MR enterography: relationship between intestinal fold pattern and the clinical presentation of adult celiac disease.
To correlate the clinical presentation of adult celiac disease with various intestinal fold patterns using MR-enterography. Fifty-four consecutive adult celiac patients (34 female, 20 male, 18 to 62 years) were studied by MR-enterography. Two radiologists blinded to the patients' clinical history evaluated in consensus MR studies, classifying the intestinal fold pattern into four categories: (a) no fold abnormalities, (b) isolated loss of folds in the duodenum, (c) jejunization of ileum, and (d) jejuno-ileal fold pattern reversal. Patients presented with the varying clinical forms of Celiac disease, classified as: (i) typical disease, (ii) atypical disease, and (iii) silent form. Twenty-three patients showed no intestinal fold abnormalities; 11 patients had isolated loss of duodenal folds; 9 patients showed jejunization of ileum and 11 had jejuno-ileal fold pattern reversal. 18/23 (78%) patients with MRI normal fold pattern had the silent clinical form of Celiac disease (Sensitivity 78%; specificity 100%; PPV = 1, NPV = 0.78); 9/11 (82%) patients with the isolated loss of duodenal folds had the atypical clinical form (sensitivity 82%; and specificity 100%; PPV = 1; NPV = 0.82). All 20 patients with the jejunization of ileum and jejuno-ileal fold pattern reversal had typical celiac disease (sensitivity and specificity of 100%; PPV and NPV = 1). MR-enterography findings in patients with celiac disease, demonstrates good correlation between MR findings and clinical severity.


Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice.
Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders.


An unanticipated discourse of HB-EGF with VANGL2 signaling during embryo implantation.
Implantation is the first direct encounter between the embryo and uterus during pregnancy, and Hbegf is the earliest known molecular signaling for embryo-uterine crosstalk during implantation. The downstream effectors of heparin-binding EGF (HB-EGF) in implantation remain elusive due to the complexity of EGF receptor family. This study shows that the formation of implantation chamber (crypt) triggered by HB-EGF is disrupted by uterine deletion of Vangl2, a key planar cell polarity component (PCP). We found that HB-EGF binds to ERBB2 and ERBB3 to recruit VANGL2 for tyrosine phosphorylation. Using in vivo models, we show that uterine VAGL2 tyrosine phosphorylation is suppressed in Erbb2/Erbb3 double conditional knockout mice. In this context, severe implantation defects in these mice lend support to the critical role of HB-EGF-ERBB2/3-VANGL2 in establishing a two-way dialogue between the blastocyst and uterus. In addition, the result addresses an outstanding question how VANGL2 is activated during implantation. Taken together, these observations reveal that HB-EGF regulates the implantation process by influencing uterine epithelial cell polarity comprising VANGL2.


Molecular genetics of the S region of the murine H-2 major histocompatibility complex.
The mouse H-2S region has been conventionally identified by the functional, serological and electrophoretic variations of two plasma proteins which constitute its primary genetic markers, C4 (the fourth component of complement) and C4-Slp (sex-limited protein). Recently, recombinant DNA procedures applied in our laboratory as well as in several others have made available molecular clones corresponding to these two nonallelic genes. This paper focuses on the progress provided by the study of C4 and C4-Slp cDNA and genomic clones, as well as by the application of such clones to the probing of the S region structure in conventional and special H-2 haplotypes. At variance with the K, I and D regions of H-2, the S region contains genes which have no obvious structural interrelationship, although in some cases they display a functional interaction. The heterogeneity of S region products is emphasized by the recent detection of steroid 21-hydroxylase genes associated with each of the C4 gene copies.


Epidemicity and clonal replacement of hypervirulent carbapenem-resistant Klebsiella pneumoniae with diverse pathotypes and resistance profiles in a hospital.
The emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a great threat to public health. There is a paramount need to increase awareness of the epidemiology, evolution, and pathogenesis of CR-hvKP. We collected strains of K. pneumoniae for over two years in a hospital. CR-hvKP strains were screened by polymerase chain reaction (PCR) with primers targeting the virulence genes. Genome sequencing was used to determine phylogenetic relationships and genetic characterization of virulence elements. The population dynamics within these strains were analyzed through epidemiological data. The string test, siderophore secretion, and murine infection experiments were performed to investigate virulence potential of different clones. A total of 1172 K. pneumoniae strains were isolated from 817 patients, and 125 isolates were identified as CR-hvKP. In all, 102 CR-hvKP strains belonged to sequence type (ST) 11. Genomic analysis demonstrated that three clones of ST11 successively replaced each other in the hospital. Among them, the strains of clade A and clade B acquired virulence plasmids and the strains of clade C acquired a new integrating conjugative element (ICE). Phenotypic experiments revealed enhanced virulence potential of the recent epidemic clone from clade B. Sequence type 11 strains were favorable hosts for the convergence of virulence and resistance, indicated by clonal replacement and acquisition patterns of virulence elements. The emergence of the enhanced virulence potential of ST11 CR-hvKP suggests that coevolution between hosts and exogenous factors can produce super-virulent CR-hvKP strains, highlighting the need to closely monitor changes in the virulence characteristics of CR-hvKP.


A novel approach to the management of pregnancies complicated by uteroplacental insufficiency and previous stillbirth.
To our knowledge, this is the first time that a combination of aspirin and glyceryl trinitrate (GTN) has been used in the prophylaxis of preeclampsia and fetal growth retardation, and their use associated with not only Doppler screening of the uterine arteries but also regular Doppler follow-up of the fetal arterial and venous circulation. Whilst future trials are needed to prove whether screening, prophylaxis and Doppler management are individually beneficial, we propose that this combination of management strategies contributed to a good outcome in the cases described. Furthermore, randomized trials are required to determine the safety and efficacy of prophylactic low-dose aspirin combined with GTN treatment in pregnancies affected by an impaired uteroplacental circulation.


Building a Traceable and Sustainable Historical Climate Database: Interdisciplinarity and DRAW.
Turning historical meteorological observations into usable data is a challenging process that is immeasurably enriched when it encompasses interdisciplinarity. Here, the McGill DRAW (Data Rescue: Archives and Weather) project shows how climatologists, geographers, archivists, data scientists, and coders together built a citizen-science-based transcription platform to transform the McGill Observatory paper records into a traceable and sustainable database.


[Immunologic disturbances in psoriatic arthropathy (author's transl)].
It was observed in 51 cases of psoriatic arthropathy (PA) an increase of blood IgA and a decrease of IgM, a not significant rise of the level of circulating immune complexes, a positive Waaler-Rose reaction in 9.7% of cases and the presence of antigammaglobulin factors (generally of IgG type) in 55,5% of studied patients. Moreover, it was noted a significant decrease of T lymphocytes as detected by E and "active" E rosettes, of EA-gamma rosettes (ox erythrocytes) and an increase of the percentage of high avidity Fc-gamma receptor bearing cells. Lymphocytes responses to mitogens were normal or slightly decreased for Concanavalin A. No correlation was found between the immunological data and the clinical features.


Head-down tilt and manual hyperinflation enhance sputum clearance in patients who are intubated and ventilated.
The purpose of this prospective randomised cross-over study was to measure peak expiratory flow rates during manual hyperinflation and to determine if the addition of a head-down tilt to physiotherapy treatment increased sputum production in patients who are intubated and ventilated. Twenty patients who were intubated, ventilated and haemodynamically stable were randomised to a sequence of physiotherapy treatment in a flat side-lying or a head-down tilt position. Peak expiratory flow rates were measured for each breath during manual hyperinflation using a Vitalograph peak flow meter. Sputum wet weight was collected for each treatment position and static pulmonary compliance was measured before and immediately following physiotherapy treatment. There was a significant increase in peak expiratory flow (p < 0.001) and sputum production (p = 0.008) in the head-down tilt position. The mean difference and 95% confidence intervals for expiratory flow were 0.17 (0.15 to 0.19) l/sec and for the wet weight of sputum 1.97 (0.84 to 3.10) g. The peak expiratory flow rate was sufficient to produce annular flow in both flat side-lying (1.97 +/- 0.09) l/sec and in the head-down tilt position (2.14 +/- 0.08) l/sec. Static pulmonary compliance improved significantly following physiotherapy treatment (p = 0.003). The mean difference and 95% confidence intervals pre- and post-treatment for static pulmonary compliance were 5.18 (2.14 to 8.22) ml/cmH(2)O. The results suggest that addition of a head-down tilt to physiotherapy treatment, including manual hyperinflation, in patients who are intubated and ventilated, increases sputum production and improves peak expiratory flow.


Plasma endothelin-1 levels, pulmonary hypertension, and lung fibrosis in patients with systemic sclerosis.
To investigate the behavior of circulating endothelin (ET)-1 concentrations in patients affected by systemic sclerosis, and to elucidate the possible relationships existing in this disease among plasma peptide levels, pulmonary hypertension, and lung fibrosis. Circulating ET-1 levels were determined by reverse-phase, high-pressure liquid chromatography followed by sensitive radioimmunoassay in 20 patients affected by systemic sclerosis (18 women and 2 men, mean age 48.1 +/- 13.7 years) with or without pulmonary hypertension as evaluated by Doppler echocardiography, or lung fibrosis as measured by a score method based on lung examination by high-resolution computed tomography (HRCT). A group of 18 normal volunteers served as controls (15 women and 3 men, mean age 45.0 +/- 10.1 years). Plasma ET-1 levels were significantly higher (P < 0.001) in patients with systemic sclerosis (1.72 +/- 0.28 pg/mL) than in control subjects (0.63 +/- 0.06 pg/mL). Pulmonary artery systolic hypertension was detected in 10 patients (50%) with systemic sclerosis (56.2 +/- 18.0 mm Hg, range 37 to 97) versus none of the control subjects (30.2 +/- 2.2 mm Hg, P < 0.0001). Lung fibrosis was present in 12 patients (60%), with an HRCT overall score of 9.0 +/- 4.6. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension (1.58 +/- 0.20 pg/mL) or without it (1.76 +/- 0.39 pg/mL, P = 0.188, not significant [NS]); or between patients with lung fibrosis (1.65 +/- 0.14 pg/mL) or without fibrosis (1.78 +/- 0.37 pg/mL, P = 0.290, NS). In particular, 6 patients had neither pulmonary hypertension nor lung fibrosis. In these patients, plasma ET-1 levels were similar compared with the others (1.85 +/- 0.49 versus 1.66 +/- 0.13, respectively; P = 0.180, NS). No correlations were observed between ET-1 levels and either pulmonary pressure levels or HRCT overall scores. The use of a sensitive assay, highly selective for ET-1, showed higher levels of circulating peptide in patients affected by systemic sclerosis than in control subjects. Neither pulmonary hypertension nor lung fibrosis was accompanied by a further rise in plasma ET-1 concentrations.


