Interactive effects of microplastics and selected pharmaceuticals on red tilapia: Role of microplastic aging.
The present study used red tilapia (Oreochromis niloticusas) as the model fish to compare the interactive effects between aged and virgin microplastics (MPs) with the antibiotic sulfamethoxazole (SMX) and the β-blocker propranolol (PRP). To this end, the ultraviolet irradiation was used to simulate the MP aging in the environment. The accumulations of MPs and pharmaceuticals, and changes in enzyme activities and genes expressions in tilapia were also evaluated. Some physical properties of MPs changed during the aging process, reflected by 0.27- and 0.16-fold increases in the specific surface area and average pore volume, respectively. And more carbonyl formation was observed on the surface of aged MPs. Compared to the 14-d coexposure with virgin MPs, the MP aging increased the accumulation of PRP by 82.3% in the brain, whereas decreased the concentration of SMX by 46.1% in the gills. The stress on tilapia caused by the MPs and PRP was alleviated by the aging process, largely related to the lower neurotoxicity and reduced lipid peroxidation damages. However, the coexposure to aged MPs and SMX would result in higher inhibitions of cytochrome P450 enzymes activities. The results of the transcriptomics showed that the MP aging mainly influenced the expression of genes related to the metabolic process, immune system process, and the genetic information process in tilapia under the coexposure to MPs and pharmaceuticals. Collectively, our results suggest that the MP aging could induce complex changes in the interactive effects between MPs and pharmaceuticals on aquatic organisms.


Chagas disease: role of parasite genetic variation in pathogenesis.
Chagas disease, caused by the parasite protozoan Trypanosoma cruzi, is characterised by a variable clinical course, from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. This variability has been attributed both to differences in the host response and to genomic heterogeneity of the parasite. This article reviews the evidence in favour of an important role of the genetic constitution of T. cruzi in determining the clinical characteristics of Chagas disease and discusses the basis of the 'Clonal-Histotropic Model' for the pathogenesis of this disease.


In vitro adhesion of K88ab-, K88ac- and K88ad-positive Escherichia coli to intestinal villi, to buccal cells and to erythrocytes of weaned piglets.
The phenotype of 21 weaned piglets, concerning adhesion of Escherichia coli possessing K88ab, K88ac or K88ad fimbriae to pig cells, was determined in an in vitro assay. Comparison was made with adhesion of these three K88 variant strains to buccal mucosal epithelial cells and to erythrocytes (haemagglutination) in the same piglets. Whereas adhesion of the three K88 variant strains to intestinal villi was piglet specific, buccal cell adhesion (BCA) and haemagglutination (HA) were not. The K88ab strain was weakly adhesive or non-adhesive in the BCA and negative in the HA test. K88ac strains consistently gave negative and K88ad consistently gave positive results in both assays. After washing the bacteria with phosphate-buffered saline, the K88ab strain revealed a positive HA test. Neither the BCA, nor HA test can be used to determine the pig intestinal adhesive phenotype.


Perceptual learning of degraded speech by minimizing prediction error.
Human perception is shaped by past experience on multiple timescales. Sudden and dramatic changes in perception occur when prior knowledge or expectations match stimulus content. These immediate effects contrast with the longer-term, more gradual improvements that are characteristic of perceptual learning. Despite extensive investigation of these two experience-dependent phenomena, there is considerable debate about whether they result from common or dissociable neural mechanisms. Here we test single- and dual-mechanism accounts of experience-dependent changes in perception using concurrent magnetoencephalographic and EEG recordings of neural responses evoked by degraded speech. When speech clarity was enhanced by prior knowledge obtained from matching text, we observed reduced neural activity in a peri-auditory region of the superior temporal gyrus (STG). Critically, longer-term improvements in the accuracy of speech recognition following perceptual learning resulted in reduced activity in a nearly identical STG region. Moreover, short-term neural changes caused by prior knowledge and longer-term neural changes arising from perceptual learning were correlated across subjects with the magnitude of learning-induced changes in recognition accuracy. These experience-dependent effects on neural processing could be dissociated from the neural effect of hearing physically clearer speech, which similarly enhanced perception but increased rather than decreased STG responses. Hence, the observed neural effects of prior knowledge and perceptual learning cannot be attributed to epiphenomenal changes in listening effort that accompany enhanced perception. Instead, our results support a predictive coding account of speech perception; computational simulations show how a single mechanism, minimization of prediction error, can drive immediate perceptual effects of prior knowledge and longer-term perceptual learning of degraded speech.


Immunological evidences for post-translational control of the parathyroid function by ionized calcium in dogs.
To outline the role of post-translational events in the control of the parathyroid function in vivo, we have studied the parathyroid function of normal dogs receiving i.v. infusions of CaCl2 and Na2EDTA with intact (I), carboxylterminal (C) and midcarboxylterminal (M) iPTH assays and evaluated the influence of ionized calcium on circulating molecular forms of iPTH via alterations in C/I, M/I and M/C iPTH ratios. Furthermore, the use of the mathematical model fitting the sigmoidal relationship between ionized calcium and iPTH ratios was improved through the generation of more iPTH ratio points in the ascending part of the sigmoid function. Quantitatively, the response to hypocalcemia was highest with M (98.7 +/- 36.8 pmol/l; P < 0.0167 vs. L and P < 0.0001 vs. I) and higher with L (83.1 +/- 26.1 pmol/l; P < 0.0001 vs. I) than with I (12.1 +/- 3.2 pmol/l). Similar results were observed for the non-suppressible fraction of iPTH measured by the three iPTH assays in hypercalcemia. The slope of the sigmoid function was more acute for I than for C or M, while all three secretion set-points were similar at 1.30 mmol/l. Qualitatively, all iPTH ratios increased from hypo- to hypercalcemia, results being more pronounced for the M/I and C/I iPTH ratios (7.66 +/- 2.57 to 73.9 +/- 41.4 and 6.76 +/- 1.93 to 49.8 +/- 27.5) than for the M/C iPTH ratio (1.24 +/- 0.48 to 1.82 +/- 1.16). The slopes of the three ratios were similar as were the set-points, but in this last case, values were higher (1.40 mmol/l) than for secretion set-points. These results indicate that dog parathyroid function is similar to that of man. The lower set-points for secretion and higher ones for regulating M/I and C/I iPTH ratios favor an optimal amount of I in face of decreasing ionized calcium and permit to control the non-suppressible fraction of iPTH secretion via M and C fragments production in face of increasing ionized calcium. These events are important to understand the implication and signification of post-translational events in the parathyroid glands and in peripheral blood in the phenomenon of PTH immunoheterogeneity. They further outline that the tools used here will be useful to study similar phenomenons in individuals in face of diseased parathyroid glands.


Hersintuzumab: A novel humanized anti-HER2 monoclonal antibody induces potent tumor growth inhibition.
Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.


Clonal outbreak caused by VIM-4-producing Proteus mirabilis in a Greek tertiary-care hospital.
Carbapenem-resistant Enterobacterales have become a major public-health issue worldwide. Here we report an outbreak caused by a clonal multidrug-resistant Proteus mirabilis strain producing VIM-4 metallo-β-lactamase (MBL) and TEM-2 β-lactamase in a Greek tertiary-care hospital. From July 2015 to February 2016, 27 imipenem-resistant P. mirabilis isolates were recovered from 14 patients hospitalised in two intensive care units (ICUs) and the internal medicine department in AHEPA University Hospital, Thessaloniki. The isolates were either susceptible or resistant to meropenem and were resistant to all remaining β-lactams except aztreonam. Phenotypic and molecular analysis revealed that all of the isolates harboured a blaVIM-4 MBL gene. Resistome analysis of a representative isolate showed the presence of an IncQ1 plasmid harbouring the blaVIM-4 carbapenemase and blaTEM-2 β-lactamase genes among resistance genes coding for resistance to β-lactams, aminoglycosides, trimethoprim, sulfonamides and lincosamides. Genotyping by pulsed-field electrophoresis (PFGE) revealed that the isolates were epidemiologically related. After recovery of the index carbapenemase-producing P. mirabilis clinical isolate, infection control measures were intensified in the affected departments. Rectal sampling for carbapenem-resistant bacteria was initiated on a weekly basis among patients admitted to the general ICU. The outbreak was finally interrupted 6 months later in February 2016. This is the first documentation of the blaVIM-4 MBL gene in P. mirabilis as well as the first hospital outbreak caused by a MBL-producing P. mirabilis strain.


Heat-induced fragmentation of human plasma fibronectin.
Human plasma fibronectin was found to undergo fragmentation during heat-denaturation, leading to artifacts in SDS-polyacrylamide gel electrophoretic analyses. Electrophoretic patterns of heated samples showed a progressive decrease in intact fibronectin chains (225 kDa) which coincided with the appearance of increasing amounts of numerous smaller components having molecular weights ranging from 10 000 to 200 000. The fragmentation was temperature-dependent, being undetectable after 2 h at 60 degrees C, but detectable after 30 min at 70 degrees C or as little as 2 min at 100 degrees C. After 2 h at 100 degrees C, the intact monomer was no longer visible. Neither mercaptoethanol nor SDS was required for fragmentation. Sterile filtration or pretreatment with inhibitors of proteolytic enzymes had no effect. Treatment with amines did not diminish the degradation, indicating that the process differs from heat-fragmentation of alpha 2-macroglobulin and complement proteins, which occurs at a reactive internal thiolester bond. Fibronectin fragmentation was highly pH-dependent, being markedly accelerated under acidic conditions, suggesting that autolytic cleavage of the peptide chain at acid-labile aspartyl bonds was responsible for this phenomenon.


