Car drivers' perceptions of electronic stability control (ESC) systems.
As a way to reduce the number of car crashes different in-car safety devices are being introduced. In this paper one such application is being investigated, namely the electronic stability control system (ESC). The study used a survey method, including 2000 private car drivers (1000 driving a car with ESC and 1000 driving a car without ESC). The main objective was to investigate the effect of ESC on driver behaviour. Results show that drivers report that they drive even more carelessly when they believe that they have ESC, than when they do not. Men are more risk prone than women and young drivers more than older drivers. Using the theory of planned behaviour the results show that attitude, subjective norm and perceived control explain between 62% and 67% of driver's variation of intentions to take risks. When descriptive norm was added to the model a small but statistically significant increase was found. The study also shows that more than 35% erroneously believe that their car is equipped with an ESC system. These findings may suggest that driver behaviour could reduce the positive effect ESC has on accidents. It also shows that drivers who purchase a new car are not well informed about what kind of safety devices the car is equipped with. These findings highlight the need for more targeted information to drivers.


Calcium-dependent intracellular degradation of parathyroid hormone: a possible mechanism for the regulation of hormone stores.
The dynamics of parathyroid hormone (PTH) biosynthesis, storage, and secretion in bovine parathyroid slices in vitro in response to alterations in the concentrations of extracellular calcium were studied. Hormone biosynthesis was evaluated by using polyacrylamide gel electrophoresis to measure incorporation of [3H]leucine into newly synthesized PTH and proparathyroid hormone (ProPTH) during short (35 min) incubations. Amounts of newly synthesized PTH stored in and secreted from the tissue slices were determined by electrophoretic analysis of [3H]PTH in extracts of tissue and media. Total PTH and ProPTH is slices and media were measured by specific radioimmunoassays. PTH secretion rates changes 5-fold when calcium was lowered from 2mM to 1mM. Secretion of some PTH continued despite high concentrations of calcium (5 mM). Biosynthesis of ProPTH was changed only slightly, and conversion of ProPTH to PTH was independent of the extracellular calcium concentration. Tissue stores of PTH increased during incubation of parathyroid slices in medium containing high amounts of calcium. The increase in stores was much less, however, than predicted by the findings of marked suppression of secretion and little change in rates of PTH biosynthesis. In high concentrations of calcium, a large fraction (up to 50%) of newly synthesized PTH was degraded within the tissue, whereas in low concentrations of calcium, little (less than 10%) of the PTH was degraded. No fragments of PTH or ProPTH were identified in either extracts of tissue or media, suggesting that degradation occurred rapidly by general proteolysis rather than by limited, specific endopeptidase activity. The data suggest that the parathyroid cell contains a calcium-sensitive degradative pathway for PTH and that this pathway may be involved in the regulation of hormone production and secretion.


[Comparative study of the vitamin activity of pyridoxal phosphate and pyridoxine used cutaneously].
In white rats with B6-avitaminosis, the B6-vitamin activity of pyridoxal-phosphate and of pyridoxine was studied in their epicutaneous and peroral application. It is revealed that pyridoxal-phosphate in epicutaneous application displays more activity than pyridoxine and pyridoxal-phosphate applied perorally. Pyridoxine in epicutaneous application does not reveal the B6-vitamin activity.


Evidence of a guanylyl cyclase natriuretic peptide receptor in the gills of the new zealand hagfish Eptatretus cirrhatus (Class Agnatha).
Natriuretic peptide binding sites were examined in the gills of the hagfish Eptatretus cirrhatus (Class Agnatha, subfamily Eptatretinae) using radio-ligand binding techniques, molecular cloning and guanylyl cyclase assays. Iodinated rat atrial natriuretic peptide ((125)I-rANP) and iodinated porcine C-type natriuretic peptide ((125)I-pCNP) bound specifically to the lamellar folds and cavernous tissue of E. cirrhatus gills, and 0.3 nmol l(-1) rat ANP competed for 50 % of specific (125)I-rANP binding sites. Affinity cross-linking of (125)I-rANP to gill membranes followed by sodium dodecylsulphate-polyacrylamide gel electrophoresis revealed a single binding site of 150 kDa. In the presence of Mn(2+), 0.1 nmol l(-1) rANP inhibited cGMP production, whereas 1 micromol l(-1) rANP stimulated cGMP production rates. At 1 micromol l(-1), pCNP also stimulated cGMP production. The production of cGMP was also measured in the presence and absence of ATP with either Mn(2+) or Mg(2+). Reverse transcriptase polymerase chain reaction (RT-PCR) of hagfish gill RNA, followed by cloning and sequencing of PCR products, produced a partial cDNA sequence of a natriuretic peptide guanylyl cyclase receptor. The deduced amino acid sequence indicated 87-91 % homology with other natriuretic peptide guanylyl cyclase receptors. This study indicates the presence of a natriuretic peptide guanylyl cyclase receptor in the gills of E. cirrhatus that is similar to the natriuretic peptide guanylyl cyclase receptors in higher vertebrates. These observations demonstrate that the coupling of natriuretic peptide receptors with guanylyl cyclase has a long evolutionary history.


[Metabolic regulation of threonine operon transcription in E. coli cells].
The threonine biosynthetic operon transcription in E. coli cells during balanced growth was studied. The rate of threonine-mRNA synthesis was measured by hybridization of impulse-labelled RNA with pYN 1107 DNA carrying the structural threonine genes A, B, C. It was shown that threonine-mRNA synthesis depends on bacterial growth rate being maximal at mu = 0.8 doublings per hour. The influence of the ppGpp on the bacterial growth rate and threonine-mRNA synthesis rate was demonstrated, using spoT-mutants and strains with several relA gene copies. The rate of threonine-mRNA synthesis is maximal at the ppGpp level of about 50-60 pmole/A450. The deviation from this ppGpp optimum level results in inhibition of the threonine-mRNA synthesis. Thus, ppGpp appears to be involved in metabolic regulation of operon transcription. A mechanism of negative regulation of threonine-mRNA synthesis by high concentrations of ppGpp is discussed.


Progestogens Are Metabolized by the Gut Microbiota: Implications for Colonic Drug Delivery.
Following oral administration, the bioavailability of progestogens is very low and highly variable, in part due to metabolism by cytochrome P450 enzymes found in the mucosa of the small intestine. Conversely, the mucosa in the colon contains much lower levels of cytochrome P450 enzymes, thus, colonic delivery of progestogens may be beneficial. Microbiota in the colon are known to metabolize a great number of drugs, therefore, it is important to understand the stability of these hormones in the presence of colonic flora before developing formulations. The aim of this study was to investigate the stability of three progestogens: progesterone, and its two synthetic analogues, medroxyprogesterone acetate (MPA) and levonorgestrel (LNG), in the presence of human colonic microbiota. Progesterone, MPA, and LNG were incubated in mixed fecal inoculum (simulated human colonic fluid) under anerobic conditions. Progesterone was completely degraded after 2 h, whereas levels of MPA and LNG were still detectable after 24 h. The half-lives of progesterone, MPA, and LNG in fecal inoculum were 28, 644, and 240 min, respectively. This study describes the kinetics of colonic microbial metabolism of these hormones for the first time. MPA and LNG show promise for delivery to the colon, potentially improving pharmacokinetics over current oral delivery methods.


Peptic ulcer in adults. Psychopathological, environmental, characterological and hereditary factors.
34 male peptic ulcer patients were compared to (a) a group of 37 healthy controls and (b) a group of 36 hospitalized controls suffering from illnesses unrelated to the gastrointestinal tract. Patients and controls were submitted to the Eysenck personality inventory, Foulds' hostility questionnaire, Langner's 22-item questionnaire, the Hopkins symptom checklist, Zung's self-rating anxiety scale, Spielberger's state-trait anxiety inventory, Zung's and Beck's rating scales for depression, and the 43-item life event inventory by Holmes and Rahe. All patients suffered from duodenal ulcer. The parameters that differentiated to a statistically significant degree the peptic ulcer patients from either one or both groups of controls were: (a) neuroticism, (b) trait and state anxiety, (c) guilt, (d) general psychopathology, and (e) stressful life events. Additionally, more than 50% of patients had at least one first-degree relative with peptic ulcer. These observations indicate that psychopathological, psychosocial, characterological and hereditary factors are important pathogenetic contributors in peptic ulcer.


Keratoconus associated with retrolental fibroplasia.
Three adult male patients with keratoconus associated with severe bilateral retrolental fibroplasia were studied. Two of these presented with acute corneal hydrops. The association may be of some interest in determining the etiology of keratoconus.


