Executive Functioning Constructs in Anxiety, Obsessive-Compulsive, Post-Traumatic Stress, and Related Disorders.
We synthesize theories proposing complex relations between cognitive functioning and anxiety-related concepts. We evaluate vulnerability theories suggesting that deficits in various cognitive functioning domains predict future anxiety-associated concepts. We examine scar theories asserting the opposite direction of effects (i.e., anxiety predicting cognitive dysfunction). Furthermore, we examine more novel frameworks on this topic. Reliable evidence exists for the scar and vulnerability theories. This includes mounting data on diverse anxiety symptoms predicting cognitive dysfunction (and conversely) unfolding at between- and within-person levels (dynamic mutualism theory). It also includes data on the stronger effects or central influence of anxiety (versus non-anxiety) symptoms on executive functioning (EF; i.e., higher-order cognitive control governing myriad thinking and action repertoires) versus non-EF domains and vice versa (network theory). In addition, it reviews emerging evidence that enhanced cognitive control can correlate with higher anxiety among children (overgeneralized control theory). The generally inverse relations between anxiety symptoms and cognitive dysfunction are bidirectional and complex within and between persons. Plausible mediators and moderators merit more attention, including immune, metabolism, and neural markers and the social determinants of health.


Urethral polyps in children: a review of the literature and report of two cases.
A solitary polyp of the urethra is a rare benign fibroepithelial growth and has often been described in boys. Its occurrence in girls is exceptional. In the present paper, two children with solitary polyps of the urethra are presented and discussed. The first case was an 18-month-old boy with a posterior urethral polyp arising from the posterior urethra and extending to the bladder. It was excised by cystostomy because of an unsuccessful endoscopic removal attempt. The second case was a 2-year-old girl with an interlabial mass arising from the posterior wall of urethra and protruding from the external urethral meatus. It was excised transurethrally.


Tomentosin inhibit cerebral ischemia/reperfusion induced inflammatory response via TLR4/ NLRP3 signalling pathway - in vivo and in vitro studies.
Stoke is a global threat, leading to 50 % of deaths worldwide and it causes permanent disability to about 5 million individuals globally each year. In this study, we assessed the potency of tomentosin to inhibit the neuroinflammation in in vivo and in vitro models. The Sprague Dawley rats were pretreated with 25 mg/kg bodyweight (b.wt) and 50 mg/kg b.wt of tomentosin for seven days followed by induction of cerebral ischemic reperfusion. The brain edema and cerebral infractions were analyzed. The levels of antioxidants and the interleukins were measured by standard methods. The NLRP3 signaling proteins expression was evaluated using qPCR analysis. In vitro studies were performed in SH-SY5Y-cells pretreated with tomentosin and subjected to OGD-R treatment. Our results depicts tomentosin scavenges the free radicals, enhances antioxidant system, inhibits the NLRP3 signaling. In vitro results substantiates with in vivo results. To conclude, our in vivo and in vitro results confirm tomentosin may be potent alternative for existing antistroke drugs.


The effectiveness of nudges in improving the self-management of patients with chronic diseases: A systematic literature review.
In this systematic literature review, we identify evidence on the effectiveness of nudges in improving the self-management of adults with chronic diseases and derive policy recommendations. We included empirical studies of any design published up to April 12th, 2018. We synthesized the results of the studies narratively by comparing statistical significance and direction of different nudge types' effects on primary study outcomes. Lastly, we categorized the nudges according to their degree of manipulation and transparency. We identified 26 studies, where 13 were of high or moderate quality. The most commonly tested nudges were reminders, planning prompts, small financial incentives, and feedback. Overall, 8 of 9 studies with a high or moderate quality ranking, focused on self-management outcomes, i.e., physical activity, attendance, self-monitoring, and medication adherence, found that nudges had significant positive effects. However, only 1 of 4 studies of high or moderate quality, analyzing disease control outcomes (e.g., glycemic control), found that nudges had a significant positive effect for one intervention arm. In summary, this review demonstrates that nudges can improve chronic disease self-management, but there is hardly any evidence to date that these interventions lead to improved disease control. Reminders, feedback, and planning prompts appear to improve chronic disease self-management most consistently and are among the least controversial types of nudges. Accordingly, they can generally be recommended to policymakers.


Aberrant Cortical Connectivity During Ambiguous Object Recognition Is Associated With Schizophrenia.
Dysfunctional connectivity within the perceptual hierarchy is proposed to be an integral component of psychosis. The fragmented ambiguous object task was implemented to investigate neural connectivity during object recognition in patients with schizophrenia (SCZ) and bipolar disorder and first-degree relatives of patients with SCZ (SREL). We analyzed 3T functional magnetic resonance imaging data collected from 27 patients with SCZ, 23 patients with bipolar disorder, 24 control subjects, and 19 SREL during the administration of the fragmented ambiguous object task. Fragmented ambiguous object task stimuli were line-segmented versions of objects and matched across a number of low-level features. Images were categorized as meaningful or meaningless based on ratings assigned by the participants. An a priori region of interest was defined in the primary visual cortex (V1). In addition, the lateral occipital complex/ventral visual areas, intraparietal sulcus (IPS), and middle frontal gyrus (MFG) were identified functionally via the contrast of cortical responses to stimuli judged as meaningful or meaningless. SCZ was associated with altered neural activations at V1, IPS, and MFG. Psychophysiological interaction analyses revealed negative connectivity between V1 and MFG in patient groups and altered modulation of connectivity between conditions from right IPS to left IPS and right IPS to left MFG in patients with SCZ and SREL. Results provide evidence that SCZ is associated with inefficient processing of ambiguous visual objects at V1, which is likely attributable to altered feedback from higher-level visual areas. We also observed distinct patterns of aberrant connectivity among low-level, mid-level, and high-level visual areas in patients with SCZ, patients with bipolar disorder, and SREL.


Expression pattern of serum cytokines in hepatitis B virus infected patients with persistently normal alanine aminotransferase levels.
About 60-80 % of chronic hepatitis B virus (HBV) carriers are characterized with persistently normal alanine transaminase (ALT). Differences of cytokine expression are associated with the prognosis of HBV infection. We investigated the expression pattern of 30 cytokines associated with anti-HBV immunity in patients with normal ALT. Four patient groups (immune tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B, and control; 10 subjects per group) were assigned. Thirty cytokines, including IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20, CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-β1, were measured using a human cytokine antibody array. Signal intensities were obtained by laser scanner. Protein-protein interactions were analyzed by STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). Significant differences of signal intensities were observed for IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29. The lowest intensity was in controls. Among three HBV infection groups, significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL-23p19, and IL-29. The highest intensity was in the inactive group. All cytokines with significant differences were involved JAK-STAT signaling that up-regulate FOXP3, SOCS3 and MX1. Differential expression of cytokines in JAK-STAT signaling is an important factor associated with prognosis of HBV infection. The elevation of γC cytokines, IL-12p70, IL-23p19, and IL-29 may promote spontaneous HBeAg seroconversion and HBV clearance.


Patients with unilateral retinal vein occlusion show reduced radial peripapillary capillary density in their fellow eyes.
To evaluate the radial peripapillary capillary (RPC) density in the fellow eyes of unilateral retinal vein occlusion (RVO) patients using optical coherence tomography angiography (OCTA), and further analyze the correlation between RPC density and peripapillary retinal nerve fiber layer (RNFL) thickness. Seventy-eight unilateral RVO patients and 70 normal controls were included in the study. OCTA was conducted with the 4.5 × 4.5-mm scan pattern centered on the optic nerve head, and the RPC density and peripapillary RNFL thickness were quantified. The peripapillary RNFL in the RVO fellow eyes was significantly thinner than in normal controls in the average, inferior-hemisphere, inferior quadrant, and temporal quadrant (P < 0.05, respectively). The RPC density in the fellow eyes was also significantly lower in the average, inferior-hemisphere, nasal quadrant, and temporal quadrant ((P < 0.05, respectively). There were no significant differences in RNFL thickness and RPC density between branch RVO fellow eyes and central RVO fellow eyes. Pearson's correlation analysis showed significant positive correlations between the RPC density and RNFL thickness in all measurements (P < 0.001, respectively). The regional RPC density was reduced in the RVO fellow eyes, which might contribute to peripapillary RNFL thinning in the corresponding region, suggesting the influence of systemic risk factors on RVO. OCTA may offer new insights into the pathophysiology of RVO.


Biogenic synthesis of highly fluorescent carbon dots using Azadirachta indica leaves: An eco-friendly approach with enhanced photocatalytic degradation efficiency towards Malachite green.
A simpler and efficient method has been developed for the green synthesis of highly fluorescent carbon dots (CDs) from Azadirachta Indica leaves. The surface morphology of developed CDs has shown the existence of spherical particles in the size range of 3-8 nm with superior biocompatibility and high quantum yield value i.e. 42.3%. The particles exhibited a highly fluorescent and crystalline nature along with a bandgap value of 4.02 eV. The prepared CDs served as a factorial design for the sensing and degradation of Malachite green among other dyes. The main perspective of the current finding is that the designed catalyst exhibits excellent sensing results towards Malachite green with a limit of detection i.e. 0.144 μM in the concentration range of 0-50 μM. Moreover, the UV triggered results of photocatalysis illustrated a good dye removal efficacy by developed CDs with an average of 90.73, 98.25, 52 and 6.13% degradation in Methylene blue (MB), Malachite green (MG), Rhodamine 6G (Rh 6G) and Methyl orange (MO) upon 70 min of irradiation with mercury lamp. Additionally, the proton NMR, FTIR and FESEM results of the recycled samples also confirm the complete degradation of MG dye with the application of N-CDs.


Determination of 35 Free Amino Acids in Tea Using Ultra-Performance Liquid Chromatography Coupled With Quadrupole Time-of-Flight Mass Spectrometry.
The purpose of this research was to develop a simple, sensitive, and accurate method for simultaneous determination of 35 free amino acids using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Tea samples were extracted with boiling water bath, and then separated by XBridge BEH Amide column by gradient elution. The exact mass and MS/MS spectra of the target compound was detected under the TOF-MS and Information dependent acquisition (IDA)-MS/MS mode. The results demonstrated good linearity (R 2 > 0.9980) in the range of 0.5-1,000 ng/mL. The limits of detection (LODs) were 0.13-25.00 mg/kg and the limits of quantitation (LOQs) were 0.25-50.00 mg/kg. The recovery rate ranged from 70.1 to 105.1% with relative standard deviations (RSDs) <11% (n = 6). This research provides a targeted strategy for developing an analysis method for amino acids in tea.


