Successful decompressive laparotomy in a neonate with abdominal compartment syndrome on extracorporeal membrane oxygenation following congenital diaphragmatic hernia repair.
Abdominal compartment syndrome (ACS) is a rare complication of extracorporeal membrane oxygenation (ECMO) and is associated with high morbidity and mortality. Despite being the treatment of choice for ACS, decompressive laparotomy (DL) has been a matter of debate in children supported with ECMO due to high bleeding risk and presumed futility. We report the first neonatal DL for ACS while on ECMO following congenital diaphragmatic hernia (CDH) repair. Given its excellent outcomes, our case challenges current literature and supports prompt bedside laparotomy to treat ACS on neonatal ECMO.


Inhibition of TF gene expression by antisense oligonucleotides in different cancer cell lines.
Human tissue factor (TF) is the initiator of blood coagulation. Beside this function it is involved in tumor angiogenesis and metastasis. In the study we have evaluated the efficiency of antisense oligonucleotides (AS-ODNs) against TF selected from computational prediction of TF mRNA structure. Fourteen different AS-ODNs were tested in three cell lines of different origin with a high TF content. In cell line MCF-7 expression of TF gene was inhibited up to 50% by the AS-ODN AS-7 in comparison to reference. To investigate the dependence of inhibition efficiency on the AS-ODN position inside a potential target motive we designed further AS-ODNs shifted 2-3 nt among AS-7. One AS-ODN was found as more effective than AS-7. In cell line T508 were obtained moderate effects in inhibition of TF gene expression of 30% by AS-4. In J82 cells TF protein was inhibited up to 68% by two AS-ODNs. In conclusion, we compared inhibition of TF gene expression in different cancer cell lines and found that all effective AS-ODNs were located in the translated region of TF mRNA. Suitability of a target region of an AS-ODN is relatively independent on cell line. In contrast, optimal transfection conditions are dependent on cell line.


Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.
Responses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually. A gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine]. The gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets. In summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.


Selection of metastatic variants with identifiable karyotypic changes from a nonmetastatic murine tumor after treatment with 2'-deoxy-5-azacytidine or hydroxyurea: implications for the mechanisms of tumor progression.
Experiments were undertaken to explore whether in vitro exposure of a nonmetastatic murine tumor to chemotherapeutic drugs would affect the ability of this tumor to metastasize spontaneously. The tumor chosen was an aneuploid (near-tetraploid) spontaneously arising intraductal mammary adenocarcinoma (CBA-SP1), which normally fails to give rise to microscopic or macroscopic metastases after s.c. inoculation of cells. The drugs tested were 5-aza-2'-deoxycytidine (5-aza-dCyd) and hydroxyurea. We found that the injection of 1 X 10(5) uncloned drug-treated cells s.c. resulted in the emergence of gross and/or microscopically detectable metastases in the lungs of CBA mice. Individual clones derived from hydroxyurea-treated cells all produced metastases in a manner similar to the bulk culture injections. Clones of 5-aza-dCyd-treated cells also produced metastases, but fewer of these produced macroscopic metastases. In addition, only 9 of 15 5-aza-dCyd-treated clones produced tumor takes because of the ability of 5-Aza-dCyd to engender Imm+ variants in CBA-SP1 cells. Lung metastases obtained after the injection of uncloned cells retained their metastatic phenotype for three generations, indicating that the phenotypic change was a heritable characteristic. Although the genetic or epigenetic mechanism for this change is unknown, we observed karyotypic changes of a similar nature in the drug-treated cell lines established from micrometastases. These involved the detection of extra copies of chromosome 8. It is possible that exposure of tumors to therapeutic agents may in some cases increase their aggressiveness through genetic or epigenetic mechanisms that lead to high frequency heritable phenotypic alterations associated with distinguishable chromosomal changes.


Automatic detection of pulmonary embolism in CTA images.
Pulmonary embolism (PE) is a common life-threatening disorder for which an early diagnosis is desirable. We propose a new system for the automatic detection of PE in contrast-enhanced CT images. The system consists of candidate detection, feature computation and classification. Candidate detection focuses on the inclusion of PE--even complete occlusions--and the exclusion of false detections, such as tissue and parenchymal diseases. Feature computation does not only focus on the intensity, shape and size of an embolus, but also on locations and the shape of the pulmonary vascular tree. Several classifiers have been tested and the results show that the performance is optimized by using a bagged tree classifier with two features based on the shape of a blood vessel and the distance to the vessel boundary. The system was trained on 38 CT data sets. Evaluation on 19 other data sets showed that the system generalizes well. The sensitivity of our system on the evaluation data is 63% at 4.9 false positives per data set, which allowed the radiologist to improve the number of detected PE by 22%.


Acute urticaria: clinical aspects and therapeutic responsiveness.
Although acute urticaria is common, its eliciting factors, clinical course and therapeutic responsiveness have not been intensively investigated. We have therefore prospectively studied all patients with acute urticaria attending the department of dermatology (n = 72) and a rural dermatology office (n = 37) during the course of 1 year. After a standardized history and physical examination, patients were randomized into treatment with either loratadine (10 mg/day for 3 days) or prednisolene (50 mg/day for 3 days). All patients were followed up until complete remission. Most patients suffered from moderate (42%) to severe (40%) disease. Possible eliciting factors were identified in less than 50% of the cases. Associated upper respiratory tract infections were found most commonly (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and suspected food intolerance (0.9%). The course of the disease was self-limited in all cases, the longest episode lasting for 3 weeks. Both treatment regimens were effective in controlling whealing, but in corticosteroid-treated patients, symptoms ceased earlier, with complete remission occurring within 3 days of treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p < 0.001). Acute urticaria is thus frequently idiopathic and only rarely associated with IgE-mediated events. It is, however, largely self-limited, with prompt response to symptomatic treatment.


The use of conversation analysis to study social accessibility of an online support group on eating disorders.
We conducted a conversation analysis of 21 threads initiated by newcomers of an online support group (OSG) on eating disorders, to examine the discursive process of entering such a group. The analysis revealed three important issues. First, many newcomers articulate that the step to join the group is extremely difficult. Second, a presentation of the self in terms of a diagnosis works as a legitimization for joining the forum. The data suggest that participants who do not fulfil the conditions for such a legitimization do not join the forum. Third, the option of acquiring a serious symptom as a solution to the legitimization problem is offered by one of the regular members. Hence, the newcomers' discourse reveals issues relevant to the accessibility for undiagnosed sufferers. We discuss these findings theoretically as a phenomenon of self-presentation in relation to community norms. The analysis generates the hypothesis that newcomers are confronted with implicit norms regarding membership legitimacy that they should obey in their self-presentation, although they may not be ready yet to actually do so. OSGs should find strategies to facilitate various possibilities for newcomers to present themselves to the group while becoming a member.


[Gastric anisakiasis diagnosed with endoscopy].
Anisakiasis is a parasitic infestation, infrequent in Spain, due to ingestion of raw or underdone by Anisakis larvae. Also it can appear after consumption of smoked, salted or dried salt fish. The disease can show under different clinical forms, depending on the part of the gastrointestinal tract where the larva settles. We report two cases of anisakiasis diagnosed in Valladolid. Both patients were women that had eaten some days before anchovies marinated with vinegar. The diagnosis was made by endoscopic examination and the problem was solved by extraction of the parasite. It worthy to note that both cases appeared in a short time interval, showing perhaps some seasonal character. Finally some hygienic-dietetic measures are proposed for combating the disease.


The importance and impact of patients' health literacy on low back pain management: a systematic review of literature.
Health literacy (HL) and the overall ability of patients to seek, understand, and apply health information play an important role in the management of chronic pain conditions. Awareness of how patients' HL skills influence their pain experience and how their ability to understand the treatment regimen and to manage chronic pain may allow physicians to adjust clinical treatment accordingly. Despite the prevalence and the substantial economic impact of chronic low back pain (LBP), little is known about the relationship between HL and the treatment and management of this common disease entity. The purpose of this systematic review of published research was to examine the importance and the implications of HL in the treatment and management of LBP. A literature search was performed in Web of Science, PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsychInfo using medical subject heading (MeSH) terms related to LBP, HL, and patient education, which yielded only three studies that directly addressed HL among patients suffering from LBP. We identified only a limited number of studies that focused specifically on HL in the LBP population that were included in this review. The majority of studies excluded from this review focused on patient levels of educational attainment and patient education programs without addressing patients' HL levels and their impact on adherence to educational programs, self-care management, and rehabilitation, among other factors. The three studies that are critically reviewed in this review either use a direct measure of HL or make an effort to address HL in their programs. All three studies emphasize the importance of considering the HL of patients in the treatment and management of LBP. Building on these studies and the narrative review of other relevant literature, we identified significant gaps in current research addressing HL in the treatment and management of LBP. We developed recommendations for future research based on an assessment of strengths and limitations of available evidence-based studies.


Effect of soil properties on lead bioavailability and toxicity to earthworms.
Soil properties are important factors modifying metal bioavailability to ecological receptors. Twenty-one soils with a wide range of soil properties (USA; http://soils.usda.gov/technical/classification/taxonomy/) were amended with a single concentration of Pb (2,000 mg/kg) to determine the effects of soil properties on Pb bioavailability and toxicity to earthworms. Earthworm mortality ranged from 0 to 100% acute mortality following exposure to the same total concentration of Pb (2,000 mg/kg) in amended field soils. Internal Pb concentrations in earthworms ranged from 28.7 to 782 mg/kg, with a mean of 271 mg/kg. Path analysis was used to partition correlations in an attempt to discern the relative contribution of each soil property. Results of path analysis indicated that pH was the most important soil property affecting earthworm mortality (p < 0.01) and internal Pb (p < 0.05). Soil pH was related inversely to mortality and internal Pb, soil solution Pb, and Pb bioavailability. The most important soil property modifying reproduction was amorphous iron and aluminum oxides (FEAL). Because FEAL is rich in pH-dependent cation-exchange sites, several soil properties, including pH, FEAL, and cation-exchange capacity, have a causal effect on Pb adsorption and soluble Pb. Path analysis is useful for assessing contaminated soils with a wide range of soil properties and can assist in ecological risk assessment and remediation decisions for contaminated sites. Soil properties are important factors modifying metal bioavailability and toxicity and should be considered during the ecological risk assessment of metals in contaminated soils.


