Vibrational excitation and relaxation of five polyatomic molecules in an electrical discharge.
Vibrational excitation and relaxation of five linear polyatomic molecules, OCS, OC3S, HC3N, HC5N, and SiC2S, have been studied by Fourier transform microwave spectroscopy in a supersonic expansion after the application of a low-current dc electric discharge. For each chain, the populations in bending and stretching modes have been characterized as a function of the applied discharge current; for stable OCS and HC3N, vibrational populations were studied as well in the absence of a discharge. With no discharge present the derived vibrational temperatures are slightly below T, the temperature of the gas before the supersonic expansion (i.e., 300 K). In the presence of the discharge, vibrational excitation occurs via inelastic collisions with the electrons and the vibrational temperatures rise as the applied current increases. Global vibrational relaxation is governed by rapid vibration-vibration (VV) energy transfer and slow vibration-translation (VT) energy transfer. The latter process is rate-determining and depends primarily on the wave number of the vibration. Vibrational modes with wave numbers near and below kT/hc (where T = 300 K and kT/hc-210 cm(-1)) are efficiently cooled by VT transfer because a sufficient number of collisions occur in the initial stages of the supersonic expansion. Vibrational modes with wave numbers around 450 cm(-l) appear to be inefficiently cooled in the molecular beam; at these energies VV and VT rates are probably comparable. For high-frequency vibrations, VV energy transfer dominates. For the longer chains OC3S and HC5N, higher-lying modes are generally not detectable and vibrational temperatures of most lower-lying modes were found to be lower than those of OCS and HC3N, suggesting that as the size of the molecules increases, intermode VV transfer becomes more efficient, plausibly due to the higher density of vibrational levels. New high resolution spectroscopic data have been obtained for several vibrationally excited states of OC3S, HC3N, and HC5N. Rotational lines of the 13C and 15N isotopic species of HC5N have been measured, yielding improved rotational and centrifugal distortion constants; 14N nitrogen quadrupole coupling constants for the isotopic species of HC5N with 13C have been determined for the first time.


Altered central integration of dual somatosensory input after cervical spine manipulation.
The aim of the current study was to investigate changes in the intrinsic inhibitory interactions within the somatosensory system subsequent to a session of spinal manipulation of dysfunctional cervical joints. Dual peripheral nerve stimulation somatosensory evoked potential (SEP) ratio technique was used in 13 subjects with a history of reoccurring neck stiffness and/or neck pain but no acute symptoms at the time of the study. Somatosensory evoked potentials were recorded after median and ulnar nerve stimulation at the wrist (1 millisecond square wave pulse, 2.47 Hz, 1 x motor threshold). The SEP ratios were calculated for the N9, N11, N13, P14-18, N20-P25, and P22-N30 peak complexes from SEP amplitudes obtained from simultaneous median and ulnar (MU) stimulation divided by the arithmetic sum of SEPs obtained from individual stimulation of the median (M) and ulnar (U) nerves. There was a significant decrease in the MU/M + U ratio for the cortical P22-N30 SEP component after chiropractic manipulation of the cervical spine. The P22-N30 cortical ratio change appears to be due to an increased ability to suppress the dual input as there was also a significant decrease in the amplitude of the MU recordings for the same cortical SEP peak (P22-N30) after the manipulations. No changes were observed after a control intervention. This study suggests that cervical spine manipulation may alter cortical integration of dual somatosensory input. These findings may help to elucidate the mechanisms responsible for the effective relief of pain and restoration of functional ability documented after spinal manipulation treatment.


[Health promotion and empowerment: a reflection based on critical-social and post-structuralist perspectives].
In this paper we describe the theoretical framework and the core strategies of health promotion followed by a critical intra- and extra-paradigmatic analysis of the key ideas of this movement. From an intra-paradigmatic perspective we privilege a critical social theory perspective for analyzing one of the key concepts of health promotion--empowerment--exploring its potential to transform community and professional practices in the field of health. Next, we reflect about health promotion from an extra-paradigmatic perspective, seeking in the post-structuralist theories new analytical possibilities for understanding the power relations that establish themselves on the basis of practices and policies of health promotion. Throughout this article, we articulate the explored theoretical principles to contextual questions and current debates in the field of health in Brazil.


Reimplantation and Repeat Infection After Cardiac-Implantable Electronic Device Infections: Experience From the MEDIC (Multicenter Electrophysiologic Device Infection Cohort) Database.
Infection is a serious complication of cardiovascular-implantable electronic device implantation and necessitates removal of all hardware for optimal treatment. Strategies for reimplanting hardware after infection vary widely and have not previously been analyzed using a large, multicenter study. The MEDIC (Multicenter Electrophysiologic Device Infection Cohort) prospectively enrolled subjects with cardiovascular-implantable electronic device infections at multiple institutions in the United States and abroad between 2009 and 2012. Reimplantation strategies were evaluated overall, and every patient who relapsed within 6 months was individually examined for clinical information that could help explain the negative outcome. Overall, 434 patients with cardiovascular-implantable electronic device infections were prospectively enrolled at participating centers. During the initial course of therapy, complete device removal was done in 381 patients (87.8%), and 220 of them (57.7%) were ultimately reimplanted with new devices. Overall, the median time between removal and reimplantation was 10 days, with an interquartile range of 6 to 19 days. Eleven of the 434 patients had another infection within 6 months, but only 4 of them were managed with cardiovascular-implantable electronic device removal and reimplantation during the initial infection. Thus, the repeat infection rate was low (1.8%) in those who were reimplanted. Patients who retained original hardware had a 11.3% repeat infection rate. Our study findings confirm that a broad range of reimplant strategies are used in clinical practice. They suggest that it is safe to reimplant cardiac devices after extraction of previously infected hardware and that the risk of a second infection is low, regardless of reimplant timing.


Unraveling Vulnerabilities in Endocrine Therapy-Resistant HER2+/ER+ Breast Cancer.
Breast tumors overexpressing human epidermal growth factor receptor (HER2) confer intrinsic resistance to endocrine therapy (ET), and patients with HER2/ estrogen receptor-positive (HER2+/HR+) breast cancer (BCa) are less responsive to ET than HER2-/ER+. However, real-world evidence reveals that a large subset of HER2+/ER+ patients receive ET as monotherapy, positioning this treatment pattern as a clinical challenge. In the present study, we developed and characterized two distinct in vitro models of ET-resistant (ETR) HER2+/ER+ BCa to identify possible therapeutic vulnerabilities. To mimic ETR to aromatase inhibitors (AI), we developed two long-term estrogen-deprived (LTED) cell lines from BT-474 (BT474) and MDA-MB-361 (MM361). Growth assays, PAM50 molecular subtyping, genomic and transcriptomic analyses, followed by validation and functional studies, were used to identify targetable differences between ET-responsive parental and ETR-LTED HER2+/ER+ cells. Compared to their parental cells, MM361 LTEDs grew faster, lost ER, and increased HER2 expression, whereas BT474 LTEDs grew slower and maintained ER and HER2 expression. Both LTED variants had reduced responsiveness to fulvestrant. Whole-genome sequencing of the more aggressive MM361 LTED model system identified exonic mutations in genes encoding transcription factors and chromatin modifiers. Single-cell RNA sequencing demonstrated a shift towards non-luminal phenotypes, and revealed metabolic remodeling of MM361 LTEDs, with upregulated lipid metabolism and antioxidant genes associated with ferroptosis, including GPX4. Combining the GPX4 inhibitor RSL3 with anti-HER2 agents induced significant cell death in both the MM361 and BT474 LTEDs. The BT474 and MM361 AI-resistant models capture distinct phenotypes of HER2+/ER+ BCa and identify altered lipid metabolism and ferroptosis remodeling as vulnerabilities of this type of ETR BCa.


Acute flaccid myelitis: not uncommon in rural Uganda?
Acute Flaccid Myelitis is a paralytic illness with significant similarities to poliomyelitis, and which affects predominantly children. It was first fully delineated only in 2014 in the USA, occurring in epidemic clusters with a likely overall increasing incidence. It has subsequently rapidly been identified in Europe, the UK, and Australasia and the Far East, confirming it to be an emerging, global, infectious neurological disease. It has, however, been very little studied in low- and middle-income countries-reflecting partly of the global imbalance in science and medical research, and partly the extremely low provision of neurological care in most low- and middle-income countries: Uganda currently has no specialized neurology services outside the capital Kampala. During extended visits over a 2-year period with involvement in acute adult and paediatric internal medicine, one of us (NS) encountered at least six new patients with acute flaccid myelitis, suggesting that both the geographical reach and the frequency of the disorder may be significantly greater than previously thought. Here, these cases are described together with their clinical features and, where available, course and (limited) investigation results. These observations have significant implications concerning the current, and potentially the future geographical spread of the disease, and its clinical phenomenology. In addition, they highlight serious problems concerning the global applicability of the current Acute Flaccid Myelitis diagnostic criteria.


Hydrotherapy, balneotherapy, and spa treatment in pain management.
The use of water for medical treatment is probably as old as mankind. Until the middle of the last century, spa treatment, including hydrotherapy and balneotherapy, remained popular but went into decline especially in the Anglo-Saxon world with the development of effective analgesics. However, no analgesic, regardless of its potency, is capable of eliminating pain, and reports of life-threatening adverse reactions to the use of these drugs led to renewed interest in spa therapy. Because of methodologic difficulties and lack of research funding, the effects of 'water treatments' in the relief of pain have rarely been subjected to rigorous assessment by randomised, controlled trials. It is our opinion that the three therapeutic modalities must be considered separately, and this was done in the present paper. In addition, we review the research on the mechanism of action and cost effectiveness of such treatments and examine what research might be useful in the future.


