Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9.
Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes.


Validation of the DSM-5 Level 1 Cross-Cutting Symptom Measure in a Community Sample.
The shift toward transdiagnostic and dimensional approaches to diagnosing mental disorders has created a need for assessment tools that efficiently measure a range of mental health symptoms and their severity. The present study aimed to evaluate the psychometric properties and diagnostic utility of the DSM-5 Level 1 Cross-Cutting Symptom Measure (CCSM), developed by the American Psychiatric Association as a brief transdiagnostic measure of mental health symptoms, in community-dwelling adults. Participants (N = 482) completed symptom measures corresponding to CCSM domains and self-reported diagnostic criteria were used to establish DSM-5 diagnoses. The results showed CCSM domains had significant validity correlations with longer measures of the same or similar mental health constructs and overall symptom severity was associated with functional impairments and current treatment status. Several domains demonstrated moderate diagnostic efficiency for corresponding DSM-5 diagnoses. The recommended thresholds for depression, anxiety, and substance use domains showed strong sensitivity (≥ 0.83) but low specificity (range = 0.60-.73), whereas the personality functioning threshold showed low sensitivity (0.51) and excellent specificity (0.92). These results suggest CCSM domains are internally consistent and valid measures of psychopathology. Further, these findings indicate the CCSM shows promise as a screening tool for specific DSM-5 disorders in community samples.


Fluorometric determination of guanidino compounds by new postcolumn derivatization system using reversed-phase ion-pair high-performance liquid chromatography.
A new postcolumn derivatization system using 1,2-naphthoquinone-4-sulfonate as fluorogenic reagent for the fluorometric determination of guanidino compounds is described. The guanidino compounds were separated by reversed-phase ion-pair high-performance liquid chromatography with an isocratic mobile phase containing the fluorogenic reagent and octane-sulfonate as the counterion. Fluorophors were derived from a condensation of guanidino compounds with the fluorogenic reagent in an alkaline solution. The chromatographic system using the mobile phase containing the fluorogenic reagent was simplified because only two pumps were required to deliver the mobile phase and the alkaline solution. Separation of guanidino compounds was completed within 25 min using a Nucleosil C8 column (5 microns, 15 cm X 4.6 mm i.d.). This method was applied to serum obtained from patients on hemodialysis therapy.


Regulation of C/EBPβ and resulting functions in cells of the monocytic lineage.
Monocyte/macrophages play an important role in orchestrating the immune response. The present review refers to C/EBPβ, which is a key transcription factor regulating monocytic gene expression. Following a general introduction to C/EBPβ, this article focuses on activators and regulators of the C/EBPβ system in monocytic cells, including differentiating agents, cytokines, and bacterial products as well as associated signaling pathways. Furthermore, C/EBPβ target genes in monocytic cells are summarized and resulting functions are described, including regulation of proliferation and differentiation as well as orchestration of processes of mainly the innate immune response. In addition, a variety of disease stages are described in which a dysregulation of the C/EBPβ system may be involved. A detailed knowledge of the C/EBPβ system in monocytic cells may help to further understand the difference between inflammatory and malignant proliferation as well as additional regulatory facets of innate immunity.


Surface-imprinted β-cyclodextrin-functionalized carbon nitride nanosheets for fluorometric determination of sterigmatomycin.
β-Cyclodextrin-functionalized carbon nitride nanosheets were modified with a molecularly imprinted polymer to obtain a fluorescent probe of type MIP@β-CD/CNNS which is shown to enable fluorometric determination of sterigmatocystin (STG). The material was characterized by transmission electron microscopy, infrared spectra, powder X-ray diffraction, X-ray photoelectron spectroscopy, and by absorption and emission spectra. The modified CNNSs have a good fluorescence quantum yield (13%), high sorption capacity for STG (86 mg·g-1), fast adsorption rate (25 min), and superior adsorption selectivity (with an imprint factor 2.56). When used as an optical probe for STG, the CNNSs act as the chromophore, while β-CD and MIP act as the recognition groups. The blue fluorescence of MIP@β-CD/CNNS (with excitation/emission maxima at 368/432 nm) is quenched by STG. Fluorescence drops linearly in the 0.15 to 3.1 μM STG concentration range. The lower detection limit is 74 nM. The method was successfully applied to the determination of STG in spiked wheat extract. Conceivably, this detection scheme based on a combination of β-CD inclusion and molecular imprinting may be extended to the detection of various other organic compounds. Graphical abstractSchematic representation of the preparation of surface-imprinted β-cyclodextrin-functionalized carbon nitride nanosheets. These are used, along with a molecularly imprinted polymer, for fluorometric determination of sterigmatomycin.


TNF-related apoptosis inducing ligand (TRAIL) gene polymorphism in Japanese patients with multiple sclerosis.
TNF-related apoptosis inducing ligand (TRAIL) has been reported to induce apoptosis of autoreactive T cells and other inflammatory cells, and thus, it is a strong candidate gene for involvement in the development of autoimmune diseases. We investigated single nucleotide polymorphisms (SNPs) in the coding region of the gene at position 1595 in exon 5 in 128 Japanese patients with conventional/classical multiple sclerosis (MS) and 158 healthy controls. Patients with optico-spinal MS (OSMS) or atypical clinical attacks were excluded from the study. The frequency of CC genotype at position 1595 was significantly different between patients and controls (p=0.0027), and the C allele was more prevalent in the patients than in the controls (p=0.0138, OR=1.546, 95% CI=1.092-2.188). Logistic analysis, adjusted for HLA-DRB1*1501-positivity, revealed the independent association of the CC genotype with susceptibility to MS (p=0.0006, OR=2.393, 95% CI=1.453-3.943). There were no significant associations between +1595 polymorphism and the clinical features of MS. The results indicate that the presence of the CC genotype at position 1595 in exon 5 represents a higher risk of MS.


Effects of Counseling on Psychological Measures in Caregivers of Patients with Disorders of Consciousness.
Caregivers represent an important and potential resource in the care network of patients due to the amount of time dedicated to the patient and to their emotional involvement. The aim of this study was to evaluate the effectiveness of psychological support to families of patients with a disorder of consciousness (DOC). A total of 48 DOC caregivers were enrolled. Participants were randomly divided into 2 groups based upon the clinical condition of their family members (vegetative state [VS] versus minimally consciousness state [MCS]). Group 1 underwent psychological support and Group 2 was the control group. The 2 groups were evaluated at T0 (baseline) and at T1 (after 6 months). The Wilcoxon signed-rank test was used for within-group comparisons whereas the Mann-Whitney-U test was used to test for between-group differences. Results show how the psychological condition of caregivers in Group 1 was modified after the intervention by the healthcare team in the post-acute rehabilitative unit. Our data confirm that psychological support improves caregivers' ability to process the experience of DOC illness, independent of type of diagnosis.


Computer simulation as a tool for tracing the conformational differences between proteins in solution and in the crystalline state.
Knowledge about the architecture of macromolecules has been derived primarily from crystallography. Therefore, it has been a matter of concern whether the conformation of a macromolecule in solution, namely in vivo, might be different from that in the crystalline state. To determine the difference between the conformations, a protein (trypsin inhibitor) dissolved in water has been simulated using the method of molecular dynamics and the results are compared with those obtained from a simulation of the full crystalline unit cell. We report here that no significant difference was found for backbone atoms, except for two more or less flexible loops extending from the core of the protein and the very flexible carboxyterminal residues. The side-chains in which the conformation in solution differs considerably from that in the crystal all belong to polar residues.


One-step synthesis of 6-acetamido-3-(N-(2-(dimethylamino) ethyl) sulfamoyl) naphthalene-1-yl 7-acetamido-4-hydroxynaphthalene-2-sulfonate and its characterization with 1D and 2D NMR techniques.
A one-step method was reported for the synthesis of 6-acetamido-3-(N-(2-(dimethylamino) ethyl) sulfamoyl) naphthalene-1-yl 7-acetamido-4-hydroxynaphthalene-2-sulfonate by treating 7-acetamido-4-hydroxy-2-naphthalenesulfonyl chloride with equal moles of N, N-dimethylethylenediamine in acetonitrile in the presence of K2CO3. The chemical structure of the obtained compounds was characterized by MS, FTIR, (1)H NMR, (13)C NMR, gCOSY, TOCSY, gHSQC, and gHMBC. The chemical shift differences of (1)H and (13)C being δ 0.04 and 0.2, respectively, were unambiguously differentiated.


Pediatric coin ingestion and aspiration.
To determine the relationship between physical characteristics of the coin (size), age of the victim, the amount of coins in circulation, and the frequency and outcome of pediatric coin ingestion and aspiration injuries. Records of coin related ingestion and aspiration injuries occurring to children 14 years of age or younger were acquired from the US Consumer Product Safety Commission (CPSC). Logistic regression was conducted to control for mutual confounding among variables. From 1994 to 2003, an estimated 252,338 children were treated in hospital emergency departments for non-fatal coin-related ingestion or aspiration, and additional 20 fatalities were reported during the same time span. Children 4 years of age or younger were at the highest risk. It is also observed that younger children are the most vulnerable victims of ingestion and/or aspiration of small coins (e.g., pennies), while older children are more likely to be treated due to ingestion and/or aspiration of larger coins (e.g., quarters). Pennies were involved in more incidents than all other coins combined. The hospitalization rate exhibited a negative correlation with the measure of the diameter and the weight of the coins. The overwhelming majority (94%) of the incidents were ingestion, whereas aspiration victims were more likely to encounter hospitalization. We hope that this study will raise public and health practitioners' awareness of the risk, and increase supervision, particular of the most vulnerable young children.