No association of Fc gamma RIIa, Fc gamma RIIIa and Fc gamma RIIIb polymorphisms with MS.
Anti-myelin IgGs occur in the cerebrospinal fluid (CSF) and serum of multiple sclerosis (MS) patients, and can induce inflammatory effector functions in leukocytes by crosslinking IgG receptors (FcgammaR). The efficiency of FcgammaR-mediated inflammatory processes is affected by functional polymorphisms of three Fcgamma receptors (FcgammaRIIa, FcgammaRIIIa, FcgammaRIIIb). The relevance of FcgammaR polymorphisms in MS was evaluated by studying the distribution of FcgammaRIIa, FcgammaRIIIa and FcgammaRIIIb genotypes in 432 MS patients and 515 healthy controls. No significant differences were found between MS patients and controls, or between subgroups of patients. We conclude that Fcgamma receptor polymorphisms influence neither susceptibility nor clinical disease course of MS.


Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane-Sodium Iodide-Promoted Vorbrüggen Glycosylation.
By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester.


Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations.
Mutations in the lamin A/C gene (LMNA) cause dilated cardiomyopathy associated with increased activity of ERK1/2 in the heart. We recently showed that ERK1/2 phosphorylates cofilin-1 on threonine 25 (phospho(T25)-cofilin-1) that in turn disassembles the actin cytoskeleton. Here, we show that in muscle cells carrying a cardiomyopathy-causing LMNA mutation, phospho(T25)-cofilin-1 binds to myocardin-related transcription factor A (MRTF-A) in the cytoplasm, thus preventing the stimulation of serum response factor (SRF) in the nucleus. Inhibiting the MRTF-A/SRF axis leads to decreased α-tubulin acetylation by reducing the expression of ATAT1 gene encoding α-tubulin acetyltransferase 1. Hence, tubulin acetylation is decreased in cardiomyocytes derived from male patients with LMNA mutations and in heart and isolated cardiomyocytes from Lmnap.H222P/H222P male mice. In Atat1 knockout mice, deficient for acetylated α-tubulin, we observe left ventricular dilation and mislocalization of Connexin 43 (Cx43) in heart. Increasing α-tubulin acetylation levels in Lmnap.H222P/H222P mice with tubastatin A treatment restores the proper localization of Cx43 and improves cardiac function. In summary, we show for the first time an actin-microtubule cytoskeletal interplay mediated by cofilin-1 and MRTF-A/SRF, promoting the dilated cardiomyopathy caused by LMNA mutations. Our findings suggest that modulating α-tubulin acetylation levels is a feasible strategy for improving cardiac function.


Applying Behavioral Economics to Enhance Safe Firearm Storage.
Behavioral economics applies key principles from psychology and economics to address obstacles to behavior change. The important topic of pediatric firearm injuries has not yet been explored through a behavioral economic lens. Pediatric firearm-related injuries are a significant public health problem in the United States. Despite American Academy of Pediatrics guidelines advising that firearms be stored unloaded, in a locked box or with a locking device, and separate from ammunition, estimates suggest that ∼4.6 million children live in homes with at least 1 loaded and unlocked firearm. In this article, we use behavioral economic theory to identify specific cognitive biases (ie, present bias; in-group, out-group bias; and the availability heuristic) that may influence parental decision-making around firearm storage. We illustrate situations in which these biases may occur and highlight implementation prompts, in-group messengers, and increased salience as behaviorally informed strategies that may counter these biases and subsequently enhance safe firearm storage. We also describe other opportunities to leverage the behavioral economic tool kit. By better understanding the individual behavioral levers that may impact decision-making around firearm storage, behavioral scientists, pediatric providers, and public health practitioners can partner to design and test tailored interventions aimed at decreasing pediatric firearm injuries. Further empirical study is warranted to identify the presence of specific biases and heuristics and determine the most effective behavior change strategies for different subpopulations.


Structure and function of the type 3 deiodinase gene.
Thyroid hormones (TH) are essential for normal growth and development in vertebrates, and are important for the maintenance of normal metabolic activity in most tissues of the body. Because the actions of TH result from the binding of 3,3',5'-triiodothyronine (T(3)) to specific nuclear receptors in the target cell, the extent of TH action in a given cell is dependent in part on the intracellular concentration of T(3). The type 3 deiodinase (D3) is a selenoenzyme that inactivates TH by catalyzing their conversion to biologically inactive metabolites. The findings that D3 activity is very high in the pregnant uterus and fetoplacental unit, and that D3-deficient mice exhibit deficits in growth, viability, and fertility strongly suggest that D3 plays an important role in development. The D3 gene (Dio3) is preferentially expressed from the paternally inherited allele and is associated with an overlapping gene transcribed from the opposite DNA strand (Dio3os). D3 mRNA expression and D3 activity are regulated by a number of hormones and growth factors as well as by genomic imprinting. Although some genomic structures appear to mediate some of these effects, many details concerning the function of the Dio3 gene are unresolved. These include the full characterization of the Dio3 and Dio3os genes, the elucidation of the mechanisms responsible for the developmental and tissue-specific patterns observed in Dio3 allelic expression, and the response of the genes to hormones and growth factors. Knowledge of these details will be important for understanding the physiologic function of an enzyme that appears to be critical for normal mammalian development.


Microsurgery Case Volume During Orthopedic Surgery Residency: A 7-Year Assessment.
Microsurgery is a specialized surgical technique with wide clinical application. The purpose of this study was to analyze case logs of graduating orthopedic surgery residents to assess trends in case volume for microsurgery procedures. Accreditation Council for Graduate Medical Education case log reports were analyzed for microsurgery experience from 2007 to 2013. The mean number of adult, pediatric, and total microsurgery cases was noted. In addition, the median number of microsurgery procedures performed by the 90th, 50th, and 10th percentiles of residents (by case volume) was recorded. Temporal changes in case volume were calculated utilizing linear regression analyses. The proportion of microsurgery procedures increased significantly (1.3% to 2%; P = .024). The mean number of adult (24.5 to 41.9; P = .01), pediatric (1.9 to 3.4; P = .011), and total (26.3 to 45.3; P = .01) microsurgery procedures also increased significantly. Similarly, residents in both the 90th (63 to 109; P = .01) and 50th (10 to 21; P = .036) percentiles sustained significant increases in the median number of microsurgery procedures. No change was noted for residents in 10th percentile (0 to 0; P > .999). Graduating residents in the 90th percentile performed over 6 times more microsurgery procedures than residents in the 50th percentile. Microsurgical caseload is increasing among graduating orthopedic residents. However, there is substantial variability in resident microsurgery case volume. Future investigations are needed to explore the educational implications of these findings and should seek to correlate microsurgical caseload with competency.


Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice.
Alzheimer's disease (AD) is a neurodegenerative disease displaying extracellular plaques formed by the neurotoxic amyloid β-peptide (Aβ), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relate to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major Aβ-degrading enzyme and a lack thereof increases Aβ levels in the brain twofold. To identify altered protein expression levels induced by increased Aβ levels, we performed a proteomic analysis of the brain of the AD mouse model APPsw and compared it to that of APPsw mice lacking neprilysin. To this end we established an LC-MS/MS method to analyze brain homogenate, using an (18) O-labeled internal standard to accurately quantify the protein levels. To distinguish between alterations in protein levels caused by increased Aβ levels and those induced by neprilysin deficiency independently of Aβ, the brain proteome of neprilysin deficient APPsw mice was also compared to that of neprilysin deficient mice. By this approach we identified approximately 600 proteins and the levels of 300 of these were quantified. Pathway analysis showed that many of the proteins with altered expression were involved in neurological disorders, and that tau, presenilin and APP were key regulators in the identified networks. The data have been deposited to the ProteomeXchange Consortium with identifiers PXD000968 and PXD001786 (http://proteomecentral.proteomexchange.org/dataset/PXD000968 and (http://proteomecentral.proteomexchange.org/dataset/PXD001786). Interestingly, the levels of several proteins, including some not previously reported to be linked to AD, were associated with increased Aβ levels.


Repair of penetrating cardiac injury using skin staples.
Cardiac stapling is a highly effective technique in the management of hemorrhage from penetrating cardiac injuries. It may allow the salvage of patients with multiple cardiac lacerations who would not otherwise survive following standard suture techniques for repair. Cardiac stapling is probably not indicated in complex injury cases such as those from gunshot, and the trauma surgeon must use judgment in applying the staple technique, though its use for cardiography in the ED and the OR will minimize the risk of contamination of personnel from a needle stick from the repair portion of the surgical procedure. Staplers are readily available, easy to use and safe to surgical personnel, and they provide rapid and effective hemostasis.


