pair-wise comparisons, we generated three lists of genes that were regulated either by the nuclear ERE-dependent, nuclear ERE-independent, or extra-nuclear actions of ERα. Pathway and gene ontology analyses revealed that genes regulated through the nuclear ERE and nuclear non-ERE pathways were largely involved in transcriptional regulation, whereas genes regulated through extra-nuclear mechanisms are involved in cytoplasmic signaling transduction pathways. We also intersected our data with genes linked to bone density and fractures from a recent genome-wide association study and found 25 of 72 genes (35%) regulated by estrogen. These data provide a comprehensive list of genes and pathways targeted by these specific modes of ERα action and suggest that "mode-specific" ligands could be developed to modulate specific ERα functionality in bone.


The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts.
The E8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide which contributes to cell transformation by conferring anchorage-independent growth. Using an in vitro translation system, we show that the E8 polypeptide binds to ductin, the 16-kDa proteolipid that forms transmembrane channels in both gap junctions and vacuolar H+-ATPase. This association is not due to nonspecific hydrophobic interactions. PPA1, a Saccharomyces cerevisiae polypeptide homologous (with 25% identity) to ductin, does not complex with E8. Furthermore, E5B, structurally similar to E8 but with no transforming activity, does not form a complex with ductin. Primary bovine fibroblasts expressing E8 show a loss of gap junctional intercellular communication, and it is suggested that this results from the interaction between E8 and ductin.


Electric urban delivery trucks: energy use, greenhouse gas emissions, and cost-effectiveness.
We compare electric and diesel urban delivery trucks in terms of life-cycle energy consumption, greenhouse gas (GHG) emissions, and total cost of ownership (TCO). The relative benefits of electric trucks depend heavily on vehicle efficiency associated with drive cycle, diesel fuel price, travel demand, electric drive battery replacement and price, electricity generation and transmission efficiency, electric truck recharging infrastructure, and purchase price. For a drive cycle with frequent stops and low average speed such as the New York City Cycle (NYCC), electric trucks emit 42-61% less GHGs and consume 32-54% less energy than diesel trucks, depending upon vehicle efficiency cases. Over an array of possible conditions, the median TCO of electric trucks is 22% less than that of diesel trucks on the NYCC. For a drive cycle with less frequent stops and high average speed such as the City-Suburban Heavy Vehicle Cycle (CSHVC), electric trucks emit 19-43% less GHGs and consume 5-34% less energy, but cost 1% more than diesel counterparts. Considering current and projected U.S. regional electricity generation mixes, for the baseline case, the energy use and GHG emissions ratios of electric to diesel trucks range from 48 to 82% and 25 to 89%, respectively.


Substrate specificity and colorimetric assay for recombinant TrzN derived from Arthrobacter aurescens TC1.
The TrzN protein, which is involved in s-triazine herbicide catabolism by Arthrobacter aurescens TC1, was cloned and expressed in Escherichia coli as a His-tagged protein. The recombinant protein was purified via nickel column chromatography. The purified TrzN protein was tested with 31 s-triazine and pyrimidine ring compounds; 22 of the tested compounds were substrates. TrzN showed high activity with sulfur-substituted s-triazines and the highest activity with ametryn sulfoxide. Hydrolysis of ametryn sulfoxide by TrzN, both in vitro and in vivo, yielded a product(s) that reacted with 7-chloro-4-nitrobenz-2-oxa-1,3-diazole (NBD-Cl) to generate a diagnostic blue product. Atrazine chlorohydrolase, AtzA, did not hydrolyze ametryn sulfoxide, and no color was formed by amending those enzyme incubations with NBD-Cl. TrzN and AtzA could also be distinguished by reaction with ametryn. TrzN, but not AtzA, hydrolyzed ametryn to methylmercaptan. Methylmercaptan reacted with NBD-Cl to produce a diagnostic yellow product having an absorption maximum at 420 nm. The yellow color with ametryn was shown to selectively demonstrate the presence of TrzN, but not AtzA or other enzymes, in whole microbial cells. The present study was the first to purify an active TrzN protein in recombinant form and develop a colorimetric test for determining TrzN activity, and it significantly extends the known substrate range for TrzN.