Unravelling the effects of gene flow and selection in highly connected populations of the silver-lip pearl oyster (Pinctada maxima).
Many marine organisms often display weak levels of population genetic structuring as a result of both environmental characteristics (e.g., ocean currents) and life history traits (e.g., widely dispersed planktonic larval stages) maintaining high levels of gene flow. This can lead to the assumption that these organisms can be managed as a single stock based on high levels of population connectivity. However, this neglects to account for other micro-evolutionary forces such as selection, which also shape these populations. This study utilizes 1130 genome-wide SNP loci to unravel the effects of gene flow and selection shaping three highly connected populations of the silver-lip pearl oyster (Pinctada maxima) in the ecologically and economically important Indo-Pacific region (Aru, Bali, and West Papua). Twenty-two loci under directional selection were identified amongst the populations, providing further supporting evidence of strong local adaptation (i.e., G×E effects) among populations in this region. Global Fst values for directional outliers (0.348) were up to eight times greater than for neutral markers (0.043). Pairwise Fst comparisons between Aru and Bali revealed the largest directional differences (0.488), while Bali and West Papua had the least (0.062). Unrooted neighbour-joining (NJ) distance trees and genetic diversity indices of directional outliers revealed that individuals from Bali and West Papua had reduced allelic variation (MAFavg=0.144, Ho=0.238 and MAFavg=0.232, Ho=0.369, respectively) compared to Aru (MAFavg=0.292, Ho=0.412). This indicates that directional selection is most likely acting upon genetic variation within the Bali and West Papua populations. NJ distance trees, discriminant analysis of principal components, and Fst analyses of directional outliers revealed two divergent groups ("Bali/West Papua"; "Aru") that had previously gone unrecognized. This study not only illustrates that relatively strong local adaptive forces are occurring despite high gene flow, but identifies the populations that are most likely experiencing selection. Additionally, this study highlights the need to understand all micro-evolutionary forces acting on populations when resolving stock structure.


A new species of the genus Ambrostoma Motschulsky (Coleoptera, Chrysomelidae, Chrysomelinae) from South Korea, with larval descriptions and biological notes.
Ambrostoma koreana sp. n. is described from South Korea. Detailed descriptions and illustrations of adult and all larval instars are provided and differences to closely related species are discussed. Ovoviviparity is reported for the first time in the genus Ambrostoma. Notes on distribution, host plant and biology are also provided.


Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer.
Programmed death-ligand 1 (PD-L1) expression has been suggested as a potential predictive biomarker of response to anti-PD-1/PD-L1 therapy. In this study, we investigated whether the expression of PD-L1 in tumour cells is affected by neoadjuvant concurrent chemoradiotherapy (CCRT) or chemotherapy in oesophageal squamous cell carcinoma. Between 2004 and 2014, we collected the medical records of locally advanced oesophageal cancer patients consecutively diagnosed and treated with neoadjuvant CCRT or chemotherapy, followed by curative resection. PD-L1 expression in acquired tissue specimens was evaluated by immunohistochemistry using the H-score. The changes in PD-L1 expression between paired samples were evaluated and we also analysed PD-L1 expression in surgical tumour specimens to evaluate its prognostic role. Twenty-eight paired tumour tissues that were acquired before and after neoadjuvant therapy were available: 19 patients with CCRT and 9 with chemotherapy before complete oesophagectomy. The PD-L1 H-score increased significantly from baseline tumour tissues to surgical tumour tissues after neoadjuvant CCRT (P = 0.007, median H-score from 28 to 52), whereas it decreased significantly after neoadjuvant chemotherapy (P = 0.048, median H-score from 53 to 22). In a total of 73 patients, including 45 additional cases for the prognosis analysis, patients with higher PD-L1 H-scores (≥ 20) had poorer overall survival (median 16.7 versus 32.9 months, P = 0.02) than those with lower H-scores (<20). PD-L1 expression in tumour cells increased in oesophageal cancer patients who received neoadjuvant CCRT. Further studies with more cases are necessary to validate these findings.


Heart transplantation 1987--2007: 20 years' experience at Chulalongkorn hospital.
After many years, heart transplantation is still the most accepted treatment for end-stage heart disease. A heart transplantation program was started at our hospital in December 1987 as the first intrathoracic organ transplantation in Southeast Asia. Herein, we have reviewed our 20 years of experience from 1987 to 2007. We followed every individual within our 52-patient cohort for up to 20 years. Three eras were studied: 1987 to 1995, 1996 to 2002, and 2003 to 2007. End points were survival, rejection, infection event, and graft coronary artery disease (CAD). There were 52 patients (39 males and 12 females). The mean age was 41.7 years (range, 12-23 years). Perioperative mortality (within 1 month) was 13.4% (n = 7) due to graft failure (n = 2), rejection (n = 3), infection (n = 1), on pulmonary hypertension (n = 1). Medium-term mortality (1-12 months) was 30.7% (n = 16) due to rejection (n = 8), infection (n = 7), or CAD (n = 1). After 1 year causes of death were rejection (n = 4), infection (n = 4), renal failure (n = 2), or CAD (n = 1). Overall actuarial 1-, 5-, and 10-year survival rates for all recipients were 54.7%, 43.3%, and 32.5%, respectively. The first patient in this series is still alive. For the period 2003 to 2007, actuarial 1-year and 4-year survival rates for all recipients were both 77.8%. The rate of rejection was reduced to just one event during this period. All surviving patients were NYHA Functional class I and II; 86% went back to work, leading almost normal lives. Improved survival in the current era may be attributed to better organ preservation, improved immunosuppression, and control of infection, as well as less graft CAD. Those who survive more than 1 year have a good quality of life.


[Should elevated beta-HCG levels be an exclusion criteria in clinical trials? A case report of paraneoplastic secretion associated with lung adenocarcinoma].
We report the case of a 55-year-old woman with pulmonary adenocarcinoma and bone metastases who was diagnosed with paraneoplastic secretion of the beta subunit of human chorionic gonadotropin (beta-HCG) while being screened for inclusion in a clinical trial. Immunohistochemistry analysis of a bone biopsy revealed strong staining of cancer cells with anti-beta HCG antibodies. Serial measurements of circulating Beta HCG seemed to be influenced by antineoplastic treatments, although they were not strictly associated with tumour evolution assessed by CT scans. Little is known about paraneoplastic secretion of beta HCG, although it has been found in 12% to 24% of non-small cell lung cancers. Usefulness of serial measurements of beta HCG for monitoring NSCLC has yet to be demonstrated, but its use as a criterion for inclusion in clinical trials needs to be questioned.


Why FRET about Ran?
The Ran GTPase drives nucleocytoplasmic transport, stabilizes mitotic spindles, and catalyzes nuclear envelope formation. A unifying explanation of these functions is that RanGTP produces an organizing field or "atmosphere" around chromatin and acts as a spatial marker. This RanGTP field has now been visualized using fluorescent biosensors.


Chronic toxicity of Dursban (chlorpyrifos) to the fathead minnow (Pimephales promelas) and the resultant acetylcholinesterase inhibition.
Fathead minnows (Pimephales promelas) were exposed to Dursban during a chronic toxicity test for 200 days including a reproductive period of their life cycle. The fish concentrated Dursban approximately 1700 times. Survival of first-generation fish was adversely affected at 2.68 micrograms/liter within 60 days. A significant increase in deformities occurred at 2.68 micrograms/liter within 30 days. Growth was significantly reduced at 2.68 micrograms/liter within 30 days and at 1.21 micrograms/liter by 60 days. Maturation of the first-generation fish was reduced at all Dursban exposures and reproduction was significantly reduced at 0.63 micrograms/liter and above. Growth and estimated biomass of 30-day-old second-generation fish were significantly reduced at 0.12 micrograms/liter, the lowest concentration tested. Brain acetylcholinesterase (AChE) activity was significantly inhibited at 0.27 micrograms/liter and above. AChE inhibition ranged from near 10% in fish exposed at 0.12 micrograms/liter to 89% for those exposed at 2.68 micrograms/liter. Inhibition results are compared to other results demonstrated during the chronic study. The use of exposure units (exposure concentration X exposure duration) is discussed as a tool for determining the effects of organophosphate pesticides on the environment.


Redo esophageal surgery: the diagnosis and management of recurrent tracheoesophageal fistula.
This article presents a 30-year review of 38 recurrent tracheoesophageal fistulas. The initial 26 cases were presented in 2009 at the annual meeting of the British Association of Pediatric Surgeons and the European Association of Pediatric Surgeons Joint Conference and published in the Journal of Pediatric Surgery (Bruchet al. J Pediatr Surg 45:337-340, 2010). In the initial cohort of 26 patients, 18 had a leak after their primary operation and 22 had respiratory symptoms leading to the discovery of the recurrent fistula. The diagnosis was made by a contrast study in 24. The repairs entailed replacing a catheter through the fistula, separating the trachea and esophagus completely using sharp dissection and placing vascularized tissue, either pleura or pericardium between the suture lines. Postoperative complications included seven anastomotic leaks, four strictures and three recurrent fistulas. Long-term follow-up (median of 84 months) showed that 21 took all of their nutrition by mouth, three were tube fed and two required a combination of both. Of the 23 patients with growth chart data, 16 fell into the first quartile of the growth chart, whereas none fell between the 75th and 100th percentile. In conclusion, this initial series of 26 patients along with the updated additional series of 12 patients is the largest series thus far reported in the literature. All 38 patients represent the characteristics of recurrent tracheoesophageal fistulas, including techniques to make the diagnosis and to provide a secure closure of the fistula, and the long-term outcomes of these patients.


Positive rolandic sharp waves in the electroencephalograms of premature neonates with intraventricular hemorrhage.
Seventy-eight electroencephalograms (EEGs) recorded from 44 premature infants with documented intraventricular hemorrhage (IVH) were retrospectively reviewed. Positive rolandic sharp waves (PRS) were observed in 13 of 44 (29.5%) patients. Among infants with grades 3 and 4 IVH, the incidence of PRS was 60% (9 of 15). During the period of study, typical PRS appeared in two EEGs of one premature infant who did not suffer an IVH. PRS were usually associated with moderately abnormal EEG backgrounds and with grades 3 and 4 IVH. Beta activity was superimposed on an average of 21.5% of PRS (beta-PRS). Infants with grades 3 and 4 IVH had a higher incidence of beta-PRS than those with smaller hemorrhages. PRS first appeared in early postnatal life, increased in abundance and then eventually disappeared from the records by 3-4 weeks of age. The field of distribution of PRS was centered at the central parasagittal region (Cz) with generous anteroposterior spread into the frontal and parietal vertices (Fz and Pz) and symmetric lateral spread into the rolandic areas (C3 and C4). Asymmetric involvement of PRS at C3 and C4 may signify differential hemispheric injury. The majority of infants whose EEGs contained PRS died or suffered serious neurologic sequelae. However, their outcomes were not significantly inferior to those without PRS.


Hospital associations put nix on billing for 'never events'.
Hospitals, associations agree that the policy is 'the right thing to do'. CMS announcement it would not reimburse for specified errors may have impacted timing of policies. Not paying for adverse events likely a trend to spread to other states.