Ayurvedic management of neurological deficits post COVID-19 vaccination - A report of two cases.
The world witnessed much research fund allocation on the COVID-19 outbreak's epidemiology, pathology, impact on lifestyles, social behaviours and treatment possibilities. The highly contagious nature of the disease compelled scientific communities and related organisations to hasten vaccine development and supplies. Well-timed international collaborations resulted in quicker development of varied forms of vaccines against COVID-19. Prospective observational studies and systematic reviews on vaccine trials reported their safety and efficacies. Nevertheless, post-marketing surveillance is quintessential to ascertain such safety and efficacy claims. There have been scattered reports lately of several adverse temporal events, such as haematological, immunological and neurological untoward occurrences following COVID-19 inoculation. There is a growing piece of evidence of the impact of COVID vaccination on patients with neurological-neuroimmunological disorders. Here two unrelated cases of neurological deficits post-COVID vaccination are reported. One was an incidence of Acute Disseminated Encephalomyelitis, while the other was an acute exacerbation of Multiple Sclerosis following vaccination. Ayurvedic treatments were effective in either of these conditions. Case series and case reports shall judiciously add information to vaccine safety data and acknowledge the necessity of clinician approval, based on detailed individualised assessments before mass vaccination.


EarWell Infant Ear Molding Device: Experience and Parent Survey.
EarWell infant ear molding device is a noninvasive, nonsurgical option to treat ear deformities in early infancy. There are no studies involving the parents' perspective to the use of the EarWell. To investigate our experience with EarWell infant ear molding device and to assess the parents' satisfaction. A retrospective case series study of infants with congenital ear deformities who were treated with EarWell device from October 2021 to November 2022. Demographic and clinical data were collected. Clinical photographs were obtained before, during, and after treatment. Parents' satisfaction level was assessed through telephone encounters and surveys, and issues associated with device application were identified. Clinical improvement of ear deformity was graded into poor, fair, good, and excellent. A total of 9 patients with congenital ear deformities were identified and included in this study (7 bilateral deformities and 2 unilateral deformities). The mean adjusted age of the initial treatment is 17 weeks (4-23 weeks), and the mean treatment duration is 5.7 weeks. The authors received full 8 responses from the parents' survey, and all parents were satisfied with post-treatment results (4 satisfied, 1 fully satisfied, and 2 very satisfied). Issues associated with device application were 3 superficial skin ulcers and 4 skin irritation. Clinical Improvement grades were: 5 excellent improvement, 2 good improvement, and 2 fair improvement. On the basis of our experience, the EarWell device has shown a high success rate and a low complication rate. It is well accepted by parents, but it needs close follow-up to detect minor device-related issues. The device is safe for multiple skin types.


Achieving integrated treatment: a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions.
Approximately 30-50% of people with serious mental illness have co-existing drug or alcohol problems (COSMHAD), associated with adverse health and social care outcomes. UK guidelines advocate both co-occurring needs being met within mental health services, but uncertainty remains about how to operationalise this to improve outcomes. Various unevaluated service configurations exist in the UK. A realist synthesis was done to identify, test, and refine programme theories of how context shapes the mechanisms through which UK service models for COSMHAD work, for whom, and in what circumstances. Structured and iterative realist searches of seven databases identified 5099 records. A two-stage screening process identified 132 papers. Three broad contextual factors shaped COSMHAD services across 11 programme theories: committed leadership, clear expectations regarding COSMHAD from mental health and substance use workforces, and clear care-coordination processes. These contextual factors led to increased staff empathy, confidence, legitimisation, and multidisciplinary ethos, which improved care coordination and increased the motivation of people with COSMHAD to work towards their goals. Our synthesis highlights that integrating COSMHAD care is complex, and both individual and cultural behavioural shifts in leadership, workforce, and service delivery are essential to ensure people with COSMHAD receive compassionate, trauma-informed care that meets their needs.


Research and Publication Trends in Pediatric Surgery in Latin America: A Bibliometric and Visual Analysis from 2012 to 2021.
Pediatric surgery is a developing specialty with increasing volume in Latin America. However, the research and scientific activity trends carried out in this region in recent years are unknown. This study aimed to analyze and visualize Latin American research in pediatric surgery from 2012 to 2021. Bibliometric cross-sectional study of scientific articles on pediatric surgery published by Latin American authors from 2012 to 2021 in Scopus was performed. Statistical and visual analysis was performed with R programming language and VOS viewer. 449 articles were found. Observational studies (44.7%; n = 201), case reports (20.4%; n = 92) and narrative reviews (11.4%; n = 51) were found to be the most common study designs. The published articles were predominantly monocentric (73.1%; n = 328), only 17% (n = 76) involved authors from 2 or more countries, and mostly there was no collaboration with high-income countries (80.6%; n = 362). The Journal of Pediatric Surgery was the journal with the highest volume of articles published (n = 37). The most used terms were Laparoscopy, Complications, and Liver Transplantation, and the countries with the highest number of articles published were Brazil and Argentina. This study found a progressive increase in the scientific activity of Latin authors in pediatric surgery from 2012 to 2021. The evidence produced was mainly from observational studies and case reports, predominantly conducted in Brazil. Multinational and international collaboration was low; the most frequent topics of interest were laparoscopy and minimally invasive surgery. IV.


Purification of terminal riboadenylate transferase from calf thymus gland.
A poly(A) polymerase has been purified from the soluble protein fraction of calf thymus gland. The activity is cytoplasmic and nonparticulate. Mn-2+ATP is the preferred substrate. On the basis of disc gel electrophoresis in sodium dodecyl sulfate-acrylamide gels, gel filtration, and sedimentation velocity in sucrose gradients, the enzyme has a molecular weight of 62,000 and appears to consist of one polypeptide chain. The enzyme preparation is shown to be nearly homogeneous by disc gel electrophoresis and isoelectric-focusing. The activity has a pI of about 7.4. The specific activity of the enzyme is about 1700 mumol per hour per mg of protein, giving a turnover number of about 1800 mol of substrate per mol of enzyme min- minus 1. The activity is highly specific for ATP and is inhibited by other ribonucleoside triphosphates. It is sensitive to high levels of RNA-polymerase inhibitors. Km for oligoadenylate is 50 muM in the presence of Mn-2+ and 200 muM in Mg-2+ and equivalent Vmax is achieved with either metal ion. The initiator function may be filled by a variety of oligoribonucleotides having a free 3'-OH.


Fertility and pregnancy outcomes in women with nonclassic 21-hydroxylase deficiency.
Overall fertility and pregnancy outcomes in patients with nonclassic congenital adrenal hyperplasia (NCCAH) have been poorly studied. It has been suggested that hydrocortisone (HC) may decrease the time to conceive (TTC) and the rate of miscarriage in these patients. To describe fertility and pregnancy outcomes in a large cohort of NCCAH women. The secondary objective was to identify factors that could impact reproductive outcomes, with a particular focus on HC dose and genetic status. Retrospective study in a referral center for congenital adrenal hyperplasia. PATIENTS AND MEASUREMENTS: One hundred seventy-three female patients with NCCAH confirmed by genetic testing, followed in our center between 2010 and 2019. Among the 173 patients, 95 women had a parental project, 86 of whom presented 176 pregnancies, 56% under glucocorticoid (GC) treatment and 44% without, and 76 women obtained 128 live births. Two-thirds of the patients regularized their cycle under GC treatment, with significant decrease of androgens and progesterone levels. This treatment was associated with a shortening of TTC (coef β = -.196, information coefficient [IC] = [-10.7; -0.91], p = .021). Androgen levels and TTC were positively correlated to the rate of miscarriage (OR = 4.8, IC = [1.15; 20.34], p = .021 for testosterone, OR = 1.4, IC = [1.05; 1.81], p = .02 for androstenedione, and OR = 1.03, IC = [1.01; 1.06], p = .015 for TTC). There was no difference in terms of obstetric outcomes between patients with or without GC treatment. CYP21A2 genotype had no impact on pregnancy outcome or TTC. Infertility is relative in patients with NCCAH. HC seems beneficial for fertility and pregnancy outcomes, especially for patients with menstrual disorders and high preconceptional androgen levels.


Heterocycles [h]fused onto 4-oxoquinoline-3-carboxylic acid, part IV. Convenient synthesis of substituted hexahydro [1,4]thiazepino[2,3-h]quinoline-9-carboxylic acid and its tetrahydroquino[7,8-b]benzothiazepine homolog.
Substituted [1,4]thiazepino[2,3-h]quinolinecarboxylic acid 3 is prepared by PPA-catalyzed thermal lactamization of the respective 8-amino-7-[(2-carboxyethyl)thio]-1,4-dihydroquinoline-3-carboxylic acid 9. The latter synthon is obtained by reduction of the 8-nitro-1,4-dihydroquinoline precursor 8 which, in turn, is made accessible via interaction of 3-mercaptopropionic acid with 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-1,4-dihydroquinoline-3-carboxylic acid 7 in the presence of triethylamine. A benzo-homolog of 3, namely tetrahydroquino[7,8-b]benzothiazepine-3-carboxylic acid 6, is analogously prepared via the reaction of 2-mercaptobenzoic acid with 7, followed by reduction of the resulting 7-[(2-carboxyphenyl)thio]-8-nitro product 10 into the corresponding 8-amino derivative 11, and subsequent lactamization. The structures assigned to 3, 6 and 8-11 are based on microanalytical and spectral (IR, MS, NMR) data.


