Analysis of the Current Status and Factors Influencing Compliance with Colonoscopic Monitoring After Endoscopic Surgery for Advanced Colorectal Adenoma.
Advanced colorectal adenomas are at a risk of malignant transformation following endoscopic resection, and colonoscopic monitoring interval after polypectomy have been widely used. This study aims to investigate the prevailing state of compliance with postoperative colonoscopic surveillance among patients with advanced colorectal adenomas and its' influencing factors at Affiliated Hospital of Jiangnan University between November 2020 and April 2021. A retrospective analysis was conducted on patients who underwent endoscopic treatment for ACA at Affiliated Hospital of Jiangnan University from November 2020 to April 2021. Compliance with postoperative colonoscopic surveillance was assessed based on established guidelines. Factors such as sociodemographic features, medical histories, and health beliefs were analyzed to determine their influence on compliance. Univariate analysis, survival analysis, and multi-factor Cox regression analysis were used for statistical evaluation. A total of 511 patients were included in the study. The compliance rate was found to be 43.2%. The univariate analysis indicated that factors such as gender, education level, work status, type of health insurance, place of residence, marital status, type of consultation, presence of gastrointestinal symptoms, number of polyps, and the maximum diameter of polyps significantly affected compliance. Multi-factor Cox regression analysis revealed that female gender, absence of gastrointestinal symptoms, outpatient endoscopic treatment, and solitary polyps were independent factors influencing compliance. Reasons for poor compliance included underestimating the severity of the disease, fear of colonoscopy, and procedural complexities. Patients with advanced colorectal adenomas had poor compliance with postoperative colonoscopy monitoring. Tailored health education programs should be designed, targeting women, outpatients undergoing endoscopic procedures, and patients with solitary polyps to enhance their compliance with colonoscopy monitoring.


Practice parameters for the management of anal fissure. The Standards Task Force American Society of Colon and Rectal Surgeons.
It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.


Characterization and evolution of MHC class II B genes in Ardeid birds.
Major histocompatibility complex (MHC) is a multi-gene family that is very suitable to investigate a wide range of open questions in evolutionary ecology. In this study, we characterized two expressed MHC class II B genes (DAB1 and DAB2) in the Grey Heron (Aves: Ardea cinerea). We further developed the primer pairs to amplify and sequence two MHC class II B loci in ten ardeid birds. Phylogenetic analysis revealed that different parts of the genes showed different evolutionary patterns. The exon 2 sequences tended to cluster two gene-specific lineages. In each lineage, exon 2 sequences from several species showed closer relationships than sequences within species, and two shared identical alleles were found between species (Egretta sacra and Nycticorax nycticorax; Egretta garzetta and Bubulcus ibis), supporting the hypothesis of trans-species polymorphism. In contrast, the species-specific intron 2 plus partial exon 3 tree suggested that DAB1 and DAB2 were subject to concerted evolution. GENECONV analyses showed the gene exchange played an important role in the ardeid MHC evolution.


Multicavity halloysite-amphiphilic cyclodextrin hybrids for co-delivery of natural drugs into thyroid cancer cells.
Multicavity halloysite nanotube materials were employed as simultaneous carriers for two different natural drugs, silibinin and quercetin, at 6.1% and 2.2% drug loadings, respectively. The materials were obtained by grafting functionalized amphiphilic cyclodextrin onto the HNT external surface. The new materials were characterized by FT-IR spectroscopy, SEM, thermogravimetry, turbidimetry, dynamic light scattering and ζ-potential techniques. The interaction of the two molecules with the carrier was studied by HPLC measurements and fluorescence spectroscopy, respectively. The release of the drugs from HNT-amphiphilic cyclodextrin, at two different pH values, was also investigated by means of UV-vis spectroscopy. Biological assays showed that the new complex exhibits anti-proliferative activity against human anaplastic thyroid cancer cell lines 8505C. Furthermore, fluorescence microscopy was used to evaluate whether the carrier was uptaken into 8505C thyroid cancer cell lines. The successful results revealed that the synthesized multicavity system is a material of suitable size to transport drugs into living cells.


[Enzyme-and immuno-histochemistry of muscle biopsies in severe infantile spinal muscular atrophy].
The basic lesions in the muscle biopsies of 11 cases of severe infantile spinal muscular atrophy showed typical neurogenic fascicular muscular atrophy. It was found through histochemistry staining that both types of muscle fibres were involved which were characterised by the presence of type grouping of the damaged fibers, anyhow, the original mosaic pattern of both types were still partially reserved. With anti-laminin immunofluorescence staining, it was demonstrated that the basal membrane of atrophied small muscle fibre was still intact. It is considered that the main manifestation of damage on spinal anterior horn neuron is denervation of the skeletal muscle; meanwhile, the function of the muscle fibre in regulations carbohydrate metabolism is not apparently obstructs. The pathologic process of this disease develops from denervation to renervation and then back to denervation again. Therefore the clinical feature of muscle atrophy in this disease is progressive and developmental.


A new method for evaluating ankle foot orthosis characteristics: BRUCE.
The mechanical characteristics of ankle foot orthoses (AFOs), such as the stiffness and neutral angle around the ankle and metatarsal-phalangeal (MTP) joints, are rarely quantified. Paradoxically, it is expected that these characteristics determine the function of the AFO in pathological gait. Therefore a device to determine these AFO characteristics named BRUCE was designed based on multidisciplinary consensus. The design is based on a replicated human leg that is manually driven and continuously registers joint configuration and force exerted by the AFO onto the device. From this information, neutral angles and stiffnesses around the ankle and MTP joints are determined using a linear fit. The reliability of the stiffnesses and neutral angles was studied by repeatedly measuring the mechanical characteristics of four different AFOs, and evaluating the inter-session, intra-session, and inter-observer errors. The reliability study revealed that ankle and MTP stiffness could be measured with very high reliability (ICC=0.98-1.00). Ankle and MTP neutral angles showed reasonable reliability (ICC=0.79-0.92). Measurement error in the neutral angles could mainly be attributed to the difference in testers. With a fixed tester excellent reliability was obtained (ICC=0.99-0.99). The results derived using BRUCE can help to gain insight into the role of the mechanical characteristics of AFOs in correcting pathological gait. Objective information of AFO characteristics is expected to lead to a better founded prescription of AFOs, resulting in optimal functional benefit for the patient.


Cigarette smoke inhalation potentiates elastase-induced emphysema in hamsters.
Cigarette smoke is shown, in this study, to potentiate emphysema induced by intratracheal administration of elastase, whereas elastase alone caused minimal disease. Elastase-treated hamsters with prior or ongoing smoke exposure uniformly had severe emphysema with decreases in lung elastic recoil and increases in mean linear intercept (Lm). In contrast, hamsters receiving elastase alone, cigarette smoke alone, or postelastase cigarette smoke developed no or barely detectable histopathologic evidence of emphysema. Lungs from these animals had normal elastic recoil and Lm. These data support the idea that cigarette smoke exposure may unmask or amplify protease-induced emphysema caused by acute lung injury.


Safer-by-design flame-sprayed silicon dioxide nanoparticles: the role of silanol content on ROS generation, surface activity and cytotoxicity.
Amorphous silica nanoparticles (SiO2 NPs) have been regarded as relatively benign nanomaterials, however, this widely held opinion has been questioned in recent years by several reports on in vitro and in vivo toxicity. Surface chemistry, more specifically the surface silanol content, has been identified as an important toxicity modulator for SiO2 NPs. Here, quantitative relationships between the silanol content on SiO2 NPs, free radical generation and toxicity have been identified, with the purpose of synthesizing safer-by-design fumed silica nanoparticles. Consistent and statistically significant trends were seen between the total silanol content, cell membrane damage, and cell viability, but not with intracellular reactive oxygen species (ROS), in the macrophages RAW264.7. SiO2 NPs with lower total silanol content exhibited larger adverse cellular effects. The SAEC epithelial cell line did not show any sign of toxicity by any of the nanoparticles. Free radical generation and surface reactivity of these nanoparticles were also influenced by the temperature of combustion and total silanol content. Surface silanol content plays an important role in cellular toxicity and surface reactivity, although it might not be the sole factor influencing fumed silica NP toxicity. It was demonstrated that synthesis conditions for SiO2 NPs influence the type and quantity of free radicals, oxidative stress, nanoparticle interaction with the biological milieu they come in contact with, and determine the specific mechanisms of toxicity. We demonstrate here that it is possible to produce much less toxic fumed silicas by modulating the synthesis conditions.


Hypergastrinemia.
Gastrin is an important hormone of the digestive system, which assists gastric acid secretion. It may be pathologically elevated in conditions such as Zollinger-Ellison syndrome, or due to common medications such as proton pump inhibitors. In this review we provide an overview of the pathophysiology and medical causes of hypergastrinemia, diagnostic testing and clinical consequences of chronic hypergastrinemia.


[Changes in the cerebral hemodynamics under the influence of piracetam and fenibut during motion sickness].
In the experiments on conscious rabbits with the electrodes implanted in the brain it was found by the methods of hydrogen clearance and polarography that piracetam (50 and 500 mg/kg) and phenibut (50 mg/kg) induced a decrease of the local blood flow in the cortex of the frontal, temporal and occipital regions and the total cerebral blood flow. The administration of the drugs before tilting prevents the occurrence of vasodilatation in the brain and results in a decrease of the blood flow in the cortex and in the confluence of the cerebral venous sinuses that is thought to be connected with the mechanism of an increase of the vestibular stability under the influence of GABA derivatives.


