A human cell panel for evaluating safe application of nano-ZrO2/polymer composite in water remediation.
Nanomaterials, such as ZrO2 nanoparticles (ZrO2 NPs), are very effective in water remediation. However, the safety issues related to nanoparticle release and toxicity to humans remain to be resolved. Here we evaluated the cytotoxicity of ZrO2 NPs and their adducts with pollutants using a human cell panel containing stomach, intestine, liver and kidney cells. We found that different pollutants or ZrO2NP/pollutant adducts targeted cells from different organs, suggesting the necessity of a cell panel to model oral exposures. The cooperation of ZrO2 NPs and pollutants was quite complex, consisting of synergistic, antagonistic, or additive effects. For example, ZrO2 NPs enhanced the cytotoxicity of Pb2+ in GES-1 cells and of Pb2+, Cd2+ in FHC cells, while alleviating the toxicity of Pb2+ and As (III) in HepG2 and Hek293 cells. Our results also indicated that even concentrations of pollutants that meet the national standard, the ZrO2 NPs concentration should be kept below 17 μg/mL to avoid ZrO2 NP/pollutant adduct synergistic toxicity.


Cryo-balloon catheter localization in X-Ray fluoroscopy using U-net.
Automatic identification of interventional devices in X-ray (XR) fluoroscopy offers the potential of improved navigation during transcatheter endovascular procedures. This paper presents a prototype implementation of fully automatic 3D reconstruction of a cryo-balloon catheter during pulmonary vein isolation (PVI) procedures by deep learning approaches. We employ convolutional neural networks (CNN) to automatically identify the cryo-balloon XR marker and catheter shaft in 2D fluoroscopy during PVI. Training data are generated exploiting established semiautomatic techniques, including template-matching and analytical graph building. A first network of U-net architecture uses a single grayscale XR image as input and yields the mask of the XR marker. A second network of the similar architecture is trained using the mask of the XR marker as additional input to the grayscale XR image for the segmentation of the cryo-balloon catheter shaft mask. The structures automatically identified in two 2D images with different angulations are then used to reconstruct the cryo-balloon in 3D. Automatic identification of the XR marker was successful in 78% of test cases and in 100% for the catheter shaft. Training of the model for prediction of the XR marker mask was successful with 3426 training samples. Incorporation of the XR marker mask as additional input for the model predicting the catheter shaft allowed to achieve good training result with only 805 training samples. The average prediction time per frame was 14.47 ms for the XR marker and 78.22 ms for the catheter shaft. Localization accuracy for the XR marker yielded on average 1.52 pixels or 0.56 mm. In this paper, we report a novel method for automatic detection and 3D reconstruction of the cryo-balloon catheter shaft and marker from 2D fluoroscopic images. Initial evaluation yields promising results thus indicating the high potential of CNNs as alternatives to the current state-of-the-art solutions.


Uncomplicated urinary tract infections in the emergency department: a review of local practice patterns.
To determine the number of urine cultures ordered for women who presented to the emergency department (ED) with symptoms of uncomplicated UTI, and whether a culture result impacted subsequent management. This was a retrospective chart review of non-pregnant women aged 18-39 presenting to one of two academic EDs with a discharge diagnosis of uncomplicated UTI over a one-year study period. Patients were excluded if there was documentation of fever, immunocompromised state, diabetes mellitus, absence of lower urinary tract symptoms, ED administration of intravenous antibiotics, a previous UTI treated with antibiotics in the last 90 days, two weeks post-partum or post-instrumentation. Of the 512 charts included in the analysis, 494 (96.5%) patients had a urinalysis, of which 463 (93.7%) had positive leukocyte esterase and 90 (18.2%) had positive nitrites. 370 patients (72.3%) had urine cultures performed, of which 236 (63.8%) were positive. 505 (98.6%) patients received antibiotics (53.9% Macrobid; 22.6% Ciprofloxacin; 15.0% Septra; 6.7% other; 1.8% not documented). 7 (1.9%) cultures grew organisms resistant to the prescribed antibiotic; 2 (0.5%) patients received new prescriptions. For the majority of young female patients with an uncomplicated UTI, urine cultures did not change management in the ED setting. However, when the diagnosis is uncertain based on symptomology and urinalyses alone, a urine culture may be warranted. Greater efforts should be directed towards educating emergency physicians on accurately diagnosing uncomplicated cystitis and the limited impact of urine cultures on treatment once a diagnosis has been made.


Nanocomposite hydrogel based on sodium alginate, poly (acrylic acid), and tetraamminecopper (II) sulfate as an efficient dye adsorbent.
In this study, a novel nanocomposite hydrogel (NCH) was prepared by in situ crosslinking and radical polymerization of acrylic acid (AA) in the presence of sodium alginate (Na-Alg), followed by loading of Cu2+ ions and reaction with ammonia. The main advantage of the synthesized NCH is the high adsorption of dye due to the large contact area. The structure of the NCH was studied by FT-IR spectroscopy, TEM, and SEM. TEM showed that the size of nanoparticles is about 5-30 nm. The adsorption of dye was studied by changing the different factors. The removal efficiency of Crystal Violet (CV) and Malachite Green (MG) was found to be more than 96% at concentration of 10 mg/L and pH = 6. The dye adsorption on the NCH is well described by Freundlich isotherm and pseudo-second-order kinetic models. The reusability experiments showed that about 95% of the initial adsorption was obtained after eight cycles.


[Cartilage-damaging effect of quinolones].
The cartilage damaging effect of quinolones on juvenile experimental animals represents an unusual effect which is unknown, in this form, for other classes of substances. Since the damage is manifested at quite low doses the manufacturers and regulatory agencies have taken the consequence of declaring these preparations counter-indicated for children and adolescents up to the end of the growing period. Motor disturbances were observed only rarely, and only in individual cases, seen after therapeutic use of these drugs for the treatment of bacterial infections. In spite of long-term and sometimes high dose treatment with nalidixic acid during the 1960s and 1970s (the arthropathogenic effect on dogs was first described in 1977) no joint alterations could be demonstrated clinically or by x-ray. From this conclusion can be drawn that the effects seen in animal experiments under therapeutic conditions do not occur with the same intensity in humans. But, since many questions concerning this unusual toxic potential are still unanswered, quinolones continue to be counter-indicated for patients who are in the growing phase. Further experimental data and clinical observations are necessary to exclude with certainty the possible danger of joint damage to young patients. Even today it is still unclear whether the generally favourable clinical observations made with nalidixic acid also hold true for the other quinolones and whether differences in the possible risks exist. It will only become possible to define, with the necessary amount of certainty, indications for the use of quinolones in pediatrics when further information is available.


Use of a renal tubule cell line (LLC-PK1) to study the nephrotoxic potential of a kappa-type Bence-Jones protein.
The cytotoxicity of a Bence-Jones protein was assessed using a porcine renal tubule cell line (LLC-PK1), with the aim of developing a model for studying the potential nephrotoxicity of these proteins. The effects of a kappa Bence-Jones protein on cell viability were studied by means of biochemical methods (supravital dye uptake and measurement of cellular enzyme activities) and morphological electron microscopy. After a 24-h-treatment with Bence-Jones protein, a moderate cytotoxicity (about 15%) was noted but only a minor difference compared to treatment with bovine albumin in the same conditions. The morphological study showed a few cells in the process of lysis, but their numbers were insufficient for the demonstration of a clear cytotoxic effect. Immunocytochemical studies showed Bence-Jones protein fixation on some cells, especially on the outer membrane. Labeling of the hyaloplasm and basal pole of a few cells pointed to internalization of protein by LLC-PK1 cells. Although the cytotoxicity of the Bence-Jones protein tested here was only moderate, the use of this model enabled its cytotoxic effect to be distinguished from that of beta-lactoglobulin. This isolate could serve as a "moderate control" for a later study with a BJP having caused acute renal failure.


Logical modelling reveals the PDC-PDK interaction as the regulatory switch driving metabolic flexibility at the cellular level.
Metabolic flexibility is the ability of an organism to switch between substrates for energy metabolism, in response to the changing nutritional state and needs of the organism. On the cellular level, metabolic flexibility revolves around the tricarboxylic acid cycle by switching acetyl coenzyme A production from glucose to fatty acids and vice versa. In this study, we modelled cellular metabolic flexibility by constructing a logical model connecting glycolysis, fatty acid oxidation, fatty acid synthesis and the tricarboxylic acid cycle, and then using network analysis to study the behaviours of the model. We observed that the substrate switching usually occurs through the inhibition of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinases (PDK), which moves the metabolism from glycolysis to fatty acid oxidation. Furthermore, we were able to verify four different regulatory models of PDK to contain known biological observations, leading to the biological plausibility of all four models across different cells and conditions. These results suggest that the cellular metabolic flexibility depends upon the PDC-PDK regulatory interaction as a key regulatory switch for changing metabolic substrates.


How psychiatrist's communication skills and patient's diagnosis affect emotions disclosure during first diagnostic consultations.
To describe how emotions are disclosed during psychiatric diagnostic consultations and the contribution of the psychiatrists in facilitating their expression. Descriptive naturalistic study. Sixteen psychiatrists recorded their first consultations with 104 patients. Emotions and the immediate response given by the psychiatrist were coded with the Verona Coding Definitions of Emotional Sequences. For each disclosed emotion, the potential link to preceding expressions with affective content (cue or concern) was checked and the immediate response given by the psychiatrist was coded. Most emotions were expressions of anxiety in terms of psycho-physiological or cognitive correlates. Concerns were present in 94% of the consultations, 47.6% were not linked to previous cues/concerns. Cues which became concerns and concerns which were further elaborated by the patient were those that had been acknowledged and handled by the psychiatrist by actively providing space to their expression. Compared to all other diagnostic groups, patients with mood disorders talked more explicitly and more often about their feelings. The type and frequency of expressed emotions varies with patient diagnosis, suggesting different cognitive processes underlining psychopathology. Psychiatrist's competence in providing space by using active listening skills is essential to uncover patients emotions.


