Clinical algorithms for the screening of women for gonococcal and chlamydial infection: evaluation of pregnant women and prostitutes in Zaire.
A substantial proportion of women with gonococcal and/or chlamydial infection are asymptomatic. Thus active case detection is problematical, particularly in developing countries, where facilities and materials for laboratory testing are limited. We assessed the diagnostic validity of the hierarchical clinical algorithms recommended by the World Health Organization as well as that of a nonhierarchical scoring system, using data for 1,160 pregnant women (a low-prevalence group) and 1,222 prostitutes (a high-prevalence group) in Kinshasa, Zaire. Neisseria gonorrhoeae and/or Chlamydia trachomatis was detected in 6.5% and 31.0% of pregnant women and prostitutes, respectively. No single variable that was both sensitive (> 60%) and specific (> 60%) was associated with infection. A simple hierarchical algorithm based only on reported symptoms had a sensitivity of 48.0% and 54.9% and a specificity of 75.2% and 52.2% for the screening of pregnant women and prostitutes, respectively. A second algorithm that included a speculum examination had a sensitivity of only 29.3% but a specificity of 85.3% in pregnant women. When a nonhierarchical scoring system was used, the sensitivity was 72.0% and 71.0% and the specificity was 73.5% and 55.8% for pregnant women and prostitutes, respectively. Scoring systems that incorporate risk markers as well as symptoms and signs may represent affordable alternative methods of screening for gonococcal and/or chlamydial infections among women in resource-poor settings.


High-Throughput Mapping and Clonal Quantification of Retroviral Integration Sites.
We describe here a method to identify the position of retroviral insertion sites and simultaneously to quantify the absolute abundance of each clone, i.e., the number of cells having the provirus inserted at a given place in the host genome. The method is based on random shearing of the host cell DNA, followed by a linker-mediated PCR to amplify the genomic regions flanking the proviruses, and high-throughput sequencing of the amplicons. The quantification of the abundance of each infected clone allowed us to develop two new metrics: i. the oligoclonality index, which quantifies the nonuniformity of the distribution of clone abundance, and ii. an estimator of the total number of clones in the body of the host. These new tools are valuable for the study of retroviral infections and can also be adapted for the tracking of gene-edited cells.


Heritability of symptom domains in otitis media: a longitudinal study of 1,373 twin pairs.
Research on risk factors and pathogenesis of otitis media has emphasized the environment, but previous twin studies suggest a strong genetic component. In those studies, no attempt was made to differentiate the role of initial acute infection from the chronic airway blockage that frequently accompanies persistent effusion. The authors estimated genetic and environmental determination of both of these aspects of otitis media histories at three time points. A large and representative subset of a total population cohort of all twins born in England and Wales in 1994, was studied prospectively at ages 2, 3, and 4 years (monozygotic, n = 715; dizygotic, n = 658). For the total symptom score, the estimated heritabilities at ages 2, 3, and 4 years were 0.49, 0.66, and 0.71, respectively. All correlations for the total score found in monozygotic twins were about 0.9, but correlations were lower for dizygotic twins (p < 0.65). Shared environmental influences declined in importance over time (0.41, 0.22, and 0.16 at ages 2, 3, and 4 years, respectively). No gender differences were found in parameter estimates. Symptoms of acute infections showed lower heritability (0.57 on average) and higher shared environment (0.18) than did chronic airway blockage (0.72 heritability and 0.10 shared environment). The strong genetic component, which this study confirms, is not unitary but distributes differently across the phenotypic aspects of otitis media and probably across pathogenetic stage.


Employees' perceptions of the implementation of affirmative action in the health sector in the Standerton District in South Africa.
Since the inception of a fully democratic government in South Africa in 1994, government and trade unions have been placing increasing pressure on government departments and public institutions to introduce steps to correct racial discrimination through the implementation of affirmative action (AA). This study, which was carried out in the Standerton Health District, assesses employees' perceptions of and attitudes towards the implementation of AA. A quantitative design was used. Data was gathered from a total population of 360 employees by means of a questionnaire. The study revealed the following major themes: Respondents feel that if AA were effectively implemented, there would be an increase in productivity. There is strong support for the implementation of AA appointments. The implementation of AA will fail if the goals of AA are not properly and effectively communicated to all employees.


MiR-29 Induces K562 Cell Apoptosis by Down-Regulating FoxM1.
Leukemia seriously threatens human life and health. MicroRNAs can regulate cell growth, proliferation, and death. This article investigated the role of miR-29 on regulating leukemia cell growth, proliferation, and apoptosis. miR-29 and scramble miRNA were transfected to K562 cells. MTT assay, colony formation assay, caspase-3 activity detection, and flow cytometry were applied to test miR-29 effect on cell growth, proliferation, and apoptosis. Western blot was used to detect Forkhead box protein M1 (FoxM1) protein expression. After we transfected miR-29, K562 cells were transfected with FoxM1 siRNA to test cell apoptosis. K562 cell growth and proliferation were inhibited after transfection with miR-29. Apoptosis phenome and caspase-3 activation were observed. FoxM1 level decreased. SiRNA FoxM1 enhanced miR-29-induced K562 cell apoptosis. FoxM1 overexpression suppressed miR-26-induced K562 cell apoptosis. MiR-29 restrained K562 cell growth and proliferation. MiR-29 induced K562 cell apoptosis through down-regulating FoxM1.


GEMALS: A promising therapy for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that currently has no cure. At present, the only approved treatment for ALS is Riluzole, a glutamate release blocker that improves life expectancy by 3-6 months. ALS-Endotherapia (GEMALS) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment. A total of 31 patients with ALS were assessed in the current study. Deceleration of the disease was observed in 83.87% (P<0.0001) of patients and mean life expectancy was increased by 38 months. Motor functions, including breathing, walking, salivation, speech, swallowing and writing, were also improved in patients treated with GEMALS. The results of the present study demonstrate that long-term treatment with GEMALS has a curative effect in patients with ALS. Furthermore, the overall effectiveness of GEMALS was assessed using the ALS Assessment Questionnaire. The score improvement was 76.2 and 100% for men and women, respectively (P<0.0001), compared with the worldwide reference score. The present study provides a promising basis for the use of GEMALS as a therapeutic treatment for patients with ALS; however, these results must be confirmed in a double-blinded and randomized clinical trial.


A review of combined psychotherapy and pharmacotherapy in the treatment of depression.
The effectiveness of combined psychotherapy and pharmacotherapy for depression is a clinical issue of increasing importance. Using a box score approach, the authors review the 17 available studies in the literature, provide a methodological critique, summarize results, and suggest directions for further research and for clinical practice. Overall, given methodological limitations in the existing literature, it appears that combined treatment is no less effective than psychotherapy or pharmacotherapy alone and may have specific advantages for subpopulations of depressed patients.


Early clinical experience with bleomycin in the United Kingdom in series of 105 patients.
The results of treating a series of 105 patients (79 with advanced squamous cell carcinoma, 21 with advanced lymphoma, and 5 with miscellaneous tumours) with bleomycin are described. The drug was usually given as a single agent. Four patients with squamous cell carcinoma showed complete regression and there was partial regression in 25. Side effects were frequent, particularly skin changes and stomatitis; death from pneumonitis occurred in one patient.


Cross-sectional association of exercise, strengthening activities, and cardiorespiratory fitness on generalized anxiety, panic and depressive symptoms.
Limited research has evaluated the individual and combined associations of physical activity (PA), cardiorespiratory fitness (CRF) and muscle strengthening activities (MSA) on generalized anxiety, panic and depressive symptoms. We evaluated this topic in a representative sample of young (20-39 years) adults, with considerations by sex. Data from the 1999-2004 National Health and Nutrition Examination Survey (N = 2088) were used. Generalized anxiety, panic and depressive symptoms were assessed via self-report as well as using the Generalized Anxiety Disorder, Panic Disorder, and Depressive Disorders modules of the automated version of the World Health Organization Composite International Diagnostic Interview (CIDI-Auto 2.1). PA and MSA were assessed via validated self-report questionnaires and CRF was determined via a submaximal treadmill-based test. An index variable was created summing the number (range = 0-3) of these parameters for each participant. For example, those meeting PA guidelines, MSA guidelines and having moderate-to-high CRF were classified as having an index score of 3. MSA was not independently associated with generalized anxiety, panic and depressive symptoms, but those with higher levels of PA and CRF had a reduced odds of these symptoms (ranging from 40 to 46% reduced odds). Compared to those with an index score of 0, those with an index score of 1, 2, and 3, respectively, had a 39%, 54% and 71% reduced odds of having generalized anxiety, panic and depressive symptoms. Results were consistent across both sexes. PA and CRF, but not MSA, were independently associated with generalized anxiety, panic and depressive symptoms. There was evidence of an additive association between PA, CRF, and MSA on these symptoms.


Approach to pulmonary embolism: A clinical care pathway.
Acute pulmonary embolism (PE) is a potentially fatal condition that is often underdiagnosed due to its ambiguous and generalized symptoms. As such, nurse practitioners (NPs) may struggle to respond in a timely and accurate manner to clients presenting with acute PE. Given the complexities of diagnosing and managing PE, we propose a visual clinical care pathway to support NPs in recognizing and stratifying clients' risks of PE. The article provides guidance regarding PE diagnostic testing and offers a summary of effective, evidence-based treatment options for adult clients, including those with cancer.


Generation of genetically modified rat models via the CRISPR/Cas9 technology.
The RNA-guided CRISPR/Cas9 genomic editing system consists of a single guide RNA (sgRNA) and a Cas9 nuclease. The two components form a complex in cells and target the genomic loci complementary to the sgRNA. The Cas9 nuclease cleaves the target site creating a double stranded DNA break (DSB). In mammalian cells, DSBs are often repaired via error prone non-homologous end joining (NHEJ) or via homology directed repair (HDR) with the presence of donor DNA templates. Micro-injection of the CRISPR/Cas9 system into the rat embryos enables generation of genetically modified rat models. Here, we describe a detailed protocol for creating gene knockout or knockin rat models via the CRISPR/Cas9 technology.


