Insurance-based Disparities in Gastro-Entero-Pancreatic Neuroendocrine Tumor Patients.
In the United States, uninsurance remains a major barrier in accessing health care for many citizens and residents. Studies have shown that uninsured patients with many cancers and chronic diseases have worse survival than insured patients. A recent study similarly showed that uninsured patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) have significantly shortened survival. While GEP-NETs are indolent tumors with generally favorable prognosis, comprehensive care involves years of surveillance, imaging, and treatment following resection, all of which carry a large financial burden. In this commentary, we expand on these findings as they relate to insurance-based disparities as well as management and policy implications.


COUP-TFII is essential for metanephric mesenchyme formation and kidney precursor cell survival.
Development of the metanephric kidney in mammals requires complex reciprocal tissue interactions between the ureteric epithelium and the mesenchyme. It is believed that Gdnf, produced in the metanephric mesenchyme, activates Ret signaling in the Wolffian duct to initiate the formation of the metanephros. However, the molecular mechanism for induction of Gdnf in the metanephric mesenchyme is not completely defined. Previous studies demonstrated that during the early stages of kidney development, loss of Osr1, Eya1, Pax2 or Wt1 gene function in the metanephric mesenchyme compromises the formation of the kidney. Moreover, it has been shown that the Hox11-Eya1-Pax2 complex activates the expression of Six2 and Gdnf in the metanephric mesenchyme to drive nephrogenesis. Here, we demonstrate that the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII, also known as Nr2f2) is required for the specification of the metanephric mesenchyme. Deletion of COUP-TFII at E7.5 results in improper differentiation of the metanephric mesenchyme and absence of essential developmental regulators, such as Eya1, Six2, Pax2 and Gdnf. Importantly, we show that COUP-TFII directly regulates the expression of both Eya1 and Wt1 in the metanephric mesenchyme. Our findings reveal, for the first time, that COUP-TFII plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of Eya1 and Wt1 expression.


Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation.
Loss of mitochondrial membrane integrity and the resulting release of apoptogenic factors may play a critical role in mediating hippocampal neurodegeneration after transient global ischemia. In the present study, the authors have cloned and characterized the rat cDNA encoding apoptosis-inducing factor (AIF), an intramitochondrial protein that promotes cell death in a caspase-independent manner upon release into nonmitochondrial compartments. In contrast to the expression patterns of a number of apoptosis-regulatory gene products during brain development, the expression of AIF protein increases gradually with brain maturation and peaks in adulthood. In a rat model of transient global ischemia, AIF was found to translocate from mitochondria to the nucleus in the hippocampal CA1 neurons after ischemia and to manifest a DNA-degrading activity that mimicked the purified AIF protein and was inhibitable by AIF immunodepletion. The temporal profile of AIF translocation after ischemia (24 to 72 hours) coincided with the induction of large-scale DNA fragmentation at the size of 50 kbp, a well-characterized hallmark of AIF-like activity but preceded the formation of internucleosomal DNA fragmentation (72 hours), a DNA degradation associated with the terminal stage of cell death. Further, the nuclear translocation of AIF after ischemia was not blocked by inhibiting caspase-3/-7 activities, but, as shown in neuronal cultures that were challenged with transient oxygen-glucose deprivation, it can be prevented by intracellular delivery of the mitochondria-associated antiapoptotic protein Bcl-xL. The results presented here strongly suggest that mitochondrial release of AIF may be an important factor, in addition to the previously reported cytochrome c and Smac, which could contribute to the selective vulnerability of CA1 neurons to transient global ischemic injury.


In vitro synthesis of biologically active transcripts of tomato black ring virus satellite RNA.
Synthetic transcripts of tomato black ring virus satellite RNA (TBRV satRNA), isolate L, were prepared from cDNA cloned in the Bluescribe transcription vector. Transcripts with 49 (T49L) or two (T2GL) extra nucleotides at their 5' ends and 42 extra nucleotides at their 3' ends were able to induce, but to different extents, the synthesis in vitro of the satRNA-encoded 48K protein. However, when inoculated into Chenopodium quinoa together with TBRV L genomic RNAs, only T2GL was biologically active, in the presence or absence of a 5' cap analogue in the transcription reactions. Analysis of the 5' and 3' termini of the satRNA isolated from plants showed that nonviral extensions were not maintained in the transcript progeny.


Fluorescent molecularly imprinted polymers based on 1,8-naphthalimide derivatives for efficiently recognition of cholic acid.
Fluorescent molecularly imprinted polymers (MIPs) have attracted increasing attentions in recent years due to their high selectivity and sensitivity for target molecules. In this study, two cholic acid imprinted fluorescent polymers, i.e., MIP1 and MIP2, were prepared using 4-dimethylamino-N-allylnaphthalimide (F1) and 4-piperazinyl-N-allylnaphthalimide (F2) as the fluorescent functional monomers, respectively. The fluorescence intensity of MIP1 decreased linearly with the increase of the template concentration in the range of 1.50-120.0 μM, while the fluorescence intensity of MIP2 increased linearly with the increase of the template concentration in the range of 0.40-110.0 μM. The detection limits of MIP1 and MIP2 for cholic acid were 0.42 and 0.083 μM, respectively. The mechanisms of the fluorescence responsive of the imprinted polymers were discussed. The results of fluorescence measurement and binding experiments demonstrated that both imprinted polymers have high recognition abilities and binding affinities for the template. The imprinted polymers have been successfully applied to the determination of cholic acid in human serums. The present study indicated that 1,8-naphthalimide can be used as a modular building block for design and construction of various fluorogenic molecularly imprinted materials for practical sensing and separation.


Beta-blockers and thoracic epidural analgesia. Cardioprotective and synergistic effects.
Seven groups of patients with and without hypertension or with ischaemic heart disease, treated with different beta blockers were investigated to study the circulatory effects of neurolept anaesthesia alone or combined with thoracic epidural analgesia from T4 to T12/L2 during abdominal surgery. The combination of thoracic epidural analgesia and neurolept anaesthesia in hypertensive subjects treated with non-cardioselective beta blockers induced slightly lower blood pressure than measured in similar patients on cardioselective beta blockers with neurolept anaesthesia only. Patients on non-selective beta blockers with intrinsic stimulatory activity (ISA) had higher blood pressure and heart rate after neurolept anaesthesia induction than patients on cardioselective blockers. During surgery, heart rate remained at a higher level in the patients treated with ISA blockers, whereas blood pressure increased to the same level as in patients with cardioselective blockers. Cardiovascular stability was, however, best maintained in the epidural group, where myocardial energy expenditure during maximal surgical stress was comparable to that in a group of healthy subjects with the same format of anaesthesia and significantly lower than in healthy subjects with neurolept anaesthesia alone. No circulatory side effects of the combination of thoracic epidural analgesia and beta blockade were seen. In patients with ischaemic heart disease, with or without non-selective beta blockade, similar haemodynamic changes were recorded following neurolept anaesthesia. During maximal surgical stress, unmasking of alpha adrenergic activity with marked rise in blood pressure was seen in the beta-blocked patients. Despite the more accelerated haemodynamic changes in the blocked patients, a lower increase in myocardial oxygen consumption was recorded compared with the non-blocked patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Influence of vehicular traffic density on hospital admissions due to respiratory tract cancer in the city of São Paulo, Brazil].
Pollution related to traffic is a major problem in urban centers and a large portion of the population is vulnerable to its health effects. This study sought to identify a potential association between hospital admissions due to respiratory tract cancer and vehicular traffic density in the city of São Paulo, Brazil. It is an ecological study of the public (Hospital Inpatient Authorization - AIH, in Portuguese) and private (Hospital Inpatient Communication - CIH, in Portuguese) health care systems, from 2004 to 2006, geocoded by individuals' residential addresses. Using a Besag-York-Mollié ecological model, we initially evaluated the relationship between number of cases of hospital admission due to respiratory tract cancer in each weighting area and the standardized co-variables: traffic density and Municipal Human Development Index (MHDI) as indicator of socioeconomic status. Using a classic Poisson model, we then evaluated the risk associated with growing traffic density categories. The Besag-York-Mollié model estimated a RR = 1.09 (95%CI: 1.02-1.15) and RR = 1.19 (95%CI: 1.10-1.29) of admission due to respiratory tract cancer for each increase of one standard deviation of traffic and MHDI, respectively. The Poisson model also showed a clear exposure-response gradient for admission due to respiratory tract cancer (IRR = 1.11; 95%CI: 1.07-1.15, for each 10 units of added traffic density). This study suggests that there is an association between residing in areas with high traffic density and hospital admissions due to respiratory tract cancer in the city of São Paulo.


Assessment of the electrochemical behavior of two-dimensional networks of single-walled carbon nanotubes.
Scanning electrochemical microscopy (SECM) has been employed in the feedback mode to assess the electrochemical behavior of two-dimensional networks of single-walled carbon nanotubes (SWNTs). It is shown that, even though the network comprises both metallic and semiconducting SWNTs, at high density (well above the percolation threshold for metallic SWNTs) and with approximately millimolar concentrations of redox species the network behaves as a thin metallic film, irrespective of the formal potential of the redox couple. This result is particularly striking since the fractional surface coverage of SWNTs is only approximately 1% and SECM delivers high mass transport rates to the network. Finite element simulations demonstrate that under these conditions diffusional overlap between neighboring SWNTs is significant so that planar diffusion prevails in the gap between the SECM tip and the underlying SWNT substrate. The SECM feedback response diminishes at higher concentrations of the redox species. However, wet gate measurements show that at the solution potentials of interest the conductivity is sufficiently high that lateral conductivity is not expected to be limiting. This suggests that reaction kinetics may be a limiting factor, especially since the low surface coverage of the SWNT network results in large fluxes to the SWNTs, which are characterized by a low density of electronic states. For electroanalytical purposes, significantly, two-dimensional SWNT networks can be considered as metallic films for typical millimolar concentrations employed in amperometry and voltammetry. Moreover, SWNT networks can be inexpensively and easily formed over large scales, opening up the possibility of further electroanalytical applications.


