Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation.
The strength and duration of B-cell-receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major substrate of a tissue-specific and developmentally regulated PTP, PTP receptor-type O truncated (PTPROt). PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-Ø, PTP-oc, and PTPu2), a group of highly conserved receptor-type PTPs that are thought to function as tumor suppressor genes. The overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events, including calcium mobilization and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR cross-linking, suggesting that the phosphatase modulates tonic BCR signaling.


A new labor theory of value for rational planning through use of the bourgeois profit rate.
To maximaze steady-state per capita consumptions, goods should be valued at their "synchronized labor requirement costs", which are shown to deviate from Marx's schemata of "values" but to coincide with bourgeois prices calculated at dated labor requirements, marked-up by compound interest, at a profit or interest rate equal to the system's rate of exponential growth. With capitalists saving all their incomes for future profits, workers get all there is to get. Departures from such an exogenous, or endogenous, golden-rule state are the rule in history rather than the exception. In the case of exponential labor-augmenting change, it is shown that competitive prices will equal historically embodied labor content.


[Comparative assessment of diagnostic capacities of thoracic fluorography, film x-ray study and small-dose digital x-ray study].
The efficiency of small-dose digital X-ray study (SDDXRS) of the chest versus film X-ray study (FXRS) and fluorography was studied during prophylactic surveys. SDDXRS competes only with FXRS in evaluating the normal anatomic structures and it compares much favourably with fluography. In chest abnormalities, SDDXRS, unlike FXRS, cannot reveal fine linear shadows, detect bullae in the lung, the upper margin of pleural exudates, changes in the bones worse, but shows soft focal shadows of the decay cavity, abnormal changes behind the shadow of the heart. The efficiency of SDDXRS was superior to fluography in detecting tuberculosis in all points, at the same time SDDXRS virtually have no spoilage that is about 18% at fluography.


Measurement of Interleukin-6 in Cerebrospinal Fluid for the Diagnosis of Bacterial Meningitis.
It is assessed whether the measurement of interleukin-6 in the cerebrospinal fluid can serve as a biomarker for the diagnosis of bacterial meningitis. Cerebrospinal fluid was obtained from 152 patients aged 0-15 years suspected of having meningitis. These patients were classified into the following groups: Bacterial meningitis (n = 85), aseptic meningitis (n = 35) and non-meningitis/control (n = 32) based on leukocyte count and bacterial identification by culture and molecular biology. Interleukin-6 concentrations in cerebrospinal fluid were measured by enzyme-linked immunosorbent assay. This study found a significant difference of the mean cerebrospinal fluid interleukin-6 level (p≤0.01) between patients with bacterial meningitis (3,538.69±2,560.78 pg mL -1) and patients with aseptic meningitis (332.51±470.69 pg mL -1) or those of the control group (205.83±79.39 pg mL -1). There was also a significant difference of the mean cerebrospinal fluid interleukin-6 level between patients with aseptic meningitis and those of the control group. Interleukin-6 had the highest area under the ROC curve: 0.94 (95% confidence interval: 0.901-0.979) compared to that of cerebrospinal fluid glucose and total protein. At a cut-off value of 1,065.96 pg mL -1, interleukin-6 had a sensitivity of 76.2% and specificity of 100%. Interleukin-6 is a potential biomarker for the differential diagnosis of meningitis.


Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome.
Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 +/- 1.6 and 29.3 +/- 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.


Cilia-mediated hedgehog signaling in Drosophila.
Cilia mediate Hedgehog (Hh) signaling in vertebrates and Hh deregulation results in several clinical manifestations, such as obesity, cognitive disabilities, developmental malformations, and various cancers. Drosophila cells are nonciliated during development, which has led to the assumption that cilia-mediated Hh signaling is restricted to vertebrates. Here, we identify and characterize a cilia-mediated Hh pathway in Drosophila olfactory sensory neurons. We demonstrate that several fundamental key aspects of the vertebrate cilia pathway, such as ciliary localization of Smoothened and the requirement of the intraflagellar transport system, are present in Drosophila. We show that Cos2 and Fused are required for the ciliary transport of Smoothened and that cilia mediate the expression of the Hh pathway target genes. Taken together, our data demonstrate that Hh signaling in Drosophila can be mediated by two pathways and that the ciliary Hh pathway is conserved from Drosophila to vertebrates.


Scanning electron microscopy of brain ventricular surfaces: a bibliography.
This bibliography is designed to facilitate the rapid identification and location of references concerning the application of scanning electron microscopy to investigations of the cerebroventricular system and related cerebrospinal fluid contacting surfaces. Because SEM provides information regarding cell surfaces, it is admirably suited to the examination of the brain ventricular system since the morphology of the CSF interface is of the utmost importance in accomplishing the diverse functions of the ependyma and associated circumventricular organs. The bibliography attests to the fact that scanning electron microscopy has provided a major impetus to the study of the structure and function of the circumventricular organs, choroid plexuses and tanycytic ependyma as well as the distribution and morphology of such supraependymal cellular elements as macrophages, neurons, and neuronal proceses. Furthermore, not only are SEM methodologies being applied to an ever lengthening list of phyla and species, but the diversity of problems amenable to the profitable application of scanning electron microscopy also is rapidly increasing. Investigations to date, for example, include studies of ventricular morphology during development and maturity, health and disease, and prior to as well as following experimental manipulation. While remarkable strides have been made toward a greater understanding of many aspects of cerebroventricula structrure and function, many significant problems clearly await the judicious application of scanning electron microscopy.


The role of productive activities in the lives of adolescents: Photovoice evidence from Malawi.
Adolescence is an important transitional period, separate from both childhood and adulthood. Critical physical and mental development occurs during adolescence, including emotional skills, physical, and mental abilities. Behaviors adopted during this lifecourse period have critical implications for adolescents' future health and well-being. The main research question of the present study is: what is the role of productive activities in the lives and development of adolescents in rural Malawi? As part of this study, selected adolescents from poor rural households were asked to take photographs of their daily (productive) activities. These photographs served as a starting point for focus group discussions. In addition to including adolescents, we conducted qualitative interviews with caregivers and teachers to triangulate and obtain a more holistic understanding of adolescent engagement in productive activities. The main themes that emerged were that 1) the work that is conducted by adolescent boys and girls inside and outside the household is not only perceived by adolescents as a product of poverty, but as a point of pride, as well as a potential means of providing for one's future, 2) there is a tension between the needs of the family and schooling, and 3) adolescent productive activities are associated with minor although not negligible hazards and injuries. We discuss that these qualitative findings help to better understand how social protection interventions, such as Malawi's Social Cash Transfer Program, may affect adolescent engagement in work and adolescent wellbeing more generally.


A short splice form of Xin-actin binding repeat containing 2 (XIRP2) lacking the Xin repeats is required for maintenance of stereocilia morphology and hearing function.
Approximately one-third of known deafness genes encode proteins located in the hair bundle, the sensory hair cell's mechanoreceptive organelle. In previous studies, we used mass spectrometry to characterize the hair bundle's proteome, resulting in the discovery of novel bundle proteins. One such protein is Xin-actin binding repeat containing 2 (XIRP2), an actin-cross-linking protein previously reported to be specifically expressed in striated muscle. Because mutations in other actin-cross-linkers result in hearing loss, we investigated the role of XIRP2 in hearing function. In the inner ear, XIRP2 is specifically expressed in hair cells, colocalizing with actin-rich structures in bundles, the underlying cuticular plate, and the circumferential actin belt. Analysis using peptide mass spectrometry revealed that the bundle harbors a previously uncharacterized XIRP2 splice variant, suggesting XIRP2's role in the hair cell differs significantly from that reported in myocytes. To determine the role of XIRP2 in hearing, we applied clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome-editing technology to induce targeted mutations into the mouse Xirp2 gene, resulting in the elimination of XIRP2 protein expression in the inner ear. Functional analysis of hearing in the resulting Xirp2-null mice revealed high-frequency hearing loss, and ultrastructural scanning electron microscopy analyses of hair cells demonstrated stereocilia degeneration in these mice. We thus conclude that XIRP2 is required for long-term maintenance of hair cell stereocilia, and that its dysfunction causes hearing loss in the mouse.


The effect of providing a USB syllabus on resident reading of landmark articles.
The acquisition of new knowledge is a primary goal of residency training. Retrieving and retaining influential primary and secondary medical literature can be challenging for house officers. We set out to investigate the effect of a Universal Serial Bus (USB) drive loaded with landmark scientific articles on housestaff education in a pilot study. We created a USB syllabus that contains 187 primary scientific research articles. The electronic syllabus had links to the full-text articles and was organized using an html webpage with a table of contents according to medical subspecialties. We performed a prospective cohort study of 53 house officers in the internal medicine residency program who received the USB syllabus. We evaluated the impact of the USB syllabus on resident education with surveys at the beginning and conclusion of the nine-month study period. All 50 respondents (100%) reported to have used the USB syllabus. The self-reported number of original articles read each month was higher at the end of the nine-month study period compared to baseline. Housestaff rated original articles as being a more valuable educational resource after the intervention. An electronic syllabus with landmark scientific articles placed on a USB drive was widely utilized by housestaff, increased the self-reported reading of original scientific articles and seemed to have positively influenced residents' attitude toward original medical literature.


