Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission.
Cucumber necrosis virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome. CNV is transmitted in nature via zoospores of the fungus Olpidium bornovanus As with other members of the Tombusvirus genus, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507-517, 2004, https://doi.org/10.1016/j.jmb.2004.03.008). P73 lies immediately adjacent to a putative zinc binding site (M. Li et al., J Virol 87:12166-12175, 2013, https://doi.org/10.1128/JVI.01965-13) that is formed by three icosahedrally related His residues in the N termini of the C subunit at the quasi-6-fold axes. To better understand how this buried residue might affect vector transmission, we determined the cryo-electron microscopy structure of wild-type CNV in the native and swollen state and of the transmission-defective mutant, P73G, under native conditions. With the wild-type CNV, the swollen structure demonstrated the expected expansion of the capsid. However, the zinc binding region at the quasi-6-fold at the β-annulus axes remained intact. By comparison, the zinc binding region of the P73G mutant, even under native conditions, was markedly disordered, suggesting that the β-annulus had been disrupted and that this could destabilize the capsid. This was confirmed with pH and urea denaturation experiments in conjunction with electron microscopy analysis. We suggest that the P73G mutation affects the zinc binding and/or the β-annulus, making it more fragile under neutral/basic pH conditions. This, in turn, may affect zoospore transmission.IMPORTANCECucumber necrosis virus (CNV), a member of the genus Tombusvirus, is transmitted in nature via zoospores of the fungus Olpidium bornovanus While a number of plant viruses are transmitted via insect vectors, little is known at the molecular level as to how the viruses are recognized and transmitted. As with many spherical plant viruses, the CNV capsid swells when exposed to alkaline pH and EDTA. We previously demonstrated that a P73G mutation that lies inside the capsid immediately adjacent to a putative zinc binding site (Li et al., J Virol 87:12166-12175, 2013, https://doi.org/10.1128/JVI.01965-13) blocks the virus from zoospore transmission while not significantly affecting replication in plants (K. Kakani, R. Reade, and D. Rochon, J Mol Biol 338:507-517, 2004, https://doi.org/10.1016/j.jmb.2004.03.008). Here, we show that the P73G mutant is less stable than the wild type, and this appears to be correlated with destabilization of the β-annulus at the icosahedral 3-fold axes. Therefore, the β-annulus appears not to be essential for particle assembly but is necessary for interactions with the transmission vector.


[CT perfusion imaging in acute ischemic cerebral infarct: comparison of cerebral perfusion maps and conventional CT findings].
To evaluate the findings of acute brain ischemia on different functional maps of cerebral perfusion CT in stroke patients and to compare the results with early ischemic changes on conventional CT. The baseline CT scans of 45 acute stroke patients were retrospectively evaluated with respect to early CT findings. For each patient the extent of cerebral ischemia as shown on the maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and "time to peak" (TP) was compared and the severity of ischemia was assigned to one of three levels based on the findings of the CBF image. In 75% of all patients conventional CT was performed within 2 hours from symptom onset. 29 of 45 patients showed early signs of ischemia on conventional CT, whereas perfusion CT revealed cerebral ischemia in all patients. Severe ischemia was found in approximately the same rate of incidence in patients with early CT changes (55.2%) and in those with normal findings (43.8%). If the perfusion impairment was judged as mild or moderate the extent of the hypoperfused area was significantly larger on the CBF and TP images than on the CBV map. This was significantly different in patients with severe hypoperfusion where a complete correspondence of the affected area between the three functional maps was found. The use of conventional CT for the assessment of stroke in the hyperacute phase is limited. Perfusion CT yields excellent information regarding the severity and extent of ischemia. The use of various perfusion maps helps to differentiate the core of infarction from the ischemic penumbra zone.


The acute effect of ethanol on adrenal cortex in female rats--possible role of nitric oxide.
The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.


The BB-rat--an authentic model of human diabetic retinopathy.
The pathogenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition. Examination of the retina in the spontaneously diabetic BB-rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with areas of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanism(s) linking the metabolic abnormalities of diabetes and the retinopathy.


The effect of meditation on physical and mental health in junior college students: a quasi-experimental study.
Physical stress and mental stress are increasingly common phenomena in our rapidly changing and stressful modern society. Research has found meditation to produce positive and demonstrable stress reduction effects on brain and immune functions. This study is grounded in traditional Chinese philosophical mores that teach a process summarized by the keynote activities of "calm, still, quiet, consider, and get" and the potential of this process to reduce stress in adolescents. The purpose of this study was to examine the effects of meditation on the physical and mental health of junior college students. This research employed a quasi-experimental design. Participants included 242 freshmen from a junior college in Taiwan selected using a convenience sampling technique. Participants were then randomly separated into experimental (n = 119) and control (n = 123) groups. The project duration was 18 weeks, during which the experimental group received 2 hours of meditation treatment per week, for a total of 36 hours. Both groups completed pretest and posttest Life Adaptation Scale forms, which included questionnaires addressing information on physical and mental distress and positive and negative coping strategies. Data were analyzed using analysis of covariance. Findings showed that the effect of the experiment treatment was significant when student physical and mental distress pretest scores were controlled. Physical and mental symptoms in the experimental group were lower than those in the control group. Meditation can help students to adapt to life stressors. This study also provides support for traditional Chinese wisdom, which promotes meditation as one way to improve health.


Use of the electronic Frailty Index to identify vulnerable patients: a pilot study in primary care.
Identifying frailty is key to providing appropriate treatment for older people at high risk of adverse health outcomes. Screening tools proposed for primary care often involve additional workload. The electronic Frailty Index (eFI) has the potential to overcome this issue. To assess the feasibility and acceptability of using the eFI in primary care. Pilot study in one suburban primary care practice in southern England in 2016. Use of the eFI on the primary care TPP SystmOne database was explained to staff at the practice where a comprehensive geriatric assessment (CGA) clinic was being trialled. The practice data manager ran an eFI report for all patients (n = 6670). Date of birth was used to identify patients aged ≥75 years (n = 589). The eFI was determined for patients attending the CGA clinic (n = 18). Practice staff ran the eFI reports in 5 minutes, which they reported was feasible and acceptable. The eFI range was 0.03 to 0.61 (mean 0.23) for all patients aged ≥75 years (mean 83 years, range 75 to 102 years). For CGA patients (mean 82 years, range 75 to 94 years) the eFI range was 0.19 to 0.53 (mean 0.33). Importantly, the eFI scores identified almost 12% of patients aged ≥75 years in this practice to have severe frailty. It was feasible and acceptable to use the eFI in this pilot study. A higher mean eFI in the CGA patients demonstrated construct validity for frailty identification. Practice staff recognised the potential for the eFI to identify the top 2% of vulnerable patients for avoiding unplanned admissions.


The difficulties in constructing a common denominator for peer review in general practice.
A helpful analysis of clinical events in general practice would be to show a doctor how his opinion compares with the use of the same opinion by other doctors. For such a comparison a common denominator, which is a measure of clinical opportunity, is required. The population of patients cared for by a doctor can be used for this purpose and this paper describes a method which uses a computer to calculate the share of a known practice population that each doctor has cared for. The computer produces details of consultations, set out in square tables, of those registered with each doctor and those seen by each doctor.


Epidemiological analysis of Arcanobacterium phocae isolated from cases of mink dermatitis of a single farm.
The present study was designed to identify nine Arcanobacterium phocae strains isolated from cases of mink dermatitis of a single farm in Finland and characterize the strains for epidemiological relationships. All nine strains and previously described A. phocae used for comparative purposes were identified and further characterized phenotypically, by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), by Fourier Transform Infrared Spectroscopy (FT-IR) and genotypically by detection of phocaelysin encoding gene phl with a previously developed loop-mediated isothermal amplification (LAMP) assay and by sequencing 16S rRNA gene and gene phl, the elongation factor tu encoding gene tuf and the β subunit of bacterial RNA polymerase encoding gene rpoB. Genetic relatedness among isolates was determined using whole-genome single nucleotide polymorphism (wgSNP) analysis. The wgSNP results, partly the MALDI-TOF MS and FT-IR analyses and sequencing of the genes, revealed that the nine A. phocae strains recovered from a single farm showed close sequence similarities among each other and differed from previously investigated A. phocae strains isolated from other farms and animals in Finland and from the A. phocae type strain. This indicated a close epidemiological relationship of the A. phocae strains isolated from a single farm and that the nine A. phocae strains of the present study might have developed from a common ancestor.


Role of ligand-ligand vs. core-core interactions in gold nanoclusters.
The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.