Delineating family needs in the transition from hospital to home for children with medical complexity: part 1, a meta-aggregation of qualitative studies.
Advances in diagnostic and therapeutic interventions for rare diseases result in greater survival rates, with on the flipside an expanding group of children with medical complexity (CMC). When CMC leave the protective hospital environment to be cared for at home, their parents face many challenges as they take on a new role, that of caregiver rather than care-recipient. However, an overview of needs and experiences of parents of CMC during transition from hospital-to-home (H2H) is lacking, which hampers the creation of a tailored H2H care pathway. Here we address this unmet medical need by performing a literature review to systematically identify, assess and synthesize all existing qualitative evidence on H2H transition needs of CMC parents. An extensive search in Medline, PsychINFO and CINAHL (up to September 2022); selection was performed to include all qualitative studies describing parental needs and experiences during H2H transition of CMC. All papers were assessed by two independent investigators for methodological quality before data (study findings) were extracted and pooled. A meta-aggregation method categorized the study findings into categories and formulated overarching synthesized findings, which were assigned a level of confidence, following the ConQual approach. The search yielded 1880 papers of which 25 met eligible criteria. A total of 402 study findings were extracted from the included studies and subsequently aggregated into 50 categories and 9 synthesized findings: (1) parental empowerment: shifting from care recipient to caregiver (2) coordination of care (3) communication and information (4) training skills (5) preparation for discharge (6) access to resources and support system (7) emotional experiences: fatigue, fear, isolation and guilt (8) parent-professional relationship (9) changing perspective: finding new routines and practices. The overall ConQual Score was low for 7 synthesized findings and very low for 2 synthesized findings. Despite the variability in CMC symptoms and underlying (rare disease) diagnoses, overarching themes in parental needs during H2H transition emerged. We will augment this new knowledge with an interview study in the Dutch setting to ultimately translate into an evidence-based tailored care pathway for implementation by our interdisciplinary team in the newly established 'Jeroen Pit Huis', an innovative care unit which aims for a safe and sustainable H2H transition for CMC and their families.


Better Together: Long-term Behaviors and Perspectives after a Practitioner-Family Writing Intervention in Clinical Practice.
An expressive writing intervention, the Three-minute Mental Makeover (3MMM), was previously associated with reduced stress for practitioners, patients, and families. The goal of this follow-up study was to evaluate long-term use of writing and perspectives after participation in the 3MMM. The original study involved patients and families in the neonatal and pediatric Intensive Care Units, inpatient units, and outpatient clinics of a children's hospital. Health-care practitioners led the intervention, writing concurrently with patients and families using the 3MMM intervention. Follow-up contact by phone was attempted for all original patient/family participants 12 to 18 months after completing the exercise. Practitioners were contacted via email 24 months after the original study. Participants were surveyed about the 3MMM and continued use of writing to cope with stressful situations. Original and follow-up survey responses were compared using the Mann-Whitney test. Of the 96 original patient/family members, 61 individuals were reached, remembered the 3MMM, and agreed to participate in the follow-up study. Among the 61 participants, 52 (85%) agreed that the 3MMM had been helpful. Thirty-six (59%) reported using writing to help cope with stress at follow-up, compared to only 23 (38%) at baseline (P = 0.005). The majority of clinicians (87%) also continued to use the 3MMM in clinical practice following the original 3MMM study period and ranked it as both feasible (75%) and worth the time investment (75%). The 3MMM demonstrated long-term perceived benefits and behavior changes. Findings provide preliminary support for using the 3MMM in routine clinical practice.


The thermodynamics of agonist and antagonist binding to dopamine D-2 receptors.
The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower temperatures. The ability of the dopamine antagonists, haloperidol, cis-flupenthixol, cis-N-(1-benzyl-1-methypyrrolidin-3-yl)-5-chloro-2-methoxy-9- methylaminobenzamide (YM 09151-2), raclopride, and clozapine, and of the agonists apomorphine and pergolide, to compete with [3H]spiperone binding was little altered by temperature. (+)-Butaclamol was more potent at higher temperatures. In contrast, the antagonists sulpiride, metoclopramide, clebopride, sultopride, tiapride, piquindone, and zetidoline were more potent at lower temperatures. The interaction of the agonists dopamine and ADTN was driven by a decrease in enthalpy, allowing an energetically unfavorable decrease in entropy. The binding of the antagonists, haloperidol, cis-flupenthixol, YM 09151-2, raclopride, (+)-butaclamol, and clozapine, and also of the agonists, apomorphine and pergolide, was entropy driven. The interaction of the antagonists sulpiride, metoclopramide, clebopride, alizapride, sultopride, tiapride, piquindone, and zetidoline differed from that of other antagonists in being enthalpy driven. The observed entropy changes correlated with the lipophilicity of the displacing drugs and not with their intrinsic activity.


A model of the acid sphingomyelinase phosphoesterase domain based on its remote structural homolog purple acid phosphatase.
Sequence profile and fold recognition methods identified mammalian purple acid phosphatase (PAP), a member of a dimetal-containing phosphoesterase (DMP) family, as a remote homolog of human acid sphingomyelinase (ASM). A model of the phosphoesterase domain of ASM was built based on its predicted secondary structure and the metal-coordinating residues of PAP. Due to the low sequence identity between ASM and PAP (approximately 15%), the highest degree of confidence in the model resides in the metal-binding motifs. The ASM model predicts residues Asp 206, Asp 278, Asn 318, His 425, and His 457 to be dimetal coordinating. A putative orientation for the phosphorylcholine head group of the ASM substrate, sphingomyelin (SM), was made based on the predicted catalysis of the phosphorus-oxygen bond in the active site of ASM and on a structural comparison of the PAP-phosphate complex to the C-reactive protein-phosphorylcholine complex. These complexes revealed similar spatial interactions between the metal-coordinating residues, the metals, and the phosphate groups, suggesting a putative orientation for the head group in ASM consistent with the mechanism considerations. A conserved sequence motif in ASM, NX3CX3N, was identified (Asn 381 to Asn 389) and is predicted to interact with the choline amine moiety in SM. The resulting ASM model suggests that the enzyme uses an SN2-type catalytic mechanism to hydrolyze SM, similar to other DMPs. His 319 in ASM is predicted to protonate the ceramide-leaving group in the catalysis of SM. The putative functional roles of several ASM Niemann-Pick missense mutations, located in the predicted phosphoesterase domain, are discussed in context to the model.


On the optical anisotropy in 2D metal-halide perovskites.
Two-dimensional metal-halide perovskites (MHPs) are versatile solution-processed organic/inorganic quantum wells where the structural anisotropy creates profound anisotropy in their electronic and excitonic properties and associated optical constants. We here employ a wholistic framework, based on semiempirical modeling (k·p/effective mass theory calculations) informed by hybrid density functional theory (DFT) and multimodal spectroscopic ellipsometry on (C6H5(CH2)2NH3)2PbI4 films and crystals, that allows us to link the observed optical properties and anisotropy precisely to the underlying physical parameters that shape the electronic structure of a layered MHP. We find substantial frequency-dependent anisotropy in the optical constants and close correspondence between experiment and theory, demonstrating a high degree of in-plane alignment of the two-dimensional planes in both spin-coated thin films and cleaved single crystals made in this study. Hybrid DFT results elucidate the degree to which organic and inorganic frontier orbitals contribute to optical transitions polarized along a particular axis. The combined experimental and theoretical approach enables us to estimate the fundamental electronic bandgap of 2.65-2.68 eV in this prototypical 2D perovskite and to determine the spin-orbit coupling (ΔSO = 1.20 eV) and effective crystal field (δ = -1.36 eV) which break the degeneracy of the frontier conduction band states and determine the exciton fine structure. The methods and results described here afford a better understanding of the connection between structure and induced optical anisotropy in quantum-confined MHPs, an important structure-property relationship for optoelectronic applications and devices.


First report on fish cysteine as a biomarker of contamination in the River Chenab, Pakistan.
The eastern and southern parts of the Faisalabad city produce considerable quantities of industrial and municipal pollutants, much of which is drained into the River Chenab, reducing the productivity of fauna and flora in the river. This study was aimed to determine whether cysteine is useful as a biomarker of exposure to polluted fresh water. The amino acid profile of fish muscle was analyzed by paper chromatography in Cirrhinus mrigala and Labeo rohita from the River Chenab to determine habitat related variations due to the pollution from industrial and domestic sources. C. mrigala showed higher level of metal contamination in muscle tissues for Sn, Cr, Pb, Zn, Mn, Cu, and Cd when compared to L. rohita. Both fish species collected from polluted areas of the river Chenab showed significantly (P < 0.01) higher levels of metals in comparison to upstream and farmed fish. Farmed C. mrigala showed cysteine concentrations in the muscle tissue as 22 ± 1 mg/g dry weight, but concentrations increased to 45 ± 2 mg/g dry weight for fish from a mildly polluted section of the river, and further increased to 83 ± 2 mg/g dry weight in more heavily polluted sections. Cysteine concentration in farmed L. rohita was detected as 28 ± 2 and 25 ± 4 mg/g dry weight, respectively for farmed fish and fish from a mildly polluted section of the river, and then increased to 94 ± 3 mg/g dry weight for fish from highly polluted water. C. mrigala from a mildly polluted area of the river also had higher levels of cysteine in the muscle, along with increases in aspartic acid, glutamic acid, and alanine. Elevated concentrations of cysteine seem to be associated with a threat to these fish species in polluted sections of the river, and thus may be used as a biomarker.


Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii.
Little is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period. IMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the β-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Fifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and β-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent. IMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination.


