Focal length variability and protein leakage as tools for measuring photooxidative damage to the lens.
Hypericin is the ingredient used to standardize the popular over-the-counter antidepressant medication St. John's Wort. Because hypericin readily produces singlet oxygen and other excited state intermediates, it is a very efficient phototoxic agent in the eye that can potentially induce the development of the cataract photooxidative mechanism. Hypericin absorbs in the UV and visible ranges, binds to the lens crystallins (alpha, beta and gamma) and damages these proteins through a photooxidative mechanism. Effects were measured previously using fluorescence, UV and mass spectrometry. We report here two additional methods to monitor lens damage: (1) measuring focal length variability using a ScanTox instrument and (2) measuring protein leakage from the damaged lens. Because nonenzymic glycation results in free radical production, we chose to use elevated glucose concentrations as a convenient model for studying oxidative stress. To compare and contrast photooxidative damage against oxidative damage to the lens, we also measured the focal length variability and protein leakage induced by the presence of elevated glucose concentrations. We found that the total accumulated protein leakage was positively correlated (r = 0.9) with variability in focal length. Lenses treated with hypericin and irradiated with UVB had an increase in focal length variability as compared with the lenses that were only UVB-irradiated. Lenses without UVB irradiation had much lower focal length variability than irradiated lenses. For non-hypericin-treated lenses, UVB-irradiated lenses had a larger variability (4.58 mm) than the unirradiated lenses (1.78 mm). The lenses incubated in elevated glucose concentrations had a focal length variability (3.23 mm) equivalent to that of the unirradiated hypericin-treated lenses (3.54 mm). We conclude that photooxidative damage by hypericin results in changes in the optical properties of the lens, protein leakage and finally cataract formation. In contrast to this, high concentrations of glucose induced protein leakage but not changes in optical properties or the opacity associated with a cataract. This work provides further evidence that people should protect their eyes from intense sunlight when taking St. John's Wort.


Low temperature aqueous synthesis of size-controlled nanocrystals through size focusing: a quantum dot biomineralization case study.
Traditional quantum dot synthesis techniques rely on the separation of nucleation and growth to control nanocrystal size. However, the same goal can be achieved through slow and continuous introduction of reactive precursors to keep the growth mechanism in the size focusing regime throughout synthesis. In this work, we demonstrate the efficacy of this approach within the framework of functional material biomineralization where, despite simultaneous nucleation and growth of particles, this growth mechanism enables size-controlled nanocrystal synthesis. Herein, the single enzyme cystathionine γ-lyase (CSE) is utilized to biomineralize CdS nanocrystals via the slow, but continuous turnover of the amino acid l-cysteine to produce H2S. Nanocrystal nucleation and growth theories confirm that consistent addition of monomers will result in a high supersaturation term, driving the nanocrystal growth mechanism into the size focusing regime. We further confirm this theory by mimicking biomineralization via chemical routes and demonstrate the influence of varying supersaturation, to further control the average nanocrystal size. Finally, altering the chelation strength of the capping agent l-cysteine is found to play a key role in balancing nanocrystal growth in solution and long-term stability.


C-H Functionalization of Polyolefins to Access Reprocessable Polyolefin Thermosets.
Upcycling plastic waste into reprocessable materials with performance-advantaged properties would contribute to the development of a circular plastics economy. Here, we modify branched polyolefins and postconsumer polyethylene through a versatile C-H functionalization approach using thiosulfonates as a privileged radical group transfer functionality. Cross-linking the functionalized polyolefins with polytopic amines provided dynamically cross-linked polyolefin networks enabled by associative bond exchange of diketoenamine functionality. A combination of resonant soft X-ray scattering and grazing incidence X-ray scattering revealed hierarchical phase morphology in which diketoenamine-rich microdomains phase-separate within amorphous regions between polyolefin crystallites. The combination of dynamic covalent cross-links and microphase separation results in useful and improved mechanical properties, including a ∼4.5-fold increase in toughness, a reduction in creep deformation at temperatures relevant to use, and high-temperature structural stability compared to the parent polyolefin. The dynamic nature of diketoenamine cross-links provides stress relaxation at elevated temperatures, which enabled iterative reprocessing of the dynamic covalent polymer network with little cycle-to-cycle property fade. The ability to convert polyolefin waste into a reprocessable thermoformable material with attractive thermomechanical properties provides additional optionality for upcycling to enable future circularity.


Vulvar dystrophies in geriatric patients.
The term vulvar dystrophies has received international acceptance and replaces the confusing terminology formerly used to describe vulvar epithelial disorders. The classification is based on histopathologic features and has provided a more rational foundation for the use of specific therapies. The risk of malignant change is small and depends on the presence or absence of atypical cells. Biopsies are mandatory for diagnosis and therapy. Vulvar dystrophies without atypia are benign lesions whose primary treatment is medical.


Neuroprotective Potential and Underlying Pharmacological Mechanism of Carvacrol for Alzheimer's and Parkinson's Diseases.
The phytochemicals have antioxidant properties to counter the deleterious effects of oxidative stress in the central nervous system and can be a promising drug candidate for neurodegenerative diseases. Among various phytochemicals, constituents of spice origin have recently received special attention for neurodegenerative diseases owing to their health benefits, therapeutic potential, edible nature, and dietary accessibility and availability. Carvacrol, a phenolic monoterpenoid, has garnered attention in treating and managing various human diseases. It possesses diverse pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial and anticancer. Alzheimer's disease (AD) and Parkinson's disease (PD) are major public health concerns that place a significant financial burden on healthcare systems worldwide. The global burden of these diseases is expected to increase in the next few decades owing to increasing life expectancies. Currently, there is no cure for neurodegenerative diseases, such as AD and PD, and the available drugs only give symptomatic relief. For a long time, oxidative stress has been recognized as a primary contributor to neurodegeneration. Carvacrol enhances memory and cognition by modulating the effects of oxidative stress, inflammation, and Aβ25-35- induced neurotoxicity in AD. Moreover, it also reduces the production of reactive oxygen species and proinflammatory cytokine levels in PD, which further prevents the loss of dopaminergic neurons in the substantia nigra and improves motor functions. This review highlights carvacrol's potential antioxidant and anti-inflammatory properties in managing and treating AD and PD.


Recent advances in toxic shock syndrome.
The pathogenesis and treatment of toxic shock has become clearer even as its epidemiology has evolved. Nonmenstrual cases due to Staphylococcus aureus can be difficult to diagnose and treat. Invasive Streptococcus pyogenes infections are life threatening.


Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: An exploratory randomized controlled trial.
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an important occurrence in the natural history of idiopathic pulmonary fibrosis (IPF), associated with high hospitalization rates, high mortality and poor prognosis. At present, there is no effective treatment for AE-IPF. Chinese herbal medicine has some advantages in treating IPF, but its utility in AE-IPF is unclear. The treatment of AE-IPF with Kangxian Huanji Granule (KXHJ), a compound Chinese herbal medicine, lacks an evidence-based justification. This study explores the efficacy and safety of KXHJ in patients with AE-IPF. We designed a randomized, double-blind, placebo-controlled, exploratory clinical trial. A total of 80 participants diagnosed with AE-IPF were randomly assigned to receive KXHJ or a matching placebo; the treatment included a 10 g dose, administered twice daily for 4 weeks, in addition to conventional treatment. Participants were followed up for 12 weeks after the treatment. The primary endpoints were treatment failure rate and all-cause mortality. Secondary endpoints included the length of hospitalization, overall survival, acute exacerbation rate, intubation rate, the modified British Medical Research Council (mMRC) score, and the St George's Respiratory Questionnaire for IPF (SGRQ-I) score. The rate of treatment failure at 4 weeks was lower in the intervention group compared to the control group (risk ratio [RR]: 0.22; 95% confidence interval [CI]: 0.051 to 0.965, P = 0.023). There was no significant difference in all-cause mortality at 16 weeks (RR: 0.75; 95% CI: 0.179 to 3.138; P > 0.999) or in the acute exacerbation rate during the 12-week follow-up period (RR: 0.69; 95% CI: 0.334 to 1.434; P = 0.317). The intervention group had a shorter length of hospitalization than the control group (mean difference [MD]: -3.30 days; 95% CI, -6.300 to -0.300; P = 0.032). Significant differences in the mean change from baseline in the mMRC (between-group difference: -0.67; 95% CI: -0.89 to -0.44; P < 0.001) and SGRQ-I score (between-group difference: -10.36; 95% CI: -16.483 to -4.228; P = 0.001) were observed after 4 weeks, and also in the mMRC (between-group difference: -0.67; 95% CI: -0.91 to -0.43; P < 0.001) and SGRQ-I (between-group difference: -10.28; 95% CI, -15.838 to -4.718; P < 0.001) at 16 weeks. The difference in the adverse events was not significant. KXHJ appears to be effective and safe for AE-IPF and can be considered a complementary treatment in patients with AE-IPF. As a preliminary exploratory study, our results provide a basis for further clinical research. Chinese Clinical Trial Registry (ChiCTR1900026289). Please cite this article as: Li JS, Zhang HL, Guo W, Wang L, Zhang D, Zhao LM, Zhou M. Efficacy and safety of Kangxian Huanji Granule as adjunctive treatment in acute exacerbation of idiopathic pulmonary fibrosis: an exploratory randomized controlled trial. J Integr Med. 2023; 21(6): 543-549.