Genetic susceptibility to Hodgkin's lymphoma and to secondary cancer: workshop report.
Although the occurrence of familial Hodgkin's lymphoma (HL) is a rare event, genetic susceptibility as a cause of HL and its influence on treatment outcome may not be rare. However, results obtained from the analysis of HL families will probably have broad implications with regard to understanding common pathogenic factors leading to the development of the disease. The description of anticipation among the affected offspring of HL patients further strengthens the view that heritable factors contribute to development of HL. Moreover, the finding that particular human leukocyte antigen (HLA) alleles are associated with susceptibility to HL may be regarded as a hint to the presence of an as yet undefined infectious agent, leading to the growth of a malignant lymphoma cell clone in those patients that are more susceptible to this agent due to their HLA genotype. In addition, since an intrinsic genomic instability was observed in a proportion of HL patients, it is plausible that these patients are not only susceptible to the causation of HL, but are also at a higher risk of developing therapy-related (TR) secondary cancers following treatment. Estimation of sister chromatid exchange was established as a tool to identify patients at higher risk of TR cancer. In this context the use of therapeutic agents known to increase genomic instability should be carefully considered prior to determing the best treatment. The future identification of heritable factors contributing to HL will be of importance both with regard to diagnosis as well as treatment of HL patients.


Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in oesophageal squamous cells of patients with Barrett's oesophagus.
In previous studies using oesophageal squamous cells from patients with Barrett's oesophagus (normal oesophageal squamous (NES)-B cells) and from patients without Barrett's oesophagus (NES-G cells), we showed that acid and bile salts induced caudal-related homeobox transcription factor 2 (CDX2) expression only in NES-B cells. CDX2, a transcription factor required to form intestinal epithelium, is a target of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signalling, which can be inhibited by aspirin. We explored mechanisms underlying differences between NES-B and NES-G cells in CDX2 expression and effects of aspirin on that CDX2 expression. We exposed NES-B and NES-G cells to acid and bile salts, with and without aspirin, and evaluated effects on IκB-NF-κB-PKAc complex activation, p65 NF-κB subunit function, and CDX2 expression. In both NES-B and NES-G cells, acid and bile salts activated nicotinamide adenine dinucleotide phosphate oxidase to generate H2O2, which activated the IκB-NF-κB-PKAc complex. NES-B cells exhibited higher levels of phosphorylated IκB and p65 and greater NF-κB transcriptional activity than NES-G cells, indicating greater IκB-NF-κB-PKAc complex activation by acid and bile salts in NES-B cells, and p65 siRNA prevented their increased expression of CDX2. Aspirin blocked IκB phosphorylation, p65 nuclear translocation, CDX2 promoter activation and CDX2 expression induced by acid and bile salts in NES-B cells. Differences between NES-B and NES-G cells in NF-κB activation by acid and bile salts can account for their differences in CDX2 expression, and their CDX2 expression can be blocked by aspirin. These findings might explain why some patients with GORD develop Barrett's oesophagus while others do not, and why aspirin might protect against development of Barrett's oesophagus.


Sample-Specific Prediction Error Measures in Spectroscopy.
In applied spectroscopy, the purpose of multivariate calibration is almost exclusively to relate analyte concentrations and spectroscopic measurements. The multivariate calibration model provides estimates of analyte concentrations based on the spectroscopic measurements. Predictive performance is often evaluated based on a mean squared error. While this average measure can be used in model selection, it is not satisfactory for evaluating the uncertainty of individual predictions. For a calibration, the uncertainties are sample specific. This is especially true for multivariate calibration, where interfering compounds may be present. Consider in-line spectroscopic measurements during a chemical reaction, production, etc. Here, reference values are not necessarily available. Hence, one should know the uncertainty of a given prediction in order to use that prediction for telling the state of the chemical reaction, adjusting the process, etc. In this paper, we discuss the influence of variance and bias on sample-specific prediction errors in multivariate calibration. We compare theoretical formulae with results obtained on experimental data. The results point towards the fact that bias contribution cannot necessarily be neglected when assessing sample-specific prediction ability in practice.


