Development of an integrated case management program for vulnerable children.
Although case management is a recognized technique to organize and coordinate human services, its use with high-risk children is relatively new. This article describes the development of a case management program for children at the Center for the Vulnerable Child at Children's Hospital, Oakland, California, a health care setting that brings together health, social work, and child welfare services. Case management was introduced into multidisciplinary clinical programs for foster children, drug-exposed infants, and adolescent mothers and their infants. Case management activities differed in each of the clinical programs in relation to the unique characteristics of each population and the different obstacles encountered. A time management analysis indicated consequent differences in case management time allocations. The implications of these findings are discussed.


Polyethylene glycol electrolyte solution (Isocolan) for constipation during pregnancy: an observational open-label study.
To evaluate the efficacy of a polyethylene glycol electrolyte solution (PEG-4000) in pregnant women affected by constipation, 40 consecutive pregnant women from 6 to 38 weeks' gestation were enrolled in this preliminary study. Constipation was defined as spontaneous evacuation less than four times a week or the presence of symptoms such as defecation pain, rectal urgency, tenesmus, anal injury, or abdominal pain. A PEG-4000 solution (Isocolan, also marketed in the United States as Golitely/Nulitely) was administered for 15 days at a dose of 250 mL by mouth once or twice a day. The number of bowel movements per week, the presence or absence of liquid stools, tenesmus, urgency, defecation pain, anal lesions, and abdominal pain were evaluated before and after 15 days of treatment. Treatment with PEG-4000 significantly increased the evacuation episodes per week (from 1.66 +/- 0.48 to 3.16 +/- 1.05; P <.01), and constipation was resolved in 27 of 37 women (73%). Defecation pain, anal injury, and abdominal pain significantly improved after PEG-4000 administration. Improvement occurred in both patients with new-onset constipation during pregnancy as well as patients with a history of constipation before pregnancy. These preliminary findings indicate that PEG-4000 may be an effective choice for the treatment of constipation during pregnancy.


Studying plant-pollinator interactions in a changing climate: A review of approaches.
Plant-pollinator interactions are potentially at risk due to climate change. Because of the spatial and temporal variation associated with the effects of climate change and the responses of both actors, research to assess this interaction requires creative approaches. This review focuses on assessments of plants' and pollinators' altered phenology in response to environmental changes, as phenology is one of the key responses. I reviewed research methods with the goal of presenting the wide diversity of available techniques for addressing changes in these interactions. Approaches ranged from use of historical specimens to multisite experimental community studies; while differing in depth of historical information and community interactions, all contribute to assessment of phenology changes. Particularly insightful were those studies that directly assessed the environmental changes across spatial and temporal scales and the responses of plants and pollinators at these scales. Longer-term studies across environmental gradients, potentially with reciprocal transplants, enable an assessment of climate impacts at both scales. While changes in phenology are well studied, the impacts of phenology changes are not. Future research should include approaches to address this gap.


Genotoxic exposure of workers creosoting wood.
In a small wood preserving industry spot samples were taken from contaminated surfaces at several places and tested for mutagenicity. The results suggest that the application of a wipe test can give a first indication of occupational exposure to mutagenic and carcinogenic substances, particularly when exposure occurs more from skin contact than from inhalation. One of the pesticide chemicals used to preserve wood is the mutagenic creosote . It was found that mutagens appeared in the urine of rats after intraperitoneal administration of creosote . Despite these results, no increase in mutagenicity could be detected in the urine of creosote workers in relation to their work.


In vitro effects of trapidil on fatty acid and prostaglandin metabolism in platelets.
The effects of trapidil, a coronary vasodilator and platelet aggregation inhibitor, on fatty acid metabolism and prostaglandin (PG) formation in platelets were studied using platelet suspensions from six normal subjects. The addition of trapidil to fatty acids in platelet phospholipids decreased palmitoleic acid and arachidonic acid, and increased an unidentified substance, X2 (palmitoleic acid, P < 0.05; arachidonic acid, P < 0.05; X2, P < 0.05). Thrombin stimulation following the addition of trapidil resulted in an increase in stearic acid and a decrease in arachidonic acid, compared with the trapidil-free control samples (stearic acid, P < 0.05; arachidonic acid, P < 0.02). The addition of trapidil tended to increase immunoreactive PGE (iPGE) and iPGF dose-dependently. On the other hand, thrombin stimulation following the addition of trapidil decreased the formation of thromboxane B2 (TXB2) significantly compared with the levels of TXB2 in the trapidil-free samples (10 micrograms/mL trapidil, P < 0.005, 100 micrograms/mL trapidil, P < 0.001). These results show that trapidil increased arachidonic acid mobilization in the platelets.


Light emission from the Fe2+ -EDTA-ascorbic acid-H2 O2 system strongly enhanced by plant phenolic acids.
Oxidative reactions can result in the formation of electronically excited species that undergo radiative decay depending on electronic transition from the excited state to the ground state with subsequent ultra-weak photon emission (UPE). We investigated the UPE from the Fe2+ -EDTA (ethylenediaminetetraacetic acid)-AA (ascorbic acid)-H2 O2 (hydrogen peroxide) system with a multitube luminometer (Peltier-cooled photon counter, spectral range 380-630 nm). The UPE, of 92.6 μmol/L Fe2+ , 185.2 μmol/L EDTA, 472 μmol/L AA, 2.6 mmol/L H2 O2 , reached 1217 ± 118 relative light units during 2 min measurement and was about two times higher (P < 0.001) than the UPE of incomplete systems (Fe2+ -AA-H2 O2 , Fe2+ -EDTA-H2 O2 , AA-H2 O2 ) and medium alone. Substitution of Fe2+ with Cr2+ , Co2+ , Mn2+ or Cu2+ as well as of EDTA with EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid) or citrate powerfully inhibited UPE. Experiments with scavengers of reactive oxygen species (dimethyl sulfoxide, mannitol, sodium azide, superoxide dismutase) revealed the dependence of UPE only on hydroxyl radicals. Dimethyl sulfoxide at the concentration of 0.74 mmol/L inhibited UPE by 79 ± 4%. Plant phenolics (ferulic, chlorogenic and caffec acids) at the concentration of 870 μmol/L strongly enhanced UPE by 5-, 13.9- and 46.8-times (P < 0.001), respectively. It is suggested that augmentation of UPE from Fe2+ -EDTA-AA-H2 O2 system can be applied for detection of these phytochemicals.


Habitat-associated Genomic Variation in a Wall Lizard from an Oceanic Island.
The lizard Teira dugesii exhibits morphological divergence between beach and inland habitats in the face of gene flow, within the volcanic island of Madeira, Portugal. Here, we analyzed genomic data obtained by genotyping-by-sequencing, which provided 16,378 single nucleotide polymorphisms (SNPs) from 94 individuals sampled from 15 sites across Madeira. Ancient within-island divergence in allopatry appears to have mediated divergence in similar species within other Atlantic islands, but this hypothesis was not supported for T. dugesii. Across all samples, a total of 168 SNPs were classified as statistical outliers using pcadapt and OutFLANK. Redundancy analysis (RDA) revealed that 17 of these outliers were associated with beach/inland habitats. The SNPs were located within 16 sequence tags and 15 of these were homologous with sequences in a 31 Mb region on chromosome 3 of a reference wall lizard genome (the remaining tag could not be associated with any chromosome). We further investigated outliers through contingency analyses of allele frequencies at each of four pairs of adjacent beach-inland sites. The majority of the outliers detected by the RDA were confirmed at two pairs of these matched sites. These analyses also suggested some parallel divergence at different localities. Six other outliers were associated with site elevation, four of which were located on chromosome 5 of the reference genome. Our study lends support to a previous hypothesis that divergent selection between gray shingle beaches and inland regions overcomes gene flow and leads to the observed morphological divergence between populations in these adjacent habitats.


P63 expression in conjunctival proliferative diseases: pterygium and laryngo-onycho-cutaneous (LOC) syndrome.
Compare expression of p63 in pterygium and laryngo-onycho-cutaneous (LOC) syndrome with normal conjunctiva. P63 immunohistochemical detection was carried out in normal, pterygium, and LOC conjunctival tissue. In vitro, growth of normal conjunctival biopsy specimens, pterygium, and LOC in growth tissue was compared. In normal conjunctiva, p63 was poorly expressed in the infranasal quadrant, with 36% of cells stained vs. 55 to 59% in other quadrants (p < 0.05). In pterygium, p63 was overexpressed (59% cells stained) compared to normal supranasal (55%) and normal infranasal conjunctiva (36%, p < 0.05). In LOC, p63 was only expressed in 39% of cells vs. 58% in normal supratemporal conjunctiva (p < 0.05). Cytokeratin 19 was expressed by all cells cultured from normal conjunctival tissue. This study emphasizes the importance of using control tissue explanted from the correspondent conjunctival quadrant when studying proliferative disorders. Different pathogenesis may account for the differences in p63 expression between pterygium and LOC.