Supernatants of stored polymorphonuclear neutrophils exhibit growth-promoting activity in several cell lines: perforin expression in polymorphonuclear neutrophils and its role in down-regulation of growth-promoting activity.
Polymorphonuclear neutrophils (PMNs) play important roles in the host immune defence. This study was performed to identify roles of PMNs other than those already known. PMNs were separated from the peripheral blood of healthy individuals and stored in vitro for 24 h in the presence or absence of an anti-human Fc receptor (FcR) gamma III antibody, namely, anti-CD16 monoclonal antibody (mAb). Stored supernatants were harvested and incubated with several leukaemia and transformed cell lines for 48 h. The increase in growth rate was assessed by the increase in the amount of 3H-thymidine incorporated into these cells. Expression of perforin on PMNs, which is thought to decrease cell viability, was elucidated by flow cytometry (FCM) analysis. The presence of perforin in the stored supernatants was determined using an enzyme-linked immunosorbent assay (ELISA). A serine protease inhibitor, which is known to block the effect of perforin, was added to the cultures of several leukaemia and transformed cell lines to confirm the effect of perforin in reducing cell viability. Growth promotion of some cell lines cultured with the stored supernatants of PMNs was observed both in the presence and absence of anti-CD16 mAb, which was used as a trigger molecule of PMNs. This was particularly notable in the case of Raji and Daudi (both Burkitt lymphoma) cell lines and Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines (B-LCLs) derived from healthy individuals. Perforin expression was observed in both freshly prepared and stored PMNs, regardless of the presence or absence of anti-CD16 mAb. ELISA also detected perforin in the stored supernatants in both the presence and absence of anti-CD16 mAb. The increase in growth rate was induced in the presence of not only a serine protease inhibitor but also an anti-perforin mAb. Stored supernatants of PMNs exhibit up-regulation of cell growth in several cell lines; this up-regulation is particularly prominent in B-lineage cell lines. Furthermore, perforin appeared to be expressed on PMNs constitutively and secreted into the extracellular fluid. Results of this study strongly suggest that the growth-promoting activity in supernatants of stored PMNs is partially inhibited by perforin, which is thought to be produced by PMNs themselves.


Combined Multimodal Cerebral Monitoring and Focused Hemodynamic Assessment in the First 72 h in Extremely Low Gestational Age Infants.
Characteristic changes in cerebral saturation (CrSO2), amplitude-integrated electroencephalography (aEEG), and echocardiography (ECHO) may be associated with intraventricular hemorrhage (IVH); however, the feasibility of their combined application is not known. The aim of this work was to investigate the feasibility and safety of combined multimodal cerebral and hemodynamic monitoring in extremely low gestational age (ELGA) infants in the first 72 h after birth. In this prospective -observational study of 50 infants born between 23 + 0 and 27 + 6 weeks gestation, we measured CrSO2 and aEEG, starting <8 h until 72 h of age. Sequential echocardiography and head ultrasound were performed at 4-8, 12-18, 24-30, and 48-60 h of age. The primary outcome was feasibility of multimodal monitoring, defined as >75% of the subjects satisfying at least 3/4 criteria: (a) CrSO2 and (b) aEEG monitoring each for >75% of the time, and (c) at least 2 out of 4 ECHO and (d) head ultrasounds (at least one by age 24 h). Adverse reactions to sensors, desaturation, and bradycardia during ultrasound studies were recorded. Fifty infants were enrolled over 14 months. Multimodal monitoring was feasible in 49 (98%) infants. Forty-one (82%) infants fulfilled all 4 criteria. Mild erythema below CrSO2 sensors lasting 3-8 h without skin breakdown was noted in 8/50 subjects (16%). Desaturation was noted during 17/197 (8.6%) of the ultrasound studies. In total, 26/50 (52%) infants developed IVH (grade I/II, n = 22; grade III/IV, n = 4). Multimodal monitoring is feasible, safe, and well tolerated in ELGA infants in the first 72 h after birth.


High Strength Concrete Columns under Axial Compression Load: Hybrid Confinement Efficiency of High Strength Transverse Reinforcement and Steel Fibers.
Addition of steel fibers to high strength concrete (HSC) improves its post-peak behavior and energy absorbing capability, which can be described well in term of toughness. This paper attempts to obtain both analytically and experimentally the efficiency of steel fibers in HSC columns with hybrid confinement of transverse reinforcement and steel fibers. Toughness ratio (TR) to quantify the confinement efficiency of HSC columns with hybrid confinement is proposed through a regression analysis by involving sixty-nine TRs of HSC without steel fibers and twenty-seven TRs of HSC with hybrid of transverse reinforcement and steel fibers. The proposed TR equation was further verified by compression tests of seventeen HSC columns conducted in this study, where twelve specimens were reinforced by high strength rebars in longitudinal and transverse directions. The results show that the efficiency of steel fibers in concrete depends on transverse reinforcement spacing, where the steel fibers are more effective if the spacing transverse reinforcement becomes larger in the range of 0.25-1 effective depth of the section column. Furthermore, the axial load-strain curves were developed by employing finite element software (OpenSees) for simulating the response of the structural system. Comparisons between numerical and experimental axial load-strain curves were carried out.


Improving total knee arthroplasty perioperative pain management using a periarticular injection with bupivacaine liposomal suspension.
Patients undergoing total knee arthroplasty (TKA) report low satisfaction with postoperative pain control. The purpose of this study is to examine if there is a difference in post-operative pain for TKA patients without femoral nerve block receiving an intra-operative pericapsular injection of bupivacaine liposome suspension (EXPAREL; Pacira Pharmaceuticals, Inc., San Diego, California) versus a concentrated multi drug cocktail. Seventy TKA patients were randomly assigned to either the bupivacaine liposome or the multi-drug cocktail. Post-operative pain scores, morphine sulfate equivalence consumption values, adverse events, and overall pain control satisfaction scores were collected. Patients reported significantly higher pain level for the cocktail group on post-op day 1 (p < .05) and post-op day 2 (p < .01) versus the bupivacaine liposome group. This same trend was found for morphine sulfate equivalence consumption in the PACU (p < .01) and post-op day 2 (p < .01). Higher satisfaction in pain control (p < .001) and overall experience (p < .01) was also found in the bupivacaine liposome group. Finally, significantly more adverse events were found in the multi-drug group versus the bupivacaine liposome group (p < .05). The study findings demonstrated a non-inferior difference, albeit not a clinically significant difference, in patient-perceived pain scores, morphine sulfate equivalence consumption, adverse events, and overall satisfaction.


The effects of an office ergonomics training and chair intervention on worker knowledge, behavior and musculoskeletal risk.
A large-scale field intervention study was undertaken to examine the effects of office ergonomics training coupled with a highly adjustable chair on office workers' knowledge and musculoskeletal risks. Office workers were assigned to one of three study groups: a group receiving the training and adjustable chair (n=96), a training-only group (n=63), and a control group (n=57). The office ergonomics training program was created using an instructional systems design model. A pre/post-training knowledge test was administered to all those who attended the training. Body postures and workstation set-ups were observed before and after the intervention. Perceived control over the physical work environment was higher for both intervention groups as compared to workers in the control group. A significant increase in overall ergonomic knowledge was observed for the intervention groups. Both intervention groups exhibited higher level behavioral translation and had lower musculoskeletal risk than the control group.


Puralpha as a cellular co-factor of Rev/RRE-mediated expression of HIV-1 intron-containing mRNA.
To ensure successful replication, HIV-1 has developed a Rev-mediated RNA transport system that promotes the export of unspliced genomic RNA from nuclei to cytoplasm. This process requires the Rev responsive element (RRE) that is positioned in the viral transcript encoding Env protein, as well as in unspliced and singly spliced viral transcripts. We identified Puralpha, a single-stranded nucleic acid binding protein as a cellular partner for Rev that augments the appearance of unspliced viral RNAs in the cytoplasm. A decrease in the level of Puralpha expression by siRNA diminishes the level of Rev-dependent expression of viral RNA. Through its nucleic acid binding domain, Puralpha exhibits the ability to interact with the multimerization and RBD domains of Rev. Similar to Rev, Puralpha associates with RRE and in the presence of Rev forms a complex with slower electrophoretic mobility than those from Rev:RRE and Puralpha:RRE. The interaction of Puralpha with RRE occurs in the cytoplasm where enhanced association of Rev with RRE is observed. Our data indicate that the partnership of Puralpha with Rev is beneficial for Rev-mediated expression of the HIV-1 genome.


Design and in vitro evaluation of a novel poly(methacrylic acid)/metronidazole antibacterial nanogel as an oral dosage form.
To overcome the undesirable side-effects of metronidazole (MTZ), ethylene glycol dimethacrylate is used as the cross-linker, and a series of poly(methacrylic acid) (PMAA) nanogels were prepared to load the MTZ. We investigated the morphology, size, in vitro release property in the simulated gastrointestinal medium, long-term antibacterial performance against Bacteroides fragilis, cytotoxicity, stability and activity of this novel MTZ/PMAA nanogel. The results indicate that the MTZ/PMAA nanogel sustained the release of MTZ in long-term antibacterial activity in the simulated gastrointestinal medium. This MTZ/PMAA nanogel exhibits less cytotoxicity than MTZ alone, suggesting that MTZ/PMAA nanogel is a more useful dosage form than MTZ for mild-to-moderate Clostridium difficile infections. The novel aspects of this study include the synthesis of a nanogel and the three-phase study of the release profile, which might be useful for other researchers in this field.


Clinical impact of dipping and nocturnal blood pressure patterns in newly diagnosed, never-treated patients with essential hypertension.
The significance of nondipping and increased nighttime systolic blood pressure (SBP) in established hypertension is well defined. We investigated whether these factors alone or combined correlate with vascular damage in early-stage hypertension. Newly diagnosed, untreated hypertensives were classified as dippers and nondippers according to ambulatory blood pressure (BP). Twenty-four-hour urinary albumin excretion and markers of arterial stiffness (pulse wave velocity, augmentation index, central and peripheral pulse pressure, central BP) and atherosclerosis (carotid intima-media thickness) were assessed. Serum asymmetric dimethylarginine, an index of endothelial dysfunction, was measured in a study subgroup; 10-year cardiovascular risk was calculated. Among 222 hypertensives, only urinary albumin excretion was increased in nondippers, compared to dippers (P = .026). When dippers were further stratified according to nighttime SBP (<120 or ≥120 mm Hg), the first group demonstrated the lowest levels of office, aortic, 24-hour, daytime and nighttime BP, compared to dippers with elevated nighttime SBP and nondippers. Although vascular measurements and asymmetric dimethylarginine were comparable between these groups, dippers with normal nighttime SBP exhibited the lowest cardiovascular risk score (P = .050). In early-stage hypertension, nondipping was accompanied by microvascular, yet not macrovascular and endothelial dysfunction. Dippers with elevated nighttime SBP appear as a distinct group with increased hemodynamic pressure load and cardiovascular risk.


