Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy.
Transcutaneous auricular vagus nerve stimulation (taVNS) has potential clinical application for autism spectrum disorder (ASD). At-home sessions are necessary to allow delivery of repeated sessions, and remove burden on patients for daily visits, and reduce costs of clinic delivery. Our objective was to validate a protocol for remote supervised administration for home delivery of taVNS using specially designed equipment and platform. An open-label design was followed involving administration by caretakers to 12 patients with ASD (ages:7-16). Daily 1-h sessions over 2 weeks were administered under remote supervision. The primary outcome was feasibility, which was assessed by completion rate, stimulation tolerability, and confirmation of programmed stimulation delivery. The secondary measures were initial efficacy assessed by Childhood Anxiety Sensitivity Index-Revised (CASI-R), Parent Rated Anxiety Scale for Youth with ASD (PRAS-ASD), and Clinician Global Impression (CGI) scales. Sleep measures were also tracked using Cleveland Adolescent Sleep Questionnaire (CASQ). Across 132 sessions, we obtained an 88.5% completion rate. A total of 22 expected adverse events were reported with headache being the most common followed by transient pain, itchiness, and stinging at the electrode site. One subject dropped out of the study unrelated to the stimulation or the study. Average scores of anxiety (CASI-R, PRAS-ASD, and CGI) and sleepiness (CASQ) were all improved at the 2 week time point. While not powered to determine efficacy, benefits were suggested in this open label pilot. Remotely supervised, proxy-administered, at-home delivery of taVNS is feasible in patients with ASD. Initial efficacy supports pursuing larger scale trials.


Sensory and central nervous elements in the avian pineal organ.
The pineal organs of the adult domestic mallard, fowl and pigeon were investigated by means of neurohistological techniques and electron microscopy. The application of opsin immunocytochemistry to the pineal organ of the domestic mallard reveals antigenic sites in the outer segments of the pinealocytes. Avian pinealocytes may establish synaptic contacts to intrapineal neurons via complex neuropil formations. Bundles of nerve fibers resembling the pineal tract of poikilothermic vertebrates were found in the pineal stalk. These findings strengthen the view that the avian pineal organ has not lost its photoreceptive capacity.


Evaluation of Key Aroma Compounds in Processed Prawns (Whiteleg Shrimp) by Quantitation and Aroma Recombination Experiments.
In our previous study on the aroma compounds of heated prawn meat, the main odorants in blanched (BPM) and fried prawn meat (FPM), respectively, were characterized by means of gas chromatography-olfactometry and aroma extract dilution analysis. In this follow-up study, these aroma compounds were quantified by means of stable isotope dilution assays, and odor activity values (OAV; ratio of concentration to odor detection threshold) were calculated. Results revealed 2-acetyl-1-pyrroline and (Z)-1,5-octadien-3-one as the most potent odor-active compounds in both prawn samples. In FPM, as compared to BPM, higher OAVs were determined for 2-acetyl-1-pyrroline, 2-acetyl-2-thiazoline, 3-methylbutanal, 3-(methylthio)propanal, phenylacetaldehyde, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, 2,3-diethyl-5-methylpyrazine, and trimethylpyrazine. Aroma recombination experiments corroborated that the overall aroma of the blanched as well as the fried prawn meat, respectively, could well be mimicked by the set of key odorants quantitated in this study.


Application of library-independent microbial source tracking methods for identifying the sources of faecal contamination in coastal areas.
Faecal contamination sources were identified in coastal areas around the Guerande-Atlantique peninsula using two microbial source tracking (MST) methods: (i) Bacteroidales host-specific 16S rRNA gene markers measured by real-time PCR and (ii) F-specific bacteriophage (FRNAPH) genotyping. Both methods were used on 63 water samples from 7 water courses. HF183 marker and bacteriophage genogroup II (FRNAPH II) were detected in all water samples and in the majority of water samples, respectively, from La Torre stream (W5), Piriac (W2), R2000 (W3) and Mazy (W7) rain water drains, and also detected, less frequently, in Le Nau drain (W4), suggesting contamination by human faecal sources at these sites. These human markers were weakly detected in Pouliguen channel (W6). Furthermore, BacR and bacteriophage genogroup I (FRNAPH I) were also detected, but at lower concentration and frequency. So, site W6 seems to be contaminated by multiple sources, though mainly human. Finally, BacR was detected twice in Pont d'Armes channel (W1), whereas HF183 was not detected. FRNAPH I and II were detected in only 3 out of 12 water samples. Site W1 seems mainly contaminated by animal sources. As a result of our findings, actions were taken to remediate water and shellfish quality.


[Portal vein embolization preparation for major hepatic resection: a new standard in liver surgery].
Preoperative portal vein embolization (PVE) is increasingly used for operative treatment of patients scheduled to undergo liver resection when the volume of the future remnant liver appears to be insufficient. Portal vein embolization should be considered when the prospective postoperative liver volume is less than 20 % or less than 40 % in patients with known liver cirrhosis. Our own results (n = 28) demonstrated an average volume increase in segments II and III of 280 +/- 95 ml to 420 +/- 98 ml within 6 weeks after selective percutaneous- transhepatic embolization of the portal vein branches (IV)-V-VIII. Thus, an expanded right resection of the liver could be performed in all patients without major complications. None of the patients suffered from clinically relevant liver insufficiency within the first few postoperative months.


Large Area Nanoparticle Alignment by Chemical Lift-Off Lithography.
Nanoparticle alignment on the substrate attracts considerable attention due to its wide application in different fields, such as mechanical control, small size electronics, bio/chemical sensing, molecular manipulation, and energy harvesting. However, precise nanoparticle positioning and deposition control with high fidelity are still challenging. Herein, a straightforward strategy for high quality nanoparticle-alignment by chemical lift-off lithography (CLL) is demonstrated. This technique creates high resolution self-assembled monolayer (SAM) chemical patterns on gold substrates, enabling nanoparticle-selective deposition and precise alignment. The fabricated nanoparticle arrangement geometries and dimensions are well-controllable in a large area. With proper nanoparticle surface functionality control and adequate substrate molecular manipulation, well-defined nanoparticle arrays with single-particle-wide alignment resolution are achieved.


INC-Seq: accurate single molecule reads using nanopore sequencing.
Nanopore sequencing provides a rapid, cheap and portable real-time sequencing platform with the potential to revolutionize genomics. However, several applications are limited by relatively high single-read error rates (>10 %), including RNA-seq, haplotype sequencing and 16S sequencing. We developed the Intramolecular-ligated Nanopore Consensus Sequencing (INC-Seq) as a strategy for obtaining long and accurate nanopore reads, starting with low input DNA. Applying INC-Seq for 16S rRNA-based bacterial profiling generated full-length amplicon sequences with a median accuracy >97 %. INC-Seq reads enabled accurate species-level classification, identification of species at 0.1 % abundance and robust quantification of relative abundances, providing a cheap and effective approach for pathogen detection and microbiome profiling on the MinION system.


Emergency, cardiac arrest! Can we teach the skills?
The European Resuscitation Council (ERC) has produced basic life support (BLS) and advanced life support (ALS) guidelines (1992) in an attempt to standardize the training and delivery of cardiopulmonary resuscitation (CPR). In response to this, the Avon and Gloucestershire College of Health, Glenside Centre (now University of the West of England), conducted a small survey, testing students' knowledge and skills in delivering CPR. Students were able to improve knowledge levels, but did not uniformly improve practical skills. Following this, the college formed a resuscitation team whose members coordinate CPR training in the curriculum, using uniform teaching packs which follow the ERC Guidelines (ERC 1992a), and resuscitation equipment purchased by the college as the result of the research findings. In addition to maintaining uniform content, sessions are compulsory and students' CPR skills are tested, with a 70% competency level set as a pass. Student results and attendance are stored on a college database, along with tutor information regarding updating of CPR skills. To achieve these developments, the college has had to consider time allocation within the curriculum, training of tutors, funding of resources and funding of a compulsory training programme, which supports a ratio of one tutor to six students. Evaluations of the changes are favourable, as students' CPR skills and knowledge show obvious improvement and the students' general confidence and enthusiasm are enhanced.


[Lung diseases during therapeutic aplasia: diagnostic and therapeutic strategy].
Lung diseases that occur in patients with drug-induced bone marrow aplasia are part of a wider group of lung diseases in immunocompromised patients. Their most common causes are infections due to Gram-negative bacilli, staphylococci or Aspergillus spp. and intra-alveolar haemorrhages. Their diagnostic approach is often limited by disorders of coagulation, risks of infection by bronchial or pulmonary seeding during endoscopy and the lethal risk of mechanical ventilation after bronchoalveolar lavage in patients with respiratory failure. The therapeutic approach is frequently empirical due to the fact that antibiotic therapy cannot be delayed, even for a few hours, and to the aforementioned diagnostic problems. In practice, the diagnostic and therapeutic approaches usually result from a rational compromise depending on whether the lung disease has occurred at the onset or at the end of an episode of bone marrow aplasia.


[The first Mental Health Act in China 2013 : An historical step towards human rights].
In the past, the mentally ill used to be relentlessly stigmatized and their basic needs grossly neglected in China. Only the coastal cities with their Western oriented universities provided Western type mental healthcare. In general, traditional Chinese medicine (TCM) embracing medicinal herbs and acupuncture was practiced. Mental hospitals were non-existent before 1889 and care of the chronically mentally ill rested with their families and the community; however, the prevalence and spectrum of mental disorders were similar to those in Western countries. After the establishment of the People's Republic of China old-fashioned mental hospitals were founded. The "Great Leap Forward" starting in 1958 envisaged the creation of a mental healthcare system based on Soviet Union standards. Psychiatry had a strong biological orientation, and psychotherapy did not exist. Psychology was rejected as not being science and was not taught at universities before 1978. With the Reform and Opening Policy in 1978 the education of psychology was stepped up. Psychology was introduced as an academic discipline in 1978 and psychotherapy and psychosomatic medicine were established in mental healthcare. The current mental healthcare in China resembles the standard in Germany before the "Psychiatrie-Enquete" (expert commission official report). With the Mental Health Act adopted in 2013 after 27 years of planning, China has laid the legal foundation for planning and establishing a humane system of mental healthcare. The Act safeguards patients' human and individual rights and increases trust in psychiatric institutions. It guarantees the right to optimal treatment and provides legal protection in cases of malpractice.