Squeezing and Overcoming the Heisenberg Scaling with Spin-Orbit Coupled Quantum Gases.
We predict that exploiting spin-orbit coupling in a harmonically trapped spinor quantum gas can lead to scaling of the optimal measurement precision beyond the Heisenberg scaling. We show that quadratic scaling with the number of atoms can be facilitated via squeezed center-of-mass excitations of the atomic motion using 1D spin-orbit coupled fermions or strongly interacting bosons (Tonks-Girardeau gas). Based on predictions derived from analytic calculations of the corresponding quantum Fisher information, we then introduce a protocol which overcomes the Heisenberg scaling (and limit) with the help of a tailored excited and entangled many-body state of a noninteracting Bose-Einstein condensate. We identify corresponding optimal measurements and argue that even finite temperature as a source of decoherence is, in principle, rather favorable for the obtainable precision scaling.


Positive feedback regulation of stgR expression for secondary metabolism in Streptomyces coelicolor.
LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in Streptomyces. Here we reported that StgR, a typical LTTR in Streptomyces coelicolor, was a negative regulator of undecylprodigiosin (Red) and γ-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes, redD and actII-orf4, respectively. Meanwhile, stgR expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover, stgR expression was positively autoregulated by direct binding of StgR to its own promoter (stgRp), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-stgRp interaction could be destroyed by the antibiotic γ-actinorhodin produced from S. coelicolor. Thus, our results suggested a positive feedback regulatory mechanism of stgR expression and antibiotic production for the rapid and irreversible development of secondary metabolism in Streptomyces.


Pregnancy and child health outcomes in pediatric and young adult leukemia and lymphoma survivors: a systematic review.
As long-term survival is high for children and young adults diagnosed with leukemia and lymphoma, delineating maternal, fetal and offspring health risks is important to their family planning. This systematic review examined data comparing these health risks between leukemia and lymphoma survivors and women without a history of cancer. Following a search of Embase, PubMed, CINAHL, Cochrane, and Web of Science, 142 articles were screened and 18 were included in this review. No higher risks of spontaneous abortion, maternal diabetes and anemia, stillbirth, birth defects, or childhood cancer in offspring were observed in survivors compared to controls. Important to counseling and clinical care, live birth rates were lower, while preterm birth and low birth weight risks were modestly higher in survivors compared to controls. Findings were largely reassuring but highlight the lack of data on maternal cardiopulmonary risks, differential risk by cancer treatment type, and interventions to decrease these risks.


Gallbladder visualization on CT shortly after angiography with ioxaglate.
Thirty-five patients underwent CT examination 15 to 30 min after abdominal angiography with ioxaglate. The gallbladder was visualized in 12 patients in the absence of clinical evidence of renal impairment. Gallbladder opacification on CT examinations shortly after angiography shows that the hepatobiliary tract is important in the excretion of ioxaglate.


EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.
Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome.


The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis.
Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblast's transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated αSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1α2, Col5α2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs.


Hyperpolarized fumarate via parahydrogen.
We produce hyperpolarized [1-13C]fumarate in the proton nuclear spin singlet state by pairwise trans-addition of parahydrogen to a molecular precursor using a ruthenium-based catalyst in water. The proton singlet state is transformed into observable carbon magnetization by radiofrequency pulses to enhance the 13C signal by a factor of 1000 using 50% para-enriched hydrogen gas.


Twendee X, a mixed antioxidant supplement, improves cognitive function, coordination, and neurotrophic factor expression in long-term vitamin E-deficient mice.
Oxidation products gradually accumulate during senescence, enhancing the risk of onset of many severe diseases. One such disease is dementia, and the number of cases of dementia, including Alzheimer's disease, has been increasing world-wide. These diseases can be prevented via attenuation of age-related physiological dysfunction; one preventive approach is the ingestion of antioxidants such as vitamin C and vitamin E. Many antioxidants are readily available commercially. Ingestion of mixed antioxidants is expected to provide further beneficial effects for human health. In this study, we used vitamin E-deficient mice as an animal model of increased oxidative stress and assessed the effects of dosing with mixed antioxidants. Administration of a commercial mixed antioxidant formula, Twendee X significantly improved cognitive function and coordination compared to untreated vitamin E-deficient animals. Furthermore, the levels of brain-derived neurotrophic factor and nerve growth factor were significantly increased in the cerebral cortex of Twendee X-dosed vitamin E-deficient mice compared to untreated animals. These results indicate that intake of a mixed antioxidant supplement may be beneficial to human health, even after oxidative stress has begun. In the next stage, it will be necessary to compare with other antioxidants and consider whether it is effective in the aged model.


Association of obesity, triglyceride-glucose and its derivatives index with risk of hyperuricemia among college students in Qingdao, China.
To analyze and compare the associations of hyperuricemia (HUA) with obesity, triglyceride-glucose (TyG), and its derivatives in college students. To provide early guidance on risk predictors of HUA in college students. This study was a cross-sectional survey including 23,411 participants (age: 17-20 years). Investigators conducted face-to-face interview surveys and physical examinations. Automated biochemical methods were used to detect biochemical indicators such as serum uric acid (UA). Calculation of obesity, TyG, and their derivatives indices were performed. Logistic regression was used to analyze the relationship between different indexes and hyperuricemia. OR value and 95% CI were also calculated. ROC curve was used for assessing the predictive ability of different indices of hyperuricemia. After adjusting for age, SBP, DBP, ALT, AST, TC, BUN, and CREA, multivariate logistic regression showed that the OR value of LAP in the obesity index was higher, especially in women (male OR: 4.347, 95%CI: 3.807, 4.964; female OR: 4.672, 95%CI: 3.800, 5.744). The other three quartiles of TyG derivatives were highly associated with hyperuricemia in men and women compared with the top quartile (all P< 0.05). The risk of hyperuricemia increased with an increase in quartiles. For college students, all indicators could distinguish the presence of hyperuricemia. For men, the area under the curve (AUC) of TyG-WC was the largest (AUC: 0.694; 95%CI: 0.684-0.704; P<0.05), according to the Maximum Youden index 0.290 with cut point value 477.853. In women, TyG-BMI showed a maximum AUC value of 0.702 (95%CI: 0.685-0.719; P<0.05), according to the maximum Youden index of 0.317 with cut point value 132.446. The TyG-WC, TyG-WHtR, TyG-LAP, and LAP indices also had relatively high AUC. In clinical practice, LAP, TYG, and their related derivatives may be used as sensitive indicators for HUA prediction in college students.


hTERT/re-caspase-3 system induce apoptosis in hTERT-positive cancer cells.
Apoptosis induction is a promising approach for the treatment of human cancer. To achieve this purpose, the design of an expression system capable to induce apoptosis specifically in cancer cells is essential. Telomerase is an attractive target for delivery of apoptotic genes as an overwhelming majority of cancers have telomerase activity whereas most normal cells have low or an absence of telomerase activity. Activation of telomerase is tightly regulated at the transcriptional level of human telomerase reverse transcriptase (hTERT). In the present study, we developed a telomerase-specific delivery system of apoptosis-inducible gene re-Caspase-3, through utilizing the promoter of the hTERT gene, and then investigated its antitumor effect on cancer cells and tissues. The reason we used the re-Caspase-3 gene is that it is capable of autocatalytic processing and inducing apoptosis independent of the initiator Caspases. Here, we demonstrated that the hTERT/re-Caspase-3 system induced apoptosis in hTERT-positive cancer cells: CNE1 (nasopharyngeal carcinoma), HRT-18 (colonic carcinoma), MGC (stomath carcinoma), but not in hTERT-low Hacat (human normal keratinize epithelium) cells. In addition, the growth of s.c. tumors in nude mice was suppressed significantly by the treatment with the hTERT/re-Caspase-3 system. Results suggested that the telomerase-specific transfer of there-Caspase-3 gene may be an effective and promising targeting approach for the treatment of cancer.


[System of values of external and internal clients evidenced in the nursing process].
We shall understand value as a permanent belief on the specific way of conduct, or the final state of existence. Ours values influence many aspects of our lives. A distinction must be made between a person's own values and those values people attribute to objects and events in their immediate environment. In this way, health exists as an end, or becomes a motivation to assure happiness or pleasure. It makes part of the system of values of an individual within the organization called hospital. We present an example such as to make us to reflect on how this value called health can be experienced and also on our own way of living and being healthy.


