Axial length and posterior staphyloma in Saudi Arabian cataract patients.
To determine the axial length distribution and prevalence of posterior staphyloma in a group of Saudi Arabian patients having cataract extraction. Tertiary care referral center. Approximately 75% of all cataract patients at the eye hospital have preoperative B-scan ultrasonography. The last 1000 B-scans performed for any reason were screened for patients having uncomplicated cataract surgery; 629 cases were included. The relationship between the presence of posterior staphyloma and patient age, sex, and axial length was studied. There were 371 (59.0%) men and 258 (41.0%) women with a mean age of 62.4 years +/- 15.7 (SD). Posterior staphyloma was identified in 67 patients (10.7%). The presence of staphyloma was not significantly related to patient sex or age. Although the mean axial length was significantly longer in eyes with staphyloma (27.43 +/- 2.36 mm) than in those without (23.18 +/- 1.64 mm), 9.3% of eyes without staphyloma had an axial length longer than 25.0 mm. No staphylomas were present in eyes with an axial length shorter than 23.3 mm. The longest axial length in an eye without a staphyloma was 32.5 mm. Posterior staphyloma was present in a high percentage of Saudi Arabian patients having cataract extraction.


Temporal relationships in the effects of protein-free diet on the activities of rat liver branched-chain ketoacid dehydrogenase complex and kinase.
Feeding rats 0% casein diet decreased liver activities of branched-chain ketoacid dehydrogenase complex (active form) and of activator protein (complete within 4 days), and increased activity of branched-chain ketoacid dehydrogenase kinase (complete within 9-10 days). Refeeding normal diet to rats fed 0% casein diet for 10 days resulted in a rapid and partial (approx. 50%) reversal of the above effects within 24 h; complete reversal required 20-30 days of refeeding.


Calcium signalling: past, present and future.
Ca2+ is a universal second messenger controlling a wide variety of cellular reactions and adaptive responses. The initial appreciation of Ca2+ as a universal signalling molecule was based on the work of Sydney Ringer and Lewis Heilbrunn. More recent developments in this field were critically influenced by the invention of the patch clamp technique and the generation of fluorescent Ca2+ indicators. Currently the molecular Ca2+ signalling mechanisms are being worked out and we are beginning to assemble a reasonably complete picture of overall Ca2+ homeostasis. Furthermore, investigations of organellar Ca2+ homeostasis have added complexity to our understanding of Ca2+ signalling. The future of the Ca2+ signalling field lies with detailed investigations of the integrative function in vivo and clarification of the pathology associated with malfunctions of Ca2+ signalling cascades.


Fetal exposure to phthalates and bisphenols and childhood general and organ fat. A population-based prospective cohort study.
Fetal exposure to phthalates and bisphenols might have long-lasting effects on growth and fat development. Not much is known about the effects on general and organ fat development in childhood. We assessed the associations of fetal exposure to phthalates and bisphenols with general and organ fat measures in school-aged children. In a population-based, prospective cohort study among 1128 mother-child pairs, we measured maternal urinary phthalate metabolites and bisphenol concentrations in first, second, and third trimester. Offspring body mass index, fat mass index by dual-energy X-ray absorptiometry, and visceral and pericardial fat indices and liver fat fraction were measured by magnetic resonance imaging at 10 years. After adjustment for confounders and correction for multiple testing, an interquartile range increase in first trimester phthalic acid concentrations remained associated with a 0.14 (95% confidence interval: 0.05, 0.22) standard deviation score increase in pericardial fat index. We also observed tendencies for associations of higher maternal low molecular weight phthalate urinary concentrations in second trimester with childhood pericardial fat index, but these were not significant after adjustment for multiple testing. High molecular weight phthalate, di-2-ethylhexyl phthalate, and di-n-octyl phthalate concentrations were not associated with childhood outcomes. Maternal urinary bisphenol concentrations were not associated with childhood adiposity. Maternal first trimester phthalic acid concentrations are associated with increased childhood pericardial fat index at 10 years of age, whereas maternal bisphenol concentrations are not associated with childhood adiposity. We did not find significant sex-specific effects. These findings should be considered as hypothesis generating and need further replication and identification of underlying mechanisms.


Characterization of an intracellular insulin-degrading enzyme in human erythrocytes.
Using conventional techniques of ammonium sulfate fractionation and Sephadex gel column chromatography, insulin-degrading enzyme was partially purified from lysate of human erythrocytes. The enzymatic activity was measured by the trichloroacetic acid precipitation method. Compared to trypsin, the enzyme was highly specific for insulin. The apparent molecular weight of the enzyme was 160,000 Da, the optimum pH was the 7.4 to 7.8 range, and the Km value for insulin for the partially purified enzyme was 162 nM. Bacitracin and N-ethylmaleimide were potent inhibitors, while chloroquine, ethylenediaminetetraacetate, antipain, and soybean trypsin inhibitor failed to inhibit the activity of the enzyme. Like most nucleated cells, human erythrocytes not only have the membranal insulin receptors, but also possess the cytosolic specific insulin-degrading enzyme. Insulin internalization and degradation are shown to be due to the receptor and the enzyme acting in concert as in many nucleated cells. Anucleated erythrocytes have both these entities for possible internalization and degradation of insulin.


Two-dimensional network formation of cardiac myocytes in agar microculture chip with 1480 nm infrared laser photo-thermal etching.
We have developed a new method that enables agar microstructures to be used to cultivate cells and that allows cell network patterns to be controlled. The method makes use of non-contact three-dimensional photo-thermal etching with a 1480 nm infrared focused laser beam, which is strongly absorbed by water and agar gel, to form the shapes of agar microstructures. It allows microstructures to be easily formed in an agar layer within a few minutes, with cell-culture holes formed by the spot heating of a 100 mW laser and tunnels by the tracing of a 100 microm s(-1), 40 mW laser. We cultivated rat cardiac myocytes in adjacent microstructures and observed synchronized beating in them 90 min after they had made physical contact. Our results indicate that the system can make and use microstructures for cell-network cultivation in a minimal amount of time without any expensive microfabrication facilities or complicated procedures.


Differential effects of heart rate modification training on college students, older males, and patients with ischemic heart disease.
Seventy male subjects participated in a six session study of feedback-mediated heart rate modification. Three groups of subjects were compared: (1) college students, (2) patients with ischemic heart disease, and (3) healthy males, age-matched to the patients. The groups did not differ in heart rate during rest or in response to a perceptual-motor tracking task. However, the college students produced significantly larger changes in cardiac rate than the other two groups when instructed to modify heart rate (speed or slow) and provided with exteroceptive feedback. The patients showed the poorest overall feedback performance. These differences between groups were greater for speeding than for the slowing task. Relationships were explored between feedback performance and resting heart and respiration rate, drug regime, and personality questionnaires. The results were consistent with the hypothesis that interdependence between psychological stimuli and cardiovascular events is reduced in heart disease.


Fluorescence of Trypan blue in frozen-dried embryos of the rat.
Freeze-drying and fluorescence microscopy techniques were combined to create a sensitive method for the visualization of the teratogenic dye, Trypan blue, in both protein-bound and free forms. In the development and initial application of this method, visceral yolk sacs of several gestational ages as well as normal appearing, 12-day embryos obtained from dye-injected rats were utilized. Observations on paraffinized sections of the yolk sac placentae demonstrated that only the protein-bound form of the dye exists in the yolk sac cavity whereas both forms of the dye exist in supranuclear regions of cells of the visceral endoderm. Paraffin sections of the normal appearing, 12-day embryos displayed the protein-bound form of dye within lumina of mid- and hind-gut, and both forms of dye in the primitive mucosa of mid- and hind-gut. The advantages of the method are derived not only from the use of fluorescence microscopy but also from the avoidance of solvents that are employed in more routine microtechniques.


Sleep-Disordered Breathing, Quality of Sleep and Chronotype in a Cohort of Adult Patients with Bardet-Biedl Syndrome.
Bardet-Biedl syndrome (BBS) is a rare but well-recognized ciliopathy with high genetic and phenotypic heterogeneity. Cardinal features include obesity, diabetes and high blood pressure (HBP), which are often associated with sleep-disordered breathing. Also, the high prevalence of blindness due to retinal dystrophy could affect circadian sleep-wake rhythms. We characterized in this cohort of adult BBS patients sleep-disordered breathing, sleep quality, daytime sleepiness and chronotype. Thirty-two patients with genetically confirmed BBS were included in this observational single center study. Overnight respiratory polygraphy was performed for sleep apnea syndrome (SAS) in 30 patients. Quality of sleep, daytime sleepiness, fatigue and chronotype were assessed in 25 patients using Pittsburgh sleep quality index (PSQI), 14-day sleep diary (SD), Epworth sleepiness scale (ESS), Pichot fatigue scale (PFS) and Horne and Ostberg morningness-eveningness questionnaire (MEQ). Patients' mean age was 32±11 years and mean BMI 32.6±7.7 kg/m2. Eleven (35%) patients had HBP and 7 (22%) diabetes. Moderate to severe sleep apnea syndrome (SAS) was present in 5 (17%) and was not associated with altered sleep, daytime sleepiness or fatigue. Most of the patients (63%) evaluated their sleep as of good quality (PSQI ≤ 5). Median scores of sleep quality, daytime sleepiness and fatigue were normal (PSQI of 3.0 [2.0-6.0], ESS of 9.0 [6.0-13.0] and PFS of 8.0 [3.0-13.0], respectively). Predominant chronotypes according to MEQ were either "intermediate" (57%) or "moderate morning" (29%). None had a free running sleep-wake cycle. 14-day SD revealed overall few awakenings at night and low daytime napping. Given the cardiovascular risk factors, systematic screening for SAS should be considered in BBS patients, regardless of sleep and daytime vigilance complaints. None of these highly visually impaired patients had a circadian sleep-wake rhythm disorder. Further objective assessments are needed to better characterize sleep and circadian rhythms in BBS patients.


