Ideological roadblocks to humanizing dentistry, an evaluative case study of a continuing education course on social determinants of health.
Front line providers of care are frequently lacking in knowledge on and sensitivity to social and structural determinants of underprivileged patients' health. Developing and evaluating approaches to raising health professional awareness and capacity to respond to social determinants is a crucial step in addressing this issue. McGill University, in partnership with Université de Montréal, Québec dental regulatory authorities, and the Québec anti-poverty coalition, co-developed a continuing education (CE) intervention that aims to transfer knowledge and improve the practices of oral health professionals with people living on welfare. Through the use of original educational tools integrating patient narratives and a short film, the onsite course aims to elicit affective learning and critical reflection on practices, as well as provide staff coaching. A qualitative case study was conducted, in Montreal Canada, among members of a dental team who participated in this innovative CE course over a period of four months. Data collection consisted in a series of semi-structured individual interviews conducted with 15 members of the dental team throughout the training, digitally recorded group discussions linked to the CE activities, clinic administrative documents and researcher-trainer field notes and journal. In line with adult transformative learning theory, interpretive analysis aimed to reveal learning processes, perceived outcomes and collective perspectives that constrain individual and organizational change. The findings presented in this article consist in four interactive themes, reflective of clinic culture and context, that act as barriers to humanizing patient care: 1) belief in the "ineluctable" commoditization of dentistry; 2) "equal treatment", a belief constraining concern for equity and the recognition of discriminatory practices; 3) a predominantly biomedical orientation to care; and 4) stereotypical categorization of publically insured patients into "deserving" vs. "non-deserving" poor. We discuss implications for oral health policy, orientations for dental education, as well as the role dental regulatory authorities should play in addressing discrimination and prejudice. Humanizing care and developing oral health practitioners' capacity to respond to social determinants of health, are challenged by significant ideological roadblocks. These require multi-level and multi-sectorial action if gains in social equity in oral health are to be made.


Maximum downward slope of sleep slow waves as a potential marker of attention-deficit/hyperactivity disorder clinical phenotypes.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly heterogeneous diagnostic category, encompassing several endophenotypes and comorbidities, including sleep problems. However, no predictor of clinical long-term trajectories or comorbidity has yet been established. Sleep EEG has been proposed as a potential tool for evaluating the synaptic strength during development, as well as the cortical thickness, which is presumed to be altered in ADHD. We investigated whether the slope of the Slow Waves (SWs), a microstructural parameter of the sleep EEG, was a potential predictive parameter for psychiatric comorbidities and neuropsychological dimensions in ADHD. 70 children (58 m; 8.76 ± 2.77 y) with ADHD who underwent psychiatric and neurologic evaluations and a standard EEG recording during naps were investigated. After sleep EEG analysis, we grouped the extracted SWs in bins of equal amplitude and then measured the associations, through generalized linear regression, between their maximum downward slopes (MDS) and the individual scores obtained from clinical rating scales. The presence of Multiple Anxiety Disorders was positively associated with MDS of medium amplitude SWs in temporo-posterior left areas. The Child Behavior Checklist scores showed negative associations in the same areas for small SWs. The presence of autistic traits was positively associated with MDS of high amplitude SWs in bilateral anterior and temporal left areas. The WISC-IV Processing Speed Index showed negative associations with MDS of small-to-medium SWs in anterior and temporal right areas, while positive associations in posterior and temporal left areas. Consistency of association clusters' localization on the scalp suggests that variations in the local MDS, revealing alterations of local synaptic strength and/or in daytime use of certain cortical circuits, could underlie specific neurodevelopmental trajectories resulting in different ADHD clinical phenotypes.


Derivation of human induced pluripotent stem cell line EURACi004-A from skin fibroblasts of a patient with Arrhythmogenic Cardiomyopathy carrying the heterozygous PKP2 mutation c.2569_3018del50.
Arrhythmogenic Cardiomyopathy (ACM) is an inherited cardiac disease characterized by arrhythmias and fibro-fatty replacement in the ventricular myocardium. Causative mutations are mainly reported in desmosomal genes, especially in plakophilin2 (PKP2). Here, using a virus-free reprogramming approach, we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of one ACM patient carrying the frameshift heterozygous PKP2 mutation c.2569_3018del50. The iPSC line (EURACi004-A) showed the typical morphology of pluripotent cells, possessed normal karyotype and exhibited pluripotency markers and trilineage differentiation potential, including cardiomyogenic capability. Thus, this line can represent a human in vitro model to study the molecular basis of ACM.


Effects of sexual behavioral manipulation on brain plasticity in adult rats.
The purpose of the present study was to determine the effects of sexual behaviorial manipulation on brain plasticity in adult male rats. Adult male Sprague-Dawley rats that copulated during male sexual behavior testing were divided into four groups: control male; gonadectomized (Gdx) male; sexually active male; and sexually nonactive male. Female animals were used as an additional control group. At the end of a 12-week experimental period, the animals were again tested for male sexual behavior and tested for sexual motivation. Sexual behavior manipulations over the 12-week period resulted in significant differences in mount latency, mount frequency, intromission latency, intromission frequency, ejaculation latency, and the postejaculation interval. In the motivation test, significant differences in the number of approaches, contacts, and crossings of an electrified grid separating the test animal from a receptive female were also observed. Sexually dimorphic nucleus of the preoptic area (SDN-POA) volumes in sexually nonactive males were significantly smaller than in control males or sexually active males. Anteroventral periventricular nucleus (AVPV) volumes in the male groups were not significantly altered by sexual behavioral manipulations, however, the nonactive AVPV vol. was the only vol. not significantly different from the control female vol. These data demonstrate that in the adult rat, sexual behavioral manipulations resulted in significant alterations in behavior and in the vol. of the SDN-POA and that the effect of sexual behavior on the AVPV needs to be further investigated.


Keratoprosthesis surgery for end-stage corneal blindness in asian eyes.
To establish a multidisciplinary surgical program for osteo-odonto-keratoprosthesis (OOKP) surgery in Asia and to evaluate efficacy and preliminary safety of this keratoprosthesis in end-stage corneal and ocular surface disease. Prospective noncomparative case series. Sixteen adults of Asian ethnic origin, bilaterally blind with end-stage corneal blindness from Stevens-Johnson syndrome, or severe chemical or thermal burns. Osteo-odonto-keratoprosthesis surgery involves 2 procedures-in stage 1, an autologous canine tooth is removed, modified to receive an optical polymethyl methacrylate cylinder, and implanted into the cheek. The ocular surface is denuded and replaced with full-thickness buccal mucosa. Stage 2 surgery, performed 2 to 4 months later, involves retrieval of the tooth-cylinder complex and implanting it into the cornea, after reflection of the buccal mucosal flap, corneal trephination, iris and lens removal, and anterior vitrectomy. Concurrent glaucoma and vitreoretinal procedures are also performed at either stage, as required. Visual acuity (VA), field of vision, anatomical integrity and stability, and ocular and oral complications related or unrelated to the OOKP device. Osteo-odonto-keratoprosthesis surgery was performed on 15 patients, with a mean follow-up of 19.1 months (range, 5-31). Intraoperative complications included expulsive hemorrhage (keratoprosthesis device not implanted), tooth fracture (n = 1), oronasal fistula (n = 1), and mild inferior optic tilt (n = 1). Anatomical stability and keratoprosthesis retention has been maintained in all eyes, with no dislocation, extrusion, retroprosthetic membrane formation, or keratoprosthesis-related infection. Other complications not directly related to device insertion included retinal detachment (RD) related to silicone oil removal (n = 1) and endophthalmitis related to endoscopic cyclophotocoagulation performed 1 year after OOKP surgery (n = 1). Eleven patients (73.3%) attained a stable best spectacle-corrected VA of at least 20/40 or better, whereas 9 (60%) attained stable 20/20 vision. Four patients achieved their best visual potential, ranging from 20/100 to counting fingers vision, related to preexisting glaucomatous optic neuropathy or previous RD. Establishment of our OOKP program suggests that OOKP surgery has the potential to restore good vision to the most severe cases of corneal blindness in an Asian setting, with minimal device-related complications. Longer follow-up of these cases is currently underway.


Assessment of public health impact of work-related asthma.
Asthma is among the most common chronic diseases in working-aged populations and occupational exposures are important causal agents. Our aims were to evaluate the best methods to assess occurrence, public health impact, and burden to society related to occupational or work-related asthma and to achieve comparable estimates for different populations. We addressed three central questions: 1: What is the best method to assess the occurrence of occupational asthma? We evaluated: 1) assessment of the occurrence of occupational asthma per se, and 2) assessment of adult-onset asthma and the population attributable fractions due to specific occupational exposures. 2: What are the best methods to assess public health impact and burden to society related to occupational or work-related asthma? We evaluated methods based on assessment of excess burden of disease due to specific occupational exposures. 3: How to achieve comparable estimates for different populations? We evaluated comparability of estimates of occurrence and burden attributable to occupational asthma based on different methods. Assessment of the occurrence of occupational asthma per se can be used in countries with good coverage of the identification system for occupational asthma, i.e. countries with well-functioning occupational health services. Assessment based on adult-onset asthma and population attributable fractions due to specific occupational exposures is a good approach to estimate the occurrence of occupational asthma at the population level. For assessment of public health impact from work-related asthma we recommend assessing excess burden of disease due to specific occupational exposures, including excess incidence of asthma complemented by an assessment of disability from it. International comparability of estimates can be best achieved by methods based on population attributable fractions. Public health impact assessment for occupational asthma is central in prevention and health policy planning and could be improved by purposeful development of methods for assessing health benefits from preventive actions. Registry-based methods are suitable for evaluating time-trends of occurrence at a given population but for international comparisons they face serious limitations. Assessment of excess burden of disease due to specific occupational exposure is a useful measure, when there is valid information on population exposure and attributable fractions.


Infectious and inflammatory diseases of the orbit.
Patients presenting with orbital inflammation must be diagnosed promptly and treated aggressively. Appropriate therapy is based on the specific diagnosis and is highly effective and rewarding.


