Phytoremediation of PAH-contaminated sediments with different organic matter contents by Potamogeton crispus L.
In this study, phytoremediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sediments with different contents of sediment organic matter (SOM) by Potamogeton crispus L. was investigated to find out the key factor controlling PAH dissipation enhancements. After a 36-day experiment, dissipation ratios of phenanthrene and pyrene in sediments were improved by P. crispus but decreased with increasing SOM content, no matter with or without P. crispus. Furthermore, the results of polyphenol oxidase activity and PAH bioavailability showed that they were both higher in planted treatments than in unplanted treatments. Finally, the enhancements of rapidly desorbing fraction (i.e., the main portion to be readily biodegradable) in sediments with SOM contents of 1.20%, 3.14%, and 5.08% by plants were 20.0%, 40.7%, and 66.7% for phenanthrene, 22.2%, 36.8%, and 58.8% for pyrene, respectively, which is consistent with the change trends of dissipation enhancements of the contaminants in sediments. However, there was no significant correlation between the enhancement of polyphenol oxidase activity and the dissipation enhancement. These results suggested that the improved bioavailability by P. crispus should be the key factor leading to the dissipation enhancements of the contaminants in sediments with different SOM contents, which provides essential information for phytoremediation of PAH-contaminated sediments.


Peritoneal insertion of shunts in children: comparison between trocar and laparoscopically guided insertion.
Ventriculo-peritoneal shunts are commonly used for treating hydrocephalus for all age groups. There are 3 main methods for shunt placement into the peritoneum: mini laparotomy, laparoscopically guided, or percutaneously with a trocar. There is limited literature comparing between these techniques in the pediatric population, and specifically-the trocar has not been compared with laparoscopy. The goal of this study is to compare trocar and laparoscopy use, with respect to safety and potential need for future shunt revisions. Data was retrospectively collected from 2 centers for children (< 18 years old) who underwent a primary insertion of a CSF shunt to the peritoneum, and had no prior abdominal surgery or significant abdominal disease. One center used a trocar, and the other laparoscopic guidance. Demographics, surgical time, and shunt complications were analyzed. Primary endpoint was distal shunt malfunction, either technique-related or non-technique-related. Two hundred fifty-seven children (220 trocar, 37 laparoscopy) were included. The groups were similar with regard to age at surgery and etiology of hydrocephalus. Trocar use was associated with a slightly higher, although statistically insignificant, rate of technique-related distal complications (4.1% vs 0, p = 0.37). Following propensity score matching, there was no statistically significant difference in any shunt complication between both groups. Trocar use was associated with shorter surgery, and less surgical personnel. In primary shunt surgery in children, abdominal placement of the catheter using a trocar or laparoscopic guidance is safe, and associated with a low distal malfunction rate, with no statistically significant differences between both techniques.


Cuproptosis-related immune checkpoint gene signature: Prediction of prognosis and immune response for hepatocellular carcinoma.
Immune checkpoint genes (ICGs), the foundation of immunotherapy, are involved in the incidence and progression of hepatocellular carcinoma (HCC). Cuproptosis is characterized by copper-induced cell death, and this novel cell death pathway has piqued the interest of researchers in recent years. It is worth noting that there is little information available in the literature to determine the relationship between cuproptosis and anti-tumor immunity. We identified 39 cuproptosis-related ICGs using ICGs co-expressed with cuproptosis-related genes. A prognostic risk signature was constructed using the Cox regression and the least absolute shrinkage and selection operator analysis methods. The signature was built using the Cancer Genome Atlas (TCGA)-Liver Hepatocellular Carcinoma database. The TCGA and International Cancer Genome Consortium cohorts were classified into two groups; the low- and high-risk groups were determined using a prognostic signature comprised of five genes. The multivariate Cox regression analysis revealed that the signature could independently predict overall survival. Furthermore, the level of immune infiltration analysis revealed the robustness of the prognostic signature-immune cell infiltration relationship observed for Tregs, macrophages, helper T cells, and naive B cells. Both groups showed significant differences in immune checkpoint expression levels. The gene enrichment analysis was used for characterization, and the results revealed that enriching various pathways such as PI3K-AKT-mTOR signaling, glycolysis, Wnt/beta-catenin signaling, and unfolded protein response could potentially influence the prognosis of patients with HCC and the level of immune infiltration. The sensitivity of the two groups of patients to various drug-targeted therapy methods and immunotherapy was analyzed. In conclusion, the findings presented here lay the foundation for developing individualized treatment methods for HCC patients. The findings also revealed that studying the cuproptosis-based pathway can aid in the prognosis of HCC patients. It is also possible that cuproptosis contributes to developing anti-tumor immunity in patients.


Local pressure for confined systems.
We derive a general closed expression for the local pressure exerted onto the corrugated walls of a channel confining a fluid medium. When the fluid medium is at equilibrium, the local pressure is a functional of the shape of the walls. It is shown that, due to the intrinsic nonlocal character of the interactions among the particles forming the fluid, the applicability of approximate schemes such as the concept of a surface of tension or morphometric thermodynamics is limited to wall curvatures that are small compared to the range of particle-particle interactions.


A new species of Microtetrameres (Nematoda, Tetrameridae) parasitizing Buteogallus urubitinga (Aves, Accipitridae) from northeastern Argentina.
A new tetramerid nematode, Microtetrameres urubitinga n. sp., is described from specimens recovered from the proventriculus of the great black-hawk, Buteogallus urubitinga (Aves: Accipitridae), from Formosa Province, Argentina. The males of the new species are characterized by having spicules unequal (length ratio of spicules 1:3.8-5.9) and dissimilar in shape (right spicule with a simple tip, left spicule with a symmetrical bifurcated tip), caudal papillae arranged asymmetrically (two pairs precloacal and two pairs postcloacal) and cloacal lips highly protruded forming a tube. The gravid females are permanently coiled clockwise or counterclockwise in a spiral and having a tail tapering gradually to a sharp point, with a cuticular fold. This is the first nominal species of Microtetrameres (Travassos, 1915) described parasitizing birds from Argentina. The relationship between the diet of B. urubitinga and the low prevalence of M. urubitinga n. sp. is discussed.


Benefits and medium-term outcome of the Sorin Pericarbon Freedom stentless aortic prosthesis in cases of acute bacterial endocarditis.
The aim of this study is to evaluate the ease of use and the advantages of Sorin Pericarbon Freedom (SPF) stentless valve in cases of acute bacterial endocarditis and to check the intermediate-term results after the implant of SPF with respect to resistance to infection, valve deterioration and durability. Between June 2003 and February 2015, 26 patients with active aortic valve bacterial endocarditis underwent aortic valve replacement with SPF pericardial stentless aortic prosthesis. The mean age was 57 ± 18 years; 73% of the patients were in preoperative NYHA class III and VI. Mean Logistic EuroSCORE was 14.2 ± 12.7. Endocarditis occurred in 18 patients with native valves, and in 9 patients with prosthetic valves (4 mechanical aortic valve prostheses; 5 aortic bioprostheses). Aortic root abscesses were observed in 16 cases (61.5%). Surgery was emergent in 3 cases (11.5%). Redo surgery was performed in 9 cases (35%). Cumulative follow-up was 126.8 patient-years (mean 4.9 ± 3.3 years). Operative hospital mortality was 0% for all patients. Residual mean prosthetic gradient at discharge was 9.4 ± 3.6 mmHg. Neither residual aortic incompetence nor residual abscess cavity was observed at discharge. Mean ejection fraction at discharge was 54 ± 8% (Min; Max: 35%; 65%). A total of 4 patients died at follow-up, all for non-cardiac causes. One patient was lost to follow-up. Two patients (8%) underwent non-valve-related reoperation with 0% mortality. Residual mean gradient at follow-up was 7.2 ± 2.1 mmHg. Three patients (17%) presented with mild/moderate aortic incompetence and 89% of patients were in NYHA Class I-II at follow-up. At 9 years, actuarial freedom from valve-related reoperation and from structural valve deterioration was 100%. The SPF aortic prosthesis is a true pericardial stentless prosthesis suitable for the treatment of acute bacterial endocarditis. Intermediate-time results in terms of freedom from reoperation, structural valve deterioration and resistance to infections are satisfactory. Haemodynamic performances are excellent since a complete exclusion of aortic root abscesses is achieved without any reduction of the aortic annular diameter, usually due to marsupialization or patch closure of the infected cavities.


A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors.
Although most pituitary tumors are benign, some are invasive or aggressive. In the absence of specific markers of malignancy, only tumors with metastases are considered malignant. To identify markers of invasion and aggressiveness, we focused on prolactin (PRL) tumors in the human and rat. Using radiology and histological methods, we classified 25 human PRL tumors into three groups (non-invasive, invasive, and aggressive-invasive) and compared them with a model of transplantable rat PRL tumors with benign and malignant lineages. Combining histological(mitoses and labeling for Ki-67, P53, pituitary transforming tumor gene (PTTG), and polysialic acid neural cell adhesion molecule) and transcriptomic (microarrays and q-RTPCR) methods with clinical data (post-surgical outcome with case-control statistical analysis), we found nine genes implicated in invasion (ADAMTS6, CRMP1, and DCAMKL3) proliferation (PTTG, ASK, CCNB1, AURKB, and CENPE), or pituitary differentiation (PITX1) showing differential expression in the three groups of tumors (P = 0.015 to 0.0001). A case-control analysis, comparing patients in remission (9 controls) and patients with persistent or recurrent tumors (14 cases) revealed that eight out of the nine genes were differentially up- or downregulated (P = 0.05 to 0.002), with only PTTG showing no correlation with clinical course (P = 0.258). These combined histological and transcriptomic analyses improve the pathological diagnosis of PRL tumors, indicating a reliable procedure for predicting tumor aggressiveness and recurrence potential. The similar gene profiles found between non-invasive human and benign rat tumors, as well as between aggressive-invasive human and malignant rat tumors provide new insights into malignancy in human pituitary tumors.