The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.
TRPML1 (mucolipin 1, also known as MCOLN1) is predicted to be an intracellular late endosomal and lysosomal ion channel protein that belongs to the mucolipin subfamily of transient receptor potential (TRP) proteins. Mutations in the human TRPML1 gene cause mucolipidosis type IV disease (ML4). ML4 patients have motor impairment, mental retardation, retinal degeneration and iron-deficiency anaemia. Because aberrant iron metabolism may cause neural and retinal degeneration, it may be a primary cause of ML4 phenotypes. In most mammalian cells, release of iron from endosomes and lysosomes after iron uptake by endocytosis of Fe(3+)-bound transferrin receptors, or after lysosomal degradation of ferritin-iron complexes and autophagic ingestion of iron-containing macromolecules, is the chief source of cellular iron. The divalent metal transporter protein DMT1 (also known as SLC11A2) is the only endosomal Fe(2+) transporter known at present and it is highly expressed in erythroid precursors. Genetic studies, however, suggest the existence of a DMT1-independent endosomal and lysosomal Fe(2+) transport protein. By measuring radiolabelled iron uptake, by monitoring the levels of cytosolic and intralysosomal iron and by directly patch-clamping the late endosomal and lysosomal membrane, here we show that TRPML1 functions as a Fe(2+) permeable channel in late endosomes and lysosomes. ML4 mutations are shown to impair the ability of TRPML1 to permeate Fe(2+) at varying degrees, which correlate well with the disease severity. A comparison of TRPML1(-/- )ML4 and control human skin fibroblasts showed a reduction in cytosolic Fe(2+) levels, an increase in intralysosomal Fe(2+) levels and an accumulation of lipofuscin-like molecules in TRPML1(-/-) cells. We propose that TRPML1 mediates a mechanism by which Fe(2+) is released from late endosomes and lysosomes. Our results indicate that impaired iron transport may contribute to both haematological and degenerative symptoms of ML4 patients.


Molecular cloning and nucleotide sequencing of human immunoglobulin epsilon chain cDNA.
DNA complementary to mRNA of human immunoglobulin E heavy chain (epsilon chain) isolated and purified from U266 cells has been synthesized and inserted into the PstI site of pBR322 by G-C tailing. This recombinant plasmid was used to transform E. coli chi 1776 to screen 1445 tetracycline resistant colonies. Nine clones (pGETI - 9) containing cDNA coding for the human epsilon chain were recognized by colony hybridization and Southern blotting analysis with a nick-translated human IgE genome fragment. The nucleotide sequence of the longest cDNA contained in pGET2 was determined. The results indicate that the sequence of 1657 nucleotides codes for 494 amino acids covering a part of the variable region and all of the constant region of the human epsilon chain. Most of the amino acid sequence deduced from the nucleotide sequence is in substantial agreement with that reported. Furthermore a termination codon after the -COOH terminal amino acid marks the beginning of a 3' untranslated region of 125 nucleotides with a poly A tail. Taking this into account, the structure of the human epsilon chain mRNA, except a part of the 5' end, is conserved fairly well in the cDNA insert in pGET2.


Improved salt iodation methods for small-scale salt producers in low-resource settings in Tanzania.
Universal salt iodation will prevent iodine deficiency disorders (IDD). Globally, salt-iodation technologies mostly target large and medium-scale salt-producers. Since most producers in low-income countries are small-scale, we examined and improved the performance of hand and knapsack-sprayers used locally in Tanzania. We studied three salt facilities on the Bagamoyo coast, investigating procedures for preparing potassium-iodate solution, salt spraying and mixing. Different concentrations of solution were prepared and tested using different iodation methods, with the aim of attaining correct and homogeneous iodine levels under real-life conditions. Levels achieved by manual mixing were compared to those achieved by machine mixing. The overall median iodation level in samples of salt iodated using previously existing methods was 10.6 ppm (range 1.1 - 110.0 ppm), with much higher levels in the top than the bottom layers of the salt bags, p < 0.0001. Experimentation using knapsack-sprayers and manual mixing led to the reliable achievement of levels (60.9 ppm +/- 7.4) that fell within the recommended range of 40 - 80 ppm. The improved methods yielded homogenous iodine concentrations in all layers of salt-bags (p = 0.58) with 96% of the samples (n = 45) falling within 40 - 80 ppm compared to only 9% (n = 45) before the experiment and training (p < 0.0001). For knapsack-spraying, a machine mixer improved the iodine levels and homogeneity slightly compared to manual mixing (p = 0.05). Supervised, standardized salt iodation procedures adapted to local circumstances can yield homogeneous iodine levels within the required range, overcoming a major obstacle to universal salt iodation.


[An analysis of the demand for laboratory tests from primary care in a health area].
To quantify the primary care demand for laboratory tests in a health area and to evaluate the variations in use in relation to the characteristics of the doctors, of organisation and of the population seen. Crossover. A health area in the Community of Valencia with 110125 inhabitants. 89 primary care doctors from the area, with 8612 requests for lab. tests over 12 weeks. All the lab. requests, including determinations (67730), diagnoses, and age and sex of patients, were recorded. Total and health consultations were calculated. The overall demand rate was 356 requests per 1000 inhabitants, with variations in the standardised rates by age of population between Districts (ranging from 242 to 548 per 1000). Lab. tests were requested for 8.6 of every 100 health consultations, with variations of up to three times this number depending on the distance from the laboratory. Women doctors asked for a higher number of determinations per request. whereas more requests were made for male than for female patients. There are substantial variations in primary care use of the laboratory, which are hard to explain by differences in underlying pathology. Some reasons for variation are organisational, but others remain to be tested. Findings indicate that interventions should be designed to improve the quality of laboratory use. Meanwhile, study of the causes of variations in demand continues.


Growth of Malignant Non-CNS Tumors Alters Brain Metabolome.
Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as "tumor brain." Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon.


Advance Care Planning in Cancer: Patient Preferences for Personnel and Timing.
Opportunities for advance care planning (ACP) discussions continue to be missed despite the demonstrated benefit of such conversations. This is in part because of a poor understanding of patient preferences. We aimed to determine oncology patients' preferences surrounding ACP with a focus on the choice of which health care providers to have the conversation with and the timing of conversations. A cross-sectional 19-question survey of surgical and medical oncology patients in a tertiary care hospital was conducted that assessed knowledge, experience, and preferences surrounding ACP. Quantitative variables were reported with descriptive statistics, and a coding structure was developed to analyze qualitative data. Two hundred patients were surveyed. Only 24% of patients reported previously having ACP discussions with their physicians despite 82.5% reporting a wish to do so. Patients felt that these discussions were a priority for them (to alleviate familial guilt, maintain control, and prevent others' values from guiding end-of-life care), but they reported that previous experiences with ACP had been neither comprehensive nor effective. Most patients (43.5%) preferred to have ACP discussions with their primary care providers (PCPs) compared with 7% preferring their surgeon and 5.5% preferring their oncologist. Trust and familiarity with PCPs arose as the dominant theme underlying this selection. Most patients (94%) preferred to have ACP discussions early, with 45% wishing such a discussion had been initiated before their cancer diagnosis. Patients with cancer prefer to have ACP discussions with their PCPs and prefer to do so early in their disease course.


Designing a global monitoring system for pilot introduction of a new contraceptive technology, subcutaneous DMPA (DMPA-SC).
In collaboration with ministries of health, PATH and key partners launched the first pilot introductions of subcutaneous depot medroxyprogesterone acetate (DMPA-SC, brand name Sayana® Press) in Burkina Faso, Niger, Senegal, and Uganda from July 2014 through June 2016. While each country implemented a unique introduction strategy, all agreed to track a set of uniform indicators to chart the effect of introducing this new method across settings. Existing national health information systems (HIS) were unable to track new methods or delivery channels introduced for a pilot, thus were not a feasible source for project data. We successfully monitored the four-country pilot introductions by implementing a four-phase approach: 1) developing and defining global indicators, 2) integrating indicators into existing country data collection tools, 3) facilitating consistent reporting and data management, and 4) analyzing and interpreting data and sharing results. Project partners leveraged existing family planning registers to the extent possible, and introduced new or modified data collection and reporting tools to generate project-specific data where necessary. We routinely shared monitoring results with global and national stakeholders, informing decisions about future investments in the product and scale up of DMPA-SC nationwide. Our process and lessons learned may provide insights for countries planning to introduce DMPA-SC or other new contraceptive methods in settings where stakeholder expectations for measureable results for decision-making are high.


Factors associated with the type of psychotropic medications purchased for common mental disorders in the largest managed care organization in Israel.
To evaluate patient and physician characteristics associated with the type of psychotropic medications (anti-anxiety, antidepressant, or both) purchased. The Clalit Health Care Services is the largest managed care health fund in Israel, a country that employs a universal healthcare system. We randomly sampled 30,000 primary care patients over the age of 22 as of January, 2006. Overall, 2,217 purchased either antidepressant or antianxiety medications at least once during the year 2006 and had no prior purchases during the last quarter of 2005. The majority (1,518; 68.4%) purchased only anti-anxiety medications and as many as 264 (12%) purchased both anti-anxiety and antidepressant medications. The remaining 435 (19.6%) patients purchased only antidepressant medications. Physician level characteristics explained only a small portion of the variance and, thus, were not included in further analysis. Several patient level characteristics, including age, somatic, and psychiatric diagnosis were associated with the purchase of different types of medications. Contrary to clinical guidelines, the purchase of anti-anxiety medications is more prevalent than the purchase of antidepressant medications. In a managed care setting, patient characteristics have a greater role in determining purchasing patterns than provider characteristics; potentially, because of the managed care characteristics that actively guide the care provided to patients.


Rapid and directly interpretable antimicrobial susceptibility profiling by continuous microvolume-electroanalysis of ferricyanide-mediated bacterial respiration.
We present a novel method for the electroanalysis of potassium ferricyanide-mediated bacterial electron transport, to rapidly assess viability and construct interpretable antimicrobial susceptibility profiles. Electrochemical minimum inhibitory concentrations (ecMICs) became determinable with a high correlation to the results from conventional assays.


Musculoplasty for mastoid cavity obliteration in the capucine monkey.
In a series of musculoplasty in 12 ears in the capucine monkey the mastoid cavity was successfully obliterated in the early follow-up months, but showed no obliteration at one year. A control using a bovine collagen preparation showed similar results. Musculoplasty appears to carry the dual risk of burying residual cholesteatomatous disease by virtue of atrophy and shrinkage of the muscle flap, and reformation of the mastoid cavity.