Comparison of Definitive Chemoradiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma.
This retrospective study was designed to estimate the efficacy and toxicity of definitive radiotherapy with concurrent or sequential docetaxel/S-1 for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Of the 62 eligible patients enrolled in this study during January 1, 2010 to December 31, 2014 from Qilu Hospital, Shandong University, Shandong Province, 39 patients received 3 cycles of docetaxel/S-1 during and after radiotherapy (concurrent chemoradiotherapy, CCRT), and 23 patients had radiotherapy followed by 3 cycles of docetaxel and S-1 (sequential chemoradiotherapy, SCRT). The CR of CCRT and SCRT groups were 48.72 and 21.74 %, respectively (p = 0.035). The median progress-free survival (PFS) of CCRT group (23.5 months) was significantly higher than SCRT group (11.7 months; p = 0.004). The median overall survival (OS) of CCRT group (33.5 months) also was significantly higher than SCRT group (24.0 months; p = 0.004). At 2 years, in this patient population, the rate of PFS of CCRT group was (44.2 ± 8.2 %), significantly higher than SCRT group (11.9 ± 9.6 %; p = 0.002). The 2-year OS rate of CCRT (68.6 ± 7.5 %) was significantly higher than SCRT group as well (42.0 ± 14.0 %; p = 0.002). The incidence of adverse events was higher in CCRT than SCRT group. No grade 4 or grade 5 adverse events occurred in our study. Definitive radiotherapy with concurrent or sequential docetaxel and S-1 for inoperable locally advanced ESCC was very well tolerated and remarkably active. In both CCRT and SCRT groups, acute toxicities were manageable. This regimen holds promises for treatment of esophageal carcinoma and warrants further investigation.


Designing an effective statewide tobacco control program--California.
In this report, the author traces the history of the development of the first statewide tobacco control program, from its early obstacles and legislative-imposed deadline through the development of its three priority areas. Woven into this review is Dr. Bal's emphasis on the role of a cohesive leadership tied into the needs of the tobacco control constituency.


Larynx motion associated with swallowing during radiation therapy.
A basis is presented for predicting the reduction in radiation dose to the larynx attributable to swallowing during radiation therapy treatment. Laryngeal movement associated with swallowing can occur during radiation therapy even when the patient's head is immobilized. Data on the extent and timing of laryngeal motions and the frequency of swallowing were used to predict the effect such motion would have on accuracy of radiation dose to the larynx. In a nontracheostomized adult the larynx elevates approximately 2 cm during a swallow and moves anteriorly less than 1 cm. The normal frequency of swallowing in the supine position is once every 1-2 min. During therapy, the likelihood of a swallow occurring during an irradiation interval depended on the duration of the interval. For irradiation intervals less than 2 min long the ratio of number of swallows to number of intervals was 0.27. For irradiation intervals between 2-3 min long the ratio was 1.76. Based on conservative estimates of radiation field dimensions, larynx motion, and incidence of swallowing, the reduction in radiation dose attributable to swallowing during treatment would be approximately 0.5%. With small fields the total dose is only decreased by 0.5% with swallowing, so the change in the total dose is insignificant.


Characteristics of IDH-mutant gliomas with non-canonical IDH mutation.
Approximately 10% of IDH-mutant gliomas harbour non-canonical IDH mutations (non-p.R132H IDH1 and IDH2 mutations). The aim of this study was to analyse the characteristics of non-canonical IDH-mutant gliomas. We retrospectively analysed the characteristics of 166 patients with non-canonical IDH mutant gliomas and compared them to those of 155 consecutive patients with IDH1 p.R132H mutant gliomas. The median age at diagnosis was 38 years in patients with non-canonical IDH mutant gliomas and 43 years in glioma patients with IDH1 p.R132H-mutant tumours. Family history of cancer was more frequent among glioma patients harbouring non-canonical IDH mutations than in patients with IDH1 p.R132H mutations (22.2% vs 5.1%; P < 0.05). Tumours were predominantly localised in the frontal lobe regardless of the type of IDH mutation. Compared to IDH1 p.R132H-mutant gliomas, tumours with non-canonical IDH mutations were more frequently found in the infratentorial region (5.5% vs 0%; P < 0.05) and were often multicentric (4.8% vs 0.9%; P < 0.05). Compared to IDH1 P.R132H-mutant gliomas, tumours with non-canonical IDH1 mutations were more frequently astrocytomas (65.6% vs 43%, P < 0.05), while those with IDH2 mutations were more frequently oligodendrogliomas (85% vs 48.3%; P < 0.05). The median overall survival was similar in patients with IDH1 p.R132H-mutant gliomas and patients with non-canonical IDH-mutant gliomas. Gliomas with non-canonical IDH mutations have distinct radiological and histological characteristics. The presence of such tumours seems to be associated with genetic predisposition to cancer development.


Binding characteristics of progesterone and antiprogestin ZK 98.299 in human endometrial and myometrial cytosol.
The binding of ZK 98.299, a synthetic progesterone antagonist, with human endometrium and myometrium cytosol was studied and compared with that of progesterone. Progesterone showed specific saturable binding to its receptors in both endometrium and myometrium. ZK 98.299 and progesterone were mutually competitive for binding to progesterone receptors; however, the relative binding affinity of ZK 98.299 was 16% that of progesterone. ZK 98.299 exchanged the progesterone-labelled receptor sites. [3H]ZK 98.299 showed specific binding which was linearly related to the cytosol protein concentration. The binding was not saturable at 15 nM of ligand. The binding capacity and binding affinity of ZK 98.299 receptor was less than that of progesterone. Progesterone also partially displaced the binding of [3H]ZK 98.299. This study suggest that ZK 98.299 and progesterone both bind to the same protein. However, whether ZK 98.299 binds to progesterone receptors alone or even to other functionally related sites is not known. It appears that ZK 98.299 when present in higher concentration than progesterone would be an effective receptor ligand.


3-Tesla MRI: Beneficial visualization of the meniscofemoral ligaments?
Recent investigations have confirmed an important stabilizing and protective function of the meniscofemoral ligaments (MFLs) to the knee joint and suggest a clinical relevance. Concerning their incidences, however, there have been discrepancies between data acquired from cadaveric studies and MRI data using 0.3- to 1.5-Tesla field strengths probably due to lower resolution. This study aims to investigate whether imaging with 3-Tesla magnetic resonance imaging (3-T MRI) is beneficial in gaining information regarding the ligaments' incidence, length, width and anatomic variation. 3-T MRI images of 448 patients (224 males, 224 females, with, respectively, 32 patients of each sex in the age groups: 0-20, 21-30, 31-40, 41-50, 51-60, 61-70, >70years) were retrospectively reviewed. The influence of the parameters 'sex' and 'age' was determined. Whereas 71% of the patients had at least one MFL, 22% had an anterior MFL (aMFL), 53% had a posterior MFL (pMFL) and five percent had coexisting ligaments. The pMFLs were more likely to be present in female patients (P<0.05) but if so, they were longer in the males (P<0.05). The pMFL was categorized according to its insertion on the medial femoral condyle. 3-T MRI enables an excellent illustration of the anatomic variations of pMFLs. By modifying an anatomic classification for radiological use we measured lengths and widths of the MFLs without any difficulties. Despite its increased resolution, 3-T MRI lends no diagnostic benefit in visualizing the course of the aMFL or filigree coexisting ligaments as compared to MRI at lower field strengths.


Focal eosinophilic infiltration of the liver mimicking hepatocellular carcinoma: case reports.
Focal eosinophilic infiltration is a rare disease entity that in patients with malignancies may mimic malignant hepatic nodules. We describe two cases in which focal eosinophilic infiltration of the liver, as well as primary liver cancer, occurred. In these patients, imaging findings similar to those observed in hepatocellular carcinoma (HCC) were noted: Enhancement at dynamic magnetic resonance (MR) imaging substantially increased perfusion at computed tomography during hepatic arteriography (CTHA) and a perfusion defect at computed tomography during arterial portography (CTAP).


Influenza A (H1N1) 2009 reinfection in Thailand.
In 2009, a novel influenza A (H1N1) virus emerged and rapidly spread around the world, leading to a pandemic. In contrast to the high rate of primary infection, reinfection with influenza A (H1N1) 2009 is rather rare. In this report, we describe a case of influenza A (H1N1) 2009 reinfection that occurred within an interval of 5 months in Thailand.


Cacao pod husks as a source of low-methoxyl, highly acetylated pectins able to gel in acidic media.
Cacao pod husks, the main by-product from cocoa production, have been investigated for pectin isolation. In the present study, the rheological properties of two low-methoxyl (LM) pectins isolated from cacao pod husks using different extraction conditions were evaluated. One pectin was obtained from optimized conditions employing aqueous nitric acid as an extractant, and the other one was extracted with boiling water. Pectin gels (0.99% galacturonic acid equivalent, w/w) were prepared at pH 2.5-3.0 in the presence of 60% sucrose (w/w) and subjected to rheological analysis. Dynamic oscillatory experiments at 25°C indicated that better gels were obtained at the lowest pH (2.5). Steady shear measurements revealed a shear-thinning behavior. The apparent viscosities of the samples increased as pH decreased. Gelation with calcium ions was not observed for either of the highly acetylated LM pectins analyzed. The rheological analysis results showed that despite their high acetyl content, LM pectins extracted by different methods from cacao pod husks were able to form gels at low pH under reduced water activity, suggesting a possible application in acidic products.


Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy.
Late normal tissue toxicity varies widely between patients and limits breast radiotherapy dose. Here we aimed to determine its relationship to DNA damage responses of fibroblast cultures from individual patients. Thirty-five breast cancer patients, with minimal or marked breast changes after breast-conserving therapy consented to receive a 4 Gy test irradiation to a small skin field of the left buttock and have punch biopsies taken from irradiated and unirradiated skin. Early-passage fibroblast cultures were established by outgrowth and irradiated in vitro with 0 or 4 Gy. 53BP1 foci, p53 and p21/CDKN1A were detected by immunofluorescence microscopy. Residual 53BP1 foci counts 24 h after in vitro irradiation were significantly higher in fibroblasts from RT-sensitive versus RT-resistant patients. Furthermore, significantly larger fractions of p53- but not p21/CDKN1A-positive fibroblasts were found in cultures from RT-sensitive patients without in vitro irradiation, and 2 h and 6 d post-irradiation. Exploratory analysis showed a stronger p53 response 2 h after irradiation of fibroblasts established from patients with severe reaction. These results associate the radiation response of fibroblasts with late reaction of the breast after RT and suggest a correlation with severity.


