The human right to adequate housing: a tool for promoting and protecting individual and community health.
The human right to adequate housing is enshrined in international law. The right to adequate housing can be traced to the Universal Declaration of Human Rights, which was unanimously adopted by the world community in 1948. Since that time, the right to adequate housing has been reaffirmed on numerous occasions and further defined and elaborated. A key component of this right is habitability of housing, which should comply with health and safety standards. Therefore, the right to adequate housing provides an additional tool for advocates and others interested in promoting healthful housing and living conditions and thereby protecting individual and community health.


Dehydrogenation of benzene on Pt(111) surface.
The dehydrogenation of benzene on Pt(111) surface is studied by ab initio density functional theory. The minimum energy pathways for benzene dehydrogenation are found with the nudge elastic band method including several factors of the associated barriers, reactive energies, intermediates, and transient states. The results show that there are two possible parallel minimum energy pathways on the Pt(111) surface. Moreover, the tilting angle of the H atom in benzene can be taken as an index for the actual barrier of dehydrogenation. In addition, the properties of dehydrogenation radicals on the Pt(111) surface are explored through their adsorption energy, adsorption geometry, and electronic structure on the surface. The vibrational frequencies of the dehydrogenation radicals derived from the calculations are in agreement with literature data.


Successful ablation of a right concealed epicardial accessory pathway using ethanol infusion.
This study describes a rare case of concealed epicardial accessory pathway (AP) successfully ablated using ethanol infusion (EI) through a variant vessel connecting the right atrium (RA) and the right ventricle (RV) surface. A 58-year-old male referred to our hospital for prior failed AP ablation. Cardiac-enhanced computerized tomography scan showed there was a variant vessel at the tip of right atrial appendage and a pulmonary artery (PA)-RA fistula at the roof of RA. The earliest activation was present at the site of the PA-RA fistula. A selective angiography showed that a small branch of the variant vessel covered the earliest excitation site of the AP. EI into this branch successfully repressed the AP without any recurrences within a follow-up period of 3 months. Endocardial ablation is challenging for epicardial APs related to cardiac structural variations. If small vascular branches near the earliest activation site can be found, EI can successfully ablate these types of epicardial APs.


Cascade Reaction of Morita-Baylis-Hillman Acetates with 1,1-Enediamines or Heterocyclic Ketene Aminals: Synthesis of Highly Functionalized 2-Aminopyrroles.
A new strategy for the construction of two kinds of fully substituted pyrroles, including 2-aminopyrroles and bicyclic pyrroles from Morita-Baylis-Hillman (MBH) acetates with 1,1-enediamines (EDAMs), or heterocyclic ketene aminals (HKAs) via base-promoted tandem Michael addition, elimination, and aromatization sequence has been developed, affording the expected products in moderate to excellent yields. This methodology is a highly efficient, concise way to access 2-aminopyrroles or bicyclic pyrroles with diversity in molecular structures from accessible building blocks under moderate reaction conditions.


Evaluation of biomechanical risk factors for neck and back disorders in traditional bakers during a work-day: Implications for ergonomics intervention.
Awkward back and neck postures have been recognized as one common problem in bakery workers. This study aimed to evaluation of the biomechanical risk factors on the back and neck of bakers. Twenty bakers of four types of bread- baking systems were randomly selected. Working postures and movements of the back and neck during work were continuously recorded with inclinometry measurements during three hours. Physical workload in bakers was characterized by awkward postures and the percentage of time spent with the neck flexed more than 20°. Besides, low angular velocity and lack of postural variation during baking shows that bakers' back is in the static position and bakers have to work with constrained back for a long time. The current findings have important implications for prioritizing ergonomic interventions and any ergonomic interventions should be focused on reducing neck flexion and constrained postures of the back.


Fibroblast Growth Factor 15/19 in Hepatocarcinogenesis.
Advanced hepatocellular carcinoma (HCC) is a neoplastic disease with a very bad prognosis and increasing worldwide incidence. HCCs are resistant to conventional chemotherapy and the multikinase inhibitor sorafenib is the only agent that has shown some clinical efficacy. It is therefore important to identify key molecular mechanisms driving hepatocarcinogenesis for the development of more efficacious therapies. However, HCCs are heterogeneous tumors and different molecular subclasses have been characterized. This heterogeneity may underlie the poor performance of most of the targeted therapies so far tested in HCC patients. The fibroblast growth factor 15/19 (FGF15/19), FGF receptor 4 (FGFR4) and beta-Klotho (KLB) correceptor signaling system, a key regulator of bile acids (BA) synthesis and intermediary metabolism, is emerging as an important player in hepatocarcinogenesis. Key Messages: Aberrant signaling through the FGF15/19-FGFR4 pathway participates in the neoplastic behavior of HCC cells, promotes HCC development in mice and its overexpression has been characterized in a subset of HCC tumors from patients with poorer prognosis. Pharmacological interference with FGF15/19-FGFR4 signaling inhibits experimental hepatocarcinogenesis, and specific FGFR4 inhibitors are currently being tested in selected HCC patients with tumoral FGF19-FGFR4/KLB expression. Interference with FGF19-FGFR4 signaling represents a novel strategy in HCC therapy. Selection of candidate patients based on tumoral FGF19-FGFR4/KLB levels as biomarkers may result in increased efficacy of FGFR4-targeted drugs. Nevertheless, attention should be paid to the potential on target toxic effects of FGFR4 inhibitors due to the key role of this signaling system in BA metabolism.


Quantum noise limited nanoparticle detection with exposed-core fiber.
Label-free biosensors are important tools for clinical diagnostics and for studying biology at the single molecule level. The development of optical label-free sensors has allowed extreme sensitivity but can expose the biological sample to photodamage. Moreover, the fragility and complexity of these sensors can be prohibitive to applications. To overcome these problems, we develop a quantum noise limited exposed-core fiber sensor providing robust platform for label-free biosensing with a natural path toward microfluidic integration. We demonstrate the detection of single nanoparticles down to 25 nm in radius with optical intensities beneath known biophysical damage thresholds.


[FEATURES OF THE CONTENT OF DRINKING WATER IN THE CITY OF MAGADAN AND POPULATION HEALTH].
By methods of atom-emission and mass spectrometry with inductively bonded argon plasma there was determined the content of 25 macro- and trace elements in tap cold drinking water used by the residents of the city of Magadan for food purposes and in hair samples of 30 young male Europeans aged of 17-23 years, who are the residents, of the city of Magadan. According to our data the content of 25 elements in drinking water conforms to standards, but that content of such essential elements as Co, Cr Cu, I, Mn, Na, Se, Zn is shown to be lower than referential indices. After boiling the water the concentration of trace elements is changed. The content of Cd, Cu, K, P Pb, Zn, Ni becomes lower significantly. In healthy young men aged of 17-23 years, from the number of natives Europeoids, residents of the North there was detected deficit of Co and I (86% and 62%, respectively), lower concentrations of Ca, Mg, Se, Zn (76%, 69%, 24%, 24%, respectively). The constant use by residents of the city of Magadan of ultrafresh brackish drinking water in food aims may be the one of the main reasons of the imbalance of macro- and micronutrients in the body, characterized by features of the so-called "northern" type with a marked deficiency of basic essential elements.


Ultrasonographic study of ovaries of 19 women with weight loss-related hypothalamic oligo-amenorrhea.
A study of 19 nonhirsute women with weight loss-related hypothalamic oligo-amenorrhea revealed evidence of multifollicular ovaries in 17. Enlarged ovaries greater than 10 cm3 were found in 8 of these subjects (42.1%). High-resolution real-time ultrasonography of the pelvis of 19 weight loss-related oligo-amenorrheic subjects revealed a mean +/- SD maximum ovarian volume (MOV) of 11.8 +/- 7.0 cm3, which was significantly different from those of control subjects whose mean +/- SD MOV was 5.2 +/- 1.9 cm3 (P = less than 0.001). The data do not allow a specific ultrasonographic distinction between hyperandrogenic women with polycystic ovarian disease and women with weight loss-related hypothalamic amenorrhea.


Global cardiovascular risk assessment in the primary prevention of cardiovascular disease in adults: systematic review of systematic reviews.
To identify, critically appraise and summarise existing systematic reviews on the impact of global cardiovascular risk assessment in the primary prevention of cardiovascular disease (CVD) in adults. Systematic review of systematic reviews published between January 2005 and October 2016 in The Cochrane Library, EMBASE, MEDLINE or CINAHL databases, and post hoc analysis of primary trials. Systematic reviews of interventions involving global cardiovascular risk assessment relative to no formal risk assessment in adults with no history of CVD. The primary outcomes of interest were CVD-related morbidity and mortality and all-cause mortality; secondary outcomes were systolic blood pressure (SBP), cholesterol and smoking. We identified six systematic reviews of variable but generally of low quality (mean Assessing the Methodological Quality of Systematic Reviews 4.2/11, range 0/11 to 7/11). No studies identified by the systematic reviews reported CVD-related morbidity or mortality or all-cause mortality. Meta-analysis of reported randomised controlled trials (RCTs) showed small reductions in SBP (mean difference (MD) -2.22 mm Hg (95% CI -3.49 to -0.95); I2=66%; n=9; GRADE: very low), total cholesterol (MD -0.11 mmol/L (95% CI -0.20 to -0.02); I2=72%; n=5; GRADE: very low), low-density lipoprotein cholesterol (MD -0.15 mmol/L (95% CI -0.26 to -0.05), I2=47%; n=4; GRADE: very low) and smoking cessation (RR 1.62 (95% CI 1.08 to 2.43); I2=17%; n=7; GRADE: low). The median follow-up time of reported RCTs was 12 months (range 2-36 months). The quality of existing systematic reviews was generally poor and there is currently no evidence reported in these reviews that the prospective use of global cardiovascular risk assessment translates to reductions in CVD morbidity or mortality. There are reductions in SBP, cholesterol and smoking but they may not be clinically significant given their small effect size and short duration. Resources need to be directed to conduct high-quality systematic reviews focusing on hard patient outcomes, and likely further primary RCTs. CRD42015019821.