Re-emerging syphilis: a detrended correspondence analysis of the behaviour of HIV positive and negative gay men.
Recent syphilis outbreaks in the UK have raised serious concerns about the sexual health of the population. Moreover, syphilis appears more likely to facilitate HIV transmission than any other sexually transmitted infection (STI). The sexual and other risk behaviour of a sample of HIV positive and negative gay men with and without syphilis was subjected to a detrended correspondence analysis (DCA). A DCA plot was used to illustrate similarity of individuals in terms of their behaviours, regardless of their infection status. The majority of those with syphilis (78%; 18/23) fell into a high-risk group with more partners, and use of anonymous sex venues and drugs during sex. However, 16% of uninfected controls (8/49) and 62% of HIV positive individuals without syphilis (8/13) also fell into this high-risk group. Using a statistical technique that is novel for this type of investigation, we demonstrate behavioural overlaps between syphilis-infected individuals in an ongoing UK outbreak and uninfected HIV positive and negative controls. Given the high-risk behaviour of a significant proportion of uninfected individuals, ongoing transmission of syphilis and HIV in this population seems likely.


The developmental epidemiology of childhood victimization.
This article examines developmental trends in the rates of different kinds of victimization across the span of childhood. The Developmental Victimization Survey was a national telephone survey of the victimization experiences of 2,030 children from ages 2 to 17. The overall mean number of victimizations during a single year increased with age, as did the percentage of children with polyvictimizations (4 or more different kinds of victimization). However, some specific types of victimization, physical bullying and sibling assaults, were highest prior to adolescence and then declined. Other types had different developmental patterns by gender. Peer assaults increased in adolescence for boys but not for girls. Child maltreatment and sexual victimization increased in adolescence for girls but not for boys. The complex and diverse patterns of developmental vulnerability to different kinds of victimization at different ages need more exploration and explanation in order to better target prevention and intervention policies.


Identification of a Moraxella catarrhalis outer membrane protein exhibiting both adhesin and lipolytic activities.
The UspA1 and Hag proteins have previously been shown to be involved in the ability of the Moraxella catarrhalis wild-type strain O35E to bind to human Chang and A549 cells, respectively. In an effort to identify novel adhesins, we generated a plasmid library of M. catarrhalis DNA fragments, which was introduced into a nonadherent Escherichia coli strain. Recombinant E. coli bacteria were subsequently enriched for clones that gained the ability to bind to Chang and A549 cells, yielding the plasmid pELFOS190. Transposon mutagenesis of this plasmid identified the potential adhesin gene mcaP (M. catarrhalis adherence protein). Sequence analysis revealed that McaP is related to autotransporter proteins and has substantial similarity with the GDSL family of lipolytic enzymes, particularly the Moraxella bovis phospholipase B. Expression of the mcaP gene product by E. coli increased adherence to Chang, A549, and 16HBE14o(-) polarized human bronchial cells 50- to 100-fold. Spectrophotometric assays with p-nitrophenol derivatives also demonstrated that McaP is an esterase. Furthermore, thin-layer chromatography revealed that McaP cleaves both phosphatidylcholine and lysophosphatidylcholine. McaP releases fatty acids and glycerophosphorylcholine upon cleavage of phosphatidylcholine, thus exhibiting phospholipase B activity. The construction and characterization of isogenic M. catarrhalis O35E mutants demonstrated that the lack of McaP expression abolishes esterase activity and considerably decreases adherence to several human cell lines.


Carpal tunnel syndrome: relationship between clinical and patient-oriented assessment.
Clinical diagnosis of carpal tunnel syndrome usually is easy and sensitive, but frequently, it is based on history and referred symptoms when no motor or sensory deficits are observed during examination. In patients with carpal tunnel syndrome, a dissociation between the severity of the disease reported by the patient and the deficits clinically evaluated by the physician often are observed. The Italian Carpal Tunnel Syndrome Study Group did a multicenter study on 740 patients (1123 hands) with carpal tunnel syndrome to assess the aspects of dissociation between the patient's and the physician's quantification of the disease severity and the ability of the patients with carpal tunnel syndrome to do daily activities. Validated patient-oriented parameters assessing symptoms and hand functional status were used. The relationship between the physician's and the patient's measurements is strong with a linear significant correlation when analyzing the functional status of the hand but not so clear and simple when analyzing the symptoms. Patients with mild-to-moderate carpal tunnel syndrome seemed to function well, although severe symptoms may be reported by the patient; however, when nerve impairment becomes severe, the patient's hand function is extremely impaired although symptoms may be milder. The data show that the patient's point of view is reliable. Carpal tunnel syndrome seems to be an ideal model to evaluate the importance of patient-oriented measurements.


Ceftriaxone pharmacokinetics in interleukin-10-treated murine pneumococcal pneumonia.
Anti-inflammatory therapy with interleukin-10 (IL-10) was previously reported to reduce pulmonary inflammation and to prevent septicaemia in murine pneumococcal pneumonia treated with ceftriaxone. In the present report, we investigated the influence of pulmonary infection and IL-10 administration on the pharmacokinetics of ceftriaxone. CD1 mice were infected with 10(7) cfu of Streptococcus pneumoniae. Treatments (intraperitoneal) with IL-10 (1 microg per mouse), ceftriaxone (20 mg/kg) or the combination of IL-10 + ceftriaxone were initiated 18 h after infection. Groups of mice were sacrificed at several time points from 5 min to 24 h after initiation of therapy. Ceftriaxone was quantified in blood and lungs using a microbiological assay. Additional groups of mice received a second dose of IL-10 at 36 h post-infection. Survival rates were recorded over 14 days. The clearance of ceftriaxone was significantly reduced in infected mice compared with that in non-infected animals (P < 0.01), whereas AUC, mean residence time, t(1/2) and AUC(lung)/AUC(serum) were significantly enhanced (P < 0.01, 0.01, 0.05, 0.05). Co-administration of IL-10 with ceftriaxone in infected animals further retained ceftriaxone in the bloodstream and reduced its volume of distribution at steady state and the ratio of AUC(lung)/AUC(serum). IL-10 alone did not modify significantly the pharmacokinetics of ceftriaxone in blood and lungs of non-infected animals. The results suggest that pulmonary infection, and therapy with IL-10, both affect the pharmacokinetics of ceftriaxone. Indeed, administration of IL-10 + ceftriaxone improved the survival rate of mice (P < 0.001 compared with therapy with ceftriaxone alone). IL-10 should be considered as an adjunctive therapy to antibiotics against severe infections.


Label-free mass spectrometry-based protein quantification technologies in proteomic analysis.
Major technological advances have made proteomics an extremely active field for biomarker discovery and validation in recent years. These improvements have lead to an increased emphasis on larger scale, faster and more efficient methods for protein biomarker discoveries in human tissues, cells and biofluids. However, most current proteomic methodologies for biomarker discovery and validation are not highly automated and generally labour intensive and expensive. Improved automation as well as software programs capable of handling a large amount of data are essential in order to reduce the cost of discovery and increase the throughput. In this review, we will discuss and describe the label-free mass spectrometry-based protein quantification technologies and a case study utilizing one of these methods for biomarker discovery.


Revisiting Ultrasound-Guided Subclavian/Axillary Vein Cannulations: Importance of Pleural Avoidance With Rib Trajectory.
The Centers for Disease Control and Prevention guidelines for the prevention of catheter-related bloodstream infections suggest using "a subclavian site, rather than an internal jugular or a femoral site, in adult patients." This recommendation is based on evidence of lower rates of thrombosis and catheter-related bloodstream infections in patients with subclavian central venous catheters (CVCs) compared to femoral or internal jugular sites. However, preference toward a subclavian approach to CVC insertion is hindered by increased risk of mechanical complications, especially pneumothorax, when compared to other sites. This is largely related to the proximity of the subclavian vein to the pleural space and the traditional "blind" or anatomic landmark approach used in subclavian vein cannulation. We revisit a method that may provide increased safety and avoidance of pneumothorax during ultrasound-guided subclavian/axillary vein cannulation. This is achieved by directing the needle toward the subclavian vein at a point where it traverses over the second rib, providing a protective rib shield between the vessel and pleura as a safety net for operators. The technique also allows for increased compressibility of the subclavian/axillary vein in the event of bleeding complication.