Fatty acid composition and genome-wide associations of a chickpea (Cicer arietinum L.) diversity panel for biofortification efforts.
Chickpea is a nutritionally dense pulse crop with high levels of protein, carbohydrates, micronutrients and low levels of fats. Chickpea fatty acids are associated with a reduced risk of obesity, blood cholesterol, and cardiovascular diseases in humans. We measured four primary chickpea fatty acids; palmitic acid (PA), linoleic acid (LA), alpha-linolenic acid (ALA), and oleic acid (OA), which are crucial for human health and plant stress responses in a chickpea diversity panel with 256 accessions (Kabuli and desi types). A wide concentration range was found for PA (450.7-912.6 mg/100 g), LA (1605.7-3459.9 mg/100 g), ALA (416.4-864.5 mg/100 g), and OA (1035.5-1907.2 mg/100 g). The percent recommended daily allowances also varied for PA (3.3-6.8%), LA (21.4-46.1%), ALA (34.7-72%), and OA (4.3-7.9%). Weak correlations were found among fatty acids. Genome-wide association studies (GWAS) were conducted using genotyping-by-sequencing data. Five significant single nucleotide polymorphisms (SNPs) were identified for PA. Admixture population structure analysis revealed seven subpopulations based on ancestral diversity in this panel. This is the first reported study to characterize fatty acid profiles across a chickpea diversity panel and perform GWAS to detect associations between genetic markers and concentrations of selected fatty acids. These findings demonstrate biofortification of chickpea fatty acids is possible using conventional and genomic breeding techniques, to develop superior cultivars with better fatty acid profiles for improved human health and plant stress responses.


Solid-phase reducing agents as alternative for reducing disulfide bonds in proteins.
Disulfide reduction of Kluyveromyces lactis and Aspergillus oryzae beta-galactosidases and beta-lactoglobulin was assessed. Reduction was performed using one of two thiol-containing agents: dithiothreitol (DTT) or thiopropyl-agarose with a high degree of substitution (1000 micromol of SH groups/g of dried gel). Both reductants allowed an increase of three- (for K. lactis beta-galactosidase) and fourfold (for A. oryzae beta-galactosidase) in the initial content of SH groups in the lactases. Nearly sevenfold fewer micromoles of SH groups per milligram of protein were needed to perform the reduction of K. lactis beta-galactosidase with thiopropyl-agarose than for the same reduction with DTT. However, for A. oryzae beta-galactosidase, nearly twice as many micromoles of SH groups per milligram of protein were needed with thiopropylagarose than with DTT. Disulfide bonds in beta-lactoglobulin were not accessible to thiopropyl-agarose, since this reduction was only possible in the presence of 6 M urea. These results proved that highly substituted thiopropyl-agarose is as good a reducing agent as DTT, for the reduction of disulfide bonds in proteins. Moreover, excess reducing agent was very simply separated from the reduced protein by filtration, making it easier to control the reaction and providing reduced protein solutions free of reductant. All these advantages substantially cut down the time required and therefore the cost of the overall process.


Comparative study of intracisternal kaolin injection techniques to induce congenital hydrocephalus in fetal lamb.
Kaolin (aluminum silicate) has been used to generate hydrocephalus by direct cisterna magna injection in animal models. The aim of the present study is to compare which method of Kaolin injection into fetal cisterna magna is feasible, safer, and more effective to induce hydrocephalus in fetal lambs. Twenty-five well-dated pregnant ewes at gestational 85-90 days (E85-90) were used to compare three different kaolin injection puncture techniques into the fetal cisterna magna. Group 1, ultrasound guidance in a maternal percutaneous transabdominal (TA); group 2, without opening the uterus in a transuterine (TU) technique; group 3, by occipital direct access after exteriorizing fetal head (EFH); and group 4, control group, was normal fetal lambs without injection. The fetal lambs were assessed using lateral ventricle diameter ultrasonographic measurements prior the kaolin injection and on the subsequent days. We analyzed the effectivity, mortality, and fetal losses to determine the best technique to create hydrocephalus in fetal lamb. After fetal intracisternal kaolin (2%, 1mL) injection, lateral ventricle diameters increased progressively in the three different interventional groups compared with the normal values of the control group (p ≤ 0.05). We observed that the transabdominal method had a 60% of fetal losses, considering failure of injection and mortality, compared with the 12.5% in the open group (EFH), and 0% for the transuterine group. Based on our study, we believe that both, open uterine (EFH) and transuterine approaches are more effective and safer than the transabdominal ultrasound-guided method to induce hydrocephalus.


The catheter wall simulating thrombus formation seen on pullout angiograms: an experimental study.
The authors investigated the nature of a radiolucent line that was seen paralleling the radiopaque catheter wall on more than 70% of 176 pullout angiograms. Although this line may indicate a thrombus sleeve, accumulation of thrombus was rarely seen at the puncture site. A series of experiments demonstrated clearly that (a) an identical line could be reproduced in a bloodless model; (b) the width varied directly with the thickness of the catheter wall and appeared irregular in contour with 6.5, 7, and 8 French catheters: and (c) this line represented the outer third of the catheter wall.


Decline of zoonotic agents in livestock waste and bedding heaps.
To measure the rates of decline of zoonotic agents introduced into heaps of spent bedding and faecal wastes generated by commercially farmed livestock and managed in a similar way to that of a working farm. Livestock isolates of Salmonella, pathogenic Listeria, Campylobacter and Escherichia coli O157 were laboratory cultured and used to inoculate 5 m3 heaps of cattle, sheep or pig wastes mixed with bedding materials. Decline of each of the infectious agents was monitored with time as was the temperature inside each heap. Temperatures of >50 degrees C were typically achieved at the core of the heaps. Pathogen decline was rapid, typically <3 days for a 1-log reduction in levels. The longest time that zoonotic agents were isolated from the heaps was 93 days. Movement of heaps of livestock bedding waste from animal pens to a secondary store, and storing them under conditions conducive for increased temperature is a simple and cost-effective treatment for rapidly lowering levels of zoonotic agents in solid farm wastes. This study demonstrates a simple and cheap treatment that can be used to help prevent the spread of zoonotic agents through agricultural environments.


The Drosophila ebony gene is closely related to microbial peptide synthetases and shows specific cuticle and nervous system expression.
The previously detected ebony (e) locus (Caizzi et al., 1987) consists of a complex gene structure that is divided into seven exons. An open reading frame encoding the putative Ebony protein of 98.5 kDa exhibits homology to a family of peptide synthetases (Stachelhaus and Marahiel, 1995), in good correlation with the proposed function as beta-alanyl-dopamine synthetase. Multiple ebony transcripts are detected throughout development. P-factor mediated transformation of genomic DNA rescues the cuticle, electrophysiological and behavioural phenotypes. Fusion of the ebony reading frame with that of beta-galactosidase of E. coli reveals expression in cuticle and nervous system. Strong staining in the first and, to a lesser extent, in the second optic neuropile may reflect the pronounced visual defect observed in ebony mutants. In addition, weak central brain and thoracic ganglion expression is detected in flies. Conservation of a multidomain protein structure known from peptide synthetases should have functional implications on the putative reaction mechanism of peptide bond formation.


Long-term immunomodulatory effect of amniotic stem cells in an Alzheimer's disease model.
Amyloid beta (Aβ) plays a major role in Alzheimer's disease (AD), and neuroinflammatory processes mediated by Aβ plaque-induced microglial cells and astrocytes contribute to AD pathogenesis. The present study examined human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs), which have potent immunomodulatory and paracrine effects in a Tg2576 (APPswe) transgenic mouse model of AD. AMSCs secreted high levels of transforming growth factor-β under in vitro inflammatory environment conditions. Six weeks after the intravenous injection of AMSCs, APPswe mice showed evidence of improved spatial learning, which significantly correlated with the observation of fewer Aβ plaques in brain. The number of ED1-positive phagocytic microglial cells associated with Aβ plaques was higher in AMSC-injected mice than in phosphate-buffered saline-injected mice, and the level of Aβ-degrading enzymes (matrix metallopeptidase-9 and insulin-degrading enzyme) was also significantly higher. Furthermore, the level of proinflammatory cytokines, interleukin-1 and tumor necrosis factor-α, was lower and that of anti-inflammatory cytokines, interleukin-10 and transforming growth factor-β, was higher in AMSC-injected mice than phosphate-buffered saline-injected mice. These effects lasted until 12 weeks after AMSC injection. Taken together, these results collectively suggest that injection of AMSCs might show significant long-lasting improvement in AD pathology and memory function via immunomodulatory and paracrine mechanisms.


Resistin: An inflammatory cytokine with multi-faceted roles in cancer.
Systemic and organ-confined inflammation has been associated with cancer development and progression. Resistin, initially described as an adipocyte-derived cytokine in mice, is mostly expressed by the macrophages in humans. It has potent pro-inflammatory properties, and its elevated serum levels are detected in cancer patients. Aberrant expression of resistin receptors is also reported in several malignancies and associated with aggressive clinicopathological features. Several lines of evidence demonstrate that resistin, acting through its different receptors, promotes tumor growth, metastasis, and chemoresistance by influencing a variety of cellular phenotypes as well as by modulating the tumor microenvironment. Racially disparate expression of resistin has also attracted much interest, considering prevalent cancer health disparities. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling and impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development.


Synthesis, spectroscopic and structural elucidation of sympathomimetic amine, tyraminium dihydrogenphosphate.
The synthesis, isolation, spectroscopic and structural elucidation of sympathomimetic amine, tyramine dihydrogenphosphate are of interest due to its biological activity and the establishing correlation between spectroscopic properties and structure. The complex approach for investigation included single crystal X-ray diffraction, new technique in linear-polarized IR-spectroscopy in solid state and quantum chemical calculations with a view to predict the electronic structure and vibrational data of interacting species in entitled compound, the correlation structure-spectroscopic properties as well as the influence of intermolecular interaction on IR-characteristic bands are carried out.