Cataract surgery in eyes with associated coloboma: Predictors of outcome and safety of different surgical techniques.
The aim of this study was to report the outcome of cataract surgery with different surgical techniques in eyes with coexisting coloboma and to define factors of prognostic importance. Retrospective case sheet review of patients presenting between January 2016 and December 2018, who underwent cataract surgery in eyes with coexisting coloboma. Of the 3,30,231 cases operated during the study period, 280 eyes of 276 patients had associated colobomatous malformation. The prevalence of coloboma in eyes undergoing cataract surgery was 0.085%. The mean age of the patients was 46.4 years (range 19 -88 years). Phacoemulsification (PE) was performed in 130 eyes (46.4%), manual small incision cataract surgery (M-SICS) was done in 115 eyes (41.1%), and 35 eyes (12.5%) underwent intra capsular cataract extraction. Intra-operative complications were noted in 26 (9%) eyes. Incidence of intra-operative and post-operative complications was comparable between PE and M-SICS groups (p = 0.94). The mean corrected distance visual acuity (CDVA) improved from logMAR 1.71 ± 0.62 to 0.87 ± 0.61 (p = 0.00009). On multivariate analysis, microcornea (p = 0.002), type 1 and 2 coloboma (p < 0.001), and intraoperative complications (p = 0.001) were associated with poor visual outcome. Favorable functional outcomes can be achieved with phacoemulsification in eyes with softer cataract and corneal diameter >8 mm and with M-SICS in eyes with hard cataracts and corneal diameter of 6-8 mm. PE should be considered as the primary choice whenever permissible by the corneal diameter and severity of nuclear sclerosis. Poor functional outcomes were seen in eyes with smaller corneal diameter, extensive chorioretinal coloboma, and intraoperative complications.


Valorization of xylose-rich hydrolysate from rice straw, an agroresidue, through biosurfactant production by the soil bacterium Serratia nematodiphila.
Biosurfactants, amphiphilic compounds that reduce interfacial tension in oil-aqueous mixtures, are used in the petroleum, pharmaceutical, food, and agriculture industries. Fermentative production of biosurfactants requires expensive sugar or lipid substrates. Lignocellulosic biomass is a relatively cheap and abundant agricultural residue that can be used as an alternative substrate. Currently, several million tonnes of rice and wheat straw are generated globally as agricultural residues, most of which is disposed by open-field burning thereby leading to severe environmental pollution. This study aimed to produce biosurfactants in xylose-rich hydrolysates generated from rice straw. The hydrolysate is also a byproduct of 2G biofuel processes that often goes underutilized. A soil bacterium capable of growing and producing biosurfactants in rice straw hydrolysates, which typically contain growth-inhibitory compounds such as furfural and hydroxymethyl furfural, was isolated. Interestingly, the organism, identified as Serratia nematodiphila, exhibited higher glycolipid formation (4.5 ± 0.6 gL-1) in xylose-rich hydrolysate than in glucose-rich enzymatic hydrolysate (3.1 ± 0.2 gL-1) despite the higher bacterial cell density observed with the latter. The biosurfactants were thermostable and possessed promising emulsifying property and anti-microbial activity against bacteria and yeast. Further optimization of C:N resulted in a 2.8-fold increase in glycolipid production from xylose-rich hydrolysates. This study demonstrates the production of glycolipid biosurfactants from lignocellulosic biomass, a low-cost substrate and offers a plausible strategy for the management of these residues. Further, it also provides insights into the generation of additional high-value compounds in a bioethanol biorefinery to improve its commercial feasibility.


Angiomatoid Fibrous Histiocytoma: A Series of Three Cases.
Angiomatoid fibrous histiocytoma (AFH) is a rare, slow-growing soft tissue tumor with an intermediate biologic potential and uncertain line of differentiation, and minimal metastatic potential. AFH may mimic both the clinical, histological, and radiological findings of several tumors; therefore, it is frequently misdiagnosed. Three cases of AFH were included in this study. A six-year-old male and two females with an age of 12 and 17 years are presented. The primary locations were in the right shoulder (case 1), left medial proximal thigh (case 2), and left lateral knee (case 3). Two cases (cases 2&3) were presented with a painful mass. In the three patients, the masses were firm, mobile, and not attached to the skin. Magnetic resonance imaging (MRI) was done, illustrating unspecific findings to reach a diagnosis. Needle biopsies were performed in all patient, and the diagnosis of AFH was reached. All three patients underwent wide surgical excision of the tumor. Patients were followed up routinely every three to four months with imaging studies to rule out recurrence and metastasis, for a period of 15 months (case 1), 26 months (case 2), and 19 months (case 3), which all resulted negatively.


[The association between genetic polymorphisms of IL-6 and the susceptibility of chronic rhinosinusitis].
To investigate the relationship between the promoter polymorphism of IL6 (-174G > C, -572G > C and -597G > A) and chronic rhinosinusitis (CRS). The case-control study consisted of 123 patients with CRS and 239 controls from a Chinese Han population from Shanghai. The genotypes of the subjects were determined by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. Besides, the concentrations of the totle immunoglobulin E (TIgE) and eosinophilic cationic protein (ECP) in the blood were also determined. The -174G > C and -597G > A polymorphisms were not detected in this study population. Significant differences in genotype and allele frequencies of -572C/G were observed between CRS patients and control groups. In CRS patients, the CC, CG, GG genotype frequencies were 69.1%, 29.3%, 1.6%, C, G allele frequencies were 83.7%, 16.3%. In control group, the genotype frequencies were 55.2%, 42.3%, 2.5%, the allele frequencies were 76.4%, 23.6%, respectively. The -572CC genotype was associated with an increased risk of developing CRS (P < 0.05, OR = 1.932, 95% CI, 1.205-3.097). There was no significant differences in the concentrations of the TIgE and ECP among each genotype. IL-6 gene -572G > C polymorphism is associated with the susceptibility to CRS. CC genotype could be an independent risk factor.


Novel Selective Detection Method of Tumor Angiogenesis Factors Using Living Nano-Robots.
This paper reports a novel self-detection method for tumor cells using living nano-robots. These living robots are a nonpathogenic strain of E. coli bacteria equipped with naturally synthesized bio-nano-sensory systems that have an affinity to VEGF, an angiogenic factor overly-expressed by cancer cells. The VEGF-affinity/chemotaxis was assessed using several assays including the capillary chemotaxis assay, chemotaxis assay on soft agar, and chemotaxis assay on solid agar. In addition, a microfluidic device was developed to possibly discover tumor cells through the overexpressed vascular endothelial growth factor (VEGF). Various experiments to study the sensing characteristic of the nano-robots presented a strong response toward the VEGF. Thus, a new paradigm of selective targeting therapies for cancer can be advanced using swimming E. coli as self-navigator miniaturized robots as well as drug-delivery vehicles.


Molecular analyses reveal the occurrence of three new sympatric lineages of velvet worms (Onychophora: Peripatidae) in the eastern Amazon basin.
In the present study, we investigated the possible existence of new lineages of peripatids through comparisons between known Neotropical species and specimens obtained from two locations in Pará, a state in eastern Brazilian Amazonia using a molecular approach based on sequences of the mtDNA genes COI, 16Sr RNA, and 18S RNA. The analyses included also sequences of Asian and African taxa for a more systematic understanding of the phylogenetic relationships within the group. The analysis of the COI, 16S rRNA and 18S RNA sequences permitted the identification of three distinct lineages (A, B and C) based on two different phylogenetic approaches (Bayesian methods and ML). The three lineages presented here are completely distinct from all other peripatid taxa so far defined by molecular data. The presence of specimens of three independent onychophoran lineages occurring in sympatry in the Amazon basin was confirmed in all the analyses, providing consistent support for the phylogenies presented in this study. These findings reinforce the importance of the Amazon region in the diversification of Neotropical peripatids, and indicate that onychophoran diversity is much greater than previously thought, given that the number of taxa found at a single site was equivalent to the total number of allopatric species described for the entire region.


[Optimization of serological diagnosis of cystic echinococcosus (granulosus) infection].
The diagnostic effectiveness of instrumental analysis of the concentration of specific antibodies, which was expressed in antibody units and titers, was compared in the test system of enzyme immunoassay using Echinococcus granulosus on 76 serum samples from patients with echinococcosis. The factors of possible influence on the instrumental readings of enzyme immunoassay are presented. A correlation was found in the specific antibody concentrations expressed in antibody units and titers.


COVID-19 in health-care workers in three hospitals in the south of the Netherlands: a cross-sectional study.
10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health.


Metal binding to brain-specific metallothionein-3 studied by electrospray ionization mass spectrometry.
Metallothionein-3 (MT-3) is a brain-specific isoform of metallothioneins, which is down-regulated in Alzheimer's disease (AD), inhibits the growth of neurons in vitro, and differs from common MTs also in gene regulation. To elucidate the differences in structure and function between MT-3 and common MTs, Zn2+ and Cd2+ binding to MT-3 and MT-1 were studied using electrospray ionization time of flight mass spectrometry (ESI TOF MS) at pH values between 7.5 and 2.7. The metal binding properties of MT-3 differ considerably from those of MT-1. After reconstitution with a metal excess, metallated MT-3 exists as a mixture of Zn7MT-3 (or Cd7MT-3, respectively) and several metalloforms with stoichiometries below and above seven. In contrast, MT-1 exists as a single Zn7MT-1 (or Cd7MT-1). Lowering of pH leads to a stepwise release of metals from metallated MT-3, first from extra sites, then from the 3-metal cluster and finally from the 4-metal cluster. At acidic pH values the 4-metal cluster of MT-3 is slightly more stable than that of MT-1. The results demonstrate higher structural plasticity, dynamics and metal binding capacity of MT-3 than of MT-1, which makes MT-3 suitable as a zinc buffer-transfer molecule in zinc-enriched neurons functioning at conditions of fluctuating zinc concentrations.