The anesthetizing sites supervised to anesthesiologist ratio is an invalid surrogate for group productivity in academic anesthesia departments when used without consideration of the corresponding managerial decisions.
When the anesthesiologist does not individually perform the anesthesia care, then to make valid comparisons among US anesthesia departments, one must consider the staffing ratio (i.e., how many cases each anesthesiologist supervises when working with Certified Registered Nurse Anesthetists [CRNAs] or Certified Anesthesiologist Assistants [CAA]). The staffing ratio also must be considered when accurately measuring group productivity. In this narrative review, we consider anesthesia departments with non-physician anesthesia providers and anesthesiology residents. We investigate the validity of such departments assessing the overall ratio of anesthetizing sites supervised per anesthesiologist as a surrogate for group clinical productivity. The sites/anesthesiologist ratio can be estimated accurately using the arithmetic mean calculated by anesthesiologist, the harmonic mean calculated by case, or the harmonic mean calculated by CRNA or CAA, but not by the arithmetic mean ratio by case. However, there is lack of validity to benchmarking the percentage time that anesthesiologists are supervising the maximum possible number of CRNAs or CAAs when some of the anesthesiologists also are supervising resident physicians. Assignments can differ in the total number anesthesiologists needed while every anesthesiologist is supervising as many sites as possible. Similarly, there is lack of validity to limiting assessment to the anesthesiologists supervising only CRNAs or CAAs. There also is lack of validity to limiting assessment only to cases performed by supervised CRNAs or CAAs. When cases can be assigned to anesthesiology residents or CRNAs or CAAs, increasing sites/anesthesiologist while limiting consideration to the CRNAs or CAAs creates incentive for the CRNAs or CAAs to be assigned cases, even when lesser productivity is the outcome. Decisions also can increase sites/anesthesiologist without increasing productivity (e.g., when one anesthesiologist relieves another before the end of the regular workday). A suitable alternative approach to fallaciously treating the sites/anesthesiologist ratio as a surrogate for productivity is that, when a teaching hospital supplies financial support, a responsibility of the anesthesia department is to explain annually the principal factors affecting productivity at each facility it manages and to show annually that decisions were made that maximized productivity, subject to the facilities' constraints.


[Three preparations of compound Chinese herbal medicines for de-adaptation to high altitude: a randomized, placebo-controlled trial].
With the increase of troops entering the plateau for a variety of missions, the occurrence of de-adaptation increased significantly when the army returned to the plains, however, until now, there has been no effective treatment for de-adaptation to high altitude. To observe the interventional effects of compound Chinese herbal preparations (Sankang Capsule, Rhodiola Rosea Capsule and Shenqi Pollen Capsule) on de-adaptation to high altitude, and provide scientific evidence for appropriate treatment methods in the army health care for future missions. A randomized, single-blind, placebo-controlled trial design was used. Soldiers of a returning army unit who exhibited de-adaptation response symptoms were selected for observation after participating in earthquake relief at high altitude. A total of 543 soldiers were divided into a Sankang Capsule group, a Rhodiola Rosea Capsule group, a Shenqi Pollen Capsule group and a placebo group for drug intervention and administered with corresponding drugs. The course of treatment was 15 days. A self-evaluation scale for de-adaptation to high altitude was used to measure the signs and symptoms exhibited by the soldiers. Effective rate of signs and symptoms of de-adaptation to high altitude was analyzed after a 15-day treatment and the differences of improvement rate of symptoms between groups were compared to evaluate the efficacy of the drugs. All three drugs improved the symptoms of de-adaptation to high altitude. Compared with the placebo group, symptoms of de-adaptation to high altitude in the drug-treated groups were remitted (P<0.05). Compared with placebo, Sankang Capsule mainly had well-marked effects on dizziness, fatigue, palpitations, cough, sputum and sore throat (P<0.05); Rhodiola Rosea Capsule significantly reduced the symptoms of fatigue, drowsiness, chest tightness, palpitations, vertigo, lack of attention and memory loss (P<0.05); Shenqi Pollen Capsule significantly reduced the symptoms of dizziness, fatigue, weakness, chest tightness, palpitations, cough, sputum, sore throat, memory loss, unresponsiveness and limb numbness (P<0.05). The symptom improvement rate of Shenqi Pollen Capsule was significantly higher than those of the other two drugs. All the three drugs played an evident role in ameliorating symptoms of de-adaptation, and the use of Shenqi Pollen Capsule was more effective than Rhodiola Rosea Capsule and Sankang Capsule.


Clinical pharmacology of imeglimin for the treatment of type 2 diabetes.
With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development. This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer's official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D. Imeglimin's mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000-1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6-11 mmol/mol (0.5-1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects. AUC: area under the curve; BID: twice daily; DPP-4: dipeptidyl peptidase 4; GLP-1R: glucagon-like peptide-1 receptor; HbA1c: glycated hemoglobin A1c; HFHSD: high-fat high-sucrose diet; OAD: oral antidiabetic; OD: once daily; OGTT: oral glucose tolerance test; PPAR-γ: peroxisome proliferator-activated receptor gamma; PTP: permeability transition pore; SGLT-2: sodium-glucose transport protein 2; STZ: streptozotocin; T2D: type 2 diabetes.


Nucleostemin stabilizes ARF by inhibiting the ubiquitin ligase ULF.
Upregulated expression of nucleolar GTPase nucleostemin (NS) has been associated with increased cellular proliferation potential and tumor malignancy during cancer development. Recent reports attribute the growth regulatory effects of NS protein to its role in facilitating ribosome production. However, the oncogenic potential of NS remains unclear, as imbalanced levels of NS have been reported to exert growth inhibitory effect by modulating p53 tumor-suppressor activity. It also remains in questions if aberrant NS levels might have a p53-independent role in regulation of cell proliferation and growth. In this study, we performed affinity purification and mass spectrometry analysis to explore protein-protein interactions influencing NS growth regulatory properties independently of p53 tumor suppressor. We identified the alternative reading frame (ARF) protein as a key protein associating with NS and further verified the interaction through in vitro and in vivo assays. We demonstrated that NS is able to regulate cell cycle progression by regulating the stability of the ARF tumor suppressor. Furthermore, overexpression of NS suppressed ARF polyubiquitination by its E3 ligase Ubiquitin Ligase for ARF and elongated its half-life, whereas knockdown of NS led to the decrease of ARF levels. Also, we found that NS can enhance NPM stabilization of ARF. Thus, we propose that in the absence of p53, ARF can be stabilized by NS and nucleophosmin to serve as an alternative tumor-suppressor surveillance, preventing potential cellular transformation resulting from the growth-inducing effects of NS overexpression.


Dynamic Video Deblurring Using a Locally Adaptive Blur Model.
State-of-the-art video deblurring methods cannot handle blurry videos recorded in dynamic scenes since they are built under a strong assumption that the captured scenes are static. Contrary to the existing methods, we propose a new video deblurring algorithm that can deal with general blurs inherent in dynamic scenes. To handle general and locally varying blurs caused by various sources, such as moving objects, camera shake, depth variation, and defocus, we estimate pixel-wise varying non-uniform blur kernels. We infer bidirectional optical flows to handle motion blurs, and also estimate Gaussian blur maps to remove optical blur from defocus. Therefore, we propose a single energy model that jointly estimates optical flows, defocus blur maps and latent frames. We also provide a framework and efficient solvers to minimize the proposed energy model. By optimizing the energy model, we achieve significant improvements in removing general blurs, estimating optical flows, and extending depth-of-field in blurry frames. Moreover, in this work, to evaluate the performance of non-uniform deblurring methods objectively, we have constructed a new realistic dataset with ground truths. In addition, extensive experimental results on publicly available challenging videos demonstrate that the proposed method produces qualitatively superior performance than the state-of-the-art methods which often fail in either deblurring or optical flow estimation.


Selection and characterization of recombinant clones that produce Mycobacterium leprae antigens recognized by antibodies in sera from household contacts of leprosy patients.
A Mycobacterium leprae expression library was constructed in the vectors EX1, pEX2, and pEX3 and screened with a pool of 19 well-absorbed sera from household contacts of leprosy patients. Twelve selected recombinants that were further characterized differed clearly from recombinants selected with murine monoclonal antibodies. Whereas the monoclonal antibodies recognized mainly six recombinant antigens, the human sera from contacts reacted with a range of different recombinant antigens. None of the contact recombinant antigens was identical or related to well-characterized antigens from M. leprae or other mycobacteria selected with monoclonal antibodies, including proteins of the heat shock families. Two groups of recombinant antigens could be distinguished: one that was recognized by all sera used in the pool and one that was recognized by only a limited number of sera. These antigens, selected with sera from household contacts of previously untreated lepromatous leprosy patients, may be relevant to the immune responses during the early phase of infection with M. leprae.


Chromosomal microarray testing in adults with intellectual disability presenting with comorbid psychiatric disorders.
Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.


Accumulation and fractionation of rare earth elements (REEs) in wheat: controlled by phosphate precipitation, cell wall absorption and solution complexation.
Previous studies on rare earth element (REE) bioaccumulation have focused on their accumulation rate and fractionation, but the processes involved remain unclear. In this study, the accumulation and fractionation of REEs in wheat (Triticum aestivum L.) were investigated using solution culture with exogenous mixed REEs. A decrease in REE contents was observed from the roots to the tops of wheat. Significant fractionations of REEs were found in wheat organs as compared to the exogenous mixed REEs. Middle REE (MREE, the elements from Sm to Gd) enrichment and an M-type tetrad effect (an effect that can cause a split of REE patterns into four consecutive convex segments) were observed in the roots, which were probably caused by phosphate precipitation of REEs in/on the roots and absorption of REEs to root cell walls. Light REE (LREE, the elements from La to Eu) and heavy REE (HREE, the elements from Gd to Lu) enrichments were observed in the stems and leaves, respectively, accompanied by conspicuous W-type tetrad effects (an opposite effect to the M-type tetrad effect) in the REE patterns. HREE enrichment decreased from the older to the younger leaves and increased upwards within a single leaf. It is suggested that the solution complexation that occurred in the xylem vessels plays an important role in REE fractionations in the above-ground parts of wheat.


