Women's anxiety about social and exercise settings.
This study involved a comparison of social physique anxiety, assessed through the application of a modified version of the Social Physique Anxiety Scale, with 28 women who were new members exercising at all-female facilities compared to 43 new female members exercising at coeducational facilities. Analyses indicated there were no significant differences in means between the groups. The scores of women attending all-female facilities were significantly more influenced by the sex of members when choosing a facility.


Work reinforcers and explanatory style for women aged 40 to 75 years.
We examined the relationship between explanatory style and work reinforcers, that is, specific sources in the work environment that appear to promote job satisfaction. Our subjects were 135 employed women aged 40 to 75 years who were asked to complete the Attributional Style Questionnaire (Peterson et al., 1982) and the Minnesota Satisfaction Questionnaire (Weiss, Dawis, England, & Lofquist, 1967). Using Pearson's product-moment correlational analysis, weak but significant relationships were found between explanatory style and the work reinforcers of ability utilization, activity, and creativity. Individuals with a depressive explanatory style experienced less job satisfaction in areas related to these reinforcers.


Atypical corneal dystrophy with stromal amyloid deposits.
Corneal dystrophies are distinctive clinically and histopathologically; however, variations do occur. We present two cases of stromal amyloidosis from one family masquerading other corneal dystrophy. The two cases are from a six-generation family with an autosomal dominant corneal dystrophy resembling Reis-Bucklers' dystrophy. In these cases, neither the propositus nor other family members showed typical lattice lines. Light and electron microscopy of the obtained corneal buttons disclosed amyloid stromal deposits. The clinicopathologic correlation of these cases suggests that this family represents a variant of stromal amyloid dystrophies.


Dendritic cells and the assessment in vitro of skin sensitizing potential.
It is now well established that dendritic cells (DC) play pivotal roles in the initiation and orchestration of adaptive immune responses, including cutaneous immune responses to chemical allergens that drive the acquisition of skin sensitization. It is not unexpected, therefore, that a large number, and wide variety, of proposed approaches for the identification of skin sensitizing chemicals in vitro are based upon the use of cultured DC or DC-like cells. The use of DC in this context is legitimate. However, with our rapidly increasing understanding of the diversity of cutaneous DC with respect to both phenotype and function, it is timely now to review briefly the potential limitations and interpretive difficulties that are associated with the use of DC-based assays. Among the important considerations are the fact that chemical-induced changes in the characteristics and function of cultured DC will not necessarily reflect accurately the events that that support the development of skin sensitization in vivo. In addition, most DC-based assays are predicated on a view that cutaneous DC have as their primary function the initiation of adaptive immune responses. However, it is now appreciated that cutaneous DC, and in particular epidermal Langerhans cells (LC), may also play important immunoregulatory roles that serve to limit and contain skin immune responses. Notwithstanding these considerations there is reason to believe that at least some in vitro DC-based assays are of value, and indeed some are currently the subject of a formal validation process. However, it is appropriate that such assays are configured and interpreted carefully, and with an appreciation of the complexity of DC biology.


van der Waals Heteroepitaxy of Germanene Islands on Graphite.
We fabricated flat, two-dimensional germanium sheets showing a honeycomb lattice that matches that of germanene by depositing submonolayers of Ge on graphite at room temperature and subsequent annealing to 350 °C. Scanning tunneling microscopy shows that the germanene islands have a small buckling with no atomic reconstruction and does not give any hints for alloy formation and hybridization with the substrate. Our density functional theory calculations of the structural properties agree well with our experimental findings and indicate that the germanene sheet interacts only weakly with the substrate underneath. Our band structure calculations confirm that the Dirac cone of free-standing germanene is preserved for layers supported on graphite. The germanene islands show a small but characteristic charge transfer with the graphite substrate which is predicted by our ab initio simulations in excellent agreement with scanning tunneling spectroscopy measurements.


A multicenter, randomized, double-blind, placebo-controlled, 8-week trial of the efficacy and tolerability of once-daily losartan 100 mg/hydrochlorothiazide 25 mg and losartan 50 mg/hydrochlorothiazide 12.5 mg in the treatment of moderate-to-severe essential hypertension.
Many patients with moderate-to-severe hypertension require multiple drug therapy to achieve blood-pressure goals. Fixed-dose combination therapy with losartan and hydrochlorothiazide may be useful in this population. This study was conducted to obtain additional data on the antihypertensive efficacy and tolerability of once-daily, fixed-dose combinations of losartan and hydrochlorothiazide. This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled trial. Patients > or = 21 years of age with moderate-to-severe essential hypertension, defined as a mean trough sitting diastolic blood pressure (SiDBP) of 105 to 115 mm Hg, were randomly assigned in a 2:2:1 ratio to receive losartan 100 mg/hydrochlorothiazide 25 mg (L100/25), losartan 50 mg/hydrochlorothiazide 12.5 mg (L50/12.5), or placebo (PBO) once daily for 8 weeks. The primary efficacy measurement was the mean change from baseline in trough SiDBP in the L100/25 versus L50/12.5 treatment groups. Responders were defined as patients with mean trough SiDBP <90 mm Hg or a > or = 10-mm Hg decrease in mean trough SiDBP. A total of 446 patients were randomly assigned to receive L100/25 (n = 173), L50/12.5 (n = 184), or PBO (n = 89). At week 8, mean trough SiDBP was significantly lower than at baseline in the L100/25 (-17.5 mm Hg), L50/12.5 (-15.2 mm Hg), and PBO groups (-8.5 mm Hg) (all P < 0.001). The difference between the active-treatment groups was statistically significant (-2.2 mm Hg; 95% Cl, range -3.8 to -0.6) (P = 0.006), as was the difference between the L100/25 and PBO groups (-9.0 mm Hg; 95% CI, range -I1.0 to -7.0) (P < 0.001) and the L50/12.5 and PBO groups (-6.7 mm Hg; 95% CI, range -8.7 to -4.8) (P < 0.001). At week 8, the percentages of responders were 86.7% (144 of 166), 78.9% (142 of 180), and 50.0% (42 of 84) in the L100/25, L50/12.5, and PBO groups, respectively. The incidence of adverse experiences (AEs) was 34.7% (60 of 173) in the L100/25 group, 23.9% (44 of 184) in the L50/12.5 group, and 32.6% (29 of 89) in the PBO group. The incidence of drug-related AEs was similar among the treatment groups (L100/25, 7.5% [13 of 173]; L50/12.5, 7.1% [13 of 184]; and PBO, 11.2% [10 of 89]). This study demonstrates the antihypertensive efficacy and tolerability of the once-daily, fixed-dose combination L50/12.5 in patients with moderate-to-severe essential hypertension. In this study, L100/25 provided additional anti-hypertensive efficacy beyond that of L50/12.5 (and both were more efficacious than PBO). Approximately 4 of 5 patients (78.9%) treated with L50/12.5 responded to therapy, as did nearly 9 of 10 patients (86.7%) treated with L100/25. The tolerability profiles of L50/12.5 and L100/25 were similar to that of PBO.


Differential regulation of perineuronal nets in the brain and spinal cord with exercise training.
Perineuronal nets (PNNs) are lattice like structures which encapsulate the cell body and proximal dendrites of many neurons and are thought to be involved in regulating synaptic plasticity. It is believed that exercise can enhance the plasticity of the Central Nervous System (CNS) in healthy and dysfunctional states by shifting the balance between plasticity promoting and plasticity inhibiting factors in favor of the former. Recent work has focused on exercise effects on trophic factors but its effect on other plasticity regulators is poorly understood. In the present study we investigated how exercise regulates PNN expression in the lumbar spinal cord and areas of the brain associated with motor control and learning and memory. Adult, female Sprague-Dawley rats with free access to a running wheel for 6 weeks had significantly increased PNN expression in the spinal cord compared to sedentary rats (PNN thickness around motoneurons, exercise=15.75±0.63μm, sedentary=7.98±1.29μm, p<0.01). Conversely, in areas of the brain associated with learning and memory there was a significant reduction in perineuronal net expression (number of neurons with PNN in hippocampus CA1-exercise 21±0.56 and sedentary 24±0.34, p<0.01, thickness-exercised=2.37±0.13μm, sedentary=4.27±0.21μm; p<0.01). Our results suggest that in response to exercise, PNNs are differentially regulated in select regions of the CNS, with a general decreased expression in the brain and increased expression in the lumbar spinal cord. This differential expression may indicate different regulatory mechanisms associated with plasticity in the brain compared to the spinal cord.


Effects of calcium on transendothelial albumin transfer and electrical resistance.
Nicolaysen, and more recently Kern and Malik, reported that chelation of calcium increased microvascular hydraulic conductivity and albumin permeability in isolated perfused lungs. To begin to understand how calcium affects endothelial function we examined the effect of calcium chelation on an in vitro endothelium. Chelation of calcium with ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid increased the rate of transendothelial albumin transfer by 125%. Reincubation of the endothelium in calcium-repleted medium restored the rate of transfer to its original value. Chelation of extracellular calcium abolished transendothelial electrical resistance. The transendothelial electrical resistance was also restored to normal by reincubation of the endothelium in calcium-repleted medium. Chelation of extracellular calcium caused adjacent endothelial cells to retract from one another, and normal apposition of adjacent cells was restored after reincubation in calcium-repleted medium. Chelation of extracellular calcium produced a centripetal retraction of the peripheral band of actin in individual endothelial cells, and the actin band resumed its normal location after reincubation in calcium-repleted medium. Calcium is an important determinant of endothelial integrity and alterations in calcium produce dynamic changes in endothelial barrier properties and in endothelial-cell shape.


