Nucleotide exchange and cGMP phosphodiesterase activation by pertussis toxin inactivated transducin.
Transducin, the signal coupling protein of retinal rod photoreceptor cells, is one of a family of G proteins that can be inactivated by pertussis toxin. We have investigated the nature of this inactivation in order to determine (1) whether it requires the toxin-catalyzed transfer of ADP-ribose from NAD+ to cysteine-347 of the alpha subunit and (2) whether it involves locking the alpha subunit in the inactive conformation characteristic of its GDP-bound state, or is limited to disruption of binding to photoexcited rhodopsin (R*). Our results indicate that all observed effects of pertussis toxin treatment, including a shift in the electrophoretic mobility of transducin's alpha subunit and functional inactivation, require NAD+ and that the appearance of the shift parallels incorporation of ADP-ribose. We have also found that, apart from interactions with photoexcited rhodopsin, the functional properties of ADP-ribosylated transducin are essentially the same as those of unmodified transducin. Normal spontaneous nucleotide exchange kinetics and the ability to activate cGMP phosphodiesterase are preserved following quantitative ADP-ribosylation, as are the abilities to hydrolyze GTP, to bind to a dye affinity column, and to display enhanced fluorescence upon addition of Al3+ and F-. Thus, ADP-ribosylation merely blocks catalysis of transducin nucleotide exchange by R* and does not lock transducin in an inactive state.(ABSTRACT TRUNCATED AT 250 WORDS)


Histopathology of Post Kala-azar Dermal Leishmaniasis.
The various lesions seen in the clinical presentation of post kala-azar dermal leishmaniasis (PKDL) are reflected in the histopathology of the type of lesion biopsied. The cells that form the dermal infiltrate include lymphocytes, histiocytes, and plasma cells in varying proportions. The infiltrate, which is mild and confined to the superficial dermis in macular lesion becomes denser with the increasing severity of the lesion. Leishman-Donovan bodies (LDB) in general are rarely demonstrable in macules and somewhat infrequently in the rest, though at times they may be numerous; mucosal lesions offer a greater chance of visualizing LDB than biopsies from the skin. A characteristic histomorphology in nodules is prominent follicular plugging with a dense plasma cell-rich lymphohistiocytic dermal infiltrate that shows an abrupt cut-off in the lower dermis, an appearance highly suggestive of PKDL even in the absence of LDB. Russell bodies within plasma cells, vascular changes, and xanthoma-like hue have been seen in plaques from chronic PKDL. The histopathologic picture in some may also mimic that seen in tuberculoid and lepromatous leprosy, and other granulomatous dermatoses. In contrast to Indian PKDL, epithelioid cell granulomas with giant cells are more common in African PKDL, and vascular changes are rare though neuritis showing LDB has been described.


Phosphorylation site specificities of glycogen synthase kinases: determination by peptide mapping using high-performance liquid chromatography.
A method is described which separates the various phosphorylation sites in glycogen synthase based on reverse phase high-performance liquid chromatography (HPLC) of tryptic 32P-peptides. Using this method we studied the phosphorylation site specificities of the kinases which act on glycogen synthase. The cAMP-dependent protein kinase phosphorylated sites 1a, 1b, and 2, whereas casein kinase II phosphorylated only site 5. Two calcium, calmodulin-dependent kinases, phosphorylase kinase and liver calmodulin-dependent synthase kinase, both phosphorylated site 2, and the latter enzyme also phosphorylated site 1b. A cAMP-independent kinase (kinase 4) purified from liver also specifically phosphorylated site 2. Synthase kinase 3 catalyzed the phosphorylation of only site 3. This HPLC method was also used to establish that all of these sites were subject to phosphorylation in vivo.


Improvement of visual field defects after focal resection for occipital lobe epilepsy: case report.
Improvement of visual field defects after surgical treatment for occipital lobe epilepsy is rare. Here, the authors report on a 24-year-old man with a 15-year history of refractory epilepsy that developed after he had undergone an occipital craniotomy to remove a cerebellar astrocytoma at the age of 4. His seizures started with an elementary visual aura, followed by secondary generalized tonic-clonic convulsion. Perimetry revealed left-sided incomplete hemianopia, and MRI showed an old contusion in the right occipital lobe. After evaluation with ictal video-electroencephalography, electrocorticography, and mapping of the visual cortex with subdural electrodes, the patient underwent resection of the scarred tissue, including the epileptic focus at the occipital lobe. After surgery, he became seizure free and his visual field defect improved gradually. In addition, postoperative 123I-iomazenil (IMZ) SPECT showed partly normalized IMZ uptake in the visual cortex. This case is a practical example suggesting that neurological deficits attributable to the functional deficit zone can be remedied by successful focal resection.


Development and application of a suite of polysaccharide-degrading enzymes for analyzing plant cell walls.
To facilitate analysis of plant cell wall polysaccharide structure and composition, we cloned 74 genes encoding polysaccharide-degrading enzymes from Aspergillus nidulans, Aspergillus fumigatus, and Neurospora crassa and expressed the genes as secreted proteins with C-terminal Myc and 6x His tags. Most of the recombinant enzymes were active in enzyme assays, and optima for pH and temperature were established. A subset of the enzymes was used to fragment polysaccharides from the irregular xylem 9 (irx9) mutant of Arabidopsis. The analysis revealed a decrease in the abundance of xylan in the mutant, indicating that the IRX9 gene, which encodes a putative family 43 glycosyltransferase, is required for xylan synthesis.


Work related respiratory symptoms in radiographers.
To determine the prevalence of work related symptoms among radiographers compared with a control group of physiotherapists. A postal questionnaire was used to collect information from radiographers and physiotherapists who registered in the United Kingdom during 1985-9. Satisfactory questionnaires were returned by 2354 (65%) of the radiographers and 3048 (69%) of the physiotherapists. There was a clear excess of work related symptoms among the radiographers. In particular, they were more likely to complain of symptoms that were worse at work, mouth soreness, sore, itchy, or runny eyes, persistent blocked nose, persistent itchy nose or sneezing, sore throat, headache, and of lower respiratory tract symptoms, which were also worse on workdays. These symptoms were associated particularly with the use of automatic processing machines. 235 radiographers gave a history of wheeze or chest tightness that had been worse at work or on days when at work. Work related symptoms suggesting irritation of the eyes and upper airways were more common in radiographers than controls, and may be related to exposure to x ray film processing chemicals. Men and women who reported work related wheeze or chest tightness will be followed up in more detail to assess the prevalence of occupational asthma in the cohort.


Gamma irradiation leads to two waves of apoptosis in distinct cell populations of the retina of newborn rats.
Gamma radiation induces apoptosis in the proliferative zone (neuroblastic layer) of the developing rat retina. We asked whether sensitivity to apoptosis might be related to distinct phases of the cell cycle. Explants of newborn rat retina or newborn pups were gamma-irradiated and apoptosis was detected by chromatin condensation, DNA fragmentation in situ and DNA electrophoresis. After 6 hours, early appearing apoptotic bodies were located mainly towards the outer tier of the neuroblastic layer. In contrast, after 24 hours, late-appearing apoptotic cells were located towards the inner margin of the neuroblastic layer, a region associated with the S phase of the cell cycle. Labeling of a cohort of cells with the nucleotide analog bromo-deoxyuridine (BrdU) at the time of irradiation, showed that these cells die in the late wave of apoptosis. BrdU given 3 hours before fixation labeled a large number of late apoptotic cells, but no early apoptotic cells. After labeling of all cycling cells with BrdU, 40% of the early apoptotic profiles were unlabeled, and thus post-mitotic. The same schedules of cell death were identified after gamma irradiation in vivo. The results show that irradiation leads to two waves of apoptosis in distinct cell populations. An early wave comprises both post-mitotic cells and proliferating cells out of the S phase. The late wave comprises cells in S phase, which pass through this phase again to die. The antioxidant pyrrolidinedithiocarbamate prevented the early but not the late wave of apoptosis following irradiation, and blocked lipid peroxidation at 6 hours after the insult, suggesting that the two waves of apoptosis are indeed mediated by distinct mechanisms.


Intrapleural Impedance Sensor Real-Time Tracking of Pneumothorax in a Porcine Model of Air Leak.
In patients with alveolar-to-pleural air leak due to recent surgery or trauma, clinicians tend to manage chest tubes with suction therapy. Nonsuction therapy is associated with shorter chest tube duration but also a higher risk of pneumothorax. We sought to develop an intrapleural electrical impedance sensor for continuous, real-time monitoring of pneumothorax development in a porcine model of air leak as a means of promoting nonsuction therapy. Using thoracoscopy, 2 chest tubes and the pleural impedance sensor were introduced into the pleural space of 3 pigs. Continuous air leak was introduced through 1 chest tube by carbon dioxide insufflation. The second chest tube was placed to suction then transitioned to no suction at increasingly higher air leaks until pneumothorax developed. Simultaneously, real-time impedance measurements were obtained from the pleural sensor. Fluoroscopy spot images were captured to verify the presence or absence of pneumothorax. Statistical Analysis Software was used throughout. With the chest tube on suction, a fully expanded lung was identified by a distinct pleural electrical impedance respiratory waveform. With transition of the chest tube to water seal, loss of contact of the sensor with the lung resulted in an immediate measurement of infinite electrical impedance. Pneumothorax resolution by restoring suction therapy was detected in real time by a return of the normal respiratory impedance waveform. Pleural electrical impedance monitoring detected pneumothorax development and resolution in real time. This simple technology has the potential to improve the safety and quality of chest tube management.