Unsubtracted Roadmap Technique for Preventing Cement Leakage During Percutaneous Vertebroplasty: A Retrospective Cohort Study.
To determine the effectiveness of the unsubtracted roadmap technique (USRT) for decreasing cement leakage (CL) during percutaneous vertebroplasty (PVP). In this retrospective cohort study, patients who underwent PVP between January and November 2018 were included. Patients were divided into the unsubtracted roadmap (UR) (n = 20) and conventional venography (CV) (n = 22) groups. USRT was performed before cement injection in the UR group. Computed tomography was performed on the first day after PVP in both groups to assess the CL. The vertebral height restoration rate was confirmed by radiography before and after the procedure. The CL location was classified as basivertebral vein (type B), segmental vein (type S), or cortical defect (type C). Visual analog scale and Oswestry Disability Index scores before and after surgery were calculated to confirm clinical outcomes. Based on the computed tomography images, CL occurred in 7 (34.78%) and 15 (63.64%) cases in the UR and CV groups, respectively. Number of CL type B, S, and C in the UR and CV groups were 2 and 6, 3 and 6, and 2 and 3, respectively. The injected cement volume was not significantly different between the UR (4.86 mL) and the CV (4.75 mL) groups (P = 0.450). Regarding vertebral body height restoration (P = 0.856) and clinical outcomes, there were no significant differences between both groups. Radiation exposure was significantly less in the UR group (P = 0.019). USRT is an effective method for reducing CL and radiation exposure during PVP.


Host/parasite interactions in bacterial endophthalmitis.
Bacterial infections within the eye arise as complications of intraocular surgery, penetrating injury, or hematogenous spread from distant anatomical sites. Because: 1) the interior surfaces of the eye are lined with sensitive, nonregenerating tissues, 2) the inner chambers of the eye are relatively sequestered from circulating immunological components, 3) the integrity of blood-ocular barriers provides poor penetration of systemically administered antibiotics, and 4) aqueous and vitreous humor represent rich, relatively acellular culture media; endophthalmitis often progresses rapidly and total loss of vision frequently results. Years of clinical experience have shown that current therapies for endophthalmitis, including antimicrobials, antiinflammatory agents, and vitrectomy, are frequently unsuccessful in ameliorating destruction of intraocular tissues. While bacterial and host factors were thought to play key roles in the course and severity of endophthalmitis, it is only recently that their contributions have been experimentally defined. Molecular-based techniques are gaining increased use in the study of infectious eye diseases. Current findings regarding the host/parasite interactions within the eye are reviewed, and a resulting integrative model of the natural course of endophthalmitis proposed. A molecular-level understanding of the roles of both bacterial and host factors during endophthalmitis will likely reveal potential targets for therapeutic intervention aimed at salvaging vision.


Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone.
It is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to -70 degrees C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by greater than or equal to 1 lamella of osteoid and greater than or equal to 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (kappa statistic, range 0.71-1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which greater than 3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP-positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP-positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level).(ABSTRACT TRUNCATED AT 250 WORDS)


Richter's type strangulated femoral hernia containing caecum and appendix masquerading as a groin abscess.
Femoral hernias are challenging conditions, not only because their diagnosis is often missed, but also because if left undiagnosed and untreated, their complications are severe and often life-threatening. The authors present the second reported case of a femoral hernia of the Richter's variety containing caecum and appendix that, following strangulation and perforation, manifested as a groin abscess.


Learning from biomedical linked data to suggest valid pharmacogenes.
A standard task in pharmacogenomics research is identifying genes that may be involved in drug response variability, i.e., pharmacogenes. Because genomic experiments tended to generate many false positives, computational approaches based on the use of background knowledge have been proposed. Until now, only molecular networks or the biomedical literature were used, whereas many other resources are available. We propose here to consume a diverse and larger set of resources using linked data related either to genes, drugs or diseases. One of the advantages of linked data is that they are built on a standard framework that facilitates the joint use of various sources, and thus facilitates considering features of various origins. We propose a selection and linkage of data sources relevant to pharmacogenomics, including for example DisGeNET and Clinvar. We use machine learning to identify and prioritize pharmacogenes that are the most probably valid, considering the selected linked data. This identification relies on the classification of gene-drug pairs as either pharmacogenomically associated or not and was experimented with two machine learning methods -random forest and graph kernel-, which results are compared in this article. We assembled a set of linked data relative to pharmacogenomics, of 2,610,793 triples, coming from six distinct resources. Learning from these data, random forest enables identifying valid pharmacogenes with a F-measure of 0.73, on a 10 folds cross-validation, whereas graph kernel achieves a F-measure of 0.81. A list of top candidates proposed by both approaches is provided and their obtention is discussed.


Advanced graphene oxide-based membranes as a potential alternative for dyes removal: A review.
Graphene oxide (GO) is one of the most well-known graphene derivatives which, due to its outstanding chemical, electrical and optical properties as well as its high oxygen content, has been recently applied in several fields such as in the construction of sensors, as antimicrobial agent for biomedical applications, as well as nanofiller material for membranes applied in wastewater treatment. In this last-mentioned field, the synthesis and functionalization of membranes with GO has proven to improve the performance of membranes applied in the treatment of wastewater containing dyes, regarding antifouling behavior, selectivity and flux. In this review, an overview of water pollution caused by effluents containing synthetic dyes, the advantages and limitations of GO-based membranes and the latest research advances on the use of GO-based membranes for dyes removal, including its impact on membrane performance, are discussed in detail. The future panorama of the applicability of GO-based membranes for the treatment of water contaminated by dyes is also provided.


Mechanistic relationship of all-terrain vehicles and pediatric renal trauma.
To identify and discuss the mechanistic risk factors associated with genitourinary (GU) trauma in pediatric all-terrain vehicle (ATV) accidents. A retrospective analysis of all pediatric trauma admissions to a level 1 trauma center from 2005 to August 2011 was performed. We identified all pediatric patients who presented with GU trauma related to an ATV accident. The demographics, injury data, mechanism of injury, and treatment records of these children were investigated. A total of 304 pediatric patients were admitted with ATV-related injuries during the study period. Of these 304 patients, 10 (3.2%) had experienced GU injuries. An analysis of the mechanism revealed that 9 of the 10 had been thrown from the ATV; 1 event was described as a rollover accident. All 10 patients sustained renal trauma: 9 renal lacerations of various grades and 1 renal pedicle injury. Hematuria was observed in all cases. Spleen and liver lacerations were commonly associated injuries (40% and 30%, respectively). Pediatric ATV-related GU injuries remain an uncommon, yet serious, problem. Renal trauma is the most commonly encountered GU injury and can be suspected by the presence of hematuria. Analysis of the mechanism of injury suggests that ejection from the ATV places pediatric patients at the greatest risk of renal injury. Additional research is recommended concerning the mechanistic relationship of ATV-related GU trauma.


Von Hippel-Lindau "Black Forest" mutation inherited in a large Chinese family.
The Von Hippel-Lindau (VHL) p.Tyr98His (Y98H) mutation is designated as the "Black Forest" founder mutation and has been previously reported in Western countries. This study reports the first recorded Chinese VHL family with the "Black Forest" mutation in Asia. Paired whole-exome sequencing (WES), Sanger sequencing and immunohistochemistry (IHC) were performed on samples from a large Chinese family to confirm the causative mutation and mutation carriers in the family. Clinical manifestations of the family were summarized and compared with those reported from other patients with the VHL Y98H mutation. The Chinese pheochromocytoma (PCC) family was identified as a VHL type 2 family with a Y98H mutation. There were 4 VHL patients and 11 currently healthy individuals with the mutation. Copy number analysis and SDHB IHC were performed to exclude interference from other pathogenic genes of PCC or paraganglioma (PGL). We report the first recorded instance of a Chinese VHL type 2 family with the "Black Forest" mutation by using WES and Sanger sequencing, which widens the currently recorded presence of the "Black Forest" mutation to China and potentially elsewhere in Asia and indicates that the "Black Forest" mutation does not uniquely evolve in occidental countries. A personalized surveillance approach, which may be more appropriate for affected families, has been recommended to improve quality of life.


Measuring satisfaction with appearance: Validation of the FACE-Q scales for double-eyelid blepharoplasty with minor incision in young Asians- retrospective study of 200 cases.
Double eye-lid surgery is one of the most popular performed aesthetic procedures in young Asians. Reliable measurement of patient reported outcomes is crucial for facial aesthetics. The FACE-Q is a new patient-reported outcome tool (PRO) composed of numerous independently functioning scales and checklists designed to measure outcomes. Here we described FACE-Q scales for double eye-lid surgery with minor incision in young Asians. 200 patients (400 eyes) aged from 21 to 30 years-old were recruited from 2012 to 2014. They underwent minor incision procedure for double-eyelid blepharoplasty, epicanthic fold correction, excessive orbit fat removal and blepharoptosis correction simultaneously. An incision of 1 cm long in the middle of upper eyelid and modified Park's Z-plasty for epicanthus correction were designed. Three stitches were carried out in levator aponeurosis-inferior dermis procedure. By the middle incision in the upper eyelid, blepharoptosis correction and excessive orbit fat removal can be executed. Those patients were asked to complete anonymously the FACE-Q by e-mail. FACE-Q scores were assessed for each domain (range, 0 to 100), with higher scores indicating greater satisfaction with appearance or superior quality of life. After a mean of 2 years' follow-up, postoperative complications included partial or complete loss of the double-eyelid fold in 8 and 0 cases, respectively, no hypertrophic scar formation, and asymmetric fold in four cases. One patient received re-operation on blepharoptosis correction. Except hematoma occurring in one female case, no obvious edema was observed. Patients demonstrated high levels of satisfaction with eye appearance overall (mean ± SD, 81.7 ± 18.3). Quality of Life Patients exhibited high levels of quality of life, including in social confidence (95.4 ± 12.6), psychological well-being (97.8 ± 10.3), and early life impact of the procedure (90.2 ± 13.4). Patients reported high satisfaction with the decision to undergo and the outcome of the procedure. Minimally invasive procedure is a reliable tool for correcting disfigurement in double-eyelid blepharoplasty. However, this method is not suitable for those cases whose upper eyelids are featured by relaxation. Excessive amount of skin must be removed. Patients who responded in this study were extremely satisfied with their decision to undergo double-eyelid surgery and the outcomes and quality of life following the procedure.