Short-term effect of a smartphone application on the mental health of university students: A pilot study using a user-centered design self-monitoring application for mental health.
Despite the widespread recognition of the importance of mental health in young people, only a small proportion of young people with a mental disorder, including university students, receive mental health care. We developed a smartphone application (Mental App) for the university students and examined the effects of the app on their mental health. The app was designed according to a questionnaire survey conducted before this study. The Mental App was installed on the students' smartphone and the psychological tests (the Link Stigma Scale, the Center for Epidemiologic Studies Depression Scale, and the 12-item General Health Questionnaire) were performed on the same day. After using the App for two weeks, the students completed a questionnaire survey and underwent the same psychological tests. We compared the results between the app user and non-user group. A total of 68 students participated, of which 57 students completed the study (app user group, n = 28; control group, n = 29). The mean number of days spent using the app was 5.66 ± 3.16 (mean ± SD). The mean total screen time of the app was 9:03 ± 06:41(min:sec). The mean number of total actions (screen taps or swipes) was 161.91 ± 107.34. There were no significant between-group differences in the ΔLink Stigma Scale score (-0.11 ± 4.28 vs. -0.59 ± 3.30, p = 0.496) or the ΔCenter for Epidemiologic Studies Depression Scale score (-4.39 ± 7.13 vs. -2.07 ± 8.78, p = 0.143). There was a significant between-group difference in the ΔGeneral Health Questionnaire score (-2.21± 2.23 vs. -0.17 ± 2.69, p = 0.007). This non-randomized controlled pilot study indicates that the app we developed, may provide effective mental health care for university students, even in the short-term. Trial registration: UMIN000040332.


Information theoretic approach for assessing image fidelity in photon-counting arrays.
The method of photon-counting integral imaging has been introduced recently for three-dimensional object sensing, visualization, recognition and classification of scenes under photon-starved conditions. This paper presents an information-theoretic model for the photon-counting imaging (PCI) method, thereby providing a rigorous foundation for the merits of PCI in terms of image fidelity. This, in turn, can facilitate our understanding of the demonstrated success of photon-counting integral imaging in compressive imaging and classification. The mutual information between the source and photon-counted images is derived in a Markov random field setting and normalized by the source-image's entropy, yielding a fidelity metric that is between zero and unity, which respectively corresponds to complete loss of information and full preservation of information. Calculations suggest that the PCI fidelity metric increases with spatial correlation in source image, from which we infer that the PCI method is particularly effective for source images with high spatial correlation; the metric also increases with the reduction in photon-number uncertainty. As an application to the theory, an image-classification problem is considered showing a congruous relationship between the fidelity metric and classifier's performance.


Clinical evaluation of the FilmArray blood culture identification panel in identification of bacteria and yeasts from positive blood culture bottles.
The FilmArray platform (FA; BioFire, Salt Lake City, UT) is a closed diagnostic system allowing high-order multiplex PCR analysis with automated readout of results directly from positive blood cultures in 1 h. In the present study, we evaluated the clinical performance of the FilmArray blood culture identification (BCID) panel, which includes 19 bacteria, five yeasts, and three antibiotic resistance genes. In total, 206 blood culture bottles were included in the study. The FilmArray could identify microorganisms in 153/167 (91.6%) samples with monomicrobial growth. Thirteen of the 167 (7.8%) microorganisms were not covered by the FilmArray BCID panel. In 6/167 (3.6%) samples, the FilmArray detected an additional microorganism compared to blood culture. When polymicrobial growth was analyzed, the FilmArray could detect all target microorganisms in 17/24 (71%) samples. Twelve blood culture bottles that yielded a positive signal but showed no growth were also negative by FilmArray. In 3/206 (1.5%) bottles, the FilmArray results were invalid. The results of the FilmArray were reproducible, as demonstrated by the testing and retesting of five bottles in the same day and a longitudinal follow-up of five other blood cultures up to 4 weeks. The present study shows that the FilmArray is a rapid identification method with high performance in direct identification of bacteria and yeasts from positive blood culture bottles.