Structure/activity investigations of 5-substituted 3-methylisoxazole[5, 4-d]1, 2, 3-triazin-4-one derivatives.
The series of 5-substituted 3-methylisoxazole[5, 4-d]1, 2, 3-triazin-4-one derivatives was obtained by diazotization of 5-amino-3-methylisoxazol-4-carboxylic acid hydrazide. The immunological activity of these compounds was investigated experimentally in several in vitro and in vivo assays in mice and human models. In the next step, quantum-chemical investigations were performed using density functional theory with the B3LYP hybrid exchange-correlation energy functional and 6-31G(d, p) basis set. The Polarizable Continuum (SCRF/PCM) solvent model was also taken into account in order to show solvent influence on electron density and electrostatic potential around the exemplary molecules. Correlations between molecular structure and biological properties were found using a stepwise selection of scales for the multiple linear regression (MLR).


Endoscopic repair of post-surgical gastrointestinal complications.
Complications following gastrointestinal surgery may require re-intervention, can lead to prolonged hospitalization, and significantly increase health costs. Some complications, such as anastomotic leakage, fistula, and stricture require a multidisciplinary approach. Therapeutic endoscopy may play a pivotal role in these conditions, allowing minimally invasive treatment. Different endoscopic approaches, including fibrin glue injection, endoclips, self-expanding stents, and endoscopic vacuum-assisted devices have been introduced for both anastomotic leakage and fistula treatment. Similarly endoscopic treatments, such as endoscopic dilation, incisional therapy, and self-expanding stents have been used for anastomotic strictures. All these techniques can be safely performed by skilled endoscopists, and may achieve a high technical success rate in both the upper and lower gastrointestinal tract. Here we will review the endoscopic management of post-surgical complications; these techniques should be considered as first-line approach in selected patients, allowing to avoid re-operation, reduce hospital stay, and decrease costs.


Primary child care adapted to community needs.
Primary health care services for children should be adapted to the different and varying needs of the community. Specially trained nurses and other health workers can make an important contribution to the primary care of children.


Revision of the xyleborine ambrosia beetle genus Microperus Wood, 1980 (Curculionidae, Scolytinae, Xyleborini) of Thailand with four new species and four newly recorded species.
Microperus Wood, 1980 ambrosia beetles in Thailand are reviewed. Four species, M.bidentatus sp. nov., M.bucolicus sp. nov., M.globodeclivis sp. nov., and M.serratus sp. nov. are described. Four new combinations are given: Microperusarmaticeps (Schedl, 1942) comb. nov., Microperusexsculptus (Eggers, 1927) comb. nov., Microperuspedellus (Schedl, 1969) comb. nov., and Microperusspicatulus (Browne, 1986) comb. nov., stat. res., all from Xyleborus. Two new synonyms are proposed: Microperuscruralis (Schedl, 1975) (= Xyleborusmyllus Browne, 1986 syn. nov.), Microperusexsculptus (Eggers, 1927) (= Xyleborusdentipennis Browne, 1983 syn. nov.). Four species are reported from Thailand for the first time: Microperuschrysophylli (Eggers, 1930), Microperusexsculptus, Microperusnanus (Browne, 1949) and Microperusquercicola (Eggers, 1926). With the inclusion of the Microperus species described and recorded herein, the diversity of Microperus is increased to 35 species, of which 18 are recorded in Thailand. An updated key to the Microperus of the Indochinese Peninsula and China is provided. The taxonomy, diagnostic characters, and distribution of species are briefly discussed.


Rapid communication: Computational simulation and analysis of a candidate for the design of a novel silk-based biopolymer.
This work theoretically investigates the mechanical properties of a novel silk-derived biopolymer as polymerized in silico from sericin and elastin-like monomers. Molecular Dynamics simulations and Steered Molecular Dynamics were the principal computational methods used, the latter of which applies an external force onto the system and thereby enables an observation of its response to stress. The models explored herein are single-molecule approximations, and primarily serve as tools in a rational design process for the preliminary assessment of properties in a new material candidate.


Freeze-dried recombinant bacteria for on-site detection of phenolic compounds by color change.
We herein report the development of a recombinant bacterial biosensor for the rapid and easy detection of phenolic compounds in the field. A plasmid was designed to encode a beta-galactosidase reporter gene under the control of capR, an activator involved in phenolic compound degradation. The construct was transformed into Escherichia coli, and transformed cells were stored after being freeze-dried in the presence of sucrose. For detection of phenolic compounds, the cells were rehydrated, and used instantly, without any growth step. In the presence of 0.1 microM-10mM phenol, we observed a red color from hydrolysis of chlorophenol red beta-D-galactopyranoside (CPRG) or an indigo color from hydrolysis of X-galactopyranoside (X-gal). Other phenolic compounds could be detected by this system, including catechol, 2-methylphenol, 2-chlorophenol, 3-methylphenol, 2-nitrophenol, and 4-chlorophenol. These results suggest that this novel bacteria biosensor may be useful for easy, on-site detection of phenolic compounds without the need for unwieldy equipment or sample pretreatment. Indeed, biosensor systems involving beta-galactosidase-expressing freeze-dried recombinant bacteria could prove useful for the in situ detection of many more compounds in the future.


Charcot neuroarthropathy versus osteomyelitis: a case series.
Patients with diabetes and peripheral neuropathy have a 25% risk of developing a foot ulcer, and these can lead to soft tissue infections that worsen and result in osteomyelitis. While Charcot neuroarthropathy is not as common as osteomyelitis, it is often misdiagnosed as osteomyelitis. Three patients presented with diabetes, neuropathy, and foot ulcers. They underwent prophylactic surgery but later developed swelling at the surgical sites. Radiographs showed fragmentations that caused concern about osteomyelitis. The authors maintained diagnoses of Charcot neuroarthropathy and treated the patients with immobilization and offloading. All patients resolved the fragmentations without antibiotics or surgery. While Charcot neuroarthropathy and osteomyelitis have similar signs and symptoms, understanding the similarities and differences between the conditions can aid providers in appropriate wound management.


Temporomandibular joint morphology following post-traumatic ankylosis in 26 patients.
This study evaluated the joint morphology on coronal computed tomography of ankylosed temporomandibular joints in 26 patients. All patients developed ankylosis following blunt trauma. Post-ankylosis joint morphology was assessed to determine if the precursor condylar fracture could be identified and this was compared to the condylar fracture prevalence to determine if any condylar fractures have an increased risk factor for ankylosis. Mean age at presentation was 20.9+/-14.41 years (range 6-58) and mean age at injury was 13.84+/-13.81 years (range 3-53). Thirty-seven joints were ankylosed in 26 patients (11 bilateral, 15 unilateral) with 27 joints in 19 patients showing vestiges of a medially dislocated condylar fracture (72.9% of joints). The prevalence of MDCF at our unit over a period of 6 months was 16.8% (16 of 95 condylar fractures). This suggests that a medially dislocated condylar fracture is more likely to ankylose than other condylar fractures. A hypothesis is proposed to explain this increased risk.


Pediatric Voice-Related Quality of Life: findings in healthy children and in common laryngeal disorders.
Although several instruments have been validated to assess voice quality, the incidence and degree of impairment in normal, healthy children has not been widely reported. It is hypothesized that healthy children outside a medical setting do not demonstrate impairment as measured by the Pediatric Voice-Related Quality of Life (PVRQOL) instrument; in contrast, patients with vocal fold paralysis (VFP), vocal nodules (VNs), and paradoxical vocal fold dysfunction (PVFD) have significant impairment as compared to control populations. The PVRQOL was measured prospectively in children with VFP, VNs, and PVFD. The findings were compared to findings in 100 children surveyed at the 2006 Wisconsin State Fair. Of the 100 surveys of healthy children and their parents, 95 were completed correctly; their mean (+/- SD) PVRQOL score was 96.8 +/- 5.85. The VFP patients (n = 11; mean PVRQOL score, 70.5 +/- 28.6) reported significant impairment (p < .0001, unpaired t-test). This was also true of patients with VNs (n = 13; PVRQOL score, 84.8 +/- 9.4; p < .0001) and PVFD (n = 25; PVRQOL score, 86.7 +/- 14.3; p < .0001); statistically significant differences were also noted for the Social-Emotional and Physical-Functional domains for each of the 3 disease states compared to the group of healthy children (p < .001). The PVRQOL scores of healthy children reveal essentially no self-reported vocal impairment. In contrast, common disorders such as VNs, VFP, and PVFD demonstrate statistically significant impairment in age-matched children for total PVRQOL, as well as for the Social-Emotional and Physical-Functional domains. This is the first report of normative PVRQOL data in children.


Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy.
Phosphatidylinositol-3-kinase (PI3K) is a key regulator of diverse biological processes including cell proliferation, migration, survival, and differentiation. While a role of PI3K in chondrocyte differentiation has been suggested, its precise mechanisms of action are poorly understood. Here we show that PI3K signaling can down-regulate Nkx3.2 at both mRNA and protein levels in various chondrocyte cultures in vitro. In addition, we have intriguingly found that p85β, not p85α, is specifically employed as a regulatory subunit for PI3K-mediated Nkx3.2 suppression. Furthermore, we found that regulation of Nkx3.2 by PI3K requires Rac1-PAK1, but not Akt, signaling downstream of PI3K. Finally, using embryonic limb bud cultures, ex vivo long bone cultures, and p85β knockout mice, we demonstrated that PI3K-mediated suppression of Nkx3.2 in chondrocytes plays a role in the control of cartilage hypertrophy during skeletal development in vertebrates.


Phrenic nerve paresis associated with the use of iced slush and the cooling jacket for topical hypothermia.
Phrenic nerve injury has been reported with the use of iced slush for topical cardiac hypothermia. To study this problem in both valve and coronary procedures, we tried to detect phrenic nerve injury in five groups of patients undergoing cardiac operations in which different techniques of topical hypothermia were used. The results indicate a 24% incidence of left phrenic nerve paresis in patients undergoing coronary bypass with iced slush used for topical hypothermia, 12.5% in patients in whom the cardiac cooling jacket was used in association with cold saline, and 22.9% in patients in whom both the cardiac cooling jacket and iced slush were used in the pericardial sac. There was no phrenic nerve injury when saline alone was used. Phrenic paresis is transient and of no clinical significance except when bilateral. Avoidance of contact of either the cooling jacket or iced slush with the phrenic nerve could avoid this complication.