Googling Service Boundaries for Endovascular Clot Retrieval Hub Hospitals in a Metropolitan Setting: Proof-of-Concept Study.
There is great interest in how endovascular clot retrieval hubs provide services to a population. We applied a computational method to objectively generate service boundaries for such endovascular clot retrieval hubs, defined by traveling time to hub. Stroke incidence data merged with population census to estimate numbers of stroke in metropolitan Melbourne, Australia. Traveling time from randomly generated addresses to 4 endovascular clot retrieval-capable hubs (Royal Melbourne Hospital [RMH], Monash Medical Center [MMC], Alfred Hospital [ALF], and Austin Hospital [AUS]) estimated using Google Map application program interface. Boundary maps generated based on traveling time at various times of day for combinations of hubs. In a 2-hub model, catchment was best distributed when RMH was paired with MMC (model 1a, RMH 1765 km2 and MMC 1164 km2) or with AUS (model 1c, RMH 1244 km2 and AUS 1685 km2), with no statistical difference between models (P=0.20). Catchment was poorly distributed when RMH was paired with ALF (model 1b, RMH 2252 km2 and ALF 676 km2), significantly different from both models 1a and 1c (both P<0.05). Model 1a had the greatest proportion of patients arriving within ideal time of 30 minutes followed by model 1c (P<0.001). In a 3-hub model, the combination of RMH, MMC, and AUS was superior to that of RMH, MMC, and ALF in catchment distribution and travel time. The method was also successfully applied to the city of Adelaide demonstrating wider applicability. We provide proof of concept for a novel computational method to objectively designate service boundaries for endovascular clot retrieval hubs.


Steering the Clinical Translation of Delivery Systems for Drugs and Health Products.
Besides the feasibility for industrial scale-up, accelerating the translation from bench to bedside of new technological strategies for controlled delivery and targeting of drugs and other actives relevant for health management, such as medical devices and nutraceuticals, would benefit from an even earlier evaluation in pre-clinical models and clinical settings. At the same time, translational medicine also performs in the opposite direction, incorporating clinical needs and observations into scientific hypotheses and innovative technological proposals. With these aims, the sessions proposed for the 2019 CRS Italy Chapter Workshop will introduce the experience of Italian and worldwide researchers on how to foster the actual work in controlled release and drug delivery towards a reliable pre-clinical and clinical assessment.


PLCE1 Polymorphisms Are Associated With Gastric Cancer Risk: The Changes in Protein Spatial Structure May Play a Potential Role.
Gastric cancer (GC) is one of the most significant health problems worldwide. Some studies have reported associations between Phospholipase C epsilon 1 (PLCE1) single-nucleotide polymorphisms (SNPs) and GC susceptibility, but its relationship with GC prognosis lacked exploration, and the specific mechanisms were not elaborated fully yet. This study aimed to further explore the possible mechanism of the association between PLCE1 polymorphisms and GC. A case-control study, including 588 GC patients and 703 healthy controls among the Chinese Han population, was performed to investigate the association between SNPs of PLCE1 and GC risk by logistic regression in multiple genetic models. The prognostic value of PLCE1 in GC was evaluated by the Kaplan-Meier plotter. To explored the potential functions of PLCE1, various bioinformatics analyses were conducted. Furthermore, we also constructed the spatial structure of PLCE1 protein using the homology modeling method to analyze its mutations. Rs3765524 C > T, rs2274223 A > G and rs3781264 T > C in PLCE1 were associated with the increased risk of GC. The overall survival and progression-free survival of patients with high expression of PLCE1 were significantly lower than those with low expression [HR (95% CI) = 1.38 (1.1-1.63), P < 0.01; HR (95% CI) = 1.4 (1.07-1.84), P = 0.01]. Bioinformatic analysis revealed that PLCE1 was associated with protein phosphorylation and played a crucial role in the calcium signal pathway. Two important functional domains, catalytic binding pocket and calcium ion binding pocket, were found by homology modeling of PLCE1 protein; rs3765524 polymorphism could change the efficiency of the former, and rs2274223 polymorphism affected the activity of the latter, which may together play a potentially significant role in the tumorigenesis and prognosis of GC. Patients with high expression of PLCE1 had a poor prognosis in GC, and SNPs in PLCE1 were associated with GC risk, which might be related to the changes in spatial structure of the protein, especially the variation of the efficiency of PLCE1 in the calcium signal pathway.


Kinetic spectrophotometric determination of ciprofloxacin in a pharmaceutical preparation.
Two kinetic spectrophotometric methods were developed for determination of ciprofloxacin (CIP) in a pharmaceutical preparation. The methods are based on oxidation of CIP with potassium permanganate in alkaline media and measurement of the enhancement in the absorbance of manganate ion at 603 nm by spectrophotometry. The calibration graphs were constructed using the initial rate and fixed time methods. The linearity range for concentrations of CIP was found to be 4.0-20.0 microg/mL. The RSD values for intraday and interday precision were 0.05-0.50 and 0.07-0.63%, respectively. The procedures were applied successfully for determination of CIP in commercial tablets. The results compared well with those from a reference HPLC method. The proposed methods can be recommended for routine analysis of CIP in QC laboratories.


Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults.
Autism spectrum (ASD) and attention deficit/hyperactivity disorders (ADHD) share genetic, neurological, and behavioural features. However, related research in Asia is limited. We collected self-reported ASD and ADHD symptoms from 2186 Hong Kong adolescents and young adults aged 15-24 years, among whom, 1200 provided 1-year data on mental health-related outcomes. Comparative and network analyses were performed. Rating scale cutoff scores were used to divide participants into ASD, ADHD, comorbid, and control groups. The prevalence rates of ASD, ADHD, and comorbidities in Hong Kong were 13.3 %, 10.6 %, and 2.7 %, respectively. Compared with the control group, the comorbid group experienced more psychotic-like experiences (PLEs), the ASD group had poorer functioning, and the ADHD group had higher depression and anxiety symptoms and a lower quality of life after 1 year. The ability to switch attention, preference for routines and difficulty with change, and problems with organisation and planning were positively associated with depressive symptoms, forgetfulness and working memory issues with anxiety symptoms, and heightened sensory input and difficulties in sustaining attention and task completion with PLEs after 1 year. Our findings provide insight into support strategies to address the needs of young Asians to improving their well-being and long-term outcomes.


Rituximab treatment for persistent scleritis associated with rheumatoid arthritis.
To report a clinical case of a patient with severe scleritis associated with rheumatoid arthritis (RA) refractive to conventional treatment that was treated effectively with rituximab. A 55-year-old man with RA, on etanercept and oral methotrexate, was referred with diagnosis of acute stromal keratitis, anterior uveitis, and anterior nodular scleritis in his right eye. Cyclophosphamide induced complete regression of acute stromal keratitis and anterior uveitis, but scleritis was still active and persistent. After two 1000-mg infusions of rituximab, scleritis regressed completely and is still in remission 9 months after the second rituximab infusion, without any concomitant use of oral steroids. Rituximab may be a treatment alternative in severe scleritis that is refractive to conventional therapy. Considering its safety profile, further studies are needed to refine its mechanism of action, optimal indications, and dosing in ocular inflammation.


A systematic evaluation of ADHD and comorbid psychopathology in a population-based twin sample.
Clinical and population samples demonstrate that attention-deficit/hyperactivity disorder (ADHD) occurs with other disorders. Comorbid disorder clustering within ADHD subtypes is not well studied. Latent class analysis (LCA) examined the co-occurrence of DSM-IV ADHD, oppositional defiant disorder (ODD), conduct disorder (CD), and depression symptoms in a population twin sample. The authors fit separate models for ADHD and comorbid disorder symptoms. Twin concordance ratios (monozygotic versus dizygotic) were compared examining genetic influence on class membership. LCA of ADHD symptoms resulted in seven classes including inattentive, combined, and hyperactive subtypes in 1,616 subjects. The few ADHD symptoms (53.4%) and severe inattentive (12.3%) classes were most frequent. LCA of ODD, CD, and depression symptoms in 1,587 subjects revealed five classes including ODD (19.4%), depression (14.5%), and two composite classes: ODD/CD (6.9%) and ODD/CD/depression (7.2%). Internalizing and externalizing comorbid disorders were present across all ADHD subtypes. Odds ratios (ORs) for twin concordance indicate genetic influence on severe inattentive (OR = 4.18; 95% confidence interval [CI], 1.52-11.53) and combined (OR = 5.25; 95% CI, 1.32-20.78) ADHD classes and ODD (OR = 1.49; 95% CI, 0.70-3.17), ODD/CD (OR = 3.32; 95% CI, 0.57-19.28), and ODD/CD/depression (OR = 1.20; 95% CI, 0.30-4.77) classes. Internalizing and externalizing disorders did not cluster differentially within ADHD subtypes. LCA may provide a more precise characterization of comorbidity with ADHD.