Cost effectiveness of patellofemoral versus total knee arthroplasty in younger patients.
Patellofemoral arthroplasty (PFA) has experienced significant improvements in implant survivorship with second generation designs. This has renewed interest in PFA as an alternative to total knee arthroplasty (TKA) for younger active patients with isolated patellofemoral osteoarthritis (PF OA). We analysed the cost-effectiveness of PFA versus TKA for the management of isolated PF OA in the United States-based population. We used a Markov transition state model to compare cost-effectiveness between PFA and TKA. Simulated patients were aged 60 (base case) and 50 years. Lifetime costs (2015 United States dollars), quality-adjusted life year (QALY) gains and incremental cost-effectiveness ratio (ICER) were calculated from a healthcare payer perspective. Annual rates of revision were derived from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Deterministic and probabilistic sensitivity analysis was performed for all parameters against a $50 000/QALY willingness to pay. PFA was more expensive ($49 811 versus $46 632) but more effective (14.3 QALYs versus 13.3 QALYs) over a lifetime horizon. The ICER associated with the additional effectiveness of PFA was $3097. The model was mainly sensitive to utility values, with PFA remaining cost-effective when its utility exceeded that of TKA by at least 1.0%. PFA provided incremental benefits at no increased cost when annual rates of revision decreased by 24.5%. Recent improvements in rates of implant of survival have made PFA an economically beneficial joint-preserving procedure in younger patients, delaying TKA until implant failure or tibiofemoral OA progression. The present study quantified the minimum required marginal benefit for PFA to be cost-effective compared with TKA and identified survivorship targets for PFA to become both less expensive and more effective. These benchmarks might be used to assess clinical outcomes of PFA from an economic standpoint within the United States healthcare system. Cite this article: Bone Joint J 2017;99-B:1028-36.


[Clinical and pharmacokinetic evaluation of ceftazidime in neonates and young infants].
Seventeen newborn and young infants including 6 premature infants were treated with ceftazidime (CAZ) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from zero to 55 days, and their body weights ranged from 1.35 to 3.87 kg. Doses of CAZ ranged 10-50 mg/kg every 6 to 12 hours for 3 to 14 days. Twelve infants with infections including meningitis, sepsis, pneumonia and urinary tract infections, were considered to have responded to the CAZ treatment. Among them, results were excellent in 2, good in 9 and fair in 1 patient. The drug was well tolerated, but 1 had diarrhea and 3 patients had eosinophilia among the 17 patients. The pharmacokinetics of CAZ was studied in 22 patients including 11 premature infants. Their ages ranged from 1 to 60 days, and body weights ranged from 0.85 to 3.96 kg. Serum concentrations in 7 patients ranged from 24.2-38.5 micrograms/ml at 30 minutes after single doses of 10 mg/kg intravenous bolus injections and 4.36-12.4 micrograms/ml at 6 hours. Mean elimination half-lives of the drug were 3.20 hours in 2 patients under 7 days of age and 2.31 hours in 5 patients from 7 days of age or older. In 8 patients, serum concentrations ranged 32.6-57.9 micrograms/ml at 30 minutes and 8.10-20.7 micrograms/ml at 6 hours after single doses of 20 mg/kg. Elimination half-lives were 3.53 hours in 4 patients under 7 days of age and 2.79 hours in 4 patients from 7 days of age or older.(ABSTRACT TRUNCATED AT 250 WORDS)


Psychometric properties of the Finnish version of the Women's Health Questionnaire.
The Women's Health Questionnaire (WHQ) is a validated and commonly used instrument for measuring climacteric-related symptoms. A revised version was previously developed. However, validation in a Finnish population is lacking. As it is important to use qualified instruments, we performed a validation study of the WHQ in a Finnish population. In all, 3,421 women, aged 41 to 54 years, formed the study population. In the original 36-item WHQ, the items were rated on a 1 to 4 scale and on a binary scale (0-1). The scaling of the revised 23-item WHQ was 0 to 100. We evaluated the psychometric properties (internal consistency, correlations between the symptom domains, factor structure, and sampling adequacy) in all three versions. For the 1 to 4 scale and on the revised version of the WHQ, the internal consistency was acceptable (the Cronbach's α coefficients >0.70) for most of the domains. On the binary scale, the majority of the coefficient values were below the acceptable level. The original symptom domains, especially those on the revised version, were recognizable from the factors in the exploratory factor analysis, but there were some limitations. The Kaiser-Meyer-Olkin values were high. The WHQ is a valid instrument for measuring climacteric-related symptoms in Finnish middle-aged women. The psychometric properties of the revised 23-item WHQ were as good or even better than those of the original 36-item WHQ. Thus, we encourage use of the revised version.


Gamma interferon does not enhance clearance of Pseudomonas aeruginosa but does amplify a proinflammatory response in a murine model of postseptic immunosuppression.
Patients that have suffered a major injury may sustain a period of immunocompromise and altered Th1/Th2 cytokine balance that can predispose them to opportunistic infections. Pseudomonas aeruginosa is frequently a causative organism for nosocomial infections in critically ill patients and is associated with high mortality. We previously mimicked this clinical scenario by challenging mice with P. aeruginosa 5 days after a cecal ligation and puncture (CLP) procedure. Mice that were subjected to CLP had reduced ability to clear bacteria, significantly lower gamma interferon (IFN-gamma) concentrations in plasma, and significantly elevated levels of interleukin 10 (IL-10) in plasma in response to the Pseudomonas challenge compared to uninjured control mice. We investigated the significance of the alteration in IFN-gamma by administering recombinant IFN-gamma to post-CLP mice at the time of Pseudomonas challenge and by challenging IFN-gamma knockout (IFN-gamma KO) mice with Pseudomonas. Administration of IFN-gamma to post-CLP mice attenuated IL-10 secretion and enhanced IL-12 secretion but did not improve bacterial clearance or survival after Pseudomonas challenge. Furthermore, IFN-gamma KO mice had significantly higher plasma IL-10 concentrations but did not exhibit impaired bacterial clearance or increased mortality following Pseudomonas challenge. These data indicate that systemic administration of IFN-gamma effectively reverses alterations in immune function that are commonly associated with immunosuppression in critically injured mice but does not improve bacterial clearance or survival following Pseudomonas challenge. Further, endogenous IFN-gamma does not appear to contribute significantly to early clearance of Pseudomonas bacteremia, nor does it affect the mortality rate after a lethal Pseudomonas challenge.


Hepatitis C virus infection in Jeddah city, Saudi Arabia: Seroprevalence and knowledge.
The infection rate of the hepatitis C virus (HCV) in Saudi Arabia is among the lowest in the world. However, it is likely that poor knowledge and awareness of HCV infection could minimize the effectiveness of prevention and control programs in the kingdom. Thus, the study objective was to estimate the prevalence of HCV infection, and to assess current knowledge about it, in the targeted population. Data on 5482 Saudi people attending primary healthcare centers in Jeddah City in 2014/2015 were analyzed in this cross-sectional study. Questions that covered the natural history, risk behavior, and prevention, and treatment of HCV were collected using a predesigned questionnaire. HCV seroprevalence was assessed using an enzyme-linked immunosorbent assay. HCV prevalence of 0.38% (95% confidence interval: 0.22-0.54) was found. The level of knowledge of the natural history, risk behavior, and prevention and treatment of HCV was poor among the participants. The lowest level of knowledge for all participants pertained to its prevention and treatment. The prevalence of HCV was low in Saudi Arabia (0.38%). However, adequate knowledge of HCV was lacking. Thus, the need to increase knowledge and awareness of HCV in the Saudi population is warranted.


Schistosoma japonicum: construction of phage display antibody library and its application in the immunodiagnosis of infection.
A monoclonal antibody would be an effective tool for the detection of circulating antigens in the serum of patients with schistosomiasis, but the traditional way of producing monoclonal antibodies is not cost-effective. The objective of this study was to find a new method for the large-scale production of monoclonal antibodies against Schistosoma japonicum (Sj). A phage display antibody library for Sj was constructed. To obtain a single-chain variable fragment antibody (scFv) against Sj, the library was screened with metabolic antigens from adult Sj worms (Sj-MAg) using enzyme-linked immunosorbent assay. The soluble scFvs selected were used to detect Sj antigens in the serum of acute and chronic schistosomiasis patients. Six positive clones with good reactivity to Sj-MAg were obtained from the phage display antibody library of about 1.07 x 10(6) individual clones. Only two of these six clones bound specifically to Sj-MAg and were chosen for further analysis. Specific soluble anti-Sj-MAg scFvs were produced by inducing the 2 clones with isopropyl-D-thiogalactopyranoside. The characteristics of the scFvs were then determined. The results of Western blot showed that these scFvs could bind to Sj-MAg specifically and had a molecular weight of about 31 kD. When testing serum from schistosomiasis patients with one of the two specific scFvs, its sensitivity was found to be 60% and 37% in acute and chronic patients, respectively, with a specificity of 90%. When the two specific scFvs were combined, their sensitivity was found to be 75% and 57% in acute and chronic patients, respectively, with a specificity of 85%. The results indicate that the scFvs are potentially useful for the diagnosis of schistosomiasis. The library construction also provides a useful tool for the further screening of other antibodies for both diagnostic and immunotherapeutic applications and for epitope analysis and vaccine design.