[Impact of hypophosphatemia on weaning from mechanical ventilation].
To explore the influence of hypophosphatemia on weaning from mechanical ventilation. An observational study was conducted. The medical records of 30 mechanical ventilated patients with hypophosphatemia admitted to intensive care unit of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to August 2020 were analyzed; another 60 mechanical ventilated patients with normophosphatemia around the same time were enrolled as controls by 1:2 case-control matching based on gender, age, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score. And then the duration of invasive mechanical ventilation, times of spontaneous breathing trial (SBT), the diaphragmatic ultrasonography movement indexes, and outcome of weaning and prognosis during hospitalization were compared between the two groups. Receiver operator characteristic curve (ROC curve) was plotted to calculate the areas under ROC curve (AUC) and cut-off values of serum phosphorus for successful weaning and hospital survival. The correlations between the diaphragmatic ultrasonography movement indexes and serum phosphorus were analyzed by Pearson partial correlation analysis. Compared with normophosphatemic group, the duration of invasive mechanical ventilation in hypophosphatemia group was significantly longer [days: 13.0 (7.0, 22.0) vs. 10.0 (5.5, 14.0), P < 0.05], and SBT attempts were more often [times: 3 (0, 5) vs. 1 (1, 2), P < 0.01], while the rate of successful weaning was lower (53.3% vs. 91.7%, P < 0.01), and the hospital mortality was higher (20.0% vs. 1.7%, P < 0.01). ROC curve analysis showed that serum phosphorus could predict successful weaning of mechanical ventilated patients, the AUC was 0.795, and the optimum cut-off value of serum phosphorus was 0.85 mmol/L with sensitivity of 73.2% and specificity of 84.2%. Serum phosphorus could predict hospital survival of mechanical ventilated patients, the AUC was 0.782, and the optimum cut-off value of serum phosphorus was 0.48 mmol/L with sensitivity of 81.9% and specificity of 85.7%. Compared with normophosphatemic group, diaphragm thickness at the end of inspiration (DTei), diaphragm thickness at the end of expiration (DTee), diaphragm thickening fraction (DTF), diaphragm excursion (DE) in hypophosphatemia group were all significantly decreased [DTei (cm): 0.19±0.07 vs. 0.27±0.08, DTee (cm): 0.14±0.05 vs. 0.19±0.06, DTF: (33.55±16.17)% vs. (45.04±18.66)%, DE (cm): 1.17±0.49 vs. 2.28±0.69, all P < 0.01]. Pearson partial correlation analysis showed that linear correlations were found between serum phosphorus and DTei, DTee, DTF, DE (r values were 0.442, 0.351, 0.293, 0.628 respectively, all P < 0.01). Serum phosphorus may have correlation with the diaphragmatic ultrasonography movement indexes. Hypophosphatemia may impair the contractile properties of diaphragm, induce more SBT attempts and longer duration of invasive mechanical ventilation, and affect outcome of weaning and prognosis.


Predictors of physical disability after age 50. Six-year longitudinal study in a runners club and a university population.
Predictors of disability were studied over 6 years among 50- to 80-year-old members of a runners club (N = 407) and a university population (N = 299). Data have been collected annually since 1984 on sociodemographic characteristics, health habits, medical history, medication use, family history, psychological parameters, and physical disability as measured by the Health Assessment Questionnaire. Members of the runners club, compared to university participants, had better overall health and less disability at baseline (0.03 versus 0.08) and at 6-year follow-up (0.04 versus 0.24). Predictors of greater subsequent disability among university participants were greater baseline disability, greater medication use, greater number of pack-years of cigarette smoking, older age, being unmarried, higher blood pressure, history of arthritis, and less physical activity compared to one's peers. In addition, changes in characteristics during follow-up that were independently associated with greater disability were development of joint pain, arthritis, or bone fracture and increased body mass index. Predictors of greater disability in the runners group included greater baseline disability, being a nonrunner at baseline, greater dietary salt intake, more years of running at baseline, and greater frequency of physician visits for running injuries. Greater disability in this group also was associated with increases in medication use, declining alcohol consumption, and development of joint pain over 6 years. Results of this study suggest that physical disability is linked to a constellation of characteristics, health habits, medical history, comorbidities, and marital status. While self-selection bias cannot be ruled out entirely, these data are consistent with the hypothesis that those who engage in high levels of physical activity beyond middle age will continue to maintain better functional abilities.


Associations Between Adolescent Problematic Internet Use and Relationship Problems in Chinese Families: Findings from a Large-scale Survey.
Problematic internet use (PIU) is prevalent among Chinese adolescents. There is a need to better understand how the quality of parent-adolescent relationship is associated with adolescent PIU to guide the development of effective prevention and early intervention programs. This study aims to evaluate parent-adolescent conflict and parenting styles as potential risk factors associated with adolescent PIU. A sample of 6552 students (aged 10-19 years) from 22 schools in Guangdong, China, was recruited. The participants completed self-report questionnaires measuring their perceptions of conflict with their parents (involving verbal conflict, emotional abuse, and physical abuse) as well as their perceptions of their parents' parenting styles (including parental care and parental control as measured by the Parental Bonding Inventory), and PIU using the Adolescent Pathological Internet Use Scale. Grade level and gender were examined as moderators of these associations. Using multiple regression analyses, we found that greater mother-adolescent conflict, father-adolescent conflict, and parental control, and lower levels of parental care, were associated with higher levels of adolescent PIU (P<.001). The association between mother-adolescent conflict and PIU was stronger in older students than in younger students (P=.04), whereas the association between father-adolescent conflict and PIU was stronger in male students than in female students (P=.02). Compared with those who reported no mother-adolescent conflict, participants who experienced verbal conflict and emotional abuse, but not physical abuse from their mothers, reported higher levels of PIU (P<.001). Compared with those who reported no father-adolescent conflict, participants who experienced verbal conflict, emotional abuse, and physical abuse from their fathers had significantly higher levels of PIU (P<.001, P<.001, and P=.02, respectively). These findings point to the value of interventions to reduce parental verbal conflict, emotional abuse, and physical abuse, and to increase positive parenting styles, to lower the risk of PIU in Chinese adolescents.


The g-values and hyperfine coupling of amino acid radicals in proteins: comparison of experimental measurements with ab initio calculations.
Electron paramagnetic resonance (EPR) spectroscopy has been extensively used to identify and characterize protein-based redox active amino acid radicals based on their g-values and hyperfine couplings. To better understand how these parameters depend on the electronic structure and environment of the radical, the theoretical g-values and proton hyperfine tensors of three models corresponding to the tyrosyl, tryptophanyl and glycyl radicals were calculated using Gaussian 03. The g-values were determined using the B3LYP/6-31+G(D,P) combination of density functional and basis set, while the hyperfine tensors were determined using the B3LYP/EPR-III and PBE0/EPR-III combinations. Comparisons are made to measured values. It was found that by appropriately accounting for hydrogen bonds and the dielectric constant of the environment, good agreement could be achieved between the calculated and measured g-values. In all three cases, the g-anisotropy arose from significant spin density on a nitrogen or oxygen atom. The calculated hyperfine tensors for the three radicals did not differ significantly from previous calculations. In the case of the tyrosyl radical, it is shown for the first time that the para-position substituent that is opposite of the C-O group can break the symmetry of the phenyl ring, leading to different hyperfine tensors for the two large ortho proton couplings. For the tyrosyl and tryptophanyl models, the calculated hyperfine couplings to hydrogen-bonding protons were in very good agreement with measured values for both the tyrosyl and tryptophanyl models.


Feelings of guilt and pride: Consumer intention to buy LED lights.
The adoption of energy-efficient lighting systems such as light-emitting diode (LED) lights is an effective strategy to address global warming and climate change. The adoption of LED light usage is largely shaped by consumer behavior. Understanding the factors that influence consumers' awareness of the advantages of using LED lights and consumers' eventual buying behavior is critical to industry players and policy-makers. The objective of this study is to investigate the significant factors that affect consumer intention to use LED lights among Malaysian households. A survey questionnaire of 1,075 potential consumers was employed and the partial least squares technique was applied in data analysis. The results show that consumer awareness creates responsibility and influences consumers' personal norms and attitudes, and their ultimate intention to buy LED lights. Feelings of guilt about contributing to air pollution and an awareness of the advantages of using LED lights both activate individual personal norms and attitudes, and influence the intention to buy LED lights. Awareness of the advantages of using LED lights, and of the negative consequences of not using them, prompts consumers to have feelings of guilt. The findings point to the importance of creating awareness among consumers.


Recent developments in predictive biomarkers of pediatric glioma.
The presence of certain cancer-related genetic and epigenetic alterations in the tumor affects patient response to specific cancer therapies. The accurate screening of these predictive biomarkers in molecular diagnostics is important since it enables the tailoring of optimal treatment based on molecular characteristics of the tumor. We searched the electronic database PubMed for preclinical as well as clinical controlled trials reporting on various multiple predictors of glioma. It was observed clearly that multiple approaches are evolving and a few of them have also shown promising results. Depending on the type of gene alteration, a wide variety of methods may be applied in biomarker testing. Among the novel methods is next-generation sequencing (NGS) technology, enabling simultaneous detection of multiple alterations. The aim of this review is to discuss the predictive or potentially predictive genetic and epigenetic alterations of diffuse gliomas. The review concludes that NGS technology is the future and may likely replace, at least to some extent, the current routinely used methods, including FISH, IHC, and PCR-based methods, in clinical diagnostics.


Ferrous sulphate does not directly affect pteroylmonoglutamic acid absorption in rats.
A variety of compounds which bind to Fe have substantial reductions in absorption when co-administered with Fe compounds. The binding of both Fe2+ and Fe3+ ions to pteroylmonoglutamic acid and the pteroylmonoglutamate dianion was examined in vitro. In dimethylsulphoxide (DMSO) alone, pteroylmonoglutamate formed a 2:1 (pteroylmonoglutamate:Fe3+ ion) complex. However, in DMSO-aqueous Bis-Tris buffer (4:1, v/v; pH 6.0) no evidence of complex formation could be seen. Likewise spectroscopic evidence was obtained for complex formation with Fe2+ ion and pteroylmonoglutamate in DMSO alone but not in the aqueous DMSO buffer. In vivo studies examined the effect of FeSO4 on pteroylmonoglutamic acid absorption in an isolated perfused rat jejunal model of nutrient absorption. The dose of pteroylmonoglutamic acid approximated a human dose of 1 mg for the rat, while the FeSO4 doses were chosen to represent 6.4 mg, 64 mg and 300 mg human doses. There was no significant effect of FeSO4 on pteroylmonoglutamic acid absorption or instability of pteroylmonoglutamic acid in vivo in the presence of FeSO4 in the rat. Although 2:1 binding of pteroylmonoglutamic acid to Fe ions could be demonstrated in DMSO alone, no binding could be demonstrated in DMSO-Bis-Tris buffer (4:1, v/v; pH 6.0). It is unlikely that there will be a significant reduction in pteroylmonoglutamic acid absorption during concurrent ingestion of Fe preparations.


