Maize tonoplast PP(i)-dependent H(+)/Ca(2+) exchange: two K(s) for Ca(2+) and inhibition by thapsigargin.
Maize root tonoplasts are able to accumulate Ca(2+) using the energy derived from the H(+) gradient formed during PP(i) hydrolysis. Oxalate increases 6- to 10-fold the amount of Ca(2+) accumulated by tonoplast. Two apparently different K(s) values for Ca(2+) with values of 0.36 and 4.70 microM were detected when oxalate was included in the medium and the free Ca(2+) concentration in the medium was buffered with the use of EGTA. Binding of Ca(2+) to the outer surface of tonoplasts inhibits the outflow of Ca(2+) previously accumulated by the tonoplast, half-maximal inhibition being observed in presence of 1 microM Ca(2+). Thapsigargin, a specific inhibitor of Ca(2+)-ATPase, inhibits the Ca(2+) uptake driven by H(+) gradient but does not inhibit the hydrolysis of PP(i) nor the formation of a H(+) gradient.


Facing ostracism: micro-coding facial expressions in the Cyberball social exclusion paradigm.
Social exclusion is often measured with the Cyberball paradigm, a computerized ball-tossing game. Most Cyberball studies, however, used self-report questionnaires, leaving the data vulnerable to reporter bias, and associations with individual characteristics have been inconsistent. In this large-scale observational study, we video-recorded 4,813 10-year-old children during Cyberball and developed a real-time micro-coding method measuring facial expressions of anger, sadness and contempt, in a multi-ethnic population-based sample. We estimated associations between facial expressions and self-reported negative feelings, explored associations of child characteristics such as sex and parental national origin with observed and self-reported feelings during social exclusion, and tested associations of observed and self-reported feelings during social exclusion with behavior problems at age 14. Facial expressions of sadness and anger were associated with self-reported negative feelings during the game, but not with such feelings after the game. Further, girls reported to have had less negative feelings during the game than boys, but no such sex-differences were found in total observed emotions. Likewise, children with parents of Moroccan origin reported less negative feelings during the game than Dutch children, but their facial expressions did not indicate that they were differently affected. Last, observed emotions related negatively to later internalizing problems, whereas self-report on negative feelings during the game related positively to later internalizing and externalizing problems. We show that facial expressions are associated with self-reported negative feelings during social exclusion, discuss that reporter-bias might be minimized using facial expressions, and find divergent associations of observed facial expressions and self-reported negative feelings with later internalizing problems.


Experience with medroxyprogesterone acetate (Depo-Provera) as an injectable contraceptive.
Depo-Provera injections appear to be a safe and effective alternative for women who cannot tolerate the estrogenic side effects associated with oral contraceptives or the pain and bleeding associated with IUDs. However, women considering the method should be fully aware of the possible risks: (a) inability to withdraw the drug promptly in the event of a serious reaction, (b) disruption of menstrual patterns, and (c) delayed return of fertility after discontinuing therapy. Some women may consider the required trip to the doctor every 3 months an additional disadvantage. For women in developing countries where anemia and nutritional problems are prevalent, Depo-Provera has additional advantages in relation to IUDs and OCs: it causes less bleeding than IUDs or OCs and, unlike oral contraceptives, it does not suppress vitamin levels (4-8). Since it requires a trip to the doctor every 3 months, it also provides a better opportunity for medical supervision and care. For postpartum women who which to breastfeed their babies, Depo-Provera has the additional advantage of causing no adverse effect on lactation (1, 2, 13, 14, 16, 18, 19, 25, 32, 36).


A rice lipid transfer protein binds to plasma membrane proteinaceous sites.
Nonspecific lipid transfer protein (nsLTP) is usually basic and secreted low-molecular-mass protein in plants. The 3-D structure of nsLTP1 resembles that of elicitin produced by the plant pathogen Phytophthora cryptogea, which can bind to the plant plasma membrane putative receptor and activate the downstream responses. It is inferred that nsLTP1 may have similar binding sites on the plasma membranes. In this work, rice recombinant protein TRX-nsLTP110 labeled with (125)I was shown to bind to rice plasma membrane preparations in a saturable curve, with an apparent K(d) of 13.6 nM and B(max) of 150 fmol/mg proteins. Competition experiments revealed that the binding of TRX-nsLTP110 was specific, in contrast to the nonspecific binding of the fusion tag thioredoxin. Protease treatment assay showed that the binding sites were proteinaceous. Our results suggest that the binding sites of nsLTPs on plasma membranes may be ubiquitous in the plant kingdom. They may be competed out from the binding sites under pathogen attack, supporting a role for nsLTP1 in host defense response to pathogens.


Safety and feasibility of umbilical cord mesenchymal stem cells in patients with COVID-19 pneumonia: A pilot study.
We aim to explore the safety and feasibility of umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in patients with severe and critically severe coronavirus disease-2019 (COVID-19). We conducted a small sample, single arm, pilot trial. In addition to standard therapy, we performed four rounds of transplantation of UC-MSCs in sixteen patients with severe and critically severe COVID-19. We recorded adverse events from enrolment to Day 28. We evaluated the oxygenation index, inflammatory biomarkers, radiological presentations of the disease and lymphocyte subsets count on the 7th day (D7 ± 1 day), the 14th day (D14 ± 1 day) and the 28th day (D28 ± 3 days). There were no infusion-related or allergic reactions. The oxygenation index was improved after transplantation. The mortality of enrolled patients was 6.25%, whereas the historical mortality rate was 45.4%. The level of cytokines estimated varied in the normal range, the radiological presentations (ground glass opacity) were improved and the lymphocyte count and lymphocyte subsets (CD4+ T cells, CD8+ T cells and NK cells) count showed recovery after transplantation. Intravenous transplantation of UC-MSCs was safe and feasible for treatment of patients with severe and critically severe COVID-19 pneumonia.


The influence of psychological flexibility on persistent post concussion symptoms and functional status after mild traumatic brain injury.
This study investigated the predictive role of psychological flexibility on long-term mTBI outcomes. Adults with mTBI (N = 147) completed a context specific measure of psychological flexibility, (AAQ-ABI), psychological distress, and mTBI outcomes at less than three months post injury (M = 6.02 weeks after injury) and 6 months later (N = 102). Structural equation modelling examined the mediating effects of psychological flexibility on psychological distress and mTBI outcomes at six months. The direct effect of psychological flexibility at less than three months on mTBI outcomes at six months was entered into the model, plus pre-injury and injury risk factors. The theoretically derived model had good overall fit (χ2 = 1.42; p = 0.09; NFI = 0.95; TLI = 0.95; CFI = 0.98 and RMSEA = 0.06). Psychological flexibility at less than 3 months was directly significantly related to psychological distress and post-concussion symptoms at six months. Psychological flexibility at 6 months significantly mediated the relationship between psychological distress and functional disability but not post-concussion symptoms at six months post injury. The exploratory findings suggest that a context specific measure of psychological flexibility assessed acutely and in the chronic phase of recovery may predict longer-term mTBI outcomes.Implications for RehabilitationPersistent post-concussion symptoms (PPCS) after mild traumatic brain injury (mTBI) can have a significant impact on wellbeing, functional status, and quality of life.In this study, psychological flexibility early in recovery, was associated with higher levels of psychological distress and more severe post-concussion symptoms six months later.Psychological flexibility at six months post-injury also mediated the relationship between psychological distress and functional disability.A context specific measure of psychological flexibility may predict poorer long-term outcomes following mTBI.


Role of GSK-3beta activity in motor neuronal cell death induced by G93A or A4V mutant hSOD1 gene.
Point mutations such as G93A and A4V in the human Cu/Zn-superoxide dismutase gene (hSOD1) cause familial amyotrophic lateral sclerosis (fALS). In spite of several theories to explain the pathogenic mechanisms, the mechanism remains largely unclear. Increased activity of glycogen synthase kinase-3 (GSK-3) has recently been emphasized as an important pathogenic mechanism of neurodegenerative diseases, including Alzheimer's disease and ALS. To investigate the effects of G93A or A4V mutations on the phosphatidylinositol-3-kinase (PI3-K)/Akt and GSK-3 pathway as well as the caspase-3 pathway, VSC4.1 motoneuron cells were transfected with G93A- or A4V-mutant types of hSOD1 (G93A and A4V cells, respectively) and, 24 h after neuronal differentiation, their viability and intracellular signals, including PI3-K/Akt, GSK-3, heat shock transcription factor-1 (HSTF-1), cytochrome c, caspase-3 and poly(ADP-ribose) polymerase (PARP), were compared with those of wild type (wild cells). Furthermore, to elucidate the role of the GSK-3beta-mediated cell death mechanism, alterations of viability and intracellular signals in those mutant motoneurons were investigated after treating the cells with GSK-3beta inhibitor. Compared with wild cells, viability was greatly reduced in the G93A and A4V cells. However, the treatment of G93A and A4V cells with GSK-3beta inhibitor increased their viability by activating HSTF-1 and by reducing cytochrome c release, caspase-3 activation and PARP cleavage. However, the treatment did not affect the expression of PI3-K/Akt and GSK-3beta. These results suggest that the G93A or A4V mutations inhibit PI3-K/Akt and activate GSK-3beta and caspase-3, thus becoming vulnerable to oxidative stress, and that the GSK-3beta-mediated cell death mechanism is important in G93A and A4V cell death.


Evolution and the drivers of water use efficiency in the water-deficient regions: a case study on Ω-shaped Region along the Yellow River, China.
Enhancement of water use efficiency (WUE) is considered highly important to cope with the water scarcity challenges in dry regions. Therefore, this study evaluated spatiotemporal characteristics of WUE and its related drivers in the Ω-shaped Region along the Yellow River aiming to provide decision support information for alleviating water shortages in this region. We employed the SBM-DEA (slacks-based measure-data envelopment analysis) model to calculate the WUE considering undesired outputs, analyze temporal and spatial variation based on GIS and statistical methods, and investigate the various factors that influence WUE based on the generalized method of moment (GMM) model. The results are as follows. (1) The WUE followed an increasing-decreasing-increasing trend, suggesting that the expanding agricultural and the second industrial structures are largely dominated by water-intensive activities which add further pressure on the water resources. (2) The spatial discrepancy of WUE among the cities is significant; however, the spatial pattern changes were stable during 2010 to 2019. (3) Analysis of influencing factors provides solutions for improving WUE in the Ω-shaped Region. Irrigation system and water conservancy infrastructure development and the acceleration of industrial transformation are necessary for improving the WUE in the Ω-shaped Region.