Therapy of disseminated or pulmonary coccidioidomycosis with ketoconazole.
Oral therapy with ketoconazole for active disseminated or progressive pulmonary coccidioidomycosis was evaluated according to defined criteria of objective improvement for 39 patients, most of whom had received other antifungal chemotherapy. Minimal inhibitory concentrations of ketoconazole for isolates of Coccidioides immitis were below mean peak serum concentrations. Eighteen patients responded at all sites of disease, one patient failed to respond, and the others either are being evaluated or cannot be evaluated. Most patients who responded to therapy required more than three months of treatment before the response was clearly noted. Responses were seen with skin, soft tissue, skeletal, and pulmonary infection as well as other conditions. Reversions of cultures for C. immitis to negative and decreases in titers of complement-fixing antibody were common. One patient relapsed after a course of therapy of only four months. In general, patients with skin disease who responded required only 200 mg per day, whereas those with skeletal disease required 400 mg per day. Adverse effects were uncommon despite extensive monitoring and were generally limited to transient nausea (with vomiting in patients receiving 400 mg per day). The data show that ketoconazole appears to be a promising new drug for treatment of coccidioidomycosis.


Tectonic implications of U-Pb zircon ages of the himalayan orogenic belt in nepal
Metasedimentary rocks of the Greater Himalaya are traditionally viewed as Indian shield basement that has been thrust southward onto Lesser Himalayan sedimentary rocks during the Cenozoic collision of India and Eurasia. Ages determined from radioactive decay of uranium to lead in zircon grains from Nepal suggest that Greater Himalayan protoliths were shed from the northern end of the East African orogen during the late Proterozoic pan-African orogenic event. These rocks were accreted onto northern Gondwana and intruded by crustal melts during Cambrian-Ordovician time. Our data suggest that the Main Central thrust may have a large amount of pre-Tertiary displacement, that structural restorations placing Greater Himalayan rocks below Lesser Himalayan rocks at the onset of Cenozoic orogenesis are flawed, and that some metamorphism of Greater Himalayan rocks may have occurred during early Paleozoic time.


Blue-Green Algae: Fine Structure of the Gas Vacuoles.
The gas vacuoles seen in several species of blue-green algae under the light microscope are shown by electron microscopy to correspond to packed arrays of cylindrical, electron-transparent vesicles. Single vesicles average 75 millimicrons in diameter, range from 0.2 micron to 1.0 micron in length, have conical ends, and are bounded by a single membrane 2 millimicrons wide. The reversible disappearance of gas vacuoles induced by sudden application of pressure is accompanied by a reversible collapse of the individual gas vesicles.


Introduction of Deep Learning in Thermographic Monitoring of Cultural Heritage and Improvement by Automatic Thermogram Pre-Processing Algorithms.
The monitoring of heritage objects is necessary due to their continuous deterioration over time. Therefore, the joint use of the most up-to-date inspection techniques with the most innovative data processing algorithms plays an important role to apply the required prevention and conservation tasks in each case study. InfraRed Thermography (IRT) is one of the most used Non-Destructive Testing (NDT) techniques in the cultural heritage field due to its advantages in the analysis of delicate objects (i.e., undisturbed, non-contact and fast inspection of large surfaces) and its continuous evolution in both the acquisition and the processing of the data acquired. Despite the good qualitative and quantitative results obtained so far, the lack of automation in the IRT data interpretation predominates, with few automatic analyses that are limited to specific conditions and the technology of the thermographic camera. Deep Learning (DL) is a data processor with a versatile solution for highly automated analysis. Then, this paper introduces the latest state-of-the-art DL model for instance segmentation, Mask Region-Convolution Neural Network (Mask R-CNN), for the automatic detection and segmentation of the position and area of different surface and subsurface defects, respectively, in two different artistic objects belonging to the same family: Marquetry. For that, active IRT experiments are applied to each marquetry. The thermal image sequences acquired are used as input dataset in the Mask R-CNN learning process. Previously, two automatic thermal image pre-processing algorithms based on thermal fundamentals are applied to the acquired data in order to improve the contrast between defective and sound areas. Good detection and segmentation results are obtained regarding state-of-the-art IRT data processing algorithms, which experience difficulty in identifying the deepest defects in the tests. In addition, the performance of the Mask R-CNN is improved by the prior application of the proposed pre-processing algorithms.


Endothelium-dependent relaxation factor released by perivascular adipose tissue.
Recent studies have demonstrated that perivascular adipose tissue (PVAT) releases vascular relaxation factor(s), but the identity of this relaxation factor remains unknown. Here, we examined if angiotensin 1-7 [Ang-(1-7)] is one of the relaxation factors released by PVAT. Morphological and functional methods were used to study aorta from adult Wistar rats. Immunohistochemical staining showed abundant presence of Ang-(1-7) in aortic PVAT. In vessels with PVAT removed but intact endothelium (PVAT - E+), contraction induced by phenylephrine was attenuated by preincubation with Ang-(1-7). PVAT - E+ vessels precontracted with phenylephrine showed a concentration-dependent relaxation response to Ang-(1-7), and this response was abolished by the removal of endothelium. Relaxation response induced by Ang-(1-7) was also prevented by Ang-(1-7) receptor (Mas) antagonist (A779), nitric oxide synthase inhibitor, and nitric oxide scavenger. Ang-(1-7) did not cause a relaxation response in aorta precontracted with KCl, and the relaxation response to Ang-(1-7) was also blocked by calcium-dependent potassium (K(Ca)) channel blockers. Incubation of PVAT + E+ vessels with A779 or angiotensin-converting enzyme 2 inhibitor DX600 or angiotensin-converting enzyme inhibitor enalaprilat increased the contraction induced by phenylephrine. Transfer of donor solution incubated with PVAT + E+ vessel to recipient PVAT - E+ vessel caused a relaxation response. This relaxation response was abolished when donor vessels were incubated with DX600 or enalaprilat or when recipient vessels were incubated with A779. Ang-(1-7) released by PVAT acts on the endothelium to cause the release of nitric oxide, and nitric oxide acts as a hyperpolarizing factor through K(Ca) channels to cause relaxation of the blood vessel.


A Comprehensive Machine Learning Benchmark Study for Radiomics-Based Survival Analysis of CT Imaging Data in Patients With Hepatic Metastases of CRC.
Optimizing a machine learning (ML) pipeline for radiomics analysis involves numerous choices in data set composition, preprocessing, and model selection. Objective identification of the optimal setup is complicated by correlated features, interdependency structures, and a multitude of available ML algorithms. Therefore, we present a radiomics-based benchmarking framework to optimize a comprehensive ML pipeline for the prediction of overall survival. This study is conducted on an image set of patients with hepatic metastases of colorectal cancer, for which radiomics features of the whole liver and of metastases from computed tomography images were calculated. A mixed model approach was used to find the optimal pipeline configuration and to identify the added prognostic value of radiomics features. In this study, a large-scale ML benchmark pipeline consisting of preprocessing, feature selection, dimensionality reduction, hyperparameter optimization, and training of different models was developed for radiomics-based survival analysis. Portal-venous computed tomography imaging data from a previous prospective randomized trial evaluating radioembolization of liver metastases of colorectal cancer were quantitatively accessible through a radiomics approach. One thousand two hundred eighteen radiomics features of hepatic metastases and the whole liver were calculated, and 19 clinical parameters (age, sex, laboratory values, and treatment) were available for each patient. Three ML algorithms-a regression model with elastic net regularization (glmnet), a random survival forest (RSF), and a gradient tree-boosting technique (xgboost)-were evaluated for 5 combinations of clinical data, tumor radiomics, and whole-liver features. Hyperparameter optimization and model evaluation were optimized toward the performance metric integrated Brier score via nested cross-validation. To address dependency structures in the benchmark setup, a mixed-model approach was developed to compare ML and data configurations and to identify the best-performing model. Within our radiomics-based benchmark experiment, 60 ML pipeline variations were evaluated on clinical data and radiomics features from 491 patients. Descriptive analysis of the benchmark results showed a preference for RSF-based pipelines, especially for the combination of clinical data with radiomics features. This observation was supported by the quantitative analysis via a linear mixed model approach, computed to differentiate the effect of data sets and pipeline configurations on the resulting performance. This revealed the RSF pipelines to consistently perform similar or better than glmnet and xgboost. Further, for the RSF, there was no significantly better-performing pipeline composition regarding the sort of preprocessing or hyperparameter optimization. Our study introduces a benchmark framework for radiomics-based survival analysis, aimed at identifying the optimal settings with respect to different radiomics data sources and various ML pipeline variations, including preprocessing techniques and learning algorithms. A suitable analysis tool for the benchmark results is provided via a mixed model approach, which showed for our study on patients with intrahepatic liver metastases, that radiomics features captured the patients' clinical situation in a manner comparable to the provided information solely from clinical parameters. However, we did not observe a relevant additional prognostic value obtained by these radiomics features.


Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation.
Primary sclerosing cholangitis (PSC) associated inflammatory bowel disease (IBD) is a unique form of IBD (PSC-IBD) with distinct clinical and histologic features from ulcerative colitis (UC) and Crohn disease (CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other. To study the histologic and clinical features of PSC patients with and without IBD. We assessed specimens from patients with UC (n = 28), CD (n = 10), PSC and UC (PSC-UC; n = 26); PSC and CD (PSC-CD; n = 6); and PSC and no IBD (PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation (OLT) were noted. PSC-UC patients had more isolated right-sided disease (P = 0.03), and less active inflammation in left colon, rectum (P = 0.03 and P = 0.0006), and overall (P = 0.0005) compared to UC. They required less steroids (P = 0.01) and fewer colectomies (P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC (P = 0.1). PSC-IBD (PSC-UC and PSC-CD) patients with OLT had severe disease in the left colon and rectum (P = 0.04). PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.


PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase lipoprotein lipase activity.
Omega-3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n-3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator-activated receptor alpha (PPARalpha). The objective was to examine the effects of n-3 FAs on LPL activity considering the occurrence of PPARalpha L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n-3 FAs. Second, transient transfections in HepG2 cells, for the L162- and V162-PPARalpha variants with the peroxisome proliferator-response element from the human LPL gene, were transactivated with n-3 FAs. In vivo results demonstrate that the LPL activity increased non-significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPARalpha-V162 allele, after n-3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162-PPARalpha than V162-PPARalpha after n-3 FAs activation. Overall, these results indicate that n-3 FA supplementation increases the transcription rate of LPL to a greater extent in L162-PPARalpha than V162-PPARalpha.


Subcellular localization of alpha-subunits of trimeric G-proteins in human platelets.
Following subcellular fractionation of platelet homogenates and Western blotting, two groups of alpha-subunits of trimeric G-proteins could be distinguished. Group 1 consisted of alpha(i)-2, alpha(i)-3, alpha(z), alpha(s), and alpha(q) and was predominantly localized in membranes. Group 2 consisted of alpha16 and alph12 and was predominantly localized in the cytosol. Plasma membranes and dense tubular system (DTS)-membranes showed the same distribution of Group 1 alpha-subunits. An exception was alpha(q), which was virtually absent in the DTS as were Group 2 subunits. In addition, this compartment showed a doublet for alpha(z). Group 1 alpha-subunits were also found in fractions with the combined secretory granules and in separate dense granules. In addition, alpha16 was found in these granule fractions, but secretion granules were devoid of alpha12. These data reveal a heterogeneous distribution of alpha-subunits in platelet compartments and may indicate that G12 and G16 play different roles in platelets than members of the G(i) and G(s) classes and other members of the G(q) class.


Extraction of tube current values from DICOM CT images for patient dose estimation.
When CT examinations are conducted with automatic mA modulation (z-axis modulation), the tube current (mA) may vary from one CT slice to next, i.e., mA is no longer a fixed constant. Hence, patient dose calculation is no longer a straightforward process. The purpose of this article is to show how the mA information may be extracted from DICOM CT images without having to manually read off "mA values" from the displayed images one at a time. A statistical programming language called "R," which is capable of reading DICOM files, is employed to extract the mA values from a series of DICOM CT images. This task is carried out with a "script" designed to read the mA values from the DICOM CT images and generate a file in "delimited ASCII" format. This file can be imported into a spreadsheet program such as Excel (a Microsoft spreadsheet program) for further processing, calculation, and chart production. A CT examination of the chest was selected to carry out this operation for demonstration purposes. The "script" generated a delimited ASCII "file" which is a two column data sheet with the slice location and its corresponding mA values. After the file is imported into Excel for calculation, and with other pertinent scan parameters, the average mA can now be plugged into a CT dosimetry calculation program such as ImPACT for calculation of CTDI*w, CTDIvol, dose-length-product, and critical organ doses. Furthermore, a graphical presentation of the "mA" vs slice location can be produced with Excel. The chart generated by Excel shows the variation in tube current as a function of slice location. The area under the mA curve is equal to a rectangle of "average mA" x "distance". Here, the distance is the range covered by the CT scan. The script that the authors have written is able to extract mA values from DICOM CT images, generating a delimited ASCII file for further processing with Microsoft Excel spreadsheet program. After the DICOM images are imported into a personal computer, this semiautomated process of extracting mA values enabled the authors to perform dose calculation for patients undergoing CT examination scanned with automatic mA modulation control.


Correlation of Histomorphological Findings with Bacteriological Index in Leprosy Patients.
Leprosy is characterized by various clinicopathological forms depending on the host's body. Therefore, the correlation of histopathological findings with bacteriological index is helpful in diagnosing, classification, and monitoring the treatment. We aimed to analyze the histomorphological findings correlation with the bacteriological index in different types of leprosy. Then, study the histopathological spectrum of leprosy. We carried out a histomorphological study of skin biopsies obtained from 100 new patients tested clinically in OPD (Out Patients Department) on the basis and calculation of bacteriological index on a slit-skin smear. The histomorphological findings correlation with the bacteriological index was to be found in different types of leprosy. In the histopathological studies, 52% of the patients were diagnosed with borderline tuberculoid (BT) followed by 20% with borderline lepromatous (BL), 13% with lepromatous leprosy (LL), 8% with tuberculoid (TT), 4% with histoid Hansen's disease, and 3% with mid-borderline (BB). On the clinical and histopathological examinations, correlation was found for 80% of the cases. Considering the correlation of histopathological features with the bacteriological index, 63% of the cases showed good correlation which was comparable with that of other studies. Because of the underlying symptoms of leprosy, there is a difference between different types of leprosy and the clinical and environmental perceptions. Thus, the correlation of clinical, histopathological, and bacteriological indices could be more helpful in the diagnosis of leprosy rather than considering only one parameter.


Requirements for Proper Immunosuppressive Regimens to Limit Translational Failure of Cardiac Cell Therapy in Preclinical Large Animal Models.
Various cell-based therapies are currently investigated in an attempt to tackle the high morbidity and mortality associated with heart failure. The need for these therapies to move towards the clinic is pressing. Therefore, preclinical large animal studies that use non-autologous cells are needed to evaluate their potential. However, non-autologous cells are highly immunogenic and trigger immune rejection responses resulting in potential loss of efficacy. To overcome this issue, adequate immunosuppressive regimens are of imminent importance but clear guidelines are currently lacking. In this review, we assess the immunological barriers regarding non-autologous cell transplantation and immune modulation with immunosuppressive drugs. In addition, we provide recommendations with respect to immunosuppressive regimens in preclinical cardiac cell-replacement studies.


Overexpression of the Long Non-coding RNA SChLAP1 Independently Predicts Lethal Prostate Cancer.
The long noncoding RNA SChLAP1 is overexpressed in a subset of prostate cancers (PCa), and high SChLAP1 expression by in situ hybridization (ISH) independently predicts biochemical recurrence after radical prostatectomy. Importantly, although biochemical recurrence is a significant clinical outcome, it is not a validated surrogate for PCa-related mortality. Thus, we evaluated the association between SChLAP1 expression and development of lethal PCa in a large cohort of American men with PCa and long-term follow-up. SChLAP1 ISH was performed on tissue microarrays containing representative formalin-fixed, paraffin-embedded PCa tissue from all patients and scored using a semiquantitative method (ISH score range 0-400). Hazard ratios (HRs) for the association between SChLAP1 expression and time to development of lethal PCa were estimated using multivariable Cox regression analysis. Of the 937 patients evaluated, 89 (9.5%) had high SChLAP1 expression (ISH score ≥100), which in patients treated with radical prostatectomy was strongly associated with development of lethal PCa independent of age, Gleason score, pathologic stage, and PTEN status (HR 2.2, 95% confidence interval 1.1-4.1). These results suggest that SChLAP1 may be a useful tissue-based biomarker for identifying PCa patients at higher risk of lethal progression. We examined expression of the RNA molecule SChLAP1 in a large group of prostate cancer patients with long-term follow-up and found that patients with high SChLAP1 expression had a significantly higher chance of developing lethal disease.


[An evaluation of the immediate results of performing esophagogastroplasty].
The results of oesophageal resection with one-staged oesophagogastroplasty were studied up in 108 patients. The mechanical suture failure occurred in 12 (16.4%) of 73 patients, after the manual-forming anastomosis conduction this complication did not occur. The method of the anastomosis forming using one-raw manual suture with plication by anterior gastric wall proved to be the most secure one. Application of this method together with prophylaxis of thromboembolic and respiratory disorders have permitted to reduce mortality by 2.5 times.


Spectroscopy of a rotating hydrogen molecule in carbon nanotubes.
A first-principles study of the spectroscopy of a single hydrogen molecule rotating inside and outside of carbon nanotubes is presented. Density functional theory (DFT)-based symmetry-adapted perturbation theory (SAPT) is applied to analyze the influence of the rotation in the dispersionless and dispersion energy contributions to the adsorbate-nanotube interaction. A potential model for the H2-nanotube interaction is proposed and applied to derive the molecular energy levels of the rotating hydrogen molecule. The SAPT-based analysis shows that a subtle balance between the dispersionless and dispersion contributions is key in determining the angular dependence of the H2-nanotube interaction, which is strongly influenced by the diameter of the carbon nanotubes. As a consequence, the structure of molecular energy levels is very different in wide and narrow nanotubes with the diameter above and below 1 nanometer, respectively. Strong anisotropy effects lead to a rather constrained rotation of molecular hydrogen inside narrow nanotubes.


Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.
Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less studied model of 'eustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.