Cobalamin status modifies the effect of zinc supplementation on the incidence of prolonged diarrhea in 6- to 30-month-old north Indian children.
The observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged (≥ 7 d duration) and acute diarrhea. Children aged 6-30 mo received zinc or placebo daily for 4 mo. We measured plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables. The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile. The OR (95% CI) for children below and above the 25th percentile for cobalamin were 0.53 (0.35-0.78) and 0.90 (0.73-1.11), respectively (P-interaction = 0.015). There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA (P-interaction = 0.045 and 0.188, respectively). Baseline folate status did not modify the effect of zinc on prolonged diarrhea. Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea. Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea.


Chromosomal characteristics of a Brazilian whip spider (Amblypygi) and evolutionary relationships with other arachnid orders.
We analyzed mitotic and meiotic cells of a Brazilian amblypygid, Heterophrynus longicornis, using conventional and molecular cytogenetic techniques (Giemsa staining, C-banding, Ag-NOR, and FISH with rDNA probe). This is the first study that focuses solely on amblypygid chromosomes; it was undertaken to add data on cytogenetic knowledge of this group and contribute to the understanding of chromosome evolution in the Arachnida. We found 2n = 66 for male and female individuals, monocentric chromosomes, and absence of morphologically differentiated sex chromosomes. C-banding showed heterochromatin in the pericentromeric region of most chromosomes. Mitotic and meiotic nuclei submitted to silver impregnation and FISH revealed, respectively, Ag-NORs and ribosomal genes in the terminal region of two chromosome pairs. Most chromosome features that we observed in H. longicornis are shared with species of other arachnid orders; however, the absence of morphologically differentiated sex chromosomes in amblypygid contrasts with the remarkable variety of sex chromosome systems recorded for the Araneae. Consequently, we conclude that analysis of species of the Tetrapulmonata clade is useful for understanding the trends of sex chromosome evolution in this arachnid group.


Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.
Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.


Regulation of the alkaloid biosynthesis by miRNA in opium poppy.
Opium poppy (Papaver somniferum) is an important medicinal plant producing benzylisoquinoline alkaloids (BIA). MicroRNAs (miRNAs) are endogenous small RNAs (sRNAs) of approximately 21 nucleotides. They are noncoding, but regulate gene expression in eukaryotes. Although many studies have been conducted on the identification and functions of plant miRNA, scarce researches on miRNA regulation of alkaloid biosynthesis have been reported. In this study, a total of 316 conserved and 11 novel miRNAs were identified in opium poppy using second-generation sequencing and direct cloning. Tissue-specific regulation of miRNA expression was comparatively analysed by miRNA microarray assays. A total of 232 miRNAs were found to be differentially expressed among four tissues. Likewise, 1469 target transcripts were detected using in silico and experimental approaches. The Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that miRNA putatively regulates carbohydrate metabolism and genetic-information processing. Additionally, miRNA target transcripts were mostly involved in response to stress against various factors and secondary-metabolite biosynthesis processes. Target transcript identification analyses revealed that some of the miRNAs might be involved in BIA biosynthesis, such as pso-miR13, pso-miR2161 and pso-miR408. Additionally, three putatively mature miRNA sequences were predicted to be targeting BIA-biosynthesis genes.


Influenza epidemiology in patients admitted to sentinel Australian hospitals in 2017: the Influenza Complications Alert Network (FluCAN).
The Influenza Complications Alert Network (FluCAN) is a sentinel-hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2017 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data are also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2017 (the 2017 influenza season), 4,359 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 52% were elderly (≥65 years), 14% were children (<16 years), 6.5% were Aboriginal and Torres Strait Islander peoples, 1.6% were pregnant and 78% had chronic comorbidities. A significant proportion were due to influenza B (31%). Estimated vaccine coverage was 72% in the elderly (≥65 years), 50% in non-elderly adults with medical comorbidities and 24% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 23% (95% CI: 7%, 36%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2017, with case numbers more than twice that reported in 2016.


Blocking of the initiation-to-elongation transition by a transdominant RNA polymerase mutation.
RNA polymerase, the principal enzyme of gene expression, possesses structural features conserved in evolution. A substitution of an evolutionarily invariant amino acid (Lys1065----Arg) in the beta subunit of Escherichia coli RNA polymerase apparently disrupts its catalytic center. The mutant protein inhibited cell growth when expressed from an inducible promoter. The assembled holoenzyme carrying the mutant subunit formed stable promoter complexes that continuously synthesized promoter-specific dinucleotides but that did not enter the elongation step. The mutant polymerase inhibited transcription by blocking the access of the wild-type enzyme to promoters.


Benign disease and unexpected histological findings after pancreaticoduodenectomy: the role of endoscopic ultrasound fine needle aspiration.
We assessed the incidence and outcome of pancreaticoduodenectomy for patients with a pre-operative benign diagnosis and in patients who had an unexpected diagnosis of benign disease following resection. We have also compared how the introduction of endoscopic ultrasound fine needle aspiration (EUS-FNA) has altered our pre-operative assessment. Between January 1997 and April 2006, 499 patients underwent pancreaticoduodenectomy at the Queen Elizabeth Hospital. Data were collected prospectively. A further 85 patients between 2006 and 2008 had a different diagnostic approach (after imaging these patients have been also studied by EUS-FNA). Overall, 78 (15.6%) patients had no malignant disease on final histology. Out of 459 patients who underwent pancreaticoduodenectomy for presumed malignancy, 49 (10.6%) had benign disease (sensitivity, 97%; positive predictive value, 89%). In a further 40 patients with a pre-operative benign diagnosis, we found 11 cases (27%) of malignancy (sensitivity, 37%; negative predictive value, 72%). Following the introduction of EUS-FNA, the sensitivity and specificity of the diagnostic work were 92% and 75%, respectively (positive predictive value, 93%; negative predictive value, 63%). The median follow-up was 35 months (range, 1-116 months). Prior to the introduction of EUS-FNA, a significant number of patients, in whom pancreaticoduodenectomy is carried out for suspected benign disease, turn out to have an underlying malignancy. The use of EUS-FNA has improved the specificity of diagnostic work-up.


A Comparison of Vibrotactile Feedback and Electrical Muscle Stimulation (EMS) for Motor Response During Active Hand Movement.
Wearable haptic technologies have garnered recent widespread attention due to increased accessibility, functionality, and affordability. These systems typically provide haptic feedback to augment the human ability to interact with their environment. This study compares two haptic feedback modalities, vibrotactile and EMS, against visual feedback to elicit a motor response during active hand movement. Forty-five participants, divided into three groups, performed a task to touch their face and received one of three possible sensory feedback cues, namely visual, vibrotactile, and electrical muscle stimulation (EMS), to interrupt their movement and avoid touching their face. Two quantitative performance measures are used in the comparison, the response time (time elapsed from stimulation to motor response) and the error rate (percentage that the user fails to avoid touching their face). Results showed that vibrotactile and EMS feedback yielded significantly faster response time than visual feedback, while no significant differences between vibrotactile and EMS were observed. Furthermore, the error rate was significantly lower for EMS compared to visual feedback, whereas no significant differences were observed between vibrotactile and visual feedback. In conclusion, it seems that EMS feedback is preferable for applications where errors are not tolerable (critical medical applications), whereas vibrotactile is superior for non-critical applications due to its low cost and higher usability (more pleasant compared to EMS).


Kinesin-1 heavy chain mediates microtubule sliding to drive changes in cell shape.
Microtubules are typically observed to buckle and loop during interphase in cultured cells by an unknown mechanism. We show that lateral microtubule movement and looping is a result of microtubules sliding against one another in interphase Drosophila S2 cells. RNAi of the kinesin-1 heavy chain (KHC), but not dynein or the kinesin-1 light chain, eliminates these movements. KHC-dependent microtubule sliding powers the formation of cellular processes filled with parallel microtubule bundles. The growth of these cellular processes is independent of the actin cytoskeleton. We further observe cytoplasmic microtubule sliding in Xenopus and Ptk2 cells, and show that antibody inhibition of KHC in mammalian cells prevents sliding. We therefore propose that, in addition to its well established role in organelle transport, an important universal function of kinesin-1 is to mediate cytoplasmic microtubule-microtubule sliding. This provides the cell with a dedicated mechanism to transport long and short microtubule filaments and drive changes in cell shape.


Pharmacokinetic interactions of cyclosporine with etoposide and mitoxantrone in children with acute myeloid leukemia.
The purpose of this study was to assess the effect of the multidrug resistance modulator cyclosporine (CsA) on the pharmacokinetics of etoposide and mitoxantrone in children with de novo acute myeloid leukemia (AML). Serial blood samples for pharmacokinetic studies were obtained in 38 children over a 24-h period following cytotoxin treatment with or without CsA on days 1 and 4. Drug concentrations were quantitated using validated HPLC methods, and pharmacokinetic parameters were determined using compartmental modeling with an iterative two-stage approach, implemented on ADAPT II software. Etoposide displayed a greater degree of interindividual variability in clearance and systemic exposure than mitoxantrone. With CsA treatment, etoposide and mitoxantrone mean clearance declined by 71% and 42%, respectively. These effects on clearance, in combination with the empiric 40% dose reduction for either cytotoxin, resulted in a 47% and 12% increases in the mean AUC for etoposide and mitoxantrone, respectively. There were no differences in the rates of stomatitis or infection between the two groups. CsA treatment resulted in an increased incidence of hyperbilrubinemia, which rapidly reversed upon conclusion of drug therapy. The variability observed in clearance, combined with the empiric 40% dose reduction of the cytotoxins, resulted in statistically similar systemic exposure and similar toxicity.