Effects of feeding of two potentially probiotic preparations from lactic acid bacteria on the performance and faecal microflora of broiler chickens.
The aim of this study was to evaluate the potential of two probiotic preparations, containing live lactic acid bacteria (Lactococcus lactis CECT 539 and Lactobacillus casei CECT 4043) and their products of fermentation (organic acids and bacteriocins), as a replacement for antibiotics in stimulating health and growth of broiler chickens. The effects of the supplementation of both preparations (with proven probiotic effect in weaned piglets) and an antibiotic (avilamycin) on body weight gain (BWG), feed intake (FI), feed consumption efficiency (FCE), relative intestinal weight, and intestinal microbiota counts were studied in 1-day posthatch chickens. The experiments were conducted with medium-growth Sasso X44 chickens housed in cages and with nutritional stressed Ross 308 broiler distributed in pens. Consumption of the different diets did not affect significantly the final coliform counts in Sasso X44 chickens. However, counts of lactic acid bacteria and mesophilic microorganisms were higher in the animals receiving the two probiotic preparations (P < 0.05). In the second experiment, although no differences in BWG were observed between treatments, Ross 308 broilers receiving the probiotic Lactobacillus preparation exhibited the lowest FCE values and were considered the most efficient at converting feed into live weight.


Highly efficient 'hit-and-run' genome editing with unconcentrated lentivectors carrying Vpr.Prot.Cas9 protein produced from RRE-containing transcripts.
The application of gene-editing technology is currently limited by the lack of safe and efficient methods to deliver RNA-guided endonucleases to target cells. We engineered lentivirus-based nanoparticles to co-package the U6-sgRNA template and the CRISPR-associated protein 9 (Cas9) fused with a virion-targeted protein Vpr (Vpr.Prot.Cas9), for simultaneous delivery to cells. Equal spatiotemporal control of the vpr.prot.cas9 and gag/pol gene expression (the presence of Rev responsive element, RRE) greatly enhanced the encapsidation of the fusion protein and resulted in the production of highly efficient lentivector nanoparticles. Transduction of the unconcentrated, Vpr.Prot.Cas9-containing vectors led to >98% disruption of the EGFP gene in reporter HEK293-EGFP cells with minimal cytotoxicity. Furthermore, we detected indels in the targeted endogenous loci at frequencies of up to 100% in cell lines derived from lymphocytes and monocytes and up to 15% in primary CD4+ T cells by high-throughput sequencing. This approach may provide a platform for the efficient, dose-controlled and tissue-specific delivery of genome editing enzymes to cells and it may be suitable for simultaneous endogenous gene disruption and a transgene delivery.


Relationship between adrenal function and prognosis in patients with severe sepsis.
It is known that the hypothalamic-pituitary-adrenal (HPA) axis is highlighted by stimulation, such as sepsis, trauma, etc, when corticortropin increases and plasma cortisol levels enhance. Relative adrenal insufficiency is not uncommon in critically ill patients and may occur in severe sepsis patients with high plasma cortisol levels. It has been demonstrated that a short corticotropin test has a good prognostic value and is helpful in identifying patients with septic shock at high risk for death, but it has not been established for all severe sepsis patients, especially in China. The aim of this study is to explore the relationship between adrenal function and prognosis in patients with severe sepsis. This prospective study was conducted between July and December 2004 in 6 teaching hospitals. Two hundred and forty patients with severe sepsis were enrolled in this study. A short corticotropin stimulation test was performed in all patients by intravenous injection of 250 microg of corticotropin. Blood samples were taken immediately before the test (T0), 30 (T30) and 60 (T60) minutes afterward, and the plasma cortisol concentration was measured by radio-immunoassay. At the onset of severe sepsis, the following parameters were recorded: age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II, heart rate, mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO(2))/fraction of inspired oxygen (FiO(2)), peripheral blood of hemoglobin, platelets and leukocyte concentration and the number of organ failure. Patients were designated into two groups (survival and non-survival groups) according to the 28-day mortality. Relative adrenal insufficiency was defined as the difference between T0 and the highest value of T30 or T60 (DeltaTmax) < or = 9 microg/dl. (1) Two hundred and forty patients with severe sepsis were included in this study, with 134 patients in the survival group and 106 in the non-survival group. The 28-day mortality was 44.2%. (2) Between the survival group and non-survival group age, APACHE II, peripheral blood of platelets, the number of organ failures, T0 and DeltaTmax showed significant differences. T0 was (23 +/- 10) microg/dl and (36 +/- 18) microg/dl in the survival group and nonsurvival group respectively. DeltaTmax was (18 +/- 9) and (10 +/- 8) microg/dl in the survival group and non-survival group respectively. The areas under the ROC curve for T0 and DeltaTmax were both 0.72, and the area under the ROC curve for APACHE II was 0.70. By multivariate analysis age, T0, the number of organ failures and relative adrenal insufficiency (DeltaTmax < or = 9 microg/dl) were independent predictors of death. (3) The incidence of relative adrenal insufficiency was 38.3% in total, 19.4% in the survival group and 62.3% in the non-survival group (P < 0.001). The 28-day mortality was 71.7% among the relative adrenal insufficiency patients but 27.0% among normal adrenal function patients. The prevalence of relative adrenal insufficiency is high in severe sepsis. Relative adrenal insufficiency has a good prognostic value for severe sepsis.


Emerging interdependence between stock values during financial crashes.
To identify emerging interdependencies between traded stocks we investigate the behavior of the stocks of FTSE 100 companies in the period 2000-2015, by looking at daily stock values. Exploiting the power of information theoretical measures to extract direct influences between multiple time series, we compute the information flow across stock values to identify several different regimes. While small information flows is detected in most of the period, a dramatically different situation occurs in the proximity of global financial crises, where stock values exhibit strong and substantial interdependence for a prolonged period. This behavior is consistent with what one would generally expect from a complex system near criticality in physical systems, showing the long lasting effects of crashes on stock markets.


Equilibrium fluctuations of the Lennard-Jones cluster surface.
Spectra of the cluster surface equilibrium fluctuations are treated by decomposition into the bulk and net capillary ones. The bulk fluctuations without capillary ones are simulated by the surface of a cluster truncated by a sphere. The bulk fluctuation spectrum is shown to be generated primarily by the discontinuity in the spatial distribution of cluster internal particles. The net capillary fluctuation slice spectrum is obtained in molecular dynamics simulation by subtraction of the bulk fluctuation spectrum from the total one. This net spectrum is in the best agreement with a theoretical estimation if we assume the intrinsic surface tension to be independent of the wave number. The wave number cutoff is brought in balance with the intrinsic surface tension and excess surface area induced by the capillary fluctuations. It is shown that the ratio of the ordinary surface tension to the intrinsic one can be considered as a universal constant independent of the temperature and cluster size.


Solitary epiphyseal enchondroma of the proximal femur in a 23-month-old girl.
A 23-month-old girl was referred to us because of a right leg limp for 10 days that had not improved despite anti-inflammatory treatment and that did not show signs of infection. Upon examination, gait was in abduction and external rotation of the hip. Plain radiographs showed a solitary lucent lesion of the posteroinferior two thirds of the epiphysis that was hyperintense on T2-weighted magnetic resonance scanning images. We approached the proximal femoral epiphysis using the "trapdoor" technique and excised the lesion by curettage and iliac crest graft. Histologically, the lesion was diagnosed as an enchondroma. We discuss the main causes of lucent epiphyseal lesions in children. Finally, we review the literature on previous reports of patients with solitary epiphyseal enchondromas. Case report.


A preliminary analysis of high-stakes decision-making for crisis leadership.
High-stakes decision-making is a critical component of crisis leadership. This study examined the decision-making processes of global, national and local crisis professionals to identify common decision-making process traits, and proposes a useful model to guide crisis leaders' high-stakes decision-making. Crises have distinct factors: they are time-sensitive, pose significant risks and require consequential decisions. A sample group of 15 national and international expert crisis professionals in leadership positions from national security, law enforcement and government sectors participated in this study. Seven popular decision-making models were deconstructed into 50 individual process traits and converted into a survey. The experts were asked to identify process traits from the survey that they felt best reflected their approach to decisionmaking. The responses of the professionals were analysed, and a new model assembled based on their expertise. The findings identified a pattern of practice across the spectrum of crisis leaders and demonstrated the potential usefulness of a new decision-making model that captures the decision-making process traits of expert crisis leaders. This research provides inexperienced crisis professionals with a model drawn from the experiences of national and global crisis experts. In addition to benefiting the novice crisis professional, the model can be used by organisations to create a personalised company crisis plan.


The effectiveness of acupoint herbal patching for constipation after stroke: A protocol for systematic review and meta-analysis.
Constipation is one of the common problems in stroke patients, which seriously affects the life quality of patients and even leads to the recurrence of cerebrovascular disease. The clinical trials of acupoint herbal patching (AHP) in the adjuvant treatment of constipation after stroke (CAS) is currently in progress. However, there is no systematic review or meta-analysis to evaluate the effects of AHP on CAS. We will search articles in 8 electronic databases including the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, Wanfang Database, and the Chinese Scientific Journal Database for randomized controlled trials of CAS treated by AHP from their inception to November 1, 2021. The primary outcome measures will be clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements. The data meeting the inclusion criteria were analyzed by RevMan V.5.4 software. Two authors evaluated the study using the Cochrane collaborative risk bias tool. We will use a scoring method to assess the overall quality of evidence supporting the main results. This study will analyze the clinical effective rate, defecation frequency, improvement of clinical symptoms including complete spontaneous bowel movements after stroke. The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for CAS. INPLASY202210065.