The role of endothelial cells in the pathogenesis of ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of treatment with fertility drugs. Using human lung microvascular endothelial cells (HUMEC-L) as an in-vitro model of OHSS, we have tested the hypothesis that the endothelium is a target of HCG in the pathogenesis of OHSS. Since OHSS is characterized by increased capillary permeability, we have investigated the production and action of vasoactive agents. When HUMEC-L were cultured with high doses of estradiol (E(2)), no significant changes were observed in the secretion of vascular endothelial growth factor (VEGF), interleukin (IL)-6 or IL-1 beta. However, the addition of HCG resulted in a significant increase in the secretion of VEGF and IL-6. Time-course experiments showed that VEGF was secreted within minutes of HCG addition, whereas IL-6 was significantly increased only after 48 h in culture. The secretion of IL-1 beta was unchanged by these hormonal conditions. The presence of HCG receptors was demonstrated in HUMEC-L in basal conditions as well as after the addition of E(2). The expression of VEGF receptors was also investigated. High doses of E(2) were unable to increase the expression of KDR, flt-1 and sfl-t, but the addition of HCG significantly upregulated the KDR concentration in endothelial cells, while no change was observed for flt. Permeability assays demonstrated that while E(2) alone did not change the arrangement of HUMEC-L in vitro, the presence of HCG caused changes in the actin fibres corresponding to increased capillary permeability. Anti-human VEGF antibodies were able to overcome these changes. In conclusion, these experiments show that the endothelium may be a primary target of HCG, causing an acute release of VEGF and a significant increase in IL-6 and resulting in an autocrine-paracrine action that may increase vascular permeability.


The prevalence and risk factors for gallstone disease in taiwanese vegetarians.
Gallstone disease (GSD) and its complications are major public health issues globally. Although many community-based studies had addressed the risk factors for GSD, little is known about GSD prevalence and risk factors among Taiwanese vegetarians. This study included 1721 vegetarians who completed a questionnaire detailing their demographics, medical history, and life-styles. GSD was ascertained by ultrasonography or surgical history of cholecystectomy for GSD. The predictive probability of GSD for male and female vegetarians was estimated from the fitted model. The prevalence of GSD was 8.2% for both male and female vegetarians. The risk of GSD is similar in men and women across all age groups, and increases steadily with increasing age. For male vegetarians, age (OR: 1.04; 95% CI: 1.00-1.08) and serum total bilirubin level (OR: 2.35; 95% CI: 1.31-4.22) predict risk for GSD. For female vegetarians, age (OR: 1.03; 95% CI: 1.01-1.05), BMI (OR: 1.07; 95% CI: 1.01-1.13), and alcohol consumption (OR: 7.85; 95% CI: 1.83-33.73) are associated with GSD. GSD is not associated with type of vegetarian diet, duration of vegetarianism, low education level, physical inactivity, diabetes, coronary artery disease, cerebral vascular accident, chronic renal failure, hepatitis C virus infection, and lipid abnormalities. GSD is also not associated with age at menarche, postmenopausal status, and multiparity in female vegetarians. Risk factors useful for predicting GSD in vegetarians are (1) age and total bilirubin level in men, and (2) age, BMI, and alcohol consumption in women. Many previously identified risk factors for general population does not seem to apply to Taiwanese vegetarians.


Linkage Effect Induced by Hierarchical Architecture in Magnetic MXene-based Microwave Absorber.
Hierarchical architecture engineering is desirable in integrating the physical-chemical behaviors and macroscopic properties of materials, which present great potential for developing multifunctional microwave absorption materials. However, the intrinsic mechanisms and correlation conditions among cellular units have not been revealed, which are insufficient to maximize the fusion of superior microwave absorption (MA) and derived multifunctionality. Herein, based on three models (disordered structure, porous structure, lamellar structure) of structural units, a range of MXene-aerogels with variable constructions are fabricated by a top-down ice template method. The aerogel with lamellar structure with a density of only 0.015 g cm-3 exhibits the best MA performance (minimum reflection loss: -53.87 dB, effective absorption bandwidth:6.84 GHz) at a 6 wt.% filling ratio, which is preferred over alternative aerogels with variable configurations. This work elucidates the relationship between the hierarchical architecture and the superior MA performance. Further, the MXene/CoNi Composite aerogel with lamellar structure exhibits >90% compression stretch after 1000 cycles, excellent compressive properties, and elasticity, as well as high hydrophobicity and thermal insulation properties, broadening the versatility of MXene-based aerogel applications. In short, through precise microstructure design, this work provides a conceptually novel strategy to realize the integration of electromagnetic stealth, thermal insulation, and load-bearing capability simultaneously.


Concentration-dependent and light-responsive self-assembly of bolaamphiphiles bearing α-cyanostilbene based photochromophore.
In this paper, a new bolaamphiphile bearing 1-cyano-1,2-bis(phenyl)ethene (CNBE) has been synthesized. The self-assembly of this molecule in aqueous solution is concentration-dependent. Two distinct morphologies, monomolecular layered lamellas and helical nanofibres have been obtained with the as-prepared molecular configuration. Note worthily, the helical nanofibres provide an experimental evidence for the pure twisted structure in the liquid crystals, which is theoretically proposed by De Gennes. Due to the photoisomerization of CNBE, the self-assembled nanostructures undergo morphological changes upon irradiation. Although various nanostructures were observed in the solution-state, only nanofibres were obtained after the solution was cast on a substrate, which was attributed to a strong dewetting effect. This work illustrates concentration-dependent and light-responsive self-assembly and provides a novel avenue for fabricating smart soft materials.


Tooth loss in generalized aggressive periodontitis: Prognostic factors after 17 years of supportive periodontal treatment.
This retrospective longitudinal study assessed the risk of and prognostic factors for tooth loss in patients with generalized aggressive periodontitis (GAgP) after periodontal treatment in a university setting. Fifty-seven patients (1,505 teeth) were examined before (T0) and after active periodontal therapy (APT, T1) as well as after 17.4 ± 4.8 [range: 9-28] years of supportive periodontal therapy (SPT, T2). Descriptive statistics and a Cox-proportional-hazards shared-frailty model were applied. Overall, 98 and 134 teeth were lost during APT and SPT, respectively, with 0.14 ± 0.18 teeth being lost per patient and year. During SPT, three patients (5%) lost ≥10 teeth, 14 (25%) lost 4-9 teeth, 40 lost 0-3 (70%) teeth, respectively. One-third (n = 19) of all patients lost no teeth. Mean PPD of the teeth surviving SPT was stable from T1 (3.5 ± 1.1 mm) to T2 (3.4 ± 1.1 mm). Nearly, 84% of all survived teeth showed stable or improved bone level at T2. Risk of tooth loss was significantly increased in active smokers (HR[95% CI]: 4.94[1.91/12.75]), the upper dental arch (1.94[1,16/3.25]), with each mm of residual PPD (1.41[1.29/1.53]), teeth with furcation involvement (FI) (HR 4.00-4.44 for different degrees) and mobility (5.39 [2.06/14.1] for degree III). Within the provided conservative treatment regimen, GAgP patients lost only few teeth.


Genome Sequence of Escherichia coli Isolated from an Adult in Kibera, an Urban Informal Settlement in Nairobi, Kenya.
An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id, blaTEM-1B, and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.


Determination of flumazenil in human plasma by liquid chromatography-electrospray ionisation tandem mass spectrometry.
A liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to determine unlabelled flumazenil (Ro 15-1788) in human plasma in [11C]flumazenil positron emission tomography (PET) studies. N-Methyl tri-deuterated flumazenil was used as an internal standard. The analyte and internal standard were extracted from plasma samples using solid-phase extraction, with a recovery of 78%. This was determined through the convenience of radioactivity measurements of 11C-labelled flumazenil. The evaporated and reconstituted eluate was analysed by LC-ESI-MS/MS. The calibration curve was linear over the tested concentration range of 0.05-0.5 nM (15-150 pg/ml) with a correlation coefficient, R2, of 0.998+/-0.001. A high precision was achieved, with mean intra-assay and inter-assay relative standard deviations of at most 6 and 7%, respectively. The accuracy of the method ranged from 95 to 104%. As a proof of concept, the validated method was applied in the determination of flumazenil in plasma from two healthy volunteers participating in a PET study with three repeated investigations. A bolus-infusion protocol was used to achieve a constant concentration level of flumazenil. The average plasma concentrations ranged from 0.11 and 0.19 nM and all measurements were within the calibration standard range. The flumazenil concentrations were relatively constant within each scan and the average intra-scan precision was 15%.


Lethal coronary air embolism caused by the removal of a double-lumen hemodialysis catheter: a case report.
Coronary air embolism is a rare event. We report a case in which an acute myocardial infarction occurred in the region supplied by the right coronary artery after the removal of a double-lumen hemodialysis catheter. Emergent coronary angiography revealed air bubbles obstructing the mid-segment of the right coronary artery with slow flow phenomenon distally. The patient expired due to myocardial infarction.