Implementation of Teleophthalmology to Improve Diabetic Retinopathy Surveillance: Qualitative Interview Study of Clinical Staff Informed by Implementation Science Frameworks.
The store-and-forward camera-based evaluation of the eye, or teleophthalmology, is an effective way to identify diabetic retinopathy, the leading cause of blindness in the United States, but uptake has been slow. Understanding the barriers to and facilitators of implementing teleophthalmology programs from those actively adopting, running, and sustaining such programs is important for widespread adoption. This study aims to understand the factors that are important in introducing teleophthalmology to improve access to diagnostic eye care for patients with diabetes in primary care clinics by using implementation science. This qualitative study in 3 urban, low-income, largely racial and ethnic minority-serving safety-net primary care clinics in Rochester, New York, interviewed nurses and physicians on implementing a teleophthalmology program by using questions informed by the Practical, Robust Implementation and Sustainability Model and the Consolidated Framework for Implementation Research. Primary care nurses operationalizing the program in their clinics saw increased work burden and a lack of self-efficacy as barriers. Continuous training on the teleophthalmology process for nurses, physicians, and administrative staff through in-service and peer training by champions and superusers were identified by interviewees as needs. Facilitators included the perceived convenience for the patient and a perceived educational advantage to the program, as it gave an opportunity for providers to discuss the importance of eye care with patients. Concerns in making and tracking referrals to ophthalmology because of challenges related to care coordination were highlighted. The financial aspects of the program (eg, patient coverage and care provider reimbursement) were unclear to many staff members, influencing adoption and sustainability. Streamlining processes and workflows, training and assigning adequate staff, effectively coordinating care between primary care and eye care to improve follow-ups, and ensuring financial viability can all help streamline the adoption of teleophthalmology.


[Effect of Trichinella spiralis infection on the development of Rauscher leukemia].
The influence of Trichinella spiralis on the course of Rausher leukemia in mice was studied. Inoculation of mice with Trichinella spiralis larvae 15, 16 and 30 days before infection with Rausher leukemia virus was shown to stimulate splenomegaly, whereas preinoculation of Rausher leukemia virus at 6, 12 and 18 days before infection with Trichinella spiralis resulted in inhibition of splenomegaly. Under the experimental conditions used, no effect of T. spiralis on reproduction of Rausher leukemia virus was observed, as virus titers in the plasm of mice with marked stimulation or inhibition of splenomegaly were identical and did not differ from those in mice without Trichinella spiralis invasion.


Chemoprevention of skin cancer and photoaging.
Skin cancer and photoaging are thought to be the result of ultraviolet radiation exposure. "Chemoprevention" refers to the prevention of photoaging and skin cancer through the use of pharmacologic agents that inhibit or reverse the process of photoaging or carcinogenesis. As both carcinogenesis and photoaging are multi-step processes, tumor development may be halted at several prospective points of intervention. A wealth of research aimed at chemoprevention is emerging. In this article, a variety of potential chemopreventive agents are discussed, including vitamins, diet, aspirin and non-steroidal anti-inflammatory drugs, and topical agents. Although further studies are warranted to identify and determine the safety and efficacy of new chemotherapeutic agents, it is expected that both systemic and topical agents may soon be available that effectively prevent photoaging and skin cancer development.


Attenuation of collagen-induced arthritis by orally available imidazoline-based NF-κB inhibitors.
The pathogenesis of rheumatoid arthritis is mainly driven by NF-κB-mediated production of cytokines, such as TNF-α. We report herein that the orally available imidazoline-based NF-κB inhibitor, TCH-013, was found to significantly reduce TNF-α signaling and attenuate collagen antibody induced arthritis in BALB/c mice.


Effects of supplemental lysine and methionine with zilpaterol hydrochloride on feedlot performance, carcass merit, and skeletal muscle fiber characteristics in finishing feedlot cattle.
Feeding zilpaterol hydrochloride (ZH) with ruminally protected AA was evaluated in a small-pen feeding trial. Crossbred steers ( = 180; initial BW = 366 kg) were blocked by weight and then randomly assigned to treatments (45 pens; 9 pens/treatment). Treatment groups consisted of no ZH and no AA (Cont-), ZH and no AA (Cont+), ZH and a ruminally protected lysine supplement (Lys), ZH and a ruminally protected methionine supplement (Met), and ZH and ruminally protected lysine and methionine (Lys+Met). Zilpaterol hydrochloride (8.3 mg/kg DM) was fed for the last 20 d of the finishing period with a 3-d withdrawal period. Lysine and Met were top dressed daily for the 134-d feeding trial to provide 12 or 4 g·hd·d, respectively, to the small intestine. Carcass characteristics, striploins, and prerigor muscle samples were collected following harvest at a commercial facility. Steaks from each steer were aged for 7, 14, 21, and 28 d, and Warner-Bratzler shear force (WBSF) was determined as an indicator of tenderness. Prerigor muscle samples were used for immunohistological analysis. Cattle treated with Met and Lys+Met had increased final BW ( < 0.3) and ADG ( < 0.05) compared to Cont- and Cont+. Supplementation of Lys, Met, and Lys+Met improved G:F ( < 0.05) compared to Cont- during the ZH feeding period (d 111 to 134) as well as the entire feeding period ( < 0.05). Zilpaterol hydrochloride increased carcass ADG ( < 0.05) when compared to non-ZH-fed steers. Methionine and Lys+Met treatments had heavier HCW ( < 0.02) than that of Cont-. Yield grade was decreased ( < 0.04) for Cont+ steers compared to steers treated with Lys, Lys+Met, and Cont-. Tenderness was reduced ( < 0.05) with ZH regardless of AA supplementation. Lysine, Met, Lys+Met, and Cont+ had less tender steaks ( < 0.05) throughout all aging groups compared to Cont-. Steaks from Lys-treated steers were less tender ( < 0.05) than those of Cont+ during the 7- and 14-d aging periods. Nuclei density was the greatest with Cont- cattle compared to all other treatments suggesting a dilution effect of the nuclei in the larger muscle fibers with ZH feeding. Supplementation of Met in conjunction with ZH feeding increased ADG and HCW although this may lead to decreased tenderness even after aging for 28 d. These findings indicated that steers fed ZH may require additional AA absorbed from the small intestine to maximize performance.


A PCR-based survey of selected Babesia and Theileria parasites in cattle in Sri Lanka.
Hemoprotozoan parasites are responsible for significant economic losses in cattle. We screened Sri Lankan cattle populations for the presence of Babesia bovis, Babesia bigemina, Theileria annulata, and Theileria orientalis, using species-specific PCR assays. Out of 316 samples collected from animals in four different districts of Sri Lanka (Nuwara Eliya, Polonnaruwa, Ampara, and Jaffna), 231 (73.1%) were positive for at least one parasite species. All four parasite species were detected among the study groups from all of the districts surveyed. The first and second commonest hemoprotozoan parasites identified were T. orientalis (53.5%) and B. bigemina (30.1%), respectively. We found that the dry zones (Polonnaruwa, Ampara, and Jaffna) had more Babesia-positive animals than the hill country wet zone (Nuwara Eliya). In contrast, T. orientalis was the predominant species detected in Nuwara Eliya, while infection with T. annulata was more common in the dry zones. In addition, 81 (35.1%) of the 231 positive samples were infected with more than one parasite species. The presence of multiple parasite species among the different cattle populations is of clinical and economic significance. Therefore, island-wide control and prevention programs against bovine babesiosis and theileriosis are needed to minimize the financial burden caused by these parasites.


Mechanism of degradation of a nitrogenous heterocycle induced by a reductive radical: decomposition of a sym-triazine ring.
Cyanuric acid is a major component of many materials and chemicals, and is the most important intermediate in the degradation processes of sym-triazine compounds in the natural environment, as well as being used for water treatment. However, the degradation mechanism of cyanuric acid is still unclear in various advanced oxidation processes (AOPs), where ˙OH is usually regarded as the dominant radical. Here, using a combination of density functional theory calculations and experimental observations, we unexpectedly show that the sym-triazine ring structure is broken efficiently by reductive free radicals - hydrogen radicals (˙H), rather than traditional ˙OH. The energy barrier of cyanuric acid reacting with ˙H to form the -NH2 group and break the sym-triazine ring is only 4.96 kcal mol-1, which is clearly lower than that of cyanuric acid reacting with ˙OH (13.32 kcal mol-1). Our theoretical predictions are further confirmed by γ photon irradiation experiments, which show that when ˙H is present in the reaction, the nitrogen in cyanuric acid (or other nitrogenous compounds including primidone and bezafibrate) rapidly degrades into NH4+. In contrast, when ˙H is scavenged, cyanuric acid stops degrading into NH4+. Our results provide new insight for understanding the decomposition of nitrogenous materials, and we are the first to shed light on the key role of ˙H in organic transformation processes.


Biomechanical analysis of anterior stabilization techniques for different partial and total vertebral corpectomy defect models.
Restoration of the anterior spinal profile and regular load-bearing are the main goals in treating anterior spinal defects in cases of fracture. In large vertebral defects, the use of vertebral body replacements (VBRs) is common. For isolated anterior operations, VBRs are usually combined with antero-lateral angular stable or polyaxial plates. In preclinical biomechanical testing of spinal fracture stabilizations, complete corpectomies are often applied for fracture simulation. Complete corpectomies are reproducible and easily standardized but present a maximum instability not indicated for isolated anterior instrumentation. Therefore, this study investigates the stabilizing effect of VBRs and anterior plating systems on three different vertebral body defect models. Using 24 thoracolumbar spines, two different partial (PC 1+2) and one total corpectomy defect (CC) models were simulated and stabilized using different combinations of two VBRs and three different anterior plating systems. After anterior stabilization, range of motion (RoM) in the three main movement planes was evaluated. RoM was significantly reduced in all three motion planes for both stabilized partial corpectomy defect models compared to the stabilized complete corpectomy model and the intact specimens. The stabilized complete corpectomy defect model did not reduce RoM in flexion/extension and axial rotation compared to the intact state. Both partial corpectomy models are suitable for biomechanical testing of isolated anterior stabilization. A complete corpectomy model is not suitable to test isolated anterior instrumentation, as this simulates a rotationally unstable fracture, where isolated anterior instrumentation is not indicated in clinical practice.