Low ejection fraction in donor hearts is not directly associated with increased recipient mortality.
Reduced left ventricular ejection fraction (EF) in the donor heart is often a contraindication for transplant. However, small studies have validated the use of hearts with evidence of myocardial dysfunction to boost the number of organs available for transplant. We hypothesize that donor hearts with reduced EF undergo myocardial recovery after transplant and result in equivalent recipient survival compared with grafts with normal function. We examined post-operative outcomes of heart recipients in the database of the United Network for Organ Sharing. Patients were grouped by donor EF as follows: <40% (reduced EF); between 40% and 50% (borderline EF); and ≥50% (normal EF). Propensity score matching was performed to compare separately reduced and borderline EF patients with normal EF patients. Of 30,993 donors from 1996 to 2015, 127 (0.4%) had reduced EF, 613 (2.0%) had borderline EF and 30,253 (97.6%) had normal EF. In each of the 2 propensity score comparisons, the odds of post-operative stroke (p = 0.139, p = 0.551), pacemaker requirement (p = 0.238, p = 0.739), primary graft failure (p = 0.569, p = 0.817), rejection (p = 0.376, p = 0.533) and death at 1 year (p = 0.124, p = 0.247) were equivalent. At roughly 1-year follow-up after transplant, the mean EF of the reduced EF group was 58.0 ± 10.3% compared with 59.5 ± 7.5% in the matched normal EF group (p = 0.289). The mean follow-up EF of the borderline EF group was 58.3 ± 9.1% compared with 59.3 ± 7.7% in the matched normal EF group (p = 0.106). Recipients of hearts with reduced EF have equivalent 1-year survival compared with recipients of hearts with normal EF. Donor hearts with reduced EF show significant functional recovery after transplant.


[Specificity of acne in women older than 25 years].
Our aim was to examine the specific clinical and therapeutic characteristics of acne in women seen in our practice. This retrospective observational study included all women older than 25 years seen in our practice between 1 January 2001 and 31 December 2003. The mean age of the 79 women included in the study was 31.8 years; 67% reported a family history of acne; 79% reported at least one acne-promoting factor, 62% regular cosmetic use. Acne began at a mean age of 16.6 years, and only 13% had lesions before menarche. Before referral, they had received an average of 2.3+/-1.6 systemic treatments and 43% had already been treated by isotretinoin. Over an average follow-up period of 11 months, 83% of those for whom we prescribed isotretinoin had complete remissions, and 17% a partial response. Acne in women seems to be a persistent form of juvenile acne. Most of the cases we saw were inflammatory acne, with extrafacial lesions in one third of cases. The high frequency of familial history and severe seborrhea suggest a genetic factor. We also noticed the influence of the premenstrual period, stress, sun exposure and cosmetic use. Isotretinoin treatment produced the best therapeutic response.


Cardiomyopathy with arrhythmias and ectodermal dysplasia: a previously unreported association.
Hidrotic ectodermal dysplasia represents a group of congenital or hereditary disorders that involve ectodermal derivatives. It is characterized by partial or complete alopecia, dystrophic nails, and dental abnormalities. Dilated cardiomyopathy has not previously been reported in association with this illness. We report the cases of three children with fatal dilated cardiomyopathy with associated cardiac arrhythmias and ectodermal dysplasia. Laboratory investigations revealed no specific cause for the cardiomyopathy. It is speculated that this association is not simply coincidental.


Predicting difficult transradial approach guiding into left internal carotid artery on unruptured intracranial aneurysms.
The transradial approach (TRA) is less invasive than the transfemoral approach (TFA), but the higher conversion rate represents a drawback. Among target vessels, the left internal carotid artery (ICA) is particularly difficult to deliver the guiding catheter to through TRA. The purpose of this study was thus to explore anatomical and clinical features objectively predictive of the difficulty of delivering a guiding catheter into the left ICA via TRA. Among 78 consecutive patients who underwent coil embolization for unruptured intracranial aneurysms through TRA in a single institution between March 1, 2021, and August 31, 2022, all 29 patients (37%) who underwent delivery of the guiding catheter into the left ICA were retrospectively analyzed. Clinical and anatomical features were analyzed to assess correlations with difficulty in guiding the catheter into the left ICA. Of the 29 aneurysms requiring guidance of a catheter into the left ICA, 9 aneurysms (31%) required conversion from TRA to TFA. More acute innominate-left common carotid artery (CCA) angle (P < 0.001) and older age (P = 0.015) were associated with a higher conversion rate to TFA. Receiver operating characteristic analysis revealed that optimal cutoff values for the innominate-left CCA angle and age to distinguish between nonconversion and conversion to TFA were 16° (area under the curve [AUC], 0.93; 95% confidence interval [CI], 0.83-1.00) and 74 years (AUC, 0.79; 95% CI, 0.61-0.96), respectively. A more acute innominate-left CCA angle and older age appear associated with difficulty delivering the guiding catheter into the left ICA for neurointervention through TRA.


Epidemiological study of 314 cases of cancer of the bladder in the administrative department of Bas-Rhin, France.
This study is composed of two epidemiological investigations. The first concerns the geographical distribution of cancer of the bladder in the department of Bas-Rhin. The geographical distribution of 314 cases of cancer of the bladder in eight districts of the Bas-Rhin has been studied. The resultant map shows considerable variations in morbidity. The urban predominance may be due to environmental factors. The second enquiry concerns the frequency of multiple cancers of different primary sites occurring in cases of cancer of the bladder. Nine such cases have been identified. There may be a common predisposing factor in such cases. All patients were heavy smokers.


Tunnel widening after ACL reconstruction with different fixation techniques: aperture fixation with biodegradable interference screws versus all-inside technique with suspensory cortical buttons. 5-year data from a prospective randomized trial.
The aim of the present study was to examine tunnel widening and clinical outcomes after anterior cruciate ligament reconstruction (ACLR) using two different fixation methods: aperture fixation with biodegradable interference screws versus all-inside ACLR with suspensory cortical buttons. Tunnel widening was assessed using volumetric and diameter measurements on magnetic resonance imaging (MRI) scans directly after surgery, as well as 6 months and 2 and 5 years postoperatively. Clinical outcomes were assessed after 5 years with instrumented tibial anteroposterior translation measurement (KT-1000), single-leg hop testing, and the IKDC, Lysholm, and Tegner activity scores. At the final follow-up, the study population consisted of 21 patients, 12 of whom underwent screw fixation and 9 of whom had button fixation. 3 patients with all-inside ACLR had sustained early repeat ruptures within 6 months after surgery and had to be excluded from the further analysis. With screw fixation, the tibial tunnel volume changed significantly more over time compared to all-inside button fixation, with a larger initial increase at 6 months (from postoperative 2.9 ± 0.2 to 3.3 ± 0.2 cm3 at 6 months versus 1.7 ± 0.1 to 1.9 ± 0.2 cm3) and a greater final decrease over 2-5 years postoperatively (from 3.1 ± 0.2 to 1.9 ± 0.2 cm3 versus 1.8 ± 0.2 ± 0.1 to 1.3 ± 0.1 cm3) (P < 0.001). The femoral tunnel volume remained comparable between the two groups throughout the follow-up period, with an initial 1.6 ± 0.1 cm3 in both groups and 1.2 ± 0.1 vs. 1.3 ± 0.1 after 5 years in the screw and button groups, respectively (P ≥ 0.314). The maximum tibial and femoral tunnel diameters were significantly larger with screw fixation at all four time points. Tibial diameters measured 11.1 ± 0.2, 12.3 ± 0.3, 12.3 ± 0.4, and 11.2 ± 0.4 mm in the screw group versus 8.1 ± 0.3, 8.9 ± 0.3, 9.1 ± 0.4 and 8.2 ± 0.5 mm in the button group (P < 0.001). Femoral diameters measured 8.6 ± 0.2, 10.5 ± 0.4, 10.2 ± 0.3, and 8.9 ± 0.3 versus 7.3 ± 0.3, 8.4 ± 0.4, 8.4 ± 0.3, 7.5 ± 0.3, respectively (P ≤ 0.007). Four patients (33%) in the screw group exceeded a diameter of 12 mm on the tibial side after 5 years versus none in the button group (not significant, P = 0.104). Tibial anteroposterior translation measurement with KT-1000 after 5 years was 2.3 ± 2.4 mm in the screw group versus 3.2 ± 3.5 mm in the button group (not significant, P = 0.602). There were no significant differences between the groups in any of the other clinical outcomes. Tibial tunnels in ACLR with screw fixation were associated with a larger increase in tunnel volume within the first 2 years and a greater decrease up to 5 years after surgery, while femoral tunnel volumes did not differ significantly. On the tibial side, the need for staged revision ACLR may be greater after biodegradable interference screw fixation if repeat ruptures occur, especially within the first 2 years after primary ACLR. Concerns may remain regarding a higher graft failure rate with all-inside ACLR. II. NCT01755819.


Immunoelectron microscopic localisation of ribosomal proteins from Bacillus stearothermophilus that are homologous to Escherichia coli L1, L6, L23 and L29.
The locations of proteins BL1, BL6, BL23 and BL29 from Bacillus stearothermophilus have been determined on the ribosomal surface by immunoelectron microscopy. All four proteins were localized in the same region of the 50S subunit as their homologous counterparts from Escherichia coli, indicating that the ribosomal architecture is the same in both species. This finding is of great importance as it allows structural data obtained on ribosomes from either organism to be incorporated into a unique ribosome model.


Determination of indicine N-oxide and indicine in plasma and urine by electron-capture gas-liquid chromatography.
A sensitive and specific method is described for the quantitative analysis of indicine N-oxide and indicine in plasma and urine. Indicine N-oxide is reduced to the tertiary amine with zinc--acetic acid (plasma) or zinc--ammonium chloride (urine). The indicine is derivatized with pentafluoropropionic anhydride to provide electron-capture detection. Assay of rabbit and human plasma and urine samples can detect 100 ng/ml (plasma) and 200 ng/ml (urine), and the method was applied to the analysis of indicine N-oxide and indicine in rabbits and one patient following administration of indicine N-oxide.


Children's Involvement in Different Sport Types Differentiates Their Motor Competence but Not Their Executive Functions.
Sports provide a context where important aspects of children's health, such as motor skills and cognitive functions, can be enhanced. However, it is unknown which type of sport may be better for the development of motor competence (MC) and executive functions (EFs). This study investigated potential differences in MC and EFs in boys and girls, being involved in different types of sports (team, individual open skill, individual closed skill). A total of 115 children (49 boys), 8-12 years old (10.30 ± 1.19 years), participated in the study. Their MC was assessed with the Bruininks-Oseretsky Test of Motor Proficiency-2 Short Form, whereas for EFs, the Attention Network Test, the digits backwards test, and the how many-what number test were utilized. Significant MC differences among participants in different types of sports were revealed, favoring those from closed-skill sports; nevertheless, their EFs were at similar levels. Furthermore, no significant gender MC and EFs differences were detected. It seems that children's participation in specific types of sports differentiates their motor skills but not their EFs, whereas boys and girls, when provided with the same opportunities, present similar levels of MC and EFs.