Diversity of endophytic bacteria in Malaysian plants as revealed by 16S rRNA encoding gene sequence based method of bacterial identification.
Bacterial endophytes do have several potential applications in pharmacy, medicine and agricultural biotech industry. The main objective of this study was to understand types of bacterial endophytes associated with dicotyledonous (dicot) and monocotyledonous (monocot) plant species. Isolation of the endophytic bacteria was performed using surface-sterilized various tissue samples, and identification of the endophytic bacterial isolates (EBIs) was completed using 16S rRNA encoding gene sequence similarity based method. In total, 996 EBIs were isolated and identified from 1055 samples of 31 monocot and 65 dicot plant species from Peninsular Malaysia. The 996 EBIs represented 71 different types of bacterial species. Twelve (12) out of 71 species are reported as endophytes for the first time. We conclude that diverse types of bacterial endophytes are associated with dicot and monocot plants, and could be useful in pharmacy, medicine and agricultural biotechnology for various potential applications.


The nutrition transition in Cuba in the nineties: an overview.
To describe and analyse the changes in diet, physical activity and body composition of the Cuban population during the 1990s and the health implications of these changes. Data on national food balance and physical activity are from government agencies and the Ministry of Public Health; nation-wide and local representative surveys were used to analyse body composition and leisure activities. Data on morbidity and mortality are from the Ministry of Public Health. The collapse of the European socialist countries and the Soviet Union, as well as the reinforced United States' blockade, provoked a sudden shortage of fuel, raw materials, imported foods and essential supplies. Per capita energy availability decreased, physical activity increased, and the prevalence of obesity decreased. Nutrition deficiencies were observed in the early 1990s, while the trend of morbidity from non-communicable disease continued to increase. The nutrition transition characteristics following the economic recovery in 1995-1996 resembled those of the 1980s because of the increased food availability, decreased physical activity and increased obesity prevalence. Programmes to deal with the complex situation generated a response in a remarkably short time. Undesirable changes in diet composition and the reduction of physical activity constitute a challenge in the current post-critical stage that must be prevented.


Midtrimester amniocentesis. Influence of operator caseload on sampling efficiency.
To evaluate the impact of operator caseload on the sampling efficiency for early and standard, midtrimester amniocentesis. Prospective ascertainment of genetic amniocenteses performed during 36 months, grouped into early (13-14 weeks' gestation) and standard procedures (15-20 weeks' gestation). Details of each amniocentesis were recorded immediately after sampling, and pregnancy outcomes were retrieved via questionnaires completed by the delivering physician. Sampling efficiency was evaluated separately in the early and standard cohorts in relation to operator caseload. In total, 193 and 707 patients underwent early and standard amniocentesis, respectively. Forty of 46 physician-operators performed < 50 total procedures during the study interval (group A). When compared to operators performing > or = 50 cases (group B, n = 6), a higher rate of single-pass success was noted among group B physicians for both early and standard procedures (A vs. B, early: 40/45 vs. 145/148, P = .018; standard: 243/295 vs. 384/412, P < .0001). Logistic regression confirmed an independent effect of physician caseload on sampling efficiency and a significant interaction between physician caseload and simultaneous ultrasound guidance in predicting single-attempt success. Operator caseload directly influenced sampling efficiency for both early and standard, midtrimester amniocentesis.


Contrast-enhanced ultrasonographic characteristics of adrenal glands in dogs with pituitary-dependent hyperadrenocorticism.
A noninvasive method for quantifying adrenal gland vascular patterns could be helpful for improving detection of adrenal gland disease in dogs. The purpose of this retrospective study was to compare the contrast-enhanced ultrasound (CEUS) characteristics of adrenal glands in 18 dogs with pituitary-dependent hyperadrenocorticism (PDH) vs. four clinically healthy dogs. Each dog received a bolus of the contrast agent (SonoVue®, 0.03 ml/kg of body weight) into the cephalic vein, immediately followed by a 5 ml saline flush. Dynamic contrast enhancement was analyzed using time-intensity curves in two regions of interest drawn manually in the caudal part of the adrenal cortex and medulla, respectively. In healthy dogs, contrast enhancement distribution was homogeneous and exhibited increased intensity from the medulla to the cortex. In the washout phase, there was a gradual and homogeneous decrease of enhancement of the adrenal gland. For all dogs with PDH, there was rapid, chaotic, and simultaneous contrast enhancement in both the medulla and cortex. Three distinct perfusion patterns were observed. Peak perfusion intensity was approximately twice as high (P < 0.05) in dogs with PDH compared with that of healthy dogs (28.90 ± 10.36 vs. 48.47 ± 15.28, respectively). In dogs with PDH, adrenal blood flow and blood volume values were approximately two- to fourfold (P < 0.05) greater than those of controls. Findings from the present study support the use of CEUS as a clinical tool for characterizing canine adrenal gland disease based on changes in vascular patterns.


The association between specific combat experiences and aspects of the Interpersonal Theory of Suicide.
Studies examining the relationship between combat exposure and suicide risk typically focus on combat exposure overall, combining numerous different combat experiences. Our study expands upon prior research by examining the association between specific combat experiences and components of both suicidal desire and the capability for suicide. We hypothesized that most combat experiences would be associated with capability for suicide. Furthermore, we hypothesized that experiences that involved direct exposure to death and injury (e.g. personally witnessing the death or injury of other soldiers) would be associated with higher levels of thwarted belongingness, perceived burdensomeness, and suicidal ideation. Participants were 400 service members drawn largely from the Army National Guard who had been deployed at least once and endorsed having experienced combat. Consistent with hypotheses, combat experiences involving direct exposure to injury or death exhibited a more pronounced pattern of associations with suicide risk factors than did other experiences. However, only a minority of combat experiences were associated with the capability for suicide. These results, while preliminary, indicate that different combat experiences are associated with different outcomes and that, in this sense, not all combat experiences are created equal with respect to suicide risk.


Re-evaluating serum angiotensin-converting enzyme in sarcoidosis.
Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and prevalence rate, and disease course largely vary with regions and populations globally. The clinical manifestations of sarcoidosis depend on the affected organs and the degree of severity, and the diagnosis is mainly based on serum biomarkers, radiographic, magnetic resonance, or positron emission tomography imaging, and pathological biopsy. Noncaseating granulomas composing T cells, macrophages, epithelioid cells, and giant cells, were observed in a pathological biopsy, which was the characteristic pathological manifestation of sarcoidosis. Angiotensin-converting enzyme (ACE) was first found in the renin-angiotensin-aldosterone system. Its main function is to convert angiotensin I (Ang I) into Ang II, which plays an important role in regulating blood pressure. Also, an ACE insertion/deletion polymorphism exists in the human genome, which is involved in the occurrence and development of many diseases, including hypertension, heart failure, and sarcoidosis. The serum ACE level, most commonly used as a biomarker in diagnosing sarcoidosis, in patients with sarcoidosis increases. because of epithelioid cells and giant cells of sarcoid granuloma expressing ACE. Thus, it serves as the most commonly used biomarker in the diagnosis of sarcoidosis and also aids in analyzing its therapeutic effect and prognosis in patients with sarcoidosis.


Biomechanics of all-out handcycling exercise: kinetics, kinematics and muscular activity of a 15-s sprint test in able-bodied participants.
This study aims to quantify the kinematics, kinetics and muscular activity of all-out handcycling exercise and examine their alterations during the course of a 15-s sprint test. Twelve able-bodied competitive triathletes performed a 15-s all-out sprint test in a recumbent racing handcycle that was attached to an ergometer. During the sprint test, tangential crank kinetics, 3D joint kinematics and muscular activity of 10 muscles of the upper extremity and trunk were examined using a power metre, motion capturing and surface electromyography (sEMG), respectively. Parameters were compared between revolution one (R1), revolution two (R2), the average of revolution 3 to 13 (R3) and the average of the remaining revolutions (R4). Shoulder abduction and internal-rotation increased, whereas maximal shoulder retroversion decreased during the sprint. Except for the wrist angles, angular velocity increased for every joint of the upper extremity. Several muscles demonstrated an increase in muscular activation, an earlier onset of muscular activation in crank cycle and an increased range of activation. During the course of a 15-s all-out sprint test in handcycling, the shoulder muscles and the muscles associated to the push phase demonstrate indications for short-duration fatigue. These findings are helpful to prevent injuries and improve performance in all-out handcycling.


[Intestinal bilharziasis with rectal bleeding: apropos of 3 cases].
The authors report three cases of Schistosoma mansoni infection among European women coming back from Burkina-Faso. Six weeks after the infestation, these three patients showed, at first, a bloody diarrhoea, then large oedemas. The treatment, with praziquantel, was not tolerate very well and all the three patients had a high fever after. This case report requests a clarification about the frequency of such symptoms. The authors focus, through this observation, on the necessity of increasing the number of stools parasitologic analysis in order to diagnose. A sole negative analysis cannot eliminate it. Sometimes, only the rectal biopsy can find the eggs of the parasite.


Rickettsia as obligate and mycetomic bacteria.
Rickettsiae are well known as intracellular pathogens of animals, humans, and plants and facultative and unorganized symbionts of invertebrates. No close relative of mitochondria has yet been associated with nutritional or developmental dependency of its host cell or organism. We have found a mycetomic Rickettsia that is a strict obligatory symbiont of the parthenogenetic booklouse Liposcelis bostrychophila (Psocoptera). These rickettsiae show an evolutionary transition from a solitary to a primary mycetomic bacterium adapted to the development of its host. These intracellular and intranuclear bacteria reside in specialized cells in several tissues. Their distribution changes markedly with the development of their host. The most advanced phenotype is a paired mycetome in the abdomen, described for the first time for Rickettsia and this host order. The mycetomic rickettsiae of two parthenogenetic book lice species are in the spotted fever group and in the basal limoniae group. While mycetomic bacteria are well known for their metabolic or light-emitting functions, these rickettsiae have an essential role in the early development of the oocyte. Removal of the Rickettsia stops egg production and reproduction in the book louse. In two phylogenetically distant psocopteran species, Rickettsia are shown to be associated with four transitional stages from free bacteria, infected cells, through single mycetocytes to organ-forming mycetomes.