Workers' Exposure to Nano-Objects with Different Dimensionalities in R&D Laboratories: Measurement Strategy and Field Studies.
With the increasing interest in the potential benefits of nanotechnologies, concern is still growing that they may present emerging risks for workers. Various strategies have been developed to assess the exposure to nano-objects and their agglomerates and aggregates (NOAA) in the workplace, integrating different aerosol measurement instruments and taking into account multiple parameters that may influence NOAA toxicity. The present study proposes a multi-metric approach for measuring and sampling NOAA in the workplace, applied to three case studies in laboratories each dedicated to materials with different shapes and dimensionalities: graphene, nanowires, and nanoparticles. The study is part of a larger project with the aim of improving risk management tools in nanomaterials research laboratories. The harmonized methodology proposed by the Organization for Economic Cooperation and Development (OECD) has been applied, including information gathering about materials and processes, measurements with easy-to-use and hand-held real-time devices, air sampling with personal samplers, and off-line analysis using scanning electron microscopy. Significant values beyond which an emission can be attributed to the NOAA production process were identified by comparison of the particle number concentration (PNC) time series and the corresponding background levels in the three laboratories. We explored the relations between background PNC and microclimatic parameters. Morphological and elemental analysis of sampled filters was done to identify possible emission sources of NOAA during the production processes: rare particles, spherical, with average diameter similar to the produced NOAA were identified in the nanoparticles laboratory, so further investigation is recommended to confirm the potential for worker exposure. In conclusion, the information obtained should provide a valuable basis for improving risk management strategies in the laboratory at work.


[SARS-CoV-2 vaccines and reaction of the immune system. Can the epidemic spread of the virus be prevented by vaccination?]
Since the end of 2019 a new coronavirus, SARS-CoV-2, first identified in Wuhan, China, is spreading around the world partially associated with a high death toll. Besides hygienic measurements to reduce the spread of the virus vaccines have been confected, partially based on the experiences with Ebola virus vaccine, based on recombinant human or chimpanzee adenovirus carrying the spike protein and its ACE2 receptor binding domain (RBD). Further vaccines are constructed by spike protein coding mRNA incorporated in lipid nano vesicles that after entry in human cells produce spike protein. Both vaccine types induce a strong immune response that lasts for months possibly for T-cell immunity a few years. Due to mutations in the coronavirus genome in several parts of the world variants selected, that were partially more pathogenic and partially easier transmissible - variants of concern (VOC). Until now vaccinees are protected against the VOC, even when protection might be reduced compared to the Wuhan wild virus.An open field is still how long the vaccine induced immunity will be sufficient to prevent infection and/or disease; and how long the time period will last until revaccination will be required for life saving protection, whether a third vaccination is needed, and whether revaccination with an adenovirus-based vaccine will be tolerated.


Laparoscopic nephrectomy, ex vivo partial nephrectomy, and autotransplantation for the treatment of complex renal masses.
In the contemporary era of minimally invasive surgery, very few T1/T2 renal lesions are not amenable to nephron-sparing surgery. However, centrally located lesions continue to pose a clinical dilemma. We sought to describe our local experience with three cases of laparoscopic nephrectomy, ex vivo partial nephrectomy, and autotransplantation. Laparoscopic donor nephrectomy was performed followed by immediate renal cooling and perfusion with isotonic solution. Back-table partial nephrectomy, renorrhaphy, and autotransplantation were then performed. Mean warm ischemia (WIT) and cold ischemic times (CIT) were 2 and 39 minutes, respectively. Average blood loss was 267 mL. All patients preserved their renal function postoperatively. Final pathology confirmed pT1, clear cell renal cell carcinoma with negative margins in all. All are disease free at up to 39 months follow-up with stable renal function. In conclusion, the described approach remains a viable option for the treatment of complex renal masses preserving oncological control and renal function.


Biological Maturation, Central Adiposity, and Metabolic Risk in Adolescents: A Mediation Analysis.
Earlier biological maturation has been related to increased metabolic risk. In this study, we verified mediating effects by central adiposity of the relationship between somatic maturity and metabolic risk factors in adolescents. In a cross-sectional study, 1034 adolescents aged 10-16 years from Londrina/PR/Brazil were evaluated. The age of peak height velocity (PHV) method was used to evaluate somatic maturity. Central adiposity was estimated through waist circumference measurements. Fasting glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C), and blood pressure were measured as metabolic risk indicators. Physical activity (Baecke questionnaire) and cardiorespiratory fitness (20-m shuttle run test) were used as covariates. Except for fasting glucose, waist circumference showed partial or full mediation of the relationship between maturity and the following metabolic risk factors with their respective z-score values: triglycerides (boys = -3.554 vs. girls = -5.031), HDL-C (boys = +5.300 vs. girls = +5.905), systolic blood pressure (boys = -3.540 vs. girls = -3.763), diastolic blood pressure (boys = -2.967 vs. girls = -3.264), and metabolic risk score (boys = -5.339 vs. girls = -6.362). The results suggest that central obesity plays a mediating role in the relationship between somatic maturation and metabolic risk during adolescence.


Challenges Facing the Use of Endothelial Progenitor Cells in Stem Cell Therapies.
The paper summarizes the difficulties to study the rare population of endothelial progenitor cells in clinical trials, based on the experience of our group in many publications in this area.


A Functional MicroRNA Screening Method for Organ Morphogenesis.
The increasing repertoire of microRNAs expressed during organ development and their role in regulating organ morphogenesis provide a compelling need to develop methods to assess microRNA function using various in vitro and in vivo experimental models. Methods to assess microRNA function during organ morphogenesis include transfection of microRNA inhibitors (antagomirs) and activators (mimics) into mouse embryonic explanted organs using liposomes, which can potentially result in low efficiency of transfection and off-target effects. We devised a method to assess microRNA function in explanted organs by transfecting antagomirs and mimics using peptide-based nanoparticles, increasing functional microRNA targeting efficiency, and decreasing off-target effects. Our method can be applied to a variety of embryonic organs that can be explanted and provides an alternative to efficiently and functionally prioritize microRNAs during organ morphogenesis for further in vivo genetic approaches. © 2017 by John Wiley & Sons, Inc.


The Relevant of Sex Hormone Levels and Acne Grades in Patients with Acne Vulgaris: A Cross-Sectional Study in Beijing.
The tests of sex hormones play pivotal roles in the clinical diagnosis and treatment of acne vulgaris, but the majority of patients with acne vulgaris present regular sex hormone levels within the normal reference range. To determine the correlation among levels of sex hormones, ratio of androgen to estrogen and acne grades in patients with acne vulgaris. A cross-sectional study was applied to collect 693 patients with acne vulgaris. All samples were screened by cluster sampling among those who underwent tests of sex hormones at Beijing Jingcheng Skin Hospital from July 2021 to June 2022. A gender stratified analysis was performed to classify acne grades I-IV. Spearman correlation analysis was used to analyze the relationship between age, sex hormones, ratio of androgen to estrogen and acne grades, with multinomial logistic regression to analyze the association of sex hormones with acne grades in patients with acne. (1) The testosterone levels were mostly within normal reference values for both males and females with varying degrees of acne. For females, the serum follicle-stimulating hormone, estradiol, progesterone, testosterone, and ratio of androgen to estrogen were significantly different between acne grades. For males, there were significant differences in serum estradiol, testosterone, and ratio of androgen to estrogen across acne grades. (2) The acne grade was negatively correlated with estradiol and positively correlated with the ratio of androgen to estrogen; the female acne grade was also negatively correlated with age and progesterone, but positively correlated with follicle-stimulating hormone. (3) Multivariate logistic regression analysis indicated that the ratio of androgen to estrogen was independently correlated with the grade of acne and that acne grade worsened as the ratio increased. The increase in the ratio of androgen to estrogen may aggravate the acne grade in patients with acne vulgaris.


Cobalt protoporphyrin accelerates TFEB activation and lysosome reformation during LPS-induced septic insults in the rat heart.
Lipopolysaccharide (LPS)-induced myocardial dysfunction is caused, at least in part, by mitochondrial dysfunction. Mitochondrial dysfunction and the oxidative damage associated with it are scavenged through various cellular defense systems such as autophagy to prevent harmful effects. Our recent study has demonstrated that cobalt protoporphyrin IX (CoPPIX), a potent inducer of heme oxygenase-1 (HO-1), ameliorates septic liver injuries by enhancing mitochondrial autophagy in rats. In our current study, we show that CoPPIX (5 mg/kg s.c.) not only accelerates the autophagic response but also promotes lysosome reformation in the rat heart treated with LPS (15 mg/kg i.p.). Lysosomal membrane-associated protein-2 (LAMP2), which is essential to the maintenance of lysosomal functions in the heart, is depleted transiently but restored rapidly during LPS administration in the rat. Activation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, was also observed, indicating a hyper consumption and subsequent reformation of the lysosome to meet the increased demand for autophagosome cleaning. CoPPIX was found to promote these processes and tended to restore the LPS-induced suppression of cardiac performances whilst chloroquine (CQ; 20 mg/kg i.p.), an inhibitor of lysosomes and autophagic protein degradation, abrogates these beneficial effects. The cardioprotective effect of CoPPIX against LPS toxicity was also observed via decreased levels of cardiac releasing enzymes in the plasma. Taken together, our current data indicate that lysosome reformation mediated by TFEB may be involved in cardioprotection against LPS-induced septic insults, and serve as a novel mechanism by which CoPPIX protects the heart against oxidative stress.


Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia.
Children with acute myelogenous leukemia (AML) have a high risk of infectious complications that might be reduced by prophylactic granulocyte colony-stimulating factor (G-CSF). However, G-CSF could induce AML blast proliferation. The prospective randomized trial AML-BFM 98 investigated the impact of G-CSF on hematopoetic recovery and infectious complications (primary endpoints) and on outcome (secondary endpoint) in children (aged 0-18 years) with de novo AML. Patients with more than 5% blasts in day-15 bone marrow or with FAB M3 were not included. Between 1998 and 2003, 161 children with AML were randomized to receive G-CSF after inductions 1 and 2, whereas 156 patients were assigned to the control group. Time of neutropenia after inductions 1 and 2 was significantly shorter in the G-CSF group (23 vs 18 days and 16 vs 11 days; P=.02 and=.001, respectively). G-CSF did not decrease the incidence of febrile neutropenia (72 and 36 patients vs 78 and 37 patients, respectively), microbiologically documented infections (27 and 25 patients vs 36 and 19 patients, respectively) and infection-associated mortality (5 vs 2 patients). Both groups had similar 5-year event-free survival (EFS; 59%+/-4% vs 58%+/-4%). Since G-CSF does not influence the risk of infectious complications or outcome in children undergoing therapy for AML, one cannot advocate the routine use of G-CSF in this patient group.