[NF-kappa B expression in cholangiocarcinoma transfected with hepatitis C virus core gene].
To study the role of hepatitis C virus (HCV) in the development of cholangiocarcinoma. Recombinant plasmid of HCV-C gene constructed by molecular cloning technique was identified with restricting enzyme map. Then, it was transfected into QBC939 cells with lipofectin. After selection with G418, the resistant colonies were obtained and analysed by immunocytochemistry and Western blotting. Their morphology was observed by transmission electron microscopy (TEM). The expression of NF-kappa B was detected by immunocytochemistry. The results suggested that the recombinant plasmid was proved to carry the target gene by restricting enzyme map. Moreover, it could express HCV-C protein efficiently in QBC939 cells. The HCV-like particles were found in the cytoplasm by TEM, which were spherical with diameter of 50-80 nm possessing an outer membrane. Moreover, NF-kappa B activation was shown in HCV core gene-transfected cells. Because HCV-C gene could express steadily in cholangiocarcinoma cells, the transfected tumor cells (QBC939-HCVc) are an experimental model for studying the effect of HCV on the development of cholangiocarcinoma. The activation of NF-kappa B may be related to escape from immune surveillance and carcinogenesis of cholangiocarcinoma.


A square peg in a round hole? Challenges with DALY-based "burden of disease" calculations in surgery and a call for alternative metrics.
In recent years, surgical providers and advocates have engaged in a growing effort to establish metrics to estimate capacity for surgical services as well the burden of surgical diseases in resource-limited settings. The burden of disease (BoD) studies have established the disability-adjusted life year (DALY) as the primary metric to measure both disability and premature mortality. Nonetheless, DALY-based approaches present methodological challenges, some of which are unique to surgical conditions, not fully addressed through the multiple iterations of the BoD studies, including the most recent study. This paper examines these challenges in detail, including issues around age-weighting and discounting, and estimates of disability-weights for specific conditions. Surgical burden measurements of specific conditions, or through the assessment of hospital wards as platforms for service delivery, still have unresolved methodological hurdles. The 2010 BoD study addresses some of these issues, but many questions still remain. Other methods estimating surgical prevalence, backlogs in treatment, and disability incurred by delays in care may provide more practical approaches to disease burden that can be useful tools for clinicians and health advocates. These approaches warrant further exploration in LMICs and these debates require active engagement by surgical providers and advocates globally.


[Congenital disorder of glycosylation type Ia (CDG Ia) - underdiagnosed entity?].
Congenital disorders of glycosylation (CDG) are a relatively recently identified group of multisystem disorders caused by defective glycosylation of N-glycosylated proteins. They mainly involve the central and peripheral nervous system, but other organ systems are involved as well. Type CDG Ia accounts for over 80% of cases, characterized by decreased activity of the enzyme phosphomannomutase caused by mutations in chromosome 16 PMM2 gene. Treatment of CDG Ia remains symptomatic.


Intensification of Penaeid Shrimp Culture: An Applied Review of Advances in Production Systems, Nutrition and Breeding.
Intensification of the shrimp sector, also referred to as vertical expansion, has been predominately driven by consecutive incidences of global disease outbreaks, which have caused enormous economic loss for the main producer countries. A growing segment of the shrimp farming industry has opted to use production systems with higher density, biosecurity, and operating control to mitigate the risks posed by disease. However, successful super-intensive shrimp production is reliant on an advanced understanding of many important biological and economic parameters in the farming system, coupled with effective monitoring, to maintain optimal production. Compared to traditional extensive or semi-intensive systems, super-intensive systems require higher inputs of feed, energy, labor, and supplements. These systems are highly sensitive to the interactions between these different inputs and require that the biological and economical parameters of farming are carefully balanced to ensure success. Advancing nutritional knowledge and tools to support consistent and efficient production of shrimp in these high-cost super-intensive systems is also necessary. Breeding programs developing breeding-lines selected for these challenging super-intensive environments are critical. Understanding synergies between the key areas of production systems, nutrition, and breeding are crucial for super-intensive farming as all three areas coalesce to influence the health of shrimp and commercial farming success. This article reviews current strategies and innovations being used for Litopenaeus vannamei in production systems, nutrition, and breeding, and discusses the synergies across these areas that can support the production of healthy and high-quality shrimp in super-intensive systems. Finally, we briefly discuss some key issues of social license pertinent to the super-intensive shrimp farming industry.


Influence of Incorporating Fluoroapatite Nanobioceramic on the Compressive Strength and Bioactivity of Glass Ionomer Cement.
In order to increase the performance of glass ionomer cement, it is reinforced with metal powders, short fibers, bioceramics and other materials. Fluoroapatite (Ca10(PO4)6F2) is found in dental enamel and is usually used in dental materials due to its good chemical and physical properties. In this study, the effects of the addition of synthesized fluoroapatite nanoceramic on the compressive strength and bioactivity of glass ionomer cement were investigated. The synthesized fluoroapatite nanoceramic particles (~ 70 nm) were incorporated into as-prepared glass ionomer powder and were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Moreover, the compressive strength values of the modified glass ionomer cements with 0, 1, 3 and 5 wt% of fluoroapatite were evaluated. Results showed that glass ionomer cement containing 3 wt% fluoroapatite nanoparticles exhibited the highest compressive strength (102.6 ± 4) compared to the other groups, including control group. Furthermore, FTIR and SEM investigations indicated that after soaking the glass ionomer cement- 3 wt% fluoroapatite composite in the simulated body fluid solution, the intensity of O-H, P-O and C-O absorption bands increased as a result of the formation of apatite layer on the surface of the sample, and the rather flat and homogeneous surface of the cement became more porous and inhomogeneous. Addition of synthesized nano-fluoroapatite to as-prepared glass ionomer cement enhanced the compressive strength as well as nucleation of the calcium phosphate layer on the surface of the composite. This makes it a good candidate for dentistry and orthopedic applications.


Wheezing after the use of acetaminophen and or ibuprofen for first episode of bronchiolitis or respiratory tract infection.
Bronchiolitis sometimes triggers the development of subsequent recurrent wheezing. Treatment with either acetaminophen or ibuprofen during the initial episode may affect the occurrence of subsequent wheezing. We did a retrospective study comparing the effect of prescribing acetaminophen, ibuprofen, or neither for a first episode of bronchiolitis on medical attendances for subsequent wheezing in infants younger than 12 months. We created our cohorts using California Medicaid data from 2003 to 2010. We used propensity score derived inverse probability weights to adjust for non-random drug assignment. We used robust negative binomial regression to model incident rate ratios (IRR) for medical attendances at 365, 30, and 14-day follow-up. We did similar analyses for the effect of antipyretics for a first medically attended upper respiratory tract infection (URI) on subsequent wheezing. Compared with no antipyretic, treatment with acetaminophen or ibuprofen for a first episode of bronchiolitis was associated with decreased wheezing at 365-day follow-up (IRR 0.18, 95% CI 0.15-0.22), and ibuprofen plus acetaminophen over ibuprofen (IRR at 0.12, 95% CI 0.05-0.32). The results were similar at 30 and 14-day follow-up. Ibuprofen alone and ibuprofen plus acetaminophen were associated with decreased visits for subsequent wheezing at 365-day (IRR 0.79, 95% CI 0.68-0.92), but not earlier timepoints, when compared with acetaminophen. A smaller effect was seen for ibuprofen at one year if prescribed for a URI (IRR 0.87, 95% CI 0.76-1.00) but not at earlier follow-up. Children who are prescribed antipyretics for a first episode of bronchiolitis may have less subsequent wheezing than those who are not. We found fewer visits for subsequent wheezing for those prescribed ibuprofen, and ibuprofen combined with acetaminophen, compared with acetaminophen alone.


Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of 512 cases.
Primary pars plana vitrectomy (PPPV) has gained widespread popularity in the treatment of rhegmatogenous retinal detachments (RRD). However, the surgical procedure is still flawed by a significant rate of anatomical and functional failures. The study was conducted to analyse the risk factors for a dissatisfying postoperative outcome. We carried out a retrospective study of 512 cases of PPPV with a minimum follow-up of 3 months from one institution over a 9-year period. Preoperatively, 24.8% of patients (127 out of 512) were pseudophakic, 16.4% (84 out of 512) highly myopic, 19.9% (102 out of 512) had preoperative proliferative vitreoretinopathy (PVR) and 14.6% (75 out of 512) had vitreous haemorrhage. The follow-up period ranged from 3 to 108 months (median 14.8). Retinal reattachment was achieved with one operation in 70.7% (362 out of 512) and after one or more operations in 97.5% of cases (499 out of 512). The major reasons for redetachments were new retinal breaks, followed by a combination of new breaks and PVR, and PVR without apparent breaks. Postoperative visual acuities of > or =0.1 and > or =0.4 were achieved in 82.8% (424 out of 512) and 48.2% (247 out of 512) respectively. Out of 376 phakic patients at study entry, 66.4% (250 out of 376) underwent cataract surgery either in combination with PPPV or during the postoperative course. Factors that were significantly associated with either anatomical or functional failure included duration of symptoms, low preoperative visual acuity, myopia, amblyopia, hypotony, macular detachment, preoperative PVR, extent of detachment, involvement of inferior quadrants, no detectable breaks, large breaks, breaks posterior to the equator, surgeon, level of surgical training, endocryotherapy, and combined scleral buckling surgery. Primary pars plana vitrectomy is still flawed by a relatively high primary redetachment rate following the initial procedure. The advantages of the technique are a high final reattachment rate and relatively good functional results in a subset of patients with more complicated types of RRD. The risk factors for postoperative failures following PPPV for RRD match to a large extent those following scleral buckling surgery (SBS). Future improvements of the technique will have to focus on modifiable risk factors, such as details of the surgical procedures, surgical training and case selection, to distinguish it from SBS.


An advanced pharmacy practice experience in sports pharmacy.
To establish and evaluate an advanced pharmacy practice experience (APPE) in sports pharmacy. Students actively participated in a variety of activities for this new 6-week elective APPE, including drug-testing collections, delivering presentations, and providing drug information. Students also learned about assays, compounding, and dispensing medications specifically for athletes, and visited various athletic medical facilities. Student were given written and practical certification examinations for drug-testing collections, and their specimen measurements were compared to those obtained by the testing laboratory for validation; satisfaction surveys were obtained from testing sites; and presentation evaluations were obtained from audience participants. Students were able to accurately measure pH and specific gravity of urine samples and all students passed the certification examination. Students rated the APPE very high. Also, students received high satisfaction ratings on surveys administered to the officials of the schools where they tested and members of the groups to whom they gave presentations. Students gained experience and insight into the various roles of pharmacists in sports pharmacy and developed confidence in their ability to conduct drug-testing collections.


Aortic valve replacement in the presence of sternal metastases from prostatic carcinoma: a case report.
A 65-year-old man was admitted with New York Heart Association Class IV heart failure, refractory to maximal medical therapy. High-grade aortic insufficiency and severe left ventricular dysfunction were demonstrated by cardiac catheterization. The patient had known prostatic carcinoma with extensive metastatic involvement of the sternum. Aortic valve replacement was performed successfully through a median sternotomy incision and the patient returned to full activities.


In vivo cartilage contact deformation of human ankle joints under full body weight.
Quantitative data on in vivo deformation of articular cartilage is important for understanding the articular joint function and the etiology of degenerative joint diseases such as osteoarthritis. This study experimentally determined the in vivo cartilage thickness distribution and articular cartilage contact strain distribution in human ankle joints under full body weight loading conditions using a combined dual fluoroscopic and magnetic resonance imaging technique. The average cartilage thickness with the joint non-weight bearing was found to be 1.43 mm +/- 0.15 mm and 1.42 mm +/- 0.18 mm in the distal tibial and proximal talar cartilage layers, respectively. During weight bearing on a single leg, the strain distribution data revealed that 42.4% +/- 15.7% of the contact area had contact strain higher than 15% in the ankle joint. Peak cartilage contact strain reached 34.5% +/- 7.3%. This quantitative data on in vivo human cartilage morphology and deformation demonstrated that the cartilage may undergo large deformations under the loading conditions experienced in human ankle joints during daily activities. The in vivo cartilage contact deformation can be used as displacement boundary conditions in three-dimensional (3D) finite element models of the joint to calculate in vivo 3D articular cartilage contact stress/strain distributions.


Biomonitoring of 4,4'-methylene dianiline by measurement in hydrolysed urine and plasma after epicutaneous exposure in humans.
Five healthy volunteers were dermally exposed for 1 h to 0.75-2.25 mumol 4,4'-methylene dianiline (MDA) dissolved in isopropanol, by use of a patch-test technique. Determination of MDA remaining in the patch units after exposure showed that a median of 28% (range 25-29%) was absorbed. By analysis of hydrolysed plasma, an initial accumulation of MDA could be shown, and then a decline. MDA was also detected in hydrolysed urine. The maximum rate of MDA excretion in urine was found 6-11 h after the onset of exposure. Within two subjects studied at three doses, the urinary excretion was proportional to the exposure. The elimination half-lives (elim-t1/2) in plasma and urine had medians of 13 and 7 h, respectively. In eight out of nine exposures, the elim-t1/2 was longer in plasma than in urine. Slow acetylation seemed to be associated with short elim-t1/2 in urine. The median of total MDA amount excreted in urine during 48 h, was 33 nmol for the five subjects exposed to 0.75 mumol, which corresponded to roughly 16% (range 2%-26%) of the absorbed dose while only a limited number of individuals were studied, the data still indicated that MDA in hydrolysed plasma or urine can be used for biological monitoring of occupational dermal exposure. However, the individual variation must be taken into account. Sampling should preferably be made several hours post shift. Urine is preferred before plasma at low exposures, because of its higher concentrations of MDA.


Reduction of redundant laboratory orders by access to computerized patient records.
From a convenience sample of 500 consecutive patients seen in the emergency department (ED), occasions were recorded when data from the Veterans Affairs Decentralized Hospital Computer Program provided immediate clinical decision support and obviated redundant laboratory tests. Patient care was improved by access to inpatient discharge summaries in 85 cases (19%), laboratory results in 34 (7%), pharmacy records of allergies and prescriptions in 30 (6%), radiologic reports in 19 (4%), and electrocardiograms in 11 (2%). Overall savings in tests, prescriptions, admissions, and errors were estimated at about $5 per visit. Availability of previous laboratory results clearly decreased ordering of redundant studies. Computer-based medical records also provided details of previous diagnoses, treatments, allergies, and current medications. On many occasions, the presumptive diagnosis had already been worked up and proven or disproven, thus simplifying the entire encounter.


County-Level Prevalence Estimates of Autism Spectrum Disorder in Children in the United States.
Prevalence estimates of autism spectrum disorder (ASD) point to geographic and socioeconomic disparities in identification and diagnosis. Estimating national prevalence rates can limit understanding of local disparities, especially in rural areas where disproportionately higher rates of poverty and decreased healthcare access exist. Using a small area estimation approach from the 2016-2018 National Survey of Children's Health (N = 70,913), we identified geographic differences in ASD prevalence, ranging from 4.38% in the Mid-Atlantic to 2.71% in the West South-Central region. Cluster analyses revealed "hot spots" in parts of the Southeast, East coast, and Northeast. This geographic clustering of prevalence estimates suggests that local or state-level differences in policies, service accessibility, and sociodemographics may play an important role in identification and diagnosis of ASD.County-Level Prevalence Estimates of Autism Spectrum Disorder in Children in the United States.


Monoclonal antibody therapy of cancer.
The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti-vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti-epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung. Cetuximab, used alone or with salvage chemotherapy, produces clinically meaningful anti-tumor responses in patients with chemotherapy-refractory cancers of the colon and rectum. In addition, the anti-HER2/neu antibody trastuzumab (Herceptin), in combination with standard adjuvant chemotherapy, has been shown to reduce relapses and prolong disease-free and overall survival in high-risk patients after definitive local therapy for breast cancer. These exciting recent results provide optimism for the development of mAbs that bind novel targets, exploit novel mechanisms of action or possess improved tumor targeting. Progress in the clinical use of radioimmunoconjugates remains hindered by complexity of administration, toxicity concerns and insufficiently selective tumor targeting.


Organic dyes containing a coplanar indacenodithiophene bridge for high-performance dye-sensitized solar cells.
A series of new organic dyes exploiting coplanar indacenodithiophene as the central π-spacer of the classical donor-(π-spacer)-acceptor configuration were synthesized and characterized for dye-sensitized solar cells. The coplanarity of the indacenodithiophene core facilitates efficient donor to acceptor charge transfer, imparting the new organic dyes significant bathochromic shifts and remarkable power conversion efficiencies of up to 6.7% (DTInDT) under AM 1.5G radiation.