Construction novel polybenzoxazine coatings exhibiting corrosion protection of mild steel at different concentrations in a seawater solution.
In this work, a new and effective polymeric coating is used to improve mild steel's corrosion resistance. The coating incorporates a Schiff base moiety into a benzoxazine (BZ) precursor, resulting in improved protection against corrosion. The SF-Tol-BZ polymerization behavior and thermal properties were studied using differential scanning calorimetry (DSC) and thermalgravimetric analysis (TGA), respectively, at different curing temperatures. The poly(SF-Tol-BZ) cured at 240 °C had a Td10 value of 604 °C and a Tg of 225 °C. The efficacy of poly(SF-Tol-BZ) coatings in protecting mild steel (MS) from corrosion in a NaCl (3.5%) solution at room temperature was evaluated using various corrosion measurements, including open circuit potential (OCP), and electrochemical impedance spectroscopy (EIS). The results showed that increasing the poly(SF-Tol-BZ) concentration led to a corresponding increase in its protective efficiency, reaching a maximum of 92% at a concentration of 300 g/L. The coatings also exhibited a 24-fold increase in Rct values and a one-order-of-magnitude reduction in CPE compared to the bare mild steel. Finally, the poly(SF-Tol-BZ) precursors demonstrated a CO2 uptake of 23 mg g-1 (measured at 298 K).


Systemic inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: state of the art and novel insights in regulation of muscle plasticity.
Systemic inflammation is a recognized hallmark of chronic obstructive pulmonary disease pathogenesis. Although the origin and mechanisms responsible for the persistent chronic inflammatory process remain to be elucidated, it is recognized that it plays an important role in skeletal muscle pathology as observed in chronic obstructive pulmonary disease and several other chronic inflammatory disorders. This article describes state-of-the-art knowledge and novel insights in the role of inflammatory processes on several aspects of inflammation-related skeletal muscle pathology and offers new insights in therapeutic perspectives.


Investigation of microbial cell deformability by filter cake compressibility using ultrafiltration membranes.
This study presents the investigation of deformability of various microbial cells in terms of filter cake compressibility during cake filtration using ultrafiltration membranes in dead-end mode. The examined microbial cells include mycoplasma, Gram-positive and Gram-negative bacteria, and Pseudomonas aeruginosa phage PP7. Polystyrene particles were used as an incompressible reference. The compressibility results were correlated to the deformability of a microbial cell, induced by its cell envelope. To determine the deformability of the different microbial cells under different process conditions, their cake resistance was measured under varying pressures from 10 to 250 kPa and temperatures from 2 to 35 °C. In addition, the influence of different culture media on the cell properties of Acholeplasma laidlawii and its behavior under different pressure and temperature was determined. The results of the pressure and temperature experiments revealed that Gram-positive S. epidermidis was found to be relatively stiff due to the thickness of the peptidoglycan layer, under different pressure and temperature conditions. No significant increase of the specific cake resistance of S. epidermidis could be determined. B. diminuta however showed a high deformation tendency when the pressure was increased indicating relatively soft cells. Mycoplasma A. laidlawii cells cultivated in three different media showed a different, but significant, effect of pressure and temperature.


Pre-meal insulin aspart compared with pre-meal soluble human insulin in type 1 diabetes.
Insulin aspart has been shown, in medium-term studies, to achieve reductions in HbA(1c) without increasing the risk of major hypoglycaemia compared with pre-meal human insulin. The aim of the present 3-year study was to evaluate the long-term safety and efficacy of insulin aspart in people with type 1 diabetes. This was a 30-month extension of a multinational, multicentre, open-label, parallel-group study of 753 people with type 1 diabetes, originally randomly allocated to treatment with insulin aspart or unmodified human insulin before meals, with NPH insulin as basal insulin. Main outcomes measures were hypoglycaemia (major or minor), adverse events and HbA(1c). As insulin aspart became commercially available in some countries before the end of the trial, analyses of HbA(1c) used 30-month data to maintain statistical power. The relative risk estimate of major hypoglycaemia was similar between treatment groups (relative risk [RR] 1.00 [95% CI 0.72, 1.39]). The risk of having a minor hypoglycaemic episode was higher with insulin aspart than with human soluble insulin (RR 1.24 [1.09, 1.39] p=0.024). Insulin aspart was significantly superior to human insulin with respect to overall glycaemic control, with a baseline-adjusted HbA(1c) difference of -0.16 (-0.32, -0.01)% (p=0.035). Insulin aspart was well tolerated and effective during long-term treatment. The HbA(1c) advantage was maintained with insulin aspart without any adverse impact on the rate of major hypoglycaemia.


In vivo Kinematics of the Knee after a Posterior Cruciate-Substituting Total Knee Arthroplasty: A Comparison between Caucasian and South Korean Patients.
This study compared in vivo kinematic differences between Caucasian and South Korean patients after a posterior-substituting total knee arthroplasty (PS-TKA). In vivo motions of 9 Caucasian and 13 South Korean knees with a PS-TKA during weight bearing single leg lunge were determined using a dual fluoroscopic imaging technique. Normalized tibiofemoral condylar motions and articular contact locations were analyzed. Femoral condylar motions of the two groups showed a similar trend in anteroposterior translation, but the South Korean patients were more anteriorly positioned than the Caucasian patients at low flexion and maximal flexion angles in both medial and lateral compartments (p<0.05). Mediolateral femoral condyle translations were similar between the two groups. For tibiofemoral articular contact kinematics, the South Korean patients had significantly more anterior contact locations at the medial compartment at low flexion angles, and more lateral contact locations at the lateral compartment at 0° and 90° flexion compared to the Caucasian patients (p<0.05). The South Korean patients had significantly larger distances between the medial and lateral contact locations at 60° and 90° flexion compared to the Caucasian patients (p<0.05). The study revealed that while the Caucasian and South Korean knees had similar femoral condylar motions, after PS-TKA the South Korean patients showed different articular contact point kinematics compared to the Caucasian patients.


Scanning Electron Microscopy of the Inner and Outer Aspects of Tiger Tail Hairs.
Tiger tail hairs, Morse hairs or pili annulati is a nonsyndromic hair shaft disorder, characterized by alternating light and dark bands along the hair shaft. The outer surface and the inner structure of longitudinally cut tiger tail hairs were examined with scanning electron microscopy. Hair specimens of five affected individuals showed small surface undulations with "curtain-like" folding of the hair cuticula (microcanaliculi). In the inner surface cord-like linear structures with serpiginous, tortuous traject were seen, associated with some cavities. These findings suggest that this condition is due to some deficient protein synthesis/arrangement, not only due to cavities in the hair cortex. The term Tiger tail hair is a descriptive clinical term of little scientific rigor. This disorder has been reported mainly as pili annulati; however, rings are not observed. In analogy to pili canaliculi, in which well-formed grooving is observed in the hair surface, we suggest the term pili microcanaliculi to describe this condition, based in the ultrastructural findings.


ANALYSIS OF FLUID VOLUME AND ITS IMPACT ON VISUAL ACUITY IN THE FLUID STUDY AS QUANTIFIED WITH DEEP LEARNING.
To investigate quantitative differences in fluid volumes between subretinal fluid (SRF)-tolerant and SRF-intolerant treat-and-extend regimens for neovascular age-related macular degeneration and analyze the association with best-corrected visual acuity. Macular fluid (SRF and intraretinal fluid) was quantified on optical coherence tomography volumetric scans using a trained and validated deep learning algorithm. Fluid volumes and complete resolution was automatically assessed throughout the study. The impact of fluid location and volumes on best-corrected visual acuity was computed using mixed-effects regression models. Baseline fluid quantifications for 348 eyes from 348 patients were balanced (all P > 0.05). No quantitative differences in SRF/intraretinal fluid between the treatment arms was found at any study-specific time point (all P > 0.05). Compared with qualitative assessment, the proportion of eyes without SRF/intraretinal fluid did not differ between the groups at any time point (all P > 0.05). Intraretinal fluid in the central 1 mm and SRF in the 1-mm to 6-mm macular area were negatively associated with best-corrected visual acuity (-2.8 letters/100 nL intraretinal fluid, P = 0.007 and -0.20 letters/100 nL SRF, P = 0.005, respectively). Automated fluid quantification using artificial intelligence allows objective and precise assessment of macular fluid volume and location. Precise determination of fluid parameters will help improve therapeutic efficacy of treatment in neovascular age-related macular degeneration.


Measuring quality in electrophysiology.
The evolving healthcare environment demands optimally measured quality of care. Performance measures are increasingly being used for quality improvement, public reporting, and reimbursement determinations. The National Quality Forum has created rigorous criteria for the evaluation of potential performance measures across medical fields. The Heart Rhythm Society has championed the development of four separate electrophysiology (EP)-specific performance measures: implantable cardioverter defibrillator complication rate, cardiac tamponade and/or pericardiocentesis following atrial fibrillation ablation, infection within 180 days of a cardiac implantable electronic device implantation, replacement, or revision, and in-person evaluation following a cardiac implantable electronic device implantation. National registries serve a key role in developing performance measures and facilitating quality improvement, particularly as they provide improved granularity and accuracy of data compared with administrative claims data. All performance measures demand continued reassessment as technology and performance gaps change and as unintended consequences may arise.


Detection of human autoantibodies specific for 5'-m7GMP and m7G(5')ppp(5')N.
An enzyme-linked immunosorbent assay was utilized for the detection of spontaneously occurring antibodies with apparent specificities for m7G, 5'-m7GMP, and m7G(5')ppp(5')C. From the sera of 50 patients containing anti-nuclear antibodies, 48 (96%) possessed antibodies which bound to one or more immobilized nucleoside-BSA antigens (A-, G-, C-, U-, and T-BSA). Additionally, 8 (16%) of these sera contained immunoglobulins that reacted with m7G-BSA antigen. In these latter sera, soluble competitors such as m7G, 5'm7GMP, and m7G(5')ppp(5')C (but not 5'-AMP, -GMP, -CMP, -UMP, and -TMP or m1G and m22G) effectively inhibited antibody-binding to immobilized m7G-BSA. These results indicate the existence of spontaneously occurring anti-m7G antibodies in autoimmune diseases which are distinct from anti-G antibody populations.