Role of Lung Ultrasound in Confirmation of Double Lumen Endotracheal Tube Placement for Thoracic Surgeries: A Prospective Diagnostic Accuracy Study.
In thoracic surgeries requiring thoracotomy incisions, correct positioning of the double-lumen endotracheal tube (DLT) is mandatory. After the pandemic of novel COVID-19, using simple, noninvasive technology such as lung ultrasound (LUS) can be important in avoiding the possibility of spreading infectious diseases or contagious infections that can follow using fiberoptic bronchoscopy (FOB). We aimed to assess the accuracy of auscultation and LUS in relation to FOB in the assessment of DLT placement and to identify the possibility of using LUS as an alternative to FOB during DLT insertion. This diagnostic accuracy study was conducted according to STARD guidelines; enrolled 120 cases requiring DLT intubation. After DLT insertion, all patients were examined by stethoscope, then by LUS for determination of DLT position, and then confirmed by FOB in the same patient. Three patients dropped out due to failed intubation, and only 117 cases were analyzed. Time was significantly longer for LUS than for auscultation and FOB and was insignificantly different between auscultation and FOB. Auscultation had 76.14% sensitivity, 34.48% specificity, and 65.81% accuracy in the determination of correct DLT placement. LUS had 92.05% sensitivity, 79.31% specificity, and 88.89% accuracy in detecting correct DLT placement. There was substantial agreement between LUS and FOB (κ = 0.705) and poor agreement between auscultation and FOB (κ = 0.104). LUS can be used as a simple, noninvasive tool for detecting DLT placement with a substantial agreement with FOB.


Upregulation of FOXP1 is a new independent unfavorable prognosticator and a specific predictor of lymphatic dissemination in cutaneous melanoma patients.
FOXP1 is a pleiotropic protein that plays important roles in immune responses (B-cell development regulation and differentiation of monocyte), organ development (cardiac valves, lung, and esophagus), and neuronal development. Besides being the primary regulator of normal human tissue development, FOXP1 also plays a role in tumorigenesis. However, the potential value of FOXP1 expression in tumor prognosis remains controversial. FOXP1 expression was assessed in tumor cells (TCs) and stromal cells (SCs) of cutaneous melanomas with the aim of analyzing the associations between FOXP1 expression and clinicopathological characteristics. We believe this article to be the first report analyzing the correlations between FOXP1 expression and clinicopathological, as well as histological, characteristics in melanoma. In total, 96 formalin-fixed, paraffin-embedded primary cutaneous melanoma tissue specimens were subjected to immunohistochemical analysis for FOXP1, and the results were correlated with classical clinicopathological features and patient survival. FOXP1 overexpression in TCs was strongly associated with the presence of metastases in sentinel lymph nodes (p=0.0003, OR=11.66) and positive status of regional lymph nodes (p=0.0006, OR=22.15). In 96% (52 of 54) of patients presenting with low FOXP1 expression, no clinical or histopathological features of lymphatic dissemination were observed. However, thinner and nonulcerated tumors were reported to have increased numbers of FOXP1-positive SCs. In addition, a strong association was observed between FOXP1 upregulation in SCs and the absence of regional lymph node metastases. There was a significant correlation between FOXP1 upregulation in TCs and shorter cancer-specific overall survival (log-rank test, p=0.0040) and disease-free survival (log-rank test, p=0.0021). FOXP1 expression was confirmed in multivariate analysis as a factor that significantly unfavorably impacts prognosis in melanoma patients (HR=3.14, p=0.0299, adjusted for age, Breslow thickness, and sex). The findings from this study indicate that FOXP1 has a major role in melanoma progression, which makes it a candidate for molecular target-based cancer therapy.


Detection of Ni2+ by a dimethylglyoxime probe using attenuated total-reflection infrared spectroscopy.
A new analytical approach for the detection of Ni2+ utilizing an attenuated total reflection (ATR) technique is discussed in this paper. Nickel detection was accomplished on a silicon ATR parallelogram crystal uniformly coated by a ca. 1.5-microm Nafion film embedded with dimethylglyoxime (DMG) probe molecules. The detection of Ni2+ is based on the appearance of a unique infrared absorption peak at 1572 cm(-1) that corresponds to the C=N stretching mode in the nickel dimethylglyoximate, Ni(DMG)2, complex. The suitable operational pH range for the nickel infrared sensor is between 6 - 8. High alkalinity in the sample solution causes a leaching of Ni(DMG)2. The detection limit of the nickel infrared sensor is 1 ppm in a sample solution of pH = 8. Interference studies revealed that Cu2+ could compete with Ni2+ for the DMG sites in the Nafion matrix. The new nickel detection methodology can be potentially utilized, after further improvement, in field analysis to locate hot spots contaminated with a high ppm of Ni2+.


Single-cell transcriptomics illuminates regulatory steps driving anterior-posterior patterning of Drosophila embryonic mesoderm.
Single-cell technologies promise to uncover how transcriptional programs orchestrate complex processes during embryogenesis. Here, we apply a combination of single-cell technology and genetic analysis to investigate the dynamic transcriptional changes associated with Drosophila embryo morphogenesis at gastrulation. Our dataset encompassing the blastoderm-to-gastrula transition provides a comprehensive single-cell map of gene expression across cell lineages validated by genetic analysis. Subclustering and trajectory analyses revealed a surprising stepwise progression in patterning to transition zygotic gene expression and specify germ layers as well as uncovered an early role for ecdysone signaling in epithelial-to-mesenchymal transition in the mesoderm. We also show multipotent progenitors arise prior to gastrulation by analyzing the transcription trajectory of caudal mesoderm cells, including a derivative that ultimately incorporates into visceral muscles of the midgut and hindgut. This study provides a rich resource of gastrulation and elucidates spatially regulated temporal transitions of transcription states during the process.


"Peripheral" benzodiazepine binding sites in the Maudsley reactive rat: selective decrease confined to peripheral tissues.
"Peripheral" benzodiazepine binding sites (PBS) were studied in both the CNS and peripheral tissues of Maudsley reactive (MR) and Maudsley non-reactive (MNR) rats using the PBS specific ligand [3H]Ro 5-4864. A statistically significant reduction in the density of PBS was found in heart and kidney of the MR compared to the MNR. Similar reductions in the density of PBS were not observed in a number of areas of the central nervous system (including cortex, hippocampus, and hypothalamus) or other peripheral tissues, such as lung and adrenal. This selective decrease in PBS in a strain selectively bred for a high degree of "fearfulness" may be related to previous findings of a reduction in the density of PBS in the same tissues in rats subjected to uncontrollable shock. These observations suggest that PBS in heart and kidney may be altered in response to fear or anxiety.


Characterization of glycoside hydrolase family 11 xylanase from Streptomyces sp. strain J103; its synergetic effect with acetyl xylan esterase and enhancement of enzymatic hydrolysis of lignocellulosic biomass.
Xylanase-containing enzyme cocktails are used on an industrial scale to convert xylan into value-added products, as they hydrolyse the β-1,4-glycosidic linkages between xylopyranosyl residues. In the present study, we focused on xynS1, the glycoside hydrolase (GH) 11 xylanase gene derived from the Streptomyces sp. strain J103, which can mediate XynS1 protein synthesis and lignocellulosic material hydrolysis. xynS1 has an open reading frame with 693 base pairs that encodes a protein with 230 amino acids. The predicted molecular weight and isoelectric point of the protein were 24.47 kDa and 7.92, respectively. The gene was cloned into the pET-11a expression vector and expressed in Escherichia coli BL21(DE3). Recombinant XynS1 (rXynS1) was purified via His-tag affinity column chromatography. rXynS1 exhibited optimal activity at a pH of 5.0 and temperature of 55 °C. Thermal stability was in the temperature range of 50-55 °C. The estimated Km and Vmax values were 51.4 mg/mL and 898.2 U/mg, respectively. One millimolar of Mn2+ and Na+ ions stimulated the activity of rXynS1 by up to 209% and 122.4%, respectively, and 1 mM Co2+ and Ni2+ acted as inhibitors of the enzyme. The mixture of rXynS1, originates from Streptomyces sp. strain J103 and acetyl xylan esterase (AXE), originating from the marine bacterium Ochrovirga pacifica, enhanced the xylan degradation by 2.27-fold, compared to the activity of rXynS1 alone when Mn2+ was used in the reaction mixture; this reflected the ability of both enzymes to hydrolyse the xylan structure. The use of an enzyme cocktail of rXynS1, AXE, and commercial cellulase (Celluclast® 1.5 L) for the hydrolysis of lignocellulosic biomass was more effective than that of commercial cellulase alone, thereby increasing the relative activity 2.3 fold. The supplementation of rXynS1 with AXE enhanced the xylan degradation process via the de-esterification of acetyl groups in the xylan structure. Synergetic action of rXynS1 with commercial cellulase improved the hydrolysis of pre-treated lignocellulosic biomass; thus, rXynS1 could potentially be used in several industrial applications.


In vitro utilization of mucin by Bacteroides fragilis.
A method for isolating pig colon mucin in a soluble high-molecular-weight form, suitable for addition to bacterial growth media, is described. This preparation was utilized as a sole carbohydrate energy source by two strains of Bacteroides fragilis. The extent of degradation was compared with that of commercial pig gastric mucin by the same strains. Gas-liquid chromatographic analysis of the mucin carbohydrates and gel chromatography of the preparations were carried out before and after in vitro degradation. The mucin carbohydrates were utilized only to a very limited extent, colon mucin being more resistant to degradation than gastric mucin. Both mucins chromatographed at or near the excluded volume on Sepharose 4B, and only in the case of ATCC 25285 grown on gastric mucin was a significant degradation peak detected. If mucins are degraded in vivo by the sequential action of several bacteria, a pure culture in vitro might be expected to degrade mucins to a limited extent only. Techniques previously used to examine mucin utilization by pure cultures may have overlooked limited mucin degradation demonstrated by the methods used in this work.