Mouse double minute 2 associates with chromatin in the presence of p53 and is released to facilitate activation of transcription.
The tumor suppressor p53 is a potent transcription factor of which the ability to mediate transcription is inhibited through an interaction with the oncoprotein mouse double minute 2 (Mdm2). The present study has tested the hypothesis that Mdm2 inhibits the p53 response in normally growing cells by binding to chromatin-associated p53. Using chromatin immunoprecipitation, we show that Mdm2 localizes with p53 at its responsive elements on the waf1 and mdm2 genes in human cell lines expressing p53, but not in cell lines lacking p53 expression, indicating that Mdm2 is recruited to regions of DNA in a p53-dependent manner. Interestingly, our results show a decrease of Mdm2 protein associated with p53-responsive elements on the waf1 and mdm2 genes when p53-induced transcription is activated either by DNA damage or through controlled overexpression of p53. Rapid activation of p53 transcriptional activity before increasing p53 protein levels was observed with addition of either small-molecule inhibitors to disrupt the p53-Mdm2 interaction or small interfering RNA to mdm2. These findings indicate Mdm2 transiently localizes with p53 at responsive elements and suggest that latent p53 results from the recruitment of Mdm2 to chromatin.


A proposal for early and personalized treatment of diabetic retinopathy based on clinical pathophysiology and molecular phenotyping.
This paper presents a new approach to the prevention and treatment of early stage diabetic retinopathy before vision is severely impaired. This approach includes two major steps. The first step is to understand the mechanisms of vision impairment and classify diabetic retinopathy on the basis of pathophysiologic adaptations, rather than on the presence of advanced pathologic lesions, as defined by current clinical practice conventions. The second step is to develop patient-specific molecular diagnoses of diabetic retinopathy so that patients can be treated based on their individual characteristics, a process analogous to the individualized diagnosis and treatment of cancer patients. This step is illustrated by proteomic analysis of vitreous fluid that reveals evidence of neuroretinal degeneration and inflammation, as well as vascular proliferation. Together, these steps may lead to improved means to preserve vision in the ever-increasing number of patients with diabetes worldwide.


Evaluation of Methyl-Binding Domain Based Enrichment Approaches Revisited.
Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the performance of the MethylMiner was deemed poor. Given our positive experience with MethylMiner, we were surprised by this report. In an attempt to reproduce these findings we here have performed a direct comparison of MethylMiner with MethylCap (Diagenode Inc, Denville, NJ, USA), the best performing kit in that study. We find that both MethylMiner and MethylCap are two well performing MBD-enrichment kits. However, MethylMiner shows somewhat better enrichment efficiency and lower levels of background "noise". In addition, for the purpose of MWAS where we want to investigate the majority of CpGs, we find MethylMiner to be superior as it allows tailoring the enrichment to the regions where most CpGs are located. Using targeted bisulfite sequencing we confirmed that sites where methylation was detected by either MethylMiner or by MethylCap indeed were methylated.


Towards high-performance solid-state Li-S batteries: from fundamental understanding to engineering design.
Solid-state lithium-sulfur batteries (SSLSBs) with high energy densities and high safety have been considered among the most promising energy storage devices to meet the demanding market requirements for electric vehicles. However, critical challenges such as lithium polysulfide shuttling effects, mismatched interfaces, Li dendrite growth, and the gap between fundamental research and practical applications still hinder the commercialization of SSLSBs. This review aims to combine the fundamental and engineering perspectives to seek rational design parameters for practical SSLSBs. The working principles, constituent components, and practical challenges of SSLSBs are reviewed. Recent progress and approaches to understand the interfacial challenges via advanced characterization techniques and density functional theory (DFT) calculations are summarized and discussed. A series of design parameters including sulfur loading, electrolyte thickness, discharge capacity, discharge voltage, and cathode sulfur content are systematically analyzed to study their influence on the gravimetric and volumetric energy densities of SSLSB pouch cells. The advantages and disadvantages of recently reported SSLSBs are discussed, and potential strategies are provided to address the shortcomings. Finally, potential future directions and prospects in SSLSB engineering are examined.


Amoebae-resisting bacteria in drinking water: risk assessment and management.
Free-living amoebae have been detected in a large number of man-made water systems, including drinking water distribution systems. Some of these amoebae can host amoebae-resisting bacteria, and thus act potentially as reservoirs and vehicles for a number of pathogens. The objectives of this study were to characterize the amoebae and amoebae-resisting bacteria present in different raw waters used for drinking water production, and to assess the efficiency of different treatments applied for drinking water production in removing or inactivating these amoebae. The preliminary results of this study confirm the presence of amoebae and amoebae-resisting bacteria in raw waters used for drinking water production. Due to their capacity to encyst, most of these amoebae are extremely resistant to disinfection processes. In these conditions, preventing the dissemination of these micro-organisms through drinking water will mainly require their physical removal by clarification and filtration processes. The particular hazard that amoebae-resisting bacteria represent in drinking water production should be taken into account in any risk assessment conducted in the framework of a water safety plan, and control strategies based on physical removal rather than disinfection should be adopted where necessary.


Applying definitions of "asbestos" to environmental and "low-dose" exposure levels and health effects, particularly malignant mesothelioma.
Although asbestos research has been ongoing for decades, this increased knowledge has not led to consensus in many areas of the field. Two such areas of controversy include the specific definitions of asbestos, and limitations in understanding exposure-response relationships for various asbestos types and exposure levels and disease. This document reviews the current regulatory and mineralogical definitions and how variability in these definitions has led to difficulties in the discussion and comparison of both experimental laboratory and human epidemiological studies for asbestos. This review also examines the issues of exposure measurement in both animal and human studies, and discusses the impact of these issues on determination of cause for asbestos-related diseases. Limitations include the lack of detailed characterization and limited quantification of the fibers in most studies. Associated data gaps and research needs are also enumerated in this review.


Coral-bleaching responses to climate change across biological scales.
The global impacts of climate change are evident in every marine ecosystem. On coral reefs, mass coral bleaching and mortality have emerged as ubiquitous responses to ocean warming, yet one of the greatest challenges of this epiphenomenon is linking information across scientific disciplines and spatial and temporal scales. Here we review some of the seminal and recent coral-bleaching discoveries from an ecological, physiological, and molecular perspective. We also evaluate which data and processes can improve predictive models and provide a conceptual framework that integrates measurements across biological scales. Taking an integrative approach across biological and spatial scales, using for example hierarchical models to estimate major coral-reef processes, will not only rapidly advance coral-reef science but will also provide necessary information to guide decision-making and conservation efforts. To conserve reefs, we encourage implementing mesoscale sanctuaries (thousands of km2 ) that transcend national boundaries. Such networks of protected reefs will provide reef connectivity, through larval dispersal that transverse thermal environments, and genotypic repositories that may become essential units of selection for environmentally diverse locations. Together, multinational networks may be the best chance corals have to persist through climate change, while humanity struggles to reduce emissions of greenhouse gases to net zero.


Posttraumatic stress symptoms predict impaired neutrophil recovery in stem cell transplant recipients.
Despite the potentially life-saving effects of stem cell transplant (SCT), many transplant patients experience traumatic stress reactions due to mortality threat, interpersonal isolation, financial and occupational loss, and invasive medical procedures. Emerging evidence suggests that trauma-related stress symptoms (TSS) predict significant health complications following SCT. The aim of the current prospective study was to examine TSS in the acute aftermath of SCT as a predictor of neutrophil recovery following SCT, a crucial component of immune defense against infection. Fifty-one autologous SCT recipients were assessed for TSS 7 days after SCT. Patients' absolute neutrophil counts were collected from medical charts for the first 30 days following SCT. Hierarchical linear growth modeling was used to test the hypothesis that TSS at day 7 would be associated with delayed recovery of neutrophil counts from days 9 to 30 post SCT, that is, when neutrophil counts began to recover. As hypothesized, TSS measured 7 days after SCT was significantly associated with slower neutrophil recovery even after pre-existing TSS, depression, distress related to physical symptoms, and potential medical confounds were statistically controlled. Exploratory analyses showed that of the TSS symptom clusters, re-experiencing symptoms and hyperarousal symptoms predicted neutrophil recovery, whereas avoidance symptoms did not. Though traumatic stress symptoms may be a normative response to SCT, our findings suggest that TSS following SCT may interfere with neutrophil recovery and overall health. These results provide further insight as to potential mechanisms by which traumatic stress translates to poor medical outcomes for SCT patients.


Mycobacterium bovis BCG-induced human T-cell clones from BCG-vaccinated healthy subjects: antigen specificity and lymphokine production.
A total of 121 human T-cell clones were raised from nine Mycobacterium bovis BCG-vaccinated healthy individuals. Three clones were autoreactive, 74 responded to BCG in the presence of antigen-presenting cells, and the others required in addition exogenous interleukin 2. Only one clone was CD8+ CD4-, and the rest were CD4+ CD8-. Testing with a panel of mycobacteria suggested that the clones were recognizing epitopes of varied specificity. Out of 44 clones tested, 15 were specific to BCG and Mycobacterium tuberculosis, 22 showed limited cross-reactivity, and 8 were broadly cross-reactive. None of the 22 BCG responder clones could differentiate between Danish, French, Prague, and Moreau strains of BCG. BCG and M. tuberculosis H37Rv also paralleled very closely; however, 6 of 18 BCG- and M. tuberculosis H37Rv-responding clones did not proliferate to Mycobacterium africanum. BCG- and M. tuberculosis H37Rv-specific as well as cross-reactive T-cell clones could be induced to produce interleukin 2, gamma interferon, and granulocyte-macrophage colony-stimulating factor activity.