Activation of vascular BK channel by tempol in DOCA-salt hypertensive rats.
Large-conductance Ca2+-activated potassium (BK) channels modulate vascular smooth muscle tone. Tempol, a superoxide dismutase (SOD) mimetic, lowers blood pressure and inhibits sympathetic nerve activity in normotensive and hypertensive rats. In the present study, we tested the hypotheses depressor responses caused by tempol are partly mediated by vasodilation. It was found that tempol, but not tiron (a superoxide scavenger), dose-dependently relaxed mesenteric arteries (MA) in anesthetized sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Tempol also reduced perfusion pressure in isolated, norepinephrine (NE) preconstricted MA from sham and DOCA-salt hypertensive rats. Maximal responses in DOCA-salt rats were twice as large as those in sham rats. The vasodilation caused by tempol was blocked by iberiotoxin (IBTX, BK channel antagonist, 0.1 micromol/L) and tetraethylammonium chloride (TEA) (1 mmol/L). Tempol did not relax KCl preconstricted arteries in sham or DOCA-salt rats, and Nomega-nitro-L-arginine methyl ester (L-NAME), apamin, or glibenclamide did not alter tempol-induced vasodilation. IBTX constricted MA and this response was larger in DOCA-salt compared with sham rats. Western blots and immunohistochemical analysis revealed increased expression of BK channel alpha subunit protein in DOCA-salt arteries compared with sham arteries. Whole-cell patch clamp studies revealed that tempol enhanced BK channel currents in HEK-293 cells transiently transfected with mslo, the murine BK channel a subunit. These currents were blocked by IBTX. The data indicate that tempol activates BK channels and this effect contributes to depressor responses caused by tempol. Upregulation of the BK channel alpha subunit contributes to the enhanced depressor response caused by tempol in DOCA-salt hypertension.


SNOR and wheeze: the asthma enzyme?
Conventionally, asthma is defined as involving both airway inflammation and airway smooth muscle hyper-responsiveness. However, Que and coworkers have recently uncoupled these concepts, showing that mice lacking an S-nitrosothiol reductase have allergen-induced airway inflammation but do not have airway hyper-responsiveness. These data are consistent with recent clinical evidence that: (i) S-nitrosothiol signaling is abnormal in human asthma, (ii) nitric oxide in exhaled air might be only a biomarker for the metabolism of more physiologically relevant nitrogen oxides and (iii) the biochemical response to airway inflammation is central to asthma pathophysiology.


Congenital Lung Malformations: Unresolved Issues and Unanswered Questions.
Advances in prenatal and postnatal diagnosis, perioperative management, and postoperative care have dramatically increased the number of scientific reports on congenital thoracic malformations (CTM). Nearly all CTM are detected prior to birth, generally by antenatal ultrasound. After delivery, most infants do well and remain asymptomatic for a long time. However, complications may occur beyond infancy, including in adolescence and adulthood. Prenatal diagnosis is sometimes missed and detection may occur later, either by chance or because of unexplained recurrent or persistent respiratory symptoms or signs, with difficult implications for family counseling and substantial delay in surgical planning. Although landmark studies have been published, postnatal management of asymptomatic children is still controversial and needs a resolution. Our aim is to provide a focused overview on a number of unresolved issues arising from the lack of an evidence-based consensus on the management of patients with CTM. We summarized findings from current literature, with a particular emphasis on the vigorous controversies on the type and timing of diagnostic procedures, treatments and the still obscure relationship between CTM and malignancies, a matter of great concern for both families and physicians. We also present an algorithm for the assessment and follow-up of CTM detected either in the antenatal or postnatal period. A standardized approach across Europe, based on a multidisciplinary team, is urgently needed for achieving an evidence-based management protocol for CTM.


Cranial Anchored Mandible Distraction Osteogenesis.
Multiple or large distance mandibular distraction osteogenesis (MDO) in the older child is often complicated by iatrogenic temporomandibular joint (TMJ) pathology. The transmission of significant force to the TMJ in these particular patients is due to the greater distance of distraction required and the relative inelasticity of the soft tissue envelope. The authors present a clinical report of a successful asymmetrically vectored large distance MDO in a 13-year-old female with bilateral craniofacial microsomia with Goldenhar syndrome. During distraction, the TMJ joints were effectively unloaded from the forces of distraction using external bilateral cranial anchored devices (Cranio-Mandibular Fixator; KLS Martin, Jacksonville, FL). Angle's occlusion, facial angle, and evidence of TMJ pathology were assessed.


A novel method for determination of beta-lactamase using the agar dilution method.
A novel test procedure is described for the rapid assay of beta-lactamase using the agar dilution method. The susceptibility to beta-lactamase was measured by adding an appropriate amount of enzyme to the diluting culture broth of a test organism in the agar dilution method. By this method, beta-lactamase susceptibility can be expressed in the same way as the MIC assay for antibiotics (microgram/ml). The results obtained with Escherichia coli beta-lactamase were closely related to the MIC patterns of the strains producing beta-lactamases.


Anti-HIV-1 antibody testing using modified gelatin particle agglutination: a large field study.
Anti-HIV testing using gelatin particle agglutination (GPA) assay was investigated in parallel with ELISAs from routine service at Siriraj Hospital. In the first strategy, 174,032 sera from a patient population with an HIV-1 seroprevalence of 13.72 per cent were assayed using reduced volumes of GPA reagents, giving a cost reduction of 40 per cent. In the second strategy, 90,560 pregnant women and 48,936 emigrant workers with an HIV-1 seroprevalence of 2.2 per cent and 0.3 per cent, respectively, were tested in pools of 4 sera using the manufacturer's recommended volumes, giving a cost saving of 67 per cent. Overall, the sensitivity and specificity were almost identical with standard methods. Thus, parallel use of either modified GPA might be considered appropriate when testing large numbers of samples. However, both modified versions of GPA are not recommended as the first assay for diagnostic or blood bank screening especially in high prevalence of HIV infection.


Dysregulation of diurnal rhythms of serotonin 5-HT2C and corticosteroid receptor gene expression in the hippocampus with food restriction and glucocorticoids.
Both serotonergic dysfunction and glucocorticoid hypersecretion are implicated in affective and eating disorders. The adverse effects of serotonergic (5-HT)2C receptor activation on mood and food intake, the antidepressant efficacy of 5-HT2 receptor antagonists, and the hyperphagia observed in 5-HT2C receptor knockout mice all suggest a key role for increased 5-HT2C receptor-mediated neurotransmission. Glucocorticoids, however, downregulate 5-HT2C receptor mRNA in the hippocampus, and it is unclear how increased 5-HT2C receptor sensitivity is achieved in the presence of elevated glucocorticoid levels in depression. Here we show a monophasic diurnal rhythm of 5-HT2C receptor mRNA expression in the rat hippocampus that parallels time-dependent variations in 5-HT2C receptor agonist-induced behaviors in open field tests. Rats entrained to chronic food restriction show marked but intermittent corticosterone hypersecretion and maintain an unaltered 5-HT2C receptor mRNA rhythm. The 5-HT2C receptor mRNA rhythm, however, is suppressed by even modest constant elevations of corticosterone (adrenalectomy + pellet) or with elevated corticosterone during the daytime (8 A.M.), whereas a normal rhythm exists in animals that have the same dose of corticosterone in the evening (6 P.M.). Thus, animals showing even a transient daytime corticosterone nadir exhibit normal hippocampal 5-HT2C receptor mRNA rhythms, even in the presence of overt corticosterone hypersecretion. Chronic food restriction also abolishes the normal diurnal variation in hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor mRNAs and produces, unusually, both elevated corticosterone and increased GR. The mismatch between elevated glucocorticoids and maintained 5-HT2C receptor and increased GR gene expression in the hippocampus provides a new model to dissect mechanisms that may underlie affective and eating disorders.


Curcumin attenuated acute Propionibacterium acnes-induced liver injury through inhibition of HMGB1 expression in mice.
Curcumin is a phenolic product isolated from the rhizome of Curcuma longa and has protective effects on inflammatory diseases. Here we investigated the protective effect of curcumin in acute Propionibacterium acnes (P. acnes)-induced inflammatory liver injury. C57BL/6 mice were primed with P. acnes followed by LPS challenge to induce fulminant hepatitis. Curcumin or vehicle control was administered perorally by gavage once daily starting 2days before P. acnes priming. We found that curcumin significantly improved mouse mortality. Then, to investigate the underlying mechanisms of curcumin in this acute inflammatory liver injury model, we primed C57BL/6 mice with P. acnes only. We found that curcumin treatment attenuated P. acnes-induced liver injury as evidenced by decreased production of ALT. In addition, curcumin treatment reduced the production of proinflammatory cytokines such as TNF-α and IFN-γ, accompanied by reduced hepatocyte apoptosis. Furthermore, curcumin treatment significantly reduced HMGB1 cytoplasmic translocation and expression by down-regulating acetylation of lysine. Taken together, our results suggest that curcumin protects mice from P. acnes-induced liver injury through reduction of HMGB1 cytoplasmic translocation and expression.


Evaluation and management of patients with chronic thromboembolic pulmonary hypertension - consensus statement from the ISHLT.
ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.