A coordination polymer nanobelt (CPNB)-based aptasensor for sulfadimethoxine.
A polymer-based aptasensor, which consisted of fluorescein amidite (FAM)-modified aptamers and coordination polymer nanobelts (CPNBs), was developed utilizing the fluorescence quenching effect to detect sulfadimethoxine residue in food products. A single-stranded DNA (ssDNA) aptamer, which was a specific bio-probe for sulfadimethoxine (Su13; 5'-GAGGGCAACGAGTGTTTATAGA-3'), was discovered by a magnetic bead-based systematic evolution of ligands by exponential enrichment (SELEX) technique, and the fluorescent quenchers CPNBs were produced by mixing AgNO(3) and 4,4'-bipyridine. This aptasensor easily and sensitively detected sulfadimethoxine in solution with a limit of detection (LOD) of 10ng/mL. Furthermore, the antibiotic dissolved in milk was also effectively detected with the same LOD value. In addition, this aptamer probe offered high specificity for sulfadimethoxine compared to other antibiotics. These valuable results provide ample evidence that the CPNB-based aptasensor can be used to quantify sulfadimethoxine residue in food products.


Gastroduodenal fistulae and double pyloric canal.
Four cases of endoscopically proven gastroduodenal fistulae (double pyloric canal) are presented, and ten case reports in the literature are reviewed. The fistula develops from a penetrating gastric ulcer. Presumably, the ulcer becomes adherent to adjacent duodenum and penetrates further to establish a fistulous connection, which ultimately becomes lined with mucosa, creating a second pyloric canal. Fistulae between the lesser curve of the antrum and superior fornix of the duodenal bulb were the commonest (9 out of 14). Fistulae also form between the lesser curve of the body of the stomach and the duodenal bulb or fourth part of the duodenum. Gastro-gastric fistula and a fistula into the inferior fornix of the duodenal bulb from a pyloric ulcer have been described. In two of the four cases in this series fistulae had formed from the greater curve of the antrum to the inferior fornix of the duodenal bulb, an entity not previously described. Radiologic appearances may be confused with an antral carcinoma, an ulcerating carcinoma, Crohn's disease, or lymphoma. The presence of previous ulceration and evidence of scarring should aid in avoiding confusion with malignancy. The term gastroduodenal fistula is suggested to describe double pyloric canal.


Anatomic, clinical, and therapeutic features of acute cardiac rupture. Successful surgical management fourteen hours after myocardial infarction.
A 62-year-old man sustained an acute myocardial infarction complicated on the thirteen hour by left ventricular rupture and acute periocardial tamponade. Echocardiography confirmed the suspicion of intrapericardial fluid, and immediate pericardiocentesis improved the hemodynamic state for a period sufficient to permit preparation for operation. Resection of ruptured and necrotic anteroapical left ventricular myocardium with primary reconstruction was successfully accomplished with the aid of temporary extracorporeal circulation. The patient has remained well for 1 year after the operation. Anatomic, clinical, and therapeutic features of acute cardiac rupture are discussed.


Specific needs for telestroke networks for thrombolytic therapy in Japan.
The concept of telestroke networks has been proposed to overcome regional disparities in stroke treatment. Such networks do not yet operate in Japan. We aimed to determine the specific needs for telestroke networks and to estimate the effects on the number of thrombolytic therapies. Five of the 47 Japanese prefectures with various population densities to estimate the nationwide effect of telestroke networks were selected. The questionnaire survey was administered at hospitals in these prefectures that are authorized to admit patients with acute stroke. Low-volume hospitals that annually treated fewer than 12 patients with acute stroke had never used tissue plasminogen activator (tPA). The number of days when telestroke support might have been needed varied depending on the size of the population aged 65 years or older within a 30-minute-driving-time area of a hospital and the annual number of patients treated within 3 hours of onset. The geographic information system analysis showed that .6%-8.3% of the population lived in areas where they could not reach a hospital for acute stroke treatment within 60 minutes. If 24/7 full telestroke support was introduced to the existing hospitals, 6.8-69.3 more patients could be treated by intravenous (IV) tPA annually. These numbers exceeded the estimated annual increases of .8-13.7 more patients if a drip-and-ship telestroke network was introduced into an underserved area outside the 60-minute-driving-time area. This study uncovered that many Japanese stroke hospitals, especially low-volume facilities located in rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support to these hospitals may be highly effective compared with the drip-and-ship network in an underserved area.


Comparison of thread-cutting behavior in three specialist predatory mites to cope with complex webs of Tetranychus spider mites.
Anti-predator defenses provided by complex webs of Tetranychus mites can severely impede the performance of generalist predatory mites, whereas this may not be true for specialist predatory mites. Although some specialist predatory mites have developed morphological protection to reduce the adverse effects of complex webs, little is known about their behavioral abilities to cope with the webs. In this study, we compared thread-cutting behavior of three specialist predatory mites, Phytoseiulus persimilis, Neoseiulus womersleyi and N. californicus, exhibited inside the complex web of T. urticae. No major difference was observed among them in the basic pattern of this behavior, using chelicerae and palps, and in the number of silken threads severed while moving inside the web. These results and observations suggest that each predator species cut many sticky silken threads to move inside the complex web without suffering from serious obstruction.


Neighborhood competition in several violet populations.
Research into local (neighborhood) competition has heretofore focused on either natural populations of long-lived woody plants or artifical populations of herbaceous annuals. To explore the usefulness of these techniques for herbaceous perennials, 1 applied them to 11 natural populations of 4 species of violet (Viola blanda, V. pallens, and V. incognita, alone and with V. adunca). Ramet density ranged from 132 to 508 per square meter. The analysis tried to account for the size of each ramet (expressed as the number of leaves) using information on the number, size, and angular aggregation of neighboring plants in three concentric annuli (0-3, 3-6, and 6-9 cm). Simple rank correlations between leaf number and these measures of local competition were usually of the expected sign, but were consistently significant in only two of the populations (1 pallens and 1 incognita). No significant correlations were of the "wrong" sign. When the spatial independent variables were combined into multiple regression equations they accounted for between 5 and 59% of the total variance in leaf number. The equations were best in predicting individual size in the Newfoundland populations of V. incognita which had the greatest range in individual size. Total plant density appeared unrelated to predictive success.The neighborhood competition approach can be applied to natural populations of herbaceous perennials, but low density, inaccurate measures of plant performance and microvariation in site quality limit its usefulness. In particular, it seems impossible to determine the mechanism by which neighbors exert their competitive effects with this approach.


Application of mathematical modelling to alginate chitosan polyelectrolyte complexes for the prediction of system behavior with Venlafaxine HCl as a model charged drug.
This work aimed to develop and analyze the performance of chitosan/alginate polyelectrolyte complex (PEC). Multiple regression and Lab fit curve fitting were applied to derive empirical models for the prediction of zeta potential of plain systems as a function of alginate chitosan ratio. Venlafaxine-HCl was loaded as a model charged drug and empirical models for prediction of its release as a function of time were also derived. Coacervation method was used for the preparation of green PECs. Preliminary studies were conducted to optimize the preparation method. Pre-adjustment of the pH of alginate and chitosan sols enabled the formation of PECs at alginate/chitosan ratios starting from 1:9 to 9:1. On mixing of alginate and chitosan sols, equal volume dilution method produced spherical particles, while direct mixing method gave fibrous particles. Twenty-seven PECs nanoparticle formulae were prepared using nine alginate/chitosan ratios and three levels of total polymer concentrations. Statistical analysis showed that Zeta potential of the nanoparticle was significantly dependent on alginate/chitosan ratio, while particle size was a function of total polymer concentration. Nine fiber formulae were prepared and evaluated for their appearance and zeta potential. Venlafaxine-HCl release followed anomalous transport mechanism. FT-IR and DSC studies confirmed complexation at the carboxylate and amine site at alginate and chitosan respectively. Chitosan/alginate PECs were successfully obtained without a cross-linker and empirical equations were obtained to help finding the best composition for loading charged drugs and to predict their release profiles.


Two-dimensional diffraction scanning of normal and cancerous human hepatic tissue in vitro.
A technique and associated equipment are described which investigate the acoustic signals backscattered from small tissue volumes and interrogated over a solid angle of transmitter/receiver positions. This two-dimensional diffraction technique produces acoustic scatter maps termed, by us "interferograms", which are analysed to determine their usefulness in discriminating between normal, freshly excised liver tissue and cancerous tissue within the intact organ. The "interferograms" are collected at three different narrow-band frequencies and have been used in investigating 26 normal liver and 13 liver tumour samples. The preliminary results indicate that this novel technique has a 97% success in discriminating normal liver from tumour, compared to an 87% success achieved by two observers when scoring conventional sector B-scan images of the same tissue regions.


Novel lysine-peptoid hybrids with antibacterial properties.
Here we report the design, synthesis and antibacterial activity of 20 lysine-peptoid hybrids. The hybrids are based on the peptoid lead structure [N-(1-naphthalenemethyl)glycyl]-[N-(4-methylbenzyl)glycyl]-[N-(1-naphthalenemethyl)glycyl]-N-(butyl)glycin amide (1) and contain between one and six lysine residues each. The compounds were tested for antibacterial activity against S. aureus ATCC 25923 and E. coli ATCC 25922. Furthermore, the hemolytic activity toward human erythrocytes was assessed. Several compounds with potent antibacterial activity and low hemolytic activity were identified.