Safety and efficacy of Salmonella gallinarum 9R vaccine in young laying chickens.
Salmonella enterica subsp. enterica serovar Gallinarum (S. gallinarum) is the agent of fowl typhoid, and the 9R vaccine is a commercially available, live vaccine for the prevention of fowl typhoid. The aim of this study was to assess the safety and efficacy of the 9R vaccine in young chickens. The mean weights of 5-week-old chickens vaccinated with one and 10 doses at 2 weeks old were 450.3+/-33.83 g and 446.8+/-35.68 g, respectively, which were statistically lower (P<0.05) than the mean weight (475.5+/-44.17 g) of the control group. Using the same procedure, the mean weights of chickens vaccinated with one and 10 doses at the age of 4 and 6 weeks were 721.3+/-64.03 g and 723.7+/-63.92 g, and 1114.2+/-92.21 g and 1078.27+/-68.93 g, respectively. Compared with the mean weights (725.7+/-49.50 g and 1104.3+/-92.34 g, respectively) of the control groups, there was no difference in terms of statistical significance (P < 0.05). In addition, all vaccinated birds showed no clinical signs and survived the time course of the experiment. When all chickens were challenged with the wild-type S. gallinarum 21 days after one-dose vaccination, the mortalities between the vaccinated group and the control group were 0% to 5% and 95% to 100%, respectively. In addition, the control group demonstrated a 95% to 100% re-isolation rate of the challenge strain in internal organs and the caecum, while in the vaccinated group only a 1% to 60% re-isolation rate was observed. In this study, we showed that adjusting the minimum vaccination age of the 9R vaccine to 4 weeks is acceptable considering the safety and efficacy of the vaccine.


Effects of patient-centered care on patient outcomes: an evaluation.
The purposes of this study were to determine the extent to which acute care nurse practitioners (ACNPs) provide patient-centered care (PCC) and to explore the effects of PCC on patients' functional status, self-care ability, and satisfaction with care. A nonexperimental design with repeated measures was used. The sample included 320 patients with acute medical and surgical conditions. Patients perceived that ACNPs provided PCC, operationalized as encouraging patients to participate in care and individualizing care to a moderate extent. Implementation of these PCC components was positively associated with some domains of self-care ability and satisfaction with care. Further investigation of the contribution of PCC to outcomes is recommended.


[X-ray combined with cytosine deaminase suicide gene therapy enhances killing of colorectal carcinoma cells in vitro].
To study the effect of X-ray on gene transfer and the antitumoral effect of X-ray combined with suicide gene therapy on colorectal carcinoma cells. Green fluorescent protein (GFP) was seen under fluorescent microscope. GFP gene was used for reporting gene to learn gene transfer efficiency and gene expressing time under the influence of radiation. G418 was used to select cytosine deaminase (CD) positive neoplasm cells and CD gene transfer efficiency was tested by cloning efficiency. Antitumoral effect of X-ray combined with CD and 5-FC on colorectal carcinoma cells was tested by MTT. 4 Gy radiation could improve supercoiled plasmid DNA transfer efficiency for about 2 - 4 times and 30 times for linearized plasmid DNA. The mean durations of GFP gene expression treated with 4 Gy radiation were 14 d for supercoiled plasmid and 21 and for linearized plasmid, while in control group, the time was 12 d. Middle-dose radiation combined with CD and 5-FC could kill 99 percent of colorectal carcinoma cells, while in the control group, 5-FC only killed 15 percent of colorectal carcinoma cells which were transduced with CD gene. X-Ray combined with suicide gene therapy may be used as a promising method for treating colorectal neoplasm.


Health care quality: the new marketing challenge.
More and more buyers of health care are evaluating the quality of care as well as the cost. To stay competitive, providers must now learn how to sell quality.


Elbow Ulnar Collateral Ligament Repair With Suture Augmentation Results in Good Clinical Results, a Return-to-Play Rate Between 67% and 93%, and a Postoperative Complication Rate Up to 11.9%: A Systematic Review.
To review the Kerlan-Jobe Orthopaedic Clinic (KJOC) scores, return-to-play rates, and complications after ulnar collateral ligament (UCL) repair with suture augmentation. A literature search of the PubMed and Scopus databases was conducted on February 17, 2023, using the terms "ulnar collateral ligament," "repair," "internal brace," and "suture augmentation." The search strategy was based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) protocol and included 4 articles published from 2019 to 2022. The inclusion criteria included studies reporting outcomes, return-to-play rates, and/or complications after UCL repair with suture augmentation. The exclusion criteria consisted of non-English language studies, case reports, cadaveric studies, animal studies, letters to the editor, studies with overlapping cohorts, and review articles. The risk of bias was evaluated using the Methodological Index for Non-Randomized Studies (MINORS) criteria. The final analysis included 4 studies with 510 patients (457 male and 53 female patients), ranging in age between 17.8 and 27.5 years, treated with repair and suture augmentation for UCL tears. In this review, we found a mean postoperative KJOC score ranging from 87.9 to 92.6. The overall rate of return to play at the preinjury level or at a higher level than the preinjury level ranged from 67% to 93%; the mean time to return to play ranged from 6.7 to 17.6 months. The postoperative complication rate in this review ranged from 0% to 11.9%. Among the complications, the most common were ulnar nerve paresthesia (range, 0%-8.2%) and postoperative medial elbow pain (range, 0%-3.1%). Overall, the reoperation rate ranged from 0% to 3.4%. No reruptures were reported. UCL repair with the use of suture augmentation results in postoperative KJOC scores ranging from 87.9 to 92.6, a return-to-play rate between 67% and 93%, and a postoperative complication rate up to 11.9%. Level IV, systematic review of Level IV studies.


Oricola nitratireducens sp. nov., a novel nitrate reducing bacterium isolated from marine sediment in East China Sea.
A novel strain designated NBU1457T, was isolated from marine sediment sampled on Meishan Island located in the East China Sea. Cells of strain NBU1457T was Gram-negative, facultatively anaerobic, non-motile and ovoid-shaped. Strain NBU1457T grew optimally at 37 °C, NaCl concentration of 2.0-3.0% (w/v) and pH 6.5-7.5. Catalase and oxidase activities, urease, nitrate reduction and H2S production were positive. Indole production, methyl red reaction, hydrolysis of starch, gelatin, casein, Tweens 20, 40, 60 and 80 were negative. Comparative analysis of the 16S rRNA gene sequence showed highest similarities to the species with validated name Oricola thermophila MEBiC13590T (98.8%), Oricola cellulosilytica CC-AMH-0 T (97.9%) and Oricola indica JL-62 T (97.9%). Phylogenetic analyses indicated that strain NBU1457T clustered with the genus Oricola and closely related to strains Oricola thermophila MEBiC13590T, Oricola cellulosilytica CC-AMH-0 T and Oricola indica JL-62 T. The average nucleotide identity and digital DNA-DNA hybridization values between strain NBU1457T and related species of genus Oricola were well below the threshold limit for prokaryotic species delineation. The DNA G + C content was 63.2%. The major cellular fatty acid was summed feature 8 (C18:1 ω7c and/or C18:1 ω6c). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, sulfoquinovosyldiacylglycerol and phosphatidylglycerol. The only respiratory quinone was ubiquinone-10 (Q-10). Combining results of our phenotypic, chemotaxonomic and genotypic data, strain NBU1457T is considered to be a representative in the genus Oricola, which the name Oricola nitratireducens sp. nov. is proposed. The type strain of the new species is NBU1457T (= KCTC 82225 T = MCCC 1K04764T).


Chondrosarcoma of the uterus: report of a case and review of the literature.
The clinical and pathologic features of a case of primary chondrosarcoma of the uterus and 12 previously described similar cases are reviewed. Pathologically the tumors resemble chondrosarcoma of bone. The clinical features, including a high degree of malignancy, resemble those of other types of pure heterologous sarcomas and the typical müllerian mixed tumors of the uterus.


Evidence for an effect of ELF electromagnetic fields on human pineal gland function.
A study was carried out to determine possible effects of 60-Hz electromagnetic-field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.


Behavior change in children at a therapeutic summer camp as a function of feedback and individual versus group contingencies.
Two contigency systems, individual and group, were evaluated for their effects on children's behavior during small group meetings. Forty-eight children, ages 8 through 14, attended a 7-week residential camp program operated on a token economy system. Ratings of the campers' behavior were made by the counselors on a 5-point rating scale at the daily meetings. Each camper received both contingency programs, in counterbalanced order. Data were gathered during baseline, two feedback and two treatment phases. An analysis of variance for repeated measures was performed on the mean weekly camper scores. The two systems were equally effective in significantly increasing the amount of desirable behavior, and there was no effect on behavior due to feedback alone. The results are discussed in terms of advantages and disadvantages of each type of contingency system, with some suggestions made regarding areas of further investigation.


Differential effect of etretinate on proliferation and extracellular matrix metabolism of human dermal fibroblasts from elderly and young individuals in a novel three-dimensional culture.
The effect of etretinate on proliferation and biosynthesis of collagens and glycosaminoglycans (GAGs) were investigated using human dermal fibroblasts in a novel three-dimensional culture supplemented with L-ascorbic acid 2-phosphate. Fibroblasts from two young and two elderly individuals were studied at different concentrations of etretinate, 0.25, 1.0 and 2.5 microg/ml. Collagens (hydroxyproline) and GAGs (disaccharide units) extracted from the cell layer were analyzed and quantified biochemically by high-performance liquid chromatography (HPLC). Etretinate showed no significant effect on fibroblast proliferation either in the monolayer or the three-dimensional culture. Etretinate increased the collagen or GAGs content in the cell layer, which was prominent at etretinate concentrations of 1.0 and 2.5 or 0.25 microg/ml, respectively in fibroblasts from the elderly (P < 0.05). This effect was not seen in dermal fibroblast from the young. These results suggest that etretinate may have the differential effect on collagen and GAG metabolisms depending on the donor age of the cultured fibroblasts.