Plasmonics Meets Biology through Optics.
Plasmonic metallic nanoparticles (NPs) represent a relevant class of nanomaterials, which is able to achieve light localization down to nanoscale by exploiting a phenomenon called Localized Plasmon Resonance. In the last few years, NPs have been proposed to trigger DNA release or enhance ablation of diseased tissues, while minimizing damage to healthy tissues. In view of the therapeutic relevance of such plasmonic NPs; a detailed characterization of the electrostatic interaction between positively charged gold nanorods (GNRs) and a negatively charged whole-genome DNA solution is reported. The preparation of the hybrid biosystem has been investigated as a function of DNA concentration by means of ζ-potential; hydrodynamic diameter and gel electrophoresis analysis. The results have pointed out the specific conditions to achieve the most promising GNRs/DNA complex and its photo-thermal properties have been investigated. The overall study allows to envisage the possibility to ingeniously combine plasmonic and biological materials and, thus, enable design and development of an original non invasive all-optical methodology for monitoring photo-induced temperature variation with high sensitivity.


CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome.
CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated by multiplex ligation-dependent probe amplification (MLPA) in order to search for intragenic deletions or duplications. Thirteen novel mutations and five previously reported mutations were detected. The mutations were scattered throughout the gene and included nonsense, frameshift and missense mutations as well as intragenic deletions. In conclusion, CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome. Screening for intragenic deletions with MLPA is recommended in cases where mutations are not found by sequencing. In addition, a CDH7 mutation was found in an individual without temporal bone malformation.


Improved Sensitivity and Separations for Phosphopeptides using Online Liquid Chromotography Coupled with Structures for Lossless Ion Manipulations Ion Mobility-Mass Spectrometry.
Phosphoproteomics greatly augments proteomics and holds tremendous potential for insights into the modulation of biological systems for various disease states. However, numerous challenges hinder conventional methods in terms of measurement sensitivity, throughput, quantification, and capabilities for confident phosphopeptide and phosphosite identification. In this work, we report the first example of integrating structures for lossless ion manipulations ion mobility-mass spectrometry (SLIM IM-MS) with online reversed-phase liquid chromatography (LC) to evaluate its potential for addressing the aforementioned challenges. A mixture of 51 heavy-labeled phosphopeptides was analyzed with a SLIM IM module having integrated ion accumulation and long-path separation regions. The SLIM IM-MS provided limits of detection as low as 50-100 pM (50-100 amol/μL) for several phosphopeptides, with the potential for significant further improvements. In addition, conventionally problematic phosphopeptide isomers could be resolved following an 18 m SLIM IM separation. The 2-D LC-IM peak capacity was estimated as ∼9000 for a 90 min LC separation coupled to an 18 m SLIM IM separation, considerably higher than LC alone and providing a basis for both improved identification and quantification, with additional gains projected with the future use of longer path SLIM IM separations. Thus, LC-SLIM IM-MS offers great potential for improving the sensitivity, separation, and throughput of phosphoproteomics analyses.


Comparison of patient satisfaction with ambulatory visits in competing health care delivery settings in Geneva, Switzerland.
To measure satisfaction with medical visits in various health care settings and to assess the extent to which differences in satisfaction scores between health care settings can be attributed to patients' characteristics. This was a cross sectional survey to measure seven dimensions of patient satisfaction. Ambulatory visits to 'gatekeepers' or specialists in a newly established managed care organisation, a private group practice, or a university hospital outpatient clinic in Geneva, Switzerland. There were altogether 1027 adult patients (81% participation rate). Patients who consulted physicians in the private group practice reported higher levels of satisfaction (overall mean 83.2 on a scale between 0 and 100) than university clinic patients (79.7), patients of independent specialists within the managed plan (78.5), and patients of managed plan gatekeepers (69.8, intergroup differences p < 0.001). Differences between settings were reduced after adjustment for sex, age, country of origin, general practitioner versus specialist visit, and scheduled versus urgent visit (adjusted scores: 80.8, 78.8, 77.6, and 72.7 in the four settings, p < 0.001). Intergroup differences were largest for general satisfaction, but small and non-significant for satisfaction with explanations given by the physician and for time spent with the patient. Patient satisfaction varied widely between health care settings. Differences in satisfaction ratings could be ascribed only partly to disparities in patient populations. Patients of managed plan gatekeepers were least satisfied, presumably because they could not choose their physician freely. Comparison of patient satisfaction across health care settings can provide a basis for targeted quality improvement initiatives.


Zyxin-mediated actin assembly is required for efficient wound closure.
Cytoskeletal regulation of cell adhesion is vital to the organization of multicellular structures. The focal adhesion protein zyxin emerged as a key regulator of actin assembly because zyxin recruits Enabled/vasodilator-stimulated phospho-proteins (Ena/VASP) to promote actin assembly. Zyxin also localizes to the sites of cell-cell adhesion and is thought to promote actin assembly with Ena/VASP. Using shRNA targeted to zyxin, we analyzed the roles of zyxin at adhesive contacts. In zyxin-deficient cells, the actin assembly at both focal adhesion and cell-cell adhesion was limited, but their migration rate was unchanged. Cell spreading on E-cadherin-coated surfaces and the formation of cell clusters were slower for zyxin-deficient cells than wild type cells. By ablating a single cell within a cell monolayer, we quantified the rate of wound closure driven by a contractile circumferential actin ring. Zyxin-deficient cells failed to recruit VASP to cell-cell junctions at the wound edge and had a slower wound closure rate than wild type cells. Our results suggest that, by recruiting VASP, zyxin regulates actin assembly at the sites of force-bearing cell-cell adhesion.


Heparin II domain of fibronectin uses alpha4beta1 integrin to control focal adhesion and stress fiber formation, independent of syndecan-4.
Co-signaling events between integrins and cell surface proteoglycans play a critical role in the organization of the cytoskeleton and adhesion forces of cells. These processes, which appear to be responsible for maintaining intraocular pressure in the human eye, involve a novel cooperative co-signaling pathway between alpha5beta1 and alpha4beta1 integrins and are independent of heparan sulfate proteoglycans. Human trabecular meshwork cells isolated from the eye were plated on type III 7-10 repeats of fibronectin (alpha5beta1 ligand) in the absence or presence of the heparin (Hep) II domain of fibronectin. In the absence of the Hep II domain, cells had a bipolar morphology with few focal adhesions and stress fibers. The addition of the Hep II domain increased cell spreading and the numbers of focal adhesions and stress fibers. Cell spreading and stress fiber formation were not mediated by heparan sulfate proteoglycans because treatment with chlorate, heparinase, or soluble heparin did not prevent Hep II domain-mediated cell spreading. Cell spreading and stress fiber formation were mediated by alpha4beta1 integrin because soluble anti-alpha4 integrin antibodies inhibited Hep II domain-mediated cell spreading and soluble vascular cell adhesion molecule-1 (alpha4beta1 ligand)-induced cell spreading. This is the first demonstration of the Hep II domain mediating cell spreading and stress fiber formation through alpha4beta1 integrin. This novel pathway demonstrates a cooperative, rather than antagonistic, role between alpha5beta1 and alpha4beta1 integrins and suggests that interactions between the Hep II domain and alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork of the human eye.


[The histopathology of keratoconus posticus circumscriptus].
The histopathology of keratoconus posticus circumscriptus is described. On the basis of electron microscopic studies a corneal development anomaly may be suspected. This hypothesis is also supported by the intercellular junctions (gap junctions) between the basal epithelial cells and the differences in the diameters of the collagen fibers (10-30 nm). The disturbance in fibrillogenesis is the result of stromal cell degeneration.


Behavioral and in vitro correlates of compulsive-like food seeking induced by operant conditioning in Aplysia.
Motivated behaviors comprise appetitive actions whose occurrence results partly from an internally driven incentive to act. Such impulsive behavior can also be regulated by external rewarding stimuli that, through learning processes, can lead to accelerated and seemingly automatic, compulsive-like recurrences of the rewarded act. Here, we explored such behavioral plasticity in Aplysia by analyzing how appetitive reward stimulation in a form of operant conditioning can modify a goal-directed component of the animal's food-seeking behavior. In naive animals, protraction/retraction cycles of the tongue-like radula are expressed sporadically with highly variable interbite intervals. In contrast, animals that were previously given a food-reward stimulus in association with each spontaneous radula bite now expressed movement cycles with an elevated frequency and a stereotyped rhythmic organization. This rate increase and regularization, which was retained for several hours after training, depended on both the reward quality and its contingency because accelerated, stereotyped biting was not induced in animals that had previously received a less-palatable food stimulus or had been subjected to nonassociative reward stimulation. Neuronal correlates of these learning-induced changes were also expressed in the radula motor pattern-generating circuitry of isolated buccal ganglia. In such in vitro preparations, moreover, manipulation of the burst frequency of the bilateral motor pattern-initiating B63 interneurons indicated that the regularization of radula motor pattern generation in contingently trained animals occurred separately from an increase in cycle rate, thereby suggesting independent processes of network plasticity. These data therefore suggest that operant conditioning can induce compulsive-like actions in Aplysia feeding behavior and provide a substrate for a cellular analysis of the underlying mechanisms.