Asexual evolution: do intragenomic parasites maintain sex?
Resolving the paradox of sex, with its twofold cost to genic transmission, remains one of the major unresolved questions in evolutionary biology. Counting this genetic cost has now gone genomic. In this issue of Molecular Ecology, Kraaijeveld et al. (2012) describe the first genome-scale comparative study of related sexual and asexual animal lineages, to test the hypothesis that asexuals bear heavier loads of deleterious transposable elements. A much higher density of such parasites might be expected, due to the inability of asexual lineages to purge transposons via mechanisms exclusive to sexual reproduction. They find that the answer is yes--and no--depending upon the family of transposons considered. Like many such advances in testing theory, more questions are raised by this study than answered, but a door has been opened to molecular evolutionary analyses of how responses to selection from intragenomic parasites might mediate the costs of sex.


Comparison between sensitivities of phase and intensity detection in surface plasmon resonance.
We have experimentally and theoretically compared intensity and phase measurements of surface plasmon resonance, in order to check the widely claimed superiority of the phase method. Both experiment and theory show a slightly higher sensitivity for intensity detection. Simulations confirm that this result is generally true for a wide range of resonance conditions. The basic reason is that phase measurements must be performed by measuring light intensities in some way, and therefore both modes of operation are limited in similar ways by photon statistics. Sensitivity can only be improved by using larger light intensities.


An International Survey of Glucose-6-Phosphate Dehydrogenase Laboratory Reporting Practices: Implications for Tafenoquine Eligibility Assessment.
Glucose-6-phosphate dehydrogenase (G6PD) activity is used in the evaluation of hemolysis risk in patients being assessed for G6PD deficiency. A long-acting 8-aminoquinoline drug (tafenoquine) used in malaria treatment is contraindicated in patients with G6PD deficiency (<70% normal G6PD activity). The current state of G6PD reporting practices to support clinical eligibility assessment is poorly understood. To assess clinical laboratory reporting practices for G6PD testing. In October 2019 and October 2020, voluntary questionnaires were distributed to 327 and 324 laboratories participating in the College of American Pathologists G6PD proficiency testing (PT). Two hundred fifty-seven and 119 laboratories responded to the 2019 and 2020 questionnaires, respectively. Few laboratories have received clinical questions about average normal G6PD activity (US/Canada, 2.0% [3 of 149]; international, 8.4% [9 of 107]), whereas slightly more have determined the average normal G6PD activity for their own assay and patient populations (US/Canada, 6.7% [10 of 149]; international, 19.4% [21 of 108]). Few laboratories report G6PD activity in percent of normal format (US/Canada, 2.7% [4 of 149]; international, 8.3% [9 of 108]). The most common unit of measurement in use for quantitative G6PD reporting is unit per gram of hemoglobin. Reference intervals vary based on assay, reaction temperature, and participant laboratory and demonstrate moderate correlation (r = .46-.51) to G6PD activity measured from a "normal" PT challenge specimen. Nearly half of participants (47.8% [85 of 178]) categorized a quantitatively "intermediate" G6PD PT challenge as "normal" when using qualitative assays. Percent of normal G6PD activity reporting would facilitate patient eligibility assessment for drugs, such as tafenoquine. Quantitative assays are better able to differentiate "intermediate" specimens than qualitative assays.


What should my hospital buy next?-Guidelines for the acquisition and application of imaging, navigation, and robotics for spine surgery.
The range of assistive technology options available for spinal fusion surgery has significantly increased. However, surgeons and hospital administrators may lack sufficient information to compare options and make purchasing decisions. We summarize currently available navigation, robotics, and imaging technologies for spinal surgery, highlighting key characteristics, utility, differences, price, and compatibility with other technologies and spinal implants. Guidelines for optimal use and combinations are provided based on surgical approach, operative site, patient anatomy, optimal image quality, and workflow efficiency. Key recommendations include the following. (I) Open-platform navigation and robotics systems that provide surgeons with access to all software and hardware features regardless of implant choice are preferred. (II) Imaging systems that have maximum compatibility with navigation and robotics platforms are optimal. (III) Navigation systems that offer a universal registration mechanism should be standard. (IV) 3D fluoroscopy provides the greatest benefit when speed, operative efficiency, and mobility are required. (V) Intraoperative CT is more useful for imaging long constructs, high BMI, or cervicothoracic anatomy. (VI) Radiation safety awareness that new 3D-fluoroscopy units can deliver radiation comparable to that of CT is needed. (VII) New robotic arm platforms require more clinical and health economic data to justify increased costs.


Respiratory diseases among union carpenters: cohort and case-control analyses.
Lung diseases, defined by ICD-9 diagnoses on medical insurance claims, were studied through the combined use of administrative records, private health insurance, and workers' compensation claims for a cohort of 10,938 active union carpenters between 1989 and 1992. The cohort defined the study base for a nested case-control study, in which cases (n = 220) were initially identified by an ICD-9 code for asthma in private health insurance or workers' compensation files. A questionnaire was used to collect information on respiratory history and potential home and workplace exposures. Questions used by Burney et al. to define a discriminant function predictor (DFP) of a bronchial response to histamine were used to reclassify cases and controls for further exploratory analyses. Bronchitis accounted for over 50% of the lung disease cases among this cohort followed by asthma, chronic obstructive airway disease, and chronic bronchitis. Incidence density rates of asthma, chronic bronchitis, and chronic obstructive airway disease adjusted for age, sex, and time in the union increased with increasing age. Using Surveillance, Epidemiology, and End Results (SEER) Program data to estimate expected lung cancer cases in our cohort, an elevated standardized incidence rate (SIR) was seen among male carpenters between the ages of 45-54. Smoking history was not available for the entire cohort. Using the ICD-9 or Burney case definition of asthma, odds ratios were significantly elevated for exposure to hay, epoxy paints, enzymes, animals, and molds. Additional exposures associated with asthma using Burney's definition, are ones to which a majority of these carpenters were exposed including cement, drywall, and demolition dusts.


Microencapsulated lysine and low-protein diets: effects on performance, carcass characteristics and nitrogen excretion in heavy growing-finishing pigs.
Two studies were conducted to assess the effects of dietary protein and Lys reduction on growth performance, carcass quality, N excretion, and plasma N profile in growing-finishing pigs from 35 to 180 kg. The growing trial was conducted with 72 gilts and 72 barrows with 6 pens per treatment and 6 gilts or 6 barrows per pen. Four diets with the same DE and NE were compared: 1) control diet, 2) diet with protein content reduced by 3% units compared with the control diet and supplemented with Lys HCl to match the requirements according to the 2012 NRC (FLys), 3) diet similar to FLys for protein level but supplemented with only 50% of the Lys HCl provided with FLys (-50% FLys), and 4) diet similar to FLys and -50% Flys for protein level with microencapsulated Lys added to supply 20% of the Lys provided by FLys (-80% MLys). Pigs fed the FLys diet performed in a similar manner and showed similar carcass characteristics to the control pigs. Pigs fed the -50% FLys diet had the lightest BW (P < 0.01) as well as the lightest carcass (P = 0.02) and trimmed thigh (P = 0.04) weights. Pigs fed the -80% MLys diet showed growth performance and carcass characteristics similar to the control pigs. The N balance study was conducted with 8 barrows arranged in a double replicated 4 × 4 Latin square design. The control pigs had greater (P < 0.01) N intake and urinary and total N excretion compared with pigs fed the low-protein diets. The reduction of the dietary protein concentration by 3% units decreased total N excretion by an average of 24.5% and the greatest reduction of total N excretion was obtained by the -80% MLys diet (26.12%) compared with the control diet throughout the trial. No effect of dietary treatment was observed on the plasma concentrations of ammonia, urea, and total AA in the 80-kg pigs. Decreased plasma ammonia (P < 0.01) and urea (P = 0.03) concentrations were detected in the 120-kg pigs fed the low-protein diets. The 160-kg pigs fed the -80% MLys pigs had less total AA, indispensable AA in particular (P < 0.01), than pigs fed the other diets and decreased ammonia (P < 0.01) and urea (P = 0.05) concentrations than the control pigs. The results showed that the use of microencapsulated Lys, compared with both Lys HCl and dietary protein-bound Lys, can save CP and synthetic AA in diet formulation and can reduce N excretion in manure without adversely affecting the growth performance and carcass quality of heavy growing-finishing pigs.


Using Network Analysis to Identify Central Symptoms of Adolescent Depression.
Experiencing depression symptoms, even at mild to moderate levels, is associated with maladaptive outcomes for adolescents. We used network analysis to evaluate which symptoms (and associations between symptoms) are most central to adolescent depression. Participants were part of a large, diverse community sample (N = 1,409) of adolescents between 13 and 19 years of age. Network analysis was used to identify the most central symptoms (nodes) and associations between symptoms (edges) assessed by the Children's Depression Inventory. We also evaluated these centrality indicators for network robustness using stability and accuracy tests, associated symptom centrality with mean levels of symptoms, and examined potential differences between the structure and connectivity of depression networks in boys and girls. The most central symptoms in the network were self-hatred, loneliness, sadness, and pessimism. The strongest associations between symptoms were sadness-crying, anhedonia-school dislike, sadness-loneliness, school work difficulty-school performance decrement, self-hatred-negative body image, sleep disturbance-fatigue, and self-deprecation-self-blame. The network was robust to stability and accuracy tests. Notably, symptom centrality and mean levels of symptoms were not associated. Boys and girls' networks did not differ in levels of connectivity, though the link between body image and self-hatred was stronger in girls than boys. Self-hatred, loneliness, sadness, and pessimism were the most central symptoms in adolescent depression networks, suggesting that these symptoms (and associations between symptoms) should be prioritized in theoretical models of adolescent depression and could also serve as important treatment targets for adolescent depression interventions.