General anesthesia with endotracheal intubation for the patient with spinal muscular atrophy: A case report.
Spinal muscular atrophy (SMA) is a rare lower motor neuron disease without sensory loss that needs special care of anesthesiologists due to increased sensitivity to muscle relaxants, potential for aspiration and respiratory weakness. We anesthetized a 10 year-old girl with type 3 SMA for resection of sebaceous cyst in her occiput. We used intravenous anesthetic technique and intubated the patient without any muscle relaxants. The anesthetic and recovery courses were successful. So we present our general anesthetic case under the endotracheal intubation without any muscle relaxants as one of the anesthetic methods for the patients with SMA.


Automatic Classification of Screen Gaze and Dialogue in Doctor-Patient-Computer Interactions: Computational Ethnography Algorithm Development and Validation.
The study of doctor-patient-computer interactions is a key research area for examining doctor-patient relationships; however, studying these interactions is costly and obtrusive as researchers usually set up complex mechanisms or intrude on consultations to collect, then manually analyze the data. We aimed to facilitate human-computer and human-human interaction research in clinics by providing a computational ethnography tool: an unobtrusive automatic classifier of screen gaze and dialogue combinations in doctor-patient-computer interactions. The classifier's input is video taken by doctors using their computers' internal camera and microphone. By estimating the key points of the doctor's face and the presence of voice activity, we estimate the type of interaction that is taking place. The classification output of each video segment is 1 of 4 interaction classes: (1) screen gaze and dialogue, wherein the doctor is gazing at the computer screen while conversing with the patient; (2) dialogue, wherein the doctor is gazing away from the computer screen while conversing with the patient; (3) screen gaze, wherein the doctor is gazing at the computer screen without conversing with the patient; and (4) other, wherein no screen gaze or dialogue are detected. We evaluated the classifier using 30 minutes of video provided by 5 doctors simulating consultations in their clinics both in semi- and fully inclusive layouts. The classifier achieved an overall accuracy of 0.83, a performance similar to that of a human coder. Similar to the human coder, the classifier was more accurate in fully inclusive layouts than in semi-inclusive layouts. The proposed classifier can be used by researchers, care providers, designers, medical educators, and others who are interested in exploring and answering questions related to screen gaze and dialogue in doctor-patient-computer interactions.


GAL4 Drivers Specific for Type Ib and Type Is Motor Neurons in Drosophila.
The Drosophila melanogaster larval neuromuscular system is extensively used by researchers to study neuronal cell biology, and Drosophila glutamatergic motor neurons have become a major model system. There are two main Types of glutamatergic motor neurons, Ib and Is, with different structural and physiological properties at synaptic level at the neuromuscular junction. To generate genetic tools to identify and manipulate motor neurons of each Type, we screened for GAL4 driver lines for this purpose. Here we describe GAL4 drivers specific for examples of neurons within each Type, Ib or Is. These drivers showed high expression levels and were expressed in only few motor neurons, making them amenable tools for specific studies of both axonal and synapse biology in identified Type I motor neurons.


The CAL: an MMPI alcoholism scale for general medical patients.
We developed a MMPI alcoholism scale based on adult medical patient samples. Our criterion group consisted of 736 inpatients (525 males; 211 females) diagnosed as having alcoholism according to DSM-III criteria. Three contrast samples that totaled 13,120 individuals were used for control purposes. MMPI items were chosen by means of logistic regression. The 33 items yielded by this procedure formed a provisional scale (CAL, for common alcoholism logistic) that worked equally well for males and females. With new cross-validation samples, with sensitivity (proportion of alcoholics correctly identified) set at 90%, the specificity (proportion of nonalcoholics correctly identified) ranged from 90% to 96% for selected contrast samples. We conclude that this scale shows promise as a screening device in similar populations.


[The efficacy of alteplase in pulmonary embolism treatment].
The results of pulmonary embolism treatment with streptase in 76 patients are discussed. All patients had submassive or massive pulmonary embolism. 66 (86%) of patients recovered. Thrombolysis with the use of heparin was performed in 9 patients, death occurred in 5 of them. Of 20 patients treated with "Actilize", death was reported in three cases. Authors consider alteplase to be highly effective in the treatment of massive pulmonary embolism. In case of late diagnostics of pulmonary embolism, especially recurrent, thrombolytic therapy remains to be effective up to 2 weeks after primary embolization.


Palliative care needs and preferences of older adults with advanced or serious chronic illnesses and their families in rural communities of Indiana, USA.
To explore the palliative care needs and preferences of older adults with advanced or serious chronic illnesses and their families. Also, to propose strategies to promote supportive palliative care in the rural communities of Indiana, USA. We conducted qualitative interviews to gather rural caregivers' experiences of palliative care. Recruitment was done in collaboration with community partners using social media, flyers, emails, invitations, and word-of-mouth. A purposive sample of family caregivers was obtained. All the interviews were conducted online. The average interview was 30-45 minutes. Data were analyzed using a thematic analysis approach. Our findings showed 6 major themes that indicated several palliative care needs and preferences of older patients and their families in rural communities that include: (1) difficulties in pain and symptom burden; (2) perceived discrimination and lack of trust; (3) longer distances to care facilities; (4) difficult conversations; (5) caregiving burden; and (6) use of telehealth in a rural palliative care context. Rural family caregivers experience several social inequities and disparities causing a lack of access to and low utilization of palliative care. All these disparities cause several challenges for patients and their families trying to manage serious illnesses and die in place with peace and comfort. Inadequate access and lack of resources cause pain and distress for both patients and their families. Provider education and trainings, initiating early palliative care models, integrating behavioral health in palliative care, and using culturally congruent care delivery approaches in support of community partners can improve palliative care services in rural communities.


Selective use of off-pump coronary bypass surgery reduces mortality and neurologic morbidity associated with high-risk coronary bypass surgery: a 400-case comparative experience.
The frequency of use of off-pump coronary artery bypass (CAB) surgery to surgically treat coronary artery disease has varied greatly from center to center and from surgeon to surgeon because of preference, training, and experience. We report an experience with 400 consecutive isolated CAB procedures selectively managed with on-pump or off-pump surgery, according to the perceived potential for aortic embolization or stroke as determined by clinical and imaging determinations. The off-pump CAB group (46 patients) was 7.1 years older (P < .05) and had an 11% lower ejection fraction (P < .03) than the on-pump group. There was no difference in gender, urgency of surgery, hemodynamic stability, angina class, or incidence of prior myocardial infarction. All 400 patients underwent intraoperative transesophageal echocardiography, and many underwent an epiaortic study to supplement image quality. Patients without palpable or imaged advanced aortic disease or deemed to be at clinically high risk for stroke (advanced age, prior strokes, or advanced cerebrovascular or peripheral vascular disease) underwent on-pump procedures requiring 55 minutes of aortic ischemia and 97 minutes of high-flow, high-pressure bypass on average. All others underwent off-pump procedures. The numbers of grafts per patient were similar (3.2 on-pump, 2.8 off-pump; = ns). There was no in-hospital or 30-day mortality in either group. Using the New York State risk-adjustment algorithm, we found the predicted mortality rate for the off-pump group was higher (2.24% on-pump versus 5.54% off-pump, P = .008). The postoperative length of stay was longer in the off-bypass group (3.67 days versus 4.31 days, P = .003). The frequencies of hospital readmission and perioperative complications (renal, pulmonary, infection, bleeding, cardiac, neurologic) were similar, and there were no postoperative strokes in either group. The selective use of off-pump surgery safely managed patients at higher risk for perioperative stroke and associated embolic multisystem organ failure and death. Individual surgeon and center-wide use of a selective approach is recommended as an alternative to a single-procedure nonselective approaches.


IL-10 down-regulates the expression of survival associated gene hspX of Mycobacterium tuberculosis in murine macrophage.
Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50ng/ml) significantly down-regulated the hspX expression. This effect was not only dependent on the concentration of the stimulus but this was time-dependent as well. A contrasting pattern of hspX expression was observed against combinations of two different concentrations of rmIFN-γ and rmIL-10. The study results suggest that rIL-10 mediated down-regulation of hspX expression, in the presence of low concentration of rIFN-γ, could be used as an important strategy to decrease the dormancy of MTB in its host and thus making MTB susceptible to the standard anti-mycobacterial therapy used for treating tuberculosis. However, as these are only preliminary results in the murine cell line model, this hypothesis needs to be first validated in human cell lines and subsequently in animal models mimicking the latent infection using clinical isolates of MTB before considering the development of modified regimens for humans.


