Systemic adjuvant treatment of high-risk melanoma: the role of interferon alfa-2b and other immunotherapies.
Until recently, the prognosis of patients with deep primary melanomas or regionally metastatic nodal disease has been poor, with 5-year survival rates of 25-50%. The results of the Eastern Cooperative Oncology Group (ECOG) trial 1684 represent the first evidence of effective adjuvant therapy for these patients. Interferon alfa-2b (IFN-alpha 2b) administered at maximally tolerated doses for 1 year significantly improved both relapse-free and overall survival. The impact of interferon therapy was observed early during treatment and the effect was durable. The results of this trial represent a breakthrough in the treatment of high-risk resected cutaneous melanoma and identify the new reference standard for new cytokines, vaccines and combinations. The favourable results provide a strong impetus for redoubled research into immunotherapy for treatment of melanoma. Specifically, ganglioside vaccines have been identified that induce antibody responses and may affect patient outcome and peptide/protein vaccines that are recognised by the T-cell have been identified in large numbers. ECOG and the U.S. Intergroup are conducting a phase III trial (E1694) that compares GM2 vaccine to IFN-alpha 2b and a phase II trial evaluating concurrent or sequential use of interferon and vaccines for patients with resectable melanoma. They are also planning phase II trials of peptides for patients with metastatic unresectable melanoma. Laboratory analyses of the immune responses induced by IFN and the several vaccines are anticipated to reveal the fundamental immune mechanisms that are important for relapse-free survival and immunological control of melanoma.


CTBP1 and CTBP2 mutations underpinning neurological disorders: a systematic review.
C-terminal binding proteins (CtBP1/2) are transcriptional coregulators that play a significant role during vertebrate neurodevelopment. This systematic review aims to identify case reports with genetic variants in CTBP1 and CTBP2 associated with brain development syndromes.We screened different databases (PubMed, Scopus, Google Scholar, LILACS) by systematically searching journals and checking reference lists and citations of background papers. We found fourteen cases (10 males) from five papers carrying two pathogenic, heterozygous variants in the CTBP1 gene (13 individuals carried the missense mutation c.991C T, p.Arg342Trp, and one subject carrying the 2-base pair deletion c.1315_1316delCA, p.Gln439ValfsTer84). These mutations were de novo in 13 cases and one case of maternal germinal mosaicism. Two variants are in the same domain of the protein: Pro-Leu-Asp-Leu-Ser (PLDLS) C terminal. Patients with these mutations exhibit a phenotype with intellectual disability, HADDTS syndrome (hypotonia, ataxia, developmental delay, and tooth enamel defects), and cerebellar volume loss. We did not identify reported cases associated with homozygous mutations harbored in CTBP1. We did not identify any report of neurodevelopment phenotypes associated with heterozygous or homozygous CTBP2 mutations. Due to CTBP2/RIBEYE being a gene with dual function, identifying and interpreting the potential pathogenic variants is challenging.Further, homozygous mutations in the CTBP2 gene may be lethal. The mechanisms involved in the pathogenesis of neurodevelopment due to variants of these proteins have not yet been elucidated, despite some functional evidence. Further studies should be conducted to understand these transcription factors and their interaction with each other and their partners.


Regional cerebral blood flow characteristics and variations with age in resting normal subjects.
Regional cerebral blood flow (rCBF) was measured during resting in 97 normal subjects, 19-68 years old. The results showed that the mean CBF level decreased progressively with age. The decrease was more prominent in frontotemporal and inferior Rolandic areas bilaterally. Frontal areas showed the highest values in all age groups. This hyperfrontality weakened somewhat with age. Mean CBF in the right hemisphere was significantly higher than in the left, as was flow in superior frontal, inferior frontal, and parietal areas. These asymmetries were age invariant. The age-related decrease of rCBF is interpreted as reflecting aging of the brain per se, although the influence of asymptomatic brain disease can not be ruled out. The flow asymmetries are interpreted as being related to functional lateralization of some aspects of attentional activation.


[Identification of Chemical Constituents of the Leaves from Acanthopanax senticosus by UPLC-Q-TOF-MS/MS].
To analyze the chemical compositions of the leaves from Acanthopanax senticosus. Rapid identification of chemical constituents in the leaves of Acanthopanax senticosus by UPLC-Q-TOF-MS / MS. The chemical constituents were identified and speculated by using Peakview data processing software, the retention time, exact relative molecular mass, and cleavage fragments of MS / MS were detected. Chromatography-mass spectrometry conditions were as follows, the analysis was performed on Waters BEH C18column( 100 mm × 2. 1 mm,1. 7 μm) in gradient elution with a mobile phase of 0. 1% formic acid aqueous solution and 0. 1%formic acid acetonitrile, the flow rate was at 0. 3 m L / min, the data was collected by the negative and positive ion mode using ESI ion source. 30 compounds were identified and speculated by the standards and compounds of MS / MS, the references and Chemispider database. This method is fast, sensitive and comprehensive with the rapid identification of chemical constituents in the leaves of Acanthopanax senticosus, which will provide the evidences for perfecting the quality standard, and clarify the efficacy material base of the leaves of Acanthopanax senticosus.


Cranial MRI of small rodents using a clinical MR scanner.
Increasing numbers of small animal models are in use in the field of neuroscience research. Magnetic resonance imaging (MRI) provides an excellent method for non-invasive imaging of the brain. Using three-dimensional (3D) MR sequences allows lesion volumetry, e.g. for the quantification of tumor size. Specialized small-bore animal MRI scanners are available for high-resolution MRI of small rodents' brain, but major drawbacks of this dedicated equipment are its high costs and thus its limited availability. Therefore, more and more research groups use clinical MR scanners for imaging small animal models. But to achieve a reasonable spatial resolution at an acceptable signal-to-noise ratio with these scanners, some requirements concerning sequence parameters have to be matched. Thus, the aim of this paper was to present in detail a method how to perform MRI of small rodents brain using a standard clinical 1.5 T scanner and clinically available radio frequency coils to keep material costs low and to circumvent the development of custom-made coils.


Caldera collapse thresholds correlate with magma chamber dimensions.
Explosive caldera-forming eruptions eject voluminous magma during the gravitational collapse of the roof of the magma chamber. Caldera collapse is known to occur by rapid decompression of a magma chamber at shallow depth, however, the thresholds for magma chamber decompression that promotes caldera collapse have not been tested using examples from actual caldera-forming eruptions. Here, we investigated the processes of magma chamber decompression leading to caldera collapse using two natural examples from Aira and Kikai calderas in southwestern Japan. The analysis of water content in phenocryst glass embayments revealed that Aira experienced a large magmatic underpressure before the onset of caldera collapse, whereas caldera collapse occurred with a relatively small underpressure at Kikai. Our friction models for caldera faults show that the underpressure required for a magma chamber to collapse is proportional to the square of the depth to the magma chamber for calderas of the same horizontal size. This model explains why the relatively deep magma system of Aira required a larger underpressure for collapse when compared with the shallower magma chamber of Kikai. The distinct magma chamber underpressure thresholds can explain variations in the evolution of caldera-forming eruptions and the eruption sequences for catastrophic ignimbrites during caldera collapse.


Heavy metals in contact dermatitis: A review.
Contact dermatitis is an inflammatory skin reaction caused by direct contact with chemical substances in the environment and can either be irritant or allergic in nature. The clinical symptoms of contact dermatitis, include local skin rash, itching, redness, swelling, and lesions. Nowadays, 15-20% of people have some degree of contact dermatitis, which can be more or less severe. Immune responses in allergic contact dermatitis (ACD) are due to the effects of cytokines and allergen-specific CD4+ and CD8+ T cells on the skin. Acids and alkalis such as drain cleaners, plants such as poinsettias, hair colors, and nail polish remover, are all prominent causes of irritant contact dermatitis (ICDs). Heavy metals are metallic elements with a high atomic weight that are hazardous in low quantities and are known to cause dermatitis after systemic or local exposure. Nickel (Ni), chromium (Cr), lead (Pb), and copper (Cu) are among the most common heavy metals used in various industries. Metal allergies may cause ACD and also systemic contact dermatitis (SCD). Contact dermatitis is detected by laboratory tests such as patch testing, lymphocyte stimulation test (LST), and evaluation of cytokine production by primary cultures of peripheral blood mononuclear cells. This article presents an update on the epidemiological and clinical characteristics of ACD and SCD caused by three heavy metals (Cr, Cu, and Pb). Ni is not discussed due to recent coverage. Furthermore, the effects of contact sensitivity to some other heavy metals, such as gold (Au), cobalt (Co), palladium (Pd), and mercury (Hg) are discussed.


[The primary study on a novel protein binding to the death domain of the death receptor 4].
To clone and identify novel proteins binding to the death domain of the death receptor 4 (DR4). The yeast two-hybrid system was used for this study. Automatic sequencing was carried out for DNA sequencing. The sequence homology and the functional domains were analyzed by BLAST and the ScanProsite Tool softwares, respectively. Co-immunoprecipitate method was used to confirm human formyl peptide receptor-like 1 (FPRL1) binding specifically with DR4CD (the cytoplasmic domain of DR4) in HEK293T cells. Two positive clones, named as pADB1 and pADB2, were obtained. BLAST searching showed that the homology of the insert sequence of pADB1 with the mRNA of FPRL1 was 97%. The insert of pADB2 shared no homology with any known peptides in GeneBank. Co-immunoprecipitate analysis further confirmed that FPRL1 could bind to DR4CD in vivo specifically. FPRL1 may associate with DR4CD in vivo specifically. The functional studies of FPRL1 in signaling pathway mediated by TNF-related apoptosis inducing ligand (TRAIL) are in active progress in our laboratory.