GABA- and peptide-immunoreactivities co-localize in the rat central extended amygdala.
The central amygdaloid nucleus and the lateral bed nucleus of the stria terminalis are two similar telencephalic structures belonging to the central extended amygdala. These regions contain numerous peptidergic and GABAergic neurones which maintain the neurones projecting to the brain stem under tight intrinsic control. Using immunocytochemistry in colchicine-treated rats, we showed that, in the lateral subdivision of the central amygdaloid nucleus and in the dorsal part of the lateral bed nucleus of the stria terminalis, a population of GABAergic neurones is able to co-synthesize either corticotropin-releasing factor or methionine-enkephalin, but never both peptides. These results suggest that, in the GABAergic intrinsic circuits of the central extended amygdala, co-liberated peptides can have a modulatory role on GABAergic actions.


Are new asthma therapies needed?
For many years, effective therapy for the management of asthma has been available. Issues of adverse side effects and questionable patient compliance with current therapies have been seen as deterrents for proven beneficial agents such as the anti-inflammatory corticosteroids and the bronchodilating beta 2-agonists. As effective as available agents are, the goal of consistent efficacy and ease of use has fueled research into new therapies that are either easier to use or have a more favorable side effect profile.


Arcobacter peruensis sp. nov., a Chemolithoheterotroph Isolated from Sulfide- and Organic-Rich Coastal Waters off Peru.
Members of the epsilonproteobacterial genus Arcobacter have been identified to be potentially important sulfide oxidizers in marine coastal, seep, and stratified basin environments. In the highly productive upwelling waters off the coast of Peru, Arcobacter cells comprised 3 to 25% of the total microbial community at a near-shore station where sulfide concentrations exceeded 20 μM in bottom waters. From the chemocline where the Arcobacter population exceeded 106 cells ml-1 and where high rates of denitrification (up to 6.5 ± 0.4 μM N day-1) and dark carbon fixation (2.8 ± 0.2 μM C day-1) were measured, we isolated a previously uncultivated Arcobacter species, Arcobacter peruensis sp. nov. (BCCM LMG-31510). Genomic analysis showed that A. peruensis possesses genes encoding sulfide oxidation and denitrification pathways but lacks the ability to fix CO2 via autotrophic carbon fixation pathways. Genes encoding transporters for organic carbon compounds, however, were present in the A. peruensis genome. Physiological experiments demonstrated that A. peruensis grew best on a mix of sulfide, nitrate, and acetate. Isotope labeling experiments further verified that A. peruensis completely reduced nitrate to N2 and assimilated acetate but did not fix CO2, thus coupling heterotrophic growth to sulfide oxidation and denitrification. Single-cell nanoscale secondary ion mass spectrometry analysis of samples taken from shipboard isotope labeling experiments also confirmed that the Arcobacter population in situ did not substantially fix CO2 The efficient growth yield associated with the chemolithoheterotrophic metabolism of A. peruensis may allow this Arcobacter species to rapidly bloom in eutrophic and sulfide-rich waters off the coast of Peru.IMPORTANCE Our multidisciplinary approach provides new insights into the ecophysiology of a newly isolated environmental Arcobacter species, as well as the physiological flexibility within the Arcobacter genus and sulfide-oxidizing, denitrifying microbial communities within oceanic oxygen minimum zones (OMZs). The chemolithoheterotrophic species Arcobacter peruensis may play a substantial role in the diverse consortium of bacteria that is capable of coupling denitrification and fixed nitrogen loss to sulfide oxidation in eutrophic, sulfidic coastal waters. With increasing anthropogenic pressures on coastal regions, e.g., eutrophication and deoxygenation (D. Breitburg, L. A. Levin, A. Oschlies, M. Grégoire, et al., Science 359:eaam7240, 2018, https://doi.org/10.1126/science.aam7240), niches where sulfide-oxidizing, denitrifying heterotrophs such as A. peruensis thrive are likely to expand.


Investigation into the specificity of angiotensin II-induced behavioral desensitization.
Angiotensin II (AngII) plays a key role in maintaining body fluid homeostasis. The physiological and behavioral effects of central AngII include increased blood pressure and fluid intake. In vitro experiments demonstrate that repeated exposure to AngII reduces the efficacy of subsequent AngII, and behavioral studies indicate that prior icv AngII administration reduces the dipsogenic response to AngII administered later. Specifically, rats given a treatment regimen of three icv injections of a large dose of AngII, each separated by 20 min, drink less water in response to a test injection of AngII than do vehicle-treated controls given the same test injection. The present studies were designed to test three potential explanations for the reduced dipsogenic potency of AngII after repeated administration. To this end, we tested for motor impairment caused by repeated injections of AngII, for a possible role of visceral distress or illness, and for differences in the pressor response to the final test injection of AngII. We found that repeated injections of AngII neither affected drinking stimulated by carbachol nor did they produce a conditioned flavor avoidance. Furthermore, we found no evidence that differences in the pressor response to the final test injection of AngII accounted for the difference in intake. In light of these findings, we are able to reject these three explanations for the observed behavioral desensitization, and, we suggest instead that the mechanism for this phenomenon may be at the level of the receptor.


Designing Mechanical Properties of 3D Printed Cookies through Computer Aided Engineering.
Additive manufacturing or 3D printing can be applied in the food sector to create food products with personalized properties such as shape, texture, and composition. In this article, we introduce a computer aided engineering (CAE) methodology to design 3D printed food products with tunable mechanical properties. The focus was on the Young modulus as a proxy of texture. Finite element modelling was used to establish the relationship between the Young modulus of 3D printed cookies with a honeycomb structure and their structure parameters. Wall thickness, cell size, and overall porosity were found to influence the Young modulus of the cookies and were, therefore, identified as tunable design parameters. Next, in experimental tests, it was observed that geometry deformations arose during and after 3D printing, affecting cookie structure and texture. The 3D printed cookie porosity was found to be lower than the designed one, strongly influencing the Young modulus. After identifying the changes in porosity through X-ray micro-computed tomography, a good match was observed between computational and experimental Young's modulus values. These results showed that changes in the geometry have to be quantified and considered to obtain a reliable prediction of the Young modulus of the 3D printed cookies.


The effect of food restriction on the regulation of gonadotropin-releasing hormone in male house finches (Haemorhous mexicanus).
Seasonal activation of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis and gonadal development is initiated by gonadotropin-releasing hormone-I (GnRH) release from the hypothalamus. In photoperiodic species, the consistent annual change in photoperiod is the primary environmental signal affecting GnRH cell activity, including changes in the synthesis and secretion of this neuropeptide. Non-photoperiodic environmental cues such as energy availability also influence HPG axis activity, but the mechanisms mediating this influence, in particular on the GnRH system, are unclear. Understanding how the neuroendocrine system integrates environmental information is critical in determining the plasticity and adaptability of physiological responses to changing environments. The primary objective of this study was to investigate GnRH-mediated changes in HPG axis activity and gonadal development in response to energy availability in a wild bird. We hypothesized that negative energy balance inhibits HPG axis activity by affecting GnRH secretion. Moderate food restriction for several weeks in male house finches, Haemorhous mexicanus, decreased body condition and inhibited photoinduced testicular growth compared to birds fed ad libitum. Food restriction did not affect plasma luteinizing hormone (LH; a correlate of GnRH release) or plasma testosterone, but it enhanced the plasma LH response to an injection of the glutamatergic agonist, N-methyl-D-aspartate (NMDA). Thus, food restriction may decrease photoinduced HPG axis activation by acting centrally, in particular by attenuating the release of accumulated GnRH stores.


Evaluation of the E test for susceptibility testing of anaerobic bacteria.
The susceptibilities of 105 clinical isolates of anaerobic bacteria were determined by a new method, the E test (AB Biodisk, Solna, Sweden), and were compared with the MICs for these organisms obtained by the reference agar dilution method by using supplemented brucella and Wilkins-Chalgren agars. The E test is a plastic strip with a predefined antibiotic gradient immobilized on one side and a MIC interpretive scale printed on the other side. Strips with cefoxitin, cefotaxime, imipenem, penicillin, metronidazole, and clindamycin were used in this study. A suspension of the test strain equal to the visual turbidity of a no. 0.5 McFarland standard was prepared and swabbed onto a 150-mm-diameter plate. The strips were applied in a radial fashion, and the plates were incubated under anaerobic conditions. After growth had occurred, an ellipse of inhibition was seen around each strip. At the point of intersection of the ellipse with the strip, the MIC was read from the interpretive scale. For most antibiotic-organism combinations, the ellipse was clear and the endpoint was sharp. The E-test MICs were interpreted after overnight and 48-h incubation for 58 of the strains. After overnight incubation, 87% of the E-test MICs were within 1 dilution of the agar dilution MICs, and 98% were within 2 dilutions. After 48 h of incubation, agreement was 86 and 97% respectively. E-test MICs obtained for the Bacteroides fragilis group after overnight incubation were more comparable than those obtained after 48 h of incubation to agar dilution MICs determined at 48 h for all drugs except clindamycin. On brucella agar, there was a 2% categorical discrepancy rate between the E-test MICs and agar dilution MICs, which occurred mostly with cefoxitin. The E test is easy to perform and read, is suitable for all anaerobes, can be used to test single patient isolates as needed, and offers the laboratory a reliable method for susceptibility testing of anaerobic bacteria.