Chiropractic spinal manipulative therapy for acute neck pain: A 4-arm clinical placebo randomized controlled trial. A prospective study protocol.
Neck pain poses enormous individual and societal costs worldwide. Spinal manipulative therapy and Non-Steroidal Anti-Inflammatory Drug treatment are frequently used despite a lack of compelling efficacy data. This protocol describes a multicentre 4-arm, clinical placebo randomized controlled trial (RCT), investigating the efficacy of chiropractic spinal manipulative therapy (CSMT) versus sham CSMT, ibuprofen, and placebo medicine for acute neck pain. This superiority study will employ parallel groups, featuring a 1:1:1:1 allocation ratio. We will randomize 320 participants equally into four groups: CSMT, sham CSMT, ibuprofen, or placebo medicine. CSMT groups are single-blinded, while the medicine groups are double-blinded. Data will be collected at baseline (Day 0), during treatment and post-treatment. The primary endpoint will assess the difference in mean pain intensity from Day 0 to Day 14 on a numeric rating scale 0-10; the CSMT group is compared to sham CSMT, ibuprofen, and placebo medicine groups, respectively. Secondary endpoints will assess mean pain intensity and mean duration at different time points, and adverse events, blinding success, and treatment satisfaction, including comparison between ibuprofen and placebo medicine. Power calculation is based on a mean neck pain rating of 5 at Day 0, with standard deviation of 1 in all groups. Mean pain reduction at Day 14 is expected to be 60% in the CSMT group, 40% in sham CSMT and ibuprofen groups, and 20% in the placebo medicine group. A linear mixed model will compare the mean values for groups with corresponding 95% confidence intervals. P values below 0.017 will be considered statistically significant. All analyses will be conducted blinded from group allocation. This RCT aims towards the highest research standards possible for manual-therapy RCTs owing to its two placebo arms. If CSMT and/or ibuprofen proves to be effective, it will provide evidence-based support for CSMT and/or ibuprofen for acute neck pain. ClinicalTrials.gov identifier: NCT05374057. EU Clinical Trials Register: EudraCT number: 2021-005483-21.


[Comorbidity of ulcerative erosive lesions of the gastroduodenal area and arterial hypertension].
Comorbidity remains an important scientific and practical medical problem especially in respect to such prevalent and socially significant diseases as arterial hypertension (AH) and ulcerative-erosive gastroduodenal lesions (UEGDL). In these diseases there are common etiological and pathogenetic factors reflecting syntropy of this combination. These factors include systemic vascular disorders, homeostatic alterations, immunological disturbances, mental diseases, metabolic syndrome, impairment of cellular membranes as a result of activation of lipid peroxidation, etc. Adequate therapy is essential in AH comorbidity with UEGDL. It should be directed not only to lowering of blood pressure and local pathogenetic factors (acidopeptic, infectious, vascular) but also predict pharmacological impact on both diseases and other risk factors to reduce probability of unfavourable outcomes, correct damaged mechanisms of adaptive regulation of the organism and improve quality of patients' life. Specificity of the comorbide course of AH and UEGDL should be considered to perform adequate treatment, goal-oriented prevention and prediction of complications.


[Pathology of the craniocervical junction as shown by magnetic resonance tomography. 68 cases].
In cases of a suspected lesion at the level of the cranio-cervical junction, MR should be considered as the imaging technique of choice. Tumours, inflammation and degenerative processes can be reliably demonstrated and diagnosed. Administration of contrast media, for example, gadolinium-DTPA, is necessary in selected cases only. Comparing "examination time" of x-ray myelography and high resolution x-ray CT with MR, one can well tolerate the long "acquisition" of MR images.


Genetic analysis of rice seedling traits related to machine transplanting under different seeding densities.
Due to the diversity of rice varieties and cropping systems in China, the limitation of seeding density and seedling quality makes it hard to improve machine-transplanted efficiency. Previous studies have shown that indica and japonica varieties varied in machine transplanting efficiency and optimal seeding density. In this study, a RIL population derived from '9311' and 'Nipponbare' were performed to explore the seedling traits variations and the genetic mechanism under three seeding densities. The parents and RIL population exhibited similar trends as the seeding density increased, including seedling height and first leaf sheath length increases, shoot dry weight and root dry weight decreases. Among the 37 QTLs for six traits detected under the three seeding densities, 12 QTLs were detected in both three seeding densities. Five QTL hotspots identified clustered within genomic regions on chromosomes 1, 2, 4, 6 and 11. Specific QTLs such as qRDW1.1 and qFLSL5.1 were detected under low and high seeding densities, respectively. Detailed analysis the QTL regions identified under specific seeding densities revealed several candidate genes involved in phytohormones signals and abiotic stress responses. Whole-genome additive effects showed that '9311' contributed more loci enhancing trait performances than 'Nipponbare', indicating '9311' was more sensitive to the seeding density than 'Nipponbare'. The prevalence of negative epistasis effects indicated that the complementary two-locus homozygotes may not have marginal advantages over the means of the two parental genotypes. Our results revealed the differences between indica rice and japonica rice seedling traits in response to seeding density. Several QTL hotspots involved in different traits and specific QTLs (such as qRDW1.1 and qFLSL5.1) in diverse seeding densities had been detected. Genome-wide additive and two-locus epistasis suggested a dynamic of the genetic control underlying different seeding densities. It was concluded that novel QTLs, additive and epistasis effects under specific seeding density would provide adequate information for rice seedling improvement during machine transplanting.


Allergic rhinitis and inflammatory airway disease: interactions within the unified airspace.
Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.


Utilizing nanotechnology and advanced machine learning for early detection of gastric cancer surgery.
Nanotechnology has emerged as a promising frontier in revolutionizing the early diagnosis and surgical management of gastric cancers. The primary factors influencing curative efficacy in GIC patients are drug inefficacy and high surgical and pharmacological therapy recurrence rates. Due to its unique optical features, good biocompatibility, surface effects, and small size effects, nanotechnology is a developing and advanced area of study for detecting and treating cancer. Considering the limitations of GIC MRI and endoscopy and the complexity of gastric surgery, the early diagnosis and prompt treatment of gastric illnesses by nanotechnology has been a promising development. Nanoparticles directly target tumor cells, allowing their detection and removal. It also can be engineered to carry specific payloads, such as drugs or contrast agents, and enhance the efficacy and precision of cancer treatment. In this research, the boosting technique of machine learning was utilized to capture nonlinear interactions between a large number of input variables and outputs by using XGBoost and RNN-CNN as a classification method. The research sample included 350 patients, comprising 200 males and 150 females. The patients' mean ± SD was 50.34 ± 13.04 with a mean age of 50.34 ± 13.04. High-risk behaviors (P = 0.070), age at diagnosis (P = 0.034), distant metastasis (P = 0.004), and tumor stage (P = 0.014) were shown to have a statistically significant link with GC patient survival. AUC was 93.54%, Accuracy 93.54%, F1-score 93.57%, Precision 93.65%, and Recall 93.87% when analyzing stomach pictures. Integrating nanotechnology with advanced machine learning techniques holds promise for improving the diagnosis and treatment of gastric cancer, providing new avenues for precision medicine and better patient outcomes.


[Glucose content in the tissues of susliks and rats of different ages under hypothermia].
A short-term cooling of adult rats and gophers up to 30, 25 and 20 degrees C is accompanied by a rise of the glucose level in blood. No dependence is found between lowering the body temperature drop and degree of glycaemia. Prolongation of hypothermia of 30 and 20 degrees C up to 3 h causes (as compared to the control) a decrease in the glucose amount in blood of gophers but not in the rats. The cooling of the eye-opening, month and adult rats up to 20 degrees C is accompanied by a significant increase in the content of glucose in the brain and skeletal muscles. Simultaneously in the eye-opening and adult animals, contrary to the month ones, the level of glucose in the liver and blood rises. The content of glucose in the brain of the normothermal gophers (61.2 mg.) is 3,4 times as high as in the rat brain. At all the studied stages of artificial hypothermia as well as at 15 and 30-day hibernation (5 degrees C) the amount of glucose of the gopher brain remains at a relatively high level (41.6-101.5 mg%).


Disaster preparedness among families of children with special health care needs.
Families with children with special health care needs may present a challenge for disaster responders. This study examined the level of personal disaster preparedness among this at-risk population in relation to the general population, and explores whether special health care needs or perception of disaster risk affects preparedness levels. A convenience sample of 145 families presenting to an urban tertiary care children's hospital was surveyed using a previously validated instrument to gather information on levels of preparedness and factors influencing preparedness. In spite of significant special health care needs and concern about disasters, families remain unprepared for a disaster event. Health care and psychosocial support workers are in a unique position to increase preparedness levels in this at-risk population.


Enhanced UV photosensitivity from rapid thermal annealed vertically aligned ZnO nanowires.
We report on the major improvement in UV photosensitivity and faster photoresponse from vertically aligned ZnO nanowires (NWs) by means of rapid thermal annealing (RTA). The ZnO NWs were grown by vapor-liquid-solid method and subsequently RTA treated at 700°C and 800°C for 120 s. The UV photosensitivity (photo-to-dark current ratio) is 4.5 × 103 for the as-grown NWs and after RTA treatment it is enhanced by a factor of five. The photocurrent (PC) spectra of the as-grown and RTA-treated NWs show a strong peak in the UV region and two other relatively weak peaks in the visible region. The photoresponse measurement shows a bi-exponential growth and bi-exponential decay of the PC from as-grown as well as RTA-treated ZnO NWs. The growth and decay time constants are reduced after the RTA treatment indicating a faster photoresponse. The dark current-voltage characteristics clearly show the presence of surface defects-related trap centers on the as-grown ZnO NWs and after RTA treatment it is significantly reduced. The RTA processing diminishes the surface defect-related trap centers and modifies the surface of the ZnO NWs, resulting in enhanced PC and faster photoresponse. These results demonstrated the effectiveness of RTA processing for achieving improved photosensitivity of ZnO NWs.