Micro sequential injection: automated insulin derivatization and separation using a lab-on-valve capillary electrophoresis system.
Automated sampling and fluorogenic derivatization of islet proteins (insulin, proinsulin, c-peptide) are separated and analyzed by a novel lab-on-valve capillary electrophoresis (LOV-CE) system. This fully integrated device is based on a micro sequential injection instrument that uses a lab-on-valve manifold to integrate capillary electrophoresis. The lab-on-valve manifold is used to perform all microfluidic tasks such as sampling, fluorogenic labeling, and CE capillary rejuvenation providing a very reliable system for reproducible CE separations. Fluorescence detection was coupled to an epiluminescence fluorescence microscope using a customized capillary positioning plate. This customized plate incorporated two fused-silica fiber optic probes that allow for simultaneous absorbance and fluorescence detection, extending the utility of this device. Derivatization conditions with respect to the sequence of addition, timing, injection position, and volumes were optimized through iterative series of experiments that are executed automatically by software control. Reproducibility in fluorogenic labeling was tested with repetitive injections of 3.45 mM insulin, yielding 1.3% RSD for peak area, 0.5% RSD for electromigration time, and 2.8% RSD for peak height. Fluorescence detection demonstrated a linear dynamic range of 3.43 to 6.87 microM for insulin (r2 = 0.99999), 0.39 to 1.96 pM for proinsulin (r2 = 0.99195) and 260 to 781 nM for c-peptide (r2 = 0.99983). By including hydrodynamic flushing immediately after the detection of the last analyte, the sampling frequency for islet protein analysis was increased. Finally, an in vitro insulin assay using rat pancreatic islet excretions was tested using this lab-on-valve capillary electrophoresis system.


Observation of self-accelerating Bessel-like optical beams along arbitrary trajectories.
We experimentally demonstrate self-accelerating Bessel-like optical beams propagating along arbitrary trajectories in free space. With computer-generated holography, such beams are designed to follow different controllable trajectories while their main lobe transverse profiles remain nearly invariant and symmetric. Examples include parabolic, snake-like, hyperbolic, hyperbolic secant, and even three-dimensional spiraling trajectories. The self-healing property of such beams is also demonstrated. This new class of optical beams can be considered as a hybrid between accelerating and nonaccelerating nondiffracting beams that may find a variety of applications.


Relationship between Structural Characteristics and Plant Sources along with Pharmacology Research of Quassinoids.
Quassinoids, one kind of triterpenoids with multiple bioactivities such as anti-cancer, anti-malarial, anti-oxidative, anti-microbial, anti-diabetic, anti-viral, and anti-inflammatory effects, have drawn much attention in recent years. Between 2004 and 2018, the structural characteristics and plant sources of 190 quassinoids were reported. Herein, the structure-activity relationships (SARs) of quassinoids along with the anti-cancer mechanisms of four representative quassinoids, eurycomanone, bruceine D, dehydrobruceine B, and brusatol are discussed. This review might be useful for further research and development of quassinoids.


Tracheobronchial gland profiles in four segmental airways.
Previously described methods of measuring the amount of submucous gland in the trachea and bronchi have various disadvantages. These have been overcome by a method in which area point counting has been used to obtain a new unit, Vgl mm3/mm2, the volume of gland per unit airway surface area; Vgl has been obtained for the trachea, the main and lobar bronchi, and for successive airway generations down 4 segmental bronchi (the left lingular , the left anterior basal, the right middle medial, and the right anterior basal) from 3 nonsmokers, and presented in profile form. The profiles have a distinctive shape, not previously appreciated, with a rise to a proximal peak and then a striking fall to low Vgl values in the subsegmental bronchi. The shape of the profile is intriguing, but at present the information required to answer the questions it raises is not available. As there were no significant differences between the profiles of the 4 airways in the individual subjects, any one of the 4 airways may be chosen to give a representative profile for an individual subject.


Symbiosis-inspired approaches to antibiotic discovery.
Covering: 2010 up to 2017Life on Earth is characterized by a remarkable abundance of symbiotic and highly refined relationships among life forms. Defined as any kind of close, long-term association between two organisms, symbioses can be mutualistic, commensalistic or parasitic. Historically speaking, selective pressures have shaped symbioses in which one organism (typically a bacterium or fungus) generates bioactive small molecules that impact the host (and possibly other symbionts); the symbiosis is driven fundamentally by the genetic machineries available to the small molecule producer. The human microbiome is now integral to the most recent chapter in animal-microbe symbiosis studies and plant-microbe symbioses have significantly advanced our understanding of natural products biosynthesis; this also is the case for studies of fungal-microbe symbioses. However, much less is known about microbe-microbe systems involving interspecies interactions. Microbe-derived small molecules (i.e. antibiotics and quorum sensing molecules, etc.) have been shown to regulate transcription in microbes within the same environmental niche, suggesting interspecies interactions whereas, intraspecies interactions, such as those that exploit autoinducing small molecules, also modulate gene expression based on environmental cues. We, and others, contend that symbioses provide almost unlimited opportunities for the discovery of new bioactive compounds whose activities and applications have been evolutionarily optimized. Particularly intriguing is the possibility that environmental effectors can guide laboratory expression of secondary metabolites from "orphan", or silent, biosynthetic gene clusters (BGCs). Notably, many of the studies summarized here result from advances in "omics" technologies and highlight how symbioses have given rise to new anti-bacterial and antifungal natural products now being discovered.


Mental Status as a Common Factor for Masticatory Muscle Pain: A Systematic Review.
Masticatory muscle pain (MMP) is the primary reason for chronic non-odontogenic orofacial pain in the human population. MMP has become a considerable social problem, which affects about 12-14% of the adult population and is 1.5-2 times more frequent in women than in men. This term defines a pain which has its origins in the masticatory muscles. Although MMP is typically felt in the face, jaws, and preauricular area, MMP can radiate to the ear, teeth, head, and neck. This systematic review explains the relationship between MMP and common mental states, such as anxiety, depression, mood and stress-related disorders, and is reported in accordance with PRISMA guidelines. We performed a search in the PubMed database for peer-reviewed articles published after November 1st 2006 in the context of MMP and mental states. According to the defined criteria, 38 studies were finally included into the systematic review, of which prospective cohort studies were found to be the most common. We investigated four primary outcomes (anxiety, depression, mood disorders, and stress-related disorders) and several secondary outcomes of search. Seventy-nine percent of studies concerned depression, 42% anxiety, 29% mood disorders, and 21% stress-related disorders. Most of the studies showed a relationship between MMP and alterations in mental status. Nonetheless, the researchers usually evidenced only the co-occurrence of psychiatric disorders and dysfunctions of the masticatory muscles among the group of patients, in large part in women. Moreover, some studies were marked with limited generalizability of the reported results, quality flaws and heterogeneity. In the light of the analyzed literature, the causal relationship between mental states and MMP is still not clearly established.


Cholesterol-secreting and statin-responsive hepatocytes from human ES and iPS cells to model hepatic involvement in cardiovascular health.
Hepatocytes play a central and crucial role in cholesterol and lipid homeostasis, and their proper function is of key importance for cardiovascular health. In particular, hepatocytes (especially periportal hepatocytes) endogenously synthesize large amounts of cholesterol and secrete it into circulating blood via apolipoprotein particles. Cholesterol-secreting hepatocytes are also the clinically-relevant cells targeted by statin treatment in vivo. The study of cholesterol homeostasis is largely restricted to the use of animal models and immortalized cell lines that do not recapitulate those key aspects of normal human hepatocyte function that result from genetic variation of individuals within a population. Hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells can provide a cell culture model for the study of cholesterol homeostasis, dyslipidemias, the action of statins and other pharmaceuticals important for cardiovascular health. We have analyzed expression of core components for cholesterol homeostasis in untreated human iPS cells and in response to pravastatin. Here we show the production of differentiated cells resembling periportal hepatocytes from human pluripotent stem cells. These cells express a broad range of apolipoproteins required for secretion and elimination of serum cholesterol, actively secrete cholesterol into the medium, and respond functionally to statin treatment by reduced cholesterol secretion. Our research shows that HLCs derived from human pluripotent cells provide a robust cell culture system for the investigation of the hepatic contribution to human cholesterol homeostasis at both cellular and molecular levels. Importantly, it permits for the first time to also functionally assess the impact of genetic polymorphisms on cholesterol homeostasis. Finally, the system will also be useful for mechanistic studies of heritable dyslipidemias, drug discovery, and investigation of modes of action of cholesterol-modulatory drugs.