Proteomic dataset: Profiling of membrane fraction of Escherichia coli isolated from Crohn's disease patients after adhesion and invasion experiments.
Crohn's disease (CD) is a type of inflammatory bowel disease (IDB). The endoscopic picture of Crohn's disease includes thickened submucosa, transmural inflammation, fissuring ulceration, and non-caseating granulomas. Intestinal microbiome dysbiosis has been described systematically in patients with IBD. In recent decades it was detailed that Escherichia coli, especially adherent-invasive E. coli (AIEC) pathotype, has been implicated in the pathogenesis of IBD, including Crohn's disease (Palmela, et al., 2018). In comparison with commensal strains of E. coli, AIEC strains have a large adhesive-invasive potential therefore its surface composition is of great interest. We presented a dataset of the membrane proteins of strains isolated from patients with Crohn's disease. From the set of Escherichia coli isolated from Crohn's disease patients [2] we chose three isolates with strongest AIEC pathotype. We performed proteome-wide LC-MS analysis of membrane fraction of this isolates after invasion or adhesion-invasion to human intestinal CaCo-2 cell line and prior to this (control). The data including LC-MS/MS raw files and exported MaxQuant search results with fasta files were deposited to the PRIDE repository project accession PXD014250.


The size of pancreatic pseudocyst does not influence the outcome of invasive treatments.
Authors generally agree that Giant Pancreatic Pseudocysts (> 10 cm) have a lower spontaneous resolution and are more difficult to treat than smaller pancreatic pseudocysts. This study was carried out on two groups of patients with larger and smaller pancreatic pseudocysts (pancreatic pseudocysts > 10 cm versus pancreatic pseudocysts < 10 cm), and aims to establish whether the size of pancreatic pseudocysts is a factor influencing treatment outcomes. In a retrospective study, we examined 71 patients with pancreatic pseudocysts following an episode of acute pancreatitis, which were treated in our hospital from 1980 to 2000. Forty-one (57.5%) patients had a large pancreatic pseudocyst. Most patients underwent invasive treatments: 9 (12.6%) had percutaneous drainage, 37 (52.1%) open surgery and 13 (18.3%) endoscopic cyst gastrostomy. 12 patients (16.9%) of the 71 were cured with medical therapy alone. As far as the aetiology of the pancreatitis, location and number of the cysts were concerned, no major differences emerged between the two groups, although large pancreatic pseudocysts followed more severe pancreatitis (P = 0.0005). All giant pancreatic pseudocysts required invasive treatments; 40% of the pancreatic pseudocysts < 10 cm were successfully treated with medical therapy alone. No statistical differences were found regarding hospital mortality, morbidity, recurrence rate and hospital stay among the patients treated invasively. Giant pancreatic pseudocysts more often require invasive therapy due to persistent symptoms or complications. Treatment outcomes do not seem to be influenced by the size of the pancreatic pseudocysts.


Structural, functional properties of protein and characteristics of tofu from small-seeded soybeans grown in the Loess Plateau of China.
The structural, functional properties of protein isolated from small-seeded soybeans were investigated and characteristics of tofu were studied. Small-seeded soybean protein had obvious α', α, β, acidic and basic subunits bands and two endothermic peaks (76.02-76.63℃ and 91.94-94.25℃). Small-seeded black soybean protein isolates (SBSPI) had more β-sheet (31.90-33.54%) structure, while small-seeded yellow soybean protein isolates (SYSPI) had more α-helix (18.89-20.72%) structure. SYSPI had higher fluorescence intensity (839.10-847.80) than SBSPI (482.70-565.10). SBSPI exhibited higher surface hydrophobicity (939.51-1252.75) and water absorption capacity (8.07-8.50 g/g). Tofu made from small-seeded yellow soybeans had higher yield (549.46-560.23 g/100 g soybean) and was brighter (L*, 74.61-77.48) and more yellowish (b*, 14.83-14.95) in color. Tofu made from Fugu small-seeded black soybean (FGSBS) had the highest hardness (178.52 g), adhesiveness (-25.77 g.sec), chewiness (87.45 g) and resilience (0.26), signifying a more compact structure.


Perceptual decision-making 'in the wild': How risk propensity and injury exposure experience influence the neural signatures of occupational hazard recognition.
While previous studies have extensively explored the neural mechanisms of perceptual decision-making, most of them used paradigms with limited real-life consequences and largely neglected participants' individual differences. In this study, to resemble a perceptual decision-making scenario with real-life consequences, construction workers were recruited for an occupational hazard recognition task by categorizing construction site images as hazardous or safe with their EEG recorded. Event-related potential (ERP) analysis revealed distinct influences of perceptual decision-making by two dispositional factors of risk propensity and injury exposure experience. Risk propensity was positively correlated with the stimulus-locked difference waveforms (hazardous minus safe) at approximately 200 ms post-stimuli-onset over right-lateralized parietal-occipital areas. The difference waveforms showed reversed polarity between groups with high and low-risk propensity. Injury exposure experience was negatively correlated with the response-locked difference waveforms approximately 450 ms before motor response over right-lateralized parietal-occipital regions. To the best of our knowledge, this study is the first to report how individuals' injury exposure experience influenced the neural signatures of one's perceptual decision-making. These results extended previous findings for perceptual decision-making by setting up a scenario with high ecological validity and suggested possibly substantial different mechanisms for individual workers by the intrinsic factor of risk propensity and the extrinsic factor of injury exposure experience.


Inflammation in neurological and psychiatric diseases.
In recent years, compelling evidence suggests that inflammation plays a critical role in the pathology of a vast number of neurological diseases such as stroke, Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis as well as neuropsychiatric diseases such as major depression and schizophrenia. Despite emerging evidence in human and animal models alike, modulating inflammatory responses have yet to be proven as an effective treatment to prevent or delay the progression of these diseases. The primary focus of this special edition is to highlight some of our current findings on the complexities of targeting neuroinflammation as a novel therapy, and its role in neurological and psychiatric disorders.


Protein and lipid carbonylation in cellular model of nitrosative stress: mass spectrometry, biochemistry and microscopy study.
Within the wide range of oxidative modifications, "carbonylation" formed by the incorporation of aldehyde/keto groups, is commonly studied due to its role in cell physiology and as prospective biomarkers for numerous disorders. Despite close biochemical and physiological links between protein and lipid carbonylation, these two types of modifications are rarely addressed simultaneously in a single study. In nitrosative stress cell model we investigated levels of protein and lipid carbonylation and addressed the main modified species by combining LC-MS, biochemical, and microscopy studies. The influence of nitrosative stress on carbonylation of proteins and lipids was investigated for primary cardiomyocytes treated with SIN-1 for different time intervals. Lipid carbonylation was quantified by RPC-ESI-MS/MS. The results demonstrate dynamic generation, degradation and adduct formations of 25 different species including alkanals, alkenals, alkadienals, alkatrienals and oxo-carboxylic acids. Several new PL-bound aldehydes were present exclusively after a long incubation period. Carbonylated proteins were identified after aldehyde reactive probe derivatization, affinity enrichment and RPC-ESI-MS/MS. More than 200 proteins were identified and evaluated by systems biology to deduce the biological significance of the protein modifications. The protein carbonylation degree was verified using oxyblot and correlated with changes in 20S/26S proteasome activities. Furthermore, a new fluorescence microscopy based technique to stain carbonylated biomolecules was developed and compared with conventional DNPH-based immunocytochemistry. Subcellular localization of carbonylated species was investigated using mitochondrial and ER-specific co-localization experiments. Thus, the combination of lipidomics, proteomics, biochemical techniques, and microscopy imaging revealed a complex molecular pattern of "carbonylation stress" in the studied nitrosative stress cell model.


Test-retest reliability of the rat N40 auditory evoked response: preliminary data.
The N40 auditory evoked potential (EP) in rats has been used to develop an animal model for the study of sensory gating mechanisms. In an examination of the test-retest reliability of sensory gating indices, derived from the rat N40 EP, six rats were tested four times daily for 5 consecutive days. A paired-click paradigm (S1-S2) was used, and both the S2/S1 amplitude ratio and the S1-S2 amplitude difference measures of sensory gating capacity were calculated. Based on the means of four daily trials, reliability coefficients were as follows; r = 0.69 for S1, and r = 0.66 for S2 amplitudes. A reliability coefficient of 0.59 was found for the S1-S2 difference measure, and one of 0.47 for the S2/S1 ratio measure. These results suggest that the N40 can be used to study sensory gating, but caution has to be exercised in interpreting the data particularly in a repeated measures design.


[Findings from a psychiatrist's screening of selected groups of the adult population in a number of regions of the USSR].
The paper is concerned with the results of a total study of representative sample groups of the population made by a psychiatrist. During such examinations 1872 individuals who demonstrated mental disorders were found. Only a part of them were previously registered in a psychoneurological dispensary. A comparison of the number of previously registered patients in the different groups of population made it possible to conclude that the detection of patients is associated with severity of the disease and with social activity of different groups of population.


Resolution of pathologic Q wave, left ventricular dysfunction and mitral regurgitation after dual coronary repair of the anomalous origin of the left coronary artery from the pulmonary artery.
Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiac defect that usually presents as dilated cardiomyopathy in infancy. From 1984 to 2005, 13 (five males and eight females, 0.13%) out of 9,950 patients with congenital heart disease were identified as ALCAPA at our institute. Corrective surgery was performed at a median age of 9 months (range: 2 months to 5 years). Eleven patients underwent direct reimplantation of the left coronary artery (LCA) to the aorta, while two received extrapulmonary baffling. The overall survival rate was 92%. Only one patient died 5 months after reimplantation of the LCA due to acute myocardial ischaemia. Left ventricular ejection fraction (LVEF) was significantly lower in the eight (62%) patients operated during infancy than in those operated beyond 5 months (median: 35% vs. 75%). Left ventricle function was normalised in 11 patients (85%). Among the eight patients without concomitant mitral annuloplasty, mitral regurgitation (MR) improved to a mild or trivial degree in six patients and remained at the pre-operative level in two patients. Pathologic Q wave was noted in 11 patients, which eventually regressed in all except two cases. The median interval of recovery was 16 days, 6 months and 24 months for MR, LVEF and electrocardiogram (ECG) changes, respectively. In conclusion, ALCAPA is also a rare disease in Asian countries, such as Taiwan. The subsequent recovery of MR, left ventricular (LV) function and even pathologic Q wave can be expected after dual coronary repair, regardless of the age at repair.