Unique ability of activated CD4+ T cells but not rested effectors to migrate to non-lymphoid sites in the absence of inflammation.
Recent studies suggest that effector T cells generated by immune responses migrate to multiple non-lymphoid sites, even those without apparent expression of antigen or inflammation. To investigate the ability of distinct CD4(+) T lymphocyte subsets to enter and persist in non-lymphoid, noninflamed compartments, we examined the migration and persistence of naïve, effector, and rested effector CD4(+) T cells generated in vitro following transfer to nonimmunized adoptive hosts. Th1 and Th2 effectors migrated to both lymphoid and non-lymphoid organs (peritoneum, fat pads, and lung). In contrast, rested effectors and naïve cells migrated only to lymphoid areas. Adhesion molecule expression, but not chemokine receptor expression, correlated with the ability to enter non-lymphoid sites. Donor cells persisted longer in lymphoid than in non-lymphoid sites. When hosts with naïve and memory donor cells were challenged with antigen, effectors developed in situ, which also migrated to non-lymphoid sites. Memory cells showed an accelerated shift to non-lymphoid migration, in keeping with memory effector formation. These results suggest that only recently activated effector T cells can disperse to non-lymphoid sites in the absence of antigen and inflammation, and as effectors return to rest, they lose this ability. These data also argue that memory cells in lymphoid sites are longer lived and not in equilibrium with those in non-lymphoid sites.


Evaluation and genotyping of multidrug-resistant cases of tuberculosis in southern Brazil.
Sixty isolates of Mycobacterium tuberculosis identified as multidrug-resistant (MDR) at a reference laboratory in Rio Grande do Sul State during the years 1999 and 2000 were analyzed using the IS6110-restriction fragment length polymorphism (RFLP) technique. We also genotyped 202 susceptible strains to compare the genotyping results, as well as the clinical and demographic data. Spacer oligotyping (spoligotyping) analysis was performed for isolates presenting low IS6110 copy number. Patients with identical DNA pattern strains were considered clustered. From 262 isolates, 94 (36%) belonged to 20 distinct RFLP clusters, and after spoligotyping analysis, 89 of the isolates (34%) remained in cluster. MDR isolates did not differ statistically in clustering proportion from susceptible strains. A significant association between the occurrence of MDR and previous tuberculosis (TB) treatment was observed (p < 0.001), as well as failure on TB treatment (p < 0.001). Human immunodeficiency virus (HIV)-positive patients were associated with susceptible tuberculosis (p = 0.024). We also identified that unmarried patients were more likely to develop TB due to recent transmission than married patients (p < 0.005). The introduction of directly observed therapy short-course (DOTS) strategy will be important in decreasing default and failure rates and avoiding the development of new MDR strains.


Abdominal aortic pulsed wave Doppler patterns reliably reflect clinical severity in patients with coarctation of the aorta.
There are situations in which standard echocardiography does not adequately define the aortic arch. We sought to determine what additional information could be gained by analyzing abdominal aortic Doppler flows in coarctation. Previously recorded echocardiographic data were reviewed in 70 controls and 248 patients with coarctation, including abdominal aortic values for pulsatility indices, pulse delay, and presence of early diastolic reversal. Ability of these variables to distinguish controls from coarctation patients and to assess coarctation severity was assessed. Corrected maximum instantaneous gradient and all abdominal aortic flow variables were associated with severity of obstruction. Early diastolic reversal was universally absent in significant coarctation. Threshold values for other parameters associated with significant obstruction were: corrected pulse delay >or=3.4 msec(1/2), pulsatility index <2.0, and systolic to diastolic velocity ratio <3.6. A combined abdominal aortic "variable" (absence of early diastolic reversal and corrected pulse delay >or=2.8 msec(1/2)) was found to be the best predictor of clinical coarctation status (positive predictive value = 93%, negative predictive value = 88%). In the absence of a ductus arteriosus, abdominal aortic Doppler parameters can reliably predict the presence of significant coarctation. When early diastolic reversal was present, obstruction was always absent. Lack of early diastolic reversal with a prolonged pulse delay was the best predictor of significant obstruction. Abdominal aortic Doppler evaluation should become a routine part of the evaluation of patients with known or suspected coarctation.


[Cholecystectomy by celioscopy. Apropos of 126 cases].
One hundred twenty-six cases who underwent laparoscopic cholecystectomy were included in the study: 28 males and 98 females with a mean age of 44.2 years. Laparoscopic cholecystectomy was performed for uncomplicated cholelithiasis (111 cases), acute cholecystitis (10 cases), biliary pancreatitis (2 cases) and cholangitis (3 cases). The mean operative time was 78 minutes. In 7 cases, a transformation into open surgery was necessary (5.5%). There were no deaths and one major complication was reported: an iatrogenic injury to the bile duct requiring secondary laparotomy. The mean hospital stay was 3.4 days. However, despite several advantages, this new technique must be performed by a surgeon with experience of biliary tract surgery.


[Genetic express-test for distinguishing between haploids and autodiploids in the yeast Saccharomyces].
Some originally haploid strains of yeast Peterhof breeding stocks obtained in tetrad analysis of diploids turned out to be spontaneous autodiploids after storage. They produced polyploid hybrids, as shown by tetrad analysis. An express-test for discrimination between haploids and autodiploids, based on the frequency of mitotic homozygotisation for a recessive marker has been developed. It is 10-100 times higher in heterozygous diploids than in duplex triploids. Tester strains bearing selective recessive lys2, sup1 or sup2 marker have been obtained. The hybrids of the tester strains and those to be tested were plated on media selective for mitotic segregants homozygous for lys2 (medium with alpha-aminoadipic acid and lysine) or sup1, sup2 (medium without adenine, while the hybrid was homozygous for ochre nonsense ade1-6 suppressible by either sup1 or sup2); UV-induced mitotic homozygotisation was scored. By our method, we have shown that spontaneous autodiploids constitute 70% of strains under investigation in Peterhof breeding stocks.


Comparative and clinical evaluation between piezoelectric and conventional rotary techniques for mandibular impacted third molar extraction.
The aim of this study was to evaluate and compare the operative and postoperative outcomes of the mandibular impacted third molar removal using piezoelectric technique and conventional rotary bur technique. The study was conducted in the department of oral and maxillofacial surgery between January 1, 2019, and January 1, 2020. Thirty patients, with an age of 18-40 years, with asymptomatic bilateral impacted mandibular third molars, were selected for the study and randomly surgical extraction was done either using piezoelectric or the conventional rotary bur technique on each site. The intraoperative time taken, postoperative pain, swelling, and trismus were assessed over a follow-up period of 7 days postoperatively. Study and control groups were compared using paired t-test. There was statistical significance in reduction of pain and swelling in the study group where the duration of surgery was increased in the study group. Even if piezoelectric technique takes more time but can be used safely as another technique to conventional surgical method with surgical bur and handpiece for removal of impacted mandibular third molars.


An electronic notification system for improving patient flow in the emergency department.
Healthcare providers make time-sensitive care decisions based on EHR data. As systems of record, the EHR is often not configured to optimally surface timely information. For patients awaiting admission, infection control concerns that potentially require private rooms can prolong stays in the Emergency Department. We aim to determine if an event-based notification platform connected with a commercial EHR can help prioritize timely information and improve patient flow in the emergency department. We undertook a pre-post analysis for patients being admitted from the emergency room who were tested for influenza. We used a primary outcome of mean time from negative test result to inpatient transfer. The median time decreased by 27%, from 4.1 hours to 3.0 hours. The distribution of transfer times pre and post-intervention were significantly different with a p-value of <0.001. Our findings support the use of event-based notification systems to improve patient flow in the emergency department.


ShIVA: a user-friendly and interactive interface giving biologists control over their single-cell RNA-seq data.
Single-cell technologies have revolutionised biological research and applications. As they continue to evolve with multi-omics and spatial resolution, analysing single-cell datasets is becoming increasingly complex. For biologists lacking expert data analysis resources, the problem is even more crucial, even for the simplest single-cell transcriptomics datasets. We propose ShIVA, an interface for the analysis of single-cell RNA-seq and CITE-seq data specifically dedicated to biologists. Intuitive, iterative and documented by video tutorials, ShIVA allows biologists to follow a robust and reproducible analysis process, mostly based on the Seurat v4 R package, to fully explore and quantify their dataset, to produce useful figures and tables and to export their work to allow more complex analyses performed by experts.


miR‑4262 inhibits colon cancer cell proliferation via targeting of GALNT4.
MicroRNAs (miRs) have been demonstrated to be important in the establishment and progression of colon cancer. However the underlying molecular mechanisms remain to be fully elucidated. Polypeptide N‑acetylgalactosaminyltransferase4 (GALNT4) participates in numerous cellular processes, including tumorigenesis. The present study used reverse transcription‑quantitative polymerase chain reaction and western blotting to investigate the expression levels of miR‑4262 and GALNT4 in tissues and cells. In addition, MTS and colony formation assays, and cell cycle analysis were performed to evaluate the effect of miR‑4262 on cell proliferation and the cell cycle. The findings demonstrated that miR‑4262 was a direct target of GALNT4 mRNA. Overexpression of miR‑4262 was demonstrated to decrease GALNT4 mRNA and protein expression levels, and thereby suppressed cell viability, growth and cell‑cycle progression in SW480 and SW620 colon cancer cells. In addition, knockdown of miR‑4262 significantly increased the cell viability, growth, and cell‑cycle progression of SW480 and SW620 cells. The expression level of miR‑4262 was observed to be downregulated as the expression of GALNT4 was upregulated in colon cancer tissues and cell lines. In conclusion, the results demonstrated that miR‑4262 may be involved in the development of colon cancer via targeting of GALNT4. The miR‑4262/GALNT4 axis may be a novel target for diagnosing and understanding the underlying molecular mechanism of colon cancer.