Stabilisation of spent mushroom substrate for application as a plant growth-promoting organic amendment.
Over three million tonnes of spent mushroom substrate (SMS) are produced in Europe every year as a by-product of the cultivation of Agaricus bisporus. The management of SMS has become an increasing challenge for the mushroom production industry, and finding environmentally and economically sustainable solutions for this organic residue is, therefore, highly desirable. Due to its physical properties and nutrient content, SMS has great potential to be employed in agricultural and horticultural sectors, and further contribute to reduce the use of non-renewable resources, such as peat. However, SMS is often regarded as not being stable and/or mature, which hampers its wide use for crop production. Here, we demonstrate the stabilisation of SMS and its subsequent use as organic fertiliser and partial peat replacement in horticulture. The stabilisation was performed in a laboratory-scale composting system, with controlled temperature and aeration. Physical and chemical parameters were monitored during composting and provided information on the progress of the process. Water soluble carbohydrates (WSC) content was found to be the most reliable parameter to predict SMS stability. In situ oxygen consumption indicated the main composting phases, reflecting major changes in microbial activity. The structure of the bacterial community was also found to be a potential predictor of stability, as the compositional changes followed the composting progress. By contrast, the fungal community did not present clear successional process along the experiment. Maturity and quality of the stabilised SMS were assessed in a horticultural growing trial. When used as the sole fertiliser source, SMS was able to support Lolium multiflorum (Italian ryegrass) growth and significantly improved grass yield with a concentration-dependent response, increasing grass biomass up to 300%, when compared to the untreated control. In summary, the results indicated that the method employed was efficient in generating a stable and mature product, which has a great potential to be applied in horticulture. This study represents a step forward in the management of SMS residue, and also provides an alternative to reduce the use of peat in horticulture, alleviating environmental impacts to peatland ecosystems.


Identification and validation of DLX4 as a prognostic and diagnostic biomarker for clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (ccRCC) is a lethal cancer, and biomarkers for exact diagnosis and predicting prognosis are urgently needed. The present study aimed to determine the roles of distal-less homeobox (DLX) family genes in ccRCC. The clinicopathological and mRNA expression data of patients with ccRCC were derived from The Cancer Genome Atlas database. Kaplan-Meier curves, univariate and multivariate Cox hazard analyses, in addition to receiver operator characteristic curves were used to evaluate the prognostic and diagnostic values. A single-sample gene set enrichment analysis was used to quantify the infiltration levels of immune cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were conducted to examine the expression levels of DLX4 in tumor and adjacent tissue; the results demonstrated that DLX4 was highly expressed in ccRCC tissues compared with normal renal tissues. Furthermore, DLX4 expression was associated with tumor stage and grade. High proportions of males, advanced pathological stage, higher tumor grade and T, N and M stage were also observed in the high DLX4 expression group. Patients with the high DLX4 expression levels tended to have lower overall survival and disease-free survival rates compared with those with low DLX4 expression. DLX4 expression also showed favorable diagnostic efficiency in ccRCC patients. Based on functional enrichment analysis, cell cycle related pathways, epithelial-mesenchymal transition, glycolysis and inflammatory response were associated with the expression levels of DLX4. Furthermore, DLX4 expression was revealed to be associated with tumor immunosuppressive microenvironment. Overall, the expression level of DLX4 may be considered a novel prognostic indicator in ccRCC and a specific diagnostic biomarker for patients with ccRCC.


Keratoconjunctivitis sicca modifies epithelial stem cell proliferation kinetics in conjunctiva.
The objective of this study was to examine the epithelial stem cell proliferation kinetics in a rat model with keratoconjunctivitis sicca (KCS). Wistar rats received a daily injection of 5-bromo-2-deoxyuridine (BrdU) at a dose of 5 mg/100 g of body weight for 2 weeks. Dry eye was induced in 2 groups of rats by subcutaneous injection of scopolamine and placed in a desiccating environment: The first group received dry eye treatment at the beginning of BrdU labeling for 2 weeks; the second group received dry eye treatment after BrdU labeling for 4 weeks. Rats receiving no dry eye treatment were used as controls. Aqueous tear production, tear clearance, and corneal barrier function of dry eye rats were compared with those of control rats. Ocular epithelial morphology and goblet cell density were also evaluated in histologic sections. One month after BrdU injection, epithelial stem cell proliferation kinetics was assessed by BrdU labeling. Significant decreases in tear fluid secretion and tear clearance were noted in rats 5 days after dry eye treatment, with significantly increased corneal carboxy fluorescein uptake. Changes in ocular surface epithelial morphology and significantly reduced density of conjunctival goblet cells were found in dry eye groups. The number of conjunctival BrdU label-retaining cells in the rats with dry eye was significantly decreased compared with control rats (P < 0.01 for both groups). Furthermore, BrdU labeling in the before dry eye induction group showed more label-retaining basal cells in the conjunctiva than labeling in the dry eye state group (P < 0.01). Experimentally induced KCS in rats causes significant modification of epithelial stem cell proliferation kinetics in conjunctiva. The modification of epithelial stem cell proliferation kinetics in conjunctiva may play a crucial role in the development of KCS and may be a therapeutic target for this condition.


Expression patterns of two fibroblast growth factor receptor genes during early chick eye development.
The expression patterns of two distinct types of fibroblast growth factor receptor (FGFR) genes, FGFR1 and FGFR2, were compared during early chick eye development. In situ hybridization was performed with riboprobes synthesized from cDNA fragments of FGFRs cloned by the polymerase chain reaction method. FGFR1 was expressed in the prospective lens, neural retina, pigment epithelium and mandibular mesenchyme. In contrast, FGFR2 was expressed predominantly in the periocular mesenchyme of a 2.5 day-old embryo. In the 5.5-day-old embryo, transcripts of FGFR2 were detected in the prospective corneal epithelium. The results suggest that expression patterns of FGFR1 and FGFR2 are complementary and ligands of each FGFR might be involved differentially in early chick eye development. It is concluded that the action of FGFs on pigment epithelium and lens cells reported so far, probably occurs through FGFR1, and both types of FGFR are involved in head mesenchymal development.


Effects of Higher Dietary Protein and Fiber Intakes at Breakfast on Postprandial Glucose, Insulin, and 24-h Interstitial Glucose in Overweight Adults.
Dietary protein and fiber independently influence insulin-mediated glucose control. However, potential additive effects are not well-known. Men and women (n = 20; age: 26 ± 5 years; body mass index: 26.1 ± 0.2 kg/m²; mean ± standard deviation) consumed normal protein and fiber (NPNF; NP = 12.5 g, NF = 2 g), normal protein and high fiber (NPHF; NP = 12.5 g, HF = 8 g), high protein and normal fiber (HPNF; HP = 25 g, NF = 2 g), or high protein and fiber (HPHF; HP = 25 g, HF = 8 g) breakfast treatments during four 2-week interventions in a randomized crossover fashion. On the last day of each intervention, meal tolerance tests were completed to assess postprandial (every 60 min for 240 min) serum glucose and insulin concentrations. Continuous glucose monitoring was used to measure 24-h interstitial glucose during five days of the second week of each intervention. Repeated-measures ANOVA was applied for data analyses. The HPHF treatment did not affect postprandial glucose and insulin responses or 24-h glucose total area under the curve (AUC). Higher fiber intake reduced 240-min insulin AUC. Doubling the amount of protein from 12.5 g to 25 g/meal and quadrupling fiber from 2 to 8 g/meal at breakfast was not an effective strategy for modulating insulin-mediated glucose responses in these young, overweight adults.


Food and Drug Administration guidances on biosimilars: an update for the gastroenterologist.
The management of inflammatory bowel disease (IBD), a significant cause of morbidity in the United States (US), has been revolutionized over the last two decades by the introduction of biologic therapies. These include antitumor necrosis factor α (TNF-α) agents. Since 2016, five biosimilar TNF-α inhibitors have been approved by the US Food and Drug Administration (FDA) for use in the treatment of IBD. The FDA has published a series of guidance documents related to the evaluation, licensing, and approval of biosimilars. The aim of this review is to provide an overview of these FDA guidances and the issues associated with biosimilars in the US.


Influence of Surface Roughness on the Properties of Nitrided Layer on 42CrMo4 Steel.
A crucial factor of a nitriding process of treated parts is surface roughness. Eight samples of 42CrMo4 steel were used to investigate the parameter represented by Ra. In the study, the innovative combined microhardness profiles were used to present results within the compound zone and diffusion layer. Therefore, two loads were applied in the compound zone, 5 gf, and diffusion layer, 500 gf. Observation with SEM and chemical analysis of the investigated samples showed a correlation between microstructure, nitrogen concentration and microhardness of the compound zone. XRD diffraction was used to identify the phase composition. Moreover, the X-ray photoelectron spectroscopy technique was also applied in the study. No distinct correlations between compound zone morphology and the Ra parameter were observed. The thickness value of the structure was constant and fluctuated around 20 µm in the vast majority of the examined cases. However, analysis of the results revealed a dependence between the Ra parameter and diffusion layer thickness. The values of this parameter varied in the range of 356-394 µm depending on the Ra parameter. A distinct nitrided layer was observed on the polished sample.


Intra-articular Focal Nodular Synovitis of the Knee.
A 32-year-old woman was referred to physical therapy by her primary care provider (PCP) for complaints of limited right knee extension and pain. Radiographs of her right knee ordered by her PCP prior to physical therapy evaluation were noncontributory. To rule out intra-articular pathology, the physical therapist ordered magnetic resonance imaging, which revealed an intra-articular mass. The radiologist recommended contrast imaging to further characterize the mass, which was found to be consistent with focal nodular synovitis. J Orthop Sports Phys Ther 2017;47(4):293. doi:10.2519/jospt.2017.7221.