Serum and urinary carnosinase-1 correlate with kidney function and inflammation.
The carnosinase dipeptidase 1 (CNDP1) gene has been reported as a susceptibility locus for the development of diabetic kidney disease (DKD). While the (CTG)5 allele affords protection in the Caucasian population, we have previously shown that this allele is less frequently present in the Chinese population and therefore a protective role for the (CTG)5 allele is difficult to demonstrate. In the present study, we sought to assess if carnosinase-1 (CN-1) concentrations in serum and/or urine are associated with progression of DKD and to what extent CN-1 influences diabetes-associated inflammation. From a total of 622 individuals that enrolled in our study, 247 patients had type 2 diabetes without DKD, 165 patients had DKD and 210 subjects served as healthy controls. Uni- and multivariate regression analyses were performed to identify potential factors predicting urinary albumin creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and CN-1 concentration in serum and urine. The results indicated that serum CN-1 indeed correlated with eGFR (p = 0.001). In addition, urinary CN-1 associated with eGFR and tubular injury indicator: urinary cystatin C (Cys-C) and urinary retinol-binding protein (RBP). Interestingly, serum CN-1 also positively correlated with inflammatory indicators: neutrophils and lymphocytes. With regard to this, a STZ injected C57BL/6 mice model with surgically made skin wound was established for the generation of skin inflammation. This animal model further proved that the expression of CN-1 in liver and kidney increased remarkably in diabetic mice with skin wound as compared to those without. In conclusion, serum and urinary CN-1 significantly related to the surrogates of impaired renal function in diabetic patients; besides, CN-1 expression might also be associated with the process of inflammation.


How the immune response to the structural proteins of SARS-CoV-2 affects the retinal vascular endothelial cells: an immune thrombotic and/or endotheliopathy process with in silico modeling.
Thrombotic events associated with SARS-CoV-2 at the vascular endothelium still remains unclear. The aim of the current study is to determine the relationship between cellular proteins on the (ocular) vascular endothelial surface and the immune thrombotic and/or endotheliopathy process elicited by SARS-CoV-2 using an in-silico modeling. The structural S (spike glycoprotein), N (nucleocapsid protein), M (membrane protein), and E (envelope protein) proteins, an accessory protein (ORF1ab) of SARS-CoV-2 and 158 cellular proteins associated with retinal vascular endothelial cell surface or structure were included in this study for comparison of three-dimensional (3D) structure and sequence. Sixty-nine of the retinal proteins were obtained from the Uniprot database. Remaining proteins not included in the database were included in the study after they were converted into 3D structures using the RaptorX web tool. Sequence and three-dimensional structure of SARS-COV-2 S, N, M, E, ORF1ab proteins and retinal vascular endothelial proteins were compared with mTM-align server. Proteins with significant similarity (score above 0.5) were validated with the TM-align web server. Immune and thrombosis-related protein-receptor interactions of similar proteins was checked with CABS-dock. We detected a high level of structural similarity between E protein and ACE, ACE2, LAT1, and TM9SF4 endothelial proteins. In addition, PECAM-1 was found to be structurally similar to ORF1ab and S protein. When we evaluated the likelihood/potential to stimulate an immune responses/a cytokine release, TLR-2 and TLR-3, which are highly susceptible to SARS-CoV2, showed a potential receptor-protein interaction with retinal vascular endothelial proteins. Our study demonstrates that SARS-CoV-2 proteins may have structural similarities with vascular endothelial proteins, and therefore, as immunological target sites, the counterpart proteins on the endothelial surface of many organs may also be secondarily affected by any immune response against SARS-CoV-2 structural proteins.


Acute, chronic, and combined pulmonary responses to swimming in competitive swimmers.
The combined effects of swimming on the inspiratory muscles and pulmonary functions are not well known. The aim of the present study was to determine the acute, chronic, and combined effects of swimming on the pulmonary functions and respiratory muscles of competitive swimmers. Thirty males (15 in the experimental group [EG] and 15 in the control group [CG]) participated in this study. The EG subjects participated in an 8-week swim training program and performed 1 day before and after an 8-week 100-m swimming event. Pulmonary functions and respiratory muscle strength were measured immediately before and after the swimming event in the EG and before and after an 8-week period in the CG. The obtained data were analyzed using repeated measures one-way analysis of variance, least significant difference, and independent- and paired-sample t-tests. Swimming exerted negative acute effects (p < 0.05) and positive chronic effects (p < 0.05) on respiratory muscle strength and pulmonary functions. Further, the negative acute effects decreased the combined effects of the chronic and acute effects of swimming on respiratory muscle strength and pulmonary functions (p < 0.05). The results indicated that swimming exerts negative acute, positive chronic, and combined effects on respiratory muscle strength and pulmonary functions.


Gang and multiple rapes during military service: health consequences and health care.
We aimed to determine whether there were differences in women veteran's health status and use of health care services by type of rape that occurred during military service. We conducted a national cross-sectional survey of women veterans who served in Vietnam and subsequent eras and were listed in Department of Veterans Affairs comprehensive women's health care registries. We used structured telephone interviews to gather socioeconomic information, violence history, use of outpatient health care services, and health status for a random sample, stratified by region and era of service. Five hundred forty women completed the interview, 28% of whom reported being raped during military service. Nineteen percent reported a single rape, 5% reported repeated rape (range 2-36), and 5% reported gang rape. Women who reported repeated and gang rapes had significantly impaired physical and emotional health compared with women with a single or no rape (p < or = .05). Repeatedly raped women were more likely to use inpatient and outpatient mental health services (p < or = .05). Gang-rape survivors reported the most severe impairment in physical functioning and general health and demonstrated a trend to seek outpatient medical services. Simply asking a woman if she has been raped is not sufficient to detect the level of consequences. More than a decade after military discharge, women who experienced repeated or gang rape during their military service had significant impairment of physical and emotional health compared with women with no or a single rape. The differential health effects associated with severe violence supports the public health importance of sexual violence screening, treatment, and prevention.


Evolutionary genomics and biosynthetic potential of novel environmental Actinobacteria.
Actinobacteria embroil Gram-positive microbes with high guanine and cytosine contents in their DNA. They are the source of most antimicrobials of bacterial origin utilized in medicine today. Their genomes are among the richest in novel secondary metabolites with high biotechnological potential. Actinobacteria reveal complex patterns of evolution, responses, and adaptations to their environment, which are not yet well understood. We analyzed three novel plant isolates and explored their habitat adaptation, evolutionary patterns, and potential secondary metabolite production. The phylogenomically characterized isolates belonged to Actinoplanes sp. TFC3, Streptomyces sp. L06, and Embleya sp. NF3. Positively selected genes, relevant in strain evolution, encoded enzymes for stress resistance in all strains, including porphyrin, chlorophyll, and ubiquinone biosynthesis in Embleya sp. NF3. Streptomyces sp. L06 encoded for pantothenate and proteins for CoA biosynthesis with evidence of positive selection; furthermore, Actinoplanes sp. TFC3 encoded for a c-di-GMP synthetase, with adaptive mutations. Notably, the genomes harbored many genes involved in the biosynthesis of at least ten novel secondary metabolites, with many avenues for future new bioactive compound characterization-specifically, Streptomyces sp. L06 could make new ribosomally synthesized and post-translationally modified peptides, while Embleya sp. NF3 could produce new non-ribosomal peptide synthetases and ribosomally synthesized and post-translationally modified peptides. At the same time, TFC3 has particularly enriched in terpene and polyketide synthases. All the strains harbored conserved genes in response to diverse environmental stresses, plant growth promotion factors, and degradation of various carbohydrates, which supported their endophytic lifestyle and showed their capacity to colonize other niches. This study aims to provide a comprehensive estimation of the genomic features of novel Actinobacteria. It sets the groundwork for future research into experimental tests with new bioactive metabolites with potential application in medicine, biofertilizers, and plant biomass residue utilization, with potential application in medicine, as biofertilizers and in plant biomass residues utilization. KEY POINTS: • Potential of novel environmental bacteria for secondary metabolites production • Exploring the genomes of three novel endophytes isolated from a medicinal tree • Pan-genome analysis of Actinobacteria genera.


Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population.
5-Lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) are essential for cysteinyl-leukotriene (cys-LT) production, critical mediators in asthma. We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility. To assess genetic association with asthma phenotypes, we genotyped 341 Caucasian families (containing two asthmatic siblings) and non-asthmatic control subjects (n=184). Genetic association was determined by case-control and transmission disequilibrium test (TDT) analyses. To determine the functional role of polymorphisms on basal transcription, we generated ALOX5AP-promoter-luciferase constructs and transiently transfected human HeLa cells. A novel G/A substitution at -336 bp and a poly(A) repeat (n=19 or 23) at position -169 to -146 bp were identified in the ALOX5AP promoter. Genotyping found the -336 A and poly(A19) alleles at frequencies of q=0.06 and 0.12, respectively. No ALOX5AP allele was associated with asthma or asthma-related phenotypes in case-control or TDT analyses. ALOX5AP-promoter-luciferase analyses did not support a functional role of the -336 or poly(A) polymorphism in determining basal transcription. The ALOX5 Sp1 polymorphism was predominantly homozygous wild-type 5/5 (frequency q=0.70) and heterozygous 4/5 (q=0.23) genotypes and no allele was associated with asthma or asthma-related phenotypes. Taken together, these data do not support a significant role for these polymorphisms in genetic susceptibility to asthma in the Caucasian population.


Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia.
Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets.