Validation of clinical-radiological scores for prognosis of mortality in acute pulmonary embolism.
Acute pulmonary embolism (APE) is a hazardous disorder with a high mortality. Combination of clinical, radiological, and serological parameters can improve risk stratification of APE. Most of the proposed combined scores were not validated in independent cohorts. Our aim was to validate the proposed clinical-radiological scores for prognosis of 7- and 30-day mortality in APE. Our sample comprised 531 patients with APE, mean age 64.8 ± 15.6 years, 221 (41.6%) females and 310 (58.4%) males. The following parameters were collected: Age and sex of the patients, mortality within the observation time of 30 days, simplified pulmonary embolism severity index (sPESI), pH troponin level (pg/ml), minimal systolic and diastolic blood pressures (mmHg), heart rate, O2 saturation, episodes of syncope, and need for vasopressors. On CT pulmonary angiography (CTPA), short axis ratio right ventricle/left ventricle (RV/LV), and reflux of contrast medium into the inferior vena cava were obtained. The following clinical-radiological scores were calculated: BOVA score, pulmonary embolism mortality score (PEMS), European Society of Cardiology (ESC) score, Kumamaru score, and Calgary acute pulmonary embolism (CAPE) score. Overall, 31 patients (5.8%) died within seven and 64 patients (12%) within 30 days. All scores showed high negative prognostic values ranging from 89.0 to 99.0%. PEMS and CAPE score demonstrated the highest specificity for 7-day mortality (93.4% and 85.0%), PEMS and BOVA for 30-day mortality (94.2% and 90.4%). The highest sensitivity was observed for ESC 2019 (96.8% and 95.3%). Kumamaru and CAPE scores had low sensitivity. All scores had low positive and high negative predictive values. For prognosis of 7- and 30-day mortality in APE, PEMS score has the highest specificity. ESC 2019 shows the highest sensitivity. All scores had low positive and high negative predictive values.


The 6-minute walking test and all-cause mortality in patients undergoing a post-cardiac surgery rehabilitation program.
The 6-minute walking test (6mWT) is used to prescribe physical activity in cardiac surgery patients. The clinical value of a pre-discharge 6mWT and its association with outcome is not well defined. We retrospectively analyzed data from 313 patients (age 66 ± 11 years, 23% females, left ventricular ejection fraction (LVEF) 52 ± 11%, Hb 10.5 ± 1.3 g/dl, serum albumin 3.9 ± 0.4 mg/dl) who were admitted to our rehabilitation institute following cardiac surgery. A 6mWT was performed at entry and at discharge and expressed as % of theoretical predicted values calculated on the basis of individual age, height, weight and sex. The endpoint was represented by all-cause mortality. The predictive value of 6mWT was tested in univariate and multivariate analysis. A pre-discharge 6mWT was completed by 284 out of 313 patients. Two patients died in hospital. During a median of 23 months, mortality was 9% (26/284) and 44% (12/27) (p < 0.0001) in patients who did or did not perform the pre-discharge 6mWT. The distance covered at the pre-discharge 6mWT as a continuous variable of % predicted values was a significant predictor of subsequent mortality (Hazard Ratio (HR) 0.97 (95% CI 0.96-0.99), p = 0.0019). After adjustment for all preselected covariates, the pre-discharge 6mWT (HR 0.97 (95% CI 0.95-0.99), p = 0.0038) and LVEF (HR 0.93 (95% CI 0.90-0.96), p < 0.0001) remained significantly associated with the outcome. In recent cardiac surgery patients, the pre-discharge 6mWT is not only a valid measurement of the impact of cardiac rehabilitation but also provides outcome information offering the possibility to identify patients who may need more intensive follow-up.


Development of RT-qPCR for quantification of human enterovirus D68 in vitro.
The common cold is the most frequent viral infectious disease of the upper respiratory tract with different intensities based on the serotype and the characteristics of the virus. Numerous human rhinoviruses have been identified and classified. Human rhinovirus 87 (HRV87), also known as enterovirus D68 (EV-D68), is one of the common viruses causing respiratory infections. In this study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was developed, optimized, and validated for the detection of EV-D68. Method development also covers specificity, sensitivity, efficiency, and inter-and-intra-assay variations. Overall, this one-step qPCR assay will permit quantitative assessments of human enterovirus D68 RNA.•Enterovirus D68 is a reemerging viral agent causing respiratory infection.•RT-qPCR assay developed for detection of human enterovirus D68.•In this article validation to secure reproducibility is done according to MIQE guidelines.


Fanconi anemia proteins counteract the implementation of the oncogene-induced senescence program.
Fanconi Anemia (FA), due to the loss-of-function of the proteins that constitute the FANC pathway involved in DNA replication and genetic stability maintainance, is a rare genetic disease featuring bone marrow failure, developmental abnormalities and cancer predisposition. Similar clinical stigmas have also been associated with alterations in the senescence program, which is activated in physiological or stress situations, including the unscheduled, chronic, activation of an oncogene (oncogene induced senescence, OIS). Here, we wanted to determine the crosstalk, if any, between the FANC pathway and the OIS process. OIS was analyzed in two known cellular models, IMR90-hTERT/ER:RASG12V and WI38-hTERT/ER:GFP:RAF1, harboring 4-hydroxytamoxifen-inducible oncogenes. We observed that oncogene activation induces a transitory increase of both FANCA and FANCD2 as well as FANCD2 monoubiquitination, readout of FANC pathway activation, followed by their degradation. FANCD2 depletion, which leads to a pre-senescent phenotype, anticipates OIS progression. Coherently, FANCD2 overexpression or inhibition of its proteosomal-dependent degradation slightly delays OIS progression. The pro-senescence protease cathepsin L, which activation is anticipated during OIS in FANCD2-depleted cells, also participates to FANCD2 degradation. Our results demonstrate that oncogene activation is first associated with FANCD2 induction and activation, which may support initial cell proliferation, followed by its degradation/downregulation when OIS proceeds.


Multiparametric assessment of sensorimotor abnormalities in vulnerable populations: A window of opportunity.
This commentary suggests that neuroscience research on young healthy heavy cannabis users and patients with cannabis-induced psychosis using multimodal assessment of sensorimotor dysfunction (e.g. neuroimaging, clinical rating scales, and instrumental assessments) may help to identify both biological resistance and vulnerability without constraints and confounder factors imposed by antipsychotic treatment or disease chronicity.


Defects in Antiviral T Cell Responses Inflicted by Aging-Associated miR-181a Deficiency.
Generation of protective immunity to infections and vaccinations declines with age. Studies in healthy individuals have implicated reduced miR-181a expression in T cells as contributing to this defect. To understand the impact of miR-181a expression on antiviral responses, we examined LCMV infection in mice with miR-181ab1-deficient T cells. We found that miR-181a deficiency delays viral clearance, thereby biasing the immune response in favor of CD4 over CD8 T cells. Antigen-specific CD4 T cells in mice with miR-181a-deficient T cells expand more and have a broader TCR repertoire with preferential expansion of high-affinity T cells than in wild-type mice. Importantly, generation of antigen-specific miR-181a-deficient CD8 effector T cells is particularly impaired, resulting in lower frequencies of CD8 T cells in the liver even at time points when the infection has been cleared. Consistent with the mouse model, CD4 memory T cells in individuals infected with West Nile virus at older ages tend to be more frequent and of higher affinity.


Comparison of different ionic liquids pretreatment for barley straw enzymatic saccharification.
Recently, application of ionic liquids due to their special solvency properties as a promising method of pretreatment for lignocellulosic biomass has received much attention. Chemical stability, temperature stability, non-flammability, low vapor pressure, wide liquidus range, and non-toxicity are among those unique properties. These solvents are also known as green solvents due to non-toxicity and low vapor pressure. The present study was set to compare the effect of five different ionic liquids namely, 1-ethyl-3-methyl imidazolium acetate, 1-ethyl-3-methyl imidazolium diethyl phosphate, 1-butyl-3-methyl imidazolium chlorides, 1,3-dimethyl imidazolium dimethyl phosphate, and 1-butyl-3-methylimidazolium-trifluoromethane sulfonate on barley straw in bioethanol production process. The performance of ionic liquids was evaluated based on the change observed in chemical structure, crystallinity index, and cellulose digestibility. Overall, 1-ethyl-3-methyl imidazolium acetate was found most effective in pretreating barely straw for bioethanol production. To the best of our knowledge, the present study reports different ionic liquids; some for the first time, for barely straw pretreatment.


HPLC-assay with electrochemical detection for the neurotoxin MPTP, its metabolite MPP+ and MPTP-analogues in biological samples after purification over Sephadex G10.
A sensitive and selective method for assaying the neurotoxin MPTP and some MPTP-analogues in mouse brain and serum is described. The method is based on isolation of the compounds from biological samples on small Sephadex G10 columns followed by reverse phase HPLC with amperometric detection. HPLC separation was performed at pH 3, after which the pH was increased to 6.8 by mixing the column effluent with 0.5 M phosphate pH 9, to provide the conditions required for electrochemical detection. A metabolite of MPTP, MPP+, was determined as MPTP after reduction with NaBH4. This assay allows the determination of brain and serum concentrations in the pmol/g range of administered MPTP and MPTP-analogues and the effects of these substances on dopamine and its metabolites in the same tissue sample.