Measurement of the nurse organizational climate of neonatal intensive care units.
The concept of organizational climate is important for the study and understanding of work organizations. Researchers have not yet studied the organizational climate of hospital intensive care units, so it is not clear that the dimensions useful in description of other work settings will be appropriate for conceptualizing neonatal intensive care units (NICU's). This study investigated nurse perceptions of the organizational climate of NICU's in a sample of 18 hospitals. The Organizational Climate Description Questionnaire was modified for use in the NICU setting. A set of homogeneous climate scales was developed from the revised instrument. The six scales of the resulting instrument, the Nursing Organizational Climate Description Questionnaire, Form B (NOCDQ-B), demonstrated median internal-consistency reliability of .69 on cross-validation. Analysis of variance indicated that each of the six NOCDQ-B dimensions served to differentiate the NICU's in the study. Further, significant relationships were found at the unit mean level between three of the six NOCDQ-B scales and nurse satisfaction, as measured by the Minnesota Satisfaction Questionnaire.


Measurement of dose distribution around Fletcher-Suit-Delcos colpostats using a Therados radiation field analyzer (RFA-3).
Using a small silicon diode and the Therados RFA-3 automated dosimetry system, the relative dose distribution around Fletcher-Suit-Delcos colpostats was measured. Thermoluminescent dosimeters (LiF) were used for absorbed dose measurements. These data provide the basis for computerized dose calculations which will account for the attenuation effects of the rectal and bladder shieldings. The stainless-steel housing attenuated the radiation of a Cs-137 source by 6%. The tungsten shields caused a further dose reduction of 15%-25%.


A conserved charged single α-helix with a putative steric role in paraspeckle formation.
Paraspeckles are subnuclear particles involved in the regulation of mRNA expression. They are formed by the association of DBHS family proteins and the NEAT1 long noncoding RNA. Here, we show that a recently identified structural motif, the charged single α-helix, is largely conserved in the DBHS family. Based on the available structural data and a previously suggested multimerization scheme of DBHS proteins, we built a structural model of a (PSPC1/NONO)(n) multimer that might have relevance in paraspeckle formation. Our model contains an extended coiled-coil region that is followed by and partially overlaps with the predicted charged single α-helix. We suggest that the charged single α-helix can act as an elastic ruler governing the exact positioning of the dimeric core structures relative to each other during paraspeckle assembly along the NEAT1 noncoding RNA.


Sex Specificity in the Mixed Effects of Blood Heavy Metals and Cognitive Function on Elderly: Evidence from NHANES.
The way that males and females react to environmental exposures and negative impacts on their neurological systems is often different. Although previous research has examined the cognitively impairing effects of solitary metal exposures, the relationship between metal mixtures and cognitive function, particularly when considering an individual's sex, remains elusive. This study aimed to investigate the sex differences in the association between multiple metal combinations and cognitive function in older Americans. This research employed the 2011-2014 NHANES survey of elderly Americans. The association between five mixed metals and four cognitive tests (the animal fluency test (AFT), the digit symbol substitution test (DSST), the instant recall test (IRT), and the delayed recall test (DRT)) were investigated with generalized linear regression model (GLM), Bayesian kernel machine regression model (BKMR), weighted quantile sum regression model (WQS), and quantile g-computation regression model (Qgcomp). A total of 1833 people, including 883 males and 950 females, enrolled in this cross-sectional study. We discovered that blood lead and blood cadmium were negatively associated with cognitive performance, while blood selenium demonstrated a positive association with cognitive function in older people. The negative relationship of heavy metal combinations on cognitive function might be somewhat reduced or even reversed via selenium. The IRT, AFT, and DSST are three of the four cognitive tests where men had more dramatic positive or negative results. There was a sex-specific connection between blood metal ratios and cognitive function among older Americans, as evidenced by the more significant relationship between mixed metals and cognitive performance in men (either positively or negatively). These results emphasize the impacts of ambient heavy metal exposure on cognitive function by employing sex-specific methods.


Outcome of Crohn's disease diagnosed before two years of age.
We describe the course of 7 patients younger than 2 years with Crohn's disease. Prolonged remission was achieved medically (5) or surgically (1), whereas one patient died of disseminated adenovirus. Three had malnutrition and growth failure. Crohn's disease very early in life does not always imply a poor prognosis; however, significant morbidity and mortality are encountered.


Prevention of streptococcal neurosis.
Despite the decrease in the incidence and severity of rheumatic fever and rheumatic heart disease in the United States, overzealous emphasis on proper diagnosis and treatment of group A streptococcal pharyngitis in order to prevent these illnesses may often result in a frustrating, anxiety-provoking condition known as "streptococcal neurosis." Physicians, parents, and patients may all suffer from this condition, which often occurs even after all possible and appropriate treatment has been used to eradicate the group A streptococci. "Streptococcal neurosis" and the perplexing problem of treatment failure can be avoided or alleviated by utilizing knowledge of the interrelationship of the human host, the group A streptococcus, and nonsuppurative sequelae.


The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery.
Radiotherapy is an important modality used in the treatment of more than 50% of cancer patients in the US. However, despite sophisticated techniques for radiation delivery as well as the combination of radiation with chemotherapy, tumors can recur. Thus, any method of improving the local control of the primary tumor by radiotherapy would produce a major improvement in the curability of cancer patients. One of the challenges in the field is to understand how the tumor vasculature can regrow after radiation in order to support tumor recurrence, as it is unlikely that any of the endothelial cells within the tumor could survive the doses given in a typical radiotherapy regimen. There is now considerable evidence from both preclinical and clinical studies that the tumor vasculature can be restored following radiotherapy from an influx of circulating cells consisting primarily of bone marrow derived monocytes and macrophages. The radiation-induced influx of bone marrow derived cells (BMDCs) into tumors can be prevented through the blockade of various cytokine pathways and such strategies can inhibit tumor recurrence. However, the post-radiation interactions between surviving tumor cells, recruited immune cells, and the remaining stroma remain poorly defined. While prior studies have described the monocyte/macrophage inflammatory response within normal tissues and in the tumor microenvironment, less is known about this response with respect to a tumor after radiation therapy. The goal of this review is to summarize existing research studies to provide an understanding of how the myelomonocytic lineage may influence vascular recovery within the irradiated tumor microenvironment.


Capsule endoscopy examination--preliminary review by a nurse.
Capsule endoscopy (CE) has been recommended as the method of choice for diagnostic endoscopy of the small bowel. An experienced nurse, after proper training, may contribute to the endoscopy procedures as previously described for sigmoidoscopy. The aim of this study was to evaluate the ability of an experienced gastroenterology nurse to prepare CE records for physician interpretation, by detecting abnormal thumbnails. A prospective, observational design was used. Fifty CE videos were pre-read by a specially trained gastroenterology nurse who thumbnailed the abnormalities detected for interpretation by the gastroenterologist. The nurse's description of the lesions and the calculated gastric and bowel transit times were compared to the interpretation of the videos made directly by the gastroenterologist (gold standard). The primary end point of the study was the quality of the nurse's pathology findings; the secondary end point was the cost effectiveness of this practice. There was complete agreement between the nurse and gastroenterologist for all 12 cases interpreted as normal by the gastroenterologist. In the remaining 38 cases, the nurse created 130 thumbnail selections and the physician, 99. Complete interobserver agreement was achieved for 93 of the 96 lesions categorized as "significant" by the physician (96.9%). After all relevant variables were taken into account, this approach saved dollar 324 per CE examination. The use of nurse practitioner to pre-read CE videos and prepare thumbnail selections for further assessment by the gastroenterologist appears to be safe, reliable, and cost effective.


Reconstruction of a mandibular segmental defect with a customized 3-dimensional-printed titanium prosthesis in a cat with a mandibular osteosarcoma.
CASE DESCRIPTION A 12-year-old neutered male domestic shorthair cat had been treated for a mass arising from the lingual aspect of the caudal right mandibular body. Cytoreductive surgery of the mass had been performed twice over a 2-year period, but the mass recurred following both surgeries. The mass was diagnosed as an osteosarcoma, and the cat was referred for further evaluation and treatment. CLINICAL FINDINGS Clinical findings were unremarkable, except for a 2-cm-diameter mass arising from the lingual aspect of the right mandible and mild anemia and lymphopenia. Pre- and postcontrast CT scans of the head, neck, and thorax were performed, revealing that the osteosarcoma was confined to the caudal right mandibular body, with no evidence of lymph node or pulmonary metastasis. TREATMENT AND OUTCOME The stereolithographic files of the CT scan of the head were sent for computer-aided design and manufacture of a customized 3-D-printed titanium prosthesis. Segmental mandibulectomy was performed, and the mandibular defect was reconstructed in a single stage with the 3-D-printed titanium prosthesis. The cat had 1 minor postoperative complication but had no signs of eating difficulties at any point after surgery. The cat was alive and disease free 14 months postoperatively. CLINICAL RELEVANCE Reconstruction of the mandible of a cat following mandibulectomy was possible with computer-aided design and manufacture of a customized 3-D-printed titanium prosthesis. Cats have a high rate of complications following mandibulectomy, and these initial findings suggested that mandibular reconstruction may reduce the risk of these complications and result in a better functional outcome.


Peptide-modified chitosan hydrogels promote skin wound healing by enhancing wound angiogenesis and inhibiting inflammation.
Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro. This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds.