Earth's Gravity Field: Relation to Global Tectonics.
An improved solution for the gravity field shows ocean rises, as well as trench and island arcs, as mass excesses. Ocean basins, areas of recent glaciation, and the Asian portion of the Alpide belt are mass deficiencies. Most features appear interpretable as varying behavior of the lithosphere in response to asthenospheric flow.


Rapid and comprehensive indicator for evaluation of performance of treatment processes and of river waters.
Naturally occurring UV active compounds, commonly present in almost all source waters, can be rapidly monitored by their ultraviolet absorbance at 260 nm (E260). Herein, the extent of correlation between the E260 and the removal efficiency of the hazardous contaminants, endocrine disrupters and dioxins, were investigated using various treatment and river source waters. The detection of various types of hazardous contaminants using sophisticated analytical methods, such as high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC)/inductively coupled plasma (ICP)/mass spectrometry (MS), as well as various short-term bioassays, can require hours or even days for results to be obtained. The removal of the E260 correlated well with those of individual contaminants, such as endocrine disruptor chemicals and dioxins, with the various treatment processes employed. In the plots of the endocrine disrupters against the DOC/E260, a correlation was found with the endocrine activity of the Korean/Japanese river waters employed in this study.


Nonrashes. 5. Atmoknesis: pruritus provoked by contact with air.
Atmoknesis, itching provoked by open exposure of the skin to air after undressing, is a common and distressing symptom. It occurs in many patients with psoriasis and atopic dermatitis, and in elderly patients with aquagenic pruritus. It also occurs in some patients with underlying systemic causes of generalized pruritus, such as hepatobiliary disease. It does not seem to be an important feature of certain other pruritic skin diseases such as dermatitis herpetiformis and bullous pemphigoid.


Lycopene Improves Bone Quality in SAMP6 Mice by Inhibiting Oxidative Stress, Cellular Senescence, and the SASP.
Cellular senescence (CS) is closely related to tissue ageing including bone ageing. CS and the senescence-associated secretory phenotype (SASP) have emerged as critical pathogenesis elements of senile osteoporosis. This study aims to investigate the effect of lycopene on senile osteoporosis. The senescence-accelerated mouse prone 6 (SAMP6) strain of mice is used as the senile osteoporosis model. Daily ingestion of lycopene for 8 weeks preserves the bone mass, density, strength, and microarchitecture in the SAMP6 mice. Moreover, these alterations are associated with a decrease in oxidative stress in the senile osteoporosis model. In addition, there is a reduction in osteoblast and osteocyte senescence and the SASP in the bone tissues of the SAMP6 mice. Lycopene improves bone health likely due to its antioxidant properties that may be linked with the regulation of CS and SASP in the SAMP6 mice. These results suggest that lycopene may be beneficial for the management of senile osteoporosis by inhibiting oxidative stress, CS, and the SASP.


Attenuation of the plasma prolactin response to restraint stress after acute and chronic administration of nicotine to rats.
We have previously shown that a single dose of nicotine elevates plasma adrenocorticotropin (ACTH) levels in rats and has a biphasic effect on plasma prolactin (PRL). The stimulatory effect of nicotine on these stress responsive hormones desensitizes after a single injection of nicotine. Continuous exposure to nicotine also induces tolerance to its locomotor depressive and hypothermic effects, which have been associated with an increase of central [3H]nicotine binding. Thus, the acute and chronic administration of nicotine might induce changes in central nicotinic cholinergic circuits that affect the ACTH and PRL responses to stress. In the present study, a single dose of nicotine (0.75-3.0 mg/kg b.wt.) significantly inhibited the elevation of plasma PRL due to restraint stress initiated 60 min afterward. Five injections of nicotine during 1 day produced a similar attenuation of the PRL response to restraint stress but neither of these paradigms affected ACTH. In contrast, intermittent delivery of nicotine for 7 days failed to affect the PRL response to restraint stress; however, after withholding nicotine for 14 hr, high dose nicotine attenuated the PRL response to stress, whereas low dose nicotine remained ineffective. On the other hand, administration of the same schedule of low dose nicotine did significantly diminish the expected release of PRL in response to a final injection of nicotine (0.5-2.0 mg/kg b.wt.) in unstressed animals. In summary, a single dose or 5 doses of nicotine in 1 day attenuated the PRL response to restraint stress, whereas, after chronic administration, this effect was lost.(ABSTRACT TRUNCATED AT 250 WORDS)


Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality.
In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear. To describe normal PTH profiles over time and the association with mortality. There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years). PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality. At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082). Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old.


Reduced impact logging minimally alters tropical rainforest carbon and energy exchange.
We used eddy covariance and ecological measurements to investigate the effects of reduced impact logging (RIL) on an old-growth Amazonian forest. Logging caused small decreases in gross primary production, leaf production, and latent heat flux, which were roughly proportional to canopy loss, and increases in heterotrophic respiration, tree mortality, and wood production. The net effect of RIL was transient, and treatment effects were barely discernable after only 1 y. RIL appears to provide a strategy for managing tropical forest that minimizes the potential risks to climate associated with large changes in carbon and water exchange.


Formin-based control of the actin cytoskeleton during cytokinesis.
Cytokinesis, the terminal event in the canonical cell cycle, physically separates daughter cells following mitosis. For cleavage to occur in many eukaryotes, a cytokinetic ring must assemble and constrict between divided genomes. Although dozens of different molecules localize to and participate within the cytokinetic ring, the core machinery comprises linear actin filaments. Accordingly, formins, which nucleate and elongate F-actin (filamentous actin) for the cytokinetic ring, are required for cytokinesis in diverse species. In the present article, we discuss specific modes of formin-based actin regulation during cell division and highlight emerging mechanisms and questions on this topic.


Determination of the validity of spectrophotometric measurements based upon cumulants of the temporal point-spread function.
Spectrophotometric measurements of scattering media are nontrivial owing to the nonlinear relationship between the observed attenuation A and the level of absorption coefficient micro(a). Presented is a method, utilizing frequency-domain measurements, capable of determining the validity of a measured change in micro(a) based purely on the characteristics of a baseline temporal point-spread function. The order of cumulant used is shown to provide variation of the sensitivity of the method, and its use is demonstrated through Monte Carlo simulations of transmission measurements taken from a scattering slab.


Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology.
Osteonecrosis of the jaw (ONJ) is a clinically important, potentially painful and debilitating condition, which can affect the quality of life of cancer patients. Since 2003, ONJ appeared as a Bisphosphonate(BP)-related class effect, and the term Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) was widespread. Under discussion in this review is the fact that ONJ cases have been reported after treatment including antiangiogenic agents and other "targeted therapy", with and without BPs. Consequently, the comprehensive term Medication-Related Osteonecrosis of the Jaw (MRONJ) has been introduced. The clinical aspects and the prognosis of ONJ associated with these new drugs are still less reported, but basing on their pharmacodynamics, they could be different from the well-known BRONJ. Accordingly, recommendations largely in use for BRONJ should be extended to these new forms, but critically applied and with respect to the individual risk assessment. There is a high risk of underdiagnoses for ONJ due to a lack of awareness, and too much restrictive or incomplete diagnostic criteria; at the same time, with regard to ONJ associated to the new non -antiresorptive agents, described here, we observe the strong need to improve the defining of any distinguished feature in their diagnosis, prevention and therapy.


Impact of lung preservation solutions, Euro-Collins vs. low-potassium dextran, on early graft function: a review of five clinical studies.
Currently, intracellular fluid type solutions that are prepared by modification of Euro-Collins solution (EC) have been the most commonly used by clinical lung transplant programs, which have been associated with a high rate of reperfusion injury. On the basis of the wealth of experimental data demonstrating the benefit of extracellular fluid type solutions over EC, one of the extracellular solutions, low-potassium dextran solution (LPD), became commercially available and has recently been applied to clinical settings. To date there have been 5 clinical studies comparing the effect of EC with LPD on early lung graft function. This article reviewed these 5 reports to determine whether the beneficial effects of LPD, as observed in experimental settings, can also be identified in clinical lung preservation. Four studies were retrospective reviews and one was a prospective non-randomized study. Of these 5 studies, 3 studies demonstrated significantly improved recipient oxygenation in the LPD group compared with the EC group in the early post-operative period. In addition, a significantly shorter duration on mechanical ventilation in the LPD group was shown in 2 studies, and improved reperfusion scores or pulmonary compliance was shown in one study each. Four of 5 studies concluded that graft preservation with LPD leads to superior early graft function after lung transplantation. The impact of LPD on prolonged lung preservation and also on long term results of graft function will be a subject of future investigation.


Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection.
Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought. A large homozygous deletion within the IL-12 p40 subunit gene was found, precluding expression of functional IL-12 p70 cytokine by activated dendritic cells and phagocytes. As a result, IFN-gamma production by lymphocytes was markedly impaired. This is the first discovered human disease resulting from a cytokine gene defect. It suggests that IL-12 is essential to and appears specific for protective immunity to intracellular bacteria such as mycobacteria and salmonella.