Current approach to the surgical management of chronic pancreatitis.
The indications for surgical intervention in chronic pancreatitis are suspicion of malignancy, local complications, and intractable pain. Chronic pancreatitis is a risk factor for development of pancreatic carcinoma, and carcinomas may present, initially with a clinical picture of chronic pancreatitis. Local complications of chronic pancreatitis such as common bile duct or duodenal obstruction and enlarging or symptomatic pseudocyst also mandate surgical intervention. Thrombosis of the splenic vein with left-sided portal hypertension is common and associated with a 10% incidence of gastric variceal hemorrhage, which requires splenectomy. The role of surgery in the management of pain associated with chronic pancreatitis is to provide relief. When the pain interferes substantially with the patient's quality of life or narcotics are required for pain relief, surgical intervention is indicated. Other factors that should be incorporated in assessing the need for surgical intervention are malnutrition due to the inability to eat or malabsorption, the need for frequent hospitalization, and the inability to work. The operation selected for chronic pancreatitis should correct or deal with all structural abnormalities, provide long-term pain relief, have a low mortality and morbidity rate, minimize subsequent exocrine and endocrine insufficiency, and have results independent of abstinence from alcohol. No single operation can provide an optimal solution to the management of pain or these diverse complications of chronic pancreatitis. The operation chosen must be individualized to treat the patient's needs.


[Effect of prolonged hypokinesia on the gonadal and adrenal function of female hamadryas baboons].
A radioimmunoassay was used to study the effect of 26-day clinostatic hypokinesia on the level of sex hormones and cortisol in the peripheral blood plasma of 10 female papio hamadryas immobilized in different phases of the menstrual cycle. A significant decrease in the level of estradiol in the follicular phase and progesterone in the luteal phase was shown whereas the levels of cortisol and testosterone did not practically vary. Dependence of the adrenal gland reactivity to an acute immobilization stress on a cycle phase with minimal values in the luteal period was shown. It is assumed that the revealed imbalance of sex steroids was one of the reasons for disturbance of menstrual function found in hypokinesia of the females in both phases of the cycle.


Skeletal advancement for the treatment of obstructive sleep apnea in children.
Maxillomandibular advancement is curative for some adult patients with obstructive sleep apnea (OSA). Little is known, however, about the efficacy of this treatment in children. The purpose of this retrospective analysis is to assess the clinical outcomes of children with medically refractory OSA who were treated with a variety of procedures to advance the maxillofacial skeleton. The records of eight children with OSA (five boys and three girls; mean age, 8.6 years; range, 2 to 17 years) were reviewed. Six children had identifiable syndromes associated with micrognathia, one child had mandibular ankylosis, and one child was nonsyndromic. In five of the children, conventional medical and surgical treatment of OSA had failed; therefore, these children were considered tracheostomy candidates. The remaining three children had had tracheostomies placed in infancy. Specific signs and symptoms with regard to each patient's OSA were identified and recorded. Bronchoscopy was performed preoperatively to evaluate the airway and localize the site of obstruction and again postoperatively if the patient's signs and symptoms recurred. Oxygen saturation and sleep patterns were monitored overnight in the five patients without tracheostomies, revealing a mean apnea index of 25.3 (range, 2.0 to 60.0) and mean lowest desaturation of 73% (range, 62% to 77%). All patients underwent a variety of skeletal procedures to advance the mandible, maxilla, and/or chin. Criteria for success after treatment were twofold: (1) decannulation and (2) cessation or improvement in symptoms facilitating avoidance of tracheostomy. Criteria for failure, likewise, were (1) inability to decannulate and (2) recurrence or nonimprovement in symptoms necessitating tracheostomy. To date, with a mean follow-up time of 7.2 years (range, 19 months to 19 years), the treatment of four of the eight children in our population can be considered a success. Two of the three children with previously placed tracheostomies were able to be decannulated within days of surgery and experienced no further signs or symptoms of OSA. Two other children experienced complete cessation of clinical signs and symptoms and elimination of previous oxygen requirements. Of the four patients in whom treatment failed, three had transient improvement (mean, 6 months) and, despite skeletal stability, eventually experienced relapse of symptoms: one patient with Down syndrome and tracheobronchomalacia required subsequent tracheostomy; the second had a central obstructive component and underwent a ventriculoperitoneal shunt for treatment of a Chiara I malformation; and the third experienced relapse of symptoms due to lack of mandibular growth. The fourth child could not be decannulated because of accompanying tracheal and laryngeal malacia. Skeletal advancement can be an effective treatment for medically refractory OSA in children. Success, however, is dependent not only on skeletal position but also on neuromuscular adaptation. Bronchoscopy is the most valuable diagnostic and predictive tool.


The direct and precursor mediated dissociation rates of H2 on a Ni(111) surface.
The dissociation and recombination rates of physisorbed H2, and the direct and steady state dissociation (i.e., the precursor mediated dissociation) rates of gas phase H2 on Ni(111), as well as the corresponding kinetic isotope effects, are calculated using the quantum instanton method, together with path integral Monte Carlo and adaptive umbrella sampling techniques. All these rates except the recombination one first decrease and then increase with the increasing temperature, and their minimum values appear at about 250, 300 and 250 K, respectively. These non-monotonic behaviors reveal that the quantum effect of H2 should be very remarkable at low temperatures. The steady state rates are smaller than the direct rates at low temperatures, however, they become larger than the direct ones at high temperatures, these two kinds of rates become equal at about 400 and 300 K on the rigid and quantum lattices, respectively. The quantum motion of the lattice can enhance the direct and steady state rates, and it increases the steady state rate much more than the direct one, for instance, the direct and steady state rates on the quantum lattice are 1.30 and 2.08 times larger than that on the rigid one at 300 K. The calculated kinetic isotope effects are much larger than 1, which reveals that H2 always has a larger rate than that of D2, and the direct process predicts much larger kinetic isotope effects than the steady state process at low temperatures. In addition, the kinetic isotope effects are not affected by the lattice motion.


The Association Between Health Information Seeking on the Internet and Physician Visits (The Seventh Tromsø Study - Part 4): Population-Based Questionnaire Study.
The internet is being widely used for seeking health information. However, there is no consensus on the association between health information seeking on the internet and the use of health care services. We examined the association between health information seeking via the internet and physician visits. In addition, we investigated the association between online health information seeking and the decisions to visit and not to visit a physician. We used the cross-sectional electronic health (eHealth) data of 18,197 participants from the seventh survey of the Tromsø Study (Tromsø 7). The participants were aged ≥40 years and living in Tromsø, Norway. We used logistic regression models to examine the association between online health information seeking and physician visits, the decision to visit a physician, and the decision not to visit a physician, with adjustment for the demographic status, socioeconomic status, and health status of the participants. The use of Web search engines was associated with a physician visit. However, the association was moderated by age, and the OR decreased as age increased. The ORs for the use of Web search engines were 1.99 (95% CI 1.94-2.02) and 1.07 (95% CI 1.03-1.12) at ages 40 and 80 years, respectively. The decision to visit a physician was associated with the use of Web search engines (OR 2.95, 95% CI 2.03-4.46), video search engines (OR 1.43, 95% CI 1.21-1.70), and health apps (OR 1.26, 95% CI 1.13-1.42). The association between social media use and the decision to visit a physician was moderated by gender. Women who used social media had 1.42 (95% CI 1.31-1.55) times higher odds of deciding to visit a physician, whereas the decision to visit a physician was not different between men who used social media and those who did not use social media. Conversely, the decision not to visit a physician was associated with the use of Web search engines (OR 2.78, 95% CI 1.92-4.18), video search engines (OR 1.27, 95% CI 1.07-1.51), social media (OR 1.28, 95% CI 1.10-1.49), and health apps (OR 1.20, 95% CI 1.07-1.35). Health information found on the internet was positively associated with both the decision to visit a physician and the decision not to visit a physician. However, the association of health information seeking with the decision to visit a physician was slightly stronger than the association with the decision not to visit a physician. This could imply that the use of eHealth services is associated with a resultant increase in physician visits. In summary, our findings suggest that the internet serves as a supplement to health care services rather than as a replacement.


YgfZ contributes to secretion of cytotoxic necrotizing factor 1 into outer-membrane vesicles in Escherichia coli.
Cytotoxic necrotizing factor 1 (CNF1), a Rho GTPase-activating bacterial toxin, has been shown to contribute to invasion by meningitis-causing Escherichia coli K1 of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. However, CNF1 is a cytosolic protein and it remains unclear how its secretion occurs, contributing to E. coli invasion of HBMEC. To investigate the genetic requirement for CNF1 secretion in E. coli K1 strain RS218, we performed mini-Tn5 in vitro mutagenesis and constructed a transposon mutant library of strain NBC, in which β-lactamase was fused to the C-terminus of CNF1 in the chromosome of strain RS218. We identified a transposon mutant (NBC-1E6) that exhibited reduced β-lactamase activity in its culture supernatant and had the transposon inserted into the ygfZ gene. When ygfZ was deleted from the genome of strain RS218 (ΔygfZ), the translocation of CNF1 into HBMEC was impaired. Subcellular localization analysis of CNF1 demonstrated that YgfZ, a periplasmic protein, contributes to secretion of CNF1 into outer-membrane vesicles (OMVs). The ΔygfZ mutant was significantly defective in invasion of HBMEC compared to the parent E. coli K1 strain. The defects of the ΔygfZ mutant in CNF1 secretion into OMVs and translocation into HBMEC as well as invasion of HBMEC were abrogated by complementation with ygfZ. Taken together, our findings demonstrate that YgfZ contributes to CNF1 secretion into OMVs in meningitis-causing E. coli K1.