[ACE inhibitors versus AR II antagonists. Their role in arterial hypertension].
The A II antagonists (RA II antagonists) are a new group of anti-hypertensive drugs with five years of clinical use. They were investigated after the knowledge of independent ways to get angiotensin II. They block AT1 receptor. It's possible that, after AT1 block, the high plasmatic levels of AII stimulate the AT2 receptors with vasodilation and anti-proliferative activity. We are waiting for the results of several big prospective studies with RA II antagonists on cardiovascular morbidity and mortality. At present time, the first indication for its use is the appearance of cough when taking ACE inhibitors. The association of ACE inhibitors and RA II antagonists can improve some clinical conditions like dilated hypertensive cardiopathy, nephropathy or refractory hypertension.


The management of coronavirus infections with particular reference to SARS.
The human coronaviruses (HCoV) OC43 and 229E are common causes of upper respiratory tract infections. Severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (SARS)-CoV in 2003. Since then, other novel CoV (NL63 and HKU1) have been described, and they have caused respiratory infections worldwide. Potentially exposed laboratory workers or animal handlers with rapidly progressive pneumonia not responding to standard antibacterial coverage must be isolated with contact and droplet, and for specific situations, airborne precautions, till rapid tests of respiratory and faecal samples are negative for SARS-CoV. Generally, the viral loads collected at different anatomical sites correlate with the severity of symptoms and mortality. Shedding of SARS-CoV peaks at day 10 after the onset of symptoms, which theoretically allows ample time for antiviral treatment. The disease is characterized by uncontrolled replication of the virus and a prominent pro-inflammatory response. No randomized controlled trials with a specific anti-coronavirus agent have been conducted with respect to therapy or prophylaxis. Reports using historical matched controls have suggested that treatment with interferon alfacon-1 (a synthetic interferon) combined with steroid, protease inhibitors together with ribavirin, or convalescent plasma containing neutralizing antibody, could be useful. Prophylaxis with interferon or hyperimmune globulin may be considered for unprotected exposure. The role of immunomodulators to decrease excessive inflammation remains elusive. Other non-SARS-CoV infections are generally milder in immunocompetent hosts, and scientific data on antiviral treatment of these viruses are scarce.


Subglottic foreign bodies in pediatric patients.
Impacted subglottic foreign bodies may produce upper airway obstruction and clinical signs simulating croup or asthma. We identified the roentgenologic and clinical features in six patients. In four of these patients, the parent had not observed the aspiration episode, so that the diagnosis was delayed. Roentgenologic studies demonstrated subglottic narrowing of the upper airway with a homogeneous, poorly defined radiodensity within the narrowed segment. These roentgenologic studies are usually diagnostic; therefore, if infants or young children present with stridor of undetermined cause, soft-tissue upper airway roentgenography is indicated.


Interleukin 22 mitigates endothelial glycocalyx shedding after lipopolysaccharide injury.
The endothelial glycocalyx (EG) on the luminal surface of endothelial cells contributes to the permeability barrier of vessels and prevents activation of the coagulation cascade. Endothelial glycocalyx damage, which occurs in the shock state, results in endotheliopathy. Interleukin (IL)-22 is a cytokine with both proinflammatory and anti-inflammatory properties, and how IL-22 affects the EG has not been studied. We hypothesized that IL-22:Fc, a recombinant fusion protein with human IL-22 and the Fc portion of human immunoglobulin G1 (which extends the protein half-life), would not affect EG shedding in endothelium after injury. Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). Lipopolysaccharide-injured cells (n = 284) were compared with HUVECs with LPS injury plus 0.375 μg/mL of IL-22:Fc treatment (n = 293) for 12 hours. These two cohorts were compared with control HUVECs (n = 286) and HUVECs exposed to IL-22:Fc alone (n = 269). Cells were fixed and stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify EG. Total RNA was collected, and select messenger RNAs were quantified by real time - quantitative polymerase chain reaction (RT-qPCR) using SYBR green fluorescence. Exposure of HUVECs to LPS resulted in degradation of the EG compared with control (5.86 vs. 6.09 arbitrary unit [AU], p = 0.01). Interleukin-22:Fc alone also resulted in degradation of EG (5.08 vs. 6.09 AU, p = 0.01). Treatment with IL-22:Fc after LPS injury resulted in less degradation of EG compared with LPS injury alone (5.86 vs. 5.08 AU, p = 0.002). Expression of the IL-22Ra1 receptor was not different for IL-22:Fc treated compared with LPS injury only (0.69 vs. 0.86 relative expression, p = 0.10). Treatment with IL-22:Fc after LPS injury resulted in less matrix metalloproteinase 2 (0.79 vs. 1.70 relative expression, p = 0.005) and matrix metalloproteinase 14 (0.94 vs. 2.04 relative expression, p = 0.02). Interleukin-22:Fc alone induces EG degradation. However, IL-22:Fc treatment after LPS injury appears to mitigate EG degradation. This protective effect appears to be mediated via reduced expression of metalloproteinases.


[Assessment of the degree of disability in narcolepsy].
This article sums up the scientific results of the past 10 years on narcolepsy reflecting its impact on socio-medical impairment of narcoleptic patients. Extensive epidemiological studies showed that major restrictions for narcolepsy patients are caused by daytime sleepiness and sleep attacks with consecutive cognitive and memory deficits high accident rates, personality, mood and sexual disorders. We suggest the minimum degree of impairment as a rule should be at least 50%, in case of drug-resistant cataplexy or permanent sleep attacks around 80%.


CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation.
Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (Kiapp=8.6 μm). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time.


Electricity generation and pollutant degradation using a novel biocathode coupled photoelectrochemical cell.
The photoelectrochemical cell (PEC) is a promising tool for the degradation of organic pollutants and simultaneous electricity recovery, however, current cathode catalysts suffer from high costs and short service lives. Herein, we present a novel biocathode coupled PEC (Bio-PEC) integrating the advantages of photocatalytic anode and biocathode. Electrochemical anodized TiO2 nanotube arrays fabricated on Ti substrate were used as Bio-PEC anodes. Field-emission scanning electron microscope images revealed that the well-aligned TiO2 nanotubes had inner diameters of 60-100 nm and wall-thicknesses of about 5 nm. Linear sweep voltammetry presented the pronounced photocurrent output (325 μA/cm(2)) under xenon illumination, compared with that under dark conditions. Comparing studies were carried out between the Bio-PEC and PECs with Pt/C cathodes. The results showed that the performance of Pt/C cathodes was closely related with the structure and Pt/C loading amounts of cathodes, while the Bio-PEC achieved similar methyl orange (MO) decoloration rate (0.0120 min(-1)) and maximum power density (211.32 mW/m(2)) to the brush cathode PEC with 50 mg Pt/C loading (Brush-PEC, 50 mg). The fill factors of Bio-PEC and Brush-PEC (50 mg) were 39.87% and 43.06%, respectively. The charge transfer resistance of biocathode was 13.10 Ω, larger than the brush cathode with 50 mg Pt/C (10.68 Ω), but smaller than the brush cathode with 35 mg Pt/C (18.35 Ω), indicating the comparable catalytic activity with Pt/C catalyst. The biocathode was more dependent on the nutrient diffusion, such as nitrogen and inorganic carbon, thus resulting in relatively higher diffusion resistance compared to the brush cathode with 50 mg Pt/C loading that yielded similar MO removal and power output. Considering the performance and cost of PEC system, the biocathode was a promising alternative for the Pt/C catalyst.


Contrast between Spain and the Netherlands in the hidden obstacles to re-entry into the labour market due to a criminal record.
This article aims at analysing the differences between European countries in the obstacles ex-offenders face due to having a criminal record. First, a comparative analytical framework is introduced that takes into account all the different elements that can lead to exclusion from the labour market by the dissemination of criminal record information. This model brings together social norms (macro level), social actors (meso level) and individual choices (micro level) in the same framework. Secondly, this model is used to compare the different impact of having a criminal record in Spain and the Netherlands. This comparison highlights three important findings: (1) the difference between norms of transparency/privacy and inclusive/exclusive ideals, (2) the significant role of social control agents, such as probation agencies and the ex-offenders' social network, in shaping the opportunities that they have, and (3) self-exclusion seems to be a key mechanism for understanding unsuccessful re-entry into the labour market.


[Nutrition and oral health].
Diet plays a key role in oral disease prevention. The aims of this report were to review the causes and consequences of a poor diet and its interrelationship with oral health. The first signs of micronutrient deficiencies are often manifest in the oral tissues. Consequently, the dentist has a considerable role in the early diagnosis of malnutrition. Furthermore, optimizing oral health is important in maximizing functional capacity to consume a healthful and varied diet. A varied diet is, otherwise, fundamental to save oral health.