Obesity and Failure of Nonsurgical Management of Pediatric Both-Bone Forearm Fractures.
In pediatric extremity fractures treated nonsurgically, maintaining reduction can be difficult in obese children owing to the larger soft tissue envelope. The purpose of this study was to investigate the relationship between obesity and failure of nonsurgical management of pediatric both-bone forearm fractures. We conducted a retrospective review of 129 skeletally immature patients older than 2 years who received nonsurgical treatment for closed radius and ulna shaft fractures at a level I pediatric trauma center between 2011 and 2014. The patients were divided into 2 groups: (1) normal-weight children and (2) overweight and obese children. The primary outcome measure was failure of nonsurgical management, defined as the indication for repeat closed reduction under anesthesia or surgical intervention owing to unacceptable angulation after initial closed treatment. Of the 129 patients included in the study, 34 patients (26%) were female and 95 patients (74%) were male. Seventy-six patients (59%) were normal weight, 27 patients (22%) were obese, and 26 patients (20%) were overweight. Eighteen percent (14 of 76) of normal-weight children failed nonsurgical management compared with 34% (18 of 53) of overweight and obese children. Twenty-nine percent (4 of 14) of normal-weight children who failed nonsurgical management required surgery compared with 56% (10 of 18) of overweight and obese children. Overweight and obese children have a significantly higher rate of failure of nonsurgical management of both-bone forearm fractures compared with normal-weight children. These patients may benefit from closer clinical follow-up and a lower threshold for surgical intervention. Prognosis II.


Heterogeneity in patterns of malarial oocyst infections in the mosquito vector.
Oocyst prevalence and intensity have been recorded in 349 laboratory infections of Anopheles stephensi with Plasmodium berghei. Intensity and prevalence of infection are shown to be predictably related. The structure and heterogeneity in the infections has been analysed with the objective of describing the biological mechanisms by which the observed negative binomial oocyst distributions are generated. The analysis has revealed that the most likely processes lie within the population dynamic events of malaria within the mosquito, namely gametogenesis, fertilization and mortality. The distribution is similar in all Plasmodium-mosquito combinations examined so far, whether they are of laboratory (P. gallinaceum in Aedes aegypti) or field (P. vivax in An. albimanus and P. falciparum in An. gambiae s.l. and An. funestus) origin. Further we conclude that there is competition between parasites in the vector. Oocyst frequency distribution analysis shows that under natural conditions of transmission intensity, and even under the best laboratory conditions, significant numbers (> 10%) of fully susceptible mosquitoes will not be infected under conditions where the mean infection is as high as 250 oocysts. Failure to infect is not therefore an absolute indicator of refractoriness. In assessing transmission data it is shown that sample sizes should not be less than 50, and ideally 100 mosquitoes, if reliable data are to be obtained. In field it is suggested that difficulties in determining the low natural intensity of oocyst infections indicate that prevalence estimates are a useful and accessible parameter to measure.(ABSTRACT TRUNCATED AT 250 WORDS)


"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature.
Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.


Regeneration of rat liver: transfer of humoral agent by cross circulation.
Carotid-to-jugular cross circulation between partially hepatectomized and normal rats, via polyethylene cannulas, stimulated incorporation of (14)C-thymidine into hepatic DNA in the normal partners when it was maintained for 19 hours at a flow rate of about 2 milliliters per minute. Cross circulation for 7 hours or less was ineffective.


Unidirectional current in a polyacetylene hetero-ionic junction.
Unidirectional electronic current is reported for a device based on the interface between an anionically functionalized and a cationically functionalized polyacetylene. The unidirectional current in this mixed ionically/electronically conducting system is electronic but is regulated by asymmetry in the ionic processes.


[Role of external fixators for treatment of humeral fractures: report of 23 cases using Orthofix fixators].
From 1991 to 1998, 23 humeral fractures has been treated using the Orthofix external fixator. Average age of the patient was 42 y and average follow-up 55.5 m. Initial trauma was: 13 traffic accidents, four falls at home, two devastating farming accidents, two sports accidents, one aggression and one gun accident. AO classification was used and location of the fracture was classified using Hackethal classification modified by de la Caffinière. Majority of fractures were located at the one-third distal humerus and the majority was also comminuted. At follow-up, elbow range of motion was 130 degrees, shoulder range of motion 161 degrees, external rotation 69.5 degrees and internal rotation 92.5 degrees. Using the classification of Stewart and Hundley, eight excellent, seven good, three fair and two bad results were obtained. There were no postoperative radial nerve palsy. Two external fixators had to be removed because of pin mobility. Failures were: non union and pin mobility in one patient which has to be reoperated on; two non unions have been grafted on and plated. There were no malunion in the postoperative X-rays. This device is our favourite for this type of injury because of its rigidity and the possibility of secondary dynamization. The external fixator was removed after union: this explains the long delay of union in our series.


Research for health: background and immediate implications.
This article examines the history surrounding the development of research activity within the English National Health Service, leading to the most recently published Research for Health strategy in 1993. It specifically focuses on the 2 most dominant professional groups; the medical and nursing professions and subsequently examines the impact of the strategy upon them.


Hormonal regulation of discrete portions of the cell cycle: commitment to DNA synthesis is commitment to cellular division.
Density-arrested human fibroblasts were stimulated to traverse G0/G1 and initiate DNA synthesis by the addition of medium containing either serum or a combination of platelet-derived growth factor and platelet-poor plasma. Medium containing a combination of epidermal growth factor and high concentrations of insulin also stimulated DNA synthesis in platelet factor-treated quiescent cells. Platelet factor was required only to initiate proliferation. Epidermal growth factor and insulin then allowed G1 traverse and commitment to DNA synthesis. Cells could complete S, G2, and M in unsupplemented medium lacking peptide growth factors.


[Guidelines for the management of thyroid tumors].
The treatment strategy for differentiated thyroid carcinoma in Japan is different from that in Western countries in terms of postoperative radioactive iodine (RAI) utilization, and therefore the publication of thyroid tumor guidelines has been shelved. However, an "endocrine-thyroid surgery specialist" system was established in 2008 in which the Japan Association of Endocrine Surgeons and Japanese Society of Thyroid Surgery played a key role. Subsequently, the need for thyroid tumor guidelines was increasingly felt, and the guidelines on the "Japan type" were published in 2010. In those guidelines, total thyroidectomy is recommended as the initial treatment of papillary carcinoma in high-risk groups such as patients with tumors larger than 5cm, obvious tumor invasion of other organs, or large lymph node metastases in lateral compartments. However, less extensive surgery is acceptable for other patients with papillary carcinomas. The indications for total thyroidectomy in papillary carcinoma are narrower than in the Western guidelines. RAI ablation after total thyroidectomy is also recommended for differentiated thyroid carcinoma with aggressive clinicopathologic features. The guidelines reflect the current standard Japanese treatment for thyroid carcinoma. An English version of the guidelines was published in the summer of 2012, making the Japanese treatment strategy available to the world. We hope that these guidelines will contribute to standardization of the treatment of thyroid carcinoma.


Part of prekallikrein removed from human plasma together with IgG--immunoblot experiments and functional tests.
With the present study, evidence is provided that prekallikrein (PK) in human plasma might be present in two different states, one of them removed along with IgG on Protein G columns. At a plasma dilution of 1 + 2.5, small amounts of an IgG fraction were left in plasma along with all of the PK. At a dilution of 1 + 11, nearly all IgG was removed. The removal in parallel of part of the PK was shown in immunoblot experiments and confirmed in amidase assays. One monoclonal antibody against PK (13G11) and two preparations of polyclonal antibodies were used for the immunoblot experiments. Different peptide substrates (S-2302, S-2222, Bz-Pro-Phe-Arg-pNA), along with protease inhibitors (soybean trypsin inhibitor, corn trypsin inhibitor, lima bean trypsin inhibitor) were used for the amidase assays. The amidase assays indicated that factors XII and XI were reduced by Protein G columns. In all experiments with extensive removal of IgG, protein recognized by the factor XII light chain mAb C6B7 was removed at the same time. This antibody preparation did not detect purified contact factors, but it did recognize a preparation of purified beta-FXIIa, and also significant amounts of protein present in plasma deficient in factor XII and not detectable in plasma deficient in PK. This protein accordingly seems to be connected with the PK fraction removed with IgG.


Shock-tube measurements of excited oxygen atoms using cavity-enhanced absorption spectroscopy.
We report the use of cavity-enhanced absorption spectroscopy (CEAS) using two distributed feedback diode lasers near 777.2 and 844.6 nm for sensitive, time-resolved, in situ measurements of excited-state populations of atomic oxygen in a shock tube. Here, a 1% O2/Ar mixture was shock-heated to 5400-8000 K behind reflected shock waves. The combined use of a low-finesse cavity, fast wavelength scanning of the lasers, and an off-axis alignment enabled measurements with 10 μs time response and low cavity noise. The CEAS absorption gain factors of 104 and 142 for the P35←S520 (777.2 nm) and P0,1,23←S310 (844.6 nm) atomic oxygen transitions, respectively, significantly improved the detection sensitivity over conventional single-pass measurements. This work demonstrates the potential of using CEAS to improve shock-tube studies of nonequilibrium electronic-excitation processes at high temperatures.