A study protocol for a cluster randomised controlled trial on mindfulness-based stress reduction: studying effects of mindfulness-based stress reduction and an additional organisational health intervention on mental health and work-related perceptions of teachers in Dutch secondary vocational schools.
Dutch teachers in secondary vocational schools suffer from stress and burnout complaints that can cause considerable problems at work. This paper presents a study design that can be used to evaluate the short-term and long-term effectiveness of mindfulness-based stress reduction (MBSR), a person-focused intervention, both within and outside of the context of an additional organisational health intervention. The proposed study comprises a cluster randomised controlled trial that will be conducted in at least three secondary vocational schools, to which teachers will be recruited from three types of courses: Care, Technology, and Economy. The allocation of the intervention programme to the participating schools will be randomised. The teachers from each school will be assigned to intervention group 1 (IG 1), intervention group 2 (IG 2), or the waiting list group (WG). IG 1 will receive MBSR training and IG 2 will receive MBSR training combined with an additional organisational health intervention. WG, that is the control group, will receive MBSR training one year later. The primary outcome variable of the proposed study is mindfulness, which will be measured using the Dutch version of the Five Facet Mindfulness Questionnaire (FFMQ-NL). In the conceptual model, the effects of teachers' mindfulness resulting from the intervention programmes (MBSR training and MBSR training combined with an additional organisational health intervention) will be related to salient (secondary outcome) variables: mental health outcomes (e.g., burnout, work engagement), work performance, work-related perceptions (job demands and job resources), and personal competencies (e.g., occupational self-efficacy). Data will be collected before (T0) and immediately after the MBSR training (T1), and 3 (T2) and 9 months (T3) after the training. The power analysis revealed a required sample size of 66 teachers (22 in each group). The proposed study aims to provide insight into (1) the short-term and long-term effects of MBSR on teachers' mental health, (2) the possible enhancing effects of the additional organisational health intervention, and (3) the teachers' experiences with the interventions (working mechanisms, steps in the mindfulness change process). Strengths of this study design are the use of both positive and negative outcomes, the wide range of outcomes, both outcome and process measures, longitudinal data, mixed methods, and an integral approach. Although the proposed study protocol may not address all weaknesses of current studies (e.g., self-selection bias, self-reporting of data, the Hawthorne effect), it is innovative in many ways and can be expected to make important contributions to both the scientific and practical debate on how to beat work-related stress and occupational burnout, and on how to enhance work engagement and work performance. Dutch Trial Register (www.trialregister.nl): NL5581. Registered on 6 July 2016.


[Preliminary study on mechanisms of total saponins from Entada phaseoloides against diabetes].
To study the effect of total saponins from Entada phaseoloides (TSEP) on islet morphology and skeletal muscle PI3K pathway-related protein expression of type 2 diabetic rats. Type 2 diabetic rats were induced by high-fat diet and low-dose streptozotocin and then randomly divided into 5 groups, i.e. the normal control, the model group, the positive control drug (200 mg x kg(-1) metformin), the low-dose TSEP (25 mg x kg(-1)) group and the high-dose TSEP (50 mg x kg(-1)). Three weeks later, the islet morphology of rat pancreas were observed by HE staining, and protein expressions of insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein tyrosine phosphatase-1B (PTP-1 B) and glucose transporter 4 (GLUT4) in rat skeletal muscle were detected by Western blot. Compared with the modal group, TSEP administration groups showed relatively normal structures, clear pancreatic cells and intact capsula structures in pancreatic tissue pathological sections, with the number of pancreatic islets close to the normal control group. Meanwhile, above TSEP administration groups showed increased IRS-1, PI3K and GLUT4 protein expressions in their skeletal muscle tissues and decreased PTP-1B protein expression compared with the model group. TSEP has an effect on protecting pancreatic tissues of type 2 diabetic rats and intervening in abnormal expression of proteins in skeletal muscle tissues.


[Application of five atmospheric correction models for Landsat TM data in vegetation remote sensing].
Based on the Landsat TM image of northeast Guangzhou City and north Huizhou City on July 18, 2005, and compared with apparent reflectance model, five atmospheric correction models including four dark object subtraction models and 6S model were evaluated from the aspects of vegetation reflectance, surface reflectance, and normalized difference vegetation index (NDVI). The results showed that the dark object subtraction model DOS4 produced the highest accurate vegetation reflectance, and had the largest information loads for surface reflectance and NDVI, being the best for the atmospheric correction in the study areas. It was necessary to analyze and to compare different models to find out an appropriate model for atmospheric correction in the study of other areas.


Utility of a Smartphone Based System (cvrPhone) to Predict Short-term Arrhythmia Susceptibility.
Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. We developed a 12-lead, blue-tooth/Smart-Phone (Android) based electrocardiogram (ECG) acquisition and monitoring system (cvrPhone), and an application to estimate RA, in real-time. In in-vivo swine studies (N = 17), 12-lead ECG signals were recorded at baseline and following coronary artery occlusion. RA was estimated using the Fast Fourier Transform (FFT) method using a custom developed algorithm in JAVA. Underlying ischemia was detected using a custom developed ischemic index. RA from each lead showed a significant (p < 0.05) increase within 1 min of occlusion compared to baseline (n = 29). Following myocardial infarction, spontaneous ventricular tachycardia episodes (n = 4) were preceded by significant (p < 0.05) increase of RA prior to the onset of the tachy-arrhythmias. Similarly, the ischemic index exhibited a significant increase following myocardial infarction (p < 0.05) and preceding a tachy-arrhythmic event. In conclusion, RA can be effectively estimated using surface lead electrocardiograms by analyzing beat-to-beat variability in ECG morphology using a smartphone based platform. cvrPhone can be used to detect myocardial ischemia and arrhythmia susceptibility using a user-friendly, clinically acceptable, mobile platform.


Thrombosis following acute cytomegalovirus infection: a community prospective study.
Infection might be associated with increased risk of venous thromboembolism (VTE) and arterial thrombosis. Specific hypotheses have been raised regarding the procoagulant response induced by acute cytomegalovirus (CMV) infection. Accordingly, we investigated the 6-month incidence of VTE and/or arterial thrombosis in patients that had been tested positive for CMV-IgM antibodies in a large health maintenance organization. Logistic regression analysis was used to identify independent risk factors for VTE and arterial thrombosis. Among 90,515 patients eligible for the VTE analysis and 90,805 patients eligible for the arterial thrombosis analysis, 6,205 (6.9%) and 6,222 (6.9%) patients were tested positive for CMV-IgM antibodies, respectively. During 6 months of follow-up from index date, the incidence rates per 1,000 capita of VTE among CMV-IgM seropositive and CMV-IgM seronegative patients were 3.06 (19 patients) and 1.36 (115 patients), respectively (odds ratio (OR) 2.25; 95% confidence intervals (95% CI) 1.38-3.66; p = 0.003). CMV-IgM seropositivity was independently associated with VTE appearance (OR 2.49; 95% CI 1.53-4.06; p < 0.0001) following adjustment for age, sex, and other confounders. The incidence rates per 1,000 capita of arterial thrombosis among CMV-IgM seropositive and CMV-IgM seronegative patients were 1.12 (7 patients) and 1.06 (90 patients), respectively (OR 1.06; 95% CI 0.49-2.28; p = 0.840). CMV-IgM seropositivity was not associated with arterial thrombosis. We conclude that acute CMV infection might be associated with an increased short-term VTE risk. To the best of our knowledge, this is the largest study ever to confirm this association.


Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus.
We randomly assigned 46 patients (mean age, 11.7 years; range, 4.5 to 32.8) with newly diagnosed insulin-dependent diabetes mellitus within two weeks of beginning insulin to receive either corticosteroids for 10 weeks plus daily azathioprine for one year or no immunosuppressive therapy. Half the 20 immunosuppressed patients completing the one-year trial had satisfactory metabolic outcomes (hemoglobin A1c less than 6.8 percent; stimulated peak C peptide greater than 0.5 nmol per liter; insulin dose less than 0.4 U per kilogram of body weight per day) as compared with only 15 percent of the controls. Three of 20 immunosuppressed patients, but no controls, were insulin independent at one year. Two of these continue to receive azathioprine without insulin after more than 27 months of follow-up. The response to immunosuppression correlated with older age, better initial metabolic status, and lymphopenia (less than 1800 lymphocytes per cubic millimeter) resulting from immunosuppression. The side effects of azathioprine included vomiting in one patient and mild hair loss in several others. Prednisone use resulted in a transient cushingoid appearance, weight gain, and hyperglycemia. The growth rate remained normal in all patients. We conclude that early immunosuppression with short-term use of corticosteroids plus daily azathioprine can improve metabolic control in some patients with insulin-dependent diabetes mellitus, but results from this unblinded study are preliminary and require further confirmation and long-term follow-up.


Tendon disorders of the foot and ankle, part 3: the posterior tibial tendon.
This article provides a review of posterior tibial tendon pathology and the authors' preferred management. The tibialis posterior musculotendinous unit is the most powerful inverter of the foot and an important dynamic stabilizer of the arch. In the stance phase of the gait cycle, it serves as an initiator of both ankle plantar flexion and subtalar inversion. This creates a rigid midfoot by stabilizing the transverse tarsal joint, and allows for increased power generation by the gastrocsoleus complex through toe-off. Injuries to the posterior tibialis tendon include traumatic laceration and dislocation, as well as tenosynovitis and tendinopathy, which can lead to attenuation and rupture. If these injuries are not addressed, significant clinical deformity and disability can result.