Entire-spine Magnetic Resonance Imaging Findings and Costs in Children With Presumed Adolescent Idiopathic Scoliosis.
Patients with adolescent idiopathic scoliosis (AIS) are commonly monitored for curve progression with spinal radiographs; however, the utility of magnetic resonance imaging (MRI) screening is unclear. The purpose of this study was to assess the findings of screening MRI for patients with a nonsurgical curve size ordered during routine clinical care and compare them with MRI ordered for patients with large curves as part of preoperative screening. All consecutive patients with presumed AIS who underwent entire-spine MRI with a presumed diagnosis of idiopathic scoliosis at a single institution between 2017 and 2019 were retrospectively reviewed. Patients were stratified based on MRI indication into the following groups: preoperative evaluation, pain, neurological symptoms, abnormal radiographic curve appearance, rapidly progressive curve, and other. Neural axis abnormalities recorded included concern for tethered spinal cord, syringomyelia, and Chiari malformation. The MRI findings of preoperative patients with large curves were compared with all other patients. The number needed to diagnose (NND) a neurological finding was calculated in patients whose MRIs were ordered during routine clinical care. The amount charged for each patient undergoing entire-spine MRI was determined by review of our institution's Financial Decision Support system. There were 344 patients included in this study with 214 (62%) MRIs performed for preoperative evaluation. Although MRI abnormalities were found in 49% of patients, only 7.0% (24/344) demonstrated neural axis abnormalities with no difference between preoperative and other indications (P=0.37). For patients with nonsurgical curves undergoing MRI due to a complaint of back pain (n=28), there were no neural axis abnormalities, and a lower rate of disk herniation/degenerative changes detected compared with preoperative MRI (3.6% vs. 18%, P=0.06). Among the 15 patients undergoing MRI for a neurological concern, 1 had a neural axis abnormality that required surgical detethering. The NND for MRI to detect a neural axis abnormality that potentially required neurosurgical intervention in nonpreoperative patients with a neurological concern was 34.4. The average cost for MRI was $17,816 (range: $2601 to $22,411) with a total cost of $2,368,439 for nonsurgical curves. Entire-spine MRI for nonpreoperative indications including pain, abnormal radiographic curve appearance, and rapid curve progression has minimal utility for patients with AIS. For patients with neurological complaints, the NND a potentially treatment-altering finding with MRI is 34.4. Level II-diagnostic.


Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients.
To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients. A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured. Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively. Both minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides.


Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in Rural Malawi.
Objective. To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion. Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.


Robust contrast enhancement method using a retinex model with adaptive brightness for detection applications.
Low light image enhancement with adaptive brightness, color and contrast preservation in degraded visual conditions (e.g., extreme dark background, lowlight, back-light, mist. etc.) is becoming more challenging for machine cognition applications than anticipated. A realistic image enhancement framework should preserve brightness and contrast in robust scenarios. The extant direct enhancement methods amplify objectionable structure and texture artifacts, whereas network-based enhancement approaches are based on paired or large-scale training datasets, raising fundamental concerns about their real-world applicability. This paper presents a new framework to get deep into darkness in degraded visual conditions following the fundamental of retinex-based image decomposition. We separate the reflection and illumination components to perform independent weighted enhancement operations on each component to preserve the visual details with a balance of brightness and contrast. A comprehensive weighting strategy is proposed to constrain image decomposition while disrupting the irregularities of high frequency reflection and illumination to improve the contrast. At the same time, we propose to guide the illumination component with a high-frequency component for structure and texture preservation in degraded visual conditions. Unlike existing approaches, the proposed method works regardless of the training data type (i.e., low light, normal light, or normal and low light pairs). A deep into darkness network (D2D-Net) is proposed to maintain the visual balance of smoothness without compromising the image quality. We conduct extensive experiments to demonstrate the superiority of the proposed enhancement. We test the performance of our method for object detection tasks in extremely dark scenarios. Experimental results demonstrate that our method maintains the balance of visual smoothness, making it more viable for future interactive visual applications.


Tolerance of Ornamental Succulent Plant Crown of Thorns (Euphorbia milli) to Chromium and its Remediation.
The potential of an ornamental shrub Crown of thorns (Euphorbia milli) was evaluated for remediation of soil contaminated with Cr. The plant is one of the rare succulent ornamental shrubs with a slow to moderate growth rate and is capable of blooming almost year-round. The plant could tolerate well up to 75 mg of applied Cr and beyond that there was mortality of plants. Though the plant could not be classified as a hyperaccumulator, the plant was still very efficient in translocating Cr from roots to shoots as evident from the data on uptake and translocation efficiency values. The translocation efficiency of over 80% in our study demonstrates that a large proportion of Cr has been translocated to the harvestable biomass of the plant and therefore, this plant could be effectively recommended for the remediation of soils contaminated with low to medium level of contamination i.e., up to 50 mg/kg soil.


Kidney allografts and remaining contralateral donor kidneys before and after transplantation: assessment by quantitative (99m)Tc-DMSA SPECT.
We used (99m)Tc-dimercaptosuccinic acid (DMSA) quantitative SPECT (QDMSA) to assess the function of kidneys before harvesting and after transplantation as well as the function of remaining donor kidneys. Nineteen kidney donors underwent a baseline QDMSA study before nephrectomy. The allografts of these kidneys were studied in recipients at 1 wk, 1-2 mo, and 6-15 mo after transplantation. The kidneys remaining in 16 donors were studied at 1-2 mo and 6-15 mo after harvesting. The parameters obtained in each SPECT study included functional volume, concentration of (99m)Tc-DMSA per cubic centimeter of renal tissue, and total kidney uptake. Clinical evaluation and determination of serum creatinine levels took place at the same time as SPECT. On the basis of the clinical evaluation, 14 grafts had normal function and 5 were impaired. The mean +/- SD of kidney uptake values expressed as percentage of baseline values were 131% +/- 30% in normal grafts versus 57% +/- 5% in impaired grafts at 1 wk (P < 0.01), 173% +/- 57% versus 65% +/- 10% at 1-2 mo (P < 0.001), and 190% +/- 50% versus 69% +/- 14% at 6-15 mo after transplantation (P < 0.01). Uptake values in the donors' remaining kidneys were 159% +/- 27% of baseline values at 1-2 mo and 164% +/- 30% at 6-15 mo after nephrectomy. Allografts and remaining kidneys showed a similar increase in total kidney uptake as a result of an increase in both functional volume and concentration. QDMSA may be a noninvasive assessment tool in kidney transplantation from living donors.


Evidence that asymmetry of the membrane/cytoskeletal complex in human red blood cell ghosts is responsible for their biconcave shape.
The main conclusion of the results reported in this article is that during centrifugation, sphered red blood cell ghosts become oriented in their attachment to a coverslip such that a dense band within the ghosts lies parallel to the centrifugal field. The result of the orientation of this dense band is that when the attached spherical ghosts are shrunken to become biconcave discs, they do so by directly collapsing on themselves without any lateral motion. This result is interpreted to suggest that a dense band, relative to the dimple, resides in the rim of the ghost and is responsible for its biconcave shape. These results confirm the conclusions reached in a previous publication in which there was the uncertainty that the shape change of the spherical ghosts to discs could not be directly imaged. The present work corrects this limitation by use of a chamber in which the tonicity of the solutions in the ghosts' surround could be altered by perfusion coupled with constant microscopic imaging. The identity of the components that are responsible for the differences in the density (mass) between the rim and the dimple regions of the cytoskeletal/membrane complex in the biconcave disk are unknown. It is also unknown what forces apply or what the explanation is for the unique orientation of the dense band during the ghosts' centrifugation, as described in this article. Nevertheless, the results reported in this article indicate the membrane's underlying cytoskeletal complex is asymmetrically distributed.


Two-Dimensional Sonographic Evaluation of Endometrial Polyps - Parameters That Are Reassuring.
To assess intra-endometrial lesions according to five two-dimensional sonographic parameters for predicting malignancy. This is a retrospective analysis of stored digital images from consecutive pathological reports of patients with benign endometrial polyps and stage 1 endometrial carcinoma. Five sonographic parameters were evaluated: heterogeneous or complex echogenicity of the lesion, presence of a 'bright edge sign,' regular endometrial-myometrial junction, the presence of a normal endometrium adjacent to the lesion, and detection of small intralesional cysts. The sensitivity, specificity, PPV, and NPV of these parameters were calculated, as well as combinations of pairs of parameters. Seventy-nine patients were eligible for the current study, 26 with benign endometrial polyps and 53 with stage 1 endometrial carcinoma. The sonographic appearance of numerous small intralesional cysts (cystic formation) was highly related to benign polyp; the presence of a lesion with heterogeneous echogenicity had sensitivity and specificity for malignancy of 63.5 and 88.5%, respectively. We have shown that asymptomatic endometrial lesions, which are homogenous, have bright edges, and small intralesional cysts are likely to be benign Determining these parameters during sonographic evaluation can assist in identifying patients who will benefit from a follow-up strategy instead of an unnecessary surgical intervention.


Dystextia as a presentation of stroke.
Cerebrovascular accident remains one of the major causes of morbidity and mortality worldwide. Understanding the presentation of this common disease will be of great benefit for early diagnosis and management. We report a newly recognised symptom of stroke where there is difficulty writing mobile phone texts, an entity called dystextia. This symptom was previously reported as a presentation of complex migraine and starts to be recognised in the symptomology of stroke. Our patient with this presentation was found to have ischaemic stroke secondary to carotid vascular disease which was operated and she had a complete resolution of her symptoms with returning to her baseline shortly after hospitalisation and before her vascular intervention.


The Real-World Utilization Pattern of Increased Utilization of Advanced Topical Adjunctive Hemostats in a Vertically Integrated Healthcare System.
Hemostasis products, such as SURGICEL®, have been increasingly used across a wide variety of surgical procedures to mitigate bleeding-related risks and complications. This retrospective observational study described the utilization pattern of the SURGICEL® family of oxidized regenerated cellulose products (SURGICEL® ORIGINAL, SURGICEL® FIBRILLAR™, SURGICEL SNoW®) in a large, vertically integrated healthcare system, by utilizing electronic medical records (EMR) extracted from August 2013 through June 2015 at Henry Ford Health System (HFHS). Descriptive measurements were compared between SURGICEL® ORIGINAL and advanced SURGICEL® products (SURGICEL® FIBRILLAR™ and SURGICEL SNoW®) for pooled common surgical procedures. Among 1471 patients, 450 received SURGICEL® ORIGINAL, and 1021 received advanced SURGICEL® products. A significantly greater proportion of patients given advanced SURGICEL® products had comorbidities (91.0% vs 85.6%, p=.0024), prior bleeding conditions (49.9% vs 30.9%, p<.0001), and prior use of anticoagulants (27.7% vs 5.3%, p<.0001). Advanced SURGICEL® products were more likely to be used in coronary artery bypass grafting (13.7% vs 1.6%, p<.0001). Among a sub-set of 1420 patients with complete package size information (988 Advanced and 432 ORIGINAL), significantly fewer mean normalized units of Advanced SURGICEL® were used per patient case (3.9 vs 5.5, p<.0001). Despite Advanced SURGICEL® products being utilized in higher risk bleeding situations compared to cases where SURGICEL® ORIGINAL was utilized, fewer overall normalized units of Advanced SURGICEL® were required per patient case. Further research is needed to investigate the implications of topical hemostat use in continuous oozing bleeding situations on outcomes, hospital costs, and resources.