The Impact of the Urban Neighborhood Environment on Marijuana Trajectories During Emerging Adulthood.
Although there is little difference in rates of marijuana use between White and Black youth, Blacks have significantly higher rates of marijuana use and disorder in young adulthood. Theory suggests that factors tied to social disadvantage may explain this disparity, and neighborhood setting may be a key exposure. This study sought to identify trajectories of marijuana use in an urban sample during emerging adulthood, neighborhood contexts that predict these trajectories and social role transitions or "turning points" that may redirect them. Data are from a longitudinal cohort study of 378 primarily Black emerging adults who were first sampled in childhood based on their residence in low-income neighborhoods in Baltimore City and followed up annually. Group-based trajectory modeling identified three groups: No Use (68.8%), Declining Use (19.6%), and Chronic Use (11.7%). Living in close proximity to an alcohol outlet, and living in a neighborhood with more female-headed households and higher rates of violent crime increased the odds of membership in the Chronic Use group relative to No Use. Living in a neighborhood with more positive social activity increased the odds of membership in the Declining Use group relative to No Use. Not receiving a high school diploma or GED, pregnancy, and parenting also increased the odds of membership in the Declining Use group relative to No Use. These findings provide support that minority youth living in socially toxic and disordered neighborhoods are at increased risk of continuing on a trajectory of marijuana use during emerging adulthood while positive social activity in neighborhoods has the potential to redirect these negative trajectories. Besides taking on the responsibilities of parenting, emerging adults in the marijuana user groups had similar educational and family outcomes, suggesting that early marijuana use may have long-term implications.


Metal β-diketonate complexes as highly efficient catalysts for chemical fixation of CO2 into cyclic carbonates under mild conditions.
The potential of metal β-diketonate complexes for the catalysis of the chemical fixation of CO2 into cyclic carbonates at 1 atm CO2 and near room temperature was demonstrated. Their potential for the capture and simultaneous conversion of CO2 in a dilute CO2 stream was also determined. The catalysts were easily synthesized and commercially available. Therefore, this CO2 transformation was less energy- and material-consuming, which made this reaction closer to true "green" chemistry.


Plasma Phosphatidylethanolamine and Triacylglycerol Fatty Acid Concentrations are Altered in Major Depressive Disorder Patients with Seasonal Pattern.
Disturbances in peripheral and brain lipid metabolism, including the omega-3 fatty acid docosahexaenoic acid (DHA), have been reported in major depressive disorder (MDD). However, these changes have yet to be confirmed in MDD with seasonal pattern (MDD-s), a subtype of recurrent MDD. The present exploratory study quantified plasma plasmalogen and diacyl-phospholipid species, and fatty acids within total phospholipids, cholesteryl esters, triacylglycerols and free fatty acids in non-medicated MDD-s participants (n = 9) during euthymia in summer or fall, and during depression in winter in order to screen for potential high sensitivity lipid biomarkers. Triacylglycerol alpha-linolenic acid concentration was significantly decreased, and myristoleic acid concentration was significantly increased, during winter depression compared to summer-fall euthymia. 1-stearyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine, a diacyl-phospholipid containing stearic acid and DHA, was significantly decreased in winter depression. Concentrations of cholesteryl ester oleic acid and several polyunsaturated fatty acids between summer/fall and winter increased in proportion to the increase in depressive symptoms. The observed changes in lipid metabolic pathways in winter-type MDD-s offer new promise for lipid biomarker development.


Window of opportunity: estrogen as a treatment for ischemic stroke.
The neuroprotection research in the last 2 decades has witnessed a growing interest in the functions of estrogens as neuroprotectants against neurodegenerative diseases including stroke. The neuroprotective action of estrogens has been well demonstrated in both in vitro and in vivo models of ischemic stroke. However, the major conducted clinical trials so far have raised concern for the protective effect of estrogen replacement therapy in postmenopausal women. The discrepancy could be partly due to the mistranslation between the experimental stroke research and clinical trials. While predominant experimental studies tested the protective action of estrogens on ischemic stroke using acute treatment paradigm, the clinical trials have mainly focused on the effect of estrogen replacement therapy on the primary and secondary stroke prevention which has not been adequately addressed in the experimental stroke study. Although the major conducted clinical trials have indicated that estrogen replacement therapy has an adverse effect and raise concern for long term estrogen replacement therapy for stroke prevention, these are not appropriate for assessing the potential effects of acute estrogen treatment on stroke protection. The well established action of estrogen in the neurovascular unit and its potential interaction with recombinant tissue Plasminogen Activator (rtPA) makes it a candidate for the combined therapy with rtPA for the acute treatment of ischemic stroke. On the other hand, the "critical period" and newly emerged "biomarkers window" hypotheses have indicated that many clinical relevant factors have been underestimated in the experimental ischemic stroke research. The development and application of ischemic stroke models that replicate the clinical condition is essential for further evaluation of acute estrogen treatment on ischemic stroke which might provide critical information for future clinical trials. This article is part of a Special Issue entitled Hormone Therapy.


Active Mechanisms of Vibration Encoding and Frequency Filtering in Central Mechanosensory Neurons.
To better understand biophysical mechanisms of mechanosensory processing, we investigated two cell types in the Drosophila brain (A2 and B1 cells) that are postsynaptic to antennal vibration receptors. A2 cells receive excitatory synaptic currents in response to both directions of movement: thus, twice per vibration cycle. The membrane acts as a low-pass filter, so that voltage and spiking mainly track the vibration envelope rather than individual cycles. By contrast, B1 cells are excited by only forward or backward movement, meaning they are sensitive to vibration phase. They receive oscillatory synaptic currents at the stimulus frequency, and they bandpass filter these inputs to favor specific frequencies. Different cells prefer different frequencies, due to differences in their voltage-gated conductances. Both Na+ and K+ conductances suppress low-frequency synaptic inputs, so cells with larger voltage-gated conductances prefer higher frequencies. These results illustrate how membrane properties and voltage-gated conductances can extract distinct stimulus features into parallel channels.


A role for polyploidy in the tumorigenicity of Pim-1-expressing human prostate and mammary epithelial cells.
Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells. When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo. Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells.


A randomized controlled trial of hamstring stretching: comparison of four techniques.
This study compared the efficacy of 4 different hamstring-stretching techniques. Flexibility can be achieved by a variety of stretching techniques, yet little research has been performed on the most effective method. The 2 basic types include active stretching, in which range of motion is increased through voluntary contraction, and passive stretching, in which range of motion is increased through external assistance. The 2 types of active stretching include neuromobilization and proprioceptive neuromuscular facilitation (PNF). Our study aims to determine which type of stretching technique is most effective in improving hamstring length. One hundred subjects between the ages of 21 and 57 were enrolled in the study. Intrarater reliability of hamstring length measurement was performed using 10 subjects. All 100 subjects were included in a randomized controlled trial of 5 different groups comparing different hamstring-stretching techniques. Outcome measures, including hamstring length and perceived level of hamstring tightness, were recorded on all subjects initially, at 4 weeks, and at 8 weeks. After 4 weeks of stretching, there was a statistically significant improvement in hamstring length (p < 0.05) using active stretches as compared with passive stretches. From weeks 4 through 8, hamstring length for the active stretching groups decreased. After 8 weeks of stretching, the straight leg raise (SLR) passive stretch group had the greatest improvement in hamstring length. There was no correlation between hamstring flexibility and age, initial tightness, or frequency of exercise per week. Improvement in hamstring flexibility was greatest for the SLR passive stretch. Also, using PNF in the 90/90 active stretch provided better knee range-of-motion improvements than the 90/90 passive methods did.


Signals for the incorporation and orientation of cytochrome P450 in the endoplasmic reticulum membrane.
Cytochrome P450b is an integral membrane protein of the rat hepatocyte endoplasmic reticulum (ER) which is cotranslationally inserted into the membrane but remains largely exposed on its cytoplasmic surface. The extreme hydrophobicity of the amino-terminal portion of P450b suggests that it not only serves to initiate the cotranslational insertion of the nascent polypeptide but that it also halts translocation of downstream portions into the lumen of the ER and anchors the mature protein in the membrane. In an in vitro system, we studied the cotranslational insertion into ER membranes of the normal P450b polypeptide and of various deletion variants and chimeric proteins that contain portion of P450b linked to segments of pregrowth hormone or bovine opsin. The results directly established that the amino-terminal 20 residues of P450b function as a combined insertion-halt-transfer signal. Evidence was also obtained that suggests that during the early stages of insertion, this signal enters the membrane in a loop configuration since, when the amino-terminal hydrophobic segment was placed immediately before a signal peptide cleavage site, cleavage by the luminally located signal peptidase took place. After entering the membrane, the P450b signal, however, appeared to be capable of reorienting within the membrane since a bovine opsin peptide segment linked to the amino terminus of the signal became translocated into the microsomal lumen. It was also found that, in addition to the amino-terminal combined insertion-halt-transfer signal, only one other segment within the P450b polypeptide, located between residues 167 and 185, could serve as a halt-transfer signal and membrane-anchoring domain. This segment was shown to prevent translocation of downstream sequences when the amino-terminal combined signal was replaced by the conventional cleavable insertion signal of a secretory protein.