Non-activatable mutant of inhibitor of kappa B kinase α (IKKα) exerts vascular site-specific effects on atherosclerosis in Apoe-deficient mice.
IKKα is an important regulator of gene expression. As IKKα kinase inactivity in bone marrow-derived cells does not affect atherosclerosis, we here investigate the impact of a whole body-IKKα kinase inactivity on atherosclerosis. Apolipoprotein E (Apoe)-deficient mice homozygous for an activation-resistant Ikkα-mutant (IkkαAA/AAApoe-/-) and Ikkα+/+Apoe-/- controls received a Western-type diet. Atherosclerotic lesion size and cellular content were analyzed using histology and immunofluorescence. Vascular protein expression and IKKα kinase activity were quantified by Luminex multiplex immuno-assay and ELISA. A vascular site-specific IKKα expression and kinase activation profile was revealed, with higher total IKKα protein levels in aortic root but increased IKKα phosphorylation, representing activated IKKα, in the aortic arch. This was associated with a vascular site-specific effect of IkkαAA/AA knock-in on atherosclerosis: in the aortic root, IkkαAA/AA knock-in decreased lesion size by 22.0 ± 7.7% (p < 0.01), reduced absolute lesional smooth muscle cell numbers and lowered pro-atherogenic MMP2. In contrast, IkkαAA/AA knock-in increased lesion size in the aortic arch by 43.7 ± 20.1% (p < 0.001), increased the abundance of lesional smooth muscle cells in brachiocephalic artery as main arch side branch and elevated MMP2. A similar profile was observed for MMP3. No effects were observed on necrotic core or collagen deposition in atherosclerotic lesions, nor on absolute lesional macrophage numbers. A non-activatable IKKα kinase differentially affects atherosclerosis in aortic root vs. aortic arch/brachiocephalic artery, associated with a differential vascular IKKα expression and kinase activation profile as well as with a vascular site-dependent impact on lesional smooth muscle cell accumulation and protein expression profiles.


Effectiveness of physical therapy interventions for low back pain targeting the low back only or low back plus hips: a randomized controlled trial protocol.
Recent evidence suggests that physical therapy interventions targeting the hips may improve outcomes, including pain and disability, for patients with low back pain (LBP). Currently, there is conflicting data in regard to whether an individual with LBP needs to have a concurrent hip impairment in order to respond to this approach. The purpose of this clinical trial will be to determine the short and long-term effectiveness of physical therapy interventions directed at the lumbar spine only, versus lumbar spine and hip(s), in individuals with a primary complaint of LBP with a concurrent hip impairment. A multi-center, randomized controlled trial of 76 adult individuals with a primary complaint of LBP, who also have at least one concurrent hip impairment. Participants will be randomized into the 'LBP only' or 'LBP+Hip' group. Treatment to the low back in both groups will be a pragmatic approach consisting of interventions targeting the low back without targeting the hip(s). Participants randomized to the LBP+Hip group will also receive a semi-prescriptive set of manual therapy and exercise techniques that target the hips. The primary outcome measures will be the modified Oswestry Disability Index and the Numeric Pain Rating Scale at discharge. These two treatment strategies are commonly utilized in physical therapy practice, but there is uncertainty which is superior. This trial will also help to provide a better understanding of the role of concurrent hip impairments in LBP. This trial has been prospectively registered at clinicaltrials.gov (ID# NCT03550014, https://clinicaltrials.gov/ct2/show/NCT03550014) on June 7, 2018.


2-({[(2S)-1-Hy-droxy-1,1,3-tri-phenyl-propan-2-yl]imino}-meth-yl)-4,6-bis-(4-methyl-phen-yl)phenol.
The title compound, C42H37NO2, crystallizes in the ortho-rhom-bic space group P212121 with one mol-ecule in the asymmetric unit. An intra-molecular hydrogen bond orients the phenol hydroxyl group toward the imine nitro-gen. The aliphatic alcohol is engaged in a weak intra-molecular hydrogen bond with the imine nitro-gen.


Liquid exfoliation of bulk g-C3N5 to nanosheets for improved photocatalytic antibacterial activity.
Liquid exfoliation of bulk g-C3N5 was applied to synthesize g-C3N5 nanosheets. In order to characterize the samples, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), X-ray photoelectron spectra (XPS), UV-Vis absorption spectra (UV-Vis), and photoluminescence spectra (PL) were examined. g-C3N5 nanosheets exhibited enhanced performance in the inactivation of Escherichia coli (E. coli) with visible light irradiation relative to bulk g-C3N5 and promoted complete inactivation of E. coli within 120 min. h+ and •O2- were the principal reactive species in the antibacterial process. In the early stages, SOD and CAT played a defensive role in resisting oxidative damage of active species. With the prolonged light exposure time, the antioxidant protection system was overwhelmed leading to the destruction of the cell membrane. The leakage of cell contents such as K+, protein, and DNA caused bacterial apoptosis ultimately. The enhanced photocatalytic antibacterial performance of g-C3N5 nanosheets is ascribed to the stronger redox property by the upward shift of CB and downward shift of VB compared with bulk g-C3N5. On the other hand, larger specific surface area and better separation efficiency of photoinduced carriers are helpful to the improved photocatalytic performance. This study systematically revealed the inactivation process toward E. coli and expanded the application range of g-C3N5-based materials with abundant solar energy.


Purification strategies, characteristics and thermodynamic analysis of a highly thermostable alkaline protease from a salt-tolerant alkaliphilic actinomycete, Nocardiopsis alba OK-5.
An alkaline protease from salt tolerant alkaliphilic actinomycetes, Nocardiopsis alba strain OK-5 was purified to homogeneity by 27 and 13 fold with a yield of 35 and 13% using two-steps and one-step method, respectively. The purification methods involved hydrophobic interaction on phenyl sapharose matrix. The apparent molecular mass was 20 kDa. The temperature optimum shifted from 70 to 80°C in 4M NaCl and 30% Na-glutamate, with significant stability at 60-80°C in Na-glutamate. Deactivation rate constant (K(d)) increased and half life (t(1/2)) decreased with the increasing temperatures from 37 to 80°C. The order of stability was: 30% Na-glutamate>4M NaCl>2M NaCl>0M NaCl. The enzyme was stable even at 80°C in 30% Na-glutamate with K(d) 4.11 and t(1/2) 168.64 min. The activation energies (E), enthalpy (ΔH*) and entropy (ΔS*) for protease deactivation in with Na-glutamate were 31.97 kJ/mole, 29.23 kJ/mole and -211.83 J/mole, respectively. The change in free energy (ΔG*) for protease deactivation at 60°C in 30% Na-glutamate was 101.70 kJ/mole. Protease had the highest activity and stability at pH 10-11. While the enzyme was highly resistant against chemical denaturation, it had varied responses to metal ions. Complete inhibition by PMSF confirmed serine nature of the protease. Na-glutamate, H(2)O(2), β-mercaptoethanol and different surfactants enhanced the activity.


Changes and results of surgical strategies for hepatocellular carcinoma: results of a 15-year study on 452 consecutive patients.
In an attempt to define better surgical strategies for patients with hepatocellular carcinoma (HCC), we conducted a retrospective analysis of 452 patients who underwent hepatic resection at our institute during a period of 15 years. The patients were divided into two groups: group A, comprising 188 patients who underwent hepatic resection before 1988, and group B, comprising 264 patients after 1989. These groups were compared clinicopathologically. The percentage of patients with Child's A disease but without cirrhosis, in group A was lower. The diameter of the resected tumor was larger in group A, and major hepatic resections and curative operations were more frequently performed in group A. In group B, there was less blood loss, the specimen weighed less, and the hospital mortality was lower. Although the tumor-free survival rates were similar between the two groups, the survival rate in group B was significantly better. While even minor hepatic resection accompanied by a lower rate of surgical margin-free surgery has contributed to making hepatic resection safer, it has not improved the tumor-free survival rate. Conversely, recent advances in imaging modalities used during follow-up for the early detection of recurrence and for planning multimodality treatment have contributed to increasing the survival rate.


Atrial automatic ectopic tachycardia due to an atrial tumor.
A dilated cardiomyopathy picture has been produced by rapid atrial and ventricular rates sustained for a long period of time in some patients. The ventricular tachycardias have in some instances been associated with ventricular tumors as the cause of the tachycardia. Once the tumor is removed, the tachycardia stops and the heart function improves. Atrial ectopic tachycardias also produce a similar picture, but have not been associated with atrial tumors. Such a case is presented with an atrial rhabdomyoma producing atrial ectopic tachycardia and a dilated, poorly contracting myocardium. The tumor was resected and the tachycardia was immediately abolished. Cardiac function quickly returned to normal.


Metabolic mechanisms of longevity: Caloric restriction in mammals and longevity mutations in Caenorhabditis elegans; a common pathway??
Several recent studies in Caenorhabditis elegans have reported significant extension of the lifespan by probable loss of function mutations in various genes. When sequenced, many of these genes exhibited significant homology to genes in the mammalian insulin signaling cascade. For example, the daf-2 gene that has been shown to regulate lifespan in C elegans shares significant sequence homology with the insulin and IGF-1 receptor genes in mammals. Another longevity gene in the nematode, age-1, is homologous with the p110 subunit of phosphatidylinositol 3-kinase in mammals. This enzyme functions early in the mammalian insulin response cascade to influence many important cellular growth and metabolic processes. These findings and others have led to the suggestion that lifespan regulation in nematodes is controlled by a mechanism similar to that involved in lifespan extension by caloric restriction in mammals. Many intriguing similarities exist between these two model systems providing some support for this idea. However, at present there is insufficient data to conclude that similar genes or mechanisms regulate lifespan determination in nematodes and in mammals.


Opportunities for cost reduction of medical care: part 3.
The level of health care spending in the United States and other developed nations is rising at a disturbingly rapid rate. However, in the United States, these increases are not justified by superior performance. Rather, most other wealthy countries' inhabitants live longer and suffer from fewer medical problems than the average American. This paper demonstrates the continued abundance of opportunities for substantially reducing health care costs without decreasing the quality of care. In particular, it emphasizes the need to reduce the practice of defensive medicine and to enlarge the cadre of non-specialist physicians who educate future doctors. Such cost-saving opportunities are not rare phenomena but are widely available and offer the United States opportunities to move toward the markedly lower cost levels that have been achieved in other countries.


Superconvergence of the local discontinuous Galerkin method for nonlinear convection-diffusion problems.
In this paper, we discuss the superconvergence of the local discontinuous Galerkin methods for nonlinear convection-diffusion equations. We prove that the numerical solution is [Formula: see text]th-order superconvergent to a particular projection of the exact solution, when the upwind flux and the alternating fluxes are used. The proof is valid for arbitrary nonuniform regular meshes and for piecewise polynomials of degree k ([Formula: see text]). The numerical experiments reveal that the property of superconvergence actually holds true for general fluxes.