Indirect plant-mediated interactions among parasitoid larvae.
Communities are riddled with indirect species interactions and these interactions can be modified by organisms that are parasitic or symbiotic with one of the indirectly interacting species. By inducing plant responses, herbivores are well known to alter the plant quality for subsequent feeders. The reduced performance of herbivores on induced plants cascades into effects on the performance of higher trophic level organisms such as parasitoids that develop inside herbivores. Parasitoids themselves may also, indirectly, interact with the host plant by affecting the behaviour and physiology of their herbivorous host. Here, we show that, through their herbivorous host, larvae of two parasitoid species differentially affect plant phenotypes leading to asymmetric interactions among parasitoid larvae developing in different hosts that feed on the same plant. Our results show that temporally separated parasitoid larvae are involved in indirect plant-mediated interactions by a network of trophic and non-trophic relationships.


Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease.
Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. Eleven to 14% of end-stage renal disease (ESRD) cases are attributable to chronic IRD. A high percentage of patients entering ESRD programs are hypertensive. Many patients with a presumed diagnosis of hypertensive nephrosclerosis actually have undiagnosed ischemic nephropathy as the etiology of their ESRD. It is important for the clinician to identify IRD, because IRD is a potentially reversible cause of chronic renal failure in a hypertensive patient. Atherosclerotic renal artery disease is common among patients with coronary artery disease and aortic and peripheral vascular disease. Atherosclerotic renal artery disease is a progressive disorder, and its progression is associated with loss of renal mass and functioning. A decrease in glomerular filtration rate sufficient to cause an elevation of the serum creatinine concentration requires injury to both kidneys. Consequently, IRD can arise from one of two main clinical situations: bilateral hemodynamically significant renal artery stenosis leading to bilateral renal ischemia; and hemodynamically significant renal artery stenosis in a solitary functioning kidney, or in a kidney that is providing the majority of a patient's glomerular filtration. The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function, or a delay in progression to ESRD. There are six major clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed upon poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient. Noninvasive testing modalities that have been used recently include the angiotensin converting enzyme inhibitor renal scan, duplex Doppler sonography, magnetic resonance angiography, and the spiral computed tomography. Treatment methods include percutaneous transluminal angioplasty, endovascular stenting, and surgical revascularization. The results of treatment for preservation of renal function have been encouraging, with stabilization or improvement in renal function observed in a significant proportion of cases.


Real-time bulk-motion-correction free Doppler variance optical coherence tomography for choroidal capillary vasculature imaging.
In this paper, we analyze the retinal and choroidal blood vasculature in the posterior segment of the human eye with optimized color Doppler and Doppler variance optical coherence tomography. Depth-resolved structure, color Doppler and Doppler variance images are compared. Blood vessels down to the capillary level were detected and visualized with the optimized optical coherence color Doppler and Doppler variance method. For in-vivo imaging of human eyes, bulk-motion induced bulk phase must be identified and removed before using the color Doppler method. It was found that the Doppler variance method is not sensitive to bulk-motion and the method can be used without correcting the bulk-motion when the sample-movement-induced velocity changes gradually. Real-time processing and displaying of the structure and blood vessel images are very interesting and is demonstrated using a dual quad-core Central Processing Unit (CPU) workstation. High resolution images of choroidal capillary of the vasculature network with phased-resolved color Doppler and Doppler variance are shown.


Describing the diurnal relationships between objectively measured mother and infant physical activity.
Evidence for the importance of accumulating sufficient physical activity in the early years is mounting. This study aimed to determine the relationship between maternal and infant objectively measured physical activity, and to examine the diurnal interactions between these behaviours while accounting for potential covariates. Mothers and infants (n = 152 pairs; infants aged 3-24 months) were recruited from Soweto, South Africa, and physical activity was measured using a wrist worn accelerometer (Axivity AX3, Axivity Ltd., Newcastle-upon-Tyne, UK) for 3-7 days. Mothers completed sleep diaries recording night time-in-bed (used as a proxy for nocturnal sleep status) for themselves and their infant; and reported times during which their infant was in their personal care (caregiver status) for each day during the measurement period. Significant correlates of infant physical activity, as well as the interactions between mother's physical activity, day of the week, sleep status, and caregiver status, were included in panel regression analyses with infant physical activity as the outcome. There was an equal distribution of boys and girls, and their age ranged from 2.6 to 24.5 months. The majority of mothers (73%) did not spend any time apart from their infant. During weekdays, the combined effect of mother's physical activity (β=0.11), the interactions between mother's physical activity and caregiver status (β=0.17), and sleep status (β= - 0.04) on infant physical activity was β=0.24; while during weekend days this association was β=0.21; and was largely moderated by the interaction between the mother being with the infant and her activity levels (β=0.23), but partly attenuated by mother's physical activity independent of other variables (β= - 0.04). For each hour of the day, for both mother and infant, peaks of physical activity were higher when the mother was not the primary caregiver. Infant physical activity levels were strongly associated with their mother's activity levels particularly during the week; this relationship was stronger when mothers were more active while looking after their infant. Mothers should be encouraged to be active when looking after their children, particularly during the week, and to provide infants with as much opportunity to be active as possible.


Our Voice in a rural community: empowering Colombian adolescents to advocate for school community well-being through citizen science.
Santa Ana is home to an Afro-descendant rural population of the island of Barú in Cartagena, Colombia. While a popular area for tourism, Santa Ana's population is affected by multidimensional poverty, precarious work conditions, homelessness, broken streets and sewer systems, limited quality education, and a lack of recreation and sport spaces. While Santa Ana's Community Action Board aims to unify efforts and resources to solve these problems, the state's capacity to meet the requirements of the Board is limited. We evaluated the relationship between healthy lifestyles and characteristics of Santa Ana's school using the Our Voice Citizen Science Research Method. This systemic approach combines information and communication technologies with group facilitation to empower adolescents to: 1) collect and discuss data about factors in their local environments that facilitate or hinder well-being within their school community; 2) identify relevant local stakeholders who could help to address the issues identified; and 3) advocate collectively for local improvements to support increased well-being at a community level. Eleven citizen scientists ages 13 to 17 years from the science club of Institución Educativa Santa Ana were recruited and together conducted 11 walks within the school to collect data about the facilitators and barriers to student well-being. They identified barriers to well-being related to school infrastructure, furniture, bathrooms, and sense of belonging. They then advocated with school stakeholders and reached agreements on concrete actions to address identified barriers, including fostering a culture among students of caring for school property and presenting their findings to the community action board. This methodology allowed the community to realize how students can become agents of change and take collective action when motivated by solution-oriented methodologies such as Our Voice. Project ripple effects, including greater empowerment and participation in collective actions by students, also were observed. This study underscores the importance of the school's built environment in the well-being of students in rural areas. The Our Voice method provided the opportunity to inform school-based interventions, and promoted ripple effects that expanded productive dialogue to the community level and generated systemic actions involving actors outside of the school community.


Early pubertal onset and its relationship with sexual risk taking, substance use and anti-social behaviour: a preliminary cross-sectional study.
In many countries age at pubertal onset has declined substantially. Relatively little attention has been paid to how this decline may affect adolescent behaviours such as substance use, violence and unprotected sex and consequently impact on public health. In the UK, two opportunistic samples (aged 16-45 years), paper-based (n = 976) and online (n = 1117), examined factors associated with earlier pubertal onset and whether earlier age of onset predicted sexual risk-taking, substance use and anti-social behaviours during early adolescence. Overall, 45.6% of females reported menarche < or = 12 years and 53.3% of males were categorised as having pubertal onset < or = 11 years. For both sexes earlier pubertal onset was associated with poorer parental socio-economic status. Other pre-pubertal predictors of early onset were being overweight, more childhood illnesses (females) and younger age at time of survey (males). For both sexes earlier puberty predicted having drunk alcohol, been drunk, smoked and used drugs <14 years as well as having a sexual debut and unprotected sex <16 years. Males with earlier pubertal onset were more likely to report fighting and aggressive responses to emotional upset during early adolescence while females were more likely to report being bullied and having taken more time off school. Results provide sufficient evidence for changes in age of pubertal onset to be further explored as a potential influence on trends in adolescent risk behaviours. Further insight into the relationship between early puberty and both obesity and socio-economic status may help inform early interventions to tackle the development of risk behaviours and health inequalities during early adolescence.


Brief Assessment of Impaired Cognition Questionnaire (BASIC-Q)-Development and validation of a new tool for identification of cognitive impairment in community settings.
Brief Assessment of Impaired Cognition (BASIC), which combines self- and informant report with cognitive testing, was previously found to be highly accurate in identification of dementia and cognitive impairment. The aim of the present study was to develop and validate a questionnaire version of BASIC, the BASIC-Q, for use in community settings. In order to construct a questionnaire version of BASIC, we substituted cognitive testing with questions regarding orientation. BASIC-Q was validated based on further analysis of data from the primary BASIC validation study, where patients consecutively referred from general practice were tested at their first memory clinic admission prior to diagnosis. Control participants were primarily recruited among participating patients' relatives. Expert clinical diagnosis was subsequently used as reference standard for estimation of classification accuracy. A high discriminative validity (sensitivity 0.92, specificity 0.97) for cognitive impairment (n = 159) vs socio-demographically matched control participants (n = 109) was found. In comparison, the MMSE had 0.76 sensitivity and 0.81 specificity. Administration time for BASIC-Q was less than 5 minutes compared to approximately 10 minutes for the MMSE. BASIC-Q is a brief, efficient and valid tool for identification of cognitive impairment in a clinical setting. Further validation in a community setting is needed.