Predicting the potential invasion suitability of regions to cassava lacebug pests (Heteroptera: Tingidae: Vatiga spp.).
Cassava (Manihot esculenta Crantz) is one of the most important staple crops for small farmers in the tropics, feeding about 800 million people worldwide. It is currently cultivated in South and Central America, Africa and Asia. The genus Vatiga is widespread throughout the Neotropical region. Its species are sympatric and feed exclusively on cassava. The main objectives of this paper are: (1) to assess the potential distribution of Vatiga, one of the most relevant pests of cassava; (2) to project the resulting models onto the world; (3) to recognize areas with suitable and optimal climates (and thus, high probability) for future colonization, and (4) to compare this model with the harvested area of cassava analyzing the climatic variables required by both the host and the pest species. Species distribution models were built using Maxent (v3.3.3k) with bioclimatic variables from the WorldClim database in 2.5 arc min resolution across the globe. Our model shows that Vatiga has the potential to expand its current distribution into other suitable areas, and could invade other regions where cassava is already cultivated, e.g., Central Africa and Asia. Considering the results and the high host specificity of Vatiga, its recent appearance in Réunion Island (Africa) poses a serious threat, as nearby areas are potentially suitable for invasion and could serve as dispersal routes enabling Vatiga to reach the continent. The present work may help prevention or early detection of Vatiga spp. in areas where cassava is grown.


Tailorable dispersion in a four-wave mixing laser.
We present experimental results demonstrating controllable dispersion in a ring laser by monitoring the lasing-frequency response to cavity-length variations. Pumping on an N-type level configuration in Rb87, we tailor the intra-cavity dispersion slope by varying experimental parameters, such as pump-laser frequency, atomic density, and pump power. As a result, we can tune the pulling factor, i.e., the ratio of the laser frequency shift to the empty cavity frequency shift, of our laser by more than an order of magnitude.


Non-traumatic splenic rupture: report of seven cases and review of the literature.
To evaluate seven patients with non-traumatic splenic rupture (NSR). NSR is an uncommon dramatic abdominal emergency that requires immediate diagnosis and prompt surgical treatment to ensure the patient's survival. Within 11 years, seven cases were evaluated for patient characteristics, anamnesis and symptoms, method of diagnosis, findings of laparotomy, and etiology of NSR. There were six (86%) male and one female (14%) patient, whose mean age was 36 +/- 12.8 (17-56) years. We report here four cases of Plasmodium vivax malaria (cases I-IV), one case of hemodialysis (case V), one case of spontaneous splenic rupture (case VI), and one case of hairy cell leukemia (case VII). Splenectomy was performed in all patients. All of them made an uneventful recovery and were discharged in stable condition. NSR is a rare entity that needs a high index of suspicion for diagnosis. Using ultrasonography or computer tomography, and peritoneal aspiration of fresh blood may assist in the diagnosis of NSR. Increased awareness of NSR can enhance early diagnosis and effective treatment.


Cystic duct remnants and biliary symptoms after cholecystectomy. A randomised comparison of two operative techniques.
To assess the importance of cystic duct remnants in causing biliary symptoms after cholecystectomy 80 patients undergoing routine cholecystectomy were randomised to have conventional cholecystectomy (n = 40) or cholecystectomy with removal of the whole cystic duct (n = 40). Fifteen were withdrawn, leaving 65 (32 who had standard cholecystectomy and 33 who had cholecystectomy by the new technique) for analysis. Thirty of the 32, and 27 of the 33, were available for follow up one, two, three, and eight years after operation; 11 of the 30 (37%) compared with 23 of the 27 (85%) were free of biliary symptoms during the eight year period (p less than 0.001). We conclude that removal of the stump of the cystic duct improves the success rate of cholecystectomy in the treatment of gallstones.


Reports of assent and permission in research with children: illustrations and suggestions.
This study ascertained reports of assent (affirmative agreement) and permission (agreement by an adult fully capable of being informed) in 114 children's research articles in 1990 in Child Development (CD), Journal of Consulting and Clinical Psychology (JCCP), Journal of Pediatric Psychology, and Journal of Clinical Child Psychology. Of the research projects, 43% failed to specify permission, and 68.5% failed to specify assent. JCCP reported assent significantly more than CD. Assent was reported significantly more in research with older children than with younger children. This lack of sensitivity to assent and permission suggests that many authors, reviewers, and editors consider reporting assent and permission unessential. We recommend specifying assent and permission in all manuscripts, highlighting children's research issues in graduate training, and using specific safeguards when conducting research with children.


Eyelid malposition: lower lid entropion and ectropion.
Correcting entropion and ectropion successfully requires knowledge of the eyelid problems, because understanding of these abnormalities is a key to planning a successful surgical procedure. Entropion is a condition in which the eyelid margin turns inwards against the globe. It is divided into following categories: congenital and acquired, which may be involutional or cicatricial. Ectropion is a malposition in which the lid falls away or is pulled away from its normal apposition to the globe. The condition is classified as congenital and acquired, which is divided into following categories: involutional, cicatricial, paralytic, and mechanical. Therefore, there are some common anatomic changes for both entropion and ectropion as well as specific changes that are unique to each eyelid malposition. Typically, instability of the eyelid is caused by either horizontal laxity or disinsertion or attenuation of the lower eyelid retractors to the inferior tarsal border, so surgical procedures should be directed at correcting the horizontal and vertical instability of the lid. Classification, etiology, underlying anatomic changes in the lid, principles of surgical treatment of entropion and ectropion are reviewed in this article.


Usefulness of Endobronchial Ultrasound in Patients with Human Immunodeficiency Virus Infection and Mediastinal Lymphadenopathy.
There are few published studies about the usefulness of endobronchial ultrasound (EBUS) in patients infected with human immunodeficiency virus (HIV). The clinical spectrum of likely diseases in this population is varied and differs from patients not infected with HIV. The aim of this study was to measure the usefulness of EBUS-guided transbronchial needle aspiration (EBUS-TBNA) in HIV-infected patients with mediastinal lymphadenopathy. We conducted an observational, cross-sectional, retrospective, descriptive study on patients with HIV infection and mediastinal lymphadenopathy who underwent EBUS-TBNA between September 2014 and April 2016. The patients' final diagnosis, regardless of the sample from which it was obtained, was considered the positive gold standard, and the absence of diagnosis was the negative. The study measured diagnostic accuracy of bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), and EBUS-TBNA. A total of 43 procedures were performed; 79.1% (34/43) of the patients were male, and the median age was 35 years (range, 22-66). The overall diagnostic yield including all types of samples was 90.7% (39/43); the yield of BAL was 50% (21), that of TBB 61.9% (26), and that of EBUS-TBNA was 60.5% (26). The combined yield of BAL with TBB was 69.8% (30); the yield of BAL with EBUS-TBNA was 86% (37) and that of TBB with EBUS-TBNA was 88.4% (38). The highest diagnostic accuracy was 97.7% for the combination of TBB and EBUS-TBNA. The most common infectious diagnoses were tuberculosis, with a higher diagnostic accuracy using EBUS-TBNA than BAL. With malignancies, both EBUS-TBNA and TBB were useful. EBUS-TBNA is a minimally invasive diagnostic tool that should be considered in these patients.


[Takayasu's disease and post-traumatic scalp necrosis].
This relates the case of a 19-years old female suffering from Takayasu's disease, who sustained injury with extradural hematoma formation calling for emergent evacuation thereof. The immediate postoperative period in this neurosurgical patient was characterized by extended necrosis of the scalp and underlying bone, due to low blood supply to the head in connection with her disease. The authors review the main characteristics of this rare inflammatory arteriopathy, and point out to the multidisciplinary collaboration which prompted healing of the patient's loss of substance.


Spectrophotometric determination of phenylephrine hydrochloride in pharmaceuticals by flow injection analysis exploiting the reaction with potassium ferricyanide and 4-aminoantipyrine.
This paper presents a method for the determination of phenylephrine hydrochloride in pharmaceuticals by spectrophotometric flow injection analysis exploiting the reaction with potassium ferricyanide and 4-aminoantipyrine, which leads to the formation of a condensation product with strong absorptivity at 500 nm. The linear dynamic range was between 0.95 and 9 mg/L, with a limit of detection of 0.2 mg/L and a sampling throughput of 120 samples per hour. The method was applied to eyewashes and nasal decongestant liquid medicines.


Guideline for the use of antenatal corticosteroids for fetal maturation.
The aim is to present a document, which is based on current evidence and serves as a guideline for use in clinical practice. The following questions are addressed: Is the use of antenatal corticosteroids (ACS) an effective therapy? Who are the candidates for antenatal corticosteroid therapy? Is there benefit after 34 weeks' gestation? When is the optimal time to treat? Which are the optimal steroids; what is the ideal dose and route of administration? Are there any contraindications to the administration of ACS? Are antenatal corticosteroids indicated in women with premature rupture of membranes (PROM)? Is the use of ACS recommended in pregnancies complicated by maternal diabetes mellitus? Should the treatment with corticosteroids be repeated?


Impact of race and baseline PSA on longitudinal PSA.
There is an increasing debate regarding the frequency of prostate-specific antigen (PSA) testing and the current primary screening modality used to detect prostate cancer. The purpose of this study is to determine whether PSA screening intervals should be based on initial PSA. Our study explores longitudinal changes of PSA levels in black and white males separately. Study participants were 768 white and 450 black males attending an annual prostate cancer screening. We fit a longitudinal repeated measures model separately for blacks and whites and estimated the probability of PSA converting to greater than 4.0 ng/ml at a follow-up year given baseline PSA range among males without an abnormal DRE. Black and white males with a baseline PSA between 0 and 1.0 ng/ml, with a healthy or enlarged prostate, have a less than 1% chance that their PSA will increase above 4.0 ng/ml over the following 5 years. Black and white males with a PSA between 1.0 and 1.9 ng/ml have a less than 1% chance of PSA conversion to greater than 4.0 ng/ml over the next year. Our findings further support that annual screening for prostate cancer may not be necessary, specifically males with a baseline PSA less than 2.0 may not need to undergo annual screening. Our results suggest that race does not affect the longitudinal trend of PSA enough to warrant setting screening intervals based on race.