Are stereotypes accurate? A perspective from the cognitive science of concepts.
In his 2012 book, Jussim suggests that people's beliefs about various groups (i.e., their stereotypes) are largely accurate. We unpack this claim using the distinction between generic and statistical beliefs - a distinction supported by extensive evidence in cognitive psychology, linguistics, and philosophy. Regardless of whether one understands stereotypes as generic or statistical beliefs about groups, skepticism remains about the rationality of social judgments.


Effectiveness of continuous femoral nerve block for pain relief after total knee arthroplasty: comparison with epidural patient-controlled analgesia and periarticular injection.
To compare the clinical outcomes among three analgesic techniques, continuous femoral nerve block (CFNB), epidural patient-controlled analgesia (EPCA) and periarticular injection (PAI), in patients undergoing total knee arthroplasty (TKA). This retrospective case-control study enrolled patients that underwent TKA. Visual analogue scale (VAS) pain scores, sleep disturbance, additional opioid consumption and incidence of opioid-related side-effects were assessed. A total of 120 patients were categorized into three groups: EPCA (group A, n = 40), PAI (group B, n = 40) and CFNB (group C, n = 40). Group C had significantly lower VAS pain scores than groups A and B at 8, 12 and 24 h after TKA. There were no significant differences in VAS pain scores among the three groups from 48 h after TKA. Sleep quality on the first day after surgery was significantly better in group C than in groups A and B. Additional opioid consumption was significantly lower in the group C than in the groups A and B. Group C showed a lower rate of opioid-related side-effects than groups A and B. CFNB was a more effective additional analgesic technique than EPCA or PAI for acute postoperative pain control within 24 h of TKA.


Tumor-derived covalent organic framework nanozymes for targeted chemo-photothermal combination therapy.
Covalent organic frameworks (COFs) have garnered enormous attention in anti-cancer therapy recently. However, the intrinsic drawbacks such as poor biocompatibility and low target-specificity greatly restrain the full clinical implementation of COF. Herein, we report a biomimetic multifunctional COF nanozyme, which consists of AIEgen-based COF (TPE-s COF) with encapsulated gold nanoparticles (Au NPs). The nanozyme was co-cultured with HepG2 cells until the cell membrane was fused with lipophilic TPE-s COF-Au@Cisplatin. By using the cryo-shocking method, we fabricated an inactivated form of the TPE-s COF-Au@Cisplatin nanozyme endocytosed in the HepG2 cell membrane (M@TPE-s COF-Au@Cisplatin), which lost their proliferative ability and pathogenicity. Upon laser irradiation, the M@TPE-s COF-Au@Cisplatin nanozymes cleaved, thereby releasing the TPE-s COF-Au nanozyme and Cisplatin to exert their photothermal and drug therapeutic effect. This work opens a new avenue to the synthesis of tumor-derived fluorescent TPE-s COF-Au nanozymes for highly efficient, synergetic, and targeted chemo-photothermal combination therapy of liver cancer.


Absence of classical MAP kinase pathway signalling in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a highly metastatic skin tumor. To assess the relevance of the Ras/Raf/MEK/MAP kinase pathway, we analyzed for activating B-Raf mutations and we elucidated the presence of the Raf Kinase Inhibitor Protein (RKIP) and extracellular signal-regulated kinase (ERK) as well as the phosphorylation status of ERK. All MCC samples were negative for the B-Raf(V600E) mutation. Remarkably, RKIP, which was shown to interfere with the activation of MEK by Raf, was highly expressed in primary as well as in metastatic MCC. Immunohistochemical analysis of the phosphorylation status of ERK revealed in 42 out of 44 samples a complete lack of activated ERK in the tumor cells although ERK is expressed; in the two positive cases phosphorylated ERK was restricted to a minor fraction of the tumor cells. Western blot analysis of three MCC-derived cell lines revealed in one case the pattern present in situ (i.e. high RKIP expression and complete absence of phosphorylated ERK). In summary, our data demonstrate the inactivity of the classical MAP kinase signal transduction pathway in MCC, which seems to be because of lack of activation as well as active deactivation. These findings should be accounted for in future therapeutic approaches for this tumor.


Recent advances in measurement of the water vapour continuum in the far-infrared spectral region.
We present a new derivation of the foreign-broadened water vapour continuum in the far-infrared (far-IR) pure rotation band between 24 μm and 120 μm (85-420 cm(-1)) from field data collected in flight campaigns of the Continuum Absorption by Visible and IR radiation and Atmospheric Relevance (CAVIAR) project with Imperial College's Tropospheric Airborne Fourier Transform Spectrometer (TAFTS) far-IR spectro-radiometer instrument onboard the Facility for Airborne Atmospheric Measurement (FAAM) BAe-146 research aircraft; and compare this new derivation with those recently published in the literature in this spectral band. This new dataset validates the current Mlawer-Tobin-Clough-Kneizys-Davies (MT-CKD) 2.5 model parametrization above 300 cm(-1), but indicates the need to strengthen the parametrization below 300 cm(-1), by up to 50 per cent at 100 cm(-1). Data recorded at a number of flight altitudes have allowed measurements within a wide range of column water vapour environments, greatly increasing the sensitivity of this analysis to the continuum strength.


Immunohistochemical and biochemical characterisation of the expression of a human embryonal carcinoma cell proteoglycan antigen in human germ cell tumours and other tissues.
In the embryonal carcinoma (EC) cell line GCT 27, monoclonal antibody GCTM-2 recognises an epitope on a 200 kD pericellular matrix keratan sulphate proteoglycan. Immunohistochemical analyses demonstrated staining of tissue sections from 21 out of 22 human non-seminomatous germ cell tumours, and from 22 out of 28 sections of seminomas. In normal human fetal tissues gut epithelium and muscle stained strongly, and certain other epithelia stained moderately. In adult tissues, the distribution of the epitope was similar, but staining intensity was weaker. Neoplastic tissues showed reactivity with embryonal rhabdomyosarcoma and colorectal carcinoma, but no other non-germ cell tumours. Immunofluorescence microscopy showed that GCTM-2 also stained cell lines from human colorectal carcinoma, embryonal rhabdomyosarcoma and choriocarcinoma. In contrast to EC cells the epitope in these other cell types required permeabilization of the cells to be visualised, and the protein bands in immunoblots lacked extensive modification with keratan sulphate and were smaller. Thus, GCTM-2 reacts with an epitope which has a previously unrecognised tissue distribution; its expression as a pericellular matrix proteoglycan is predominantly a characteristic of human EC cells.


Liver segmentation with new supervised method to create initial curve for active contour.
The liver performs a critical task in the human body; therefore, detecting liver diseases and preparing a robust plan for treating them are both crucial. Liver diseases kill nearly 25,000 Americans every year. A variety of image segmentation methods are available to determine the liver's position and to detect possible liver tumors. Among these is the Active Contour Model (ACM), a framework which has proven very sensitive to initial contour delineation and control parameters. In the proposed method based on image energy, we attempted to obtain an initial segmentation close to the liver's boundary, and then implemented an ACM to improve the initial segmentation. The ACM used in this work incorporates gradient vector flow (GVF) and balloon energy in order to overcome ACM limitations, such as local minima entrapment and initial contour dependency. Additionally, in order to adjust active contour control parameters, we applied a genetic algorithm to produce a proper parameter set close to the optimal solution. The pre-processing method has a better ability to segment the liver tissue during a short time with respect to other mentioned methods in this paper. The proposed method was performed using Sliver CT image datasets. The results show high accuracy, precision, sensitivity, specificity and low overlap error, MSD and runtime with few ACM iterations.


Optimising UK training in aesthetic surgery: A prospective national study using operative logbooks and questionnaires to determine factors associated with trainee participation.
We aimed to determine the proportion of UK aesthetic surgery training taking place in the independent sector, how this experience is gained, and factors associated with trainee participation. We also aimed to draw comparisons between training in the National Health Services (NHS) and independent sectors. Plastic Surgery Trainees were asked to complete a 10-item questionnaire, in addition to their usual operative entry on eLogbook, when logging a procedure with an aesthetic operative code, prospectively over a 6-month period. Anonymised data was exported and analysed using SPSS. A total of 285 questionnaires were completed; all UK training regions were represented. The majority were for NHS procedures (88%), of which 56% were for breast surgery, 23% facial surgery, 19% body contouring, and 2% non-surgical. Trainees were significantly more likely to participate in procedures when they were performed in the NHS (odds ratio, OR, 9.7, p < 0.01) or when they were body contouring surgery (OR 1.5, p < 0.01). Trainees were more likely to participate in perioperative care in an NHS setting (p < 0.01). When trainees attend the independent sector, it was usually within contracted training hours (57%) with their consultant trainer with whom they are working in the NHS (63%). The majority of aesthetic surgery training occurs in the NHS but this is not representative of UK aesthetic practice. There is a need to engage the independent sector to provide formal aesthetic surgery training as part of the plastic surgery training programme, including procedural participation and perioperative care. Additional aesthetic fellowships and mechanisms for mentorship by established consultants should be developed.