Investigation of Combined Carotid Endarterectomy and Coronary Artery Bypass Graft Surgery Outcomes and Adverse Event Risk Factors in the Vascular Quality Initiative.
The purpose of this study was to investigate outcomes of simultaneous CEA and CABG utilizing the Vascular Quality Initiative (VQI). Additionally, we seek to investigate risks for both perioperative and long-term mortality and adverse neurological outcomes. All carotid endarterectomies in the VQI between January 2003 and May 2022 were queried. We identified 171,816 CEA in the database. We extracted 2 cohorts from these CEA. The first group was patients who underwent simultaneous carotid endarterectomy (CEA) and coronary artery bypass (CABG) (N = 3137). The second group encompassed patients who underwent CABG or percutaneous coronary artery angioplasty/stent within 5 years of ultimately undergoing CEA (N = 27,387). We investigated the following outcomes in a multivariable fashion: 1. Risks for mortality in long term follow-up for both cohorts combined; 2. Risks for ischemic event in the cerebral hemisphere ipsilateral to the CEA site after index hospital admission in follow up for both cohorts combined. Tertiary outcomes are also investigated in the manuscript. On multivariable analysis, patients undergoing simultaneous combined CEA and CABG had equivalent long-term survival to patients who underwent coronary revascularization within 5 years of ultimately undergoing CEA. Five-year survival is noted to be 84.5% vs 86% with a Cox regression non-significant P-value (.203). Significant multivariable risks for reduced long term survival (P < .03 for all) included: advancing age (HR 2.48/year); smoking history (HR 1.26); Diabetes (HR 1.33); history of CHF (HR 1.66); history of COPD (HR 1.54); baseline renal insufficiency at the time of surgery (HR 1.30); anemia (HR1.64); lack of preoperative aspirin (HR 1.12); and lack of preoperative statin (HR 1.32); lack of patch placement at CEA site (HR 1.16); perioperative MI (HR 2.04); perioperative CHF (1.66); perioperative dysrhythmia (HR 1.36); cerebral reperfusion injury (HR 2.23); perioperative ischemic neurological event (HR 2.48); and lack of statin at discharge (HR 2.04). Amongst patients with documented neurological status in follow up, combined CEA and CABG had over 99% freedom from ischemic cerebral event ipsilateral to the CEA site after discharge. Combined CEA and CABG provides excellent long-term mortality prevention in patients with co-existing severe coronary and carotid atherosclerosis. Simultaneous CEA and CABG provides equivalent stroke prevention and long-term survival to both a cohort of patients undergoing coronary revascularization within 5 years of CEA and patients undergoing isolated CEA or CABG in the literature. The two most impactful modifiable risk factors towards long-term stroke and mortality prevention for patients undergoing simultaneous CEA-CABG are patch placement at CEA site and adherence to statin medication therapy.


Learning, memory, and executive control in individuals with obstructive sleep apnea syndrome.
A range of neuropsychological deficits have been identified in individuals with obstructive sleep apnea syndrome (OSAS) and have been related to disruptions in function of the frontal cortex of the brain. We hypothesized that impairments in the use of strategic, frontally-mediated processes that facilitate learning and memory would be associated with deficits in the long-term episodic memory of verbal material (i.e., word lists). We evaluated 28 adults with OSAS and 24 controls (ranging from 28 to 60 years of age) using the California Verbal Learning Test. General executive abilities were assessed using the Wisconsin Card Sorting Test, Letter fluency, and Category fluency. Individuals with OSAS exhibited poorer recall across learning trials, less efficient use of semantic clustering, and poorer use of semantic cues. Retention of previously encoded information and recognition, however, were intact. With the exception of letter fluency, deficits were not observed in general executive control. Results are discussed within the context of disruptions in the interactions between long-term memory and executive abilities that are subserved by frontal and distal brain regions.


Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda.
Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis.


Organic Phosphorescence Nanowire Lasers.
Organic solid-state lasers (OSSLs) based on singlet fluorescence have merited intensive study as an important class of light sources. Although the use of triplet phosphors has led to 100% internal quantum efficiency in organic light-emitting diodes (OLEDs), stumbling blocks in triplet lasing include generally forbidden intersystem crossing (ISC) and a low quantum yield of phosphorescence (ΦP). Here, we reported the first triplet-phosphorescence OSSL from a nanowire microcavity of a sulfide-substituted difluoroboron compound. As compared with the unsubstituted parent compound, the lone pair of electrons of sulfur substitution plus the intramolecular charge transfer interaction introduced by the nitro moiety lead to an highly efficient T1 (π,π*) ← S1 (n,π*) ISC (ΦISC = 100%) and a moderate ΦP (10%). This, plus the optical feedback provided by nanowire Fabry-Perot microcavity, enables triplet-phosphorescence OSSL emission at 650 nm under pulsed excitation. Our results open the door for a whole new class of laser materials based on previously untapped triplet phosphors.


Sedimentary signals of recent faulting along an old strand of the San Andreas Fault, USA.
Continental transform fault systems are fundamental features in plate tectonics. These complex systems often constitute multiple fault strands with variable spatio-temporal histories. Here, we re-evaluate the complex history of the San Andreas Fault along a restraining bend in southern California (USA). The Mission Creek strand of the San Andreas Fault is a major geologic structure with ~90 km of strike-slip displacement but is currently mapped as inactive. Quaternary deposits record sediment dispersal across the fault from upland catchments and yield key markers of the fault's displacement history. Our sediment provenance analysis from the Deformed Gravels of Whitewater and the Cabezon Fanglomerate provide detrital geochronologic and lithologic signatures of potential sources within the San Bernardino Mountains and Little San Bernardino Mountains. Statistical analysis shows that the Cabezon Fanglomerate is most compatible with the Mission Creek and Morongo Valley Canyon sources, rather than the Whitewater Canyon as previously suggested. We propose that displacement since deposition ~500-100 ka across the Mission Creek strand has separated these deposits from their original sources. These findings challenge the current paradigm that the Mission Creek strand is inactive and suggest that the fault continues to be a primary structure in accommodating deformation along the Pacific-North American plate boundary.


Quantifying head impacts and neurocognitive performance in collegiate boxers.
Head impacts and neurocognition were quantified in 27 intercollegiate male boxers engaged in two, two-minute sparring rounds. Head impacts were measured using Instrumented Boxing Headgear (IBH). Pre and post-sparring neurocognitive performance was compared using two computerized neuropsychological test batteries (CNTs): Immediate Post-concussion Assessment and Cognitive Testing (ImPACT™) and Automated Neuropsychological Assessment Metrics - Military Battery (ANAM4® MIL). An average of 27.63 ± 17.87 impacts above the 9.6 g IBH threshold were recorded per boxer, with average peak linear acceleration of 23.48 ± 15.20 g and average peak rotational acceleration of 1761.40 ± 1064.34 rad/s2. Small, but measurable declines in delayed memory and improvement in response time from pre- to post-bout were noted. Number of impacts and concussion history predicted degraded memory performance. This is a unique quantification of head impacts in collegiate boxing, which were similar in frequency and location, but lower in magnitude as compared to amateur boxing. Improved understanding of impact kinematics may enhance safety in boxing and other contact sports. Subtle post-bout decrements in delayed memory performance and mild improvement in response time reinforce prior research and provide evidence of congruence in our two CNT assessments, which may facilitate comparisons of outcomes across settings utilizing these tests.


Impact of dendritic size and dendritic topology on burst firing in pyramidal cells.
Neurons display a wide range of intrinsic firing patterns. A particularly relevant pattern for neuronal signaling and synaptic plasticity is burst firing, the generation of clusters of action potentials with short interspike intervals. Besides ion-channel composition, dendritic morphology appears to be an important factor modulating firing pattern. However, the underlying mechanisms are poorly understood, and the impact of morphology on burst firing remains insufficiently known. Dendritic morphology is not fixed but can undergo significant changes in many pathological conditions. Using computational models of neocortical pyramidal cells, we here show that not only the total length of the apical dendrite but also the topological structure of its branching pattern markedly influences inter- and intraburst spike intervals and even determines whether or not a cell exhibits burst firing. We found that there is only a range of dendritic sizes that supports burst firing, and that this range is modulated by dendritic topology. Either reducing or enlarging the dendritic tree, or merely modifying its topological structure without changing total dendritic length, can transform a cell's firing pattern from bursting to tonic firing. Interestingly, the results are largely independent of whether the cells are stimulated by current injection at the soma or by synapses distributed over the dendritic tree. By means of a novel measure called mean electrotonic path length, we show that the influence of dendritic morphology on burst firing is attributable to the effect both dendritic size and dendritic topology have, not on somatic input conductance, but on the average spatial extent of the dendritic tree and the spatiotemporal dynamics of the dendritic membrane potential. Our results suggest that alterations in size or topology of pyramidal cell morphology, such as observed in Alzheimer's disease, mental retardation, epilepsy, and chronic stress, could change neuronal burst firing and thus ultimately affect information processing and cognition.