Resource heterogeneity and patterns of movement in foraging bumblebees.
Differences in the foraging behavior of B. terricola workers on white clover, Trifolium repens, were examined on previously unvisited (filled) and depleted flowers, and as a function of flower-head density. 1. The number of florets visited per unit time was independent of flower head density from 20 to at least 290 heads/m2, in part because the bees utilized more florets per head at low flower head densities, and also because they approached but rejected more flower heads at high rather than at low flower head densities. 2. Previously visited clover-heads were approached but often rejected, while unvisited heads were not rejected. 3. The bees behaved markedly different while foraging in patches of flowers which were available to all foragers, than in those which had been screened and contained on the average 3.9 times more sugar; they tendent to move through depleted areas and to concentrate in rich areas. On successive flower-head visits in depleted areas they moved more forward than backward (82% vs. 18%), while in rich areas they tended to move almost as much backward as forward 47% vs. 53%). 4. The distances of inter-head moves were approximately twice as long in depleted as in rich areas. 5. The bees visited almost as many florets per unit time in the rich as in the depleted areas (32 vs. 35 per min). But in the rich patches they probed on the average into 11.6 florets per head in contrast to only 2.3 florets per depleted head. 6. In an experiment with B. vagans workers foraging from Aconitum napellus inflorescences, the bees did not reject previously visited flowers, and they moved upward in successive flower visits on inverted as well as on unaltered inflorescences. On horizontal inflorescences they moved both right and left. The movements are not a direct response to nectar differences, nor to differences in average nectar distributions. The systematic foraging behavior on vertical inflorescences may thus be a mechanism of reducing the revisiting of just-emptied flowers.


Quantification of denitrification potential in carbonaceous trickling filters.
Biofilm samples from a carbonaceous trickling filter (TF) were evaluated in bench scale reactors to determine their maximum potential denitrification rates. Intact, undisturbed biofilms were placed into 0.6 L bench-scale reactors filled with sterilized, primary clarifier effluent spiked with nitrate to a final concentration of 16-18 mg/L as N. Dissolved oxygen concentrations were maintained between 2 and 4 mg/L in the bulk aqueous phase. Nitrate loss from the reactors was monitored over a 5h period. Denitrification rates of 3.09-5.55 g-N/m(2)day were observed with no initial lag period. This suggests that the capacity for denitrification is inherent in the biofilm and that denitrification can take place even when oxygen is present in the bulk aqueous phase. There were no significant differences in denitrification rates per unit area of media (g-N/m(2)day) either between (a). experimental runs or (b). sampling locations over the trickling filter. This suggests that denitrification potentials are uniform over the entire volume of the full-scale TF. For wastewater treatment plants with TFs that currently nitrify downstream, this approach may be used to meet less stringent permitted discharge concentrations and may allow some facilities to postpone or eliminate construction of additional unit processes for denitrification.


Roux-en-Y choledochojejunostomy using novel magnetic compressive anastomats in canine model of obstructive jaundice.
The traditional hand-sewn Roux-en-Y choledochojejunostomy is technically complicated, and the incidence of postoperative complications has remained high. A set of novel magnetic compressive anastomats was introduced to facilitate choledochojejunostomy and improve the prognosis of patients. After ligating the common bile duct for 7 days, 16 dogs were randomly divided into two groups (n=8 per group). Anastomats were used in the study group, and the traditional hand-sewn method was used in the control group for standard Roux-en-Y choledochojejunostomy. We compared the operation time, incidence of complications, gross appearance, and pathological disparity in stoma between the two groups in 1-month and 3-month follow-up examinations. The time spent on constructing the anastomosis for the study group was significantly shortened. Although no anastomotic stenosis occurred in the two groups, the narrowing rate of biliary-enteric anastomosis was much higher in the control group. There was one case of bile leakage in the control group, whereas no bile leakage occurred in the study group. A smoother surface, an improved layer apposition, and a lower local inflammatory response were identified in the anastomosis of the study group. The structures of the novel magnetic compressive anastomats are simple, and they are time-saving, safe and efficient for performing Roux-en-Y choledochojejunostomy procedures in a canine model of obstructive jaundice.


Pediatric organ donation: what factors most influence parents' donation decisions?
To identify factors that influence parents' decisions when asked to donate a deceased child's organs. Cross-sectional design with data collection via structured telephone interviews. One organ procurement organization in the Southeastern United States. Seventy-four parents (49 donors, 25 nondonors) of donor-eligible deceased children who were previously approached by coordinators from one organ procurement organization in the southeastern United States. None. Multivariate analyses showed that organ donation was more likely when the parent was a registered organ donor (odds ratio [OR] = 1.4, confidence interval [CI] = 1.1, 2.7), the parent had favorable organ donation beliefs (OR = 5.5, CI = 2.7, 12.3), the parent was exposed to organ donation information before the child's death (OR = 2.6, CI = 1.7, 10.3), a member of the child's healthcare team first mentioned organ donation (OR = 1.4, CI = 1.2, 3.7), the requestor was perceived as sensitive to the family's needs (OR = 0.4, CI = 0.2, 0.7), the family had sufficient time to discuss donation (OR = 5.2, CI = 1.4, 11.6), and family members were in agreement about donation (OR = 2.8, CI = 1.3, 5.2). This study identifies several modifiable variables that influence the donation decision-making process for parents. Strategies to facilitate targeted organ donation education and higher consent rates are discussed.


Consequences of plant-pollinator and floral-herbivore interactions on the reproductive success of the Canary Islands endemic Canarina canariensis (Campanulaceae).
Pollination is a critical phase for plant reproduction, but ecological and evolutionary outcomes by pollinators may be counteracted by floral herbivores. These interacting assemblages may also be altered (directly or indirectly) by introduced species, especially on oceanic islands. In this study, we analyzed the effects of opportunistic nectar-feeding passerine birds and native (semi-slugs) and introduced (rats) floral herbivores on the reproductive success of Canarina canariensis. • Manual pollination experiments were conducted to determine plant breeding system and pollen limitation. We also identified floral visitors and their visitation frequencies by censuses. Bird pollination effectiveness was evaluated by selective exclosures. The intensity of floral herbivory by native vs. introduced herbivores and its effect on plant fitness was estimated in different areas within the Canary island of Tenerife. • Canarina canariensis had a very low spontaneous selfing ability and high pollen limitation, despite being self-compatible. Birds increased fruit set and the percentage of viable seeds per fruit, while florivores, the principal floral visitors, reduced them. Semi-slugs mainly consumed male reproductive organs, while rats preferred female. There was a strong within-island spatial variation in the herbivory intensity. • Opportunistic nectar-feeding birds increase the production of viable seeds in C. canariensis, but their beneficial effects are counteracted by the high incidence of floral herbivory. Because native semi-slugs damaged anthers more frequently than did introduced rats, these florivores may differ in their effects on male and female plant reproductive success.


How individuals make choices explains addiction's distinctive, non-eliminable features.
In keeping with the goals of this Special Issue, this paper poses the following questions: What are addiction's non-eliminable features and can they be explained by one or more general principles? I have added the qualifier "distinctive" to these goals, as in "distinctive non-eliminable features." The result is a highly heterogeneous list, which includes features of addiction's natural history, such as its high remission rates, its unique idioms (e.g., "kicking the habit"), and its patented interventions, such as Alcoholics Anonymous. I show that each of these distinctive features reflects how individuals make choices. In particular, they reflect the competing claims of two basic choice processes: global maximizing of the sort assumed in introductory economics textbooks and Herrnstein's matching law, which has empirical rather than theoretical roots. These are basic choice processes, which apply to all decision making, not just drugs and not just addicts. Nevertheless, they can result in addiction when one of the options has the capacity to undermine the value of competing interests and undermine global maximizing. Conversely, the analyses also show that the two basic choice processes combine so as to predict that addiction is a semi-stable state that is biased to resolve in favor of remission. These predictions are supported by the high rates of addiction, by the high rates of remission from addiction, and by the fact that remission is often unassisted or "spontaneous." The analyses fail to support the idea that pathological psychological processes lead to addiction. Rather they show that addiction emerges from the interactions of normal choice processes and the behaviorally toxic effects of drugs.


Characterization of the humoral and cellular immunity induced by a recombinant BCG vaccine for the respiratory syncytial virus in healthy adults.
The human respiratory syncytial virus (hRSV) is responsible for most respiratory tract infections in infants. Even though currently there are no approved hRSV vaccines for newborns or infants, several candidates are being developed. rBCG-N-hRSV is a vaccine candidate previously shown to be safe in a phase I clinical trial in adults (clinicaltrials.gov identifier #NCT03213405). Here, secondary immunogenicity analyses were performed on these samples. PBMCs isolated from immunized volunteers were stimulated with hRSV or mycobacterial antigens to evaluate cytokines and cytotoxic T cell-derived molecules and the expansion of memory T cell subsets. Complement C1q binding and IgG subclass composition of serum antibodies were assessed. Compared to levels detected prior to vaccination, perforin-, granzyme B-, and IFN-γ-producing PBMCs responding to stimulus increased after immunization, along with their effector memory response. N-hRSV- and mycobacterial-specific antibodies from rBCG-N-hRSV-immunized subjects bound C1q. Immunization with rBCG-N-hRSV induces cellular and humoral immune responses, supporting that rBCG-N-hRSV is immunogenic and safe in healthy individuals. https://classic.clinicaltrials.gov/ct2/show/, identifier NCT03213405.


A review on the sustainable procurement of microalgal biomass from wastewaters for the production of biofuels.
The feasibility of microalgal biomass as one of the most promising and renewable sources for the production of biofuels is being studied extensively. Microalgal biomass can be cultivated under photoautotrophic, heterotrophic, photoheterotrophic, and mixotrophic cultivation conditions. Photoautotrophic cultivation is the most common way of microalgal biomass production. Under mixotrophic cultivation, microalgae can utilize both organic carbon and CO2 simultaneously. Mixotrophic cultivation depicts higher biomass productivity as compared to photoautotrophic cultivation. It is evident from the literature that mixotrophic cultivation yields higher quantities of polyunsaturated fatty acids as compared to that photoautotrophic cultivation. In this context, for economical biomass production, the organic carbon of industrial wastewaters can be valorized for the mixotrophic cultivation of microalgae. Following the way, contaminants' load of wastewaters can be reduced while concomitantly producing highly productive microalgal biomass. This review focuses on different aspects covering the sustainable cultivation of different microalgal species in different types of wastewaters.