Flexoelectric effects in model and native membranes containing ion channels.
An experimental study of flexoelectricity in model membranes containing ion pores and native membranes containing ion channels has been undertaken with the objective of determining the relationship, if any, between flexoelectricity and ion transport. Model membrane patches containing ion pores induced by a blue-green algal toxin, microcystin-LR, and locust muscle membrane patches containing potassium channels were studied using patch-clamp techniques. A correspondence was established between the presence of open channels and pores and the amplitude of the 1st harmonic of the total membrane current when the membranes or patches were subjected to pressure oscillations. The 2nd harmonic of the membrane current provided a measure of the amplitude of a membrane curvature induced by pressure, thus making it possible to determine the membrane flexoelectric coefficient. This study shows that flexoelectricity could be an effective driving force for ion transport through membrane pores and channels, thus further highlighting the possible biological significance of this mechano-electric phenomenon.


Development and evaluation of a TaqMan MGB RT-PCR assay for detection of H5 and N8 subtype influenza virus.
Highly pathogenic influenza A (H5N8) viruses have caused several worldwide outbreaks in birds and are of potential risk to humans. Thus, a specific, rapid and sensitive method for detection is urgently needed. In the present study, TaqMan minor groove binder probes and multiplex real-time RT-PCR primers were designed to target the H5 hemagglutinin and N8 neuraminidase genes. A total of 38 strains of avian influenza viruses and other viruses were selected to test the performance of the assay. The results showed that only H5 and N8 avian influenza viruses yielded a positive signal, while all other subtypes avian influenza viruses and other viruses were negative. High specificity, repeatability, and sensitivity were achieved, with a detection limit of 10 copies per reaction. The developed assay could be a powerful tool for rapid detection of H5N8 influenza viruses in the future.


Effect of nintedanib in patients with systemic sclerosis-associated interstitial lung disease and risk factors for rapid progression.
To investigate the rate of decline in forced vital capacity (FVC), and the effect of nintedanib on the rate of decline in FVC, in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD) who had risk factors for rapid decline in FVC. The SENSCIS trial enrolled subjects with SSc and fibrotic ILD of ≥10% extent on high-resolution CT. The rate of decline in FVC over 52 weeks was analysed in all subjects and in those with early SSc (<18 months since first non-Raynaud symptom), elevated inflammatory markers (C reactive protein ≥6 mg/L and/or platelets ≥330×109/L) or significant skin fibrosis (modified Rodnan skin score (mRSS) 15-40 or mRSS ≥18) at baseline. In the placebo group, the rate of decline in FVC was numerically greater in subjects with <18 months since first non-Raynaud symptom (-167.8 mL/year), elevated inflammatory markers (-100.7 mL/year), mRSS 15-40 (-121.7 mL/year) or mRSS ≥18 (-131.7 mL/year) than in all subjects (-93.3 mL/year). Nintedanib reduced the rate of FVC decline across subgroups, with a numerically greater effect in patients with these risk factors for rapid FVC decline. In the SENSCIS trial, subjects with SSc-ILD who had early SSc, elevated inflammatory markers or extensive skin fibrosis had a more rapid decline in FVC over 52 weeks than the overall trial population. Nintedanib had a numerically greater effect in patients with these risk factors for rapid ILD progression.


Mesenchymal Stromal Cell-derived Extracellular Vesicles in Preclinical Animal Models of Tumor Growth: Systematic Review and Meta-analysis.
Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) have been implicated in the regulation of tumor growth. Studies remain preclinical with effects ranging from inhibition of tumor growth to cancer progression. A systematic review and meta-analysis is needed to clarify the effect of MSC-EVs on tumor growth to facilitate potential translation to clinical trials. A systematic search of the literature (MEDLINE, Embase, and BIOSIS databases to June 1, 2019) identified all pre-clinical controlled studies investigating the effect of MSC-EVs on tumor growth. Study selection and data extraction were performed in duplicate. Potential risk of bias was assessed using the SYRCLE tool. A random effects meta-analysis of reduction in tumor weight/volume (primary outcome) was performed. We identified 29 articles and 22 reported data on tumor responses that were included for meta-analysis. Studies were associated with unclear risk of bias in a large proportion of domains in accordance with the SYRCLE tool for determining risk of bias in preclinical studies. A high risk of bias was not identified in any study. MSC-EVs had a mixed response on tumor progression with some studies reporting inhibition of tumor growth and others reporting tumor progression. Overall, MSC-EVs exerted a non-significant reduction in tumor growth compared to controls (standardized mean difference (SMD) -0.80, 95 % CI -1.64 to 0.03, p = 0.06, I2 = 87 %). Some studies reported increased tumor growth which aligned with their stated hypothesis and some interrogated mechanisms in cancer biology. EVs isolated from MSCs that overexpressed anti-tumor RNAs were associated with significant tumor reduction in meta-analysis (SMD - 2.40, 95 % CI -3.36 to -1.44, p < 0.001). Heterogeneity between studies was observed and included aspects of study design such as enrichment of MSC-EVs with specific anti-tumor molecules, tissue source of MSCs, method of EV isolation, characterization of MSCs and EVs, dosage and administration schedules, and tissue type and source of tumor cells studied. MSC-EVs are associated with mixed effects on tumor growth in animal models of cancer. In studies where anti-tumor RNAs are packaged in EVs, a significant reduction in tumor growth was observed. Reducing heterogeneity in study design may accelerate our understanding of the potential effects of MSC-EVs on cancer. [274 words] Forest plot of MSC-EV effect on tumor growth accordinggenetic modification of EVs in animal studies identified from a systematicreview of the literature. All cohorts from studies with multiple interventiongroups are presented separately with control groups divided equally among thegroups. M, modified; H, hypoxia.


Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with delayed gastric emptying.
People who are severely obese due to melanocortin-4 receptor (MC4R) deficiency experience hyperphagia and impaired fullness after a meal (satiety). Meal-induced satiety is influenced by hormones, such as peptide-YY (PYY), which are released by enteroendocrine cells upon nutrient delivery to the small intestine. We investigated whether gastric emptying and PYY levels are altered in MC4R deficiency. Gastric emptying was measured with a gastric scintigraphy protocol using technetium-99m (99 Tcm )-Tin Colloid for 3.5 h in individuals with loss of function MC4R variants and a control group of similar age and weight. In a separate study, we measured plasma PYY levels before and at multiple time points after three standardised meals given to individuals with MC4R deficiency and controls. Fasting PYY (basal secretion) and postprandial PYY levels were measured and the area under the curve and inter-meal peak were calculated. We found that gastric emptying time was significantly delayed and percentage meal retention increased in individuals with MC4R deficiency compared to obese controls. In addition, fasting and mean PYY secretion throughout the day were decreased in MC4R deficiency, whereas postprandial PYY secretion was unaltered. Delayed gastric emptying and reduced basal PYY secretion may contribute to impaired satiety in people with obesity due to MC4R deficiency.


Racial Disparities in Epigenetic Aging of the Right vs Left Colon.
There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.


Promises and pitfalls of topological data analysis for brain connectivity analysis.
Developing sensitive and reliable methods to distinguish normal and abnormal brain states is a key neuroscientific challenge. Topological Data Analysis, despite its relative novelty, already generated many promising applications, including in neuroscience. We conjecture its prominent tool of persistent homology may benefit from going beyond analysing structural and functional connectivity to effective connectivity graphs capturing the direct causal interactions or information flows. Therefore, we assess the potential of persistent homology to directed brain network analysis by testing its discriminatory power in two distinctive examples of disease-related brain connectivity alterations: epilepsy and schizophrenia. We estimate connectivity from functional magnetic resonance imaging and electrophysiology data, employ Persistent Homology and quantify its ability to distinguish healthy from diseased brain states by applying a support vector machine to features quantifying persistent homology structure. We show how this novel approach compares to classification using standard undirected approaches and original connectivity matrices. In the schizophrenia classification, topological data analysis generally performs close to random, while classifications from raw connectivity perform substantially better; potentially due to topographical, rather than topological, specificity of the differences. In the easier task of seizure discrimination from scalp electroencephalography data, classification based on persistent homology features generally reached comparable performance to using raw connectivity, albeit with typically smaller accuracies obtained for the directed (effective) connectivity compared to the undirected (functional) connectivity. Specific applications for topological data analysis may open when direct comparison of connectivity matrices is unsuitable - such as for intracranial electrophysiology with individual number and location of measurements. While standard homology performed overall better than directed homology, this could be due to notorious technical problems of accurate effective connectivity estimation.


Effective removal of heavy metals from water using porous lignin-based adsorbents.
Multifunctional composite materials are the key to improving removal capacity and environmental utility. Here, the adsorbent (SLCA) was obtained by free-radical polymerization of acrylic acid with sodium lignosulfonate and citric acid. FTIR, SEM, TGA and XPS characterization methods were used to prove the structure and properties of SLCA adsorbents. The maximum uptake capacities of the optimized SLCA adsorbent is 276 mg g-1 of Cu2+ and 323 mg g-1 of Pb2+, respectively. The Langmuir isotherm and the second-order kinetic model were established to illustrate that the capture of Cu2+ and Pb2+ by the adsorbent belongs to chemisorption on the monolayer. XPS analysis confirmed that complexation and electrostatic attraction are the mechanism of pollutant removal. Not only that, as-resulting adsorbent revealed no significant adsorption cycle efficiency reduction even after 5 runs of sorption-desorption cycle, manifesting that it is of great stability and could be regarded as a promising candidate adsorbent. The purpose of this research was to develop a green lignin-based adsorbent with strong environmental protection and regeneration ability based on cheap polyacrylic resin.