Qualitative study of ethanol content in tequilas by Raman spectroscopy and principal component analysis.
Using Raman spectroscopy, with an excitation radiation source of 514.5 nm, and principal component analysis (PCA) was elaborated a method to study qualitatively the ethanol content in tequila samples. This method is based in the OH region profile (water) of the Raman spectra. Also, this method, using the fluorescence background of the Raman spectra, can be used to distinguish silver tequila from aged tequilas. The first three PCs of the Raman spectra, that provide the 99% of the total variance of the data set, were used for the samples classification. The PCA1 and PCA2 are related with the water (or ethanol) content of the sample, whereas the PCA3 is related with the fluorescence background of the Raman spectra.


Effect of copper oxide nanoparticles on two varieties of sweetpotato plants.
Little information is available on the interaction of CuO nanoparticles (nCuO) with tuberous roots. In this study, Beauregard-14 (B-14, low lignin) and Covington (COV, high lignin) sweetpotato varieties were cultivated until maturity in soil amended with nCuO, bulk copper oxide (bCuO) and CuCl2 at 25-125 mg/kg. The Cu treatments had no significant influence on chlorophyll content. Gas exchange parameters were not affected in B-14. In COV, however, at 125 mg/kg treatments, bCuO reduced the intercellular CO2 (11%), while CuCl2 increased it by 7%, compared with control (p ≤ 0.035). At 25 mg/kg nCuO increased the length of COV roots (20.7 ± 2.0 cm vs. 14.6 ± 0.8 cm, p ≤ 0.05). In periderm of B-14, nCuO, at 125 mg/kg, increased Mg by 232%, while the equivalent concentration of CuCl2 reduced P by 410%, compared with control (p ≤ 0.05). The data suggest the potential application of nCuO as nanofertilizer for sweetpotato storage root production.


A single-blind, parallel-group randomised trial of a Technology-assisted and remotely delivered Cognitive Behavioural Therapy intervention (Tech-CBT) versus usual care to reduce anxiety in people with mild cognitive impairment and dementia: study protocol for a randomised trial.
Anxiety is commonly experienced by people living with mild cognitive impairment (MCI) and dementia. Whilst there is strong evidence for late-life anxiety treatment using cognitive behavioural therapy (CBT) and delivery via telehealth, there is little evidence for the remote delivery of psychological treatment for anxiety in people living with MCI and dementia. This paper reports the protocol for the Tech-CBT study which aims to investigate the efficacy, cost-effectiveness, usability and acceptability of a technology-assisted and remotely delivered CBT intervention to enhance delivery of anxiety treatment for people living with MCI and dementia of any aetiology. A hybrid II single-blind, parallel-group randomised trial of a Tech-CBT intervention (n = 35) versus usual care (n = 35), with in-built mixed methods process and economic evaluations to inform future scale-up and implementation into clinical practice. The intervention (i) consists of six weekly sessions delivered by postgraduate psychology trainees via telehealth video-conferencing, (ii) incorporates voice assistant app technology for home-based practice, and (iii) utilises a purpose-built digital platform, My Anxiety Care. The primary outcome is change in anxiety as measured by the Rating Anxiety in Dementia scale. Secondary outcomes include change in quality of life and depression, and outcomes for carers. The process evaluation will be guided by evaluation frameworks. Qualitative interviews will be conducted with a purposive sample of participants (n = 10) and carers (n = 10), to evaluate acceptability and feasibility, as well as factors influencing participation and adherence. Interviews will also be conducted with therapists (n = 18) and wider stakeholders (n = 18), to explore contextual factors and barriers/facilitators to future implementation and scalability. A cost-utility analysis will be undertaken to determine the cost-effectiveness of Tech-CBT compared to usual care. This is the first trial to evaluate a novel technology-assisted CBT intervention to reduce anxiety in people living with MCI and dementia. Other potential benefits include improved quality of life for people with cognitive impairment and their care partners, improved access to psychological treatment regardless of geographical location, and upskilling of the psychological workforce in anxiety treatment for people living with MCI and dementia. This trial has been prospectively registered with ClinicalTrials.gov: NCT05528302 [September 2, 2022].


β-Cyclocitric acid enhances drought tolerance in peach (Prunus persica) seedlings.
The β-cyclocitric acid (β-CCA) is a bioactive apocarotenoid previously shown to improve drought tolerance in annual plants. However, the underlying molecular mechanism of this process remains largely elusive. Moreover, the question about the activity of β-CCA in perennial fruit crops is still open. Here, we found that treatment of β-CCA enhances drought tolerance in peach seedlings. The application of β-CCA significantly increased the relative water content and root activity and reduced the electrolyte leakage of peach seedlings under drought stress. Moreover, treatment with β-CCA under drought stress increased chlorophyll fluorescence, indicating a positive effect on photosynthesis, while also enhancing superoxide dismutase and peroxidase activity and reducing reactive oxygen species (ROS) levels. Consistent with these alterations, transcriptome analysis revealed an up-regulation of photosynthesis and antioxidant-related genes upon the application of β-CCA under drought stress. We also detected an induction in genes related to detoxification, environmental adaptation, primary metabolism, phytohormone, phenylpropanoid and the biosynthesis of cutin, suberine and wax, which might contribute to the induction of drought resistance. Altogether, our study reveals that β-CCA positively modulates peach drought tolerance, which is mainly mediated by enhancing photosynthesis and reducing ROS, indicating the potential of utilizing β-CCA for drought control in peach and perhaps other fruit crops.


Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells.
This report is an integrated study to include the molecular simulation, physicochemical characterization and biological analysis of a paclitaxel-loaded PHBV nanoparticle that demonstrates uptake, release and cytotoxicity in cancer cell lines. Taking this nanoparticle one step closer to its use in a clinical setting, we demonstrate that it causes significant cell death in primary cultures of stage IIIc serous ovarian cancer cells isolated from six patients. Molecular simulations revealed a high affinity of paclitaxel for the water-polymer interface, thus the drug is delivered only when the polymer near it is degraded. The Fourier transform infrared spectroscopy suggests the formation of a short-lived crystalline phase, also observed in the CG simulations, and transmission electron microscopy revealed branched structures on the surface of particles, which disappeared after 4 days. Biological analyses indicated that these particles have a 48-h window of toxicity protection, allowing for the endocytosis of the particle by the cells; this finding was corroborated by confocal microscopy and flow cytometry. The low cost to synthesize PHBV using microorganisms and the potential chemical modifications of the polymer make it attractive for inexpensive, large-scale pharmaceutical production.


2-Fluoro-beta-alanine, a previously unrecognized substrate for bile acid coenzyme A:amino acid:N-acyltransferase from human liver.
Our laboratory has demonstrated recently that conjugates of 2-fluoro-beta-alanine (FBAL) and bile acids are the major biliary metabolites of 5-fluorouracil (FUra) in cancer patients. Bile acids are normally conjugated with glycine or taurine, and therefore the identification of the FBAL-bile acid conjugates suggested that FBAL may also be a substrate for the bile acid conjugating enzyme, bile acid CoA:amino acid:N-acyltransferase. Enzyme activity detected using glycine and taurine as substrates was purified 8-fold from human liver cytosol using a DEAE-cellulose column. This preparation when tested for its activity towards beta-alanine and FBAL using cholyl CoA as the bile acid substrate only catalyzed the formation of FBAL-cholate. beta-Alanine was not a substrate. Confirmation of FBAL-cholate as the enzymatic product was demonstrated by (1) coelution of the product of this reaction on HPLC with authentic FBAL-cholate, (2) specific hydrolysis of this product by cholylglycine hydrolase, and (3) molecular weight of the product (497) being identical to that of the authentic FBAL-cholate. Kinetic experiments demonstrated that the enzyme had an affinity for FBAL (Km 1.45 mM) comparable to taurine (Km 1.32 mM), but greater than glycine (Km 6.45 mM). Formation of FBAL-cholate was inhibited competitively by taurine (Ki 1.27 mM) and glycine (Ki 4.47 mM), suggesting that a single enzyme is responsible for conjugation of glycine, taurine and FBAL with bile acids. These data indicate that the formation of the FBAL-bile acid conjugates in patients receiving FUra results from high affinity of the bile acid conjugating enzyme for FBAL.


Bad wrap: Myelin and myelin plasticity in health and disease.
Human central nervous system myelin development extends well into the fourth decade of life, and this protracted period underscores the potential for experience to modulate myelination. The concept of myelin plasticity implies adaptability in myelin structure and function in response to experiences during development and beyond. Mounting evidence supports this concept of neuronal activity-regulated changes in myelin-forming cells, including oligodendrocyte precursor cell proliferation, oligodendrogenesis and modulation of myelin microstructure. In healthy individuals, myelin plasticity in associative white matter structures of the brain is implicated in learning and motor function in both rodents and humans. Activity-dependent changes in myelin-forming cells may influence the function of neural networks that depend on the convergence of numerous neural signals on both a temporal and spatial scale. However, dysregulation of myelin plasticity can disadvantageously alter myelin microstructure and result in aberrant circuit function or contribute to pathological cell proliferation. Emerging roles for myelin plasticity in normal neurological function and in disease are discussed. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 123-135, 2018.


Brief assessment of severe language impairments: initial validation of the Mississippi aphasia screening test.
To validate the Mississippi Aphasia Screening Test (MAST) which includes nine sub-scales measuring expressive and receptive language abilities. Evaluation of inpatients admitted to neurology, neurosurgery or rehabilitation units at two local hospitals and who were within 60 days of onset of a unilateral ischemic or haemorrhagic stroke (left hemisphere (LH; n=38); right hemisphere (RH; n=20)). Additional participants were recruited from the community to comprise a non-patient control sample (NP; n=36). Data collection included administration of the MAST and chart review. The LH group showed more impairment than the RH and NP groups on summary scores. The LH group performed worse than the NP group on all sub-scales. The object recognition and verbal fluency sub-scales did not discriminate the stroke groups. Analyses suggest good criterion validity for the MAST in differentiating communication impairments among clinical and control samples.