Positive regulatory gamma delta T cells in contact sensitivity: augmented responses by in vivo treatment with anti-gamma delta monoclonal antibody, or anti-V gamma 5 or V delta 4.
Contact sensitivity (CS) responses, induced by skin painting with reactive haptens like picryl chloride or oxazolone, are classical examples of in vivo immunity mediated by alpha beta T cells. Our previous studies showed that gamma delta T cells were required to assist the alpha beta CS-effector T cells in the successful adoptive cell transfer of CS responses. These spleen and lymph node-derived gamma delta+ CS-assisting regulatory cells were CD3+, CD4-CD8+, non-antigen-specific, and non-MHC-restricted, and preferentially expressed V gamma 5 and V delta 4 variable regions. In the current study we show that systemic treatment of mice in vivo with anti-gamma delta mAb, produced a similar positive influence on CS responses in two different systems: i.e. active sensitization, or adoptive cell transfer. In addition to augmented CS responses produced by treatment with pan anti-gamma delta TCR mAb, anti-gamma delta-V region mAb were examined, and augmentation of CS also was produced by anti-V gamma 5 and anti-V delta 4 mAb, the V regions determined previously to be preferentially expressed on gamma delta CS-assisting cells. We speculate that the positive influence of anti-gamma delta mAb was not caused by quantitative changes in gamma delta T cells, because FACS studies demonstrated a lack of in vivo depletion of peripheral blood and lymphoid gamma delta T cells, and also no depletion of epidermal dendritic gamma delta T cells (DETC), in mice treated with anti-gamma delta TCR mAb. Instead, our data favor the hypothesis that CS-assisting gamma delta T cells can be activated in vivo by anti-gamma delta TCR mAb interacting with their gamma delta TCR, at least with the short term protocols we employed, resulting in augmentation of CS responses perhaps by releasing positively-acting factors, such as certain cytokines.


Evaluation of a Serum Lung Cancer Biomarker Panel.
A panel of 3 serum proteins and 1 autoantibody has been developed to assist with the detection of lung cancer. We aimed to validate the accuracy of the biomarker panel in an independent test set and explore the impact of adding a fourth serum protein to the panel, as well as the impact of combining molecular and clinical variables. The training set of serum samples was purchased from commercially available biorepositories. The testing set was from a biorepository at the Cleveland Clinic. All lung cancer and control subjects were >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21-1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO-1 (New York esophageal cancer-1 antibody) was measured using immunoassay techniques. The multiple of the median method, multivariate logistic regression, and random forest modeling was used to analyze the results. The training set consisted of 604 patient samples (268 with lung cancer and 336 controls) and the testing set of 400 patient samples (155 with lung cancer and 245 controls). With a threshold established from the training set, the sensitivity and specificity of both the 4- and 5-biomarker panels on the testing set was 49% and 96%, respectively. Models built on the testing set using only clinical variables had an area under the receiver operating characteristic curve of 0.68, using the biomarker panel 0.81 and by combining clinical and biomarker variables 0.86. This study validates the accuracy of a panel of proteins and an autoantibody in a population relevant to lung cancer detection and suggests a benefit to combining clinical features with the biomarker results.


Are neurological soft signs pre-existing markers in individuals with an at-risk mental state for psychosis?
Neurological soft signs (NSS) are more common in schizophrenic psychoses and in genetically high-risk individuals than in healthy controls. But nothing is known so far regarding individuals with a clinical at-risk mental state (ARMS). The goals of our study therefore were (a) to compare the NSS frequency in ARMS individuals to that of first-episode psychosis (FEP) patients and (b) to test whether NSS could predict the transition to psychosis. Neurological soft signs were assessed using a shortened version of the Neurological Evaluation Scale (NES). Fifty-three ARMS individuals (16 with later transition to psychosis=ARMS-T, and 37 without transition=ARMS-NT) and 27 FEP patients were recruited through the Basel Early Detection Clinic FePsy. Of the FEP patients 37% showed NSS. We found no significant differences between FEP and ARMS-T patients or between ARMS-NT and ARMS-T. Our findings of NSS being present already before transition to psychosis to the same extent as after transition provide further support to the neurodevelopmental hypothesis of schizophrenic psychoses. Furthermore, our findings might indicate that ARMS-NT individuals also suffer from some sort of neurodevelopmental abnormalities.


Chiral HPLC Separation, Absolute Structural Elucidation, and Determination of Stereochemical Stability of trans-Bis[2-(2-pyridinyl)aminophenolato] Cyclotriphosphazene.
Chiral high-performance liquid chromatography (HPLC) separation of trans-bis[2-(2-pyridyl)aminophenolato] dichlorocyclotriphosphazene was achieved and the absolute configuration of was assigned to be S,S by single-crystal X-ray structural analysis. The optically pure 1,2-diphenyl-1,2-ethanediolate derivatives (+)- and (-)- were synthesized by the reactions of and with (R,R)-hydrobenzoin, respectively, in refluxing toluene in the presence of an excess amount of triethylamine and a catalytic amount of 4-(dimethylamino)pyridine. The racemization of the enantiomers of and the epimerization of diastereomers of 2 were not observed in refluxing toluene neither under acidic nor basic conditions. The stereochemistry of was confirmed by the crystal structure of (+)- and bis[(4-methyl-2-pyridyl)oxy]cyclotriphosphazene derived from . Chirality 28:556-561, 2016. © 2016 Wiley Periodicals, Inc.


Note: Hollow cathode lamp with integral, high optical efficiency isolation valve: a modular vacuum ultraviolet source.
The design and operating conditions of a hollow cathode discharge lamp for the generation of vacuum ultraviolet radiation, suitable for ultrahigh vacuum (UHV) application, are described in detail. The design is easily constructed, and modular, allowing it to be adapted to different experimental requirements. A thin isolation valve is built into one of the differential pumping stages, isolating the discharge section from the UHV section, both for vacuum safety and to allow lamp maintenance without venting the UHV chamber. The lamp has been used both for ultraviolet photoelectron spectroscopy of surfaces and as a "soft" photoionization source for gas-phase mass spectrometry.


You're the Flight Surgeon.
Haight SP, Sholes PC, Pokorny WB, Brandenburg LR. You're the flight surgeon: other causes of mechanical low back pain. Aerosp Med Hum Perform. 2018; 89(4):411-413.


Attitudes and barriers to the introduction of umbilical cord blood gas and lactate analysis at birth.
Despite a growing body of evidence demonstrating the value of universal umbilical cord blood gas analysis (UCBGA), there remains reluctance in some maternity units to adopt universal testing. Identify perceived barriers and benefits of universal UCBGA. Medical and midwifery staff involved in intrapartum care at four level two maternity units (one metropolitan and three regional) completed questionnaires evaluating attitudes to UCBGA. Questionnaires included 13 statements with responses ranging from strongly agree to strongly disagree and background demographic data. Most respondents considered UCBGA beneficial to perinatal care (n = 72; 67.3%), with only nine individuals (8.4%) believing UCBGA had no place in perinatal care. The majority of respondents considered benefits of UCBGA to include being an effective and objective marker of neonatal status (n = 64; 59.8%), as well as playing a role in medicolegal issues (n = 74; 69.2%) and audit and teaching (n = 64; 59.8%). Respondents considered that barriers to universal UCBGA introduction included insufficient time following delivery, increased workload and encroachment of technology into birth. The majority of respondents indicated support for UCBGA. Information derived from this study may be useful in identifying and resolving concerns prior to the introduction of UCBGA. Further, it could be useful in the preparation of education and implementation packages necessary for introduction of UCBGA.


Distribution of types for six PCR-based loci; LDLR, GYPA, HBGG, D7S8, GC and HLA-DQA1 in central Pyrenees and Teruel (Spain).
The PCR-based DNA loci LDLR, GYPA, HBGG, D7S8, GC and HLA DQA1 are widely used in forensic casework analyses. Population data on the distribution of allele frequencies are desired to estimate the rarity of a DNA profile. We studied the allele distributions at these forensically important DNA markers in two Spanish populations (Central Pyrenees and Teruel). Results were in agreement with Hardy-Weinberg expectations. Furthermore, there was little evidence for departures from expectation of independence between loci within the two sample populations. Tests for homogeneity were carried out between the two Spanish populations and a U.S. Caucasian population.


Pancoast's syndrome due to metastatic carcinoma from the stomach.
We describe here a case of Pancoast's syndrome due to metastatic carcinoma from the stomach. Although obtaining a tissue diagnosis is often difficult with apical lesions, transbronchial or percutaneous needle biopsy is the procedure of choice since a certain number of these cases are potentially curable.


Nursing research on the health of low-income women.
The purpose of this paper is to describe the scope of published nursing research on the health of low-income women. Williams' (1990) model of the relationship between socioeconomic status and health was used as a framework for the analysis. This model includes three major components: Medical Care, Psychosocial Factors, and Health Outcomes. There is a body of published nursing research that addresses a range of health issues of low-income women. Our search of English language literature published between 1989 and 1995 retrieved 49 articles that met the inclusion criteria. Most of the nursing studies examined a portion of Williams' model but did not address multiple components. The most frequently addressed component was Psychosocial Factors, particularly health practices, stress and coping, and social ties. Williams' model was an effective framework to classify nursing research. Results of our analysis suggest that further research is needed on the pathways by which low income influences health and on the effectiveness of nursing interventions.


Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.
Twenty asthmatic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients, 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.


Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers.
Except for the role of NO in the activation of guanylate cyclase, which is well established, the involvement of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in signal transduction remains controversial, despite a large body of evidence suggestive of their participation in a variety of signaling pathways. Several problems have limited their acceptance as signaling molecules, with the major one being the difficulty in identifying the specific targets for each pathway and the chemical reactions supporting reversible oxidation of these signaling components, consistent with a second messenger role for ROS and RNS. Nevertheless, it has become clear that cysteine residues in the thiolate (i.e., ionized) form that are found in some proteins can be specific targets for reaction with H(2)O(2) and RNS. This review focuses on the chemistry of the reversible oxidation of those thiolates, with a particular emphasis on the critical thiolate found in protein tyrosine phosphatases as an example.


Prediction of solid fraction from powder mixtures based on single component compression analysis.
The aim of this study was to provide a systematic evaluation of various compression models (Percolation, Kawakita, Exponential model) in respect to predict tablet́s solid fraction for direct compression mixtures, based on single component compression analysis. Four mixtures were compressed over a wide pressure range at various fractions of microcrystalline cellulose (MCC) and pre-agglomerated lactose monohydrate (LAC) to compare an adjusted Percolation, Kawakita and a simple Exponential model. Based on single compression analysis of the pure excipients and application of these models, it was possible to predict the solid fraction of all mixtures. The Kawakita model showed overall superior prediction accuracy, whereas the Percolation model resulted in the best fit for mixtures containing microcrystalline cellulose in a range of 72%-48%. Both models were in good agreement at residuals below 3%.


CA-125 in Disease Progression and Treatment of Lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, levels of cancer antigen 125 (CA-125), an ovarian cancer biomarker, can be elevated in patients with LAM. We hypothesized that elevated serum CA-125 levels seen in some patients with LAM were due to LAM, not other malignancies, and might respond to sirolimus treatment. Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by using immunohistochemical analysis. Almost 25% of patients with LAM had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV1, premenopausal status, and pleural effusion in a multivariate model (each P < .001). Serum CA-125 levels decreased following sirolimus treatment (P = .002). CA-125 and α-smooth muscle actin were co-expressed in LAM lung nodules. Higher serum CA-125 levels were associated with pleural effusions and reduced pulmonary function and were decreased with sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.


Regulation of NRAMP1 gene expression by 1alpha,25-dihydroxy-vitamin D(3) in HL-60 phagocytes.
The natural resistance-associated macrophage protein 1 (Nramp1) is a proton-dependent transporter of divalent metals. We studied NRAMP1 expression during HL-60 differentiation induced by VD and VD agonists. NRAMP1 and CD14 gene expression differed in kinetics of induction, mRNA levels and stability, and response to VD combined with PMA, whereas a combination of VD and IFN-gamma induced similar up-regulation. NRAMP1 protein expression paralleled the accumulation of mRNA and was localized in the phagosomal membrane after phagocytosis. A promoter construct extending 647 bp upstream of NRAMP1 ATG showed myeloid-specific transcription in transient transfection assays, which was up-regulated by VD in HL-60. In HL-60 clones stably transfected with this construct, transcription was apparently induced through indirect VD genomic effects, and there was accordance between the levels of reporter transcription and endogenous NRAMP1 mRNA in response to VD but not to IFN-gamma. Thus, VD genomic effects stimulate NRAMP1 transcription and protein expression in maturing phagocytes.


Large sample test of defibrillation waveform sensitivity.
An unknown mechanism causes defibrillation efficacy to be sensitive to the temporal pattern (waveform) of the delivered energy. Using a guinea pig model, we tested hypotheses in 140 defibrillation waveforms. Two hundred seven male guinea pigs (950 +/- 100 g) were instrumented to continuously monitor the ECG and an optical plethysmographic signal from a forepaw. Two amplifiers served as a voltage-based defibrillator with a maximum output of 400 V at 2 A. Defibrillation electrodes (12-mm diameter) were placed 40 mm apart on the thorax. Thirty ventricular fibrillation episodes were induced where the first 10 episodes were used to estimate ED50 for a biphasic pulse (7/2 msec) and the remaining episodes were defibrillated with 18 test waveforms and two control waveforms all at the ED50 energy. Seven groups of 20 waveforms were tested. We directly tested hypotheses based on charge banking/burping, frequency concentration, and stimulus strength/duration. Of the hypotheses tested, nine are able to predict at least a 10% change in efficacy (P < 0.05): parabolic fit to duration; maximum, minimum, and remaining delivered charge; power at peak frequency; stimulus charge; and maximum, minimum, and maximum of the absolute value of stimulus strength. However, of these, only three are independent predictors of waveform efficacy (P < 0.05, near-minimum residual variance): power at peak frequency; parabolic fit to the stimulus duration; and minimum stimulus strength. Stimulus strength and duration are the main determinants of the efficacy of a defibrillation waveform.


Fish allergy: in review.
Globally, the rising consumption of fish and its derivatives, due to its nutritional value and divergence of international cuisines, has led to an increase in reports of adverse reactions to fish. Reactions to fish are not only mediated by the immune system causing allergies, but are often caused by various toxins and parasites including ciguatera and Anisakis. Allergic reactions to fish can be serious and life threatening and children usually do not outgrow this type of food allergy. The route of exposure is not only restricted to ingestion but include manual handling and inhalation of cooking vapors in the domestic and occupational environment. Prevalence rates of self-reported fish allergy range from 0.2 to 2.29 % in the general population, but can reach up to 8 % among fish processing workers. Fish allergy seems to vary with geographical eating habits, type of fish processing, and fish species exposure. The major fish allergen characterized is parvalbumin in addition to several less well-known allergens. This contemporary review discusses interesting and new findings in the area of fish allergy including demographics, novel allergens identified, immunological mechanisms of sensitization, and innovative approaches in diagnosing and managing this life-long disease.


Self-management treatment of drooling: a case series.
Behavioral treatment of drooling is advocated widely, but evidence of its effectiveness is lacking. In a center-based case-series study, 10 participants with severe drooling were taught self-management skills to reduce drooling. Following treatment, all participants remained dry for intervals of 30-60 min, while being engaged in daily activities. Generalization to the classroom occurred in each participant. For three participants, maintenance of treatment effect was established at 6 and 24 weeks. Seven participants failed to maintain self-management skills at follow-up. Although the self-management procedure showed promising results, further adaptations are required to improve efficacy, generalization, and maintenance.


DXA variations and fractures after simultaneous pancreas-renal transplantation: results of a long-term follow-up.
Simultaneous pancreas-kidney transplant (SPKT) has been associated with an increased risk of fracture. We prospectively evaluated the long-term effects of SPKT on bone mineral density (BMD) and fracture risk. During 1998 to 1999, 29 participants were consecutively monitored, and 18 completed the 10-year follow-up. Laboratory blood parameters, lumbar-dorsal radiography, and DEXA were determined at baseline, 1 year, and 10 years. The medical record was reviewed for peripheral fragility fractures. The BMD revealed no changes between baseline and 1 or 10 years after SPKT. Lumbar-dorsal radiography showed 0% asymptomatic vertebral fractures at baseline and after 1 year with 16.7% at 10 years. Vertebral asymptomatic fractures were correlated with acute rejection episodes (P = 0.025). During the first year, no nonvertebral fractures were identified. At the end of the follow-up, 5 nonvertebral fractures in 4 patients were reported. Dorsal and lumbar spine fractures correlated with lumbar spine t score (r = -0.591, P =0.022) and peripheral fractures with femoral neck t score (r = -0.633, P = 0.013). Patients with SPKT did not show long-term significant loss of BMD. The incidence of vertebral fractures was low and related to steroid treatment; the incidence of peripheral fractures was higher and independent of clinical or biochemical parameters.


An isolated vestibulocochlear symptom preceding brainstem infarction due to basilar artery occlusion.
To describe unilateral hearing loss preceding brainstem infarction due to basilar artery occlusion. Clinical capsule report. University hospital. A 67-year-old woman presented with unilateral acute hearing loss with dizziness as a sole prodromal manifestation of basilar artery occlusion for 2 weeks before the appearance of motor and oculomotor deficits. Otologic examinations and magnetic resonance imaging (MRI) were performed. A pure-tone audiogram showed unilateral profound sensorineural hearing loss preceding brainstem occlusion. Diffusion-weighted MR image demonstrated acute infarction around the paramedian area of the upper and middle pons, although T2-weighted MR image showed a normal brain image except for occlusion of the basilar artery. Acute unilateral hearing loss could be a prodrome of basilar artery occlusion. Clinicians must consider this possibility, especially in patients at high risk of brainstem infarction.


Characterizing cross-subject spatial interaction patterns in functional magnetic resonance imaging studies: A two-stage point-process model.
We develop a two-stage spatial point process model that introduces new characterizations of activation patterns in multisubject functional Magnetic Resonance Imaging (fMRI) studies. Conventionally multisubject fMRI methods rely on combining information across subjects one voxel at a time in order to identify locations of peak activation in the brain. The two-stage model that we develop here addresses shortcomings of standard methods by explicitly modeling the spatial structure of functional signals and recognizing that corresponding cross-subject functional signals can be spatially misaligned. In our first stage analysis, we introduce a marked spatial point process model that captures the spatial features of the functional response and identifies a configuration of activation units for each subject. The locations of these activation units are used as input for the second stage model. The point process model of the second stage analysis is developed to characterize multisubject activation patterns by estimating the strength of cross-subject interactions at different spatial ranges. The model uses spatial neighborhoods to account for the cross-subject spatial misalignment in corresponding functional units. We applied our methods to an fMRI study of 21 individuals who performed an attention test. We identified four brain regions that are involved in the test and found that our model results agree well with our understanding of how these regions engage with the tasks performed during the attention test. Our results highlighted that cross-subject interactions are stronger in brain areas that have a more specific function in performing the experimental tasks than in other areas.