Assessing seasonal variation of synthetic musks in beach sands from Oporto coastal area: A case study.
Synthetic musk compounds are widely used in the formulation of several cosmetics, personal care and household products. Due to their massive and widespread use, together with some health concerns, they are considered emerging pollutants and have been detected in different environmental compartments. This study focused on the evaluation of the concentration of synthetic musks (five nitro, five polycyclic and one macrocyclic musks) in beach sands, from Oporto coastal area (Portugal), contributing to the enhancement of the knowledge of levels, trends and behaviour of these compounds in this particular matrix. To accomplish this task, a QuEChERS methodology ("Quick, Easy, Cheap, Effective, Rugged, and Safe") coupled to gas chromatography-mass spectrometry (GC-MS) was successfully used to determine synthetic musks from beach sand. The chosen methodology proved to be suitable, achieving satisfactory results for precision (relative standard deviation values below 15%), accuracy (average recovery of 97%) and limits of detection (below 38 pg g-1). Synthetic musks were detected in all 45 analysed samples, in concentrations ranging from 0.01 to 27 ng g-1dw. Tonalide (93%), exaltolide (89%) and galaxolide (76%) were the most commonly detected compounds, but also those detected in higher concentrations (up to 27 ng g-1dw). Musk ambrette, moskene, tibetene and xylene were not detected in any of the samples. Higher concentrations were as expected detected in the Summer (total average concentration of 9.21 ng g-1dw), namely in samples from Valadares Sul (29 ng g-1dw), Francelos (25 ng g-1dw) and Castelo do Queijo (25 ng g-1dw). The preliminary environmental risk assessment study based on the determination of hazard quotients revealed that the presence of analysed compounds (tonalide, galaxolide and musk ketone) seems to pose no risk to the studied environmental compartment.


Effect of sintering temperature on the physiochemical properties, microstructure, and compressive strength of a bioceramic root canal sealer reinforced with multi-walled carbon nanotubes and titanium carbide.
Bioceramic root canal sealers like BioRoot RCS have received significant attention for use in endodontics. The addition of a nanophase material like multi-walled carbon nanotubes (MWCNTs) and titanium carbide (TC) to its matrix combined with pressureless sintering might have the potential for improved physiochemical, microstructure, and compressive strength properties. ology: MWCNTs and TC nanomaterials were added at a percentage of 1 wt% to a definite weight of pristine BioRoot RCS. Two composites were prepared by ball milling followed by pressureless sintering in static nitrogen at temperatures 600 °C and 800 °C. The setting time, solubility, pH, compressive strength, and density were determined and compared to pristine BioRoot RCS. The microstructural properties of the composites were investigated by XRD, FTIR, Raman spectroscopy, and SEM. The final setting time before and after sintering at 600 °C of the composites was accelerated compared to Bioroot RCS (p = 0.016). The solubility of Bioroot/TC sintered at 600 °C was the lowest (p = 0.07) and its compressive strength was the highest among the sintered samples (p = 0.01). The incorporation of MWCNTs and TC had a significant increase in the compressive strength of Bioroot RCS (p < 0.05). The obtained results support the addition of nanomaterials to Bioroot RCS and the use of pressureless sintering.


Intracytoplasmic inclusion bodies in the chondrocytes of type I lethal achondrogenesis.
Lethal achondrogenesis in the past has been frequently confused with achondroplasia. Clinical and radiologic advances in the last decade have led to clear differentiation of this condition from other types of bone dysplasia. It is further separated into two types on the basis of radiographic and pathologic findings. Re-evaluation of the histologic features has led to the recognition of heretofore unrecognized intracytoplasmic inclusion bodies in the chondrocytes of type 1 achondrogenesis. The finding of inclusions strengthens the differentiation of the two types and may have implications for the pathogenesis of the form of chondrodystrophy.


Sonication fluid culture of antibiotic-loaded bone cement spacer has high accuracy to confirm eradication of infection before reimplantation of new prostheses.
Sonication fluid culture of antibiotic-loaded bone cement spacer has been used to predict reinfection of two-stage revision, but its value remains disputable. This study aims to evaluate the association between the culture result of the sonicated spacer and the status of patients with periprosthetic joint infection receiving two-stage revision. A comprehensive electronic literature search was performed through four databases including PubMed, Embase/Ovid, and EBSCO, and the Cochrane Library to retrieve studies in which sonication fluid culture of the antibiotic spacer was conducted before reimplantation. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the association between the culture result of sonicated spacer and prognosis of the two-stage revision. Eleven eligible studies comprising 603 artificial joints with PJI (134 suffering a clinical failure of two-stage revision) were included in the quantitative analysis. The pooled incidences of positive culture of sonicated spacer and intraoperative tissue were 0.14 (95% confidence interval [CI] 0.08-0.21) and 0.14 (95% CI 0.08-0.20), respectively. A positive culture of sonicated antibiotic-loaded bone cement spacer illustrated moderate sensitivity (0.31, 95% CI 0.13-0.58) but high specificity (0.94, 95% CI 0.86-0.98) for the diagnosis of therapeutic failure of two-stage revision; the pooled DOR was 7.67 (95% CI, 3.63-16.22). Meanwhile, the pooled sensitivity, specificity, and DOR of intraoperative tissue culture during the two-stage revision to predict therapeutic failure were 0.32 (95% CI, 0.20-0.47), 0.96 (95% CI, 0.92-0.98), and 10.62 (95% CI, 4.90-23.01), respectively. Sonication fluid culture of antibiotic-loaded bone cement spacer revealed high accuracy for confirming eradication of infection before reimplantation of new prostheses and therefore could be used as a supplement for assessing therapeutic effect for PJI. However, both sonication fluid culture and intraoperative tissue culture from antibiotic-loaded bone cement spacer showed restricted yield for the prediction of a septic failure after the two-stage revision of PJI. Large-scale, prospective studies are still needed to testify current findings.


Comparison of high-flow and conventional nasal cannula oxygen in patients undergoing endobronchial ultrasonography.
Oxygen therapy is required to prevent hypoxaemia during the endobronchial ultrasonography (EBUS) procedure. To compare the effectiveness of oxygen therapy delivered through high-flow nasal cannula (HFNC) and conventional nasal cannula (CNC) in patients undergoing EBUS. The primary outcome was the proportion of patients who desaturated. Patient compliance and satisfaction were also evaluated. This single-centre prospective interventional study was conducted in a tertiary hospital among patients who presented to the EBUS unit in 2018 and 2019. Patients were randomly assigned to the HFNC group or the CNC group. The study included 170 patients (111 men and 59 women) with a mean age of 58 ± 14 years. The number of patients experiencing desaturation while receiving oxygen was statistically significantly lower (P < 0.001) in the HFNC group (n = 5) compared with the CNC group (n = 26). Oxygen therapy was adjusted in two patients in the CNC group due to desaturation. Saturation was significantly higher in the HFNC group (P < 0.0001) at the end of the EBUS procedure. Heart rate at the end of EBUS was lower in the HFNC group, but this difference was not statistically significant (96 ± 16 vs 101 ± 19, P = 0.13). Five patients in the HFNC group and 18 patients in the CNC group reported discomfort during the procedure (P = 0.006). Oxygen therapy delivered by HFNC seems to be safer and more effective than by CNC in patients undergoing EBUS. Oxygen therapy with HFNC may be considered as an alternative to CNC because it may increase patient comfort and thereby improve compliance.


Mechanical properties of additively manufactured variable lattice structures of Ti6Al4V.
Engineered micro- and macro-structures via additive manufacturing (AM) or 3D-Printing can create structurally varying properties in part, which is difficult via traditional manufacturing methods. Herein we have utilized powder bed fusion-based selective laser melting (SLM) to fabricate variable lattice structures of Ti6Al4V with uniquely designed unit cell configurations to alter the mechanical performance. Five different configurations were designed based on two natural crystal structures - hexagonal closed packed (HCP) and body-centered cubic (BCC). Under compressive loading, as much as 74% difference was observed in compressive strength and 71% variation in elastic modulus, with all samples having porosities in a similar range of 53 to 65%, indicating the influence of macro-lattice designs alone on mechanical properties. Failure analysis of the fracture surfaces helped with the overall understanding of how configurational effects and unit cell design influence these samples' mechanical properties. Our work highlights the ability to leverage advanced manufacturing techniques to tailor the structural performance of multifunctional components.


Recovery from physical limitations among older Mexican adults.
This paper examines the key determinants of the likelihood of recovery from a physical disability among older adults. Data come from the Mexican Health and Aging Study (MHAS), a national sample of adults born in 1951 or earlier, including a baseline survey in 2001 and follow-ups in 2003, 2012 and 2015. At baseline, we divided our sample of older adults aged 60+ by dimensions of physical limitations (ADLs, IADLs, mobility) and classified respondents as having physical limitations in zero, one, two or three dimensions. Each respondent was then categorized as "same", "worse", "improved" or "died" depending on the number of physical dimensions with a limitation in a 2-year span (2001-2003) and again, separately, in a 3-year span (2012-2015). We then used a multinomial logistic regression to analyze the relative risk of transitioning from one category to another. Around 21 % of our sample exhibited some recovery in 2003 and around 20 % recovered in 2015. Age, gender, poor self-rated health, depression and some chronic conditions were significant for shifting the relative risk from staying the same to getting worse, dying or even improving. Disability from a physical limitation is a reversible and dynamic process. Our results reflect the importance of considering the dimensions of physical ability while analyzing recovery, and illustrate that the presence of a chronic condition or depressive symptoms does not necessarily imply permanent disability.