The influence of socioeconomic status on future risk for developing Type 2 diabetes in the Canadian population between 2011 and 2022: differential associations by sex.
Articulating future risk of diabetes at the population level can inform prevention strategies. While previous studies have characterized diabetes burden according to socioeconomic status (SES), none have studied future risk. We quantified the influence of multiple constructs of SES on future diabetes risk using the Diabetes Population Risk Tool (DPoRT), a validated risk prediction algorithm that generates 10-year rates of new diabetes cases. We applied DPoRT to adults aged 30-64 in the 2011-2012 Canadian Community Health Survey (n = 65,372) and calculated risk for 2021-22. A multi-category outcome was created classifying risk as low (≤5%), moderate (greater than 5% and less than 20%), and high (≥20%), then assessed the impact of individual-level SES indicators, and area-level measures of marginalization on being moderate or high risk using multinomial logistic regression, stratified by sex. We found nuanced profiles of social determinants by sex, where women are more sensitive to social context. Women living in households where highest educational attainment was less than secondary school were at greater risk [odds ratio (OR) of high compared to low diabetes risk 3.10, 95% confidence interval (CI) 2.19-4.40, p < 0.0001). The same relationship was less pronounced for males (OR 2.17, 95% CI 1.42-3.32, p = 0.0004). Lower household income and being food insecure predicted high future diabetes risk for women (OR 1.37, 95% CI 1.01-1.86, p = 0.0418 comparing quintile 1 to quintile 5; OR 2.64, 95% CI 1.78-3.92, p < 0.0001 comparing severely food insecure to food secure), but not men (OR 1.15, 95% CI 0.84-1.57, p = 0.3818 and OR 1.22, 95% CI 0.71-2.10, p = 0.4815). At the area-level, material deprivation was significantly associated with increased future risk comparing the most to the least deprived (OR females 2.39, 95% CI 1.77-3.23; OR males 1.61, 95% CI 1.22-2.14). Additionally, a strong protective effect was observed for women living in ethnically dense areas (OR 0.75, 95% CI 0.63-0.89, p = 0.0011) which was not as pronounced for men (OR 0.95, 95% CI 0.76-1.18, p = 0.6351). This study characterized socio-contextual predictors for future diabetes risk, showing sex-specific effects. Diabetes prevention must consider factors beyond individual-level behavioral lifestyle change and actively take steps to mitigate the adverse impacts of socio-contextual factors.


Serum leptin and risk of cognitive decline in elderly italians.
US studies suggest that leptin, a fat-derived hormone, may be protective against the development of dementia. To investigate the complex relationship between leptin levels and cognitive decline in elderly Italians. We studied circulating fasting leptin levels in 809 elderly adults free from dementia who participated in the prospective Italian population-based InCHIANTI study between 1998 and 2009 (mean follow-up of 8.0 years). Global cognitive decline was defined as a reduction of ≥5 points on the Mini-Mental State Examination (MMSE). Trail-Making Tests A and B were also incorporated, with cognitive decline defined as discontinued testing or the worst 10% of change from baseline. We also investigated whether any association could be explained by midlife weight and whether cognitive decline was associated with changing leptin levels. The multivariate adjusted relative risk ([RR]; 95% confidence interval [CI]) of cognitive decline on the MMSE was 0.84 (95% CI 0.73-0.97) in relation to baseline sex-standardized log-leptin levels. High leptin levels showed a non-significant trend toward a reduced risk of decline on the Trail-Making Tests A (RR = 0.85, 95% CI 0.71-1.02) and B (RR = 0.90, 0.79-1.02). Adjusting for midlife weight or change in weight did not alter the pattern of results, and cognitive decline was not associated with changing leptin levels. High leptin levels were independently associated with a reduced risk of cognitive decline in elderly Italians.


Pharmacological characterization of the interaction between umeclidinium and vilanterol in human bronchi.
The long-acting β2-agonist (LABA) / long-acting muscarinic antagonist (LAMA) fixed dose combination (FDC) therapy represents the cornerstone for the treatment of chronic obstructive pulmonary disease (COPD). Nevertheless, conflicting clinical findings still exist on the real benefit of the LABA/LAMA FDCs. Therefore, we investigated whether combining the LABA vilanterol with the LAMA umeclidinium may induce synergistic bronchorelaxant effect in isolated airways. The effect of umeclidinium and vilanterol, administered alone, in combination at the ratio of concentrations reproducing the doses delivered by Anoro® Ellipta® (55:22), or at isoeffective low concentrations, was investigated on the cholinergic contractile tone induced by the parasympathetic activation of human isolated airways. The interaction was analyzed by using the Bliss Independence and Unified Theory models. Umeclidinium and vilanterol induced a concentration-dependent relaxation of isolated bronchi, with umeclidinium significantly (P < 0.05) more potent than vilanterol (Emax at 10Hz: umeclidium 102.6 ± 6.8%, vilanterol 75.1 ± 13.8%; pEC50 at 10Hz: umeclidinium 8.6 ± 0.4, vilanterol 6.9 ± 0.6). When administered at 55:22 concentration-ratio, umeclidinium plus vilanterol completely relaxed the isolated airways (Emax at 10Hz: 99.6 ± 8.0%; pEC50 at 10Hz: 8.2 ± 0.4). No synergistic interaction was detected for umeclidinium/vilanterol combined at 55:22 ratio, whereas strong synergism was elicited when the drugs were administered at low isoeffective concentrations (+ 41.4 ± 5.8% vs. monocomponents), leading to submaximal relaxant effect (81.4 ± 5.8%). Umeclidinium and vilanterol are imbalanced when combined at 55:22 ratio, with umeclidinium over-dosed, or vice versa vilanterol under-dosed. Specific studies are needed to identify the dose ratio of umeclidinium/vilanterol combination to guarantee equipotency concentrations of each component into the lung, and induce synergistic bronchodilation.


Perceived control moderates the relationship between anxiety and in-hospital complications after ST segment elevation myocardial infarction.
Anxiety is a common psychological response after acute myocardial infarction and might be associated with higher levels of in-hospital complications. Perceived control might moderate this relationship, but the effect of this method has not been checked in developing countries. Therefore, the objectives of this study were as follows: 1) to check if anxiety was an independent predictor of in-hospital complications after acute myocardial infarction; and 2) to check if perceived control moderates the relationship between anxiety and in-hospital complications after acute myocardial infarction. This was a prospective observational study among 500 patients with a confirmed diagnosis of ST segment elevation myocardial infarction recruited from three private hospitals in Amman, Jordan. Anxiety was measured by the Anxiety subscale of Hospital Anxiety and Depression Scale, and perceived control was measured by the Arabic version of the Control Attitude Scale-Revised. One hundred and forty patients (28%) developed at least one complication during hospitalization. Two hundred and fifty-five patients had low anxiety scores (≤7), and 245 patients had high anxiety scores (≥8). Patients with high levels of perceived control had lower levels of anxiety (mean [SD]; 5.3 [3.6] vs 14.1 [6.3], P<0.001) than those with low perceived control. In logistic regression, anxiety was an independent predictor of in-hospital complications after controlling for sociodemographic and clinical variables (odds ratio: 1.24, 95% CI, 1.08-1.41, P<0.01). Moreover, the interaction of anxiety and perceived control was a significant predictor of complications. Anxiety was associated with increased risk of in-hospital complications after acute myocardial infarction independent of sociodemographic and clinical variables. Perceived control had a moderating effect for this association since the combination of low perceived control and high anxiety scores was associated with the greatest risk for complications. Supporting patients' levels of perceived control can decrease complications, morbidities, and mortality after acute myocardial infarction.


Following the solvent directly during ultrafast excited state proton transfer.
Excited state intramolecular proton transfer in 1-chloroacetylaminoanthraquinone is investigated from the perspective of the solvent. Using a new two-dimensional nonlinear optical spectroscopy the solvent response is probed directly as the proton transfer takes place. The measurements indicate that solvent reorganization controls the proton transfer in acetonitrile by dynamically shifting the position of equilibrium in the excited state, even on subpicosecond time scales.


Mock trial jury decisions as a function of adolescent juror guilt and hostility.
A fictitious court case involving child abuse was presented to 277 male adolescent jurors (138 college freshmen, means age = 19.25 years, 139 junior high school males, means age = 13.47 years) in an effort to determine if the tendency to deal harshly with alleged criminals is dependent upon certain personality characteristics of adolescent jurors. The Mosher Hostility Guilt Scale and the Siegel Manifest Hostility Scale were used to detect the presence of such trends. The results indicate that older adolescents attributed more of the responsibility for the crime to the defendant and administered less severe sentences than younger adolescent jurors. Hostility guilt and manifest hostility levels were not significantly related to attribution of responsibility for a criminal act; however, Ss scoring high in hostility guilt tended to give significantly shorter sentences, while Ss scoring high in manifest hostility tended to give longer sentences. Implications for adolescent peer practices are discussed.