Sequence variation in the E7 gene of human papillomavirus type 18 in tumor and non-tumor patients and antibody response to a conserved seroreactive epitope.
We have determined nucleotide sequences of the E7 open reading frame (ORF) of human papillomavirus type 18 (HPV-18) isolates obtained from 18 cervical carcinomas from Tanzanian and German patients and 8 cervical scrapings from Tanzanian non-tumor patients. The HPV-18 prototype sequence was detected in only 3 out of 26 isolates. Silent mutations were found at nt positions 640 and 751, whereas the mutations observed at nt positions 770, 806, 864 and 865 all change the respectively encoded amino acid. The HPV-18 isolates of 3 German carcinomas showed the same mutations (at position 751) as those of 2 established cervical carcinoma cell lines (HeLa and C4-1), whereas different mutations were found in 16/23 African isolates (at positions 640 and 864), to which the isolate of cell line SW756 was similar (changes at positions 640 and 865). Seven out of 15 HPV-18-positive Tanzanian tumor patients (46.7%) reacted in a peptide ELISA against a recently described seroreactive epitope of the HPV-18 E7 ORF (nt positions 704-769). Mutational changes of the E7 ORF were excluded as a possible explanation for the lack of antibody response, because there was no correlation with the serological results. The seroreactive region appears to be well conserved despite geographically varying mutations within the E7 ORF of HPV-18.


Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-κB signaling pathways.
NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC50 value of 30 μg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.


KLF7 promotes adipocyte inflammation and glucose metabolism disorder by activating the PKCζ/NF-κB pathway.
In the obesity context, inflammatory cytokines secreted by adipocytes lead to insulin resistance and are key to metabolic syndrome development. In our previous study, we found that the transcription factor KLF7 promoted the expression of p-p65 and IL-6 in adipocytes. However, the specific molecular mechanism remained unclear. In the present study, we found that the expression of KLF7, PKCζ, p-IκB, p-p65, and IL-6 in epididymal white adipose tissue (Epi WAT) in mice fed a high-fat diet (HFD) was significantly increased. In contrast, the expression of PKCζ, p-IκB, p-p65, and IL-6 was significantly decreased in Epi WAT of KLF7 fat conditional knockout mice. In 3T3-L1 adipocytes, KLF7 promoted the expression of IL-6 via the PKCζ/NF-κB pathway. In addition, we performed luciferase reporter and chromatin immunoprecipitation assays, which confirmed that KLF7 upregulated the expression of PKCζ transcripts in HEK-293T cells. Collectively, our results show that KLF7 promotes the expression of IL-6 by upregulating PKCζ expression and activating the NF-κB signaling pathway in adipocytes.


Fat Grafting for Facial Rejuvenation Using Stromal Vascular Fraction Gel Injection.
This study used stromal vascular fraction gel (SVF-gel), a mechanically processed fat-derived product, to treat eye bag and tear trough deformity. SVF-gel is prepared by a process of centrifugation and intersyringe shifting and is particularly rich in SVF cells and native adipose extracellular matrix. SVF-gel injection is used alone or combined with transconjunctival eye bag removal. High satisfaction was noted among patients treated with SVF-gel injection for periorbital rejuvenation with fairly low complication rates. SVF-gel injection is a good alternative to assist transconjunctival lower eyelid blepharoplasty and correct the palpebromalar groove, tear trough deformity, and supraorbital hollow.


Upregulated circular RNA circ-102004 that promotes cell proliferation in prostate cancer.
Prostate cancer (PCa) is one of the most prevalent cancers affecting men worldwide. However, the biological functions of circRNAs in PCa are still largely unknown. Real-time PCR (RT-PCR) and immunohistochemistry were performed to characterize the circ-102004 expression in both human PCa tissues and cell lines. The apoptosis and cell cycle status of prostate immortalized cell lines that were overexpressed with circ-102004 by transfection was analyzed using flow cytometry. The scratch test and the Transwell assay were conducted to evaluate the ability of transfected cells to migrate and invade. RNA sequencing, pathway analysis, and Western blotting were performed to probe the associations of circ-102004 with the classical cancer signaling pathways after functionally evaluating circ-102004 in a xenograft tumor model. In the present study, circ-102004 expression was found to be significantly higher in PCa samples than in the matched normal tissues. In functional experiments, circ-102004 is shown to play an oncogenic role in PCa by stimulating cancer cell migration and invasion. Circ-102004 overexpression was also accompanied by significant alterations in many signaling pathways, such as ERK, JNK, and Hedgehog, which are known to cause different types of cancers. Circ-102004 is a potential oncogenic gene that regulates the development and progression of PCa. This study provides a scientific basis for targeting circ-102004 for either diagnosis or therapy.


Linking Prenatal Androgens to Gender-Related Attitudes, Identity, and Activities: Evidence From Girls With Congenital Adrenal Hyperplasia.
Key questions for developmentalists concern the origins of gender attitudes and their implications for behavior. We examined whether prenatal androgen exposure was related to gender attitudes, and whether and how the links between attitudes and gendered activity interest and participation were mediated by gender identity and moderated by hormones. Gender attitudes (i.e., gender-role attitudes and attitudes about being a girl), gender identity, and gender-typed activities were reported by 54 girls aged 10-13 years varying in degree of prenatal androgen exposure, including 40 girls with classical congenital adrenal hyperplasia (C-CAH) exposed to high prenatal androgens and 14 girls with non-classical (NC) CAH exposed to low, female-typical, prenatal androgens. Both girls with C-CAH and NC-CAH reported positive attitudes about being a girl and egalitarian gender attitudes, consistent with their female-typical gender identity. In contrast, girls with C-CAH had more male-typed activity interest and participation than girls with NC-CAH. Gender attitudes were linked to activities in both groups, with gender identity mediating the links. Specifically, gender-role attitudes and positive attitudes about being a girl were associated with feminine gender identity, which in turn was associated with decreased male-typed activity interests and participation, and increased female-typed activity interests. Our results are consistent with schema theories, with attitudes more closely associated with gender identity than with prenatal androgens.


Investigation on synthesis of ternary g-C3N4/ZnO-W/M nanocomposites integrated heterojunction II as efficient photocatalyst for environmental applications.
The rapid industrialization of the world is disparagingly manipulating our environment and natural ecosystem. The researchers are taking keen interest to invent novel material as photocatalyst for non-degradable organic pollutants. Solar energy-driven practices employing semiconductors are a novel approach towards wastewater remediation. Here in, we successfully synthesized a vigorous photocatalysts comprising of g-C3N4 and doped ZnO-W/M (M = Co, Ce, Yb, Sm) by co-precipitation followed by metals doping via calcination approach. The structural, morphological, and photocatalytic applications for organic pollutants of synthesized heterostructure nanocomposites were examined by XRD, FTIR, SEM, EDX and UV visible spectrophotometer. Diffraction peaks attributed to both g-C3N4 and ZnO-W were detected in the XRD spectra. The FTIR spectra also inveterate the formation of g-C3N4/ZnO-W/M composites. The SEM images reveal an agglomerated morphology and EDS analysis also confirmed close contact between g-C3N4, ZnO-W and doped metals. The abridged energy band gap of g-C3N4/ZnO-W/M (M = Ce, Yb, Sm, Co) nanocomposites calculated via Tauc plot are 2.68, 2.88, 3.24 and 3.29 eV respectively. Narrowing of bandgap is considered an imperative triumph for the degradation of industrial effluents. The photocatalytic activity was performed against four different dyes and follows the trend Ce > Yb > Sm > Co. The recyclability tests were carried out for different dyes and no substantial catalytic activity loss was observed even after the fourth experimental run, which proves that reported ternary heterojunctions exhibit high mechanical stability and reusability.The species trapping experiment exposed that generated h+ are the principal active specie for dye photodegradation reactions. This work disseminates a novel photocatalyst for the removal of synthetic dyes.


Language-impaired 4-year-olds: distinguishing transient from persistent impairment.
In a prospective, longitudinal study, 87 language-impaired children were assessed at the ages of 4, 4 1/2, and 5 1/2 years on a battery of language measures. In 37% of children, who were termed the "good outcome group," the language disorder had resolved by the age of 5 1/2 years so that children were indistinguishable from a control group. If one restricted consideration only to those 68 children whose nonverbal ability was within normal limits, the figure rose to 44%. Outcome for individual children (good or poor) could be predicted with 90% accuracy on the basis of test measures obtained at 4 years. The best predictor was ability to tell back a simple story to pictures. The one language measure that did not relate to outcome was phonological competence.


General Care Considerations for the Pediatric Trauma Patient.
Trauma is a leading cause of morbidity and mortality for children in the United States. Access to trauma care, injury burden, and outcomes following injury, are inequitable. There are many anatomic and physiologic differences between children and adults that affect injury patterns and necessary trauma treatment. The principles of advanced trauma life support (ATLS) should be used by clinicians in high-resource settings for the immediate in-hospital treatment of the injured child.


Surgery for children in low-income countries affected by humanitarian emergencies from 2008 to 2014: The Médecins Sans Frontières Operations Centre Brussels experience.
Pediatric surgical care is deficient in developing countries disrupted by crisis. We aimed to describe pediatric surgical care at Médecins Sans Frontières-Brussels (MSF-OCB) projects to inform resource allocation and define the pediatric-specific skillset necessary for humanitarian surgical teams. Procedures performed by MSF-OCB from July 2008 to December 2014 were reviewed. Project characteristics, patient demographics and clinical data were described. Multivariable logistic regression was performed to determine predictors of perioperative death. Of 109,828 procedures, 26,284 were performed for 24,576 children (22% of all procedures). The most common pediatric operative indication was trauma (13,984; 57%). Nine percent of all surgical indications were due to violence (e.g., land mines, firearms, gender-based violence, etc.). The majority of procedures (19,582; 75%) were general surgical, followed by orthopedic (4350; 17%), and obstetric/gynecologic/urologic (2135; 8%). Perioperative death was low (42; 0.17%); independent predictors of death included age <1year, use of general anesthesia with a definitive airway, and operation during conflict. Surgical care for children comprised nearly a quarter of all procedures performed by MSF-OCB between 2008 and 2014. Attention to trauma surgery and infant perioperative care is particularly needed. These findings are important when resourcing projects and training surgical staff for humanitarian missions.