Direct and correlative phenotypic selection on life-history traits in three pre-industrial human populations.
Because natural selection acts simultaneously on several correlated traits, can be under both direct and correlative selection simultaneously. Correlative selection may either weaken or magnify the association between a trait and fitness. Direct effect of a single trait on fitness can be assessed by removing the effects of correlative selection with multivariate techniques. We studied the phenotypic selection on demographic life-history traits in three pre-industrial human populations, which experienced different mortality environments. We used path-analysis to estimate direct and correlative selection on different traits in females and males. Our results indicate substantial differences among the sexes in the force of phenotypic selection on key life-history traits. For females, the most important component of reproductive success was the age at first reproduction. Most important component of fitness for males was the quality of mate. In addition, our analysis revealed considerable among-population variation in the selection on life-history traits. These differences are in accord with the historical notes of among-population variation in the lifestyle and harshness of the environment, suggesting that among-population variation in life-history traits may have been a response to the environmental variation.


[Effects of 6-Shogaol on Notch signaling pathway in colonic epithelial cells of ulcerative colitis mice].
To observe the regulatory effect of 6-Shogaol on Notch signal pathway in colonic epithelial cells of mice with ulcerative colitis. Forty Kunming mice were randomly divided into normal group (n=10) and model group (n=30). The model of ulcerative colitis was induced by free drinking of 2% dextran sulfate sodium salt(DSS). After 15 days, the mice were divided into model group, 6-gingerenol group and positive control group with 10 mice in each group. Normal group and model group were treated with normal saline, 6-gingerenol group was treated with 6-Shogaol 100 mg/(kg·d), positive control group was treated with sulfasalazine 100 mg/(kg·d), for 20 days. The histopathological changes of colon were observed, and the expressions of Hes-1 and Math-1protein in colonic epithelial cells were detected by immunofluorescence double labeling method. The expressions of Notch-1, Hes-1 and Math-1 mRNA in colonic epithelial tissue were detected by RT-PCR. The expressions of Notch-1, Hes-1 and Math-1 protein in colonic epithelial tissue was detected by Western blot. Compared with the normal group, the expression of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of model group were significantly increased (P<0.01), while the relative expressions of Math-1 mRNA and protein were decreased significantly (P<0.01). Compared with the model group, the expressions of Notch-1 and Hes-1 protein and the relative expression of mRNA in colonic epithelium of 6-Shogaol group and sulfasalazine group were decreased significantly(P<0.01), while the relative expressions of Math-1 mRNA and protein were increased significantly(P<0.01). 6-Shogaol can inhibit the over activation of Notch pathway and regulate the balance of differentiation between colonic epithelialabsorptive cell line and secretory cell line and repair damaged mucosal tissue.


Corrective photoepilation for improper hairline placement after hair transplantation.
Noncoherent filtered flashlamp pulsed light has not been used for correction of surgical problems after hair transplantation. To evaluate the clinical results of photoepilation in a patient with improper hairline placement after hair transplantation. A noncoherent filtered flashlamp pulsed light source was used to photoepilate the misplaced frontal hairline in a 37-year-old Caucasian man, skin phototype IV (Fitzpatrick scale), who suffered from common baldness grade IV (Ebling scale) and had undergone a hair transplant 6 years before. The frontal hairline received three treatment sessions at 2-month intervals with the following treatment parameters: 695 nm cutoff filter, fluence 38 J/cm2, 3.5-msec pulse duration, triple-pulse mode, and 30-msec delay. The gulfs received two treatment sessions with the same protocol. Final clinical aspect was good and no hair regrowth in the frontal hairline has been observed after 1.5 years of follow-up. Noncoherent filtered flashlamp pulsed light is a novel therapeutic choice that offers a nonsurgical solution to unnatural hairline after hair transplantation.