Ocular Features in a Case of Nevus of Ota.
Oculodermal melanocytosis, also known as Nevus of Ota, is a hamartomatous melanocytic nevus of dermal melanocytes. It presents as a bluish grey patch on the face, which may be congenital or acquired involving the area of distribution of the ophthalmic and maxillary branches of the trigeminal nerve. The nevus can be unilateral or bilateral, and, in addition to skin, it may involve ocular and oral mucosal surfaces. It is a rare disorder and the ocular complications, such as glaucoma and melanoma, may be vision or life-threatening. Here, we report a 26-year male who presented with decreased vision in his left eye. On detailed examination, he turned out to be a case of nevus of Ota.


Should Genetic Testing be Offered for Children? The Perspectives of Adolescents and Emerging Adults in Families with Li-Fraumeni Syndrome.
Whether children should be offered genetic testing for cancer risk is much debated but young voices are rarely heard in these conversations. The current study explored perspectives of genetic testing held by adolescents and emerging adults in families with Li Fraumeni syndrome (LFS). Twelve 12- to 25-year-olds in families with LFS completed qualitative interviews for this study. All believed that testing should be offered for children but many qualified this statement saying parental approval would be needed and testing should be optional. Genetic testing was seen as way to learn of risk status, allow for disease prevention efforts, and reduce uncertainty and anxiety. Perceived disadvantages included negative emotions associated with the testing result. Participants generally felt that children should be involved in the testing decision, but that parents could unilaterally decide to have a child tested in certain circumstances (e.g., young age, high risk). All who were aware of having been tested and of their test result (n = 7; 4 positive) said testing had no negative impact on their outlook and they agreed with the decision to undergo testing. Implications of these findings for clinical practice and future research are discussed.


Echocardiogram Unmasked Hemodynamic Advantage of Atrial Pacing in Securing Ventricular Preload in a Fontan Patient with Junctional Rhythm.
While the advancement of perioperative management has expanded Fontan candidacy, not all patients have a successful postoperative course. Our case was a right isomerism patient who could not leave the ICU due to high central venous pressure and low output syndrome. Initial observation of the monitor ECG showed his rhythm to be supraventricular, however, an echocardiogram indicated simultaneous contraction of the atrium and ventricle, implying a junctional rhythm. While neither central venous pressure nor blood pressure improved with temporary pacing, better central venous and pulmonary venous blood flow patterns during pacing unraveled its positive impact. The patient successfully left the ICU after permanent pacing implantation. Hemodynamic study revealed a beneficial impact of atrial pacing in securing cardiac output and ventricular preload, lowering central venous pressure, and shortening blood transit time, which is partly attributed to the optimization of the fenestration function in reservation of the preload. Our case emphasizes the significant advantage of atrial pacing in a failing Fontan patient with junctional rhythm by reducing venous congestion and maximizing the benefit of fenestration.


Maternal sleep quality during pregnancy is associated with neonatal auditory ERPs.
Poor maternal sleep quality during pregnancy may act as a prenatal stress factor for the fetus and associate with neonate neurocognition, for example via fetal programming. The impacts of worsened maternal sleep on neonatal development and, more specifically on neonatal auditory brain responses, have not been studied. A total of 155 mother-neonate dyads drawn from the FinnBrain Birth Cohort Study participated in our study including maternal self-report questionnaires on sleep at gestational week 24 and an event-related potential (ERP) measurement among 1-2-day-old neonates. For sleep quality assessment, the Basic Nordic Sleep Questionnaire (BNSQ) was used and calculated scores for (1) insomnia, (2) subjective sleep loss and (3) sleepiness were formed and applied in the analyses. In the auditory ERP protocol, three emotionally uttered pseudo words (in happy, angry and sad valence) were presented among neutrally uttered pseudo words. To study the relations between prenatal maternal sleep quality and auditory emotion-related ERP responses, mixed-effects regression models were computed for early (100-200 ms) and late (300-500 ms) ERP response time-windows. All of the selected BNSQ scores were associated with neonatal ERP responses for happy and angry emotion stimuli (sleep loss and sleepiness in the early, and insomnia, sleep loss and sleepiness in the late time-window). For sad stimuli, only maternal sleep loss predicted the neonatal ERP response in the late time-window, likely because the overall ERP was weakest in the sad condition. We conclude that maternal sleep quality during pregnancy is associated with changes in neonatal auditory ERP responses.


Metabolic Labeling and Profiling of Transfer RNAs Using Macroarrays.
Transfer RNAs (tRNA) are abundant short non-coding RNA species that are typically 76 to 90 nucleotides in length. tRNAs are directly responsible for protein synthesis by translating codons in mRNA into amino acid sequences. tRNAs were long considered as house-keeping molecules that lacked regulatory functions. However, a growing body of evidence indicates that cellular tRNA levels fluctuate in correspondence to varying conditions such as cell type, environment, and stress. The fluctuation of tRNA expression directly influences gene translation, favoring or repressing the expression of particular proteins. Ultimately comprehending the dynamic of protein synthesis requires the development of methods able to deliver high-quality tRNA profiles. The method that we present here is named SPOt, which stands for Streamlined Platform for Observing tRNA. SPOt consists of three steps starting with metabolic labeling of cell cultures with radioactive orthophosphate, followed by guanidinium thiocyanate-phenol-chloroform extraction of radioactive total RNAs and finally hybridization on in-house printed macroarrays. tRNA levels are estimated by quantifying the radioactivity intensities at each probe spot. In the protocol presented here we profile tRNAs in Mycobacterium smegmatis mc2155, a nonpathogenic bacterium often used as a model organism to study tuberculosis.


Limited phenotypic plasticity in range-edge populations: a comparison of co-occurring populations of two Agrimonia species with different geographical distributions.
Increased importance of genetic drift and selection for stress resistance have been predicted to lead to a reduction in the degree of phenotypic plasticity in populations at margins of a species' geographical range, relative to those in the centre. We examined the effect of population positioning within the species range on degree of active morphological plasticity to vegetation shade. Importantly, we discriminated between active, size-independent morphological adjustments in response to shade and passive changes in morphology caused by the dependence of morphological traits on plant size, as only the former are considered to be adaptive. Two closely related and ecologically similar Agrimonia species were examined in the same geographical location, where one species reaches the edge of its distribution (Agrimonia pilosa) and the other does not (A. eupatoria). Plasticity to light availability is likely to be advantageous for both species as they occupy habitats with variable light conditions. However, we hypothesised that high levels of environmental stress should lead to reduced active plasticity in marginal compared with more central populations. Agrimonia eupatoria exhibited active adjustments in leaf morphology in response to tree shade, and in elongation of stems and inflorescences in response to herbaceous shade. In contrast, A. pilosa exhibited very limited active plasticity. High active plasticity allowed A. eupatoria to retain constant shoot growth in a wide range of light conditions, while the lack of active plasticity in A. pilosa resulted in a strong dependence of shoot growth on light availability. We propose that high levels of environmental stress in marginal areas of a species' range may lead to a significant reduction in the degree of active plasticity. Our results clearly indicate that discrimination between active and passive plasticity is crucial for reaching valid conclusions about differences in adaptive plasticity between marginal and non-marginal populations.


Medical surveillance of workers previously exposed to asbestos.
According to current Italian law health surveillance of workers exposed to asbestos in the past must be maintained even after cessation of asbestos exposure (D.Lgs. 277/91). The law, however, makes no reference to timescales or time limits for clinical monitoring, nor to who is responsible. The main aims of health surveillance of individuals formerly exposed to asbestos can be summarized as follows: early diagnosis of the principal diseases associated with asbestos; counselling for workers; work-related disease certification; epidemiological studies. Medical check-ups entail a complete personal and work history, Chest X-Ray, respiratory function tests, TLCO. In all cases the worker must undergo a LDCT. We propose two new possible biological markers for the health surveillance of past-exposed patients: serum mesothelin and osteopontin.


State-of-the-art of the hyphenation of capillary electrochromatography with mass spectrometry.
The high separation efficiency and loading capacity of capillary electrochromatography (CEC) make it an attractive separation mode for coupling with mass spectrometry (MS), which has the ability to unambiguously identify analytes with high selectivity and sensitivity. We present an overview of recent advances on both instrumentation and separation columns employed in CEC-MS systems. In particular, the main characteristics of the stationary phases, as well as the configurations of the column outlet that are related with the coupling arrangements of the MS ionization sources, are reported. At present, packed columns and conventional electrospray ionization (ESI) sources are mainly employed in CEC-MS. Nevertheless, the use of monolithic capillary columns and nanoelectrospray sources has the potential for wide acceptance in the next future. Moreover, the main features of several mass analyzers including ion trap, quadrupole, time-of-flight, magnetic sector, and Fourier transform-ion cyclotron resonance are examined. Finally, current applications of this technology, mainly in the pharmaceutical field and proteomics, are reviewed.