Propionibacteria as a cause of shunt and postneurosurgical infections.
Propionibacterium acnes was isolated from postoperative specimens from nine neurosurgical patients. The role of P. acnes in postneurosurgical infection is discussed.


Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer.
To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.


Does a clinical varicocele influence the relationship between testicular volume by ultrasound and testicular function in patients with infertility?
To determine whether varicocele influences the testicular volume-function relationship. Retrospective clinical study. University hospital. One hundred fifty infertile patients with varicocele and 299 without varicocele. Semen analyses, scrotal ultrasound, and serum FSH, LH, and T levels. The mean testicular volume was measured by ultrasound. To evaluate the testicular volume-function relationship in infertile patients with varicocele and in those without varicocele, the patients were divided into seven and 10 groups, respectively, according to the mean testicular volume. The semen density, total sperm count, and serum FSH levels significantly correlated with the mean testicular volume in both patient groups, but patients without varicocele had a greater correlation coefficient than those with varicocele. The mean testicular volume with mean sperm densities indicating oligozoospermia was greater in the patients with varicocele than in patients without varicocele (12.5 and 10.0 mL, respectively). The mean testicular volume with mean FSH concentration exceeding the normal range was higher in patients with varicocele (15.0 mL) than in patients without varicocele (12.5 mL). The testicular volume-function correlation differed between patients with varicocele and those without varicocele. The presence of varicocele therefore influences the relationship between the testicular volume and the testicular function.


Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression-TRANSFORM-3.
Elderly patients with major depression have a poorer prognosis, are less responsive to treatment, and show greater functional decline compared with younger patients, highlighting the need for effective treatment. This phase 3 double-blind study randomized patients with treatment-resistant depression (TRD) ≥65 years (1:1) to flexibly dosed esketamine nasal spray and new oral antidepressant (esketamine/antidepressant) or new oral antidepressant and placebo nasal spray (antidepressant/placebo). The primary endpoint was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to day 28. Analyses included a preplanned analysis by age (65-74 versus ≥75 years) and post-hoc analyses including age at depression onset. For the primary endpoint, the median-unbiased estimate of the treatment difference (95% CI) was -3.6 (-7.20, 0.07); weighted combination test using MMRM analyses z = 1.89, two-sided p = 0.059. Adjusted mean (95% CI) difference for change in MADRS score between treatment groups was -4.9 (-8.96, -0.89; t = -2.4, df = 127; two-sided nominal p = 0.017) for patients 65 to 74 years versus -0.4 (-10.38, 9.50; t = -0.09, two-sided nominal p = 0.930) for those ≥75 years, and -6.1 (-10.33, -1.81; t = -2.8, df = 127; two-sided nominal p = 0.006) for patients with depression onset <55 years and 3.1 (-4.51, 10.80; t = 0.8, two-sided nominal p = 0.407) for those ≥55 years. Patients who rolled over into the long-term open-label study showed continued improvement with esketamine following 4 additional treatment weeks. Esketamine/antidepressant did not achieve statistical significance for the primary endpoint. Greater differences between treatment arms were seen for younger patients (65-74 years) and patients with earlier onset of depression (<55 years).


Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system.
The biological significance of occult metastases in axillary lymph nodes of breast cancer patients is controversial. The purpose of the study was to determine the prognostic significance of occult micrometastases using the current American Joint Committee on Cancer (AJCC) staging system in a cohort of women with node-negative breast cancer, of whom 5% received adjuvant systemic therapy and who all had long-term follow-up. We studied a cohort of 214 consecutive histologically node-negative breast cancer patients with a median follow-up of 8 years. Blocks of the axillary lymph nodes were assessed for occult micrometastases by examination of an additional hematoxylin-eosin-stained slide and by immunohistochemical staining using an antibody to low molecular weight keratin. Occult metastases were classified according to the sixth edition of the AJCC cancer staging manual. We examined the prognostic effects of occult micrometastases and other clinicopathologic features on recurrence outside the breast with disease-free interval (DFI) and survival from breast cancer with disease-specific survival (DSS). Cytokeratin-positive tumor cells were identified in the lymph nodes in 29 of 214 cases (14%). Two cases had isolated tumor cells and no cluster larger than 0.2 mm [pN0(i+)], whereas 27 of 214 (13%) had micrometastases (larger than 0.2 mm and <or=2.0 mm] (pN1mi). None of the cases had macrometastases. With median 8 years follow-up, occult micrometastases were not significantly associated with any of the clinicopathologic features. In addition, occult micrometastases were not significantly associated with DFI or DSS and thus were not included in the multivariate analysis. On multivariate analysis, lymphovascular invasion was significantly associated with DFI (p < 0.001) and DSS (p = 0.02), whereas percentage S-phase was significantly associated with DSS (p = 0.02). This study, in which 95% of patients did not receive adjuvant systemic therapy, suggests that breast cancer patients with occult micrometastases in axillary lymph nodes have a similar prognosis to those with no micrometastases. This information is important with regard to the practice of sentinel node biopsy and subsequent axillary node dissection and to the decision to administer adjuvant therapy based on detection of micrometastases in lymph nodes.


Bronchoplastic procedures for lung cancer.
Twenty patients with lung cancer have undergone bronchoplastic procedures September, 1965, to June, 1976 in our hospital. Bronchoplastic procedures are considered to be indicated for early cases of hilar lung cancer rather than for somewhat advanced cases. Endoscopic examination and roentgenograms of the bronchial arteries are needed to delineate resectional lines of bronchus, the former for deciding the mucosal extent and the latter the intrabronchial extent of the tumor. The bronchoplastic procedures we adopted were free from the risks and dangers generally accompanying the operation, and there were no postoperative deaths. For the prevention of postoperative complications, careful attention to suture technique is needed, and postoperative bronchoscopic suction of intrabronchial secretions is absolutely necessary. These procedures assure good quality of life postoperatively and improvement in the survival rate by preserving pulmonary function, enhancing curability, and increasing the operative indications. These advantages warrant high evaluation of the operation.


A novel unknown-input and single-output approach to extract vibration patterns via a roving continuous random excitation.
Operating deflection shape analysis allows investigating the dynamic behaviour of a structure during operation. It normally requires simultaneous, multi-point measurements to capture the response from an unknown excitation source (unknown-input and multiple-output), which can complicate its usage for structures without ease of access. A novel vibration pattern testing method is proposed based on a roving continuous random excitation employing a small robotic Hexbug device and a single-point measurement. The Hexbug introduces a random excitation in consecutive locations while roaming over the structure. The resulting multi-modal, time and location dependent response of the system is captured in a single location, and then analysed with a newly developed method based on empirical wavelet transform, multiscale morphological filtering and optimization to extract the excited vibration patterns. The efficiency of the proposed method is experimentally demonstrated on a free-free and a cantilevered beam with comparison to mode shapes extracted by hammer test. The validation highlights its ability to extract several vibration patterns from a long slender structure with good accuracy and robustness, with the general ability to expand the usability of an operating deflecting shape analysis.


Applications of deep eutectic solvents to quantitative analyses of pharmaceuticals and pesticides in various matrices: a brief review.
Pharmaceuticals and pesticides are important analytes of interest in clinical, environmental, and food analyses for ensuring public health. Sample pretreatment steps are often prerequisites for the quantitative analysis of these compounds, which are generally present in low concentrations in samples with complex matrices. In compliance with the current trend towards green analytical chemistry, the replacement of conventional toxic organic solvents with ecofriendly and safe solvents has been pursued in developing sample pretreatment methods. Subsequent to several reports in 2017, deep eutectic solvents (DESs) have been increasingly applied as desirable alternative solvents in numerous types of sample pretreatment methods for the analysis of pharmaceuticals and pesticides. The present review summarizes analytical methods involving DESs as extraction solvents and as the reaction media or functional materials for preparing adsorbents to quantify pharmaceuticals and pesticides in various matrices.


Resilience of cactus pear genotypes in a tropical semi-arid region subject to climatic cultivation restriction.
The cactus pear has demonstrated productive potential in arid and semi-arid regions due to its photosynthetic process of crassulacean acid metabolism. Thus, this study aimed to evaluate agronomic characteristics and chemical composition of three genotypes of cactus pear at different locations of a tropical semiarid region classified as non-suitable for cactus pear cultivation. A completely randomized design in a factorial arrangement (3 × 7) (three genotypes of cactus pear [Miúda, Baiana (Nopalea cochenillifera) and Orelha de Efefante Mexicana - OEM (Opuntia stricta)] and seven locations) was used. The climatic conditions characterized an environment that restricts the growth of cactus pear genotypes, mainly due to the air relative humidity values. All morphological characteristics of the cactus pear genotypes were influenced by the interaction genotype x location, with higher expression of the characteristics on the different genotypes under hot semi-arid climate and tropical wet and dry climate. An effect of the interaction genotype x location was observed (p < 0.05) on water use efficiency, water accumulation and carrying capacity, where the highest values were observed for genotype Baiana at location 1. Also, there was influence of the interaction genotype x location over the chemical composition of the cactus pear. The cultivation of cactus pear is recommended under restricted climatic conditions in semi-arid tropical regions, especially the genotype Baiana, based on growth factors, biomass production and chemical composition.


Characterization of detector modulation-transfer function with noise, edge, and holographic methods.
We developed a new method for characterization of detector performance used in the transmission electron microscope (TEM) based on the measured contrast of holographic fringes. The new method changes spatial frequency of the measured holographic fringes, generated by an electrostatic biprism and Schottky or cold field-emission gun, to sample the modulation-transfer function (MTF) of the detector. The MTF of a Gatan Ultrascan™ 1000 charged-coupled detector (CCD) is evaluated using the new method and the results are compared to the established noise and slanted-edge method results. Requirements for accuracy of the edge and noise MTF methods are discussed. We consider issues surrounding incomplete read-out and how it affects the gain reference normalization of the detector. We evaluate how the MTF affects optimization of experimental parameters in the TEM.


Developing a multidisciplinary protocol for enteral feeding.
The management of planned change is discussed using a change model. Protocols are described and defined. The process of multidisciplinary protocol development is identified. Nurses are encouraged to reflect upon the process of practice change.