Recruitment and in situ renewal regulate rapid accumulation of CD11c+ cells in the lung following intranasal superantigen challenge.
Staphylococcusaureus, a primary source of bacterial superantigen, is known to colonize the human respiratory tract and has been implicated in airway inflammation. The potential pathological effect of staphylococcal enterotoxins on the respiratory tract necessitates a detailed understanding of how they regulate innate immune cells, particularly CD11c-expressing dendritic cells (DCs). C57BL/6 mice were challenged intranasally with staphylococcal enterotoxin A (SEA) and at indicated time points lung tissue was perfused, digested and analyzed for CD11c+ expressing cells. The pulmonary CD11c+ cells can be divided into two major populations based on their MHC II expression. One day following intranasal SEA challenge, there was rapid accumulation of CD11c+ cells expressing medium to high levels of MHC II. The peak accumulation of CD11c+ MHC II- population was observed 2 days after SEA challenge; however, careful examination of this cell population revealed that they were heterogeneous, being comprised of cells bearing CD3, CD19, NK1.1 and F4/80 along with varying levels of CD11c. Nevertheless, there was a 2-fold increase of CD11c+ MHC II- (CD3- CD19- NK1.1- F4/80-) cells in the lungs. The mechanism of increase in the CD11c+ MHC II- immune progenitor population was mainly due to cellular division rather than migration from blood to lung. In contrast, the early and rapid accumulation of CD11c+ MHC II(hi) cells, conventionally known as DCs, in the lung on day 1 was mostly due to migration from blood. Thus this study examines the pulmonary innate immune response to a powerful immune stimulus.


Alteration in airway microvascular leakage induced by sensorineural stimulation in rats exposed to inhaled formaldehyde.
Inhaled formaldehyde can rapidly produce microvascular leakage in the airway through stimulation of tachykinin NK1 receptors by tachykinins released from sensory nerves. Tachykinin NK1 receptors are known to be internalized in the cytoplasm after being stimulated, thus leading to transient attenuation of their action. We investigated time changes in airway microvascular leakage during formaldehyde inhalation for 45 min, and whether pre-inhalation of formaldehyde (5 ppm, 30 min) decreases the responses induced by subsequent inhaled formaldehyde (5 ppm, 15 min), intravenous capsaicin (75 μg/kg) and intravenous substance P (10 μg/kg) in rat airway. Evans blue dye content extravasated into the tissues was measured as an index of plasma leakage. Formaldehyde rapidly produced dye leakage in the airway, a response that ended within 15 min after the start of formaldehyde inhalation. Pre-inhalation of formaldehyde markedly decreased the responses induced by formaldehyde and capsaicin, but not substance P. However, dye leakage induced by formaldehyde was significantly enhanced by formaldehyde inhalation 20 h earlier. Our results suggest that tachyphylaxis in neurogenic airway microvascular leakage seen after formaldehyde inhalation may be due to impairment of tachykinin release from sensory nerves or decreases in tachykinins within sensory nerves. However, desensitization of tachykinin NK1 receptors was unlikely to be important in the tachyphylactic response.


Proteomic Analysis of Glucose-Induced Cardiac Myoblasts and the Potential Role of mir-92b-5p in Regulating Sarcomere Proteins Under a Hyperglycemic Environment.
Diabetes mellitus, a common metabolic disorder that causes high blood glucose, is due to impaired insulin secretion. Prolonged high blood sugar is associated with heart disease. Many proteins are involved in metabolic pathways and contractility of cardiac cells regulate cardiac hypertrophy, altering normal cardiac physiology and function. Moreover, microRNAs are essential regulators of these proteins. Thus, there is a need to study the protein and microRNA alterations in cardiomyocytes to better understand the mechanisms activated during cardiac stress. The study aims to profile differentially expressed sarcomere proteins in H9C2 cell lines under high glucose conditions compared with normal conditions, along with the identification of miRNAs regulating these proteins. Cardiac myoblast cell lines were treated with D-Glucose at three concentrations (10 mM, 25 mM, and 50 mM). Total cell protein was analyzed by Tandem Mass spectrometry Nano LCMS/ MS. Furthermore, next-generation sequencing data were analyzed for detecting microRNAs regulating cardiac cell protein expression. Bioinformatics databases such as Uniprot, Ingenuity Pathway Analysis (IPA), PANTHER, and Target scan were used. The Nano LC-MS/MS analysis showed 2891 protein, 1351 protein groups, and 4381 peptide groups in both glucose-treated and control samples. Most proteins were metabolite interconversion enzymes, translation proteins, and proteins regulating the cytoskeleton. IPA analysis revealed differentially expressed proteins involved in EIF2 signaling, actin cytoskeleton signaling, cardiac fibrosis, and cell death. Moreover, the proteins troponin, tropomyosin, myosin, alpha-actin, and ATP synthase were found to be downregulated, thus responsible for altering sarcomere protein expression. Rno-mir-92b-5p was observed to be highly upregulated at 50 mM. Its target genes namely TPM2, ATP1A2, and CORO1C were mostly components of the sarcomere complex and its regulators. A combination of proteomic profile and microRNA profile of hyperglycemic cells provides an insight into advanced therapeutics. Our study has highlighted the role of sarcomere proteins, activation of Eukaryotic Initiation Factor 2 (EIF2) signaling, and suppression of actin cytoskeleton signaling in the pathophysiology of cardiomyopathy. MiR-92b-5p has an important role in regulating sarcomere protein complex activated.


Validation of Quintero stage III sub-classification for twin-twin transfusion syndrome based on visibility of donor bladder: characteristic differences in pathophysiology and prognosis.
To validate the Quintero stage III subclassification for twin-twin transfusion syndrome (TTTS) based on visibility of the bladder of the donor twin. Between July 2002 and August 2006, there were 131 pregnant Japanese women affected by severe TTTS before 26 weeks' gestation, treated with fetoscopic laser surgery at five centers in Japan, whose pregnancies continued beyond 22 weeks. Outcome data were available in all cases and surviving infants were followed up for at least 6 years. This study focused on the Stage III TTTS patients. These were subclassified into Stage III atypical (abnormal Doppler flow with visible donor bladder) and Stage III classical (abnormal Doppler flow with non-visible donor bladder) groups. Perioperative data and postnatal outcomes were compared between the groups. Seven Stage I, 22 Stage II, 82 Stage III and 20 Stage IV pregnancies continued beyond 22 weeks. There was a significantly higher incidence of absent or reversed end-diastolic velocity in the umbilical artery (UA-AREDV) of the donor in Stage III atypical than in Stage III classical patients (83.8% vs. 53.3%, P = 0.004). Stage III atypical cases also had a significantly higher incidence of arterioarterial (AA) anastomoses (72.9% vs. 17.8%, P < 0.001) and intrauterine fetal demise (IUFD) of the donor (43.2% vs. 13.3%, P = 0.002). However, there were no differences in overall survival or in abnormal brain scans of surviving infants. Donors with both UA-AREDV and AA anastomoses had a significantly higher incidence of IUFD compared with the others (53.3%, P < 0.001). Quintero stage III atypical was characterized by a high incidence of AA anastomoses and UA-AREDV of the donor, resulting in IUFD. Subclassification of Stage III based on visibility of the bladder of the donor twin was adequate for and compatible with differentiating prognosis and pathophysiology.


Combined dynamics of EEG and evoked potentials. II. Studies of simultaneously recorded EEG-EPograms in the auditory pathway, reticular formation, and hippocampus of the cat brain during sleep.
This study is carried out on single (not averaged) recordings combining the spontaneous activity preceding the stimulus onset and the EP recorded upon acoustical stimulation. These recordings, which we call EEG-EPograms, are measured simultaneously from different subdural structures, such as the auditory cortex, medial geniculate nucleus, inferior colliculus, reticular formation and the hippocampus of the cat brain during the slow wave sleep stage. Using a combined analysis procedure (C.A.P.), the relevant frequency components of spontaneous EEG and EPs, recorded simultaneously from these brain nuclei, are analyzed according to the consistent selectivity bands depicted by the determined amplitude-frequency characteristics for the SWS-stage. In parallel with the results which we obtained for the waking stage, these analyses provide also the following information: (1) there is an important congruency in the time courses of simultaneous response components in common frequency bands, especially in the alpha and beta frequency ranges; (2) there exist significant coupling and synchrony between the evoked amplitude enhancements in the simultaneously recorded single response components; (3) the inter-nuclei coherency in the brain's electrical activity is enormously increased upon stimulation;(4) the evoked response magnitude can be predicted, with reasonable accuracy, from the spontaneous activity preceding the stimulus. All these findings are discussed with reference to those obtained for the waking stage.