Paratesticular leiomyosarcoma with metastasis to the extremities and lungs.
Paratesticular leiomyosarcoma is a rare malignant tumor deriving from the smooth muscle of structures surrounding the testes, including the epididymis or scrotum. With few cases of genitourinary soft tissue sarcomas reported in the literature, little is known about progression, management, and treatment. Herein, we report a case of metastatic paratesticular leiomyosarcoma in a 47-year-old male with no past urological history. The patient initially presented with a firm, painless right scrotal mass, and ultimately developed soft tissue and pulmonary metastases.


Spirituality, emotional distress, and post-traumatic growth in breast cancer survivors and their partners: an actor-partner interdependence modeling approach.
The association between spirituality and emotional health has been well documented in healthy individuals. A small literature has shown that spirituality plays a role in well-being for some breast cancer (BC) survivors; however, this link is virtually unexplored in partners/spouses of survivors. The current study aimed to assess the relationship between spirituality, emotional distress, and post-traumatic growth for BC survivors and their partners using a dyadic analyses approach. A total of 498 couples who were 3-8 years post-BC diagnosis were recruited from the Eastern Oncology Group database. For BC survivors and their partners, greater levels of spirituality were associated with increases in their own post-traumatic growth. There was no relation between BC and partner spirituality and their own emotional distress, but partner's spirituality was associated with reduced occurrence of intrusive thoughts in the BC survivor. In contrast, BC survivors' spirituality was found to be wholly unrelated to partner's mental health and adjustment. Following diagnosis and treatment, spirituality appears to associate with positive growth in BC survivors and their partners. However, BC survivor and partner spirituality seem to be ineffective at impacting the other's post-traumatic growth or emotional distress, with the exception of intrusive thoughts. Dyadic analysis takes into account the reciprocal influence of close relationships on health and is an important and under-utilized methodology in behavioral oncology research and clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.


Snapshot: Choroid plexus brain barrier.
Located in each brain ventricle, choroid plexus (ChP) tissue forms a blood-CSF barrier and produces cerebrospinal fluid (CSF) and other supportive factors. Sheets of ChP epithelial cells enclose a vascularized stroma of mesenchymal, immune, and neuron/glia-like cells. Burgeoning ChP studies are revealing its complex set of functions across the lifespan. To view this SnapShot, open or download the PDF.


PERK signaling through C/EBPδ contributes to ER stress-induced expression of immunomodulatory and tumor promoting chemokines by cancer cells.
Cancer cells experience endoplasmic reticulum (ER) stress due to activated oncogenes and conditions of nutrient deprivation and hypoxia. The ensuing unfolded protein response (UPR) is executed by ATF6, IRE1 and PERK pathways. Adaptation to mild ER stress promotes tumor cell survival and aggressiveness. Unmitigated ER stress, however, will result in cell death and is a potential avenue for cancer therapies. Because of this yin-yang nature of ER stress, it is imperative that we fully understand the mechanisms and dynamics of the UPR and its contribution to the complexity of tumor biology. The PERK pathway inhibits global protein synthesis while allowing translation of specific mRNAs, such as the ATF4 transcription factor. Using thapsigargin and tunicamycin to induce acute ER stress, we identified the transcription factor C/EBPδ (CEBPD) as a mediator of PERK signaling to secretion of tumor promoting chemokines. In melanoma and breast cancer cell lines, PERK mediated early induction of C/EBPδ through ATF4-independent pathways that involved at least in part Janus kinases and the STAT3 transcription factor. Transcriptional profiling revealed that C/EBPδ contributed to 20% of thapsigargin response genes including chaperones, components of ER-associated degradation, and apoptosis inhibitors. In addition, C/EBPδ supported the expression of the chemokines CXCL8 (IL-8) and CCL20, which are known for their tumor promoting and immunosuppressive properties. With a paradigm of short-term exposure to thapsigargin, which was sufficient to trigger prolonged activation of the UPR in cancer cells, we found that conditioned media from such cells induced cytokine expression in myeloid cells. In addition, activation of the CXCL8 receptor CXCR1 during thapsigargin exposure supported subsequent sphere formation by cancer cells. Taken together, these investigations elucidated a novel mechanism of ER stress-induced transmissible signals in tumor cells that may be particularly relevant in the context of pharmacological interventions.


3'-[Hy-droxy(4-oxo-4H-chromen-3-yl)meth-yl]-2-oxospiro-[indoline-3,2'-pyrrolidine]-3'-carbonitrile.
In the title compound, C(23)H(19)N(3)O(4), the pyran ring adopts a half-chair conformation, while the pyrrolidine (with a C atom as the flap atom) and the five-membered ring in the indoline (with a C atom as the flap atom) ring system adopt slight envelope conformations. The pyrrolidine ring makes dihedral angles of 83.3 (1) and 60.4 (1)° with the mean plane through all non-H atoms of the indoline and chromene ring systems, respectively. In the crystal, mol-ecules are connected by two unique N-H⋯O and O-H⋯O hydrogen-bonding inter-actions, which form centrosymmetric patterns described by graph-set motifs R(2) (2)(18) and R(2) (2)(14). These two motifs combine to form a hydrogen-bonded chain which propagates in the a-axis direction. The crystal structure is also stablized by C-H⋯O inter-actions and by aromatic π-π stacking inter-actions between the pyran and benzene rings of neighbouring mol-ecules [centroid-centroid distance = 3.755 (1) Å and slippage = 1.371 (2) Å].


Comparative immunohistochemical study of the distribution of neuropeptide Y, growth hormone-releasing factor and the carboxyterminus of precursor protein GHRF in the human hypothalamic infundibular area.
It is now well documented that various polyclonal antisera to the human growth hormone-releasing factor (hGHRF, somatocrinin) visualize in the brain by immunohistochemistry the classical hypothalamic hypophysiotropic neurons and also antigens present in otherwise characterized peptidergic neuronal systems. The nature of these antigens is still an open question. One of these hGHRF antisera, raised against an immunogen of hGHRF1-44NH2, labels in the arcuate nucleus of the human mediobasal hypothalamus the neuropeptide Y (NPY) containing neurons which for the most part constitute a tuberoextrainfundibular system. The identity of the hGHRF-like substance present in these neurons with true somatocrinin has been assessed by performing a comparative immunohistochemical study including sequential double and triple labeling using the antiserum to hGHRF1-44NH2 in conjunction with antisera to the carboxyterminus of preprosomatocrinin (CTPG) and to NPY. This made it feasible to dissociate the hGHRF1-44NH2-immunoreactive neurons into two major subpopulations costaining either for CTPG of NPY, and a minor neuronal group displaying simultaneously the three labelings. A subset of arcuate neurons also showed NPY staining only. These results suggest that (1) the hGHRF-like antigen present in the majority of the NPY neurons is not true somatocrinin, or alternatively that preprosomatocrinin undergoes a unique maturational processing in these neurons, and (2) a subset of tuberoinfundibular somatocrininergic neurons produces and releases NPY which may be involved in the multifactorial control of the pituitary function.


[New technologies in the optimization of CRT programming].
After implanting a CRT device, consistent and scheduled patient follow-up is mandatory. Besides determining electrode parameters and reviewing arrhythmic episodes, these follow-ups focus on monitoring and optimizing congestive heart failure therapy. Therefore new CRT devices present methods for heart failure surveillance and telemetric transmission of the acquired data, which allows the physician to respond immediately to the varying needs of the respective heart failure patient. In addition to cardiac resynchronization, optimization of atrioventricular (AV) and interventricular (VV) delay provide major hemodynamic benefits. As echocardiographic optimization of AV and VV delay is time consuming it is often not feasible during daily clinical practice. Therefore implemented algorithms that automatically determine and adapt AV and VV delays with respect to the fluctuating needs of the patients are essential. This article presents the current state of monitoring and optimization methods in CRT devices.


A piRNA-like Small RNA Induces Chemoresistance to Cisplatin-Based Therapy by Inhibiting Apoptosis in Lung Squamous Cell Carcinoma.
Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models. Further, targeting upregulated piR-L-138 led to increased apoptosis in CDDP-treated LSCC cells and LSCC xenograft mice treated with CDDP. In addition, piR-L-138 directly interacted with p60-MDM2 and inhibited CDDP-activated apoptosis in p53-mutated LSCC. We identified the upregulated piR-L-138 upon CDDP-based chemotherapy, confirmed the enhanced sensitivity of LSCC to agents by targeting the upregulated piR-L-138 both in vitro and in vivo, and revealed mechanisms underlying piR-L-138 in chemoresistance, bolstering a new emerging clinical modality where novel functional piR-Ls provide potential strategies to overcome chemoresistance for patients with LSCC.


The odontogenic keratocyst: a benign cystic tumor?
Three hundred nineteen odontogenic keratocysts from 255 patients (167 males and 88 females, a 2:1 ratio) were histologically and clinically examined. The cysts sometimes occurred as multiple or recurrent lesions or in association with Gorlin's syndrome. The rate of recurrence for the total population was 27%. The 116 patients who were tentatively diagnosed as having keratocyst prior to surgery had a recurrence rate of 26%. There was no direct correlation between a large number of different histopathologic parameters and the propensity of a lesion to recur. Based on these data, a theory for the growth mechanism of these lesions is presented, and it is that the odontogenic keratocyst should be regarded as a benign cystic neoplasm and treated accordingly.


MR diagnosis of herniation of the left ventricle through a pericardial window.
The diagnosis of herniation of the left ventricle through a pericardial window was made using MRI. This is a rare type of herniation because it presented 6 years after a pericardial window was made for pericarditis. Herniation of the heart through congenital, traumatic and post surgical pericardial defects are discussed.


Two-dimensional electrophoresis of soluble leaf proteins, isolated from two wheat species (Triticum durum and Triticum aestivum) differing in sensitivity towards NaCl.
Plants of two wheat species (Triticum aestivum cv. Tanit and T. durum cv. Ben Bachir), differing in their sensitivity to NaCl were cultivated in the presence or absence of 100 mM NaCl for 21 days. Soluble proteins extracted from leaves were analyzed by two-dimensional electrophoresis in order to detect NaCl-induced changes in the polypeptide patterns. In all, 500 spots were detected. Results showed species-dependent differences. The greatest alterations in the polypeptide profiles following salt stress were found in the most sensitive cultivar: among the 12 spots (molecular mass, 15-31 kDa) specifically considered in the acidic region of the gel, 11 declined, even disappeared in the NaCl-sensitive leaf profiles, while in the tolerant species only five spots were affected by the salt treatment and five remained untouched; moreover in the latter, two new polypeptides were shown to be induced by NaCl.