Association between systemic immune-inflammation index and serum uric acid in U.S. adolescents: A population-based study.
Serum uric acid (SUA) has been reported to be associated with inflammation, and elevated SUA is increasingly prevalent in adolescents. The systemic immune-inflammation index (SII) is an innovative and integrated inflammatory indicator that has not yet been studied with SUA in adolescents. We therefore aimed to investigate the potential relationship between SII and SUA in U.S. adolescents. A total of 5,568 adolescents aged 12-19 years from NHANES 2009-2018 were analyzed. SII was calculated as platelet count × neutrophil count/lymphocyte count. Elevated SUA was defined as ≥ 5.5 mg/dL. SII was Ln-transformed for analysis for the skewed distribution. Multivariate linear and multiple logistic regression analyses were conducted to explore the association of SII with SUA and elevated SUA. A generalized additive model and a fitted smoothing curve were also performed. The prevalence of elevated SUA was 35.4 %. Multivariate linear regression analyses indicated that LnSII was positively associated with SUA level (β = 0.15, 95 % CI: 0.09-0.20). Multiple logistic analyses indicated that LnSII was associated with a 38 % increased risk of elevated SUA (OR = 1.38, 95 % CI: 1.11-1.70). The smooth curve fitting showed that the associations of LnSII with SUA and elevated SUA were linear. Besides, subgroup analyses showed a stronger association between LnSII and SUA in adolescents aged ≥17 years (P for interaction <0.05). SII was positively associated with SUA level and elevated SUA in U.S. adolescents, particularly in populations aged ≥17 years.


The Stress-Inducible Peroxidase TSA2 Underlies a Conditionally Beneficial Chromosomal Duplication in Saccharomyces cerevisiae.
Although chromosomal duplications are often deleterious, in some cases they enhance cells' abilities to tolerate specific genetic or environmental challenges. Identifying the genes that confer these conditionally beneficial effects to particular chromosomal duplications can improve our understanding of the genetic and molecular mechanisms that enable certain aneuploidies to persist in cell populations and contribute to disease and evolution. Here, we perform a screen for spontaneous mutations that improve the tolerance of haploid Saccharomyces cerevisiae to hydrogen peroxide. Chromosome IV duplication is the most frequent mutation, as well as the only change in chromosomal copy number seen in the screen. Using a genetic mapping strategy that involves systematically deleting segments of a duplicated chromosome, we show that the chromosome IV's duplication effect is largely due to the generation of a second copy of the stress-inducible cytoplasmic thioredoxin peroxidase TSA2 Our findings add to a growing body of literature that shows the conditionally beneficial effects of chromosomal duplication are typically mediated by a small number of genes that enhance tolerance to specific stresses when their copy numbers are increased.


Enhancing the robustness of a multiplex network leads to multiple discontinuous percolation transitions.
Determining design principles that boost the robustness of interdependent networks is a fundamental question of engineering, economics, and biology. It is known that maximizing the degree correlation between replicas of the same node leads to optimal robustness. Here we show that increased robustness might also come at the expense of introducing multiple phase transitions. These results reveal yet another possible source of fragility of multiplex networks that has to be taken into the account during network optimization and design.


Engaging clinicians in health informatics projects.
This chapter gives an educational overview of: * The importance of the engagement of clinicians within a health informatics project * Strategies required for an effective involvement of clinicians throughout a change management process within a clinical context for the implementation of a health informatics project * The critical aspects for a successful implementation of a health informatics project that involves clinicians as end users * Key factors during the administration of changes during the implementation of an informatics project for an information system in clinical practice.


Onset of microglial entry into developing quail retina coincides with increased expression of active caspase-3 and is mediated by extracellular ATP and UDP.
Microglial cell precursors located in the area of the base of the pecten and the optic nerve head (BP/ONH) start to enter the retina of quail embryos at the 7th day of incubation (E7), subsequently colonizing the entire retina by central-to-peripheral tangential migration, as previously shown by our group. The present study demonstrates a precise chronological coincidence of the onset of microglial cell entry into the retina with a striking increase in death of retinal cells, as revealed by their active caspase-3 expression and TUNEL staining, in regions dorsal to the BP/ONH area, suggesting that dying retinal cells would contribute to the microglial cell inflow into the retina. However, the molecular mechanisms involved in this inflow are currently unclear. Extracellular nucleotides, such as ATP and UDP, have previously been shown to favor migration of microglia towards brain injuries because they are released by apoptotic cells and stimulate both chemotaxis and chemokinesis in microglial cells via signaling through purinergic receptors. Hence, we tested here the hypothesis that ATP and UDP play a role in the entry and migration of microglial precursors into the developing retina. For this purpose, we used an experimental model system based on organotypic cultures of E6.5 quail embryo retina explants, which mimics the entry and migration of microglial precursors in the in situ developing retina. Inhibition of purinergic signaling by treating retina explants with either apyrase, a nucleotide-hydrolyzing enzyme, or suramin, a broad spectrum antagonist of purinergic receptors, significantly prevents the entry of microglial cells into the retina. In addition, treatment of retina explants with either exogenous ATP or UDP results in significantly increased numbers of microglial cells entering the retina. In light of these findings, we conclude that purinergic signaling by extracellular ATP and UDP is necessary for the entry and migration of microglial cells into the embryonic retina by inducing chemokinesis in these cells.


Children and youth perceive smoking messages in an unbranded advertisement from a NIKE marketing campaign: a cluster randomised controlled trial.
How youth perceive marketing messages in sports is poorly understood. We evaluated whether youth perceive that the imagery of a specific sports marketing advertisement contained smoking-related messages. Twenty grade 7 to 11 classes (397 students) from two high schools in Montréal, Canada were recruited to participate in a cluster randomised single-blind controlled trial. Classes were randomly allocated to either a NIKE advertisement containing the phrase 'LIGHT IT UP' (n = 205) or to a neutral advertisement with smoking imagery reduced and the phrase replaced by 'GO FOR IT' (n = 192). The NIKE logo was removed from both advertisements. Students responded in class to a questionnaire asking open-ended questions about their perception of the messages in the ad. Reports relating to the appearance and text of the ad, and the product being promoted were evaluated. Relative to the neutral ad, more students reported that the phrase 'LIGHT IT UP' was smoking-related (37.6% vs. 0.5%) and that other parts of the ad resembled smoking-related products (50.7% vs. 10.4%). The relative risk of students reporting that the NIKE ad promoted cigarettes was 4.41 (95% confidence interval: 2.64-7.36; P < 0.001). The unbranded imagery of an advertisement in a specific campaign aimed at promoting NIKE hockey products appears to have contained smoking-related messages. This particular marketing campaign may have promoted smoking. This suggests that the regulation of marketing to youth may need to be more tightly controlled.


Panoramic search: the interaction of memory and vision in search through a familiar scene.
How do observers search through familiar scenes? A novel panoramic search method is used to study the interaction of memory and vision in natural search behavior. In panoramic search, observers see part of an unchanging scene larger than their current field of view. A target object can be visible, present in the display but hidden from view, or absent. Visual search efficiency does not change after hundreds of trials through an unchanging scene (Experiment 1). Memory search, in contrast, begins inefficiently but becomes efficient with practice. Given a choice between vision and memory, observers choose vision (Experiments 2 and 3). However, if forced to use their memory on some trials, they learn to use memory on all trials, even when reliable visual information remains available (Experiment 4). The results suggest that observers make a pragmatic choice between vision and memory, with a strong bias toward visual search even for memorized stimuli.


Theoretical and computational investigations into mechanobactericidal activity of nanostructures at the bacteria-biomaterial interface: a critical review.
Mechanobactericidal surfaces kill bacteria upon contact by posing landscapes hostile to them and have rapidly gained popularity amongst researchers over the past decade. But several fundamental aspects of the physical interactions between bacteria and nanostructures and the underlying killing mechanisms are still poorly understood. This is partly attributable to the difficulties associated with the characterization of the bacteria-nanostructure interface in a biological environment during the killing process and to the stochastic and non-linear behaviors generally associated with biological systems. However, several analytical and computational models have presented and analyzed possible killing routes and have proven useful in understanding different aspects of the phenomena. Analytical models formulate equations, often based on energy considerations, and aim to predict optimal nanostructure dimensions. They are more widely used than computational models that try to simulate the killing process and the stress or strain fields in the cell membrane through numerical methods. These models provide insights into the forces responsible for the spontaneous penetration of the cell into the nanostructures, which are still highly debated in the field. They have also helped to correlate the nanostructure dimensions with their bactericidal activity to optimize such values and facilitate the translation of this technology to physiological conditions. This review focuses on the rupture of the bacterial cell wall by nanopillars or similar high aspect ratio structures and applying these principles to the deformation of the cell membrane. Many recent interesting experimental results that either refute our current understanding or have the potential to challenge the current consensus are also discussed. Lastly, the limitations of the current strategies and opportunities to address the unresolved gaps in the field are also presented.


Design criteria for semi-central sanitation with low pressure network and membrane bioreactor-the ENREM project.
MBR-technology is able to fulfil similar or even higher standard for nutrients removal than conventional activated sludge processes. This paper presents the optimisation of the membrane bioreactor technology, together with a low pressure sewer, to equip a remote and yet unsewered area of Berlin requiring high quality wastewater treatment. The hydraulic flow pattern of the entire system has to be studied carefully due to the small collection system (no time delay between wastewater discharge and treatment to minimise the daily profile). The pollutant concentrations in the wastewater exhibit also stronger variations. In order to flatten out the hydraulic and load profile, and therefore to reduce the size of the biological reactor and the membrane surface, a buffer tank was installed before the MBR-plant. A full analysis of the influent hydraulic flow and wastewater characterisation is provided for the demonstration MBR-plant.