Does the hormonal situation modify lipid effects by lifestyle factors in middle-aged women? Results from a population-based study of Swedish women: the women's health in the Lund area study.
The aim of the study was to outline whether the influence by lifestyle factors on serum lipids was modified by the hormonal situation in middle-aged women. Six thousand nine hundred eight women, aged 50 to 59 years, participated in a health assessment program, including a serum lipid profile evaluation. The women were grouped according to their hormonal status into premenopausal (PM) (n = 492), postmenopausal without hormone therapy (HT) (PM0) (n = 3600), and postmenopausal with HT (PMT) (n = 2816). From the PMT group, we analyzed oral (n = 901) and transdermal HT (n = 351) regimens, containing norethisterone acetate and 17beta-estradiol. Serum lipids and lipoproteins were determined by conventional methods. Lifestyle factors included smoking and physical activity at leisure time and at work. Multivariate linear regression analysis controlling for age, education, and dietary habits showed that current smoking was positively associated with triglycerides in the PM, PM0, PMT, and oral HT groups. In the PM0, PMT, and oral HT groups, current smoking was positively associated with total cholesterol and low-density lipoprotein and negatively associated with high-density lipoprotein (HDL). Low physical activity at leisure time was positively associated with triglycerides in the PM and PMT groups and negatively associated with HDL in the PM0 and PMT groups. High physical activity at work was positively associated with triglycerides in the PMT group and with total cholesterol in the PM0 group, but negatively associated with HDL in the PMT and transdermal groups. Body mass index was positively associated with triglycerides and negatively with HDL in all the groups regardless of the hormonal situation. The serum lipid profile as influenced by lifestyle factors was modified by the hormonal situation. Compared with the postmenopausal women without HT use, the use of HT contributes to fewer "negative" effects by lifestyle factors on serum lipids.


Uridine diphosphate reductase of Ehrlich ascites tumor is insensitive to hydroxyurea.
Uridine diphosphate (UDP) reductase was isolated in the supernatant fraction obtained after the acidification of the cytosol of Ehrlich ascites tumor cells, and was found insensitive to 10 mM hydroxyurea. However, cytidine diphosphate (CDP) reductase, being separated concurrently in the precipitate fraction, was readily inhibited. In the cytosol fraction of either Ehrlich ascites tumor, Yoshida ascites sarcoma or regenerating rat liver after partial hepatectomy, UDP reduction activity, in contrast to CDP reduction activity, is not sensitive to hydroxyurea.


The effect of positive airway pressure during pre-oxygenation and induction of anaesthesia upon duration of non-hypoxic apnoea.
Positive end-expiratory pressure (PEEP) applied during induction of anaesthesia may prevent atelectasis formation in the lungs. This may increase the duration of non-hypoxic apnoea by increasing the functional residual capacity. We studied the benefit of PEEP applied during the induction of anaesthesia on the duration of apnoea until the SpO2 reached 90%. Forty ASA I-II patients were randomly allocated to one of two groups. In the PEEP group (n = 20) patients were pre-oxygenated using 100% O2 administered using a CPAP device (6 cmH2O) for 5 min. Following induction of anaesthesia, patients were mechanically ventilated (PEEP 6 cm H2O) for a further 5 min. In the ZEEP group (n = 20), no CPAP or PEEP was used. The duration of apnoea until SpO2 reached 90% was measured. Non-hypoxic apnoea duration was longer in the PEEP group compared to ZEEP group (599 +/- 135 s vs. 470 +/- 150 s, p = 0.007). We conclude that the application of positive airway pressure during induction of anaesthesia in adults prolongs the non-hypoxic apnoea duration by > 2 min.


Desulphurisation kinetics of thiophenic compound by sulphur oxidizing Klebsiella oxytoca SOB-1.
The major aims of this study are to determine the capability of sulphur oxidizing bacterium (SOB-1) to desulphurize dibenzothiophene (DBT) and crude oil, detection of the reaction kinetics and identify the proposed pathway of DBT desulphurization. The isolate was genetically identified based on 16S rRNA gene sequencing as Klebsiella oxytoca and deposited in the Genebank database under the accession number: MT355440. The HPLC analysis of the remaining DBT concentration revealed that, SOB-1 could desulphurize 90% of DBT (0·25 mmol l-1 ) within 96 h. The maximum production of sulphate ions from the desulphurization of DBT (0·36 mmol l-1 ) and crude oil (0·4 mmol l-1 ) could be quantitatively detected after 48 h of incubation at 30°C. The high values of correlation coefficient (R2 ) obtained at all studied concentrations; suggested that biodesulfurization kinetics of DBT follows the first-order reaction model. The kinetics studies showed that, DBT may have an inhibitory effect on SOB-1 when the initial concentration exceeded 0·75 mmol l-1 . The GC-MS analysis exhibited four main metabolites rather than DBT. The most important ones are 2-hydroxybiphenyl (2-HBP) and methoxybiphenyl n(2-MBP). Klebsiella oxytoca SOB-1 catalyzes the desulphurization of DBT through 4S pathway and forms four main metabolic products. The release of sulphate ion and formation of 2-HBP indicating the elimination of sulphur group without altering the carbon skeleton of DBT. The bacterial strain could also catalyzes desulphurization of crude oil. The desulphurization kinetics follows the first-order reaction model. Klebsiella oxytoca SOB-1 could be used as a promising industrial and environmental biodesulfurizing agent as it is not affecting carbon skeleton of thiophenic compounds and forming less toxic metabolic product (2-MBP).


Risk factors in transmission of non-A, non-B posttransfusion hepatitis. The role of hepatitis B antibody in donor blood.
Risk of developing icteric hepatitis in a transfusion study involving cardiac surgery patients was 0.2 per cent per unit of blood transfused with the ratio of icteric to anicteric cases being 1:4. Risk of developing hepatitis was proportional to the number of units transfused: one to four units, 4 per cent; six to ten units, 8 per cent; 11 to 20 units, 19 per cent; greater than 21 units, 42 per cent. The prevalence of type B hepatitis was low (6 per cent), with the vast majority of patients being shown to have non-A non-B hepatitis. However, a greater incidence of hepatitis type B serologic events was observed among recipients of anti-HBs positive blood than those transfused only with units not containing antibody (p = 0.04. A significantly greater incidence of non-A, non-B hepatitis was observed among patients transfused with blood containing anti-HBs when compared with a group who received blood without antibody (p less than 0.01). Caution should be exercised in interpretation of this difference because patients transfused with blood containing anti-HBs received significantly more units of blood. However, utilization of stepwise regression analysis to unconfound the two dependent variables suggest that the use of blood containing anti-HBs increases the hepatitis risk (p = 0.06) although the number of units transfused was the more significant factor (p less than 0.001). Additional data from carefully designed studies are needed to determine if donor blood containing anti-HBs significantly increases the risk of transmitting non-A, non-B hepatitis.


Bivalve esterases as biomarker: identification and characterization in European cockles (Cerastoderma edule).
This study characterized esterase activity in Cerastoderma edule tissues using different substrates and specific inhibitors and identified the tissue distribution of esterases in this species. Synthetic thiocholines and thioacetate esters and specific inhibitors (eserine, BW284C51 and iso-OMPA) were used to identify and quantify cholines and carboxyl esterases. The results demonstrated the presence of a non-specific propionyl thiocholine (PrSCh)-cleaving cholinesterase (ChE) and a large amount of carboxylesterases (CaE). For further studies using C. edule esterases as biomarkers, our results suggest that the adductor muscle, with PrSCh (5 mM) as substrate should be used to analyze ChE, and for CaE analyses, phenyl thioacetate should be used in digestive gland extracts (PSA, 5 mM).


[Protective effect of natural dietary antioxidants on space radiation-induced damages].
This paper described the radiation-induced damage on human body in space and summarized the studies of antioxidants such as Vit C, Vit E, Vit A, beta-carotene, flavonoids, polysaccharide, green-tea and Spirulina protection against radiation-induced damage. Application prospects of natural antioxidants in space food were also put forward in this article.


Supply chain resilience reactive strategies for food SMEs in coping to COVID-19 crisis.
The ability of small- and medium-sized enterprises in the food industry (FSMEs) in cultivating resilience against the COVID-19 pandemic is vital food security. However, there is limited supply chain resilience literature to guide FSMEs in overcoming disruptions caused by pandemic. This review aims to provide a broad view of SCRes reactive strategies for FSMEs in dealing with crises in the context of COVID-19. Attention is given to the literature on resilience in other types of supply chain and situated in the context of food settings. The factors are monitored or controlled to contribute to FSME resiliency.Key findings and conclusion: Four quadrants, i.e., (1) rapid with low cost, (2) rapid with high cost, (3) slow with low cost and (4) slow with high cost, are offered based on the limitations and the time needed to react, and the strategies of each quadrant are explained in depth. This review also provides a better understanding of and guidance on reactive strategies for SCRes as options for FSMEs in dealing with the COVID-19 pandemic. This review suggests future directions as extensions based on the logical flow of this review.