Tumor PD-L1 and VEGF Expression, and CD8 T Cell Infiltration Predict Clinical Response to Immune Checkpoint Inhibitors in Non-small Cell Lung Cancer.
We evaluated the efficacy of "the tumor immune microenvironment (TIME) classification" for predicting clinical response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). In addition, we aimed to evaluate the "modified TIME classification", which adds the vascular endothelial growth factor (VEGF) status to TIME. Programmed cell death receptor ligand-1 (PD-L1), CD8 T cell tumor-infiltrating lymphocytes (CD8+TILs) count and VEGF expression analyses were performed using immuno - histochemistry in 44 patients who had undergone ICI monotherapy. Regarding TIME classification, type-I (PD-L1 high and CD8+TILs high) had a significantly higher response than the other types. Using the modified TIME classification, type-IA (PD-L1 high, CD8+TILs high, and VEGF low) had a significantly higher response than the other types. The modified TIME classification, which adds tumor VEGF expression to "the TIME classification", could be useful in predicting clinical response to ICI monotherapy.


Effects of water turbidity on the survival of Staphylococcus aureus in environmental fresh and brackish waters.
Staphylococcus aureus is an opportunistic pathogen frequently detected in environmental waters and commonly causes skin infections to water users. S. aureus concentrations in fresh, brackish, and marine waters are positively correlated with water turbidity. To reduce the risk of S. aureus infections from environmental waters, S. aureus survival (stability and multiplication) in turbid waters needs to be investigated. The aim of this study was to measure S. aureus in turbid fresh and brackish water samples and compare the concentrations over time to determine which conditions are associated with enhanced S. aureus survival. Eighteen samples were collected from fresh and brackish water sources from two different sites on the east side of O'ahu, Hawai'i. S. aureus was detected in microcosms for up to 71 days with standard microbial culturing techniques. On average, the greatest environmental concentrations of S. aureus were in high turbidity fresh waters followed by high turbidity brackish waters. Models demonstrate that salinity and turbidity significantly predict environmental S. aureus concentrations. S. aureus persistence over the extent of the experiment was the greatest in high turbidity microcosms with T90 's of 147.8 days in brackish waters and 80.8 days in freshwaters. This study indicates that saline, turbid waters, in the absence of sunlight, provides suitable conditions for enhanced persistence of S. aureus communities that may increase the risk of exposure in environmental waters. PRACTITIONER POINTS: Staphylococcus aureus concentrations, survival, and persistence were assessed in environmental fresh and brackish waters. Experimental design preserved in situ conditions to measure S. aureus survival. Higher initial S. aureus concentrations were observed in fresh waters with elevated turbidity, while sustained persistence was greater in brackish waters. Water turbidity and salinity were both positively associated with S. aureus concentrations and persistence. Climate change leads to more intense rainfall events which increase water turbidity and pathogen loading, heightening the exposure risk to S. aureus.


Analysis of the condensation step in elongation of very-long-chain saturated and tetraenoic fatty acyl-CoAs in swine cerebral microsomes.
The condensation products in the elongation of exogenous arachidoyl-CoA (20:0-CoA) and endogenous fatty acids in adult swine cerebral microsomes were isolated and purified by using HPLC and a radioanalyzer. A saponification product of the condensation reaction of 20:0-CoA with malonyl-CoA was identified by gas chromatography-mass spectrometry as 2-heneicosanone (21:0-2-one). The endogenous substrates (16:0-CoA and 20:4-CoA) were likewise identified as 2-heptadecanone (17:0-2-one) and 2-heneicosatetraenone (21:4-2-one). Quantitative analysis of condensation activity was performed using electron-impact mass fragmentography. A characteristic fragment ion (m/z 59) of 21:0-2-one was used to estimate the condensation activity for 20:0-CoA, and fragment ions at m/z 58 and 80 were monitored for the endogenous substrates (16:0-CoA and 20:4-CoA, respectively). The molecular ion for each product was detected using chemical ionization. A comparative study of the condensation of 20:0-CoA and endogenous substrates was carried out for microsomes obtained from white matter, gray matter, and isolated neuronal cells; the activity for 20:0-CoA was significantly lower in gray matter and neuronal cells than in white matter, whereas the activity for endogenous substrates was almost the same for microsomes obtained from gray and white matter. This result suggests that the condensation enzyme for 20:0-CoA may be different from that for endogenous 16:0-CoA or 20:4-CoA in swine cerebral microsomes.


Detection of glutaric acidemia type 1 in infants through tandem mass spectrometry.
Glutaric acidemia type 1 (GA1) is a rare inherited metabolic disorder which goes underdiagnosed due to its latency period and subtle presentation. A pilot clinical study was conducted to assess the usefulness, specificity and sensitivity of the tandem mass (MS/MS) spectrometer, specifically the Abbott (AB) Sciex 3200, in the screening for GA1 using dried blood spots. A total of 17,100 specimens, comprising pediatric patients and healthy newborns, were screened from June 2012 to June 2014. A selection criterion was applied to increase the range of samples tested. 14 of the total specimens tested presumptive positive for GA1, of whom all were symptomatic. The diagnosis was confirmed in 4 of the 14 cases and they were started on treatment. 4 cases expired before confirmation. The remaining cases were empirically started on treatment. Most of the patients responded favorably to the dietary management. One important observation was that the older symptomatic children diagnosed with GA1 had poorer outcomes in terms of recovery of delayed milestones and mental deterioration, further emphasizing the need for early diagnosis of organic acidemias along with the other biochemical defects. Tandem mass spectrometry was found to be more than 93.33% sensitive and more than 99.42% specific. The screening test proved to be very simple and economical.


Torsion of a wandering spleen: acute abdominal presentation.
Torsion of a wandering spleen is a rare but fulminant condition and is part of the differential diagnosis in patients presenting with acute abdominal pain. It results due to absence or laxity of the various ligaments supporting the spleen. Patients may be asymptomatic or may present with acute abdominal pain. It may occur in people of all ages, with a predilection for male patients under 10 years of age and for female patients in older age groups, being most common in multiparous women. Early intervention is necessary to reduce the risk of splenic infarction and other complications. An awareness of the condition together with use of appropriate medical imaging can lead to the correct diagnosis.


Surgical management of acoustic neuromas during the last five years. Part I.
A consecutive series of 94 patients with acoustic neuromas, who were treated in the years 1980-1984, was reviewed. Hearing loss was the most common presenting symptom. During 1980-1984, all acoustic neuromas were treated surgically; 93 cases had a total excision and only one case had a subtotal excision. Mortality and morbidity were low and patients who had a fair to poor outcome rating had large tumors. Overall, cranial nerve VII was preserved in 64.1% of cases, while cranial nerves VII and VIII were anatomically preserved in 27% of cases.


Feeling low and unhappy together? An actor-partner-interdependence model uncovering the linkage between different operationalizations of relationship quality and depression in different-sex couples.
Some studies suggest a bi-directional association between low relationship quality and depression. However, the social impact of depression and the potential preventative effects of healthy relationships are not yet sufficiently understood, as studies have shown heterogenous results for effects in both directions. Therefore, the main aim of this study was to differentiate the actor and partner effects of this association more comprehensively using two measures to capture characteristics of relationship quality-firstly regarding general aspects of social system quality and secondly considering specific aspects of the romantic relationship. 110 different-sex couples were included, being separated in partners with highly pronounced depressive symptoms in women (Cw/DW) versus partners with low depressive symptoms (LDCs). We investigated effects cross-sectionally using multi-group analyses to predict relationship (couple specific questionnaire: PFB) versus system quality (general system quality questionnaire: EVOS) in a step-by-step approach, modelling actor and partner effects with variation within and across both groups and then comparing the results to models with equal actor and partner effects. Depression was measured with the PHQ-9. With regard to the relationship between depressive symptoms and system quality, the model that constrained actor and partner effects to be equal across both groups was preferred and showed negative significant actor effects across gender and groups. Concerning the association between depressive symptoms and relationship quality, the model constraining actor and partner effects to be equal within groups had the best fit to the data and revealed a negative partner effect in LDCs. Conclusions Controlling for the moderating variable of clinically relevant depressive symptoms, we found evidence for actor and partner effects, which differed between the two relationship measures. This underlines the importance to reflect how relationship quality is operationalized. The negative partner effect on relationship quality in LDCs emphasizes that even in a non-clinical context, depressive symptoms negatively impact the perceived relationship quality of both women and men. This suggests that addressing the relationship is important in non-clinical preventive contexts and calls for integrating the partner into counselling or trainings.


Inter-agency perspective: Translating advances in biomarker discovery and medical countermeasures development between terrestrial and space radiation environments.
Over the past 20+ years, the U.S. Government has made significant strides in establishing research funding and initiating a portfolio consisting of subject matter experts on radiation-induced biological effects in normal tissues. Research supported by the National Cancer Institute (NCI) provided much of the early findings on identifying cellular pathways involved in radiation injuries, due to the need to push the boundaries to kill tumor cells while minimizing damage to intervening normal tissues. By protecting normal tissue surrounding the tumors, physicians can deliver a higher radiation dose to tumors and reduce adverse effects related to the treatment. Initially relying on this critical NCI research, the National Institute of Allergy and Infectious Diseases (NIAID), first tasked with developing radiation medical countermeasures in 2004, has provided bridge funding to move basic research toward advanced development and translation. The goal of the NIAID program is to fund approaches that can one day be employed to protect civilian populations during a radiological or nuclear incident. In addition, with the reality of long-term space flights and the possibility of radiation exposures to both acute, high-intensity, and chronic lower-dose levels, the National Aeronautics and Space Administration (NASA) has identified requirements to discover and develop radioprotectors and mitigators to protect their astronauts during space missions. In sustained partnership with sister agencies, these three organizations must continue to leverage funding and findings in their overlapping research areas to accelerate biomarker identification and product development to help safeguard these different and yet undeniably similar human populations - cancer patients, public citizens, and astronauts.