Changes in the beta-adrenergic system due to beta-adrenergic therapy: clinical consequences.
Continued exposure to a hormonal agonist often leads to a blunted response to that agonist. This process has been termed desensitization, refractoriness, tolerance or tachyphylaxis. Continued exposure to beta-adrenergic therapy has been shown to reduce the beta-adrenergic response of white blood cells as well as the number of beta-adrenergic binding places on those cells. Since white blood cells possess a great number of beta 2-adrenergic receptors, these findings seem to argue against the continuous use of beta-agonists as prophylactic and therapeutic therapy in asthmatic patients. However, lung function measurements in these asthmatic patients have not provided hard evidence for desensitization. In this paper, a review of the discrepancy between the findings on white blood cells and lung function measurements during continuous beta-adrenergic therapy is given and the possible clinical consequences are considered.


Effect of conditioner and moisture content on flowability of yellow cornmeal.
Flow characterization of ground materials based on standard physical properties is not always accurate and must be complemented with other properties that help characterize their flowability. The flow properties of yellow cornmeal as a function of moisture content (10.0%, 13.5% 17.0%, and 20.0% wet basis) and concentrations of added conditioner (calcium stearate, a caking agent classified at GRAS, at 0.50%, 0.75%, and 1.00% wt/wt) were measured. The optimum flow behavior characteristics of the cornmeal were achieved at 0.50% wt/wt calcium stearate and 10.0% (w.b.) moisture content based on the flow function test. Overall, the material's flowability decreased with increased moisture content based on very high values for Hausner's ratio, Carr's Index, and angle of repose. The flow index (ffc) obtained by the flow function test decreased from 6.47 to 3.82 as moisture increased, indicating increased cohesivity. Calcium stearate increased the flowability of the material at 0.50% wt/wt, beyond which the flowability was not affected (p > .05). Samples were very hygroscopic and classified as Class IV. The Hausner's ratio, Carr's Index, and angle of repose showed a strong linear relationship with the flow index with correlation values of 0.91, 0.88, and 0.88, respectively. Isotherms together with physical properties should be used to determine the flow characteristics of granulated materials such as yellow cornmeal to establish the best storage and processing conditions.


Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats.
Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats' brains when compared against control rats (P < 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P < 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats' cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.


Norsesquiterpenes from the Latex of Euphorbia dentata and Their Chemical Defense Mechanisms against Helicoverpa armigera.
Euphorbia dentata (Euphorbiaceae), an invasive weed, is rarely eaten by herbivorous insects and could secrete a large amount of white latex, causing a serious threat to local natural vegetation, agricultural production and human health. In order to prevent this plant from causing more negative effects on humans, it is necessary to understand and utilize the chemical relationships between the latex of E. dentata and herbivorous insects. In this study, three new norsesquiterpenes (1-3), together with seven known analogues (4-10), were isolated and identified from the latex of E. dentata. All norsesquiterpenes (1-10) showed antifeedant and growth-inhibitory effects on H. armigera with varying levels, especially compounds 1 and 2. In addition, the action mechanisms of active compounds (1-3) were revealed by detoxifying enzyme (AchE, CarE, GST and MFO) activities and corresponding molecular docking analyses. Our findings provide a new idea for the development and utilization of the latex of E. dentata, as well as a potential application of norsesquiterpenes in botanical insecticides.


Predicting factors of patient satisfaction after varicose vein surgery at a university hospital in Nepal.
Varicose veins are a common vascular problem with a high prevalence, yet they are often neglected. The main objective of this study was to explore the patient satisfaction after varicose vein surgery, along with its predicting factors. To our knowledge, no similar study has been conducted in Nepal to date. This retrospective cross-sectional study included patients who underwent varicose vein surgery at Dhulikhel Hospital from September 2019 to February 2020. The satisfaction level after the surgery was assessed using a 10-point Likert scale questionnaire during a telephone interview with their verbal consent. Descriptive statistics and linear regression were performed to identify the predicting factors of patient satisfaction. Among a total of 84 patients interviewed, 53.6% were male. The mean age of the participants was 43.13 ± 13.62 years. The mean patient satisfaction score was 42 ± 5.5, with nursing service, discharge teaching and hospital service being the highest scoring items in terms of patient satisfaction. Linear regression revealed age ≤40 years as a predictor of higher patient satisfaction (β=0.258, p=0.015) while early stage of varicose veins (β=-0.233, p=0.026) and duration of post-operative follow-up (β=-0.25, p=0.021) were negative predictors of patient satisfaction. This means that patients with C2-C3 venous disease and longer duration of postoperative follow-up tended to have lower satisfaction scores. The overall patient satisfaction following varicose vein surgery was very good, and the major predictors of better satisfaction were age ≤40 years, C4-C6 clinical classification of venous disease and the shorter duration of follow-up after surgery.


Use of ketoconazole in the treatment of Cushing's syndrome.
The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period. Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another. The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.


An exported kinase family mediates species-specific erythrocyte remodelling and virulence in human malaria.
The most severe form of human malaria is caused by Plasmodium falciparum. Its virulence is closely linked to the increase in rigidity of infected erythrocytes and their adhesion to endothelial receptors, obstructing blood flow to vital organs. Unlike other human-infecting Plasmodium species, P. falciparum exports a family of 18 FIKK serine/threonine kinases into the host cell, suggesting that phosphorylation may modulate erythrocyte modifications. We reveal substantial species-specific phosphorylation of erythrocyte proteins by P. falciparum but not by Plasmodium knowlesi, which does not export FIKK kinases. By conditionally deleting all FIKK kinases combined with large-scale quantitative phosphoproteomics we identified unique phosphorylation fingerprints for each kinase, including phosphosites on parasite virulence factors and host erythrocyte proteins. Despite their non-overlapping target sites, a network analysis revealed that some FIKKs may act in the same pathways. Only the deletion of the non-exported kinase FIKK8 resulted in reduced parasite growth, suggesting the exported FIKKs may instead support functions important for survival in the host. We show that one kinase, FIKK4.1, mediates both rigidification of the erythrocyte cytoskeleton and trafficking of the adhesin and key virulence factor PfEMP1 to the host cell surface. This establishes the FIKK family as important drivers of parasite evolution and malaria pathology.


Persistent absence of ring-enhancement on CT with an encapsulated brain abscess.
Ring-enhancement on CT (RECT) is generally considered a sine qua non in diagnosing a cerebral abscess. We describe a 16-year-old female who presented with headaches, vomiting and drowsiness, which over 2 weeks rapidly progressed to coma. CT demonstrated a moderately large left frontal extradural abscess, associated with contiguous left frontal osteomyelitis, and underlying frontal and ethmoidal sinusitis. In addition, there was a large circular low density area within the left frontal lobe associated with midline shift that, owing to negative RECT, was assumed to represent nascent ischaemic cerebritis. Despite emergency twist-drill drainage of the extradural abscess, and antibiotic/corticosteroids administration, her clinical condition continued to deteriorate and two episodes of uncal herniation were reversed medically. Repeated CT, however, continued to demonstrate negative enhancement within the left frontal low density, although significant enhancement continued to be apparent with recurrent contiguous extradural suppuration. At definitive craniotomy, a large, well-encapsulated abscess cavity was excised from the left frontal lobe corresponding precisely to the area of previously negative enhancement, along with drainage of the recurrent extradural abscess. Thus, in addition to well-known 'false-positives' for RECT with a cerebral abscess, our case highlights the rare occurrence of a 'false-negative'. A low density mass lesion on CT with persistent negative RECT can neither be assumed to represent early cerebritis nor to exclude a mature abscess.


In vivo and vitro studies on formation of bile acids in patients with Zellweger syndrome. Evidence that peroxisomes are of importance in the normal biosynthesis of both cholic and chenodeoxycholic acid.
The last step in bile acid formation involves conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid (THCA) into cholic acid and 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) into chenodeoxycholic acid. The peroxisomal fraction of rat and human liver has the highest capacity to catalyze these reactions. Infants with Zellweger syndrome lack liver peroxisomes, and accumulate 5 beta-cholestanoic acids in bile and serum. We recently showed that such an infant had reduced capacity to convert a cholic acid precursor, 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol into cholic acid. 7 alpha-Hydroxy-4-cholesten-3-one is a common precursor for both cholic acid and chenodeoxycholic acid. Intravenous administration of [3H]7 alpha-hydroxy-4-cholesten-3-one to an infant with Zellweger syndrome led to a rapid incorporation of 3H into biliary THCA but only 10% of 3H was incorporated into cholic acid after 48 h. The incorporation of 3H into DHCA was only 25% of that into THCA and the incorporation into chenodeoxycholic acid approximately 50% of that in cholic acid. The conversion of intravenously administered [3H]THCA into cholic acid in another infant with Zellweger syndrome was only 7%. There was a slow conversion of THCA into 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-C29-dicarboxylic acid. The pool size of both cholic- and chenodeoxycholic acid was markedly reduced. Preparations of liver from two patients with Zellweger syndrome had no capacity to catalyze conversion of THCA into cholic acid. There was, however, a small conversion of DHCA into chenodeoxycholic acid and into THCA. It is concluded that liver peroxisomes are important both for the conversion of THCA into cholic acid and DHCA into chenodeoxycholic acid.