Genetic modification of the diarrhoeal pathogen Cryptosporidium parvum.
Recent studies into the global causes of severe diarrhoea in young children have identified the protozoan parasite Cryptosporidium as the second most important diarrhoeal pathogen after rotavirus. Diarrhoeal disease is estimated to be responsible for 10.5% of overall child mortality. Cryptosporidium is also an opportunistic pathogen in the contexts of human immunodeficiency virus (HIV)-caused AIDS and organ transplantation. There is no vaccine and only a single approved drug that provides no benefit for those in gravest danger: malnourished children and immunocompromised patients. Cryptosporidiosis drug and vaccine development is limited by the poor tractability of the parasite, which includes a lack of systems for continuous culture, facile animal models, and molecular genetic tools. Here we describe an experimental framework to genetically modify this important human pathogen. We established and optimized transfection of C. parvum sporozoites in tissue culture. To isolate stable transgenics we developed a mouse model that delivers sporozoites directly into the intestine, a Cryptosporidium clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system, and in vivo selection for aminoglycoside resistance. We derived reporter parasites suitable for in vitro and in vivo drug screening, and we evaluated the basis of drug susceptibility by gene knockout. We anticipate that the ability to genetically engineer this parasite will be transformative for Cryptosporidium research. Genetic reporters will provide quantitative correlates for disease, cure and protection, and the role of parasite genes in these processes is now open to rigorous investigation.


MicroRNA-886-3P functions as a tumor suppressor in small cell lung cancer.
Small cell lung cancer (SCLC) is a highly aggressive disease and miRNAs may play an important role in modulating SCLC progression. We have previously screened 924 miRNAs and found that miR-886-3P was negatively associated with SCLC survival. In the current study, we further investigated the role of miR-886-3P mimic in regulating SCLC cell phenotypic alteration in vitro and xenograft tumor formation in vivo. We found that transfection of miR-886-3P mimic significantly inhibited SCLC cell proliferation, migration, and colony formation, and induced mesenchymal-epithelial transition (MET) by suppressing TGF-ß1 synthesis in vitro. Furthermore, intra-tumor injection of miR-886-3P mimic lead to necrosis and suppression of tumor invasion to the surrounding tissue in the subcutaneous xenograft tumor, and intra-vein injection of miR-886-3P mimic suppressed xenograft lung cancer growth in vivo. These findings suggested that miR-886-3P functions as a tumor suppressor in SCLC and thus, it might be a potential therapeutic molecule in the treatment of lung cancer.


Intraoperative ERCP: What role does it have in the era of laparoscopic cholecystectomy?
In the treatment of patients with symptomatic cholelithiasis and choledocholithiasis (CBDS) detected during intraoperative cholangiography (IOC), or when the preoperative study of a patient at intermediate risk for CBDS cannot be completed due to the lack of imaging techniques required for confirmation, or if they are available and yield contradictory radiological and clinical results, patients can be treated using intraoperative endoscopic retrograde cholangiopancreatography (ERCP) during the laparoscopic treatment or postoperative ERCP if the IOC finds CBDS. The choice of treatment depends on the level of experience and availability of each option at each hospital. Intraoperative ERCP has the advantage of being a single-stage treatment and has a significant success rate, an easy learning curve, low morbidity involving a shorter hospital stay and lower costs than the two-stage treatments (postoperative and preoperative ERCP). Intraoperative ERCP is also a good salvage treatment when preoperative ERCP fails or when total laparoscopic management also fails.


High levels of inflammatory biomarkers are associated with increased allele-specific apolipoprotein(a) levels in African-Americans.
A role of inflammation for cardiovascular disease (CVD) is established. Lipoprotein(a) [Lp(a)] is an independent CVD risk factor where plasma levels are determined by the apolipoprotein(a) [apo(a)] gene, which contains inflammatory response elements. We investigated the effect of inflammation on allele-specific apo(a) levels in African-Americans and Caucasians. We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and C-reactive protein (CRP) levels in 167 African-Americans and 259 Caucasians. Lp(a) levels were increased among African-Americans with higher vs. lower levels of CRP [<3 vs. > or =3 mg/liter (143 vs. 108 nmol/liter), P = 0.009] or fibrinogen (<340 vs. > or =340 mg/liter, P = 0.002). We next analyzed allele-specific apo(a) levels for different apo(a) sizes. No differences in allele-specific apo(a) levels across CRP or fibrinogen groups were seen among African-Americans or Caucasians for small apo(a) sizes (<22 kringle 4 repeats). Allele-specific apo(a) levels for medium apo(a) sizes (22-30 kringle 4 repeats) were significantly higher among African-Americans, with high levels of CRP or fibrinogen compared with those with low levels (88 vs. 67 nmol/liter, P = 0.014, and 91 vs. 59 nmol/liter, P < 0.0001, respectively). No difference was found for Caucasians. Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in African-Americans but not in Caucasians. These findings indicate that proinflammatory conditions result in a selective increase in medium-sized apo(a) levels in African-Americans and suggest that inflammation-associated events may contribute to the interethnic difference in Lp(a) levels between African-Americans and Caucasians.


Cell membrane ionic permeability, calcium ion, mitochondria, and carcinogenesis.
The interrelations between changes in cell membrane permeability, increase of intracellular concentration of calcium ion and alterations of the bioenergetic and genetic mechanisms of the mitochondria are formalized in a hypothesis of carcinogenesis. It seems very likely that changes in the permeability of the cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+. This phenomenon produces mitochondrial damage associated with permanent modifications of the structural and functional characteristics of the cell membranes as well as of the genetic mechanisms controlling cell division.


Crystal structure of the Leishmania major MIX protein: a scaffold protein that mediates protein-protein interactions.
Infection by Leishmania and Trypanosoma causes severe disease and can be fatal. The reduced effectiveness of current treatments is largely due to drug resistance, hence the urgent need to develop new drugs, preferably against novel targets. We have recently identified a mitochondrial membrane-anchored protein, designated MIX, which occurs exclusively in these parasites and is essential for virulence. We have determined the crystal structure of Leishmania major MIX to a resolution of 2.4 Å. MIX forms an all α-helical fold comprising seven α-helices that fold into a single domain. The distribution of helices is similar to a number of scaffold proteins, namely HEAT repeats, 14-3-3, and tetratricopeptide repeat proteins, suggesting that MIX mediates protein-protein interactions. Accordingly, using copurification and mass spectroscopy we were able to identify several proteins that may interact with MIX in vivo. Being parasite specific, MIX is a promising new drug target and, thus, the structure and potential interacting partners provide a basis for structure-guided drug discovery.


[Evaluation of non-linear adaptive smoothing filter by digital phantom].
As a result of the development of multi-slice CT, diagnoses based on three-dimensional reconstruction images and multi-planar reconstruction have spread. For these applications, which require high z-resolution, thin slice imaging is essential. However, because z-resolution is always based on a trade-off with image noise, thin slice imaging is necessarily accompanied by an increase in noise level. To improve the quality of thin slice images, a non-linear adaptive smoothing filter has been developed, and is being widely applied to clinical use. We developed a digital bar pattern phantom for the purpose of evaluating the effect of this filter and attempted evaluation from an addition image of the bar pattern phantom and the image of the water phantom. The effect of this filter was changed in a complex manner by the contrast and spatial frequency of the original image. We have confirmed the reduced effect of image noise in the low frequency component of the image, but decreased contrast or increased quantity of noise in the image of the high frequency component. This result represents the effect of change in the adaptation of this filter. The digital phantom was useful for this evaluation, but to understand the total effect of filtering, much improvement of the shape of the digital phantom is required.


Deep learning with attention supervision for automated motion artefact detection in quality control of cardiac T1-mapping.
Cardiac magnetic resonance quantitative T1-mapping is increasingly used for advanced myocardial tissue characterisation. However, cardiac or respiratory motion can significantly affect the diagnostic utility of T1-maps, and thus motion artefact detection is critical for quality control and clinically-robust T1 measurements. Manual quality control of T1-maps may provide reassurance, but is laborious and prone to error. We present a deep learning approach with attention supervision for automated motion artefact detection in quality control of cardiac T1-mapping. Firstly, we customised a multi-stream Convolutional Neural Network (CNN) image classifier to streamline the process of automatic motion artefact detection. Secondly, we imposed attention supervision to guide the CNN to focus on targeted myocardial segments. Thirdly, when there was disagreement between the human operator and machine, a second human validator reviewed and rescored the cases for adjudication and to identify the source of disagreement. The multi-stream neural networks demonstrated 89.8% agreement, 87.4% ROC-AUC on motion artefact detection with the human operator in the 2568 T1 maps. Trained with additional supervision on attention, agreements and AUC significantly improved to 91.5% and 89.1%, respectively (p < 0.001). Rescoring of disagreed cases by the second human validator revealed that human operator error was the primary cause of disagreement. Deep learning with attention supervision provides a quick and high-quality assurance of clinical images, and outperforms human operators.


Infantile nephrotic syndrome.
The clinical features and renal histology of twelve chinldren who developed nephrotic syndrome in the first year of life were studied. Six suffered from microcystic disease and six from primary mesangial cell proliferation and/or sclerosis. A consistent family history, premature birth, large placenta pressence of other congenital abnormalities, onset in the first two months of life and lower plasma albumin level all suggested microcyste disease, but the most reliable distinction was histological. All microcystic children died within two years, whereas four with primary mesangial disease survived indefinitely. Corticosterid and immunosuppressive herapy failed to help either group and most deaths were due to sepsis, especialy with E. coli.