Experimentally unsupervised deconvolution for light-sheet microscopy with propagation-invariant beams.
Deconvolution is a challenging inverse problem, particularly in techniques that employ complex engineered point-spread functions, such as microscopy with propagation-invariant beams. Here, we present a deep-learning method for deconvolution that, in lieu of end-to-end training with ground truths, is trained using known physics of the imaging system. Specifically, we train a generative adversarial network with images generated with the known point-spread function of the system, and combine this with unpaired experimental data that preserve perceptual content. Our method rapidly and robustly deconvolves and super-resolves microscopy images, demonstrating a two-fold improvement in image contrast to conventional deconvolution methods. In contrast to common end-to-end networks that often require 1000-10,000s paired images, our method is experimentally unsupervised and can be trained solely on a few hundred regions of interest. We demonstrate its performance on light-sheet microscopy with propagation-invariant Airy beams in oocytes, preimplantation embryos and excised brain tissue, as well as illustrate its utility for Bessel-beam LSM. This method aims to democratise learned methods for deconvolution, as it does not require data acquisition outwith the conventional imaging protocol.


Impact of oral hygiene on head and neck cancer risk in a Chinese population.
Although the impact of oral hygiene on head and neck cancer risk has been investigated, few studies have been conducted among the Asian population. We conducted a multicenter case-control study to investigate this potential association. We performed unconditional multiple logistic regression models adjusted by potential confounders. We observed an inverse association of frequency of dental visits with head and neck cancer risk, with an adjusted odds ratio (OR) of 3.70 (95% CI 2.51-5.45) for never dental visits compared with ≥1 time/year (Ptrend < .001). We also observed a positive association between the number of missing teeth and head and neck cancer risk, with an adjusted OR for ≥5 missing teeth compared with <5 missing teeth of 1.49 (95% CI 1.08-2.04). Combining multiple oral hygiene indicators, poor oral hygiene scores increased head and neck cancer risk. Poor oral hygiene may increase head and neck cancer risk in the Chinese population. Therefore, improving oral hygiene may contribute to reducing the head and neck cancer risk in the Chinese population.


Cancer cell intrinsic TIM-3 induces glioblastoma progression.
Glioblastoma (GBM) is identified to share common signal pathways between glioma and immune cells. Here, we find that T cell immunoglobulin domain and mucin domain protein 3 (TIM-3) is one of the most common co-inhibitory immune checkpoints in GBM shared by tumor and non-tumor cells. Glioma cell-intrinsic TIM-3 is involved in not only regulating malignant behaviors of glioma cells but also inducing macrophage migration and transition to anti-inflammatory/pro-tumorigenic phenotype by a TIM-3/interleukin 6 (IL6) signal. In mechanism, as one of the major regulators of IL6, TIM-3 regulates its expression through activating NF-κB. Blocking this feedback loop by Tocilizumab, an IL6R inhibitor, inhibited the above effects and repressed the tumorigenicity of GBM in vivo. Our work identifies glioma cell-intrinsic functions of TIM-3/IL6 signal mediating the crosstalk feedback loop between glioma cells and tumor-associated macrophages (TAMs). Blocking this feedback loop may provide a novel therapeutic strategy for GBM.


To be reassured or to understand? A dilemma in communicating normal cervical screening results.
Receiving negative test results may be associated with two problems: (a). not being reassured and wanting further, unnecessary screening; and (b). not understanding residual risk and not attending future recommended screening. To test two hypotheses: (1). Emphasizing test accuracy and low residual risk when giving negative test results reduces a desire for further unnecessary screening, while also reducing a correct understanding of the meaning of the result. (2). The effect of emphasizing low risk on desire for future screening is mediated by lack of reassurance. Experimental, vignette-based study, with a 2 x 2 factorial design. A sample of 184 women was asked to imagine that they had recently undergone a cervical screening test and received a normal result. They were given one of four hypothetical letters from their GP,differing in whether or not it emphasized test accuracy and low residual risk of developing cervical cancer. Participants completed a questionnaire assessing perceived risk, reassurance about test results, desire for further screening within six months and understanding of the test results. Emphasizing test accuracy and low residual risk increases desire for inappropriate screening while reducing the understanding of residual risk. These effects are interactive, in that presenting both together has a larger effect than the sum of the two individual effects. The effect of emphasizing low risk on desire for future screening was mediated by reassurance. Emphasizing low residual risk and test accuracy is a double-edged sword: it reduces a desire for unnecessary screening, but also reduces correct understanding of the result.


Lipid-based dispersions of exemestane for improved dissolution rate and intestinal permeability: in vitro and ex vivo characterization.
Current study aimed to develop lipid dispersions of poorly water soluble exemestane by employing lipid carriers such as Gelucire 44/14 and TPGS with porous calcium silicate (PCS) as an adsorbent carrier and formulate into a solid dosage form. The lipid dispersions at 1:5 ratio showed the highest solubility and dissolution compared to pure exemestane. Further, the ex vivo intestinal permeation studies showed improved apparent permeability (Papp, cm/s) of exemestane from the lipid dispersions (GLD1:5 1.3 × 10-2 cm/s; TLD1:5 1.8 × 10-2 cm/s) compared to pure exemestane (0.7 × 10-2 cm/s). The optimized lipid dispersions (GLD1:5 and TLD1:5) were evaluated for scalability to develop into capsules.


Short-term outcome analysis of radiofrequency ablation using ClosurePlus vs ClosureFast catheters in the treatment of incompetent great saphenous vein.
Radiofrequency ablation (RFA) is a widely accepted alternative to high ligation with proximal stripping of the great saphenous vein (GSV) in the treatment of lower extremity venous insufficiency. This study compared short-term outcomes of two generations of (VNUS Closure) RFA catheters, ClosurePlus (CP) and ClosureFast (CF). From February 2005 to April 2009, a total of 667 consecutive office-based RFA procedures were performed in our institution. CP catheters were used in the initial 312 lower extremity cases and CF catheters in the 355 cases that followed. The technique used for both catheters were as per the manufacturer's recommendations. Postoperative duplex scans were completed to document the following endpoints: GSV obliteration; incidence of deep venous thrombosis (DVT); superficial venous thrombosis (SVT); and presence of loose or floating thrombus proximal to the treated GSV segment. Of the 667 cases, 98% had available duplex scan studies within 1 week from completion of the procedure. Complete obliteration of the GSV on duplex scan studies was noted in 98% of 343 cases using the CF catheter and 88% of 312 cases using the CP catheter (P < .001). No case of DVT was detected in those treated with the CF catheter, whereas DVT occurred in 3.5% of cases treated with the CP catheter (P < .001). Incidence of SVT was 10% and 15%, respectively, for CF and CP (P < .08). Loose thrombus proximal to the GSV was identified in 7% of cases using CF and 6% of cases using CP (P = .80). No embolic episodes were observed clinically. CF catheters are superior to CP catheters in terms of GSV obliteration and nonincidence of postoperative DVT. The absence of DVT may likely be due to the commencement of ablation at 2 cm from the GSV-common femoral vein junction.


Deposition of tocopherol and tocotrienol in the tissues of red hybrid tilapia, Oreochromis sp., fed vitamin E-free diets supplemented with different plant oils.
Vitamin E, a potent antioxidant consisting of four isomers each (α, β, γ, δ) of tocopherol (T) and tocotrienol (T3), is found naturally in plant oils at different concentrations. In this study, four semi-purified isonitrogenous and isolipidic (10 %) diets containing canola oil, cold-pressed soybean oil, wheat germ oil, or palm fatty acid distillates (PFAD) as the sole vitamin E source were fed to triplicate groups of red hybrid tilapia (Oreochromis sp.) fingerlings (14.82 ± 0.05 g) for 45 days. Vitamin E concentrations and composition were measured in the muscle, liver, skin, and adipose tissue. Deposition of α-T (53.4-93.1 % of total vitamin E) predominated over deposition of other isomers, except in the liver of fish fed the SBO diet, where α-T and γ-T deposition was in the ratio 40:60. T3 deposition (2.6-29.4 %) was only detected in tissues of fish fed the PFAD diet; adipose tissue was the major storage depot. Fish fed the SBO diet contained significantly more (P < 0.05) muscle thiobarbituric acid-reactive substances. Muscle fatty acid composition reflected dietary fatty acid profile. This is the first study to compare the deposition in fish tissues of the naturally occurring vitamin E isomers present in plant oils. The type and concentration of endogenous vitamin E and the fatty acid composition of plant oils can affect the oxidative stability of tilapia tissues.


[Oxidative stress in the pathogenesis of stroke].
Free radical oxidation of lipids and proteins is the universal process constantly proceeding in cells, tissues and organs during the lifetime of organism. In certain conditions, this process can be a basis of pathology, one of the mechanisms of disease development, including stroke.


Preparation and Characterization of Macroalgae Biochar Nanomaterials with Highly Efficient Adsorption and Photodegradation Ability.
In this study, carbonized kelp biochar (AKB) modified by KOH impregnation and photocatalytic Bi₂MoO₆/AKB composite (BKBC) nanomaterials were the first time successfully synthesized for efficient removal of dyes in aqueous solution. BET, XRD, FT-IR, and SEM were employed to characterize as-prepared samples. UV-vis and other test results indicated that the removal efficiency of methylene blue (MB) was 61.39% and 94.12% for BKBC and AKB, respectively, which was up to 13 times and 20 times higher in comparison with pure Bi₂MoO₆ (PBM). In addition, the equilibrium adsorption capacity of MB could reach up to 324.1 mg/g for AKB. This high dyes adsorption performance could be likely attributed to its high specific surface area (507.177 m²/g) and its abundant presence of various functional groups such as ⁻OH and =C⁻H on AKB. Particularly, the existing of amorphous carbon and transition metal oxides, such as Fe₂O₃ and Mn₅O₈, could be beneficial for the photodegradation of MB for AKB. Meanwhile, experimental data indicated that adsorption kinetics complied with the pseudo-second order model well, and all of the tests had satisfactory results in terms of the highly efficient adsorption and photodegradation activity of AKB nanomaterials, which suggested its great potential in wastewater treatment.