New hydroxylated metabolites of 4-monochlorobiphenyl in whole poplar plants.
Two new monohydroxy metabolites of 4-monochlorobiphenyl (CB3) were positively identified using three newly synthesized monohydroxy compounds of CB3: 2-hydroxy-4-chlorobiphenyl (2OH-CB3), 3-hydroxy-4-chlorobiphenyl (3OH-CB3) and 4-hydroxy-3-chlorobiphenyl (4OH-CB2). New metabolites of CB3, including 2OH-CB3 and 3OH-CB3, were confirmed in whole poplars (Populus deltoides × nigra, DN34), a model plant in the application of phytoremediation. Furthermore, the concentrations and masses of 2OH-CB3 and 3OH-CB3 formed in various tissues of whole poplar plants and controls were measured. Results showed that 2OH-CB3 was the major product in these two OH-CB3s with chlorine and hydroxyl moieties in the same phenyl ring of CB3. Masses of 2OH-CB3 and 3OH-CB3 in tissues of whole poplar plants were much higher than those in the hydroponic solution, strongly indicating that the poplar plant itself metabolizes CB3 to both 2OH-CB3 and 3OH-CB3. The total yield of 2OH-CB3 and 3OH-CB3, with chlorine and hydroxyl in the same phenyl ring of CB3, was less than that of three previously found OH-CB3s with chlorine and hydroxyl in the opposite phenyl rings of CB3 (2'OH-CB3, 3'OH-CB3, and 4'OH-CB3). Finally, these two newly detected OH-CB3s from CB3 in this work also suggests that the metabolic pathway was via epoxide intermediates. These five OH-CB3s clearly showed the complete metabolism profile from CB3 to monohydroxylated CB3. More importantly, it's the first report and confirmation of 2OH-CB3 and 3OH-CB3 (new metabolites of CB3) in a living organism.


[Isolation and study of hybrid plasmids carrying Escherichia coli threonine operon genes].
A fragment of Escherichia coli chromosome containing the intact threonine operon or its distinct genes has been cloned on the pBR322 plasmid. This fragment has been mapped using some restriction endonucleases. Cloning results in an increased level of appropriate enzyme activity in cells containing hybrid plasmids. Those carrying the complete threonine operon are capable of accumulating threonine up to 5 g/l in culture medium during 48 h. When multi-copy plasmids are used for gene cloning, interpretation of experiments aimed at transformation of auxotrophic bacterial strains, might be complicated. For example, transformation of appropriate threonine auxotrophs by a hybrid plasmid carrying mutation in the threonine gene, might result in prototrophic phenotype. It is possible that the great amount of mutant enzyme molecules compensated their low activity. On the contrary, the presence of a gene within the plasmid, as shown by restriction and biochemical analysis, did not always ensure the growth on a minimal medium of auxotrophs transformed by this plasmid.


Ten year research update (2001-2010): evaluations for competence to stand trial (adjudicative competence).
This article reviews and evaluates publications during 2001-2010 with relevance for assessments of competence to stand trial, referred to in this article as adjudicative competence. The review focuses specifically on articles that provide new concepts or data supported by research or case analyses. The studies are reviewed under the following headings: (i) systemic issues, (ii) conceptual guidelines for AC evaluations, (iii) AC assessment methods, (iv) empirical correlates of AC judgments and psycholegal abilities, (v) quality of AC evaluations and reports, (vi) interpretive issues, (vii) special populations (defendants who are elderly, defendants with intellectual disabilities), (viii) AC evaluations of juveniles, and (ix) treatment of incompetent defendants. Suggestions are offered for further research to advance the quality of clinical evaluations of adjudicative competence.


Validation and comparison of four handheld tonometers in normal ex vivo canine eyes.
To determine the accuracy and precision of the Icare® TONOVET Plus rebound tonometer and the Tono-Pen AVIA Vet™ applanation tonometer for intraocular pressure (IOP) measurement in normal ex vivo canine eyes and comparison to earlier models of these tonometers. The anterior chambers of six normal dog eyes were cannulated ex vivo. IOP was measured with the TONOVET (TV01), TONOVET Plus, Tono-Pen Vet™, and Tono-Pen AVIA Vet™ at manometric IOPs ranging from 5 to 70 mm Hg. Data were analyzed by linear regression, ANOVA and Bland-Altman plots. A P value ≤ .05 was considered significant. Intraocular pressure values obtained using the TONOVET Plus and TV01 were significantly more accurate than with the Tono-Pen VET and Tono-Pen AVIA Vet, particularly at higher IOPs (30-70 mm Hg). Accuracy was not significantly different between any of the devices in the low to normal physiologic IOP range (5-25 mm Hg). Level of precision was high for all devices, though the TONOVET Plus was more precise than the Tono-Pen Vet in the 5-25 mmHg range and the TV01 was more precise than the Tono-Pen AVIA Vet over the whole IOP range. All devices underestimated IOP, particularly at higher pressures. Rebound tonometers were more accurate over the full range of IOP tested and in the high IOP range; however, there were no significant differences in accuracy among devices in the physiologic IOP range. All tonometers can provide clinically useful IOP readings in dogs, but rebound and applanation tonometers should not be used interchangeably.


PON3 is upregulated in cancer tissues and protects against mitochondrial superoxide-mediated cell death.
To achieve malignancy, cancer cells convert numerous signaling pathways, with evasion from cell death being a characteristic hallmark. The cell death machinery represents an anti-cancer target demanding constant identification of tumor-specific signaling molecules. Control of mitochondrial radical formation, particularly superoxide interconnects cell death signals with appropriate mechanistic execution. Superoxide is potentially damaging, but also triggers mitochondrial cytochrome c release. While paraoxonase (PON) enzymes are known to protect against cardiovascular diseases, recent data revealed that PON2 attenuated mitochondrial radical formation and execution of cell death. Another family member, PON3, is poorly investigated. Using various cell culture systems and knockout mice, here we addressed its potential role in cancer. PON3 is found overexpressed in various human tumors and diminishes mitochondrial superoxide formation. It directly interacts with coenzyme Q10 and presumably acts by sequestering ubisemiquinone, leading to enhanced cell death resistance. Localized to the endoplasmic reticulum (ER) and mitochondria, PON3 abrogates apoptosis in response to DNA damage or intrinsic but not extrinsic stimulation. Moreover, PON3 impaired ER stress-induced apoptotic MAPK signaling and CHOP induction. Therefore, our study reveals the mechanism underlying PON3's anti-oxidative effect and demonstrates a previously unanticipated function in tumor cell development. We suggest PONs represent a novel class of enzymes crucially controlling mitochondrial radical generation and cell death.


Blood flow to the pancreatic islet parenchyma of the Atlantic hagfish (Myxine glutinosa).
The islet organ of the Atlantic hagfish, a cyclostome, phylogenetically is the most original islet parenchyma. It is well equipped with blood vessels, but lacks nerves. The aim of the present study was to evaluate the relative proportions between regional blood flows in these animals with a microsphere technique and with laser-Doppler flowmetry. As regards the results obtained in the kidneys, gills, and islet organ, the data were essentially the same found using both methods. Approximately 20% of the injected microspheres were found in the kidneys; when corrected for weight, the gill bodies and the islet organ were also found to have the same blood perfusion. The blood flow to the brain and that of the gut and the liver were only approximately 30% and 10%, respectively, of that to the kidney. Topical application of the nitric oxide donor, sodium nitroprusside failed to affect the islet blood flow. Apart from this observation, this non-innervated "primitive" islet parenchyma did not differ from that of the amply innervated mammalian islets with regard to their high basal blood perfusion.


A random effects multinomial logit analysis of using Medicare and VA healthcare among veterans with dementia.
This study aimed to examine longitudinal patterns of VA-only use, dual VA and Medicare use, or Medicare-only use among veterans with dementia. Data on VA and Medicare use (1998-2001) were obtained from VA administrative datasets and Medicare claims for 2,137 male veterans with a formal diagnosis of Alzheimer's disease or vascular dementia enrolled in the National Longitudinal Caregiver Study. A random effects multinomial logit model accounting for unobserved individual heterogeneity was used to estimate the effects of patient and caregiver characteristics on use group over time. Compared to VA-only use, dual VA and Medicare use was associated with being white, married, higher education, having private insurance, Medicaid, low VA priority level, more functional limitations, and having lived in a nursing home or died in that year. Medicare-only use was associated with older age, being married, higher education, having private insurance, low VA priority level, living further from a VA Medical Center, having more comorbidities, functional limitations, and having lived in a nursing home or died. Veterans whose caregivers reported better health were more likely to be dual users, but those whose caregivers reported more comorbidities were more likely to use Medicare only. Different aspects of veterans' needs and caregiver characteristics have differential effect on where veterans seek care. Efforts to coordinate care between VA and Medicare providers are necessary to ensure patients receive high quality care.


Antipsychotic-induced alterations in CB1 receptor-mediated G-protein signaling and in vivo pharmacology in rats.
Dysregulation of the endocannabinoid and dopamine systems has been implicated in schizophrenia. The purpose of this study was to examine the effects of sub-chronic treatment with two antipsychotics on CB1 receptor-mediated in vitro and in vivo effects. Adult and adolescent male and female rats were injected twice daily with haloperidol (0.3 mg/kg), clozapine (10 mg/kg), or saline for 10 days. Subsequently, CB1 receptor number and function were assessed by [3H]SR141716 and WIN55,212-2-stimulated [35S]GTPgammaS binding, respectively. The effects of sub-chronic antipsychotic treatment on the in vivo actions of Delta9-tetrahydrocannabinol (Delta9-THC) were also evaluated. In adult female rats, antipsychotic treatment attenuated maximal stimulation of CB1 receptor-mediated G-protein activity in the striatum (clozapine) and prefrontal cortex (both antipsychotics), but not in the ventral midbrain. Associated changes in CB1 receptor number were not observed, suggesting that this attenuation was not due to downregulation. In vivo, sub-chronic treatment with clozapine, but not haloperidol, attenuated Delta9-THC-induced suppression of activity in adult females, whereas neither drug altered hypothermia or catalepsy. In contrast, antipsychotic treatment did not change CB1 receptor-mediated G-protein activation in any brain region in adult male rats and in adolescents of either sex. In vivo, haloperidol, but not clozapine, enhanced Delta9-THC-mediated suppression of activity and hypothermia in adult male rats whereas neither antipsychotic affected Delta9-THC-induced in vivo effects in adolescent rats. These findings suggest that modulation of the endocannabinoid system might contribute in a sex- and age-selective manner to differences in motor side effects of clozapine versus haloperidol.