Line Graph Neural Networks for Link Prediction.
We consider the graph link prediction task, which is a classic graph analytical problem with many real-world applications. With the advances of deep learning, current link prediction methods commonly compute features from subgraphs centered at two neighboring nodes and use the features to predict the label of the link between these two nodes. In this formalism, a link prediction problem is converted to a graph classification task. In order to extract fixed-size features for classification, graph pooling layers are necessary in the deep learning model, thereby incurring information loss. To overcome this key limitation, we propose to seek a radically different and novel path by making use of the line graphs in graph theory. In particular, each node in a line graph corresponds to a unique edge in the original graph. Therefore, link prediction problems in the original graph can be equivalently solved as a node classification problem in its corresponding line graph, instead of a graph classification task. Experimental results on fourteen datasets from different applications demonstrate that our proposed method consistently outperforms the state-of-the-art methods, while it has fewer parameters and high training efficiency.


ALiGN: Attention based Line Guided Network for Vertebral Comprssion Fracture Detection.
Vertebral Compression Fracture (VCF) is one of the common fractures, especially for elderlies. As it affects postural deformation that may cause secondary disorders in the respiratory or digestive system if not treated in time, diagnosis of VCF is crucial. Using deep learning model based detection technology in diagnosis can reduce the workload of healthcare workers and misdiagnosis. Hence in this work, we propose ALiGN, a compression fracture detection model in the lumbar vertebra based on a deep convolutional neural network (CNN). Specifically, we take the location of each vertebral body into account via a feature pyramid network with an attention mechanism. Our proposed model outperforms the earlier works with a sensitivity 0.9729, specificity 0.9914, and mAP 0.7882.


Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study.
Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk. In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005-2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12-1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88-1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93-1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73-0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04-0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs). In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.


Status of Residual Refractive Error, Ocular Aberrations, and Accommodation After Myopic LASIK, SMILE, and TransPRK.
To analyze residual refractive error, ocular aberrations, and visual acuity (VA) during accommodation simultaneously with ocular aberrometry in eyes after laser-assisted in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), and transepithelial photorefractive keratectomy (TransPRK). Ocular aberrometry (Tracey Technologies, Houston, TX) was performed 3 months after LASIK (n = 95), SMILE (n = 73), and TransPRK (n = 35). While measuring the aberrations, VA was measured at distance (20 ft), intermediate (60 cm), and near (40 cm) targets. The examinations were done monocularly. A parallel group of age-matched normal eyes (n = 50) with 20/20 Snellen distance VA also underwent aberrometry. Distribution of residual spherical error of LASIK eyes matched the normal eyes the best, followed by SMILE and TransPRK. However, the distribution of cylindrical error of the SMILE eyes was distinctly different from the rest (P < .05). The SMILE eyes tended to be undercorrected by approximately 0.25 diopters (D) on average at all reading targets compared to LASIK eyes (P < .05). The undercorrection was greater when the magnitude of the preoperative cylinder exceeded 0.75 D (P < .05). The VA of LASIK and SMILE eyes was similar to normal eyes at all targets, but the TransPRK eyes were marginally inferior (P < .05). Only the ocular defocus changed differentially between the study groups during accommodation and the magnitude of change was least for TransPRK eyes (P < .05). However, postoperative near and intermediate accommodation of LASIK eyes were similar to normal eyes, followed by SMILE eyes and then TransPRK eyes. The refractive and aberrometric status of the LASIK eyes was closest to the normal eyes. The SMILE procedure may benefit from slight overcorrection of the preoperative refractive cylinder. [J Refract Surg. 2019;35(10):624-631.].


Tau PET and relative cerebral blood flow in dementia with Lewy bodies: A PET study.
Alpha-synuclein often co-occurs with Alzheimer's disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology (DLB-AD+). Receptor parametric mapping (cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p > 0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p < 0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p < 0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ = 0.72) and category fluency (stβ = 0.69) tests. Lower parietal R1 was related to lower delayed (stβ = 0.50) and immediate (stβ = 0.48) recall, VOSP number location (stβ = 0.70) and fragmented letters (stβ = 0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ = 0.61), all p < 0.05. The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET.


Patient satisfaction with quality of primary health care in Benghazi, Libya.
The Libyan National Health System (LNHS) is debated for the paradox of its performance versus impact. It has poor performance, but the national health statistics are good and competitive. There are concerted efforts to manage health care services and to regain the lost trust. A primary health care (PHC) system that focuses on preventive and promotive care is the core focus of LNHS efforts. To assess patient satisfaction with quality of PHC assessed in terms of (a) customer profile, (b) patient satisfaction, and (c) health care-seeking behavior. A sample of nine health centers and seven polyclinics from various locations in Benghazi, Libya were selected for gathering information by structured face-to-face interviews. A total of 310 beneficiaries were interviewed by using an Arabic translation of the Charleston Psychiatric Outpatient Satisfaction Scale. The beneficiaries appear to be quite satisfied with the quality of services. Geographical zone, marital status of beneficiary, and type of facility are satisfaction-related factors. There are preferences for facilities located within the City Centre over those located elsewhere. There is also an interaction effect of the geographical zone and the type of facility in creating differences in satisfaction. A customer-friendly facility concept that emphasizes reception, physician interaction, and cordiality shall add value. Polyclinics require more attention as does the Al Slawy area. A few utility services might also be considered.


[Anesthetic management of six patients with surgically repaired tetralogy of Fallot undergoing the second intra-cardiac surgery].
In Japan, more than 9,000 patients with congenital heart disease reach adulthood every year with improved medical treatment, and perioperative encounter with patients requiring the second intra-cardiac operation in adulthood is more often. Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, and long-term prognosis is good. Therefore, we have more chances to care the postoperarive adult patients with TOF. This is a retrospective study in 6 patients with TOF who underwent the second intra-cardiac operation in adulthood from 2008 to 2012. Among the six patients, six had pulmonary valve replacement; four had tricuspid valve replacements or valvuloplastys; four had ventricular septal defect closures; two had right ventricular outflow tract obstruction releases; one had aortic valve replacement; and three had cryoablations. Right ventricular end-diastolic volume was 194.1 +/- 83.5 ml x m(-2) (mean +/- SD), and right ventricular ejection fraction was 38.2 +/- 4.8%. The factors which influence the anesthetic management were as follows: right cardiac failure by abnormality of the pulmonary valve; residual disease and deuteropathy of two or more combination; the risks associated with the second open chest surgery such as long operative time and severe bleeding. Perioperative management of an adult with congenital heart disease requires full understanding of its pathophysiology such as congenital heart disease, adult-specific complications, and the second open chest surgery.


New CCR5 variants associated with reduced HIV coreceptor function in southeast Asia.
Despite multiple exposure to HIV-1, some individuals remain uninfected. This resistance has been associated with homozygosity for a 32 base pair deletion in the gene for the CCR5 receptor. This variant occurs frequently in Caucasians but is extremely rare in Asians or Africans. To identify variations in CCR5 receptor gene that affect susceptibility to HIV infection in non-Caucasians. CCR5 coding region polymorphisms were screened in three groups of Vietnamese subjects: 47 HIV-1 infected intravascular drug users, 50 highly HIV-1-exposed but seronegative intravascular drug users and 37 HIV-1-unexposed seronegative individuals. DNA was analysed by denaturing high performance liquid chromatography; this was followed by examination of the biochemical and HIV coreceptor properties of the coding regions. Five CCR5 coding region variants were identified in this Vietnamese population. The S185R, I254T and C269F mutations have not been previously described; G106R and R223Q have already been found in other Asian populations, but the functional properties of G106R is not known. These variants differed in biochemical and HIV coreceptor properties. S185R and I254T variants had receptor and coreceptor activities comparable to that of the wild type, whereas C269F and G106R behaved differently. This latter pair are poorly expressed at the cell surface, weakly bind macrophage inflammatory protein 1beta (CCL4) and RANTES (CCL5), and display reduced HIV-1 coreceptor efficiency. Among the five CCR5 variants found in this Vietnamese population, G106R and C269F displayed significant modifications of their receptor and coreceptor properties, which may contribute to susceptibility to HIV-1 infection and/or disease progression within this population.


Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model.
Inflammation, characterized by redness, swelling, pain and a sensation of heat, is one of the body's self-defense systems. Although the inflammation response has an important role in host survival, it also leads to chronic inflammatory diseases. Linalool is a natural compound of the essential oils in several aromatic plants species. It possesses anti-inflammatory, antinociceptive, and other bioactive properties. In the present study, we investigated the protective effects of linalool on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and an LPS-induced in vivo lung injury model. We evaluated the effects of linalool on LPS-induced production of inflammatory mediators in Raw 264.7 murine macrophages by enzyme-linked immunosorbent assay and Western blot. To confirm the anti-inflammatory activity of linalool in vivo, we induced an acute lung injury in an LPS-induced mouse model. Linalool attenuated the production of LPS-induced tumor necrosis-α and interleukin-6 both in vitro and in vivo. Furthermore, phosphorylation of IκBα protein, p38, c-Jun terminal kinase, and extracellular signal-regulated kinase in LPS-stimulated RAW 264.7 cells was blocked by linalool. Our in vivo study also found that linalool attenuated lung histopathologic changes in mouse models. The results suggest that linalool inhibits inflammation both in vitro and in vivo, and may be a potential therapeutic candidate for the treatment of inflammatory diseases.