Successful Treatment of Intractable Rectal Varices with Gelfoam Slurry Embolisation and Coiling.
A 57-year-old male with heart failure and decompensated alcoholic liver cirrhosis presented with recurrent haematochesia due to rectal varices. After multiple failed therapy with endoscopic band ligation and surgical sclerotherapy, a discussion with an interventional radiologist was arranged. A transjugular intrahepatic portosystemic shunt (TIPS) was deferred due to a history of heart failure. A shared decision to proceed with transhepatic Gelfoam® slurry embolisation with coiling was made. During the procedure, a variant anatomy of the superior rectal vein was identified. The superior rectal vein was found to drain directly into the left portal vein with no connectivity between the inferior mesenteric vein and the rectal varices. As planned, Gelfoam slurry embolisation and coiling was done to the left and right superior rectal vein along with the common trunk it drains. The patient did not develop any further episodes of gastrointestinal bleeding or worsening ascites on follow-up after 6 months. This case represents a successful treatment of bleeding rectal varices when TIPS is contraindicated. Rectal varices are an infrequent outcome of portal hypertension formed by portocaval anastomosis between the superior rectal vein with the inferior mesenteric vein of the portal system upstream, and the middle and inferior rectal vein draining into the internal iliac and internal pudendal vein of the systemic circulation, respectively. Portal system variations are extremely rare.Most common modality of recurrent rectal varices bleed is a transhepatic intrajugular portosystemic shunt. The absolute contraindications to this include congestive heart failure among others.In the presence of multiple co-morbidities and contraindication for TIPS, various interventional radiological modalities on a case-by-case basis are available including percutaneous transhepatic rectal varices obliteration.


Malignant middle cerebral artery (MCA) infarction: pathophysiology, diagnosis and management.
'Malignant MCA infarction' is the term used to describe rapid neurological deterioration due to the effects of space occupying cerebral oedema following middle cerebral artery (MCA) territory stroke. Early neurological decline and symptoms such as headache and vomiting should alert the clinician to this syndrome, supported by radiological evidence of cerebral oedema and mass effect in the context of large hemispheric infarction. The prognosis is generally poor, and death usually occurs as a result of transtentorial herniation and brainstem compression. Treatment options include general measures and pharmacological agents to limit the extent of oedema, and surgical decompression to relieve the pressure effects. Until recently there has been little evidence to guide appropriate treatment, though in the last few years randomised data have been published addressing the role of surgical decompression. A pooled analysis of three European randomised controlled trials suggests that hemicraniectomy performed within 48 h significantly reduces mortality, and improves functional outcome in selected patients, and this has been reflected in recent national guidelines.


Pretargeted Immuno-PET of Pancreatic Cancer: Overcoming Circulating Antigen and Internalized Antibody to Reduce Radiation Doses.
5B1 is a fully human, monoclonal antibody that has shown promise for the PET imaging of cancers expressing carbohydrate antigen 19.9 (CA19.9)--a carbohydrate prevalent in cells with aberrant glycosylation and an established effector of metastasis. The long physiologic half-life of the antibody and interference from circulating CA19.9 may increase the time required to generate quality images as well as the risk of radiation exposure to healthy tissues during repeated PET imaging. Pretargeting methodologies are an effective approach to expeditiously acquire PET images, but in this case, the pretargeting approach is complicated by the internalization of 5B1 by CA19.9-expressing cells. We sought to adapt and optimize a pretargeting strategy that exploits the bioorthogonal reaction between transcyclooctene (TCO) and tetrazine (Tz) to overcome these complications. 5B1 was modified with TCO, and a novel NOTA-PEG7-Tz radioligand was synthesized with the goal of improving on a previously reported analog. BxPC3 and Capan-2 cells were evaluated for their ability to internalize anti-CA19.9 antibodies using a fluorometric assay, and xenografts of the same lines were used for in vivo studies. The pretargeting approach was optimized, and the 2 radioligands were compared using biodistribution and PET imaging in murine models of pancreatic cancer. BxPC3 and Capan-2 cells were shown to rapidly internalize anti-CA19.9 monoclonal antibodies, including 5B1. (64)Cu-NOTA-PEG7-Tz showed improved in vivo pharmacokinetics relative to (64)Cu-NOTA-Tz using 5B1-TCO as the targeting vector. PET imaging and biodistribution studies showed that injecting the radioligand 72 h after the administration of 5B1-TCO resulted in the best uptake (8.2 ± 1.7 percentage injected dose per gram at 20 h after injection) and tumor-to-background activity concentration ratios. Dosimetry calculations revealed that the pretargeting system produced a greater than 25-fold reduction in total body radiation exposure relative to (89)Zr-desferrioxamine-5B1. PET/CT imaging in an orthotopic Capan-2 xenograft model--which secretes large amounts of CA19.9 and more rapidly internalizes anti-CA19.9 antibodies--showed that this approach is viable even in the difficult circumstances presented by a circulating antigen and internalized targeting vector. The 5B1-TCO and (64)Cu-NOTA-PEG7-Tz system evaluated in these studies can delineate CA19.9-positive xenografts in murine models of pancreatic cancer despite the challenges posed by the combination of circulating antigen and internalization of the 5B1-TCO.


The reproducibility of late gadolinium enhancement cardiovascular magnetic resonance imaging of post-ablation atrial scar: a cross-over study.
Cardiovascular magnetic resonance (CMR) imaging has been used to visualise post-ablation atrial scar (PAAS), generally employing a three-dimensional (3D) late gadolinium enhancement (LGE) technique. However the reproducibility of PAAS imaging has not been determined. This cross-over study is the first to investigate the reproducibility of the technique, crucial for both future research design and clinical implementation. Forty subjects undergoing first time ablation for atrial fibrillation (AF) had detailed CMR assessment of PAAS. Following baseline pre-ablation scan, two scans (separated by 48 h) were performed at three months post-ablation. Each scan session included 3D LGE acquisition at 10, 20 and 30 min post administration of gadolinium-based contrast agent (GBCA). Subjects were allocated at second scan post-ablation to identical imaging parameters ('Repro', n = 10), 3 T scanner ('3 T', n = 10), half-slice thickness ('Half-slice', n = 10) or half GBCA dose ('Half-gad', n = 10). PAAS was compared to baseline scar and then reproducibility was assessed for two measures of thresholded scar (% left atrial (LA) occupied by PAAS (%LA PAAS) and Pulmonary Vein Encirclement (PVE)), and then four measures of non-thresholded scar (point-by-point assessment of PAAS, four normalisation methods). Thresholded measures of PAAS were evaluated against procedural outcome (AF recurrence). A total of 271 3D acquisitions (out of maximum 280, 96.7%) were acquired. At 20 and 30 min, inter-scan reproducibility was good to excellent (coefficient of variation at 20 min and 30 min: %LA PAAS 0.41 and 0.20; PVE 0.13 and 0.04 respectively for 'Repro' group). Changes in imaging parameters, especially reduced GBCA dose, reduced inter-scan reproducibility, but for most measures remained good to excellent (ICC for %LA PAAS 0.454-0.825, PVE 0.618-0.809 at 30 min). For non-thresholded scar, highest reproducibility was observed using blood pool z-score normalisation technique: inter-scan ICC 0.759 (absolute agreement, 'Repro' group). There was no significant relationship between indices of PAAS and AF recurrence. PAAS imaging is a reproducible finding. Imaging should be performed at least 20 min post-GBCA injection, and a blood pool z-score should be considered for normalisation of signal intensities. The clinical implications of these findings remain to be established in the absence of a simple correlation with arrhythmia outcome. United Kingdom National Research Ethics Service 08/H0802/68 - 30th September 2008.


High bile duct strictures.
The diagnosis and surgical treatment of carcinoma of the common hepatic duct present diffucult problems. Accurate preoperative localization of the obstructive lesion is essential and slim needle transhepatic percutaneous cholangiography is the investigation of choice. Worth while palliation may be achieved if biliary-enteric flow can be reestablished by introducing a plastic stenton through the obstructive lesion in the bile duct. Three patients are reviewed who survive 36, 31 and 26 months after this operation. A further patient died of metastases after 5 months.


[Applying temporally-adjusted land use regression models to estimate ambient air pollution exposure during pregnancy].
The impact of maternal air pollution exposure on offspring health has received much attention. Precise and feasible exposure estimation is particularly important for clarifying exposure-response relationships and reducing heterogeneity among studies. Temporally-adjusted land use regression (LUR) models are exposure assessment methods developed in recent years that have the advantage of having high spatial-temporal resolution. Studies on the health effects of outdoor air pollution exposure during pregnancy have been increasingly carried out using this model. In China, research applying LUR models was done mostly at the model construction stage, and findings from related epidemiological studies were rarely reported. In this paper, the sources of heterogeneity and research progress of meta-analysis research on the associations between air pollution and adverse pregnancy outcomes were analyzed. The methods of the characteristics of temporally-adjusted LUR models were introduced. The current epidemiological studies on adverse pregnancy outcomes that applied this model were systematically summarized. Recommendations for the development and application of LUR models in China are presented. This will encourage the implementation of more valid exposure predictions during pregnancy in large-scale epidemiological studies on the health effects of air pollution in China.


Network Security Situation Prediction Based on Optimized Clock-Cycle Recurrent Neural Network for Sensor-Enabled Networks.
We propose an optimized Clockwork Recurrent Neural Network (CW-RNN) based approach to address temporal dynamics and nonlinearity in network security situations, improving prediction accuracy and real-time performance. By leveraging the clock-cycle RNN, we enable the model to capture both short-term and long-term temporal features of network security situations. Additionally, we utilize the Grey Wolf Optimization (GWO) algorithm to optimize the hyperparameters of the network, thus constructing an enhanced network security situation prediction model. The introduction of a clock-cycle for hidden units allows the model to learn short-term information from high-frequency update modules while retaining long-term memory from low-frequency update modules, thereby enhancing the model's ability to capture data patterns. Experimental results demonstrate that the optimized clock-cycle RNN outperforms other network models in extracting the temporal and nonlinear features of network security situations, leading to improved prediction accuracy. Furthermore, our approach has low time complexity and excellent real-time performance, ideal for monitoring large-scale network traffic in sensor networks.


Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study.
The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1-3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), Neurotoxicity Subscale (FACT/GOG-NTX subscale), and Brief Pain Inventory (BPI). One hundred eighty-six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. MVAC's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.


Endocrinological and cardiological late effects among survivors of childhood acute lymphoblastic leukemia.
Survival rates for childhood acute lymphoblastic leukemia (ALL) have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders) and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%), with 8 of them (21%) having multiple problems. Six (16%) of the survivors were obese and 8 (21%) of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21%) subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21%) patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least one adverse event occurred in most of our cases. None declared.


Synthetic redesign of plant lipid metabolism.
Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non-native host is considered. The advantages of a particular oilseed crop, Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio-based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more (computationally) directed manipulations of metabolism.


Fine mapping of the Asian soybean rust resistance gene Rpp2 from soybean PI 230970.
Asian soybean rust (ASR) resistance gene Rpp2 has been fine mapped into a 188.1 kb interval on Glyma.Wm82.a2, which contains a series of plant resistance ( R ) genes. Asian soybean rust (ASR), caused by the fungus Phakopsora pachyrihizi Syd. & P. Syd., is a serious disease in major soybean [Glycine max (L.) Merr.] production countries worldwide and causes yield losses up to 75 %. Defining the exact chromosomal position of ASR resistance genes is critical for improving the effectiveness of marker-assisted selection (MAS) for resistance and for cloning these genes. The objective of this study was to fine map the ASR resistance gene Rpp2 from the plant introduction (PI) 230970. Rpp2 was previously mapped within a 12.9-cM interval on soybean chromosome 16. The fine mapping was initiated by identifying recombination events in F2 and F3 plants using simple sequence repeat (SSR) and single nucleotide polymorphism (SNP) markers that flank the gene. Seventeen recombinant plants were identified and then tested with additional genetic markers saturating the gene region to localize the positions of each recombination. The progeny of these selected plants were tested for resistance to ASR and with SSR markers resulting in the mapping of Rpp2 to a 188.1 kb interval on the Williams 82 reference genome (Glyma.Wm82.a2). Twelve genes including ten toll/interleukin-1 receptor (TIR)-nucleotide-binding site (NBS)-leucine-rich repeat (LRR) genes were predicted to exist in this interval on the Glyma.Wm82.a2.v1 gene model map. Eight of these ten genes were homologous to the Arabidopsis TIR-NBS-LRR gene AT5G17680.1. The identified SSR and SNP markers close to Rpp2 and the candidate gene information presented in this study will be significant resources for MAS and gene cloning research.


A Study on the Personality Traits and Their Influencing Factors of Children from Poor Families from the Perspective of Psychological Education.
The problem of poor children's psychological development has been widely concerned by governments all over the world. At present, the research results of poor children's psychological development show that poor children mainly have cognitive, mental health, and behavioral problems. This paper studies the personality traits and their influencing factors of children from poor families from the perspective of psychological education. By giving the definition of children from poor families and poor families, this paper analyzes the psychological development of poor children, analyzes the personality traits and influencing factors of children from poor families from the perspective of psychological education, obtains the standard scores of 16 personality traits and their dimensional personality factors and personality factors, and uses the clustering method to realize the difference analysis of personality characteristics of various samples. From the perspective of quantitative psychological education, this paper analyzes the correlation between personality traits and influencing factors of children from poor families in order to provide basis and reference for the government and society to implement targeted poverty alleviation and cut off the intergenerational transmission of poverty.


The Role of Peroxisome Proliferator-Activated Receptor Gamma (PPARG) in Adipogenesis: Applying Knowledge from the Fish Aquaculture Industry to Biomedical Research.
The tropical freshwater zebrafish has recently emerged as a valuable model organism for the study of adipose tissue biology and obesity-related disease. The strengths of the zebrafish model system are its wealth of genetic mutants, transgenic tools, and amenability to high-resolution imaging of cell dynamics within live animals. However, zebrafish adipose research is at a nascent stage and many gaps exist in our understanding of zebrafish adipose physiology and metabolism. By contrast, adipose research within other, closely related, teleost species has a rich and extensive history, owing to the economic importance of these fish as a food source. Here, we compare and contrast knowledge on peroxisome proliferator-activated receptor gamma (PPARG)-mediated adipogenesis derived from both biomedical and aquaculture literatures. We first concentrate on the biomedical literature to (i) briefly review PPARG-mediated adipogenesis in mammals, before (ii) reviewing Pparg-mediated adipogenesis in zebrafish. Finally, we (iii) mine the aquaculture literature to compare and contrast Pparg-mediated adipogenesis in aquaculturally relevant teleosts. Our goal is to highlight evolutionary similarities and differences in adipose biology that will inform our understanding of the role of adipose tissue in obesity and related disease.


Bioaccumulation of perfluoroalkyl acids by earthworms (Eisenia fetida) exposed to contaminated soils.
The presence of perfluoroalkyl acids (PFAAs) in biosolids-amended and aqueous film-forming foam (AFFF)-impacted soils results in two potential pathways for movement of these environmental contaminants into terrestrial foodwebs. Uptake of PFAAs by earthworms (Eisenia fetida) exposed to unspiked soils with varying levels of PFAAs (a control soil, an industrially impacted biosolids-amended soil, a municipal biosolids-amended soil, and two AFFF-impacted soils) was measured. Standard 28 day exposure experiments were conducted in each soil, and measurements taken at additional time points in the municipal soil were used to model the kinetics of uptake. Uptake and elimination rates and modeling suggested that steady state bioaccumulation was reached within 28 days of exposure for all PFAAs. The highest concentrations in the earthworms were for perfluorooctane sulfonate (PFOS) in the AFFF-impacted Soil A (2160 ng/g) and perfluorododecanoate (PFDoA) in the industrially impacted soil (737 ng/g). Wet-weight (ww) and organic carbon (OC)-based biota soil accumulation factors (BSAFs) for the earthworms were calculated after 28 days of exposure for all five soils. The highest BSAF in the industrially impacted soil was for PFDoA (0.42 goc/gww,worm). Bioaccumulation factors (BAFs, dry-weight-basis, dw) were also calculated at 28 days for each of the soils. With the exception of the control soil and perfluorodecanoate (PFDA) in the industrially impacted soil, all BAF values were above unity, with the highest being for perfluorohexanesulfonate (PFHxS) in the AFFF-impacted Soil A (139 gdw,soil/gdw,worm). BSAFs and BAFs increased with increasing chain length for the perfluorocarboxylates (PFCAs) and decreased with increasing chain length for the perfluoroalkyl sulfonates (PFSAs). The results indicate that PFAA bioaccumulation into earthworms depends on soil concentrations, soil characteristics, analyte, and duration of exposure, and that accumulation into earthworms may be a potential route of entry of PFAAs into terrestrial foodwebs.


Effect of DOTS Treatment on Vitamin D Levels in Pulmonary Tuberculosis.
Vitamin D (Vit D) modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. Vit D Deficiency (VDD) is been implicated as a cause in diabetes, immune dysfunction and Tuberculosis (TB). Impaired metabolism of Vit D and an adverse outcome is associated with Pulmonary Tuberculosis (PTB). Directly Observed Treatment Short Course (DOTS) consist of drugs like rifampicin and isoniazid, which respectively cause accelerated loss of Vit D due to increased clearance and impairment of 25-hydroxylation causing diminished Vit D action. The aim of the present study was to estimate and compare serum Vit D status in newly diagnosed PTB patients before and after DOTS to validate the supplementation of Vit D in PTB patients. Forty four newly diagnosed PTB patients of both the sexes in the age group of 18 to 60 years before starting DOTS were recruited to participate in this non- randomized controlled trial with their voluntary consent. Vit D status in these patients and the effect of DOTS on Vit D were evaluated. Mean Vit D levels of the study population aged 43±13 years was 20.74 ng/ml (normal >30 ng/ml) at the time of diagnosis. After completion of six months of therapy mean Vit D reduced to 17.49 ng/ml (p-value=0.041). On individual observations, 70% of the participants showed a decrease in Vit D levels from their baseline, whereas 30% showed an increase. Comparison between the two groups indicated the possible role of younger age in the improved status. VDD was seen in PTB patients, which worsened in majority of the study population after treatment; hence it would be advisable to recommend Vit D supplementation in PTB patients for a better outcome.


An innovative approach to health promotion experiences in community health nursing: a university collaborative partnership.
The number of nurses working in community-based practices with a population focus is increasing rapidly, whereas the rate of employment for nurses in hospitals is expected to grow more slowly. The shift in health care toward primary health care and health promotion requires nurse educators to ensure that students learn to practice in collaborative partnerships in community settings. This article describes an innovative collaborative partnership with the Capstone College of Nursing and the Office of Health Promotion and Wellness at The University of Alabama. Through this partnership, community health nursing students provide health promotion for university employees in the University's wellness program. The program provides nursing students with a unique opportunity for interprofessional collaboration while improving their clinical and communication skills. This innovative collaborative approach serves as a useful model for nursing faculty members when delivering community health instruction.