Electrophysiologic effects of atropine and isoproterenol on the cardiac conduction system in familial amyloid polyneuropathy.
In ten patients with familial amyloid polyneuropathy (FAP), the effects of atropine and isoproterenol on the cardiac conduction system were studied using surface electrocardiogram (ECG) and His bundle electrograms. Intravenous administration of atropine sulfate, 1 mg, prolonged the sinus cycle length ( SNCL ) in 6 of 8, sinus node recovery time (SNRT) in 3 of 6, automaticity recovery time of the atrioventricular (A-V) node in one, A-H interval in 4 of 7, effective refractory periods of the atrium and A-V node in 4 of 6 and in 3 of 7 patients, respectively. Continuous intravenous administration of isoproterenol, 0.5 micrograms/min, shortened the SNCL , SNRT, A-H interval and refractory periods of the atrium and A-V node in all patients. We conclude that the therapeutic doses of atropine may be useless or potentially detrimental for bradyarrhythmias or conduction blocks in some patients with FAP, but that isoproterenol may have beneficial effects on those arrhythmias in FAP.


Isolation and characterization of sake yeast mutants deficient in gamma-aminobutyric acid utilization in sake brewing.
Sake yeasts take up gamma-aminobutyric acid (GABA) derived from rice-koji in the primary stage of sake brewing. The GABA content in sake brewed with the UGA1 disruptant, which lacked GABA transaminase, was higher than that brewed with the wild-type strain K701. The UGA1 disruptant derived from sake yeast could not grow on a medium with GABA as the sole nitrogen source. We have isolated the sake yeast mutants of K701 that were unable to grow on a medium containing GABA as the sole nitrogen source. The growth defect of GAB7-1 and GAB7-2 mutants on GABA plates was complemented by UGA1, which encodes GABA transaminase, and UGA2, which encodes succinic semialdehyde dehydrogenase (SSADH), respectively. DNA sequence analysis revealed that GAB7-1 had a homozygous nonsense mutation in UGA1 and GAB7-2 had a heterozygous mutation (G247D) in UGA2. The GABA transaminase activity of GAB7-1 and the SSADH activity of GAB7-2 were markedly lower than those of K701. These GAB mutants displayed a higher intracellular GABA content. The GABA contents in sake brewed with the mutants GAB7-1 and GAB7-2 were 2.0 and 2.1 times higher, respectively, than that brewed with the wild-type strain K701. These results suggest that the reduced function of the GABA utilization pathway increases the GABA content in sake.


Carbon Monoxide Releasing Molecule-2-Upregulated ROS-Dependent Heme Oxygenase-1 Axis Suppresses Lipopolysaccharide-Induced Airway Inflammation.
The up-regulation of heme oxygenase-1 (HO-1) is mediated through nicotinamaide adenine dinucleotide phosphate (NADPH) oxidases (Nox) and reactive oxygen species (ROS) generation, which could provide cytoprotection against inflammation. However, the molecular mechanisms of carbon monoxide-releasing molecule (CORM)-2-induced HO-1 expression in human tracheal smooth muscle cells (HTSMCs) remain unknown. Here, we found that pretreatment with CORM-2 attenuated the lipopolysaccharide (LPS)-induced intercellular adhesion molecule (ICAM-1) expression and leukocyte count through the up-regulation of HO-1 in mice, which was revealed by immunohistochemistrical staining, Western blot, real-time PCR, and cell count. The inhibitory effects of HO-1 by CORM-2 were reversed by transfection with HO-1 siRNA. Next, Western blot, real-time PCR, and promoter activity assay were performed to examine the HO-1 induction in HTSMCs. We found that CORM-2 induced HO-1 expression via the activation of protein kinase C (PKC)α and proline-rich tyrosine kinase (Pyk2), which was mediated through Nox-derived ROS generation using pharmacological inhibitors or small interfering ribonucleic acids (siRNAs). CORM-2-induced HO-1 expression was mediated through Nox-(1, 2, 4) or p47phox, which was confirmed by transfection with their own siRNAs. The Nox-derived ROS signals promoted the activities of extracellular signal-regulated kinase 1/2 (ERK1/2). Subsequently, c-Fos and c-Jun-activator protein-1 (AP-1) subunits-were up-regulated by activated ERK1/2, which turned on transcription of the HO-1 gene by regulating the HO-1 promoter. These results suggested that in HTSMCs, CORM-2 activates PKCα/Pyk2-dependent Nox/ROS/ERK1/2/AP-1, leading to HO-1 up-regulation, which suppresses the lipopolysaccharide (LPS)-induced airway inflammation.


Studies on the mechanism of hypertriglyceridemia in the genetically obese Zucker rat.
The possibility that impaired removal of lipoprotein triglyceride from the circulation may be a participating factor in the hypertriglyceridemia of the obese Zucker rat was examined. We found no significant differences in the heparin-released lipoprotein lipase (LPL) activities of the adipose tissue, skeletal muscle, and heart (expressed per gram of tissue) from the lean and obese Zucker rats. Furthermore, the kinetic properties of adipose tissue and heart LPL from the lean and obese rats were similar, indicating that the catalytic efficiency of the enzyme was unaltered in the obese animals. The postheparin plasma LPL activities of lean and obese rats were also similar. However, the postheparin plasma hepatic triglyceride lipase (H-TGL) activity in the obese rats was elevated. The higher activity of H-TGL could not alleviate the hypertriglyceridemia in these animals. Since hypertriglyceridemia in the obese rats could also be due to the hepatic production of triglyceride-rich lipoproteins which are resistant to lipolysis, we therefore isolated very low density lipoproteins (VLDL) from lean and obese rat liver perfusates and examined their degradation by highly purified human milk LPL. Although certain differences were observed in hepatic VLDL triglyceride fatty acid composition, the kinetic patterns of LPL-catalyzed triglyceride disappearance from lean and obese rat liver perfusate VLDL were similar. The isolated liver perfusate VLDL contained sufficient apolipoprotein C-II for maximum lipolysis. These results indicate that impaired lipolysis is not a contributing factor in the genesis of hypertriglyceridemia in the genetically obese Zucker rat. The hyperlipemic state may be attributed to hypersecretion of hepatic VLDL and consequent saturation of the lipolytic removal of triglyceride-rich lipoproteins from the circulation.


A trypanosome structure involved in transmitting cytoplasmic information during cell division.
African trypanosomes are protozoan parasites that cause sleeping sickness in humans through a tsetse fly vector. The procyclic form of Trypanosoma brucei has a single, attached flagellum that describes a helical path along the cell from posterior to anterior. During division, a specific flagellum-flagellum connection is elaborated between the new and old flagellum. This connector was present only during cell duplication and was found to be involved in the replication of the helical cell pattern and polarity. This finding implicates the concept of cytotaxis in cell morphogenesis in trypanosomes.


Small bowel MR enterography: problem solving in Crohn's disease.
Magnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn's disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition. Main Messages • MR enterography (MRE) is the preferred imaging investigation to assess Crohn's disease. T2-weighted, post-contrast and diffusion-weighted imaging (DWI) can be used. • MRE offers no radiation exposure, high-contrast resolution, multiplanar ability and cine imaging. • MRE can help define disease activity, a key question in the management of Crohn's disease. • MRE can help distinguish between inflammatory, stricturing and penetrating disease. • MRE can demonstrate both mural and extramural complications.


Surgeon Experience and Complications of Transvaginal Prolapse Mesh.
To measure the proportion of women with transvaginal prolapse mesh complications and their association with surgeon volume. We conducted a retrospective, population-based cohort study of all women who underwent a mesh-based prolapse procedure using administrative data (hospital procedure and physician billing records) between 2002 and 2013 in Ontario, Canada. The primary outcome was surgical revision of the mesh. Primary exposure was surgeon volume: high (greater than the 75th percentile, requiring a median of five [interquartile range 5-6] procedures per year) and very high (greater than the 90th percentile, requiring a median of 13 [interquartile range 11-14] procedures per year) volume mesh implanters were identified each year. Primary analysis was an adjusted Cox proportional hazards model. A total of 5,488 women underwent mesh implantation by 1 of 368 unique surgeons. Median follow-up time was 5.4 (interquartile range 3.0-8.0) years. We found that 218 women (4.0%) underwent mesh reoperation a median of 1.17 (interquartile range 0.58-2.90) years after implantation. The hazard of reoperation for complications was only lower for patients of very high-volume surgeons (3.0% [145/3,001] compared with 4.8% [73/2,447], adjusted hazards ratio 0.59, 95% confidence interval 0.40-0.86). In multivariable modeling, younger age, concomitant hysterectomy, blood transfusion, and increased medical comorbidity were all associated with vaginal mesh reoperation. Approximately 5% of women who underwent mesh-based prolapse surgery required reoperation for a mesh complication within 10 years. The risk of reoperation was lowest for surgeons performing 14 or more procedures per year.