A rapid dynamic in vivo near-infrared fluorescence imaging assay to track lung vascular permeability after acute radiation injury.
To develop a dynamic in vivo near-infrared (NIR) fluorescence imaging assay to quantify sequential changes in lung vascular permeability-surface area product (PS) in rodents. Dynamic NIR imaging methods for determining lung vascular permeability-surface area product were developed and tested on non-irradiated and 13 Gy irradiated rats with/without treatment with lisinopril, a radiation mitigator. A physiologically-based pharmacokinetic (PBPK) model of indocyanine green (ICG) pulmonary disposition was applied to in vivo imaging data and PS was estimated. In vivo results were validated by five accepted assays: ex vivo perfused lung imaging, endothelial filtration coefficient (Kf) measurement, pulmonary vascular resistance measurement, Evan's blue dye uptake, and histopathology. A PBPK model-derived measure of lung vascular permeability-surface area product increased from 2.60 ± 0.40 [CL: 2.42-2.78] mL/min in the non-irradiated group to 6.94 ± 8.25 [CL: 3.56-10.31] mL/min in 13 Gy group after 42 days. Lisinopril treatment lowered PS in the 13 Gy group to 4.76 ± 6.17 [CL: 2.12-7.40] mL/min. A much higher up to 5× change in PS values was observed in rats exhibiting severe radiation injury. Ex vivo Kf (mL/min/cm H2O/g dry lung weight), a measure of pulmonary vascular permeability, showed similar trends in lungs of irradiated rats (0.164 ± 0.081 [CL: 0.11-0.22]) as compared to non-irradiated controls (0.022 ± 0.003 [CL: 0.019-0.025]), with reduction to 0.070 ± 0.035 [CL: 0.045-0.096] for irradiated rats treated with lisinopril. Similar trends were observed for ex vivo pulmonary vascular resistance, Evan's blue uptake, and histopathology. Our results suggest that whole body dynamic NIR fluorescence imaging can replace current assays, which are all terminal. The imaging accurately tracks changes in PS and changes in lung interstitial transport in vivo in response to radiation injury.


Response of starter pigs to supplementation of corn-soybean meal diets with organic acids.
Four growth experiments were conducted to assess the effects of organic acid supplementation on performance of starter and finisher pigs. Three 4-wk starter experiments utilized 392 pigs fed simple corn-soybean meal diets. A fourth experiment employed 135 finisher pigs in a 6-wk study. Each of the starter experiments was initiated immediately after weaning; piglets were 30 +/- 3 d of age. In Exp. 1, weanling pigs fed a 19% crude protein, simple corn-soybean meal diet were compared with pigs fed similar diets supplemented with 2% propionic, fumaric, or citric acid. Addition of each acid improved (P less than .07) efficiency of gain, while propionate depressed (P less than .05) feed intake. Additions of 1, 2, 3 or 4% fumarate were made in Exp. 2, resulting in linear daily gain and feed efficiency improvements (P less than .05). In Exp. 3, a possible protein-sparing effect of fumaric acid was investigated. Increasing protein levels from 16 to 20% improved daily gain (P less than .01) and feed efficiency (P less than .0001); fumarate supplementation (2%) increased (P less than .01) gain:feed. However, there was no protein X fumaric acid interaction. In Exp. 4, no treatment effects were noted with performance of finisher pigs fed a 14% crude protein, corn-soybean meal diet was compared with that of pigs fed similar diets supplemented with 1.5 or 3% fumaric acid.


[Nerve growth factor and brain-derived neurotrophic factor: a possible etiopathogenic role in sensorineural hearing loss. Preliminary data].
Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are members of a family of structurally related secreted proteins, termed neurotrophins, which promote and regulate the survival of many kinds of neurons in the peripheral nervous system. Aim of the study is to dose the serum level of NGF and BDNF in 8 patients affected by sensorineural hearing loss (SNHL). The results show that in these patients the amount of circulating NGF, but not of BDNF, is significantly lower in comparison to that found in age-matched controls. The preliminary data of the present study suggest that NGF might have a crucial role in the auditory pathway, promoting the survival and preventing the degeneration of sensorineural cells.


Protein Kinase C Facilitation of Acetylcholine Release at the Rat Neuromuscular Junction.
Protein kinase C (PKC) is a Ca2+-dependent enzyme involved in synaptic transmission, which can be experimentally activated by the phorbol ester, phorbol 12-myristate-13-acetate (TPA). We studied the effects of TPA application on acetylcholine (ACh) release at the rat neuromuscular junction by means of the focal recording technique; possible effects of TPA at the postsynaptic site had been ruled out in preliminary studies. In extracellular solutions containing 2 mM Ca2+ and at the stimulation frequency of 0.1 Hz, TPA increased endplate current (EPC) amplitude. In non-stimulated preparations spontaneous current frequency was increased at a similar rate. The similar time course of TPA action on evoked and spontaneous currents suggests that an increased presynaptic Ca2+ efficacy can be considered to be the probable mechanism of action. The interactions of PKC with ACh release were further investigated. In 0.1 mM Ca2+ extracellular solutions, TPA enhanced evoked currents only at stimulation frequencies (e.g. 40 Hz) that were themselves capable of inducing facilitation. This facilitation is classically associated with presynaptic Ca2+ accumulation, indicating that PKC interacts synergistically with Ca2+ to facilitate ACh release. In particular, since mean quantum size and release probability remained almost unchanged during TPA facilitation, it was concluded that PKC acted by enlarging the immediately available store. Interestingly, TPA also increased the presynaptic currents that were observed to be largely brought about by Ca2+-dependent K+ currents: evidence was obtained to suggest that increases in these currents provide negative feedback against excess release activation rather than being an expression of enhanced Ca2+ influx.


Cardiometabolic risks during anabolic hormone supplementation in older men.
To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging. A double-masked, partially placebo controlled study in 112 men 65-90 years-old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5 μg/kg/day) were administered for 16-weeks. Measurements included testosterone and IGF-1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL-cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment. Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL-cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCSs) improved (-0.69 ± 1.55, P < 0.001). In multivariate analyses, QUICKI, triglycerides, and HDL-cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually. Testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4-months. The long-term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater functional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks.


Supracerebellar Transtentorial Approach for Occipital Meningioma to Maximize Visual Preservation: Technical Note.
Surgery for resection of tentorial meningiomas compressing primary visual cortex carries a significant risk of worsening vision. This concern is especially acute in patients with a preexisting visual deficit. Approaches that involve mechanical retraction of the occipital lobe further threaten visual function. The supracerebellar transtentorial (SCTT) approach, which does not carry a risk of occipital retraction injury, should be considered for patients with occipital tentorial meningiomas to maximize functional visual outcomes. A 54-yr-old woman underwent 2 resections and radiation therapy for a right occipital oligodendroglioma as a teenager. She was left with a complete left homonymous hemianopsia. The patient now presented with progressive vision loss in her remaining right visual field. Imaging revealed a left occipital superiorly projecting tentorial meningioma. To preserve her remaining visual function the SCTT approach was chosen for resection. A Simpson grade 1 removal was achieved without disrupting the occipital lobe pia or requiring mechanical cerebellar retraction. A diagnosis of a WHO grade II meningioma (presumably radiation induced) was made. The patient's vision returned to premorbid baseline 1 wk after surgery. The SCTT approach should be considered for the surgical management of patients with occipital tentorial meningiomas when visual preservation is at risk. This approach avoids transgression of visual cortex and minimizes the risk of venous infarction or contusions from retraction injury.


MEM-FET: Essential protein prediction using membership feature and machine learning approach.
Proteins are played key roles in different functionalities in our daily life. All functional roles of a protein are a bit enhanced in interaction compared to individuals. Identification of essential proteins of an organism is a time consume and costly task during observation in the wet lab. The results of observation in wet lab always ensure high reliability and accuracy in the biological ground. Essential protein prediction using computational approaches is an alternative choice in research. It proves its significance rapidly in day-to-day life as well as reduces the experimental cost of wet lab effectively. Existing computational methods were implemented using Protein interaction networks (PPIN), Sequence, Gene Expression Dataset (GED), Gene Ontology (GO), Orthologous groups, and Subcellular localized datasets. Machine learning has diverse categories of features that enable to model and predict essential macromolecules of understudied organisms. A novel methodology MEM-FET (membership feature) is predicted based on features, that is, edge clustering coefficient, Average clustering coefficient, subcellular localization, and Gene Ontology within a compartment of common neighbors. The accuracy (ACC) values of the predicted true positive (TP) essential proteins are 0.79, 0.74, 0.78, and 0.71 for YHQ, YMIPS, YDIP, and YMBD datasets. An enriched set of essential proteins are also predicted using the MEM-FET algorithm. Ensemble ML also validated the proposed model with an accuracy of 60%. It has been predicted that MEM-FET algorithms outperform other existing algorithms with an ACC value of 80% for the yeast dataset.


Long-term outcomes of carotid stenting in a single neurovascular center: up to 12-year retrospective analysis with a focus on the influence of comorbidities.
The aim of this study was to evaluate long-term outcomes in patients who underwent carotid artery stenting (CAS) for symptomatic or asymptomatic high-grade stenosis. A total of 1158 patients (asymptomatic, n = 636; symptomatic, n = 522) underwent CAS at our center between 2009 and 2020. A total of 560 patients or contacts (asymptomatic, n = 316; symptomatic, n = 244) were interviewed by telephone to evaluate long-term outcomes with a mean follow-up of 5 years. Mortality from all causes, myocardial infarction, and stroke, as well as comorbidities influencing their occurrence, including overall survival and stroke-free survival, were examined. The overall survival rate for all-cause mortality was 91.6% at 1 year, 77.1% at 5 years, and 55.7% at 10 years. A total of 39 (6.9%) patients had an ischemic stroke during long-term follow-up. The stroke-free survival rates at 1 year, 5 years, and 10 years were 97.9%, 92.7%, and 86.6%, respectively. Stroke-free survival and overall survival did not differ significantly between the symptomatic and asymptomatic groups (overall survival, p = 0.304; stroke-free survival, p = 0.336). Regular physical activity reduced the risk of stroke and death and was associated with better long-term clinical outcomes. Age at treatment and diabetes mellitus were statistically significantly associated with death during follow-up. Long-term follow-up data confirmed the effectiveness and durability of CAS as a therapy option for both symptomatic and asymptomatic patients. In patient selection for CAS, special consideration should be paid to patient age, ability to engage in physical activity, and diabetes mellitus.