Effects of feeding broiler breeder hens a coextruded full-fat flaxseed and pulses mixture without or with multienzyme supplement.
The effects of coextruded full-fat flaxseed and pulses (FFF; 1:1 wt/wt) mixture on n-3 polyunsaturated fatty acids (PUFA) enrichment in egg yolk, hepatic attributes, apparent retention (AR) of components, and ceca metabolites were evaluated in broiler breeder hens. The diets were as follows: 1) corn-soybean control, 2) control diet plus 18% FFF (FFF-), and 3) FFF plus enzyme supplement (FFF+) containing galactanase, protease, mannanase, glucanase, xylanase, amylase, and cellulase activities. Twenty-six-week-old Cobb 500 broiler breeder hens were allocated to 30 identical cages (2 hens/cage) and given 1-week adaptation period. The 3 diets were assigned to 10 replicate cages based on postadaptation BW and fed based on breeder curve for 30 D. Excreta samples were collected from day 24 to 27 for determination of AR of components, and eggs were collected from day 28 to 30 for yolk polyunsaturated fatty acids analyses. On day 30, birds were weighed, killed via cervical dislocation, liver weighed, and stored for fat analyses. Ceca digesta samples were taken for concentration of short-chain fatty acids. Liver and yolk weights as well as total yolk FA were not influenced by diets (P > 0.05). Control birds had lower yolk concentration of α-linolenic acid than birds fed either FFF- or FFF+ (P < 0.01) corresponding to 7.5, 36.8, and 37.3 mg/g for the control, FFF-, and FFF+, respectively. Control birds also exhibited lower yolk concentration of docosahexaenoic acid (P < 0.01). Control birds had higher hepatic concentration of crude fat and apparent retention of dry matter and crude protein compared with either the FFF- or FFF+ birds (P < 0.05). Birds fed FFF- diet had lower ceca digesta concentration of lactic acid than control and FFF+ (P < 0.05) birds. Results showed broiler breeder hens enriched egg yolk with n-3 polyunsaturated fatty acids without effects on the liver while the supplemental enzyme did not improve the utilization of FFF.


Clinical-electrophysiological correlations in a long-term case of subacute sclerosing panencephalitis with partial clinical improvement.
An electrophysiological follow-up was performed in a rare case of subacute sclerosing panencephalitis (SSPE) that from the vegetative stage had an extremely favourable course, lasting 4 years, in which clinical conditions passed, according to the Risk and Haddad scale, from stage 3 to stage 1. In this period of time, 5 CT scans and a series of EEGs, visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) were performed to investigate the correlation between clinical course and electrophysiological diagnostic data. The results showed a significant improvement in diagnostic results, directly correlated with the remission of clinical symptoms. Electrophysiological signs of improvement in VEPs were obtained before observable improvement was seen on CT scans. These results indicate that an accurate electrophysiological study (through cerebral evoked potentials) has an important role in investigating suspected cases of SSPE, in following the clinical evolution of this disease and providing prognostic data.


Differences in MBL levels between juvenile patients newly diagnosed with type 1 diabetes and their healthy siblings.
The incidence of type 1 diabetes (T1D) has during the last few decades been increasing in children and juveniles. Multi-factorial courses combining genetic disposition and environmental factors might be in play, and through the years, there has been a mounting interest in the innate immune system's role in the development of T1D. The aim of this study was to determine mannose binding lectin (MBL) levels in newly diagnosed children with T1D (n=481) over a period of 10 years (1997-2005) and to compare these levels with corresponding levels in their healthy siblings (n=479). Furthermore, the aims were to evaluate if MBL-levels in patients and siblings were influenced by season, age autoimmunity and/or changed over time. The study found that MBL levels differed between patients and their healthy siblings when adjusted for age, gender, season and period. More patients than siblings had MBL levels above 0.8 μg/ml, associated with high producing MBL genotypes, and the elevated MBL levels were associated with high levels of four T1D related cytokines (IL-1β, IL-12, IL-18 and TNF-α). MBL levels increased during the study period and siblings had seasonal variance in concentrations with the lowest level during wintertime (Dec-Feb). In conclusion, more patients than siblings had a high MBL level, and high levels of MBL were related to high levels of T1D specific cytokines, supporting a role of the innate immune system and MBL on the risk of developing T1D.


The effects of a virtual simulation-based, mobile technology application on nursing students' learning achievement and cognitive load: Randomized controlled trial.
The use of virtual simulation methods in nursing education offers potential advantages for students to experience and learn in a safe and realistic environment by acquiring skills and attitudes to prepare for clinical experiences. The study's aim was to test the hypothesis that nursing students who used a mobile learning app would have significantly (1) higher levels of knowledge about medication administration and nasotracheal suctioning, (2) better development of skill performances on medication administration and nasotracheal suctioning, (3) higher satisfaction, and (4) lower cognitive load than a control group. A randomized experimental study with pretest and posttest design. One hundred nursing students were randomly assigned to an experimental or control group at a Southern Taiwan university's school of nursing. The experimental group received the virtual simulation-based mobile learning app and the control group used traditional paper materials. Participants were assessed on knowledge before and after the intervention. Skill performance and intrinsic and extraneous cognitive load were measured after the intervention. The experimental group who used the mobile app had significantly higher knowledge scores, significantly lower intrinsic and extraneous cognitive load, better skill performance, and higher satisfaction than the control group. The implementation of a mobile app for simulation learning had a positive impact on nursing students' knowledge and skill performances as well as the reduction of learning cognitive loading. Nurse educators and researchers should collaborate in developing virtual learning resources to support clinical nursing education. Tweetable abstract: The mobile app for learning achieved higher knowledge and satisfaction scores, demonstrated better skill performance without increasing cognitive load.


Lipoprotein receptor 'CK'--dependent signalling in human platelets.
The study addressed to understand whether or not lipoproteins at low concentrations could modulate Receptor-'C' dependent platelet signalling revealed that LDL, like exogenous cholesterol, had the capacity to initiate PLD-dependent platelet signalling in a dose dependent fashion and this effect was inhibited in presence of HDL; cAMP; DTT; Zn++ and butanol whereas cGMP had no effect upon this PLD-dependent signalling. Further Receptor 'C' from platelet in the purified-form displayed LDL-or cholesterol-dependent autophosphorylation at the tyrosine residues and this Receptor-'C' tyrosine kinase (Receptor-Ck) activity contributed to the observed LDL-or cholesterol -dependent PLD activity in human platelets. Based upon these results coupled with earlier results, an attempt was made to define the lipoprotein-dependent platelet signalling pathway.


(E)-3-(2-{2-[1-(3-Hy-droxy-phen-yl)ethyl-idene]hydrazin-yl}-1,3-thia-zol-4-yl)-2H-chromen-2-one.
In the title compound, C(20)H(15)N(3)O(3)S, the thia-zole ring is approximately planar, with a maximum deviation of 0.003 (1) Å, and makes dihedral angles of 7.44 (6) and 1.88 (6)° with the hy-droxy-substituted phenyl ring and the pyran ring, respectively. The hydroxyl group is disordered over two sets of sites, with an occupancy ratio of 0.567 (3):0.433 (3). In the crystal, the major disorder component mol-ecules are connected via bifurcated (three-centre) O-H⋯O and C-H⋯O hydrogen bonds, generating R(1) (2)(6) motifs and resulting in supra-molecular chains along the a axis. In the minor occupancy component, however, mol-ecules are connected via C-H⋯O hydrogen bonds, forming supra-molecular chains along the b axis. Furthermore, the crystal structure is stabilized by π-π inter-actions between the thia-zole rings [centroid-centroid distance = 3.5476 (7) Å].


Trends in the care of radical prostatectomy in the United States from 2003 to 2006.
• o determine differences in surgical outcomes by surgical approach during a period of rapid adoption of minimally invasive surgical approaches in radical prostatectomy. • We identified 19 542 men undergoing minimally invasive (MIRP), perineal (PRP), and retropubic (RRP) radical prostatectomy from 2003 to 2006 from the MarketScan® Medstat database, a national employer-based administrative database. • We assessed for temporal trends in perioperative complications, use of postoperative cystography and anastomotic strictures by surgical approach. • Between 2003 and 2006, MIRP use increased 33.6% vs 31.8% and 1.7% decreases in RRP and PRP, respectively. During the 4-year study, median length of stay for MIRP decreased from 2.0 to 1.0 day (P = 0.004) and overall perioperative complications decreased from 13.8 to 10.7%, (P = 0.023). • These findings were driven by reductions in genitourinary complications (3.3 to 2.5%, P = 0.049), miscellaneous surgical complications (3.6 to 2.3%, P = 0.006) and intestinal injury (1.5 to 0.1%, P= 0.009). • Median length of stay for RRP decreased from 3.2 to 2.9 days, (P < 0.001), overall perioperative complications decreased from 18.1 to 14.6%, (P = 0.007), because of reductions in both wound/bleeding complications (2.0 to 1.1%, P = 0.002) and heterologous blood transfusions. • Men undergoing MIRP vs RRP were less likely to have perioperative complications (12.5 vs 17.1%, P < 0.001), blood transfusions (1.5 vs 8.9%, P < 0.001) and anastomotic strictures (6.3 vs 12.8%, P < 0.001), and they had shorter mean lengths of stay (1.8 vs 3.1 days, P < 0.001) during the study period. • The increased use of MIRP corresponds with a decreasing trend for complications, blood transfusions, lengths of stay and need for reoperation. Additionally, MIRP was found to have fewer associated complications compared with men undergoing open procedures. Further study is needed to assess the impact of tumour characteristics and surgeon volume on these perioperative outcomes as well as effects on long-term cancer control.


Cohort profile: biological pathways of risk and resilience in Syrian refugee children (BIOPATH).
The BIOPATH cohort was established to explore the interplay of psychosocial and biological factors in the development of resilience and mental health problems in Syrian refugee children. Based in Lebanon, a middle-income country significantly impacted by the refugee crisis, it is the first such cohort of refugees in the Middle East. Families were recruited from informal tented settlements in the Beqaa region using purposive cluster sampling. At baseline (October 2017-January 2018), N = 3188 individuals participated [n = 1594 child-caregiver dyads; child gender, 52.6% female; mean (SD) age = 11.44 (2.44) years, range = 6-19]. Re-participation rate at 1-year follow-up was 62.8%. Individual interviews were conducted with children and primary caregivers and biological samples collected from children. Measures include: (1) children's well-being and mental health problems (using tools validated against clinical interviews in a subsample of the cohort); (2) psychosocial risk and protective factors at the level of the individual (e.g. coping strategies), family (e.g. parent-child relationship), community (e.g. collective efficacy), and wider context (e.g. services); (3) saliva samples for genetic and epigenetic (methylation) analyses; (4) hair samples to measure cortisol, dehydroepiandrosterone (DHEA) and testosterone. This cohort profile provides details about sampling and recruitment, data collection and measures, demographic data, attrition and potential bias, key findings on resilience and mental health problems in children and strengths and limitations of the cohort. Researchers interested in accessing data should contact Professor Michael Pluess at Queen Mary University of London, UK (e-mail: firstname.lastname@example.com).