Blood Pressure Management for Acute Ischemic and Hemorrhagic Stroke: The Evidence.
Hypertension is the most common modifiable risk factor for stroke (both ischemic and hemorrhagic types). In the hyperacute phase, a majority of patients shows an elevated blood pressure (BP) at the time of presentation because of sympathetic hyperactivity or a physiological response to tissue ischemia. Therefore, BP may decrease spontaneously in a few hours and may drop further when complete recanalization is achieved. In stroke guidelines, an elevated BP is usually left untreated up to a systolic BP (SBP) of 220 mm Hg and a diastolic BP of 120 mm Hg. This recommendation is based on the BP level that corresponds to the upper limit of the pressure autoregulation zone above which cerebral blood flow is directly dependent on BP. However, in patients in whom administration of recombinant tissue-type plasminogen activator is indicated, BP should be controlled to a level < 185/110 mm Hg before infusion and should be maintained at levels < 180/105 mm Hg to limit the risk of intracerebral hemorrhage (ICH). In cases where endovascular thrombectomy is considered, the optimal intra- and postprocedural BP target have not yet been clearly identified. Expert opinion recommends that intraprocedural BP reduction could be associated with a risk of poor outcomes, and therefore, SBP may be reduced only to 120 to 140 mm Hg after successful reperfusion therapy. However, this recommendation is primarily based on observational studies and requires validation in prospective trials. It has been observed that in patients presenting with an ICH, there is no perihematomal penumbra noted and rapid BP reduction is generally well tolerated without a risk of neurological worsening. Multiple trials describing acute reduction of BP recommend SBP reduction only to 140 mm Hg because while there is no benefit of better functional outcomes below that level, there exists a definite risk of increased renal complications.


Aggressor and victim perspective-related differences in perceived legitimacy of aggression in soccer.
The purpose of this role-playing study was to explore the perceived legitimacy of aggression in soccer as a function of perspective-related differences (aggressor vs victim) and type of aggression (instrumental vs hostile). 120 soccer players watched videotaped aggressive interactions in soccer and took the perspective of the actors (aggressor then victim or the reverse). Then they rated the legitimacy of each aggressive behavior depending on its ultimate goal (instrumental then hostile or the reverse). When participants adopted the aggressor perspective, they perceived instrumental aggression as more legitimate than hostile aggression. In contrast, when participants took the perspective of the victim, no significant difference was found regardless of the type of aggression. The discussion focussed on implications and consequences of such divergences in aggressive sport situations.


Outcomes of mini-hypoglossal nerve transfer and direct muscle neurotization for restoration of lower lip function in facial palsy.
Most reconstructions for lower lip palsy focus on paralyzing the contralateral normal lip or providing static support on the affected side. The authors' unit has reported dynamic strategies for lower lip reanimation and use of 40 percent of the hypoglossal nerve (mini-hypoglossal) in facial reanimation. They report their experience with mini-hypoglossal nerve transfer for lower lip palsy. Between 1987 and 2005, 29 patients with unilateral facial palsy had lower lip reanimation with the mini-hypoglossal as the motor donor. Twenty patients had transfer of the mini-hypoglossal to the cervicofacial branch of the facial nerve and nine had direct depressor muscle neurotization. Five patients had a mean denervation time of 14.60 +/- 4.50 months (<2 years), and the rest had a mean denervation time of 10.63 +/- 9.23 years. In late cases, the facial nerve was in-continuity, and preoperative needle electromyographs of depressors showed at least fibrillations. Standardized videos taken preoperatively and at 2 years postoperatively were available for 27 patients and assessed by three independent reviewers. Needle electromyographic results were analyzed. Thirteen patients (48.15 percent) achieved excellent and good results, nine (33.33 percent) had moderate results, and five (18.52 percent) obtained fair results. The difference between the averaged preoperative and postoperative scores was statistically significant, as was the difference in electromyographic outcomes (p < 0.0001, Wilcoxon signed rank test). The nerve transfer and direct neurotization groups had no statistically significant difference in clinical and electromyographic outcomes. Four patients required muscle transfer for further outcome upgrading. Use of the mini-hypoglossal either for nerve transfer or for direct muscle neurotization of lower lip depressors can provide reinnervation and satisfactory clinical function, even for muscles with prolonged partial denervation.


The Patient Centered Assessment Method (PCAM): integrating the social dimensions of health into primary care.
Social dimensions of health are known to contribute to what is often termed "patient complexity," which is particularly common among patients with multimorbidity. Health-care professionals require tools to help them identify and manage these aspects of patient needs. To examine: (i) the Patient Centered Assessment Method (PCAM), a tool for assessing patient complexity in ways that are sensitive to the biopsychosocial dimensions of health, in primary care settings in Scotland; (ii) the impact of the PCAM on referral patterns and its perceived value; and (iii) the PCAM's perceived applicability for use in a complex patient population. Two studies are described: (i) a mixed-methods prospective cohort study of the implementation of the PCAM in primary care clinics; and (ii) a qualitative exploratory study that evaluated the value of the PCAM in a complex patient population. Use of the PCAM did not impact patient satisfaction or perception of practitioners' empathy, but it did increase both the number of onward referrals per referred patient (9-12%) and the proportion of referrals to non-medical services addressing psychological, social, and lifestyle needs. Nurses valued the PCAM, particularly its ability to help them address psychological and social domains of patients' lives, and found it to be highly relevant for use in populations with known high complexity. The PCAM represents a feasible approach for assessing patient needs with consideration to the social dimensions of health, and allows practitioners to refer patients to a broader range of services to address patient complexity.


Porous polyvinyl fluoride coated cellulose beads for efficient removal of Cd(II) from phosphoric acid.
In order to enhance the removal of cadmium from phosphoric acid, it is imperative to explore novel resources that may be utilized for the development of highly effective and environmentally sustainable adsorbents. Cellulose beads are composed of naturally occurring polysaccharide fibers and find extensive utilization across several industrial sectors and applications. Within this framework, this research paper presents a green and simple method for producing porous cellulose beads using date palm fibers as the preferred raw material. The innovation lies in immersing the obtained cellulose beads in a Polyvinyl fluoride (PVDF)/N,N-dimethylformamide (DMF) suspension as a coating polymer with different concentrations (2.5, 5, 10 %) to maintain their stability in an acidic environment. The surface of cellulose/PVDF beads were subjected to multiple characterizations like Fourier transform infrared (FTIR) spectroscopy, Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA), size distribution then pH stability confirming that the coating has been perfectly achieved and conserved well the shape of the beads. The coated cellulose/PVDF-2.5 % underwent evaluation by the process of batch adsorption experiments while different parameters were varied including contact time (5, 10, 20, 30, 60, 90 min), temperature (25, 35, 45 and 55 °C), and adsorbent mass (20, 40, 60, 80 and 100 mg). The obtained ICP data showed that the adsorption rate of Cd (II) from phosphoric acid medium decreased while increasing both temperature from 25 to 55 °C and contact time from 5 to 90 min while adding more adsorbent dosage from 20 to 100 mg enhanced the removal percentage. The cellulose/PVDF-2.5 % was more effective with an adsorption capacity equal to 3.4998 mg/g at optimal conditions including 25 °C as the temperature after 5 min as contact time and by adding a mass 100 mg of the biosorbent while the pH = 2 of the solution is maintained the same. The examined material's adsorption processes proved to be exothermic and non-spontaneous, and it proved that the pseudo-second-order model provided the best match for the cellulose/PVDF-2.5 % beads kinetics data. Furthermore, the cellulose beads exhibited exceptional reusability for up to four repeated cycles without undergoing desorption. The present study offers a viable approach for producing environmentally sustainable biomass-derived adsorbents. Additionally, the study validates the potential of cellulose/PVDF beads as an intriguing material for phosphoric acid decadmiation.


An operational definition of a statistically meaningful trend.
Linear trend analysis of time series is standard procedure in many scientific disciplines. If the number of data is large, a trend may be statistically significant even if data are scattered far from the trend line. This study introduces and tests a quality criterion for time trends referred to as statistical meaningfulness, which is a stricter quality criterion for trends than high statistical significance. The time series is divided into intervals and interval mean values are calculated. Thereafter, r(2) and p values are calculated from regressions concerning time and interval mean values. If r(2) ≥ 0.65 at p ≤ 0.05 in any of these regressions, then the trend is regarded as statistically meaningful. Out of ten investigated time series from different scientific disciplines, five displayed statistically meaningful trends. A Microsoft Excel application (add-in) was developed which can perform statistical meaningfulness tests and which may increase the operationality of the test. The presented method for distinguishing statistically meaningful trends should be reasonably uncomplicated for researchers with basic statistics skills and may thus be useful for determining which trends are worth analysing further, for instance with respect to causal factors. The method can also be used for determining which segments of a time trend may be particularly worthwhile to focus on.


Apoptotic Body-Rich Media from Tenocytes Enhance Proliferation and Migration of Tenocytes and Bone Marrow Stromal Cells.
The intrinsic healing following tendon injury is ideal, in which tendon progenitor cells proliferate and migrate to the injury site to directly bridge or regenerate tendon tissue. However, the mechanism determining why and how those cells are attracted to the injury site for tendon healing is not understood. Since the tenocytes near the injury site go through apoptosis or necrosis following injury, we hypothesized that secretions from injured tenocytes might have biological effects on cell proliferation and migration to enhance tendon healing. Tenocyte apoptosis was induced by 24 h cell starvation. Apoptotic body-rich media (T-ABRM) and apoptotic body-depleted media (T-ABDM) were collected from culture media after centrifuging. Tenocytes and bone marrow-derived stem cells (BMDSCs) were isolated and cultured with the following four media: (1) T-ABRM, (2) T-ABDM, (3) GDF-5, or (4) basal medium with 2% fetal calf serum (FCS). The cell activities and functions were evaluated. Both T-ABRM and T-ABDM treatments significantly stimulated the cell proliferation, migration, and extracellular matrix synthesis for both tenocytes and BMDSCs compared to the control groups (GDF-5 and basal medium). However, cell proliferation, migration, and extracellular matrix production of T-ABRM-treated cells were significantly higher than the T-ABDM, which indicates the apoptotic bodies are critical for cell activities. Our study revealed the possible mechanism of the intrinsic healing of the tendon in which apoptotic bodies, in the process of apoptosis, following tendon injury promote tenocyte and stromal cell proliferation, migration, and production. Future studies should analyze the components of the apoptotic bodies that play this role, and, thus, the targeting of therapeutics can be developed.