Early-born neurons in type II neuroblast lineages establish a larval primordium and integrate into adult circuitry during central complex development in Drosophila.
The central complex is a multimodal information-processing center in the insect brain composed of thousands of neurons representing more than 50 neural types arranged in a stereotyped modular neuroarchitecture. In Drosophila, the development of the central complex begins in the larval stages when immature structures termed primordia are formed. However, the identity and origin of the neurons that form these primordia and, hence, the fate of these neurons during subsequent metamorphosis and in the adult brain, are unknown. Here, we used two pointed-Gal4 lines to identify the neural cells that form the primordium of the fan-shaped body, a major component of the Drosophila central complex. We found that these early-born primordium neurons are generated by four identified type II neuroblasts that amplify neurogenesis through intermediate progenitors, and we demonstrate that these neurons generate the fan-shaped body primordium during larval development in a highly specific manner. Moreover, we characterize the extensive growth and differentiation that these early-born primordium neurons undergo during metamorphosis in pupal stages and show that these neurons persist in the adult central complex, where they manifest layer-specific innervation of the mature fan-shaped body. Taken together, these findings indicate that early-born neurons from type II neuroblast lineages have dual roles in the development of a complex brain neuropile. During larval stages they contribute to the formation of a specific central complex primordium; during subsequent pupal development they undergo extensive growth and differentiation and integrate into the modular circuitry of the adult brain central complex.


Particle dynamics and deposition in true-scale pulmonary acinar models.
Particle transport phenomena in the deep alveolated airways of the lungs (i.e. pulmonary acinus) govern deposition outcomes following inhalation of hazardous or pharmaceutical aerosols. Yet, there is still a dearth of experimental tools for resolving acinar particle dynamics and validating numerical simulations. Here, we present a true-scale experimental model of acinar structures consisting of bifurcating alveolated ducts that capture breathing-like wall motion and ensuing respiratory acinar flows. We study experimentally captured trajectories of inhaled polydispersed smoke particles (0.2 to 1 μm in diameter), demonstrating how intrinsic particle motion, i.e. gravity and diffusion, is crucial in determining dispersion and deposition of aerosols through a streamline crossing mechanism, a phenomenon paramount during flow reversal and locally within alveolar cavities. A simple conceptual framework is constructed for predicting the fate of inhaled particles near an alveolus by identifying capture and escape zones and considering how streamline crossing may shift particles between them. In addition, we examine the effect of particle size on detailed deposition patterns of monodispersed microspheres between 0.1-2 μm. Our experiments underline local modifications in the deposition patterns due to gravity for particles ≥0.5 μm compared to smaller particles, and show good agreement with corresponding numerical simulations.


The effect of the mode of delivery on the maternal-neonatal erythrocyte membrane acetylcholinesterase activity.
Free radical production and high catecholamine levels are implicated with the modulation of acetylcholinesterase (AChE) activity. To investigate the effect of the mode of delivery on maternal-neonatal erythrocyte membrane AChE activity. Some women with normal pregnancy (N = 30) were divided into two groups: group A (N = 16) with normal labour and vaginal delivery and group B (N = 14) with scheduled Cesarean section, twenty non-pregnant women were the controls. Blood was obtained from controls and from mothers pre- vs post-delivery as well as from the umbilical cord (CB). Total antioxidant status (TAS), membrane AChE activities and catecholamine blood levels were measured with a commercial kit, spectrophotometrically and HPLC methods, respectively. TAS and catecholamine levels as well as membrane AChE activities were similar in the two groups of mothers pre-delivery and in controls. TAS levels were reduced whereas AChE activities and catecholamine levels were increased post-delivery in mothers of group A and unaltered in group B at the same times of study. AChE activity was similarly lower in the CB of neonates than those of their mothers pre-delivery. During a normal delivery process, the low TAS, the increased levels of catecholamines and the increased AChE activity, post-delivery, may be due to the increased stress due to the participation of uterus and skeletal muscles as during endurance exercise. The low AChE activity in newborns may be related to perinatal immaturity.


Liquid chromatographic and fluorescent derivative aerobic degradation studies of dehydroascorbic acid in aqueous solution at elevated temperatures.
The aqueous degradation of dehydroascorbic acid (DHA) has been studied in the temperature range 52-90 degrees C. The DHA was determined by reversed-phase liquid chromatography and by derivatisation of DHA with o-phenylenediamine to form the fluorescent quinoxaline. The pseudo-first-order degradation of DHA has been verified and rate constants for the process are presented. The role of DHA in the degradation of ascorbic acid and previous DHA solution stability studies are discussed.


Implementation of a multimodal infection control program during an Acinetobacter outbreak.
Acinetobacter in the ICU presents a challenge worldwide due to its capacity for long-term survival on environmental surfaces. This report describes a multimodal infection control program designed to control a sustained outbreak Acinetobacter colonization. Multimodal interventions implemented by unit-appointed infection control nurses in an Australian intensive care unit (ICU) during a sustained outbreak of Acinetobacter colonization. In the first 12 months of the outbreak, the mean monthly colonization rate was 3.1 (+/-1.2) cases per 100 bed-days (increased from 0.5 [+/-0.4] in the previous 6 months). In the subsequent 20-months, the mean monthly colonization rates declined to 1.5 (+/-1.5) cases per 100 bed-days (P=0.004). Hand hygiene compliance increased from 33% (95% CI 30-36%) before action plan implementation to 49% (95% CI 46-52%) measured 6-months after implementation. Compliance subsequently dropped to 39% (95% CI 36-42%) 12-months after implementation. The median volume of alcohol/chlorhexidine hand rub solution used per 1000 bed-days increased from 24L (interquartile range (IQR) 12-47L) to 148L (IQR 120-165L) per 1000 bed-days (P<0.001). Introduction of ICU-appointed infection control nurses, who then led multimodal interventions, was effective in reducing the rate of Acinetobacter colonization.


Radiological characterisation and radon equilibrium factor in the outdoor air of a post-industrial urban area.
The radiological characterisation of outdoor air is always a complicated task due to the several radioactive emissions coming from the different radionuclides and also because of the very short half-lives of radionuclides in the natural radioactive series. In some places, this characterisation could result in unusual values because the natural presence of radionuclides with terrestrial origin can be modified by manmade activities. Nonetheless, this characterisation is useful not only for air quality control purposes but also because radon and its progeny in the outdoor air are the main contributors to human exposure from natural sources. In this study, we have carried out air particle sampling, followed by gamma-ray spectrometry, alpha spectrometry and beta counting determinations for this purpose. Subsequently, the outdoor air has been radiologically characterised through the obtained data and using a pre-existing analytical method to take into account the radioactive decays of short half-life radionuclides during sampling, sample preparation and measuring times. Bilbao was chosen to carry out this work. It is a medium-sized town located in northern Spain, close to the Atlantic Ocean and at sea level. This city has a recent industrial past as there were numerous steel mills and other heavy industries, including some quarries, and some open pit mines close to it, which concluded in a remediation program. So, it is a place where the air is potentially modified by manmade activities. The obtained results show that activity concentration values for long-lived radionuclides that precede radon and thoron are in the order of 10(-6) Bq m(-3) and long-lived ones after radon are around 10(-4) Bq m(-3). Thoron progeny are around 2 × 10(-2) Bq m(-3) and radon progeny are around 1.8 Bq m(-3). The mean radon equilibrium factor was 0.18. All of these values are close to the minimum UNSCEAR values, but show some variability, which highlights the importance of determining activity concentrations for each naturally occurring radionuclide and the equilibrium factor in the outdoor air.


Albumin alleviated esketamine-induced neuronal apoptosis of rat retina through downregulation of Zn2+-dependent matrix metalloproteinase 9 during the early development.
Esketamine upregulates Zn2+-dependent matrix metalloproteinase 9 (MMP9) and increases the neuronal apoptosis in retinal ganglion cell layer during the early development. We aimed to test whether albumin can alleviate esketamine-induced apoptosis through downregulating Zn2+-dependent MMP9. We investigate the role of Zn2+ in esketamine-induced neuronal apoptosis by immunofluorescence. MMP9 protein expression and enzyme activity were investigated by zymography in situ., western blot and immunofluorescence. Whole-mount retinas from P7 Sprague-Dawley rats were used. We demonstrated that esketamine exposure increased Zn2+ in the retinal GCL during the early development. Zn2+-dependent MMP9 expression and enzyme activity up-regulated, which eventually aggravated apoptosis. Albumin effectively down-regulated MMP9 expression and activity via binding of free zinc, ultimately protected neurons from apoptosis. Meanwhile albumin treatment promoted activated microglia into multi-nucleated macrophagocytes and decreased the inflammation. Albumin alleviates esketamine-induced neuronal apoptosis through decreasing Zn2+ accumulation in GCL and downregulating Zn2+-dependent MMP9.


Cranial nerve injuries during carotid endarterectomy.
Our experience with patients undergoing carotid endarterectomy over a 10 year period has been retrospectively reviewed. Nerve injuries were detected by reviewing postoperative progress and clinic notes. One hundred twenty-nine procedures were performed on 112 patients, 12 of whom (9.3 percent) sustained major nerve injuries. These included five vagal nerve injuries causing ipsilateral vocal cord paralysis and hoarseness, four injuries of the marginal mandibular nerve, and three injuries of the hypoglossal nerve. Evidence of nerve dysfunction was not present preoperatively. None of the patients with nerve injury sustained a stroke as a result of carotid operation. Vocal cord paralysis was documented by indirect laryngoscopy. The incidence of cranial nerve injury during carotid endarterectomy appears to be higher than expected, particularly if asymptomatic patients are investigated; however, most injuries are transient and result not from transection but from trauma during dissection, retraction, and clamping of the vessels. The pertinent anatomy and techniques for preventing these injuries have been reviewed.