Graph-guided joint prediction of class label and clinical scores for the Alzheimer's disease.
Accurate diagnosis of Alzheimer's disease and its prodromal stage, i.e., mild cognitive impairment, is very important for early treatment. Over the last decade, various machine learning methods have been proposed to predict disease status and clinical scores from brain images. It is worth noting that many features extracted from brain images are correlated significantly. In this case, feature selection combined with the additional correlation information among features can effectively improve classification/regression performance. Typically, the correlation information among features can be modeled by the connectivity of an undirected graph, where each node represents one feature and each edge indicates that the two involved features are correlated significantly. In this paper, we propose a new graph-guided multi-task learning method incorporating this undirected graph information to predict multiple response variables (i.e., class label and clinical scores) jointly. Specifically, based on the sparse undirected feature graph, we utilize a new latent group Lasso penalty to encourage the correlated features to be selected together. Furthermore, this new penalty also encourages the intrinsic correlated tasks to share a common feature subset. To validate our method, we have performed many numerical studies using simulated datasets and the Alzheimer's Disease Neuroimaging Initiative dataset. Compared with the other methods, our proposed method has very promising performance.


Ultrasound studies in ectopic pregnancies.
Early diagnosis of ectopic pregnancy reduces the mortality and morbidity associated with the disease, and the morbidity associated with the therapy. When diagnosis was limited to the cases presenting with tubal rupture, salpingectomy was the only possible treatment. If ectopic pregnancy can be diagnosed earlier, clinicians are able to use new therapies such as laparoscopic microsurgery or medical therapy with methrotrexate, which are less invasive and less tissue destructive. Transvaginal ultrasound has proven to be an essential tool in the early diagnosis of ectopic pregnancy. Colour Doppler capacities further enhance the diagnostic sensitivity of transvaginal ultrasound for the early recognition of abnormal and normal intrauterine pregnancy, and small extrauterine masses. The aim of this paper is to provide an overview of the major sonographic signs and pitfalls in the ultrasound diagnosis of ectopic pregnancy.


Efficacy and tolerance of metronidazole and miconazole nitrate in treatment of vaginitis.
To evaluate the efficacy and tolerability of a vaginal pessary containing 750 mg of metronidazole and 200 mg of miconazole nitrate used daily for 7 days in the treatment of vaginitis. Ninety-two women with vaginitis participated in this phase 3 study using one vaginal pessary daily for 7 days. Gynecological and microbiological evaluations were carried out prior to and following treatment. Reductions occurred in symptoms and signs of vaginitis. Clinical cure rate was 87.7%, while the cure rates according to microscopy and Candida albicans culture were 81.8% and 73.9%, respectively. The cure rate for bacterial vaginosis was 75% and culture of Gardnerella vaginalis turned negative in 63.6% of cases following treatment. The medication was well tolerated. Use of a combination of 750 mg of metronidazole and 200 mg of miconazole in a single daily application was found to be effective in the treatment of the most common causes of vaginitis.


The anti-virulence activity of the non-mevalonate pathway inhibitor FR900098 towards Burkholderia cenocepacia is maintained during experimental evolution.
Burkholderia cenocepacia infections are difficult to treat and there is an urgent need for alternative (combination) treatments. The use of anti-virulence therapies in combination with antibiotics is a possible strategy to increase the antimicrobial susceptibility of the pathogen and to slow down the development of resistance. In the present study we evaluated the β-lactam and colistin-potentiating activity, and anti-virulence effect of the non-mevalonate pathway inhibitor FR900098 against B. cenocepacia in various in vitro and in vivo models. In addition, we evaluated whether repeated exposure to FR900098 alone or when combined with ceftazidime leads to increased resistance. FR900098 potentiated the activity of colistin and several β-lactam antibiotics (aztreonam, cefepime, cefotaxime, ceftazidime, mecillinam and piperacillin) but not of imipenem and meropenem. When used alone or in combination with ceftazidime, FR900098 increased the survival of infected Galleria mellonella and Caenorhabditis elegans. Furthermore, combining ceftazidime with FR900098 resulted in a significant inhibition of the biofilm formation of B. cenocepacia. Repeated exposure to FR900098 in the C. elegans infection model did not lead to decreased activity, and the susceptibility of the evolved B. cenocepacia HI2424 lineages to ceftazidime, FR900098 and the combination of both remained unchanged. In conclusion, FR900098 reduces B. cenocepacia virulence and potentiates ceftazidime in an in vivo C. elegans model, and this activity is not lost during the experimental evolution experiment carried out in the present study.


A novel control scheme for inducing angiostatin-human IgG fusion protein production using recombinant CHO cells in a oscillating bioreactor.
In this study, a novel control scheme for inducing protein production using a recombinant CHO cell line in a BelloCell bioreactor was developed. This control scheme was applied in a simple regular semi-batch process. Production of angiostatin-human IgG fusion protein in a suspension recombinant CHO cell culture and a protein-free medium was used for this study. The bottom holding time (BH) was the sole operating variable to control the exposure time of the cells immobilized on the carriers to the air and allow the nutrient remained on the liquid film of the carriers to be consumed to a threshold level so that the cells can be arrested and promoted for protein production. In the cell cultures with various BH (1.5-90 min), final cell densities of 1.6-4.0 x 10(9) have been obtained in 20 days while total angiostatin-human IgG production of 228-388 mg have been harvested. In general, low BH will minimize the nutrient limitation and favor the cell growth, while high BH will restrict the nutrient and promote the production in this type of non-growth associated production systems. It was found that specific production rate was generally inversely proportional to the specific growth rate. In this case of study, BH of 30 and 60 min were found to be about 72% better than BH of 1.5 min and 35% better than BH of 9 and 90 min in term of the total angiostatin-human IgG production. In comparison to a conventional spinner flask study, a 3.8-fold increase of the total angiostatin-human IgG production was realized in a 35-day culture. This study illustrated that a simple method of using BH in a semi-batch process can effectively control the apparent nutrient concentration to the cells, and thus regulate the cell growth and protein production in a novel oscillating bioreactor.


[Immunologic and genetic aspects of endometriosis physiopathology].
This article reviews the pathological mechanism of endometriosis. We concentrate on immunological and genetical factors which play a role in the developing of endometriosis. We present the possible network of interactions between immune cells, hormones and matrix metalloproteases system in the ectopic endometrial tissue.


Some new molluscan hosts of Dicrocoelium dendriticum in Spain.
Twenty species of the family Helicidae (Gastropoda, Pulmonata) from the N.W. of Spain were tested as hosts for D. dendriticum in experimental conditions. The relationship between the egg hatching in the digestive tract and the development of sporocysts (108-110 days after egg ingestion) was studied. Three species were found to be new intermediate hosts of this trematode: Candidula intersecta , Helicella corderoi and H. jamuzensis . On the basis of the results obtained, the ecological value of the positive species in the life cycle of the parasite is discussed.


Outcomes After Derotational Distal Femoral Osteotomy for Recurrent Patellar Dislocations With Increased Femoral Anteversion: A Systematic Review and Meta-analysis.
An increased femoral anteversion angle (FAA) is a predisposing factor for recurrent patellar dislocations (RPDs), and combined procedures including derotational distal femoral osteotomy (DDFO) have been shown to be good options. To investigate the safety and effectiveness of combined DDFO on clinical and radiological outcomes to treat RPDs with an increased FAA. Systematic review; Level of evidence, 4. This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. We searched 7 databases for articles from inception to March 10, 2023, that reported outcomes after combined DDFO in patients with an RPD and increased FAA. Two reviewers independently extracted data and assessed study quality. Outcomes evaluated were functional scores, redislocation rates, complications, satisfaction, and radiological parameters. A meta-analysis was performed to pool functional scores, with data reported as mean differences (MDs) and 95% confidence intervals (CIs). Included were 8 studies of 189 knees from 183 patients, with a mean patient age of 22.4 years and a mean follow-up of 33.4 months. The mean preoperative FAA ranged from 31° to 42.70°, and the mean postoperative FAA ranged from 10° to 19.08°. Significant improvements were found in the Kujala score (MD, 26.96 [95% CI, 23.54 to 30.37]), Lysholm score (MD, 26.17 [95% CI, 22.13 to 30.22]), visual analog scale score for pain (MD, -2.61 [95% CI, -3.12 to -2.10]), and Tegner activity score (MD, 1.33 [95% CI, 0.86 to 1.79]). No subluxation or redislocation occurred. The overall complication rate was 10.6%, and most of the complications were pain (60%) and limited knee activity (20%). The overall satisfaction rate was 83.3%. The patellar tilt angle significantly decreased from 40.7° ± 11.9° to 20.5° ± 8.7° and from 26.35° ± 6.86° to 11.65° ± 2.85° in 2 studies. Combined DDFO was found to be safe and effective for the treatment of RPDs and an increased FAA by addressing both patellar dislocations and torsional malalignment. However, because of the lack of comparisons, it remains to be investigated when DDFO should be combined in such patients.


Ultrafast excited-state dynamics of tetraphenylethylene studied by semiclassical simulation.
Detailed simulation study is reported for the excited-state dynamics of photoisomerization of cis-tetraphenylethylene (TPE) following excitation by a femtosecond laser pulse. The technique for this investigation is semiclassical dynamics simulation, which is described briefly in the paper. Upon photoexcitation by a femtosecond laser pulse, the stretching motion of the ethylenic bond of TPE is initially excited, leading to a significant lengthening of ethylenic bond in 300 fs. Twisting motion about the ethylenic bond is activated by the energy released from the relaxation of the stretching mode. The 90 degrees twisting about the ethylenic bond from an approximately planar geometry to nearly a perpendicular conformation in the electronically excited state is completed in 600 fs. The torsional dynamics of phenyl rings which is temporally lagging behind occurs at about 5 ps. Finally, the twisted TPE reverts to the initial conformation along the twisting coordinate through nonadiabatic transitions. The simulation results provide a basis for understanding several spectroscopic observations at molecular levels, including ultrafast dynamic Stokes shift, multicomponent fluorescence, viscosity dependence of the fluorescence lifetime, and radiationless decay from electronically excited state to the ground state along the isomerization coordinate.


Human T cell cyclophilin18 binds to thiol-specific antioxidant protein Aop1 and stimulates its activity.
Cyclophilins (CyPs) define a family of proteins binding to the immunosuppressive drug cyclosporin A (CsA). They are evolutionary highly conserved proteins being present in both pro- and eukaryotes and in different subcellular locations. CyPs possess enzymatic activity, namely peptidyl-prolyl cis-trans isomerase (PPIase) activity and are involved in cellular protein folding and protein interactions. Here we describe a novel interaction of human T cell cyclophilin18 (hCyP18). Abundant cytosolic hCyP18 binds to the thiol-specific antioxidant protein Aop1 and stimulates its enzymatic activity. Aop1 belongs to a family of proteins thought to be involved in defense of oxidative stress. The interaction of both proteins seem to be specific, since other PPIases do not have any stimulatory effect on Aop1.