First detection of Anopheles stephensi in Ghana using molecular surveillance.
The invasive Anopheles stephensi mosquito has been rapidly expanding in range in Africa over the last decade, spreading from the Indian sub-continent to several East African countries (Djibouti, Ethiopia, Sudan, Somalia and Kenya) and now in West Africa, Nigeria. The rapid expansion of this invasive vector poses a major threat to current malaria control and elimination efforts. In line with the WHO's strategy to stop the spread of this invasive species by enhancing surveillance and control measures in Africa, we incorporated morphological and molecular surveillance of An. stephensi into routine entomological surveillance of malaria vectors in the city of Accra, Ghana. Here, we report on the first detection of An. stephensi in Ghana. An. stephensi mosquitoes were confirmed using PCR and sequencing of the ITS2 regions. These findings highlight the urgent need for increased surveillance and response strategies to mitigate the spread of An. stephensi in Ghana.


An approach to pruritus in atopic dermatitis: a critical systematic review of the tacrolimus ointment literature.
Persistent pruritus, or itch, is one of the earliest symptoms of atopic dermatitis (AD). When pruritus is untreated, the incessant scratching response by the patient can increase the inflammatory response, resulting in aggravation of disease symptoms and severity, increasing flares and worsening patient quality of life. Therefore, it is essential that pruritus be treated effectively, rapidly and safely for optimal management of AD. In this article, the authors review clinical trials using tacrolimus ointment, a topical calcineurin inhibitor, to treat adult and pediatric patients with AD over a wide range of disease severity focusing on its efficacy in rapidly reducing pruritus. Furthermore, the authors evaluate trials in which tacrolimus ointment was directly compared with topical corticosteroids, the mainstay of AD treatment, and pimecrolimus cream, another topical calcineurin inhibitor, as well as long-term safety trials in which patients applied tacrolimus ointment for extended periods.


The capsules of Corynebacterium equi and Streptococcus equi.
The capsules of Corynebacterium equi and Streptococcus equi were examined by electron microscopy after staining with ruthenium red. They were compared with the capsule of Klebsiella pneumoniae which had previously been examined using the same procedure (Springer & Roth, 1973). The capsule of C. equi had a laminated appearance. When S. equi was grown on solid medium, its capsule appeared as radially arranged projections capped by a thick electron dense layer. When grown in liquid medium, S. equi produced a capsule which showed as short thick projections with no layer external to them.


Evaluation of radioimmunoassays: comparison of dose interpolation calculations by four parameter logistic and spline functions.
Two computerized methods for dose interpolation calculation were compared. Generated data sets with a known coefficient of variation as well as laboratory RIA data were analysed. The four parameter logistic method, which is based on an approximation of the mass action law, performed better than the Spline method, a procedure which makes no a priori assumptions about the data. Correct weighting of the data was important for obtaining satisfactory fits. The determination of the response error relationship proved to be the most satisfactory approach in obtaining suitable weighting factors.


[Shared-housing arrangements for care-dependent older persons - characteristics, development and drivers].
Shared-Housing Arrangements (SHA) for care-dependent older persons gain increasing importance as a setting for nursing care in Germany, both in terms of numbers and user preference. This article aims to answer the questions in which phases SHA have developed over time, what the initiator's objectives are, and what factors contributed to SHA proliferation. A systematic review of the literature was conducted that finally included 73 articles. As a result it can be demonstrated that SHA started from "individual user initiatives", became "developing novel services" and finally established themselves as "regular services" in the nursing setting. A typology of different models of SHA can be organised along two dimensions: Firstly the temporal dimension of care organisation and secondly the way care services are purchased. Objectives formulated by the initiators of SHA are: Establishment of a family - like environment, inclusion of relatives, community orientation, security of care provision and maintenance of self-determination. Tailor-made financial and legal regulations supported the spread of SHAs. In reflection of the available literature it becomes evident that no satisfactory consensus on those elements exist that are constitutive for SHAs. Furthermore, there is a dearth of research on whether postulated objectives and other health related goals are actually being met in SHAs. Open questions pertain also the level of self-determination achieved in practice and other outcomes attained.


Comparisons of mycelia- and spherule-derived antigens in cellular immune assays of Coccidioides immitis-infected guinea pigs.
The biological activities of four Coccidioides antigens were compared in skin test, macrophage migration inhibitory factor (MIF), and lymphocyte transformation (LT) assays fo 137 Coccidioides-infected and 20 noninfected guinea pigs. Antigens included: C-ASWS-M, the alkali-soluble, water-soluble cell wall extract from mycelia of C. immitis; C-ASWS-S, the alkali-soluble, water-soluble cell wall extract from spherules; CDN-TS, a toluene-induced lysate of C. immitis mycelia; and spherulin, an autolysate obtained from spherules. CDN-TS proved significantly more reactive (P less than 0.0001) in skin tests, eliciting a mean induration of 11.6 mm as compared with indurations of 6.6, 6.4, and 6.1 mm obtained with C-ASWS-S spherulin, and C-ASWS-M, respectively. CDN-TS, C-ASWS-S, and spherulin were equally reactive in MIF assays and elicited migration inhibitions of 31.8, 30.8, and 30.7%. C-ASWS-M was significantly less reactive (P less than 0.001), with a mean response of 23.5%. The highest level of activity in LT assays was obtained with C-ASWS-S with a mean response of 5,636 delta cpm as compared with responses of 3,624, 3,439, and 3,580 delta cpm with CDN-TS, spherulin, and C-ASWS-M, respectively (P less than 0.01). All antigens were effective in distinguishing responses of infected versus noninfected guinea pigs.


Combined gastric and duodenal perforation through blunt abdominal trauma.
Blunt abdominal traumas are uncommonly encountered despite their high prevalence, and injuries to the organ like duodenum are relatively uncommon (occurring in only 3%-5% of abdominal injuries) because of its retroperitoneal location. Duodenal injury combined with gastric perforation from a single abdominal trauma impact is rarely heard. The aim of this case report is to present a rare case of blunt abdominal trauma with combined gastric and duodenal injuries.


Women's Experiences of Undergoing Total Knee Joint Replacement Surgery.
The purpose of the study was to describe women's experiences of undergoing total knee joint replacement surgery. A qualitative approach was used. A content analysis of the text from interviews with five women was conducted. The time before surgery was marked by the experience of constant pain, which affected the women negatively in their everyday lives. During surgery, the information provided by the staff gave each woman a sense of security; the women handed over responsibility to the staff and experienced a sensation of relief. The postoperative period was characterized by a feeling of joy when the surgery was over, although a rough and tedious rehabilitation phase then began. Challenges in everyday life were a factor for motivation and confidence, although postoperative pain was experienced as discouraging. Support from health care staff is an important factor for coping with everyday life during the preoperative, perioperative and postoperative phases of undergoing knee joint replacement.


Graphene as Barrier to Prevent Volume Increment of Air Bubbles over Silicone Polymer in Aqueous Environment.
The interaction of air bubbles with surfaces immersed in water is of fundamental importance in many fields of application ranging from energy to biology. However, many aspects of this topic such as the stability of surfaces in contact with bubbles remain unexplored. For this reason, in this work, we investigate the interaction of air bubbles with different kinds of dispersive surfaces immersed in water. The surfaces studied were polydimethylsiloxane (PDMS), graphite, and single layer graphene/PDMS composite. X-ray photoelectron spectroscopy (XPS) analysis allows determining the elemental surface composition, while Raman spectroscopy was used to assess the effectiveness of graphene monolayer transfer on PDMS. Atomic force microscopy (AFM) was used to study the surface modification of samples immersed in water. The surface wettability has been investigated by contact angle measurements, and the stability of the gas bubbles was determined by captive contact angle (CCA) measurements. CCA measurements show that the air bubble on graphite surface exhibits a stable behavior while, surprisingly, the volume of the air bubble on PDMS increases as a function of immersion time (bubble dynamic evolution). Indeed, the air bubble volume on the PDMS rises by increasing immersion time in water. The experimental results indicate that the dynamic evolution of air bubble in contact with PDMS is related to the rearrangement of surface polymer chains via the migration of the polar groups. On the contrary, when a graphene monolayer is present on PDMS, it acts as an absolute barrier suppressing the dynamic evolution of the bubble and preserving the optical transparency of PDMS.


45,X karyotype in an infertile man: how is this possible?
The case was male, 32 years old, with a nonobstructive azoospermia diagnosis and an initial 45,X karyotype. We evaluated by classical cytogenetic methods, C and NOR banding, fluorescent in situ hybridization, and polymerase chain reaction investigations. After investigation, we found the following karyotype: 45,X,dic(Y;22)(q11.223;p11.2). This investigation contributes to our understanding of how chromosome rearrangements can influence fertility processes and how important it is to perform a cytogenetic analysis in infertility cases.


Physical Therapy for a Child With Infantile Idiopathic Scoliosis and Motor Delay.
The purpose of this case report is to describe physical therapy (PT) for a child with infantile idiopathic scoliosis and motor delay. A 10-month-old boy with a 28° left thoracolumbar scoliosis was referred for PT and was seen weekly in his home over a 6-month period following a diagnosis of scoliosis and delayed gross motor milestones. Before the initiation of PT, the child was scheduled to undergo serial casting for correction of the spinal curve and was not yet rolling or transitioning in or out of sitting. By the end of the 6-month intervention period, the spinal curve had resolved to 12° without the need for serial casting and the child was walking independently. PT appeared to have a positive effect on reduction of the spinal curve and achievement of gross motor milestones.