Functional characterization of the vertebrate primary ureter: structure and ion transport mechanisms of the pronephric duct in axolotl larvae (Amphibia).
Three kidney systems appear during vertebrate development: the pronephroi, mesonephroi and metanephroi. The pronephric duct is the first or primary ureter of these kidney systems. Its role as a key player in the induction of nephrogenic mesenchyme is well established. Here we investigate whether the duct is involved in urine modification using larvae of the freshwater amphibian Ambystoma mexicanum (axolotl) as model. We investigated structural as well as physiological properties of the pronephric duct. The key elements of our methodology were: using histology, light and transmission electron microscopy as well as confocal laser scanning microscopy on fixed tissue and applying the microperfusion technique on isolated pronephric ducts in combination with single cell microelectrode impalements. Our data show that the fully differentiated pronephric duct is composed of a single layered epithelium consisting of one cell type comparable to the principal cell of the renal collecting duct system. The cells are characterized by a prominent basolateral labyrinth and a relatively smooth apical surface with one central cilium. Cellular impalements demonstrate the presence of apical Na+ and K+ conductances, as well as a large K+ conductance in the basolateral cell membrane. Immunolabeling experiments indicate heavy expression of Na+/K+-ATPase in the basolateral labyrinth. We propose that the pronephric duct is important for the subsequent modification of urine produced by the pronephros. Our results indicate that it reabsorbs sodium and secretes potassium via channels present in the apical cell membrane with the driving force for ion movement provided by the Na+/K+ pump. This is to our knowledge the first characterization of the pronephric duct, the precursor of the collecting duct system, which provides a model of cell structure and basic mechanisms for ion transport. Such information may be important in understanding the evolution of vertebrate kidney systems and human diseases associated with congenital malformations.


Simultaneously tuning the luminescent color and realizing an optical temperature sensor by negative thermal expansion in Sc2(WO4)3:Tb/Eu phosphors.
At present, many researchers are focusing on trivalent lanthanide (Ln3+)-doped thermally enhanced upconversion luminescent (UCL) materials with negative thermal expansion (NTE) properties. However, selective anti-thermal quenching downshifting emissions of the activator and thermal quenching of the sensitizer in a phosphor with NTE properties are not implemented. Herein, Tb3+/Eu3+ co-doped Sc2(WO4)3 phosphors synthesized by the solid-state method are explored in selectively enhanced red emission (Eu3+:5D0 → 7F2) due to the energy-transfer efficiency from Tb3+ to Eu3+ and the promoted radiative transition probability. The selective thermally quenched green emission (Tb3+:5D4 → 7F5) is owing to the change of energy transfer from Tb3+ to Eu3+ as the temperature increased. Moreover, under ultraviolet 365 nm excitation, the thermally stimulated color emission tuned from yellow to red with the increase in temperature. Based on the radically different thermal response downshifting the luminescence of the activator and sensitizer, the luminescence intensity ratio (LIR) of non-thermally coupled levels (NTCLs) for 5D0 (Eu3+) and 5D4 (Tb3+) is adopted for optical temperature sensing. The optimal relative sensitivity of temperature sensing in the Sc2(WO4)3:25%Tb3+/3%Eu3+ sample could reach 2.94% K-1 at 347 K. All these indicate that this Sc2(WO4)3:Tb3+/Eu3+ material is a promising candidate for high-sensitivity optical temperature sensing.


Employer-sponsored insurance coverage for alcohol and drug abuse treatment, 1988.
This paper uses 1988 Bureau of Labor Statistics data to analyze the content of insurance coverage for alcohol and drug abuse treatment offered by medium and large private sector firms. Ninety percent of workers had medical insurance. Of these, 81% had coverage for alcohol abuse treatment and 75.5% had coverage for drug abuse treatment. The coverages were almost always offered together, and the benefits were generally identical for both. Coverage for inpatient detoxification was most common, followed by outpatient care and inpatient rehabilitation. Self-insured plans, although exempt from state-mandated benefits, were as likely to include alcohol and drug abuse coverage as Blue Cross and Blue Shield and commercial plans, and their specific benefits were no less generous. Coverage limitations tended to be more restrictive for these illnesses than for others. The nature of the limitations varied greatly, although day and dollar limits were most common for inpatient treatment, and visit limits and higher copayments were most common for outpatient treatment.


Macrophage migration inhibitory factor and autism spectrum disorders.
Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components. Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available. There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms. These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.


D-(-)-poly-beta-hydroxybutyrate in membranes of genetically competent bacteria.
D-(-)-Poly-beta-hydroxybutyrate is a constituent of the membranes and the cytoplasms of genetically competent Azotobacter vinelandii, Bacillus subtilis, and Haemophilus influenzae cells. Within each species the concentration of D-(-)-poly-beta-hydroxybutyrate in the membranes and cytoplasm correlates with transformability. Fluorescence analysis of the thermotropic lipid phase transitions in A. vinelandii and B. subtilis cells indicates that D-(-)-poly-beta-hydroxybutyrate forms an organized gel structure in the membranes which is very labile. The concentration of organized D-(-)-poly-beta-hydroxybutyrate in the membranes, which can be estimated from the intensity of its phase transition, can be used to assess the competence of a culture.


Fluorometric probing of the lipase level as acute pancreatitis biomarkers based on interfacially controlled aggregation-induced emission (AIE).
As a sudden inflammation of the pancreas, acute pancreatitis presents severe complications and a high mortality rate, despite treatment. Lipase in serum serves as an essential biomarker of acute pancreatitis and even pancreatic cancer. Therefore, developing robust, convenient and sensitive probing of lipase levels is greatly needed. In this work, we present glutamate functionalized tetraphenylethylene (TPE) as a "turn-on" fluorescent probe (S1) based on the aggregation-induced emission (AIE) mechanism for lipase levels with new recognition units. In heterogeneous media, the hydrophilic amino and carboxyl groups in the probe were specifically introduced to facilitate its full access to lipase at the oil-water interface and achieve an interfacially controlled AIE process. The linear response of fluorescence ranging from 0 to 80 U L-1, which included the concentration range of the lipase level in human serum, considering the dilution factor if necessary, the limit of detection as low as 0.13 U L-1, and the fast response time (7 min) were determined. The value of the apparent Michaelis-Menten constant (Km) was obtained as 4.23 μM, which indicated superior affinity between lipase and the probe molecule. The selectivity, photostability, dynamic monitoring of the enzymatic reaction, and preliminary commercial enzyme activity screening were summarized. As far as we know, this is the fastest, easiest and most sensitive method for lipase level probing in the reported literature. Finally, probing the lipase level for the first time in real human serum samples was also conducted successfully.


Sumoylation in gene regulation, human disease, and therapeutic action.
Similar to ubiquitination, sumoylation covalently attaches a small ubiquitin-like modifier (SUMO) protein (92-97 amino acids) to the ε-amino group of a lysine residue. This is quite different from the classically defined post-translational modifications, such as phosphorylation, acetylation, and methylation, which typically add a small chemical group to the targeted residue. Sumoylation has been well studied at the molecular and cellular levels, focusing mostly on site-specific conjugation of human SUMO1, SUMO2, and SUMO3, as well as their homologues in various species. In this short review, we will discuss some recent examples to highlight (a) emerging trends about the coordinated regulation of sumoylation and other post-translational modifications in modulating the function of some transcription factors and pathway-specific regulators, (b) diverse roles of sumoylation in gene regulation implicated in stem cells and different pathogenic conditions, and (c) potential therapeutic strategies related to some of the diseases stated above.


Is the Medial Sural Artery Perforator Flap a New Workhorse Flap? A Systematic Review and Meta-Analysis.
The medial sural artery perforator flap offers thin, pliable tissue with a relatively long pedicle and low donor-site morbidity. This study explores the characteristics and uses of the medial sural artery perforator flap along with postoperative outcomes and complications. A systematic literature review was performed using PubMed, Embase, and Cochrane Central Register of Controlled Trials to identify all cases of medial sural artery perforator flap reconstruction. Descriptive and meta-analyses were performed on pooled outcomes. Multivariate logistic regression identified factors associated with increased complication rates. Thirty-five studies encompassing 526 medial sural artery perforator flaps were included for analysis. The most common reasons for surgery were oncologic (47.6 percent) and traumatic injuries (31.8 percent). The oral cavity was the most common recipient location (45.5 percent). Average flap dimensions were 6.0 ± 2.3 cm × 9.8 ± 3.6 cm, with an average pedicle length of 10.1 ± 6.6 cm. Meta-analysis revealed an overall complication rate of 14.3 percent (Q value = 22.16; p = 0.877; I(2)= -39.9). Use of chimeric medial sural artery perforator flaps was associated with significantly higher rates of complications (OR, 3.92; p = 0.039; 95 percent CI, 1.10 to 13.89). The majority of flap donor sites were closed primarily (68 percent) versus 32 percent that were covered with split-thickness skin grafts. A flap width greater than 5.75 cm had an odds ratio of 5.3 (95 percent CI, 1.3 to 21.8; p = 0.014) of having a donor-site complication if closed primarily. The medial sural artery perforator flap offers thin, pliable tissue with a relatively long pedicle and has minimal donor-site morbidity when the donor site is managed appropriately. As such, it should be considered a workhorse flap for both head and neck and extremity reconstruction.


Inhibitory effect of potassium on blood pressure in DOCA salt hypertension in rats.
The present study was performed to assess the influence of potassium on blood pressure in deoxycorticosterone (DOCA) salt hypertensive rats. The effects of potassium administration on the systolic blood pressure, fluid intake, urine volume, excretion of sodium and potassium, serum sodium and potassium, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were investigated both during the first 2 weeks of development of DOCA salt hypertension and during the next 2 weeks of established DOCA salt hypertension. Potassium administration prevented the development of DOCA salt hypertension and reduced the blood pressure in established DOCA salt hypertension. Fluid intake, urine volume, and excretion of sodium and potassium appeared to be markedly increased in rats treated with potassium. The levels of serum sodium and potassium were unchanged by potassium loading. Both the PRA and PAC which were suppressed in DOCA salt hypertensive rats, were reversed in rats treated by potassium loading. It is suggested that the elevation of blood pressure may be prevented and the increased blood pressure reduced mainly by the diuresis and natriuresis caused by potassium loading.