Study of the interaction of proteins with curcumin and SDS and its analytical application.
It is found that protein and sodium dodecyl sulphonate (SDS) can enhance resonance light scattering (RLS) of curcumin (CU). Based on this phenomenon, a new quantitative method for protein in aqueous solution has been developed. In the BR (pH 3.5) buffer, the RLS intensity of CU-SDS system is greatly enhanced by protein. The enhanced RLS is proportional to the concentration of protein in the range of 0.00020-20.0 microgml(-1) for bovine serum albumin (BSA) and 0.00040-1.0 microgml(-1) for human serum albumin (HSA) and their detection limits are 0.16 and 0.041 ngml(-1), respectively. An actual sample is satisfactorily determined. In addition, the interaction mechanism between protein and CU-SDS is also studied by using multi-techniques such as RLS, absorption spectroscopy and fluorescence, zeta potential assay measurement.


ZiMM: A deep learning model for long term and blurry relapses with non-clinical claims data.
This paper considers the problems of modeling and predicting a long-term and "blurry" relapse that occurs after a medical act, such as a surgery. We do not consider a short-term complication related to the act itself, but a long-term relapse that clinicians cannot explain easily, since it depends on unknown sets or sequences of past events that occurred before the act. The relapse is observed only indirectly, in a "blurry" fashion, through longitudinal prescriptions of drugs over a long period of time after the medical act. We introduce a new model, called ZiMM (Zero-inflated Mixture of Multinomial distributions) in order to capture long-term and blurry relapses. On top of it, we build an end-to-end deep-learning architecture called ZiMM Encoder-Decoder (ZiMM ED) that can learn from the complex, irregular, highly heterogeneous and sparse patterns of health events that are observed through a claims-only database. ZiMM ED is applied on a "non-clinical" claims database, that contains only timestamped reimbursement codes for drug purchases, medical procedures and hospital diagnoses, the only available clinical feature being the age of the patient. This setting is more challenging than a setting where bedside clinical signals are available. Our motivation for using such a non-clinical claims database is its exhaustivity population-wise, compared to clinical electronic health records coming from a single or a small set of hospitals. Indeed, we consider a dataset containing the claims of almost all French citizens who had surgery for prostatic problems, with a history between 1.5 and 5 years. We consider a long-term (18 months) relapse (urination problems still occur despite surgery), which is blurry since it is observed only through the reimbursement of a specific set of drugs for urination problems. Our experiments show that ZiMM ED improves several baselines, including non-deep learning and deep-learning approaches, and that it allows working on such a dataset with minimal preprocessing work.


Case of immunoglobulin G4-related cholangitis accompanying autoimmune pancreatitis: diagnosis by peroral cholangioscopy and treatment by endoscopic biliary stenting.
Recently, the progress of endoscopy has made it possible to evaluate bile duct mucosa by peroral cholangioscopy. Herein, we report a case of immunoglobulin G4-related sclerosing cholangitis accompanying autoimmune pancreatitis in a patient who improved with treatment by steroid therapy and endoscopic biliary stenting, and observed the bile duct mucosa by peroral cholangioscopy before and after treatment.


Development of two cytogenetically abnormal clones from multipotential hematopoietic stem cells in a patient with juvenile myelomonocytic leukemia.
We report a patient with juvenile myelomonocytic leukemia who had two cytogenetically independent clones at the time of diagnosis. Fluorescence in situ hybridization analyses showed that 42.5% of myeloperoxidase(+) cells and 27.3% of CD20(+) cells had three signals for chromosome 8, while 13.1% of myeloperoxidase(+) cells and 6.0% of CD20(+) cells had del (Y). However, a great majority of CD3(+) cells had no numerical aberration of the two chromosomes. The two karyotypically abnormal clones might have developed from multipotential hematopoietic stem cells with the potential to differentiate into myeloid and B-lymphoid lineages, but not T-lymphoid lineage.


QIAamp MinElute virus kit effectively extracts viral nucleic acids from cerebrospinal fluids and nasopharyngeal swabs.
Nucleic acid preparation from a variety of clinical specimens requires efficient target recovery and amplification inhibitor removal and is critical for successful molecular diagnosis. The QIAamp MinElute Virus kit (Qiagen Inc., Valencia, CA) was compared to the two existing methods currently used in our laboratory, IsoQuick (Orca Research Inc., Bothell, WA) for DNA extraction and RNAzol B (Leedo Laboratories Inc., Houston, TX) for RNA extraction, of viral nucleic acids. A total of 150 clinical specimens, including cerebrospinal fluid (CSF) and nasopharyngeal swabs (NPS), were used to determine the extraction efficiency of the MinElute compared to the other two methods. Nucleic acid recovery, hands-on time, turn-around-time and cost were compared across all kits. There was complete concordance between the MinElute and IsoQuick/RNAzol kits when herpes simplex virus (HSV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), influenza A virus or enteroviruses were detected using a colorimetric microtiter plate PCR system. The kits were equivalent in their ability to detect either DNA or RNA with superior ability to recover a high quality and quantity of RNA. With the potential to process larger specimen volumes, the MinElute kit can significantly shorten processing time from 2h to 50-55min. Although relatively high test kit costs were noted, the MinElute kit provides another rapid and user-friendly specimen processing tool in the diagnostic molecular microbiology laboratory.


[Clinical and radiological evolution of a group of untreated acoustic neuromas].
The acoustic neuroma is a benign tumour that originates in the vestibular branch of the eighth cranial nerve. The main treatment is surgery, but many authors suggest that with elderly patients or in small neuromas we can opt for watchful waiting. This was a retrospective study from 2007 to 2013 that included 27 patients diagnosed of acoustic neuroma that had not been treated due to the size of the tumour, age and comorbidities, or by patient choice. We evaluated overall condition, hearing thresholds, degree of canal paresis and central disorders. After 6 years of follow up, clinical manifestations of 18 patients remained unchanged, 5 patients underwent hearing loss and developed tinnitus, 2 cases had more intense tinnitus and 2 cases had dizziness. The radiological controls by magnetic resonance imaging showed that the initial maximum diameters (5-16mm) increased by 1.7mm on average, with annual growth rates below 0.5mm. In selected cases, such as for small neuromas and in elderly patients, the conservative option of close monitoring with magnetic resonance imaging is an important alternative given that, in our cases, clinical features and radiological image did not suffer major changes. If there were any such changes, therapeutic options could be proposed.


Practical guide for the treatment of leishmaniasis.
This article summarises the clinical features of visceral, cutaneous and mucocutaneous leishmaniasis, and leishmaniasis in HIV-coinfected patients. The characteristics and clinical use of pentavalent antimonials and the traditional drugs used in all forms of leishmaniasis are described. There have been important developments in therapy, such as aminosidine (paromomycin) conventional amphotericin B and lipid-associated amphotericin B. In most cases of leishmaniasis there is a range of treatment options which is determined by the geographical and clinical features. This review is intended to assist the clinician in choosing treatment and in using unfamiliar drugs with safety and efficacy.


Single-stage, immediate loading, and flapless surgery.
With appropriate patient selection, single-stage surgery, immediate loading, and flapless site preparation are dependable treatment approaches that offer significant benefits to implant patients. This paper briefly reviews the history of these approaches and describes the conditions necessary to achieve long-term success. Case studies also are included.


The changing needs of patients after primary rehabilitation: an overlooked entity.
The need for rehabilitation should not be viewed as a single event that may occur during a lifetime. This theme is explored. A case of a man who lost the distal portions of all four limbs, is reported. He was rehabilitated and spent many years as an active member of the community. The physical changes, owing to advancing age, were overlooked. Attention is drawn to the fact that long term re-evaluation of function is periodically required.


Antigen-antibody interactions: an NMR approach.
With recent advances in methodology, it now appears that NMR can be used at an unprecedented level of sophistication to obtain new insights into the solution structure and dynamics of the antibody combining site, both free and in its complex with antigen. Most promising in this regard is the Fv fragment (molecular weight approximately 25 kD) which can be produced by genetic engineering in a form suitable for NMR studies. Isotopic labeling is required to make specific resonance assignments. NMR can also provide information on the conformational preferences of immunogenic peptides and can be used to probe the conformation and dynamics of peptides (appropriately labeled with 13C or 15N) bound to the Fab fragment (molecular weight approximately 50 kD) of antipeptide antibodies.


Core-Shell Structured Layered Lanthanide-Organic Complexes with Stilbazolium-type Dye Encapsulation for Multifunctional Performances.
Host-guest encapsulation of functional organic dye into a porous metal-organic framework can give rise to the development of new functional materials. In this work, by intercalating the stilbazolium-type dye (DEAST)I (4'-diethylamino-N-methyl stilbazolium) into four lanthanide layered metal-organic complexes (Ln-LMOCs), i. e. {[Ln(BTB)(H2 O)2 ]⋅3(DMF)⋅2(H2 O)}n (Ln=La (1), Nd (2), Sm (3), Er (4)), four responsive (DEAST)I@Ln-LMOC composites have been prepared, serving as multifunctional performance platform. The core-shell structures of (DEAST)I@Ln-LMOC composites have been fully characterized by IR, UV/Vis, PXRD, SEM, TEM, TGA and ESR. Significantly, after intercalation of dyes, the (DEAST)I@Ln-LMOC composites exhibit enhanced luminescent sensing properties in detecting Fe3+ with much higher water stabilities. The luminescent sensing behavior stems from the fluorescence resonance energy transfer (FRET) from the π-electron-rich BTB ligands to the Fe3+ , and their higher water stabilities are induced by electrostatic interactions and lower porosity. Specially, the characteristic emissions of Sm3+ will not be affected after the encapsulation guest dyes, which provide a theoretical guide for the modulation of luminescence devices. Finally, better ion conductivities and diminished photocurrents can be achieved after the embedding of the functional organic dye. In all, the formation of (DEAST)I@Ln-LMOC composites with core-shell structures can be utilized as a multifunctional platform with good stability.