Severe traumatic hemorrhagic shock induces compromised immune barrier function of the mesenteric lymph node leading to an increase in intestinal bacterial translocation.
Critically ill patients have increased susceptibility to translocation of gut bacteria. However, the mechanisms are complicated and remain unclear, and the aim of this study was to explore these mechanisms. Rats exposed to different levels of shock were orally administrated with bioluminescent Citrobacter. We found that severe shock caused an increase in bacterial translocation to the visceral organs, such as liver, spleen and blood, compared with mild shock. Surprisingly, bacterial translocation to mesenteric lymph node (MLN) was unchanged between the two shock groups. Various methods, including flow cytometry, a co-culture model and western blots, were used to evaluate MLN-associated immune function. Specifically, we focused on mesenteric lymph node dendritic cells (MLN-DCs), the critical antigen presenting cells involved in the construction of the immune barrier in MLN. We also found that severe shock impaired the phenotypic maturation of MLN-DCs and induced a tolerogenic phenotype. Furthermore, co-culture assays of DCs with naive CD4+ T cells showed that DCs subject to severe shock were more inclined to polarize native CD4+ T cells into Th2 and Treg cells. This study successfully reproduced the clinical phenomenon of severe shock resulting in increased bacterial translocation to extraintestinal tissues, and this may be related to the compromised immune barrier function of MLN, as maturation and function of MLN-DC's were badly impaired.


Self-affirmation increases reemployment success for the unemployed.
Losing a job is one of life's most stressful events. Furthermore, maladaptive reactions to unemployment can trap people in a vicious cycle that derails their reemployment efforts. The current research tested whether a brief values-based self-affirmation intervention increases the odds of reemployment after a job loss and during unemployment, which presumably breaks this vicious cycle. Two field experiments, including one with a governmental employment agency, found that a 15-min self-affirmation exercise-i.e., reflecting on one's most important values-increased key employment-related outcomes after 4 wk, including the probability and speed of reemployment and the number of job offers. Because the ordeal of job loss and the probability of reemployment may be particularly challenging for individuals above the age of 50 y, we also explored whether the intervention was equally effective for those above and below 50 y of age. Demonstrating the generality of this effect, the efficacy of the intervention did not differ between individuals below and above the age of 50, and it was also effective for both recently unemployed and chronically unemployed individuals. Because self-affirmations have more typically been tested in educational contexts, the current research demonstrates the wide-ranging value of this intervention. By diminishing the vicious cycle of unemployment, the present studies show how a simple self-affirmation intervention can help individuals succeed in the labor market.


Laboral outcome after acute unilateral vestibulopathy.
Sixty-five adult patients who had acute peripheral vestibulopathy (APV) were followed-up to determine their functional outcome. During the acute phase, they were treated with betahistine and mobilization. In the entire study population, APV was not significantly associated with a change in occupational activities, physical work or driving ability. Older individuals had significantly attributed a change in work to disease other than APV. Change attributed to APV occurred significantly more frequently in women than in men. The therapeutic approach seems beneficial.


Characterization of T-DM1-resistant breast cancer cells.
The development of targeted therapies has drastically improved the outcome of patients with different types of cancer. T-DM1 (trastuzumab-emtansine) is an antibody-drug conjugate used for the treatment of HER2-positive breast cancer combining the FDA approved mAb (monoclonal antibody) trastuzumab and the microtubule cytotoxic agent DM1 (emtansine). Despite clinical successes achieved by targeted therapies, a large number of patients develop resistance during treatment. To explore mechanisms of resistance to T-DM1, the MDA-MB-361 HER2-positive breast cancer cell line was exposed in vitro to T-DM1 in the absence or presence of ciclosporin A. Previously reported mechanisms of resistance such as trastuzumab-binding alterations, MDR1 upregulation, and SLC46A3 downregulation were not observed in these models. Despite a decrease in HER2 expression at the cell surface, both resistant cell lines remained sensitive to HER2 targeted therapies such as mAbs and tyrosine kinase inhibitors. In addition, sensitivity to DNA damaging agents and topoisomerase inhibitors were unchanged. Conversely resistance to anti-tubulin agents increased. Resistant cells displayed a decreased content of polymerized tubulin and a decreased content of βIII tubulin although the downregulation of βIII tubulin by siRNA in the parental cell line did not modified the sensitivity to T-DM1. Both cell lines resistant to T-DM1 also presented giant aneuploid cells. Several SLC (solute carrier) transporters were found to be differentially expressed in the resistant cells in comparison to parental cells. These results suggest that some characteristics such as increased baseline aneuploidy and altered intracellular drug trafficking might be involved in resistance to T-DM1.


Overview of periodontal clinical trials utilizing anti-infective or host modulating agents.
Issues in periodontal trials designed to evaluate anti-infective or host modulating agents for the prevention and treatment of periodontal diseases are reviewed in this paper. Clinical trial designs, prevention versus treatment, disease activity, utility of new measurement technologies, ethical and safety issues, selection of outcome variables, and clinical significance are discussed. In general, randomized parallel arm, double-blinded, controlled clinical trials are most appropriate for testing anti-infective and host modulating agents. New measurement technologies may offer increased measurement resolution and automated data capture; but, depending on their specific application and level of examiner reproducibility, these technologies may or may not result in lowered thresholds for declaring change. Mechanical therapy for common plaque-associated gingivitis and adult periodontitis is effective, has low risk, and is widely accepted as a minimum standard of care. New agents for treatment of these diseases must carry minimal risk and have equal or greater effectiveness than this standard of care. Outcome variables for gingivitis trials should include a visual index of gingival inflammation and a separate or component index of gingival bleeding. Prevention studies of periodontitis require a longer duration than treatment studies. Maintenance of mean clinical attachment level should be a primary outcome measure for all prevention studies of adult periodontitis. Maintenance of alveolar bone support is an essential additional outcome for agents specifically acting on bone. The design and conduct of clinical trials for anti-infective and host modulating agents depend on the specific hypothesis to be tested and the ethical demands of providing safe and effective care for all study volunteers.


Modulation of the blood-brain barrier in oncology: therapeutic opportunities for the treatment of brain tumours?
Systemically administered chemotherapy is not very effective in the treatment of primary or metastatic brain tumours. An important reason for this low efficacy is insufficient drug delivery to the tumour site due to the presence of the blood-brain barrier (BBB). In this review, we give an overview of strategies that were tested to bypass the BBB or to increase its permeability for anticancer drugs. Local drug administration through intracerebral implants offers only little benefit to patients with brain tumours, probably due to the limited diffusion of the drugs in brain tissue. Temporary disruption of the BBB can be achieved with intracarotid infusions of hypertonic mannitol. This method has been used with some success; however, toxic side effects and the high complexity of the surgical procedure limit its usefulness. More recently, the use of the bradykinin agonist cereport was shown to be useful in preclinical studies, but unfortunately clinical studies did not show improved efficacy. Since P-glycoprotein in the BBB restricts the brain entry of many anticancer drugs, inhibition of this drug transporter may be an option for improved drug delivery to brain tumours. Pre-clinical studies have shown the feasibility to enhance the penetration of paclitaxel into the brain by co-administration with a potent P-glycoprotein inhibitor and further clinical research is warranted.


Effect of cromoglycate on anaphylactic histamine release from rat peritoneal mast cells.
Cromoglycate (1-30 muM) produced a concentration-dependent inhibition of anaphylactic histamine release from actively sensitized rat peritoneal mast cells but at lower concentrations (0.01-0.1 muM) occasionally produced a concentration-dependent enhancement of histamine release.


Congenital microcoria associated with late-onset developmental glaucoma.
To demonstrate that developmental glaucoma (instead of the term goniodysgenetic glaucoma is used in this paper), defined as glaucoma with goniodysgenesis resulting from a fetal maldevelopment of the iridocorneal angle, develops in association with congenital microcoria. Three subjects descended from a family with autosomal dominant congenital microcoria and goniodysgenesis were followed up for more than 25 years. The extended family consisted of 3 generations including 8 males and 10 females. In the second generation, 2 of 7 subjects who presented with a history of congenital microcoria had late-onset goniodysgenetic glaucoma. In the third generation, all 3 descendants of the second generation subjects with congenital microcoria had congenital microcoria with goniodysgenesis. Two of these subjects developed late-onset goniodysgenetic glaucoma in both eyes during the 25-years follow-up period. They were both treated with a trabeculectomy in both eyes to control the glaucoma. Histologically, the iridocorneal angle tissues from the patients showed thick juxtacanalicular connective tissue with accumulations of a basement membrane-like extracellular matrix. Congenital microcoria are considered to be frequently associated with the incidence of late-onset goniodysgenetic glaucoma.