[Antibodies to type antigens of group A streptococcal cell walls in erysipelas patients].
The passive hemagglutination test was used to determine antibodies to type antigens of the cell wall of streptococcus group A in 167 patients suffering from erysipelas, from whom 488 sera were obtained. Antibodies were revealed in 97.2% of the sera. There was a definite relationship between the clinical form of the disease and the level of antibodies: their lowest level and the absence of elevation in the course of the disease was noted in continuous-relapsing form of erysipelas; the appearance of antibodies to the new types of streptococcus was usually noted in late relapses of the disease, which permitted to attribute their occurrence to infection by the new types of the microbes. In individual cases the appearance of antibodies to the new types of streptococcus was observed at the early relapses of erysipelas; this could be explained by the exacerbation of a focus of chronic (endogenous) infection in the skin in the absence of reinfection. Continuous prophylactic administration of bicillin-5 produced no depressive effect on the antibody level in patients with relapsing erysipelas.


Perinatal outcomes after intrauterine growth restriction and umbilical artery Doppler pulsatility index of less than the fifth percentile.
Objective: To analyze perinatal morbidity and stillbirth after intrauterine growth restriction (IUGR) with an umbilical artery Doppler pulsatility index (UA PI) less than the fifth centile.Study design: This retrospective cohort study included nonanomalous singleton, IUGR pregnancies receiving UA PI testing at a tertiary-care prenatal diagnostic center. Women with persistently elevated UA PI, absent or reversed end-diastolic flow on UA PI, or who had only one UA PI result were excluded. Low UA PI was defined as having ≥1 UA PI <5%. Women with low UA PI were matched by gestational age at IUGR diagnosis in a random 1 case: 4 control computer-generated algorithm to those with normal UA PI (≤95% and ≥5%). The primary outcome was composite neonatal morbidity and mortality (stillbirth, mechanical ventilation, sepsis, intraventricular hemorrhage, and necrotizing enterocolitis). Secondary outcomes included 5-minute Apgar, umbilical artery pH, delivery type, and interval from IUGR diagnosis to delivery. We compared outcomes after low UA PI to those after normal UA PI with multivariable logistic regression, adjusting for gestational age at delivery, betamethasone use, infant gender, and maternal factors.Results: Of the 1893 IUGR pregnancies, 25 (1.3%) had low UA PI <5% and were randomly matched via computer algorithm to 100 controls. There were no stillbirths in either group; the odds of composite neonatal morbidity was similar among IUGR pregnancies with UA PI <5% versus normal (adjusted odds ratio 0.89 (95% confidence interval 0.27-2.75)). There was no difference in 5-minute Apgars, umbilical artery pH, rate of cesarean delivery for fetal distress, or interval from IUGR diagnosis to delivery between the two groups.Conclusion: Among IUGR pregnancies, UA PI <5% is uncommon and not associated with improved neonatal outcomes compared to normal UA PI. These findings suggest low UA PI can continue to be managed as normal UA PI.


BolA is a transcriptional switch that turns off motility and turns on biofilm development.
Bacteria are extremely versatile organisms that rapidly adapt to changing environments. When bacterial cells switch from planktonic growth to biofilm, flagellum formation is turned off and the production of fimbriae and extracellular polysaccharides is switched on. BolA is present in most Gram-negative bacteria, and homologues can be found from proteobacteria to eukaryotes. Here, we show that BolA is a new bacterial transcription factor that modulates the switch from a planktonic to a sessile lifestyle. It negatively modulates flagellar biosynthesis and swimming capacity in Escherichia coli. Furthermore, BolA overexpression favors biofilm formation, involving the production of fimbria-like adhesins and curli. Our results also demonstrate that BolA is a protein with high affinity to DNA and is able to regulate many genes on a genome-wide scale. Moreover, we show that the most significant targets of this protein involve a complex network of genes encoding proteins related to biofilm development. Herein, we propose that BolA is a motile/adhesive transcriptional switch, specifically involved in the transition between the planktonic and the attachment stage of biofilm formation. Escherichia coli cells possess several mechanisms to cope with stresses. BolA has been described as a protein important for survival in late stages of bacterial growth and under harsh environmental conditions. BolA-like proteins are widely conserved from prokaryotes to eukaryotes. Although their exact function is not fully established at the molecular level, they seem to be involved in cell proliferation or cell cycle regulation. Here, we unraveled the role of BolA in biofilm development and bacterial motility. Our work suggests that BolA actively contributes to the decision of bacteria to arrest flagellar production and initiate the attachment to form structured communities, such as biofilms. The molecular studies of different lifestyles coupled with the comprehension of the BolA functions may be an important step for future perspectives, with health care and biotechnology applications.


Cryptococcal Pleuritis Presenting with Lymphocyte-predominant and High Levels of Adenosine Deaminase in Pleural Effusions Coincident with Pulmonary Tuberculosis.
Co-infection with cryptococcus and tuberculosis has rarely been reported. We herein report a case of an 80-year-old man with cryptococcal pleuritis concurrent with pulmonary tuberculosis. He was admitted for progression of left pleural effusion and consolidation in the left upper lobe. Culture for Mycobacterium tuberculosis was positive in sputum, and analyses of pleural effusion revealed lymphocyte-predominant high levels of adenosine deaminase (ADA). Medical thoracoscopy revealed massive infiltration of Cryptococcus neoformans in pleura without granuloma. This is the first case report of cryptococcal pleuritis coincident with pulmonary tuberculosis. Cryptococcal pleuritis should be ruled out when the adenosine deaminase levels are elevated in pleural effusion.


Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17.
Accumulating evidences have identified the immunoregulatory features of stem cells. In this study, the immunoregulation of bone marrow-derived stem cells (BMSCs) transplanted into patients with HBV-related decompensated cirrhosis and mouse model of liver injury induced by carbon tetrachloride (CCl4) administration was observed. Compared with healthy controls, patients with HBV-related decompensated cirrhosis showed significantly higher levels of TNF-alpha, IL-12, TGF-beta1, IL-17, and IL-8. However, only IL-17 was markedly decreased after autologous BMSCs transplantation during their follow-up. The same results were found in the CCl4-treated mice. Furthermore, we found that exogenous IL-17 partly abolished the therapeutic effect of BMSCs whereas IL-17-specific antibody promoted improvement of liver injury in CCl4-treated mice, resembling the therapeutic effect of BMSCs transplantation. These data suggested that BMSCs transplantation induces a decrease of IL-17 level, which at least in part delineates the mechanisms of stem cells-mediated therapeutic benefit on liver disease.


Exploring the cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results.
Gastric cancer is the second leading cause of cancer-related deaths worldwide. Treatment for Helicobacter pylori infection, the leading causal risk factor, can reduce disease progression, but the long-term impact on cancer incidence is uncertain. Using the best available data, we estimated the potential health benefits and economic consequences associated with H. pylori screening in a high-risk region of China. An empirically calibrated model of gastric cancer was used to project reduction in lifetime cancer risk, life-expectancy and costs associated with (i) single lifetime screening (age 20, 30 or 40); (ii) single lifetime screening followed by rescreening individuals with negative results and (iii) universal treatment for H. pylori (age 20, 30 or 40). Data were from the published literature and national and international databases. Screening and treatment for H. pylori at age 20 reduced the mean lifetime cancer risk by 14.5% (men) to 26.6% (women) and cost less than $1,500 per year of life saved (YLS) compared to no screening. Rescreening individuals with negative results and targeting older ages was less cost-effective. Universal treatment prevented an additional 1.5% to 2.3% of risk reduction, but incremental cost-effectiveness ratios exceeded $2,500 per YLS. Screening young adults for H. pylori could prevent one in every 4 to 6 cases of gastric cancer in China and would be considered cost-effective using the GDP per capita threshold. These results illustrate the potential promise of a gastric cancer screening program and provide rationale for urgent clinical studies to move the prevention agenda forward.


An electrically conductive 3D scaffold based on a nonwoven web of poly(L-lactic acid) and conductive poly(3,4-ethylenedioxythiophene).
This study was to demonstrate that an extremely thin coating of poly(3,4-ethylenedioxythiophene) (PEDOT) on nonwoven microfibrous poly(l-lactic acid) (PLLA) web is of sufficient electrical conductivity and stability in aqueous environment to sustain electrical stimulation (ES) to cultured human skin fibroblasts. The PEDOT imparted the web a surface resistivity of approximately 0.1 KΩ/square without altering the web morphology. X-ray photoelectron spectroscopy demonstrated that the surface chemistry of the PLLA/PEDOT is characteristic of both PLLA and PEDOT. The PEDOT-coated web also showed higher hydrophilicity, lower glass transition temperature and unchanged fiber crystallinity and thermal stability compared with the PLLA web. The addition of PEDOT to the web marginally increased the web's tensile strength and lowered the elongation. An electrical stability test showed that the PLLA/PEDOT structure was more stable than a polypyrrole treated PLLA fabric, showing only a slow deterioration in conductivity when exposed to culture medium. The cytotoxicity test showed that the PLLA/PEDOT scaffold was not cytotoxic and supported human dermal fibroblast adhesion, migration, and proliferation. Preliminary ES experiments have demonstrated that this conductive web mediated effective ES to fibroblasts. Therefore, this new conductive biodegradable scaffold may be used to electrically modulate cellular activity and tissue regeneration.