Graphene Coated Ti-6Al-4V Exhibits Antibacterial and Antifungal Properties Against Oral Pathogens.
This study aimed to explore the antimicrobial properties of graphene coated Ti-6Al-4V to oral pathogens. Graphene directly synthesized on Ti-6Al-4V alloy was characterized by scanning electron microscopy (SEM) and Raman spectroscopy. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, live/dead fluorescent staining and SEM were used to analyze the antimicrobial properties of graphene coated Ti-6Al-4V alloy to Porphyromonas gingivalis (P. gingivalis), Fusobacterium nucleatum (F. nucleatum), and Candida albicans (C. albicans). Reactive oxygen species (ROS) generation was monitored to reveal the antimicrobial mechanism. Graphene coated Ti-6Al-4V alloy caused a significant reduction in the presence of both bacterial and fungal pathogens as compared to uncoated Ti-6Al-4V alloy. P. gingivalis, F. nucleatum, and C. albicans on graphene coated Ti-6Al-4V alloy were less active than on uncoated Ti-6Al-4V alloy, and tended to become shrunk and deformed. Meanwhile, graphene coated Ti-6Al-4V alloy induced more generation of ROS in the pathogens than uncoated Ti-6Al-4V alloy. Graphene coated Ti-6Al-4V alloy exhibited antimicrobial properties against oral pathogens, the induction of oxidative stress might be involved in its antimicrobial mechanisms.


Marcus Gunn Jaw-Winking Synkinesis With Ipsilateral Eyelid Myokymia.
To describe a novel observation of ipsilateral eyelid myokymia in the context of Marcus Gunn jaw-winking synkinesis (MGJWS). A retrospective case series of 5 patients observed to have myokymia in the context of MGJWS in 2 tertiary hospitals in Riyadh, Saudi Arabia was conducted. Demographic profile including age and gender, and clinical features were analyzed. Five patients (3 males and 2 females) with MGJWS were noted to demonstrate the phenomenon of ipsilateral eyelid myokymia. All but 1 had right-sided MGJWS. The myokymia was seen as upper eyelid twitching in a vertical fashion along the levator palpebrae superioris muscle field of action. All subjects also had ipsilateral Monocular elevation deficiency. Ipsilateral upper eyelid myokymia is a potential feature of MGJWS. Monocular elevation seems to be a constant feature among MGJWS patients with levator muscle myokymia.Marcus Gunn jaw-winking synkinesis (MGJWS) is not well understood. Ipsilateral eyelid myokymia is a potential feature of MGJWS. This finding suggests that peripheral dysinnervation is likely to be a part of MGJWS.Supplemental Digital Content is available in the text.


[Asymptomatic electrocardiographic abnormalities during antiblastic chemotherapy].
In patients under antiblastic treatment electrocardiographic abnormalities without subjective symptomatology were observed. The genesis of these abnormalities is discussed in the light of wath is known from the literature. Periodical electrocardiographic control of patients treated with antiblastic drugs is highly recommended.


A dose-response study of the effects of alcohol on the perceptions of pain and discomfort due to electric shock in men at high familial-genetic risk for alcoholism.
Alcoholics have previously been found to be more sensitive to painful stimulation than controls, and more sensitive to the pain-reducing effects of alcohol. The present study was designed to examine these effects in men at high familial-genetic risk for alcoholism and controls. Subjects were assigned to one of four alcohol doses [0.135 (active placebo), 0.50, 0.75, or 1.00 ml 95% USP alcohol/kg body weight]. Ratings of the amount of discomfort and pain experienced during an aversive shock procedure were taken immediately post-shock, both while subjects were sober and after they had consumed one of the four alcohol doses. High risk men were found to rate the experience of the shock as more uncomfortable and painful overall than the low risk controls. Pharmacologically significant levels of alcohol were found to reduce or eliminate these group differences, suggesting that alcohol has a "normalizing" effect on pain and discomfort perceptions in high risk men. Only the higher doses of alcohol were found significantly to dampen subjects' shock rating scores. High risk males' increased sensitivity to pain and discomfort, combined with the negatively reinforcing effects of reducing these perceptions at moderate to high alcohol doses, may play a role in predisposing high risk males for the development of alcoholism.


Beneficial effects of Aucubin on restoration of rabbits with cartilage defect.
Osteochondral grafts are suitable materials for repair of articular cartilage defect and plastic and reconstructive surgery. In our study, osteochondral allografts from rabbits were preserved in vitro for 28 days, and chondrocyte death, degradation of collagen and proteoglycan, morphological alterations, and inflammatory reaction were observed in the grafts. Supplementing of Aucubin with 10 or 20 μM in the preservation solution inhibited chondrocyte death, matrix degradation, pathological alterations and inflammation in allografts preserved in vitro, compared with that preserved in standard preservation solution. In addition, after transplantation of 20 μM Aucubin-treated allografts, the osteochondral repair and regeneration of rabbits with knee joint defect were accelerated. In conclusion, Aucubin was beneficial for maintaining chondrocyte viability and normal morphology, and inhibiting inflammatory occurrence in rabbit osteochondral grafts preserved in vitro, and facilitated osteochondral repair and regeneration of rabbits with knee defect. These findings might provide novel insights for preservation of grafts for clinical articular cartilage repair and plastic surgery.


Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II.
A new fractionation procedure separates a whole-cell HeLa extract into three components required for accurate in vitro transcription. One component (Sp1) is a promoter-specific factor required for transcription of the SV40 early and late promoters, but not for transcription of other promoters we have tested. The second component (Sp2) is a general factor required for transcription of the SV40 promoters and a series of others, including the adeno-virus 2 major late promoter, the human beta-globin promoter and the avian sarcoma virus promoter. The third component is a fraction containing the endogenous RNA polymerase II. When SV40 and adenovirus templates were present simultaneously in an in vitro transcription reaction, addition of the Sp1 factor stimulated SV40 early promoter transcription 40-fold, and inhibited adenovirus major late promoter transcription by 40%. This finding suggests that Sp1 is involved in promoter selection, and is not merely a general transcription stimulatory factor.


Dupilumab-Associated Arthritis: A Dermatology-Rheumatology Perspective.
Dupilumab is an interleukin (IL)-4/13 inhibitor approved by the US FDA for multiple atopic indications. It is well-known to have favorable efficacy and safety profiles; however, emerging reports of dupilumab-associated arthritis suggest an underrecognized potential adverse effect. In this article, we summarize the literature to date to better characterize this clinical phenomenon. Arthritic symptoms were most commonly peripheral, generalized, and symmetric. Onset was generally within 4 months following initiation of dupilumab, and most patients resolved fully after a matter of weeks following discontinuation. Mechanistic insights suggest that suppression of IL-4 may lead to increased activity of IL-17, a prominent cytokine in inflammatory arthritis. We propose a treatment algorithm that stratifies patients by severity, recommending that patients with more mild disease continue dupilumab and treat through symptoms, while patients with more severe disease discontinue dupilumab and consider switching to another class (e.g., Janus kinase inhibitors). Lastly, we discuss important ongoing questions that should be addressed in future studies.


Current surgical management of the vitreous wick syndrome.
We successfully treated three consecutive cases of the vitreous wick syndrome by combining repair of the fistula with closed vitrectomy to remove vitreous gel from the anterior chamber and from the internal aspect of the fistula. In two cases, the fistula seemed to be formed by the tract of an externally tied corneoscleral suture. In two cases the external opening of the fistula was large, and we covered it by a partial-thickness, anteriorly hinged scleral flap. One patient developed an epithelial ingrowth, which was successfully treated by transscleral and transcorneal cryotherapy combined with the use of an intraocular gas bubble to provide a thermal insulating effect to enhance the cryotherapy.


Barriers to the detection and management of depression by palliative care professional carers among their patients: perspectives from professional carers and patients' family members.
Clinical depression is highly prevalent yet underdetected and poorly managed within palliative care settings. This qualitative study explored the identification, monitoring, and management of symptoms of depression in patients receiving palliative care from 2 juxtaposed perspectives that are of care providers and care recipients' family members. Examining the barriers that restrict professional carers detecting and managing depression in their patients was a central focus of the study. Focus groups were held with 18 professional carers, including 8 holding managerial positions, across 2 palliative care services, 1 regional and 1 metropolitan, which provided both inpatient and community-based care. Individual interviews were conducted with 10 family members of patients who had received or were receiving palliative care through these services. Thematic analysis of these data identified that both professional carers and family members perceived that depression is a wide-spread concern for patients receiving palliative care; however, numerous barriers were identified that affect professional carers' ability to identify depression. These included knowledge and training deficits, low self-efficacy, prioritization of physical concerns and time constraints, patient/family characteristics, and system/process issues. These themes (and related subthemes) are discussed in this article. Specialized training in depression is recommended for professional carers in order to improve their depression-related knowledge, detection skills, and self-efficacy. The ultimate goal of such training is to increase the rate of recognition of depression that in turn will lead to appropriate treatment for depressed patients.