The effects of bacterial infection on human sperm nuclear protamine P1/P2 ratio and DNA integrity.
The purpose of this study was to detect the effects of bacterial infection on human sperm nuclear protamines and DNA fragmentation. In this study, 120 semen samples were collected from unselected male partners of couples consulting for infertility in infertility and obstetrics clinic. All the samples were screened bacteriologically according to World Health Organization guidelines, and also sperm parameters and DNA fragmentation were evaluated. The concentrations of protamines P1 and P2 were quantified using acid urea acrylamide gel electrophoresis. Of a total number of 120 sample, 36 (30%) of them were infected with bacteria. Nine species of bacteria belonging to five genera, Staphylococcus, Escherichia, Streptococcus, Enterococcus and Klebsiella, were identified. The comparison between infected (36) and noninfected (84) samples appeared the negative impact of bacterial infection on sperm parameters and P1/P2 ratios. The percentages of P1/P2 ratio abnormality were significantly higher in infected patients. Sperm concentration, motility, progression and chromatin condensation were significantly lower in infected patients (p < .010). Depending on these results, we concluded that the bacterial infections have significant negative effects on sperm chromatin condensation and protamine P1/P2 ratio. Moreover, the negative relationship between the bacterial infections and sperm parameters, such as concentration, motility and progressive motility, has been shown.


Off the Shelf Cloud Robotics for the Smart Home: Empowering a Wireless Robot through Cloud Computing.
In this paper, we explore the possibilities offered by the integration of home automation systems and service robots. In particular, we examine how advanced computationally expensive services can be provided by using a cloud computing approach to overcome the limitations of the hardware available at the user's home. To this end, we integrate two wireless low-cost, off-the-shelf systems in this work, namely, the service robot Rovio and the home automation system Z-wave. Cloud computing is used to enhance the capabilities of these systems so that advanced sensing and interaction services based on image processing and voice recognition can be offered.


Recurrent erysipelas led to diagnosis of hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is a risk of infection, such as by brain abscess associated with pulmonary arteriovenous malformations. However, association between HHT and recurrent erysipelas is not well described. HHT can cause vessel malformations in organs, leading to various serious outcomes. Prophylactic treatment is effective, but many people with HHT are undiagnosed. HHT is not described as a risk factor for soft tissue infection, but may increase the risk of serious infections requiring hospitalization. Our 72-year-old female patient was admitted for recurrent erysipelas. Pulmonary nodules indicated pulmonary arteriovenous fistula on chest computed tomography. By recognizing this combination, although seemingly unrelated problems, we could diagnose HHT and the patient could receive adequate treatment to prevent life-threatening events. The recurrent erysipelas was likely associated with HHT. Recurrent erysipelas is an important presentation which may facilitate early diagnosis of HHT.


Genome-wide mapping and allelic fingerprinting provide insights into the genetics of resistance to wheat stripe rust in India, Kenya and Mexico.
Stripe or yellow rust (YR) caused by Puccinia striiformis Westend. f. sp. tritici Erikss. is a persistent biotic-stress threatening global wheat production. To broaden our understanding of the shared genetic basis of YR resistance across multi-site and multi-year evaluations, we performed a large genome-wide association study using 43,706 YR observations on 23,346 wheat lines from the International Maize and Wheat Improvement Center evaluated between 2013 and 2019 at sites in India, Kenya and Mexico, against predominant races prevalent in the countries. We identified 114 repeatable markers tagging 20 quantitative trait loci (QTL) associated with YR on ten chromosomes including 1D, 2A, 2B, 2D, 3A, 4A, 4D, 5A, 5B and 6B, among which four QTL, QYr.cim-2DL.2, QYr.cim-2AS.1, QYr.cim-2BS.2 and QYr.cim-2BS.3 were significant in more than ten datasets. Furthermore, we report YR-associated allelic fingerprints for the largest panel of wheat breeding lines (52,067 lines) till date, creating substantial opportunities for YR favorable allele enrichment using molecular markers. Overall, the markers and fingerprints reported in this study provide excellent insights into the genetic architecture of YR resistance in different geographical regions, time-periods and wheat germplasm and are a huge resource to the global wheat breeding community for accelerating YR resistance breeding efforts.


Superior in vitro anticancer effect of biomimetic paclitaxel and triptolide co-delivery system in gastric cancer.
As a well-known anticancer drug, paclitaxel (PTX), a first-line chemotherapeutic agent, remains unsatisfactory for gastric cancer therapy. It is reported that triptolide (TPL) could enhance the anti-gastric cancer effect of PTX. Considering the poor solubility of both drugs, we developed a red blood cell membrane-biomimetic nanosystem, an emerging tool in drug delivery, to co-load paclitaxel and triptolide (red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid) [PLGA] nanoparticles, RP(P/T)). The successful preparation was confirmed in terms of particle size, morphology, and surface markers assays. This biomimetic system could prolong circulation and escape immune surveillance. And these properties were verified by stability, in vitro drug release, and cellular uptake assays. Moreover, the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T) to free drugs. The enhanced antitumor effects of RP(P/T) on migration and invasion were also evaluated by wound-healing and transwell assays. Overall, the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.


Diaphragmless single-pulse shock tube for high-temperature chemical kinetics studies.
Single-pulse shock tubes are effective tools for measuring chemical kinetics at high temperatures, typically (900-1400) K. However, the use of a diaphragm for shock generation leads to significant shock-to-shock inconsistencies in temperature for a constant initial pressure ratio across the discontinuity. Diaphragms also require replacement after each shock and demand care in cleaning to ensure that the fragments do not contaminate the apparatus. A piston-driven valve design is presented that leads to a highly reproducible postreflected shock temperatures (0.41% at 1147 K and 0.61% at 967 K) in a single pulse varying from (500 to 1200) µs in width over the temperature range of interest. Characterization of the valve was accomplished using both shock-speed measurements and independent measurements of the pulse temperature using reference thermal decomposition reactions.


Hydrogen Bonding-Assisted Complete Ferroelectric β-Phase Conversion in Poly(vinylidene fluoride) Thin Films: Exhibiting an Excellent Memory Window and Long Retention.
Organic nonvolatile memory with low power consumption is a critical research demand for next-generation memory applications. Ferroelectric switching characteristics of poly(vinylidene fluoride) (PVDF) thin films modified with a trace amount of hydrated Cu salt (CuCl2·2H2O) are explored in the present study. Herein, a Cu salt-mediated PVDF (Cu/PVDF) thin film with preferential edge-on β-crystallites is fabricated through the orientation-controlled spin coating (OCSC) technique. This work proposes a convenient and effective approach to produce edge-on-oriented electroactive PVDF thin films with a high degree of polar β-phase, so as to realize the favorable switching under low operating voltages. Herein, chemically modified PVDF is anticipated to form a complex intermediate, which attains its stability by undergoing favorable hydrogen bonding that reorients the C-C structure of PVDF to obtain the β-conformation. Such information is verified by X-ray photoelectron spectroscopy (XPS). Grazing incidence Fourier transform infrared (GI-FTIR) spectroscopy revealed that the Cu salt incorporated into the PVDF matrix favored the formation of the electroactive β-phase with edge-on crystallite lamellae. Consequently, the Cu/PVDF thin film demonstrates a good contrast between electric field-assisted written and erased data bits in the piezoresponse force microscopy (PFM) phase image. Furthermore, to obtain the ferroelectric memory window, a metal-ferroelectric-insulator-semiconductor (MFIS) diode with Cu/PVDF as a ferroelectric layer has been fabricated. The capacitance-voltage (C-V) characteristic of the MFIS diode exhibits a memory window of 12 V with a long-term retention behavior (∼longer than 7 days). In a nutshell, we tried to represent a clear understanding of the interfacial interactions of the Cu salt with PVDF, which favor the edge-on formation that results in the promising low-voltage ferroelectric switching and excellent retention response, where any additional electrical poling and/or external stretching is completely possible to be ruled out, thus offering a new prospect for the evolution of devices with long-lasting nonvolatile memories.


Pharmacological modulation of plaque instability.
Atherosclerotic plaque rupture is promoted by metalloproteinase (MMP)-2 and MMP-9, enzymes that degrade the fibrous cap leading to plaque erosion. MMP biosynthesis is mediated by prostaglandin (PG)E2, the product of cyclooxygenase (COX)-2/inducible PGE synthase (mPGES) activity. We have recently reported the overexpression of COX-2/mPGES-1 in vulnerable plaques as a basis of MMP-mediated plaque instability. Hypercholesterolemia and hypertension are two important risk factors for atherosclerosis. Recent trial showed that statins and AT1 receptor blockers significantly reduce the incidence of cardiovascular events in humans. Since anti-inflammatory effects have been reported in association to therapy with statins or AT1 receptor blockers, in two different studies we hypothesized that these drugs can stabilize atherosclerotic plaques through modulation of COX-2/mPGES-1-dependent MMP biosynthesis. Our data demonstrated the stabilizing effect of atherosclerotic plaques by simvastatin or irbesartan, that is due, at least in part, to the reduction of inflammatory burden and suppression of PGE2-dependent metalloproteinases release.


Impact of Insulin Degrading Enzyme and Neprilysin in Alzheimer's Disease Biology: Characterization of Putative Cognates for Therapeutic Applications.
Alzheimer's disease (AD) is a neurodegenerative process primarily characterized by amyloid-β (Aβ) agglomeration, neuroinflammation, and cognitive dysfunction. The prominent cause for dementia is the deposition of Aβ plaques and tau-neurofibrillary tangles that hamper the neuronal organization and function. Aβ pathology further affects numerous signaling cascades that disturb the neuronal homeostasis. For instance, Aβ deposition is responsible for altered expression of insulin encoding genes that lead to insulin resistance, and thereby affecting insulin signaling pathway and glucose metabolism in the brain. As a result, the common pathology of insulin resistance between Type-2 diabetes mellitus and AD has led AD to be proposed as a form of diabetes and termed 'Type-3 diabetes'. Since accumulation of Aβ is the prominent cause of neuronal toxicity in AD, its clearance is the prime requisite for therapeutic prospects. This purpose is expertly fulfilled by the potential role of Aβ degrading enzymes such as insulin degrading enzyme (IDE) and Neprilysin (NEP). Therefore, their molecular study is important to uncover the proteolytic and regulatory mechanism of Aβ degradation. Herein, (i) In silico sequential and structural analysis of IDE and NEP has been performed to identify the molecular entities for proteolytic degradation of Aβ in the AD brain, (ii) to analyze their catalytic site to demonstrate the enzymatic action played by IDE and NEP, (iii) to identify their structural homologues that could behave as putative partners of IDE and NEP with similar catalytic action and (iv) to illustrate various IDE- and NEP-mediated therapeutic approaches and factors for clearing Aβ in AD.