Oxidative changes in brain of aniline-exposed rats.
Oxidative stress in rat cerebellum, cortex and brain stem after a short-term high-dose exposure to aniline vapors under conditions akin to those after major chemical accidents, was studied. Significant increases in superoxide dismutase isozyme activities and formation of thiobarbituric acid reactive material along with depletion of ascorbic acid and non-protein sulfhydryl content suggest impairment of antioxidant defenses 24 h after single exposure to 15,302 ppm aniline vapors for 10 min.


In vitro actin filament sliding velocities produced by mixtures of different types of myosin.
Using in vitro motility assays, we examined the sliding velocity of actin filaments generated by pairwise mixings of six different types of actively cycling myosins. In isolation, the six myosins translocated actin filaments at differing velocities. We found that only small proportions of a more slowly translating myosin type could significantly inhibit the sliding velocity generated by a myosin type that translocated filaments rapidly. In other experiments, the addition of noncycling, unphosphorylated smooth and nonmuscle myosin to actively translating myosin also inhibited the rapid sliding velocity, but to a significantly reduced extent. The data were analyzed in terms of a model derived from the original working cross-bridge model of A.F. Huxley. We found that the inhibition of rapidly translating myosins by slowly cycling was primarily dependent upon only a single parameter, the cross-bridge detachment rate at the end of the working powerstroke. In contrast, the inhibition induced by the presence of noncycling, unphosphorylated myosins required a change in another parameter, the transition rate from the weakly attached actomyosin state to the strongly attached state at the beginning of the cross-bridge power stroke.


First In Vivo Experience With Biventricular Circulatory Assistance Using a Single Continuous Flow Pump.
Biventricular assist device (BVAD) implantation is the treatment of choice in patients with severe biventricular heart failure and cardiogenic shock. Our team has developed a miniaturized continuous flow, double-ended centrifugal pump intended for total artificial heart implant (CFTAH). The purpose of this initial in vivo study was to demonstrate that the scaled-down CFTAH (P-CFTAH) can be appropriate for BVAD support. The P-CFTAH was implanted in 4 acute lambs (average weight, 41.5 ± 2.8 kg) through a median sternotomy. The cannulation was performed through the left and right atria, and cannulae length adjustment was performed for atrial and ventricular cannulation. The BVAD system was tested at 3 pump speeds (3000, 4500, and 6000 rpm). The BVAD performed very well for both atrial and ventricular cannulation within the 3000-6000 rpm range. Stable hemodynamics were maintained after implantation of the P-CFTAH. The self-regulating performance of the system in vivo was demonstrated by the left (LAP) and right (RAP) pressure difference (LAP-RAP) falling predominantly within the range of -5 to 10 mm Hg with variation, in addition to in vitro assessment of left and right heart failure conditions. Left and right pump flows and total flow increased as the BVAD speed was increased. This initial in vivo testing of the BVAD system demonstrated satisfactory device performance and self-regulation for biventricular heart failure support over a wide range of conditions. The BVAD system keeps the atrial pressure difference within bounds and maintains acceptable cardiac output over a wide range of hemodynamic conditions.


YTHDC2 control of gametogenesis requires helicase activity but not m6A binding.
Mechanisms regulating meiotic progression in mammals are poorly understood. The N6-methyladenosine (m6A) reader and 3' → 5' RNA helicase YTHDC2 switches cells from mitotic to meiotic gene expression programs and is essential for meiotic entry, but how this critical cell fate change is accomplished is unknown. Here, we provide insight into its mechanism and implicate YTHDC2 in having a broad role in gene regulation during multiple meiotic stages. Unexpectedly, mutation of the m6A-binding pocket of YTHDC2 had no detectable effect on gametogenesis and mouse fertility, suggesting that YTHDC2 function is m6A-independent. Supporting this conclusion, CLIP data defined YTHDC2-binding sites on mRNA as U-rich and UG-rich motif-containing regions within 3' UTRs and coding sequences, distinct from the sites that contain m6A during spermatogenesis. Complete loss of YTHDC2 during meiotic entry did not substantially alter translation of its mRNA binding targets in whole-testis ribosome profiling assays but did modestly affect their steady-state levels. Mutation of the ATPase motif in the helicase domain of YTHDC2 did not affect meiotic entry, but it blocked meiotic prophase I progression, causing sterility. Our findings inform a model in which YTHDC2 binds transcripts independent of m6A status and regulates gene expression during multiple stages of meiosis by distinct mechanisms.


Inventory and composting of yard waste in Serdang, Selangor, Malaysia.
Composting of yard waste is one of the waste management approaches in the Malaysian Agricultural Research and Development Institute (MARDI) in Serdang, Selangor, Malaysia. The yard waste inventory was developed in the headquarters' area and a pilot-scale study was performed on the potential compost product. The total amount of yard waste generated from June 2017 to December 2017 was 16.75 tonnes with an average generation of 0.60 tonnes per week on the dry weight (d.w.) basis. The collected yard waste consisted of three major characteristics, namely dry leaves, fresh green leaves, and grass cuttings, and a waste estimation technique was applied to determine the composition of these three elements. The acquired information was used to formulate the initial compost mixture. The wastes were then mixed with an appropriate amount of livestock manure and other wastes to obtain the optimum initial C/N ratio, which was then found in the analysis to range between 25:1 and 42:1. Meanwhile, the C/N ratios obtained from the matured compost product were from 10:1 and 15:1. Moreover, most of the compost yield ranged between 50% and 70% (w w-1 d.w. basis), while the percentage of the seed germination in the compost was over 95%. The viability of the project was indicated from the economic analysis, with benefit to cost ratio (BCR) values of more than 1. The results also suggested that the large scale composting of yard waste in MARDI was feasible and its applicability is continuous. This technique also fulfilled the objective of producing quality compost, which was suitable for agricultural use.


Genetic association of lipids and lipid-lowering drug target genes with non-alcoholic fatty liver disease.
Some observational studies found that dyslipidaemia is a risk factor for non-alcoholic fatty liver disease (NAFLD), and lipid-lowering drugs may lower NAFLD risk. However, it remains unclear whether dyslipidaemia is causative for NAFLD. This Mendelian randomisation (MR) study aimed to explore the causal role of lipid traits in NAFLD and evaluate the potential effect of lipid-lowering drug targets on NAFLD. Genetic variants associated with lipid traits and variants of genes encoding lipid-lowering drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). Summary statistics for NAFLD were obtained from two independent GWAS datasets. Lipid-lowering drug targets that reached significance were further tested using expression quantitative trait loci data in relevant tissues. Colocalisation and mediation analyses were performed to validate the robustness of the results and explore potential mediators. No significant effect of lipid traits and eight lipid-lowering drug targets on NAFLD risk was found. Genetic mimicry of lipoprotein lipase (LPL) enhancement was associated with lower NAFLD risks in two independent datasets (OR1 = 0.60 [95% CI 0.50-0.72], p1 = 2.07 × 10-8; OR2 = 0.57 [95% CI 0.39-0.82], p2 = 3.00 × 10-3). A significant MR association (OR = 0.71 [95% CI, 0.58-0.87], p = 1.20 × 10-3) and strong colocalisation association (PP.H4 = 0.85) with NAFLD were observed for LPL expression in subcutaneous adipose tissue. Fasting insulin and type 2 diabetes mediated 7.40% and 9.15%, respectively, of the total effect of LPL on NAFLD risk. Our findings do not support dyslipidaemia as a causal factor for NAFLD. Among nine lipid-lowering drug targets, LPL is a promising candidate drug target in NAFLD. The mechanism of action of LPL in NAFLD may be independent of its lipid-lowering effects. Capital's Funds for Health Improvement and Research (2022-4-4037). CAMS Innovation Fund for Medical Sciences (CIFMS, grant number: 2021-I2M-C&T-A-010).


Are North Carolina clinicians delivering opioid use disorder treatment to Medicaid beneficiaries?
Medicaid is a public health insurance program in the United States that serves low-income individuals. Medicaid beneficiaries have elevated risk of opioid use disorder (OUD), yet face barriers to receiving medications for OUD (MOUD). To inform efforts to increase MOUD receipt among Medicaid beneficiaries, this study: (1) estimated Medicaid participation prevalence among clinicians authorized to prescribe buprenorphine and (2) estimated the association between clinician characteristics and OUD care delivery to Medicaid beneficiaries. Retrospective study of North Carolina, USA licensed physicians, physician assistants and nurse practitioners. Licensure data from 2018 were merged with 2019 US Drug Enforcement Administration (DEA) data to identify clinicians who received the DEA waiver required to prescribe buprenorphine (n = 1714). Medicaid claims data were used to characterize clinician engagement in OUD care delivery. Outcomes were indicators of any Medicaid professional claims and any Medicaid prescription claims for buprenorphine and/or naltrexone. Predictors included clinician characteristics (e.g. gender and race) and characteristics of clinicians' practice location (e.g. area opioid overdose death rate). Most waivered clinicians delivered services to Medicaid beneficiaries, ranging from 67.0% of behavioral health clinicians to 82.9% of specialist physicians. Among waivered clinicians with Medicaid professional claims, prevalence of prescribing buprenorphine to Medicaid beneficiaries ranged from 30.3% among specialist physicians to 51.6% among behavioral health clinicians. The probability of prescribing MOUD to Medicaid beneficiaries was higher among waivered clinicians identifying as male compared with female (8.5 percentage points, P = 0.004) or black compared with white (9.9 percentage points, P = 0.007), older clinicians (0.5 percentage point increase per year, P < 0.001) and clinicians in counties with a higher opioid overdose death rate (5.0 percentage point increase per additional death per 10 000 residents, P = 0.010). Among clinicians in North Carolina, USA who are authorized to prescribe buprenorphine, 67-83% (depending on type of specialist) deliver services to Medicaid beneficiaries, but only 30-52% of those prescribe medications for opioid use disorder (OUD) to Medicaid beneficiaries. Engagement in OUD care delivery to Medicaid beneficiaries varies by clinician demographic and area characteristics.