Cost analysis of plastic solid waste recycling in an urban district in Turkey.
The usage of plastics has exponentially increased in our daily lives over the past 50 years because of its durability, low costs and potential for diverse applications, such as widespread use as disposable items. In this study, first, the recycling cost of plastic wastes has been estimated by using actual data taken from a recycling centre, where plastic solid wastes were collected separately. The total amount of plastic wastes recycled at the centre was approximately 695 tonnes. The operating cost of plastics separation at the recycling centre, the transport of plastic wastes, labouring, maintenance, electricity, insurance and chemical costs were taken into consideration in the cost evaluation. Accordingly, the unit cost of recycling was calculated as US$0.40 kg-1 of plastic waste. This cost was compared with the predicted plastic recycling cost in the same region using statistical values. The predicted recycling cost was estimated based on assuming segregated collection by the municipalities of all PSW in municipal solid waste. Then the resulting unit cost of recycling was found to be US$0.25 kg-1 of plastic waste. In addition, the recycling costs were also evaluated including the revenue from the sales of recycled plastic granular. According to the evaluated total cost of plastic recycling, it can be concluded that mechanical recycling of plastics can only be an economical option if the recovery of plastics is improved.


The first evidence for vertical transmission of Babesia canis in a litter of Central Asian Shepherd dogs.
Tick-borne infections constitute an increasing health problem in dogs and may lead to death, especially in young or elderly individuals. Canine babesiosis constitutes a serious health problem in dogs worldwide. The aim of the study was to verify the probability of vertical transmission of Babesia canis between the bitch and the pups. In Autumn 2011, cases of babesiosis were diagnosed in a litter of 6-week-old puppies of a Central Asian Shepherd dog. Immediately following the first case of infection, blood samples were collected from all the pups in the litter (n=10) and from the female. Detection of Babesia infection was performed by molecular and microscopical techniques. The presence of B. canis DNA was detected using PCR in three pups, presenting at the time or 24-48 hours later with babesiosis symptoms, and in their asymptomatic mother. The isolates derived from the pups and the female - 520 bp 18S rRNA gene fragment - were compared and analyzed. All isolates from the pups and their mother were identical and showed 100% homology with B. canis group B (EU622793), supporting the same source of infection. Additionally, the USG of the peritoneal cavity was performed in the female, presenting evidence for splenomegaly. On the basis of (1) the same timing of three pup cases; (2) the identical B. canis sequences derived from all positive dogs; (3) evident splenomegaly in the asymptomatic female, this provides the first evidence of the vertical transmission of this piroplasm in dogs.


Selective fitness of four episomal shuttle-vectors carrying HIS3, LEU2, TRP1, and URA3 selectable markers in Saccharomyces cerevisiae.
A comparison of the selective fitness of four 2-microm-based shuttle-plasmids carrying the yeast genes HIS3, LEU2, TRP1, and URA3 was performed. The effect of each marker on long-term growth rate and plasmid maintenance was measured. In selective medium, the LEU2 and URA3 plasmids were maintained at the lowest and the highest levels, respectively, while the HIS3 and TRP1 plasmids were maintained at an intermediate level. In synthetic complete medium, plasmid loss rate was lower for the genes TRP1 and URA3 than for the other two markers, and a similar pattern was observed for cells growing in rich medium. These results were confirmed by competition experiments among transformants with different plasmids in complete and rich media, indicating a different degree of fitness for the markers used. A potential correlation of the energy cost of plasmid maintenance with the secondary DNA structure and the level of expression of the selective markers is also investigated.


Spectroscopic and chromatographic quantification of an antioxidant-stabilized ultrahigh-molecular-weight polyethylene.
The oxidative stability of various antioxidant-containing ultrahigh-molecular-weight polyethylene (UHMWPE) formulations has been widely reported. Depending on which specific antioxidant is used, the process by which it is incorporated into UHMWPE, and the amount of the antioxidant incorporated, there could be substantial differences in the material and toxicological properties of the UHMWPE formulation. Pentaerythritol tetrakis (3-[3,5-di tertiary butyl-4-hydroxyphenyl] propionate) (PBHP) has been extensively used as an efficient antioxidant in various applications. However, it has not thus far been used to stabilize UHMWPE in orthopaedic implants. It is therefore important to characterize and verify the concentration and homogeneity of distribution of PBHP in the composition, the chemical consequence of exposure of the antioxidant to gamma irradiation, and to assess the toxicological risk of use by the identification and quantification of leachables before the use of PBHP-containing UHMWPE in implantable devices. (1) Can the concentration and uniformity of distribution of the antioxidant PBHP in UHMWPE powder and in the consolidated, preirradiated formulation be verified? (2) Can the leachable compounds in the gamma radiation crosslinked PBHP/UHMWPE formulation be identified and quantified? PBHP in GUR 1020 UHMWPE was quantified by Fourier transform infrared (FTIR) and ultraviolet-visible (UV-Vis) spectroscopy. The chemical byproducts generated by gamma irradiation of PBHP were identified using gas chromatography in conjunction with mass spectrometry followed by a second-stage mass spectrometry (GC-MS/MS). When GC-MS/MS was coupled with Stir Bar Sorptive extraction, leachable components in the UHMWPE formulation were identified and quantified. The percent concentration of PBHP in UHMWPE powder was confirmed by UV-Vis spectroscopy and the concentration and uniform distribution of PBHP in UHMWPE after consolidation and before radiation crosslinking was verified through FTIR spectroscopy. GC-MS/MS analysis enabled the identification and quantification of 16 gamma irradiation byproducts of PBHP. These 16 compounds were verified as potentially leachable compounds in PBHP-stabilized UHMWPE and were found to be well below the safety threshold concern of 150 ng/device in orthopaedic knee inserts made from PBHP-stabilized UHMWPE. Spectroscopic analysis has been successfully used to demonstrate the ability to reliably quantify the amount as well as the distribution of PBHP in UHMWPE in orthopaedic bearings. State-of-the-art chemical extraction and analytical techniques have enabled the identification of the gamma radiation-induced byproducts of PBHP and the quantification of these components as leachables from the PBHP-stabilized UHMWPE formulation. Antioxidant-stabilized UHMWPE materials being considered for orthopaedic bearings must be fully characterized for composition before use because it is apparent that exposure to high doses of gamma radiation would cause the formation of new chemical entities. It is important to verify the identities and quantities of chemical species that could leach out of implanted devices in the long term to enable their toxicological risk assessment.


Brook Rearrangement as Trigger for Carbene Generation: Synthesis of Stereodefined and Fully Substituted Cyclobutenes.
Through a sequence that can be performed in a single vessel, involving regio- and diastereoselective copper-catalyzed carbomagnesiation of cyclopropenes, reaction with acylsilanes, and addition of THF as cosolvent, Brook rearrangement can be triggered to furnish a wide range of cyclobutenes with exceptional diastereoselectivity. Accordingly, stereodefined and highly substituted cyclobutenes with contiguous quaternary carbon centers can be synthesized easily and in high yield. The new strategy constitutes an unprecedented application of Brook rearrangement, one which involves the intermediacy of carbene species.


Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth.
The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells. In this study, we compared ROCK1 and 2 protein expression in a large panel of benign and malignant vascular tumors to that of normal vasculature. We then utilized shRNA technology to knockdown the expression of ROCK1 and 2 in SVR tumor-forming vascular cells, and evaluated tumor size and proliferation rate in a xenograft model. Finally, we employed proteomics and metabolomics to assess how knockdown of the ROCK paralogs induced alterations in protein expression/phosphorylation and metabolite concentrations in the xenograft tumors. Our findings revealed that ROCK1 was overexpressed in malignant vascular tumors such as hemangioendotheliomas and angiosarcomas, and ROCK2 was overexpressed in both benign and malignant vascular tumors including hemangiomas, hemangioendotheliomas, hemangiopericytomas, and angiosarcomas. shRNA-mediated knockdown of ROCK2, but not ROCK1, in xenograft vascular tumors significantly reduced tumor size and proliferative index compared to control tumors. Proteomics and metabolomics analysis of the xenograft tumors revealed both overlapping as well as unique roles for the ROCK paralogs in regulating signal transduction and metabolite concentrations. Collectively, these data indicate that ROCK proteins are overexpressed in diverse vascular tumors and suggest that specific targeting of ROCK2 proteins may show efficacy against malignant vascular tumors.


The economics of home nocturnal hemodialysis: how should we cost the benefits?
Home nocturnal hemodialysis (HNHD) has been established as a safe and effective way to provide dialysis for patients who require renal replacement therapy. Non-randomized studies have shown that patients switched to HNHD have improvements in blood pressure, left ventricular mass and quality of life. At present, there are no RCTs or long-term observational studies demonstrating a clear reduction in cardiovascular events or mortality. Several HNHD centers have published articles documenting the costs of this modality as compared to conventional HD. Some of these studies have found HNHD to provide significant cost savings, while others have found the two modalities to be relatively equivalent in terms of costs. In this paper, we review the results of these costing studies and illustrate some of the limitations associated with these studies including the lack of randomization, inconsistent reporting of HNHD start-up costs, potential patient selection biases and limited follow-up. On balance, it appears premature to conclude that HNHD is cost-saving in comparison to conventional hemodialysis. However, two ongoing randomized trials, which are collecting resource use information, will help to answer this question. Once these data are available, a formal economic evaluation should be done to determine the impact of HNHD on both clinical outcomes and costs. This information will assist decision-makers in determining whether to make HNHD more widely available.


Collagen fibril structure in lamprey.
X-ray diffraction and electron microscopy are used to compare the molecular and higher order structure of collagen fibrils in three tissues of the lamprey: the dermis, perinotochord and notochord sheath. These lamprey tissues are known to contain five distinct genetic types of fibrillar collagen. The modes of axial and lateral packing of collagen molecules in fibrils of the lamprey tissues demonstrate the three major motifs seen in higher vertebrate D-periodic collagen fibrils. In particular, lamprey dermis was found to have a decreased D period resulting from a molecular tilt that is seen in skins of higher vertebrates. Our results suggest the molecular-packing motifs for collagen fibrils were in place at the dawn of vertebrate evolution and have been conserved since. In contrast, the diameters of fibrils and their spatial orientation in lamprey tissues do not in general, correspond to features found in mammalian tissues. Only for lamprey notochord is there a strong similarity, with fibril diameters and organization closely resembling those seen in type II tissues of higher vertebrates. This suggests that for all tissues except those with type II collagen, higher level organization of fibrils evolved along with the diversification of vertebrates.