Evaluation of TP53 Pro72Arg and MDM2 SNP285-SNP309 polymorphisms in an Italian cohort of LFS suggestive patients lacking identifiable TP53 germline mutations.
Li-Fraumeni syndrome (LFS) is a rare genetic cancer predisposition disease, partly determined by the presence of a TP53 germline mutation; lacking thereof, in presence of a typical LFS phenotype, defines a wide group of 'LFS Suggestive' patients. Alternative LFS susceptibility genes have been investigated without promising results, thus suggesting other genetic determinants involvement in cancer predisposition. Hence, this study explores the single and combined effects of cancer risk, age of onset and cancer type of three single nucleotide polymorphisms (SNPs)-TP53 Pro72Arg, MDM2 SNP285 and SNP309-already described as modifiers on TP53 mutation carriers but not properly investigated in LFS Suggestive patients. This case-control study examines 34 Italian LFS Suggestive lacking of germline TP53 mutations and 95 tumour-free subjects. A significant prevalence of homozygous MDM2 SNP309 G in the LFS Suggestive group (p < 0.0005) confirms its contribute to cancer susceptibility, also highlighted in LFS TP53 positive families. Conversely its anticipating role on tumour onset has not been confirmed, as in our results it was associated with the SNP309 T allele. A strong combined outcome with a 'dosage' effect has also been reported for TP53 P72 and MDM2 SNP309 G allele on cancer susceptibility (p < 0.0005). Whereas the MDM2 SNP285 C allele neutralizing effect on MDM2 SNP309 G variant is not evident in our population. Although it needs further evaluations, obtained results strengthen the role of MDM2 SNP309 as a genetic factor in hereditary predisposition to cancer, so improving LFS Suggestive patients management.


Adjuvant Abemaciclib Combined with Endocrine Therapy: Efficacy Results in monarchE Cohort 1.
The monarchE Cohort 1 patient population was enrolled based on high-risk clinicopathological features that can easily be identified as part of routine clinical breast cancer evaluation. Efficacy data from Cohort 1 demonstrate substantial evidence of benefit for adjuvant abemaciclib+ET in patients with HR+, HER2- early breast cancer at high risk of recurrence (ClinicalTrials.gov: NCT03155997 [monarchE]).


Perioperative management of patient with chronic obstructive pulmonary disease.
There have been many changes in the prevention and therapy of postoperative pulmonary complications in the patient with COPD. Attention to patient analgesia and maintaining lung volumes are the keys to prevention. Recent advances in the therapy of bronchospasm are decreasing side effects and increasing success.


On the relationship between side of onset and cognition in Parkinson disease.
We read with interest the article of Pellicano et al. who evaluated whether the side of onset of Parkinson disease (PD) influences cognitive and neuropsychiatric symptoms in a cohort of early, untreated patients. They results are commented on and put into the context of previously published research.


Microcomputer-based low-cost method for measurement of spatial and temporal parameters of gait.
The instantaneous velocity of the forward-going foot is measured throughout the swing phase during several successive gait cycles using punched paper tapes attached to the feet. The velocity profiles thus obtained show clearly any asymmetry or departure from the normal walking pattern. The data are processed to provide the spatial and temporal parameters of gait, i.e. step lengths, stride times, double-support times, cadence and walking speed. The equipment is low-cost, easy to set up and use, and the results, which are presented on the VDU or as hard copy, are readily interpreted and related to the underlying pathology.


Studies on the in vitro effects of auto-anti-IgE. Inhibition of total and specific serum IgE detection by a human IgG autoantibody to IgE.
We isolated a human IgG anti IgE autoantibody by affinity chromatography on a myelomatous IgE (N.D.) coated Sepharose column, from the serum of a patient with atopic eczema, and probed its ability to inhibit IgE recognition by heteroantisera to IgE used in commonly available assays for serum total and specific IgE determinations (Paper radio-immunosorbent test--PRIST and Phadezym radioallergosorbent test--RAST, both from Pharmacia, Uppsala--Sweden). Our results indicate that IgG anti IgE decrease total IgE results by 10-90% according to its weight ratio to IgE molecules present in samples devoid of endogeneous anti-IgE. Sera with high content of specific IgE to house dust mite (RAST class 3 or 4) are less affected by this autoantibody, but RAST class 2 may be significantly lowered when purified IgG anti IgE is added. These data imply that anti IgE can affect both total and specific IgE determinations.


Techniques of measurement of body composition. Part I.
The measurement of lean body and fat mass has developed with the increase in sports participation and the prescription of exercise. Quantification of body fat is also related to the treatment of obesity and to assess nutritional status. Different levels of evaluation have been proposed depending on expertise and need. Body density estimation from skinfold measurements has the advantage of simplicity, low cost and reasonable validity with predictions to within 3 to 4% for 70% of the population. The choice of prediction equation will depend on whether a generalised equation or a population-specific equation is appropriate. In all cases tester reliability and standard error of estimation should be established. There is strong evidence that a quadratic equation should be applied and that measures of the lower limb should be included with circumference and diameter measures to strengthen the prediction. Methodological errors need to be reduced by careful training of experimenters. Crossvalidation of regression equation will strengthen their validity, particularly when fat loss is to be quantified. The popularity of skinfold assessment of body fat is enhanced by the use of nomograms to predict body fat, although some accuracy will be lost. Skinfold estimation of body fat will continue to be a useful guide to adiposity for epidemiological studies and for popular usage. The hydrostatic weighing procedure to estimate body density is considered by many to be the criterion method. Under carefully controlled conditions with maximum subject compliance, it is highly reliable, particularly if residual volume can be determined accurately. The conversion of body density to percentage body fat is based on a number of assumptions which need to be considered with respect to the population being studied. Simple methods for adiposity include various weight for height indices, for example, the body mass index of weight (kg) divided by height2 (m) which is often used to define obesity, frame size for the prediction of ideal weight and visual estimation for predicting body fat. Differences in the literature concerning fat cell size and number have their origins in variations of methodology. The choice of site for removal of tissue will influence the size of adipocytes, those obtained from deep sites are generally smaller than subcutaneous fat cells. If total cell number is determined from cell size, there will also be variability of cell number. The correlation between different methods of sizing cells is high for most techniques, but as the validity of the criterion method is not based on statistical evidence, the validity of the other methods cannot be readily accepted.(ABSTRACT TRUNCATED AT 400 WORDS)


Voluntary hyperventilation: the influence of duration and depth on the development of symptoms.
Hyperventilation is considered an important factor in the development of somatic symptoms or even panic attacks, though its role has recently been disputed. Arguments are often based on findings from the so-called Hyperventilation Provocation Test (HVPT), which is a procedure consisting of voluntarily overbreathing. The HVPT has been widely used for diagnosing Hyperventilation Syndrome and for experimentally eliciting panic attacks. Almost no attention, however, has been paid to standardizing the test and determining critical values with respect to depth and duration of hyperventilation. In the present study, symptom development was examined in 16 healthy subjects who underwent four HVPTs that differed in depth of hyperventilation (end-tidal PCO2 < 2.4 kPa or < 1.9 kPa), as well as duration of hyperventilation (2 or 5 min). Both depth and duration appeared to have an independent effect on the development of symptoms. In the 5-min condition, symptoms appeared mainly within the first 3 min. To be sure that the HVPT is long enough and deep enough to elicit symptoms in most people, a minimum duration of 3 min is advised, with end-tidal PCO2 decreasing to at least 1.9 kPa or dropping well over 50% of baseline.


De novo trisomy 20p characterized by array comparative genomic hybridization: report of a novel case and review of the literature.
We report on a boy with speech delay, mental retardation, motor clumsiness, hyperactivity, dysmorphic facial features, brachytelephalangy and short stature. Electrocardiogram, echocardiography, renal ultrasound, electroencephalogram, fundoscopic exam and auditory brainstem responses were all normal. Brain magnetic resonance imaging showed a left temporal arachnoid cyst and a small pineal gland cyst. High resolution karyotype and FISH analysis detected a de novo duplication of the short arm of chromosome 20. A molecular characterization of the chromosomal anomaly was performed by array-CGH, confirming a 17.98 Mb duplication of the short arm of chromosome 20 associated with a small duplication on chromosome 3p, that was shown to be maternally inherited. This is one of the few cases of de novo trisomy 20p with extensive workup, characterization at molecular level and close follow-up from the neonatal period to age 30 months. We also compared the phenotype of our patient with that previously reported in literature, therefore contributing to better define the trisomy 20p syndrome and helping pediatricians and geneticists to better counsel families about the developmental prognosis of these children.


Azlocillin, cephalothin, and tobramycin therapy in febrile solid tumor patients with chemotherapy-induced leukopenia.
Although the semisynthetic broad-spectrum acylureido-penicillin, azlocillin has been demonstrated to have significant antibiotic activity in leukemic patients, its role in combination therapy of febrile granulocytopenic patients with chemotherapy-treated solid tumors has not been clearly delineated. Thirty-five solid tumor patients with chemotherapy-induced absolute granulocytopenia (less than 1000 granulocytes/ml) associated with fever (greater than 38.3 degrees C) were treated on a prospective study with a combination of azlocillin 4 g intravenously (IV) every 6 hours, cephalothin 2 g IV every 6 hours, and tobramycin 80 to 100 mg IV every 8 to 12 hours. Prior chemotherapy included doxorubicin combinations in 18 patients and other combinations in 17 patients. Granulocyte counts preantibiotic therapy were greater than 100 granulocyte/ml in 14 patients, 100 to 499 in nine patients, and 500 to 1000 in 12 patients. Granulocyte nadirs were less than 100 in 20 patients, 100 to 499 in nine patients, and 500 to 1000 in six patients. Times for granulocytes to rise towards normal were 1 to 3 days in eight patients, 4 to 6 days in 18 patients, and 7 or more days in nine patients. Tobramycin levels were primarily in the peak range of 3 to 6 micrograms/ml and trough range of 0 to 1.9 micrograms/ml. The site and pathogen were identified in nine patients, the infection site clinically documented without isolated pathogen in three patients, and no site or pathogen identified in 23 patients. Of the 35 patients, 34 had good responses to the antibiotic combination (complete disappearance of fever and other evidence of infection). Serum creatinine rose 0.4 to 0.6 mg/dl in nine patients, 0.7 to 1.5 in four patients, and 1.5 in one patient (obstructive uropathy). The only other noted antibiotic-related side effect was hypokalemia. This antibiotic combination had little toxicity with marked efficacy.