A variant of KSHV-associated inflammatory cytokine syndrome in elderly men of Mediterranean descent.
The spectrum of HHV-8-associated disorders includes Kaposi's sarcoma, primary effusion lymphoma, multicentric Castleman's disease, and the recently described KSHV inflammatory cytokine syndrome (KICS), a life-threatening disorder complicating HIV infection. There have been no reports in the literature concerning non-immunosuppressed individuals affected with KICS. We report here a KICS-like illness occurring in two elderly Greek men without HIV infection or other recognizable cause of immunosuppression.


Supersaturated dissolution data and their interpretation: the TPGS-carbamazepine model case.
This study was undertaken to investigate the effect of d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the dissolution of carbamazepine (CBZ) commercial tablets (Tegretol(®)) as a function of temperature and to modify the reaction-limited model of dissolution for the description of classical supersaturated dissolution data. Solubility studies were performed using various concentrations of (i) TPGS and (ii) silicon dioxide and microcrystalline cellulose, which are excipients of Tegretol(®) at 10, 25 and 37°C. Dissolution studies were carried out using Tegretol(®) tablets, 200 mg/tab. The solubility of CBZ in the presence of TPGS was found to increase in a concentration-dependent manner at all temperatures studied. Classical supersaturated dissolution curves with concentration maxima higher than the corresponding solubility values in the presence of TPGS were observed only at 10°C. The model developed was based on a time-dependent expression for the forward microconstant of the CBZ-TPGS reaction at the solid-liquid interface and it was fitted successfully to the dissolution data of CBZ in the presence of TPGS at 10°C. Vitamin E TPGS increased the solubility of CBZ at all temperatures studied. The modification of the reaction-limited model of dissolution allowed us to describe classical supersaturated dissolution curves.


High-efficient nutrient removal in a single-stage electrolysis-integrated sequencing batch biofilm reactor (E-SBBR) for low C/N sanitary sewage treatment.
To efficiently remove nutrients from low C/N sanitary sewage by conventional biological process is challenging due to the lack of sufficient electron donors. A novel electrolysis-integrated sequencing batch biofilm reactor (E-SBBR) was established to promote nitrogen and phosphorus removal for sanitary sewage with low C/N ratios (3.5-1.5). Highly efficient removal of nitrogen (>79%) and phosphorus (>97%) was achieved in the E-SBBR operating under alternating anoxic/electrolysis-anoxic/aerobic conditions. The coexistence of autotrophic nitrifiers, electron transfer-related bacteria, and heterotrophic and autohydrogenotrophic denitrifiers indicated synergistic nitrogen removal via multiple nitrogen-removing pathways. Electrolysis application induced microbial anoxic ammonia oxidation, autohydrogenotrophic denitrification and electrocoagulation processes. Deinococcus enriched on the electrodes were likely to mediate the electricity-driven ammonia oxidation which promoted ammonia removal. PICRUSt2 indicated that the relative abundances of key genes (hyaA and hyaB) associated with hydrogen oxidation significantly increased with the decreasing C/N ratios. The high autohydrogenotrophic denitrification rates during the electrolysis-anoxic period could compensate for the decreased heterotrophic rates resulting from insufficient carbon sources and nitrate removal was dramatically enhanced. Electrocoagulation with iron anode was responsible for phosphorus removal. This study provides insights into mechanisms by which electrochemically assisted biological systems enhance nutrient removal for low C/N sanitary sewage.


Development of a highly sensitive one-tube nested real-time PCR for detecting Mycobacterium tuberculosis.
Rapid, accurate detection of Mycobacterium tuberculosis is crucial in the diagnosis of tuberculosis (TB), but conventional diagnostic methods have limited sensitivity and specificity or are time consuming. A new highly sensitive nucleic acid amplification test, combined nested and real-time polymerase chain reaction (PCR) in a single tube (one-tube nested real-time PCR), was developed for detecting M. tuberculosis, which takes advantage of two PCR techniques, i.e., nested PCR and real-time PCR. One-tube nested real-time PCR was designed to have two sequential reactions with two sets of primers and dual probes for the insertion sequence (IS) 6110 sequence of M. tuberculosis in a single closed tube. The minimum limits of detection of IS6110 real-time PCR and IS6110 one-tube nested real-time PCR were 100 fg/μL and 1 fg/μL of M. tuberculosis DNA, respectively. AdvanSure TB/non-tuberculous mycobacteria (NTM) real-time PCR, IS6110 real-time PCR, and two-tube nested real-time PCR showed 100% sensitivity and 100% specificity for clinical M. tuberculosis isolates and NTM isolates. In comparison, the sensitivities of AdvanSure TB/NTM real-time PCR, single IS6110 real-time PCR, and one-tube nested real-time PCR were 91% (152/167), 94.6% (158/167), and 100% (167/167) for sputum specimens, respectively. In conclusion, IS6110 one-tube nested real-time PCR is useful for detecting M. tuberculosis due to its high sensitivity and simple manipulation.


The ancient Greek roots of the term Toxic.
In ancient Greek literature the adjective toxic (Greek: τoξικόν) derives from the noun τόξo, that is the arc. This noun according to the Liddell - Scott - Jones lexicon had several meanings. Apart from the meaning that someone is able to use a bow or the military department of the archers, the medical context of the term is that a substance has the characteristic of a poison. This concept of the term survived until today with little differentiation.


ADAPTIVE BEHAVIORS IN YOUNG CHILDREN: A UNIQUE CULTURAL COMPARISON IN ITALY.
On account of a series of unique historical events, the present-day denizens of South Tyrol inhabit a cultural, political, and linguistic autonomous region that intercalates Italians and Austrian/German Italians. We compared contemporary Italian and Austrian/German Italian girls' and boys' adaptive behaviors in everyday activities in this region. Using the Vineland Adaptive Behavior Scales, we first interviewed mothers about their children's communication, daily living, socialization, and motor skills. Main effects of local culture (and no interactions with gender) emerged: Austrian/German Italian children were rated higher than Italian children in both adaptive daily living and socialization skills. Next, we explored ethnic differences in childrearing. Austrian/German Italians reported fostering greater autonomy in their children than Italians, and children's autonomy was associated with their adaptive behavior. Children living in neighboring Italian and Austrian/German Italian cultural niches appear to experience subtle but consequentially different conditions of development that express themselves in terms of differing levels of adaptive behaviors.


Clinical application of platelet-rich fibrin to enhance dental implant stability: A systematic review and meta-analysis.
To investigate the effect of platelet-rich fibrin application on implant stability. Five databases, namely, PubMed, Embase, Web of Science, Wiley, and China National Knowledge Infrastructure, were searched for reports published up to November 20, 2022. Randomized controlled trials (RCT), including parallel RCTs and split-mouth RCTs, with at least 10 patients/sites were considered for inclusion. After screening based on the inclusion criteria, ten RCTs were included. Low heterogeneity was observed in study characteristics, outcome variables, and estimation scales (I2 = 27.2%, P = 0.19). The qualitative and meta-analysis results showed that PRF increased the effect of implant stabilizers after implant surgery. The results of the present systematic review and meta-analysis suggest that PRF can increase implant stability after implant surgery. PRF may also have a role in accelerating bone healing and tends to promote new bone formation at the implant site.


A High-Energy-Density Magnesium-Air Battery with Nanostructured Polymeric Electrodes.
The greenhouse emissions are biggest challenge of the present era. The renewable power sources are required to have characteristics of good charge capacity, energy density with proven charging discharging cycles for energy storage and applications. Mg-air batteries (MABs) are an alternative renewable power source due to their inexpensive cost. In particular, the previous reports presented the metal-air battery structure, with a specific energy overall output of 765 W h kg-1. This paper is focused mainly on the MAB, which employed nanocomposite polymeric electrodes with a proven energy density of 545 W h kg-1 and a charge capacity of 817 mA h g-1 when electrolyzed at a cycling current density of 7 mA cm-2.


Low conductance states of a single ion channel are not 'closed'.
We have used a polymer-exclusion method to estimate the sizes of the high- and low-conductance states of Staphylococcus aureus alpha-toxin channels across planar lipid bilayers. Despite a > 10-fold difference in conductance between high- and low-conductance states, the size differs by < 2-fold. We conclude that factors other than the dimensions have a strong influence on the conductance of alpha-toxin channels. We also show that the high conductance state is destabilized by the presence of high molecular weight polymers outside the channel, compatible with the removal of channel water as the high conductance state "shrinks" to the low conductance state.


Dietary polyunsaturated fatty acids reduce retinal stress induced by an elevation of intraocular pressure in rats.
N-6 and n-3 polyunsaturated fatty acids (PUFAs) have been shown to prevent tissue release of inflammatory molecules. We have shown that a combination of n-6 and n-3 PUFAs is more efficient than single supplementations on the long-term consequences of intraocular pressure elevation. We hypothesized that such an association is also more effective during early retinal stress by modifying retinal proinflammatory prostaglandin and cytokine productions. Rats were supplemented for 3 months with n-6 PUFAs, n-3 PUFAs, or both n-6 and n-3 PUFAs. After 3 months, a surgical elevation of intraocular pressure was induced. Retinal morphometry and glial cell activation were evaluated 24 hours after laser treatment. The retinal levels of prostaglandin E(1) (PGE(1)) and prostaglandin E(2) (PGE(2)) and the messenger RNA levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Retinal glial cell activation after laser treatment was partly prevented by dietary n-6, n-3, and n-6 and n-3 PUFAs. Retinal PGE(1) was unaffected by the laser treatment or by the diet. Dietary n-6 and/or n-3 PUFAs prevented the increase in PGE(2) levels observed in laser-treated retinas without affecting the induction of interleukin-1β, interleukin-6, and tumor necrosis factor-α messenger RNAs. This study shows that not only a combination of n-6 and n-3 PUFAs but also single supplementations can preserve the retina from early glial cell activation and PGE(2) release. The protective effect is not mediated by changes in cytokine expression but may be related to modifications in retinal prostaglandin metabolism.