Resource utilization of cytomegalovirus immune globulin in prevention and treatment of cytomegalovirus infection in pediatric heart transplantation.
There is debate whether cytomegalovirus immunoglobulin (CMV-Ig) is also needed for CMV prevention in heart transplant recipients in the era of good anti-viral drugs. We conducted a cost-savings quality initiative on CMV-Ig eventually leading to discontinuation of routine use of CMV-Ig for CMV prevention. Subsequently, a retrospective cohort study was conducted, comparing patients in cohort I (CMV-Ig plus anti-viral drugs, 2013-2015) to cohort II (anti-virals alone, 2015-2017). The medication acquisition costs and outcomes of CMV infection were assessed. There were 39 total patients: 22/39(56%) in cohort I, with mean follow-up of 35.14 ± 17.38 months and 17/39(44%) in cohort II, mean follow-up of 19.12 ± 7.08 months. In cohort I, 5/22(22.7%) patients died from causes unrelated to CMV and 0/17 in cohort II died. There were 5/22(22.7%) patients in cohort I, and 2/17(9%) patients in cohort II that developed CMV infection (P = .508). Freedom from rejection was 81.8% (18/22) in cohort I, and 71% (12/17) in cohort II (P = .46), and 100% for allograft vasculopathy. There was significant reduction in medication acquisition cost following the protocol change of $260 839 or $15 343 per patient. Our study demonstrated an acquisition cost savings with similar clinical outcomes utilizing anti-viral CMV prophylaxis alone vs anti-viral prophylaxis plus CMV-Ig.


The multiple promoter methylation profile of PR gene and ERalpha gene in tumor cell lines.
The changes of methylation status of various gene promoters are a common feature of malignant cells and these changes can occur early in the progression process. Therefore, abnormal methylation can be used as cancer marker. Such studies will first require the development of a panel of methylated markers that are methylated in cancer tissues but unmethylated in normal tissues or methylated status is different between cancer tissues and normal tissues. By using methylation-specific PCR (MSP) assay method, we observed alterations in DNA methylation at the double promoter regions of the progesterone receptor (PR) gene and estrogen receptor (ERalpha) gene in various tumor cell lines. Compared with normal white blood cell, the methylation status of PRA promoter in various cancer cell lines changed from unmethylation pattern to methylation pattern. That of PRB promoter changed from both unmethylated and methylated alleles to only methylated allele. The methylation status of ERalpha-A and ERalpha-B promoter in various cancer cell lines are cell -specific. This study indicates that PR promoter methylation may be a molecular marker in various cancer detections. And the methylation status of ERalpha-A and ERalpha-B is cell-specific.


Prophylactic inferior vena cava filter placement prior to lumbar surgery in morbidly obese patients: Two-case study and literature review.
Preoperative "prophylactic" placement of inferior vena cava (IVC) filters in morbidly obese patients (e.g., body mass index [BMI] >40 or BMI over 35 with hypertension/diabetes) undergoing multilevel decompressive lumbar laminectomies may reduce the risk of postoperative pulmonary embolism (PE), and death. Two patients, ages 69 and 68, with morbid obesity (BMI's of 40.4 and 37.5 both with hypertension and diabetes), received prophylactic IVC filters prior to L1-S1 laminectomies. Intraoperatively and postoperatively, both received alternating compression stocking prophylaxis, and received subcutaneous heparin 5000 U q12 h 48 h after surgery until discharge; none developed deep venous thrombosis (DVT) or PE, and both filters were uneventfully removed within 3 postoperative months. The spinal surgical literature largely supports the placement of IVC filters for major risk factors; obesity (BMI >40), a history of DVT/PE, cancer, fusions, hypercoagulation syndromes, pulmonary/circulatory disorders, preoperative/postoperative immobility, staged procedures (five spinal levels), combined anterior-posterior surgery, iliocaval manipulation, age >80, and prolonged surgery (e.g., >261 min vs. >8 h). Although the safety and efficacy of prophylactic IVC filters for spine surgery in patients with morbidly obesity are well substantiated, those for bariatric patients are less clear. Prophylactic IVC filters were successfully placed/retrieved in 2 morbidly obese patients, ages 68 and 69, undergoing L1-S1 lumbar decompressions. Although the spine surgery literature documents the safety/efficacy of prophylactic IVC filters in patients with morbid obesity, the bariatric literature still has major concerns.


Malformations of the maxillofacial region induced by retinoids in an experimental system.
Treatment of pregnant Sprague-Dawley rats with etretinate or retinoic acid on pregnancy Day 8.5-9.0 resulted in craniofacial malformations in 100% of the embryos. A morphological investigation of the maxillofacial malformations was undertaken. Retinoid-exposed embryos showed a reduced skull base, flattened and elongated occiput and micrognathia. The malar bones were reduced or missing. Meckel's cartilage was delayed in differentiation as was the mandibular bone. The fusion between different facial processes was disturbed which resulted in facial and palatal clefts. Disturbance of the development of the hypophysis was combined with persisting Rathke's pouch. Aplasia of incisor and molar tooth buds was seen as was aplasia of salivary gland ducts. The facial artery was hyperplastic.


Congenital rickets. Study of the evolution of secondary hyperparathyroidism.
A case of congenital rickets of nutritional origin is described in a light-for-date premature infant (gestational age 34 weeks, birthweight 1 100 g). X-rays of the long bones showed spread, frayed and cupped metaphyses at birth and at the age of 16 days. Serum calcium was 8.2 mg/100 ml, phosphorus 3.4 mg/100 ml and alkaline phosphatase (A.P):323 IU/ml (N less than or equal to 200) at the age of 3 days. Very high level of serum immunoreactive parathroid hormone (iPTH) was found at the age of 16 days=295 micronlEq/ml (N less than or equal to 50). Evidence of maternal vitamin D deficiency was demostrated by low plasma 25-hydroxycholecalciferol (25-OH-CC):1.0 ng/ml (N:13.2+/-4.2) soon after delivery; it was found to be normal (10.2 ng/ml) six months later. Ca infusion (15 mg/kg/3 h) resulted in a marked fall of serum iPTH (280 to 84 micronlEq/ml). Administration of vitamin D2 (2400 IU/day for 10 days) induced some healing of the metaphyses; A. P. remained elevated (400 IU/ml); plasma 25-OH-CC was normal 10.2 ng/ml and serum iPTH was 115 micronlEq/ml. When 25-OH-CC was given orally for ten days (15 microng/day), plasma 25-OH-CC rose to 64.5 ng/ml with a minor change of serum iPTH (94 micronlEq/ml); X-rays of the bones showed osteoporosis. These results suggest a reduced convertion of 25-OH-CC into 1-25-(OH)2-CC.


Evaluation of antifertility effect of gel formulation containing sperm immobilizing factor: In vitro and in vivo studies.
Sexually active women often seek protection against unplanned pregnancies. Latter can be effectively controlled by consistent use of spermicides during each coital act. However, side effects associated with the use of available synthetic spermicidal agents have directed the interest towards identifying newer and safer agents. Present studies were undertaken to formulate a vaginal contraceptive gel, containing sperm immobilizing factor (SIF) isolated from Staphylococcus aureus using 1% w/v Carbopol. SIF loaded gel formulation was characterized for various in vitro parameters i.e. pH, spreadability, texture profiling, rheological properties, and in vitro release studies. The prepared formulation was found to possess significant spreading properties, gel firmness and strength, and released about 80% of SIF within 30min. Latter can completely immobilize human spermatozoa within 20s, at a dose of 200μg/ml. SIF in the proposed gel formulation showed 100% contraceptive effect when used at amount as low as of 10μg, thus confirming the possibility to develop it as a potent vaginal contraceptive for future use.


Migraine With Exclusive Olfactory Aura: Case Report and Literature Review.
To report the case of a patient enduring migraine attacks preceded by hallucinatory olfactory symptoms, with characteristics which typically define migraine with aura (MWA). MWA accounts for about 30-40% of the total cases of migraine and is almost always preceded by visual disorders; and in rare cases migraine attacks are preceded by olfactory hallucinations which have not been so far recognized as a type of aura. We describe a 51-year-old male whose migraine attacks are preceded, unusually for migraine sufferers, only by olfactory hallucinations; in 10% of the attacks, the olfactory symptoms are not followed by any pain but always appear with the same characteristics. These hallucinations began with the onset of a history of cephalea. This case suggests that olfactory hallucinations should be considered as actual pre-migraine symptoms, like visual symptoms or other disorders, and added to the criteria for the diagnosis of MWA.


Seed-mediated synthesis of copper nanoparticles on carbon nanotubes and their application in nonenzymatic glucose biosensors.
In this paper, for the first time, Cu nanoparticles (CuNPs) were prepared by seed-mediated growth method with Au nanoparticles (AuNPs) playing the role of seeds. Carbon nanotubes (CNTs) and AuNPs were first dropped on the surface of glassy carbon (GC) electrode, and then the electrode was immersed into growth solution that contained CuSO(4) and hydrazine. CuNPs were successfully grown on the surface of the CNTs. The modified electrode showed a very high electrochemical activity for electrocatalytic oxidation of glucose in alkaline medium, which was utilized as the basis of the fabrication of a nonenzymatic biosensor for electrochemical detection of glucose. The biosensor can be applied to the quantification of glucose with a linear range covering from 1.0×10(-7) to 5×10(-3)M and a low detection limit of 3×10(-8)M. Furthermore, the experiment results also showed that the biosensor exhibited good reproducibility and long-term stability, as well as high selectivity with no interference from other oxidable species.