Evidence Accumulation and Neural Correlates of Uncertainty in Obsessive-Compulsive Disorder.
Decision making is frequently associated with risk taking under uncertainty. Elevated intolerance of uncertainty is suggested to be a critical feature of obsessive-compulsive disorder (OCD). However, impairments of latent constructs of uncertainty processing and its neural correlates remain unclear in OCD. In 83 participants (24 OCD patients treated with capsulotomy, 28 OCD control participants, and 31 healthy control participants), we performed magnetic resonance imaging using a card gambling task in which participants made decisions whether to bet or not that the next card would be larger than the current one. A hierarchical drift diffusion model was used to dissociate speed and amount of evidence accumulated before a decisional threshold (i.e., betting or no betting) was reached. High uncertainty was characterized by a smaller amount of evidence accumulation (lower thresholds), thus dissociating uncertainty from conflict tasks and highlighting the specificity of this task to test value-based uncertainty. OCD patients exhibited greater caution with poor performance and greater evidence accumulation overall along with slower speed of accumulation, particularly under low uncertainty. Bilateral dorsal anterior cingulate and anterior insula distinguished high- and low-uncertainty decision processes in healthy control participants but not in the OCD groups, indicating impairments in anticipation of differences in outcome variance and salience network activity. There were no behavioral or imaging differences relating to capsulotomy despite improvements in OCD symptoms. Our findings highlight greater impairments particularly in more certain trials in the OCD groups along with impaired neural differentiation of high and low uncertainty and suggest uncertainty processing as a trait cognitive endophenotype rather than a state-specific factor.


Modeling the infrared cascade spectra of small PAHs: the 11.2 μm band.
The profile of the 11.2 μm feature of the infrared (IR) cascade emission spectra of polycyclic aromatic hydrocarbon (PAH) molecules is investigated using a vibrational anharmonic method. Several factors are found to affect the profile including: the energy of the initially absorbed ultraviolet (UV) photon, the density of vibrational states, the anharmonic nature of the vibrational modes, the relative intensities of the vibrational modes, the rotational temperature of the molecule, and blending with nearby features. Each of these factors is explored independently and influence either the red or blue wing of the 11.2 μm feature. The majority impact solely the red wing, with the only factor altering the blue wing being the rotational temperature.


Reduction of neutral gene flow due to the partial sterility of heterozygotes for a linked chromosome mutation.
The effect of linkage between a chromosome mutation producing partially sterile heterozygotes and a neutral locus in reducing the gene flow at the neutral locus is studied using a two-population deterministic model. Chromosome mutations are more efficient in reducing gene flow with low migration rates than with high ones. The interaction between high values of partial heterozygote sterility and low recombination rates can produce, in the low migration pattern, a drastic reduction of gene flow. Nevertheless, since only chromosome mutations with low values of partial heterozygote sterility are likely to be involved in chromosomal speciation, a significant reduction of gene flow will probably occur only for a very limited part of the genome. Therefore, a single chromosome mutation is unlikely to play a primary role in speciation.


Anatomic landmarks of the buccal branches of the facial nerve.
The aim of this study was to classify the buccal branches of the facial nerve in relation to the parotid duct and its relevance to surgical procedures such as rhytidectomy and parotid gland surgery. In this study, 30 cadaver heads (60 specimens) were dissected. The vertical and horizontal relationships between the buccal branches of the facial nerve and tragus, and parotid duct were recorded and analyzed. The buccal branches of the facial nerve were classified into four types: Type I: a single buccal branch of the facial nerve at the point of emergence from the parotid gland and inferior to the parotid duct. Type II: a single buccal branch of the facial nerve at the point of emergence from the parotid gland and superior to the parotid duct. Type III: buccal and other branches of the facial nerve formed a plexus. Type IV: two branches of buccal branch; one superior and one inferior to the duct at the point of emergence from the parotid gland. The buccal branches of the facial nerve are very vulnerable to surgical injury because of its location in the midface. For this reason, the surgeons who are willing to operate on this area should have a true knowledge about the anatomy of these branches.


Do you 'see' what I 'see'? Differentiation of visual action words.
Dickinson and Szeligo (Can J Exp Psychol 62(4):211-222, 2008) found that processing time for simple visual stimuli was affected by the visual action participants had been instructed to perform on these stimuli (e.g., see, distinguish). It was concluded that these effects reflected the differences in the durations of these various visual actions, and the results were compared to participants' subjective ratings of word meaning but it was also possible that word characteristics like length might have influenced response times. The present study takes advantage of word length differences between French and English visual action words in order to address this issue. The goals of the present study were to provide evidence that (1) the processing time differences previously found were due to differences in the cognitive actions represented by these words (and not due to characteristics to the words themselves), and (2) that individuals subjectively differentiate visual action words in such a way that allows for predictable differences in behaviour. Participants differentiated 14 French visual action words along two dimensions. Four of these words were then used in the instructions for a size-discrimination task. Processing time depended on the visual action word in the instruction to the task and differed in a predictable manner according to word meaning but not word length.


Modulation of the catalytic activity of neutrophil collagenase MMP-8 on bovine collagen I. Role of the activation cleavage and of the hemopexin-like domain.
The cleavage of bovine collagen I by neutrophil collagenase MMP-8 has been followed at pH 7.4, 37 degrees C. The behavior of the whole enzyme molecule (whMMP-8), displaying both the catalytic domain and the hemopexin-like domain, has been compared under the same experimental conditions with that of the catalytic domain only. The main observation is that whMMP-8 cleaves bovine collagen I only at a single specific site, as already reported by many others (Mallya, S. K., Mookhtiar, K. A., Gao, Y., Brew, K., Dioszegi, M., Birkedal-Hansen, H., and van Wart, H. E. (1990) Biochemistry 29, 10628-10634; Knäuper, V., Osthues, A., DeClerk, Y. A., Langley, K. A., Bläser, J., and Tschesche, H. (1993) Biochem. J. 291, 847-854; Marini, S., Fasciglione, G. F., De Sanctis, G., D'Alessio, S., Politi, V., and Coletta, M. (2000) J. Biol. Chem. 275, 18657-18663), whereas the catalytic domain lacks this specificity and cleaves the collagen molecule at multiple sites. Furthermore, a meaningful difference is observed for the cleavage features displayed by two forms of the catalytic domain, which differ for the N terminus resulting from the activation process (i.e. the former Met(80) of the proenzyme (MetMMP-8) and the former Phe(79) of the proenzyme (PheMMP-8)). Thus, the PheMMP-8 species is characterized by a much faster k(cat)/K(m), fully attributable to a lower K(m), suggesting that the conformation of the catalytic domain, induced by the insertion of this N-terminal residue in a specific pocket (Reinemer, P., Grams, F., Huber, R., Kleine, T., Schnierer, S., Piper, M., Tschesche, H., and Bode, W. (1994) FEBS Lett. 338, 227-233), brings about a better, although less discriminatory, recognition process of cleavage site(s) on bovine collagen I.


Factors associated with physical activity of patients with osteoarthritis of the lower limb.
In patients with osteoarthritis (OA), moderate physical activity (PA) can reduce the progress of joint damage. PA is therefore an important target of in the non-surgical treatment of OA. To know about factors associated with PA can increase the success of interventions aiming at increasing PA. The aim of the study was to determine predictors of PA in patients suffering from OA to the hip or to the knee. In total, 1250 outpatients from 75 general practices were consecutively approached, 1021 returned questionnaires containing sociodemographic data, and short forms of the International Physical Activity Questionnaire (IPAQ), the Arthritis Impact Measurement Scale and the Patient Health Questionnaire to assess concomitant depression. A hierarchical stepwise multiple linear regression analysis with the IPAQ continuous score as dependent variable was performed. Comparison of our findings with General population suggests that the overall PA of OA patients is decreased. Main predictors of PA were physical limitation to the lower body (beta = -0.179; P = 0.001), social contacts (P = -0.134; P < 0.001), pain (beta =-0.120; P = 0.001), age (beta = -0.110; P = 0.004) and the body mass index (beta =-0.043; P < 0.001). The findings emphasize the influence of physical as well as psychosocial factors on PA of patients with OA and should help to tailor future interventions more appropriately. Further research is needed to determine if these tailored interventions will result in better compliance and in increased PA.


General and anomalous sperm disappearance characteristics found in a large vasectomy series.
There is no accepted standard for the time after vasectomy before infertility is achieved. To help address this question, the records of 5,233 vasectomy patients who had had at least 12 ejaculations and had completed semen tests were reviewed. Seventy-five percent were able to fulfill a designated criterion for success by 4 months postoperatively, nearly 90% by 6 months, and nearly 99% by 1 year. Also found were a number of individual anomalies, including five instances of transient reappearance of sperm, four late spontaneous reversals after proof of success, and one late "delayed success" after evidence of failure. Patients can be reassured by the overall efficacy of male sterilization, but physicians also may wish to be aware of the possibility of capriciously intermittent-fitful-sperm.


Neonatal resuscitation: toward improved performance.
As part of a continuous quality assurance process which we instituted in 1999, we review videotapes of selected high-risk deliveries at our hospital. We utilized our reviews to evaluate the occurrence of errors, and to evaluate team and leader functions during neonatal resuscitation. We established accepted behavior for members of resuscitation teams and the team leader. The actual conduct of the resuscitation was judged against the standard of the guidelines of the Neonatal Resuscitations Program of the American Heart Association, and the American Academy of Pediatrics. The videotapes of resuscitations were reviewed, and significant deviations from accepted practices were noted, and discussed by a specifically developed quality assurance committee, including, whenever possible, the actual resuscitators. We were able to detect a number of problems, which included inappropriate leader and team member activities, inappropriate preparation, communication, and coordination, and made a number of changes to our practice. We believe that neonatal resuscitation may be improved by the provision of teaching about team and leader functions, encouraging debriefing following complicated resuscitations, developing a minimal form to be completed for any patient requiring compressions or epinephrine within the delivery room, and providing more direct observations regarding the actual conduct of resuscitation.