Non-targeted Screening of Natural Products from 288 Fungal Endophytes from Canadian Fruit Crops.
Many diverse species of fungi naturally occur as endophytes in plants. The majority of these fungi produce secondary metabolites of diverse structures and biological activities. Culture extracts from 288 fungi isolated from surface-sterilized blueberries, cranberries, raspberries, and grapes were analyzed by LC-HRMS/MS. Global Natural Products Social (GNPS) Molecular Networking modeling was used to investigate the secondary metabolites in the extracts. This technique increased the speed and simplicity of dereplicating the extracts, targeting new compounds that are structurally related. In total, 60 known compounds were dereplicated from this collection and seven new compounds were identified. These previously unknown compounds are targets for purification, characterization, and bioactivity testing in future studies. The fungal endophytes characterized in this study are potential candidates for providing bio-protection to the host plant with a reduced reliance on chemical pesticides.


Rapid test for the detection of methicillin-resistance of staphylococci by ATP-dependent bioluminescence.
Methicillin resistance of staphylococci is a marker of multiple resistance to antimicrobial drugs. The authors present their own variant of applying ATP-dependent bioluminescence for the rapid testing of methicillin resistance. It consists in the measurements of the total bacterial ATP obtained by extraction. The authors test the method on 23 Staphylococcus strains and compare the results with those obtained by the diffusion method, the screening method with the antibiotic included in the agar and the broth dilutions method. The results obtained by ATP-dependent bioluminescence were in agreement with those obtained by broth dilutions method.


Population-based risk factors for tuberculosis and adverse outcomes among Tibetan refugees in India, 1994-1996.
Tibetan refugees in India, 1994-1996. To determine tuberculosis (TB) incidence, independent risk factors for TB, and predictors of adverse outcomes. Data from a house-to-house census/demographic survey were merged with TB patient data. Separate multivariable models for each birthplace were developed for outcomes of interest. From 1994 to 1996, 47,491 Tibetans were surveyed and 1197 TB cases confirmed (incidence 835/ 100,000). Risk factors for TB in separate multivariable models differed by place of birth. Independent predictors of death for Tibet-born refugees included age >50 years, extra-pulmonary TB, and second-line therapy, while for India-born refugees they included second-line therapy and no improvement at the end of treatment. No significant risk factors for default were identified for Tibet-born refugees, while region of residence and the absence of a BCG scar were independent predictors among those born in India. Predictors of receipt of second-line therapy among Tibet-born refugees included region, years in camps, and prior TB, while among those born in India they were region, age > or =20 years, sputum-positive at diagnosis, and previous TB. TB incidence in Tibetan refugee settlements exceeds the highest national TB rates, and country of birth determines risk factors. TB control efforts in India should include this population.


Nonlinear solitary waves in particle metamaterials with local resonators.
In this work, solitary wave solutions of particle mechanical metamaterials are studied, in which the mass-in-mass structure with local resonators is considered. The Hertzian contact theory is used to describe adjacent particles in a precompressed granular chain. The governing wave equations are decoupled, and the expressions of bright, dark, and peaked solitary waves are derived, respectively. According to the results, both the wave velocity and prestress can affect the propagation of solitary waves. The amplitudes of bright and peaked solitary waves are smaller when a larger prestress is applied, which are different from the dark solitons. Furthermore, the wave widths become larger as the prestress increases.


Assessing psychometric properties of the Turkish version of the Fear of COVID-19 Scale for Nurses.
The purpose of this study was to evaluate the validity and reliability of the Turkish version of the Fear of COVID-19 Scale (FCV-19S). The study used a descriptive design and was conducted between April and May 2020. The participants were 213 nurses who were working in 12 hospitals in eight cities in Turkey. Content validity index, exploratory factor analysis and confirmatory factor analysis were used to evaluate validity. Cronbach's alpha, item-scale correlation and test-retest reliability were used to evaluate reliability. The CVI was 0.92 (0.81-1.00). A one-factor solution was identified and the factor loading of items in scale varied from 0.377 to 0.909. The Cronbach's alpha value was 0.889 in the current study. Item-scale correlations ranged between 0.570 and 0.815. Intraclass correlation coefficient ranged from 0.71 to 0.93. The Turkish version of the FCV-19S for nurses was found to be valid and reliable measure of the fear of nurses towards COVID-19.


A novel untrained SSVEP-EEG feature enhancement method using canonical correlation analysis and underdamped second-order stochastic resonance.
Compared with the light-flashing paradigm, the ring-shaped motion checkerboard patterns avoid uncomfortable flicker or brightness modulation, improving the practical interactivity of brain-computer interface (BCI) applications. However, due to fewer harmonic responses and more concentrated frequency energy elicited by the ring-shaped checkerboard patterns, the mainstream untrained algorithms such as canonical correlation analysis (CCA) and filter bank canonical correlation analysis (FBCCA) methods have poor recognition performance and low information transmission rate (ITR). To address this issue, a novel untrained SSVEP-EEG feature enhancement method using CCA and underdamped second-order stochastic resonance (USSR) is proposed to extract electroencephalogram (EEG) features. In contrast to typical unsupervised dimensionality reduction methods such as common average reference (CAR), principal component analysis (PCA), multidimensional scaling (MDS), and locally linear embedding (LLE), CCA exhibits higher adaptability for SSVEP rhythm components. This study recruits 42 subjects to evaluate the proposed method and experimental results show that the untrained method can achieve higher detection accuracy and robustness. This untrained method provides the possibility of applying a nonlinear model from one-dimensional signals to multi-dimensional signals.


Electrical coupling of longitudinal and circular intestinal muscle.
Space constants (lambda) were determined for longitudinal-circular muscle strips of cat jejunum by the partition method. Pulses of hyperpolarizing current spread along the major axes of circular muscle cells. In the absence of electrical coupling lambda measured from the longitudinal side of the strips should have been approximately 20 times shorter than lambda measured from the circular side. Median values were found to be statistically the same, 2.4 mm for the longitudinal side (n = 13) and 2.9 mm for the circular (n = 25). Methyl blue, iontophoretically injected into cells on the longitudinal side after recording large hyperpolarizing responses, was found in muscle cells located superficially in the longitudinal layer. The radial lambda for longitudinal muscle, determined from the change in magnitude of the hyperpolarizing response as the microelectrode was advanced through the layer, was 0.27 mm. This is too large to cause differences in depth of recording to significantly affect the circumferential lambda in this layer. These data provide evidence for a high degree of electrical coupling between the two muscle layers of cat jejunum.


Emx2 homeodomain transcription factor interacts with eukaryotic translation initiation factor 4E (eIF4E) in the axons of olfactory sensory neurons.
We report that Emx2 homeogene is expressed at the mRNA and protein levels in the adult mouse olfactory neuroepithelium. As expected for a transcription factor, Emx2 is present in the nucleus of immature and mature olfactory sensory neurons. However, the protein is also detected in the axonal compartment of these neurons, both in the olfactory mucosa axon bundles and in axon terminals within the olfactory bulb. Emx2 axonal staining is heterogeneous, suggesting an association with particles. Subcellular fractionations of olfactory bulb synaptosomes, combined with chemical lesions of olfactory neurons, confirm the presence of Emx2 in axon terminals. Significant amounts of Emx2 protein cosediment with high density synaptosomal subfractions containing eukaryotic translation initiation factor 4E (eIF4E). Nonionic detergents and RNase treatments failed to detach eIF4E and Emx2 from these high-density fractions enriched in vesicles and granular structures. In addition, Emx2 and eIF4E can be coimmunoprecipitated from olfactory mucosa and bulb extracts and interact directly, as demonstrated in pull-down experiments. Emx2 axonal localization, association with high-density particles and interaction with eIF4E strongly suggest that this transcription factor has new nonnuclear functions most probably related to the local control of protein translation in the olfactory sensory neuron axons. Finally, we show that two other brain-expressed homeoproteins, Otx2 and Engrailed 2, also bind eIF4E, indicating that several homeoproteins may modulate eIF4E functions in the developing and adult nervous system.


Comparison of different regression models to fit the force-velocity relationship of a knee extension exercise.
The aims of this study were to compare the goodness of fit and the concurrent validity of three regression models of the force-velocity relationship in a unilateral knee extension exercise. The force-velocity relationship and the one-repetition-maximum load in the dominant and non-dominant leg were obtained in 24 male sports sciences students by a progressive protocol. Additionally, the maximum voluntary contraction (MVC) of the knee extensor muscles was recorded. Individual force-velocity relationships were obtained by the linear, quadratic polynomial and exponential regression models. Although the adjusted coefficients of determination of all three models were high, the polynomial model's coefficient was slightly but significantly higher than the rest of the models (p < 0.05), while the standard error of estimate was slightly higher for the linear than for polynomial model (p = 0.001). MVC was underestimated by F 0 calculated from the linear and polynomial models, while the maximum power was accurately estimated by the linear model. In summary, while the polynomial model revealed somewhat better fit, the linear model more accurately estimates the maximum power and provides the parameters of apparent physiological meaning. Therefore, we recommend using the linear model in research and routine testing of mechanical capacities of knee extensors.