The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system.
The aim of the present study was to identify the signaling mechanism(s) responsible for the modulation of growth hormone secretagogue receptor type 1a (GHSR1a)-associated Akt activity. Ghrelin leads to the activation of Akt through the interplay of distinct signaling mechanisms: an early G(i/o) protein-dependent pathway and a late pathway mediated by β-arrestins. We found that the Src homology 2-containing protein tyrosine phosphatase (SHP-1) was an essential molecule in both G(i/o) protein-dependent and β-arrestin-mediated pathways. More specifically, the role of SHP-1 in the G(i/o) protein-dependent pathway was demonstrated by the fact that the overexpression of a catalytically defective SHP-1 augments tyrosine phosphorylation of the PI3K regulatory subunit p85, leading to an increase in the phosphorylation of cSrc and phosphoinositide-dependent protein kinase 1, and finally activating Akt. The presence of SHP-1 in the β-arrestin-scaffolded complex and its attenuating effect on the cSrc and Akt activities verified that SHP-1 regulates not only the G(i/o) protein-dependent pathway but also the β-arrestin-mediated pathway. Assays performed in preadipocyte and adipocyte 3T3-L1 cells showed SHP-1 expression. According to our results in HEK-GHSR1a cells, ghrelin stimulated SHP-1 phosphorylation in 3T3-L1 cells. The increase in ghrelin-induced Akt activity was enhanced by small interfering RNA of SHP-1 in preadipocyte 3T3-L1 cells. These results were reproduced in white adipose tissue obtained from mice, in which SHP-1 exhibited higher expression in omental than in subcutaneous tissue. Furthermore, this pattern of expression was inverted in mice fed a high-fat diet, suggesting a role for SHP-1 in controlling ghrelin sensitivity in adipose tissue. Indeed, SHP-1 deficiency was associated with augmented ghrelin-evoked Akt phosphorylation in omental tissue, as well as decreased phosphorylation under overexpression of SHP-1 in subcutaneous tissue. These findings showed a novel role for SHP-1 in the regulation of Akt activity through the modulation of the ghrelin/GHSR1a system signaling.


Viruses detected in cells explanted into tissue culture from naturally occurring malignant lymphoma in rhesus monkeys.
During a 4-year period 43 cases of spontaneous lymphoma occurred in macaques at the California Primate Research Center. In an attempt to determine if there might be a common viral etiology to the outbreak, lymphoma tissues from 10 rhesus monkeys were explanted into tissue culture and examined for the presence of virus. Electron microscopic studies of the cultured lymphoma cells revealed viruses morphologically characteristics of adenovirus, reovirus, foamy virus, and herpesvirus. Cell-free filtrates from tissue cultures possessing the latter three viruses produced cytopathology in virus-free indicator cells. Virus particles typical of the explant culture were demonstrable in the infected indicator cells. Type-C RNA tumor virus particles were not observed electron microscopically in any of the lymphoma tissues or lymphoma cell cultures examined.


Use of ultrasound to confirm guidewire position in hemodialysis catheter implantation.
Hemodialysis is the most used dialysis modality in Brazil for the treatment of end-stage chronic kidney disease and severe acute kidney injury. Non-tunneled, short-term, double-lumen catheters allow immediate vascular access in patients without a definitive vascular access for dialysis treatment. Implantation is performed using the Seldinger technique, traditionally based on anatomical landmarks or with puncture under direct visualization by ultrasonography. Confirmation of the placement of the catheter is usually made with a chest X-ray after the end of the procedure. To describe the use of ultrasonography to confirm the proper positioning of the guidewire during catheter implantation in real time, ensuring the desired path. We used the Seldinger technique for catheter implantation. The confirmation of the position of the guidewire occurred after the introduction of 50 cm of this wire, as described in the aforementioned technique. A convex transducer was placed longitudinally below the xiphoid process to visualize the guidewire in the inferior vena cava, or transversely at the same location to visualize it in the cavoatrial junction or right ventricle, using the two-dimensional mode of the ultrasound device. After viewing the guidewire, the catheter implantation proceeded. The technique was performed in 1549 patients, and regarded 2596 catheter implantations over a period of 5 years and 9 months. The only complication observed was local hematoma, occurring in 0.1% of cases. Confirmation of guidewire position with ultrasonography during catheter implantation is recommended because it is safe, low cost and ensures correct catheter direction.


Decoupled stochastic parallel gradient descent optimization for adaptive optics: integrated approach for wave-front sensor information fusion.
A new adaptive wave-front control technique and system architectures that offer fast adaptation convergence even for high-resolution adaptive optics is described. This technique is referred to as decoupled stochastic parallel gradient descent (D-SPGD). D-SPGD is based on stochastic parallel gradient descent optimization of performance metrics that depend on wave-front sensor data. The fast convergence rate is achieved through partial decoupling of the adaptive system's control channels by incorporating spatially distributed information from a wave-front sensor into the model-free optimization technique. D-SPGD wave-front phase control can be applied to a general class of adaptive optical systems. The efficiency of this approach is analyzed numerically by considering compensation of atmospheric-turbulence-induced phase distortions with use of both low-resolution (127 control channels) and high-resolution (256 x 256 control channels) adaptive systems. Results demonstrate that phase distortion compensation can be achieved during only 10-20 iterations. The efficiency of adaptive wave-front correction with D-SPGD is practically independent of system resolution.


Flood risk assessment of Wuhan, China, using a multi-criteria analysis model with the improved AHP-Entropy method.
Floods are one of the most frequent global natural hazards resulting in significant human and economic losses. Therefore, assessing and mapping flood hazard levels is essential to reduce the severity of future flood disasters. This study developed an integrated methodology to evaluate flood risk using an improved Analytic Hierarchy Process (AHP) and Entropy Weight (AHP-EW) method based on cosine similarity (COS-AHP-EW). This method has more scientific results because it combines subjective and objective information. The proposed method's viability was then tested in Wuhan, China. Fourteen flood-inducing indicators were identified for the flood hazard, vulnerability, and restorability index system, with the indicator weights calculated using the COS-AHP-EW. This study utilized the Jenks method to develop the Wuhan flood risk map. We observed that the very high risk and high-risk areas covered 2.43% and 11.54% of the total study area and were mainly distributed in the highest economic and urbanization development and low-permeability districts, respectively. The validation with the historical waterlogging points reflected the accuracy and reliability of the COS-AHP-EW. The superiority of the proposed method was further verified by comparing it with single-evaluation methods (AHP and Entropy Weight) and another combined weight method (combined AHP-EW based on ideal point theory, namely, Ideal-AHP-EW). The comparison results indicated that the COS-AHP-EW was more accurate at predicting the risk in flood-prone area. Flood risk maps generated using the COS-AHP-EW could be applied to improve flood risk assessments, and the proposed method could be extended to other study areas to provide reliable flood management information.


Wide-field mid-infrared hyperspectral imaging of adhesives using a bolometer camera.
By combining a bolometer detector with an imaging-type interferometer, an inexpensive, easy-to-handle wide-field mid-infrared hyperspectral imaging apparatus was produced. We measured the distributions of four types of thin adhesive layers on an aluminium plate and analysed the results using correlation coefficients to visualise the distribution of various adhesives that cannot be discerned by the naked eye or conventional methods such as visible/near-infrared spectroscopic/fluorescent photography. The measurement wavelength range, obtained spectrum's wavenumber resolution, and measurement time was 8-14 μm, about 9 cm-1, and about 30 s, respectively. Using conventional methods, adhesives could not be distinguished from the others. By using this method, we found that adhesives could be precisely distinguished by setting an appropriate threshold value for the correlation coefficient. Thus, our approach can accurately measure the spatial distribution of different types of adhesive that cannot be discriminated by conventional methods.


Assignment of the human connexin 32 gene (GJB1) to band Xq13.
The chromosomal localization of the human gene coding for connexin 32 (GJB1) was determined by in situ suppression hybridization (ISSH). The results allowed assignment of the gene to band Xq13, thus refining previous localization data obtained by means of somatic cell hybrid analysis.


Expression of PGAM1 in renal clear cell carcinoma and its clinical significance.
This study is aimed to evaluate the expression of phosphoglycerate mutase 1 (PGAM1) in normal kidney and clear cell renal cell carcinoma (CCRCC), also to evaluate the correlation between PGAM1 expression and clinicopathological features in CCRCC. PGAM1 expression was detected in 80 cases of normal kidney and 192 cases of CCRCC by immunohistochemistry (IHC). Meanwhile, PGAM1 expression measured in 8 cases of CCRCC and matched normal kidney tissues by Western blot. Then, the correlation between PGAM1 expression and clinicalpathological features was analyzed in CCRCC. IHC results exhibited that the high-expression rate of PGAM1 in CCRCC tissues was 45.8%, which was significantly higher than those in normal kidney tissues (32.5%, P=0.044). Meanwhile, PGAM1 expression in CCRCC was significantly greater compared with those in normal kidney by Western blot. Moreover, PGAM1 expression was significantly associated with age, tumor size and T stage in CCRCC. PGAM1 is highly expressed in CCRCC and correlated with clinicalpathological features, which may contribute to tumor formation and progression.


An investigation into the reduction in flow rate of intravenous fluid by antireflux valves.
We have investigated the extent to which antireflux (non-return) valves impede the maximum flow rate of crystalloid in intravenous infusion systems when administered either under gravity or with 300 mmHg added pressure. When used with a 16G cannula, a reduction in flow rate of 19-38% was consistently seen. With a 20G cannula, no significant reduction in flow was found. The valve tested that produced the least reduction in flow was the Westcott Sae-flo valve.


Treatment with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine improves vascular function and lowers blood pressure in adult spontaneously hypertensive rat.
High vascular arginase activity and subsequent reduction in vascular nitric oxide production were recently reported in animal models of hypertension. The present study investigated the effects of in-vivo arginase inhibition on blood pressure and vascular function in adult spontaneously hypertensive rats. Ten-week-old spontaneously hypertensive rats and normotensive age-matched Wistar-Kyoto rats were treated with or without the selective arginase inhibitor N-hydroxy-nor-L-arginine for 3 weeks (10 or 40 mg/kg per day, intraperitoneally). Systolic blood pressure and cardiac rate were measured before and during treatment. Flow and pressure-dependent reactivity as well as remodeling of mesenteric arteries, acetylcholine-dependent vasodilation of aortic rings, cardiac hypertrophy, arginase activity and nitric oxide production were investigated in 13-week-old spontaneously hypertensive rats. In spontaneously hypertensive rats, N-hydroxy-nor-L-arginine treatment decreased arginase activity (30-40%), reduced blood pressure ( approximately 35 mmHg) and improved the reactivity of mesenteric vessels. However, vascular and cardiac remodeling was not different between treated and untreated spontaneously hypertensive rats. In Wistar-Kyoto rats, N-hydroxy-nor-L-arginine did not affect blood pressure. Finally, arginase inhibition was associated with increased nitric oxide production. Consistent with this, the response of aortic rings to acetylcholine was fully restored by N-hydroxy-nor-L-arginine, and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the effect of N-hydroxy-nor-L-arginine on flow-dependent vasodilation. Pharmacological inhibition of arginase in adult spontaneously hypertensive rats decreases blood pressure and improves the reactivity of resistance vessels. These data represent in-vivo argument in favor of selective arginase inhibition as a new therapeutic strategy against hypertension.