Developmental environment contributes to rapid trait shifts among newly colonized subterranean habitats.
Recent colonization of extreme environments provides unique opportunities to study the early steps of adaptation and the potential for rapid convergent evolution. However, phenotypic shifts during recent colonization may also be due to plasticity in response to changes in the rearing environment. Here, we analyzed a suite of morphological and behavioral traits in paired surface, subterranean, and facultatively subterranean Mexican tetras ( Astyanax mexicanus) from recent introductions in two separate watersheds outside of their native range. We found a variety of phenotypic and behavioral shifts between subterranean and surface populations that are similar to those observed in relatively ancient populations in Mexico. Despite this rapid morphological divergence, we found that most of these trait differences were due to plasticity in response to rearing environments. While most trait assays in common-garden, lab-raised fish indicated that phenotypic shifts in wild fish were the result of plasticity, we also found evidence of genetic control in several traits present in subterranean populations. Interestingly, wall-following behavior, an important subterranean foraging behavior, was greater in lab-born subterranean fish than in lab-born surface fish, suggesting rapid divergence of this trait between subterranean and surface populations. Thus, this study sheds light on the early steps of subterranean evolution, identifies potential rapid behavioral evolution, and suggests that plasticity in traits involving exploratory behavior may facilitate subterranean colonization.


Correlates of adiposity in a Caribbean pre-school population.
To evaluate ethnic and anthropometric correlates of adiposity among a nationally representative, multi-ethnic, Trinidadian pre-school population. Cross-sectional study conducted between June 2008 and July 2009. Government and privately owned Early Childhood Care and Education Centres in Trinidad. A total of 596 pre-school children (aged 31-73 months) from thirty-four schools had their weight, height, mid-upper arm circumference, waist circumference, biceps and triceps skinfold thicknesses measured by a registered dietitian using standard procedures. Percentage body fat was estimated using a foot-to-foot bioelectric impedance analyser (Tanita 531, Tokyo, Japan). Date of birth, religion and ethnicity were extracted from school records and pre-schoolers' ethnicity was categorized as East Indian, African, Mixed (a combination of two or more ethnicities), Chinese or Caucasian. Anthropometric variables explained significantly more of the variance in adiposity among girls (67·4-88·1 %) than boys (24·4-39·2 %; P < 0·0 0 1). Pre-schoolers of African descent were significantly taller, heavier and had higher abdominal fat and mid-upper arm circumference than their East Indian and Mixed counterparts (all P < 0·001). The overall prevalence of excess adiposity (≥25 % body fat) as determined by bioelectrical impedance was 14·6 %, while 2·9 % of the children were undernourished according to WHO weight-for-age criteria. Differences in anthropometry were non-existent between children attending government and private pre-schools. Gender, ethnicity and anthropometry all explained excess adiposity in these pre-schoolers. These findings highlight the need to elucidate the mechanisms that may be involved in explaining these differences, particularly those of ethnic origin.


Phase II/III Randomized Controlled Trial of Concomitant Hyperfractionated Radiotherapy plus Cetuximab (Anti-EGFR Antibody) or Chemotherapy in Locally Advanced Head and Neck Cancer.
Globally, there is marked variation in overall incidence and presentation of head and neck cancers, these cancers account for 11.5 per 100,000 population in G.C.C states. Concomitant chemotherapy and external beam radiotherapy (EBRT) is indicated in such cancers with aim of organ preservation, control and possible cure. Hyper fractionated radiotherapy with concomitant chemotherapy or cetuximab is a lesser explored option. In this study we wish to assess the tolerability and efficacy of cetuximab with altered fractionation and compare this with the chemotherapy (cisplatin). This is a randomized controlled study from a single institute in Kuwait. Locally advanced head and neck cancer cases excluding cancer nasopharynx are enrolled for the study. Stage III or stage IV-A cases were enrolled with histopathology squamous cell carcinoma. Patients were randomized into 2 arms. Arm A: to receive platinum-based CT i.e. cisplatin in a dose of 100 mg/m2 3-weekly or 40 mg/m2 weekly during radiation; Arm B: received cetuximab with a loading dose 400 mg/m², one week before radiation followed by weekly dose of 250 mg/m² during radiation. Radiotherapy was delivered using intensity modulated radiotherapy (IMRT) or 3D-conformal radiotherapy (CRT). The primary objective was to evaluate whether the use of cetuximab with concurrent hyperfractionated radiation regimen will have loco regional control rates (LC) and Disease-free survival (DFS) that are comparable to concurrent cisplatin in patients with LAHNC. The secondary endpoints were to compare the impact of using concurrent cetuximab vs chemotherapy regimen on Overall Survival of patients (OS) and acute and late adverse events. From November 2012 to November 2017, 40 patients were randomized. The median age of was 51 years (range 27-72 years). Thirty-five patients are male and remaining was female. 14 patients have their primaries in larynx, 11 in oropharynx, 8 in oral cavity, and 5 has tumor in hypopharynx. Two patients had disease in nasal sinus or overlapping subsides. 50% has T4 lesions while 35% has T3 lesions, Nodal status was (N0-1) in 20 patients and (N2-3) in 20 patients. Overall staging showed a majority to have stage IV disease (63%). HPV was negative in 2 cases in Arm 1 and positive in 2 cases in Arm 2. 22 patients were randomly allocated in Arm A (platinum-based) while 18 were in Arm B (cetuximab). CR was achieved in 59% in arm A vs 50% in Arm B, while PR was 27.3% and 27.8% respectively. Disease progressed in 2 patients in Arm B only. Out of these 40 patients, 14 patients failed (6 and 8 in arm A and B respectively). Locoregional failure was documented in 6 (27.3%) vs 7 (38.9%) of arm A and B respectively, which was statistically not significant possibly related with lower number of cases. 2 years DFS was 56.5% vs 77.3% in cisplatin vs cetuximab arm (denoting nonsignificant increase of relapse rate in cisplatin arm). However, 2 years OS was 80.7% vs 57.3% in cisplatin and cetuximab arm respectively (p value=0.04). Though cetuximab has lesser side effects but it is not indicated in treatment of LAHNC. Concurrent cisplatin is a trusted option for concomitant setting regardless of the HPV status and tumor location. However, in the context of cisplatin ineligible patients, cetuximab should be used only with hyper fractionation. This preliminary study could represent a good core of large international multicenter RCT.


Clinical efficacy of antibiotics in the treatment of peri-implantitis.
The aim of the present study was to review the pertinent literature with reference to the clinical efficacy of antibiotics in the treatment of peri-implantitis. To address the focused question 'Are locally and systemically delivered antibiotics useful in the treatment of peri-implantitis?' PubMed/Medline and Google-scholar databases were explored from 1992 until February 2013 using a combination of the following keywords: 'antibiotic,' 'dental implant,' 'inflammation,', 'peri-implantitis' and 'treatment'. Letters to the editor, case-reports and unpublished data were excluded. Ten studies were included. In six studies, peri-implantitis was treated using a non-surgical approach (scaling and root planing), whereas in four studies, a surgical approach was adopted for treating peri-implantitis. In three studies systemic antibiotics were administered and in six studies locally delivered antibiotics were used for treatment. One study used the oral route for antibiotic delivery. In three studies, minocycline hydrochloride was locally delivered as an adjunctive therapy to non-surgical mechanical debridement of infected sites. Nine studies reported that traditional peri-implantitis treatment with adjunct antibiotic therapy reduces gingival bleeding, suppuration and peri-implant pocket depth. In one study, despite surgical debridement of infected sites and systemic antibiotic cover, nearly 40% of the implants failed to regain stability. There was no placebo or control group in eight out of the nine studies included. The significance of adjunctive antibiotic therapy in the treatment of peri-implantitis remains debatable.


Onset of synchronization in complex gradient networks.
Recently, it has been found that the synchronizability of a scale-free network can be enhanced by introducing some proper gradient in the coupling. This result has been obtained by using eigenvalue-spectrum analysis under the assumption of identical node dynamics. Here we obtain an analytic formula for the onset of synchronization by incorporating the Kuramoto model on gradient scale-free networks. Our result provides quantitative support for the enhancement of synchronization in such networks, further justifying their ubiquity in natural and in technological systems.


[Bone tissue metabolism in systematic lupus erythematosus patients treated with glucocorticosteroids].
The present study has been undertaken to evaluate bone turn-over in patients with systemic lupus erythematosus (SLE) treated with glucocorticosteroids. Thirty-eight patients with definite SLE has been investigated. The following parameters have been determinated. Some proinflammatory cytokine: interleukin-IL-1 alpha (IL-1 alpha), interleukin-IL-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony stimulating factor (GM-CSF) and some biochemical markers of osteoporosis: osteocalcin (BGP), alkaline phosphatase-bone formation (AP-B), procollagen type I carboxyterminal propeptide (PICP), carboxyterminal telopeptides of type I collagen (CTx) deoxypyridinoline (Dpd) and calcium/creatinin ratio have been determined. The forearm densitometry measurement was performed in all patients. We did not notice statistically significant decrease in bone mineral content and bone mineral density in spite of long term glucocorticosteroids treatment. Based on statistically significant correlation between carboxyterminal telopeptides of type I collagen (CTx) and calcium/creatinin ratio we observed increased bone resorption in analysed group of patients.


Expression patterns and prognostic value of m6A RNA methylation regulators in adrenocortical carcinoma.
Adrenocortical carcinoma (ACC) is considered a rare cancer with poor prognosis. We used public datasets from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to assess the relationships between N6-methyladenosine (m6A)-related genes and ACC.We used the Wilcoxon signed-rank test to compare m6A-related gene expression in ACC tissues with that in normal tissues. Then, ACC patients were grouped based on a cluster analysis of m6A-related gene expression. m6A-related genes that were significantly associated with survival were incorporated into a risk signature, and 2 groups were divided according to median risk score. Fisher exact tests were utilized to analyze differences in clinical variables between groups. We compared the overall survival (OS) rates of the groups by means of Kaplan-Meier curves and Cox regression analyses.We found that RBM15, ZC3H3, YTDHF1, YTDHF2, and ALBH5 were overexpressed in ACC and that KIAA1429, YTHDC1, HNRNPC, WTAP, METTL3, and FTO were down regulated in ACC. In addition, membership in cluster 2 or the high-risk group was associated with advanced clinical factors and poor prognosis. The univariable and multivariable Cox regression analyses showed that risk score can be considered an independent prognostic factor for ACC.We found that the expression of m6A-related genes could be used as an independent prognostic factor in ACC. However, the current study has some limitations, and further studies of m6A-related genes in ACC are needed.