Prenatal concentrations of Perfluoroalkyl substances and early communication development in British girls.
Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative sub-scores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38months of age varied by maternal age at delivery. In daughters of younger mothers (<25years of age), every 1ng/mL of PFOS was associated with a 3.82 point (95% confidence interval (CI): -6.18, -1.47) lower vocabulary score at 15months and a 0.80 point (95% CI: -1.74, 0.14) lower language score at 38months. Prenatal exposure to select PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints.


TALK NERDY TO ME: THE ROLE OF INTELLECTUAL STIMULATION IN THE SUPERVISOR-EMPLOYEE RELATIONSHIP.
This study investigates (1) if communication with one's supervisor is related to empowerment through establishing perceptions of leader integrity, and (2) the extent to which the relationship between leader integrity and empowerment is moderated by intellectual stimulation. Due to the dynamic nature of today's organizational environment, understanding the nuances among these variables is vital to effective performance at the individual and organizational level. Hierarchical multiple regression tests were performed with a sample of 259 nurses in two regional healthcare facilities in the Midwestern United States. The results support a moderated-mediation relationship such that open communication with one's supervisor is positively related to empowerment through perceptions of leader integrity, but the relationship between leader integrity and empowerment varies across levels of intellectual stimulation. Specifically, while supervisor integrity mediates the relationship between patient safety communication and empowerment, this mediated relationship is only significant for followers who experience high intellectual stimulation, and is not significant for followers who report low intellectual stimulation. Thus, open communication and leader integrity will only empower followers if the leader is intellectually stimulating. This research clarifies how leaders in health care environments should communicate with their followers to empower them to think and act by their own initiative. Specifically, followers who communicate openly with their supervisor will feel more empowered, but only if they experience high intellectual stimulation which can improve their job performance and patient safety overall.


Vocal warm-up and cool-down in teachers: a quasi-experimental controlled study.
To verify the effects of vocal warm-up (VWU) and vocal cool-down (VCD) strategies on teachers. A quasi-experimental exploratory blind-evaluator study with control group that included teachers from a public secondary school. Teachers assigned to the experimental group (EG) performed VW prior to classes and VCD after classes. Teachers in the control group (CG) did not perform VWU and simply got voice rest after classes. Intergroup (EG vs. CG) and intragroup (pre-test versus post-test) comparisons were drawn from an auditory-perceptual evaluation, acoustic analysis, and self-reported discomfort. The mean acoustic and discomfort indicators and the percentage of improvement or worsening of vocal quality were calculated with a statistically significance level of p<0.05. EG and CG did not differ from each other in the intergroup analysis. The intragroup analysis showed that VWU improved voice quality and decreased the degree of body-related discomfort. VCD decreased both the fundamental frequency (f0) and the degree of discomfort, particularly in relation to the voice aspects. Vocal rest did not show any statistical difference. VWU showed positive effects on the auditory-perceptual evaluation and self-reported discomfort (body). VCD impacted f0 and self-reported discomfort (voice). Due to the exploratory nature of the research, the statistical power was not enough to demonstrate a difference in the comparison between EG and CG. However, the results indicate a potential for protecting teachers' voice and may be incorporated into daily work settings. Further controlled studies with random samples and greater numbers of participants should be conducted to confirm these results.


Cannabis Treatment in Children with Epilepsy: Practices of Canadian Neurologists.
Medical cannabis has recently emerged as a treatment option for children with drug-resistant epilepsy. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about the attitudes of neurologists toward cannabinoid treatment of children with epilepsy. A 21-item online survey was distributed via email to 148 pediatric neurologists working in hospitals and community clinics across Canada. Questions were related to clinical practice and demographics. This survey achieved a response rate of 38% (56 Canadian neurologists). These neurologists were treating 668 pediatric epilepsy patients with cannabinoids. While 29% of neurologists did not support cannabis treatment in their patients, 34% prescribed cannabis, and 38% referred to another authorizing physician, mostly to community-based non-neurologists. The majority of neurologists considered cannabis for patients with Dravet syndrome (68%) and Lennox-Gastaut syndrome (64%) after an average of three failed anticonvulsants. Twenty-seven percent considered it for patients with idiopathic generalized epilepsy, and 18% for focal epilepsy. No neurologist used cannabis as a first-line treatment. All neurologists had at least one hesitation regarding cannabis treatment in pediatric epilepsy. The most common one was poor evidence (66%), followed by poor quality control (52%) and high cost (50%). The majority of Canadian pediatric neurologists consider using cannabis as a treatment for epilepsy in children. With many gaps in evidence and high patient-driven demand for cannabis therapy, this survey provides immediate information from the "wisdom of the crowd," to aid neurologists until further evidence is available.


Tattooing: profile and discourse of individuals with marks in the body.
Tattooing is an atavist and diffuse phenomenon of interest to various areas of knowledge. Its practice by specific groups such as prisoners and psychiatric patients has turned it into a stigma. To investigate the discourse of tattooed individuals about the discrimination and the construction of stigmas resulting from marks in the body. 42 individuals were interviewed and the data were analyzed. The profile of the participants was as follows: most were women; with 2 to 4 tattoos; who were about 23 years old when they got their first tattoo; with an undergraduate degree; who viewed tattooing as a trend; who did not report any important fact that made them get a tattoo; who classified the pain of getting a tattoo as tolerable, who stated that never felt discriminated and never felt the need to hide the tattoos; who find that tattoos make them more sexually attractive; who do not view tattooing as a form of cultural resistance; who said they would not have done it if they believed it caused them professional problems; who stated that they were not drunk when they got the tattoos; who said they were not habitual drugs users, who believed that tattooing is a form of expression and aesthetic sense. A difference between the discourse of tattooed individuals and their acts was observed in relation to the social context. In addition, there has been an important shift in the meaning of the practice to tattooed individuals.


[Antimicrobial approaches to periodontal therapy].
The relationship between the periodontal microbiota and the threshold for periodontal disease is dependent on the specific bacterial composition of the plaque and the resistance of the host. Supragingival plaque is the cause of gingivitis and plays a primary role in the initiation of periodontitis. The 0.2% chlorhexidine mouthwash (twice a day) is safe and most effective antiplaque and anti-gingivitis agent. The use of adjunctive tetracycline for 2 week periods (1 gm daily) with root debridement is highly effective against Actinobacillus actinomycetemcomitans and many of suspected virulence microorganisms, the major etiological agents of juvenile periodontitis. For rapidly progressive periodontitis and refractory adult periodontitis, metronidazole for 1-2 week periods (600 mg.daily) has excellent activity against strictly anaerobic bacteria such as Bacteroides gingivalis, Spirochetes and others. Clinical use of antimicrobial agent in adjuvant with scaling, root planing, and personal oral hygiene instruction cause a significant improvement of the periodontium.


How to distinguish seizures from non-epileptic manifestations.
The first and most important step in establishing diagnosis of epilepsy consists of careful history taking from patients and witnesses. The clinical evaluation of the event will lead the indication for further diagnostic tests including e.g. EEG and MRI. Hence, identifying the paroxysmal event as epileptic or non-epileptic is the very first step in the diagnostic process. Paroxysmal events pose a clinical challenge, as these are unpredictable and do not usually occur in the doctor's office. History taking, hunting for witness reports and home-video recordings are the main tools to conclude whether a paroxysmal event is a seizure or not. In this review, we describe the most common differential diagnoses of epileptic seizures, including syncope, psychogenic non-epileptic seizures, as well as a variety of paroxysmal conditions and behaviours of all age groups. Misdiagnosis of non-epileptic events as epilepsy may not only defer the correct diagnosis and treatment but also poses additional risk by prescribing antiepileptic drugs unnecessarily. Moreover, missing the diagnosis of epilepsy implies risk of additional seizures and therefore possibly injuries, sudden death in people with epilepsy, or status epilepticus. Studies have shown that patient and witness accounts are unreliable in a high percentage of cases. Therefore, the core competency of doctors and medical professionals assessing paroxysmal events is knowledge of the clinical features that help define the different aetiologies, thus empowering them to establish the most accurate appraisal of an event. [Published with video sequences].


Multiparametric MRI-based nomograms in predicting positive surgical margins of prostate cancer after laparoscopic radical prostatectomy.
Positive surgical margins (PSMs) are an independent risk factor of biochemical recurrence in patients with prostate cancer (PCa) after laparoscopic radical prostatectomy; however, limited MRI-based predictive tools are available. This study aimed to develop a novel nomogram combining clinical and multiparametric MRI (mpMRI) parameters to reduce PSMs by improving surgical planning. One hundred and three patients with PCa (55 patients with negative surgical margins [NSMs] and 48 patients with PSMs) were included in this retrospective study. The following parameters were obtained using GE Functool post-processing software: diffusion-weighted imaging (DWI); intravoxel incoherent motion model (IVIM); and diffusion kurtosis imaging (DKI). Patients were divided into different training sets and testing sets for different targets according to a ratio of 7:3. The least absolute shrinkage and selection operator (LASSO) regression algorithm was used to analyze the data set to select the optimal MRI predictors. Preoperatively clinical parameters used to build a clinical nomogram (C-nomogram). Multivariable logistic regression analysis was used to build an MRI nomogram (M-nomogram) by introducing the MRI parameters. Based on the MRI and clinical parameters, build an MRI combined with clinical parameters nomogram (MC-nomogram). Comparisons with the M-nomogram and MC-nomogram were based on discrimination, calibration, and decision curve analysis (DCA). A 3-fold cross-validation method was used to assess the stability of the nomogram. There was no statistical difference in AUC between the C-nomogram (sensitivity=64%, specificity=65% and AUC=0.683), the M-nomogram (sensitivity=57%, specificity=88% and AUC=0.735) and the MC-nomogram (sensitivity= 64%, specificity=82% and AUC=0.756). The calibration curves of the three nomograms used to predict the risk of PSMs in patients with PCa showed good agreement. The net benefit of the MC-nomogram was higher than the others (range, 0.2-0.7). The mpMRI-based nomogram can predict PSMs in PCa patients. Although its AUC (0.735) is not statistically different from that of the clinical-based nomogram AUC (0.683). However, mpMRI-based nomogram has higher specificity (88% VS. 63%), model stability, and clinical benefit than clinical-based nomogram. And the predictive ability of mpMRI plus clinical parameters for PSMs is further improved.