Senolysis-Based Elimination of Chemotherapy-Induced Senescent Breast Cancer Cells by Quercetin Derivative with Blocked Hydroxy Groups.
Drug-induced senescence program may be activated both in normal and cancer cells as a consequence of chemotherapeutic treatment, leading to some adverse side effects such as senescence-associated secretory phenotype (SASP), secondary senescence, and cancer promotion. Targeted elimination of senescent cells can be achieved by drugs with senolytic activity (senolytics), for example, the plant-derived natural compound quercetin, especially when co-treated with kinase inhibitor dasatinib. In the present study, three quercetin derivatives were synthesized and tested for improved senolytic action against etoposide-induced senescent human normal mammary epithelial cells and triple-negative breast cancer cells in vitro. Transformation of catechol moiety into diphenylmethylene ketal and addition of three acetyl groups to the quercetin molecule (QD3 derivative) promoted the clearance of senescent cancer cells as judged by increased apoptosis compared to etoposide-treated cells. A QD3-mediated senolytic effect was accompanied by decreased SA-beta galactosidase activity and the levels of p27, IL-1β, IL-8, and HSP70 in cancer cells. Similar effects were not observed in senescent normal cells. In conclusion, a novel senolytic agent QD3 was described as acting against etoposide-induced senescent breast cancer cells in vitro. Thus, a new one-two punch anti-cancer strategy based on combined action of a pro-senescence anti-cancer drug and a senolytic agent is proposed.


Fas engagement accelerates liver regeneration after partial hepatectomy.
Fas (CD95) is a receptor involved in induction of apoptotic cell death of Fas-bearing cells, including hepatocytes and T cells. Injection of Fas-specific antibodies into mice leads to fulminant hepatic failure and death. Fas also transduces growth-promoting signals in proliferating T cells, fibroblasts and some tumor cells. Here we show that partial hepatectomy, which triggers the immediate onset of liver regeneration, protected mice against the lethal effects of Fas-specific antibodies and prevented hepatocyte apoptosis in response to Fas engagement in vivo. Furthermore, Fas engagement accelerated liver regeneration after partial hepatectomy. Liver regeneration kinetics were delayed in mutant mice with decreased cell surface Fas expression (lpr mice). In contrast, regeneration was not delayed in lpr-cg mutant mice, which have a Fas mutation that prevents Fas-induced death but not Fas-dependent proliferative stimulation. Our results indicate that Fas engagement on cells in regenerating or healing tissues may promote cell growth.


Grapefruit juice substantially increases plasma concentrations of buspirone.
Buspirone has a low oral bioavailability because of extensive first-pass metabolism. The effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of orally administered buspirone is not known. In a randomized, 2-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water 3 times a day for 2 days. On day 3, each subject ingested 10 mg buspirone with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours after buspirone administration. Timed blood samples were collected up to 12 hours after ingestion, and the effects of buspirone were measured with 6 psychomotor tests up to 8 hours after ingestion. Grapefruit juice increased the mean peak plasma concentration of buspirone 4.3-fold (range, 2-fold to 15.6-fold; P < .01) and the mean area under the plasma buspirone concentration-time curve 9.2-fold (range, 3-fold to 20.4-fold; P < .01). The time of the peak concentration (tmax) of buspirone increased from 0.75 to 3 hours (P < .01), and the elimination half-life (t1/2) was slightly increased (P < .01) by grapefruit juice. A significant increase in the pharmacodynamic effects of buspirone by grapefruit juice was seen only in subjective overall drug effect (P < .01). Grapefruit juice considerably increased plasma buspirone concentrations. The probable mechanism of this interaction is delayed gastric emptying and inhibition of the cytochrome P450 3A4-mediated first-pass metabolism of buspirone caused by grapefruit juice. Concomitant use of buspirone and at least large amounts of grapefruit juice should be avoided.


Caucasian patients with type 2 diabetes mellitus have elevated levels of monocyte chemoattractant protein-1 that are not influenced by the -2518 A-->G promoter polymorphism.
To investigate the association of serum levels and the -2518 A-->G promoter polymorphism of the gene for chemokine monocyte chemoattractant protein-1 (MCP-1), a major chemoattractant of monocytes and activated lymphocytes, with metabolic parameters as well as insulin, leptin and the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in 534 Caucasian patients with type 2 diabetes mellitus. MCP-1 concentrations were measured by enzyme-linked immunosorbent assay. MCP-1 genotyping was performed by RFLP analysis in a subset of 426 patients. Two hundred and thirty-one (54.2%) patients were homozygous for the wildtype allele (AA), 156 (36.6%) were heterozygous (AG) and 39 (9.2%) were homozygous for the mutated allele (GG). Allelic frequency was similar to non-diabetic populations (wildtype allele A: 0.73; mutated allele G: 0.27). MCP-1 mean concentrations and percentiles were substantially higher in non-diabetic populations but were not influenced by the genotype (AA: 662.0 +/- 323.0 pg/ml; AG: 730.6 +/- 491.4 pg/ml; GG: 641.2 +/- 323.8 pg/ml). MCP-1 serum levels and genotypes were only marginally related to hormones (insulin and leptin) and cytokines (TNF-alpha and IL-6). This is the first study providing MCP-1 levels, percentiles and genotype frequency in a large and representative cohort of patients with type 2 diabetes mellitus. Compared to the literature, MCP-1 levels were found to be substantially higher in patients with type 2 diabetes mellitus. In contrast, genotype frequencies were similar compared to those in non-diabetic patients and were not related to MCP-1 levels. The mechanisms behind these elevated MCP-1 serum levels in type 2 diabetes are not to be explained by simple associations with hormones, cytokines or genotypes.


Monoclonal antibody-mediated detection of CTX-M β-lactamases in Gram-negative bacteria.
Gram-negative bacteria (GNB) that express CTX-M β-lactamases have become a serious threat to the clinical management of GNB infections. While antibody-based platforms have been successfully used in research settings to study and detect other β-lactamases-including SHV, CMY, and TEM enzymes-there is currently a lack of antibody-based tools to detect the CTX-M enzymes. Here we describe the development of an anti-CTX-M sandwich ELISA based on a pair of monoclonal antibodies (mAbs)-mAb 6101-33 and mAb 6101-19-used as the capture and detection antibody, respectively. This antibody pair detected CTX-M variants from group 1 (CTX-M-15), group 2 (CTX-M-2), group 8 (CTX-M-8), and group 9 (CTX-M-14) that were expressed by a training set of clinical GNB isolates. The limit of detection for this sandwich ELISA was 30ng of recombinant CTX-M-15, and CTX-Ms expressed by 106 lysed CFU of GNB. When tested against a blinded panel of 78 clinical isolates, the sandwich ELISA demonstrated a sensitivity of 96% and a specificity of 100%. The mAb pair did not cross-react with bacteria that contained other β-lactamases, including TEM, SHV, OXA, KPC, NDM, CMY, and DHA. In conclusion, we developed a highly sensitive and specific sandwich ELISA, capable of detecting CTX-M enzyme production in GNB pathogens.


[How junior internists imagine the future of their specialty in France?].
Understanding the motivation of physicians to become internist is critical to recruitment efforts within the specialty of internal medicine. A questionnaire was designed by "the French young internist association (FYIA)" to analyze the quality of life of young specialists and their vision of the internal medicine specialty, in France. The questionnaire was administered online to the young internists (resident and junior hospital assistants) who had already chosen the specialty of internal medicine and collated through the FYIA. The majority of young internists in France work more than 60hours per week (57%) and have a very high intellectual interest for their specialty. For 89% of young internists, the specialty field should include management of patients with systemic or rare diseases as well as patients who need hospitalization after their admission from the emergency department. In the context of medical ultraspecialization, and because of a wide medical knowledge and a global approach of the patient's problems, French internists appear as an expert clinician specialist of difficult diagnosis and management of patients with multiple diseases. Because of these specificities, this specialty is attractive for medical students.


Recognition and management of ileus.
Ileus may occur in horses of all ages secondarily to drug administration, colic, exhaustion, peritonitis, or metabolic disorders. Ileus most commonly occurs following abdominal surgery for colic and is a significant cause of postoperative mortality in these horses. The most common clinical signs of ileus are decreased or absent intestinal sounds and gastric reflux. Ileus is treated by eliminating the initiating causes, correcting metabolic imbalances, decompressing distended bowel, providing analgesia, stimulating motility with drugs, and regulating exercise and feed and water intake.


The effects of intrinsic and extrinsic acids on nanofilled and bulk fill resin composites: Roughness, surface hardness, and scanning electron microscopy analysis.
The objective of this study was to examine the effects of extrinsic or intrinsic acids on nanofilled and bulk fill resin materials in vitro. A total of 90 disks were prepared using dental restorative material (Filtek Z350XT, GrandioSO, Filtek Bulk Fill, X-tra fil). Thirty disks of each material were sub-divided into three groups (n = 10) that were immersed for 7 days in deionized water (DW), 5% citric acid (CA-pH 2.1), or 0.1% hydrochloric acid (HCl-pH = 1.2). Surface hardness and roughness (stylus profilometer by Ra parameter) analysis were performed before and after immersion. Morphological changes were evaluated by scanning electron microscopy. The data were analyzed by two-way ANOVA and Tukey's test (α = 0.05). All tested materials did not show significant differences in the effects of the DW, CA, or HCl solutions on surface roughness (p = .368). Likewise, the hardness loss was not affected by the solutions tested (p = .646), but there was a difference in the resin type (p = .002). Filtek Bulk Fill resin hardness was less affected, while Filtek Z350XT and GrandioSO presented the most hardness loss after 7 days of solution immersion. In terms of this experimental study, the results demonstrate the effectiveness of the mechanical properties (roughness and hardness surface) of nanofilled and bulk fill resin materials to resist erosion from extrinsic and intrinsic acids, therefore being potential candidates for dental applications.


Colorimetric detection of melamine in milk by citrate-stabilized gold nanoparticles.
Here, we report a simple and sensitive colorimetric method for detection of melamine in milk using gold nanoparticles (AuNPs). AuNPs of 21-nm size were synthesized by the citrate reduction method. The method is based on the principle that the melamine causes the aggregation of AuNPs and, hence, the wine red color of AuNPs changes to blue or purple. This change in color can be visualized with the naked eye or an ultraviolet-visible (UV-Vis) spectrometer. Under optimized conditions, AuNPs are highly specific for melamine and can detect melamine down to a concentration of 0.05 mg L(-1).