Review and comparison of the long acting methylphenidate preparations.
The stimulants have been the mainstay of pharmacologic treatment for over fifty years. Methylphenidate is the most frequently prescribed of the stimulant agents. In the past, one of the main drawbacks of these agents was the abbreviated duration of action. Over the last few years three longer acting methylphenidate preparations have been released to the market. Though all these agents contain the same chemical compound they do vary in a number of ways. In this article we will present how the formulations compare in their technology and the differences in their delivery systems. We will also compare the available literature that focus on head to head comparisons in terms of pharmacokinetics studies and those reports that present efficacy data. Finally, we will suggest based on a theoretical framework on how to approach selecting an agent based on the results of these trials and the individual needs of the patient.


Advantages of Japanese response criteria for estimating the survival of patients with primary gastric cancer.
BACKGROUND: We conducted a retrospective study to investigate the adequacy of the Efficacy Criteria for Primary Lesions in the Japanese Classification of Gastric Cancer (Japanese criteria) for evaluating the anti-tumor efficacy of chemotherapies and the relationship between tumor regression and the prognosis of gastric cancer.METHODS: The data for 90 patients with inoperable ad-vanced gastric cancer who received various chemotherapies, consisting of fluorinated pyrimidines and cisplatin, were retrospectively analyzed. Based on the Japanese criteria, we investigated the efficacy of the chemotherapies and the relationship between the response in primary lesions and survival. We also compared the efficacy of chemotherapies evaluated by the Japanese criteria to that evaluated by the WHO criteria.RESULTS: All 90 patients were evaluable by the Japanese criteria. The overall response rate was 53.3% (Partial response [PR] in 48 patients and no change + progressive disease [NC + PD] in 42 patients). The primary lesions were classified as measurable (a-lesions) in 27 patients, evaluable but not measurable (b-lesions) in 31 patients, and diffusely infiltrating (c-lesions) in 32 patients. Overall median survival time (MST) was 9.4 months. The MSTs of the responders and non-responders were 12.6 and 7.8 months, respectively. In contrast, by the WHO criteria, 49 patients (54.4%) were evaluable; the other 41 patients had gastric primary lesions alone but were not measurable by WHO criteria. The overall response rate was 67.3% (33/49), and overall MST was 9.4 months. The MSTs of the responders evaluated by both sets of criteria were both 12.6 months.CONCLUSIONS: We suggest that the Japanese criteria are useful for evaluating the anti-tumor effect of gastric cancer chemotherapies and that prospective studies to reconfirm their usefulness are warranted in Japan, and in Western countries.


Substance use and health activities of pregnant adolescents.
Little is known about substance use by pregnant adolescents or the possible effects of such use on their offspring. In this case-control study, substance use and selected health and social variables of 119 pregnant and 313 nonpregnant inner-city high school students are assessed. The most commonly used substances are alcohol, cigarettes, and marijuana. Pregnant subjects used substances similarly to their nonpregnant counterparts, but were more likely to smoke cigarettes. Pregnant and nonpregnant subjects thought a baby is put at great risk for harm if its mother uses a substance during pregnancy. Pregnant subjects demonstrated more positive health behaviors than nonpregnant subjects. Recommendations for intervention are discussed.


Phylogenetic analysis of rhinovirus isolates collected during successive epidemic seasons.
Human rhinoviruses (HRV) have been shown to be the major causative agent for mild respiratory infections, but also associated with more serious diseases, such as acute otitis media and pneumonia in children, and asthma. Despite the economical and medical importance of HRV, little is known about the circulation and genetic diversity of HRV during a given season. The aim of this study was to genetically characterize HRV strains causing acute respiratory infections in a cohort of small children during a 2 years follow-up time. Genetic relationships between 61 HRV field isolates were studied using partial genomic sequencing in the VP4/VP2 region (420 nt) and phylogenetic analysis of these sequences. Sequences from the clinical isolates clustered in the two previously known phylogenetic clades, the designated genetic group 2 (including HRV 14) being more predominant. The maximum genetic variation within group 1 was 32.3% and within group 2 it was 32.7%. Several distinct clusters could be observed, some of which were strictly seasonal, whereas some other variants were detected during several seasons. The results of this study show striking genetic diversity of the HRV strains circulating in a given community during a short time.


The mode is the message.
In this issue of Neuron, Khazali et al.1 record neural activity during coordinated reaches and saccades. They find that excitatory neurons link arm and eye movement regions of parietal cortex, creating a multiregional mode that predicts movement timing and direction.


Association of Upon-Diagnosis Blood Eosinophilic Count with Frequency and Severity of Annual Exacerbation in Chronic Obstructive Pulmonary Disease: A Prospective Longitudinal Analysis.
There is a controversy regarding the relationship between blood eosinophil count and COPD exacerbation. We aimed to determine whether peripheral eosinophils upon COPD diagnosis could affect the frequency and severity of annual acute exacerbation of COPD (AECOPD). This prospective study was conducted on 973 newly diagnosed COPD patients who were under 1-year follow-up in a pulmonology center in Iran. The Cox proportional model, polynomial regression, and receiver operator characteristic curves were conducted to evaluate the impact of the eosinophil levels on AECOPD. A linear regression model was conducted to evaluate the continuous association of eosinophilic count with AECOPDs. Patients with eosinophil >200 cells/microliter were higher pack-year smokers with more pulmonary hypertension prevalence compared to COPD patients with <200 cells/microliter. There was a positive correlation between the eosinophilic count and the frequency of AECOPDs. Eosinophil >900 cells/microliter and eosinophil >600 cells/microliter had a sensitivity of 71.1% and 64.3%, respectively, in predicting the occurrence of more than one AECOPD. Eosinophilic count cutoff of 800 cells/microliter had the highest Youden index with sensitivity and specificity of 80.2% and 76.6%, respectively, for incident AECOPD in newly diagnosed patients. Using a linear model, increasing 180 cells/microliter in serum eosinophils was associated with further exacerbation. Evaluating gender, BMI, smoking pack-year, FEV1/FVC, CAT score, GOLD score, pulmonary hypertension, annual influenza, pneumococcal vaccinations, leukocytosis, and blood eosinophils, only blood eosinophils (hazard ratio (HR) = 1.44; 95% confidence interval = 1.33-2.15; p value = 0.03) and GOLD score (HR = 1.19; 95% CI = 1.30-1.52; p value = 0.03) were found as independent risk factors of AECOPD >3 episodes/year. Requirement for ICU admission, invasive ventilation, and mortality rate due to AECOPDs was similar between eosinophilic and noneosinophilic groups. Eosinophilia upon COPD diagnosis is a factor of recurrent AECOPDs. To reduce the risk of AECOPDs and the burden of disease, clinicians may consider inhaler corticosteroids and domiciliary oxygen with a lower threshold for eosinophilic-COPD patients regardless of their clinical status.


Prevalence and prediction of medical distrust in a diverse medical genomic research sample.
Medical distrust has been identified as a persistent barrier to medical care, affecting preventative screening, treatment uptake, and treatment adherence. Despite this, little research to date has examined medical distrust in a genomic medicine context. The goal of this work was to assess the prevalence of medical distrust in a genomic medicine research study and examine patient-level demographic, access-related, and health-status characteristics that predict medical distrust. We assessed medical distrust in a research sample of adults (N = 967) receiving genomic sequencing to screen for hereditary risk of cancer syndromes in the United States. We used multiple predictive variable selection models to determine predictors of medical distrust followed by marginal mean analyses to characterize the relationships. The prevalence of medical distrust was 32%. The final model indicated that Black and African American race/ethnicity; trans, nonbinary, or nonidentifying gender identity; high education; low income; low access to health care; and poor Short Form 12 mental health composite scores predict medical distrust. Medical distrust may pose similar challenges to genomic sequencing, as it does in other medical contexts. The pattern of variables that predict distrust suggest that increasing access and accommodation for stigmatized and underserved communities may help overcome the negative effects of medical distrust.


Esophageal Foreign Bodies in Pediatric Age Group with Different Durations of time from Ingestion to Effective Treatment.
A foreign body(FB) is any object in a region it is not meant to be, where it can cause harm by its mere presence if immediate medical attention is not sought. Foreign body is particularly common in the pediatric population especially below 5 years of age and in whom prevalence was reported to vary between 57% and 80%. Endoscopic interventions are indicated when the foreign objects fail to pass spontaneously. The standard methods to remove these foreign bodies include push technique and retrieval methods using various endoscopic instruments. Study of 302 patients admitted with the final diagnosis of esophageal foreign body during January 2017 - April 2018, for sex, age, diagnosis on admission, estimated duration and site of impaction, type and number of foreign body removed. During the study period, 302 patients (169 males and 133 females) of different ages, maximum in the age group of 1-5 years i.e 197 cases were admitted with the diagnosis of esophageal foreign body. 11% of patients were less than 1 year of age & 23% were more than 5 years of age at the time of admission. Most of them presented to hospital within 24 hours of ingestion of foreign body i.e 85%. In this study all the children with suspected foreign body esophagus underwent Xray and FB was found in 300/302 i.e its diagnostic accuracy (sensitivity) is 98%. Rigid esophagoscopy was done in all 302 pts with 100% diagnostic accuracy. Different types of foreign bodies ingested most common being coin i.e in 91% patients followed by FB battery in 17 patients and safety pin in 6 patients. Majority of foreign bodies were located in the cricopharynx (198) followed by upper esophagus (67) and mid-esophagus (25) and only 10 cases involved the lower esophagus and spontaneous passage was found in 2 cases. The most common foreign bodies in children are coins and toys. Sharp foreign bodies are difficult to remove but need to be removed carefully at the earliest to prevent dreaded complications like - retropharyngeal abscess and mediastinitis. The online version contains supplementary material available at 10.1007/s12070-023-03578-8.