Bone metabolism in quadriplegia: dissociation between calciuria and hydroxyprolinuria.
Relationships between duration of paralysis, recumbency, muscular activity, and urinary loss of calcium (Cau), phosphorus (Pu), and hydroxyproline (OHPu) were studied daily in 32 traumatic quadriplegic patients during comprehensive rehabilitation and randomly in those readmitted for treatment. Within days after onset, quadriplegic patients had increases in Pu, then OHPu, and finally, Cau. Patients actively engaged in rehabilitation exercises showed a steady fall in OHPu, whereas CAU remained high for up to 18 months. Patients paralyzed for over 18 months (late) had low Cau, Pu and OHPu; but if the patients were kept in bed, OHPu increased rapidly. Patients with early quadriplegia have an increased bone remodeling, suggesting that the excess OHPu and Cau are derived from resorbed bone. Patients with late quadriplegia have little bone remodeling, therefore the excess OHPu occurring during recumbency may be derived from the resorption of new collagen produced during the removal of weight bearing without further change in muscular activity. Resorbed new collagen is excreted in part as large, OHP-containing polypeptides; these were found in the urine of quadriplegic patients, and therefore were present in blood and may play a role in initiating ectopic bone and renal calculi. The presence of OHP in 11 bladder calculi from quadriplegic patients tends to support this hypothesis. These studies indicate that muscular activity and weight bearing influence the bone metabolism of quadriplegic patients and suggest that the presence in body fluids of increased catabolic products from bone may have a role in bone-related complications.


Forecasting Groundwater Temperature with Linear Regression Models Using Historical Data.
Although temperature is an important determinant of many biogeochemical processes in groundwater, very few studies have attempted to forecast the response of groundwater temperature to future climate warming. Using a composite linear regression model based on the lagged relationship between historical groundwater and regional air temperature data, empirical forecasts were made of groundwater temperature in several aquifers in Switzerland up to the end of the current century. The model was fed with regional air temperature projections calculated for greenhouse-gas emissions scenarios A2, A1B, and RCP3PD. Model evaluation revealed that the approach taken is adequate only when the data used to calibrate the models are sufficiently long and contain sufficient variability. These conditions were satisfied for three aquifers, all fed by riverbank infiltration. The forecasts suggest that with respect to the reference period 1980 to 2009, groundwater temperature in these aquifers will most likely increase by 1.1 to 3.8 K by the end of the current century, depending on the greenhouse-gas emissions scenario employed.


Time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis of the application of a cationic conditioner to "clean" hair.
In this study the applicability of the surface-sensitive ToF-SIMS technique to hair analysis and associated aqueous processing is evaluated. ToF-SIMS analysis of "as received" human hair indicates the presence of silicones, anionic surfactants, and cationic conditioners, from previous treatments, on the fiber surface. Cleaning of the hair with SLS or SLES results in adsorption of the surfactants onto the fiber surface. In particular, the more non-polar surfactant components have greater substantivity for the fiber surface, as indicated by the relative increase in their ToF-SIMS intensity. Application of the Incroquat Behenyl 18-MEA conditioner to both "virgin" and bleached hair results in the adsorption of the cationic C18, C20, C22, and C21 surfactant components onto the hair surface. The ToF-SIMS data indicate higher levels of conditioner on the bleached hair relative to the undamaged hair.


Multidrug-Resistant Aeromonas veronii Recovered from Channel Catfish (Ictalurus punctatus) in China: Prevalence and Mechanisms of Fluoroquinolone Resistance.
To emphasize the importance of the appropriate use of antibiotics in aquaculture systems, the prevalence of resistance to 25 antimicrobials was investigated in 42 Aeromonas veronii strains isolated from farm-raised channel catfish in China in 2006-2012. All experiments were based on minimal inhibitory concentrations (MICs), and susceptibility was assessed according to the Clinical and Laboratory Standards Institute. Some isolates displayed antibiotic resistance to the latest-generation fluoroquinolones (i.e., ciprofloxacin, levofloxacin, and norfloxacin) in vitro. Therefore, we screened for genes conferring resistance to fluoroquinolones and performed conjugation experiments to establish the resistance mechanisms. The antibiotic resistance rates were 14.29-21.42% to three kinds of fluoroquinolones: ciprofloxacin, levofloxacin, and norfloxacin. Among the 42 strains isolated, 15 carried the qnrS2 gene. The MICs of the fluoroquinolones in transconjugants with qnrS2 were more than fourfold higher compared with the recipient. Among the fluoroquinolone-resistant A. veronii strains, eight had point mutations in both gyrA codon 83 (Ser83→Ile83) and parC codon 87 (Ser87→Ile87). However, five isolates with point mutations in parC codon 52 remained susceptible to the three fluoroquinolones. In conclusion, the mechanisms of fluoroquinolone resistance in A. veronii isolates may be related to mutations in gyrA codon 83 and parC codon 87 and the presence of the qnrS2 gene.


Survey of state funds available for rehabilitation of patients with cleft lip/palate.
An effort was made to determine the amount of funds budgeted in each of the 50 U.S. states for total rehabilitation of patients with cleft lip and/or cleft palate. Questionnaires were sent following a pilot letter to the directors of each state Department of Health. Total funds per patient ranged from $17,442 for Delaware to a low of $426 for Wisconsin. Dental funds per patient ranged from $4,214 dollars for Wyoming to a low of $192 for New York.


Behavioral traits are affected by selective breeding for increased wheel-running behavior in mice.
Voluntary physical activity may be related to personality traits. Here, we investigated these relations in two mouse lines selectively bred for high voluntary wheel-running behavior and in one non-selected control line. Selection lines were more explorative and "information gathering" in the open-field test, either with increased upright positions or horizontal locomotion toward the middle ring. Furthermore, one of the selection lines had an increased risk-taking behavior relative to the control line in approaching a novel object placed in the center of the open field. However, anxiety behavior was increased in selection lines during the plus-maze test. Maze learning was not statistically different among lines, but routine behavior was increased in both selection lines when the maze exit after 2 days of testing was displaced. Specifically, in the displaced maze, selected mice traveled more frequently to the old, habituated exit, bypassing the new exit attached to their home cage. Although the generality of the results would need to be confirmed in future studies including all eight lines in the selection experiment, the increased routine and exploratory behavior (at least in the lines used in the present study) may be adaptive to sustain high activity levels.


Anteromedial Petrous (Gardner's) Triangle: Surgical Anatomy and Relevance for Endoscopic Endonasal Approach to the Petrous Apex and Petroclival Region.
Triangular corridors have been used as reliable surgical entry points for open transcranial approaches to the petrous apex (PA) and petroclival region (PCR). The endoscopic endonasal approaches have grown rapidly in the last decade, and the indications have advanced. The knowledge of accurate and reliable anatomic landmarks through endoscopic endonasal route is essential and remain to be established. The purpose of this study was to describe the feasibility and surgical exposure of the anteromedial petrous (Gardner's) triangle as a novel corridor to the PA and PCR. Five anatomic specimens were dissected. The PA and PCR were accessed through endoscopic endonasal approaches and contralateral transmaxillary approach. The limits of the anteromedial petrous (Gardner's) triangle were identified and dissected and associated measurements performed. The dissection was divided into 6 steps. The limits of the anteromedial petrous (Gardner's) triangle were identified and defined by the paraclival internal carotid artery anterolaterally, the abducens nerve posteromedially, and the petroclival synchondrosis inferiorly. Three lines were established following the limits of the triangle. The mean distance of the anterolateral limit was 10.03 mm (SD = 0.94), of the posteromedial limit was 20.06 mm (SD = 2.90), and of the inferior limit was 17.99 mm (SD = 2.99). The mean area was 87.56 mm2 (SD = 20.06). The 3 anatomic landmarks with a critical role to safely define the triangle were the pterygosphenoidal fissure, the petrosal process of the sphenoid bone, and the petroclival synchondrosis. The anteromedial (Gardner's) triangle is a well-defined bone corridor which provides access to the entire petrous bone and petroclival junction through endoscopic endonasal route. Regardless of the anatomic variations or tumor location, the landmarks of the abducens nerve, paraclival internal carotid artery, and petroclival synchondrosis are key for understanding lateral access to tumors extending from the clivus.


Retrofitting of a satellite repeat DNA-based murine artificial chromosome (ACes) to contain loxP recombination sites.
A satellite DNA-based mammalian artificial chromosome (ACes) was generated and subsequently modified by targeting of a loxP-red fluorescent protein (RFP) expression cassette via homologous recombination into a ribosomal DNA (rDNA)-containing locus. Clones containing correctly targeted ACes were identified by PCR from populations of RFP-expressing cells enriched by FACS sorting and were further characterized by fluorescent in situ hybridization. The targeted ACes maintained its ability to be purified to near homogeneity. Studies are currently underway to further characterize the functionality, carrying capacity, stability and transfectability of this modified ACes.


Genomic Diversity of Phages Infecting Probiotic Strains of Lactobacillus paracasei.
Strains of the Lactobacillus casei group have been extensively studied because some are used as probiotics in foods. Conversely, their phages have received much less attention. We analyzed the complete genome sequences of five L. paracasei temperate phages: CL1, CL2, iLp84, iLp1308, and iA2. Only phage iA2 could not replicate in an indicator strain. The genome lengths ranged from 34,155 bp (iA2) to 39,474 bp (CL1). Phages iA2 and iLp1308 (34,176 bp) possess the smallest genomes reported, thus far, for phages of the L. casei group. The GC contents of the five phage genomes ranged from 44.8 to 45.6%. As observed with many other phages, their genomes were organized as follows: genes coding for DNA packaging, morphogenesis, lysis, lysogeny, and replication. Phages CL1, CL2, and iLp1308 are highly related to each other. Phage iLp84 was also related to these three phages, but the similarities were limited to gene products involved in DNA packaging and structural proteins. Genomic fragments of phages CL1, CL2, iLp1308, and iLp84 were found in several genomes of L. casei strains. Prophage iA2 is unrelated to these four phages, but almost all of its genome was found in at least four L. casei strains. Overall, these phages are distinct from previously characterized Lactobacillus phages. Our results highlight the diversity of L. casei phages and indicate frequent DNA exchanges between phages and their hosts.