The ERBB network facilitates KRAS-driven lung tumorigenesis.
KRAS is the most frequently mutated driver oncogene in human adenocarcinoma of the lung. There are presently no clinically proven strategies for treatment of KRAS-driven lung cancer. Activating mutations in KRAS are thought to confer independence from upstream signaling; however, recent data suggest that this independence may not be absolute. We show that initiation and progression of KRAS-driven lung tumors require input from ERBB family receptor tyrosine kinases (RTKs): Multiple ERBB RTKs are expressed and active from the earliest stages of KRAS-driven lung tumor development, and treatment with a multi-ERBB inhibitor suppresses formation of KRASG12D-driven lung tumors. We present evidence that ERBB activity amplifies signaling through the core RAS pathway, supporting proliferation of KRAS-mutant tumor cells in culture and progression to invasive disease in vivo. Brief pharmacological inhibition of the ERBB network enhances the therapeutic benefit of MEK (mitogen-activated protein kinase kinase) inhibition in an autochthonous tumor setting. Our data suggest that lung cancer patients with KRAS-driven disease may benefit from inclusion of multi-ERBB inhibitors in rationally designed treatment strategies.


Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations.
Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over time through negative frequency-dependent (FD) selection, can evolve in short-lived species with no generational overlap, where they produce rapid morph frequency cycles. However, most species have overlapping generations and thus, rapid RPS dynamics are thought to require stronger FD selection, the existence of which yet needs to be proved. Here, we experimentally demonstrate that two cumulative selective episodes, FD sexual selection reinforced by FD selection on offspring survival, generate sufficiently strong selection to generate rapid morph frequency cycles in the European common lizard Zootoca vivipara, a multi-annual species with major generational overlap. These findings show that the conditions required for the evolution of RPS games are fulfilled by almost all species exhibiting genetic polymorphisms and suggest that RPS games may be responsible for the maintenance of genetic diversity in a wide range of species.


Relationship Between Symptoms and Health-related Quality-of-life Benefits in Patients With Carcinoid Syndrome: Post Hoc Analyses From TELESTAR.
Patients with metastatic neuroendocrine tumors and carcinoid syndrome (CS) may experience chronic, recurring symptoms despite somatostatin analogue therapy. Little is known about the relationship between bowel movement (BM) frequency, patient-reported symptoms and health-related quality of life (QoL). Data from the TELESTAR study were used in exploratory, post hoc analyses to understand the relationship between durable reductions in BM frequency, symptom relief, and health-related QoL. Patients with metastatic neuroendocrine tumors and CS in the Phase III TELESTAR study were randomized (1:1:1) to receive telotristat ethyl (TE) 250 mg, TE 500 mg, or placebo three times daily (TID) during a 12-week double-blind treatment period (DBTP). All patients received TE 500 mg TID in an open-label extension (OLE) to Week 48. Durable response was predefined. Analyses compared durable responders (DRs) and non-durable responders (NDRs), irrespective of treatment group, at Weeks 12, 24, and 48. At the start of the DBTP, 135 patients were randomized, 45 patients each to TE 250 mg, TE 500 mg, and placebo. After the 12-week DBTP, 48 of 135 patients were DRs (TE 250 mg, n = 20; TE 500 mg, n = 19; placebo, n = 9). Of the 115 patients who entered the OLE, 35 were DRs initially randomized to TE 250 mg (n = 18) or 500 mg (n = 17), 29 of whom maintained a durable response throughout the OLE. Of the 71 DBTP-NDRs (inclusive of patients initially randomized to placebo), 28 became OLE-DRs. There were 29 NDRs initially randomized to placebo who entered the OLE, 16 of whom became DRs when switched to TE 500 mg. DRs during the DBTP had greater symptom improvements in the DBTP; these improvements continued over the OLE. DBTP-DRs also maintained more meaningful QoL improvements in EORTC QLQ-C30 global health status, nausea and vomiting, pain, diarrhea, and EORTC QLQ-GINET21 gastrointestinal symptoms over the DBTP and OLE periods than DBTP-NDRs. These results suggest that sustained improvements in BM frequency in patients with CS may have multifaceted, long-term effects on a patient's well-being. ClinicalTrials.gov identifiers: NCT01677910.


Kidney Disease Profiles Among Adolescents In Indonesia.
Each kidney injury may develop into chronic kidney disease (CKD) and end stage renal disease (ESRD) that associates with high mortality and socio-economic burden. There is limited data about clinical characteristics of children having CKD in developing countries, espesially in Indonesia. To describe clinical profiles and characteristics of kidney diseases in adolescents aged 15-18 years. This study was a cross-sectional study which used data from National Basic Health Survey (Riskesdas) 2013. There were 2 data groups. The first data group included questionnaires about history of kidney stone disease, hypertension, chronic renal failure, antihypertension administration, and blood pressure measurement. The second data group included subsamples of the first group which had laboratory test results, i.e. hemoglobin and serum creatinine levels. All of the data were classified by nutritional status, estimated glomerulofiltration rate (eGFR), blood pressure classification, and hemoglobin level. Among 52,454 adolescents in the first data group, 20,537 (39%) had kidney diseases with female predominance and good nutritional status. Other findings found were history of kidney stone disease (0.2%), chronic renal failure (0.1%), history of hypertension (0.6%), antihypertensive agents consumption (0.1%). Prehypertension and hypertension were found in 51% and 48.3% of adolescents, respectively. Adolescents with decreased eGFR were accounted for 1.4%. The proportion of prehypertension and hypertension in adolescents aged 15-18 years in Indonesia is high. Hence, routine blood pressure measurement is important for early detection and prevention of kidney disease progression.


Intrinsic projections within visual cortex: evidence for orientation-specific local connections.
The functional organization of intrinsic connections within area 18 of cat visual cortex was studied using combined electrophysiological and anatomical techniques. Physiological recordings were first used to map the distribution of orientation preference, ocular dominance, and receptive-field location relative to the cortical surface. Next, localized injections of lectin-conjugated horseradish peroxidase were made into physiologically identified regions within area 18. We found that (i) the local cortical interconnections are made preferentially between cell populations with orthogonal preferred orientations and are independent of the ocular dominance of the cortical cells, (ii) the map of visual space in the cortex is anisotropic with the magnification factor for vertical at least twice that for horizontal visual space, and (iii) the pattern of cortical projections compensates for the functional asymmetry so that a population of interconnected cells represents a roughly circular region of visual space.


Thromboelastography Reaction-Time Thresholds for Optimal Prediction of Coagulation Factor Deficiency in Trauma.
Coagulopathy is common in multitrauma patients and repletion of procoagulant factor deficiency with fresh frozen plasma (FFP) improves hemostasis. Optimal kaolin-thromboelastography thresholds for FFP transfusion in trauma patients have not been well established. Adult trauma patients with an Injury Severity Score ≥15 were included in this retrospective observational cohort study. The primary end point was area under the receiver operating characteristic curve (AUROC) for reaction time (R-time) to detect procoagulant factor deficiency, as reflected by an elevated international normalized ratio (INR) or aPTT. Test characteristics for the optimal R-time threshold calculated in our study were compared against thresholds recommended by the American College of Surgeons for FFP transfusion. Six hundred and ninety-four pairs of thromboelastography and conventional coagulation tests were performed in 550 patients, with 144 patients having additional pairs of tests after the first hour. The R-time was able to detect procoagulant factor deficiency (INR ≥1.5 AUROC 0.80; 95% CI, 0.75 to 0.85; aPTT ≥40 seconds AUROC 0.85; 95% 0.80 to 0.89) and severe procoagulant factor deficiency (INR ≥2.0 AUROC 0.82; 95% CI, 0.73 to 0.99; aPTT ≥60 seconds AUROC 0.89; 95% CI, 0.81 to 0.98) with good accuracy. Optimal thresholds to maximize sensitivity and specificity were 3.9 minutes for detection of INR ≥1.5, 4.1 minutes for detection of aPTT ≥40 seconds, 4.3 minutes for detection of INR ≥2.0, and 4.3 for detection of aPTT ≥60 seconds. Currently recommended R-time thresholds for FFP transfusion had 100% specificity for detecting procoagulant factor deficiency, but low sensitivity (3% to 7%). R-time can detect procoagulant factor deficiency in multitrauma patients with good accuracy, but currently recommended R-time thresholds are highly specific and not sensitive. Use of low-sensitivity thresholds might result in undertreatment of many patients with procoagulant factor deficiency.