MR cholangiopancreatography: prospective comparison of a breath-hold 2D projection technique with diagnostic ERCP.
The aim of this study was to compare prospectively a breath-hold projection magnetic resonance cholangiopancreatography (MRCP) technique with diagnostic endoscopic retrograde cholangiopancreatography (ERCP). Seventy-six patients with suspected strictures or choledocholithiasis were referred for MRCP and subsequent ERCP examination, which were performed within 4 h of each other. The MRCP technique was performed using fat-suppressed rapid acquisition with relaxation enhancement (RARE) projection images obtained in standardised planes with additional targeted projections as required by the supervising radiologist. Two radiologists (in consensus) assessed the MRCP results prospectively and independently for the presence of bile duct calculi, strictures, non-specific biliary dilatation and pancreatic duct dilatation, and recorded a single primary diagnosis. The ERCP was assessed prospectively and independently by a single endoscopist and used as a gold standard for comparison with MRCP. Diagnostic agreement was assessed by the Kappa statistic. The MRCP technique failed in two patients and ERCP in five. In the remaining 69 referrals ERCP demonstrated normal findings in 23 cases, strictures in 19 cases, choledocholithiasis in 9 cases, non-specific biliary dilatation in 14 cases and chronic pancreatitis in 4 cases. The MRCP technique correctly demonstrated 22 of 23 normal cases, 19 strictures with one false positive (sensitivity 100 %, specificity 98 %), all 9 cases of choledocholithiasis with two false positives (sensitivity 100 %, specificity 97 %), 12 of 14 cases of non-specific biliary dilatation and only 1 of 4 cases of chronic pancreatitis. There was overall good agreement for diagnosis based on a kappa value of 0.88. Breath-hold projection MRCP can provide non-invasively comparable diagnostic information to diagnostic ERCP for suspected choledocholithiasis and biliary strictures and may allow more selective use of therapeutic ERCP.


Analysis of the tertiary structure of the ribonuclease P ribozyme-substrate complex by site-specific photoaffinity crosslinking.
Bacterial ribonuclease P (RNase P), an endonuclease involved in tRNA maturation, is a ribonucleoprotein containing a catalytic RNA. The secondary structure of this ribozyme is well-established, and a low-resolution model of the three-dimensional structure of the ribozyme-substrate complex has been proposed based on site-specific crosslinking and phylogenetic comparative data [Harris ME et al., 1994 EMBO J 13:3953-3963]. However, several substructures of that model were poorly constrained by the available data. In the present analysis, additional constraints between elements within the Escherichia coli RNase P RNA-pre-tRNA complex were determined by intra- and intermolecular crosslinking experiments. Circularly permuted RNase P RNAs were used to position an azidophenacyl photoactive crosslinking agent specifically at strategic sites within the ribozyme-substrate complex. Crosslink sites were mapped by primer extension and confirmed by analysis of the mobility of the crosslinked RNA lariats on denaturing acrylamide gels relative to circular and linear RNA standards. Crosslinked species generally retained significant catalytic activity, indicating that the results reflect the native ribozyme structure. The crosslinking results support the general configuration of the structure model and predicate new positions and orientations for helices that were previously poorly constrained by the data set. The expanded library of crosslinking constraints was used, together with secondary and tertiary structure identified by phylogenetic sequence comparisons, to refine significantly the model of RNase P RNA with bound substrate pre-tRNA. The crosslinking results and data from chemical-modification and mutational studies are discussed in the context of the current structural perspective on this ribozyme.


Nerve growth factor maintains regulation of intracellular calcium in neonatal sympathetic neurons but not in mature or aged neurons.
We examined the effects of nerve growth factor on the regulation of intracellular calcium levels of superior cervical ganglion neurons in terms of postnatal maturation and ageing. Rat superior cervical ganglion neurons from three age groups (neonatal: 0 to one-day-old, young adult: three to six-month-old, and aged: more than 24-month-old) were dissociated and cultured in the presence or absence of 100 ng/ml of nerve growth factor. Intracellular free calcium levels ([Ca2+]i) were measured using the fura-2 microfluorometry. Nerve growth factor treatment increased the resting [Ca2+]i of neonatal neurons, although it had no effect on those of mature and aged neurons. We further examined the effects of nerve growth factor on the transient increase of [Ca2+]i induced by methacholine (0.1 mM), caffeine (20 mM) or high-potassium medium (40 mM K+). Nerve growth factor pre-treatment significantly increased the population of neonatal superior cervical ganglion neurons which responded to methacholine, whereas almost all young adult and aged neurons responded to methacholine regardless of pre-treatment of nerve growth factor. Caffeine induced a cyclic alteration of [Ca2+]i (oscillation) in 45% of the neonatal superior cervical ganglion neurons when they were maintained without nerve growth factor, but nerve growth factor treatment suppressed the oscillation to 10% of neurons. In contrast to neonatal neurons, all of the young adult and aged neurons showed only a transient increase of [Ca2+]i in response to caffeine independent of nerve growth factor treatment. There was no significant effect of nerve growth factor on K+ depolarization-induced [Ca2+]i elevations at any of the ages studied. Nerve growth factor did not substantially alter the pattern of the transients induced by these three agents. Our results indicate that exogenous nerve growth factor is necessary to maintain normal acetylcholine receptor-mediated [Ca2+]i responses as well as Ca(2+)-induced Ca2+ release from intracellular calcium storage in neonatal superior cervical ganglion neurons. In mature superior cervical ganglion neurons, Ca2+ homeostasis becomes independent of exogenous nerve growth factor, and Ca2+ homeostasis and its independency are well preserved in aged neurons.


Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster.
Methylation of histone H3 lysine 9 (H3K9) is a key feature of silent chromatin and plays an important role in stabilizing the interaction of heterochromatin protein 1 (HP1) with chromatin. Genomes of metazoans such as the fruit fly Drosophila melanogaster generally encode three types of H3K9-specific SET domain methyltransferases that contribute to chromatin homeostasis during the life cycle of the organism. SU(VAR)3-9, dG9a, and dSETDB1 all function in the generation of wild-type H3K9 methylation levels in the Drosophila genome. Two of these enzymes, dSETDB1 and SU(VAR)3-9, govern heterochromatin formation in distinct but overlapping patterns across the genome. H3K9 methylation in the small, heterochromatic fourth chromosome of D. melanogaster is governed mainly by dSETDB1, whereas dSETDB1 and SU(VAR)3-9 function in concert to methylate H3K9 in the pericentric heterochromatin of all chromosomes, with dG9a having little impact in these domains, as shown by monitoring position effect variegation. To understand how these distinct heterochromatin compartments may be differentiated, we examined the developmental timing of dSETDB1 function using a knockdown strategy. dSETDB1 acts to maintain heterochromatin during metamorphosis, at a later stage in development than the reported action of SU(VAR)3-9. Surprisingly, depletion of both of these enzymes has less deleterious effect than depletion of one. These results imply that dSETDB1 acts as a heterochromatin maintenance factor that may be required for the persistence of earlier developmental events normally governed by SU(VAR)3-9. In addition, the genetic interactions between dSETDB1 and Su(var)3-9 mutations emphasize the importance of maintaining the activities of these histone methyltransferases in balance for normal genome function.


The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial.
To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease. A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial. Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups. Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.


Trends in teenage smoking during pregnancy. Washington State: 1984 through 1988.
Smoking rates in the United States have decreased since 1963, but this trend is less apparent in adolescents, especially girls. Using data on birth certificates from 1984 through 1988, we analyzed smoking trends during pregnancy in teenagers in Washington State. There was a small but significant increase in the overall smoking prevalence during pregnancy between 1984 (32%) and 1988 (37%). Smoking rates varied by mother's age, race and ethnicity, marital status, and prenatal care. Whites had the highest smoking prevalence, and native Americans showed the largest increase in smoking prevalence over time. In the 5 years studied, unmarried pregnant teenagers had a smoking prevalence of 42.8%, compared with a rate of 31.7% in married teenagers. Compared with other studies of smoking rates in nonpregnant teenagers, pregnant teenagers in Washington State had a much higher smoking prevalence than their nonpregnant peers, and the differences between these two groups did not appear to diminish over time. This study suggests that there is little movement toward meeting the 1990 Health Objectives for the Nation regarding smoking in Washington State teenagers who become pregnant.


Predictors for choosing the specialty of Family Medicine from undergraduate knowledge and attitudes.
A cold climate towards primary care (PC) within medical academia could form a barrier against choosing family medicine (FM) as a career option. This study was designed to determine whether medical students' knowledge of and attitudes towards FM predicted their career choice. Cohort study conducted at two different medical schools. After completing a PC course at the Albacete Medical School in 2005-2006, 81 second-year students were asked to give responses to a questionnaire. In their sixth year (2009-2010), 79 students in Albacete and 42 in Seville (taken as an unexposed cohort) were asked to give responses too. Their choice of specialty was investigated in 2011. In Albacete, the questionnaire was answered by 79 second-year and 76 sixth-year students; in Seville, it was answered by 26 sixth-year students. After completing the PC course, 69.3% said they would like to become a family doctor. This percentage decreased to 40.3% at the end of the undergraduate course (P < 0.0001). In the sixth year, the attitudes towards FM worsened, yet these were significantly more favorable than those in Seville. Only 12 students chose FM; they obtained significantly worse scores in their specialty selection examination than their peers (P < 0.0001). In the Albacete Medical School, the students' opinion about FM worsened over the undergraduate course, although it was still better than the Seville students' stance. In any case, FM was seen to be a minority option.