Optimization of the straightness measurements on rough surfaces by Monte Carlo simulation.
The straightness error of a coordinate measuring machine (CMM) is determined by measuring a rule standard. Thanks to a reversal technique, the straightness uncertainty of the CMM is theoretically dissociated from the straightness uncertainty of the rule. However, stochastic variations of the whole measurement system involve uncertainties of the CMM straightness error. To quantify these uncertainties, different sources of stochastic variations are listed with their associated probability density functions. Then Monte Carlo methods are performed first to quantify error and secondly to optimize measurement protocol. It is shown that a 5-measurement distance from 0.1 mm to each measurement coordinate allows a double reduction of uncertainties, principally due to the rule roughness amplitude (R(a) = 0.35 µm) and because this optimal distance of 0.1 mm is equal to the autocorrelation length of the rule roughness. With this optimal configuration, the final uncertainly on the straightness error of the CMM studied is less than 1 µm on the whole evaluated length of the rule (1 m). An algorithm, including Probe Tip Radius of the CMM and surface roughness of the piece, is finally proposed to increase CMM reliability by minimizing error measurements due to surface roughness of the measured piece.


Biphasic modulation of paracellular claudin-5 expression in mouse brain endothelial cells is mediated through the phosphoinositide-3-kinase/AKT pathway.
Blood-brain barrier (BBB) integrity is compromised in many central nervous system disorders. Complex astrocyte and vascular endothelial cell interactions that regulate BBB integrity may be disturbed in these disorders. We previously showed that systemic administration of 3-chloropropanediol [(S)-(+)-3-chloro-1,2-propanediol] induces a transitory glial fibrillary acidic protein-astrocyte loss, reversible loss of tight junction complexes, and BBB integrity disruption. However, the intracellular signaling mechanisms that induce BBB integrity marker loss are unclear. We hypothesize that 3-chloropropanediol-induced modulation of tight junction protein expression is mediated through the phosphoinositide-3-kinase (PI3K)/AKT pathway. To test this hypothesis, we used a mouse brain endothelial cell line (bEnd.3) exposed to 3-chloropropanediol for up to 3 days. Results showed early reversible loss of sharp paracellular claudin-5 expression 90, 105, and 120 minutes after 3-chloropropanediol (500 μM) treatment. Sharp paracellular claudin-5 profiles were later restored, but lost again by 2 and 3 days after 3-chloropropanediol treatment. Western blot and immunofluorescence studies showed increased p85-PI3K expression and transitory increased AKT (Thr308) phosphorylation at 15 and 30 minutes after 3-chloropropanediol administration. PI3K inhibitors LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one hydrochloride; 2.5-25 μM] and PI-828 [2-(4-morpholinyl)-8-(4-aminopheny)l-4H-1-benzopyran-4-one; 0.1-10 μM] prevented the 3-chloropropanediol-induced AKT (Thr308) phosphorylation and both early and late loss of paracellular claudin-5. However, AKT inhibitors only prevented the early changes in claudin-5 expression. This mechanistic study provides a greater understanding of the intracellular signaling pathways mediating tight junction protein expression and supports a hypothesis that two independent pathways triggered by PI3K mediate early and late loss of paracellular claudin-5 expression.


Families' experiences with patients who died after assisted suicide: a retrospective interview study in southern Switzerland.
In Switzerland, if certain conditions are met, assisted suicide is not prosecuted. International debate suggests that requests for hasten death are often altered by the provision of palliative care. Aims of the study were to explore patients' reasons for choice of assisted suicide and family perceptions of the interactions with health care professionals. This is a qualitative study upon 11 relatives of 8 patients cared for by a palliative care team, deceased of assisted suicide. Pain and symptom burden were not regarded by patients as key reasons to seek assisted suicide: existential distress and fear of loss of control were the determinants. Most patients had made pre-illness decisions to use assisted suicide. A general need for perceived control and fear of dependency were reported as a common characteristic of these patients. Patients held misunderstandings about the nature and purpose of palliative care, and the interviewed indicated that patients did not regard provision of palliative care services as influential in preventing their decision. Assisted suicide was preferred despite provision of palliative care. Better understanding of the importance placed on perceived control and anticipated dependency is needed. Further research is needed to develop appropriate support for patients contemplating assisted suicide.


Risk of cancer among offspring of childhood-cancer survivors. Association of the Nordic Cancer Registries and the Nordic Society of Paediatric Haematology and Oncology.
Increasing numbers of children with cancer survive and reach reproductive age. However, the risk of cancer (other than retinoblastoma) in the offspring of survivors of childhood and adolescent cancer is uncertain. Using data from national cancer and birth registries, we assessed the risk of cancer among 5847 offspring of 14,652 survivors of cancer in childhood or adolescence diagnosed since the 1940s and 1950s in Denmark, Finland, Iceland, Norway, and Sweden. The offspring were followed up for a diagnosis of cancer for 86,780 person-years, and standardized incidence ratios were calculated. Among the 5847 offspring, 44 malignant neoplasms were diagnosed (standardized incidence ratio, 2.6; 95 percent confidence interval, 1.9 to 3.5). There were 17 retinoblastomas, yielding a standardized incidence ratio of 37. There were 27 neoplasms other than retinoblastoma (standardized incidence ratio, 1.6; 95 percent confidence interval, 1.1 to 2.4). The second most common primary site of cancer among the offspring was the brain and nervous system, in which eight tumors were observed (standardized incidence ratio, 2.0; 95 percent confidence interval, 0.9 to 3.9.) There were between zero and four apparently sporadic cases of cancer in other primary sites among the offspring. Excluding 4 likely cases of hereditary cancer and 2 subsequent cancers among the offspring with hereditary retinoblastoma, there were 22 sporadic cancers, for a standardized incidence ratio of 1.3 (95 percent confidence interval, 0.8 to 2.0). There is no evidence of a significantly increased risk of nonhereditary cancer among the offspring of survivors of cancer in childhood.


Mycobacterial ES-31 serine protease--a biomarker for mycobacterium tuberculosis--a preliminary report.
There is a need for simple and reliable method to identify Mycobacterium tuberculosis from AFB smear positive cases. Utility of mycobacterial ES-31 serine protease as a marker to detect Mycobacterium tuberculosis bacilli was explored using Fluorescein isothiocyanate conjugated anti-ES-31 serine protease antibody. The presence of ES-31 serine protease in bacilli was indicated by green fluorescence on the cell surface. Green fluorescence was observed with M.tb.H37Ra bacilli and M.tb.H37Rv bacilli while no Fluorescence was observed with M. chelonae, Nocardia farcinicum as well as in E. coli showing the usefulness of ES-31 serine protease as a marker for identification of mycobacterium tubercle bacilli in cultures.


Polyvinylidene fluoride dust detector response to particle impacts.
Polyvinylidene fluoride (PVDF) dust detectors have flown on many space missions since their first use on the Vega 1 and 2 spacecraft. The fundamental operating principle of these detectors is the production of a charge upon impact by a hypervelocity dust particle. This measured signal, N, depends on the speed, v, and mass, m, of the particle. The relationship between N, v, and m was first empirically derived by Simpson and Tuzzolino. All of the PVDF dust instruments prior to the Student Dust Counter on the New Horizons mission use their formula for the calibration of the detectors. This paper provides additional dust impact calibration data, proposes a modification in the exponents for m and v, and investigates the relationship between detector temperature and detector signal.


Nucleotide sequences at the 5'-termini of the alfalfa mosaic virus RNAs and the intercistronic junction in RNA 3.
Nucleotide sequences at the 5'-termini of the alfalfa mosaic virus genomic RNAs and the intercistronic junction in RNA 3 were deduced and compared to identify possible common recognition signals for replicating enzymes in the corresponding minus-stranded viral RNAs. Homology between the 5'-terminal sequences is less than 11 nucleotides and no complementarity with the homologous sequence occurring at the 3'-end of the viral RNAs was observed. Homology between the 5'-terminus and intercistronic region in RNA 3 is compatible with the synthesis of subgenomic RNA 4 by internal initiation of transcription on the RNA 3 minus strands. The sequence around the intercistronic junction can be folded into a very stable secondary structure.


Choriocarcinoma-presenting as a primary lesion of the cervix.
A 25 year old nulliparous Russian lady presented to the hospital complaining of abdominal pain and mild vaginal bleeding. In 1999 she was diagnosed with a molar gestation and required a dilatation and curettage. On this occasion, Beta human Chorionic Gonadotrophin (BhCG) levels were elevated and a trans-vaginal ultrasound scan suggested the presence of a left-sided pelvic mass. Investigations confirmed the presence of a choriocarcinoma of the cervix. Complete assessment by a multidisciplinary team was performed and chemotherapy (methotrexate) was commenced. This case of a twenty-five year old nulliparous woman highlights the importance of appropriate follow-up in cases of irregular genital tract bleeding with a past history of trophoblastic disease.


Origin of cyanide in cultures of a psychrophilic basidiomycete.
An unidentified psychrophilic basidiomycete used valine and isoleucine as precursors to hydrocyanic acid (HCN). As probable intermediates in the pathway from valine and isoleucine two cyanogenic glucosides, linamarin and lotaustralin, were demonstrated in fungus cultures. The fungus contained two beta-glucosidases and an oxynitrilase which, acting together, were capable of releasing cyanide from both linamarin and lotaustralin. The two beta-glucosidases were purified and compared as to pH optimum, Michaelis constant, energy of activation, thermal stability, and substrate specificity. The products of methyl ethyl ketone cyanohydrin and acetone cyanohydrin dissociation by the oxynitrilase were demonstrated to be HCN together with methyl ethyl ketone and acetone, respectively. The oxynitrilase attacked aliphatic hydroxynitriles, but showed no activity on aromatic hydroxynitriles.