Probing the Contribution of Vertical Processing Layers of the Retina to White-Noise Electrical Stimulation Responses.
Optimal stimulus parameters for epiretinal prostheses have been investigated by analyzing retinal ganglion cell (RGC) spiking responses to white-noise electrical stimulation, through a spike-triggered average (STA) analysis technique. However, it is currently unknown as to activation of which retinal cells contribute to features of the STA. We conducted whole-cell patch clamping recordings in ON and OFF RGCs in response to white-noise epiretinal electrical stimulation by using different inhibitors of synaptic transmission in a healthy retina. An mGluR6 agonist, L-AP4, was firstly used to selectively block the output of photoreceptors (PRs) to ON bipolar cells (BCs). We subsequently fully blocked all synaptic inputs to RGCs using a combination of pharmacological agents. Our data shows that PRs dominate the ability of ON RGCs to integrate electrical pulses and form a unique STA shape, while BCs do not contribute in any way. In addition, our results demonstrate that the ability of OFF RGCs to integrate pulses is consistently impaired after blocking the PR to ON BC pathway. We hypothesise that the mechanisms underlying this co-effect are related to the narrow field AII amacrine cells connecting ON and OFF pathways.Clinical Relevance-Recent retinal studies recorded mirror-inverted STAs in ON and OFF retinal pathways, thus raising the possibility of designing a stimulation approach that can differentially activate ON and OFF pathways with electrical stimulation. However, the detailed contribution of three major retinal cell layers in forming characteristic STAs is still unclear. It is of great clinical relevance to investigate the isolated contribution of PRs to the electrically driven STA since PRs progressively degenerate in the course of retinal disease.


Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study.
To characterize contemporary use of tranexamic acid (TXA) in combat injury and to assess the effect of its administration on total blood product use, thromboembolic complications, and mortality. Retrospective observational study comparing TXA administration with no TXA in patients receiving at least 1 unit of packed red blood cells. A subgroup of patients receiving massive transfusion (≥10 units of packed red blood cells) was also examined. Univariate and multivariate regression analyses were used to identify parameters associated with survival. Kaplan-Meier life tables were used to report survival. A Role 3 Echelon surgical hospital in southern Afghanistan. A total of 896 consecutive admissions with combat injury, of which 293 received TXA, were identified from prospectively collected UK and US trauma registries. Mortality at 24 hours, 48 hours, and 30 days as well as the influence of TXA administration on postoperative coagulopathy and the rate of thromboembolic complications. The TXA group had lower unadjusted mortality than the no-TXA group (17.4% vs 23.9%, respectively; P = .03) despite being more severely injured (mean [SD] Injury Severity Score, 25.2 [16.6] vs 22.5 [18.5], respectively; P < .001). This benefit was greatest in the group of patients who received massive transfusion (14.4% vs 28.1%, respectively; P = .004), where TXA was also independently associated with survival (odds ratio = 7.228; 95% CI, 3.016-17.322) and less coagulopathy (P = .003). The use of TXA with blood component-based resuscitation following combat injury results in improved measures of coagulopathy and survival, a benefit that is most prominent in patients requiring massive transfusion. Treatment with TXA should be implemented into clinical practice as part of a resuscitation strategy following severe wartime injury and hemorrhage.


Oral pyogenic granulomas.
Pyogenic granulomas are benign growth occurring in various oral mucosal sites. They are thought to be caused by tissue response to non-specific irritation. Surgical excision and removal of irritants are the usual treatments, and recurrence is rare. The exception is the 'pregnancy epulis', where excision should only be considered if there is incomplete regression following childbirth.


Effects of amoxicillin-clavulanate combination on the motility of the small intestine in human beings.
The amoxicillin-clavulanate combination (Augmentin) frequently induces gastric complaints and diarrhea by an unknown mechanism. The aim of this study was to assess the effects of two orally therapeutic regimens of amoxicillin-clavulanate on small bowel motility in human beings. Duodeno-jejunal manometric recordings were performed in six healthy subjects treated in a cross-over double-blind study with placebo; amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h for 3 days; or amoxicillin-clavulanate, 1 g plus 250 mg per os every 12 h on day 3 only (1-day regimen). Recordings were all performed on day 3 during a diurnal fasting period, a fed state after a standard dinner, and a nocturnal fasting period. Amoxicillin-clavulanate did not affect the motility of the small intestine during the diurnal fast or the fed state. During the nocturnal fast, amoxicillin-clavulanate significantly increased the motility index of the nonpropagated contractions and tended to increase the duration and the amplitude of the propagated contractions. The same digestive motor effect was already observed on the first day of treatment (1-day regimen). This study demonstrates that the oral administration of a therapeutic regimen of amoxicillin-clavulanate is associated, in most cases, with the occurrence of small intestinal motor disturbances.


Estimated Nonreimbursed Costs for Care Coordination for Children With Medical Complexity.
: media-1vid110.1542/5852348672001PEDS-VA_2017-3562Video Abstract BACKGROUND AND OBJECTIVES: Multidisciplinary care teams may improve health and control total cost for children with medical complexity (CMC). We aim to quantify the time required to perform nonreimbursed care coordination activities by a multidisciplinary care coordination program for CMC and to estimate the direct salary costs of that time. From April 2013 to October 2015, program staff tracked time spent in practicably measured nonbilled care coordination efforts. Staff documented the discipline involved, the method used, and the target of the activity. Cost was estimated by multiplying the time spent by the typical salary of the type of personnel performing the activity. Staff logged 53 148 unique nonbilled care coordination activities for 208 CMC. Dietitians accounted for 26% of total time, physicians and nurse practitioners 24%, registered nurses 29%, and social workers 21% (1.8, 2.3, 1.2, and 1.4 hours per CMC per month per full-time provider, respectively). Median time spent in nonreimbursed care coordination was 2.3 hours per child per month (interquartile range 0.8-6.8). Enrollees required substantially greater time in their first program month than thereafter (median 6.7 vs 2.1 hours per CMC per month). Based on 2015 national salary data, the adjusted median estimated cost of documented activities ranged from $145 to $210 per CMC per month. In this multidisciplinary model, care coordination for CMC required substantial staff time, even without accounting for all activities, particularly in the first month of program enrollment. Continued advocacy is warranted for the reimbursement of care coordination activities for CMC.


Sex-Specific Associations of Risk-Based Alcohol Drinking Level with Cardiovascular Risk Factors and the 10-Year Cardiovascular Disease Risk Scores.
To assess sex-specific associations between risk-based alcohol drinking levels and the 10-year cardiovascular disease (CVD) risk scores and cardiovascular (CV) risk factors. Data from 9,995 Koreans (4,249 men, 5,746 women), aged 40 to 79 years who did not have CVD and participated in the 2011 to 2013 Korea National Health and Nutrition Examination Survey, were used to assess risk-based alcohol drinking levels in the past year (no drinking, drinking at low risk, and drinking at risk) categorized by the National Institute on Alcohol Abuse and Alcoholism, components of the 10-year CVD risk scores using the Adult Treatment Panel III risk score and the 10-year hard atherosclerotic CVD risk score, CV risk factors, and confounding factors (age, smoking status, body mass index, educational attainment, income level, and physical activity). Drinking levels had positive associations with blood pressure and levels of glucose, triglycerides, and high-density lipoprotein cholesterol (HDL-C) and inverse associations with levels of low-density lipoprotein cholesterol and non-HDL-C and ratio of total cholesterol (TC) to HDL-C in men, while higher drinking levels were associated with higher HDL-C levels and lower ratio of TC to HDL-C in women after adjusting for confounding factors (p for trend < 0.001). With respect to the 10-year CVD risk scores, higher drinking levels were associated with lower scores in both sexes (p for trend < 0.001). Risk-based drinking levels were more likely to have dose-dependent associations with CV risk factors in men than in women and had inverse relationships with 10-year CVD risk in both men and women.