[Establishment and rudimentary application of the method of recording auditory brainstem responses electrically stimulated via round-window niche in cochlear implants].
To establish the method of recording auditory brainstem responses electrically stimulated via round-window niche in cochlear implants. Self-made platinum iridium alloy as a spherical electrode stimulation electrode, modified cochlear implants connected to in vitro speech processor as a electro-stimulator and evoke potential instrument for Bio-logic Navigator Pro, 17 cochlear implant patients with various ages and of different causes, including auditory neuropathy (2 cases), ossified cochlea (1 case), inner ear malformation (5 cases), leukodystrophy (1 case), unknown and reason (8 cases) were investigated during cochlear implant surgery. Before cochlear implantation, stimulation electrode was placed in the round-window niche while charge balanced biphasic constant current was used as electrical stimulation via round window niche, and then electrically evoked auditory brainstem response was recorded. Electrically evoked auditory brainstem response waveforms were clearly recorded in all 17 cases. The latencies of III and V waves were (2.12 +/- 0.18) ms and (4.18 +/- 0.19) ms respectively, with threshold as (220.0 +/- 16.04) CL. The waveforms of the 2 patients with auditory neuropathy, 5 patients with inner ear malformation, 1 patient with ossified cochlea and 1 patient with leukodystrophy were well differentiated. Monitoring electrically evoked auditory brainstem response was an objective nerve electrophysiological testing method that accurately reflects function completeness of auditory pathway. It had important value for helping making the judgment whether patients could acquire auditory response after cochlear implantation. This method was safe and gave high emission of auditory response, therefore should be spread widely.


Borderline personality disorder and mental health care utilization: The role of self-harm.
The current study examined the associations for borderline personality disorder (BPD) and a specific trait of the disorder, self-harm, with mental health care utilization. Our sample consisted of 145 psychiatric inpatients who completed 3 measures of BPD (Personality Diagnostic Questionnaire-4 [PDQ-4], McLean Screening Inventory for borderline personality disorder [MSI-BPD], Structured Clinical Interview for DSM-IV Axis II Disorders-Personality Questionnaire [SCID-II-PQ]) and the Self-Harm Inventory (SHI). In relationship to mental health care utilization, the correlation for the SHI was significantly larger than those for the PDQ-4, MSI-BPD, or SCID-II-PQ. Thus, self-harm was significantly better at detecting mental health care utilization than was the overall BPD construct, which indicates that some of the more severe manifestations of the disorder are the most predictive of impairment in functioning. These findings also call into question whether BPD (and by extension, personality pathology in general) is most useful in these symptom constellations as opposed to focusing on specific maladaptive traits. (PsycINFO Database Record


The advection of microparticles, MCF-7 and MDA-MB-231 breast cancer cells in response to very low Reynolds numbers.
The lymphatic system is an extensive vascular network that serves as the primary route for the metastatic spread of breast cancer cells (BCCs). The dynamics by which BCCs travel in the lymphatics to distant sites, and eventually establish metastatic tumors, remain poorly understood. Particle tracking techniques were employed to analyze the behavior of MCF-7 and MDA-MB-231 BCCs which were exposed to lymphatic flow conditions in a 100 μm square microchannel. The behavior of the BCCs was compared to rigid particles of various diameters (η = dp/H= 0.05-0.32) that have been used to simulate cell flow in lymph. Parabolic velocity profiles were recorded for all particle sizes. All particles were found to lag the fluid velocity, the larger the particle the slower its velocity relative to the local flow (5%-15% velocity lag recorded). A distinct difference between the behavior of BCCs and particles was recorded. The BCCs travelled approximately 40% slower than the undisturbed flow, indicating that morphology and size affects their response to lymphatic flow conditions (Re < 1). BCCs adhered together, forming aggregates whose behavior was irregular. At lymphatic flow rates, MCF-7s were distributed uniformly across the channel in comparison to the MDA-MB-231 cells which travelled in the central region (88% of cells found within 0.35 ≤ W ≤ 0.64), indicating that metastatic MDA-MB-231 cells are subjected to a lower range of shear stresses in vivo. This suggests that both size and deformability need to be considered when modelling BCC behavior in the lymphatics. This finding will inform the development of in vitro lymphatic flow and metastasis models.


Investigation of the Cs2(Mo,Te)O4 Solid Solution and Implications on the Joint Oxyde-Gaine System in Fast Neutron Reactors.
The formation of a thin layer, the so-called Joint Oxyde-Gaine (JOG), between the (U,Pu)O2 fuel pellets and the cladding has been observed in fast neutron reactors, due to the accumulation of volatile fission products. Cs2MoO4 is known to be one of the major components of the JOG, but other elements are also present, in particular tellurium and palladium. In this work, an investigation of the structural and thermodynamic properties of Cs2TeO4 and Cs2Mo1-xTexO4 solid solution is reported. The existence of a complete solubility between Cs2MoO4 and Cs2TeO4 is demonstrated, combining X-ray diffraction (XRD), neutron diffraction (ND), and X-ray absorption spectroscopy (XAS) results. High-temperature XRD measurements were moreover performed on Cs2TeO4, which revealed the existence of a α-β phase transition around 712 K. Thermal expansion coefficients were also obtained from these data. Finally, phase equilibra points in the Cs2MoO4-Cs2TeO4 pseudobinary phase diagram were collected using differential scanning calorimetry and used to develop a thermodynamic model for this system using a regular solution formalism.


Vindoline Exhibits Anti-Diabetic Potential in Insulin-Resistant 3T3-L1 Adipocytes and L6 Skeletal Myoblasts.
Type 2 diabetes mellitus (T2DM) emerged as a major health care concern in modern society, primarily due to lifestyle changes and dietary habits. Obesity-induced insulin resistance is considered as the major pathogenic factor in T2DM. In this study, we investigated the effect of vindoline, an indole alkaloid of Catharanthus roseus on insulin resistance (IR), oxidative stress and inflammatory responses in dexamethasone (IR inducer)-induced dysfunctional 3T3-L1 adipocytes and high-glucose-induced insulin-resistant L6-myoblast cells. Results showed that dexamethasone-induced dysfunctional 3T3-L1 adipocytes treated with different concentrations of vindoline significantly enhanced basal glucose consumption, accompanied by increased expression of GLUT-4, IRS-1 and adiponectin. Similarly, vindoline-treated insulin-resistant L6 myoblasts exhibited significantly enhanced glycogen content accompanied with upregulation of IRS-1 and GLUT-4. Thus, in vitro studies of vindoline in insulin resistant skeleton muscle and dysfunctional adipocytes confirmed that vindoline treatment significantly mitigated insulin resistance in myotubes and improved functional status of adipocytes. These results demonstrated that vindoline has the potential to be used as a therapeutic agent to ameliorate obesity-induced T2DM-associated insulin resistance profile in adipocytes and skeletal muscles.


A Double-Blind Randomized Placebo-Controlled Pilot Study of Azithromycin in Youth with Acute-Onset Obsessive-Compulsive Disorder.
Sudden and severe onset of obsessive-compulsive disorder (OCD) may present secondary to infectious and/or immune-mediated triggers. We assessed the preliminary efficacy, tolerability, and safety of azithromycin compared with placebo in the treatment of OCD and associated symptoms in children with pediatric acute-onset neuropsychiatric syndrome (PANS). Thirty-one youth aged 4-14 years (M = 8.26 ± 2.78 years, 62.5% male) were randomized to receive either placebo or azithromycin for 4 weeks (10 mg/kg up to 500 mg per day). Both groups were administered twice daily probiotics. The primary outcome, obsessive-compulsive symptom severity, was assessed using the OCD Clinical Global Impressions Severity (CGI-S OCD) and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Participants in the azithromycin group (n = 17) showed significantly greater reductions in OCD severity on the CGI-S OCD than the placebo group (n = 14) posttreatment (p = 0.003), although there were no significant differences on the CY-BOCS. Significantly more participants in the azithromycin condition met treatment responder criteria on the CGI-I OCD at the end of week 4 (41.2%, n = 7) in comparison to the placebo group (7.1%, n = 1; p = 0.045). Tic severity moderated treatment response, with greater tic severity being associated with enhanced treatment response on the CGI-S OCD. Azithromycin was well tolerated with minimal adverse effects and no study dropouts due to side effects. However, the azithromycin group showed a trend toward significantly greater electrocardiography QTc (p = 0.060) at the end of week 4, and significantly more reports of loose or abnormal stools (p = 0.009). This double blind pilot study suggests that azithromycin may be helpful in treating youth meeting the PANS diagnosis, especially those with elevated levels of both OCD and tic symptoms. Azithromycin was well tolerated, but the potential for cardiac risks suggests that additional monitoring may be needed to ensure safety.


A Rare Case of Digoxin Associated Gingival Overgrowth.
This case report presents a case of drug induced gingival overgrowth in a 28-year-old female patient with history of Coronary Artery Disease (CAD) and was prescribed digoxin in combination with furosemide and acitrom for the same. On clinical examination, the patient presented with severe gingival overgrowth. The volume of enlargement seen did not correlate solely with the diagnosis of inflammatory Gingival Enlargement (GE), hence an added drug induced component to the Gingival Overgrowth (GO) was suspected. It was decided to treat the condition using initial therapy {meticulous Scaling and Root Planning (SRP)} followed by a period of observation and maintenance. On recall, since there was no marked improvement, surgical intervention was planned. Periodic treatment combining surgery and maintenance ultimately produced the desired results clinically. Thus, this article within limits highlights that because of time-relationship between the starting of the medication that is digoxin and manifestation of GO, a causal relationship is likely.