Surveillance of human Group A rotavirus in Ningxia, China (2015-2021): Emergence and prevalence of G9P[8]-E2 and G3P[8]-E2 genotypes.
Group A rotaviruses (RVA) are the primary pathogens of acute gastroenteritis. Currently, two live attenuated RVA vaccines, LLR and RotaTeq, have been introduced into mainland China but are not included in the national immunization program. Because of the unknown genetic evolution of group A rotavirus in an all-age population in Ningxia, China, we monitored the epidemiological characteristics and circulating genotypes of RVA as a reference for developing vaccine strategies. We conducted seven years of consecutive surveillance of RVA based on stool samples from patients with acute gastroenteritis in sentinel hospitals in Ningxia, China, from 2015 to 2021. Reverse transcription quantitative polymerase chain reaction(RT-qPCR) was used to detect RVA in stool samples. Genotyping and phylogenetic analysis of VP7, VP4 and NSP4 genes were performed by reverse transcription-polymerase chain reaction(RT-PCR) and nucleotide sequence determination. RVA was detected in 16.58% (1436/8662) of 8662 stool samples. The positive rates were 7.17% (201/2805) and 21.09% (1235/5857) in adults and children, respectively. The most affected age group was infants and children aged 12-23 months, with a positive rate of 29.53% (p < 0.05). A significant winter/spring seasonality was observed. 23.29% positive rate in 2020 was the highest in 7 years (p < 0.05). The region with the highest positive rate in the adult group was Yinchuan, and the children's group was Guyuan. A total of 9 genotype combinations were found to be distributed in Ningxia. The dominant genotype combinations in this region gradually changed from G9P[8]-E1, G3P[8]-E1, G1P[8]-E1 to G9P[8]-E1, G9P[8]-E2, and G3P[8]-E2 during these seven years. Rare strains (e.g., G9P[4]-E1, G3P[9]-E3 and G1P[8]-E2) were occasionally detected during the study. During the study period, changes in the significant RVA circulating genotype combinations and the emergence of reassortment strains were observed, particularly the emergence and prevalence of G9P[8]-E2, G3P[8]-E2 reassortants in the region. These results indicate the importance of continuous monitoring of the molecular evolution and recombination characteristics of RVA, and should not be limited to G/P genotyping but should consider multi-gene fragment co-analysis and whole genome sequencing.


Structural revision of sesbagrandiflorains A and B, and synthesis and biological evaluation of 6-methoxy-2-arylbenzofuran derivatives.
Sesbagrandiflorains A (1) and B (2), isolated from the stem bark of the Indonesian fabaceous plant Sesbania grandiflora, were reported to be 6-methoxy-2-(2´,3´-dihydroxy-5´-methoxyphenyl)-1-benzofuran-3-carbaldehyde and 6-hydroxy-2-(2´,3´-dihydroxy-5´-methoxyphenyl)-1-benzofuran-3-carbaldehyde, respectively. However, based on reevaluation of their 1D and 2D NMR data, the chemical structures of 1 and 2 have been revised to 4-hydroxy-2-(4´-hydroxy-2´-methoxyphenyl)-6-methoxybenzofuran-3-carbaldehyde and 4-hydroxy-2-(4´-hydroxy-2´-hydroxyphenyl)-6-methoxybenzofuran-3-carbaldehyde, respectively. In addition, seven new derivatives of 1 have been synthesized from the natural product in good yields (65 - 93%). The chemical structures of the synthetic compounds-one diester (6), four ethers (7-10), one secondary amine (11), and one oxime (12)-were confirmed by MS and NMR analysis. Compound 6 exhibited moderate antibacterial activity against the plant pathogen Rhodococcus fascians with a MIC of 0.1 mg/mL. Compounds 8 and 12 demonstrated respectable cytotoxicity against A375 melanoma cancer cells line with the relative IC50 values of 22.8 and 32.7 μM, respectively.


Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy.
Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes. We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan-Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test. We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0-56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19-3.76) or new onset irAE (OR 3.21, 95% CI 0.83-13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52). The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.


Bioconversion of natural gas to liquid fuel: opportunities and challenges.
Natural gas is a mixture of low molecular weight hydrocarbon gases that can be generated from either fossil or anthropogenic resources. Although natural gas is used as a transportation fuel, constraints in storage, relatively low energy content (MJ/L), and delivery have limited widespread adoption. Advanced utilization of natural gas has been explored for biofuel production by microorganisms. In recent years, the aerobic bioconversion of natural gas (or primarily the methane content of natural gas) into liquid fuels (Bio-GTL) by biocatalysts (methanotrophs) has gained increasing attention as a promising alternative for drop-in biofuel production. Methanotrophic bacteria are capable of converting methane into microbial lipids, which can in turn be converted into renewable diesel via a hydrotreating process. In this paper, biodiversity, catalytic properties and key enzymes and pathways of these microbes are summarized. Bioprocess technologies are discussed based upon existing literature, including cultivation conditions, fermentation modes, bioreactor design, and lipid extraction and upgrading. This review also outlines the potential of Bio-GTL using methane as an alternative carbon source as well as the major challenges and future research needs of microbial lipid accumulation derived from methane, key performance index, and techno-economic analysis. An analysis of raw material costs suggests that methane-derived diesel fuel has the potential to be competitive with petroleum-derived diesel.


Violence Victimization and Condomless Anal Intercourse Among Transgender Women in China: Mediating Role of Depression.
Transgender women (TGW) worldwide report disproportionate violence victimization, depression and condomless anal intercourse (CAI), but the mechanism of the coexistence remains unclear. Using snowball sampling, we recruited 198 self-identified TGW in Shenyang, China between April 2017 and July 2017, and conducted confidential questionnaire survey among them. Positive HIV status was reported by 49 (24.7%) participants. 117 (59.1%) reported at least one type of lifetime violence victimization, with transactional sexual partners being the main violence perpetrators. 108 (54.5%) reported mild to severe depression. 105 (53.0%) reported having CAI with their sexual partners during the last 6 months. Path analysis showed that the association between participants' violence victimization and CAI was fully mediated by their depression (indirect effect: 0.083, p = 0.014; direct effect: 0.137, p = 0.121). We suggest to incorporate violence screening and prevention and mental health services into intervention strategies to prevent CAI among Chinese TGW.


Genome size drives morphological evolution in organ-specific ways.
Morphogenesis is an emergent property of biochemical and cellular interactions during development. Genome size and the correlated trait of cell size can influence these interactions through effects on developmental rate and tissue geometry, ultimately driving the evolution of morphology. We tested whether variation in genome and body size is related to morphological variation in the heart and liver using nine species of the salamander genus Plethodon (genome sizes 29-67 gigabases). Our results show that overall organ size is a function of body size, whereas tissue structure changes dramatically with evolutionary increases in genome size. In the heart, increased genome size is correlated with a reduction of myocardia in the ventricle, yielding proportionally less force-producing mass and greater intertrabecular space. In the liver, increased genome size is correlated with fewer and larger vascular structures, positioning hepatocytes farther from the circulatory vessels that transport key metabolites. Although these structural changes should have obvious impacts on organ function, their effects on organismal performance and fitness may be negligible because low metabolic rates in salamanders relax selective pressure on function of key metabolic organs. Overall, this study suggests large genome and cell size influence the developmental systems involved in heart and liver morphogenesis.


Catechol-O-methyltransferase mRNA in the kidney and its appearance during ontogeny.
Catechol-O-methyltransferase (COMT), primarily present as a soluble cytosolic form (S-COMT), inactivates catechols. The recent cloning of the rat and human S-COMT from placenta has allowed us to synthesize complementary oligonucleotide probes to study the localization of COMT mRNA during development in the rat kidney and in the adult human kidney using in situ hybridization histochemistry. In the adult rat kidney, COMT mRNA was detected in segment S3 of proximal tubule cells in the outer stripe of the outer medulla, and thick ascending limb of loop of Henle (TAL) in the inner stripe. COMT mRNA was detected in the prenatal rat kidney as early as on day 18. In the human kidney, strong hybridization signal was seen in the medulla and in tubule segments of the cortex. In the adult rat kidney, COMT mRNA was in addition demonstrated in the transitional epithelium of the ureter. The results suggest synthesis of COMT and inactivation of catechols along the distal parts of proximal tubules, in TAL cells, and in the epithelium of the ureter.


Crystal structure of the unusual coordination polymer catena-poly[[gold(I)-μ-1,2-bis-(di-phenyl-phosphino-thio-yl)ethane-κ2 S:S'] di-bromido-aurate(I)].
In the title compound, {[Au(C26H24P2S2)][AuBr2]} n , the gold(I) centres of the cation are coordinated by the P=S groups of the di-sulfide ligands to form a chain polymer parallel to the c axis. Both independent gold atoms lie on the same twofold axis, and the midpoint of the H2C-CH2 bond lies on an inversion centre. The anions flank the polymeric chain; they are connected to it by short aurophilic inter-actions and C-H⋯Br contacts, and to each other by Br⋯Br contacts.