Management of acute sigmoid volvulus: an institution's experience over 9 years.
Management of sigmoid volvulus is often challenging because of its prevalence in high-risk patients and the associated perioperative morbidity and mortality rates. This study was designed to review the management and outcome of all patients admitted with sigmoid volvulus. A retrospective review of all patients who were admitted for sigmoid volvulus from October 2001 to June 2009 was performed. Diagnosis was confirmed on clinical evaluation, radiological studies, and/or intraoperative findings. Seventy-one patients, median age 73 (range, 17-96) years, were admitted a total of 134 times for acute sigmoid volvulus during the study period. The majority (n = 51, 71.8%) were older than aged 60 years, and 41 (57.7%) had at least one premorbid condition. Seven (9.9%) patients underwent emergency surgery on presentation. The remaining 64 (90.1%) patients were initially managed conservatively using a flatus tube and/or sigmoidoscopic decompression. One patient had an endoscopic-related perforation and required emergency surgery. Another ten patients failed conservative management for which nine underwent operative intervention. The last patient refused surgery and died subsequently. Fifty-three (74.6%) patients had successful conservative management; seven of them underwent elective surgery subsequently. Of the remaining 46 patients, 28 (60.9%) were admitted for recurrent sigmoid volvulus. Of these 28 patients, 12 eventually had elective surgery after successful decompression, whereas the remaining 16 were not operated. In our series, three patients died after emergency surgery and there was no mortality after elective surgery. Another six patients died from medical conditions that were unrelated to sigmoid volvulus. Acute sigmoid volvulus is a surgical emergency, although the majority (75%) can be successfully decompressed nonoperatively. Emergency surgery in these patients is associated with a mortality of 17.6% in our series. Elective definitive surgery is suggested in view of the high recurrence rate (>60%) and the considerable risks of emergency surgery.


Eurasian beaver - A semi-aquatic ecosystem engineer rearranges the assemblage of terrestrial mammals in winter.
There is increasing awareness of the ecosystem engineering services provided by recovering populations of Eurasian beaver. By modifying aquatic environments, this species has a significant, positive influence on biodiversity. Beaver activity affects not only aquatic ecosystems but also terrestrial habitats and organisms. Our study compares and evaluates the species richness and activity of terrestrial mammals in winter at beaver ponds (N = 65) and randomly-selected reference sites along nearby watercourses unmodified by beavers (N = 65) in Poland (central Europe). Mammal assemblages were investigated near pond/watercourse edges, and also at some distance from them. The species richness of mammal and numbers of their tracks were respectively 25% and 33% greater on the beaver than on the reference sites. The higher species richness on beaver sites extended to areas 40-60 m distant from ponds, devoid any signs of beaver activity. Twenty-three mammal species were recorded on beaver sites (mean species richness 3.8 ± 1.6 SD), and 20 on reference ones (3.0 ± 1.5 SD). The numbers of tracks of grey wolf, least weasel and European polecat were higher on beaver than reference sites. Mammal species richness and activity were related to the existence of beaver ponds, but were also correlated with the numbers of snags and coverage of grass, bramble and coniferous saplings in neighbouring terrestrial habitats. Large and small carnivores occurred more frequently and were more active on beaver sites. The frequencies of occurrence of mesocarnivores, mesoherbivores and small herbivores were correlated with habitat characteristics, regardless of whether beavers were present or not. Our results highlight the fact that both pond creation and the habitat changes resulting from the presence of beavers rearrange the occurrence and activity of the terrestrial mammal assemblage.


Single-bundle posterior cruciate ligament reconstruction and mini-open popliteofibular ligament reconstruction in knees with severe posterior and posterolateral rotation instability: clinical results of minimum 2-year follow-up.
The aim of this study was to assess the clinical outcome of arthroscopy-assisted posterior cruciate ligament (PCL) reconstruction and mini-open popliteofibular ligament (PFL) reconstruction for severe posterior and posterolateral rotation instability of the knee with lateral collateral ligament intact. Arthroscopic PCL reconstruction and mini-open PFL reconstruction were performed consecutively in 24 patients with chronic posterior and posterolateral rotation instability of the knee. The inclusion criteria for surgery were a side-to-side difference in posterior translation of more than 12 mm measured with stress radiography and tibial external rotation of 10 degrees more than that of the contralateral uninjured knee without varus laxity. The exclusion criterion was combined anterior cruciate ligament injury. The patients underwent single-bundle PCL reconstruction with Achilles tendon allograft. A mini-open PFL reconstruction was performed with anterior tibialis allograft. A 2-cm incision was made on the lateral epicondyle to build the femoral tunnel, and a 3-cm incision was made near the fibular head for the fibular tunnel. The minimum follow up was 2 years. At final follow up, 18 patients (75% [18 of 24]) were enrolled in the study group and 6 patients were lost. Postoperatively, mean posterior tibial translation (side-to-side difference) in our patients was reduced from 17.3 +/- 4.1 mm to 4.6 +/- 3.2 mm. Tibial external rotation was decreased from a mean of 14.7 degrees +/- 4.6 degrees to -2.8 degrees +/- 3.8 degrees, as compared with the contralateral uninjured knee. These differences were statistically significant. The International Knee Documentation Committee grade preoperatively was grade D in all 18 patients, whereas postoperatively, 5 were classified as grade A, 8 as grade B, and 5 as grade C. In this small clinical series, single-bundle PCL reconstruction combined with mini-open PFL reconstruction was proven to correct pathologic excessive posterior and posterolateral rotation instability. Level IV, therapeutic case series (no control or historical group).


Function of the arachidonate-deficient spontaneously hypertensive rat kidney.
In order to assess the effect of renal prostaglandins on the glomerular filtration rate (GFR) and electrolyte excretion in the spontaneously hypertensive rat (SHR), we perfused isolated SHR and normotensive Wistar-Kyoto (WKY) kidneys after pretreatment with either a control diet or a diet deficient in arachidonate, the precursor of prostaglandins. When perfusion pressures were increased from 100 to 160 mm Hg, renal vascular resistances (RVR) increased by 32-41%. RVR of SHR kidneys always exceeded that of WKY kidneys by a nearly constant amount, and arachidonate deficiency had little effect on this relationship. In contrast to RVR, the GFR increased severalfold. GFR and urine flow were greater in WKY than in SHR kidneys, a relationship unaffected by arachidonate deficiency. Changes in sodium and chloride excretion occurred in parallel with GFR. Although arachidonate-deficient SHR and WKY kidneys manifested potassium wastage compared to controls, arachidonate deficiency did not result in altered sodium or chloride excretion. The results suggest that direct actions of arachidonate or renal prostaglandins are not responsible for most functional differences between SHR and WKY kidneys.


The efficacy of negative-pressure wound therapy for head and neck wounds: A systematic review and update.
Despite the established benefits of negative-pressure wound therapy (NPWT) in various wound healing contexts, its application in head and neck surgical cases remains under-explored. This study aimed to systematically review its effectiveness, safety, and comparative efficacy. Thirty-one studies from a systematic literature search were identified and analyzed for wound healing response, overall success rate, improvements compared to conventional wound care, and variation in pressure settings, treatment lengths, and dressing change frequency. NPWT showed enhanced outcomes across diverse head and neck wounds, particularly complex post-reconstructive wounds and severe infections. Despite the predominantly case report/series evidence and lack of standardized NPWT protocols, its benefits over conventional care were clear. NPWT emerges as a promising approach for head and neck wound management, potentially improving patient outcomes and reducing complications. More randomized controlled trials are needed to solidify the evidence and standardize NPWT application protocols.


Priming for novel object associations: Neural differences from object item priming and equivalent forms of recognition.
The neural substrates of associative and item priming and recognition were investigated in a functional magnetic resonance imaging study over two separate sessions. In the priming session, participants decided which object of a pair was bigger during both study and test phases. In the recognition session, participants saw different object pairs and performed the same size-judgement task followed by an associative recognition memory task. Associative priming was accompanied by reduced activity in the right middle occipital gyrus as well as in bilateral hippocampus. Object item priming was accompanied by reduced activity in extensive priming-related areas in the bilateral occipitotemporofrontal cortex, as well as in the perirhinal cortex, but not in the hippocampus. Associative recognition was characterized by activity increases in regions linked to recollection, such as the hippocampus, posterior cingulate cortex, anterior medial frontal gyrus and posterior parahippocampal cortex. Item object priming and recognition recruited broadly overlapping regions (e.g., bilateral middle occipital and prefrontal cortices, left fusiform gyrus), even though the BOLD response was in opposite directions. These regions along with the precuneus, where both item priming and recognition were accompanied by activation, have been found to respond to object familiarity. The minimal structural overlap between object associative priming and recollection-based associative recognition suggests that they depend on largely different stimulus-related information and that the different directions of the effects indicate distinct retrieval mechanisms. In contrast, item priming and familiarity-based recognition seemed mainly based on common memory information, although the extent of common processing between priming and familiarity remains unclear. Further implications of these findings are discussed.