Biomass-based activated carbons produced by chemical activation with H3PO4 as catalysts for the transformation of α-pinene to high-added chemicals.
In the era of ecology and careful care for the environment, it becomes important to use renewable raw materials of plant origin, which are often more easily available and cheaper. One of the important and rapidly developing directions of research are works related to the use of waste plant biomass; an example of this trend is the production of activated carbons from food industry waste. One of the examples of the application of derived from biomass activated carbons can be using them as catalysts for the isomerization of terpene compounds. Carbons based on waste biomass are characterized by the minimal amount of waste formation during their manufacture, and their use in the isomerization reaction allows to obtain high conversion of organic raw material and high selectivities of transformation to the desired products, making these carbons environmentally friendly substitutes for the catalysts used usually in this process. In this work, obtained carbonaceous catalysts were tested in the process of isomerization of α-pinene to high value chemicals (mainly camphene and limonene). Under the most favorable conditions (activated carbon from sunflower husks content in reaction mixture 5 wt%, temperature 180 °C, and reaction time 100 min), α-pinene was completely converted (conversion 100 mol%) with high selectivity towards camphene (54 mol%). To prepare activated carbons, biomass precursors (orange peels, sunflower husks, spent coffee grounds) were activated with 85% H3PO4 through the chemical activation. The obtained materials were characterized by such methods as sorption N2 at - 196 °C, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and X-ray fluorescence (XRF) to determine the relationship between their textural-chemical properties and catalysts activity in isomerization process. The synthesized materials were characterized by a specific surface area in the range of 930-1764 m2, total pore volume in the range of 0.551-1.02 cm3/g, and total acid-site concentrations in the range of 1.47-2.33 mmol/g. These results showed that textural parameters of the obtained activated carbons have the important role in the isomerization of α-pinene.


[The usability of information material for refugees. An exemplary evaluation of Saxony-Anhalt's "Health Booklet for Asylum Seekers"].
In response to the large number of asylum seekers coming to Germany since 2015, lots of informational materials, translation aids, leaflets, etc. have been developed. However, hardly any of these materials have been evaluated with respect to their acceptance and usability in clinical practice. The aim of the present study was to exemplarily evaluate the 'Health Booklet for Asylum Seekers' that has been in use in Saxony-Anhalt since 2017. A cross-sectional survey was combined with qualitative interviews in an explanatory sequential mixed methods design. The survey included general practitioners (n=41), nursing staff (n=7), refugees (n=19) and other stakeholders (n=30); the Systems Usability Scale (SUS) was used to assess the usability of the booklet. The qualitative part of the study involved 35 interviews with the above-mentioned participants and two focus group discussions with physicians and refugees; the aim was to better understand the different actors' perception of usability. Most general practitioners did not know the booklet and had never used it before, but were eager to make use of it in the future. Overall, the booklet was rated as highly usable by 65 % of all respondents, while the median score in the SUS was above the threshold value for good usability. Respondents explained that the booklet improved patient care, helped patients to better understand the health care system and their health issues, increased patient autonomy and has symbolic value as an expression of diversity management. The different stakeholders predominantly perceived the health booklet to be a useful tool and assumed that its application in clinical practice would help alleviate some of the practical problems in providing medical care for asylum seekers.


Perinatal complications among ethnic Somalis in Norway.
The majority of ethnic Somali women in Norway have undergone an elaborate form of circumcision (infibulation). The aim of this study was to examine the risk of perinatal complications among ethnic Somalis and to discuss its relation to circumcision. We conducted a cross-sectional population-based registry study. Data on all births to women born in Somalia (1733) and Norway (702 192) from 1986 to 1998 was provided from the Medical Birth Registry of Norway. We analyzed the risk of perinatal complications among women of Somali origin vs. ethnic Norwegians using univariate and multivariate methods. Perinatal complications were more frequent among women of Somali origin than among ethnic Norwegians. These included induction of labor, fetal distress, secondary arrest, prolonged second stage of labor, operative delivery and perinatal death. Particularly elevated odds ratios were found for fetal distress (odds ratio=2.6, 95% confidence interval (CI); 2.2-3.0), emergency cesarean sections (odds ratio=3.0, 95% confidence interval 2.6-3.4), Apgar scores below seven (odds ratio = 3.1, 95% confidence interval 2.4-4.0) and prelabor fetal deaths (odds ratio=2.5, 95% confidence interval 1.7-3.7). Similar findings in infibulated vs. noncircumcised women have been demonstrated previously in other studies indicating that circumcision could play a role. The current study is the first to be conducted among Somali women in Europe. However, the results are not informative on whether the adverse birth outcomes are caused by infibulation as such or in combination with suboptimal perinatal care, intercurrent diseases and sociocultural factors. Somali women represent a high-risk group in obstetrics, calling for special attention and care.


Apraxic agraphia following thalamic damage: Three new cases.
Apraxic agraphia (AA) is a so-called peripheral writing disorder following disruption of the skilled movement plans of writing while the central processes that subserve spelling are intact. It has been observed in a variety of etiologically heterogeneous neurological disorders typically associated with lesions located in the language dominant parietal and frontal region. The condition is characterized by a hesitant, incomplete, imprecise or even illegible graphomotor output. Letter formation cannot be attributed to sensorimotor, extrapyramidal or cerebellar dysfunction affecting the writing limb. Detailed clinical, neurocognitive, neurolinguistic and (functional) neuroimaging characteristics of three unique cases are reported that developed AA following a thalamic stroke. In marked contrast to impaired handwriting, non-handwriting skills, such as oral spelling, were hardly impaired. Quantified Tc-99m ECD SPECT consistently showed a decreased perfusion in the anatomoclinically suspected prefrontal regions. The findings suggest crucial involvement of the anterior (and medial) portion of the left thalamus within the neural network subserving the graphomotor system. Functional neuroimaging findings seem to indicate that AA after focal thalamic damage represents a diaschisis phenomenon.


Genomic testing among patients with newly diagnosed advanced non-small cell lung cancer in the United States: A contemporary clinical practice patterns study.
According to 2018 United States and international lung cancer and pathology guidelines, testing of EGFR, ALK, ROS1 and BRAF genes is a minimum requirement to identify targeted therapy options in patients with advanced non-small cell lung cancer (aNSCLC). We describe real-world use and clinical features of next-generation sequencing (NGS) and other non-NGS testing technologies in these patients. Patients were from the Flatiron Health electronic health record-derived de-identified database and were newly diagnosed with non-squamous aNSCLC between 1 January 2018 and 30 June 2019. We describe occurrence and patterns of NGS- (including comprehensive genomic profiling [CGP]) and non-NGS-based genomic testing before the start of first-line therapy, unsuccessful genotyping (<4 genes tested) and incidence of potentially missed targeted therapy options (<4 genes tested with no positive results). Among 3050 patients, 2356 received any type of genomic testing (NGS: 1406 [59.7%]). Unsuccessful genotyping occurred in 13.2% and 52.2% of NGS- and non-NGS-tested patients, respectively. Among NGS-tested patients, 10.0% had a potentially missed targeted therapy option (CGP: 2.9%), compared with 40.2% in the non-NGS tested group. While all four guideline-recommended genes were tested in ≥ 92% of patients who had NGS testing, when only non-NGS testing was used, although EGFR and ALK had similarly high testing proportions, BRAF and ROS1 (56.1% and 83.7%, respectively) were examined less often. Our findings suggest that in aNSCLC clinical practice, NGS testing may help to avoid potentially missed targeted therapy options and improve testing uptake for recently approved biomarkers. Results therefore support the use of guideline-recommended broad-panel NGS testing in clinical practice.


Pulmonary capillary hemangiomatosis arising in hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant inherited disease characterized by epistaxis, telangiectases, and visceral arteriovenous malformations that can lead to hemorrhage and other complications. We report the case of a 56-year-old female patient with HHT and pulmonary hypertension who died with intractable pulmonary and gastrointestinal bleeding. Autopsy revealed vascular malformations in the lungs, gastrointestinal tract, liver, spleen, and brain. Capillary proliferations in the pulmonary alveolar walls, characteristic of pulmonary capillary hemangiomatosis, were identified, as was evidence of pulmonary hypertensive arteriopathy. To our knowledge, this is the first report of pulmonary capillary hemangiomatosis arising in HHT. The histopathologic findings of HHT and pulmonary capillary hemangiomatosis are reviewed, and a possible role for diminished capillary expression of endothelial nitric oxide synthase is discussed.


Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area.
Recent studies have identified several neuropeptide systems in the hypothalamus that are critical in the regulation of body weight. The lateral hypothalamic area (LHA) has long been considered essential in regulating food intake and body weight. Two neuropeptides, melanin-concentrating hormone (MCH) and the orexins (ORX), are localized in the LHA and provide diffuse innervation of the neuraxis, including monosynaptic projections to the cerebral cortex and autonomic preganglionic neurons. Therefore, MCH and ORX neurons may regulate both cognitive and autonomic aspects of food intake and body weight regulation. The arcuate nucleus also is critical in the regulation of body weight, because it contains neurons that express leptin receptors, neuropeptide Y (NPY), alpha-melanin-stimulating hormone (alpha-MSH), and agouti-related peptide (AgRP). In this study, we examined the relationships of these peptidergic systems by using dual-label immunohistochemistry or in situ hybridization in rat, mouse, and human brains. In the normal rat, mouse, and human brain, ORX and MCH neurons make up segregated populations. In addition, we found that AgRP- and NPY-immunoreactive neurons are present in the medial division of the human arcuate nucleus, whereas alpha-MSH-immunoreactive neurons are found in the lateral arcuate nucleus. In humans, AgRP projections were widespread in the hypothalamus, but they were especially dense in the paraventricular nucleus and the perifornical area. Moreover, in both rat and human, MCH and ORX neurons receive innervation from NPY-, AgRP-, and alpha-MSH-immunoreactive fibers. Projections from populations of leptin-responsive neurons in the mediobasal hypothalamus to MCH and ORX cells in the LHA may link peripheral metabolic cues with the cortical mantle and may play a critical role in the regulation of feeding behavior and body weight.


Characterization of neurotransmitters and related metabolites in Daphnia magna juveniles deficient in serotonin and exposed to neuroactive chemicals that affect its behavior: A targeted LC-MS/MS method.
Neurotransmitters are endogenous metabolites that play a crucial role within an organism, at the chemical synapses. There is a growing interest in their analytical determination for understanding the neurotoxic effect of contaminants. Daphnia magna represents an excellent aquatic model for these environmental studies, due to its similarities with vertebrates in several neurotransmitters and related gene pathways and because of its wide application in ecotoxicological studies. Within this study, an accurate and sensible method of analysis of 17 neurotransmitters and related precursors and metabolites was developed. The method was validated in terms of sensitivity, reproducibility, precision, and accuracy, and also matrix effect was evaluated. As an independent probe of method validation and applicability, the method was applied to two different scenarios. First, it was used for the study of neurotransmitter levels in genetically mutated tryptophan hydrolase D. magna clones, confirming the absence of serotonin and its metabolite 5-HIAA. Additionally, the method was applied for determining the effects of chemical compounds known to affect different neurotransmitter systems and to alter Daphnia behavior. Significant changes were observed in 13 of the analyzed neurotransmitters across treatments, which were related to the neurotransmitter systems described as being affected by these neurochemicals. These two studies, which provide results on the ways in which the neurotransmitter systems in D. magna are affected, have corroborated the applicability of the presented method, of great importance due to the suitability of this organism for environmental neurotoxicity studies.