Compendium of 530 metagenome-assembled bacterial and archaeal genomes from the polar Arctic Ocean.
The role of the Arctic Ocean ecosystem in climate regulation may depend on the responses of marine microorganisms to environmental change. We applied genome-resolved metagenomics to 41 Arctic seawater samples, collected at various depths in different seasons during the Tara Oceans Polar Circle expedition, to evaluate the ecology, metabolic potential and activity of resident bacteria and archaea. We assembled 530 metagenome-assembled genomes (MAGs) to form the Arctic MAGs catalogue comprising 526 species. A total of 441 MAGs belonged to species that have not previously been reported and 299 genomes showed an exclusively polar distribution. Most Arctic MAGs have large genomes and the potential for fast generation times, both of which may enable adaptation to a copiotrophic lifestyle in nutrient-rich waters. We identified 38 habitat generalists and 111 specialists in the Arctic Ocean. We also found a general prevalence of 14 mixotrophs, while chemolithoautotrophs were mostly present in the mesopelagic layer during spring and autumn. We revealed 62 MAGs classified as key Arctic species, found only in the Arctic Ocean, showing the highest gene expression values and predicted to have habitat-specific traits. The Artic MAGs catalogue will inform our understanding of polar microorganisms that drive global biogeochemical cycles.


Biomechanical model of batoid (skates and rays) pectoral fins predicts the influence of skeletal structure on fin kinematics: implications for bio-inspired design.
Growing interest in the development of bio-inspired autonomous underwater vehicles (AUVs) has motivated research in understanding the mechanisms behind the propulsion systems of marine animals. For example, the locomotive behavior of rays (Batoidea) by movement of the pectoral fins is of particular interest due to their superior performance characteristics over contemporary AUV propulsion systems. To better understand the mechanics of pectoral fin propulsion, this paper introduces a biomechanical model that simulates how batoid skeletal structures function to achieve the swimming locomotion observed in nature. Two rays were studied, Dasyatis sabina (Atlantic ray), and Rhinoptera bonasus (cownose ray). These species were selected because they exhibit very different swimming styles (undulation versus oscillation), but all use primarily their pectoral fins for propulsion (unlike electric rays or guitarfishes). Computerized tomography scans of each species were taken to image the underlying structure, which reveal a complex system of cartilaginous joints and linkages. Data collected from these images were used to quantify the complete skeletal morphometry of each batoid fin. Morphological differences were identified in the internal cartilage arrangement between each species including variations in the orientation of the skeletal elements, or radials, and the joint patterns between them, called the inter-radial joint pattern. These data were used as the primary input into the biomechanical model to couple a given ray skeletal structure with various swimming motions. A key output of the model is an estimation of the uniaxial strain that develops in the skeletal connective tissue in order for the structure to achieve motions observed during swimming. Tensile load tests of this connective tissue were conducted to further investigate the implications of the material strain predictions. The model also demonstrates that changes in the skeletal architecture (e.g., joint positioning) will effect fin deformation characteristics. Ultimately, the results of this study can be used to guide the design of optimally performing bio-inspired AUVs.


Prevalence and incidence of the metabolic syndrome in the European Lacidipine Study on Atherosclerosis (ELSA) and its relation with carotid intima-media thickness.
The European Lacidipine Study on Atherosclerosis (ELSA) randomized 2334 hypertensive patients to either the lipophilic calcium antagonist lacidipine or the beta-blocker atenolol for 4 years. About 35% of subjects in both groups received additional hydrochlorothiazide (12.5-25 mg/day). The patients were followed up for carotid intima-media thickness (IMT) changes for 3.7 years. The present post-hoc analyses were aimed at: describing the prevalence of the metabolic syndrome (MS) at baseline; investigating the effect of long-term antihypertensive therapy (and separately of atenolol and lacidipine) on MS prevalence; exploring whether MS at baseline influenced changes in carotid IMT and incidence of cardiovascular events during treatment; and describing the relations between MS and new cases of diabetes developing during treatment. At baseline 2034 patients had, in addition to blood pressure (BP), measurements of blood glucose, serum high-density lipoprotein (HDL)-cholesterol, triglycerides and body mass index (BMI > 28.8 for men and > 26.2 for women were taken to correspond to waist circumference > 102 and > 88 cm, respectively). These measurements were repeated after 4 years of treatment in 1444 patients. MS was defined according to Adults Treatment Panel III (ATP III). A high proportion of ELSA patients (33.3%) had MS at baseline, with no difference between atenolol and lacidipine. Baseline IMT was slightly greater in MS patients, but only the difference in mean maximum IMT at common carotids and bifurcations (CBMmax) achieved significance (P = 0.0325). Progression of CBMmax was also slightly greater in MS patients (P = 0.0241), but significance was lost when adjusted for covariates. No significant difference was found in the incidence of new cardiovascular events between patients with and without MS. The incidence of new MS was 21.4%, and significantly greater in patients under atenolol (25.2%) than lacidipine (17.7%; P = 0.0045). New-onset diabetes occurred in 5.54% of ELSA patients, and was three times higher among patients with than those without MS (10.28 versus 3.43%, P > 0.0001). Our analyses show a high prevalence of MS in ELSA hypertensives, a substantial incidence of new cases of MS and diabetes, the latter mostly among patients with MS. These analyses also show that in ELSA lacidipine was superior to atenolol, not only in showing a lower progression of carotid atherosclerosis, but also in causing a significantly lower incidence of new MS.


Scanning electron microscopy of in vitro chemically transformed mouse embryo cells.
A cloned nontumorigenic control cell line of C3H mouse embryo cells (C3H/1OT1/2CL8) and two cell lines derived from it by treatment in vitro with 7,12-dimethylbenz(a)anthracene (DMBA) or 3-methylcholanthrene (MCA) were studied by scanning electron microscopy. Confluent control cells were polygonal in shape and extensively flattened with smooth surfaces. Both in vitro transformants were pleomorphic to fusiform in shape, thicker than the control cells, and lacked contact inhibition. Microvilli of variable length and small marginal ruffles were characteristic surface alterations of the MCA-transformed cells, while blebs and numerous cytoplasmic strands extending between cells were typical of the DMBA transformant. Inoculation of the DMBA-transformed cells into C3H mice and re-establishment of cells from one of the subsequent fibrosarcomas in culture revealed an increased number of microvilli on the surface of the cells and an alteration in growth pattern. Other surface characteristics remained the same. A possible relationship between surface topography and outer membrane glycolipids is discussed.


Immune cell infiltration of primary and metastatic lesions: mechanisms and clinical impact.
The infiltration of tumors and their metastases by hematopoietic cells can contribute both positively and negatively to tumor growth, invasion, and patient outcomes. These differing outcomes are associated with both tumor heterogeneity and the diversity of leukocytes infiltrating neoplastic lesions. Tumors infiltration by histiocytes (macrophages and dendritic cells (DCs)) is associated with poor clinical outcomes, although infiltration by a subset of DCs is related to improved outcomes. T-cell infiltration of tumors and metastases are surrogates for positive outcomes, although subset analysis suggests that not all infiltrating T-cells have this potential. Overall, tumor infiltration by CD8(+) T-cells is associated with a positive outcome, while the frequency of infiltrating CD4(+) cells may be a negative predictor. In addition to tumor infiltration by macrophages and T-cells, recent studies have shown that myeloid-derived suppressor cells (MDSCs), also infiltrate tumors, inhibiting T-cell and DC number and function and facilitate tumor growth, angiogenesis, and metastasis. In summary, hematopoietic cell infiltration of tumors can regulate tumor progression and provide a useful diagnostic surrogate. Further, strategies focused on the manipulation of cellular infiltration via cellular, gene and molecular immunotherapies have the potential to provide a novel target for adjuvant therapy.


Polymer-grafted nanoparticles prepared via a grafting-from strategy: a computer simulation study.
Nanoparticles (NPs) grafted with polymer chains prepared via a grafting-from strategy are studied through coarse-grained molecular dynamics simulations combined with our stochastic reaction model. A system involving multiple individual NPs, with grafting-from processes for all the NPs induced simultaneously, is simulated, so that chain growth competition on the same NP, as well as between neighbouring NPs, are both naturally considered. Our results imply that there should be an optimized range of NP sizes, as compared to monomer size, in which initiator sites are most easily induced. Besides, when the initiator density is high, a shielding effect from the sparse long chains on the most short chains or initiators evidently yields an extremely unbiased distribution of chains. We also adopt a representative polymer-tethered NP prepared via a grafting-from strategy to study the potential of mean force between NPs, so that the dispersion and stabilization abilities of such polymer-grafted NPs in a polymer matrix can be generally predicted during the preparation of polymer nanocomposite materials. Our study helps to elucidate the cause of chain dispersity during the grafting-from process and could act as a guide for better design and to improve the performance of polymer nanocomposites.