Role of fomites in SARS transmission during the largest hospital outbreak in Hong Kong.
The epidemic of severe acute respiratory syndrome (SARS) had a significant effect on global society in the early 2000s and the potential of its resurgence exists. Studies on the modes of transmission of SARS are limited though a number of outbreak studies have revealed the possible airborne route. To develop more specific and effective control strategies, we conducted a detailed mechanism-based investigation that explored the role of fomite transmission in the well-known Ward 8A outbreak. We considered three hypothetical transmission routes, i.e., the long-range airborne, fomite and combined routes, in 1,744 scenarios with combinations of some important parameters. A multi-agent model was used to predict the infection risk distributions of the three hypothetical routes. Model selection was carried out for different scenarios to compare the distributions of infection risk with that of the reported attack rates and select the hypotheses with the best fitness. Our results reveal that under the assumed conditions, the SARS coronavirus was most possible to have spread via the combined long-range airborne and fomite routes, and that the fomite route played a non-negligible role in the transmission.


From emotional intelligence to suicidality: a mediation analysis in patients with borderline personality disorder.
Borderline personality disorder (BPD) is a serious mental illness with a high suicidality rate between 40 and 85%. However, little is known concerning psychosocial risk and protective factors associated with suicidal behaviors in this clinical group. The main focus of the present study was on examining the relationship of emotional intelligence (EI) with suicidal behaviors and its mediators (e.g., depression, self-esteem, addiction potential, and disorder severity) among patients with BPD. In this cross-sectional study, a total of 220 participants (including 110 patients with BPD and 110 healthy controls) in Zahedan, Iran, were examined using clinical interviewing and self-report measures of EI, suicidal behaviors, depression, self-esteem, addiction potential, and BPD symptom severity. The data were analyzed using SPSS v25.0 software at the significance level of p < 0.05. Our preliminary analysis showed higher levels of EI, depression, and self-esteem in the BPD group in comparison to healthy controls (p < 0.001). Furthermore, our findings showed that higher levels of addiction potential, BPD symptom severity, and depression and lower levels of self-esteem and EI were likely to be related to suicidal behaviors of the BPD group. Our results also supported the overall hypothesis that addiction potential, depression, BPD symptom severity, and self-esteem had a mediating role in the impact of EI on suicidal behaviors in the BPD group. According to these findings, we have come to believe that training EI possibly plays a directly and/or indirectly potential preventive and therapeutic role in suicidal behaviors among patients with BPD. However, further longitudinal studies must be carried out to clarify the cause and effect relationship between EI, depression, self-esteem, addiction potential, BPD symptom severity, and suicidal behaviors.


Recent Advances and New Strategies in Targeting Plk1 for Anticancer Therapy.
Polo-like kinase 1 (Plk1) plays key roles in regulating mitotic processes that are crucial for cellular proliferation. Overexpression of Plk1 is tightly associated with the development of particular cancers in humans, and a large body of evidence suggests that Plk1 is an attractive target for anticancer therapeutic development. Drugs targeting Plk1 can potentially be directed at two distinct sites: the N-terminal catalytic kinase domain (KD), which phosphorylates substrates, and the C-terminal polo-box domain (PBD) which is essential for protein-protein interactions. In this review we summarize recent advances and new challenges in the development of Plk1 inhibitors targeting these two domains. We also discuss novel strategies for designing and developing next-generation inhibitors to effectively treat Plk1-associated human disorders.


Individual work support for employed patients with low back pain: a randomized controlled pilot trial.
To investigate the feasibility and effectiveness of individual work support for employed patients with low back pain. Pilot randomized controlled trial of a 16-week vocational intervention with six-month follow-up. Community/outpatient. Fifty-one employed participants concerned about their ability to work due to low back pain. Outcome data was obtained for 38 participants at six-month follow-up. The intervention group received up to eight individually targeted vocational sessions in conjunction with group rehabilitation for low back pain. The control group received group rehabilitation. The feasibility of the intervention was assessed by the recruitment rate, drop-out and loss to follow-up of the participants and the content and delivery of the intervention as recorded by the researcher. The primary outcome measure was perceived work ability. Seventy-three participants were referred to the study over six months. Eighty-seven individual work support sessions were delivered. Thirty-one participants (61% of those retained in the study) attended more than half of the group rehabilitation sessions. The intervention was influenced by the uptake of group rehabilitation, the willingness of the participants to involve their workplace and of their workplace to involve the research therapist. The effect of the intervention on work ability was equivocal. Although it was possible to recruit participants and to deliver the intervention, considerable methodological problems were identified. However, even if these were addressed, the impact of such interventions is likely to be limited unless there is an integrated approach between healthcare, employers and employees. Further research is required to evaluate work-focused interventions with this client group.


Multi reflection of Lamb wave emission in an acoustic waveguide sensor.
Recently, an acoustic waveguide sensor based on multiple mode conversion of surface acoustic waves at the solid-liquid interfaces has been introduced for the concentration measurement of binary and ternary mixtures, liquid level sensing, investigation of spatial inhomogenities or bubble detection. In this contribution the sound wave propagation within this acoustic waveguide sensor is visualized by Schlieren imaging for continuous and burst operation the first time. In the acoustic waveguide the antisymmetrical zero order Lamb wave mode is excited by a single phase transducer of 1 MHz on thin glass plates of 1 mm thickness. By contact to the investigated liquid Lamb waves propagating on the first plate emit pressure waves into the adjacent liquid, which excites Lamb waves on the second plate, what again causes pressure waves traveling inside the liquid back to the first plate and so on. The Schlieren images prove this multi reflection within the acoustic waveguide, which confirms former considerations and calculations based on the receiver signal. With this knowledge the sensor concepts with the acoustic waveguide sensor can be interpreted in a better manner.


Laser and serum opsonic activity.
The purpose of this study was to investigate the effects of low level laser (LLL: GaA1As diode laser; 830 nm) on serum opsonic activity, which was assessed by neutrophil-associated chemiluminescence (CL) response to zymosan opsonized with sera irradiated in vitro with various doses of LLL. We used both lucigenin-dependent CL (LgCL) for superoxide (O2-) detection and luminol-dependent CL (LmCL) which detects myeloperoxidase (MPO)-dependent formation of hypochlorous acid in combination with MPO inhibitor, sodium azide (NaN3). When serum opsonic activity was assessed by LgCl, NaN3, markedly enhanced the responses, suggesting that O2- is accumulated due to the MPO blockade, leading to the excitation of LgCl. However, LLL-irradiation had no effects on serum opsonic activity. On the other hand, when serum opsonic activity was assessed by LmCl, NaN3, strongly inhibited the response. The effects of LLL at different output powers were characterized by similar values, but significantly higher values were observed at the highest dose tested (60 mW for 1 min) in the absence of NaN3. Since this enhancement effect disappeared with NaN3, it was suggested that high dose LLL-irradiation probably activated the opsonic activity by facilitating neutrophils to degranulate MPO. However, lower doses used for therapeutic purposes had no effects at any output powers tested.


Human pituitary prolactin (hPRL): the entire linear amino acid sequence.
For the first time the entire linear amino acid sequence of hPRL has been ascertained. The sequence features 198 amino acid residues, leucine at the NH2-terminus, and 6 half custines. hPRL sequence identity with porcine, ovine, and rat PRL is 77, 73, and 60%, respectively. However, hPRL sequence identity with hGH is only 16%, and with human placental lactogen 13%.


Metabolic Profiling of Urine by Capillary Electrophoresis-Mass Spectrometry Using Non-covalently Coated Capillaries.
In the field of metabolomics, capillary electrophoresis-mass spectrometry (CE-MS) can be considered a very useful analytical tool for the profiling of polar and charged metabolites. However, variability of migration time is an important issue in CE. An elegant way to minimize this problem is the use of non-covalently coated capillaries that is dynamic coating of the bare fused-silica capillary with solutions of charged polymers. In this protocol, an improved strategy for the profiling of cationic metabolites in urine by CE-MS using multilayered non-covalent capillary coatings is presented. Capillaries are coated with a bilayer of polybrene (PB) and poly(vinyl sulfonate) (PVS) or with a triple layer of PB, dextran sulfate (DS), and PB. The bilayer- and triple-layer-coated capillaries have a negative and positive outside layer, respectively. It is shown that the use of such capillaries provides very repeatable migration times.


Ethically involving students in faculty research.
Students in nursing education programs have a right to privacy as they engage in their learning. At the same time, their faculty may be engaged in nursing education research in order to facilitate student learning. These two goals may conflict when faculty engage students as participants in nursing education research while at the same time facilitating their learning. Faculty as researchers with their students may encounter a conflict of interest in collecting data for their research while providing learning experiences for the same students. As a basic principle, students must be engaged as participants in an ethical manner that respects their rights for privacy. In this article, we explore the issues of faculty as researchers of their students and suggest strategies for addressing these issues.


A case report: a rare case of severe aortic incompetence.
Aneurysms of the sinus of Valsalva (SOV) are thin-walled outpouchings most commonly involving the right or non-coronary sinuses. Because they are asymptomatic, they are rarely discovered before they rupture and form an aorto-cardiac fistula. We present a rare case of unruptured aneurysm of the right coronary SOV burrowing into the interventricular septum with severe aortic incompetence and left ventricular dysfunction. To our knowledge, burrowing of the SOV aneurysm (SVA) into the interventricular septum and its large sac-like appearance has never been described using three dimensional (3D) echocardiography before. A 37-year-old man presented to the cardiology outpatient department with complaints of dyspnoea and palpitations (New York Heart Association Class II-III) for the last 6 months. He was evaluated with transthoracic echocardiography which showed a large mobile sac-like structure with irregular borders bulging and prolapsing into the left ventricular cavity with each cardiac cycle along with severe aortic incompetence. On transoesophageal echocardiogram, the right coronary cusp showed malcoaptation with deformed aortic sinus causing severe aortic incompetence. Cardiac computed tomography showed sparing of right coronary artery at the origin. A diagnosis of SVA was made. The patient underwent aortic valve replacement along with partial resection of the aneurysm. The patient had an uneventful postoperative course. Follow-up echocardiography after 4 weeks showed well-seated aortic valve prosthesis with residual SVA. The ejection fraction decreased from 46-48% to 36-38%. Comprehensive multimodality imaging can be used for management strategy of SVA.


Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis.
A disintegrin and metalloproteinases (ADAMs) are a family of mSultidomain, membrane-anchored proteases that regulate diverse cellular functions, including cell adhesion, migration, proteolysis and other cell signaling events. Catalytically-active ADAMs act as ectodomain sheddases that proteolytically cleave type I and type II transmembrane proteins and some GPI-anchored proteins from the cellular surface. ADAMs can also modulate other cellular signaling events through a process known as regulated intramembrane proteolysis (RIP). Through their proteolytic activity, ADAMs can rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g. inflammation) and play a central role in coordinating intercellular communication. Dysregulation of these processes through aberrant expression, or sustained ADAM activity, is linked to chronic inflammation, inflammation-associated cancer and tumorigenesis. ADAM10 was the first disintegrin-metalloproteinase demonstrated to have proteolytic activity and is the prototypic ADAM associated with RIP activity (e.g. sequential Notch receptor processing). ADAM10 is abundantly expressed throughout the gastrointestinal tract and during normal intestinal homeostasis ADAM10 regulates many cellular processes associated with intestinal development, cell fate specification and maintenance of intestinal stem cell/progenitor populations. In addition, several signaling pathways that undergo ectodomain shedding by ADAM10 (e.g. Notch, EGFR/ErbB, IL-6/sIL-6R) help control intestinal injury/regenerative responses and may drive intestinal inflammation and colon cancer initiation and progression. Here, I review some of the proposed functions of ADAM10 associated with intestinal crypt homeostasis and tumorigenesis within the gastrointestinal tract in vivo. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.


Satisfaction and quality of life in cochlear implant users with long sensory deprivation.
The aim of the study was to verify the level of satisfaction of CI users with long periods of hearing deprivation, highlighting the positive and negative aspects of the use of the device and their quality of life. This is a analytical research, of the type observational cross-sectional study. The study was performed with 24 patients from a private Institute of Otorhinolaryngology. Three surveys were applied: Satisfaction with Amplification in Daily Life (SADL), International Outcome Inventory - Cochlear Implant (IOI - CI) to assess cochlear implant satisfaction and WHOQOL- bref to assess the quality of life. The results in the pre and post lingual groups were compared. The highest degree of satisfaction was reported with regard to personal image, positive effects, and how the users feel about their CI. The lowest degree of satisfaction was reported regarding the cost-benefit of the CI and the competitive noise. In the WHOQOL-bref assessment, the highest scores were found in physical, psychological and social relations domains. When comparing the results of the surveys, the pre and post-lingual groups showed no difference in relation to the achieved scores. The participants had a high level of satisfaction with the use of cochlear implants. The longer the sensory deprivation time, the greater the degree of satisfaction with the device. The use of the CI electronic device reflects on the individual's quality of life.


Controversies in the management of stage IIIA non-small-cell lung cancer.
New developments in the management of non-small-cell lung cancer, as well as recent proposals for changing the current lung cancer staging system, are posing a challenge in the therapeutic decision making regarding this disease. For the last two decades, the management of stage IIIA (N2) disease has been controversial and the target for clinical trials has been to determine the best therapeutic approach that may result in better survival outcomes without increasing toxicity. For many years, combined modality treatment (systemic chemotherapy plus radiation therapy) became the standard of care in this setting. However, the poor outcomes seen with combined modality for N2 has obligated us to explore other possibilities. In this sense, recent clinical trials in the neoadjuvant setting using chemotherapy alone or combined modality are providing fruitful results and shifting the paradigm on this stage. A recent, large randomized multicenter trial argues against what has slowly become a current practice in some centers - the use of preoperative modality for N2 disease. Another controversy that we will discuss here is the acceptance of adjuvant therapy for resected stage IB-IIIA non-small-cell lung cancer. It was not long ago that adjuvant radiation therapy was still the standard of care for patients who have pathological nodal disease. We will present the current data on these debatable issues and how to implement this new knowledge into clinical practice.


Control of mode of crystal networking during monolayer assembly of microcrystals on water.
A series of hydrocarbon (HC)-coated cubic zeolite microcrystals (1.7 microm) was prepared. The HCs were n-octyl, n-dodecyl, methyl n-undecanoate, n-octadecyl, and n-heptadecafluorodecyl. The measured water contact angles (theta) of the corresponding HC-coated glass plates were 64, 77, 82, 102, and 105 degrees, respectively, indicating that the hydrophobicity of the surface-tethered hydrophobic chain (HC) increased in the above order. The HC-coated zeolite microcrystals readily formed closely packed monolayers at the air-water interface through interdigitation of surface-tethered HCs, and on glass plates after transferring onto glass plates by dip coating. Interestingly, while the mode of networking was face-to-face (FTF) contacting with n-octyl or n-dodecyl (theta < or =77 degrees) as HC, it changed to edge-to-edge (ETE) contacting mode with n-octadecyl or n-heptadecafluorodecyl (theta > or = 102 degrees) as HC. With methyl n-undecanoate (theta = 82 degrees) as HC, both modes appeared in the monolayers, with about equal populations. The resulting monolayers of cubic zeolite microcrystals with their three-fold axes oriented perpendicular to substrates would be useful for application of the zeolite monolayers for advanced materials.


Investigation of diastereoselective acyclic α-alkoxydithioacetal substitutions involving thiacarbenium intermediates.
Reported herein is an experimental and theoretical study that elucidates why silylated nucleobase additions to acyclic α-alkoxythiacarbenium intermediates proceed with high 1,2-syn stereocontrol (anti-Felkin-Anh), which is opposite to what would be expected with corresponding activated aldehydes. The acyclic thioaminals formed undergo intramolecular cyclizations to provide nucleoside analogues with anticancer and antiviral properties. The factors influencing the selectivity of the substitution reaction have been examined thoroughly. Halothioether species initially form, ionize in the presence (low dielectric media) or absence (higher dielectric media) of the nucleophile, and react through SN2-like transition structures (TS A and D), where the α-alkoxy group is gauche to the thioether moiety. An important, and perhaps counterintuitive, observation in this work was that calculations done in the gas phase or low dielectric media (toluene) are essential to locate the product- and rate-determining transition structures (C-N bond formation) that allow the most reasonable prediction of selectivity and isotope effects for more polar solvents (THF, MeCN). The ΔΔG(⧧) (G(TSA-TSD)) obtained in silico are consistent with the preferential formation of 1,2-syn product and with the trends of stereocontrol displayed by 2,3-anti and 2,3-syn α,β-bis-alkoxydithioacetals.


Chemopreventive effects of a Tamarindus indica fruit extract against colon carcinogenesis depends on the dietary cholesterol levels in hamsters.
Tamarind has significant antioxidant potential. We showed that tamarind protects hypercholesterolemic hamsters from atherosclerosis. Hypercholesterolemia might increase the risk of colon cancer. We investigated whether tamarind extract modulates the risk of colon cancer in hypercholesterolemic hamsters. Hamsters (n = 64) were given tamarind and a hypercholesterolemic diet for 8 weeks. The groups were the control, tamarind treatment, hypercholesterolemic, and hypercholesterolemic treated with tamarind groups. Half of each group was exposed to the carcinogen dimethylhydrazine (DMH) at the 8th week. All hamsters were euthanatized at the 10th week. In carcinogen-exposed hypercholesterolemic hamsters, tamarind did not alter the cholesterol or triglyceride serum levels, but it reduced biomarkers of liver damage (alanine transaminase [ALT], and aspartate aminotransferase [AST]). Tamarind decreased DNA damage in hepatocytes, as demonstrated by analysis with an anti-γH2A.X antibody. In liver and serum samples, we found that this fruit extract reduced lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) and increased endogenous antioxidant mechanisms (glutathione peroxidase [GPx] and superoxide dismutase [SOD]). However, tamarind did not alter either lipid peroxidation or antioxidant defenses in the colon, which contrasts with DMH exposure. Moreover, tamarind significantly increased the stool content of cholesterol. Although tamarind reduced the risk of colon cancer in hypercholesterolemic hamsters that were carcinogenically exposed to DMH by 63.8% (Metallothionein), it was still ∼51% higher than for animals fed a regular diet. Staining colon samples with an anti-γH2A.X antibody confirmed these findings. We suggest that tamarind has chemoprotective activity against the development of colon carcinogenesis, although a hypercholesterolemic diet might impair this protection.


Genome-scale identification and characterization of moonlighting proteins.
Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins. First, we analyzed Gene Ontology (GO) annotations of known moonlighting proteins. We found that the GO annotations of moonlighting proteins can be clustered into multiple groups reflecting their diverse functions. Then, by considering the observed GO term separations, we identified 33 novel moonlighting proteins in Escherichia coli and confirmed them by literature review. Next, we analyzed moonlighting proteins in terms of protein-protein interaction, gene expression, phylogenetic profile, and genetic interaction networks. We found that moonlighting proteins physically interact with a higher number of distinct functional classes of proteins than non-moonlighting ones and also found that most of the physically interacting partners of moonlighting proteins share the latter's primary functions. Interestingly, we also found that moonlighting proteins tend to interact with other moonlighting proteins. In terms of gene expression and phylogenetically related proteins, a weak trend was observed that moonlighting proteins interact with more functionally diverse proteins. Structural characteristics of moonlighting proteins, i.e. intrinsic disordered regions and ligand binding sites were also investigated. Additional functions of moonlighting proteins are difficult to identify by experiments and these proteins also pose a significant challenge for computational function annotation. Our method enables identification of novel moonlighting proteins from current functional annotations in public databases. Moreover, we showed that potential moonlighting proteins without sufficient functional annotations can be identified by analyzing available omics-scale data. Our findings open up new possibilities for investigating the multi-functional nature of proteins at the systems level and for exploring the complex functional interplay of proteins in a cell. This article was reviewed by Michael Galperin, Eugine Koonin, and Nick Grishin.