Association Between Obesity and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Mendelian Randomization Studies.
Although dyslipidemia has been consistently shown to be associated with atherogenesis, an association between obesity and cardiovascular disease outcomes remains controversial. Mendelian randomization can minimize confounding if variables are randomly and equally distributed in the population of interest. To assess evidence from mendelian randomization studies to provide a less biased estimate of any association between obesity and cardiovascular outcomes. Systematic searches of MEDLINE and Scopus from database inception until January 2018, supplemented with manual searches of the included reference lists. Studies that used mendelian randomization methods to assess the association between any measure of obesity and the incidence of cardiovascular events and those that reported odds ratios (ORs) with 95% CIs estimated using an instrumental variable method were included. The 5 studies included in the final analysis were based on a consensus among 3 authors. Two investigators independently extracted study characteristics using a standard form and pooled data using a random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Obesity associated with type 2 diabetes, coronary artery disease, or stroke. The hypothesis was formulated prior to data collection. Of 4660 potentially relevant articles, 2511 titles were screened. Seven studies were included in the systematic review, and 5 studies with 881 692 participants were eligible to be included in the meta-analysis. Pooled estimates revealed that obesity was significantly associated with an increased risk of type 2 diabetes (OR, 1.67; 95% CI, 1.30-2.14; P < .001; I2 = 93%) and coronary artery disease (OR, 1.20; 95% CI, 1.02-1.41; P = .03; I2 = 87%). No association between obesity and stroke was found (OR, 1.02; 95% CI, 0.95-1.09; P = .65; I2 = 0%). The present meta-analysis suggests that obesity is associated with type 2 diabetes and coronary artery disease. Although this analysis of mendelian randomization studies does not prove causality, it is supportive of a causal association. Hence, health care practitioners should continue to emphasize weight reduction to combat coronary artery disease.


Reliability of interviewer and subject assessments of nevus counts in a study of melanoma.
Several types of data are presented concerning the reliability of counting or estimating the density of nevi (moles), a major risk factor for melanoma, using methods typically employed in epidemiologic studies. First, interviewer-derived counts of nevi on the arm produced estimates of inter-observer, inter-subject, temporal and random variability, and their interactions. Second, interviewer-derived arm counts and respondent self-reports of whole body nevus density were compared. Finally, we compared male and female cases and controls with respect to their reported rates of having a relative with a malignant mole. Overall, the intra-observer reliability ranged from 55 to 81%, and was better for observers with more experience. The correlation between the interviewer counts and respondents' self-reported estimates was 0.41. The data on malignant moles in relatives suggest higher reporting rates in male cases and lower reporting in male controls relative to their female counterparts, but there is little difference by sex in the reporting of one's own nevus density.


Lung cancer in women: the differences in epidemiology, biology and treatment outcomes.
Although the prevalence of lung cancer in men has been decreasing, it has been increasing in women. Without a doubt, lung cancer is a major health problem for women in the USA, not only owing to its high incidence rate but, more alarming, the high mortality rate. Lung cancer kills more women each year than breast, ovarian and uterine cancers combined. One of the most important risk factors for the development of lung cancer in both men and women is cigarette smoking. Unfortunately, the prevalence of smoking among women has increased significantly since 1980, which is a major concern as epidemiologic data suggest that women may be more susceptible to developing lung cancer than men. Many will argue, however, that after adjusting for tobacco exposure, some studies have failed to show that women are at a higher risk for developing lung cancer. Indeed, the increased risk of lung cancer in women remains controversial. There is, however, little controversy to the fact that the biology of lung cancer differs between the sexes. This paper summarizes the explanations for the sex differences in lung cancer, including differences in molecular abnormalities, growth factor receptors, hormonal influences, differences in cytochrome P-450 enzymes and DNA repair capacity, as well as variations in treatment outcomes.


Home-based treatment for children and families affected by HIV and AIDS. Dealing with stigma, secrecy, disclosure, and loss.
The compelling needs of HIV-affected children and families sometimes appear to represent human struggles under the magnifying glass. The multiple assaults on the healthy psychologic development of children through disruptions in caregiving, loss, and abandonment require interventions that are mindful of their mental health needs and longer-term developmental trajectories. An ongoing relationship with a clinical team who can understand and respond to the vicissitudes of the illness and provide calibrated psychotherapeutic and case management services can aid both children and parents in the painful tasks that AIDS presents. Whereas clinically informed case management services can offer respectful and thoughtful concrete help, psychotherapy can offer the opportunity for children to pull together the often fragmented narratives of their family lives and integrate object loss to be free to continue on a normative developmental path. Comprehensive, wraparound home-based services of the type described in this article represent a mostly new tradition in psychiatry, but one that ensures that mental health services are provided to the most vulnerable children and families. For those affected by HIV or AIDS, home-based services can be the key to healthcare and treatment compliance. In addition, when services are well integrated within a community context, such that regular communication with other healthcare providers (AIDS clinics, visiting nurse services, and AIDS care agencies) is ongoing, what is provided constitutes continuity of care in the truest sense.


Three-dimensional biotemplate-loaded nickel sulfide vacancies engineered to promote the absorption of electromagnetic waves.
Vacancy engineering offers an appealing strategy for modifying the electronic structure of transition metals. Transition metals with abundant sulfur vacancies can significantly contribute to the microwave absorption capabilities of absorbers. In this study, an NixSy@De composite material was synthesized through a straightforward hydrothermal synthesis technique. The effective absorption bandwidth (EAB) of this composite material reached 9.86 GHz at 1.44 mm. A minimum reflection loss (RLmin) of -33.61 dB at 1 mm was achieved, and after mild etching, the RLmin further improved to -93.53 dB at 1.16 mm to achieve a high-attenuation microwave absorption. The exceptional performance of NixSy@De for the absorption of electromagnetic waves (EMWs) is based on its high dielectric loss, substantial magnetic loss, and excellent impedance matching. This work combines transition metal sulfides with three-dimensional biotemplated diatomite, providing valuable insights into the design of advanced EMW absorbing materials.


Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies.
Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa-IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%-1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin-based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.


Normal dispersion femtosecond fiber optical parametric oscillator.
We propose and demonstrate a synchronously pumped fiber optical parametric oscillator (FOPO) operating in the normal dispersion regime. The FOPO generates chirped pulses at the output, allowing significant pulse energy scaling potential without pulse breaking. The output average power of the FOPO at 1600 nm was ∼60 mW (corresponding to 1.45 nJ pulse energy and ∼55% slope power conversion efficiency). The output pulses directly from the FOPO were highly chirped (∼3 ps duration), and they could be compressed outside of the cavity to 180 fs by using a standard optical fiber compressor. Detailed numerical simulation was also performed to understand the pulse evolution dynamics around the laser cavity. We believe that the proposed design concept is useful for scaling up the pulse energy in the FOPO using different pumping wavelengths.


[Anti-aquaporin-4 antibody autoimmune syndrome with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. A case report].
A 45-year-old female was positive for anti-aquaporin-4 antibody with disturbance of consciousness, respiratory failure, and ophthalmoplegia associated with extensive brain stem involvement with intractable hiccup and nausea as an initial manifestation. Her level of consciousness and state of respiration worsened approximately one month later. There was no abnormality in the cerebrospinal fluid examination. A lesion was found in the medullary tegmentum on brain MRI. The patient received steroid pulse therapy and her level of consciousness improved the next day. However, her state of respiration worsened, and she had extensively clinical involvement of the brain stem. Her symptoms gradually improved with intravenous administration of prednisolone and intravenous immunoglobulin therapy (IVIg). The patient had almost completely recovered, but she relapsed with cervical myelitis extending over 3 vertebral segments approximately 10 months later. She underwent steroid pulse therapy, oral prednisolone, and IVIg again and improved.


Diurnal rhythm of rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA synthase.
Rat liver cytosolic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase exhibits a diurnal rhythm of enzyme activity which coincides with the diurnal rhythm of HMG-CoA synthase protein. The peaks of activity and protein (determined by SDS/PAGE and immunoblotting) both occur at D10 (the tenth hour of the daily 12 h dark cycle). The peak of mRNA levels (measured by slot-blot hybridization of liver RNA) is slightly advanced with respect to that of protein, by about 4 h, and shows a maximum at D6. Cytosolic HMG-CoA synthase activity and protein in rats fed on a normal diet were approx. 2-fold higher during the peak at D10 than in the nadir at D2. HMG-CoA synthase mRNA levels were approx. 4-fold higher during the peak at D6 than in the nadir at D2. These results point to a transcriptional and translational regulation of the cytosolic HMG-CoA synthase.


T cell proliferative responses to malondialdehyde-acetaldehyde haptenated protein are scavenger receptor mediated.
Malondialdehyde-acetaldehyde (MAA) haptenated proteins have been described in disease processes related to prolonged oxidative stress (via malondialdehyde production), such as alcohol liver disease (ALD), non-alcoholic non-steatohepatitis (NASH) and atherosclerosis. Experimentally, high titer IgG1 antibody responses are seen after immunization without adjuvant; however, T cell proliferative responses and the role of scavenger receptors in this immunogenicity has not previously been described. In this study, T cell proliferative responses to the carrier protein, but not the MAA hapten itself, were identified in vitro. Moreover, these T proliferative responses were inhibited when MAA-hen egg lysozyme (HEL) was co-immunized with excess scavenger receptor ligand polyG (poly-guanylic acid), implicating the role of (a) scavenger receptor(s) in initiating the T helper cell response. Activated B cells were unable to process and present MAA-HEL preferentially to T cells, while thioglycollate-elicited (but not Con A-elicited) macrophages and dendritic cells (DC) did so with approximately 32-fold less MAA-HEL than native antigen necessary to initiate equal proliferative responses. While this preferential processing and presentation may be related to several factors, preferential binding of MAA haptenated proteins mediated by scavenger receptors may be one mechanism. IL-4 was absent from the supernatants of T proliferative assays despite a strong IgG1 response in vivo, although the TH2 cytokines IL-6 and IL-10 were expressed. Since the modification of proteins by the MAA have previously been shown to occur after ethanol consumption in vivo, the ability of MAA haptens to experimentally enhance immune responses, specifically humoral and T cell responses, may represent mechanisms by which autoimmune phenomena found in ALD occur.