Changes of overweight and obesity in the adult Swiss population according to educational level, from 1992 to 2007.
In many high income developed countries, obesity is inversely associated with educational level. In some countries, a widening gap of obesity between educational groups has been reported. The aim of this study was to assess trends in body mass index (BMI) and in prevalence of overweight and obesity and their association with educational level in the adult Swiss population. Four cross-sectional National health interview surveys conducted in 1992/93 (n = 14,521), 1997 (n = 12,474), 2002 (n = 18,908) and 2007 (n = 17,879) using representative samples of the Swiss population (age range 18-102 years). BMI was derived from self-reported data. Overweight was defined as BMI > or = 25 and <30 kg/m(2), and obesity as BMI > or = 30 kg/m(2). Mean (+/- standard deviation) BMI increased from 24.7 +/- 3.6 in 1992/3 to 25.4 +/- 3.6 kg/m2 in 2007 in men and 22.8 +/- 3.8 to 23.7 +/- 4.3 kg/m(2) in women. Between 1992/3 and 2007, the prevalence of overweight + obesity increased from 40.4% to 49.5% in men and from 22.3% to 31.3% in women, while the prevalence of obesity increased from 6.3% to 9.4% in men and from 4.9% to 8.5% in women. The rate of increase in the prevalence of obesity was greater between 1992/3 and 2002 (men: +0.26%/year; women: +0.31%/year) than between 2002 and 2007 (men: +0.10%/year; women: +0.10%/year). A sizable fraction (approximately 25%) of the increasing mean BMI was due to increasing age of the participants over time. The increase was larger in low than high education strata of the population. BMI was strongly associated with low educational level among women and this gradient remained fairly constant over time. A weaker similar gradient by educational level was apparent in men, but it tended to increase over time. In Switzerland, overweight and obesity increased between 1992 and 2007 and was associated with low education status in both men and women. A trend towards a stabilization of mean BMI levels was noted in most age categories since 2002. The increase in the prevalence of obesity was larger in low education strata of the population. These findings suggest that obesity preventive measures should be targeted according to educational level in Switzerland.


Echium oil is better than rapeseed oil in improving the response of barramundi to a disease challenge.
Pathogen infection stimulates the fatty acid (FA) metabolism and the production of pro-inflammatory derivatives of FA. Barramundi, Lates calcarifer, was fed on a diet rich in preformed long-chain (⩾C20) polyunsaturated fatty acids (LC-PUFA) from fish oil (FO), to compare with diets containing high levels of C18 precursors for LC-PUFA - stearidonic (SDA) and γ-linolenic acid (GLA) - from Echium plantagineum (EO), or rapeseed oil (RO) rich in α-linolenic acid (ALA), but a poor source of LC-PUFA and their precursors. After 6weeks, when growth rates were similar amongst the dietary treatments, a sub-lethal dose of Streptococcus iniae was administered to half of the fish, while the other half were maintained unchallenged and were pair-fed with the infected fish. Under a disease challenge situation, the tissue FA depots depleted at 3days post-infection (DPI) and were then restored to their previous concentrations at 7DPI. During the infection period, EO fish had a higher content of n3 and n6 PUFA in their tissues, higher n3:n6 PUFA ratio and reduced levels of the eicosanoids, TXB2 and 6-keto-PGF1α, in their plasma compared with RO fish. Fish fed on FO and EO had a longer lasting and enduring response in their FA and eicosanoid concentrations, following a week of bacterial infection, compared with those fed on RO. EO, containing SDA and GLA and with a comparatively higher n3:n6 PUFA ratio, proved more effective than RO in compensating for immunity stress.


Simultaneous bilateral trochanteric fractures during squatting in a patient with multiple myeloma.
Pathologic bone fractures are usually confined to the trunk in multiple myeloma (MM). But bilateral trochanteric fractures have not been reported in patients with MM before. Radiographic, histological and immunoelectrophoresis revealed typical features of MM. This report points out the importance of physical rehabilitation of patients in addition to chemotherapy in adaptation to the activities of daily living.


Prevalence, severity and associated risk factors of anemia among human immunodeficiency virus-infected adults in Sawla General Hospital, Southern Ethiopia: A facility-based cross-sectional study.
Anemia is a significant public health problem in HIV/AIDS patients worldwide. This study is aimed to determine the prevalence of anemia and its risk factors among HIV-infected adults in Sawla General Hospital, southern Ethiopia. A facility-based cross-sectional study involving HIV-infected adults was conducted in ART clinic of Sawla General Hospital from April 01 to May 31, 2019. A systematic random sampling technique was employed to recruit the study participants. Socio-demographic and clinical data were collected using a structured questionnaire and checklist. Hemoglobin concentration from venous blood was determined by HemoCue® 301 analyzer. Descriptive and inferential statistics, by Statistical Package for Social Science version 26.0, were applied; p-values ≤ 0.05 in the multivariable logistic regression analysis were considered statistically significant. A total of 220 HIV-infected adults participated in this study. The prevalence of anemia was 38.6%, from which 90.6, 7.1, and 2.3% are mild, moderate, and severe anemia, respectively. Anemia among HIV-infected adults was significantly associated with CD4 cell count below 200 cells/mm3 (AOR: 4.32; 95% CI: 2.10-8.86), clinical stage III or above (AOR: 4.20; 95% CI: 1.06-16.62), five or more years duration of HIV infection (AOR: 2.32; 95% CI: 1.08-4.94) and BMI below 18.5 kg/m2 (AOR: 3.82; 95% CI: 1.83-8.00). Anemia is a moderate public health problem among the study population. Longer duration of HIV infection, advanced clinical stage, lower CD4 cell count, and BMI are risk factors for anemia. Therefore, early ART enrolment for HIV-infected adults with nutritional support and rigorous monitoring of CD4 cell count are essential to lower the prevalence.


West of Ireland facial injury study. Part 2.
The pattern, presentation, and volume of facial injury in the west of Ireland are subjectively different from those in the United Kingdom. We know of no prospective regional study of facial injury in Ireland to date, and nationally there is no system in place to collect data on injury. The epidemiology of facial trauma has important implications for the development of health services, the education and training of clinicians, workforce planning, prevention of injury, and promotion of health. Over 1 week we did a multicentre prospective data collection study involving all emergency departments in the west of Ireland. All patients who attended with facial injuries were included (n=325), and those with injuries solely of the scalp and neck were excluded. The proforma recorded a patient's characteristics, details of injury and presentation, treatment and follow-up. It also included relation with sport, alcohol, assault, and animals. Eighty-two fractures were suspected, of which 46% were nasal. Accidents caused 75% of injuries and sport caused 27%. Fractures were sustained by 63% (n=5) of those wearing helmets while playing hurling, but by only 22% of those who were not. Helmets did, however, reduce the total number of injuries. Injuries were associated with alcohol (23%), assault (14%), falls (38%), and motor vehicle crashes (11%). Because of the differences in aetiology, different avenues and methods are required to prevent injury. Staff in emergency departments will need training in this area, given the large proportion of facial trauma in the region.


Reiter's syndrome.
Reiter's syndrome is a multisystem disease commonly triggered by a genitourinary infection or bacterial enteric infection. After a short latent period, ocular symptoms, oligoarthritis, and mucocutaneous involvement may occur. Classic cutaneous manifestations of Reiter's syndrome include keratoderma blennorrhagicum and balanitis circinata, both of which are microscopically similar to pustular psoriasis.


Assumed Lighting Direction in the Interpretation of Cast Shadows.
Assumed lighting direction in cast-shadow interpretation was investigated. Experiment 1 used an ambiguous object-shadow-matching task to measure bias in shadow-matching direction. The shadow-matching bias was largest when the lighting direction was on average 38.3° left from above (a median of 25.1°). Experiment 2 tested the effect of body posture (head orientation) on cast-shadow interpretation using stimuli aligned in a head-centrically vertical or horizontal orientation. The below-shadow (light-from-above) bias in the head-centric frame was robust across the sitting upright, reclining-on-the-left-side, reclining-on-the-right-side, and supine conditions. A right-shadow (light-from-left) bias in the head-centric frame was found for the sitting upright and reclining-on-the-right-side conditions. In the reclining-on-the-left-side condition, shadow biases to the gravitational below direction and head-centric right direction may have cancelled each other out. These results are consistent with findings from previous shape-from-shading studies, suggesting that the same light-source assumption is applied to shading and shadow interpretations.


Identification of Single Nucleotide Polymorphisms Related to the Resistance Against Acute Hepatopancreatic Necrosis Disease in the Pacific White Shrimp Litopenaeus vannamei by Target Sequencing Approach.
Acute hepatopancreatic necrosis disease (AHPND) is a major bacterial disease in Pacific white shrimp Litopenaeus vannamei farming, which is caused by Vibrio parahaemolyticus. AHPND has led to a significant reduction of shrimp output since its outbreak. Selective breeding of disease-resistant broodstock is regarded as a key strategy in solving the disease problem. Understanding the relationship between genetic variance and AHPND resistance is the basis for marker-assisted selection in shrimp. The purpose of this study was to identify single nucleotide polymorphisms (SNPs) associated with the resistance against AHPND in L. vannamei. In this work, two independent populations were used for V. parahaemolyticus challenge and the resistant or susceptible shrimp were evaluated according to the survival time after Vibrio infection. The above two populations were genotyped separately by a SNP panel designed based on the target sequencing platform using a pooling strategy. The SNP panel contained 508 amplicons from DNA fragments distributed evenly along the genome and some immune-related genes of L. vannamei. By analyzing the allele frequency in the resistant and susceptible groups, 30 SNPs were found to be significantly associated with the resistance of the shrimp against V. parahaemolyticus infection (false discovery rate corrected at P < 0.05). Three SNPs were further validated by individual genotyping in all samples of population 1. Our study illustrated that target sequencing and pooling sequencing were effective in identifying the markers associated with economic traits, and the SNPs identified in this study could be used as molecular markers for breeding disease-resistant shrimp.