Plant root transcriptome profiling reveals a strain-dependent response during Azospirillum-rice cooperation.
Cooperation involving Plant Growth-Promoting Rhizobacteria results in improvements of plant growth and health. While pathogenic and symbiotic interactions are known to induce transcriptional changes for genes related to plant defense and development, little is known about the impact of phytostimulating rhizobacteria on plant gene expression. This study aims at identifying genes significantly regulated in rice roots upon Azospirillum inoculation, considering possible favored interaction between a strain and its original host cultivar. Genome-wide analyzes of Oryza sativa japonica cultivars Cigalon and Nipponbare were performed, by using microarrays, seven days post-inoculation with Azospirillum lipoferum 4B (isolated from Cigalon) or Azospirillum sp. B510 (isolated from Nipponbare) and compared to the respective non-inoculated condition. A total of 7384 genes were significantly regulated, which represent about 16% of total rice genes. A set of 34 genes is regulated by both Azospirillum strains in both cultivars, including a gene orthologous to PR10 of Brachypodium, and these could represent plant markers of Azospirillum-rice interactions. The results highlight a strain-dependent response of rice, with 83% of the differentially expressed genes being classified as combination-specific. Whatever the combination, most of the differentially expressed genes are involved in primary metabolism, transport, regulation of transcription and protein fate. When considering genes involved in response to stress and plant defense, it appears that strain B510, a strain displaying endophytic properties, leads to the repression of a wider set of genes than strain 4B. Individual genotypic variations could be the most important driving force of rice roots gene expression upon Azospirillum inoculation. Strain-dependent transcriptional changes observed for genes related to auxin and ethylene signaling highlight the complexity of hormone signaling networks in the Azospirillum-rice cooperation.


Trends in deaths following drug use in England before, during, and after the COVID-19 lockdowns.
This research aimed to describe how the characteristics of deaths following drug use changed during the COVID-19 pandemic in England, and how this can inform future strategy to support the health and social care of people who use drugs in future emergency scenarios. All deaths reported to the National Programme on Substance Abuse Deaths which occurred between January 2018 and December 2021 inclusive were extracted for analysis. Exponential smoothing models were constructed to determine any differences between forecasted vs. actual trends. Following the first lockdown period in England there were significant increases in the proportion of people who died at home beyond the 95% confidence bounds of the exponential smoothing model and concurrent decreases in the proportion of people who died in hospital. Whilst the overall proportion of deaths attributable to opioids did not significantly deviate from the forecasted trend, there were significant increases in methadone-related deaths and decreases in heroin/morphine-related death beyond the 95% confidence bounds. The proportion of deaths concluded as suicide increased, as did those implicating antidepressant use. There were no changes in the proportion of deaths following use of other drug classes, alcohol use in combination with psychoactive drugs, or on decedent demographics (gender, age, and drug user status). A small number of deaths due to drug use had COVID-19 infection itself listed as a cause of death (n = 23). For people who use drugs, the impact of the restrictions due to the COVID-19 pandemic was greater than that of infection from the virus itself. The health and social care strategy for these people needs to be pre-emptively adapted to mitigate against the specific risk factors for fatal drug overdose associated with future emergency scenarios.


Efficacy of hepatitis B immunisation.
Hepatitis B virus (HBV) infection is endemic to Singapore, the carrier rate being highest among the Chinese. It is the cause of significant morbidity and mortality. The prevention of this condition is therefore an important objective. Plasma derived vaccines have been shown to be effective in the prevention of perinatal as well as horizontal spread of HBV. However, the high cost of production together with deep-seated, though unfounded fears of the possibility of transmission of other viruses has limited its use. The advent of recombinant yeast vaccine is therefore an important event since the unfounded fears can now be laid to rest, and the cost of immunisation should eventually decrease as production increases. The efficacy of recombinant yeast vaccine has been found to be comparable to that of plasma derived vaccine.


Cardiorenal Disease in COVID-19 Patients.
Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in the genetic coding and the variations in the spike proteins are critical for the virus's mechanism of facilitating fusion with the human host, making the disease more severe. Recent research indicates that comorbidities including diabetes, hypertension, renal disease, heart failure, and atherosclerosis play a significant role in the severity and high mortality rates of (COVID-19), suggesting that perhaps the metabolic syndrome and its components are associated with COVID-19 morbidity. Primarily, angiotensin-converting enzyme 2 (ACE2) receptor is identified as the entrance receptor of SARS-CoV-2. Increased ACE2 expression, endothelial dysfunction plays a vital role in the progression and severity of complications developed due to COVID-19. In this review, we will discuss the association and management of cardiorenal disease and COVID-19.


An Integrative Review of Pediatric Fall Risk Assessment Tools.
Patient fall prevention begins with accurate risk assessment. However, sustained improvements in prevention and quality of care include use of validated fall risk assessment tools (FRATs). The goal of FRATs is to identify patients at highest risk. Adult FRATs are often borrowed from to create tools for pediatric patients. Though factors associated with pediatric falls in the hospital setting are similar to those in adults, such as mobility, medication use, and cognitive impairment, adult FRATs and the factors associated with them do not adequately assess risk in children. Articles were limited to English language, ages 0-21years, and publish date 2006-2015. The search yielded 22 articles. Ten were excluded as the population was primarily adult or lacked discussion of a FRAT. Critical appraisal and findings were synthesized using the Johns Hopkins Nursing evidence appraisal system. Twelve articles relevant to fall prevention in the pediatric hospital setting that discussed fall risk assessment and use of a FRAT were reviewed. Comparison between and accuracy of FRATs is challenged when different classifications, definitions, risk stratification, and inclusion criteria are used. Though there are several pediatric FRATs published in the literature, none have been found to be reliable and valid across institutions and diverse populations. This integrative review highlights the importance of choosing a FRAT based on an institution's identified risk factors and validating the tool for one's own patient population as well as using the tool in conjunction with nursing clinical judgment to guide interventions.


The development of a genetic investigation centre at a maternity hospital.
The development of a centre for the investigation of genetic aspects of still birth, neonatal deaths and mental deficiency is described. It is suitably located in a maternity hospital and provides counselling early enough to prevent the brith of a subsequent affected infant in high-risk groups. A variety of laboratory and other facilities are in close proximity. This has the advantage of allowing procedures, such as amniocentesis and ultrasound examination for prenatal diagnosis, to be arranged in consultation with hospital staff members. The aetiology of the first 120 cases seen, their reason for referral, recurrence risk, and "decision made", are reported in detail elsewhere. The mode of operation with regard to source of case, appointments, staff and records is outlined fully in this paper. The conclusion to be reached is that, within two years of its inception, the genetic investigation centre is already providing a useful community service.


Objective speckle velocimetry for autonomous vehicle odometry.
Speckle velocimetry is investigated as a means of determining odometry data with potential for application on autonomous robotic vehicles. The technique described here relies on the integration of translation measurements made by normalized cross-correlation of speckle patterns to determine the change in position over time. The use of objective (non-imaged) speckle offers a number of advantages over subjective (imaged) speckle, such as a reduction in the number of optical components, reduced modulation of speckles at the edges of the image, and improved light efficiency. The influence of the source/detector configuration on the speckle translation to vehicle translation scaling factor for objective speckle is investigated using a computer model and verified experimentally. Experimental measurements are presented at velocities up to 80 mm s(-1) which show accuracy better than 0.4%.


Support vector machine based training of multilayer feedforward neural networks as optimized by particle swarm algorithm: application in QSAR studies of bioactivity of organic compounds.
Multilayer feedforward neural networks (MLFNNs) are important modeling techniques widely used in QSAR studies for their ability to represent nonlinear relationships between descriptors and activity. However, the problems of overfitting and premature convergence to local optima still pose great challenges in the practice of MLFNNs. To circumvent these problems, a support vector machine (SVM) based training algorithm for MLFNNs has been developed with the incorporation of particle swarm optimization (PSO). The introduction of the SVM based training mechanism imparts the developed algorithm with inherent capacity for combating the overfitting problem. Moreover, with the implementation of PSO for searching the optimal network weights, the SVM based learning algorithm shows relatively high efficiency in converging to the optima. The proposed algorithm has been evaluated using the Hansch data set. Application to QSAR studies of the activity of COX-2 inhibitors is also demonstrated. The results reveal that this technique provides superior performance to backpropagation (BP) and PSO training neural networks.


Minireview: aldosterone biosynthesis: electrically gated for our protection.
Aldosterone produced by adrenal zona glomerulosa (ZG) cells plays an important role in maintaining salt/water balance and, hence, blood pressure homeostasis. However, when dysregulated, aldosterone advances renal and cardiovascular disease states. Multiple steps in the steroidogenic pathway require Ca(2+), and the sustained production of aldosterone depends on maintained Ca(2+) entry into the ZG cell. Nevertheless, the recorded membrane potential of isolated ZG cells is extremely hyperpolarized, allowing the opening of only a small fraction of low-voltage-activated Ca(2+) channels of the Ca(v)3.x family, the major Ca(2+) conductance on the ZG cell membrane. As a consequence, to activate sufficient Ca(2+) channels to sustain the production of aldosterone, aldosterone secretagogs would be required to affect large decreases in membrane voltage, a requirement that is inconsistent with the exquisite sensitivity of aldosterone production in vivo to small changes (0.1 mm) in extracellular K(+). In this review, we evaluate the contribution of membrane voltage and voltage-dependent Ca(2+) channels to the control of aldosterone production and consider data highlighting the electrical excitability of the ZG cell. This intrinsic capacity of ZG cells to behave as electrical oscillators provides a platform from which to generate a recurring Ca(2+) signal that is compatible with the lengthy time course of steroidogenesis and provides an alternative model for the physiological regulation of aldosterone production that permits both amplitude and temporal modulation of the Ca(2+) signal.