Aneuploidy, polyploidy and ploidy reversal in the liver.
Polyploidy has been described in the liver for over 100 years. The frequency of polyploid hepatocytes varies by age and species, but up to 90% of mouse hepatocytes and approximately 50% of human hepatocytes are polyploid. In addition to alterations in the entire complement of chromosomes, variations in chromosome copy number have been recently described. Aneuploidy in the liver is pervasive, affecting 60% of hepatocytes in mice and 30-90% of hepatocytes in humans. Polyploidy and aneuploidy in the liver are closely linked, and the ploidy conveyor model describes this relationship. Diploid hepatocytes undergo failed cytokinesis to generate polyploid cells. Proliferating polyploid hepatocytes, which form multipolar spindles during cell division, generate reduced ploidy progeny (e.g., diploid hepatocytes from tetraploids or octaploids) and/or aneuploid daughters. New evidence suggests that random hepatic aneuploidy can promote adaptation to liver injury. For instance, in response to chronic liver damage, subsets of aneuploid hepatocytes that are differentially resistant to the injury remain healthy, regenerate the liver and restore function. Future work is required to elucidate the mechanisms regulating dynamic chromosome changes in the liver and to understand how these processes impact normal and abnormal liver function.


Can operations achieve good outcomes in elderly patients with Sanders II-III calcaneal fractures?
The aim of this study was to compare the clinical effect of operative treatment and nonoperative treatment for elderly patients with Sanders II-III calcaneal fractures.The study consisted of 60 patients with Sanders II-III calcaneal fractures who were treated in our institution from January 2007 to April 2012. The clinical effect between the operative treatment group of 32 patients and the nonoperative treatment group of 28 patients was studied. Böhler angle, Gissane angle, subtalar joint motion, calcaneal width, and calcaneal height were measured before and after treatment, and these indexes were also measured on the uninjured foot. All patients were followed-up for at least 2 years, and at the last follow-up, we evaluated foot function that was assessed with the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score system. A 10-cm visual analog scale (VAS) was used to measure the degree of pain.Böhler angle, Gissane angle, calcaneal width, and calcaneal height, which were preoperatively and postoperatively measured, had a significant difference in the operative group (P < .001), but there was no significant difference between pretreatment and post-treatment in the nonoperative group. Subtalar joint motion was measured pre-treatment and post-treatment and had a significant difference in the 2 groups. When we compared the values of Böhler angle, Gissane angle, subtalar joint motion, calcaneal width, and calcaneal height between post-treatment and the uninjured foot, there was no significant difference in the operative group, but there was a significant difference in the nonoperative group. The values measured after treatment in the 2 groups had a significant difference. Finally, the AOFAS score in the operative group and the nonoperative group were 83.4 ± 9.7 and 74.7 ± 10.3, respectively, and there was a significant difference (P < .001). Also, the 10-cm VAS had a significant difference between the 2 groups.Good clinical result could be obtained with operative treatment in elderly patients with Sanders II-III calcaneal fractures. Open reduction and internal fixation should be performed if there is no surgical contraindication.


Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma treatment.
Quantitative susceptibility mapping (QSM) offers a consistent hemorrhage volume measurement independent of imaging parameters. To investigate the magnetic susceptibility of intracerebral hemorrhage (ICH) as a quantitative measurement for monitoring treatment in hematoma patients. Prospective. Twenty-six patients with acute ICH were recruited and enrolled in treatment including surgery or medication (mannitol) for 1 week. A 3D gradient echo sequence at 3.0T. The hematoma volumes on computed tomography (CT) and QSM were calculated and used for correlation analysis. Magnetic susceptibility changes from pre- to posttreatment were calculated and compared to the National Institutes of Health stroke scale (NIHSS) measure of neurological deficit for each patient. Mean susceptibility values were calculated over each region of interest (ROI). A one-sample t-test was used to assess the changes of total volumes and mean magnetic susceptibility of ICH identified between pre- and posttreatment images (P < 0.05 was considered significant) and the Bland-Altman analysis with 95% limits of agreement (average difference, ±1.96 SD of the difference). Regression of volume measurements on QSM vs. CT and fitted linear regression of mean susceptibility vs. CT signal intensity for hematoma regions were conducted in all patients. Good correlation was found between hemorrhage volumes calculated from CT and QSM (CT volume = 0.94*QSM volume, r = 0.98). Comparison of QSM pre- and posttreatment showed that the mean ICH volume was reduced by a statistically insignificant amount from 5.74 cm3 to 5.45 cm3 (P = 0.21), while mean magnetic susceptibility was reduced significantly from 0.48 ppm to 0.38 ppm (P = 0.004). A significant positive association was found between changes in magnetic susceptibility values and NIHSS following hematoma treatment (P < 0.01). QSM in hematoma assessment, as compared with CT, offers a comparably accurate volume measurement; however, susceptibility measurements may enable improved monitoring of ICH treatment compared to volume measurements alone. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:907-915.


Application of Metagenomic Next-Generation Sequencing in the Etiological Diagnosis of Infective Endocarditis During the Perioperative Period of Cardiac Surgery: A Prospective Cohort Study.
The present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE). From May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS. In the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases. mNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.


Extracellular vesicles and PD-L1 suppress macrophages, inducing therapy resistance in TP53-deficient B-cell malignancies.
Genetic alterations in the DNA damage response (DDR) pathway are a frequent mechanism of resistance to chemoimmunotherapy (CIT) in B-cell malignancies. We have previously shown that the synergy of CIT relies on secretory crosstalk elicited by chemotherapy between the tumor cells and macrophages. Here, we show that loss of multiple different members of the DDR pathway inhibits macrophage phagocytic capacity in vitro and in vivo. Particularly, loss of TP53 led to decreased phagocytic capacity ex vivo across multiple B-cell malignancies. We demonstrate via in vivo cyclophosphamide treatment using the Eμ-TCL1 mouse model that loss of macrophage phagocytic capacity in Tp53-deleted leukemia is driven by a significant downregulation of a phagocytic transcriptomic signature using small conditional RNA sequencing. By analyzing the tumor B-cell proteome, we identified a TP53-specific upregulation of proteins associated with extracellular vesicles (EVs). We abrogated EV biogenesis in tumor B-cells via clustered regularly interspaced short palindromic repeats (CRISPR)-knockout (KO) of RAB27A and confirmed that the EVs from TP53-deleted lymphoma cells were responsible for the reduced phagocytic capacity and the in vivo CIT resistance. Furthermore, we observed that TP53 loss led to an upregulation of both PD-L1 cell surface expression and secretion of EVs by lymphoma cells. Disruption of EV bound PD-L1 by anti-PD-L1 antibodies or PD-L1 CRISPR-KO improved macrophage phagocytic capacity and in vivo therapy response. Thus, we demonstrate enhanced EV release and increased PD-L1 expression in TP53-deficient B-cell lymphomas as novel mechanisms of macrophage function alteration in CIT resistance. This study indicates the use of checkpoint inhibition in the combination treatment of B-cell malignancies with TP53 loss.


Morphological substrate for the reversibility and irreversibility of pulmonary hypertension.
The reversibility of pulmonary hypertension in hypertensive pulmonary vascular disease depends, in the first place, on the feasibility of eliminating the cause of the elevation of pressure. Equally important in this respect are the type, the severity, and the extent of the pulmonary vascular lesions. This implies that various forms of pulmonary hypertension have completely different tendencies for regression. In thrombotic arteriopathy, whether caused by primary thrombosis or by embolism, the chance of regression of pulmonary hypertension, and of the vascular lesions, is limited. On the other hand, in many patients pulmonary venous hypertension and the associated vasculopathy, even when severe, appear potentially reversible. Experimental evidence suggests that the same is true in cases of hypoxic pulmonary hypertension as long as prominent complicating vascular alterations, as often observed in chronic obstructive lung disease, are absent. In plexogenic arteriopathy regression of pulmonary hypertension, following elimination of its cause, is observed whenever the vascular lesions have not progressed beyond a certain stage that can be considered a point of no return. Thereafter, there is not only no regression but a distinct tendency to progression of pulmonary vascular disease.


Balancing Clinical and Pathologic Relevence in the Machine Learning Diagnosis of Epilepsy.
The application of machine learning to epilepsy can be used both to develop clinically useful computer-aided diagnostic tools, and to reveal pathologically relevant insights into the disease. Such studies most frequently use neurologically normal patients as the control group to maximize the pathologic insight yielded from the model. This practice yields potentially inflated accuracy because the groups are quite dissimilar. A few manuscripts, however, opt to mimic the clinical comparison of epilepsy to non-epileptic seizures, an approach we believe to be more clinically realistic. In this manuscript, we describe the relative merits of each control group. We demonstrate that in our clinical quality FDG-PET database the performance achieved was similar using each control group. Based on these results, we find that the choice of control group likely does not hinder the reported performance. We argue that clinically applicable computer-aided diagnostic tools for epilepsy must directly address the clinical challenge of distinguishing patients with epilepsy from those with non-epileptic seizures.