Clostridioides difficile: innovations in target discovery and potential for therapeutic success.
Clostridioides difficile infection (CDI) remains a worldwide clinical problem. Increased incidence of primary infection, occurrence of hypertoxigenic ribotypes, and more frequent occurrence of drug resistant, recurrent, and non-hospital CDI, emphasizes the urgent unmet need of discovering new therapeutic targets. We searched PubMed and Web of Science databases for articles identifying novel therapeutic targets or treatments for C. difficile from 2001 to 2021. We present an updated review on current preclinical efforts on designing inhibitory compounds against these drug targets and indicate how these could become the focus of future therapeutic approaches. We also evaluate the increasing exploitability of gut microbial-derived metabolites and host-derived therapeutics targeting VEGF-A, immune targets and pathways, ion transporters, and microRNAs as anti-C. difficile therapeutics, which have yet to reach clinical trials. Our review also highlights the therapeutic potential of re-purposing currently available agents . We conclude by considering translational hurdles and possible strategies to mitigate these problems. Considerable progress has been made in the development of new anti-CDI drug candidates. Nevertheless, a greater comprehension of CDI pathogenesis and host-microbe interactions is beginning to uncover potential novel therapeutic targets, which can be exploited to plug gaps in the CDI drug discovery pipeline.


Symbolic-Based Recognition of Contact States for Learning Assembly Skills.
Imitation learning is gaining more attention because it enables robots to learn skills from human demonstrations. One of the major industrial activities that can benefit from imitation learning is the learning of new assembly processes. An essential characteristic of an assembly skill is its different contact states (CS). They determine how to adjust movements in order to perform the assembly task successfully. Humans can recognize CSs through haptic feedback. They execute complex assembly tasks accordingly. Hence, CSs are generally recognized using force and torque information. This process is not straightforward due to the variations in assembly tasks, signal noise and ambiguity in interpreting force/torque (F/T) information. In this research, an investigation has been conducted to recognize the CSs during an assembly process with a geometrical variation on the mating parts. The F/T data collected from several human trials were pre-processed, segmented and represented as symbols. Those symbols were used to train a probabilistic model. Then, the trained model was validated using unseen datasets. The primary goal of the proposed approach aims to improve recognition accuracy and reduce the computational effort by employing symbolic and probabilistic approaches. The model successfully recognized CS based only on force information. This shows that such models can assist in imitation learning.


Cabergoline for reducing ovarian hyperstimulation syndrome in assisted reproductive technology treatment cycles. A prospective randomized controlled trial.
To investigate whether cabergoline (Cb2), a dopamine agonist, reduces ovarian hyperstimulation syndrome (OHSS) in high-risk women undergoing assisted reproductive technology (ART), and to analyze whether cabergoline affects the outcome of ART. Forty infertile women at risk of developing OHSS were enrolled in the trial. The inclusion criteria were as follows: infertile women undergoing IVF with serum estradiol concentration > 4,000 pg/mL or with > 20 follicles > 12 mm on the day of human chorionic gonadotropin (hCG) administration, and 18-40 years of age. They were randomized into 2 groups: the Cb2 group (n = 20) received 0.5 mg oral Cb2 per day for 8 consecutive days beginning on the day of hCG, and the control group (n = 20) received no medication. Ascites was significantly lower (p = 0.008) in the Cb2 group as compared with the control group. The incidence of moderate OHSS was also significantly lower (p = 0.04) in the Cb2 as compared to the control group. There was no evidence of statistically significant differences regarding the parameters of ART outcome. Our data supports the use of Cb2 in the management of high-risk women undergoing ART and, consequently, achieving lowered risk of OHSS, with no deleterious impact on ART outcomes.


The influence of the Battle of Jutland on plastic surgery.
The Battle of Jutland was fought between the British and German fleets in the gray wastes of the North Sea in May 1916. Because the battle was fought close to English shores, burn victims fared better than previously had been possible. From the Battle of Jutland came major advances in the clinical care of the acutely injured, as well as new concepts of reconstruction after healing had taken place.


A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women.
To evaluate and compare the lipid-altering effects of conjugated estrogens and pravastatin, alone and in combination, in postmenopausal women with hypercholesterolemia. This was a double-blind, randomized, placebo-controlled clinical trial with 4 parallel groups. Participants (N = 76) were randomly assigned to receive conjugated estrogens, 0.625 mg/d; pravastatin sodium, 20 mg/d; conjugated estrogens plus pravastatin; or a placebo for 16 weeks. Primary end points were changes in serum lipid parameters. Among participants treated with conjugated estrogens, levels of non-high density lipoprotein cholesterol (non-HDL-C) (13.0%) and calculated low density lipoprotein cholesterol (LDL-C) (13.5%) decreased, while levels of HDL-C (22.5%) and triglycerides (4.2%) increased. Participants in the pravastatin group achieved reductions of 23.7% and 25.4% in non-HDL-C and calculated LDL-C levels, respectively. Levels of HDL-C increased slightly (3.7%) and triglycerides decreased by 12.1%. Among participants treated with a combination of conjugated estrogens plus pravastatin, the non-HDL-C (-25.2%) and calculated LDL-C (-28.7%) responses were similar to those of the pravastatin group, and the HDL-C response (21.2%) was similar to that observed in the conjugated estrogens group. Triglyceride levels remained similar to baseline (-0.9%) in the combined treatment group. Administration of conjugated estrogens resulted in potentially antiatherogenic changes in levels of non-HDL-C, HDL-C, and calculated LDL-C. The HDL-C response to combined treatment was similar to that observed in women taking conjugated estrogens alone, while the non-HDL-C and LDL-C responses to combined treatment were similar to those produced by pravastatin therapy alone. These findings support the position of the National Cholesterol Education Program that estrogen replacement, with a progestin where indicated, should be given consideration as a therapeutic option for the management of hypercholesterolemia in postmenopausal women.


Costs of abduction treatment in developmental dysplasia of the hip. Analysis of 900 patients.
Developmental dysplasia of the hip (DDH) is a disorder of hip development that leads to dysplasia, subluxation, or total hip dislocation. Early detection of DDH is important, and early initiation of abduction treatment is key to successful correction of the hip joint. However, mild forms of DDH, including hip instability without complete dislocation, have good spontaneous healing potential, and a watchful waiting strategy in mild DDH has been found to be safe. In this study, we aimed to evaluate the cost differences between different treatment strategies for DDH. Data were collected retrospectively from the medical records of all children diagnosed with diagnosis and treatment of DDH in Tampere University hospital between 1998 and 2018. In total, 948 patients were included in the study. Patients who underwent casting or operative treatment (n = 48) were excluded from the analysis. All Ortolani positive children were subjected to early abduction treatment. Children with Ortolani negative DDH were subjected to either watchful waiting or early abduction treatment, based on the clinicians' decision. The regression model estimates for the number of clinical visits with and without ultrasound examination were assessed together with cost reports from Tampere University Hospital for the calculation of savings per patient in spontaneous recovery. Alpha angles at one month of age (p < 0.001) and treatment method (p < 0.001) affected the number of clinical visits and ultrasound examinations during the treatment follow-up. A low alpha angle predicted closer follow-up, and children with spontaneous recovery had lower numbers of clinical visits and ultrasound examinations than children in abduction treatment. Spontaneous recovery was found to result in approximately 375€/patient savings compared to successful abduction treatment. With correct patient selection, a watchful waiting strategy is cost-effective in treating mild developmental dysplasia of the hip, considering the high percentage of spontaneous recovery.


The impact of total factor mobility on rural-urban symbiosis: Evidence from 27 Chinese provinces.
The rational flow and optimal allocation of urban and rural factors is the key to solving the problem of unbalanced and insufficient urban and rural development. This study draws on the theory of ecological symbiosis to examine the mechanism of factor flow and urban-rural symbiosis. It analyzes panel data from 27 Chinese provinces and autonomous regions between 2010 and 2020 to empirically demonstrate the influence of labor, capital, technology, and land mobility on urban-rural symbiosis. The study found that: (1) The relationship between the total factor flow and urban-rural symbiosis is U-shaped nonlinear, and the time when cities feed the development of rural areas has come; (2) The impact of labor factor flow on urban-rural symbiosis exhibits an inverted U-shaped relationship, the impact of capital factor flow displays a positive U-shaped relationship, the impact of land factor flow shows an inverted U-shaped relationship, and the impact of technical factor flow on urban-rural symbiotic development is not significant. (3) The factor flow exerts a region-oriented impact on the level of urban-rural symbiosis. In developed areas, total factor flow does not affect urban-rural symbiosis, but the level of labor flow and the urban-rural symbiosis demonstrates an inverted U-shaped relationship, the flow of technological factors has a U-shaped impact on the urban-rural symbiosis level, the flow of land factors and the urban-rural symbiosis show an inverted U-shaped relationship, and the flow of capital factors has no impact on the urban-rural symbiosis relationship. In underdeveloped areas, the impact of the total factor flow on urban-rural symbiosis shows a significantly positive U-shaped characteristic, the labor mobility level and urban-rural symbiosis show an inverted U-shaped relationship, the flow of capital factors has a U-shaped impact on the urban-rural symbiosis level, and the flow of lands and technology does not have a remarkable impact on urban-rural symbiosis in underdeveloped areas.


[Clinical assessment of critical ischemia is always to be done prior to amputation].
Patients with critical limb ischemia (rest pain and/or ulcer/gangrene, together with low ankle pressure) are at risk of amputation, and should therefore undergo arterial reconstruction if that is at all technically possible. Thorough clinical investigation will usually distinguish patients in need of further evaluation by a vascular surgeon. No amputation should be undertaken without such evaluation. Diabetic patients belong to a special category, in that neuropathy makes it difficult to evaluate pain, and ankle pressure is often falsely high due to medial arterios sclerosis.