Sexually transmitted diseases in homosexual adolescents.
In 1986, an estimated 13 million cases of sexually transmitted diseases (STDs) were diagnosed in the United States, with the highest incidence rates occurring within the adolescent age group. Homosexual adolescent men are at particularly high risk for STDs. Because of the myriad clinical presentations of STD in gay men, these diseases are often not recognized as being sexually transmitted. In this paper, the epidemiology and clinical features of STDs in gay adolescents are discussed. The sexual history is emphasized as an integral tool in developing a differential diagnosis. A priori, the sexual history also can give a risk-assessment profile for STD. Clinical aspects of STD are reviewed using a syndrome approach, and the diagnostic workup is outlined for the etiologic agents most likely implicated in each syndrome. Clinical signs and symptoms of urethritis, genital ulcers and papular lesions, pharyngitis, and hepatitis are reviewed. Sexually acquired gastrointestinal disorders are described. As the AIDS epidemic continues, disease prevention, risk reduction, and patient education are becoming more important. Current recommendations for "safer sex" practices are reviewed.


Inhibition of TREM-1 ameliorates Lipopolysaccharide-induced depressive-like behaviors by alleviating neuroinflammation in the PFC via PI3K/Akt signaling pathway.
Neuroinflammation is closely related to depression and is a key pathophysiological process of depression. Triggering receptor expressed on myeloid cells 1 (TREM-1) has been proven to exert proinflammatory effects in various diseases. However, the role of TREM-1 in depression has not been elucidated. Thus, we hypothesized that TREM-1 inhibition might have protective effects in depression. Here, lipopolysaccharide (LPS) was used to induce depressive-like behaviors in mice, LP17 was treated to inhibit TREM-1, and LY294002 was administrated to inhibit phosphatidylinositol 3-kinase (PI3K) which is one of the downstream of TREM-1. Physical and neurobehavioral tests, Western blot analysis, and immunofluorescence staining were performed in this study. We found that LPS caused significant depressive-like behaviors in mice, including body weight decline, anodynia (sucrose preference decrease), lack of locomotor activity, and desperation in tail suspension test (TST) and forced swimming test (FST). Next, we revealed that TREM-1 was expressed on microglia, neurons, and astrocytes in the prefrontal cortex (PFC) after LPS administration. TREM-1 inhibition by LP17 suppressed the expression of TREM-1 in the PFC. In addition, LP17 could alleviate neuroinflammation and microglial activation in the PFC. Meanwhile, LP17 could prevent damage of LPS to neuronal primary cilia and neuronal activity. Finally, we revealed that PI3K/Akt might exert crucial role in the protective effects of TREM-1 inhibition to depressive-like behaviors induced by LPS. Taken together, TREM-1 inhibition by LP17 could alleviate depressive-like behaviors induced by LPS by mitigating neuroinflammation in the PFC via PI3K/Akt signaling pathway. Finally, we demonstrated that TREM-1 might be a promising therapeutic target for treatment of depression.


A procedure for inducing sustained hyperlipemia in rats by administration of a surfactant.
Tyloxapol (Triton WR 1339) is a non-ionic detergent that inhibits lipoprotein lipase and thereby raises levels of serum lipids. It is used frequently for acute studies on lipids in rats but not for subacute or chronic studies. In the present work, we found that tyloxapol must be injected intravenously three times each week in order to have high and sustained levels of serum cholesterol and triglycerides for 1, 2, or 3 weeks. These results make it possible to extend the use of tyloxapol into chronic studies of hyperlipemia and vascular disease.


Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder which causes neonatal jaundice in most cases, and under certain conditions, can cause a spectrum of hemolytic manifestations. To determine the local prevalence of G6PD deficiency in newborns. Cross-sectional. University hospital. Infants born during 2015 were prospectively screened for G6PD deficiency. Dried blood spot samples on filter paper were collected in collaboration with the central laboratories of the Ministry of Health. Quantitative measurement of G6PD enzyme activity was measured from the blood samples using fluorometric analysis. A value.


Case report: A novel reciprocal ROS1-CD74 fusion in a NSCLC patient partially benefited from sequential tyrosine kinase inhibitors treatment.
The clinical significance of majority oncogenic novel fusions is still unknown due to scarcity. Reciprocal ROS1 translocation is a rare form of ROS1 fusion and has not yet been clearly analyzed. A 44-year-old Chinese woman with a large dimension in the left lobe of the lung was admitted to the hospital with IVB lung adenocarcinoma. It was discovered that intron 28 of ROS1 and intron 6 of CD74 produced a unique reciprocal ROS1 rearrangement. In addition, the dual CD74-ROS1 fusions were discovered using the RNA next-generation sequencing (NGS) findings. Although benefiting from crizotinib and lorlatinib sequential treatment, the overall prognosis of the patient was relatively poor, whose progression-free survival was 4 and 5 months for crizotinib treatment and lorlatinib treatment, respectively. In summary, a novel ROS1-CD74 fusion identified by DNA NGS was translated into dual CD74-ROS1 transcripts. Furthermore, this patient with non-small cell lung cancer benefited from consecutive tyrosine kinase inhibitor therapy. Our discovery broadened the range of targetable ROS1 fusions and underlined the importance of sequential DNA and RNA sequencing in identifying uncommon but beneficial fusions, which eventually bring benefits to the patients.


A radioassay for pyrimidine-5'-nucleotidase activity.
A simple method for the determination of pyrimidine-5'-nucleotidase activity in red cells is described. The radioactive uridine released after incubation with [5-3H]] uridine 5-monophosphate (UMP) is separated on DEAE-cellulose paper and counted. This method does not require preliminary dialysis of the hemolysate and is 50-fold more sensitive than that based on the measurement of the inorganic phosphate released. One patient with pyrimidine-5'-nucleotidase deficiency was detected with this method.


Enhanced growth suppression of Philadephia1 leukemia cells by targeting bcr3/abl2 and VEGF through antisense strategy.
An antisense strategy by targeting both bcr3/abl2 and VEGF was designed to suppress the growth of Philadephia1 leukemia cells in vitro and in vivo in mice. In vitro, although bcr3/abl2 or VEGF antisense oligodeoxyribonucleotides (AS-ODNs) alone was able to inhibit the proliferation of K562 cells, the combination of bcr3/abl2 and VEGF AS-ODNs produced an additive inhibitory effect on the growth of K562 cells and significantly enhanced the sensibility of K562 cells to apoptosis-inducing stimuli including STI571. In vivo, the nude mice xenografted with K562 cells received intratumoral injections of bcr3/abl2 and VEGF AS-ODNs showed a significant reduction in leukemia tumor size and microvessel density and an increase of apoptosis in the tumors when compared to the mice that received an individual agent. These results demonstrate that targeting both bcr3/abl2 and VEGF can result in an additive tumor-suppressive action and may represent an excellent strategy to augment the efficacy of chemotherapy in CML.


Naloxone and intestinal motility.
It was supposed that the inhibition of intestinal peristalsis seen in animals and humans after abdominal surgery might be related to the release of endorphins, endogenous opiate receptor agonists, caused by the surgical stress and pain. However, naloxone, a potent morphine and endorphin antagonist, failed to block this peristaltic inhibition in rats, which leaves the mechanism of this inhibition, and thus the function of intestinal endorphins, still very much in doubt.


[Fetal echocardiography in 83 fetuses with omphalocele from Dept. for Diagnoses and Prevention of Fetal Malformations, Research Institute Polish Mother's Memorial Hospital, and Medical University of Lodz, (1999-2006)].
It was a retrospective analysis of fetal echocardiography results (analysis of congenital heart defect (CHD) and functional abnormalities in normal heart anatomy) in 83 fetuses diagnosed and treated in the same institution. In our group of fetuses, the most common structural defect, in addition to omphalocele, proved to be CHD. In the group of omphalocele, normal heart anatomy and functional abnormalities (tricuspid regurgitation, myocardial hypertrophy, arrhythmias), the hospital stay was longer comparing to the group of omphalocele, normal heart anatomy and normal heart study (t-test p = 0.005). CHD was a bad prognostic factor and most fetuses/newborns did not survive (Chi-square 0.0005, Fisher test 0.000032). In the group of omphalocele and normal heart anatomy based on fetal echocardiography, the survival rate was 70%. The omphalocele and CHD survivors (n=3) had been only those who did not require a cardiac surgery in first month of postnatal life. Echocardiography exam of fetus with omphalocele and CHD and functional abnormalities has diagnostic and prognostic value.


Enhanced cosyntropin stimulation test performance enabled by electronic medical record.
To improve performance of the cosyntropin stimulation test (CST) used for diagnosis of adrenal-cortisol insufficiency by implementing an electronic medical record (EMR) system protocol. We implemented a SmartForm protocol of the validated CST in our EMR system (CS-Link™, EPIC) system and compared medical staff test performance before and after protocol implementation. Correct performance of the CST improved significantly after EMR implementation. The number of correctly performed CSTs increased from 16.1 % before to 53.5 % after implementation (p < 0.0001) while those performed incorrectly and were uninterpretable decreased from 36.2 to 7.1 % (p < 0.0001). This performance improvement result in a calculated cost savings of $50,414 for every 100 tests performed. The EMR system is useful for guiding medical staff to accurately perform the CST, reduce the number of wasted tests, and maximize staff time and resources.


Identification of common sequence motifs shared exclusively among selectively packed exosomal pathogenic microRNAs during rickettsial infections.
We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia-infected endothelial cells (R-ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life-threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R-ECExos-induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R-ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE-cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA-dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy-relevant miR23a-27a-24 cluster and miR30b are selectively enriched in R-ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively-enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy-relevant miR23a-27a-24 and miR30b, and subsequently results in their selective enrichments in R-ECExos.