[Necrotizing enterocolitis].
Necrotizing enterocolitis (NEC) is an important cause of neonatal morbidity and mortality. During the last few years, there was an increase in the incidence of this disease, associated with a better knowledge of NEC, and an increase in survival rate, associated with the development, even from a technological point of view, of neonatal intensive care units. In this study, the authors first perform the diagnostic procedures and describe the anatomical and clinical characteristics of NEC, then evaluate by standard criteria a series of patients observed during the last 5 years, revising the various surgical treatments adopted and the results obtained.


On the voltage dependence of the mitochondrial permeability transition pore. A critical appraisal.
The mitochondrial permeability transition pore, a cyclosporin A-sensitive channel, can be opened by the addition of protonophoric uncouplers such as carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) after energy-dependent accumulation of Ca2+. We have proposed that the relevant effect of FCCP on the pore is membrane depolarization, suggesting that this channel is voltage-dependent (Bernardi, P. (1992) J. Biol. Chem. 267, 8334-8339). Here, we reconsider this hypothesis in the light of recent observations suggesting that increased production of reactive oxygen species and/or direct effects of FCCP, rather than membrane depolarization, could be the actual triggers of the FCCP-dependent permeability transition. We show that although reactive oxygen species can contribute to the permeability transition, pore opening by FCCP can still be observed under strict anaerobiosis after ATP-dependent Ca2+ accumulation and that the permeability transition can be induced by the addition of valinomycin to respiring mitochondria treated with nigericin in low potassium medium. In this system, pore opening in increasing fractions of mitochondria depends on the concentration of valinomycin, i.e. on the magnitude of the potassium current that determines the extent of membrane depolarization. We conclude that the permeability transition pore is directly modulated by the membrane potential in intact isolated rat liver mitochondria.


A theoretical and experimental investigation of the nonlinear acoustic response of acoustic insertion elements.
In a previous paper, a model was developed for the nonlinear acoustic resistance for compact insertion elements. Within the model, two loss coefficients are used to tune the model for each type of element, and data were used to empirically determine these coefficients for an area contraction. This paper extends the nonlinear model, developing expressions based on physical principles for the forward and reverse loss coefficients for both an area contraction and orifice. In addition, experimental data for the acoustic resistance of both elements was taken using an impedance tube. Utilizing the expressions developed, the model compares favorably with the experimental data.


Combination therapy of cancer with cancer vaccine and immune checkpoint inhibitors: A mathematical model.
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages. To address this question, we develop a mathematical model using a system of partial differential equations. The variables include dendritic and cancer cells, CD4+ and CD8+ T cells, IL-12 and IL-2, GM-CSF produced by the vaccine, and a T cell checkpoint inhibitor associated with PD-1. We use the model to explore the efficacy of the two drugs, separately and in combination, and compare the simulations with data from mouse experiments. We next introduce the concept of synergy between the drugs and develop a synergy map which suggests in what proportion to administer the drugs in order to achieve the maximum reduction of tumor volume under the constraint of maximum tolerated dose.


Development of an in vivo-relevant drug product performance method for an amorphous solid dispersion.
The purpose of this work was to develop a meaningful in vitro dissolution method for evacetrapib spray-dried dispersion (SDD) tablets that is discriminating for crystalline drug substance (DS) content. Justification of the method conditions included evaluation of dissolution media, rotation speed, surfactant selection and level of surfactant to achieve sink conditions. Discrimination was illustrated by testing SDD tablets spiked with 10%, 20%, and 30% crystalline DS. The results demonstrated a 13%, 22% and 32% drop in the dissolution end point, respectively, as compared to unspiked SDD tablets. Additionally, tablets containing crystalline DS and tablets containing SDD were tested in a relative bioavailability (RBA) study. Utilizing the proposed dissolution method, the dissolution end point of SDD tablets was determined to be approximately 4 fold higher than that of the tablets containing crystalline DS. These results compare favourably to the in vivo RBA study results where SDD tablets had a 4.6 fold increase in exposure compared to tablets containing crystalline DS.


Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening.
Telomere overhangs are essential for telomere end protection and telomerase extension, but how telomere overhangs are generated is unknown. Leading daughter strands synthesized by conventional semiconservation DNA replication are initially blunt, while lagging daughter strands are shorter by at least the size of the final RNA primer, which is thought to be located at extreme chromosome ends. We developed a variety of new approaches to define the steps in the processing of these overhangs. We show that the final lagging RNA primer is not terminal but is randomly positioned ~70-100 nucleotides from the ends and is not removed for more than an hour. This identifies an important intrinsic step in replicative aging. Telomeric termini are processed in two distinct phases. During the early phase, which occupies 1-2 h following replication of the duplex telomeric DNA, several steps occur on both leading and lagging daughters. Leading telomere processing remains incomplete until late S/G2, when the C-terminal nucleotide is specified-referred to as the late phase. These observations suggest the presence of previously unsuspected complexes and signaling events required for the replication of the ends of human chromosomes.


[Thoracic findings in neurofibromatosis].
Neurofibromatosis type 1 (von Recklinghausen' disease) is an autosomal dominant hereditary syndrome. It is characterized with multiple light brown (café-au-lait) spots, Lisch nodules and neurofibromas. Thorax and lungs are affected in various forms. Four cases with symptoms of thoracic involvement were investigated in our clinic. Mean age was 46. All cases had dyspnoea and cough; two of them had chest pain. Skin lesions of neurofibromatosis type 1 (NF 1) were pathologically confirmed in all cases. Moreover, case 3 had diffuse interstitial fibrosis and honeycomb pattern. Case 2 had thorax deformity, kyphoscoliosis and intrathoracic benign mass. Case 1 had two neurofibrosarcoma masses on the right hemithorax. Case 4 had multiple intrathoracic neurofibromas. Cases 1 and 3 died within two years after diagnosis due to malignancy and respiratory failure, respectively. Cases 2 and 4 are still under our control.


PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.
A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug.


Infusional 5-fluorouracil and X-ray therapy for non-resectable esophageal cancer.
Six patients with unresectable carcinoma of the esophagus received a combined course of external radiation therapy (1000 rads in four fractions in four days commencing on day 2) combined with constant infusional 5-fluorouracil (20 mg/kg every 24 hours for five days beginning on day 1). This program was repeated every other week to give a total x-ray dose of 6000 rads. This regimen has been well-tolerated by the majority of the patients and resulted in a complete response rate within the x-ray treatment field of 83% (5/6). All patients who showed a demonstrable systemic response to 5-fluorouracil reached complete response. The median survival has not yet been reached at six months with post-treatment survivors alive and without disease (four patients) at one, six, nine, and 22 months. Our previous median survival by x-ray therapy alone was 4 1/2 months. Toxicity consists primarily of hematologic suppression at a subclinical level. Although the length of therapy is substantial (11 weeks), the program appears tolerable and is capable of inducing long-term remissions. The program is currently being studied for dose escalation because neither local nor systemic side effects of a dose-limiting nature have been observed at 20 mg/kg 5-FU.


The role of stressful life events on the cortisol reactivity patterns of breast cancer survivors.
Atypical patterns of cortisol secretion following an acute stressor have been commonly reported in breast cancer survivors. Stressful life events have been associated with blunted acute cortisol levels in other populations. The purpose of this study was to explore the role of stressful life events on cortisol secretion patterns of breast cancer survivors following an acute stressor. The Trier Social Stress (TSST) was used to elicit a moderate stress response in breast cancer survivors (n = 19) and a control group (n = 17). Saliva samples were collected before, during and after the TSST to provide cortisol concentrations. During recovery, we recorded the frequency and subjective impact of stressful life events in the past year using the Life Experience Survey. Simple regressions analyses were performed; results suggest no group differences between the total number of stressful life events and their subjective impact. However, the total number of stressful life events as well as their subjective impact correlated negatively with the peak cortisol concentration in breast cancer survivors. The cumulative effect of stressful life events, positive and negative, may impact the endocrine stress system of breast cancer survivors more so than that of women with no history of cancer.


Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets.
Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues. Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression. Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species.


Trends in Hospital Admissions, Operative Approaches, and Mortality Related to Abdominal Aortic Aneurysms in England Between 1998 and 2020.
To assess trends in abdominal aortic aneurysm (AAA) hospital admissions, interventions, and aneurysm related mortality in England, and to examine the impact of endovascular repair on mortality for the years 1998 - 2020. Hospital admission and operative approach (endovascular aortic aneurysm repair, or open surgical repair [OSR]) using Hospital Episodes Statistics (HES), and aneurysm related mortality data from the Office for National Statistics for England standardised to the 2013 European Standard Population, were analysed using linear regression and Joinpoint regression analyses. Aneurysm related mortality was compared between the pre-endovascular era (1998 - 2010) and the endovascular era (2011 - 2019). A declining trend in hospital admission incidence was observed, mainly due to a decline in ruptured admissions from 34.6 per 100 000 (95% confidence interval [CI] 33.5 - 35.6) to 13.5 per 100 000 (95% CI 12.9 - 14.2; βi = -1.04, r2 = .97, p < .001). Operative interventions have been declining over the last 23 years mainly due to the statistically significant decline in open procedures (41.2 per 100 000 in 2000 [95% CI 40 - 42.3] to 9.6 per 100 000 [95% CI 9.1 - 10.1]; βi = -1.92, r2 = .95; p < .001). There was an increasing trend toward endovascular procedures (5.8 per 100 000 [95% CI 5.3 - 6.2] in 2006 to 16.9 per 100 000 [95% CI 16.2 - 17.5] in 2020; βi = .82, r2 = .30, p = .040). Reductions in aneurysm related mortality due to AAAs were observed for males and females, irrespective of age and rupture status. A significant decrease in hospital admissions for AAAs was observed over the last 23 years in England, paralleled by a shift toward endovascular repair and a decline in OSR. Declines in aneurysm related mortality were observed overall, and in the endovascular era irrespective of age, sex, and rupture status.