Water, Sanitation, and Hygiene and Infection Prevention and Control in Jordanian Hospitals in the Context of COVID-19: A National Assessment.
To identify areas that need improvement in Jordanian health centers regarding infection prevention and control (IPC) programs; water, sanitation, and hygiene (WASH) services; and other protective measures, especially in the context of coronavirus disease (COVID-19). This is a national assessment study that comprised hospitals of different sectors in Jordan, including, Ministry of Health (MoH), private, and military hospitals. The study included 23 Jordanian hospitals. Assessment tools were developed and adapted mainly from the WASH Facility Improvement Tool (WASH FIT) and other tools. Hospitals were assessed to meet targets based on whether indicators were fully met, partially met, or not met. The mean percentage of the 150 indicators that met the standards was 83.2% (72.6% for MoH, 84.5% for private, and 90.4% for military hospitals). The percentage of indicators, both WASH/IPC and training and education indicators, that met the targets were higher in military hospitals than in MoH and private hospitals. However, in context of COVID-19, only 64.7% of indicators related to precautionary measures were met by all hospitals. The data available on WASH/IPC in Jordan are scarce, and the study findings will help in preventing severe consequences of the COVID-19 pandemic. There is scope for improvement in many WASH/IPC aspects, and urgent actions should be taken, especially to fill the gaps in COVID-19 precautionary measures.


Inhibition of B-cell receptor signaling disrupts cell adhesion in mantle cell lymphoma via RAC2.
Inhibition of the B-cell receptor (BCR) signaling pathway is highly effective in B-cell neoplasia through Bruton tyrosine kinase inhibition by ibrutinib. Ibrutinib also disrupts cell adhesion between a tumor and its microenvironment. However, it is largely unknown how BCR signaling is linked to cell adhesion. We observed that intrinsic sensitivities of mantle cell lymphoma (MCL) cell lines to ibrutinib correlated well with their cell adhesion phenotype. RNA-sequencing revealed that BCR and cell adhesion signatures were simultaneously downregulated by ibrutinib in the ibrutinib-sensitive, but not ibrutinib-resistant, cells. Among the differentially expressed genes, RAC2, part of the BCR signature and a known regulator of cell adhesion, was downregulated at both the RNA and protein levels by ibrutinib only in sensitive cells. RAC2 physically associated with B-cell linker protein (BLNK), a BCR adaptor molecule, uniquely in sensitive cells. RAC2 reduction using RNA interference and CRISPR impaired cell adhesion, whereas RAC2 overexpression reversed ibrutinib-induced cell adhesion impairment. In a xenograft mouse model, mice treated with ibrutinib exhibited slower tumor growth, with reduced RAC2 expression in tissue. Finally, RAC2 was expressed in ∼65% of human primary MCL tumors, and RAC2 suppression by ibrutinib resulted in cell adhesion impairment. These findings, made with cell lines, a xenograft model, and human primary lymphoma tumors, uncover a novel link between BCR signaling and cell adhesion. This study highlights the importance of RAC2 and cell adhesion in MCL pathogenesis and drug development.


Highly sensitive GC/MS/MS method for quantitation of amino and nonamino organic acids.
Metabolite profiling methods are important tools for measurement of metabolite pools in biological systems. While most metabolite profiling methods report relative intensities or depend on a few internal standards representing all metabolites, the ultimate requirement for a quantitative description of the metabolite pool in biological cells and fluids is absolute concentration determination. We report here a high-throughput and sensitive gas chromatography/tandem mass spectrometry (GC/MS/MS) targeted metabolite profiling method enabling absolute quantification of all detected metabolites. The method is based on methyl chloroformate derivatization and quantification by spiking samples with metabolite standards separately derivatized with deuterated derivatization reagents. The traditional electron impact ionization is replaced with positive chemical ionization since the latter to a much larger extent preserve the molecular ion and other high molecular weight fragments. This made it easier to select unique MS/MS transitions among the many coeluting metabolites. Currently, the novel GC/MS/MS method comprises 67 common primary metabolites of which most belong to the groups of amino and nonamino organic acids. We show the applicability of the method on urine and serum samples. The method is a significant improvement of present methodology for quantitative GC/MS metabolite profiling of amino acids and nonamino organic acids.


Rare Pediatric Non-Hodgkin Lymphomas: A Report From Children's Oncology Group Study ANHL 04B1.
Non-Hodgkin lymphoma (NHL) is a relatively common malignancy in pediatric patients; however, a small subgroup have unusual lymphoma subtypes for the pediatric population. The Children's Oncology Group Rare and Cutaneous NHL registry's (protocol ANHL 04B1) main objectives were to determine the pathologic, biologic, and clinical features of rare and cutaneous pediatric NHL and establish a bank of centrally reviewed tissue specimens. We report the clinical data, treatment data, and outcome for rare pediatric NHL. In 101 lymphomas, there is a 97.8% concordance between the reviewing study pathologists and an 87.6% concordance between the central and institutional pathology review. Samples in the specimen bank include primary tumor tissue that is snap frozen, in paraffin blocks, or H&E-stained and unstained paraffin slides as well as blood, serum, and bone marrow. This descriptive analysis shows that children with pediatric follicular lymphoma, mucosa-associated lymphoid tissue, nodal marginal zone lymphoma, primary cutaneous, primary central nervous system lymphoma, and subcutaneous panniculitis-like T-cell lymphomas have 100% survival at a median of 2 years from enrollment. There are early deaths, mostly from progressive disease, in subjects with peripheral T-cell (not otherwise specified), NKT, and hepatosplenic T-cell lymphomas. This registry provides high-quality biologic specimens with clinical data to investigators working on the biology of these unusual pediatric diseases.


Teacher Distress and the Role of Experiential Avoidance.
Teachers' psychological wellbeing is important for teachers and students, but is highly stressful, particularly in special education. We examined the role of experiential avoidance (EA) in the wellbeing of 529 middle and elementary school teachers. EA involves the tendency to avoid thoughts, feelings, and other internal experiences even when doing so causes long-range consequences. Using a teacher-specific measure, we investigated its relationship to stress associated with student misbehavior and limited social support. We assessed EA's relationship to burnout and depression, finding EA significantly and moderately correlated with depression and all scales of Maslach's Burnout Inventory. Mediation analyses showed EA mediated the relationship between stress associated with student behavior and measures of wellbeing. We found 26.8% of teachers mildly, 8.9% moderately, and 2.8% moderately severely or severely depressed. This evidence concurs with studies showing the value of mindfulness-based interventions and points to the utility of implementing interventions aimed at decreasing EA in teachers.


Effects of climate change on subterranean termite territory size: a simulation study.
In order to study how climate change affects the territory size of subterranean termites, a lattice model was used to simulate the foraging territory of the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), and the minimized local rules that are based on empirical data from the development of termites' foraging territory was applied. A landscape was generated by randomly assigning values ranging from 0.0 to 1.0 to each lattice site, which represented the spatially distributed property of the landscape. At the beginning of the simulation run, N territory seeds - one for each founding pair, were randomly distributed on the lattice space. The territories grew during the summer and shrank during the winter. In the model, the effects of climate change were demonstrated by changes in two variables: the period of the summer season, T, and the percentage of the remaining termite cells, σ, after the shrinkage. The territory size distribution was investigated in the size descending order for the values of T (= 10, 15, ... , 50) and σ (= 10, 15, ... , 50) at a steady state after a sufficiently long time period. The distribution was separated into two regions: the larger-sized territories and the smaller-sized territories. The slope, m, of the distribution of territory size on a semi-log scale for the larger-sized territories was maximal with T (45 ≤ T ≤ 50) in the maximal range and with σ in the optimal range (30 ≤ σ ≤ 40), regardless of the value of N. The results suggest that the climate change can influence the termite territory size distribution under the proper balance of T and σ in combination.


Relationship between cathepsin B and thrombin in rheumatoid arthritis.
To investigate the pathophysiological significance of cathepsin B and thrombin in synovial fluid (SF) from patients with rheumatoid arthritis (RA). Thrombin and cathepsin B activities of samples from patients with RA and osteoarthritis (OA) were measured using fluorogenic synthetic substrates. The concentration of interleukin 8 (IL-8) in SF was measured by ELISA. The effect of thrombin on the proliferation of synovial fibroblast-like cells (SFC) was examined by measuring 3H-thymidine incorporation. The effect of thrombin on the release of IL-8 and cathepsin B from SFC was investigated. The expression of IL-8 mRNA in SFC after stimulation with thrombin was evaluated using real-time quantitative RT-PCR. The effect of recombinant IL-8 on the activation of cathepsin B was examined using the knee joints of rabbits. In SF supernatants, cathepsin B and thrombin-like activity was significantly higher in RA than in OA, and there was a significant correlation between them. Cathepsin B activity was also significantly higher in SF cells and synovial tissue extracts from RA patients than in those from OA patients. There was a significant correlation between cathepsin B activity and the concentration of IL-8 in RA SF. Thrombin enhanced the proliferation of SFC in a dose-dependent manner. Thrombin significantly enhanced the release of IL-8 from SFC as well as the expression of IL-8 mRNA in SFC. IL-8 induced activation of cathepsin B in the knee joints of rabbits. However, thrombin did not directly increase cathepsin B activity in SFC. In RA, thrombin was found to be related to the enhanced growth of SFC and the release of IL-8 from these cells; thus thrombin is probably related to worsening of inflammation through the recruitment of leukocytes (neutrophils), which release cathepsin B into the SF. Thrombin can induce activation of cathepsin B in SFC via increased expression of IL-8.