The Transcription Factor RORα Preserves ILC3 Lineage Identity and Function during Chronic Intestinal Infection.
Innate lymphoid cells (ILCs) are critical for host defense and tissue repair but can also contribute to chronic inflammatory diseases. The transcription factor RORα is required for ILC2 development but is also highly expressed by other ILC subsets where its function remains poorly defined. We previously reported that Rorasg/sg bone marrow chimeric mice (C57BL/6J) were protected from Salmonella-induced intestinal fibrosis due to defective ILC3 responses. In this study, single-cell RNA analysis of ILCs isolated from inflamed tissues indicates that RORα perturbation led to a reduction in ILC3 lineages. Furthermore, residual Rorasg/sg ILC3s have decreased expression of key signature genes, including Rorc and activating cytokine receptors. Collectively, our data suggest that RORα plays a key role in preserving functional ILC3s by modulating their ability to integrate environmental cues to efficiently produce cytokines.


Kinetics of a sulfadiazine-trimethoprim combination.
The pharmacokinetics of a combination of sulfadiazine and trimethoprim has been studied in 16 patients with varying degrees of reduced renal function. In normal renal function, the serum half-life (t1/2) of active sulfadiazine, total sulfadiazine, and trimethoprim were quite close: 7.7, 9.6, and 12.1 hr, respectively. There was a gradual increase in serum t1/2 with reduction in renal function for both active and total sulfadiazine and for trimethoprim. With accurate determinations of endogenous renal clearance, t1/2 estimates may be made from regression curves presented. The relative distribution in the body was unrelated to renal function. It was similar for the two fractions of sulfonamide and higher for trimethoprim. The means were 0.371, 0.176, and 1.104 L/kg, respectively, for active and total sulfadiazine, and trimethoprim.


Assessing the function of motor cortex: single-neuron models of how neural response is modulated by limb biomechanics.
Do neurons in primary motor cortex encode the generative details of motor behavior, such as individual muscle activities, or do they encode high-level movement attributes? Resolving this question has proven difficult, in large part because of the sizeable uncertainty inherent in estimating or measuring the joint torques and muscle forces that underlie movements made by biological limbs. We circumvented this difficulty by considering single-neuron responses in an isometric task, where joint torques and muscle forces can be straightforwardly computed from limb geometry. The response for each neuron was modeled as a linear function of a "preferred" joint torque vector, and this model was fit to individual neural responses across variations in limb posture. The resulting goodness of fit suggests that neurons in motor cortex do encode the kinetics of motor behavior and that the neural response properties of "preferred direction" and "gain" are dual components of a unitary response vector.


Pain management as an antidepressant: long-term resolution of pain-associated depression.
Of 100 consecutive patients admitted to a pain management program for patients without malignant disease who had chronic pain, 54 were definitely or probably depressed and 46 were not depressed by Research Diagnostic Criteria. As a result of 98% improvement of depression and low frequency (2%) of new development of depression, 98 of the original 100 patients were not depressed at the time of dismissal. This progress was maintained at long-term follow-up (average, 11.6 months): 89 of 100 patients remained non-depressed.


A meta-analysis of single-stage versus two-stage management for concomitant gallstones and common bile duct stones.
To conduct a randomized controlled trial (RCT) meta-analysis to evaluate the safety and effectiveness of single-stage [laparoscopic cholecystectomy (LC)+laparoscopic common bile duct exploration (LCBDE)] vs. two-stage management [preoperative endoscopic retrograde cholangiopancreatography (ERCP)+LC] for concomitant gallstones and common bile duct stones. RCTs that met the inclusion criteria for data extraction were identified from electronic databases (PubMed, Embase, Science Citation Index, and the Cochrane Library) up to August 2014. The relevant congressional proceedings were also searched. The primary outcomes were stone clearance from the common bile duct, postoperative morbidity and mortality. The secondary outcomes were conversion to other procedures, length of hospital stay, total operative time, and hospitalization charges. The outcomes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using RevMan 5.2. Eight RCTs, which included 1130 patients, were identified for analysis in our study. The meta-analysis revealed that the common bile duct stone clearance rate in the single-stage group was higher (OR=1.56, 95% CI: 1.05 to 2.33, P=0.03). The lengths of hospital stay (MD=-1.02, 95% CI: -1.99 to -0.04, P=0.04) and total operative times (MD=-16.78, 95% CI: -27.55 to -6.01, P=0.002) were also shorter in the single-stage group. There was no statistically significant difference between the two groups regarding postoperative morbidity (OR=1.12, 95% CI: 0.79 to 1.59, P=0.52), mortality (OR=0.29, 95% CI: 0.06 to 1.41, P=0.13) and conversion to other procedures (OR=0.82, 95% CI: 0.37 to 1.82, P=0.62). Single- and two-stage management for cholecysto-choledocholithiasis had similar mortality and complication rates; however, the single-stage strategy was better in terms of stone clearance, hospital stay and total operative time.


Levels of house dust mite-specific IgE and cockroach-specific IgE and their association with lower pulmonary function in Taiwanese children.
Sensitization to an aeroallergen is known to diminish pulmonary function in young children and adults; however, it remains unclear whether it produces similar effects in adolescents. This study, therefore, examined the relationship between serum allergen-specific IgE levels and pulmonary function in adolescents. Middle-school children were invited for a physician's evaluation and pulmonary function test when not experiencing an asthma attack and for the determination of serum levels of specific IgE to common allergens. National Cheng Kung University Hospital, Taiwan. Middle-school children in southern Taiwan, who had completed both a nationally administered Chinese version of the International Study of Asthma and Allergies in Childhood questionnaire and a pulmonary function test in October 1996. Forty-two then currently asthmatic children, 38 children with asthma in remission (no reported attack for > 12 months), and 69 children without asthma completed the study. Children with asthma had a significantly lower adjusted forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)) and FEV(1)/FVC than children without asthma. A greater percentage of children with asthma were more sensitized to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and German cockroach but not cat dander or dog dander. Children with asthma with Der f-specific IgE > 100 IU/mL, or cockroach-specific IgE > 0.7 IU/mL showed lower pulmonary function. No such association was found in children without asthma. Our findings suggest that sensitization to Der f and German cockroach was a critical factor for the lower pulmonary function observed in middle-school children with asthma.


Unbalanced translocation (1;7) in childhood myelodysplasia.
We have identified an unusual pediatric patient among twelve patients with myelodysplasia and an unbalanced translocation involving chromosomes 1 and 7: -7, +der(1)t(1;7)(p11;p11). This 16-year-old male patient developed myelodysplasia and evolving acute leukemia, which were preceded by a 7-year history of marrow hypoplasia. The remaining patients were adults with clinical and hematologic findings similar to other reported cases with this chromosomal abnormality. The late appearance of this unbalanced clonal abnormality in this patient with marrow hypoplasia documents the importance of close cytogenetic follow-up of all patients with suspected bone marrow injury.


A synthetic peptide corresponding to the third cytoplasmic loop (residues 533 to 555) of the testicular follicle-stimulating hormone receptor affects signal transduction in rat testis membranes and in intact cultured rat Sertoli cells.
Involvement of the third cytoplasmic (3i) loop (residues 533 to 555) of the rat testicular FSH receptor in the mechanism of FSH signal transduction was examined using light membranes prepared from immature rat testes, monolayer cultures of rat Sertoli cells, and a synthetic peptide strategy. This region of the FSH receptor is structurally related to G protein-activator regions identified in other G protein-coupled receptors. FSHR-(533-555) peptide amide stimulated guanine nucleotide exchange in rat testis light membranes, presumably via its interaction with membrane-associated G protein. The peptide failed to inhibit FSH binding to testis membrane receptors, indicating that the nucleotide exchange effect was not a result of peptide interaction with receptor. When incubated with cultured Sertoli cells from immature rat testes, FSHR-(533-555) peptide amide consistently and significantly inhibited FSH stimulation of cAMP and estradiol biosynthesis, but failed to inhibit forskolin stimulation of each. The peptide effect, therefore, was not due to a direct interaction with adenylyl cyclase. Since FSHR-(533-555) peptide amide did not inhibit FSH binding to membrane receptor, these results imply entry of the peptide into the Sertoli cell, possibly by vesicular internalization or diffusion. Indeed, the inhibitory effects of FSHR-(533-555) peptide amide on FSH-stimulated estradiol biosynthesis were prevented by pretreating Sertoli cells with phenylarsine oxide, an inhibitor of FSH receptor internalization. FSHR-(533-555) was without effect on basal levels of cAMP and estradiol biosynthesis, indicating absence of toxicity at the concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)


DNA sequence organization in the genomes of five marine invertebrates.
The arrangement of repetitive and non-repetitive sequence was studied in the genomic DNA of the oyster (Crassostrea virginica), the surf clam (Spisula solidissima), the horseshoe crab (Limulus polyphemus), a nemertean worm (Cerebratulus lacteus) and a jelly-fish (Aurelia aurita). Except for the jellyfish these animals belong to the protostomial branch of animal evolution, for which little information regarding DNA sequence organization has previously been available. The reassociation kinetics of short (250-300 nucleotide) and long (2,000-3,000 nucleotide) DNA fragments was studied by the hydroxyapatite method. It was shown that in each case a major fraction of the DNA consists of single copy sequences less than about 3,000 nucleotides in length, interspersed with short repetitive sequences. The lengths of the repetitive sequences were estimated by optical hyperchromicity and S1 nuclease measurements made on renaturation products. All the genomes studied include a prominent fraction of interspersed repetitive sequences about 300 nucleotides in length, as well as longer repetitive sequence regions.


Biochemical studies of taste sensation--VIII. Partial characterization of alanine-binding taste receptor sites of catfish Ictalurus punctatus using mercurials, sulfhydryl reagents, trypsin and phospholipase C.
1. Taste receptors for L-alanine in the channel catfish Ictalurus punctatus have been partially characterized. The binding activity, which is localized to a sedimentable fraction (Fraction P2), was assayed with L-[3H]alanine as the ligand. 2. Addition of HgCl2 or p-mercuribenzoate to the assay at 0.1-1 mM markedly inhibited binding. The effect was not reversible and was unaffected by increased L-alanine in the binding assay. 3. The sulfhydryl reagents iodoacetate, 5,5'-dithiobis(2-nitrobenzoic acid), arsenite, and N-ethylmaleimide did not show appreciable inhibition of binding. The results suggest that the inhibitory effect of mercurials is not on specific sulfhydryl groups at alanine-binding sites. 4. Treatment of Fraction P2 with phospholipase C decreased binding activity and treatment with trypsin led to increased binding activity.