Overexpression of ferritin light chain as a poor prognostic factor for breast cancer.
Ferritin light chain (FTL) is involved in tumor progression, but the specific molecular processes by which FTL affects the development of breast cancer (BRCA) have remained unknown. In this research, the clinicopathological significance of FTL overexpression in BRCA was investigated. To investigate the role of FTL in BRCA, we utilized multiple online databases to analyse FTL expression levels in BRCA. Next, we reviewed the expression and localization of the FTL protein in BRCA by immunohistochemistry (IHC), Western blot (WB) and immunofluorescence (IF) staining. To assess the impact of FTL on patient prognosis, we conducted Kaplan‒Meier, univariate and multivariate survival analyses. The relationship between FTL and immune infiltration in BRCA was also analysed in the TISCH and SangerBox databases. MTT, malondialdehyde (MDA) and reactive oxygen species (ROS) assays were carried out to investigate the molecular mechanisms of FTL action in BRCA cells. FTL was significantly upregulated in BRCA compared to normal tissues. Its expression significantly linked to histological grade (P = 0.038), PR expression (P = 0.021), Her2 expression (P = 0.012) and Ki-67 expression (P = 0.040) in patients with BRCA. Furthermore, the expression of the FTL protein was higher in the BRCA cell lines than in the normal breast cells and mainly localized in the cytoplasm. Compared to patients with a low level of FTL expression, patients with a high level of FTL expression showed lower overall survival (OS). More convincingly, univariate and multivariate statistical analyses revealed that FTL expression (P = 0.000), ER expression (P = 0.036) and Her2 expression (P = 0.028) were meaningful independent prognostic factors in patients with BRCA. FTL was associated with immune infiltration in BRCA. Functional experiments further revealed that FTL knockdown inhibited the capacity of proliferation and increased the level of oxidative stress in BRCA cells. Overexpression of FTL was associated with the progression of BRCA. FTL overexpression may become a biomarker for the evaluation of poor prognosis in patients with BRCA.


An instructive role for retinal waves in the development of retinogeniculate connectivity.
A central hypothesis of neural development is that patterned activity drives the refinement of initially imprecise connections. We have examined this hypothesis directly by altering the frequency of spontaneous waves of activity that sweep across the mammalian retina prior to vision. Activity levels were increased in vivo using agents that elevate cAMP. When one eye is made more active, its layer within the LGN is larger despite the other eye having normal levels of activity. Remarkably, when the frequency of retinal waves is increased in both eyes, normally sized layers form. Because relative, rather than absolute, levels of activity between the eyes regulate the amount of LGN territory devoted to each eye, we conclude that activity acts instructively to guide binocular segregation during development.


A comparison of picture description abilities in individuals with vascular subcortical lesions and Huntington's Disease.
The lexical-semantic and syntactic abilities of a group of individuals with chronic nonthalamic subcortical (NS) lesions following stroke (n=6) were investigated using the Western Aphasia Battery (WAB) picture description task [Kertesz, A. (1982). The Western aphasia battery. New York: Grune and Stratton] and compared with those of a group of subjects with Huntington's Disease (HD) (n=6) and a nonneurologically impaired control group (n=6) matched for age, sex, and educational level. The performance of the NS and HD subjects did not differ significantly from the well controls on measures of lexical-semantic abilities. NS and HD subjects provided as much information about the target picture as control subjects, but produced fewer action information units. Analysis of syntactic abilities revealed that the HD subjects produced significantly more grammatical errors than both the NS and control subjects and that the NS group performed in a similar manner to control subjects. These findings are considered in terms of current theories of subcortical language function. As a result of this activity, the reader will obtain information about the debate surrounding the role of subcortical language mechanisms and be provided with new information on the comparative picture description abilities of individuals with known vascular and degenerative subcortical pathologies and healthy control participants.


Numerical simulations with the P-Hydroslag model to predict phosphorus removal by steel slag filters.
The first version of the P-Hydroslag model for numerical simulations of steel slag filters is presented. This model main original feature is the implementation of slag exhaustion behavior, crystal growth and crystal size effect on crystal solubility, and crystal accumulation effect on slag dissolution. The model includes four mineral phases: calcite, monetite, homogeneous hydroxyapatite (constant size and solubility) and heterogeneous hydroxyapatite (increasing size and decreasing solubility). In the proposed model, slag behavior is represented by CaO dissolution kinetic rate and exhaustion equations; while slag dissolution is limited by a diffusion rate through a crystal layer. An experimental test for measurement of exhaustion equations is provided. The model was calibrated with an experimental program made of three phases. Firstly, batch tests with 300 g slag sample in synthetic solutions were conducted for the determination of exhaustion equation. Secondly, a slag filter column test fed with synthetic solution was run for 623 days, divided into 9 cells and sampled at the end of the experiment. Finally, the column was dismantled, sampled and analyzed with XRD, TEM and SEM. Experimental column curves for pH, oPO4, Ca and inorganic carbon were well predicted by the model. Crystal sizes measured by XRD and TEM validated the hypothesis for homogeneous precipitation while SEM observations validated the thin crystal layer hypothesis. A preliminary validation of the model resulted in successful predictions of a steel slag filter longevity fed with real wastewater.


Quantification of 2-aminothiazoline-4-carboxylic acid as a reliable marker of cyanide exposure using chemical derivatization followed by liquid chromatography-tandem mass spectrometry.
In this research, we have developed a novel and simple liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) method for quantification of 2-aminothiazoline-4-carboxylic acid (ATCA), which is produced by the direct reaction of cyanide (CN) with endogenous cystine. In forensic science, detection of CN is important because CN is a poison that is often used for murder or suicide, in addition to being produced by the thermal decomposition of natural or synthetic materials. However, because CN disappears rapidly from body tissue, ATCA is thought to be a more reliable indicator of CN exposure. For the method reported herein, human blood samples (20 μL) were subjected to protein precipitation followed by derivatization with 4-bromoethyl-7-methoxycoumarin. Blood spiked with ATCA at concentrations ranging from 50 to 1500 ng/mL was used to prepare a calibration curve (lower limit of quantification; 50 ng/mL, lower limit of detection; 25 ng/mL). Our method uses chemical derivatization, so unlike previously reported methods, it does not require tedious pretreatment procedures, hydrophilic interaction liquid chromatography columns, or specialized equipment. In addition, our method allows for repeatable and accurate quantification of ATCA, with intra- and inter-assay coefficients of variation of below 5.0% and below 6.0%, respectively. We used the method to analyze ATCA in postmortem human blood samples, including samples from people who had intentionally ingested CN or were fire victims. Blood ATCA concentrations were higher among people who had ingested CN or were fire victims than among people in a control group (P < 0.0001). The data reported herein demonstrate that our LC/ESI-MS/MS method can be used to detect and quantify ATCA in postmortem blood samples and that CN exposure strongly affects ATCA concentration, providing a useful tool for detection of CN poisoning.


Isolation and whole genome sequencing of a Ruminococcus-like bacterium, associated with irritable bowel syndrome.
In our previous studies on the intestinal microbiota in irritable bowel syndrome (IBS), we identified a bacterial phylotype with higher abundance in patients suffering from diarrhea than in healthy controls. In the present work, we have isolated in pure culture strain RT94, belonging to this phylotype, determined its whole genome sequence and performed an extensive genomic analysis and phenotypical testing. This revealed strain RT94 to be a strict anaerobe apparently belonging to a novel species with only 94% similarity in the 16S rRNA gene sequence to the closest relatives Ruminococcus torques and Ruminococcus lactaris. The G + C content of strain RT94 is 45.2 mol% and the major long-chain cellular fatty acids are C16:0, C18:0 and C14:0. The isolate is metabolically versatile but not a mucus or cellulose utilizer. It produces acetate, ethanol, succinate, lactate and formate, but very little butyrate, as end products of glucose metabolism. The mechanisms underlying the association of strain RT94 with diarrhea-type IBS are discussed.


Integrated analysis of miRNA and mRNA profiles enables target acquisition in human cancers.
miRNAs play a role in post-transcriptional gene regulation by translational repression and/or mRNA degradation in a very tissue-specific manner. In order to understand the function of a miRNA, it is best to identify the genes that it regulates. Putative mRNA targets of miRNAs identified from seed sequence matches are available using computational algorithms in various web-based databases. However, these tend to have high false-positive rates and, owing to a whole-genome approach, cannot identify tissue/tumor specificity of regulation. The evaluated article presents a large amount of data analyzing global RNA expression in breast cancer and examines whether miRNAs are prognostic due to their effects on mRNA targets. This valuable and important resource of combined miRNA and mRNA expression in breast cancer and its subtypes has been summarized. Many studies have now investigated the integrated analysis of miRNA:mRNA profiles in human malignancies, the goal as always being to identify novel biomarkers and therapeutic targets for each tumor.


Large-scale dosimetric assessment of Monte Carlo recalculated doses for lung robotic stereotactic body radiation therapy.
Owing to its short computation time and simplicity, the Ray-Tracing algorithm (RAT) has long been used to calculate dose distributions for the CyberKnife system. However, it is known that RAT fails to fully account for tissue heterogeneity and is therefore inaccurate in the lung. The aim of this study is to make a dosimetric assessment of 219 non-small cell lung cancer CyberKnife plans by recalculating their dose distributions using an independent Monte Carlo (MC) method. For plans initially calculated by RAT without heterogeneity corrections, target coverage was found to be significantly compromised when considering MC doses. Only 35.4% of plans were found to comply to their prescription doses. If the normal tissue dose limits were respected in the treatment planning dose, the MC recalculated dose did not exceed these limits in over 97% of the plans. Comparison of RAT and recalculated-MC doses confirmed the overestimation of RAT doses observed in previous studies. An inverse correlation between the RAT/MC dose ratio and the target size was also found to be statistically significant (p<10-4), consistent with other studies. In addition, the inaccuracy and variability in target coverage incurred from dose calculations using RAT without heterogeneity corrections was demonstrated. On average, no clinically relevant differences were observed between MC-calculated dose-to-water and dose-to-medium for all tissues investigated (⩽1%). Patients receiving a dose D95% larger than 119 Gy in EQD210 (or ≈52 Gy in 3 fractions) as recalculated by MC were observed to have significantly superior loco-regional progression-free survival rates (p=0.02) with a hazard ratio of 3.45 (95%CI: 1.14-10.5).