Relationship between irradiation-induced neuro-inflammatory environments and impaired cognitive function in the developing brain of mice.
Radiation-induced brain injury (RIBI) is the most common side-effect after cranial radiation therapy (CRT). In the present study, the RIBI mice model was established and the changes in the expression of tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) mRNA, and the related signal pathways in the hippocampus of this model were investigated. 10 Gy CRT or sham-irradiation was given to the three-week old mice. The water maze test was used to test the RIBI model in mice. The expression of pro-inflammatory cytokines was detected by real-time polymerase chain reaction (PCR) in vivo. The changes of microglial activation and neurogensis in the hippocampus were analyzed by immunofluorescence and immunohistochemistry. The cytoplasm to nuclei translocation of Nuclear factor kappa B (NF-κB), and the protein expressions of IkappaB-alpha (IκB-α), NF-κB essential modulator (NEMO), p53-induced protein with a death domain (PIDD), TNF-α and IL-1β were examined by Western blotting. A RIBI model was established by Morris water maze test 6 weeks after 10 Gy CRT in three-week old C57BL/6J mice. The mRNA and protein expression levels of TNF-α and IL-1β reached the peak during the early phase after CRT. Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. Neurogensis was significantly inhibited in the hippocampus with an increase of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells. The total number of microglia was decreased after CRT, but microglial activation was significantly increased. Western blotting revealed, in the RIBI mice, the expression of IκB-α was down-regulated, accompanied by the up-regulated expression of NEMO and regulated auto-proteolysis of PIDD. Also the NF-κB pathway activation was observed in BV-2 cells after irradiation. CRT-induced pro-inflammatory cytokines release in the brain tissues and inhibition of neurogenesis in the hippocampus might be contributed by the microglial activation and play an important role in RIBI.


Modafinil effects on behavior and oxidative damage parameters in brain of wistar rats.
The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.


Case Report: Congenital Pseudoacorea in an Ocular Axenfeld-Rieger Syndrome: What is it?
This is a descriptive summary of the case of a patient with Axenfeld-Rieger syndrome associated with a congenital malformation of the iris and consequent pupillary morphological alteration of an atypical characteristic reported. This anomaly is unique in scientific literature and exhibits a peculiarity that we have called pseudoacorea: Hidden pupil. Other associated abnormal clinical findings were posterior embryotoxon, astigmatism, amblyopia, and exotropia. Diagnosis was achieved by instilling ocular mydriatics into the cul-de-sac that revealed this peculiarity. It is necessary to make a differential diagnosis with other pupillary pathologies such as corectopia, acorea and microcoria. Early detection of pathology and surgical management is necessary, since it would lead to a better visual prognosis for both amblyopia and strabismus. Among the malformations of the pupil, we can find polycoria (more than one pupil), dyscoria (abnormal pupil shape), corectopia (abnormal pupil position) and acorea (absence of pupil). In addition, morphologically normal pupils can denote other anomalies such as the microcoria described by Holth in 1923. Acorea is a rare anomaly, congenital or acquired, characterized by an absolute absence of the pupil both at rest and in mydriasis. In our case we prefer to differentiate it and name it pseudoacorea, since although there is a total absence of the pupil at rest thanks to the application of ocular mydriatics, a micropupil with discoric and corectopic characteristics is achieved. It is worth noting that we have not detected in the scientific literature any case described as the one that we will develop here. The case of a patient with Axenfeld-Rieger syndrome associated with a congenital malformation of the iris and consequent atypical pupillary morphological alteration is presented. This anomaly is unique in the scientific literature and presents a peculiarity that we have called pseudoacorea: Hidden pupil. Early detection of pathology and surgical management is necessary, since it would lead to a better visual prognosis for both amblyopia and strabismus.


Soluble CD163 predicts incident chronic lung, kidney and liver disease in HIV infection.
To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma-soluble CD163 (sCD163) and incident non-AIDS comorbidities in well treated HIV-infected individuals. Prospective single-center cohort study. Plasma sCD163 was quantified by ELISA technique at study entry in 2004/2005, and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision diagnosis codes and registry linkage in 2015. Associations between sCD163 and incident comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. In HIV-1-infected individuals (n = 799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease [adjusted hazard ratio (aHR), 3.2; 95% confidence interval (CI): 1.34; 7.46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer, cardiovascular disease or diabetes mellitus. sCD163 was independently associated with incident chronic kidney disease, chronic lung disease and liver disease in treated HIV-1-infected individuals, suggesting that monocyte/macrophage activation may be involved in the pathogenesis of non-AIDS comorbidity and a potential target for therapeutic intervention.


Looking back over 10 years of Materials Horizons.
Current Editorial Board Chair Martina Stenzel reflects on the last 10 years of the journal in celebration of the 10th anniversary of Materials Horizons, looking back at her time as Scientific Editor, and now Chair of the Editorial Board.


Absence of glyphosate-induced effects on ovarian folliculogenesis and steroidogenesis.
Glyphosate (GLY) is an herbicidal active ingredient and both in vitro and in vivo studies suggest that GLY alters ovarian function. To determine if a chronic GLY exposure model affected steroidogenesis or folliculogenesis in vivo, postnatal day 42 C57BL6 female mice were orally delivered vehicle control (saline) or GLY (2 mg/Kg) from a pipette tip five days per week for either five or ten weeks. Mice were euthanized at the pro-estrus stage of the estrous cycle. GLY exposure did not impact body weight gain, organ weights, or healthy follicle numbers. In addition, GLY exposure did not affect abundance of ovarian mRNA encoding kit ligand (Kitlg), KIT proto-oncogene receptor tyrosine kinase (c-Kit), insulin receptor (Insr), insulin receptor substrate (Irs1 or Irs2) and protein thymoma viral proto-oncogene 1 (AKT) or phosphorylated AKT. Ovarian mRNA or protein abundance of Star, 3β-hydroxysteroid dehydrogenase (Hsd3b1), Cyp11a1 or Cyp19a were also not altered by GLY. Circulating 17β-estradiol and progesterone concentration were unaffected by GLY exposure. In conclusion, chronic GLY exposure for five or ten weeks did not affect the ovarian endpoints examined herein.


IL28B inhibits hepatitis C virus replication through the JAK-STAT pathway.
The combination of pegylated interferon (IFN) α and ribavirin (RBV) is the standard therapy for patients with chronic HCV infection. However, it produces a sustained virologic response (SVR) in only half of the treated individuals and is associated with significant side effects. Recently, several single-nucleotide polymorphisms (SNPs) near the IL28B locus, also known as IFNλ3, were identified to be strong predictors of SVR in patients receiving PEG-IFN and RBV. We sought to determine whether IL28B was capable of inhibiting HCV replication and to determine the pathway by which IL28B exhibits anti-HCV activity. Using the full-length HCV replicon OR6 and the infectious HCV clones JFH1 and Jc1, we assessed the anti-HCV effect of IL28B on HCV and characterized the key steps of the JAK-STAT pathway by real time PCR, luciferase assay, and Western blot. Finally, we evaluated the anti-HCV effect of IL28B in the presence of JAK-STAT pathway inhibitors such as blocking antibodies, a pharmacological inhibitor, and siRNAs. We found that IL28B inhibits HCV replication in a dose- and time-dependent manner. Like IFNα, IL28B induces the phosphorylation of STAT1 and STAT2, ISRE-driven transcription, and expression of known ISGs. The anti-HCV effects of IL28A, IL28B, and IL29 were abrogated by an IL10R2 blocking antibody, a pharmacological inhibitor of JAK1/TYK2, and by siRNA against IL28R1, STAT1, STAT2, and IRF9. Our data demonstrate that IL28A, IL28B, and IL29 signal through the JAK-STAT pathway to inhibit HCV. These data suggest possible applications of new approaches in HCV treatment.


LncRNA SNHG4 promotes neuroblastoma proliferation, migration, and invasion by sponging miR-377-3p.
Long non-coding RNAs (lncRNAs) have been demonstrated to act as essential regulators in the growth and progression of neuroblastoma. In the present research, the high expression of lncRNA small nucleolar RNA host gene 4 (SNHG4) in neuroblastoma was tested via quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and then the function of SNHG4 was explored and verified by CCK-8 assay, EdU assay, cell cycle assay, cell apoptosis test, wound healing test and invasion test in neuroblastoma cell lines. It was discovered that lncRNA SNHG4 exhibited high expression in neuroblastoma tissues and cell lines, and the expression of SNHG4 was associated with the survival of neuroblastoma patients. Additionally, SNHG4 decrement markedly repressed neuroblastoma cells to proliferate and stimulate their apoptosis in vivo and in vitro. Moreover, SNHG4 decrement impeded the abilities of SH-SY5Y and IMR-32 cells to migrate and invade as well as epithelial-mesenchymal transition (EMT). In mechanism, we found that SNHG4 acted as a competing endogenous RNA to sponge miR-377-3p, which was downregulated in neuroblastomas and inhibited cell proliferation and invasion. The findings manifested that SNHG4 was inversely associated with miR-377-3p expression in neuroblastoma cases. Collectively, we revealed the functions of SNHG4 and miR-377-3p in neuroblastoma.


Multiple imputation in a longitudinal cohort study: a case study of sensitivity to imputation methods.
Multiple imputation has entered mainstream practice for the analysis of incomplete data. We have used it extensively in a large Australian longitudinal cohort study, the Victorian Adolescent Health Cohort Study (1992-2008). Although we have endeavored to follow best practices, there is little published advice on this, and we have not previously examined the extent to which variations in our approach might lead to different results. Here, we examined sensitivity of analytical results to imputation decisions, investigating choice of imputation method, inclusion of auxiliary variables, omission of cases with excessive missing data, and approaches for imputing highly skewed continuous distributions that are analyzed as dichotomous variables. Overall, we found that decisions made about imputation approach had a discernible but rarely dramatic impact for some types of estimates. For model-based estimates of association, the choice of imputation method and decisions made to build the imputation model had little effect on results, whereas estimates of overall prevalence and prevalence stratified by subgroup were more sensitive to imputation method and settings. Multiple imputation by chained equations gave more plausible results than multivariate normal imputation for prevalence estimates but appeared to be more susceptible to numerical instability related to a highly skewed variable.


Predicting the Efficacy of Neoadjuvant Chemotherapy for Pancreatic Cancer Using Deep Learning of Contrast-Enhanced Ultrasound Videos.
Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.