Identifying problematic Internet users: development and validation of the Internet Motive Questionnaire for Adolescents (IMQ-A).
Internationally, up to 15.1% of intensive Internet use among adolescents is dysfunctional. To provide a basis for early intervention and preventive measures, understanding the motives behind intensive Internet use is important. This study aims to develop a questionnaire, the Internet Motive Questionnaire for Adolescents (IMQ-A), as a theory-based measurement for identifying the underlying motives for high-risk Internet use. More precisely, the aim was to confirm the 4-factor structure (ie, social, enhancement, coping, and conformity motives) as well as its construct and concurrent validity. Another aim was to identify the motivational differences between high-risk and low-risk Internet users. A sample of 101 German adolescents (female: 52.5%, 53/101; age: mean 15.9, SD 1.3 years) was recruited. High-risk users (n=47) and low-risk users (n=54) were identified based on a screening measure for online addiction behavior in children and adolescents (Online-Suchtverhalten-Skala, OSVK-S). Here, "high-risk" Internet use means use that exceeds the level of intensive Internet use (OSVK-S sum score ≥7). The confirmatory factor analysis confirmed the IMQ-A's 4-factor structure. A reliability analysis revealed good internal consistencies of the subscales (.71 up to .86). Moreover, regression analyses confirmed that the enhancement and coping motive groups significantly predicted high-risk Internet consumption and the OSVK-S sum score. A mixed-model ANOVA confirmed that adolescents mainly access the Internet for social motives, followed by enhancement and coping motives, and that high-risk users access the Internet more frequently for coping and enhancement motives than low-risk users. Low-risk users were primarily motivated socially. The IMQ-A enables the assessment of motives related to adolescent Internet use and thus the identification of populations at risk. The questionnaire enables the development of preventive measures or early intervention programs, especially dealing with internal motives of Internet consumption.


Do Income Supplemental Programs for Older Adults' Help Reduce Primary Caregiver Burden? Evidence from Mexico.
In countries such as Mexico without formal public long-term care policies, informal care becomes the main source of support for older adults. Alternative social programs, such as supplemental income programs, for older adults could alleviate caregiver burden, especially if supplemental income were to be used for paid care or to compensate non-paid family caregivers. This work is the first to analyze the effects of a supplemental income program for older adults on primary caregiver burden. To identify how such a program might affect caregiver burden, we analyze rich panel data on 433 adults 70 years and older in two communities, one receiving a supplemental income program and the other not, in Yucatan, Mexico. Data were collected in 2008 and 2009 among treatment and control groups before and 6 months after program introduction. We employ a difference-in-differences approach. In our sample, most care is provided by non-paid female caregivers. We find that individuals in both the treatment and control groups received fewer hours of care over time. The decrease was lower for older adults who received the supplemental income, but the difference with those who did not was not statistically significant. We also observe few changes on caregiving burden; even after program introduction, more than 98% of caregivers remained unpaid and the same primary caregiver remained. Altogether, our work suggests supplemental income programs have negligible effects on caregiving, making evident the urgent need for other strategies to support non-paid caregivers who bear most of the burden for old-age care in Mexico.


Dihydromyricetin inhibited ovalbumin-induced mice allergic responses by suppressing the activation of mast cells.
Dihydromyricetin (DMY) is a natural flavonoid compound derived from Lysionotus pauciflorus Maxim and has been found to possess numerous biological activities. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that DMY could upregulate the rectal temperature, suppress the development of diarrhea, decrease the levels of serum specific immunoglobulin (Ig)E, histamine, and mouse mast cell protease-1, and promote the production of interleukin-10 in ovalbumin-allergic mice. Moreover, DMY downregulated the population of B cells and mast cells and upregulated the population of regulatory T cells in the spleens of ovalbumin-allergic mice. Furthermore, DMY blocked the high affinity IgE receptor (FcεRI)-IgE interaction, inhibited the release of β-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells, and alleviated passive cutaneous anaphylaxis reactions. These findings indicated that L. pauciflorus derived DMY might have the potential to alleviate food hypersensitivity or allergic diseases.


Clinical evaluation of the air removal characteristics of an oxygenator with integrated arterial filter in a minimized extracorporeal circuit.
The use of minimized extracorporeal circuits (MECC) in cardiac surgery is an important measure to increase the biocompatibility of cardiopulmonary bypass during coronary artery bypass grafting (CABG). These circuits eliminate volume storage reservoirs and bubble traps to minimize the circuit. However, the reduction in volume may increase the risk of gaseous microemboli (GME). The MECC system as used by our group consists of a venous bubble trap, centrifugal pump, and an oxygenator. To further reduce the risk of introducing GME, an oxygenator with an integrated arterial filter was developed based on the concept of minimal volume and foreign surface. We studied the air removal characteristics of this oxygenator with and without integrated arterial filter. The quantity and volume of GME were measured with precision at both the inlet and outlet of the devices. Our results showed that integration of an arterial filter into this oxygenator increased GME reducing capacity from 69.2% to 92%. Moreover, we were able to obtain data on the impact of an arterial filter on the exact size-distribution of GME entering the arterial line. The present study demonstrates that an MECC system and oxygenator with integrated arterial filter significantly reduces the volume and size of GME. The use of an integrated arterial filter in an MECC system may protect the patient from the deleterious effects of CPB and may further improve patient safety.


Midface anomalies in children.
A variety of congenital midface anomalies occur in children. High-resolution computed tomography (CT) and magnetic resonance (MR) imaging have proved helpful in determining the nature and extent of dysplasia, thereby facilitating treatment planning. A classification system has been developed that groups these anomalies into four categories based on embryogenesis and anatomic location. These categories comprise anomalies that are related to the nasal cavity, nasofrontal region, nasolacrimal apparatus, and craniofacial syndromes. CT is the imaging modality of choice in children with possible choanal atresia, pyriform aperture stenosis, or anomalies of the nasolacrimal duct (eg, nasolacrimal duct stenosis, dacryocystoceles). MR imaging is the modality of choice in patients with congenital midface masses (eg, dermoid and epidermoid cysts, nasal gliomas, encephaloceles) and craniofacial syndromes (eg, Apert syndrome, Crouzon syndrome, Treacher Collins syndrome). In many cases, however, both CT and MR imaging are required to adequately evaluate midface anomalies. Familiarity with the characteristic imaging features of these anomalies along with knowledge of midface embryogenesis and normal developmental anatomy is essential to prevent misinterpretation of anatomic variations that may simulate disease.


Prospective evaluation of emergency physician performed bedside ultrasound to detect acute appendicitis.
To evaluate the accuracy of emergency physicians using bedside ultrasound to detect appendicitis (BUSA). Patients presenting to the emergency department with a clinical suspicion of appendicitis were prospectively enrolled and received a 5-min BUSA. Patients received routine work-up for acute appendicitis as deemed appropriate by the attending physician. Radiologists and consulting surgeons were blinded to BUSA results. The criterion standard for the presence or absence of acute appendicitis was the pathology report for patients who received appendectomies, and telephone follow-up for patients discharged home without surgical intervention. A total of 132 patients were enrolled. In 44 cases BUSA was positive. Of these, 37 had surgical pathology reports consistent with acute appendicitis, whereas seven did not have appendicitis. In 82 cases, BUSA was negative. Of these, 62 were determined not to have appendicitis, whereas 20 had appendicitis by pathology. Sensitivity for BUSA was 65% [95% confidence interval (CI) 52-76], specificity was 90% (95% CI 81-95), positive predictive value was 84% (95% CI 71-92), and negative predictive value was 76% (95% CI 65-84). The likelihood ratio of a positive BUSA was 6.4 (95% CI 3.1-13.2). Five patients discharged home with a diagnosis other than appendicitis were unable to be reached by telephone, and were excluded from data analysis. Our study gives insufficient evidence to support the use of bedside ultrasound by emergency physicians to rule out appendicitis. The high specificity in our study, however, suggests that with further training, BUSA may be useful to rule-in appendicitis in some patients.


Multi-omics analysis of hiPSCs-derived HLCs matured on-chip revealed patterns typical of liver regeneration.
Maturation of human-induced pluripotent stem cells (hiPSCs)-derived hepatocytes-like cells (HLCs) toward a complete hepatocyte phenotype remains a challenge as primitiveness patterns are still commonly observed. In this study, we propose a modified differentiation protocol for those cells which includes a prematuration in Petri dishes and a maturation in microfluidic biochip. For the first time, a large range of biomolecular families has been extracted from the same sample to combine transcriptomic, proteomic, and metabolomic analysis. After integration, these datasets revealed specific molecular patterns and highlighted the hepatic regeneration profile in biochips. Overall, biochips exhibited processes of cell proliferation and inflammation (via TGFB1) coupled with anti-fibrotic signaling (via angiotensin 1-7, ATR-2, and MASR). Moreover, cultures in this condition displayed physiological lipid-carbohydrate homeostasis (notably via PPAR, cholesterol metabolism, and bile synthesis) coupled with cell respiration through advanced oxidative phosphorylation (through the overexpression of proteins from the third and fourth complex). The results presented provide an original overview of the complex mechanisms involved in liver regeneration using an advanced in vitro organ-on-chip technology.