Adiabatic processes like isothermal processes.
The objective of this work is to show that adiabatic processes can be very similar to isothermal ones. First, we show that the criteria for the compatibility of linear-response theory with the second law of thermodynamics for thermally isolated systems are the same as those for systems performing isothermal processes. Motivated by such a result, we explore the thermodynamic consequences of the time-average excess work, observing an unexpected existence of a well-defined relaxation time for thermally isolated systems that obeys the second law of thermodynamics. This is justified by recognizing that such systems, in the usual sense, present random relaxation time, which can be "averaged" by taking the time average of the relaxation function. Such a proceeding is very similar to what happens in isothermal processes, where a stochastic average must be done on the relaxation function to have a well-defined relaxation time. In the end, we analyze the Landau-Zener model from this new point of view, discussing the construction of slowly-varying processes from linear-response theory and observing negative entropy production rates for nonmonotonic and rapid protocols.


IDH1/2 but not DNMT3A mutations are suitable targets for minimal residual disease monitoring in acute myeloid leukemia patients: a study by the Acute Leukemia French Association.
Acute myeloid leukemia (AML) is a heterogeneous disease. Even within the same NPM1-mutated genetic subgroup, some patients harbor additional mutations in FLT3, IDH1/2, DNMT3A or TET2. Recent studies have shown the prognostic significance of minimal residual disease (MRD) in AML but it remains to be determined which molecular markers are the most suitable for MRD monitoring. Recent advances in next-generation sequencing (NGS) have provided the opportunity to use multiple molecular markers. In this study, we used NGS technology to assess MRD in 31 AML patients enrolled in the ALFA-0701 trial and harboring NPM1 mutations associated to IDH1/2 or DNMT3A mutations. NPM1 mutation-based MRD monitoring was performed by RTqPCR. IDH1/2 and DNMT3A mutations were quantified by NGS using an Ion Torrent Proton instrument with high coverage (2 million reads per sample). The monitoringof IDH1/2 mutations showed that these mutations were reliable MRD markers that allowed the prediction of relapse in the majority of patients. Moreover, IDH1/2 mutation status predicted relapse or disease evolution in 100% of cases if we included the patient who developed myelodysplastic syndrome. In contrast, DNMT3A mutations were not correlated to the disease status, as we found that a preleukemic clone with DNMT3A mutation persisted in 40% of the patients who were in complete remission, reflecting the persistence of clonal hematopoiesis.


Connecting our resources: Louisiana's approach to community health network development.
Louisiana's rural community health systems are in crisis because of pressures fueled by the rising costs of health care, sustained poor health status, state budget shortfalls and changes in priorities, and a sliding rural economy. The development of community health networks is providing new infrastructure and capacity for communities to reprioritize, formulate innovative partnerships, and leverage new resources. Successful elements of Louisiana's network development experience include community commitment to engage in study and action; the availability of capable and motivated technical assistance; an approach that involves open-engagement, community-driven decision-making; and data-driven problem definition, prioritization, and solutions. Louisiana's experiences illustrate the benefits of developing networks along with, or as a result of, a community health plan. When a community owns its health improvement plan, it is more likely to support the new network as a structure for implementation. Broad-scale participation is also a principle of success. When social service agencies are included along with health agencies, more comprehensive strategies result, and they bring additional resources, resulting in more holistic solutions. The cases of 2 networks are presented as illustrations. One involves the facilitation of a community planning process for an existing network. The plan helped to expand the network's community connections and support and provided the content for a successful application for a Health Resources and Services Administration Community Access Program grant. In the second case, a new network was developed, and it leveraged federal funds from the federal Office of Rural Health Policy's Network Development Grant Program.


Mechanism of the ventilatory response to carbon monoxide.
The effects of carbon monoxide on ventilation were studied in unanesthetized goats. Responses to single breaths of 10-25% CO in O2, which rapidly raised carboxyhemoglobin (COHb) from 5 to 60%, were considered to reflect peripheral chemoreceptor-mediated reflexes whereas responses to continuous inhalation of 1% CO in O2, which slowly raised COHb from 0 to 60%, were considered to reflect both peripheral chemoreceptor and nonperipheral chemoreceptor mechanisms. In each of six goats, single breaths of CO failed to elicit any immediate ventilatory response. However, slow buildup of carboxyhemoglobinemia in the same animals always elicited ventilatory stimulation (from a mean of 7.43 to 16.02 liter/min, P less than 0.001) beginning 5-6 min after onset of 1% CO in O2 inhalation when COHb saturation reached 50-60%. In eight studies of six animals HCO3- concentration fell (from 21.3 to 15.8 meq/liter; P less than 0.001) and lactate concentration rose (from 2.5 to 4.2 meq/liter; P less than 0.05) in the cisternal cerebrospinal fluid during the CO-induced hyperpnea. Additional studies ruled out ventilatory stimulation from left heart failure or enhanced chemo-sensitivity to carbon dioxide. Although the delayed hyperpnea was associated with a hyperdynamic cardiovascular response to CO, blockade of these circulatory effects with propranolol (2 mg/kg) failed to abolish the delayed hyperpnea; however, the propranolol did unmask an element of ventilatory depression which preceded the hyperpnea. Conclusions were: (a) hyperventilation in response to CO inhalation is not mediated by the carotid bodies; (b) the delayed hyperpnea in response to CO inhalation is primarily due to brain-cerebrospinal fluid acidosis; (c) mobilization of body CO2 stores due to the circulatory response to CO may obscure an initial depression of ventilation by CO.


[Extracorporeal shock wave therapy for Peyronie's disease].
The efficiency of extracorporeal shock waves (SW) for Peyronie's disease (PD) is controversial. A systematic review of the literature published between 2000 and 2019 was conducted using the PRISMA methodology. We used Medline data with the following. "extracorporeal shock wave therapy" ; "Peyronie's disease"; "Sexuality"; Penile erection. Thirteen articles were selected. Our review showed that SW were beneficial in terms of pain. Regarding plaques size and penile curvature, the results remain divergent. SW may be useful in the management of pain in selected patients with PD. Its effectiveness on plaques size and penile curvature needs to be demonstrated through controlled and randomized trials. The population has to be targeted, and the treatment protocol must also be standardized.


Reuse of balloon catheters for coronary angioplasty: a potential cost-saving strategy?
This study was designed to determine the effectiveness, safety and costs associated with reuse of angioplasty catheters and to compare these results with those of a contemporary center that employed a single-use strategy. Coronary angioplasty is an important but expensive procedure. To overcome the financial constraints of the Canadian health care system, reuse of angioplasty catheters is routinely practiced in some institutions. In a prospective observational study, data forms were completed after each angioplasty procedure and before patient discharge over a 10-month period. A total of 693 patients underwent coronary angioplasty in the two centers. Clinical and lesion characteristics were similar except for a higher incidence of unstable angina at the reuse center (p < 0.005). The angiographic success rate was identical (88%) at both centers. The reuse center utilized more balloon catheters/lesion (mean +/- SD 2.4 +/- 1.5 vs. 1.2 +/- 0.5, p < 0.00001) and had a higher incidence of initial balloon failure (10.2% vs. 3.3%, p < 0.0001). Significant prolongation of the procedure time (81 +/- 41 vs. 68 +/- 32 min, p < 0.0001) and increased volume of contrast medium (201 +/- 86 vs. 165 +/- 61 ml, p < 0.0001) were seen in the reuse center. A higher rate of adverse clinical events (7.8% vs. 3.8%, p < 0.025) was observed in the reuse center, especially in patients with unstable angina. The reuse strategy was associated with a higher rate of adverse events, prolonged procedure time and increased use of contrast medium, especially in lesions that were not crossed by the initial balloon and in patients with unstable angina. Whether these differences are related to the reuse strategy or to differences in patient groups cannot be ascertained by this observational study. A multicenter randomized trial is required to further assess the safety and the cost/benefit ratio of this strategy.