Cognitive impairment following chemotherapy for breast cancer: The impact of practice effect on results.
Chemotherapy-Related Cognitive Impairment (CRCI) can be an adverse effect in women treated for breast cancer. Some longitudinal studies reported deficits in attention, memory, and executive function following treatment, but other studies did not find cognitive changes. It is known that practice effects (PE) on repeated assessments with cognitive tests contribute to the discrepancies in these results, but its influence on scores has not been systematically explored. The present study examines the impact of PE on retest scores in a group of women with breast cancer treated with chemotherapy and evaluated longitudinally. 51 women with breast cancer treated with a combination of 5-fluorouracil, epirubicin, and cyclophosphamide with or without taxanes were assessed after surgery but before chemotherapy (T1), post-chemotherapy (T2), and at one year after T2 (T3). Longitudinal changes on cognitive performance were analyzed twice: when retest scores were not corrected for PE and when correction for PE was applied to T2 and T3 scores. When PE was not corrected, progressive improvement over time in measures of memory and divided attention at T2 and T3 was observed. In contrast, when PE was corrected, worsening was found in measures of memory, fluency, executive function, and attention at T2 and in attention and executive function at T3. Results after correction for PE are in line with previous longitudinal studies that report cognitive impairment after treatment with chemotherapy for breast cancer. Accounting for PE is recommended to identify true change on cognition through treatment with chemotherapy for breast cancer.


Iron Deficiency is Prevalent among HIV-Infected Kenyan Adults and is Better Measured by Soluble Transferrin Receptor than Ferritin.
Iron deficiency (ID) and human immunodeficiency virus (HIV) infection frequently coexist. Little data exist on ID in HIV-infected individuals, partly because the iron marker ferritin is altered by inflammation common in HIV infection. We measured iron biomarkers (ferritin, soluble transferrin receptor [sTfR], hepcidin) and red cell indices (hemoglobin, mean corpuscular volume [MCV]) in newly diagnosed, antiretroviral therapy-naive, HIV-infected (N = 138) and uninfected (N = 52) Kenyan adults enrolled in a study of the immune response to malaria. We compared markers between infected and uninfected groups with t test and Wilcoxon Rank-Sum, used Spearman correlation to determine the association between iron and inflammatory markers, and applied logistic regression to determine which markers best predicted anemia. HIV-infected individuals had lower hemoglobin (P < 0.001), lower MCV (P < 0.001), higher sTfR (P = 0.003), and a greater prevalence of ID (sTfR > 8.3 mg/L) than uninfected individuals. Ferritin was elevated in HIV-infected individuals and was more strongly correlated with C-reactive protein (ρ = 0.43, P < 0.001) and hepcidin (ρ = 0.69, P < 0.001) than with hemoglobin. The best predictor of anemia in HIV-infected participants was sTfR, with a one log-unit increase in sTfR associated with a 6-fold increase in the odds of anemia (odds ratio = 6.3, 95% confidence interval: 1.8-21.8). These data suggest a significant burden of ID among treatment-naive HIV-infected Kenyan adults. Soluble transferrin receptor may be a reliable marker of ID in HIV-mediated inflammation.


Mitigation efforts will not fully alleviate the increase in water scarcity occurrence probability in wheat-producing areas.
Global warming is expected to increase the frequency and intensity of severe water scarcity (SWS) events, which negatively affect rain-fed crops such as wheat, a key source of calories and protein for humans. Here, we develop a method to simultaneously quantify SWS over the world's entire wheat-growing area and calculate the probabilities of multiple/sequential SWS events for baseline and future climates. Our projections show that, without climate change mitigation (representative concentration pathway 8.5), up to 60% of the current wheat-growing area will face simultaneous SWS events by the end of this century, compared to 15% today. Climate change stabilization in line with the Paris Agreement would substantially reduce the negative effects, but they would still double between 2041 and 2070 compared to current conditions. Future assessments of production shocks in food security should explicitly include the risk of severe, prolonged, and near-simultaneous droughts across key world wheat-producing areas.


Electrodeposition of thick palladium coatings from a palladium(II)-containing ionic liquid.
The first palladium-containing Liquid Metal Salts (LMS) are presented and shown to be suitable electrolytes for the electrodeposition of palladium. The homoleptic LMS of formula [Pd(MeIm)4][Tf2N]2 or [Pd(EtIm)4][Tf2N]2 (MeIm = N-methylimidazole, EtIm = N-ethylimidazole) have higher melting points than the heteroleptic [Pd(MeIm)2(EtIm)2][Tf2N]2, which is proved to be the most promising electrolyte. The deposition reaction in these LMS was found to be irreversible but smooth and dense palladium layers can be deposited that are crack-free up to a thickness of 10 microns.


Supernatural beliefs, aetiological models and help seeking behaviour in patients with schizophrenia.
Few studies have evaluated the supernatural beliefs of patients with schizophrenia. This study aimed to study the personal beliefs, aetiological models and help seeking behaviour of patients with schizophrenia using a self-rated questionnaire. Seventy three patients returned the completed supernatural Attitude questionnaire. 62% of patients admitted that people in their community believed in sorcery and other magico-religious phenomena. One fourth to half of patients believed in ghosts/evil spirit (26%), spirit intrusion (28.8%) and sorcery (46.6%). Two-third patients believed that mental illness can occur either due to sorcery, ghosts/evil spirit, spirit intrusion, divine wrath, planetary/astrological influences, dissatisfied or evil spirits and bad deeds of the past. 40% of the subjects attributed mental disorders to more than one of these beliefs. About half of the patients (46.6%) believed that only performance of prayers was sufficient to improve their mental status. Few patients (9.6%) believed that magico-religious rituals were sufficient to improve their mental illness but about one-fourth (24.7%) admitted that during recent episode either they or their caregivers performed magico-religious rituals. Supernatural beliefs are common in patients with schizophrenia and many of them attribute the symptoms of mental disorders to these beliefs.


[Characteristics of acoustic neuroma in the group of schwannomas of different localizations].
Neurinomas and schwannomas affect sensitive fibers almost exclusively. Among craniocerebral neurinomas, nerve VIII neurinomas account for 90%, occurring 30 to 40 times more frequently as compared to nerve V neurinomas. The latter circumstance may be determined by more complex evolution of the vestibular ganglion as compared to the Gasserian ganglion. Nerve VIII neurinoma never becomes malignant whereas the peripheral spinal nerves and radicles undergo degeneration to sarcomas in 17% of cases. As for neurologic oncology, there are no sex differences in the disease incidence. However, women get afflicted with nerve VIII neurinoma several times more often than men.


Active Range of Motion Measurement System Using an Optical Sensor to Evaluate Hand Functions.
Impairment of hand function greatly affects the independence of a human being. Proper assessment of hand function before and after any treatment for functional restoration is important to decide better treatment strategies. Despite traditional techniques of hand function evaluation, individual joint based assessment is vital to better track the details of the hand function. Current clinical assessments with goniometers are labour intensive, cumbersome and highly depend on the skill level of the practitioner. This study introduces an active range of motion (AROM) measurement system to measure individual range of motion of finger joints using an optical sensor. The proposed method is highly efficient, and the results demonstrated that the measurements are instant, repeatable and can successfully be employed in a clinical setup for patient evaluations.Clinical Relevance-Closely working with clinician to develop rehabilitation systems, we have identified that the assessment of patient hand functions is time consuming, and accuracy can be depended on the skill level of the practitioner in measuring joint range of motions (ROM). System introduced in this study can measure the joint AROMs instantly and independent of the practitioner's skill level and hence can provide a reliable, repeatable assessment of patient's hand function.


Hyponatremia in dogs and cats.
To review the pathophysiology, diagnostic approach, and treatment recommendations for hyponatremia in dogs and cats. Hyponatremia almost always results from an increase in total body water (TBW), and not from loss of sodium. Abnormalities in antidiuretic hormone (ADH) are commonly part of the etiology of hyponatremia. Diagnosis of hyponatremia focuses on the cause of the increase of TBW. Assessment of the patient's volume status and measurement of urine sodium concentration are important factors. Measurement or calculated estimation of plasma osmolality can also guide the assessment of hyponatremia. Too rapid correction of serum sodium can precipitate osmotic demyelination syndrome. As a general rule, serum sodium concentration should be raised ≤10 mmol/L over 24 hours, but rapid increases in serum sodium are indicated if neurologic abnormalities are evident. Serum sodium can be increased using hypertonic saline, with dosing based on the patient's calculated sodium deficit. Treatment of the underlying cause of water ingestion or retention is also required to fully resolve hyponatremia. Mortality rates are significantly higher in dogs and cats with hyponatremia compared to those with normal serum sodium concentrations, even in patients with mild hypontremia (<5 mmol/L below the lower value of the reference interval). Hyponatremia is also associated with increased risk of death if present during specific disease states in dogs.


Multiscale simulation of the focused electron beam induced deposition process.
Focused electron beam induced deposition (FEBID) is a powerful technique for 3D-printing of complex nanodevices. However, for resolutions below 10 nm, it struggles to control size, morphology and composition of the structures, due to a lack of molecular-level understanding of the underlying irradiation-driven chemistry (IDC). Computational modeling is a tool to comprehend and further optimize FEBID-related technologies. Here we utilize a novel multiscale methodology which couples Monte Carlo simulations for radiation transport with irradiation-driven molecular dynamics for simulating IDC with atomistic resolution. Through an in depth analysis of [Formula: see text] deposition on [Formula: see text] and its subsequent irradiation with electrons, we provide a comprehensive description of the FEBID process and its intrinsic operation. Our analysis reveals that simulations deliver unprecedented results in modeling the FEBID process, demonstrating an excellent agreement with available experimental data of the simulated nanomaterial composition, microstructure and growth rate as a function of the primary beam parameters. The generality of the methodology provides a powerful tool to study versatile problems where IDC and multiscale phenomena play an essential role.