In vitro and in vivo anti-inflammatory activity of 17-O-acetylacuminolide through the inhibition of cytokines, NF-κB translocation and IKKβ activity.
17-O-acetylacuminolide (AA), a diterpenoid labdane, was isolated for the first time from the plant species Neouvaria foetida. The anti-inflammatory effects of this compound were studied both in vitro and in vivo. Plant extracts were initially tested against LPS-stimulated release of tumor necrosis factor alpha (TNF-α) from murine macrophages (RAW264.7 cells). Based on bioassay-guided fractionation, the active compound was identified as AA. AA was tested for its ability to reduce nitric oxide (NO) production, and the inducible nitric oxide synthase (iNOS) expression. The inhibition of a panel of inflammatory cytokines (TNF, IL-1β, IL-6, KC, and GM-CSF) by AA was assessed at the expression and the mRNA levels. Moreover, the effect of AA on the translocation of the transcription factor nuclear factor kappa B (NF-κB) was evaluated in LPS-stimulated RAW264.7 cells and in TNF-stimulated L929 cells. Subsequently, AA was tested in the inhibitor of NF-κB kinase beta (IKKβ) activity assay. Lastly, the anti-inflammatory activity of AA in vivo was evaluated by testing TNF production in LPS-stimulated Balb/c mice. AA effectively inhibited TNF-α release with an IC(50) of 2.7 µg/mL. Moreover, AA significantly inhibited both NO production and iNOS expression. It significantly and dose-dependently inhibited TNF and IL-1β proteins and mRNA expression; as well as IL-6 and KC proteins. Additionally, AA prevented the translocation of NF-κB in both cell lines; suggesting that it is acting at a post receptor level. This was confirmed by AA's ability to inhibit IKKβ activity, a kinase responsible for activating NF-κB, hence providing an insight on AA's mechanism of action. Finally, AA significantly reduced TNF production in vivo. This study presents the potential utilization of this compound, as a lead for the development of an anti-inflammatory drug.


Biochemical aspects of conceptus--endometrial interactions.
Mammalian conceptuses must provide a chemical signal to the maternal system to insure maintenance of corpus luteum (CL) function and of progesterone production and continuation of uterine endometrial secretory activity. These events insure that the developing conceptus is provided with appropriate nutrients, regulatory enzymes and endocrine state to allow successful establishment and maintenance of pregnancy. Pig blastocysts begin to produce estrogens by Day 11 of pregnancy, which prevents secretion of the uterine luteolytic factor (PGF2 alpha) in an endocrine direction, but allows secretion in an exocrine direction, i.e., into the uterine lumen. Therefore, CL are "protected." Blastocyst estrogens also trigger secretion of a group of proteins, including uteroferrin, an iron transport protein, and a family of protease inhibitors whose biosynthesis within the uterine glandular epithelium is under the control of progesterone. Estrogen also appears to promote accumulation of glucose and fructose within the uterine lumen. A complex in vivo "culture medium" is thereby established to promote conceptus development. Pig blastocysts do not undergo invasive implantation within the uterine lumen although they produce the protease, plasminogen activator. Invasion may be prevented by endometrial secretion of progesterone-induced protease inhibitors which are produced in large amounts. In addition to estrogens of conceptus origin, calcium and prostaglandins PGF2 alpha and E2 may affect the uterine vasculature, water and electrolyte transport, capillary permeability, conceptus steroid production, and related events during pregnancy. The blastocysts of the large domestic animals also secrete proteins which include a large glycoprotein (Mr approximately 600,000) and a small acidic protein (Mr approximately 17,000). The latter has been purified from sheep and named ovine trophoblast protein I. These proteins may play unique roles in early pregnancy with respect to establishment and maintenance of pregnancy in the ewe, sow, mare, and cow.


Motor Skills, Heart Rate Variability, and Arterial Stiffness in Children with Autism Spectrum Disorder.
The prevalence of autism spectrum disorder (ASD) among children has been recently increasing. The severity of symptoms greatly varies between individuals with ASD, ranging from relatively mild to extremely severe. It is important to have a clearer understanding of the possible adverse consequences resulting from this disorder, such as delayed motor development, autonomic dysregulation, and arterial stiffness. Thus, the objective of this study was to investigate differences in motor skills, heart rate variability (HRV), and arterial stiffness between children with ASD and typically developing children. In this study, the school-aged children with mild symptoms of ASD (n = 17, 11.1 ± 1.0 years old) and typically developing peers (n = 15, 11.0 ± 0.5 years old) were recruited. Motor skills, HRV, and arterial stiffness were measured in these two groups. Motor skills were evaluated by the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition. Moreover, HRV was measured through a short-term recording using the Polar heart rate monitor, and arterial stiffness was assessed by non-invasive computerized oscillometry. Compared with the typically developing group, children with ASD displayed significant deficits in some areas of motor skills, including manual coordination, strength and agility, and total motor composite. Moreover, children with ASD exhibited significantly reduced HRV, including time- and frequency-domain measures. However, the results did not demonstrate any statistically significant differences in arterial stiffness between the groups. Our findings demonstrated the presence of motor skill deficits and autonomic dysregulation in children with ASD.


Alcohol dependence and suicidal behavior: from research to clinical challenges.
Epidemiological and clinical data suggest high rates of suicidal behavior in alcohol-dependent individuals. Suicide attempters are likely to be young, to be single or separated, and to have made prior attempts. They differ from non-attempters by higher levels of impulsive aggression, drug use, and psychiatric comorbidity, particularly personality and depressive disorders. Treatment-seeking, alcohol-dependent individuals often present with multiple risk factors. Early recognition of suicidal behavior is hindered, however, by insufficient data regarding the acute phenomenology of imminent risk. Similarly, little research is available to guide intervention efforts. Initial trials support the use of fluoxetine for the treatment of suicidal, alcohol-dependent persons with comorbid depressive disorders. Future studies may clarify the relative efficacy of various psychotherapeutic and pharmacological approaches to treating these patients.


Tire-Derived Transformation Product 6PPD-Quinone Induces Mortality and Transcriptionally Disrupts Vascular Permeability Pathways in Developing Coho Salmon.
Urban stormwater runoff frequently contains the car tire transformation product 6PPD-quinone, which is highly toxic to juvenile and adult coho salmon (Onchorychus kisutch). However, it is currently unclear if embryonic stages are impacted. We addressed this by exposing developing coho salmon embryos starting at the eyed stage to three concentrations of 6PPD-quinone twice weekly until hatch. Impacts on survival and growth were assessed. Further, whole-transcriptome sequencing was performed on recently hatched alevin to address the potential mechanism of 6PPD-quinone-induced toxicity. Acute mortality was not elicited in developing coho salmon embryos at environmentally measured concentrations lethal to juveniles and adults, however, growth was inhibited. Immediately after hatching, coho salmon were sensitive to 6PPD-quinone mortality, implicating a large window of juvenile vulnerability prior to smoltification. Molecularly, 6PPD-quinone induced dose-dependent effects that implicated broad dysregulation of genomic pathways governing cell-cell contacts and endothelial permeability. These pathways are consistent with previous observations of macromolecule accumulation in the brains of coho salmon exposed to 6PPD-quinone, implicating blood-brain barrier disruption as a potential pathway for toxicity. Overall, our data suggests that developing coho salmon exposed to 6PPD-quinone are at risk for adverse health events upon hatching while indicating potential mechanism(s) of action for this highly toxic chemical.


Genetic epidemiology of osteoporosis across four microsatellite markers near the VDR gene.
The large amount of positive genetic association data in a number of bone diseases suggests functional consequences of Vitamin D receptor (VDR) gene polymorphism. In the present study, four microsatellite markers viz., D12S1633, D12S1635, D12S347, and D12S96, that lie in the vicinity of the VDR gene on chromosome 12 were selected to assess the allele distribution pattern and diversity among three groups of individuals - normal, osteopenia and osteoporosis. Genetic association study was performed using allele frequency data. Total genomic DNA was isolated from the whole blood of 226 individuals, after recording their bone mineral density (BMD) using Dual X-ray absorptiometry (DXA). All DNA samples were subjected to multiplex Polymerase Chain Reaction (PCR) - genotyping. Allele frequencies and genetic diversity parameters like - number of alleles, average variance and average heterozygosity across all the four markers among three groups were computed. Effect of population stratification was excluded by investigating population structure. A trend of decreasing genetic diversity across four loci from normal to pre- and post-disease condition has been observed. Lesser recombination rate (θ) indicates linkage between studied microsatellite markers and VDR gene. Statistically significant linkage disequilibrium was detected for the allele - 22 of locus D12S96 with osteoporosis. A positive association of allele - 22 suggests susceptibility to disease whereas predominance of allele - 27 among non - diseased group implicates its association with normal bone health.


The Impact of Endoscopic Linear Stapling Device Stability in Thoracic Surgery: A Delphi Panel Approach.
Objectives: To develop consensus statements outlining the impact of endoscopic linear stapling device stability on potential complications of thoracic surgery and the stress/concern of thoracic surgeons. Methods: Eight thoracic surgeons representing 8 countries participated in a Delphi panel process using 2 anonymous surveys. The first included binary, multiple-response, and Likert scale-type questions, which were converted into affirmative statements for survey 2 if an adequate number of respondents answered similarly. Consensus was defined a priori when ≥70% agreed with the affirmative statement in survey 2. Results: All panelists completed both surveys. Panelists unanimously agreed that: 1) an endoscopic linear stapling device with improved stability would result in less stress/concern for critical firings, surgeries where a fellow is trained, and robot-assisted surgeries requiring an assistant; 2) reduced unintentional tissue/structure damage and reduced tension on tissue being fired upon may result from use of an endoscopic linear stapling device that provides improvement in stability; and 3) endoscopic linear stapling device stability had more clinical importance in video-assisted thoracic surgery compared to open thoracic surgery. Conclusions: Improved endoscopic linear stapling device stability is a critical component of thoracic surgery likely to result in more frequent positive surgical outcomes when compared to a device with greater instability.