Otoscopic signs of otitis media.
Lack of agreed-upon diagnostic criteria for acute otitis media (AOM) has led to inconsistencies in clinical care, misleading research results, and misguided educational efforts. The objective of this study was to examine findings that expert otoscopists use when diagnosing AOM. A group of experienced otoscopists examined 783 children presenting for primary care. In addition, endoscopic still images of the tympanic membranes (TMs) were obtained. A random sample of 135 of these images was sent for review to a group of 7 independent physicians who were expert otoscopists. We examined the findings that both groups of observers used to distinguish between AOM, otitis media with effusion (OME), and no effusion. Among both groups of observers, bulging of the TM was the finding judged best to differentiate AOM from OME: 96% of ears and 93% of ear image evaluations assigned a diagnosis of AOM by members of the 2 groups were reported as showing bulging of the TM, compared with 0% and 3%, respectively, of ears and ear image evaluations assigned a diagnosis of OME. Opacification of the TM was the finding that best differentiated OME from no effusion. We describe findings that are used by experienced otoscopists to diagnose AOM and OME. The findings point to the advisability under most circumstances of restricting antimicrobial treatment for AOM to children who have TM bulging, and they call into question clinical trials of the treatment of AOM in which TM bulging has not been a required element for participation.


CircHIPK3 Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Cells Proliferation and Metastasis via Altering of miR-508-3p/CXCL13 Signal.
Accumulating evidence has demonstrated that circular RNAs (circRNAs) play a key role in the tumorigenesis of various types of cancers, including clear cell renal cell carcinoma (ccRCC). Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of circRNA homeodomain interacting protein kinase 3 (circHIPK3) and microRNAs (miRNAs), including miR-508-3p. The clinical measurement of circHIPK3 was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic analysis. Cell Counting Kit-8 and Transwell chamber assays were performed to determine the changes in the proliferative and metastatic ability of A498 and 786-O cells. C-X-C motif chemokine ligand 13 (CXCL13) protein expression was detected by Western blot analysis. The targeted binding effect between miR-508-3p and circHIPK3 or CXCL13 was confirmed by constructed luciferase and RNA immunoprecipitation (RIP) assays, respectively. Fluorescence in situ hybridization (FISH) assay was used to measure the subcellular localization of circHIPK3 and miR-508-3p. It was found that circHIPK3 was markedly upregulated in ccRCC tissue and cell lines, and circHIPK3-upregulation was closely correlated with poor clinicopathological features in patients with ccRCC. It was found that both miR-508-3p and circHIPK3 were localized in the cytoplasm of ccRCC cells. The up- and downregulation of circHIPK3 positively regulated ccRCC cell proliferation and metastasis, and this regulatory effect was reversed by miR-508-3p. Through luciferase and RIP assays, it was confirmed that circHIPK3 could interacted with miR-508-3p. Furthermore, it was revealed that CXCL13, which was negatively correlated with miR-508-3p, was upregulated in ccRCC. It was also shown that CXCL13 was a downstream target of miR-508-3p. miR-508-3p suppressed ccRCC cell proliferation and metastasis by targeting CXCL13. Lastly, it was demonstrated that circHIPK3 promoted CXCL13 to facilitate ccRCC cell proliferation and metastasis by decoying miR-508-3p. In brief, the results of the present study showed that circHIPK3 promoted ccRCC cell proliferation and metastasis by altering miR-5083p/CXCL13 signaling. The present findings might provide a novel target for the molecular treatment of ccRCC.


Ovarian cancer: epidemiology and risk factors.
The present overview of ovarian cancer epidemiology summarizes the main results for a network of case-control studies in Italy and from the Collaborative Group on Epidemiological Studies of Ovarian Cancer. There are consistent inverse relations between parity, oral contraceptive use and the risk of ovarian cancer. For other menstrual and hormonal factors (i.e. early age at menarche and late menopause), there are established associations, but of limited impact on ovarian cancer incidence on a population level. Serous and endometrioid ovarian cancers (but not mucinous or clear cell types) are related to current and recent use of hormone replacement therapy in menopause. There are no strong associations with alcohol and tobacco overall, but a direct link for tobacco with (borderline) mucinous cancers, of limited impact, however, on overall ovarian cancer mortality. There are direct associations of ovarian cancer risk with height and BMI, as well as possible relations with selected dietary factors - in the absence, however, of consistent findings - and a possible inverse association with physical activity. There is a strong association with a family history of ovarian cancer (and a few selected other neoplasms, including colorectum and endometrium). Recognized risk factors explain only a limited proportion of ovarian cancer cases on a population level. A key reason for the recent favourable trends of ovarian cancer incidence and mortality in several high-income countries is the widespread use of oral contraceptive in the generations born after 1930.


Young Men's Disclosure of Same Sex Behaviors to Healthcare Providers and the Impact on Health: Results from a US National Sample of Young Men Who Have Sex with Men.
Many men who have sex with men (MSM) do not disclose their same sex behaviors to healthcare providers (HCPs). We used a series of logistic regression models to explore a conceptual framework that first identified predictors of disclosure to HCPs among young MSM (YMSM), and subsequently examined young men's disclosure of male-male sexual behaviors to HCPs as a mediator between sociodemographic and behavioral factors and three distinct health outcomes [HIV testing, sexually transmitted infection (STI) testing, and human papillomavirus (HPV) vaccination]. We determined the predictors of disclosure to HCPs among YMSM and examined the relationship between disclosure and the receipt of appropriate healthcare services. Data were collected online through a US national sample of 1750 YMSM (ages 18-29 years) using a social and sexual networking website for MSM. Sexual history, STI/HIV screening history, sexual health, and patient-provider communication were analyzed in the logistic regression models. Participants were predominantly white (75.2%) and gay/homosexual (76.7%) with at least some college education (82.7%). Young men's disclosure of male-male sexual behaviors to HCPs was associated with the receipt of all healthcare outcomes in our model. Disclosure was a stronger mediator in HPV vaccination than in HIV and STI testing. Disclosure to non-HCP friends and family, HCP visit in the past year, and previous STI diagnosis were the strongest predictors of disclosure. Young men's disclosure of male-male sexual behaviors to HCPs is integral to the receipt of appropriate healthcare services among YMSM. HPV vaccination is more dependent on provider-level interaction with patients than HIV/STI testing.


Digital Ophthalmology in the UK - Diabetic Retinopathy Screening and Virtual Glaucoma Clinics in the National Health Service.
The customary doctor and patient interactions are currently undergoing significant changes through technological advances in imaging and data processing and the need for reducing person-to person contacts during the COVID-19 crisis. There is a trend away from face-to-face examinations to virtual assessments and decision making. Ophthalmology is particularly amenable to such changes, as a high proportion of clinical decisions are based on routine tests and imaging results, which can be assessed remotely. The uptake of digital ophthalmology varies significantly between countries. Due to financial constraints within the National Health Service, specialized ophthalmology units in the UK have been early adopters of digital technology. For more than a decade, patients have been managed remotely in the diabetic retinopathy screening service and virtual glaucoma clinics. We describe the day-to-day running of such services and the doctor and patient experiences with digital ophthalmology in daily practice.


Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels.
Hydrogels with tunable mechanical properties have provided a tremendous opportunity to regulate stem cell differentiation. Hydrogels with osteoid (about 30-40 kPa) or higher stiffness are usually required to induce the osteogenic differentiation of mesenchymal stem cells (MSCs). It is yet difficult to achieve the same differentiation on very soft hydrogels, because of low environmental mechanical stimuli and restricted cellular mechanotransduction. Here, we modulate cellular spatial sensing of integrin-adhesive ligands via quasi-hexagonally arranged nanopatterns to promote cell mechanosensing on hydrogels having low stiffness (about 3 kPa). The increased interligand spacing has been shown to regulate actomyosin force loading to recruit extra integrins on soft hydrogels. It therefore activates mechanotransduction and promotes the osteogenic differentiation of MSCs on soft hydrogels to the level comparable with the one observed on osteoid stiffness. Our work opens up new possibilities for the design of biomaterials and tissue scaffolds for regenerative therapeutics.


Left in limbo: patients' views on care across the primary/secondary interface.
To discover the views of patients about their experiences across the interface between primary and secondary health care, including referral from general practitioners, outpatient and inpatient care, discharge, and aftercare. A qualitative study involving individual and focus group interviews of patients and interviews of carers. 33 patients who had attended at least one outpatient appointment or had been an inpatient between two and four months previously, and eight carers of patients with chronic conditions. Three acute hospitals and one community health service in Leicestershire. Common themes in the views of patients and carers towards their experiences of care. Five themes emerged. The first four were: "getting in" (access to appropriate care), "fitting in" (orientation of care to the patient's requirements), "knowing what's going on" (provision of information), and "continuity" (continuity of staff and coordination and communication among professionals). The fifth theme was "limbo" (difficulty in making progress through the system), which was influenced by failures in care in relation to the other four themes. The concept of progress is central to patients' views of care. It involves both progress through the healthcare system and progress towards recovery or adjustment to an altered health state. Patients' views on how well they progress through the healthcare system may be an appropriate indicator for monitoring health service performance.