Role of p38 MAPK in ICAM-1 expression of vascular endothelial cells induced by lipopolysaccharide.
Lipopolysaccharide (LPS) stimulation of endothelial cells induces the expression of intercellular adhesion molecule-1 (ICAM-1), a critical adhesion molecule involved in the adhesive interaction between leukocytes and endothelial cells in shock and inflammation. Although there is little literature about role of p38 mitogen-activated protein kinase (MAPK) in ICAM-1 protein expression of LPS-induced endothelial cells, it is still not defined whether gene transcription is regulated by p38 MAPK in ICAM-1 expression of LPS-induced endothelial cells. In this study, the potential role of p38 MAPK in ICAM-1 expression of LPS-induced endothelial cells was studied in vitro and in vivo. In vitro studies, the results showed that compared with basic expression of ICAM-1 protein on cultured human umbilical vein endothelial cells (HUVECs), the ICAM-1 expression was increased initially at 2 h after LPS stimulation, reached peak value at 24 h, and descended at 36 h obviously. A dose-dependent relationship existed between LPS concentration and ICAM-1 expression. The abundance of ICAM-1 mRNA in cytoplasma of endothelial cells was upregulated significantly by LPS stimulation at 2 h and was maintained at a high level from 4 to 36 h. The upregulation of ICAM-1 protein and mRNA expression of LPS-induced HUVECs was markedly inhibited by SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole], a highly specific inhibitor of p38 MAPK. Activity of p38 MAPK in HUVECs was increased at 15 min after LPS stimulation and reached the maximum at 60 min, then descended significantly. Activity of p38 MAPK was inhibited significantly by SB203580 in vitro. In vivo studies, administration of SB203580 (12.5 or 25 mg/kg, per ora) markedly reduced LPS-induced expression of ICAM-1 protein and mRNA of lung tissues of male BALB/c mice. These data highlight that the upregulation of ICAM-1 expression of LPS-induced endothelial cells in vitro and in vivo is mediated by p38 MAPK pathway at the level of gene transcription. The ICAM-1 expression of LPS-induced endothelial cells is characteristic of time dependence and dose dependence, and tolerates to chronic LPS stimulation. Inhibition of the p38 MAPK signal pathway may be used as an approach to attenuate ICAM-1 production in the treatment of septic shock.


An ecological risk assessment for chlorpyrifos in an agriculturally dominated tributary of the San Joaquin River.
Single-species toxicity testing of ambient water samples and national-scale probabilistic risk assessment have implicated the organophosphorous (OP) insecticide chlorpyrifos (O, O-diethyl O-(3,5,6-trichloro-2-pyridyl)-phosphorothioate) as a potential chemical stressor of aquatic organisms residing in the lower San Joaquin River basin. This site-specific aquatic ecological risk assessment was conducted to determine the probability of adverse effects occurring from exposure to chlorpyrifos in an agriculturally dominated tributary of the San Joaquin River and to assess the ecological significance of such effects. Assessment endpoints were fish population persistence and invertebrate community productivity. Daily chemical measurements collected over a period of one year were analyzed temporally for frequency, duration, and spacing between events for acute and chronic exposure episodes. Effects thresholds for fish and freshwater lotic invertebrates were determined from single-species laboratory toxicity tests. Potential risk was characterized by the degree of overlap of distributions of exposure events and effects, with consideration given to additive toxicity of other OP insecticides, recovery periods, and duration of chronic exposure (> or = 21 d). Ecological significance was determined by analysis of fish assemblage dietary and reproductive habits in relation to the surrogate invertebrate taxa judged at risk. Results of analysis indicated no direct effects on fish, and indirect effects on fish through elimination of invertebrate food items were considered unlikely. Biological survey information will be necessary to address uncertainty in this risk conclusion, especially as it relates to the benthic invertebrate community. Results of this site-specific risk analysis suggest that fish population persistence and invertebrate community productivity were not adversely affected by measured chlorpyrifos residues during a year-long monitoring period.


Accessing specialty consultations and procedures in Centre-Val de Loire region
In the Centre-Val de Loire region, the demography of specialty care is characterized by a strong deficit and many territorial inequalities that lead to significant difficulties in accessing care. The study has being conducted at the level of the Professional Territorial Health Communities (CPTS) which structuring the region, which is the ideal framework for implementing public health actions resulting from this study. The aim of this study was to objectify these difficulties and their geography, based on the calculation of the comparative consumption index (CCI), in order to measure the differences between expected consumption and observed consumption, and to quantify the number of "missing" doctors to meet the needs of the population. The study shows a deficit in care-seeking for specialty care, in particular an incompatibility between care needs and care offers in the living environment, as well as strong territorial inequalities, with marked differences between private consumption and hospital consumption. The region experiences a deficit of 25% of liberal medical specialists in order to meet the needs of its population. Accessibility to care is not only defined by the proximity of doctors, and their density; the proximity of areas of activity being a factor associated with better access to health care. This study also makes it possible to identify priority areas of action, specialty by specialty, to strengthen access to specialty care, and propose a fairer distribution of the care offer, in particular through interns' internships, and the coordinated and territorial organization of specialist doctors.


Management of upper cervical spine injuries: a review.
Upper cervical spine injuries are commonly associated with trauma and require significant forces to produce. When these injuries occur they can have devastating functional consequences. The distinctive anatomy of the upper cervical spine leads injuries to occur in predictable patterns. Injuries can occur to the unique osseus structures or ligamentous connections. Common injuries include occipital condylar fractures, atlanto-occipital dislocation, fractures of the ring of C1, ligamentous injuries involving the ring of C1, and the three types of fractures of C2, pars fractures, odontoid fractures and C2 body fractures. We present these common injuries found in the occipital-atlantoaxial complex and their management based on the current and historical literature.


Molecular level lignin patterns of genetically modified Bt-maize MON88017 and three conventional varieties using tetramethylammonium hydroxide (TMAH)-induced thermochemolysis.
Bt-maize MON88017, its near-isogenic line DKC5143, and the two conventional varieties DK315 and Benicia were subjected to tetramethylammonium hydroxide (TMAH)-induced thermochemolysis to reveal molecular level lignin patterns. MON88017 is genetically modified to express the Cry3Bb1 protein aimed at the Western corn rootworm Diabrotica virgifera virgifera, a serious threat for European maize production. The results indicated that roots of the Bt-maize were characterized by a slightly enhanced total lignin content (by approximately 7%) compared to the near-isogenic line, whereas the molecular-based patterns, expressed by the relative fractions of p-hydroxyphenyl, guaiacyl, and syringyl breakdown products (P-, G-, and S-units, respectively) were virtually identical for both lines. No effects regarding either total lignin or molecular-based lignin patterns could be observed for leaves, indicating that biogenesis of lignin was not pleiotropically affected by the genetic modification. Significant differences for both total lignin and different lignin proxies existed between the conventional maize lines. Molecular level lignin analysis by means of TMAH-induced thermochemolysis is able to distinguish conventional maize varieties. Further work is necessary to evaluate lignin-related pleiotropic effects in genetically modified maize plants. The validation and application of a commonly accepted method for lignin analysis, capable of characterizing lignin at the molecular level, is a prerequisite.


Molecular characterisation of the species of the genus Zygosaccharomyces.
The restriction fragments polymorphisms of the mitochondrial DNA and the PCR fragment that comprised the internal transcribes spacers and the 5.8S rRNA gene, together with the electrophoretic karyotypes of 40 strains from the 10 species of the genus Zygosaccharomyces, including the new species Z. lentus were examined. The RFLP's of the ITS-5.8S region showed a specific restriction pattern for each species, including the new species Z. lentus. The only exception were the species Z. cidri and Z. fermentati that produced identical restriction profiles. The electrophoretic chromosome patterns confirmed the differences between the species of this genus, including the phylogenetic closest species Z. cidri and Z. fermentati. They present few chromosomes ranging from 3 bands (4 or 5 chromosomes) for Z. florentinus to 7 bands (8 to 10 chromosomes) for Z. cidri and Z. fermentati. The strain level resolution power of RFLP's of mtDNA of this genus enabled the characterisation of strains from the same species, even where they are isolated from the same substrate. However, in the cases of Z. bailii and Z. lentus, electrophoretic karyotyping there was considerable variation.


Rapid HIV screening for women in labor.
Women now comprise approximately half of all HIV-infected individuals and the epidemic of pediatric HIV disease continues unabated in the developing world. The issue of mother-to-child transmission has been a major concern for public health officials since the early years of this epidemic. Not uncommonly, the first opportunity to ascertain the HIV status is when a woman presents to a hospital in labor. Rapid HIV tests can provide fast results, allowing time for the provider to offer antiretroviral therapy. Several effective antiretroviral regimens are now available for the intrapartum patient whose rapid HIV test comes back as positive. Antiretroviral therapy should be initiated as soon as possible after a positive rapid HIV test result and prior to standard confirmatory testing. This article summarizes the epidemiology of HIV and focuses on testing policies, technologies for rapid screening for HIV infection and antiretroviral regimens that can reduce the risk of perinatal transmission from the intrapartum patient whose rapid HIV test comes back positive.


Prevention of neural tube defects: vitamins, enzymes and genes.
Neural tube defects can be prevented by folic acid, although the mechanism of this action is unclear. Studies of a series of folate-related enzymes have so far failed to pin-point the nature of the metabolic defect in the neurulation-stage embryo that is corrected by folic acid. Approximately 30% of neural tube defects appear resistant to folic acid and recent work in a mouse genetic model system suggests that administration of myo-inositol may be a complementary therapeutic option. The large number of mouse genes known to cause neural tube defects provide a starting point for identifying the genetic basis of the human defects.


Maximal respiratory pressures in children.
Maximal inspiratory ( PImax ) and expiratory ( PEmax ) pressures were measured 7 separate times during 1 month in 40 children (13 males and 27 females, 101 to 208 months of age). After an initial period of learning, the Pimax for 20 repeated efforts was 11.1 +/- 2.4 kPa and the PEmax was 14.0 +/- 3.6 kPa. Mean values for the 20 efforts were 83% of PImax and 84% of PEmax . Individual coefficient of variation was 10% for PImax and 11% for PEmax . Postpubertal boys had higher pressures than did girls, primarily related to their greater muscle area. Pressures correlated with upper arm muscle area in both sexes and with age and height in boys. The PEmax was lower in these children than in previously reported normal adults, probably because of less muscle development. The PImax was similar to adult values, suggesting that a factor in addition to muscle strength influences inspiratory pressures in children.