Prevalence, Outcomes, and Costs According to Patient Frailty Status for 2.9 Million Cardiac Electronic Device Implantations in the United States.
Little is known about the impact of frailty on length of stay (LOS), cost, and in-hospital procedural outcomes of cardiac implantable electronic device (CIED) implantation procedures. All de novo CIED implantations recorded in the United States (2004-2014) from a national database were stratified according to the Hospital Frailty Risk Score into low-risk (LRF; <5), intermediate-risk (IRF; 5-15), and high-risk (HRF; > 15) frailty groups. Regression analyses were performed to assess the association between frailty and procedural outcomes. Of 2,902,721 implantations, LRF, IRF, and HRF were 77.6%, 21.2%, and 1.2%, respectively. Frailty increased from 2004 to 2014 (IRF: 14.3% to 32.5%, HRF: 0.2% to 3.3%). Complications were 2- to 3-fold higher in the IRF and HRF groups, whereas all-cause mortality was 4- to 9-fold higher in the IRF (2.9%) and HRF (5.3%) groups, depending on the type of CIED (P < 0.001 for all). Rates of complications increased over the study years and all-cause mortality declined, especially in the higher frailty risk groups (2004 vs 2014; mortality: IRF: 3.8% vs 2.2%, HRF: 9.9% vs 4.5%; bleeding: IRF: 3.7% vs 9.0%, HRF: 3.9% vs 12.2%; thoracic: IRF: 4.3% vs 6.0%, HRF: 2.9% vs 9.1%; cardiac: IRF: 0.5% vs 0.9%, HRF: 0.5% vs 0.9%). Rising frailty was associated with an increase in cost (P < 0.001) and LOS (median 3, 8, 11 days for LRF, IRF, HRF, respectively, P < 0.001). The cost for patients with HRF receiving a defibrillator was approximately a quarter million USD$ per patient. Frailty is associated with worse clinical outcomes, higher cost, and LOS independent of age or CIED type. Our findings emphasize the importance of frailty assessment.


Immunohistochemical identification and localization of endogenous endostatin and its related peptides in murine tumors.
Endostatin, a fragment of the C-terminal domain of mouse collagen XVIII, is a recently demonstrated endogenous inhibitor of tumor angiogenesis. Although endostatin can be detected in blood and urine of tumor-bearing as well as normal mice, the exact localization of the endogenous protein and its related peptides in tumor tissues is unknown. We used immunohistochemistry and immunoblotting to identify endostatin tissue location and staining patterns in tumor, as well as to determine the differences in the levels of endostatin expression between tumor cells (in vitro) and tumor tissues (in vivo). Using a specific polyclonal antibody against murine endostatin, we quantitatively determined the levels of endostatin in five murine mammary tumors and the KHT sarcoma by Western blotting. The staining patterns for this protein in tumor sections were examined histologically by immunohistochemistry. Our results show that: (1) Endogenous endostatin and its related peptides are widely distributed in all in vivo tumor types tested, but not in most of the cultured tumor cell lines. (2) Endogenous endostatin stained most tumor stromal components, including vessel walls, basement membranes, extracellular spaces, and tumor cells. (3) Staining patterns and localization of endostatin and thrombospondin-1 were similar in these tumor sections.


Complexity science and participation in decision making among Taiwanese nurses.
The perspective of interconnection in complexity science is used to examine the concept of participation in decision making among Taiwanese nurses in the context of Chinese communication culture. Participation in decision making among nurses has been widely discussed and tested in the Western healthcare systems. Many studies have shown that participation in decision making relates to nurses' autonomy, job satisfaction and quality of care. However, participation in decision making has not been fully discussed in Taiwan's nursing community. In a different cultural environment, participation in decision making may have different effects. The concept of participation in decision making is analysed in three facets of Chinese communication culture: (1) hierarchical social relationship; (2) harmony maintenance; and (3) insider effects. Key issues Taiwanese nurses might establish different levels of participation and need to use different strategies to enhance participation in decision making for desired outcomes. While applying participation in decision making in a different context, it is very important to consider the social and cultural differences. Two implications are made. First, nursing leaders/managers who are working with a multicultural team should be aware of the cultural difference in the pattern of interaction in the process of participation in decision making. Second, leaders/managers should be creative and try to apply different strategies to encourage staff's participation in decision making.


Describing the "white" ethnic group and its composition in medical research.
The routine use in medical research of an ostensibly homogeneous "white" category in ethnic group classifications has meant that white minorities, such as the Irish, Turks and Cypriots, have remained hidden, even though such groups are subject to discrimination and disadvantage common to other minority groups. The terms "white" and "Caucasian" are frequently and increasingly employed in the scientific literature in spite of widespread concern about the medicalization of race. Moreover, in Great Britain ethnic monitoring of hospital inpatients has revealed negligible interest in utilising codes that subdivide the white group. Yet recent research has shown, for example, substantially elevated age standardised limiting long-term illness rates in the first generation Irish and excess mortality in the second generation living in Britain. The health needs of these white minorities can only properly be identified through the availability of census denominator data of the kind now collected in the U.S. and Canadian decennial census questions on ethnic origin. The opportunity for government to make such provision in the forthcoming Great Britain 2001 Census should be seized whilst it is still available and recommendations for subdividing the "white" group are made.


Classifying Sustainable Development Goal trajectories: A country-level methodology for identifying which issues and people are getting left behind.
How useful are the Sustainable Development Goals for conducting empirical analysis at the country level? We develop a methodological framework for answering this question, with special emphasis on the SDGs' normative ambition of "no one left behind." We first classify all 169 SDG targets and find that 78 incorporate an outcome-focus that is quantitatively assessable at the country level, including 43 through a systematic approach to establishing "proxy targets." We then present a framework for diagnosing the embedded diversity of absolute and relative indicator trajectories in a harmonized manner, based on a country's share of its starting gap on course to be closed by the relevant deadline. In turn, we present a method for estimating the human consequences of falling short on targets, measured by the number of lives at stake and people's basic needs at stake. As a case study, we apply the framework to Canada, an economy not commonly examined in the context of global goals. We are able to assess a total of 61 targets through the use of 70 indicators, including 28 indicators drawn from the United Nations' official database. Overall, we find Canada is on course to succeed on 18 indicators; to cover at least half but less than the full objective on 7 indicators; to cover less than half the required distance on 33 indicators; and to remain stagnant or move backwards on 12 indicators. Among indicators assessed, the country is only fully on track to achieve one SDG. Shortfalls suggest approximately 54,000 Canadian lives at stake and millions of people left behind on issues like poverty, education, intimate partner violence, and access to water and sanitation. Our diagnostic framework enables considerable, if only partial, quantification of a country's SDG challenges, recognizing the wide range of contexts for underlying data availability and societal problems.


Further Evidence of Contrasting Phenotypes Caused by Reciprocal Deletions and Duplications: Duplication of NSD1 Causes Growth Retardation and Microcephaly.
Microduplications of the Sotos syndrome region containing NSD1 on 5q35 have recently been proposed to cause a syndrome of microcephaly, short stature and developmental delay. To further characterize this emerging syndrome, we report the clinical details of 12 individuals from 8 families found to have interstitial duplications involving NSD1, ranging in size from 370 kb to 3.7 Mb. All individuals are microcephalic, and height and childhood weight range from below average to severely restricted. Mild-to-moderate learning disabilities and/or developmental delay are present in all individuals, including carrier family members of probands; dysmorphic features and digital anomalies are present in a majority. Craniosynostosis is present in the individual with the largest duplication, though the duplication does not include MSX2, mutations of which can cause craniosynostosis, on 5q35.2. A comparison of the smallest duplication in our cohort that includes the entire NSD1 gene to the individual with the largest duplication that only partially overlaps NSD1 suggests that whole-gene duplication of NSD1 in and of itself may be sufficient to cause the abnormal growth parameters seen in these patients. NSD1 duplications may therefore be added to a growing list of copy number variations for which deletion and duplication of specific genes have contrasting effects on body development.


CO(2) laser vaporization as primary therapy for human papillomavirus lesions. A prospective observational study.
Human papillomavirus manifestations occur with increased frequency and severity amongst sexually active people. Several therapeutic approaches have been suggested to treat this viral disease. The aim of this prospective observational study was to assess the effectiveness of CO(2) laser vaporization for human papillomavirus warts. Eighty healthy sexually active women with cytologically, colposcopically and histologically diagnosed human papillomavirus urogenital and perianal warts were enrolled and then treated by CO(2) laser (16-18 W). Male partners were also investigated, and interferon-beta was eventually administered. All patients were then followed up for twelve months consecutively. At twelve-month follow-up, warts clearance was observed in 70 (87.5%) women. Recurrence was reported in ten (12.5%) women with multiple partners and affected by flat or endophytic condiloma of the cervix. Moreover, there were no complaints of pain, scar tissue deformity or other side effects. CO(2) laser vaporization is an effective, as well as safe and simple therapeutic approach for treatment of human papillomavirus warts. Its use should be encouraged for condyloma acuminata not associated with malignancy, as well as during pregnancy.


Somatosensory cortical potentials evoked by stimulation of leg nerves: analysis of normal values and variability; diagnostic significance.
An attempt was undertaken to assess the diagnostic value of sensory potentials evoked by stimulation of leg nerves. Findings in normal persons were as follows. First, stimulation of the sural nerve was superior to other methods, especially stimulation of the tibial nerve. Second, variations in latency were considerable and not attributable to age, height, or skin temperature. In many normal persons latency was not stable in either short-time or long-time trials. Amplitudes varied to such an extent that they could not help in diagnosis with the possible exception of extreme side-to-side differences. Finally, both amplitudes and latencies varied in relation to stimulus intensity, repetition rate, and filtering. Since sensory potentials from the leg nerves varied considerably, normal values must extend over a range that is wide enough to avoid mistaken diagnosis of abnormality. Hence, slight disturbances of nerve conduction such as those found in certain neuropathies, root damage and many extramedullary intraspinal space-occupying lesions could not be identified, whereas extensive demyelination in all parts of the sensory neuronal chain was readily discovered.


Extracorporeal shockwaves versus ultrasound-guided percutaneous lavage for the treatment of rotator cuff calcific tendinopathy: a randomized controlled trial.
Extracorporeal shockwave treatment (ESWT) and ultrasound-guided percutaneous lavage (UGPL) are two effective ways of treating rotator cuff calcific tendinopathy (RCCT). The aim of the present study was to compare the effectiveness of these techniques in the treatment of RCCT. Prospective, randomized, controlled trial. Patients treated in our sports medicine and rehabilitation center (Centro Médico Deyre, Madrid. Spain) between January 2007 and December 2013. This randomized study compares the results achieved with these techniques over one year following their use to treat the above condition. Eighty patients received ESWT and 121 received UGPL. A visual analogue scale was used to measure pain, and ultrasound to determine the extent of calcification, at 3, 6, and 12 months after treatment. Pain and the amount of calcification were significantly reduced by both techniques at 3, 6 and 12 months (P<0.001 for each), but significantly more so by UGPL (P<0.001). Both techniques are valid for the treatment of RCCT, although UGPL is associated with a greater reduction of calcification and greater reduction in pain. The results obtained applying UGPL, the low cost and the lack of complications should therefore make the treatment of choice in centers that are appropriately equipped and staffed.