Optimizing adherence to advice from antimicrobial stewardship audit and feedback rounds.
We examined adherence to antimicrobial stewardship prospective audit and feedback rounds in a rehabilitation service compared with the remainder of the acute hospital, and explored the reasons for this. Between October 2014 and December 2015, we retrospectively assessed the rate of non-adherence to advice from antimicrobial stewardship prospective audit and feedback rounds between the rehabilitation service and the acute hospital, along with the source of the patient referral. Compared with the rehabilitation service, acute hospital medical staff were almost twice as likely to not adhere to advice provided on antimicrobial stewardship prospective audit and feedback rounds (13.8% vs. 7.6%, p < 0.0001, relative risk 1.8 [95% confidence interval 1.3, 2.5]). In the rehabilitation service, referrals were more likely to come from medical staff (61.9% vs. 16.3%, p < 0.0001). These findings may be explained by regular, direct engagement of the antimicrobial stewardship team with the rehabilitation service clinical team, a model potentially applicable to other settings.


Influence of antiepileptic drugs on amplitude-integrated electroencephalography.
Amplitude-integrated electroencephalography monitors different aspects of cerebral function in neonatal intensive care units. To examine the influence of various antiepileptic drugs on the background patterns and voltage of amplitude-integrated electroencephalography recordings, we screened 191 tracing segments originating from 77 newborns treated with antiepileptic drugs. The influences of lorazepam, diazepam, and phenobarbital given as bolus doses, and midazolam and lidocaine given in continuous infusion, were examined. Voltages and patterns before and after drug administration were assessed. Time taken to return to previous voltage was assessed in clinically significant cases. Chi-square and Wilcoxon tests were used for statistical analyses. Significant changes were evident after lorazepam, diazepam, phenobarbital, and midazolam administration. Depending on the voltage-assessment method, a clinically significant depression of the lower voltage border occurred in 25-35% of tracings, and of the upper border in 16-32%. In 12% of tracings, change to a worse pattern was noted. The average time for recovery to predrug administration voltage was 2.5 hours (range, 15 minutes to 15 hours). Changes in amplitude-integrated electroencephalography tracings occur after antiepileptic drugs are infused. These changes include deterioration of pattern and depression of voltage that may persist for a considerable period. The potential depressing effects of these drugs should be taken into consideration when assessing amplitude-integrated electroencephalogram tracings.


Two cases of accessory middle cerebral artery associated with intracranial aneurysm.
Two rare cases of accessory middle cerebral artery associated with intracranial aneurysm are reported and the pertinent previous literature is reviewed.


Chemical biology of steroid and nuclear hormone receptors.
The nuclear hormone receptors are ligand-gated transcription factors that modulate gene expression by directly acting upon genomic DNA, and have been of profound interest across all biological disciplines. Recent advancements in this area have included the expansion of transgene activation through ligand-receptor engineering, drug development from structural design and the exploitation of innate ligand-specific associations towards developing novel conditional protein-based recombinant and diagnostic tools. These advancements come on the heels of exciting new modes of hormone action that challenge and expand upon the classic paradigms of hormone receptor function.


LARYNGEAL CHONDROSARCOMA: SUCCESSFUL USE OF VIDEO LARYNGOSCOPE IN ANTICIPATED DIFFICULT AIRWAY MANAGEMENT.
Laryngeal chondrosarcoma is a rare mesenchymal tumor, most frequently affecting cricoid cartilage. The objective of this report is to present successful video laryngoscope usage in a patient with anticipated difficult airway who refused awake fiberoptic endotracheal intubation (AFOI). A 59-year-old male patient was admitted in our hospital due to difficulty breathing and swallowing. On clinical examination performed by ENT surgeon, preoperative endoscopic airway examination (PEAE) could not be performed properly due to the patient's uncooperativeness. Computed tomography revealed a spherical tumor that obstructed the subglottic area almost entirely. Due to the narrowed airway, the first choice for the anticipated difficult airway management was AFOI, which the patient refused. Consequently, we decided to perform endotracheal intubation with indirect laryngoscope using a C-MAC video laryngoscope (Karl Storz, Tuttlingen, Germany). Reinforced endotracheal tube (6.0 mm internal diameter) was placed gently between the tumor mass and the posterior wall of the trachea in the first attempt. Confirmation of endotracheal intubation was done by capnography. In a patient with subglottic area chondrosarcoma refusing PEAE and AFOI, video laryngoscope is a particularly helpful device for difficult airway management when difficult airway is anticipated.


IL-2-dependent HTLV-I-infected T cells escape from non-specific, MHC-unrestricted cellular cytotoxicity.
The susceptibility of NK cell-mediated cytolysis was compared between 5 human HTLV-I-transformed T cell lines and 10 newly established IL-2-dependent HTLV-I-infected lines. None of the cell lines were killed after 4 hr incubation with normal PBMC. However, after 20 hr, 3 HTLV-I-transformed lines were significantly lysed. All the HTLV-I-infected lines, except 2, weakly inhibited the NK cell-mediated lysis of K562 targets. They showed a reduced ability to bind normal PBMC as compared with control NK-sensitive T cell lines. The IL-2-dependent lines remained unaffected by PBMC from HTLV-I-infected individuals, including the autologous donors. In contrast to the HTLV-I-transformed lines, they were weakly lysed or not lysed at all by LAK cells and only 5 were killed by ADCC with HTLV-I+ sera and normal PBMC. Taken together, the results show that IL-2-dependent HTLV-I-infected T cells strongly resist NK cell-mediated cytolysis at a post-binding level and suggest that such cells may escape in vivo from non-specific, MHC-unrestricted cellular cytotoxicity.


Perinatal Outcomes of Neonates with Complex and Simple Gastroschisis after Planned Preterm Delivery-A Single-Centre Retrospective Cohort Study.
This research analysed early neonatal outcomes of complex and simple gastroschisis following planned elective preterm delivery in relation to prenatal ultrasound assessment of bowel conditions. A retrospective study of 61 neonates with prenatal gastroschisis diagnosis, birth, and management at a single tertiary centre from 2011 to 2021 showed a 96.72% survival rate with no intrauterine fatalities. Most cases (78.7%) were simple gastroschisis. Neonates with complex gastroschisis had longer hospital stays and time to full enteral feeding compared to those with simple gastroschisis-75.4 versus 35.1 days and 58.1 versus 24.1 days, respectively. A high concordance of 86.90% between the surgeon's and perinatologist's bowel condition assessments was achieved. The caesarean delivery protocol demonstrated safety, high survival rate, primary closure, and favourable outcomes compared to other reports. Prenatal ultrasound effectively evaluated bowel conditions and identified complex gastroschisis cases.


Tracking medication information across medical records.
A patient's electronic medical record can consist of a large number of reports, especially for an elderly patient or for one affected by a chronic disease. It can thus be cumbersome for a physician to go through all of the reports to understand the patient's complete medical history. This paper describes work in progress towards tracking medications and their dosages through the course of a patient's medical history. 923 reports associated with 11 patients were obtained from a university hospital. Drug names were identified using a dictionary look-up approach. Dosages corresponding to these drugs were determined using regular expressions. The state of a drug (ON, OFF), which determines whether or not the drug was being taken, was identified using a support vector machine with features based on expert knowledge. Results were promising: prec. approximately recall approximately 87%. The output is a timeline display of the drugs which the patient has been taking.


Clock genes, hair growth and aging.
Hair follicles undergo continuous cycles of growth, involution and rest. This process, referred to as the hair growth cycle, has a periodicity of weeks to months. At the same time, skin and hair follicles harbor a functional circadian clock that regulates gene expression with a periodicity of approximately twenty four hours. In our recent study we found that circadian clock genes play a role in regulation of the hair growth cycle during synchronized hair follicle cycling, uncovering an unexpected connection between these two timing systems within skin. This work, therefore, indicates a role for circadian clock genes in a cyclical process of much longer periodicity than twenty four hours.


POLYTOMIES AND THE POWER OF PHYLOGENETIC INFERENCE.
Although phylogenetic hypotheses can provide insights into mechanisms of evolution, their utility is limited by our inability to differentiate simultaneous speciation events (hard polytomies) from rapid cladogenesis (soft polytomies). In the present paper, we tested the potential for statistical power analysis to differentiate between hard and soft polytomies in molecular phytogenies. Classical power analysis typically is used a priori to determine the sample size required to detect a particular effect size at a particular level of significance (a) with a certain power (1 - β). A posteriori, power analysis is used to infer whether failure to reject a null hypothesis results from lack of an effect or from insufficient data (i.e., low power). We adapted this approach to molecular data to infer whether polytomies result from simultaneous branching events or from insufficient sequence information. We then used this approach to determine the amount of sequence data (sample size) required to detect a positive branch length (effect size). A worked example is provided based on the auklets (Charadriiformes: Alcidae), a group of seabirds among which relationships are represented by a polytomy, despite analyses of over 3000 bp of sequence data. We demonstrate the calculation of effect sizes and sample sizes from sequence data using a normal curve test for difference of a proportion from an expected value and a t-test for a difference of a mean from an expected value. Power analyses indicated that the data for the auklets should be sufficient to differentiate speciation events that occurred at least 100,000 yr apart (the duration of the shortest glacial and interglacial events of the Pleistocene), 2.6 million years ago.


[Exosomes and Immune Cells].
In addition to the cytokines and cytotoxic granules, exosomes have been known as the intercellular communicator and cytotoxic missile of immune cells for the past decade. It has been well known that mature dendritic cell(DC)-derived exosomes participate in the T cell and natural killer(NK)cell activation, while immature DCs secrete tolerogenic exosomes for regulatory T(Treg)cell generation. Treg cell-derived EVs act as a suppressor against pathogenic type-1 T helper(Th1)cell responses. CD8+ T cells produce tumoricidal exosomes for preventing tumor invasion and metastasis transiently after T cell receptor(TCR)-mediated stimulation. Thus, immune cells produce functional exosomes in the activation state- and/or differentiation stage-dependent manner. In this review, the role of immune cell-derived exosomes will be introduced, focusing mainly on immune reaction against tumor.