Production of nanostructured systems: Main and innovative techniques.
In the constant search for the development of more-specific and more-selective drugs, especially with regard to the challenge of encapsulating hydrophilic molecules, polymer nanotechnologies are remarkable for their biocompatible and biodegradable properties. The most-used nanoencapsulation methods consist of emulsification procedures, where emulsified droplets of a given polymer and drug solidify into nanoparticles after solvent extraction from the polymeric phase. This review introduces conventional emulsification methods but also highlights new emulsification technologies such as microfluidics, membrane emulsification and other techniques, including spray drying, inkjet printing and electrospraying.


Analysis of Protein Kinetics Using Fluorescence Recovery After Photobleaching (FRAP).
Fluorescence recovery after photobleaching (FRAP) is a cutting-edge live-cell functional imaging technique that enables the exploration of protein dynamics in individual cells and thus permits the elucidation of protein mobility, function, and interactions at a single-cell level. During a typical FRAP experiment, fluorescent molecules in a defined region of interest within the cell are bleached by a short and powerful laser pulse, while the recovery of the fluorescence in the region is monitored over time by time-lapse microscopy. FRAP experimental setup and image acquisition involve a number of steps that need to be carefully executed to avoid technical artifacts. Equally important is the subsequent computational analysis of FRAP raw data, to derive quantitative information on protein diffusion and binding parameters. Here we present an integrated in vivo and in silico protocol for the analysis of protein kinetics using FRAP. We focus on the most commonly encountered challenges and technical or computational pitfalls and their troubleshooting so that valid and robust insight into protein dynamics within living cells is gained.


Protocol of Detection of West Nile Virus in Clinical Samples.
West Nile virus (WNV) is one of the leading causes of arboviral encephalitis in the United States but is often underdiagnosed. Despite the wide breadth of WNV-induced clinical disease syndromes, many of the symptoms associated with WNV are nonspecific at the time of presentation; thus, choosing the right diagnostic tool is essential to not only understand the true burden of disease but also provide pathogen-directed interventions for WNV-infected patients. In this chapter, we briefly discuss the three most common types of diagnostic methods for WNV in human clinical samples: nucleic acid detection, enzyme-linked immunoassay (ELISA), and plaque reduction neutralization test (PRNT) and present the method for PRNT.


Mapping of Mycobacterium tuberculosis cases in post-conflict Liberia, 2008-2012: A descriptive and categorical analysis of age, gender and seasonal pattern.
Tuberculosis (TB) is a major public health. problem in Liberia and it is among the first five most important infectious diseases. Fourteen years of civil war in Liberia caused a large internal displacement and external migration of its citizens to neighbouring countries such as Guinea, Ivory Coast, Sierra Leone, Ghana and Nigeria. Current spatio-temporal pattern of TB cases in Liberia is essential for identifying risk factors among humans for optimal resource allocation. Surveillance data from January, 2008 to December, 2012 were retrieved from two national TB referral hospitals in the country: TB Annex Hospital (TBAH) (Montserrado County) and Ganta TB and Leprosy Rehabilitation Hospital (GTBLRH) (Nimba County). Geographic coordinates of TB patient's locations were captured based on records in the hospital case-files using Global Positioning System (GPS). The coordinates were mapped using Geographic Information Systems (GIS) software. Data on age, gender, date of illness, dry and wet season frequency were used to compute a descriptive and categorical analysis. Kulldorff's spatio-temporal scan statistic was used to identify clusters of TB in the two Counties. A total of 2,890 laboratory-confirmed cases were reported during the study period. There were 1,365 (47.23%) and 1,525 (52.77%) cases from TBAH and GTBLRH respectively. The mean age of patient was 45.19 years ± 19.49 (SD). Of this, 1,450 (50.17%) were male. There was significant association between year of TB occurrence and treatment outcome (χ2 = 14.38; p = 0.006). The paper presents TB spatial pattern, summarizing 5-year records of post-conflict surveillance of the disease in Liberia.


Nursing knowledge development through research: using the Roy adaptation model.
Almost half of the ancillary propositions tested in the metaparadigm category were related to the concept of person, and 94% were supported. Theoretically and empirically, there is support for Roy's conceptualization of the person as an adaptive system. Almost 25% of the ancillary propositions tested were related to the concept of health, of which the great majority were supported. Theoretically and empirically, there is support for Roy's conceptualization of health as an outcome of adaptation. Approximately 75% of the ancillary propositions tested were related to the concept of person or health. Of these, only 5 out of 55 ancillary propositions were not supported, or less than 10%. Less than 13% of the ancillary propositions that were tested focused on the metaparadigm concepts of environment or nursing. Of these, 15% were not supported. These findings are not surprising, because conceptual clarity is the foundation of practice theory. The hierarchy of research, according to the classic work by Dickoff and James (1968), progresses from understanding and describing phenomena to situation-producing theory. Nursing models are relatively young. Research is required to validate the concepts within the models. Situation-producing theory, based on the concepts, guides nursing actions and is necessary for a practice discipline to maintain its status as a profession. Based on the findings of the integrative research review, adequate research has provided support for Roy's conceptualization of the metaparadigm concepts of person and health. Future research needs to be directed toward testing propositions derived from the RAM concepts of environment and nursing. Intervention studies need to be designed based on concepts that have been supported. Knowledge development through research and testing of propositions based on the RAM continues to contribute to nursing science. Future directions for RAM research are clear.


Pathologic changes in otitis externa.
Otitic lesions must be evaluated in the context of the whole animal. Accurate historical and clinical assessments are important aids to the pathologist attempting to reach an accurate diagnosis. Primary lesions of the pinna, with or without involvement of the external ear canal, may be an extension of a more generalized dermatologic problem or may specifically involve the ear because of its unique gross and histologic characteristics.


Quality of Life After Off-Label Thrombolysis for Ischemic Stroke in Elderly Patients.
The use of intravenous thrombolysis with alteplase for ischemic stroke in Europe is restricted to subjects aged <80 years. Recent studies have reported the efficacy and safety of alteplase in older patients. However, data concerning the quality of life (QOL) of these elderly subjects are sparse. The aim of this study was to compare the QOL of patients aged ≥80 years with that of patients aged <80 years at 3 months after thrombolysis. This was a prospective study comprising French-speaking patients aged >18 years treated using thrombolytic therapy for ischemic stroke at the Hospital of Tours (Tours, France) between June 2012 and January 2013. QOL was assessed using the Stroke Impact Scale (SIS). The presence of mood disorders or cognitive impairments was also assessed. QOL was evaluated for 62 subjects among the 83 enrolled patients who received thrombolytic treatment; 21 patients were aged >80 years. Concerning scores on the SIS, using a multivariate analysis, only the memory and thinking score was significantly and negatively associated with the elderly population [odds ratio (OR) 0.036, 95% confidence interval (CI) 0.004-0.339; p = 0.004]. No significant difference was observed among all the other QOL scores. Neurological recovery and functional status did not differ between the two groups. QOL after intravenous thrombolysis in the elderly population was comparable to that of younger subjects. Despite its small sample size, this study showed promising results in favor of intravenous thrombolysis in the elderly population and highlighted the importance of systematic screening for post-stroke cognitive impairment, particularly in this population.


The Relation Between Dermatoglyphics And Mesiodistal Width Of The Deciduous Second Molar And Permanent First Molar.
Dermatoglyphics is one of the important diagnostic tools used in the recent days for identification of an individual. Dermatoglyphics is the study of type of patterns present on digits, palms and foot. The mesiodistal diameter of the tooth is an important factor which reveals the tooth-bone discrepancy. Deciduous second molar and permanent first molar exhibit least degree of variation. Both the dermal ridges and the enamel layer of the tooth originate from ectodermal layer and during the same period of intrauterine life. To determine and compare the dermatoglyphics with the mesiodistal width of the deciduous second molar and permanent first molar. A sample of 120 child ranaged between 6-12 years were included in the study whose digital and palmer traits were recorded using ink method and the mesiodistal widths of the deciduous second molar and permanent first molar were recorded using a vernier caliper. The data was subjected to statistical analysis using unpaired t test. The 'ATD' angle was found in the range of 40°-50°. The loop patterns were more common followed by whorls and arch patterns. Girls expressed a greater mesiodistal diameter of deciduous second molar than boys. No significant correlation was found in between the dermatoglyphics and tooth size. There was no significant correlation between the finger print patterns, 'ATD' angle and the mesiodistal diameter of the deciduous second molar and the permanent first molar.


Genome-based prediction of agronomic traits in spring wheat under conventional and organic management systems.
Using phenotype data of three spring wheat populations evaluated at 6-15 environments under two management systems, we found moderate to very high prediction accuracies across seven traits. The phenotype data collected under an organic management system effectively predicted the performance of lines in the conventional management and vice versa. There is growing interest in developing wheat cultivars specifically for organic agriculture, but we are not aware of the effect of organic management on the predictive ability of genomic selection (GS). Here, we evaluated within populations prediction accuracies of four GS models, four combinations of training and testing sets, three reaction norm models, and three random cross-validations (CV) schemes in three populations phenotyped under organic and conventional management systems. Our study was based on a total of 578 recombinant inbred lines and varieties from three spring wheat populations, which were evaluated for seven traits at 3-9 conventionally and 3-6 organically managed field environments and genotyped either with the wheat 90 K SNP array or DArTseq. We predicted the management systems (CV0M) or environments (CV0), a subset of lines that have been evaluated in either management (CV2M) or some environments (CV2), and the performance of newly developed lines in either management (CV1M) or environments (CV1). The average prediction accuracies of the model that incorporated genotype × environment interactions with CV0 and CV2 schemes varied from 0.69 to 0.97. In the CV1 and CV1M schemes, prediction accuracies ranged from - 0.12 to 0.77 depending on the reaction norm models, the traits, and populations. In most cases, grain protein showed the highest prediction accuracies. The phenotype data collected under the organic management effectively predicted the performance of lines under conventional management and vice versa. This is the first comprehensive GS study that investigated the effect of the organic management system in wheat.