Experimental infections reveal that common Thai crustaceans are potential carriers for spread of exotic Taura syndrome virus.
Taura syndrome virus (TSV) was first reported as a serious cause of shrimp mortality limited to reared Penaeus (Litopenaeus) vannamei in the Americas, where it spread principally through regional and international transfer of live post larvae (PL) and broodstock. Subsequently, through importation of infected broodstock, TSV outbreaks spread to Asia, first to Taiwan and China and then to Thailand, Indonesia and Korea. Since its introduction to Thailand, outbreaks have occasionally been reported from rearing ponds stocked with batches of specific pathogen free (SPF) P. vannamei PL that tested negative for TSV by nested RT-PCR assay. Since it was possible that the outbreaks may have occurred via horizontal transfer of TSV from wild carrier species, we tested 5 common native crustaceans that live in and around shrimp ponds (2 palaemonid shrimp species, Palaemon styliferus and Macrobrachium lanchesteri, and 3 species of crabs, Sesarma mederi, Scylla serrata and Uca vocans) for susceptibility to TSV in experimental challenges. We found that U. vocans, S. serrata and S. mederi did not die but, respectively, gave strong RT-PCR reactions indicating heavy viral load at 5, 10 and 15 d post-injection of TSV and 10, 15 and up to 50 d after feeding with TSV-infected P. vannamei carcasses. Also after feeding, P. styliferus did not die, but a high proportion gave strong RT-PCR reactions at 5 d post-challenge and no reactions at 15 d. Similarly after feeding, M. lanchesteri showed no mortality and gave only light RT-PCR reactions at 2 d, moderate reactions at 5 d and no reaction at 15 d. By contrast, transmission experiments from the TSV-infected crabs and palaemonid shrimp via water or feeding resulted in death of all the exposed P. vannamei from 8 to 12 d post-challenge and all were positive for heavy viral load by RT-PCR assay. Despite the results of these laboratory challenge tests, natural TSV infections were not detected by nested RT-PCR in samples of these species taken from the wild. These results indicated that transmission of TSV from infected crabs and palaemonid shrimp via water or feeding might pose a potential risk to shrimp aquaculture.


The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.
The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.


Diagnosis of haemophilic synovitis.
The pathophysiology of haemophilic synovitis is complex and not as well understood on a molecular level as we have thought. The repeated bleeding episodes and synovial hypertrophy occurring within the joint. Iron and other red-cell debris are phagocytized, and hydrolytic enzymes are produced leading to the destruction of articular cartilage is a simplistic model. However, how iron stimulates this destructive cascade remains speculative and poorly understood. Diagnostic options include radiographic examination using horizontal beam technique, which may reveal a fat blood fluid level, and computed tomography scanning or magnetic resonance imaging.


Relationship of glutathione S-transferase genotypes with side-effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus.
Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE. DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile-->Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay. Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients. The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.


Urethral stricture after transurethral resection.
After 101 transurethral resections, iatrogenic postoperative urethral strictures have occurred in 10 cases due to pathologic changes in the bladder and bladder neck. Urethral stricture after transurethral resection (TUR) thus has represented the most common postoperative complication. No morbidity increase of urethral strictures after TUR could be demonstrated in one of the analysed groups. Fifty per cent of the incidence rate of strictures was localized in the pars pendulans urethrae. Factors causing the stricture have been demonstrated, and the incidence rate of strictures was reduced when these factors were taken into consideration. Preference is given either to conservative or surgical therapy depending on the localization of the stricture, even though endoscopic methods are used more frequently now in the treatment of stenoses of the urethra.


Secondary and within-session analyses to improve the feasibility and precision of assessments of sociability.
Previous research has improved the feasibility and precision of assessments of sociability, but further progress is warranted. The purpose of this study was to evaluate secondary measures and within-session analyses to further improve the feasibility and precision of assessments of sociability. We reanalyzed previously published assessment results to evaluate whether initial and conditional (i.e., on therapist movement) approach and avoidance may approximate established continuous measures. Results indicated that both measures were strongly correlated with the percentage of session on the social side and may provide a more feasible approximation for use in clinical practice. We also conducted within-session analyses of these assessment results to evaluate whether they may improve precision or clarity. Correlational and matching-based analyses of the within-session data suggest that clear conclusions may be drawn from the results of a single session and facilitate a richer understanding of sociability. Implications for clinical practice and future research are discussed.


Neuropsychological profile of Alzheimer's disease based on amyloid biomarker findings results from a South American cohort.
Increased life expectancy and exponential growth of adults suffering from Alzheimer's disease (AD) worldwide, has led to biomarkers incorporation for diagnosis in early stages. Use of neuropsychological testing remains limited. This study aimed to identify which neuropsychological tests best indicated underlying AD pathophysiology. One hundred and forty-one patients with MCI (Mild Cognitive Impairment) were studied. A neuropsychological test battery based on the Uniform Data Set (UDS) from the Alzheimer's Disease Centers program of the National Institute on Aging (NIA) was performed and amyloid markers recorded; according to presence or absence of amyloid identified by positive PIB-PET findings, or low CSF Aβ42 levels, patients were separated into MCI amyloid-(n:58) and MCI amyloid + (n = 83) cases. Statistical differences were found in all memory tests between groups. Delayed recall score at thirty minutes on the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of amyloid pathology presence (AUC 0.68), followed by AVLT total learning (AUC 0.66) and AVLT Recognition (AUC 0.59) scores, providing useful cut off values in the clinical setting. Use of neuropsychological testing, specifically AVLT scores with cutoff values, contributed to the correct diagnosis of MCI due to AD in this SouthAmerican cohort.


Spectrum of mandibular fractures at a tertiary care dental hospital in Lahore.
Mandible being the only mobile bone of the facial skeleton plays a major role in mastication, speech and deglutition. Among the maxillofacial trauma, mandible is the high risk exponent. Its fractures result in severe loss of function and disfigurement. The increased vehicular accidents, conditions of our roads and other assaults have focused attention in recent years to prevent injuries. A descriptive case series of 126 patients with mandibular fractures attending a tertiary referral centre over a six-month period is presented. Data concerning the patients' demographics, aetiology and pattern were obtained and analysed. Approximately 56% of the patients sustained fractures from road traffic accidents and 34% of the fractures occurred in the 21-30 year age range. There was a male preponderance with a male to female ratio of 9:1. Parasymphyseal fractures were the most common followed by those of the condylar and subcondylar regions. We need to encourage further research work in this field to provide better record keeping and quality of services to the injured people. Amendments in the traffic rules and legislation about seat-belt usage and traditional kite flying to reduce frequency of fractures are required.


[The meaning of illness among Korean Americans with chronic hepatitis B].
This ethnography was done to explore the meaning of illness in Korean Americans with chronic hepatitis B. The participants were 6 patients with chronic hepatitis B and 6 general informants who could provide relevant data. Data were collected from iterative fieldwork with ethnographic interviews within Korean communities in two cities in the United States. Data were analyzed using causal chain analysis developed by Wolcott. The analyses revealed three meanings for the illness: hidden disease, intentionally hidden disease, and inevitably hidden disease. The contexts of meaning of illness included characteristics of the illness, social stigma, structure of health care system and communication patterns and discourse between health care providers and clients. The meaning of illness was based on folk illness concepts and constructed in the sociocultural context. Folk etiology, pathology and interpretation of one's symptoms were factors influencing illness behavior. These findings could be a cornerstone for culture specific care for Korean Americans with chronic hepatitis B.


Dihydrostreptomycin toxicity in the Mongolian gerbil, Meriones unguiculatus.
A fatal syndrome of acute toxicity was produced in Mongolian gerbils following the injection of a penicillin-dihydrostreptomycin-procaine combination. The toxicity was determined to be due to the dihydrostreptomycin component. Fifty milligrams of dihydrostreptomycin produced 80-100% mortality in 55-65 g gerbils.


The role of 133Xe ventilation studies in the scintigraphic detection of pulmonary embolism.
The angiographic, scintigraphic, and clinical data of 40 patients were reviewed in order to define the role of 133Xe ventilation studies in the radionuclide detection of pulmonary embolism. Two independent observers interpreted the perfusion images, and several weeks later reinterpreted them in conjunction with 133Xe ventilation studies. Overall diagnostic accuracy was significantly improved (p less than 0.05) when the xenon studies were included. The combined studies were slightly more sensitive and significantly more specific (p less than 0.05) for pulmonary embolism than the perfusion images alone.


Vision-force-fused curriculum learning for robotic contact-rich assembly tasks.
Contact-rich robotic manipulation tasks such as assembly are widely studied due to their close relevance with social and manufacturing industries. Although the task is highly related to vision and force, current methods lack a unified mechanism to effectively fuse the two sensors. We consider coordinating multimodality from perception to control and propose a vision-force curriculum policy learning scheme to effectively fuse the features and generate policy. Experiments in simulations indicate the priorities of our method, which could insert pegs with 0.1 mm clearance. Furthermore, the system is generalizable to various initial configurations and unseen shapes, and it can be robustly transferred from simulation to reality without fine-tuning, showing the effectiveness and generalization of our proposed method. The experiment videos and code will be available at https://sites.google.com/view/vf-assembly.