Acute para-esophageal hernia in Ehlers-Danlos Syndrome.
Para-esophageal herniation is a recognized complication of the Ehlers-Danlos syndrome. While chronic herniation is well described, acute symptomatic herniation is far less common. We describe a case of acute, life-threatening para-esophageal herniation of the abdominal viscera in a young woman with Ehlers-Danlos syndrome. Careful anaesthetic assessment and surgical management resulted in a successful clinical outcome.


[The genetic polymorphisms of 6 short tandem repeat loci in native Han population in Jiangxi province].
To investigate the genetic polymorphisms of 6 short tandem repeats (STR) loci, namely, D6S1043, D2S1772, D7S3048, D22-GATA198B05, D8S1132 and D11S2368 in native Han population of Jiangxi province, China. Two hundred and twelve blood samples of unrelated subjects of Han population in Jiangxi province were collected. Genotyping was performed by using multiplex polymerase chain reaction-polyacrylamide gel electrophoresis. Thirteen alleles and 52 genotypes in the D6S1043 locus, 13 alleles and 66 genotypes in D2S1772, 12 alleles and 48 genotypes in D7S3048, 11 alleles and 44 genotypes in D22-GATA198B05, 10 alleles and 38 genotypes in D8S1132, 10 alleles and 41 genotypes in D11S2368 locus, were detected in the 212 subjects. The observed heterozygosity (h) in D6S1043, D2S1772, D7S3048, D22-GATA198B05, D8S1132 and D11S2368 loci ranged from 0.8019 to 0.8774. The expected heterozygosity (H) varied from 0.8553 to 0.8896. The discriminating power (DP) ranged from 0.9559 to 0.9735. The probability of exclusion (PE) ranged from 0.7053 to 0.7751. The polymorphism information content (PIC) varied from 0.8452 to 0.8774. All the 6 loci were of Hardy-Weinberg equilibrium. The genetic polymorphism of the 6 STR loci in Han population of Jiangxi province was high. The allelic distribution data at the 6 loci are valuable in population study, individual identification and paternity test for this population.


Staphylococcus aureus isolates encode variant staphylococcal enterotoxin B proteins that are diverse in superantigenicity and lethality.
Staphylococcus aureus produces superantigens (SAgs) that bind and cross-link T cells and APCs, leading to activation and proliferation of immune cells. SAgs bind to variable regions of the β-chains of T cell receptors (Vβ-TCRs), and each SAg binds a unique subset of Vβ-TCRs. This binding leads to massive cytokine production and can result in toxic shock syndrome (TSS). The most abundantly produced staphylococcal SAgs and the most common causes of staphylococcal TSS are TSS toxin-1 (TSST-1), and staphylococcal enterotoxins B and C (SEB and SEC, respectively). There are several characterized variants of humans SECs, designated SEC1-4, but only one variant of SEB has been described. Sequencing the seb genes from over 20 S. aureus isolates show there are at least five different alleles of seb, encoding forms of SEB with predicted amino acid substitutions outside of the predicted immune-cell binding regions of the SAgs. Examination of purified, variant SEBs indicates that these amino acid substitutions cause differences in proliferation of rabbit splenocytes in vitro. Additionally, the SEBs varied in lethality in a rabbit model of TSS. The SEBs were diverse in their abilities to cause proliferation of human peripheral blood mononuclear cells, and differed in their activation of subsets of T cells. A soluble, high-affinity Vβ-TCR, designed to neutralize the previously characterized variant of SEB (SEB1), was able to neutralize the variant SEBs, indicating that this high-affinity peptide may be useful in treating a variety of SEB-mediated illnesses.


The power of putting a label on it: green labels weigh heavier than contradicting product information for consumers' purchase decisions and post-purchase behavior.
Green products are appealing. Thus, labeling products as environmentally friendly is an effective strategy to increase sales. However, the labels often promise more than the products can actually deliver. In the present research, we examined the expectation that consumers with high ecological motivation have strong preferences for green-labeled products - even when presented product information contradicts the label's image. This unsettling hypothesis is grounded in the labels' potential to create a cognitive match between the labeled product and consumers' motives. For labels indicating environmental friendliness (green product labels), this link should be strongest when consumers' ecological motivation is high. Findings in a series of three experiments support our assumption, showing that consumers with high ecological motivation had strong preferences (i.e., product evaluations, purchase intentions, and simulated purchase decisions) for green-labeled products as compared to consumers with low ecological motivation (Studies 1-3). Crucially, these preferences were robust, despite contradicting environmental product information (Studies 1 and 2). We extended our findings by additionally examining the impact of product labels and motivation on moral self-regulation processes. This was established by assessing participants' pro-social behavior after the purchase task: participants with high ecological motivation acted, consistent with their motives, more pro-socially in post-decision occasions. In accordance with moral cleansing effects, pro-social behavior was intensified after purchasing conventional products (Studies 2 and 3). Green labels protected participants with high ecological motivation from moral threats due to the purchase, thus making pro-social behavior less likely. Findings suggest that highly ecologically motivated consumers are most susceptible to green labels, which may override detailed product information.


'Write Right': The GSAHS Clinical Documentation Project.
The Clinical Documentation Project was piloted at one site in Greater Southern Area Health Service (GSAHS) in New South Wales; it aimed to improve the standard of clinical documentation by 50% between March and August 2005. The main intervention was the use of a Self Directed Documentation Learning Package (SDDLP). Results achieved a 75% improvement in clinical documentation within six months and a 46.5% improvement in clinicians' confidence in their level of knowledge on documentation requirements.


Plasmalogen homeostasis - regulation of plasmalogen biosynthesis and its physiological consequence in mammals.
Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis-defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.


Seronegative spondarthritis and human leucocyte antigen association.
The human leucocyte antigen (HLA) B27 has been associated with seronegative spondarthritis universally, but the associations varies (19-94%) in different Indian population groups. It is possible that this variation is due to patient selection bias. Here, we use strict clinical, radiological and serological criteria to select 79 patients with seronegative spondarthritis (SSA) and compare them with 110 healthy, normal individuals from the same ethnic background. The standard National Institute of Health (NIH) microlymphocytotoxicity assay is used to evaluate HLA B27 status in both groups. Significant association between HLA B27 and AS disease was found (odds ratio [OR]: 72.22; P<0.0001; confidence interval [CI]=1.5-3.8) when compared to the control group. Furthermore, HLA B5 was decreased when compared to the control group (OR: 0.39; P<0.01). Those in the 20-40 age group were more vulnerable, with a male preponderance (7:1) over females. These findings confirm the strong association of the HLA B27 allele with various types of spondarthritis and suggest that allele detection would help in the diagnosis of AS where clinical presentation is unclear and in identifying family members at risk.


[Preparation and identification of monoclonal antibodies against human programmed cell death 10 (PDCD10)].
To obtain monoclonal antibodies against programmed cell death 10 (PDCD10) for further study of the structure and function of PDCD10 protein. Balb/c mice were immunized with recombinant PDCD10, hybridoma cell lines secreting monoclonal antibodies against PDCD10 were screened by regular cell fusion and subcloning approach. The specificities of these monoclonal antibodies were determined by ELISA, Western blotting and Immunofluorescence assay. Three hybridoma cell lines (5G1, 4F7 and 3H5) stable in secreting specific monoclonal antibodies were successfully obtained. Subclass of IgG belonged to IgG1 (4F7 and 5G1) and IgG2b (3H5), respectively. The ascite titers of these monoclonal antibodies reached 1:10(7). They could specifically bind to recombinant PDCD10 and endogenous and overexpressed PDCD10 proteins proved by ELISA and Western blotting. They failed to react with E.coli lysates and glutathione S-transferase (GST). In addition, these three monoclonal antibodies could recognize different epitopes of PDCD10 proteins assessed by immune fluorescence competitive binding assay. Both endogenous and overexpressed PDCD10 protein mainly located in the nucleus. Monoclonal antibodies against PDCD10 with high titers and specificity have been successfully prepared, which has laid the foundation for further study of PDCD10 protein.


The prevalence of HIV among adults with pulmonary TB at a population level in Zambia.
Tuberculosis and HIV co-infection is one of the main drivers of poor outcome for both diseases in Zambia. HIV infection has been found to predict TB infection/disease and TB has been reported as a major cause of death among individuals with HIV. Improving case detection of TB/HIV co-infection has the potential to lead to early treatment of both conditions and can impact positively on treatment outcomes. This study was conducted in order to determine the HIV prevalence among adults with tuberculosis in a national prevalence survey setting in Zambia, 2013-2014. A countrywide cross sectional survey was conducted in 2013/2014 using stratified cluster sampling, proportional to population size for rural and urban populations. Each of the 66 countrywide clusters represented one census supervisory area with cluster size averaging 825 individuals. Socio-demographic characteristics were collected during a household visit by trained survey staff. A standard symptom-screening questionnaire was administered to 46,099 eligible individuals across all clusters, followed by chest x-ray reading for all eligible. Those symptomatic or with x-ray abnormalities were confirmed or ruled out as TB case by either liquid culture or Xpert MTBRif performed at the three central reference laboratories. HIV testing was offered to all participants at the survey site following the national testing algorithm with rapid tests. The prevalence was expressed as the proportion of HIV among TB cases with 95% confidence limits. A total of 265/6123 (4.3%) participants were confirmed of having tuberculosis. Thirty-six of 151 TB survey cases who accepted HIV testing were HIV-seropositive (23.8%; 95% CI 17.2-31.4). The mean age of the TB/HIV cases was 37.6 years (range 24-70). The majority of the TB/HIV cases had some chest x-ray abnormality (88.9%); were smear positive (50.0%), and/or had a positive culture result (94.4%). None of the 36 detected TB/HIV cases were already on TB treatment, and 5/36 (13.9%) had a previous history of TB treatment. The proportion of TB/HIV was higher in urban than in the rural clusters. The HIV status was unknown for 114/265 (43.0%) of the TB cases. The TB/HIV prevalence in the general population was found to be lower than what is routinely reported as incident TB/HIV cases at facility level. However; the TB/HIV co-infection was higher in areas with higher TB prevalence. Innovative and effective strategies for ensuring TB/HIV co-infected individuals are detected and treated early are required.