Hand Contamination, Cross-Transmission, and Risk-Associated Behaviors: An Observational Study of Team Members in ORs.
Team members in ORs have frequent hand contact with many surfaces and sites during high workload, thus increasing the risk for microorganism cross-transmission. This study aimed at identifying risks for hand contamination and microorganism cross-transmission during invasive procedures in ORs. We carried out observations during 22 daytime sessions and analyzed data using qualitative content analysis. The results revealed that clinicians' hands may be contaminated by self-contamination, via objects, or by touching the patient. Contamination may occur before, during, or directly after performing an invasive procedure requiring the use of aseptic technique, which risks cross-transmitting microorganisms. The results of the study contribute detailed knowledge about risk-associated activities and behaviors in relation to performing invasive procedures in the OR. This knowledge provides clinicians, managers, and educators with specific information that can be used in nursing and medical education and in quality improvement projects aimed at improving hand hygiene routines and enhancing aseptic technique.


Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: A novel in vitro cholestatic model.
Drug-induced cholestasis is a leading cause of drug withdrawal. However, the use of primary human hepatocytes (PHHs), the gold standard for predicting cholestasis in vitro, is limited by their high cost and batch-to-batch variability. Mature hepatocyte characteristics have been observed in human induced hepatocytes (hiHeps) derived from human fibroblast transdifferentiation. Here, we evaluated whether hiHeps could biosynthesize and excrete bile acids (BAs) and their potential as PHH alternatives for cholestasis investigations. Quantitative real-time PCR (qRT-PCR) and western blotting indicated that hiHeps highly expressed BA synthases and functional transporters. Liquid chromatography tandem mass spectrometry (LC-MS/MS) showed that hiHeps produced normal intercellular unconjugated BAs but fewer conjugated BAs than human hepatocytes. When incubated with representative cholestatic agents, hiHeps exhibited sensitive drug-induced bile salt export pump (BSEP) dysfunction, and their response to cholestatic agent-mediated cytotoxicity correlated well with that of PHHs (r2 = 0.8032). Deoxycholic acid (DCA)-induced hepatotoxicity in hiHeps was verified by elevated aspartate aminotransferase (AST) and γ-glutamyl-transferase (γ-GT) levels. Mitochondrial damage and cell death suggested DCA-induced toxicity in hiHeps, which were attenuated by hepatoprotective drugs, as in PHHs. For the first time, hiHeps were reported to biosynthesize and excrete BAs, which could facilitate predicting cholestatic hepatotoxicity and screening potential therapeutic drugs against cholestasis.


Clenbuterol-Induced Myocarditis: A Case Report.
We present a case of a 22-year-old bodybuilder diagnosed with myocarditis secondary to clenbuterol use. The patient was primarily managed conservatively by the discontinuation of clenbuterol and the temporary use of dual anti-platelets, beta-blockers and nitrates. Clenbuterol is a long-acting beta-2 agonist primarily used in veterinary medicine. In recent years, it has been illegally marketed as a weight loss supplement because of its anabolic properties and is popular among fitness enthusiasts. It is our aim to use this case to underscore the adverse effects of this drug with hopes that tighter regulations will be instituted to stem its illegal distribution. Clenbuterol is primarily a veterinary drug with bronchodilator and tocolytic properties.It is illegally used as a performance enhancer by athletes and bodybuilders because of its anabolic properties.Clenbuterol misuse can result in myocardial injury.


Novel tumor therapy strategies targeting endoplasmic reticulum-mitochondria signal pathways.
Organelles form tight connections through membrane contact sites, thereby cooperating to regulate homeostasis and cell function. Among them, the contact between endoplasmic reticulum (ER), the main intracellular calcium storage organelles, and mitochondria has been recognized for decades, and its main roles in the ion and lipid transport, ROS signaling, membrane dynamic changes and cellular metabolism are basically determined. At present, many tumor chemotherapeutic drugs rely on ER-mitochondrial calcium signal to function, but the mechanism of targeting resident molecules at the mitochondria-associated endoplasmic reticulum membranes (MAM) to sensitize traditional chemotherapy and the new tumor therapeutic targets identified based on the signal pathways on the MAM have not been thoroughly discussed. In this review, we highlight the key roles of various signaling pathways at the ER-mitochondria contact site in tumorigenesis and focus on novel anticancer therapy strategies targeting potential targets at this contact site.


OH. treatment of tetanus toxin reduces its susceptibility to limited proteolysis with more efficient presentation to specific T cells.
At inflammatory sites, before their processing, antigens are exposed to oxygen free radicals released by activated cells. The effect of hydroxyl radicals (OH.) on the structure of a protein antigen, tetanus toxin (TT) was investigated, as well as the consequences on processing and presentation. A chemical system composed of Fe-EDTA, ascorbate and H2O2 was used to produce physiological amounts of OH. radicals. TT exposed to OH. radicals presented a marked decrease of its intrinsic fluorescence with a concomitant increase of the content of bityrosine, but no fragmentation of the protein was detected by SDS-PAGE. Processing of the modified TT was analysed, by incubating TT at acidic pH with fractions enriched in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL). Proteolysis of OH.-treated TT was less important than proteolysis of native TT, especially upon prolonged incubations. Oxidized TT presented by LCL cells induced a greater proliferation of three different TT specific T cell clones, compared to native TT. When proteolytic digests of TT were presented by fixed LCL cells to a homologous T cell line, the proliferative response obtained in the presence of digests of OH.-treated TT was sustained, even in the case of prolonged proteolysis, whereas the response to digests of native TT fell rapidly. The relative resistance of OH.-treated TT to proteolysis appears thus responsible for its greater presentation to specific T cells, probably by protecting epitopes.


Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation.
Cellular immunity mediated by CD8+ T cells plays an indispensable role in bacterial and viral clearance and cancers. However, persistent antigen stimulation of CD8+ T cells leads to an exhausted or dysfunctional cellular state characterized by the loss of effector function and high expression of inhibitory receptors during chronic viral infection and in tumors. Numerous studies have shown that glycogen synthase kinase 3 (GSK3) controls the function and development of immune cells, but whether GSK3 affects CD8+ T cells is not clearly elucidated. Here, we demonstrate that mice with deletion of Gsk3α and Gsk3β in activated CD8+ T cells (DKO) exhibited decreased CTL differentiation and effector function during acute and chronic viral infection. In addition, DKO mice failed to control tumor growth due to the upregulated expression of inhibitory receptors and augmented T-cell exhaustion in tumor-infiltrating CD8+ T cells. Strikingly, anti-PD-1 immunotherapy substantially restored tumor rejection in DKO mice. Mechanistically, GSK3 regulates T-cell exhaustion by suppressing TCR-induced nuclear import of NFAT, thereby in turn dampening NFAT-mediated exhaustion-related gene expression, including TOX/TOX2 and PD-1. Thus, we uncovered the molecular mechanisms underlying GSK3 regulation of CTL differentiation and T-cell exhaustion in anti-tumor immune responses.


Are elevated admission calcium levels associated with better outcomes after ischemic stroke?
Calcium (Ca(2+)) and magnesium (Mg(2+)) influence the molecular pathways of ischemic neuronal death. The authors evaluated the impact of admission serum Ca(2+) and Mg(2+) levels, on incident stroke severity and discharge functional outcome. After adjusting for covariates, higher admission Ca(2+) was significantly associated with lesser stroke severity and better discharge functional outcome. Admission Mg(2+) was not an independent clinical outcome prognosticator.


Photocatalytic reduction for graphene oxide by PbTiO3 with high polarizability and its electrocatalytic application in pyrrole detection.
Quick recombination of photogenerated electrons and holes in photocatalytic process remains a huge challenge. And the routine efforts are concentrated on heterojunction, metal decoration and surface defect strategies. PbTiO3 as a typical perovskite ferroelectrics is with a strong built-inelectric field as self-junction caused by internal spontaneous polarization, facilitating the charge separation in the photocatalytic process. Here, under UV irradiation, L-shaped PbTiO3 with active (1 1 0) facet as a photocatalyst was applied to photo-reduce graphene oxide (GO), where a specific reduced graphene oxide (rGO)/PbTiO3 composite was synthesized in presence of isopropanol, a hole-trapping agent. According to the linear optical properties, the polarizability of PbTiO3 is calculated to 1.01 × 10-23 cm3 (2.68 times that of P25 (TiO2)), inducing the photo-excited charge separation by PbTiO3. Based on XPS characterization, a TiOC chemical bond is identified on the interface between rGO and PbTiO3. The response peak current for an electrochemical sensor based on rGO/PbTiO3 was proportional to the concentration of pyrrole (6.6 × 10-9-3.1 × 10-7 M, R2 = 0.999), and an extremely low limit reaches to 2.38 × 10-9 M. In addition, polypyrrole during the pyrrole detection was realized by the multi-cycle oxidation process. And also, the electrochemical detection has been successfully applied for the pyrrole quantification in real samples.


Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients.
Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-)). This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D-/R+), all managed with preemptive therapy. Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24). These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection.


Innovations in academic and practice partnerships: new collaborations within existing models.
New models in academic institutions that engage practice experts accelerate innovative thinking, productivity, and quality. A successful model in a southwest university college of nursing and health innovation is presented. In this article, the authors provide experiences specific to identifying needs, developing partnerships, integrating experts into the college, and challenges in sustaining partnerships and their potential for transforming the academic and service relationship in the age of reform.


Giant cell tumor of tendon sheath: spectrum of radiologic findings.
Giant cell tumor of tendon sheath is the second most common tumor of the hand. It can also occur in larger joints. Radiologic features include a soft-tissue mass with or without osseous erosion. Less commonly, it can cause periostitis or permeative osseous invasion; it may rarely calcify. The entire imaging spectrum of this lesion is presented, with emphasis on atypical appearances which can mimic other lesions.