[Patent and occult intra-alveolar hemorrhage in leptospirosis].
Pulmonary involvement (PI) is common in leptospiral infection, usually characterized by hemoptysis and diffuse bilateral infiltrates on chest radiographs. Alveolar haemorrhage (AH) has already been proved by autopsy and some case-reports with fiberoptic bronchoscopy (FB) and bronchoalveolar lavage (BAL). The purpose of this study was 1/to evaluate the incidence of AH in leptospirosis 2/to define the impact of BAL on the early diagnosis of the infection. FB with BAL were performed in 23 consecutive patients with leptospirosis (13 patients with patent signs of PI: group 1, 10 patients without: group 2). AH was defined by a percentage of siderophages > or = 20% and/or a Golde score > 100 and/or an haemorrhagic aspect of BAL fluid. Culture tests were performed on specific medium. We diagnosed AH in all patients of group 1 and in 7 patients of group 2. Filaments were seen in 6 specimens of BAL fluid, initially thought to be leptospires, but culture tests were negative. AH is identified in all cases of leptospirosis with PI. Occult AH often occurs to patients without any respiratory symptom. Physicians should consider leptospiral infection in the differential diagnosis of AH. Culture-tests for leptospirosis in BAL do no help in diagnosing leptospirosis.


Robot-assisted simple prostatectomy for prostates greater than 100 g.
Efforts are ongoing to treat severe benign prostatic hyperplasia as traditional endoscopic treatment options are often difficult to perform and associated with significant complications. This manuscript highlights our initial experience of robot-assisted simple prostatectomy [RASP] with minimum a year follow-up. We also compared our outcomes with published literature. After an Institution Review Board approval, we gathered data of 50 cases of RASP between Jan 2014 and May 2021. Patients with prostate volume > 100 cc [calculated from magnetic resonance imaging (MRI)] and prostate biopsy confirmed benign prostate were candidates for RASP. Patients underwent RASP via transperitoneal route either by suprapubic or trans-vesical approach. Preoperative demographics, peri-operative parameters and post-operative parameters such as hospital stay, catheter removal, urinary continence and uroflow were recorded in standard database and presented as descriptive statistics. Patients presented with a baseline median International Prostate Symptom Score (IPSS) of 23 (inter-quartile range (IQR) 21,25) and a median PSA of 7.7 ng/ml (IQR 6.4,8.7). Median preoperative prostate volume was 167 ml (IQR, 136,198 ml). Median console time was 118 min, and median estimated blood loss was 148 ml (IQR 130, 167 ml). None of our cohort needed intraoperative transfusion, conversion to open surgery or developed any complications. Median time to Foley removal was 10 days (IQR 8,12). Significant drop in the IPSS score and improvement in Qmax was noted over the period of follow-up. RASP is associated with considerable improvements in urinary symptoms. However, comparative studies with endoscopic treatment options of large prostatic adenomas are warranted and ideally include cost analysis of different procedures.


Rotavirus vaccines.
Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licensed vaccines are either animal-human re-assortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.


Assessment of the Perception and Worries of Saudi Healthcare Providers About the Application of Artificial Intelligence in Saudi Health Facilities.
Objective This study is aimed at assessing the perception and worries of Saudi healthcare providers about the application of artificial intelligence (AI) in Saudi healthcare facilities. Methods The study adopted a cross-sectional study involving 1026 Saudi healthcare providers between January 2023 and April 2023. The target population was healthcare providers across Saudi health facilities. Online questionnaires were administered through social media platforms. Data were analyzed using SPSS Statistics, version 26.0 (IBM Corp., Armonk, NY) to obtain important insights. Results The results of this study indicated that more than half (55.2%) of the respondents had good knowledge of AI, with (48.1%) of them being familiar with the application of AI in their specialty. A good proportion of the participants (57.9%) knew at least one term about the difference between machine learning and deep learning. More than half (69.9%) of the participants indicated that they had at one point in time used speech recognition or transcription application in their work. A large section (73.3%) of healthcare providers believed that AI would replace them at their job. A vast majority (84.9%) of the participants agreed that collaboration between medical schools with engineering and computer science faculties could be a game changer to provide a road for incorporating AI into medical curricula. The mean perception of AI in this study was 37.6 (SD=8.41; range 0-241). Age, level of health, health profession, and working experience all significantly impacted the positive perception score (p=0.021; p=0.031; p=0.041; p=0.026). However, there was no significant association between gender, nationality, and Saudi regions with a mean positive perception score. Conclusion There was a positive perception of AI among Saudi healthcare providers. Even though a substantial majority of Saudi healthcare providers were worried that AI would replace their jobs, the study revealed that AI serves as a crucial practitioner's tool rather than a physician's replacement.


Site-directed mutagenesis and protein 3D-homology modelling suggest a catalytic mechanism for UDP-glucose-dependent betanidin 5-O-glucosyltransferase from Dorotheanthus bellidiformis.
In livingstone daisy (Dorotheanthus bellidiformis), betanidin 5-O-glucosyltransferase (UGT73A5) is involved in the regiospecific glucosylation of betanidin and various flavonols. Based on sequence alignments several amino acid candidates which might be essential for catalysis were identified. The selected amino acids of the functionally expressed protein, suggested to be involved in substrate binding and turnover, were substituted via site-directed mutagenesis. The substitution of two highly conserved amino acids, Glu378, located in the proposed UDP-glucose binding site, and His22, located close to the N-terminus, led to the complete loss of enzyme activity. A 3D model of this regiospecific betanidin and flavonoid glucosyltransferase was constructed and the active site modelled. This model was based on the crystallographic structure of a bacterial UDP-glucose-dependent glucosyltransferase from Amycolatopsis orientalis used as a template and the generated null mutations. To explain the observed inversion in the configuration of the bound sugar, semiempirical calculations favour an SN-1 reaction, as one plausible alternative to the generally proposed SN-2 mechanism discussed for plant natural product glucosyltransferases. The calculated structural data do not only explain the abstraction of a proton from the acceptor betanidin, but further imply that the reaction mechanism might also involve a catalytic triad, with similarities described for the serine protease family.


Adaptive Neural Control of Nonlinear Nonstrict Feedback Systems With Full-State Constraints: A Novel Nonlinear Mapping Method.
In this work, a neural-networks (NNs)-based adaptive asymptotic tracking control scheme is presented for a class of uncertain nonstrict feedback nonlinear systems with time-varying full-state constraints. First, we construct a novel exponentially decaying nonlinear mapping to map the constrained system states to new system states without constraints. Instead of the traditional barrier Lyapunov function methods, the feasible conditions which require the virtual control signals satisfying the constraint requirements are removed. By employing the Nussbaum design method to eliminate the effect of unknown control gains, the general assumption about the signs of the unknown control gains is relaxed. Then, the nonstrict feedback form of the system can be pulled back to the strict feedback form through the basic properties of radial basis function NNs. Simultaneously, the intermediate control signals and the desired controller are constructed by the backstepping process and the Nussbaum design method. The designed controller can ensure that all signals in the whole closed-loop system are bounded without the violation of the constraints and hold the asymptotic tracking performance. In the end, a practical example about a brush dc motor driving a one-link robot manipulator is given to illustrate the effectiveness of the proposed design scheme.


Inter- and intraobserver variation in staging patients with proven avascular necrosis of the hip.
Diagnosis and treatment of avascular necrosis of the hip has long been predicated on the evaluation of plain radiographs, though other modalities (such as magnetic resonance imaging) are being increasingly used to aid in this evaluation. The Ficat classification is commonly used to assess plain radiographs and to help determine what treatment is appropriate for a given patient. It also is used to help evaluate patient outcome after surgical or nonsurgical treatment. This study was designed to evaluate the adequacy of plain radiographs in the evaluation of avascular necrosis of the hip. The plain radiographs of 25 hips with avascular necrosis were analyzed on 3 occasions by 6 readers (450 total readings). A clinically significant difference in radiographic staging was defined as a Stage I or II reading of the radiographs of a given hip on 1 reading and a separate reading of the same radiographs as Stage III or IV. By this definition, interobserver variability for the first reading resulted in clinically significant differences in 10 (40%) of the 25 hips. Intraobserver variability resulted in clinically significant differences for 10 (40%) of the 25 hips as well. The most experienced readers in the study (a total joint specialist and a musculoskeletal radiologist) were consistent internally in their readings in 90% of cases, and had a clinically significant difference in only 1 case (1%); however, these same 2 readers disagreed with one another on the staging of 9 (36%) of 25 hips, with 4 (16%) of 25 hips having a clinically significant difference in readings.(ABSTRACT TRUNCATED AT 250 WORDS)


Temperature-inducible outer membrane protein of Yersinia pseudotuberculosis and Yersinia enterocolitica is associated with the virulence plasmid.
A strain of Yersinia pseudotuberculosis which harbors a 63-kilobase plasmid was found to cause a lethal infection in Swiss albino mice. The rate of infection paralleled the ability of the pathogenic organism to attach to a monolayer of HeLa cells. One novel outer membrane protein (protein 1) with a molecular weight of 140,000 was found to be associated with the possession of the 63-kilobase plasmid not at 26 degrees C, and expression was moderately affected by the concentration of calcium in the growth medium. Moreover, it was found that synthesis of protein 1 associated outer membrane protein showing similar properties was also found to be expressed in plasmid-containing strains of Yersinia enterocolitica. The properties of protein 1 indicate that it could be identical to the previously described virulence W antigen.