Biokinetics and bacterial communities of propionate oxidizing bacteria in phased anaerobic sludge digestion systems.
Phased anaerobic digestion is a promising technology and may be a potential source of bio-energy production. Anaerobic digesters are widely used for sewage sludge stabilization and thus a better understanding of the microbial process and kinetics may allow increased volatile solids reduction and methane production through robust process operation. In this study, we analyzed the impact of phase separation and operational conditions on the bio-kinetic characteristics and communities of bacteria associated with four phased anaerobic digestion systems. In addition to significant differences between bacterial communities associated with different digester operating temperatures, our results also revealed that bacterial communities in the phased anaerobic digestion systems differed between the 1st and 2nd phase digesters and we identified strong community composition correlations with several measured physicochemical parameters. The maximum specific growth rates of propionate oxidizing bacteria (POB) in the mesophilic and thermophilic 1st phases were 11 and 23.7 mgCOD mgCOD(-1) d(-1), respectively, while those of the mesophilic and thermophilic 2nd-phase digesters were 6.7 and 18.6 mgCOD mgCOD(-1) d(-1), respectively. Hence, the biokinetic characteristics of the POB population were dependent on the digester loading. In addition, we observed that the temperature dependency factor (θ) values were higher for the less heavily loaded digesters as compared to the values obtained for the 1st-phase digesters. Our results suggested the appropriate application of two sets of POB bio-kinetic that reflect the differing growth responses as a function of propionate concentration (and/or organic loading rates). Also, modeling acetogenesis in phased anaerobic sludge digestion systems will be improved considering a population shift in separate phases. On the basis of the bio-kinetic values estimated in various digesters, high levels of propionate in the thermophilic digesters may be best explained by the establishment of POB with low affinities (high K(s)) for propionate. Achieving low levels of propionate with either thermophilic or short HRT digesters is challenging and a relatively long HRT mesophilic digester should be employed for this purpose.


After-effects of repetitive stimulation at low frequency on fast-contracting motor units of cat muscle.
Twitch and tetanic contractions of single motor units of the cat peroneus tertius muscle were examined after application of a test allowing their identification as either fast fatigable (f.f.) or fast fatigue-resistant (f.r.) or fast intermediate (f.i.) or slow units as established by Burke, Levine, Tsairis & Zajac (1973). The test was found to leave two kinds of after-effects in f.f., f.r. and f.i. units whereas it did not affect slow units. The first after-effect was an early and brief potentiation of twitch tension occurring in all f.r. and f.i. units and in most f.f. units. The second after-effect, termed 'delayed fatigue', was a prolonged depression of tension output, that developed slowly following the early potentiation in all f.f. and f.i. units and more than half of the f.r. units. One hour after the test, unfused tetanic contractions elicited by 20-40/sec stimulation were deeply depressed in motor units that had been left without stimulation since the end of the test. Recovery took place in 3-5 hr. Motor units affected by delayed fatigue could nevertheless be made to develop nearly normal tension by gradual build-up upon prolonged stimulation at 30-40/sec. Maximal tetanic contractions elicited by 200/sec stimulation were much less depressed during delayed fatigue than unfused tetanic contractions. These observations suggest that contractile mechanism were not impaired by delayed fatigue. Since absence of change in muscle action potential indicated that excitation of muscle fibres was not affected either, delayed fatigue might be due to a temporary failure of excitation-contraction coupling.


Ru(II)-Catalyzed Synthesis of Fused Imidazo[1,2-a]pyridine-chromenones and Methylene-Tethered Bis-imidazo[1,2-a]pyridines and Regioselective O-Acetoxylation of Imidazo[1,2-a]pyridines.
Herein, we disclose an unprecedented protocol via ruthenium-catalyzed annulation for the synthesis of 6H-chromeno[4',3':4,5]imidazo[1,2-a]pyridin-6-one, and functionalized 2-(3-formylimidazo[1,2-a]pyridin-2-yl)phenyl acetate has been revealed by intramolecular chelation-assisted C-H activation. Additionally, a one-pot approach for creating bis(2-phenylimidazo[1,2-a]pyridin-3-yl)methane (BIP) has been realized through ruthenium catalysis with the use of formic acid. This method was used in gram-scale synthesis of BIP and step-economical late-stage functionalization of a marketed drug, zolimidine, in good yield.


Adenoviral vector as a gene delivery system into cultured rat neuronal and glial cells.
Previous studies have demonstrated that a defective recombinant adenovirus can infect a wide range of postmitotic and slowly proliferating cell types such as hepatocytes, myotubes, pneumocytes and intestinal cells (Stratford-Perricaudet et al., Hum. Gene Ther., 1, 241-256, 1990; Quantin et al., Proc. Natl. Acad. Sci. USA, 89, 2581-2584, 1992; Jaffe et al., Nature Genetics, 1, 372-378, 1992). We have used a defective recombinant adenovirus, Ad.RSV beta gal, containing the Escherichia coli beta-galactosidase gene targeted to the nucleus under the transcriptional control of the Rous sarcoma virus long terminal repeat promoter (Stratford-Perricaudet et al., J. Clin. Invest., 90, 626-630, 1992) to infect non-dividing neural cells in primary culture. We show that 80-100% of neuronal and astroglial cells infected with a viral titre lower than 10(9) p.f.u./ml express beta-galactosidase for at least 1 month without cell damage. These results demonstrate the potential usefulness of recombinant adenovirus infection for the analysis of brain-specific gene regulation and for the transfer of genes into neural cells before their transplantation into the brain.


Evaluation of an inference-based approach to treating obsessive-compulsive disorder.
This study evaluated an inference-based approach (IBA) to the treatment of obsessive-compulsive disorder (OCD) by comparing its efficacy with a treatment based on the cognitive appraisal model (CAM) and exposure and response prevention (ERP). IBA considers initial intrusions in OCD (e.g. "Maybe the door is open", "My hands could be dirty") as idiosyncratic inferences about possible states of affairs arrived at through inductive reasoning. In IBA such primary inferences represent the starting point of obsessional doubt, and the reasoning maintaining the doubt forms the focus for therapy. This is unlike CAM, which regards appraisals of intrusions as the maintaining factors in OCD. Fifty-four OCD participants, of whom 44 completed, were randomly allocated to CAM, ERP or IBA. After 20 weeks of treatment all groups showed a significant reduction in scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Padua Inventory. Participants with high levels of obsessional conviction showed greater benefit from IBA than CAM. Appraisals of intrusions changed in all treatment conditions. Strength of primary inference was not correlated with symptom measures except in the case of strong obsessional conviction. Strength of primary inference correlated significantly with the Y-BOCS insight item. Treatment matching for high and low conviction levels to IBA and CAM, respectively, may optimize therapy outcome.


Worse than feared? Failure induction modulates the electrophysiological signature of error monitoring during subsequent learning.
This study examined how self-relevant failure influences error monitoring--as reflected in the error-related negativity (Ne/ERN) --and behavioral adaptation during subsequent feedback-based learning. We applied two phases (pre- and posttest) of a probabilistic learning task. Between pre- and posttest, participants were assigned to one of two groups receiving either failure feedback or no feedback during a visual search task described as diagnostic of intellectual abilities. To disentangle the effects of failure and motivational disengagement due to prolonged task performance, we linked the posttest to intelligence (Experiment 1) or described it in neutral terms (Experiment 2). Failure induction was associated with an increase in Ne/ERN amplitude at posttest in both experiments, although there were no differences in overall performance. In contrast, the Ne/ERN decreased from pre- to posttest in the no-failure-feedback group, particularly in Experiment 2. Furthermore, failure feedback affected error-related behavioral adjustments, suggesting a shift toward a reactive, error-driven mode of behavior control. These findings emphasize the importance of affective-motivational state in error processing and subsequent behavioral adaptation.


Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis.
HFE-associated hereditary haemochromatosis is a recessive, iron-overload disorder that affects about one in 200 north Europeans and that can be easily prevented. However, genetic screening for this disease is controversial, and so we assessed whether such screening was suitable for communities. Cheek-brush screening for the Cys282Tyr HFE mutation was offered to individuals in the workplace. Outcomes were assessed by questionnaires before and after testing. 11,307 individuals were screened. We recorded no increase in anxiety in individuals who were homozygous for the Cys282Tyr mutation or non-homozygous. Self-reported tiredness before testing was significantly higher in homozygous participants than in non-homozygous participants (chi2 test, p=0.029). Of the 47 homozygous individuals identified, 46 have taken steps to treat or prevent iron accumulation. Population genetic screening for HFE-associated hereditary haemochromatosis can be practicable and acceptable.


Long-term serial echocardiographic examination of late anthracycline cardiotoxicity and its prevention by dexrazoxane in paediatric patients.
The authors conducted an 8-year prospective non-randomised study to determine whether dexrazoxane (ICRF-187) would reduce late anthracycline-induced cardiotoxicity in patients treated in childhood for haematological malignancy. The authors examined prospectively 75 patients (40 male/35 female) aged 2-17 years (median 6.5 years) at the time of diagnosis. The cardioprotection was given to 53 patients (26 male/17 female) and the standard protocol was used in 22 patients (14 male/8 female). The prospective echocardiographic evaluation was done before and after the chemotherapy and every year during the follow-up period. Dynamic stress echocardiography (DSE) was assessed in the final year. The clinical cardiotoxicity was not diagnosed. Higher cumulative doses of anthracycline were given in the dexrazoxane group (234+/-58 mg/m(2), median 240 mg/m(2) versus 203+/-86 mg/m(2), median 210 mg/m(2), P <0.04) and a significantly higher percentage of patients received cumulative doses >240 mg/m(2) of anthracycline ( P <0.05). During the follow-up period, the fractional shortening (FS) declined in the no-dexrazoxane group only in the 8th year and was significantly lower compared to the dexrazoxane group ( P <0.05). The pathological decrease in FS was present in 24% of patients; 41% in the no-dexrazoxane and 17% in the dexrazoxane groups, respectively ( P <0.05). DSE demonstrated lower rest EF and cardiac index (CI) in the no-dexrazoxane group ( P <0.05); however, neither the response of EF and CI to the stress echocardiography nor the exercise tolerance significantly differed between sub-groups. A higher number of patients in the dexrazoxane group had very good exercise tolerance (ET) >3 Watts/kg ( P <0.05) and a lower number responded with a decreased ET <2 Watts/kg ( P <0.05) compared to the no-dexrazoxane group. Dexrazoxane seems to reduce the risk of late subclinical cardiotoxicity. Dexrazoxane-treated patients revealed better exercise tolerance; however the haemodynamic response to the stress was no different in both sub-groups.