Non-communicable diseases in the South-East Asia region: burden, strategies and opportunities.
Non-communicable diseases (NCDs) are a global health and developmental emergency, as they cause premature deaths,exacerbate poverty and threaten national economies. In 2008, they were the top killers in the South-East Asia region, causing 7.9 million deaths; the number of deaths is expected to increase by 21% over the next decade. One-third of the 7.9 million deaths (34%) occurred in those <60 years of age (compared to 23% in the rest of the world). Of the total deaths in the South-East Asia region (14.5 million), cardiovascular diseases accounted for 25%, chronic respiratory diseases 9.6%, cancer 7.8% and diabetes 2.1%. NCDs are largely attributable to a few preventable risk factors, all of which are highly prevalent in the region-tobacco use, unhealthy diet, lack of physical activity and harmful use of alcohol. Key strategies for the prevention and control of NCDs include (i) reducing exposure to risk factors through health promotion and primary prevention, (ii) early diagnosis and management of people with NCDs, and (iii) surveillance to monitor trends in risk factors and diseases. Tackling NCDs calls for a paradigm shift: from addressing each NCD separately to collectively addressing a cluster of diseases in an integrated manner, and from using a biomedical approach to a public health approach guided by the principles of universal access and social justice. High levels of commitment and multisectoral actions are needed to reverse the growing burden of NCDs in the South-East Asia region.


[COMPUTER TECHNOLOGY FOR ACCOUNTING OF CONFOUNDERS IN THE RISK ASSESSMENT IN COMPARATIVE STUDIES ON THE BASE OF THE METHOD OF STANDARDIZATION].
There was performed an analysis of the accounting of the impact of concomitant variables (confounders), introducing a systematic error in the assessment of the impact of risk factors on the resulting variable. The analysis showed that standardization is an effective method for the reduction of the shift of risk assessment. In the work there is suggested an algorithm implementing the method of standardization based on stratification, providing for the minimization of the difference of distributions of confounders in groups on risk factors. To automate the standardization procedures there was developed a software available on the website of the Institute of Industrial Ecology, UB RAS. With the help of the developed software by numerically modeling there were determined conditions of the applicability of the method of standardization on the basis of stratification for the case of the normal distribution on the response and confounder and linear relationship between them. Comparison ofresults obtained with the help of the standardization with statistical methods (logistic regression and analysis of covariance) in solving the problem of human ecology, has shown that obtaining close results is possible if there will be met exactly conditions for the applicability of statistical methods. Standardization is less sensitive to violations of conditions of applicability.


A Novel Dichoptic Optokinetic Nystagmus Paradigm to Quantify Interocular Suppression in Monocular Amblyopia.
To develop a novel dichoptic optokinetic nystagmus (OKN) paradigm and investigate its effectiveness in objectively quantifying the interocular suppression in subjects with monocular amblyopia. Centripetal moving gratings with different contrast ratios and constant velocity were dichoptically presented to eight monocular anisometropic amblyopes and eight normal subjects. We analyzed the OKN records with an eye tracker (EyeLink; SR-Research, Ontario, Canada) to obtain the relationship between ocular-dominance of OKN and the interocular contrast ratio by fitting power curves, and examined the correlation between the effective contrast ratio for a balanced OKN and the visual acuity of the amblyopic eye in amblyopes. In normal subjects, the OKN pursuit times were roughly balanced for opposite directions when stimulated with centripetal gratings of same contrast; however, in amblyopes, the OKN pursuit times of the dominant eye exceeded that of the amblyopic eye. Increasing the contrast of one eye's grating led to an increase in its OKN dominance. The OKN directional ratio (y) could be well fitted by a power function of the interocular contrast ratio (x): y = axb. Moreover, in amblyopes, the effective contrast ratio (xb) for a balanced OKN correlated significantly positively with the visual acuity of the amblyopic eye (Spearman's correlation coefficient, 0.9698). The OKN induced by dichoptic gratings moving centripetally could be used as a reliable measure to objectively quantify the interocular suppression. This paradigm, avoiding the need for subjective report from patients, offers a promising alternative index for research on the mechanisms of amblyopia and in clinical practice.


Exploring the Use of Photo-Stories and Fiction Writing to Address HIV Stigma Among Health Professions Students.
HIV/AIDS stigma exists in healthcare and is harmful to people living with HIV (PLWH). Few anti-stigma interventions target undergraduate health professions students, although evidence supports reaching providers early in their training. We developed two different arts-based interventions based on Intergroup Contact Theory: a Photovoice intervention in which they viewed photo-stories of PLWH and a fiction writing intervention in which they developed characters with HIV. We present the results of a qualitative analysis of the post-intervention interviews, to elaborate on what and how students learned from both interventions. Via theme analysis, we identified three similar patterns among both sets of intervention participants. Interventions helped students to understand PLWH as "people first," experience emotional responses to PLWH, and complicated their understanding of who was living with HIV. All three themes illustrate how Photovoice and fiction writing interrupted stereotypes about PLWH and humanized PLWH to health professions students.


Skin mounted accelerometer system for measuring knee range of motion.
Sufficient range of motion of the knee joint is necessary for performing many activities of daily living. Ambulatory monitoring of knee function can provide valuable information about progression of diseases like knee osteoarthritis and recovery after surgical interventions like total knee arthroplasty. In this paper, we describe a skin-mounted, conformal, accelerometer-based system for measuring knee angle and range of motion that does not require a skilled operator to apply devices. We establish the accuracy of this technique with respect to clinical gold standard goniometric measurements on a dataset collected from normative subjects during the performance of repeated bouts of knee flexion and extension tests. Results show that knee angle and range of motion estimates are highly correlated with goniometer measurements, and track differences in knee angle and range of motion to within 1%. These results demonstrate the ability of this system to characterize knee angle and range of motion, enabling future longitudinal monitoring of knee motion in naturalistic environments.


Manipulation of Innate and Adaptive Immunity through Cancer Vaccines.
Although cancer immunotherapy has shown significant promise in mediating efficacious responses, it remains encumbered by tumor heterogeneity, loss of tumor-specific antigen targets, and the regulatory milieu both regionally and systemically. Cross talk between the innate and adaptive immune response may be requisite to polarize sustained antigen specific immunity. Cancer vaccines can serve as an essential fulcrum in initiating innate immunity while molding and sustaining adaptive immunity. Although peptide vaccines have shown tepid responses in a therapeutic setting with poor correlates for immune activity, RNA vaccines activate innate immune responses and have shown promising effects in preclinical and clinical studies based on enhanced DC migration. While the mechanistic insights behind the interplay between innate and adaptive immunity may be unique to the immunotherapeutic being investigated, understanding this dynamic is important to coordinate the different arms of the immune response in a focused response against cancer antigens.


Concurrent Antisolvent Electrospraying: A Novel Continuous Crystallization Technique.
Pharmaceutical co-crystals (CCs) are multicomponent materials that enable the development of novel therapeutic products by enhancing the properties of active pharmaceutical ingredients, such as solubility, permeability and bioavailability. Currently, CCs are a commercial reality; nonetheless, their industrial production remains a challenge due to problems related to scale up, control and mode of preparation, which usually relies on batch production rather than continuous. This paper describes the implementation of a concurrent coaxial antisolvent electrospray (Co-E), as a new manufacturing technique, for the synthesis of CCs in a rapid, continuous and controlled manner. The features of Co-E were sized against other co-crystallization methods such as antisolvent crystallization, neat and liquid assisted grinding. Three pairs of amino acids were used as model compounds to demonstrate the features of this new system. The Co-E displayed exclusive product characteristics, including spherical particle morphology and enhanced CC formation. This technique exhibited robustness against process disturbances, displaying consistent product characteristics. Co-E represents a new alternative for the reliable production of CCs and other pharmaceutical products.


Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients.
Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesion molecules and leukocyte-endothelium cell interactions were evaluated. Testosterone levels were lower in diabetic patients. Total and mitochondrial ROS were increased and mitochondrial membrane potential, SOD and GSR expression levels were reduced in diabetic patients. TNFα, ICAM-1 and VCAM-1 levels, leukocyte rolling flux and adhesion were all enhanced in diabetic patients, while rolling velocity was reduced. Testosterone levels correlated negatively with glucose, HOMA-IR, HbA1c, triglycerides, nonHDL-c, ApoB, hs-CRP and AIP, and positively with HDL-c and ApoA1. The multivariable regression model showed that HDL-c, HOMA-IR and age were independently associated with testosterone. Furthermore, testosterone levels correlated positively with membrane potential and rolling velocity and negatively with ROS production, VCAM-1, rolling flux and adhesion. Our data highlight that low testosterone levels in diabetic men are related to impaired metabolic profile and mitochondrial function and enhanced inflammation and leukocyte-endothelium cell interaction, which leaves said patients at risk of cardiovascular events.


Identity and diversity of coral endosymbionts (zooxanthellae) from three Palauan reefs with contrasting bleaching, temperature and shading histories.
The potential of corals to associate with more temperature-tolerant strains of algae (zooxanthellae, Symbiodinium) can have important implications for the future of coral reefs in an era of global climate change. In this study, the genetic identity and diversity of zooxanthellae was investigated at three reefs with contrasting histories of bleaching mortality, water temperature and shading, in the Republic of Palau (Micronesia). Single-stranded conformation polymorphism and sequence analysis of the ribosomal DNA internal transcribed spacer (ITS)1 region was used for genotyping. A chronically warm but partly shaded coral reef in a marine lake that is hydrographically well connected to the surrounding waters harboured only two single-stranded conformation polymorphism profiles (i.e. zooxanthella communities). It consisted only of Symbiodinium D in all 13 nonporitid species and two Porites species investigated, with the remaining five Porites harbouring C*. Despite the high temperature in this lake (> 0.5 degrees above ambient), this reef did not suffer coral mortality during the (1998) bleaching event, however, no bleaching-sensitive coral families and genera occur in the coral community. This setting contrasts strongly with two other reefs with generally lower temperatures, in which 10 and 12 zooxanthella communities with moderate to low proportions of clade D zooxanthellae were found. The data indicate that whole coral assemblages, when growing in elevated seawater temperatures and at reduced irradiance, can be composed of colonies associated with the more thermo-tolerant clade D zooxanthellae. Future increases in seawater temperature might, therefore, result in an increasing prevalence of Symbiodinium phylotype D in scleractinian corals, possibly associated with a loss of diversity in both zooxanthellae and corals.