GLC analysis of lidocaine in plasma using a novel nitrogen-sensitive detector.
A simple, rapid GLC method for the determination of therapeutic levels of lidocaine in plasma or blood is described. After extraction with benzene from alkalinized plasma, the compound is analyzed by GLC using a nitrogen-sensitive detector. Quantitation is accomplished using an internal standard and a standard curve, which was linear over the 0.1-10-mug range. The limit of detection was approximately 10 ng/ml. Recovery of the parent compound was essentially quantitative. Plasma data are presented to demonstrate the utility of the method.


Intracellular calcium regulation in inner hair cells from neonatal mice.
The mechanisms that regulate the concentration of ionized intracellular calcium (Ca(2+)(i)) in the base of neonatal mouse inner hair cells, close to synaptic sites, were investigated using confocal microscopy combined with conventional patch-clamp electrophysiology. Cells were depolarized under whole-cell voltage clamp to load the cell with C a(2+) through voltage-activated Ca(2+) channels. Repeated depolarizations produced Ca(2+)(i) increases with similar amplitudes and time-courses of recovery. The rate of recovery from depolarization-induced Ca(2+)(i) loads was used to assess the mechanisms responsible for Ca(2+)(i) regulation. Removal of extracellular sodium had no effect on resting Ca(2+)(i) or the rate of recovery of Ca(2+)(i) suggesting no role for Na:Ca exchange in these cells. Inhibitors of intracellular store uptake such as thapsigargin, 2,5-di(tert-butyl)hydroquinone (BHQ) and cyclopiazonic acid (CPA) caused an increase in resting Ca(2+)(i) and slowed the rate of recovery, indicating that Ca(2+) can be taken up intracellularly. However, 5mM caffeine failed to cause a detectable release of Ca(2+) from intracellular stores. FCCP, a mitochondrial inhibitor, slowed the rate of recovery from Ca(2+)(i) loads, indicating a role for mitochondrial Ca(2+) uptake. The largest effects were seen with intracellular vanadate (1mM) which caused an irreversible rise in resting Ca(2+)(i) and depolarization-induced increases in Ca(2+)(i) failed to recover fully. Together, these data indicate that both thapsigargin-sensitive stores and mitochondria can take up Ca(2+)(i), but that Ca(2+) efflux from the cell occurs solely via a plasma membrane Ca(2+)-ATPase.


Identification of Plasma Inflammatory Markers of Adolescent Depression Using the Olink Proteomics Platform.
The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression. In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA). We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=-0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735-0.904). We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.


Molecular orientation and the infrared dichroism of a chiral smectic liquid crystal in a homogeneously aligned cell at different temperature and bias fields.
The molecular orientation and the dichroic behavior of the vibrational bands of a homogeneously aligned helical cell containing chiral smectic liquid crystal (R)-(-)-1-methylheptyl 4-(4(')-dodecyloxybiphenyl-4-ylcarbonyloxy)-3-fluorobenzoate are studied at various temperatures as a function of the bias field. These temperatures correspond to the various phase states of the sample at zero field. For those bands that exhibit significant dichroism, the field dependencies of the dichroic parameters (the dichroic ratio and the polarization angle of maximum absorbance) are found to be dependent on temperature, phase state, and helical unwinding. For the SmA* and SmC(*)(alpha) phases, the phenyl band dichroic ratio and the corresponding orientational order parameter are found to be almost independent of the bias field. The temperature dependence of the orientational order for zero field is discussed by taking into account the structures of the phases and the molecular tilt angles. The field dependencies of the phenyl band dichroic parameters for the SmC(*)(A) and SmC(*)(gamma) phases yield results about the distribution of directors in the layers of their unit cells and the state of helical unwinding. The azimuthal orientational distribution function of the carbonyl transition moments with respect to the long molecular axis has been determined. It is found that the degrees of the polar and quadrupolar biasing increase with decrease in temperature and the azimuthal biasing angle for the chiral carbonyl group increases significantly with a reduction in temperature.


Practical Considerations When Performing Neurodiagnostic Studies on Patients with COVID-19 and Other Highly Virulent Diseases.
The coronavirus disease 2019, SARS-COV-2 (the cause of COVID-19), has led to a worldwide shortage of personal protective equipment (PPE) and an increased stress on hospital resources, which has resulted in a spike in the anxiety of the frontline healthcare workers. News reports and information about the virus are rapidly changing. We present a case of a patient with COVID-19 who had a seizure-like spell for which an EEG was performed. In early to mid-March, there were no clear guidelines or recommendations available from neurodiagnostic-related organizations or hospitals on how to adapt procedure workflow to those with COVID-19. When caring for COVID-19 patients, as when caring for any patient with an infectious disease, it is hospital protocol to follow contact, droplet/airborne precautions by wearing appropriate PPE. However, because we knew very little about the coronavirus, this case was different. In this article, we discuss our experience with our EEG workflow and concerns for staff exposure. We then discuss our adaptations and modifications to our standard procedures and protocols. A time analysis comparing our standard EEG protocol with our modified COVID-19 protocol revealed a significant decrease in technologist exposure time (99 minutes versus 51 minutes), which theoretically would reduce the chance of virus transmission to our technologist. At this critical moment in time, we hope such modifications will allow us to continue delivering high quality patient care while optimizing resource utilization and above all keeping our technologists safe.


Oral pemphigus vulgaris: clinicopathologic study of 20 cases.
Pemphigus vulgaris (PV) is a vesiculobullous lesion that produces intraepithelial blisters in skin and mucous membrane. The oral mucosa is often the first site to be affected by the disease. Although oral PVis a well characterized condition, the detailed clinical and histopathological study in Malabar population has not been reported. A clinicopathologic study of 20 cases of oral PV observed over a span of 2 years from January 2004 to January 2006 is reported. For these 20 cases, the mean age was 42.3 years and male:female ratio was 2:3. The most commonly affected sites were the buccal mucosa and palate. Histopathologic examination with direct immunofluorescence was the method of diagnosis in all cases. Suprabasilar clefting with acantholytic cells can be seen histopathologically and IgG positivity in direct immunofluorescence in all cases that have been studied.


Gastroprotective Activity of Neoglaziovia variegata (Arruda) Mez. (Bromeliaceae) in Rats and Mice.
Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) is a medicinal plant popularly known as "caroá." The leaves are made up of highly resistant fibers, which is of great commercial value to the handicraft and textile industry. Some studies have demonstrated that ethanolic extract of N. variegata have gastroprotective properties. This study aimed to investigate the gastroprotective activity and cytoprotective mechanisms of ethyl acetate (Nv-AcOEt), hexane (Nv-Hex), and chloroform (Nv-CHCl3) fractions of N. variegata leaves. The gastroprotective activity of Nv-AcOEt, Nv-Hex, and Nv-CHCl3 was evaluated using the ethanol and ethanol/HCl-induced gastric injury model. To elucidate the gastroprotective mechanisms, the functions of prostaglandins (PGs), nitric oxide (NO), and KATP channels were evaluated. In addition, the nonprotein sulfhydryl groups and the mucus content in the gastric tissues were analyzed. All fractions of N. variegata leaves at oral doses of 100, 200, and 400 mg/kg significantly decreased ethanol and ethanol/HCl-induced gastric lesions, leading to gastroprotection, accompanied by an increase in reduced glutathione (GSH) and gastric mucus. Gastroprotective activity of Nv-AcOEt was inhibited after pretreatment with ibuprofen and N(G)-nitro-L-arginine (L-NOARG). Gastroprotective effect of Nv-Hex and Nv-CHCl3 was also inhibited after pretreatment with L-NOARG and with glibenclamide. The results indicate that N. variegata (Arruda) Mez exhibits promising gastroprotective activity with the possible participation of NO, PGs, mucus, sulfhydryl groups, and KATP.


Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system. I. Sensitivity and specificity, comparison with other markers.
UGF is a mixture of human chorionic gonadotropin free beta-subunit and its fragments, and is detected in pregnancy and trophoblast disease urines. An examination of 67 nonpregnant cancer-free women showed average urine levels of 0.13 ng/ml. Six of the 67 (8.9%) had levels exceeding a selected cutoff value, 0.2 ng/ml. Of 112 woman with active gynecologic cancer, 72 (64%) had urine UGF levels exceeding this cutoff value. When urines were limited to those with creatinine greater than 0.5 mg/ml, or to first morning samples (mean creatinine 1.0 ng/ml), the sensitivity of UGF for all gynecologic cancers was raised to 76%. The sensitivity of UGF for cervical (73%), for endometrial (65%), and for ovarian (83%) cancers exceeded that of plasma CA 125 and lipid-associated sialic acid in plasma (LASA) in the same population. UGF is an exciting new tumor marker which warrants further evaluation.


Post concussion syndrome: brainstem seizures, a case report.
Following head injury and associated unconsciousness, a 19 year old woman developed chronic intractable headaches, absence attacks and a cluster of other symptoms which did not respond to conventional medical therapy. During the course of implanting a brain stimulation electrode for the treatment of chronic and recurring incapacitating headaches, diagnostic electrographic recordings revealed focal abnormal discharges in the mesothalamus. Electrical stimulation attenuated the discharges and alleviated the headaches and associated symptoms. A retrospective analysis of this case suggested that a head injury-induced brain stem gliosis was the source of the brainstem abnormal discharges. It is speculated that various biologic systems represented within the brainstem were implicated by the reticular formation generated discharges. Symptoms making up the chronic pain syndrome were thus thought to emanate from the electric malfunctioning of those biologic systems.


Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays.
The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe. We evaluated and compared the clinical performance of the two assays in 426 patients with newly diagnosed AL amyloidosis. We found suboptimal agreement between the two methods, with differences between values obtained with the Freelite and N latex FLC assays increasing with the concentration of clonal FLC. The diagnostic sensitivity of the Freelite (82%) and N latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. The concentration of FLC measured with both methods had prognostic significance. Less pronounced decreases in FLC best predicted improved survival with the N latex FLC assay (33% vs. 50%), and there was poor concordance (84%) in discrimination of responders. The two assays have similar diagnostic and prognostic performance. However, they are not interchangeable, and follow-up should be done with either one. New response criteria are needed for the N latex FLC assay.


Hole-transport materials with greatly-differing redox potentials give efficient TiO2-[CH3NH3][PbX3] perovskite solar cells.
Two diacetylide-triphenylamine hole-transport materials (HTM) with varying redox potential have been applied in planar junction TiO2-[CH3NH3]PbI3-xClx solar cells leading to high power-conversion efficiencies up to 8.8%. More positive oxidation potential of the HTM gives higher VOC and lower JSC illustrating the role of matching energy levels, however both HTMs gave efficient cells despite a difference of 0.44 V in their redox potentials.


Global burden of new-onset hypertension associated with severe acute respiratory syndrome coronavirus 2 infection.
Several reports documented a specific effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on blood pressure (BP), during and after the acute phase of infection. Clinical studies demonstrated that coronavirus disease 2019 (COVID-19) is associated with an increased risk of a persistent increase in BP requiring a new or intensified anti-hypertensive treatment during hospitalization. The picture is further complicated by the evidence from large databases showing an increased risk of new-onset hypertension in COVID-19 survivors on the long term. To further elucidate the epidemiological burden of this phenomenon, we performed a pooled analysis of 4 studies reporting crude incidence rates of new-onset hypertension among COVID-19 patients and contemporary controls. Overall, COVID-19 was associated with a 65% increased risk of new-onset hypertension when compared with controls (p<0.0001); furthermore, incidence of new-onset hypertension was 9% and 5% among COVID-19 patients and controls, respectively. In both the acute phase and recovery from infection, the interaction between spike proteins of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) receptors remain the most plausible mechanism explaining the raise in BP (ranking new onset hypertension as one of the most prevalent cardiovascular sequelae of COVID-19). In this area of research, it is worth to mention that new variants of SARS-CoV-2 exhibit specific mutations in the spike protein that promotes entry into viral cells via ACE2. Thus, the enhanced spike affinity for ACE2 of new variants has the potential to increase the risk of new-onset hypertension when compared with the original Wuhan strain.


Quantifying the Establishment Likelihood of Invasive Alien Species Introductions Through Ports with Application to Honeybees in Australia.
The cost of an uncontrolled incursion of invasive alien species (IAS) arising from undetected entry through ports can be substantial, and knowledge of port-specific risks is needed to help allocate limited surveillance resources. Quantifying the establishment likelihood of such an incursion requires quantifying the ability of a species to enter, establish, and spread. Estimation of the approach rate of IAS into ports provides a measure of likelihood of entry. Data on the approach rate of IAS are typically sparse, and the combinations of risk factors relating to country of origin and port of arrival diverse. This presents challenges to making formal statistical inference on establishment likelihood. Here we demonstrate how these challenges can be overcome with judicious use of mixed-effects models when estimating the incursion likelihood into Australia of the European (Apis mellifera) and Asian (A. cerana) honeybees, along with the invasive parasites of biosecurity concern they host (e.g., Varroa destructor). Our results demonstrate how skewed the establishment likelihood is, with one-tenth of the ports accounting for 80% or more of the likelihood for both species. These results have been utilized by biosecurity agencies in the allocation of resources to the surveillance of maritime ports.


Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?
The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Treatment plans (n = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.


Temperature performance of a macrobending single-mode fiber-based refractometer.
We present, theoretically and experimentally, an investigation of temperature dependence of a macrobending single-mode fiber-based refractometer utilizing a ratiometric scheme. The conventional scalar approximation method is utilized for predicting the temperature dependent loss of the proposed fiber refractometer. An all-fiber ratiometric measurement system is built to allow the comparison of modeled and measured results. Calculated and measured results for an SMF28 refractometer are in good agreement and confirm the effect of temperature on refractive index measurements. Both calculated and measured ratio responses monotonically change with temperature, which allows for a temperature correction process.


Facile Homobifunctional Imidoester Modification of Advanced Nanomaterials for Enhanced Antibiotic Synergistic Effect.
Resistance to antibiotics because of misuse and overuse is one of the greatest public health challenges worldwide. Despite the introduction of advanced nanotechnology in the production of antibiotics, the choice of appropriate medicines is limited due to side effects such as blood coagulation, toxicity, low efficacy, and low biocompatibility; therefore, novel nanomaterial composites are required to counter these repercussions. We first introduce a facile method for synthesizing a homobifunctional imidoester-coated nanospindle (HINS) zinc oxide composite for enhancement of antibiotic efficacy and reduction of toxicity and blood coagulation. The antibiotic efficacy of the composites is twice that of commercialized zinc nanoparticles; in addition, they have good biocompatibility, have increased surface charge and solubility owing to the covalent acylation groups of HI, and produce a large number of Zn+ ions and defensive reactive oxygen species (ROS) that effectively kill bacteria and fungi. The synergistic effect of a combination therapy with the HINS composite and itraconazole shows more than 90% destruction of fungi in treatments with low dosage with no cytotoxicity or coagulation evident in intravenous administration in in vitro and in vivo experiments. Thus, HINS composites are useful in reducing the effect of misuse and overuse of antibiotics in the medical field.


A Novel Role for MiR-520a-3p in Regulating EGFR Expression in Colorectal Cancer.
MicroRNAs (miRNAs) have been consistently demonstrated to be involved in colorectal cancer as either tumour oncogenes or tumour suppressors. However, the detailed role of miR-520a-3p in colorectal cancer remains poorly understood. Quantitative RT-PCR and western blotting assays were used to measure miR-520a-3p and EGFR expression levels in colorectal cancer tissues, respectively. Luciferase reporter assay was employed to validate the direct targeting of EGFR by miR-520a-3p. Cell migration, apoptosis and cell cycle assays were performed to analyse the biological functions of miR-520a-3p and EGFR in colorectal cancer cells. In vivo experiment was performed to analyse the effects of miR-520a-3p and EGFR on the growth of colorectal cancer xenografts in mice. In this study, we found that miR-520a-3p was most likely to target the EGFR 3'-UTR, which was experimentally validated. In addition, we investigated the biological effects of EGFR inhibition by miR-520a-3p both in vitro and In vivo and found that miR-520a-3p could suppress cell migration, promote apoptosis, lead to colorectal cancer cell cycle arrest at the G0/G1 phase, and decelerate tumour growth in xenograft mice, potentially by targeting EGFR. This study highlights a tumour suppressor role for miR-520a-3p in colorectal cancer via the regulation of EGFR expression. Thus, miR-520a-3p may be a novel molecular therapeutic target for colorectal cancer.


Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates.
Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure; it has a high mortality rate. Although a number of studies have attempted to determine the crucial factors behind the onset of STSS, the responsible genes in group A Streptococcus have not been clarified. We previously reported that mutations of csrS/csrR genes, a two-component negative regulator system for multiple virulence genes of Streptococcus pyogenes, are found among the isolates from STSS patients. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models, similar to the csrS mutants, and precluded their being killed by human neutrophils, mainly due to an overproduction of SLO. When we assessed the mutation frequency of csrS, csrR, and rgg genes among S. pyogenes isolates from STSS (164 isolates) and non-invasive infections (59 isolates), 57.3% of the STSS isolates had mutations of one or more genes among three genes, while isolates from patients with non-invasive disease had significantly fewer mutations in these genes (1.7%). The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors.


[Exploring correlation between molecular state and nanofiltration mass transfer process of synephrine from Citrus aurantium].
Based on the solution-diffusion effect and the charge effect theory in nanofiltration separation, the correlation between initial concentration and mass transfer coefficient was constructed to establish a mathematic model of synephrine in mass transfer process and verify its applicability. The experimental results showed that there was a linear relationship between operation pressure and membrane flux. Meanwhile, the membrane flux was gradually decayed with the increase of solute concentration. Besides, mass transfer coefficient and initial concentration of synephrine showed power function correlation with each other by solution-diffusion effect and the charge effect, and the regression coefficients were greater than 0.9. The mass transfer coefficient of dissociation synephrine was less than that in the state of free and free-dissociation. Moreover, on the basis of power function relationship between mass transfer coefficient and initial concentration, the results showed that the predicted rejections of synephrine from Citrus aurantium water extract by use of the mathematical model approximated well to real ones, verifying that the model was practical and feasible. The unclear separation mechanism of nanofiltration for alkaloids was clarified preliminary by the predicted model of nanofiltration separation with synephrine as the example, providing theoretical and technical support for nanofiltration separation, especially for traditional Chinese medicine with alkaloids.