Valve-in-Valve Implantation Using the ACURATE Neo in Degenerated Aortic Bioprostheses: An International Multicenter Analysis.
This study reports an international experience using the transfemoral ACURATE neo transcatheter heart valve (Boston Scientific, Marlborough, Massachusetts) for the treatment of degenerated surgical aortic bioprostheses. Transcatheter valve-in-valve procedures have emerged as an alternative to redo surgery. Supra-annular prostheses might be particularly useful in this indication. This is an international multicenter analysis including 85 patients from 14 centers in Europe and Canada undergoing an ACURATE neo valve-in-valve procedure from March 2015 to February 2019. Internal diameter of the degenerated bioprosthesis was 20.3 ± 2.1 mm. Prosthesis size S was used in 70 (82%) procedures. The median depth of implantation was 3 mm and the upper crown of the ACURATE neo was positioned above the stent posts of the degenerated bioprosthesis in 54 (64%) and inside in 31 (36%). Mean transvalvular gradient before discharge was significantly lower if the upper crown was above the degenerated bioprosthesis (13.7 ± 5.9 mm Hg vs. 19.5 ± 10.0 mm Hg; p = 0.001). However, a high position of the ACURATE neo resulted in embolization in 1 patient, conversion to open-heart surgery in 1, and need for reintervention due to transcatheter heart valve failure within the first 18 months of follow-up in 4. This early experience shows that a high implantation of the ACURATE neo with the upper crown above the stent posts of the degenerated bioprosthesis resulted in lower mean transvalvular gradients but a higher rate of malpositioning and early valve degeneration.


A kinetic hairpin transfer model for parvoviral DNA replication.
The DNAs encapsidated by parvoviruses show distinctly different patterns with respect to the ratio of plus-to-minus strands and sequence heterogeneity at the ends. A kinetic model, based on differential rates of hairpin transfer at 3' termini, is described and shown to account for all known parvoviral DNA distributions.


Immunoglobulin-bearing stem cells for clones of B (bursa-derived) lymphocytes.
Treatment of neonatal chickens with cyclophosphamide depletes bursal lymphocytes while maintaining the bursal epithelium intact. The bursae of normal young chickens contain "bursal stem cells" which can reconstitute the lymphoid compartment in the bursa of the cyclophosphamide-treated recipient. Using bursal stem cells from IgM allotype-heterozygous donors we show that most bursal follicles in the reconstituted host are colonized by single stem cells which are committed to the expression of one or other IgM allotype. In addition we show that the reconstituting bursal stem cells express allelically excluded surface IgM at the time of transfer. Our results suggest that B lymphocyte numbers in hatched chickens are maintained by self-renewal of committed precursors rather than by de novo production from multipotential stem cells.


A molecular mechanics force field for biologically important sterols.
A parameterization has been performed of the biologically important sterols cholesterol, ergosterol, and lanosterol for the CHARMM27 all-atom molecular mechanics force field. An automated parameterization method was used that involves fitting the potential to vibrational frequencies and eigenvectors derived from quantum-chemical calculations. The partial charges were derived by fitting point charges to quantum-chemically calculated electrostatic potentials. To model the dynamics of the hydroxyl groups of the sterols correctly, the parameter set was refined to reproduce the energy barrier for the rotation of the hydroxyl group around the carbon connected to the hydroxyl of each sterol. The frequency-matching plots show good agreement between the CHARMM and quantum chemical normal modes. The parameters are tested in a molecular dynamics simulation of the cholesterol crystal structure. The experimental geometry and cell dimensions are well reproduced. The force field derived here is also useful for simulating other sterols such as the phytosterols sigmasterol, and campesterol, and a variety of steroids.


A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer.
This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed > or = 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v. and 5-FU 425 mg/m2, i.v. daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. Thirty-three patients (28 chemotherapy-naïve and five with prior adjuvant treatment completed > 1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. The alternating schedule of CPT-11 350 mg/m2 with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.


Pregnancy in a couple with a male partner born with severe bladder exstrophy.
Bladder exstrophy is a rare congenital condition, with variable degrees of reproductive dysfunction, from mild exstrophy allowing regular intercourse and reproduction, to severe forms with significant cosmetic deformity and failure to reproduce spontaneously. This is a case report of a patient with severe congenital bladder exstrophy and failure to reproduce spontaneously due to microphallism and anejaculation, treated with testicular sperm aspiration and intracytoplasmic sperm injection (ICSI), resulting in the conception and birth of a healthy unaffected singleton male infant. This the first case report of bladder exstrophy of such a severe degree with a successful reproductive outcome. It illustrates that artificial reproductive techniques can be successful in achieving conception and ongoing pregnancy, including birth of a healthy infant, in patients where intercourse is impossible due to specific genital defects.


Reply to comment on, hydroxyl radical scavenging by solid mineral surfaces in oxidative treatment systems: Rate constants and implications. water research 169, 9. 10.1016/j.watres.2019.115240.
The comments (Kopinke, 2020) do not accurately represent the experimental conditions, parameter values, and conceptual model used in our study (Rusevova and Huling, 2020), leading to a misinterpretation of the results. The kinetic analysis used to determine the surface scavenging rate constant (kS) involved competition kinetics between the probe and the mineral surfaces (Rusevova and Huling, 2020); similar competition kinetic methods have been used regarding other widely reported rate constants (Buxton et al., 1988; Dorfman and Adams, 1973). Assuming mass transport limitations prevented ·OH reaction at mineral surfaces, as proposed in the comments, estimates of kS would be very small, or 0. However, the addition of solid phase media was found to effectively and consistently compete with the probe. The propensity of data, supporting data, and high degree of quality assurance and quality control measures provide multiple lines of evidence indicating a high level of certainty that ·OH scavenging occurred by solid surfaces.


Structure of the triose-phosphate/phosphate translocator reveals the basis of substrate specificity.
The triose-phosphate/phosphate translocator (TPT) catalyses the strict 1:1 exchange of triose-phosphate, 3-phosphoglycerate and inorganic phosphate across the chloroplast envelope, and plays crucial roles in photosynthesis. Despite rigorous study for more than 40 years, the molecular mechanism of TPT is poorly understood because of the lack of structural information. Here we report crystal structures of TPT bound to two different substrates, 3-phosphoglycerate and inorganic phosphate, in occluded conformations. The structures reveal that TPT adopts a 10-transmembrane drug/metabolite transporter fold. Both substrates are bound within the same central pocket, where conserved lysine, arginine and tyrosine residues recognize the shared phosphate group. A structural comparison with the outward-open conformation of the bacterial drug/metabolite transporter suggests a rocker-switch motion of helix bundles, and molecular dynamics simulations support a model in which this rocker-switch motion is tightly coupled to the substrate binding, to ensure strict 1:1 exchange. These results reveal the unique mechanism of sugar phosphate/phosphate exchange by TPT.


Cyclization of the substituted N-(ortho-cyclopropylphenyl)-N'-aryl ureas and thioureas in the gas phase and solution.
Electron ionization (EI), chemical ionization (CI), tandem mass spectrometry, high-resolution measurements, and labeling studies as well as quantum chemical calculations were used to understand the behavior of the molecular radical cations (EI) and protonated molecules (CI) of substituted N-(ortho-cyclopropylphenyl)-N'-aryl ureas and N-(ortho-cyclopropylphenyl)-N'-aryl thioureas in a mass spectrometer. Fragmentation schemes and possible mechanisms of primary isomerization were proposed. According to the fragmentation pattern, formation of the corresponding benzoxazines and benzothiazines was considered as the major process of isomerization of the original M(+.) and MH(+), although some portions of these ions definitely transformed into other structures. The treatment of N-(ortho-cyclopropylphenyl)-N'-phenyl urea and N-(ortho-cyclopropylphenyl)-N'-phenylthiourea in solution with strong acids formed predicted 4-ethyl-N-phenyl-4H-3,1-benzoxazin-2-amin and 4-ethyl-N-phenyl-4H-3,1-benzothiazin-2-amine as principal products.


Cell membrane alterations in the stria vascularis of the guinea pig after ethacrynic acid treatment studied by freeze-fracture.
A freeze-fracture examination of the stria vascularis during the first 2 h after injection of ethacrynic acid was performed. This showed a re-distribution of the particles on the membrane fracture faces of both marginal and intermediate cells. As oedematous spaces developed, particle-poor, vesicle-like structures were found associated with both cell types. The tight junctions at the apices of the marginal cells and around basal cells were unaffected.


Educational interventions to promote sun-protection behaviors in adolescents in the United States: A systematic review.
The most prevalent modifiable risk factor for skin cancer is cumulative lifetime exposure to ultraviolet (UV) radiation, supporting the development of interventions promoting the early adoption of sun-protection behaviors. This systematic review summarizes behavioral interventions designed to promote sun-protection behaviors and reduce harmful UV exposure among U.S. adolescents. Ten studies describing 15 intervention arms were ultimately included in this review and comprised seven cross-sectional studies, a cohort study, a quasi-experimental study, and a randomized controlled trial. Most interventions included in this review were effective in increasing awareness of skin cancer and knowledge of the risk factors for skin cancer, but knowledge did not correlate with self-reported frequency of sun-protection behaviors in this population.