Molecular systematics of Middle American harvest mice Reithrodontomys (Muridae), estimated from mitochondrial cytochrome b gene sequences.
We estimated phylogenetic relationships among 16 species of harvest mice using sequences from the mitochondrial cytochrome b (cyt b) gene. Gene phylogenies constructed using maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) optimality criteria were largely congruent and arranged taxa into two groups corresponding to the two recognized subgenera (Aporodon and Reithrodontomys). All analyses also recovered R. mexicanus and R. microdon as polyphyletic, although greater resolution was obtained using ML and BI approaches. Within R. mexicanus, three clades were identified with high nodal support (MP and ML bootstrap, Bremer decay and Bayesian posterior probabilities). One represented a subspecies of R. mexicanus from Costa Rica (R. m. cherrii) and a second was distributed in the Sierra Madre Oriental of Mexico. The third R. mexicanus clade consisted of mice from southern Mexico southward to South America. Polyphyly between the two moieties of R. microdon corresponded to the Isthmus of Tehuantepec in southern Mexico. Populations of R. microdon microdon to the east of the isthmus (Chiapas, Mexico) grouped with R. tenuirostris, whereas samples of R. m. albilabris to the west in Oaxaca, Mexico, formed a clade with R. bakeri. Within the subgenus Reithrodontomys, all analyses recovered R. montanus and R. raviventris as sister taxa, a finding consistent with earlier studies based on allozymes and cyt b data. There was also strong support (ML and BI criteria) for a clade consisting of ((R. megalotis, R. zacatecae) (R. sumichrasti)). In addition, cytb gene phylogenies (MP, ML, and BI) recovered R. fulvescens and R. hirsutus (ML and BI) as basal taxa within the subgenus Reithrodontomys. Constraint analyses demonstrated that tree topologies treating the two subgenera (Aporodon and Reithrodontomys) as monophyletic (ML criterion) was significantly better (p>0.036) and supported polyphyly of R. mexicanus (both ML and MP criteria - p>0.013) and R. microdon (MP criterion only for certain topologies; p>0.02). Although several species-level taxa were identified based on multiple, independent data sets, we recommended a conservative approach which will involve thorough analyses of museum specimens including material from type localities together with additional sampling and data from multiple, nuclear gene markers.


[Clinical substantiation of nootropic preparation use for premedication in outpatient stomatology].
The clinico-pharmacological description of nooclerin is given. The premedication effectiveness in patients with various individual typological features in out-patient stomatologic treatment was studied.


Chronic treatment with FK506 increases p70 S6 kinase activity associated with reduced nitric oxide synthase activity in rabbit hearts.
FK506, an immunosuppressant, modulates phosphorylation of nitric oxide (NO) synthase, and induces cardiac hypertrophy in clinical settings. Having recently reported that chronic treatment with an inhibitor of NO synthase induces cardiac hypertrophy associated with the activation of 70-kD S6 kinase (p70S6K), which plays an important role in cardiac hypertrophy by regulating protein synthesis, we investigated the effects of chronic administration of FK506 on NO synthase and p70S6K activities in hearts. Twenty rabbits were divided into four groups: untreated rabbits, those treated with low-dose FK506 (0.10 mg/kg), those treated with medium-dose FK506 (0.20 mg/kg), and those treated with high-dose FK506 (0.40 mg/kg). FK506 was administered intravenously twice a day. After 4 weeks of treatment with FK506, calcium-dependent NO synthase activity in myocardium in the high-dose FK506 group was lower (P < 0.05) than in the untreated group. p70S6K activity in myocardium in the high-dose group was higher (P < 0.05) than in the untreated group. There was a significant (P < 0.05) inverse correlation between NO synthase and p70S6K activities in myocardium. However, the endothelial-dependent vasodilation of aortic rings or plasma levels of NO metabolites during experimental protocols did not differ among the groups studied. These findings suggest that chronic treatment of FK506 activates p70S6K and reduces NO synthase activity in rabbit hearts. Reduced NO synthase and/or activated p70S6K activities in hearts might contribute to the cardiac hypertrophy observed in some patients receiving FK506.


Sodium alginate edible coating containing Ferulago angulata (Schlecht.) Boiss essential oil, nisin, and NaCl: Its impact on microbial, chemical, and sensorial properties of refrigerated chicken breast.
This study aimed to investigate the effects of sodium alginate (ALG) coating incorporated with Ferulago angulata (Schlecht.) Boiss essential oil (FAEO, 10 and 20 mg/mL), nisin (N, 500 and 1000 IU/mL), and NaCl (2 %) on microbial (lactic acid bacteria, LAB; total viable bacteria, TVC; psychrotrophic bacteria; Pseudomonas; Enterobacteriaceae, and yeast and mold), chemical (pH, PV, TVB-N, and TBARS), sensory (color, odor, texture, and overall acceptance), and antioxidant properties of refrigerated (4 °C) chicken breasts. GC-MS analysis revealed that trans-β-ocimene (45.36 %) and α-pinene (18.01 %) constituted most of the components in FAEO. The antioxidant properties of FAEO were evaluated via the DPPH method. The IC50 value of FAEO was 562 mg/mL. The results of antimicrobial evaluations indicated that there was no significant difference between control and ALG treatments (p > 0.05). The highest antimicrobial effect was associated with ALG + FAEO2 + N2 + NaCl treatment. The logarithmic reduction of the TVC, psychrotrophic count, Pseudomonas count, Enterobacteriaceae, LAB, as well as yeast and mold count in the ALG + FAEO2 + N2 + NaCl treatment were 1.40, 0.92, 1.20, 1.02, 0.88, and 1 log CFU/g, respectively compared to the control treatment. The initial level of TVB-N in the control treatment was 8.26 mg/100 g, which reached 42.84 mg/100 g at the end of the storage period. In ALG+ FAEO2 + N2 + NaCl treatment, the lowest TVB-N was observed, being 36.37 mg/100 g at the end of the storage period. The initial level of PV in the control treatment was 0.14 meq/kg, which reached 3.04 meq/kg at the end of the storage period. In the treatments containing FAEO, PV was lower than in other treatments, indicating the antioxidant properties of FAEO. There was a significant difference between control and other treatments in pH and TBARS evaluation (p < 0.05). The samples treated with FAEO had a lower pH than control. At the end of the storage period, the TBARS level in the control treatment reached 1.20 mg MDA/kg, while in the treatment of ALG+ FAEO2 + N2 + NaCl treatment, its level was 0.36 mg MDA/kg. The results of sensory properties indicated that in evaluating the color, odor, texture, and overall acceptance on the final days, treatments containing FAEO, nisin, and NaCl had higher scores due to their antimicrobial and antioxidant properties. In conclusion, this study indicated that adding FAEO, nisin, and NaCl to ALG coating would enhance the shelf-life of chicken meat.


Cuticular hydrocarbons and soldier defense secretions of Reticulitermes in southern California: a critical analysis of the taxonomy of the genus in North America.
Cuticular hydrocarbons (CHC) and soldier defense secretions (SDS) were characterized for collections of Reticulitermes from six counties (Los Angeles, Orange, Riverside, San Bernardino, San Diego, and Santa Barbara) in southern California. Collection sites included the type locality for R. hesperus, Lake Arrowhead (formerly known as Little Bear Lake) in the San Bernardino Mountains. In southern California, there are two CHC phenotypes, SC-A and SC-B, which are easily distinguished by the presence or absence of 5-methyl pentacosane, 5-methyl heptacosane, 5,17-dimethyl pentacosane, and 5,17-dimethyl heptacosane. These phenotypes are similar, but not identical, to previously designated phenotypes of Reticulitermes from northern California. The SDS of termites collected from southern California were characterized; (-)-germacrene A was abundant in all but the four samples from Lake Arrowhead. Soldiers of phenotype SC-A produced >79% germacrene A. The four samples from Lake Arrowhead produced no germacrene A, but contained >78% gamma-cadinene. The SDS from the Lake Arrowhead samples were more similar to those of CA-A/CA-A' from northern California than to any of the CHC phenotypes from southern California. Soldiers of CHC phenotype SC-B produced germacrene A, with the proportion varying from 16.2 to 98.7%. The SDS of SC-B were more similar to those of SC-A than to any of the phenotypes from northern California. The CHC phenotype SC-A found in southern California likely represents R. hesperus and SC-B appears to be a new, as yet undescribed species. We discuss the state of current taxonomic research on Reticulitermes.


Development of the area centralis and visual streak in the grey kangaroo Macropus fuliginosus.
To further our understanding of area centralis and visual streak formation we have investigated the distribution and number of the total cell population in the retinal ganglion cell layer of the western grey kangaroo Macropus fuliginosus using adults and young from 7-200 days postnatal. This species was chosen since, as we describe, the adult possesses a particularly prominent area centralis and visual streak. By studying the total cell population we were able to compare cell distributions in immature retinae, in which cell types could not be distinguished, with topography in the adult. By 57 days postnatal a weak visual streak was apparent; a pronounced area centralis and visual streak were seen by 84 days although densities across the retina, particularly in the far periphery, were still considerably higher than in the adult. Dying cells were also observed up to 160 days, but not at 188 days or in the adult. The fall of approximately one third in the total cell number as the area centralis and visual streak developed is presumably related to cell death. Furthermore, at 57 days, dying cells were seen preferentially in retinal regions outside the immature visual streak and may therefore play a part in refining density gradients to their mature form. As the area centralis and visual streak developed, the relative lengths of the dorso-ventral and naso-temporal axes remained similar, suggesting that differential radial growth cannot underlie the changing live cell density gradients.


CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters.
Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.


The molecular diversity and evolution of Rice tungro bacilliform virus from Indian perspective.
Rice tungro disease is caused by a combination of two viruses: Rice tungro spherical virus and Rice tungro bacilliform virus (RTBV). This study was performed with the objective to decipher the molecular variability and evolution of RTBV isolates present in the tungro-affected states of Indian subcontinent. Phylogenetic analysis based on ORF-I, ORF-II, and ORF-IV sequences showed distinct divergence of Indian RTBV isolates into two groups; one consisted isolates from Hyderabad (Andhra Pradesh), Cuttack (Orissa), and Puducherry and another from West Bengal, Chinsura West Bengal, and Kanyakumari (Tamil Nadu). The results obtained from phylogenetic analysis were further supported with the single nucleotide polymorphisms (SNPs), insertion and deletion (INDELs) and evolutionary distance analysis. In addition, sequence difference count matrix revealed a maximum of 56 (ORF-I), 13 (ORF-II) and 73 (ORF-IV) nucleotides differences among all the Indian RTBV isolates taken in this study. However, at the protein level these differences were not significant as revealed by K (a)/K (s) ratio calculation. Sequence identity at nucleotide and amino acid level was 92-100 % (ORF-I), 96-100 % (ORF-II), 94-100 % (ORF-IV) and 86-100 % (ORF-I), 98-100 % (ORF-II) and 95-100 % (ORF-IV), respectively, among Indian isolates of RTBV. The divergence of RTBV isolates into two independent clusters of Indian and non-Indian was shown with the help of the data obtained from phylogeny, SNPs, and INDELs, evolutionary distance analysis, and conserved motifs analysis. The important role of ORF-I and ORF-IV in RTBV diversification and adaptation to different rice growing regions is also discussed.