Adverse outcome of nonoperative management of intimal injuries caused by penetrating trauma.
The objective of this study was to determine adverse outcomes associated with the nonoperative management of intimal injuries. A five-year retrospective review of 118 patients admitted with soft signs of vascular injury to two level I trauma centers was conducted. All injuries evaluated were isolated penetrating injuries. The number of major arteries at risk were 16 axillary, 31 brachial, 36 common femoral, 22 superficial femoral, and 13 deep femoral. Twenty-three angiographic abnormalities were identified in 23 limbs. Seven injuries were categorized as "minor" intimal flaps and treated with observation alone. The remainder were explored during operation. During the follow-up period, six of the seven patients treated without operation returned to either the outpatient clinic or emergency department with acute onset of pain or paresthesia in the previously injured limb. The following abnormalities were identified with angiography: one axillary artery thrombosis, one brachial artery pseudoaneurysm, two common femoral thromboses, two superficial femoral artery/superficial femoral vein fistulas, and one deep femoral artery pseudoaneurysm. All the abnormalities were repaired with operation. The benign nature of intimal injury identified with angiography may be overemphasized. The results of long-term follow-up in patients with this type of injury must be reviewed before "observation alone" can be recommended as standard treatment.


Melatonin receptor RNA expression in Xenopus retina.
Melatonin is an indolamine hormone presumably synthesized by retinal photoreceptors, and may act as a paracrine signal of darkness within the retina. Previous studies have suggested that melatonin, acting through specific receptors, may be involved in cyclic retinal functions such as photoreceptor outer segment disc shedding and phagocytosis, and modulation of neurotransmitter release in the inner retina. The goal of this study was to determine if melatonin receptor mRNA is expressed in the neural retina and retinal pigment epithelium (RPE) of Xenopus laevis. Sheets of RPE, devoid of contaminating cells, were obtained from Xenopus eyes, and epithelial cultures were subsequently established on microporous membrane filters in a defined medium. Total RNA was isolated from whole brain, neural retina, fresh RPE sheets, and cultured RPE cells. RNA expression of the three known Xenopus melatonin receptor subtypes (MEL1A, 1B, and 1C) was determined by reverse-transcription/polymerase chain reaction (RT/PCR) amplification, followed by Southern hybridization with RNA probes. PCR-amplified cDNA encoding melatonin receptor subtypes 1B and 1C, but not 1A, were detected in reverse-transcribed RNA obtained from brain, neural retina and RPE. RPE cells grown in culture for two weeks also demonstrated 1B and 1C receptor RNA expression. This study suggests that RNA encoding the 1B and 1C melatonin receptor subtypes is expressed in the neural retina and RPE of Xenopus retina, and the expression persists in RPE cells when grown in culture. The expression of melatonin receptor RNA in the RPE may reflect a regulatory role for melatonin in some diurnal events that occur in this tissue, such as phagocytosis of photoreceptor outer segment membranes, and intracellular migration of pigment granules.


De novo 7p partial trisomy characterized by subtelomeric FISH and whole-genome array in a girl with mental retardation.
Chromosome rearrangements involving telomeres have been established as one of the major causes of idiopathic mental retardation/developmental delay. This case of 7p partial trisomy syndrome in a 3-year-old female child presenting with developmental delay emphasizes the clinical relevance of cytogenetic diagnosis in the better management of genetic disorders. Application of subtelomeric FISH technique revealed the presence of interstitial telomeres and led to the ascertainment of partial trisomy for the distal 7p segment localized on the telomeric end of the short arm of chromosome 19. Whole-genome cytogenetic microarray-based analysis showed a mosaic 3.5 Mb gain at Xq21.1 besides the approximately 24.5 Mb gain corresponding to 7p15.3- > pter. The possible mechanisms of origin of the chromosomal rearrangement and the clinical relevance of trisomy for the genes lying in the critical regions are discussed.


Emerging Racial Differences in Heart Transplant Waitlist Outcomes for Patients on Temporary Mechanical Circulatory Support.
Temporary mechanical circulatory support (tMCS) is increasingly used for patients awaiting heart transplantation. Although examples of systemic inequity in cardiac care have been described, biases in tMCS use are not well characterized. This study explores the racial disparities in tMCS use and waitlist outcomes. The United Network for Organ Sharing database was used to identify adults listed for first-time heart transplantation from 2015 to 2021. White and non-White patients on extracorporeal membrane oxygenation, intra-aortic balloon pump, or temporary left ventricular assist device were identified. Waitlist outcomes of mortality, transplantation, and delisting were analyzed by race using competing risks regression. The effect of the new heart allocation system was also assessed. A total of 16,811 patients were included in this study, with 10,377 self-identifying as White and 6,434 as non-White. White patients were more often male, privately ensured, and had less co-morbidities (p <0.05). tMCS use was found to be significantly higher in non-White patients (p <0.001). Among those on tMCS, non-White patients were more likely to be delisted because of illness (subhazard ratio 1.34 [1.09 to 1.63]) and less likely to die while on the waitlist (subhazard ratio 0.76 [0.61 to 0.93]). This disparity was not present before the implementation of the new heart allocation system. tMCS use was proportional to the risk factors identified in the non-White cohort. After the implementation of the new heart allocation system, White patients were more likely to die, whereas non-White patients were more likely to be delisted. Further work is needed to determine the causes of and potential solutions for disparities in the waitlist outcomes.


Inhibition kinetics and selectivity of the tyrosine kinase inhibitor erbstatin and a pyridone-based analogue.
The inhibition mechanisms of the epidermal growth factor (EGF) receptor tyrosine kinase and the cAMP-dependent kinase activities by erbstatin and its analogue, RG 14921, were studied by kinetic analysis. Both compounds were slow-binding inhibitors of the EGF receptor kinase. Erbstatin inhibited the EGF receptor kinase as a partial competitive inhibitor with respect to both ATP and the peptide substrate, suggesting that it binds at a site distinct from the ATP and peptide binding sites of the enzyme, and thus lowers the binding affinities of the enzyme for both substrates. In contrast, the analogue RG 14921 inhibited EGF receptor kinase activity as a non-competitive inhibitor with respect to both ATP and the peptide substrate. The distinct modes of inhibition by structurally related compounds suggest a dynamic and possibly extended structure of the catalytic center of the kinase domain of the receptor. Erbstatin and RG 14921 exerted similar effects on cAMP-dependent protein kinase activity. In this system, both compounds displayed potent inhibition and acted by a mode of competitive inhibition with respect to ATP and non-competitive with the peptide substrate.


Does marine ecological compensation policy have improved marine carbon emission efficiency? Evidence from coastal areas in China.
The marine ecological compensation (MEC) policy is a scheme for protecting and restoring marine ecology. The previous studies have verified that the policy has improved the marine environment, ignoring the comprehensive performance of the economy and environment. Is the MEC policy actually effective for reducing marine carbon emission considering resource input and economy output? To address the question, this paper evaluates the impact of MEC policy on marine carbon emission efficiency by introducing the multi-stage difference-in-difference with propensity score matching. The results show that the MEC policy significantly improves marine carbon emission efficiency, and the positive effects dynamically enhance over time. Low-carbon technology innovation is confirmed to play a mediating role by which the MEC policy improves marine carbon emission efficiency. Therefore, gradually popularizing the MEC policy and accelerating low-carbon technology innovation are crucial measures to improve marine carbon emission efficiency and achieve sustainable marine development.


Ketamine-induced relaxation in intact and skinned smooth muscles of the rabbit ear artery.
1. The effects of ketamine, an intravenous anaesthetic, on the rabbit ear artery were investigated by measuring the tension in intact and saponin-treated skinned smooth-muscle fibres. 2. Ketamine dose-dependently inhibited contractions of intact smooth-muscle fibres induced by high K+ solution and by noradrenaline (NA) or histamine in Krebs solution. This drug similarly attenuated both phasic and tonic contractions induced by high K+ solution. 3. Ketamine also inhibited NA- or histamine-induced contractions in Ca2+-free solution containing 2mM EGTA, but it did not affect the caffeine-induced contraction in this solution. 4. Because the pCa-tension relationship of saponin-treated skinned smooth-muscle fibres was not affected, it can be proposed that ketamine does not have an effect on the contractile proteins. 5. In the presence of 5mM NaN3, 20 microM inositol 1,4,5-trisphosphate (InsP3) or 25mM caffeine produced a contraction in skinned smooth-muscle fibres after accumulation of Ca2+ by intracellular stores. Analysis of the InsP3- or caffeine-induced contractions indicates that ketamine does not have an effect on the Ca2+ accumulation into and Ca2+ release from the intracellular stores. 6. These results indicate that the relaxant effects produced by ketamine in the rabbit ear artery are not likely to be due to an intracellular action. The inhibitory effects of ketamine could be caused by a decrease of the Ca2+ influx through the plasma membrane or interference with the process of signal transduction between receptors on the plasma membrane and intracellular stores.


Structure and order of the protein and carbohydrate domains of prothrombin fragment 1.
The three-dimensional structure of prothrombin fragment 1 has been determined by X-ray crystallography at 3.8 A resolution. The fragment is composed of a number of structural units, some of which are ordered while others are disordered. The ordered part of the structure includes a compact kringle unit, a helical domain and a carbohydrate chain. The kringle structure is organized around a close pair of buried disulfide bridges. One of its carbohydrate chains, that attached to Asn 101, is fully ordered, but the carbohydrate chain attached to Asn 77 appears to be disordered. The calcium binding unit is composed of a disordered part containing all ten gamma-carboxyglutamic acid residues and an ordered part forming the helical domain. The highly conserved residues Phe 41, Trp 42 and Tyr 45, which form a hydrophobic cluster on the first helix, interact around a crystallographic two-fold axis with the equivalent residues in another molecule to form a dimer in the crystal.


Systemic antifungal strategies in allogeneic hematopoietic stem cell recipients hospitalized in french hematology units: a post-hoc analysis of the cross-sectional observational AFHEM study.
Invasive fungal diseases (IFD) remain a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) and are associated with high mortality rates in patients receiving alloHSCT. Antifungal prophylaxis is increasingly being used in the management of IFDs in patients receiving alloHSCT. A post-hoc analysis of the cross-sectional observational AFHEM study was carried out to describe the use of antifungal drugs in real-life clinical practice in alloHSCT recipients hospitalized in French hematological units. A total of 147 alloHSCT recipients were enrolled; most were adults (n = 135; 92%) and had received alloHSCT < 6 months prior to enrollment (n = 123; 84%). Overall, 119 (81%) patients received a systemic antifungal therapy; of these, 95 (80%) patients received antifungal prophylaxis. Rates of patients receiving systemic antifungal treatment were similar irrespective of transplant time, neutropenic, and graft-versus-host disease status. Among patients on systemic antifungal treatment, 83 (70%) received an azole, 22 (18%) received an echinocandin, and 16 (13%) received a polyene. This work provides evidence of the antifungal strategies used in alloHSCT recipients hospitalized in French hematological units. Unlike earlier studies, the AFHEM study showed that prophylaxis appears to be the leading antifungal strategy used in alloHSCT recipients in France.