Sectioning the anterolateral ligament did not increase tibiofemoral translation or rotation in an ACL-deficient cadaveric model.
The anterolateral ligament (ALL) has been proposed as a possible extra-articular stabiliser of the knee. Injury to the ALL may result in residual instability following surgical reconstruction of a ruptured anterior cruciate ligament (ACL). Few studies have evaluated the biomechanical role of the ALL. The purpose of this study was to investigate whether sectioning the ALL would have an influence on tibiofemoral translation or rotation during the anterior drawer, Lachman, pivot shift, external rotation, and internal rotation tests in an ACL-deficient knee. Only whole-body specimens having an ALL were included in this study. Lachman, anterior drawer, external rotation, and internal rotation tests were performed manually. Pivot shift test was done using a mechanised pivot shifter. The amount of tibiofemoral translation and rotation was recorded by a navigation system. Each specimen was tested in its native state, after sectioning the ACL, and after combined sectioning of the ACL and the ALL. In six out of 14 cadaveric knees, an ALL could be identified. The ACL-deficient knee had significantly more tibiofemoral translation and rotation compared to the native knee (P < 0.05). However, no changes in the magnitudes of translation or rotation were seen after subsequent sectioning of the ALL compared to the ACL-deficient knee (P > 0.05). Adding an ALL lesion in an ACL-deficient knee did not increase tibiofemoral instability in this cadaveric model. It remains unclear whether injury to the ALL would result in substantial knee instability in the setting of ACL injury in vivo. Further research is warranted to fully elucidate the role of the ALL during knee kinematics and to determine in which scenarios ALL repair would be warranted. Understanding the function of the ALL may improve the current treatment strategies for ACL ruptures.


Bias in conceptual priming.
In recent years, Ratcliff, McKoon, and colleagues have argued that priming in perceptual implicit memory tests is the result of biases in information processing. Three experiments are presented that extend this framework to the conceptual implicit memory domain. Participants studied a list of words before receiving a set of general knowledge questions. For some questions, participants studied the correct answer; for others, they studied a similar but incorrect answer. Although study of a correct answer facilitated performance, study of the similar alternative hurt performance. Costs and benefits of previous study were observed in both production and forced-choice tasks. However, there was no benefit of previous study when participants studied both the correct answer and the similar but incorrect alternative. The pattern of results indicates that participants were biased to respond with previously studied words on the conceptual implicit memory test. This pattern is concordant with the biased information-processing approach to priming.


Outcomes after reirradiation for recurrent nasopharyngeal carcinoma: North American experience.
The purpose of this article was to report outcomes of reirradiation for locoregionally recurrent nasopharyngeal carcinoma (NPC). A retrospective review was conducted of all patients with locoregionally recurrent NPC who received reirradiation between 2001 and 2012. Overall survival (OS), local control, regional control, distant control, and Radiation Therapy Oncology Group (RTOG) grades 3 to 4 late toxicity were examined. A total of 42 recurrent cases treated with intensity-modulated radiotherapy (IMRT; 27 patients) or non-IMRT (stereotactic radiotherapy [RT], 12 patients; 3D conformal RT, 3 patients) were identified. Median time from initial RT to recurrence was 4.6 years. Hyperfractionation with 1.1 to 1.4 Gy/fraction twice daily to a total of 40 to 60 Gy was used in 27 IMRT and 5 non-IMRT patients. The remaining 10 patients received conventional fractionation 1.8 to 2.0 Gy/fraction to 50 to 60 Gy. Median follow-up was 3.0 years. The 3-year OS, local control, regional control, distant control, and late toxicity rates were 49%, 46%, 71%, 79%, and 37%, respectively. Reirradiation for recurrent NPC, delivered mostly with hyperfractionated IMRT, can result in durable disease control with acceptable late toxicity. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1102-E1109, 2016.


Increased case finding of tuberculosis from sputum and sputum deposits after magnetic bead concentration of mycobacteria.
Concentration of mycobacteria from sputum by centrifugation prior to acid-fast microscopy increases case finding compared to direct microscopy of the sputum (direct smear). However, centrifugation has to be performed outside the safety cabinet and many laboratories do not have access to a centrifuge. Magnetic bead extraction of the mycobacteria is an alternative method that can be performed in a cabinet with just a magnet. Magnetic TB-Bead (Microsens Medtech Ltd) extraction of mycobacteria from sputum prior to microscopy was compared to direct smear on 78 sputum samples. Microscopy of the TB-Bead extracts identified all of 26 of the direct smear positive samples either with the same microscopy score or, in 19/27 of samples, with an increased microscopy score which aided microscopy detection. In addition, microscopy of the TB-Bead extracts identified 10 additional positive samples compared to direct smear; which represents a statistically significant increase in case finding of 38% (p = 0.002) compared to direct smear. In a separate study, TB-Beads enabled further 4 positive samples to be detected from 30 centrifuged pellets that were originally smear negative; two of these were subsequently found to be positive when the original deposits were reinvestigated by smear microscopy. By concentrating mycobacteria from sputum and sputum deposits, TB-Beads have been demonstrated to increase the number of positive sputum samples which could increase case-finding. The TB-Bead method is simple and rapid and compatible with use within a safety cabinet.


Domain function dissection and catalytic properties of Listeria monocytogenes p60 protein with bacteriolytic activity.
The major extracellular protein p60 of Listeria monocytogenes (Lm-p60) is an autolysin that can hydrolyze the peptidoglycan of bacterial cell wall and has been shown to be required for L. monocytogenes virulence. The predicted three-dimensional structure of Lm-p60 showed that Lm-p60 could be split into two independent structural domains at the amino acid residue 270. Conserved motif analysis showed that V30, D207, S395, and H444 are the key amino acid residues of the corresponding motifs. However, not only the actual functions of these two domains but also the catalytic properties of Lm-p60 are unclear. We try to express recombinant Lm-p60 and identify the functions of two domains by residue substitution (V30A, D207A, S395A, and H444A) and peptide truncation. The C-terminal domain was identified as catalytic element and N-terminal domain as substrate recognition and binding element. Either N-terminal domain truncation or C-terminal domain truncation presents corresponding biological activity. The catalytic activity of Lm-p60 with a malfunctioned substrate-binding domain was decreased, while the substrate binding was not affected by a mulfunctioned catalytic domain. With turbidimetric method, we determined the optimal conditions for the bacteriolytic activity of Lm-p60 against Micrococcus lysodeikficus. The assay for the effect of Lm-p60 on the bacteriolytic activity of lysozyme revealed that the combined use of Lm-p60 protein with lysozyme showed a strong synergistic effect on the bacteriolytic activity.


Vertical transmission of herpes simplex virus acquired after primary outbreak in second trimester of a dichorionic twin gestation.
The incidence of genital herpes simplex virus (HSV) has increased in recent years, particularly among women of reproductive age. This places more neonates at risk for severe morbidity and mortality. Treatment recommendations for primary disease in pregnancy are lacking, particularly for those who acquire. HSV remote from term. A patient at 17 weeks of gestation carrying dichorionic twins developed primary herpes with subsequent vertical transmission of the virus and significant neonatal morbidity. Data regarding risks and benefits of treatments such as acyclovir and immunoprophylaxis are lacking at a time when the incidence of HSV infection is on the rise.


The emerging role of proteases in retinal ganglion cell death.
Retinal ganglion cell (RGC) death is an important issue in Primary Open Angle-Glaucoma (POAG) in terms of both vision loss and health care costs. Yet, the pathophysiology underlying RGC death in glaucoma is unclear. A growing body of evidence indicates that proteases that modulate the extracellular matrix (ECM) milieu in the retina, either directly or indirectly, play an important role in dictating the fate of RGCs. Recent evidence indicates that proteases, in addition to ECM-remodeling, have broader functional roles in glutamate receptor processing and predisposing RGCs to secondary damage. This review is focused on discussing the role of two groups of proteases, the matrix metalloproteinases (MMPs) and the plasminogen activators (PAs), in RGC death. In a long-run, a better understanding of the mechanisms involved in the regulation of proteases may lead to the development of adjunctive treatment options to attenuate RGC death and improve vision loss in glaucoma.


XPG genetic polymorphisms and clinical outcome of patients with advanced non-small cell lung cancer under platinum-based treatment: a meta-analysis of 12 studies.
A number of studies on the relationship between xeroderma pigmentosum group G (XPG) polymorphisms and clinical outcomes in non-small cell cancer (NSCLC) have led to inconclusive results. This meta-analysis evaluates the predictive value of XPG polymorphisms on the treatment response rate and overall survival of patients with NSCLC. To measure the correlative strength of the relationship between XPG polymorphisms and outcomes of patients with NSCLC, we searched electronic databases, including PubMed and China National Knowledge Infrastructure, to retrieve studies up to August 2016. We also employed pooled odds ratios (ORs) and hazard ratios (HRs) corresponding to 95% confidence intervals (95% CIs). Twelve studies involving 2877 patients with NSCLC were included: 8 studies involving 1473 patients examined the correlation between XPG polymorphisms and tumor response rate and 7 studies involving 2329 patients reported on the correlation of XPG polymorphisms with overall survival. None of the XPG His1104Asp(C>G)/His46His(C>T) polymorphisms exhibited a correlation with treatment response rate or overall survival. However, in a further stratified analysis by ethnicity, carriers of the 1104G allele were associated with good response among Asians in the homozygote model (GG vs. CC: OR = 1.57, 95% CI: 1.05-2.34, P = 0.027). Meanwhile, further stratified by ethnicity, His46His polymorphism was not associated with RR and OS in any genetic models. No strong evidence was found to support the use of XPG polymorphisms as tumor response and prognostic factors of patients with NSCLC receiving a platinum-based treatment regimen, which is attributed to marginal association. Studies with large-scale and multiple ethnicities need to be conducted to verify the conclusion.


The drugs industry and peasant self-defence in a Peruvian cocaine enclave.
This article gives a detailed account of the cocaine industry and the related violence in the Peruvian Upper Huallaga. It is argued that in this cocaine producing region violence increased during state-led forced eradication operations of the coca plants. Most of the violent incidents were closely related to the diminishing cocaine industry, but they were also related to the actions of the state security forces. Instead of receiving support from the state's security apparatus, the population mobilized its own forces to fight the violence. As will be argued, the causes of violence in this cocaine enclave are part of a dynamic interaction amongst many factors - an interaction that is influenced by the local context, a partial state vacuum, and the social utility and the economic advantages of violence. One needs to be aware that motivations of those who engage in the violent behaviour can change over time, as underlying power structures are influenced by changes in local conditions. The study covers an in-depth account of events taking place in the Upper Huallaga during the years 2003-2007. The research material was collected by several ethnographical fieldwork methods.