[A broad program of vaccination in the Ivory Coast].
This paper is a description of a vaccination programme against the most frequent communicable diseases among children: measles, tuberculosis, diphtheria, tetanus, whooping-cough and poliomyelitis. The programme is to be carried out in three different climate zones (town, forest and savanna) and over a period of six years. The project is supported by US-AID and UNICEF.


Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins.
Plasma membrane monoamine transporter (PMAT) is a polyspecific organic cation transporter that is highly expressed in the central nervous system. This study aimed to investigate the effect of lipopolysaccharide on PMAT expression at the blood-brain barrier and the interaction between PMAT and neurotoxins. As a result, PMAT mRNA was identified in brain microvessels (BMVs), brain microvascular endothelial cells (BMECs), astrocytes, and pericytes isolated from C57BL/6 mice and/or Wistar rats using RT-qPCR. The immunofluorescence staining confirmed the expression of PMAT protein in BMVs and striatum of C57BL/6 mice. Western blotting demonstrated its localization at the luminal and abluminal sides of BMECs. In C57BL/6 mice, PMAT protein was significantly increased in BMVs 24 h after an intraperitoneal injection of 3 mg/kg lipopolysaccharide. Lipopolysaccharide treatment also significantly increased PMAT expression in cerebral cortex and the striatum in a time-dependent manner, as well as the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ). In isolated cells, lipopolysaccharide treatment significantly increased PMAT mRNA in brain astrocytes and the BMECs co-cultured with astrocytes. In addition to 1-methyl-4-phenylpyridinium, the kinetic study indicated that both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-benzyl-TIQ are substrates of human PMAT. These findings suggest that inflammation can change PMAT expression at the blood-brain barrier, which may affect PMAT-mediated transport of neurotoxins. We demonstrated the expression of plasma membrane monoamine transporter (PMAT; mRNA or protein) at several subunits of the blood-brain barrier. Lipopolysaccharide treatment can significantly increase the expression of PMAT in vivo (in brain microvessels, cerebral cortex, and the striatum of C57BL/6 mice) and in vitro (in brain astrocytes and brain microvascular endothelial cells co-cultured with astrocytes). Lipopolysaccharide treatment also increased the brain-to-plasma ratio of 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ) in mice, where 1-benzyl-TIQ competitively inhibited 1-methyl-4-phenylpyridinium (MPP(+)) uptake in MDCK-human PMAT (hPMAT) cells and its uptake in MDCK-hPMAT is concentration dependent.


Recurrent hypersomina: a case report with polysomnographic findings.
Recurrent hypersomnia is an uncommon clinical problem that can be misdiagnosed and mistreated. I report a case of idiopathic recurrent hypersomnia. The clinical features, differential diagnoses, polysomnographic findings, possible aetiologies, and treatment are discussed.


Open to MOOCs? Evidence of their impact on labour market outcomes.
This paper investigates the effect that participation in massive open online courses (MOOCs) ecosystem can have on workers' labour market outcomes, mainly employment retaining. We use primary data collected between 2015 and 2017 and obtained from two surveys (pre-course and follow-up questionnaires) sent to participants in six MOOCs. The treatment group is composed of individuals participating in MOOCs in 2015 and the control group is composed of individuals who enrolled in MOOCs for the first time in 2017. Using a differences-in-differences approach, we find that participation in MOOCs can improve workers' employment retaining but not their wages. The positive effect on employment retaining is homogeneous in different geographical and economic areas and tends to be higher for individuals who have participated in more MOOCs in the past.


Biochemical characterization of I-Ak proteins from mutant antigen-presenting B-cell--B-lymphoma hybridomas.
Chemically induced mutants of an I-Ak,d expressing antigen-presenting B-cell--B-lymphoma hybridoma have recently been generated by immunoselection in vitro and were found to possess alterations in some of their serologically and functionally defined I-Ak region dependent functions. In order to identify at the structural level the origin of the differences in serological and functional properties of these mutants, I-Ak molecules from several of these mutant hybridomas were compared biochemically to wild-type I-Ak polypeptides by two-dimensional gel electrophoresis and high-pressure liquid chromatographic tryptic peptide analyses. Two-dimensional gel electrophoresis indicated that no major structural alterations, resulting in changes in mol. wt or charge, had occurred in the Ak alpha or Ak beta polypeptides from the mutant cells. Likewise, Ak alpha peptide maps of the mutants were indistinguishable from the normal Ak alpha peptide maps. However, two of the three mutants studied did exhibit one additional peptide in their Ak beta peptide maps. These results suggest that the major deficiencies in T-cell-activating functions of these mutants are a result of a limited alteration in the Ak beta polypeptide primary structure.


Acute Achilles tendon rupture: Skip the surgery?
Nonoperative management for acute Achilles tendon rupture results in patient-reported outcomes similar to surgery at 1 year-but higher rates of rerupture.


Posterior Wall Isolation for Atrial Fibrillation: Effects on Echocardiographic Parameters of cardiac function.
Posterior wall isolation (PWI) in addition to circumferential pulmonary vein isolation (CPVA) requires more ablation of left atrial tissue. We compared the effect of PWI versus non-PWI methods (CPVA + linear lesions) on echocardiographic parameters of left atrial and left ventricular function. We selected patients who had pre and post ablation echocardiogram at our institution. Parameters assessed were: Left ventricular outflow tract velocity time integral (VTI), left ventricular ejection fraction (LVEF), atrial Doppler velocity across mitral valve (A), E/E', and deceleration time. Of the 72 patients studied, 32.5% had PWA in addition to CPVA. The mean duration between echocardiograms was 650 + 542 days. PWA group had an average postoperative VTI 0.21 + 0.05 vs 0.21 + 0.05 in the non-PWA (p=0.61) group. Average improvement compared to pre ablation parameters: VTI was 0.03 + 0.06 vs 0.008 + 0.05 (p=0.17), postoperative A was 0.49 + 0.19 vs 0.57 + 0.19 (p=0.16), postoperative LVEF was 57.5 + 9.9% vs 57.8 + 10.8 % (p=0.89), with average change in LVEF 1.5 ± 7.8 vs 0.86 ± 9.7 (p=0.78) in PWA and non-PWA groups respectively. There was no significant difference in change in deceleration time or E/E' when comparing the two groups. PWA did not adversely affect echocardiographic parameters of left atrial function or left ventricular systolic or diastolic function when compared to other types of ablation.


Behavioral Health Assessments and Interventions of Psychology Trainees and Residents During Dual Interviewing: Replication and Extension.
The integration of psychologists and other behavioral health providers in primary care practice continues to evolve and reshape approaches to patient care. This study is a replication and extension of a 2013 study describing dual interviewing encounters involving psychology trainees and family medicine residents within an integrated primary care clinic as it relates to behavioral health assessments and interventions. Psychology trainees provided descriptions of 400 collaborative patient encounters involving 337 single and 63 repeat encounters. Psychology trainees coded the frequency of behavioral health assessments and interventions by the psychology trainee, family medicine resident, or both. Seventy-eight percent of encounters contained an assessment, and 20% contained interventions. Compared to the 2013 study, there were significantly fewer behavioral health interventions offered and a significantly greater number of psychoeducation/supportive interventions offered collaboratively. It was discovered that discussions between psychology trainees and family medicine residents immediately after patient encounters occurred 50% of the time and involved issues of case conceptualization. These informal discussions may be an important source of behavioral health education for family medicine residents. This study adds to efforts to better understand what occurs during these encounters.


Prevalence of anti-seizure medication nonadherence and its associated factors, among people with epilepsy in North Shewa, Ethiopia, 2021.
Epilepsy is a worldwide neurologic illness, characterized by recurrent unprovoked epileptic seizures and can affect people of all age groups. Patients who are receiving drug therapy for chronic diseases, such as epilepsy, must fit complex medication regimens into their everyday routines. Managing medication schedules may pose a significant burden on patients' lives. Anti-seizure medication choices should therefore be tailored to patients' factors that may limit medication use. The study aimed to determine the prevalence and Predictors of anti-seizure medication nonadherence among patients with epilepsy. An institutional-based cross-sectional study was conducted among 352 people with epilepsy who were selected by systematic random sampling method at government hospitals in North Shewa Ethiopia. Data were collected by reviewing patients' charts and interviewing people with epilepsy by using structured and pretested questionnaires. Data obtained were encoded into EPI-INFO software and exported to SPSS version 25 for analysis. Logistic regression was employed to assess independent factors associated with medication non-adherence. The prevalence of anti-seizure medication non-adherence was 40%. Being female [AOR = 3.37, 95%, CI: 1.84, 6.18], Divorced [AOR = 9.13, 95%, CI: 1.80, 46.34], Being jobless [AOR = 7.33, 95%, CI: 3.24, 16.56], Perceived poor social support [AOR = 2.73, 95%, CI: 1.28, 5.82], perceived stigma [AOR = 5.07, 95%, CI: 2.40, 10.68], polytherapy [AOR = 2.23, 95%, CI: 1.06, 4.71], drug side effects[AOR = 6.03, 95%, CI: 3.17, 11.45], buying medications [AOR = 5.81, 95%, CI: 3.63,16.79] and duration of stay on treatment [AOR = 4.31, 95%, CI: 1.863, 9.97] were significant predictors of anti-seizure medication non-adherence. Non-adherence to anti-seizure medication among people with epilepsy in the study area was relatively higher as compared with study reports from different parts of the country. Health and clinical, socio-economy, and patients' psychological mindset were among the determinant factors affecting the consistency of epilepsy treatment adherence. Enhanced professional, health education for patients as well as for society and financial support, are basic pillars to reduce the constraints of effective treatment.