An Innovative Approach to Clinical Practice Guideline Adaptation in the Nursing Profession in a Developing Country.
Healthcare professionals should seek the necessary resources to improve the quality of care. Given the cultural, social, and economic differences, in every health care system, there are increasing needs for the adapted versions of clinical practice guidelines (CPGs). This study aimed to introduce an innovative CPG adaptation approach for nurses working in a developing country. This study is comprised of three sections: a. An extensive systematic search of the literature, b. The adaptation process, c. Interviews, which were held with stakeholders, users and/or the target population. We applied all of the stages of guideline adaptation process according to Adaptation Resource Toolkit, with the integration of the findings of a systematic literature search and a qualitative content analysis in an "adolopted" new CPG. In this study, we applied a mix of three methods namely adoption, adaptation and development (adolopment) of recommendations to save time, cost, and manpower efficiently. Moreover, we integrated the utilized qualitative research method and literature review with the adolopment approach to develop the recommendations. Given there is a paucity of nursing clinical practice guidelines (NCPGs) in the nursing management of cancer therapy-induced mucositis and to save time and costs, the findings emerging from the adoption, adaptation, and de novo guideline development by a panel of experts and qualitative content analysis (QCA) method were integrated to achieve a more comprehensive nursing practice guideline.


Which venous system to choose for anastomosis in head and neck reconstructions?
It has been postulated that venous thrombosis in free flap surgery necessitates the use of 2 venous anastomoses into different venous systems. We retrospectively analyzed a single surgeon's 10-year experience (August 1993 to August 2003) in primary free flap reconstruction for malignant tumors of the head and neck. Of 492 primary reconstructions that did not need a vein graft, vein loop, or cephalic turnover procedure, 251 used the internal jugular venous system as venous outflow, 140 used the subclavian system as outflow, and 101 used both. Two hundred thirty-eight of 251 (95%) of flaps utilizing the internal jugular venous system for outflow were successful compared with 129 of 140 (92%) of flaps utilizing the subclavian system. Where both venous systems were used the success rate was 101 of 101 (100%) (P < 0.05). Where possible, a second venous anastomosis should be performed utilizing both venous drainage systems.


Acute and long-term biological effects of mechanically and chemically dispersed oil on lumpsucker (Cyclopterus lumpus).
Concentration dependent differences in acute and long-term effects of a 48 h exposure to mechanically or chemically dispersed crude oil were assessed on juvenile lumpsucker (Cyclopterus lumpus). Acute or post-exposure mortality was only observed at oil concentrations representing higher concentrations than reported after real oil spills. Acute mortality was more apparent in chemically than mechanically dispersed oil treatments whereas comparable EC50s were observed for narcosis. There was a positive correlation between EROD activity and muscle PAH concentration for the lower oil concentrations whereas higher concentrations inhibited the enzyme activity. The incidence of gill tissue lesions was low with no difference between dispersion methods or oil concentrations. A concentration dependent decrease in swimming- and feeding behavior and in SGR was observed at the start of the post-exposure period, but with no differences between corresponding oil treatments. Three weeks post-exposure, fish from all treatments showed as high SGR as the control fish.


Forces acting in the direction of propagation in pulsed ultrasound fields.
This paper considers some non-thermal effects resulting from absorption of acoustic energy from an ultrasound beam. An experimental investigation of the location of the 'source pump', responsible for the generation of streaming in high amplitude diagnostic fields in water, is reported. Acoustically transparent membranes were inserted in the ultrasound field in order to restrict the streaming volume. It is shown that the major contribution to an acoustic stream is generated in the region near to the focus of a transducer where the intensity in the beam and the degree of non-linear distortion are both high. In the second part of the paper a simple model of non-linear propagation is used to predict the magnitude of the maximum pressure gradient induced in a medium by the absorption of acoustic energy from a beam. Propagation in water, in tissue and in amniotic fluid are considered. Within the limitations of this model it is shown that the pressure gradients induced in pulsed acoustic fields do not result in the ultimate shear stress of tissue being exceeded.


Mode, load, and specific climate impact from passenger trips.
The climate impact from a long-distance trip can easily vary by a factor of 10 per passenger depending on mode choice, vehicle efficiency, and occupancy. In this paper we compare the specific climate impact of long-distance car travel with coach, train, or air trips. We account for both, CO2 emissions and short-lived climate forcers. This particularly affects the ranking of aircraft's climate impact relative to other modes. We calculate the specific impact for the Global Warming Potential and the Global Temperature Change Potential, considering time horizons between 20 and 100 years, and compare with results accounting only for CO2 emissions. The car's fuel efficiency and occupancy are central whether the impact from a trip is as high as from air travel or as low as from train travel. These results can be used for carbon-offsetting schemes, mode choice and transportation planning for climate mitigation.


Cognitive and linguistic effects of narrative-based language intervention in children with Developmental Language Disorder.
Narrative-based language intervention provides a naturalistic context for targeting overall story structure and specific syntactic goals in children with Developmental Language Disorder (DLD). Given the cognitive demands of narratives, narrative-based language intervention also has the potential to positively impact related abilities such as working memory and academic skills. Ten children (8-11 years old) with DLD completed 15 sessions of narrative-based language intervention. Results of single subject data revealed gains in language for five participants, four of whom improved on a probe tapping working memory. An additional four participants improved on a working memory probe only. On standardized measures, clinically significant gains were noted for one additional participant on a language measure and one additional participant on a visuospatial working memory. Carry over to reading was noted for three participants and to math for one participant. Across measures, gains in both verbal and visuospatial working memory were common. A responder analysis revealed that improvement in language may be associated with higher verbal short-term memory and receptive language at baseline. Those with working memory impairments were among those showing the fewest improvements across measures. Narrative-based language intervention impacted verbal skills in different ways across individual children with DLD.Implications: Further research is needed to gain an understanding of who benefits most from narrative-based language intervention.


Constructing a Culturally Informed Spanish Decision-Aid to Counsel Latino Parents Facing Imminent Extreme Premature Delivery.
Objective How Latino parents perceive and understand antenatal counseling for extreme prematurity, < 26 weeks of gestational age (GA), is not clear. We aim to characterize Latino parental perceptions of antenatal counseling in order to construct and validate a Spanish decision-aid (SDA) to improve parental knowledge of prematurity after antenatal consults. Methods This is a three-phased, prospective, multicenter study. First, interviews of 22 Latino parents with a history of birth < 26 weeks GA were conducted. Thematic analysis identified themes valued during antenatal counseling for decisions regarding neonatal resuscitation. Next, we incorporated these themes into the SDA. Finally, improvement in knowledge of prematurity in two Spanish-speaking groups, 'experienced' parents with a history of extremely premature birth and 'naïve' adult Latino volunteers, was measured using a multiple choice test before and after simulated counseling with the SDA. Result Twenty-two interviews generated seven unique themes. An SDA was constructed that preserved six themes paralleled by those found in a previously studied English population, and addressed a novel theme of "intercultural linguistic barriers" unique to our population. Knowledge scores rose in "naive" volunteers, 41 ± 12% to 71 ± 15% (P < 0.001), after simulated counseling with the SDA. 'Experienced' parents had a ceiling effect in knowledge scores, 62 ± 9% to 65 ± 11% (P = 0.22). The SDA was well received by participants. Conclusions for Practice Interviews of Latino parents with a history of premature birth generated similar themes to English-speaking parents, with intercultural linguistic barriers as a novel theme. An SDA for Latino parents facing extremely premature birth may improve comprehension of antenatal counseling.


Emission of Per- and Polyfluoroalkyl Substances from a Waste-to-Energy Plant─Occurrence in Ashes, Treated Process Water, and First Observation in Flue Gas.
Per- and polyfluoroalkyl substances (PFASs) are a large group of compounds commonly used as industrial chemicals and constituents of consumer products, e.g., as surfactants and surface protectors. When products containing PFASs reach their end of life, some end up in waste streams sent to waste-to-energy (WtE) plants. However, the fate of PFASs in WtE processes is largely unknown, as is their potential to enter the environment via ash, gypsum, treated process water, and flue gas. This study forms part of a comprehensive investigation of the occurrence and distribution of PFASs in WtE residues. Sampling was performed during incineration of two different waste mixes: normal municipal solid waste incineration (MSWI) and incineration of a waste mix with 5-8 wt % sewage sludge added to the MSWI (referred to as Sludge:MSWI). PFASs were identified in all examined residues, with short-chain (C4-C7) perfluorocarboxylic acids being the most abundant. Total levels of extractable PFASs were higher during Sludge:MSWI than during MSWI, with the total annual release estimated to be 47 and 13 g, respectively. Furthermore, PFASs were detected in flue gas for the first time (4.0-5.6 ng m-3). Our results demonstrate that some PFASs are not fully degraded by the high temperatures during WtE conversion and can be emitted from the plant via ash, gypsum, treated process water, and flue gas.