Novel nonsense IL-12Rβ1 mutation associated with recurrent tuberculosis.
The interleukin (IL)-12/interferon(IFN)γ axis plays an important role in the control of mycobacterial diseases as demonstrated by the increased susceptibility to mycobacterial species in patients with an inborn error of the IL-12-dependent IFNγ immunity. Here, we report a novel mutation in the IL-12Rβ1 gene in a female Pakistani patient who was born in a consanguineous marriage and developed severe bacille Calmette-Guérin (BCG) infection and recurrent tuberculosis. After reviewing the patient's clinical records, she was investigated for IL-12/IFNγ defects using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and DNA genetic Sanger sequencing. Quantification of secretory cytokines from the patient's peripheral blood mononuclear cells (PBMCs) revealed significantly reduced IFNγ production. Flow cytometric analysis revealed no surface expression of IL-12Rβ1 on PHA-activated T lymphocytes. In addition, IL-12-induced impaired STAT4 phosphorylation in the patient's lymphocytes when compared with those from five healthy controls. The genetic analysis of IL-12Rβ1 gene identified a novel nonsense mutation c.199G>T/p.E67* within exon 3, which encodes part of the cytokine-binding region (CBR). In silico analysis indicates that this novel nonsense mutation generates a truncated protein with an apparent inactivating effect. Our data expand the genetic spectrum of IL-12Rβ1 deficiency. Moreover, our findings highlight the need for developing newborn screening for patients with primary immunodeficiency associated with mycobacterial infections in areas where BCG vaccination is mandatory in order to improve the treatment of patients, and consequently their quality of life.


An improved microscopic traffic model for heterogeneous vehicles using the vehicle's mass effect.
This study aims to develop a traffic model for heterogeneous vehicle movement, which introduces the vehicle's heterogeneity by considering the internal mass effect. We explore the behavioral characteristics of the flow field generated by the proposed model and provide a comparative analysis of the conventional model. A linear stability condition is deduced to showcase the model's capacity to neutralize flow. Nonlinear analysis is employed to derive the modified Korteweg-de Vries (mKdV) equation and its corresponding analytical solution, enabling the observation of traffic flow behavior in proximity to the neutral stability condition. A numerical simulation is then conducted, considering cyclic boundary conditions. The results indicate that the mass effect tends to absorb traffic jams provided no time delay is imposed.


Detection of Leishmania infantum DNA in Pintomyia evansi and Lutzomyia longipalpis in Honduras.
The two most abundant sand fly species on the Honduran Pacific coast are Lutzomyia (Lutzomyia) longipalpis and Pintomyia (Pifanomyia) evansi. Both species are known vectors of Leishmania (Leishmania) infantum, the etiological agent of visceral leishmaniasis (VL) in the Americas. Although VL and non-ulcerative cutaneous leishmaniasis (NUCL) are endemic on the Pacific versant of the Central American Pacific, the latter is the most frequent manifestation of leishmaniasis there. We evaluated the circulation of Leishmania spp. in the sand fly species on El Tigre Island, an endemic area of NUCL. We collected 222 specimens of six sand fly species. Lu. longipalpis (180 specimens; 81%) and Pif. (Pi.) evansi (35 specimens; 16%) were the most abundant species. L. (L.) infantum DNA was detected in nine of the 96 specimens analyzed; seven of these specimens were identified as Lu. longipalpis, and the remaining two were Pi. evansi, with an infection rate of 9.4% and 2.7%, respectively. We present the first record of L. (L.) infantum DNA in Pi. evansi from a NUCL endemic region of Central America. Our results suggest that Pi. evansi could be a secondary vector of L. (L.) infantum in the transmission cycle of leishmaniasis. The detection of natural infections of L. (L.) infantum in sand flies in this region contributes to an understanding of the epidemiology of leishmaniasis in Honduras.


Micromagnetic simulation of exchange coupled ferri-/ferromagnetic heterostructures.
Exchange coupled ferri-/ferromagnetic heterostructures are a possible material composition for future magnetic storage and sensor applications. In order to understand the driving mechanisms in the demagnetization process, we perform micromagnetic simulations by employing the Landau-Lifshitz-Gilbert equation. The magnetization reversal is dominated by pinning events within the amorphous ferrimagnetic layer and at the interface between the ferrimagnetic and the ferromagnetic layer. The shape of the computed magnetization reversal loop corresponds well with experimental data, if a spatial variation of the exchange coupling across the ferri-/ferromagnetic interface is assumed.


STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia.
Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type I IFN is not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival of leukemia-bearing animals is not diminished in the absence of type I IFN signaling, suggesting that STING may not be triggered by AML. However, the STING agonist, DMXAA, induces expression of IFN-β and other inflammatory cytokines, promotes dendritic cell (DC) maturation, and results in the striking expansion of leukemia-specific T cells. Systemic DMXAA administration significantly extends survival in two AML models. The therapeutic effect of DMXAA is only partially dependent on host type I IFN signaling, suggesting that other cytokines are important. A synthetic cyclic dinucleotide that also activates human STING provided a similar anti-leukemic effect. These data demonstrate that STING is a promising immunotherapeutic target in AML.


Effect of sulfur application on sulfur-oxidizing bacteria and yield of two leguminous crops.
The effect of elemental sulfur application at the rate of 50, 100, 200, and 400 kg/feddan on broad-bean and lentil was tested in field experiments. Sulfur application resulted in increasing the numbers of the autotrophic sulfur-oxidizing bacteria as well as in the concentration of available sulfate in the soil; the increases were proportional to the level of sulfur added. The sulfur treatments neither affected the soil pH nor the nodulation of the leguminous plants tested. The application of sulfur at the rates used slightly increased seed yield and nitrogen content of lentil seeds, but had no effect on broadbean.


Validation of the Swedish Diabetes Re-Grouping Scheme in Adult-Onset Diabetes in China.
This study applied the Swedish novel data-driven classification in Chinese newly diagnosed diabetic patients and validated its adoptability. This study aimed to validate the practicality of the Swedish diabetes regrouping scheme in Chinese adults with newly diagnosed diabetes. Patients were classified into 5 subgroups by K-means and Two-Step methods according to 6 clinical parameters. Ambulatory care. A cross-sectional survey of 15 772 patients with adult-onset newly diagnosed diabetes was conducted in China from April 2015 to October 2017. None. Six parameters including glutamate decarboxylase antibodies (GADA), age of onset, body mass index (BMI), glycated hemoglobin A1c (HbA1c), homoeostatic model assessment 2 estimates of β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR) were measured to calculate the patient subgroups. Our patients clustered into 5 subgroups: 6.2% were in the severe autoimmune diabetes (SAID) subgroup, 24.8% were in the severe insulin-deficient diabetes (SIDD) subgroup, 16.6% were in the severe insulin-resistance diabetes (SIRD) subgroup, 21.6% were in the mild obesity-related diabetes (MOD) subgroup and 30.9% were in the mild age-related diabetes (MARD) subgroup. When compared with the Swedish population, the proportion of SIDD subgroup was higher. In general, Chinese patients had younger age, lower BMI, higher HbA1c, lower HOMA2-B and HOMA2-IR, and higher insulin use but lower metformin usage than the Swedish patients. The Swedish diabetes regrouping scheme is applicable to adult-onset diabetes in China, with a high proportion of patients with the severe insulin deficient diabetes. Further validations of long-term diabetes complications remain warranted in future studies.


Association between use of antihypertensive drugs and the risk of cancer: a population-based cohort study in Shanghai.
Previously studies shown a potential risk of antihypertensive medicines in relation to cancer susceptibility, which creating significant debate in the scientific community and public concern. We sought to investigate the relationship between antihypertensive medicines and cancer risk, by drug type and class. We conducted a population-based cohort study and enrolled patients diagnosed with hypertension from community healthcare centers in Changning District, Shanghai, China. Antihypertensive drug administration were classified as five common antihypertensive drugs. The main outcomes were incidence of total cancer and by major cancer type. Between January 2013 and December 2017, a total of 101,370 hypertensive patients were enrolled in this cohort. During a mean follow-up of 5.1 (SD 1.3) years, 4970 cancer cases were newly diagnosed in the cohort. CCBs were the most frequently used antihypertensives which were associated with a moderately increased risk of total cancer (hazard ratio, HR = 1.11, 95% CI: 1.05-1.18). The second commonly used drug ARBs were also associated with increased risk of total cancer (HR = 1.10, 95%CI: 1.03-1.17) as well as lung and thyroid cancers (HR = 1.21, 95%CI: 1.05-1.39; HR = 1.62 95%CI: 1.18-2.21, respectively). No significant association was found between cancer and other antihypertensives. Hypertensive patients who use more than one class of antihypertensives drugs had a higher risk of total cancer (HR: 1.22, 95%CI: 1.10-1.35 for two classes; HR: 1.22, 95%CI: 1.03-1.45 for three or more classes), and a possible dose-response relationship was suggested (P for trend < 0.001). The risk of thyroid cancer was higher in hypertensive patients prescribed with three or more antihypertensive classes. Use of ARBs or CCBs may be associated with an increased risk of total cancer. Taking more than one class of antihypertensives drugs appeared to have a higher risk for total cancer.


Clinical and radiological efficacy of spino-pelvic fixation in the treatment of neuromuscular scoliosis.
Pelvic fixation is performed to obtain proper coronal and sagittal alignment when the pelvic obliquity is more than 15º in patients with neuromuscular scoliosis (NMS). Since many NMS patients were wheelchair or bed-ridden status, there has been controversy on the effect of pelvic fixation. Therefore, the purpose of this study is to analyze the effects of pelvic fixation on correction of spinal deformity and quality of life (QoL) in NMS patients. A total of 77 NMS patients who underwent deformity correction were divided into three groups and retrospectively analyzed preoperatively, postoperatively, and at 2-year follow-up: pelvic fixation group (Group A, n = 16), fixed to S1 (Group B, n = 33), and fixed to L5 (Group C, n = 28). The correction rate of scoliosis was 60.0%, 58.0%, and 56.7% in groups A, B, and C, respectively, with no statistical difference (P > 0.05). The correction rate of pelvic obliquity was 61.3%, 42.8%, and 57.5% in respective groups A, B, and C, with no significance (P > 0.05). The correction loss of scoliosis and pelvic obliquity showed no statistical significance between three groups for 2-year follow-up (all Ps > 0.05). There were no significant differences regarding clinical outcomes and postoperative complications among the three groups (all Ps > 0.05). Therefore, pelvic fixation using iliac screws is not substantially influencing radiological and clinical outcomes in the patients with NMS.