Surgical and Radiologic Prognostic Factors in Intramedullary Spinal Cord Lesions.
The present study aimed to perform a comprehensive data analysis of 47 consecutive patients treated in 8 years and to observe how clinical, radiologic, and surgical factors affect early and long-term outcomes, recurrence rate, and survival. Clinical, radiologic, and surgical data were collected retrospectively from the review of a prospectively collected database. The neurologic disability was evaluated according to the modified Rankin Scale (mRS). Radiologic data were obtained by direct measurement performed on magnetic resonance imaging (MRI). Univariate and multivariate statistical analysis was performed. From 2008 to 2016, 47 consecutive patients underwent microsurgical resection of intramedullary lesions (28 males and 19 females; mean age, 41.2 years). Ependymoma (53.2%), astrocytoma (14.9%), hemangioblastoma (14.9%), and cavernous angioma (6.4%) were the most frequent tumor histology. The mean follow-up duration was 69.3 months. Gross total tumor resection was performed in 80.8% of cases. Forty-two patients (89.4%) were alive at last follow-up. Five-year overall survival and recurrence-free survival were 92% and 82%, respectively. Among the examined variables, age seemed to strongly correlate with outcomes; better chances of recovery and a good postoperative outcome were observed in younger patients. Surfacing lesions had a better early functional outcome than did intramedullary located lesions. Patients' preoperative neurologic and functional status (mRS score ≤2) had a significant impact on late neurologic outcome. Progression-free survival correlated with the extent of tumor resection. Surgery should probably be performed before patients' neurologic decline, aiming to achieve maximal resection without compromising patients' quality of life.


[Evaluation of different ultrasonic modalities for prenatal screening congenital heart diseases].
To evaluate the value of four chamber view, outflow tract view and color Doppler echocardiography for detecting the fetal congenital heart defects among high-risk populations. And to discuss the significance of screening congenital heart defects by three methods and select the suitable method for wider applications. The echocardiographic records of all pregnant women performed at our hospital from January 2006 to December 2007 were reviewed retrospectively by screening of clinical epidemiology. All cases received ultrasonic examinations. The abnormal cases with postnatal confirmation by echocardiogram or autopsy were included. The abnormalities detected in each view were analyzed and classified. A total of 52 fetuses with congenital heart defects were detected by gray scale sonography and color Doppler sonography in 1310 cases. Each specific cardiac defect had its typical finding in these three planes. The sensitivities of three methods were 61.5%, 88.5% and 96.1% respectively. Four chamber view, outflow tract view and color Doppler sonography have played an important role in screening fetal common congenital heart defects. Outflow tract view is easy to operate and it may be recommended as a suitable method.


Older patients in Sweden and their experience of the emotional support received from the registered nurse--a grounded theory study.
This study intends to explore older patients' experiences of the emotional support received from registered nurses (RNs). We also aimed to gain deeper knowledge about the process of how getting the support they need is managed by the patient. The study was conducted using the grounded theory method. Data were collected by interviewing 18 patients between 80 and 96 years old. Reasons why older patients experienced the emotional support received from the RN are reflected in the categories 'Meets my needs when I am irresolute', 'Meets my needs when I am vulnerable' and 'Meets my needs when I am in need of sympathy'. Reasons to the emotional support resulted in that patients experienced 'A sense of being able to hand over', which is therefore the core category of this study. Older patients' experiences of emotional support are about obtaining relief. Patients were active participants and had strategies for which they wanted to share their emotions with the RN. In order to develop participatory care for older patients, we need more knowledge about how emotional support can be used as a nursing intervention.


It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.
The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.


Photopolymerized monolithic capillary columns for rapid micro high-performance liquid chromatographic separation of proteins.
The preparation of monolithic poly(butyl methacrylate-co-ethylene dimethacrylate) capillary columns using photoinitiated in situ polymerization within 200 microm i.d. capillaries and their application for microHPLC separations of proteins have been studied. The low resistance to flow characteristic of monolithic columns, enabled the use of very high flow rates of up to 100 microL/min representing a flow velocity of 87 mm/s. Very good separations of a model protein mixture consisting of ribonuclease A, cytochrome c, myoglobin, and ovalbumin was achieved in less than 40 s using a very simple single step gradient of the mobile phase. Interestingly, no effect of the pore size on the separations of proteins was observed for these monolithic columns within the size range of 0.66-2.2 microm. The monolithic microHPLC columns are found very robust and no changes in the long term separation performance and back pressure were observed.


Cultural bias: a comparison of semantic responses by 126 students from Pakistan and the United Kingdom to a wheelchair when viewed against a congruent and incongruent background.
Converging visual behavioural and attentional allocation studies within neuroscience have shown culture influences the processing of visual information obtained from the visual field. While attending (reviewing) a visual scene, individuals from a collectivist culture attend more to the context (background) compared to those from an individualist culture who view more the focal object. This highlights the effect of cultural conditioning in terms of holistic and analytical processing of visual information. This study aimed to demonstrate these principles in the context of an assistive product, a wheelchair, highlighting the key visual elements of the form; and, how a congruent background (hospital room) or incongruent (athletics track) influenced cultural bias during visual processing and assigned meaning. A combination of research methods (Semantic Differential Scale and eye-tracking) was used to triangulate the results. A total of 126 adult student participants, (Pakistani/collectivist, n = 57) and the (UK/individualist, n = 69), viewed a visual presentation of a wheelchair with semantically congruent and then an incongruent background and responded via an online questionnaire. A sub-sample completed the survey whilst monitored via eye-tracking. Pakistani respondents used shorter and less frequent fixations on the foreground compared to the responses of their counterparts (UK respondents). The wheel of the wheelchair was highlighted as the prominent form by both groups. Results demonstrate a culture-influenced pattern of visual processing even when the product was displayed against a semantically incongruent background. The findings from this study also validate and extend the outcomes of similar studies revealing a more specific, yet consistent, cultural effect on individuals' visual perception. Finally, the efficacy of triangulated research methods in their relationship to exploring the AT product's semantics was discussed.IMPLICATIONS FOR REHABILITATIONThe knowledge of AT products' semantics will be significant to investigate, for their improved social acceptance, particularly when considered from a diverse cultural standpoint.A model of best practice, focussing on semantics manipulation, will provide AT product designers, practitioners, and those involved in their marketing, Internationally, with a suitable process/tool to positively reframe the perception of these devices.Finally, this research will help product and industrial designers to consider cultural cognitive styles in the design of products for the better adoption of products within the global marketplace.


Antimicrobial, modulatory, and antibiofilm activity of tt-farnesol on bacterial and fungal strains of importance to human health.
In this study, we analyzed the antimicrobial, antibiofilm, and modulatory activities of trans-trans-farnesol (tt-farnesol). The minimum inhibitory concentration (MIC) of this sesquiterpene was evaluated against 31 Gram-positive and Gram-negative bacterial strains and 4 species of the genus Candida. Furthermore, we examined its inhibitory action on biofilm production as well as antibiotic modulation. Only Gram-positive species presented susceptibility to tt-farnesol (MIC ranging from 8 µg/mL to 128 µg/mL). No synergistic or antagonistic effects were observed between tt-farnesol (1/4 and 1/8 of MIC) and first-choice antibiotics against multidrug resistant strains. However, the modulatory action of tt-farnesol (1/2 and 1/4 of the MIC) decreased 8 × MIC of non-inhibitory β-lactam antibiotic against a Methicillin-resistant strain. In the antibiofilm assay, tt-farnesol inhibited biofilm formation, especially in Methicillin-resistant Staphylococcus aureus (MRSA) strains, at concentrations ranging from 2 μg/mL to 128 μg/mL. Additionally, in the molecular docking study, the tt-farnesol molecule demonstrated a remarkable binding affinity with important proteins involved in the biofilm production, such as IcaA and Srt proteins. The antimicrobial action of tt-farnesol on Streptococcus pyogenes and Streptococcus agalactiae strains was evaluated for the first time, presenting an MIC of 16 µg/mL for both strains. Our findings reveal the antibacterial, antibiofilm, and modulatory potential of tt-farnesol to aid in the fight against infectious processes.


Possible occurrence and meaning of lymphocytes bearing autoanti-idiotypic receptors during the immune response.
During an immune response, the increase in binding affinity of antibodies is followed by a fall. Lymphocytes bearing autoanti-idiotypic receptors were detected during a normal immune response. The kinetics of appearance and disappearance of such lymphocytes led us to propose a network model to explain the changes occurring in antibody properties during an immune response.


Impact of Genetic Testing in Transthyretin (ATTR) Cardiac Amyloidosis.
The review's main focus centers on the genetics of hereditary cardiac amyloidosis, highlighting the opportunities and challenges posed by the widespread availability of genetic screening and diagnostic cardiac imaging. Advancements in cardiac imaging, heightened awareness of the ATTR amyloidosis diagnosis, and greater access to genetic testing have all led to an increased appreciation of the prevalence of ATTR cardiac amyloidosis. Elucidation of the TTR molecular structure and effect of mutations on TTR function have allowed for novel TTR therapy development leading to clinical implementation of transthyretin stabilizers and transthyretin gene silencers. The transthyretin amyloidoses are a diverse group of protein misfolding disorders with cardiac and peripheral/autonomic nervous system manifestations due to protein deposition. Genetic screening allows for the early identification of asymptomatic TTR mutation carriers. With the advent of TTR-specific therapeutics, clinical guidance is necessary for the management of individuals with mutations in the TTR gene without evidence of disease.