Evolution of a stream ecosystem in recently deglaciated terrain.
Climate change and associated glacial recession create new stream habitat that leads to the assembly of new riverine communities through primary succession. However, there are still very few studies of the patterns and processes of community assembly during primary succession for stream ecosystems. We illustrate the rapidity with which biotic communities can colonize and establish in recently formed streams by examining Stonefly Creek in Glacier Bay, Alaska (USA), which began to emerge from a remnant glacial ice mass between 1976 and 1979. By 2002, 57 macroinvertebrate and 27 microcrustacea species had become established. Within 10 years of the stream's formation, pink salmon and Dolly Varden charr colonized, followed by other fish species, including juvenile red and silver salmon, Coast Range sculpin, and sticklebacks. Stable-isotope analyses indicate that marine-derived nitrogen from the decay of salmon carcasses was substantially assimilated within the aquatic food web by 2004. The findings from Stonefly Creek are compared with those from a long-term study of a similarly formed but older stream (12 km to the northeast) to examine possible similarities in macroinvertebrate community and biological trait composition between streams at similar stages of development. Macroinvertebrate community assembly appears to have been initially strongly deterministic owing to low water temperature associated with remnant ice masses. In contrast, microcrustacean community assembly appears to have been more stochastic. However, as stream age and water temperature increased, macroinvertebrate colonization was also more stochastic, and taxonomic similarity between Stonefly Creek and a stream at the same stage of development was <50%. However the most abundant taxa were similar, and functional diversity of the two communities was almost identical. Tolerance is suggested as the major mechanism of community assembly. The rapidity with which salmonids and invertebrate communities have become established across an entire watershed has implications for the conservation of biodiversity in freshwater habitats.


The relation between mood, activity, and interaction in long-term dementia care.
The aim of the study is to identify the degree of association between mood, activity engagement, activity location, and social interaction during everyday life of people with dementia (PwD) living in long-term care facilities. An observational study using momentary assessments was conducted. For all 115 participants, 84 momentary assessments of mood, engagement in activity, location during activity, and social interaction were carried out by a researcher using the tablet-based Maastricht Electronic Daily Life Observation-tool. A total of 9660 momentary assessments were completed. The mean age of the 115 participants was 84 and most (75%) were women. A negative, neutral, or positive mood was recorded during 2%, 25%, and 73% of the observations, respectively. Positive mood was associated with engagement in activities, doing activities outside, and social interaction. The type of activity was less important for mood than the fact that PwD were engaged in an activity. Low mood was evident when PwD attempted to have social interaction but received no response. Fulfilling PwD's need for occupation and social interaction is consistent with a person-centred dementia care focus and should have priority in dementia care.


Studies on the heterogeneity of subfragment-1 preparations. Isolation of a new proteolytic fragment of the heavy chain of myosin.
1. The physical, chemical and enzymic properties of subfragment 1 prepared from myosin of rabbit skeletal muscle by using two different concentrations of insoluble papain were compared. 2. Subfragment 1 prepared by using a myosin/papain ratio of 2000: 1 (by wt.) migrated on electrophoresis in non-dissociating conditions as a single enzymically active band. When prepared with a myosin/papain ratio of 200: 1 the preparation consisted of two enzymically active components of slightly different electrophoretic mobility. 3. The two types of preparation were obtained in similar yield and possessed similar specific adenosine triphosphatase activities when determined in the presence of Ca(2+). 4. Gel electrophoresis in the presence of 8m-urea showed that both preparations contained three light components. The component of molecular weight 15500 was apparently identical with one of the light-chain components of myosin (Ml(1)). The other two light-chain components of subfragment 1 were not identical with any of the light-chain components of myosin. 5. The heavy-chain fraction of subfragment 1 prepared by using low concentrations of papain dissociated into components with molecular weights of 87000, 69000 and 26000 on electrophoresis in sodium dodecyl sulphate. The heavy-chain fraction of subfragment 1 prepared by using higher concentrations of papain contained components with molecular weights of 69000 and 53000 and relatively increased amounts of the component of molecular weight 26000. 6. The isolated 26000 dalton component had an amino acid composition similar to that of the heavy-chain fraction of subfragment 1 and contained 3-methylhistidine and mono-and tri-N(epsilon)-methyl-lysine. It was homogeneous on electrophoresis in the presence of sodium dodecyl sulphate but gave two bands on electrophoresis in 8m-urea.


Clinical course, treatment responses and outcomes in Chinese paediatric neuromyelitis optica spectrum disorder.
Few data exists on paediatric neuromyelitis optica spectrum disorder (NMOSD). Here, we investigated the clinical presentation, treatment responses and long-term prognoses in a large cohort of patients with NMOSD and compared between children and adults with aquaporin-4 antibody (AQP4-IgG). A retrospective chart review of patients followed in multiple centres identified 127 patients with NMOSD (31 children; 96 adults). Data were collected through medical records and structured questionnaire. In the paediatric cohort, median age at onset was 14 (range 7-17) years; 87% were female. AQP4 and myelin oligodendrocyte glycoprotein antibodies were detected in 82% and 16%, respectively. During a median disease duration of 48 months, 23% developed visual acuity of <6/60 Snellen, 3% were wheelchair-dependent. The frequency of brain/brainstem phenotype (18% vs 9%, p = 0.018) was more common in AQP4-IgG-positive children, while AQP4-IgG-positive adults were more likely to present transverse myelitis (TM) (44% vs 29%, p = 0.005) of all 452 episodes. Multivariable analyses showed that sustained disability was independently associated with the presence of TM (p = 0.030), brain/brainstem symptoms (p = 0.010), annualized relapse rate (p < 0.001) and possibly age of onset (p = 0.069). The reduction of ARR after azathioprine was more prominent in adults (79%) than in children (48%). Mycophenolate mofetil and rituximab decreased the relapse frequency of children, with a reduction of 94% and 100%, respectively. paediatric NMOSD is a severely disabling disorder characterized by repeated brain attacks and early disability accrual. Prompt therapy including mycophenolate mofetil and rituximab should be considered to improve paediatric care.


Multifunctional Pt(iv) complexes containing a glutathione S-transferase inhibitor lead to enhancing anticancer activity and preventing metastasis of osteosarcoma cells.
Cisplatin has been clinically applied in the treatment of osteosarcoma (OS), but its efficacy is severely limited due to drug resistance and metastasis. One of the chief culprits is the overexpression of glutathione S-transferases (GSTs) in cancer cells, which can accelerate the interaction of glutathione (GSH) with cisplatin, reducing its biological effects. In this study, three Pt(iv) complexes derived from cisplatin conjugated with a GST inhibitor (NBDHEX) were designed and synthesized. The stabilities and releasing capabilities of these complexes, as well as their abilities to inhibit GSTs, were investigated together with their in vitro anticancer activities toward osteosarcoma cells. Among them, complex 2, bearing one NBDHEX derivative and a hydroxyl group at the axial positions, could markedly kill human OS cells due to its suitable stability and prominent ability to inhibit GSTs. Meanwhile, it can prevent the metastasis of OS via down-regulating Akt. Thus, complex 2 has the potential for further research for the treatment of OS.


Cough modulation by upper airway stimuli in cat - potential clinical application?
The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and / or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and / or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.


Pericoronary pseudotumor caused by helicobacter cinaedi.
Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We here report a case of a pericoronary tumor-like lesion surrounding the right coronary artery in a 39-year-old man who presented with fever and chest pain. Although clarithromycin was administered for 1 week, his fever persisted. Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary artery. After administration of ceftriaxone, the tumor-like lesion diminished in size according to meticulous computed tomography examinations. We therefore concluded that it was caused by H. cinaedi infection. The patient has been followed up closely for 1 year and remains asymptomatic.


Minority language education in unbalanced bilingual situations: a case for the linguistic interdependence hypothesis.
This paper is placed in the linguistic and sociocultural context of Eastern Aragon, a region of Spain where two contact languages (Spanish and Catalan) coexist in an unbalanced situation favoring Spanish. The research was prompted by the regulation for the teaching of Catalan in that area, by means of the Cooperation Agreement signed by the Spanish Educational Ministry (MEC) and the local autonomous Cultural and Educational Department of the Diputación General de Aragon in November 1986. A comparative analysis is made between Eastern Aragon students' linguistic competence in Catalan and Spanish; a further comparison is established between these students and others living in bilingual Catalonia and in monolingual Aragon. We conclude by pointing out that the Linguistic Interdependence Hypothesis accounts for the results obtained in the study.