Pregnancy probabilistically augments potential precursors to chronic, immune-mediated or autoimmune lacrimal gland infiltrates.
This study asked whether pregnancy, a risk factor for dry eye disease associated with both chronic, immune-mediated- and autoimmune etiologies, augments development of clusters of coordinately functioning cells (CCFC) that may be precursors to pathological lacrimal gland infiltrates. Lacrimal glands were from six virgin- and six term-pregnant rabbits of the same age and environmental exposure history. Seventy-two immune response-related gene transcripts were assayed by real time RT-PCR. Principal component (PC) analysis identified transcript signatures of CCFC contributing negative (⊖) or positive (⊕) PC loadings and determined gland PC projections, which reflect levels of CCFC development. Three CCFC were of interest as potential precursors to pathological infiltrates. CCFC 1⊖ was suggestive of an ectopic lymphoid structure with resting T cells and B cells. CCFC 1⊕ was suggestive of an immune-mediated infiltrate with TH1 cells and mature, cytotoxic B cells. CCFC 2⊖ was suggestive of an ectopic lymphoid structure with activated T cells, mature B cells, germinal center, and plasmacytes. CCFC 4⊖ and CCFC 5⊖ also included plasmacytes. Pregnancy augmented CCFC 1⊖ in some glands; augmented CCFC 1⊕ in others; and augmented CCFC 2⊖, CCFC 4⊖, and CCFC 5⊖ different combinations. Potential precursors of pathological infiltrates form in the lacrimal glands by the time of sexual maturity. Pregnancy augments lacrimal gland plasmacyte populations, and it can augment development of potential precursors to either chronic, immune-mediated infiltrates or autoimmune infiltrates of various phenotypes. Systemic and strictly local, probabilistic phenomena interact with pregnancy to determine which combinatorial phenotypes are favored.


The potential role and regulatory mechanism of IL-33/ST2 axis on T lymphocytes during lipopolysaccharide stimulation or perinatal Listeria infection.
Interleukin-33 (IL-33) is a member of the interleukin-1 family, which is reported to be important across a range of diseases. However, the mechanisms underlying IL-33/ST2 axis in infectious diseases have not yet been fully addressed. We established both lipopolysaccharide (LPS)-induced injuryin T cells and Listeria monocytogenes (Lm) infection model to determine the effect of IL-33 on infectious immunity. The T cell proliferation was inhibited by LPS while IL-33 could reverse the outcome. Further, apoptosis was significantly promoted after serum stimulation (ST)2 knockdown, suggesting IL-33, acting through its receptor ST2, may attenuate the inhibitory effect of LPS on T cells through the apoptotic signaling pathway. In this study, we also identified an IL-33-mediated mechanism of T cell differentiation in pregnant mice infected with Lm. Here, we observed the elevated expression of IL-33 in pregnant mice infected with Lm. Furthermore, we revealed that blocking IL-33 markedly decreased the abortion rate and placental bacterial load, but weakened placental inflammatory repair, by inhibiting Th2 cell-mediated immune responses and relatively intensifying Th1-dominent immunoreaction. These findings reveal a previously unidentified mechanism underlying IL-33/ST2 axis. IL-33 signaling and targeting T cell-mediated immunity may present a new therapeutic strategy for the treatment of infectious diseases.


Modeling antiretroviral drug responses for HIV-1 infected patients using differential equation models.
We review mathematical modeling and related statistical issues of HIV dynamics primarily in response to antiretroviral drug therapy in this article. We start from a basic model of virus infection and then review a number of more advanced models with consideration of pharmacokinetic factors, adherence and drug resistance. Specifically, we illustrate how mathematical models can be developed and parameterized to understand the effects of long-term treatment and different treatment strategies on disease progression. In addition, we discuss a variety of parameter estimation methods for differential equation models that are applicable to either within- or between-host viral dynamics.


Pulmonary embolism in very old patients.
Diagnosis of pulmonary embolism (PE) in the elderly remains difficult and is often late, although its incidence increases steadily with age. Since few studies have reported the clinical picture of this disease in very old patients, the aim of our study was to focus on clinical, instrumental and laboratory aspects in patients 75 years of age and over with suspected PE. Symptoms, signs, risk factors for venous thromboembolic diseases, 12-lead electrocardiograms, B-mode echocardiograms, chest X-rays, leg compression venous ultrasonography, latex-assay quantitative D-dimer, and arterial blood gas analyses were collected for 96 elderly patients of 75 years and over (mean age 81.22 +/- 4.81) with suspected PE, admitted to our acute geriatric ward from 1997 to 2000. Patients were divided into two groups: 59 patients with PE (PE+) confirmed by pulmonary angiography, scintigraphic lung scan or necropsy, and 37 patients with normal lung scan or without PE at necropsy (PE-). Dyspnea and chest pain were the most common symptoms in both groups, but significantly more frequent in the PE+ group. Tachycardia, fever, cyanosis, and tachypnea were the most common objective signs in both groups; tachycardia and tachypnea were not significantly different between the two groups. Bed rest, venous insufficiency and leg deep vein thrombosis were the most common venous risk factors in PE+ and significantly different with respect to PE-. Sinus tachycardia, ST-T abnormalities and right bundle branch block were the most common electrocardiographic aspects in PE+; echocardiograms showed significantly more frequent acute involvement of right heart in PE+, whereas chest X-rays were rarely compatible with PE and did not reveal differences between the two groups. D-Dimer was significantly higher in PE+ but was below 500 ng/mL only in 25% of cases in PE-. More severe hypoxemla, oxy-hemoglobin hyposaturation and increased alveolar-arterial oxygen gradients were found at arterial blood gas analysis in PE+. Although many analyzed clinical, instrumental and laboratory aspects were significantly more frequent in the PE+ group, they were all non-specific and not conclusive for diagnosis of PE. Our retrospective study focus may add information about the picture and diagnostic difficulties of PE in very old patients.


Endobronchial telangiectasias and hemoptysis in scleroderma.
Hemoptysis is considered a rare event in scleroderma and to date only two previous cases could be identified. The occurrence of hemoptysis with bleeding and friable telangiectasias is reported in a patient with rapidly progressing systemic sclerosis. This represents the first report of this association, although bleeding telangiectasias have been reported in other systems. A brief review of the relevant literature is included.


Proopiomelanocortin (POMC) expression and conditioned place aversion during protracted withdrawal from chronic intermittent escalating-dose heroin in POMC-EGFP promoter transgenic mice.
In heroin-dependent individuals, the drive to avoid or ameliorate the negative affective/emotional state associated with the discontinuation of heroin contributes to the chronic relapsing nature of the disease. Here, we investigate changes in proopiomelanocortin (POMC) expression at three time points across an extended period of heroin withdrawal in a clinically relevant rodent model of addiction using conditioned place aversion (CPA) in POMC-EGFP (POMC-enhanced green fluorescent protein) bacterial artificial chromosome (BAC) transgenic mice. Neurons expressing POMC-EGFP were found in the medial nucleus of the amygdala (MeA), basomedial amygdala (BMA) and dentate gyrus of hippocampus (DG), as well as the arcuate nucleus of hypothalamus (ARC). Heroin-treated mice displayed robust CPA after acute spontaneous withdrawal (12h), which persisted across the extended (14days) withdrawal period. After 12-h withdrawal, heroin-treated mice showed lower signal intensity of POMC-EGFP-positive cells in the ARC, higher levels of POMC mRNA in the amygdala but lower levels in the hippocampus than saline controls. After 7-d withdrawal, heroin-treated mice showed fewer POMC-EGFP-positive cells in the MeA and lower POMC mRNA in the amygdala than saline controls. After extended (14days) withdrawal, heroin-treated mice showed more POMC-EGFP-positive cells in BMA and DG, increased intensity of POMC-EGFP signal in DG, and higher POMC mRNA levels in the hippocampus compared to controls. Our results show dynamic changes in POMC in hypothalamic and extra-hypothalamic regions that may contribute to the negative affective/emotional state of heroin withdrawal shown by CPA from acute to extended periods of heroin withdrawal.


Variations in microviscosity values induced by different rotational behaviour of fluorescent probes in some aliphatic environments.
Recently there have been large developments in the indirect estimation of phospholipid bilayer and membrane microviscosities through the use of fluorescent probes with the help of paraffin oils as standard solvents. Before applying this semi-empirical method to membrane systems, it seemed necessary to test: first, a large variety of probes (this has been done by many authors) and secondly, a large variety of aliphatic oils (there is little literature on these tests). The present paper shows the variations of the rotational relaxation rates of three probes in relation to the viscosities of some aliphatic oils. When changing the oil but keeping constant the macroscopic viscosity, large differences appear in the relaxation rates of a given fluorphore (a ratio of 30/1 is observed in the extreme cases). The microviscosities of membranes deduced from the probe motion will consequently exhibit large uncertainty, as is shown with dipalmitoyl phosphatidylcholine. The cause of these different behaviours must be looked for in the properties of the oil. Particularly, the anisotropy of the solute-solvent interaction in the site where the probe is located depends in part on the internal order of the solvent which is used as a reference.


Oxidative stress and aging: the potential role of iron.
According to the free radical theory of aging proposed by Denham Harman more than 50 years ago, oxidatively modified cellular components accumulate continuously in the cells during the organism's lifespan leading to progressive decline of cellular functions. Since then, it has been shown that proteins, lipids, nucleic acids and other cell components undergo reversible and/or irreversible oxidative modifications during aging. Moreover, oxidized cell components can undergo further oxidative modifications leading to formation of products that cell degradation systems are incapable of removing. Accumulation of such non-degradable aggregates further inhibits the functionality of degradation systems, thus aggravating the effects and leading to a vicious cycle. In this presentation, we propose that the availability of intracellular iron in its redox active form (labile iron) represents the main catalyst that mediates extensive oxidative modifications of cellular components and ultimately leads to their accumulation and consequent cellular dysfunction. It is tempting to speculate that regulated restriction of labile iron may have positive effects on health in general and aging in particular.