The direct determination of urinary oxalate by non-suppressed ion chromatography.
In this paper we describe a simple ion chromatographic method for determination of oxalate in urine. Acidified urine was diluted 1:2 with 0.03 mol/l benzidine hydrochloride in 0.3 mol/l boric acid to precipitate sulphate. The supernatant was passed through a C18-cartridge and 100 microliters of eluant were injected into an ion chromatographic system. Oxalate was measured by nonsuppressed conductivity detection. The detection limit for urinary oxalate was 0.05 mmol/l. The recovery for spiked urine samples was 101.5% with a CV of 4.5%. The within- and between-assay coefficients of variation were less than 4.5% and 2.5%, respectively. We found the results obtained by this method to be statistically equivalent to an enzymatic assay and a different ion-chromatographic method.


Use of free composite graft for a large defect in the anterior skull base.
Until recently, most skull base tumors, particularly those extending into the orbit or anterior or middle cranial fossa base, were excised incompletely because of the technical difficulty in performing en bloc resections. However, improved craniofacial surgical techniques, recent developments in technology and equipment, improved imaging techniques, interdisciplinary collaboration, and improved anesthetic techniques have enabled a wide range of attempts resulting in successful clinical outcome. We present a case of recurrent meningioma with intracranial and extracranial extension in which three previous operations left a large craniectomy defect in the frontal area as well as a frontal lobe defect. After removal of the tumor, we reconstructed the large defect using composite graft (free bone and fascia lata).


Beneficial effects of the micronized purified flavonoid fraction (MPFF, Daflon® 500 mg) on microvascular damage elicited by sclerotherapy.
To evaluate if the micronized purified flavonoid fraction (MPFF) treatment could reduce the side effects of sclerotherapy (a procedure frequently used to treat venous disease manifestations) by minimizing the inflammatory response within the surrounding tissues. Twenty-two male New Zealand rabbits were treated by gavage with micronized purified flavonoid fraction (MPFF; 300 mg/kg/day) or vehicle (10% lactose solution) during 21 consecutive days, starting 7 days before sclerotherapy. The sclerotherapy consisted of an injection containing 5% ethanolamine oleate solution in the rabbit's dorsal ear vein. Before and after sclerotherapy, venular and arteriolar diameters, microvascular permeability, functional capillary density (FCD), number of rolling and sticking leukocytes were evaluated on ear microcirculation. Images of the sclerotherapy site were taken before and after the procedure. Compared to placebo, MPFF treatment prevented the increase in venular diameter, preserved FCD (P < 0.001) and reduced the number of leaky sites (P < 0.001) and sticking leukocytes (P < 0.001). Imaging confirmed these effects on thrombosis and perivascular edema of the sclerosed vein, 14 days after procedure. MPFF treatment limited the postsclerotherapy inflammation in surrounding microvascular network, suggesting that MPFF may prevent undesirable secondary effects of the procedure in this animal model. This study warrants further investigation for its use in clinical conditions.


Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies.


Preliminary evaluation of in-vitro antimycobacterial properties of N1-(aryliden)-2-pyridinecarboxyamidrazones.
After preliminary in vitro screening of 17 newly synthesized compounds belonging to the chemical class of N1-(aryliden)-2-pyridinecarboxyamidrazones, active against Mycobacterium tuberculosis H37Rv, the minimum inhibitory concentrations (MICs) of the ten most promising agents against three clinical isolates were determined by agar dilution. Compounds 12 and 14 were the most active, each inhibiting strain H37Rv at concentrations of 8 microg/ml and having a MIC of 16 microg/ml against the human isolates. The results obtained in this preliminary study confirmed the interesting antitubercular properties of these newly synthesized compounds and allowed us to carry out our investigations over a large number of isolated clinical strains.


Visualization of gastric varices using angiographic C-arm CT during retrograde transvenous sclerotherapy.
During retrograde transvenous sclerotherapy for gastric varices, sufficient opacification of the target varices on venography is essential for successful treatment. However, venography sometimes cannot identify target varices due to overlapping adjacent collateral vessels or leakage of contrast medium to other outflow veins. We report how C-arm CT images acquired using a flat-panel detector angiography system helped to identify target varices and predict the distribution of a sclerosant, which resulted in safer sclerotherapy and increased operator confidence.


Reflex sympathetic dystrophy syndrome due to arteriovenous fistula.
A patient with end-stage renal disease presented with reflex sympathetic dystrophy syndrome (RSDS) on her left hand 1 month after arteriovenous fistula (AVF) surgery. Magnetic resonance angiography revealed steal syndrome at the AVF level. Bone scintigraphy revealed early-stage RSDS. We considered that arterial insufficiency because of steal phenomenon following AVF surgery and underlying occlusive arterial disease triggered RSDS development.


Applying GRADE-CERQual to qualitative evidence synthesis findings-paper 7: understanding the potential impacts of dissemination bias.
The GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) approach has been developed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group. The approach has been developed to support the use of findings from qualitative evidence syntheses in decision-making, including guideline development and policy formulation. CERQual includes four components for assessing how much confidence to place in findings from reviews of qualitative research (also referred to as qualitative evidence syntheses): (1) methodological limitations, (2) coherence, (3) adequacy of data and (4) relevance. This paper is part of a series providing guidance on how to apply CERQual and focuses on a probable fifth component, dissemination bias. Given its exploratory nature, we are not yet able to provide guidance on applying this potential component of the CERQual approach. Instead, we focus on how dissemination bias might be conceptualised in the context of qualitative research and the potential impact dissemination bias might have on an overall assessment of confidence in a review finding. We also set out a proposed research agenda in this area. We developed this paper by gathering feedback from relevant research communities, searching MEDLINE and Web of Science to identify and characterise the existing literature discussing or assessing dissemination bias in qualitative research and its wider implications, developing consensus through project group meetings, and conducting an online survey of the extent, awareness and perceptions of dissemination bias in qualitative research. We have defined dissemination bias in qualitative research as a systematic distortion of the phenomenon of interest due to selective dissemination of studies or individual study findings. Dissemination bias is important for qualitative evidence syntheses as the selective dissemination of qualitative studies and/or study findings may distort our understanding of the phenomena that these syntheses aim to explore and thereby undermine our confidence in these findings. Dissemination bias has been extensively examined in the context of randomised controlled trials and systematic reviews of such studies. The effects of potential dissemination bias are formally considered, as publication bias, within the GRADE approach. However, the issue has received almost no attention in the context of qualitative research. Because of very limited understanding of dissemination bias and its potential impact on review findings in the context of qualitative evidence syntheses, this component is currently not included in the GRADE-CERQual approach. Further research is needed to establish the extent and impacts of dissemination bias in qualitative research and the extent to which dissemination bias needs to be taken into account when we assess how much confidence we have in findings from qualitative evidence syntheses.


Implementation of an Inhaled Nitric Oxide Weaning Protocol and Stewardship in a Level 4 NICU to Decrease Inappropriate Use.
Inhaled nitric oxide (iNO) is an effective but expensive treatment of pulmonary hypertension in newborns, with limited data regarding weaning. Our institution implemented a multidisciplinary iNO weaning protocol and stewardship to reduce inappropriate use of iNO. The objective of this study was to evaluate our institutional iNO usage before and after implementation. Single-center study comparing a retrospective control group to a prospective cohort after implementation of an iNO weaning protocol. All infants in the neonatal intensive care unit (NICU) who received iNO during the study timeframe were included. The primary outcome was duration of iNO per course. A total of 47 courses of iNO occurred during the pre-protocol timeframe compared with 37 courses in the post-protocol timeframe. Median iNO usage per course was 149 hours (IQR, 63-243) in the pre-protocol group versus 59 hours (IQR, 37-122) in the post-protocol group (p = 0.008). Length of stay was significantly longer in the pre-protocol group (p = 0.02), likely related to significantly longer ventilator days in the pre-protocol group (p = 0.02). Compliance with initiation of weaning when recommended per the protocol was 72%, and the incidence of successful weaning was 74%. The implementation of an iNO weaning protocol in the NICU significantly decreased iNO usage by approximately 60% with no notable negative effects.


Task Encoding across the Multiple Demand Cortex Is Consistent with a Frontoparietal and Cingulo-Opercular Dual Networks Distinction.
Multiple-demand (MD) regions of the human brain show coactivation during many different kinds of task performance. Previous work based on resting-state functional magnetic resonance imaging (fMRI) has shown that MD regions may be divided into two closely coupled subnetworks centered around the lateral frontoparietal (FP) and cingulo-opercular cortex. Here, we used on-task fMRI to test whether this division is apparent during the performance of an executive task. Furthermore, we investigated whether there is a difference in the encoding of task between the two subnetworks. Using connectivity methods, we found that activity across the entire MD cortex is correlated during task performance. Meanwhile, however, there was significantly stronger connectivity within each of the subnetworks than between them. Using multivoxel pattern analysis, we also found that, although we were able to decode task-relevant information from all regions of the MD cortex, classification accuracy scores were significantly higher in the FP subnetwork. These results suggest a nested picture with MD regions as a whole showing coactivation and broad rule representation, but with significant functional distinctions between component subnetworks. Multiple-demand (MD) regions of frontal and parietal cortex appear essential for the orchestration of goal-directed behavior and problem solving. Understanding the relative specialization of regions within the MD cortex is crucial to understanding how we can coordinate and execute complex action plans. By examining functional connectivity during task performance, we extend previous findings suggesting that the MD cortex can be divided into two subnetworks centered around the frontoparietal (FP) and cingulo-opercular (CO) cortex. Furthermore, using multivoxel pattern analysis, we show that, compared with the CO subnetwork, the FP subnetwork manifests more differentiated coding of specific task events.