The effect of curcumin on the stability of Aβ dimers.
Aβ oligomers are potential targets for the diagnosis and therapy of Alzheimer's disease (AD). On the other hand, the molecule curcumin has been shown to possess significant therapeutic potential in many areas. In this paper, we use all-atom explicit solvent molecular dynamics simulations to study the effect of curcumin on the stability of Aβ amyloid protein oligomers. We observed that curcumin decreases the β-sheet secondary structural content within the Aβ oligomers without reducing the contacts between the monomers. The breaking of the β-sheet is found to be preceded by a deformation of the β-sheet structure due to hydrophobic interaction from the nearby curcumin. Furthermore, the π-stacking interaction between curcumin (keto ring and enol ring) and the aromatic residues of Aβ, which exists throughout the simulations, has also contributed to the diminishing of the β-sheet structure. Our analysis of the underwrapped amide-carbonyl hydrogen bonds reveals several stable dehydrons of the oligomer, especially the dehydron pair 34L and 41I, which curcumin tends to hover over. We have examined the paths of curcumin on the Aβ proteins and determined the common routes where curcumin lingers as it traverses around the Aβ. In consequence, our study has provided a detailed interaction picture between curcumin and the Aβ oligomers.


Persistent primitive trigeminal artery aneurysm evaluated by MR imaging and angiography.
The primitive trigeminal artery is the most common of the persistent carotid-basilar anastomoses with an angiographic incidence of 0.6%. Fifteen cases of aneurysms of a persistent primitive trigeminal artery have been reported in the literature. A 16th patient is presented in whom an incidental trigeminal artery aneurysm and a thrombosed aneurysm of the vertebrobasilar system are evaluated by magnetic resonance imaging and angiography.


Analysis of a French cohort of patients with large granular lymphocyte leukemia: a report on 229 cases.
Large granular lymphocyte leukemia is a rare lymphoproliferative disorder associated with autoimmune diseases and impaired hematopoiesis. This study describes the clinical and biological characteristics of 229 patients with T-cell or NK-cell large granular lymphocyte leukemia. The diagnosis was based on a large granular lymphocyte expansion (> 0.5x10(9)/L) lasting more than 6 months. Monoclonal T-cell receptor gamma gene rearrangement was detected in all the cases of T-cell large granular lymphocyte leukemia. Patients with chronic NK-cell lymphocytosis had an indolent disease, while those with multiorgan large granular lymphocyte infiltration and an aggressive clinical disease were considered to have NK-cell large granular lymphocyte leukemia. The diagnosis of T-cell large granular lymphocyte leukemia was confirmed in 201 cases, chronic NK-cell lymphocytosis in 27 cases and NK-cell large granular lymphocyte leukemia in one case. Associated autoimmune diseases or other neoplasms were present in 74 and 32 cases, respectively. One hundred patients (44%) required treatment, mainly for neutropenia-associated infections (n=45), symptomatic autoimmune diseases (n =24), transfusion-dependant anemia (n=18), and other causes (n=13). Patients were treated with steroids (n= 33), methotrexate (n=62), cytoxan (n=32), or cyclosporine (n=24) either as first-, second-, third- or fourth-line therapy. The overall response rate at 3 months and complete response rate for the various treatments were as follows: steroids (12% and 3%), methotrexate (55% and 21%), cytoxan (66% and 47%), cyclosporine (21% and 4%), respectively. Four out of 13 patients responded to splenectomy. Eleven out of 15 patients responded to cytoxan after methotrexate treatment had failed. The mean number of treatments was 3.4 (range, 1-7). There were 15 large granular lymphocyte leukemia-related deaths. Patients with T-cell large granular lymphocyte leukemia and chronic NK-cell lymphocytosis have similar clinical and biological features and responses to treatment. First-line therapy with cytoxan should be tested in a prospective trial.


U.S. dental school applicants and enrollees, 2005 entering class.
There were 10,731 applicants to the entering dental school class in 2005. This represents a 13.8 percent increase over the number of applicants to the 2004 entering class and almost a 45 percent increase over the number of applicants in 2001. Dental schools reported 4,558 first-time, first-year enrollees in 2005, an increase of 101 first-time, first-year enrollees over the number reported in 2004. The percent of applicants that were enrolled in 2005 was 42.5. The percent of applicants enrolled in 2001 was 57.6. Women were 44.2 percent of the applicants and 43.8 percent of the first-time, first-year enrollees in 2005, slight increases from what they were in 2004. Underrepresented minorities comprised 12.8 percent of the applicants and 12.6 percent of the first-time, first-year enrollees in 2005. These percentages are little changed from those reported in 2001. The average GPA of the first-time, first-year enrollees increased slightly in 2005, from 3.4 to 3.5; there was little change in DAT scores, standing at 18.9 for Academic Average, 17.4 for Perceptual Ability, and 18.4 for Total Science.


Experiences and attitudes towards end-of-life decisions amongst Danish physicians.
In this survey we have investigated the experiences and attitudes of Danish physicians regarding end-of-life decisions. Most respondents have made decisions that involve hastening the death of a patient, and almost all find it acceptable to do so. Such decisions are made more often, and considered ethically more acceptable, with the informed consent of the patient than without. But both non-resuscitation decisions, and decisions to provide pain relief in doses that will shorten the patient's life, have been made and found acceptable by at least 50% of the respondents, even when there is no informed consent. Furthermore, 12% have doubled morphine dosages with fixed intervals, thus providing doses substantially higher than that necessary to control pain, without the informed consent of the patient. Two percent have helped in assisted suicide, and 5% have administered a lethal injection at the patient's request. Respectively 37% and 34% find these last two practices ethically acceptable. Amongst those that do not find them acceptable, the most important reasons to be opposed are, the doctrine of double effect, the doctrine of doing and allowing, and the view that human life is sacred. Amongst supporters, the most important reasons mentioned are, that the patient's right to self-determination should be respected, the view that a patient should not be forced to suffer, and the view that the patient has a right to be helped to a dignified death.


Employment barriers and work motivation for Navajo rehabilitation clients.
The Navajo nation provides vocational rehabilitation (VR) services to Navajo clients residing on and off the Navajo reservation. To evaluate motivation among disabled Navajo workers participating in VR programs, this study investigated the sociocultural meanings of work and its importance in the self-identity of contemporary Navajo workers and clients who apply for these services. Selected sociocultural variables that focused on cultural identity and perceptions as well as attitudes towards work were included as part of an assessment designed to predict motivation for employment success. The results of this study suggest that VR counsellors who work with Native American clients should recognize sociocultural history and the cultural perceptions of work as important factors in the rehabilitation and vocational planning process.


Securing maize reproductive success under drought stress by harnessing CO2 fertilization for greater productivity.
Securing maize grain yield is crucial to meet food and energy needs for the future growing population, especially under frequent drought events and elevated CO2 (eCO2) due to climate change. To maximize the kernel setting rate under drought stress is a key strategy in battling against the negative impacts. Firstly, we summarize the major limitations to leaf source and kernel sink in maize under drought stress, and identified that loss in grain yield is mainly attributed to reduced kernel set. Reproductive drought tolerance can be realized by collective contribution with a greater assimilate import into ear, more available sugars for ovary and silk use, and higher capacity to remobilize assimilate reserve. As such, utilization of CO2 fertilization by improved photosynthesis and greater reserve remobilization is a key strategy for coping with drought stress under climate change condition. We propose that optimizing planting methods and mining natural genetic variation still need to be done continuously, meanwhile, by virtue of advanced genetic engineering and plant phenomics tools, the breeding program of higher photosynthetic efficiency maize varieties adapted to eCO2 can be accelerated. Consequently, stabilizing maize production under drought stress can be achieved by securing reproductive success by harnessing CO2 fertilization.


[Correlation between human herpesvirus 6 activation and acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation].
To study the potential relationship between HHV-6 activation and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HSCT). Peripheral blood samples were collected before and weekly after HSCT from 72 consecutive recipients. HHV-6 DNAemia was monitored by nested polymerase chain reaction (PCR). The genotypes of HHV-6 were identified by Hind III restriction assay. Of the 72 patients, HHV-6 DNAemia were detected in 45 (62.5%) on a median of day 14 (range, 7 - 63 days) after HSCT. Grade I - IV aGHVD occurred in 40 (55.6%) on a median of day 26 (range, 9 -73 days). The median onset time of HHV-6 DNAemia was significantly earlier than that of aGHVD (P = 0.018). Compared with that in HHV-6 DNAemia negative [HHV-6(-)] patients, the cumulative incidence of grade I - IV aGHVD was higher (68.9% vs. 33.3% , P = 0.003) in HHV-6 (+) patients. Cumulative incidence of grade II - IV aGVHD in HHV-6 (+) cohort was also higher than that in HHV-6 (-) cohort (35.6% vs 14.8% , P = 0.027). Cumulative incidence of grade I - IV aGVHD was higher in patients with both HHV-6 and CMV positive (CMV+/HHV-6+) than in those with either CMV (CMV+/HHV-6-) or HHV-6 positive (CMV+/HHV-6+) and neither of them positive (CMV-/HHV-6-) [78.9% (30/38), 55. 6% (5/9) , 14. 3% (1/7) and 22. 2% (4/18), respectively, P = 0. 0001]. Cumulative incidence of grade II - IV aGVHD in CMV+/HHV-6+ group was also higher than that in CMV+/HHV-6-, CMV-/HHV-6+ and CMV-/HHV-6- groups [42.1% (16/38), 22.2% (2/9), 0% (0/7) and 11.1% (2/18), P = 0. 008]. Patients with HHV-6 activation or HHV-6/CMV co-infection maybe involved in the occurrence of aGVHD after HSCT.