Developing ROS scavenging agents for pharmacological purposes: recent advances in design of manganese-based complexes with anti-inflammatory and anti- nociceptive activity.
Reactive oxygen and nitrogen species, which are normal products of cell metabolism, may play a dual beneficial/deleterious role, depending on local concentration and mode of generation. As such, they have been identified as key pathogenic factors for many inflammatory and degenerative disorders, carcinogenesis, nociception and ageing. In this perspective, low molecular weight transition metal complexes with organic ligands have been and are still viewed as promising pharmaceutical agents with antioxidant/free radical scavenging properties, owing to their ability to interact and/or react with reactive oxygen or nitrogen species and counterbalance excessive endogenous free radical generation in biological systems. Among these compounds, manganese(II/III) complexes have resulted effective as ROS scavengers both in vitro and in vivo. In particular, Mn(III) complexes with porphyrins and salen derivatives as well as Mn(II) complexes with macrocyclic pentaamines and polyamine-polycarboxylic acids have been recently analyzed as ROS scavengers for therapeutic purposes. In this article, we summarize the chemical and biological properties of manganese complexes with low molecular weight synthetic ligands as scavengers of pro-oxidant species, with particular attention to the mechanisms operating at the metal center in the scavenging process. A proper design of the organic scaffolds may yield manganese complexes capable to catalyze different scavenging reactions, including superoxide and/or hydrogen peroxide dismutation and peroxynitrite decomposition. These manganese complexes can be viewed either as a novel class of drugs helpful to reduce oxidative tissue injury or as useful tools to get further light on the role played by ROS in biological systems.


Application of biosensors in cancers, an overview.
The deadliest disease in the world, cancer, kills many people every year. The early detection is the only hope for the survival of malignant cancer patients. As a result, in the preliminary stages of, the diagnosis of cancer biomarkers at the cellular level is critical for improving cancer patient survival rates. For decades, scientists have focused their efforts on the invention of biosensors. Biosensors, in addition to being employed in other practical scenarios, can essentially function as cost effective and highly efficient devices for this purpose. Traditional cancer screening procedures are expensive, time-consuming, and inconvenient for repeat screenings. Biomarker-based cancer diagnosis, on the other hand, is rising as one of the most potential tools for early detection, disease progression monitoring, and eventual cancer treatment. As Biosensor is an analytical device, it allows the selected analyte to bind to the biomolecules being studied (for example RNA, DNA, tissue, proteins, and cells). They can be divided based on the kind of biorecognition or transducer elements on the sensor. Most biosensor analyses necessitate the analyte being labeled with a specific marker. In this review article, the application of distinct variants of biosensors against cancer has been described.


Genetics of osteoarthritis.
Osteoarthritis genetics has been transformed in the past decade through the application of large-scale genome-wide association scans. So far, over 100 polymorphic DNA variants have been associated with this common and complex disease. These genetic risk variants account for over 20% of osteoarthritis heritability and the vast majority map to non-protein coding regions of the genome where they are presumed to act by regulating the expression of target genes. Statistical fine mapping, in silico analyses of genomics data, and laboratory-based functional studies have enabled the identification of some of these targets, which encode proteins with diverse roles, including extracellular signaling molecules, intracellular enzymes, transcription factors, and cytoskeletal proteins. A large number of the risk variants correlate with epigenetic factors, in particular cartilage DNA methylation changes in cis, implying that epigenetics may be a conduit through which genetic effects on gene expression are mediated. Some of the variants also appear to have been selected as humans adapted to bipedalism, suggesting that a proportion of osteoarthritis genetic susceptibility results from antagonistic pleiotropy, with risk variants having a positive role in joint formation but a negative role in the long-term health of the joint. Although data from an osteoarthritis genetic study has not yet directly led to a novel treatment, some of the osteoarthritis associated genes code for proteins that have available therapeutics. Genetic investigations are therefore revealing fascinating fundamental insights into osteoarthritis and can expose options for translational intervention.


Multiple Roles of HIV-1 Capsid during the Virus Replication Cycle.
Human immunodeficiency virus-1 capsid (HIV-1 CA) is involved in different stages of the viral replication cycle. During virion assembly, CA drives the formation of the hexameric lattice in immature viral particles, while in mature virions CA monomers assemble in cone-shaped cores surrounding the viral RNA genome and associated proteins. In addition to its functions in late stages of the viral replication cycle, CA plays key roles in a number of processes during early phases of HIV-1 infection including trafficking, uncoating, recognition by host cellular proteins and nuclear import of the viral pre-integration complex. As a result of efficient cooperation of CA with other viral and cellular proteins, integration of the viral genetic material into the host genome, which is an essential step for productive viral infection, successfully occurs. In this review, we will summarize available data on CA functions in HIV-1 replication, describing in detail its roles in late and early phases of the viral replication cycle.


Left atrial assist device function at various heart rates using a mock circulation loop.
We are developing a new left atrial assist device (LAAD) for patients who have heart failure with preserved ejection fraction (HFpEF). This study aimed to assess the hemodynamic effects of the LAAD under both normal heart conditions and various diastolic heart failure (DHF) conditions using a mock circulatory loop. A continuous-flow pump that simulates LAAD, was placed between the left atrial (LA) reservoir and a pneumatic ventricle that simulated a native left ventricle on a pulsatile mock loop. Normal heart (NH) and mild, moderate, and severe DHF conditions were simulated by adjusting the diastolic drive pressures of the pneumatic ventricle. With the LAAD running at 3200 rpm, data were collected at 60, 80, and 120 bpm of the pneumatic ventricle. Cardiac output (CO), mean aortic pressure (AoP), and mean LA pressure (LAP) were compared to evaluate the LAAD performance. With LAAD support, the CO and AoP rose to a sufficient level at all heart rates and DHF conditions (CO; 3.4-3.8 L/min, AoP; 90-105 mm Hg). Each difference in the CO and the AoP among various heart rates was minuscule compared with non-pump support. The LAP decreased from 21-23 to 17-19 mm Hg in all DHF conditions (difference not significant). Furthermore, hemodynamic parameters improved for all DHF conditions, independent of heart rate. The LAAD can provide adequate flow to maintain the circulation status at various heart rates in an in vitro mock circulatory loop.


Enhancing the usefulness of cross dehydrogenative coupling reactions with a removable protecting group.
A removable protecting group has been identified that allows the products of widely-used cross dehydrogenative couplings to be synthetically elaborated. The method can be used with enantiopure amines with no loss of enantiomeric excess. The methodology is exemplified by a new synthesis of enantiopure praziquantel, the drug used in the treatment of millions of people suffering from the neglected tropical disease, schistosomiasis.


Improving communication outcomes for young offenders: a proposed response to intervention framework.
Speech, language and communication needs (SLCN) are strongly overrepresented in young offender populations, and there is growing commitment internationally to ensuring access to speech-language therapy services for such young people. However there is currently no framework in which such interventions might be conceptualized, delivered and evaluated. This is significant given the role of language competence in the development of prosocial skills and also in the transition to literacy. To present Response to Intervention (RTI) as a framework in which SLCN of young offenders might be systematically addressed and evaluated within youth justice settings, led by speech-language therapists, in conjunction with other education and welfare team members. Literature regarding prevalence rates of SLCN in young offenders is reviewed, together with the limited extant evidence on interventions for this group. The importance of applying evidence-based interventions is argued, and a framework for adapting RTI for SLCN in custodial settings is outlined. A framework for adapting RTI to design, deliver and evaluate speech-language therapy interventions in youth custodial settings is presented. Speech-language therapy interventions for young offenders will be better addressed at policy, practice and research levels if a framework such as an RTI adaptation is employed. It is expected, however, that this model will evolve over time, as intervention evidence pertaining to the youth offender population emerges.


The Effect of Microvascular Decompression on Hemifacial Spasm With Atherosclerosis of Vertebral Artery.
Microvascular decompression (MVD) is the most useful treatment for hemifacial spasm (HFS). In patients of vertebral artery (VA) compression of the facial nerve, MVD is often difficult. Many of the VA are obviously atherosclerotic. In this study, the authors retrospectively compared the effect of MVD for HFS associated with the atherosclerosis of vertebral artery (aVA) with that of MVD for HFS with normal vertebral artery (nVA). A retrospective study of HFS treated by MVD was conducted between January 2014 and October 2015. There were 186 patients with VA-associated HFS who underwent their first MVD at the authors' institution. Among them, 52 patients of HFS were associated with aVA and 134 patients were associated with nVA. At 1 day, 7 days, 1 month, 3 months, and 1 year after MVD surgery, in aVA group, the effective rate of MVD was 80.77%, 80.77%, 82.00%, 79.59%, and 82.61%, the incidence rate of complication was 15.83%, 13.46%, 14.00%, 12.24%, and 10.87%; in nVA group, the effective rate of operation was 94.03%, 94.78%, 95.42%, 94.53%, and 95.12% (P < 0.05), the incidence rate of complication was 4.48%, 4.48%, 3.82%, 3.13%, and 1.63% (P < 0.05). When the HFS was associated with the aVA, the effective rate of MVD was lower and the incidence of complication was higher than those associated with nVA. In MVD of HFS associated with aVA, the full decompression of the facial nerve and the minimal traction of surrounding tissue in the operation are the key to the success of MVD.


The endocrinology of the urinary bladder.
The urinary bladder primarily functions as a reservoir for urine. Apparently, it serves only a mechanical and passive role in the urinary tract, but closer scrutiny reveals that it has several meaningful endocrine interactions. This vital organ has an intricate plexus of neurons that release neurohormones concerned with the functioning of the bladder. Endocrine disorders, most notably diabetes, can cause a broad spectrum of bladder dysfunction. The current review explores the bladder as a source of neurotransmitters, a target for organ damage due to uncontrolled endocrinopathy, a beneficiary of hormonal therapy, and a tool to improve endocrine health.