Cellular and humoral immune responses after a third dose of SARS-CoV-2 mRNA vaccine in lung transplant recipients in Japan.
Lung transplant (LTx) recipients are at higher risk of infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). There is an increasing demand for additional analysis regarding the efficacy and safety of after the initial series of mRNA SARS-CoV-2 vaccines in Japanese transplant recipients. In this open-label, nonrandomized prospective study carried out at Tohoku University Hospital, Sendai, Japan, LTx recipients and controls received third doses of either the BNT162b2 or the mRNA-1273 vaccine, and the cellular and humoral immune responses were analyzed. A cohort of 39 LTx recipients and 38 controls participated in the study. The third dose of SARS-CoV-2 vaccine promoted much greater humoral responses at 53.9 % of LTx recipients than after the initial series at 28.2 % of patients without increasing the risk of adverse events. However, still fewer LTx recipients responded to the SARS-CoV-2 spike protein with the median IgG titer of 129.8 AU/mL and with the median IFN-γ level of 0.01 IU/mL when compared to controls with those of 7394 AU/mL and 0.70 IU/mL, respectively. Although the third dose of mRNA vaccine in LTx recipients was effective and safe, impaired cellular and humoral responses to SARS-CoV-2 spike protein were noted. Given lower antibody production and establishing vaccine safety, repeating the administration of mRNA vaccine will lead to robust protection in such a high-risk population (jRCT1021210009).


The formation mechanisms of turbidity maximum in the Pearl River estuary, China.
The formation and dynamics of turbidity maxima (TM) in the Pearl River estuary (PRE) are not well understood but the existence of TM in the estuary have great potential engineering and environmental impacts. Based on the measurements of two large-scale field surveys conducted in the wet season of 1978 (July of 1978) and the dry season of 1979 (March of 1979), the existence and seasonal variations of TM in the PRE focusing on the two major natural navigation channels have been studied. The sediment transport fluxes over two consecutive tidal cycles have been analyzed in detail. The analysis results reveal that the formation mechanisms of TM in the estuary are rather complex. In general, gravitational circulation, tidal trapping, and sediment resuspension and deposition processes are the primary TM formation mechanisms in the PRE. The clockwise back flow pattern around Lingding Island also leads to the formation of TM in the West channel of the PRE. The occurrence of TM far upstream of the salt water wedge is the result of the complex hydrodynamic and sediment transport processes generated by the runoff of the major rivers.


Resolving the role of podoplanin in the motility of papillary thyroid carcinoma-derived cells using RNA sequencing.
The intracellular level of podoplanin (PDPN), a transmembrane protein of still unclear function, is frequently altered in metastatic tumors. High expression of PDPN is frequently observed in papillary thyroid cancer (PTC) specimens. Similarly, PTC-derived cell lines (BCPAP and TPC1, harboring the BRAF V600E mutation and RET/PTC1 fusion, respectively), also present enhanced PDPN yield. We previously reported that depletion of PDPN impairs migration of TPC1 cells, but augments metastasis of BCPAP cells. Interestingly, this phenomenon stays in contrast to the migratory pattern observed for wild-type cells, where TPC1 exhibited higher motility than BCPAP cells. Here, we aimed to elucidate the potential role of PDPN in regulation of molecular mechanisms leading to the diverse metastatic features of the studied PTC-derived cells. We consider that this phenomenon may be caused by alternative regulation of signaling pathways due to the presence of the mutated BRAF allele or RET/PTC1 fusion. The high-throughput RNA sequencing (RNA-seq) technique was used to uncover the genes and signaling pathways affected in wild-type and PDPN-depleted TPC1 and BCPAP cells. We found that changes in the expression of various factors of signaling pathways, like RHOA and RAC1 GTPases and their regulators, are linked with both high PDPN levels and presence of the BRAF V600E mutation. We imply that the suppressed motility of wild-type BCPAP cells results from overactivation of RHOA through natively high PDPN expression. This process is accompanied by inhibition of the PI3K kinase and consequently RAC1, due to overactivation of RAS-mediated signaling and the PTEN regulator.


Measuring the dynamics of chromatin proteins during differentiation.
Chromatin-protein interactions are important in determining chromosome structure and function, thereby regulating gene expression patterns. Most chromatin associated proteins bind chromatin in a transient manner, with residence times on the order of a few seconds to minutes. This is especially pertinent in mouse embryonic stem cells (ESCs), where hyperdynamic binding of chromatin associated proteins to chromatin is thought to regulate genome plasticity. In order to quantitatively measure binding dynamics of such chromatin proteins in living cells, a combination of GFP-fusion proteins and photobleaching-based assays such as fluorescence recovery after photobleaching (FRAP) and fluorescence loss in photobleaching (FLIP) are advantageous over other existing biochemical assays, because they are applied in living cells at a single cell level. In this chapter we describe a detailed protocol for performing FRAP and FLIP assays for measuring structural chromatin protein dynamics such as Heterochromatin Protein 1 (HP1) and linker histone H1 in mouse ESCs and during ESC differentiation.


An item response theory analysis of an item pool for the recovering quality of life (ReQoL) measure.
ReQoL-10 and ReQoL-20 have been developed for use as outcome measures with individuals aged 16 and over, experiencing mental health difficulties. This paper reports modelling results from the item response theory (IRT) analyses that were used for item reduction. From several stages of preparatory work including focus groups and a previous psychometric survey, a pool of items was developed. After confirming that the ReQoL item pool was sufficiently unidimensional for scoring, IRT model parameters were estimated using Samejima's Graded Response Model (GRM). All 39 mental health items were evaluated with respect to item fit and differential item function regarding age, gender, ethnicity, and diagnosis. Scales were evaluated regarding overall measurement precision and known-groups validity (by care setting type and self-rating of overall mental health). The study recruited 4266 participants with a wide range of mental health diagnoses from multiple settings. The IRT parameters demonstrated excellent coverage of the latent construct with the centres of item information functions ranging from - 0.98 to 0.21 and with discrimination slope parameters from 1.4 to 3.6. We identified only two poorly fitting items and no evidence of differential item functioning of concern. Scales showed excellent measurement precision and known-groups validity. The results from the IRT analyses confirm the robust structure properties and internal construct validity of the ReQoL instruments. The strong psychometric evidence generated guided item selection for the final versions of the ReQoL measures.


Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer.
The prevalence of BRCA1 somatic mutations status in triple-negative breast cancer (TNBC) has not been well documented. The aims of this study were to determine the frequency of BRCA1 somatic mutations and to investigate the association between BRCA1 deleterious somatic mutation status and response to neoadjuvant chemotherapy in women with TNBC. Two hundred and five TNBC patients without BRCA1 germline mutations were enrolled in this study. Fresh tumor tissues were available for this cohort of 205 patients, including 112 patients with fresh core needle biopsy tumor tissues before treatment and 93 patients with fresh tumor tissues procured after surgery. BRCA1 somatic mutations were determined in the tumor samples using PCR-direct sequencing assay. Among the 112 patients with core needle biopsy samples, 97 patients received neoadjuvant chemotherapy. Eight patients (3.9%) carried a BRCA1 pathogenic somatic mutation in this cohort of 205 TNBC patients. These eight BRCA1 deleterious somatic mutations included five frameshift or nonsense mutations (c.191_212del22, c.1664delA, c.4674_4675+17del, c.3671_3672insTTCC, c.1162A>T), one splicing site mutation (c.134+2T>G) and two missense mutations (c.5511G>C and c.286G>A). No significant differences in tumor characteristics between BRCA1 deleterious somatic mutation carriers and non-carriers were observed. The pCR (pathologic complete response) rate was 32.0% in the 97 patients who received neoadjuvant chemotherapy. BRCA1 deleterious somatic mutation carriers (n=5) had a higher pCR rate than did non-carriers (n=92) (BRCA1 carriers vs non-carriers, 60.0% vs 30.4%, P=0.32), although it did not reach a significance due to a small sample size. A small subset of TNBC patients carried a BRCA1 deleterious somatic mutation; BRCA1 somatic mutation carriers are likely to respond to neoadjuvant chemotherapy.


Diagnostic accuracy of optical coherence tomography parameters in predicting in-stent hemodynamic severe coronary lesions: validation against fractional flow reserve.
By means of optical coherence tomography (OCT), coronary dimensions can be assessed accurately. However, whether OCT can identify hemodynamic significant coronary lesions as determined by fractional flow reserve (FFR) in patients with an in-stent lesion is not known. Therefore, we tried to assess the predictive value of OCT parameters in this setting as compared to FFR. In patients who underwent a percutaneous coronary intervention for an in-stent restenotic lesion, pre-, post-procedural and 6-month follow-up OCT and FFR acquisitions were performed. In case of an FFR ≤ 0.80, a lesion was classified as hemodynamically severe. Diagnostic efficiency of several OCT parameters were assessed with receiver operating characteristic curves. In 27 patients, 66 coupled OCT and FFR segments were analyzed and compared. The diagnostic efficiencies of OCT-based minimal luminal diameter (MLD) and minimal luminal area (MLA) are good, with an area under the curve (AUC) of 0.83 (95% confidence interval: 0.74-0.93) and 0.83 (0.73-0.93), and a best cutoff value of 1.77 mm (sensitivity 74% and specificity 78%) and 2.54 mm(2) (sensitivity 71% and specificity 84%), respectively. The diagnostic efficiency of OCT-based maximum neointimal area is moderate [AUC 0.73 (0.61-0.85)], and regarding maximum neointimal area stenosis, it is poor [0.39 (0.25-0.53)]. The corresponding best cutoff values are 5.01 mm(2) (sensitivity 66% and specificity 72%) and 49% (sensitivity 40% and specificity 66%), respectively. With OCT, a good diagnostic efficiency can be achieved in identifying coronary severity in in-stent lesions in a per-group analysis. This hallmark provides an extra dimension, next to morphological information, when acquiring OCT images in scientific studies. However, OCT seems limited in a per-patient clinical decision making process due to reasonable but limited sensitivity and specificity in predicting coronary severity.