Ash problems and prevention measures in power plants burning high alkali fuel: Brief review and future perspectives.
Large-scale utilization of high-alkali fuels is considered an effective solution for alleviating energy shortages and reducing CO2 emissions. However, combustion of high-alkali fuels in boilers releases alkali metals into the flue gas, which leads to severe ash deposition and corrosion on the heating surface. Consequently, research into the efficient use of highly alkaline fuels has been conducted in recent years. In this review, ash issues and measures for their prevention during high-alkali fuel combustion are summarized. First, the characteristics of fly ash produced from high-alkali fuel combustion are reviewed, and the form, migration, and deposition characteristics of alkali metals are summarized. Subsequently, research progress of high alkali fuel ash is introduced in detail. Mechanisms of slagging, fouling, corrosion on the heating surface and the selective catalytic reduction (SCR) unit deactivation are summarized. Prevention and control methods for the high-alkali fuel ash problem are then introduced. Finally, based on current research, existing problems and future development directions for high-alkali fuel research are proposed. Through this review, we hope to provide insights into the effective utilization of high-alkali fuels.


Responses of alloantigen-primed lymphocytes in vitro. The specificity of secondary responses assayed by titration of primed lymphocyte populations.
Maximal proliferative responses were observed at lower responder cell densities in alloantigen-primed lymphocyte populations when restimulated with the specific priming cell than when restimulated with other allogeneic cells. This relationship was due to the larger number of lymphocytes within the primed population which responded to the specific sensitizing cell than to unrelated stimulator cells. As a result, at high responder cell densities, stimulator cells unrelated to the specific sensitizing cells elicited a disproportionately high response relative to the response stimulated by the specific cells. Restimulation of decreasing numpacity of different cells. Because primed populations contain a larger number of lymphocytes that responde to the specific stimulator than to other stimulators, responses of primed lymphocytes could be made operationally monospecific. Limiting dilution analysis demonstrated that low numbers of primed cells were stimulated by the specific sensitizing cells but not by unrelated stimulator cells.


Health and medical news on the Web: comparing the results of news-providing Web resources.
News changes constantly. That change and the abundance of Web-based news resources available complicate finding the news. This paper reviews sixteen different online news sources for their coverage of recent health and medical issues; both general-interest and medical news sites are included. Three health-related news stories were searched in all resources within set time-frames to provide a comparison of coverage. Features and types of resources are described. The use of RSS feeds and weblogs to find news is also discussed with suggestions for using news aggregators to control the flow of information.


Ionic (liquid) matrices for matrix-assisted laser desorption/ionization mass spectrometry-applications and perspectives.
A large number of matrix substances have been used for various applications in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The majority of matrices applied in ultraviolet-MALDI MS are crystalline, low molecular weight compounds. A problem encountered with many of these matrices is the formation of hot spots, which lead to inhomogeneous samples, thus leading to increased measurement times and hampering the application of MALDI MS for quantitative purposes. Recently, ionic (liquid) matrices (ILM or IM) have been introduced as a potential alternative to the classical crystalline matrices. ILM are equimolar mixtures of conventional MALDI matrix compounds such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxycinnamic acid (CCA) or sinapinic acid (SA) together with organic bases [e.g., pyridine (Py), tributylamine (TBA) or N,N-dimethylethylenediamine (DMED)]. The present article presents a first overview of this new class of matrices. Characteristic properties of ILM, their influence on mass spectrometric parameters such as sensitivity, resolution and adduct formation and their application in the fields of proteome analysis, the measurement of low molecular weight compounds, the use of MALDI MS for quantitative purposes and in MALDI imaging will be presented. Scopes and limitations for the application of ILM are discussed.


[Mucinous cystic neoplasm of the liver: a case report and review of the literature].
Mucinous cystic neoplasm (MCN) of the liver is an unusual cyst-forming epithelial neoplasm, typically showing no communication with the bile ducts. This neoplasm represents less than 5% of all cystic lesions of the liver and there are only 250 cases in the world literature. We present the case of a 23-year-old female with a 13.5 x 10.2 cm lesion, hypodense, lobulated, with multiple septa up to 2.5 mm thick and small cystic images inside, which produces intrahepatic bile duct and common bile duct dilatation. The pathological study concluded that the tumor corresponded to a mucinous cystic neoplasm of the liver.


Fine-tunable fluorescence quenching properties of core-satellite assemblies of gold nanorod-nanosphere: Application in sensitive detection of Hg2.
In this work, we developed a simple, effective fluorescence method to detect Hg2+ by inhibiting core-satellite assemblies of gold nanorods (AuNRs) and gold nanospheres (AuNPs). The fluorescence of Rhodamine 6G (Rh6G), which was simply mixed with the nanoassemblies, was efficiently quenched by the inner filter effect (IFE). When the heterogenous core-satellite nanostructures were assembled, the corresponding local surface plasmon resonance (LSPR) absorption shifts and broadens which results in the increase of the spectral overlap between the emission peak and the absorption band and more efficient energy transfer from Rh6G to nanoparticles. Fluorescence quenching efficiency is related to the size and number density of satellite nanoparticles. It is interesting that the AuNR-AuNP assemblies with the moderate size and high density of AuNPs have the best fluorescence quenching efficiency. In the presence of Hg2+, p-aminothiophenol (p-ATP) breaks away from the surface of AuNRs and competitively bounds to Hg2+, resulting in a low yield of the AuNR-AuNP assemblies, which further leads to the decrease of fluorescence quenching efficiency. Under the optimum conditions, the limit of detection (LOD) for Hg2+ was 0.18 nM, with an excellent linear response from 0.6 to 800 nM. Interference experiment and real samples detection indicate that these nanosensors endowed with higher sensitivity and selectivity for the detection of Hg2+ in the real samples. Compared with the conventional Hg2+ detection techniques, this method based on Hg2+ induced inhibition of core-satellite AuNR-AuNP assemblies has better performance and is suitable for the detection of Hg2+.


Sweating distribution and active sweat glands on the scalp of young males in hot-dry and hot-humid environments.
We investigated the effects of humidity on regional sweating secretion and active sweat gland density on the scalp during passive heating in hot environments. Eight male subjects shaved their heads prior to expose to dry (30%RH; H30%) and humid (85%RH; H85%) conditions at an air temperature of 32 °C. Total sweat rate, local sweat rates (frontal, vertex, temporal, and occipital regions), active sweat glands on the scalp (2 frontal, 2 parietal, 2 temporal, 1 occipital, and 1 vertex), and rectal and skin temperatures were measured during leg immersion in 42 °C water for 60 min. (1) Total sweat rates were greater for H30% (179.4 ± 35.6 g h-1) than for H85% (148.1 ± 27.2 g h-1) (P < 0.05). (2) Scalp sweat secretion tended to be greater in the H85% than the H30%. (3) Head sweat rates were greater on the frontal than on the vertex for both humidity conditions (P < 0.05). (4) Active sweat gland density on the scalp was greater for H85% (82 ± 13 glands cm-2) than for H30% (62 ± 17 glands cm-2) (P < 0.05). (5) No significant difference was found in rectal temperature between H30% and H85%, whereas mean skin temperature was significantly lower for H30% (34.8 ± 0.7 °C) than for the H85% condition (36.0 ± 0.3 °C) (P < 0.05). These results indicate that the thermoregulatory sweating responses for the scalp region were significantly increased in the hot-humid condition compared to the hot-dry condition. Among the regions on the scalp surface, the vertex was the least sensitive to the change in humidity.


Homicide in Alabama: an analysis of urban, suburban and rural murders in the Deep South.
Eleven hundred forty-four (1144) homicides occurring in Alabama, U.S.A. during a 2-year period are presented and analyzed according to the demographic parameters of the victims, location in urban, suburban, or rural community, type of homicide based on a medical examiner's classification, presence of drugs, weapon employed and other factors. Urban dwellers, Blacks and males are found to be at high risk. Alcohol is much more prevalent than other drugs in homicide victims. Although the handgun is the weapon most commonly used throughout the state, in the rural regions the longgun is used almost as often. The difficulty of making valid comparisons with other homicide studies is discussed and the establishment of a uniform classification of homicides urged.


IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.
Chronic inflammation is integral to the development of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although the latter has not been associated with reflux esophagitis. The L2-IL-1β transgenic mice, expressing human interleukin (IL)-1β in the oral, esophageal and forestomach squamous epithelia feature chronic inflammation and a stepwise development of Barrett's esophagus-like metaplasia, dysplasia and adenocarcinoma at the squamo-columnar junction. However, the functional consequences of IL-1β-mediated chronic inflammation in the oral and esophageal squamous epithelia remain elusive. We report for the first time that in addition to the previously described Barrett's esophagus-like metaplasia, the L2-IL-1β mice also develop squamous epithelial dysplasia with progression to squamous cell carcinoma (SCC) in the esophagus and the tongue. L2-IL-1β showed age-dependent progression of squamous dysplasia to SCC with approximately 40% (n = 49) and 23.5% (n = 17) incidence rates for esophageal and tongue invasive SCC respectively, by 12-15 months of age. Interestingly, SCC development and progression in L2-IL-1β was similar in both Germ Free (GF) and Specific Pathogen Free (SPF) conditions. Immunohistochemistry revealed a T cell predominant inflammatory profile with enhanced expression of Ki67, Sox2 and the DNA double-strand break marker, γ-H2AX, in the dysplastic squamous epithelia of L2-IL-1β mice. Pro-inflammatory cytokines, immunomodulatory players, chemoattractants for inflammatory cells (T cells, neutrophils, eosinophils, and macrophages) and oxidative damage marker, iNOS, were significantly increased in the esophageal and tongue tissues of L2-IL-1β mice. Our recent findings have expanded the translational utility of the IL-1β mouse model to aid in further characterization of the key pathways of inflammation driven BE and EAC as well as ESCC and Oral SCC.