Methodology and Early Findings of the Third Survey of CASPIAN Study: A National School-based Surveillance of Students' High Risk Behaviors.
A school-based surveillance system entitled the childhood and adolescence surveillance and prevention of Adult Noncommunicable disease (CASPIAN) Study is implemented at national level in Iran. This paper presents the methods and primary findings of the third survey of this surveillance system. This national survey was performed in 2009-2010 in 27 provinces of Iran among 5570 students and one of their parents. In addition to physical examination, fasting serum was obtained. Body mass index was categorized based on the World Health Organization growth charts. Data of 5528 students (2726 girls, 69.37% urban, mean age 14.7 ± 2.4 years) were complete and are reported. Overall, 17.3% (17.3% of girls and 17.5% of boys) were underweight, and 17.7% (15.5% of girls and 19.9% of boys) were overweight or obese. Abdominal obesity was documented in 16.3% of students (17.8% of girls and 15% of boys). 57.6% of families consumed breads, the staple food for Iranians, prepared with white flour. Most families (43.8% in urban areas and 58.6% in rural areas) used solid hydrogenated fats. 22.7% of students did not add salt to the table food. 14.2% of students reported to have a regular daily physical activity for at least 30 min a day. Overall, 10.4% of students (11.7% in urban areas and 7.3% in rural areas) reported that they used tobacco products, often waterpipe. 32.8% of students experienced at least three times of bullying in the previous 3 months. During the year prior to the survey, 14.46% of students had an injury needing the interference by school health providers. This survey is confirmatory evidence on the importance of establishing surveillance systems for risk behaviors to implement action-oriented interventions.


Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.
Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy.


Microtubular patterns in spermatozoa of coccid insects in relation to bending.
Flagella-like motion occurs in filamentous spermatozoa of coccid insects, which have diameters (0.16-0.65 micro) and lengths (150-300 micro) similar to those of long flagella, but have no doublets or 9 + 2-like arrangements of microtubules. Light and electron microscope investigations of spermatozoa from 10 species reveal many bizarre patterns of microtubules and suggest some basic similarities to flagella. Detailed analyses of spermatozoa which are naturally bent in definable planes during their elongation in the male and their storage in the female provide evidence that a constant topographical relationship is maintained between their unorthodox patterns of microtubules, as viewed in transections, and the direction of bending. The configuration common to most coccid spermatozoa consists of an acentrically positioned crescent of microtubules surrounded by one to several concentric rings. A line drawn to connect the two ends of the crescent appears to remain perpendicular to the plane of bending, and it defines a plane in which bisection of the spermatozoon produces halves with unequal numbers of microtubules. Bisection of the 9 + 2 motile apparatus in a plane perpendicular to that of bending also appears to produce halves with unequal numbers of microtubules. Therefore, the indispensable elements for flagellar and flagella-like motion may be microtubules arranged in "asymmetric" patterns.


Ultrafast all-optical differentiators.
We report the experimental realization of an ultrafast all-optical temporal differentiator. Differentiation is obtained via all-fiber filtering based on a simple diffraction grating-assisted mode coupler (uniform long-period fiber grating) that performs full energy conversion at the optical carrier frequency. Due to its high bandwidth, this device allows processing of arbitrary optical signals with sub-picosecond temporal features (down to 180-fs with the specific realizations reported here). Functionality of this device was tested by differentiating a 700-fs Gaussian optical pulse generated from a fiber laser (@ 1535nm). The derivative of this pulse is an odd-symmetry Hermite-Gaussian waveform, consisting of two linked 500-fs-long, pi-phase-shifted temporal lobes. This waveform is noteworthy for its application in advanced ultrahigh-speed optical communication systems.


Influence of environment on passive immunity in calves.
Passive immunity in neonatal calves is influenced by environment. Placing newly born Holstein calves (108 head) in three different housing environments (shade, cooled shade, hutch) during hot weather produced differences in body temperature, serum cortocosteroids, immunoglobulin IgG1 concentrations, and mortality. Experimental design permitted examination of effects due to treatments, time, differences in colostrum, and climatic environment in an analysis of variance. Calves exposed to the hotter, less desirable environment responded by having a higher mortality, higher serum corticosteroid concentration, and lower serum immunoglobulin IgG1 at 2 and 10 days after birth. All of these were correlated. Calves that died had serum immunoglobulin IgG1 falling below the mean for all experimental calves.


Comparison of R128Q mutations in human, ovine, and chicken leptins.
Human leptin and its R128Q mutant, as well as the R128Q mutants of ovine and chicken leptins, were prepared, expressed in Escherichia coli, refolded, and purified to homogeneity yielding electrophoretically pure, over 95% monomeric protein. R128Q mutations did not change the binding properties to BAF/3 cells stably transfected with the long form of human leptin receptor compared, respectively, to non-mutated human, ovine, and chicken leptins. In contrast, the biological activity tested in a proliferation assay in the same cells was drastically changed. Human leptin R128Q lost its activity and even became a weak antagonist, whereas the activities of ovine and chicken leptins were reduced 25- and 80-fold. If dimerization models were applicable leptin receptor activation, the present results would suggest that site 2 of the hormone was impaired. Two models, the human growth hormone:human growth hormone receptor (hGH:hGHR) (1:2) and the granulocyte-colony stimulating factor:granulocyte-colony stimulating factor receptor (GCSF:GCSFR) (2:2) complexes, were used for modeling. Superimposing the leptin structure on the hGH and GCSF models in the complex structures did not indicate any role for R128 in receptor binding. This made it impossible to correlate the results shown in the present work with the currently available models. Therefore, leptin may bind its receptors in a manner different than those proposed until now.


Tele-assistance in chronic respiratory failure: patients' characterization and staff workload of 5-year activity.
The issue of how to optimize the routine use of tele-assistance (TA) in the clinical care remains to be addressed. Skills and costs of human resources represent the major component to care for chronic patients with TA. We investigated (1) the change in patient population, mortality, and staff utilization/cost during the first 5-year activity of a TA program (24-h availability of a call center, pulse oxygen device, and second medical opinion) dedicated to chronic respiratory failure patients and (2) the staff time dedicated to each new patient admitted to the service. Three-hundred and ninety-six patients (age 64 +/- 17 years; 296 men) were reviewed across 5 years of activity. Patients followed/year increased over time, particularly for amyotrophic lateral sclerosis subjects. Calls/month dramatically increased from 60 to 290, with a 5-year number of calls equal to 12.952. The doctor's time dedicated to TA decreased over time, whereas the nurse's time increased allowing a cost saving of 39% when compared with budgeted salary costs. The number of home ventilated patients did not change, remaining over 78%. The mortality rate increased over time (from 6% to 11%). Both chronic obstructive pulmonary disease (COPD) and No-COPD patients used the TA service more frequently during the winter, and COPD used it also in the summer. A stable TA service dedicated to chronic respiratory failure may be reached after 4 years. Across years, (1) number of patients increased, with COPD and ventilated subjects being the most representative; (2) calls varied during seasons; (3) doctor's workload decreased, saving salary costs; and (4) each new enrolled patient may require 73 and 27 min/month of nurse and doctor, respectively.


Subject-level Normalization to Improve A-phase Detection of Cyclic Alternating Pattern in Sleep EEG.
Automatic detection systems for activation phases (A-phase) of the cyclic alternating pattern (CAP) in electroencephalograms (EEG) are designed to automatically score A-phases in any individual but typically fail to factor in EEG signal variations between individuals, e.g. due to sleep disorders, recording site differences or equipment differences. Here, we investigate the effect of subject-level normalization on the performance of an automatic A-phase detection system consisting of a recurrent neural network. We compared the classification performance of various subject-level normalization methods to the standard training set normalization. Systems were trained and tested on subjects with different sleep disorders using the publicly available CAP Sleep Database on Physionet. Subject-level normalization using Zscore or median and interquartile range (IQR) increases the F1-score for A1-phases by +11-22% (Z-Score: +11-20%, Median/IQR: +16-22%), for A2-phases by +2-9% (Z-Score: +59%, Median/IQR: +2-7%), for A3-phases by -1 - +8% (Z-Score: +3-8%, Median/IQR: -1-+5%) as compared to the standard training data normalization when tested across sleep disorders. Our results show that subject-level normalization drastically improves the precision of A-phase detection in case the training population differs from the testing population.Clinical Relevance- Subject-level normalisation improves the automatic CAP scoring system performances for the general population by minimizing the effect of individual EEG differences.


Nonhomologous recombination in the parvovirus chromosome: role for a CTATTTCT motif.
The mechanism of nonhomologous recombination in murine cells infected with the parvovirus minute virus of mice (MVM) has been investigated by analysis of DNA sequences at recombination junctions in naturally occurring deletion variants of the virus. We report here that nonhomologous recombination in the MVM chromosome is characterized by short homologies, by insertion at recombination junctions of foreign DNA sequences that are enriched for preferred eucaryotic topoisomerase I cleavage sites, and by an association with a common DNA sequence motif of the type 5'-CTATTTCT-3'. Additional analyses of broken MVM chromosomes provided evidence for specific enzymatic cleavage within 5'-CTTATC-3' and 5'-CTATTC-3' sequences. The results indicate that the 5'-CTATTTCT-3' motif is an important genetic element for nonhomologous recombination in the parvovirus chromosome.