Can Behenic Acid (C22:0) Levels be a Prognostic Factor in Glial Tumors?
Inhibition of fatty acid synthase leads to apoptosis in cancers, which leads to high levels of fatty acid synthesis. This indicates that cancer cells depend on fatty acid in order to survive. In this study, we investigated whether or not there was a relationship between the glial tumor grade and free fatty acid level of tumor tissue. Twenty patients who had high grade glial tumors and 20 patients who had low grade glial tumors, were included in the study. Tumors samples were obtained intraoperatively in order to measure the fatty acid levels. The fatty acids were studied in three groups: saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids. They were analyzed with gas chromatography. The oleic acid, linoleic acid, eicosadienoic acid, arachidonic acid, and docosadienoic acid levels were high in the tumor tissue of low grade tumors. The myristic acid, palmitic acid, stearic acid, alpha linoleic acid, eicosenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, and ceramide levels were high in the tumor tissue of high grade glial tumors. However, none of these high values were statistically significant. The high values of behenic acid, a saturated fatty acid, in low grade glial tumors were statistically significant. High levels of behenic acid in patients with low grade glial tumor is important as it indicates persistence of the tissue integrity and tissue resistance. behenic acid levels can be a prognostic factor in glial tumors. Le taux d'acide béhénique (C22:0) peut-il constituer un facteur de pronostic dans les tumeurs gliales?


Haemophilus paraphrophilus endocarditis.
We have described a previously healthy medical student who had endocarditis due to Haemophilus paraphrophilus necessitating replacement of the mitral valve. We compared this case to the 11 previously reported cases of endocarditis caused by this organism, stressing the fastidious nature of the organism, its destructive nature, and its propensity for thromboembolism.


Full-field optical coherence tomography for the analysis of fresh unstained human lobectomy specimens.
Full-field optical coherence tomography (FFOCT) is a real-time imaging technique that generates high-resolution three-dimensional tomographic images from unprocessed and unstained tissues. Lack of tissue processing and associated artifacts, along with the ability to generate large-field images quickly, warrants its exploration as an alternative diagnostic tool. One section each from the tumor and from adjacent non-neoplastic tissue was collected from 13 human lobectomy specimens. They were imaged fresh with FFOCT and then submitted for routine histopathology. Two blinded pathologists independently rendered diagnoses based on FFOCT images. Normal lung architecture (alveoli, bronchi, pleura and blood vessels) was readily identified with FFOCT. Using FFOCT images alone, the study pathologists were able to correctly identify all tumor specimens and in many cases, the histological subtype of tumor (e.g., adenocarcinomas with various patterns). However, benign diagnosis was provided with high confidence in roughly half the tumor-free specimens (others were diagnosed as equivocal or false positive). Further analysis of these images revealed two major confounding features: (a) Extensive lung collapse and (b) presence of smoker's macrophages. On a closer inspection, however, the smoker's macrophages could often be identified as distinct from tumor cells based on their relative location in the alveoli, size and presence of anthracosis. We posit that greater pathologist experience, complemented with morphometric analysis and color-coding of image components, may help minimize the contribution of these confounders in the future. Our study provides evidence for the potential utility of FFOCT in identifying and differentiating lung tumors from non-neoplastic lung tissue. We foresee its potential as an adjunct to intra-surgical frozen section analysis for margin assessment, especially in limited lung resections.


Effects of Using Soybean Protein Emulsion as a Meat Substitute for Chicken Breast on Physicochemical Properties of Vienna Sausage.
The aim of this study is to determine the effects of using emulsion manufactured with soybeans (ES) to substitute chicken breast in Vienna sausages. Four types of Vienna sausages (S1: 10% ES and 50% chicken, S2: 20% ES and 40% chicken, S3: 30% ES and 30% chicken, and S4: 40% ES and 20% chicken) for this study were made. The pH, color, proximate composition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), microphotographs, cooking yields, and texture profile analysis of sausages were examined. The pH value of uncooked and cooked sausages increased significantly with increasing ES content (p<0.05). The crude protein contents of S2, S3, and S4 were significantly higher than that of the control (p<0.05). Furthermore, the SDS-PAGE results showed that α-conglycinin, β-conglycinin, and the acidic subunit of glycinin all increased with increasing ES content. Microphotographs revealed that increasing the ES content decreased the size of fat globules. The cooking yields of samples increased significantly with increasing ES content (p<0.05). The hardness values of ES treated samples were significantly lower than that of the control (p<0.05). Therefore, 30% substitute of chicken breast with ES can improve the quality and structure of Vienna sausage, without inducing critical defects.


[Various clinical characteristics of remission in patients with recurrent schizophrenia].
Altogether 194 patients suffering from attack-like schizophrenia lasting not less than 15 years since the manifest attack were examined for the clinico-dynamic features of the remission conditions as dependent on a number of endogenous and process factors: the disease period, disease duration from the manifest attack, the number of the attacks suffered by the patient. The data obtained can be used in elaboration of the socio-rehabilitation and medicamentous measures in patients suffering from attack-like schizophrenia.


The impact of peer victimization, parent distress and child depression on barrier formation and physical activity in overweight youth.
With the prevalence of childhood overweight reaching epidemic proportions, there is an increased need to identify factors which may aid in the development of successful weight intervention programs. Given that lower levels of physical activity are inversely correlated with weight status in children, research has focused on identifying and addressing reported barriers to physically activity. A relationship exists between the number of reported barriers and weight status such that children who are overweight report more barriers to being physically active. However, important demographic and psychosocial correlates of barriers have not been examined. This study investigates the relationship among parent distress, peer victimization, childhood depression, barriers to physical activity, and physical activity among a sample of 95 clinically overweight children and adolescents. Higher levels of parent distress, peer victimization, and childhood depression are predictive of a variety of barriers to physical activity, with peer victimization emerging as the strongest predictor of barriers. Barriers to physical activity mediate the relationships between peer victimization, parent distress, child depression and physical activity. These findings have significant implications for the development/design of weight intervention programs. Interventions targeting increases in physical activity should not only focus on the barriers children report, but should also include a psycho-emotional component to address factors such as parent distress, peer victimization and child mood that may contribute to barrier formation/maintenance. Future interventions may benefit from the identification of additional factors that impact barrier formation and physical activity levels among children.


Evidence of a thermal unfolding dimeric intermediate for the Escherichia coli histone-like HU proteins: thermodynamics and structure.
The Escherichia coli histone-like HU protein pool is composed of three dimeric forms: two homodimers, EcHUalpha(2) and EcHUbeta(2), and a heterodimer, EcHUalphabeta. The relative abundance of these dimeric forms varies during cell growth and in response to environmental changes, suggesting that each dimer plays different physiological roles. Here, differential scanning calorimetry and circular dichroism (CD) were used to study the thermal stability of the three E.coli HU dimers and show that each of them has its own thermodynamic signature. Unlike the other HU proteins studied so far, which melt through a single step (N(2)<-->2D), this present thermodynamic study shows that the three E.coli dimers melt according to a two-step mechanism (N(2)<-->I(2)<-->2D). The native dimer, N(2), melts partially into a dimeric intermediate, I(2), which in turn yields the unfolded monomers, D. In addition, the crystal structure of the EcHUalpha(2) dimer has been solved. Comparative thermodynamic and structural analysis between EcHUalpha(2) and the HU homodimer from Bacillus stearothermophilus suggests that the E.coli dimer is constituted by two subdomains of different energetic properties. The CD study indicates that the intermediate, I(2), corresponds to an HU dimer having partly lost its alpha-helices. The partially unfolded dimer I(2) is unable to complex with high-affinity, single-stranded break-containing DNA. These structural, thermodynamic and functional results suggest that the N(2)<-->I(2) equilibrium plays a central role in the physiology of E.coli HU. The I(2) molecular species seems to be the EcHUbeta(2) preferential conformation, possibly related to its role in the E.coli cold-shock adaptation. Besides, I(2) might be required in E.coli for the HU chain exchange, which allows the heterodimer formation from homodimers.


Development and validation of a machine learning-based fall-related injury risk prediction model using nationwide claims database in Korean community-dwelling older population.
Falls impact over 25% of older adults annually, making fall prevention a critical public health focus. We aimed to develop and validate a machine learning-based prediction model for serious fall-related injuries (FRIs) among community-dwelling older adults, incorporating various medication factors. Utilizing annual national patient sample data, we segmented outpatient older adults without FRIs in the preceding three months into development and validation cohorts based on data from 2018 and 2019, respectively. The outcome of interest was serious FRIs, which we defined operationally as incidents necessitating an emergency department visit or hospital admission, identified by the diagnostic codes of injuries that are likely associated with falls. We developed four machine-learning models (light gradient boosting machine, Catboost, eXtreme Gradient Boosting, and Random forest), along with a logistic regression model as a reference. In both cohorts, FRIs leading to hospitalization/emergency department visits occurred in approximately 2% of patients. After selecting features from initial set of 187, we retained 26, with 15 of them being medication-related. Catboost emerged as the top model, with area under the receiver operating characteristic of 0.700, along with sensitivity and specificity rates around 65%. The high-risk group showed more than threefold greater risk of FRIs than the low-risk group, and model interpretations aligned with clinical intuition. We developed and validated an explainable machine-learning model for predicting serious FRIs in community-dwelling older adults. With prospective validation, this model could facilitate targeted fall prevention strategies in primary care or community-pharmacy settings.