Invasive line placement in critically ill patients: do hemostatic defects matter?
Blood components are often given prophylactically before the placement of invasive lines in patients with coagulation defects. Little, however, is known about the epidemiology of defects in these patients. The purpose of this study is to ascertain what proportion of intensive care patients who receive invasive lines have hemostatic defects, what actions are taken by physicians to correct these abnormalities before invasive line insertion, and what the incidence is of bleeding complications after invasive line placement. Charts were retrospectively reviewed for 490 intensive care patients in whom 938 arterial, pulmonary artery, and central venous lines were placed. At least one defect in hemostasis was documented for 388 patients (41%) before line placement, with 253 (27%) of these patients evidencing severe abnormalities. Seventeen percent of patients had no preprocedure laboratory evaluation. Trauma patients showed the highest numbers of abnormalities in hemostatic testing, but medical patients had more-severe defects. The occurrence of isolated abnormal laboratory values did not predict bleeding, but a score derived from a consideration of multiple defects did. Correction of the abnormalities was attempted in 37 percent of patients with hemostatic defects. Sixteen patients had bleeding complications, but only two had complications that were life-threatening. None of the complications were fatal. Invasive lines are used frequently in patients with hemostatic defects, often without any attempt to correct the abnormalities. Nevertheless, rates of hemorrhage are low and appear to be closely related to the level of experience of the physician rather than to defects in hemostasis. These findings suggest that the use of blood components for preprocedure correction of hemostatic defects is not necessary, except in those patients who have the most severe hemostatic abnormalities.


Ultrasound-targeted HSVtk and Timp3 gene delivery for synergistically enhanced antitumor effects in hepatoma.
Cancer gene therapy has great potential for decreasing tumor-induced mortality but has been clinically limited by non-targeted and insufficient gene transfer. We evaluated gene therapy targeting hepatocellular carcinoma (HCC) using the herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system and the tissue inhibitor of metalloproteinase 3 (Timp3) gene. Ultrasound-targeted microbubble destruction (UTMD) targeted gene delivery to the tumor tissue, and the α-fetoprotein promoter targeted HSVtk expression to the HCC cells. Human HepG2 cells transfected with the HSVtk or Timp3 gene demonstrated a reduction in cell viability by >40% compared with the vector control. Cell viability was further inhibited by over 50% with co-transfection of the genes. HepG2 cells were inoculated subcutaneously into athymic mice to induce tumors. UTMD-mediated delivery of HSVtk or Timp3 suppressed tumor growth by >45% and increased survival of tumor-bearing animals (P<0.01 vs vector control). Co-delivery of the genes resulted in a further 30% improvement in tumor suppression and significant extension of animal survival (P<0.01 vs vector control). Targeted gene delivery increased the number of apoptotic cells and decreased the vascular density of the tumors. Targeted co-delivery of the genes synergistically improved the antitumor effects and may provide an effective therapy for HCC.


Improving the biocidal activity of outdoor coating formulations by using zeolite-supported silver nanoparticles.
Zeolite/nanoparticle composites are synthesized and used as additive for waterborne formulations in replacement of traditional isothiazolinone-based biocides. Silver nanoparticles dispersed onto micrometer-sized crystals of A-type zeolite were prepared by thermal treatment or chemical reduction methods applied to the Ag-exchanged zeolite. The antifungal efficiency against Trichoderma sp. of waterborne outdoor coatings containing the supported silver nanoparticles, measured in terms of inhibition halo development, shows similar results to those obtained by using traditional organic biocides, the type, size and size distribution of the nanoparticles being the main factors affecting the biocidal action of the prepared coatings.


Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart.
Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats' hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.


Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy.
Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses. Case scenarios and review of the literature. Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of -2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m2, 212% of the 95th percentile, 63.7% FP and MFR z-score of -2.34], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of -1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of -1.13) with normalization of liver transaminases. Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications. Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.


The effect of solvent concentration on the use of palladized-iron for the step-wise dechlorination of polychlorinated biphenyls in soil extracts.
This report describes the application of palladized iron (Pd/Fe) to the dechlorination of polychlorinted biphenyls (PCBs) at ambient temperature. Experiments supported by congener-specific analyses demonstrated that dechlorination occurs in a step-wise fashion with the meta-chlorines being more reactive than ortho-chlorines. Over the course of the laboratory experiments, complete conversion to biphenyl was observed. The process was also tested with PCBs dissolved in high (40-60%) concentrations of ethanol and isopropanol as a means of simulating solutions generated by commercial soil and solid waste extraction processes. The reaction rate was sensitive to the percentage of solvent but complete dechlorination was still indicated. Tests with soil extracts from a contaminated site demonstrated that there were no apparent interferences from asphalt and other miscellaneous debris. Short-duration tests with highly contaminated PCB solutions from a hazardous waste site demonstrated efficient dechlorination although there was a reduction in reaction rate with time.


Tumor suppressor CYLD regulates acute lung injury in lethal Streptococcus pneumoniae infections.
Streptococcus pneumoniae (S. pneumoniae) causes high early mortality in pneumococcal pneumonia, which is characterized by acute lung injury (ALI). The molecular mechanisms underlying ALI and the high early mortality remain unknown. Despite recent studies that identify deubiquitinating enzyme cylindromatosis (CYLD) as a key regulator for T cell development, tumor cell proliferation, and NF-kappaB transcription factor signaling, its role in regulating bacteria-induced lethality, however, is unknown. Here, we showed that CYLD deficiency protected mice from S. pneumoniae pneumolysin (PLY)-induced ALI and lethality. CYLD was highly induced by PLY, and it inhibited MKK3-p38 kinase-dependent expression of plasminogen activator inhibitor-1 (PAI-1) in lung, thereby potentiating ALI and mortality. Thus, CYLD is detrimental for host survival, thereby indicating a mechanism underlying the high early mortality of pneumococcal pneumonia.


Redo composite valve graft replacement.
Redo composite valve graft replacement remains a challenging problem, that may lead to increased surgical mortality. In our experience from September 1976 through December 1999, eight consecutive patients (seven men and 1 woman) underwent eight redo composite valve graft replacements. The mean age at reoperation was 43.1 years (range 31 to 51 years). Seven patients had stigmata of Marfan's syndrome. Reoperation was indicated for pseudoaneurysm formation in five patients, coronary ostial aneurysms in two patients, and active fungal endocarditis in one patient. Previous root replacement had been performed in all eight patients using a composite mechanical valve. The techniques used at previous procedures were the Bentall technique in seven and Carrel's button technique in one. The mean interval between primary root replacement and redo root replacement was 10 years (range 2 to 18 years). The patient with active fungal endocarditis having a stuck valve was subjected to emergency operation. The techniques used at the reoperations included Carrel's button technique in five patients, the interposition technique (Phieler) in two patients, and Cabrol's technique in one patient. Aortic arch aneurysm repair was performed in five patients. There were two hospital deaths (2 [25%] of 8). One patient died on postoperative day 1 with low cardiac output and the other suffered a sudden cardiac arrest on postoperative day 14. The mean follow-up was 34.6 months (range 1 to 85 months). There was one late death. The cause of death was multiple organ failure due to recurrence of fungal endocarditis 6 months after redo composite and total arch replacement. Redo composite graft replacement can be accomplished with lower early mortality, and therefore, this operation should not be delayed given the appropriate clinical circumstances. Many causes of failure of composite valve graft replacement can be avoided if the appropriate surgical technique is chosen.


Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control.
ErbB3-binding protein 1 (EBP1) is implicated in diverse cellular functions, including apoptosis, cell proliferation, and differentiation. Here, by generating genetic inactivation of Ebp1 mice, we identified the physiological roles of EBP1 in vivo. Loss of Ebp1 in mice caused aberrant organogenesis, including brain malformation, and death between E13.5 and 15.5 owing to severe hemorrhages, with massive apoptosis and cessation of cell proliferation. Specific ablation of Ebp1 in neurons caused structural abnormalities of brain with neuron loss in [Nestin-Cre; Ebp1flox/flox ] mice. Notably, global methylation increased with high levels of the gene-silencing unit Suv39H1/DNMT1 in Ebp1-deficient mice. EBP1 repressed the transcription of Dnmt1 by binding to its promoter region and interrupted DNMT1-mediated methylation at its target gene, Survivin promoter region. Reinstatement of EBP1 into embryo brain relived gene repression and rescued neuron death. Our findings uncover an essential role for EBP1 in embryonic development and implicate its function in transcriptional regulation.


Ureteropelvic junction obstructions: prenatal diagnosis and neonatal surgery in 47 cases.
In a series of 150 patients with congenital urologic disorders diagnosed in utero and managed in the neonatal period from 1980 to 1985, 48 cases were ureteropelvic junction obstructions. One was a false positive, and 47 were documented pyelocaliceal distension and retention; 12 of them were bilateral. Five cases had a spontaneous resolution. Three had a nephrectomy performed (destroyed kidney). Fifty kidneys have been operated on (Anderson-Hynes dysmembered pyeloplasty). Ninety percent of the cases are reported as clinically, biologically, and radiologically fair. Six percent postoperative complications are reported. The authors pointed out the great interest in neonatal repair of this condition, using microsurgical techniques without stent or nephrostomy. A comparison is made of the overall results with an identical series of older patients operated on during the same period.