Comparative phylogenetic analysis of microbial communities in pristine and hydrocarbon-contaminated Alpine soils.
A molecular characterization of pristine and petroleum hydrocarbon-contaminated Alpine soils sampled in Tyrol (Austria) was performed. To identify predominant bacteria, PCR-amplified 16S rRNA gene fragments from five pristine and nine contaminated soils were analysed using denaturing gradient gel electrophoresis (DGGE). Sequencing and phylogenetic analyses demonstrated that the majority of the DGGE bands represented bacteria in the Actinobacteria and Proteobacteria phyla: 18 and 73%, respectively, in pristine soils, compared with 20 and 76%, respectively, in contaminated soils. A different distribution pattern of bacterial classes in the Proteobacteria was observed between pristine and contaminated soils. The relative proportion of microorganisms belonging to the Alphaproteobacteria was larger in pristine (46%) than in contaminated (24%) soils, while Betaproteobacteria and Gammaproteobacteria were detected only in the hydrocarbon-contaminated soils. This result compared favourably with earlier work in which hydrocarbon-degradation genotypes, largely pseudomonads and Acinetobacter, belonging to the Gammaproteobacteria, were enriched following oil hydrocarbon contamination. In contrast, members of the Actinobacteria phylum, represented by Rhodococcus and Mycobacterium, were found in pristine soils where contamination events had not occurred. The results demonstrate a significant shift in the microbial community structure in Alpine soils following contamination. Furthermore, more potentially novel phylotypes were found in the pristine soils than in the contaminated soils.


Effect of oral glutamine supplementation during bone marrow transplantation.
Because all patients receiving bone marrow transplant (BMT) and peripheral blood progenitor cell transplant (PBPCT) experience gastrointestinal (GI) toxicity from the preparative regimen of chemotherapy, with or without radiation, oral glutamine was administered during the preparatory regimen and after transplant to maintain GI structure and function. To evaluate effects of oral glutamine on nutritional status and overall outcome, a prospective, randomized, double-blinded study was performed on 58 autologous and allogeneic BMT patients. Patients received 30 g of oral glutamine or placebo daily. The trends of decreased median length of stay and the median number of days of total parenteral nutrition (TPN) were seen in the group supplemented with the >0.285-g/kg (the recommended dosage) dose of glutamine; however, there was no statistically significant difference in the nutritional status and overall patient outcome as assessed by days receiving TPN, number of days required until oral intake resumed, length of hospitalization, number of days and highest grade of mucositis, and quantity and number of days of diarrhea. This study does not support the hypothesis that oral glutamine may offer benefit. Further investigation is required regarding clinical tools for determining effectiveness, administration for tolerance and compliance, dosage, and potential of oral glutamine usage.


Tuning the performance of Fe-porphyrin aerogel-based PGM-free oxygen reduction reaction catalysts in proton exchange membrane fuel cells.
Fe-N-C catalysts are currently the leading candidates to replace Pt-based catalysts for the oxygen reduction reaction in proton exchange membrane fuel cells. To maximize their activity, it is necessary to optimize their structure to allow high active site density on one hand, and hierarchical porous structure that will allow good mass transport of reactants and products to and from the active sites on the other hand. Hence, the hierarchical structure of the catalyst plays an important role in the balance between the electrochemical active site density and the mass transport resistance. Aerogels were synthesized in this work to study the interplay between these two parameters. Aerogels are covalent organic frameworks with ultra-low density, high porosity, and large surface area. The relative ease of tuning the composition and pore structure of aerogels make them prominent candidates for catalysis. Herein, we report on a tunable Fe-N-C catalyst based on an Fe porphyrin aerogel, which shows high electrocatalytic oxygen reduction reaction activity with tunable hierarchical pore structure and studied the influence of the porous structure on the overall performance in proton exchange membrane fuel cells.


Complexation of uranyl (UO2)2+ with bidentate ligands: XRD, spectroscopic, computational, and biological studies.
Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.