Sequence conservation of apolipoprotein A-I affords novel insights into HDL structure-function.
We performed alignment of apolipoprotein A-I (apoA-I) sequences from 31 species of animals. We found there is specific conservation of salt bridge-forming residues in the first 30 residues of apoA-I and general conservation of a variety of residue types in the central domain, helix 2/3 to helix 7/8. In the lipid-associating domain, helix 7 and helix 10 are the most and least conserved helixes, respectively. Furthermore, eight residues are completely conserved: P66, R83, P121, E191, and P220, and three of seven Tyr residues in human apoA-I, Y18, Y115, and Y192, are conserved. Residue Y18 appears to be important for assembly of HDL. E191-Y192 represents the only completely conserved pair of adjacent residues in apoA-I; Y192 is a preferred target for site-specific oxidative modification within atheroma, and molecular dynamic simulations suggest that the conserved pair E191-Y192 is in a solvent-exposed loop-helix-loop. Molecular dynamics testing of human apoA-I showed that M112 and M148 interact with Y115, a microenvironment unique to human apoA-I. Finally, conservation of Arg residues in the α11/3 helical wheel position 7 supports several possibilities: interactions with adjacent phospholipid molecules and/or oxidized lipids and/or binding of antioxidant enzymes through cation-π orbital interactions. We conclude that sequence alignment of apoA-I provides unique insights into apoA-I structure-function relationship.


[How I treat ...scalp psoriasis].
Scalp involvement by psoriasis requires a ted treatment suited to the particularities of the anatomical site In course of time, the improvement of therapeutic agents and the galenic refinement have enhanced both the efficacy and cosmetic acceptability of the scalp care. The main therapeutic classes encompass keratolytics, dermocorticosteroids and vitamine D3 analogues. The patient compliance is reported to be best for the liquid or foam formulations.


Surfactant-Type Catalyst for Aerobic Oxidative Coupling of Hydrazine with Thiol in Water.
A series of PEG-functionalized nitrogen ligands were developed to conduct an aerobic oxidative cross-coupling reaction between alkyl- or aryl-hydrazines with thiols in water. This surfactant-type catalyst enables high efficiencies and selectivities, while tolerating a large variety of functional groups. The mother liquor is still catalytically active after five runs.


Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors.
The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10-15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.


Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.
We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.


LiG Metrology, Correlated Error, and the Integrity of the Global Surface Air-Temperature Record.
The published 95% uncertainty of the global surface air-temperature anomaly (GSATA) record through 1980 is impossibly less than the 2σ = ±0.25 °C lower limit of laboratory resolution of 1 °C/division liquid-in-glass (LiG) thermometers. The ~0.7 °C/century Joule-drift of lead- and soft-glass thermometer bulbs renders unreliable the entire historical air-temperature record through the 19th century. A circa 1900 Baudin meteorological spirit thermometer bulb exhibited intense Pb X-ray emission lines (10.55, 12.66, and 14.76 keV). Uncorrected LiG thermometer non-linearity leaves 1σ = ±0.27 °C uncertainty in land-surface air temperatures prior to 1981. The 2σ = ±0.43 °C from LiG resolution and non-linearity obscures most of the 20th century GSATA trend. Systematic sensor-measurement errors are highly pair-wise correlated, possibly across hundreds of km. Non-normal distributions of bucket and engine-intake difference SSTs disconfirm the assumption of random measurement error. Semivariogram analysis of ship SST measurements yields half the error difference mean, ±½Δε1,2, not the error mean. Transfer-function adjustment following a change of land station air-temperature sensor eliminates measurement independence and forward-propagates the antecedent uncertainty. LiG resolution limits, non-linearity, and sensor field calibrations yield GSATA mean ±2σ RMS uncertainties of, 1900-1945, ±1.7 °C; 1946-1980, ±2.1 °C; 1981-2004, ±2.0 °C; and 2005-2010, ±1.6 °C. Finally, the 20th century (1900-1999) GSATA, 0.74 ± 1.94 °C, does not convey any information about rate or magnitude of temperature change.


ReHabgame: A non-immersive virtual reality rehabilitation system with applications in neuroscience.
This paper proposes the use of a non-immersive virtual reality rehabilitation system "ReHabgame" developed using Microsoft Kinect™ and the Thalmic™ Labs Myo gesture control armband. The ReHabgame was developed based on two third-person video games that provide a feasible possibility of assessing postural control and functional reach tests. It accurately quantifies specific postural control mechanisms including timed standing balance, functional reach tests using real-time anatomical landmark orientation, joint velocity, and acceleration while end trajectories were calculated using an inverse kinematics algorithm. The game was designed to help patients with neurological impairment to be subjected to physiotherapy activity and practice postures of daily activities. The subjective experience of the ReHabgame was studied through the development of an Engagement Questionnaire (EQ) for qualitative, quantitative and Rasch model. The Monte-Carlo Tree Search (MCTS) and Random object (ROG) generator algorithms were used to adapt the physical and gameplay intensity in the ReHabgame based on the Motor Assessment Scale (MAS) and Hierarchical Scoring System (HSS). Rasch analysis was conducted to assess the psychometric characteristics of the ReHabgame and to identify if these are any misfitting items in the game. Rasch rating scale model (RSM) was used to assess the engagement of players in the ReHabgame and evaluate the effectiveness and attractiveness of the game. The results showed that the scales assessing the rehabilitation process met Rasch expectations of reliability, and unidimensionality. Infit and outfit mean squares values are in the range of (0.68-1.52) for all considered 16 items. The Root Mean Square Residual (RMSR) and the person separation reliability were acceptable. The item/person map showed that the persons and items were clustered symmetrically.


A Transfer Learning Based Super-Resolution Microscopy for Biopsy Slice Images: The Joint Methods Perspective.
Higher-resolution biopsy slice images reveal many details, which are widely used in medical practice. However, taking high-resolution slice images is more costly than taking low-resolution ones. In this paper, we propose a joint framework containing a novel transfer learning strategy and a deep super-resolution framework to generate high-resolution slice images from low-resolution ones. The super-resolution framework called SRFBN+ is proposed by modifying a state-of-the-art framework SRFBN. Specifically, the structure of the feedback block of SRFBN was modified to be more flexible. Besides, it is challenging to use typical transfer learning strategies directly for the tasks on slice images, as the patterns on different types of biopsy slice images are varying. To this end, we propose a novel transfer learning strategy, called Channel Fusion Transfer Learning (CF-Trans). CF-Trans builds a middle domain by fusing the data manifolds of the source domain and the target domain, serving as a springboard for knowledge transfer. Thus, in the transfer learning setting, SRFBN+ can be trained on the source domain and then the middle domain and finally the target domain. Experiments on biopsy slice images validate SRFBN+ works well in generating super-resolution slice images, and CF-Trans is an efficient transfer learning strategy.


A moving-part-free protamine-sensitive polymeric membrane electrode for sensitive biomedical analyses.
Traditional potentiometric polyion-sensitive electrodes can only work effectively in samples with vigorous convection fulfilled by magnetic stirrer, electrode rotator, or other moving components. The dependence on complex moving parts prohibits the fabrication of compact, cost-effective, and energy-effective test devices from the commercial point of view. In this paper, a novel potentiometric sensing protocol without using any moving parts has been proposed for polycationic protamine. In contrast to traditional protamine-sensitive electrodes conditioned by discriminated ion (Na(+)), the proposed electrode is conditioned with primary ion (protamine). Upon a medium exchange from the conditioning solution into an unstirred sample solution without protamine, protamine loaded in the membrane is stripped into the aqueous phase via ion exchange with aqueous sodium ion, thereby inducing a large potential drop. Interestingly, when the sample solution initially contains protamine, the ion-exchange process has been found to be sensitively inhibited by the sample protamine, and thus the potential drop is suppressed, which forms the basis of the moving-part-free potentiometric polyion sensing strategy. Utilizing the digestion ability of protease to protamine, the electrode was employed to determine the activity of trypsin with a detection limit at least one order of magnitude lower than traditional potentiometric methods. The trypsin inhibitor in both buffer and plasma samples was also sensitively detected with the moving-part-free protamine-sensitive electrode. Finally, the ability of the proposed electrode to detect polyanionic heparin was demonstrated.


Prompt laboratory diagnosis in timely containment of a plague outbreak in India.
A focal outbreak of pneumonic plague occurred in a hamlet of village Hatkoti, district Shimla, Himachal Pradesh in the first fortnight of February, 2002. A total of 16 cases with 4 deaths were reported. Diagnosis of plague was confirmed by the laboratory in 10 (63%) cases. Y. pestis was isolated from clinical samples of 3 cases and confirmed by bacteriophage lysis. Molecular tests confirmed the presence of Y. pestis specific pla and F1 genes in 4 cases; DNA fingerprinting had identity with the known sequence of plague bacilli. Paired samples from 5 cases showed more than 4 fold rise and 1 case showed more than 4 fold fall in antibodies against F1 antigen of Y. pestis. The present communication emphasises that timely and systematic laboratory investigations give confirmatory diagnosis in shortest possible time which forms the backbone of the outbreak control in a timely fashion and prevents confusion and controversy.


The legacy of parents' marital discord: consequences for children's marital quality.
Drawing on a national longitudinal study of 297 parents and their married offspring, the authors found that parents' marital discord was negatively related to offspring's marital harmony and positively related to offspring's marital discord. The transmission of marital quality was not mediated by parental divorce, life-course variables, socioeconomic attainment, retrospective measures of parent-child relationships, or psychological distress. Offspring's recollections of parental discord, however, mediated about half of the association between parents' reports of marital discord and offspring's reports of discord in their own marriages. Parental behaviors most likely to predict problematic marriages among offspring included jealousy, being domineering, getting angry easily, being critical, being moody, and not talking to the spouse.