Influence of CYP2C9, 2C19 and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine.
The antidepressant fluoxetine is administered as racemic mixture of two enantiomers (S- and R-fluoxetine). While S- and R-fluoxetine are equipotent in blocking serotonin reuptake, the enantiomers of the demethylated metabolite, norfluoxetine, show marked differences in pharmacological activity, S-norfluoxetine being about 20 times as potent as R- norfluoxetine as a serotonin reuptake inhibitor. In vitro and in vivo data suggest that the metabolism of fluoxetine to norfluoxetine is stereoselective and mediated, at least in part, by the polymorphic cytochrome P450 (CYP) isoenzymes CYP2D6, CYP2C9 and CYP2C19. In the present study, the influence of CYP2D6, CYP2C9 and CYP2C19 polymorphisms on the steady-state plasma concentrations of fluoxetine and norfluoxetine enantiomers was evaluated in 78 patients receiving chronic fluoxetine treatment (10-60 mg/day). The plasma concentrations of fluoxetine and norfluoxetine enantiomers were measured and CYP2D6, CYP2C9 and CYP2C19 genotypes were analyzed. No statistically significant relationship was identified between CYP2D6 or CYP2C19 genotypes and the dose normalised plasma concentrations of any of the enantiomers or the active moiety (i.e. the sum of S-fluoxetine, R-fluoxetine and S-norfluoxetine). However, the plasma concentration of S-norfluoxetine was very low in the only CYP2D6 poor metaboliser. Furthermore, the median S-norfluoxetine/S-fluoxetine ratios were higher in homozygous than in heterozygous extensive metabolisers (P<0.05). Among homozygous extensive metabolizers for CYP2D6, patients homozygous for CYP2C9*1 had lower dose-normalized R-fluoxetine concentrations and lower active moiety levels compared with those carrying detrimental CYP2C9 alleles (P<0.05). These results suggest that CYP2D6 and CYP2C9 polymorphisms contribute to the interindividual variability in fluoxetine pharmacokinetics at steady-state.


Elevated Plasma Fibrinogen Is Associated With Excessive Inflammation and Disease Severity in COVID-19 Patients.
The coronavirus disease-19 (COVID-19) is characterized with intense inflammatory response, cardiac involvement, and coagulopathy. Fibrinogen, as a biomarker for inflammation, cardiovascular disease, and coagulation, has not been fully investigated yet. The aim of this study was to assess the clinical application of fibrinogen in COVID-19 patients. We retrospectively analyzed the demographic and laboratory characteristics of 119 COVID-19 patients in the University of Alabama of Birmingham Medical Center. Correlations of fibrinogen on admission with intensive care unit (ICU) admission, disease severity, and laboratory parameters were analyzed. Among the 119 COVID-19 patients, 77.3% (92/119) had severe disease, and 59.5% (71/119) patients were admitted to the ICU. Elevated fibrinogen was detected in 67.2% (80/119) of the patients. Fibrinogen levels were significantly associated with inflammatory markers and disease severity, but not with cardiac injury biomarker high sensitivity troponin I. Patients with severe disease had increased fibrinogen levels upon admission compared to patients with non-severe disease (P = 0.001). Fibrinogen level at 528.0 mg/dl was the optimal cutoff to predict disease severity, with a sensitivity and specificity of 66.7% and 70.3% (area undty -60er the curve [AUC] 0.72, P = 0.0006). Fibrinogen is commonly elevated in COVID-19 patients, especially in those with severe disease. Elevated fibrinogen correlates with excessive inflammation, disease severity, and ICU admission in COVID-19 patients.


Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver.
Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive liver transplant and are subsequently immunosuppressed. As further follow-up of previously reported patients (Di Nicuolo et al. 2005), an assessment of PERV infection was made in the same patient population pharmacologically immunosuppressed for several years after BAL treatment and in healthcare workers (HCWs) involved in the clinical trial at that time. Plasma and peripheral blood mononuclear cells (PBMCs) from eight patients treated with the Academic Medical Center-BAL (AMC-BAL), who survived to transplant, and 13 HCWs, who were involved in the trial, were assessed to detect PERV infection. A novel quantitative real-time polymerase chain reaction assay has been used. Eight patients who received a liver transplant after AMC-BAL treatment are still alive under long-term pharmacological immunosuppression. The current clinical follow-up ranges from 5.6 to 8.7 yr after BAL treatment. A new q-real-time PCR assay has been developed and validated to detect PERV infection. The limit of quantification of PERV DNA was ≥ 5 copies per 1 × 10(5) PBMCs. The linear dynamic range was from 5 × 10(0) to 5 × 10(6) copies. In both patients and HCWs, neither PERV DNA in PBMCs nor PERV RNA in plasma and PBMC samples have been found. Up to 8.7 yr after exposure to treatment with porcine liver cell-based BAL, no PERV infection has been found in long-term immunosuppressed patients and in HCWs by a new highly sensitive and specific q-real-time PCR assay.


The economics of routine childhood hepatitis A immunization in the United States: the impact of herd immunity.
Because of the herd-immunity phenomenon, the benefits of immunization against hepatitis A extend beyond those received by those who are vaccinated. This analysis estimates the impact of herd immunity on the cost-effectiveness of routine hepatitis A immunization among US children. In an economic model, the costs and benefits of hepatitis A immunization were estimated for immunizing all US children at age 1 year over a 10-year period starting in 2005. The future burden of disease from hepatitis A was also estimated with this model, and the fraction that would be prevented by herd immunity was modeled by using a previously published analysis of the relationship between hepatitis A vaccination coverage and declines in hepatitis A incidence. Without accounting for herd-immunity effects, the costs of routine immunization would average 32,000 dollars per quality-adjusted life-year gained for the first 10 cohorts immunized starting with the 2005 birth cohort. Herd-immunity effects would be expected to produce substantial additional benefits, lowering the cost of the immunization program to 1000 dollars per quality-adjusted life-year gained for the first 10 cohorts. Herd-immunity benefits would be greatest for the first few cohorts, more than doubling the benefits of immunization, and would decline over time. In a univariate sensitivity analysis, estimates were most sensitive to vaccination costs but remained below 20,000 dollars per quality-adjusted life-year under all of the assumptions. Herd-immunity effects more than double the savings from hepatitis A immunization during the first 10 years of the program. After accounting for these effects, immunization is close to cost-neutral on a cost-per-quality-adjusted-life-year basis.


Management of COPD in End-of-Life Care by Spanish Pulmonologists.
Chronic obstructive pulmonary disease is progressive and in its advanced stage is associated with major disability. Previous studies suggest that patients with this disease receive little palliative care, even in very advanced stages. Given this, our objectives were to describe the clinical practice of Spanish pulmonologists in the care of patients with end-stage chronic obstructive pulmonary disease, to identify potential barriers to implementing palliative care in these patients and to correlate these responses with doctor's years of experience. A link to an online survey was sent to pulmonologists on (a) symptom management, (b) structure of their department and collaboration with other services, (c) specialized medical training in palliative care, (d) communication with patients and their families, and (e) limiting barriers identified in the management of these patients. A total of 387 responses were received. The majority used opioids to treat dyspnea (52.9%) or pain (54.2%) and many treated anxiety/depression (41%). Around half of the respondents had no established routines in their departments to offer palliative care to patients with chronic obstructive pulmonary disease. There was little communication with end-of-life patients and their families on disease course, mainly associated with a lack of medical training (83% of cases) and changes in patient wishes regarding care through the disease course (81%). In our setting, communication with end-of-life patients with chronic obstructive pulmonary disease is poor. The key challenges identified are insufficient medical training and changing desires of patients. No substantial differences in attitude were found as a function of experience.


Utility of culture redox potential for identifying metabolic state changes in amino acid fermentation.
We investigated the relationship of dissolved oxygen and culture redox potential (CRP) on amino acid production. Corynebacterium glutamicum ATCC 14296 was used for all experiments. The fermentation can be divided into a growth phase and a production phase. Our results indicate that in order to get higher amino acid production, a lower oxygen supply during the exponential phase is favored. A higher oxygen supply rate appears to be necessary during the production phase. Culture redox potential (CRP) was used to monitor the fermentation. CRP readings were observed to drop to a characteristic minimum value as the metabolic state changed from a growth to production phase. This was evidenced by the commencement of amino acid production and a simultaneous uptake of lactate. Upon lactate exhaustion, the CRP increased abruptly. At the same time, maximal amino acid yields were observed. By the use of minimum CRP as an indication of metabolic phase changes, the agitation rate was changed to increase oxygen supply during the production phase. This significantly increased amino acid production. These results show that culture redox potential measurements can be used to monitor and optimize amino acid production by process manipulation.


Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.
The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the Rh2 criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well.


Localization of pulmonary carbonyl reductase in guinea pig and mouse: enzyme histochemical and immunohistochemical studies.
We studied the localization of carbonyl reductase (E.C. 18.104.22.168) in guinea pig and mouse lung by enzyme histochemistry and immunohistochemistry, using antibodies against the guinea pig lung enzyme which crossreacted with the lung enzymes of both animals. Carbonyl reductase activity was detectable in the bronchiolar epithelial cells of small airways and in alveolar cells. In the immunohistochemical staining for carbonyl reductase, the reaction was strongest in the non-ciliated bronchiolar cells (Clara cells) and was weak in the ciliated cells and type II alveolar pneumocytes. Injection of a single dose of naphthalene led to significant impairment of carbonyl reductase activity and of microsomal mixed-function oxidase activities in mouse lung, with a marked decrease in both activity and immunoreactive staining in the bronchiolar epithelial cells. The results indicate that carbonyl reductase is localized primarily in the Clara cells, which are known to be sites of pulmonary drug metabolism.