Effect of bovine lactoferrin on the immune responses of captive bottlenosed dolphins (Tursiops truncatus) being transported over long distances.
Bovine lactoferrin was administered orally, in feed, to six bottlenosed dolphins (Tursiops truncatus) before they were transported for approximately six hours; their stress responses were compared with those of five untreated dolphins. During the journey the dolphins had an increased plasma concentration of cortisol, and lymphopenia, eosinopenia and mild neutrophilia, indicating a stress response. The administration of lactoferrin did not affect the function of the dolphins' polymorphonuclear leucocytes, but affected their leucogram by maintaining the number of circulating eosinophils.


[Pulmonary flow-resistance relation in allografts ten days after single lung transplantation in dogs].
In order to evaluate the applicability of single lung transplantation as a treatment of pulmonary hypertension, I investigated the relationships between the pulmonary flow and its resistance in allografts ten days after single lung transplantation in dogs. Fourteen dogs underwent single lung transplantation. All dogs received azathioprine (50 mg; given orally) and methylprednisolone sodium succinate (125 mg; given intravenously) every day after operation. Eight dogs survived up to ten days after operation. In the survived recipients and the five healthy dogs, pulmonary flow-resistance relations were investigated. Pulmonary flow was exactly regulated by the pump system, which drained from both cavae and returned to right atrium via azygos vein. The pulmonary artery of native lung or right lung was clamped prior to the measurement. Pulmonary vascular resistance was recorded with the increase of pulmonary flow at the range from 0.3 L/min. to 2.0 L/min. by 0.1 L/min. Lung water was measured by means of Wood's method. Radiographical and pathological examinations were appended. The five allografts received complete studies (successful group) were twice lung water of the healthy lungs (control group) (successful group; 95.6 +/- 16.7 g, control group; 47.8 +/- 7.5 g), and chest roentgenograms of successful group showed mild or moderate consolidation. The other allo-grafts (unsuccessful group), including ones died before investigations, were four times lung water of control group (unsuccessful group; 211.0 +/- 89.6 g), and the chest roentgenograms showed severe consolidation. But any difference was not found in any pulmonary flow between the pulmonary resistance in successful group and in control group. These results show that the allografts, which is under about twice lung water of normal lung, maintains enough pulmonary vascular function, and I concluded that single lung transplantation can be an effective treatment for pulmonary hypertension.


Further evidence for tonically functioning presynaptic beta-adrenoceptors in guinea-pig pulmonary arteries.
Effects of dl- and d-carteolol alone on the release of tritium evoked by transmural field stimulation at 1 Hz were investigated in spirally cut guinea-pig pulmonary arteries preloaded with [3H]-norepinephrine. Cumulatively applied dl-carteolol 10(-8) M, 10(-7) M and 10(-6) M readily inhibited the release of tritium in a concentration-dependent manner, whereas the same concentrations of d-carteolol produced no effect. In conclusion, presynaptic beta-adrenoceptors in guinea-pig pulmonary arteries tonically function to facilitate the release of the transmitter norepinephrine.


Oral-Maxillofacial Injury Surveillance of U.S. Military Personnel in Iraq and Afghanistan, 2001 to 2014.
Cranial and oral-maxillofacial injuries accounted for 33% of military visits to in-theater (Level III) military treatment facilities for battle injuries during Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Even after years of conflict, the size and scope of oral-maxillofacial injuries in military armed conflict is still not fully understood. This study reports U.S. Department of Defense (DoD) rates of oral-maxillofacial injuries that can be used for further surveillance and research. The populations studied were military personnel deployed to Afghanistan in OEF or Iraq in OIF and Operation New Dawn (OND), who sought care at a Level III military treatment facility for one or more oral-maxillofacial injuries. Injuries were identified in the DoD Trauma Registry (DoDTR) using diagnosis codes associated with oral-maxillofacial battle and nonbattle injuries. All oral-maxillofacial injuries incurred from October 19, 2001, to June 30, 2014, were included. The Defense Manpower Data Center provided DoD troop strength numbers to serve as the study denominators. Battle injuries accounted for 80% of oral-maxillofacial injuries in OEF. There were 2,504 oral-maxillofacial injuries in OEF. The Army accounted for 1,820 (72.7%), the Marines 535 (21.3%), the Air Force 75 (3.0%), and the Navy 74 (3.0%). The oral-maxillofacial injury rates in OEF for the Army ranged from 1.10 to 4.90/1,000 person years (PY), for the Marines from 0.57 to 9.39/1,000 PY, for the Navy from 0 to 3.29/1,000 PY, and for the Air Force from 0 to 3.38/1,000 PY. The Army tended to have the highest incidence of all services in the early and latter part of the conflict, whereas Marines tended to have the highest incidence in the middle years. The Marines, Army, and Navy all had their individual highest incidences in 2009, the first year of the 2009 to 2011 OEF troop surge. Battle injuries accounted for 75% of oral-maxillofacial injuries in OIF/OND. There were 3,676 oral-maxillofacial injuries in OIF/OND. The Army accounted for 2,798 (76.1%), the Marines 731 (19.9%), the Navy 91 (2.5%), and the Air Force 56 (1.5%). The injury rates in OIF/OND for the Army ranged from 0.66 to 8.69/1,000 PY, for the Marines from 0.88 to 42.7/1,000 PY, for the Navy from 0.35 to 19.16/1,000 PY, and for the Air Force from 0.24 to 1.13/1,000 PY. In OIF/OND, the Marines had the highest overall oral-maxillofacial injury rate (42.70/1,000 PY) in 2003. The other services had their individual peak incidences in either 2003 or 2004. This is the first study, which quantified the incidence of oral-maxillofacial injury in theaters of conflict over prolonged periods. The Army has the highest number of injuries. The Marines had the highest incidences during the initial stages of OIF and the OEF troop surge. Intensity of the conflict could account for the upswing in rates. These increases in injury rates highlight the need for additional health care personnel to be deployed near the battlefield to treat these injuries.


Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant Klebsiella pneumoniae infection.
The recent emergence of carbapenem resistance among Enterobacteriaceae is a major threat for hospitalized patients, and effective strategies are needed. To assess the effect of an intensified intervention, which included active surveillance, on the incidence of infection with carbapenem-resistant Klebsiella pneumoniae. Sheba Medical Center, a 1,600-bed tertiary care teaching hospital in Tel Hashomer, Israel. Quasi-experimental study. The medical records of all the patients who acquired a carbapenem-resistant K. pneumoniae infection during 2006 were reviewed. An intensified intervention was initiated in May 2007. In addition to contact precautions, active surveillance was initiated in high-risk units. The incidence of clinical carbapenem-resistant K. pneumoniae infection over time was measured, and interrupted time-series analysis was performed. The incidence of clinical carbapenem-resistant K. pneumoniae infection increased 6.42-fold from the first quarter of 2006 up to the initiation of the intervention. In 2006, of the 120 patients whose clinical microbiologic culture results were positive for carbapenem-resistant K. pneumoniae, 67 (56%) developed a nosocomial infection. During the intervention period, the rate of carbapenem-resistant K. pneumoniae rectal colonization was 9%. Of the 390 patients with carbapenem-resistant K. pneumoniae colonization or infection, 204 (52%) were identified by screening cultures. There were a total of 12,391 days of contact precautions, and of these, 4,713 (38%) were added as a result of active surveillance. After initiation of infection control measures, we observed a significant decrease in the incidence of carbapenem-resistant K. pneumoniae infection. The use of active surveillance and contact precautions, as part of a multifactorial intervention, may be an effective strategy to decrease rates of nosocomial transmission of carbapenem-resistant K. pneumoniae colonization or infection.


Theory of the thermal Hall effect in quantum magnets.
We present a theory of the thermal Hall effect in insulating quantum magnets, where the heat current is totally carried by charge-neutral objects such as magnons and spinons. Two distinct types of thermal Hall responses are identified. For ordered magnets, the intrinsic thermal Hall effect for magnons arises when certain conditions are satisfied for the lattice geometry and the underlying magnetic order. The other type is allowed in a spin liquid which is a novel quantum state since there is no order even at zero temperature. For this case, the deconfined spinons contribute to the thermal Hall response due to Lorentz force. These results offer a clear experimental method to prove the existence of the deconfined spinons via a thermal transport phenomenon.


Chrysogine Biosynthesis Is Mediated by a Two-Module Nonribosomal Peptide Synthetase.
Production of chrysogine has been reported from several fungal genera including Penicillium, Aspergillus, and Fusarium. Anthranilic acid and pyruvic acid, which are expected precursors of chrysogine, enhance production of this compound. A possible route for the biosynthesis using these substrates is via a nonribosomal peptide synthetase (NRPS). Through comparative analysis of the NRPSs from genome-sequenced producers of chrysogine we identified a candidate NRPS cluster comprising five additional genes named chry2-6. Deletion of the two-module NRPS (NRPS14 = chry1) abolished chrysogine production in Fusarium graminearum, indicating that the gene cluster is responsible for chrysogine biosynthesis. Overexpression of NRPS14 enhanced chrysogine production, suggesting that the NRPS is the bottleneck in the biosynthetic pathway.


Triphalangeal thumb.
Triphalangeal thumb (TPT), a rare malformation of uncertain pathogenesis, may occur as an isolated defect, in association with other malformations of the hands, or as a feature of a syndrome or sequence. Isolated TPT occurs in two functional types: opposable and non-opposable. The latter appears to be inherited as a simple autosomal dominant trait, while the former is generally sporadic. TPT is associated with a number of specific malformations of the hand or foot, several of which have a well documented autosomal dominant pattern of inheritance. TPT is a feature of a number of specific syndromes. In this setting it may be associated with radial hypoplasia, bone marrow dysfunction, congenital heart disease, lung hypoplasia or agenesis, anorectal malformations, sensorineural hearing loss, onychodystrophy, mental retardation, and other disorders. TPT serves as a useful marker in such patients; in conjunction with the clinical and radiological findings, it can help to establish the correct diagnosis, leading to appropriate management and genetic counselling.