Growth hormone secretagogue receptors in rat and human gastrointestinal tract and the effects of ghrelin.
The peptide hormone ghrelin is known to be present within stomach and, to a lesser extent, elsewhere in gut. Although reports suggest that gastric function may be modulated by ghrelin acting via the vagus nerve, the gastrointestinal distribution and functions of its receptor, the growth hormone secretagogue receptor (GHS-R), are not clear and may show signs of species-dependency. This study sought to determine the cellular localisation and distribution of GHS-R-immunoreactivity (-Ir) using immunofluorescent histochemistry and explore the function of ghrelin in both human and rat isolated gastric and/or colonic circular muscle preparations in which nerve-mediated responses were evoked by electrical field stimulation. The expression of GHS-R-Ir differed to a greater extent between species than between gut regions of the same species. Both the human and rat gastric and colonic preparations (n=3 each) expressed GHS-R-Ir within neuronal cell bodies and fibres, cells associated with gastric glands and putative entero-endocrine and/or mast cells. Smooth muscle cells and epithelia were devoid of GHS-R-Ir and only rat preparations expressed GHS-R-Ir on nerve fibres associated with the muscle layers. GHS-R-Ir was fully competed in all cases in pre-adsorption studies and antiserum specificity was confirmed using a cell line transiently expressing the rat GHS-R. In rat isolated forestomach circular muscle, ghrelin 0.1-10 microM had no effect on smooth muscle tension but concentration-dependently facilitated the amplitude of contractions evoked by excitatory nerve stimulation (n=4-7; P<0.05 for each concentration versus vehicle; n=18). When examined under similar conditions, in both rat distal colon (n=4-6, P>0.05 each) and human ascending (n=3) and sigmoid (n=1) colon, these concentrations of ghrelin were without effect (P>0.05 each). The data suggest that ghrelin has the potential to profoundly affect gastrointestinal functions in both species and at least one of these functions is to exert a gastric prokinetic activity. Moreover, we suggest that this activity of ghrelin is mediated via the enteric nervous system, in addition to known vagus nerve-dependent mechanisms.


Union instability as an engine of fertility? A microsimulation model for France.
Opportunities for conceiving and bearing children are fewer when unions are not formed or are dissolved during the childbearing years. At the same time, union instability produces a pool of persons who may enter new partnerships and have additional children in stepfamilies. The balance between these two opposing forces and their implications for fertility may depend on the timing of union formation and parenthood. In this article, we estimate models of childbearing, union formation, and union dissolution for female respondents to the 1999 French Etude de l'Histoire Familiale. Model parameters are applied in microsimulations of completed family size. We find that a population of women whose first unions dissolve during the childbearing years will end up with smaller families, on average, than a population in which all unions remain intact. Because new partnerships encourage higher parity progressions, repartnering minimizes the fertility gap between populations with and those without union dissolution. Differences between the two populations are much smaller when family formation is postponed-that is, when union formation and dissolution or first birth occurs after age 30, or when couples delay childbearing after union formation.


Association of scrotal hyperthermia with impaired spermatogenesis in infertile men.
Scrotal temperatures, testicular volumes, and sperm characteristics were studied in 150 infertile, nonazoospermic men and in 37 fertile men, used as a control group. The mean scrotal temperature values of the infertile men were significantly greater than those observed in the fertile men (+0.4 degrees C for the right; +0.5 degrees C for the left). In the infertile men, it was found that the higher the scrotal temperature, the more alterated the sperm characteristics. The only clinical element that seemed to be linked to the existence of scrotal hyperthermia in the infertile men was testicular hypotrophy. Although the scrotal temperatures of the infertile men with varicocele were significantly higher than those of the fertile men, they did not significantly differ from those of the infertile men without varicocele. No other specific pathologic factor, infectious or surgical urogenital history was found to be responsible for the scrotal hyperthermia observed in the infertile men.


Social support, psychosocial risks, and cardiovascular health: Using harmonized data from the Jackson Heart Study, Mediators of Atherosclerosis in South Asians Living in America Study, and Multi-Ethnic Study of Atherosclerosis.
Social support may have benefits on cardiovascular health (CVH). CVH is evaluated using seven important metrics (Life's Simple 7; LS7) established by the American Heart Association (e.g., smoking, diet). However, evidence from longitudinal studies is limited and inconsistent. The objective of this study is to examine the longitudinal relationship between social support and CVH, and assess whether psychosocial risks (e.g., anger and stress) modify the relationship in a racially/ethnically diverse population. Participants from three harmonized cohort studies - Jackson Heart Study, Mediators of Atherosclerosis in South Asians Living in America, and Multi-Ethnic Study of Atherosclerosis - were included. Repeated-measures modified Poisson regression models were used to examine the overall relationship between social support (in tertiles) and CVH (LS7 metric), and to assess for effect modification by psychosocial risk. Among 7724 participants, those with high (versus low) social support had an adjusted prevalence ratio (aPR) and 95% confidence interval (CI) for ideal or intermediate (versus poor) CVH of 0.99 (0.96-1.03). For medium (versus low) social support, the aPR (95% CI) was 1.01 (0.98-1.05). There was evidence for modification by employment and anger. Those with medium (versus low) social support had an aPR (95% CI) of 1.04 (0.99-1.10) among unemployed or low anger participants. Corresponding results for employed or high anger participants were 0.99 (0.94-1.03) and 0.97 (0.91-1.03), respectively. Overall, we observed no strong evidence for an association between social support and CVH. However, some psychosocial risks may be modifiers. Prospective studies are needed to assess the social support-CVH relationship by psychosocial risks in racially/ethnically diverse populations.


Immunocytochemical localization of GABA immunoreactivity in dentate granule cells of normal and kindled rats.
In order to identify lasting alterations in gamma-aminobutyric acid (GABA) neurons in the kindling model of epilepsy, immunocytochemical techniques were used to quantify the number of GABA-immunoreactive (IR) neurons in different regions of the hippocampal formation (HCF) of amygdala-kindled rats, 40 days after the last fully kindled seizure. A new, highly specific monoclonal GABA antibody was used for these experiments. Unexpectedly, the antibody not only stained neurons in CA1, CA3, and hilus, but also intensively stained granule cells (GCs) in the dentate gyrus (DG) of both kindled rats and non-kindled controls, indicating that GCs may be capable of synthesizing GABA. Comparison with a polyclonal GABA and a glutamate decarboxylase antibody showed that staining of GCs with the monoclonal GABA antibody was much more intense. The number of GABA-IR cells that were counted in different regions of the HCF, including the DG, did not differ significantly between kindled rats and controls, which does not support the hypothesis of loss of hippocampal GABAergic neurons to explain the permanency of kindled epileptogenesis.


Successful surgical management of sixth nerve palsy by transposition of a previously snapped and retrieved inferior rectus muscle.
To report a case of intraoperative rupture of inferior rectus muscle, which was retrieved and later successfully transposed for management of sixth nerve palsy. Case report. A 36-year-old woman presented with traumatic right sixth nerve palsy and esotropia following a car accident five years earlier. During the originally planned vertical transposition surgery, the inferior rectus muscle snapped, but was retrieved and resutured to the sclera 3 mm posterior to the original insertion. After a few months, the second attempt of transposition of vertical recti (including the previously snapped and reattached inferior rectus) was successful, and the patient achieved satisfactory postoperative alignment. Intraoperative rupture of an extraocular muscles is a rare and serious complication encountered during strabismus surgery. However, if successfully retrieved, this muscle has still the chance of future re-operation.


Development of a quantification method for the analysis of malodorous sulphur compounds in gaseous industrial effluents by solid-phase microextraction and gas chromatography-pulsed flame photometric detection.
A quantification method for malodorous sulphur compounds in gaseous industrial effluents using solid-phase microextraction sampling followed by gas chromatography-pulsed flame photometric detection has been developed. A comparative study showed that polydimethylsiloxane-Carboxen fibre led to sufficient sensitivity to achieve the microg m(-3) human perception levels of the five analytes studied (hydrogen sulphide, methanethiol, ethanethiol, dimethyl sulphide, dimethyl disulphide). However, this coating is known to suffer from competitive adsorption, which may lead to inaccurate quantification. Therefore, external calibration can only be used under a limited range of concentrations, which were determined from Fick's diffusion law. This approach was tested on a real gaseous sample and compared with the standard addition method. Good correlations were found for ethanethiol, dimethyl sulphide and dimethyl disulphide. However, for more volatile sulphur compounds (i.e., hydrogen sulphide and methanethiol), the easy-to-use external calibration could not be applied and standard additions had to be performed for accurate quantification.


The Impact of Renal Function on Hepatic Encephalopathy Following TIPS Placement for Refractory Ascites.
The impact of renal function on hepatic encephalopathy (HE) following transjugular intrahepatic portosystemic shunt (TIPS) placement for refractory ascites is poorly understood. We investigated the role of renal function on HE following TIPS placement. A retrospective study was performed for patients undergoing TIPS for refractory ascites from 2007-2019. Patients were stratified by GFR at time of TIPS placement and by whether they were on hemodialysis (HD). Chronic kidney disease (CKD) stage 3 or higher was defined as pre-TIPS GFR < 60 for at least 3 months. Logistic regression analyses were used to identify the role of GFR and CKD at time of TIPS placement on HE within 60 days post TIPS placement. Among 201 TIPS patients for refractory ascites (61% male; mean age 59.1), 78 (39%) patients were in CKD, and 16 (21%) were on HD. Mean GFR at time of TIPS placement was 62.7 ± 28.2 for all non-HD patients (n = 185). Compared with the GFR ≥ 90 group, GFR < 30 or HD (OR, 3.56; 95%CI, 1.19-10.7; p = 0.023) and CKD (OR, 2.52; 95%CI, 1.40-4.53; p = 0.002) at time of TIPS placement were significant predictors of post-TIPS placement HE within 60 days. GFRs between 30-60 and 60-90 were not significant predictors. In TIPS patients for recurrent ascites, patients with acutely impaired renal function or chronic renal dysfunction were at an increased risk for HE after TIPS.


Automated determination of total plasma cholesterol: a serum calibration technique.
The automated (AutoAnalyzer II) determination of cholesterol in nine serum pools in the concentration range 3.465-8.871 mmol/l, gave results that were approximately 10% higher than reference values when the analyses were based on unesterified cholesterol standards containing the same amount of water as the sample extracts (1963 analyses in 12 laboratories during a 12 month period; automated value = 0.032 + 1.10 X (Reference value)). A serum calibration procedure was successful ilues, and was equally effective in correcting the values observed for aliquots of 368 fresh-frozen plasma samples analyzed in each of the 12 laboratories during a 38 month period.