Identification of a novel pathogenic variant in KCNH2 in an Iranian family with long QT syndrome 2 by whole-exome sequencing.
Long QT syndrome (LQTS) is a lethal cardiac condition. However, the clinical implementation of genetic testing has now made LQTS eminently treatable. Next-generation sequencing has remarkable potential for both clinical diagnostics and research of LQTS. Here, we investigated the genetic etiology in an LQTS-suspected Iranian pedigree by whole-exome sequencing and collected all KCNH2 variants with consensus based on publications. WES was performed on the proband of this pedigree to reveal the underlying cause of sudden cardiac death (SCD). The variant found was validated and segregated by polymerase chain reaction and Sanger sequencing. Based on the literature review, KCNH2 variants were retrospectively analyzed to identify pathogenic variants, likely pathogenic variants, and variants of uncertain significance by using different prediction tools. WES identified an autosomal dominant nonsense variant, c.1425C>A: p.Tyr475Ter, in the KCNH2 gene, which appeared to be the most likely cause of LQTS in this pedigree. Moreover, our comprehensive literature review yielded 511 KCNH2 variants in association with the LQTS phenotype, with c.3002G>A (CADD Phred=49) being the most pathogenic variant. Variants in the KCNH2 gene are considered a major cause of LQTS worldwide. The detected c.1425C>A is a novel variant to be reported from Iran for the first time. This result indicates the importance of KCNH2 screening in a pedigree with SCD cases.


Short- and long-term outcomes in Bankart repair vs. conservative treatment for first-time anterior shoulder dislocation: a systematic review and meta-analysis of randomized controlled trials.
First-time anterior shoulder dislocations are associated with a high rate of residual instability. Therefore, many surgeons support initial Bankart repair surgery over conservative management to address this issue. However, the optimal treatment remains controversial because of uncertainty regarding long-term surgical outcomes. The primary objective of this systematic review and meta-analysis was to compare the short- and long-term rates of residual instability following Bankart repair or conservative management after a first-time anterior shoulder dislocation. PubMed/MEDLINE, Embase, The Cochrane Library, Web of Science, CINAHL, and ScienceDirect databases were accessed for randomized controlled trials (RCTs) comparing Bankart repair to conservative management. RoB (Risk of Bias) 2 was used to check study quality. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were followed in assessing primary outcomes. The inverse-variance method for continuous variables and the Mantel-Haenszel method for dichotomous variables was used. A total of 348 patients from 6 RCTs published across 8 articles, with a mean age of 23.7 years, were included. Bias was graded low in 3 studies, some concerns in 3 studies, and high in 2 studies. In the short term (2-3 years), surgery lowered recurrent instability (risk ratio [RR] 0.15, 95% confidence interval [CI] 0.08, 0.27; I2 = 0%; P < .0001). Similar findings were seen in the long term (5-12 years) (RR 0.23, 95% CI 0.14, 0.39; I2 = 0%; P < .0001). No difference was observed in return to sport (RR 1.18, 95% CI 0.91, 1.52; I2 = 78%; P = .21). Initial surgery lowered subsequent stabilization surgery in the short (RR 0.19, 95% CI 0.09, 0.43; I2 = 0%; P < .0001) and long term (RR 0.17, 95% CI 0.07, 0.39; I2 = 25%; P < .0001). Western Ontario Shoulder Instability Index (WOSI) scores did not differ in the short term (MD, 2.54, 95% CI -0.51, 5.59; I2 = 48%; P = .1) but were higher in the surgical group at long-term follow-up. Patient satisfaction was also higher with surgery (RR 1.75, 95% CI 1.4, 2.2; I2 = 88%; P < .0001). Certainty of evidence was low for only 1 long-term outcome measure. Bankart repair surgery for first-time anterior shoulder dislocation results in a large reduction in the risk of recurrent shoulder instability and subsequent stabilization surgery in both short- (2-3 years) and long-term (5-12 years) follow-up intervals. Additionally, slight improvements in overall patient satisfaction and WOSI score can be seen at long-term follow-up. However, surgical intervention failed to significantly improve the rate of return to sport when compared with conservative management.


Effects of ghrelin on the electrical activities of substantia nigra dopaminergic neurons treated with MPP.
Ghrelin, a 28 amino acid brain-gut peptide, has attracted increasing attention for its neuroprotective effect in Parkinson's disease (PD). In view of the pivotal role of excitability of dopaminergic neurons in substantia nigra pars compacta (SNc) in the function of nigrostriatal system, it is of great significance to elucidate the regulation of electrical activity of dopaminergic neurons by ghrelin, especially in PD pathogenesis. In this study, we tackled this issue by probing the effects of ghrelin on the electrophysiological properties of dopaminergic neurons in acute application of Methyl-4-phenylpyridinium (MPP+), a potent parkinsonizing agent in primates and rodents, with whole cell patch clamp technique. We first observed that MPP+ (10, 20 and 50 μM) inhibited the spontaneous firing activity of dopaminergic neurons with dose-dependent and time-dependent properties. MPP+ also hyperpolarized the membrane potential, inhibited the evoked firing activity and reduced the amplitude of the inward rectification characteristic (Sag) in dopaminergic neurons. Importantly, ghrelin (100 nM) could improve the above effects of MPP+ on the electrical activities of dopaminergic neurons. The potential mechanism of this phenomenon may be that ghrelin upregulated hyperpolarization-activated cyclic nucleotide-gated channel current (Ih) to antagonize the inhibition of MPP+ on Ih, thereby improving the electrical activities of dopaminergic neurons.


[Modular cemented knee prosthesis Kinemax--is manual mobilization during extended contraction justified?].
Early results of 12 total Kinemax knee replacements have been presented. Maximal active flexion has been recorded on 8th, 15th day and half a year after operation. Standard rehabilitation of the operated joint has been conducted. No manual mobilisation was employed despite of the only one case of knee flexion close to 90 degrees 2 weeks after surgery. Half a year later flexion has reached or exceeded the right angle in all cases.


The history of paediatric surgery in the United Kingdom and the influence of the national health service on its development.
Details of the modern history of paediatric surgery in the United Kingdom with particular emphasis on the 3 main training centres in England in the 1960s to 1970s are discussed. The genesis of the National Health Service and of the British Association of Paediatric Surgeons and their influence on the establishment and sitting of regional centres, education and training, and centralization of rare conditions is highlighted.


Eliminating vascular interference from the Spot Sign contributes to predicting hematoma expansion in individuals with spontaneous cerebral hemorrhages.
The computed tomography angiography (CTA) Spot Sign is an effective means of predicting hematoma expansion (HE) in the context of spontaneous intracerebral hemorrhage (ICH). We investigated whether continuous CTA source images could differentiate the Spot Sign and blood vessels in the hematoma, and whether it would improve Spot Sign accuracy as an HE predictor. We screened for the presence of CTA Spot Sign in individuals affected by spontaneous ICH within 24 h of symptom development. Based on our findings, we determined the sensitivity, specificity, and positive/negative predictive values of this sign as a predictor of HE both on its own and following the exclusion of blood vessels. In addition, a receiver-operating characteristic approach was used to assess the accuracy of Spot Sign with and without elimination of vascular interference. A total of 265 patients were included in this study. The Spot Sign was observed in 100 patients, including in 29 patients wherein it was confirmed to be blood vessels as determined based upon continuous CTA source images. With respect to predicting HE, Spot Sign sensitivity, specificity, positive predictive values, and negative predictive values were 57%, 71%, 48% and 78%, respectively. Following the exclusion of blood vessels, these values were 57%, 87%, 68% and 81%, respectively. Spot Sign area under the curve after excluding blood vessels was 0.718, which was higher than that of the Spot Sign (0.638). After continuous CTA, source images are used to exclude blood vessels in the hematoma, the Spot Sign is thus more accurate in predicting HE.


Kinetics and Characterization of Degradation Products of Dihydralazine and Hydrochlorothiazide in Binary Mixture by HPLC-UV, LC-DAD and LC-MS Methods.
Dihydralazine and hydrochlorothiazide were stored at high temperature and humidity, under UV/Vis light and different pH, as individual drugs and the mixture. Then, a sensitive and selective HPLC-UV method was developed for simultaneous determination of dihydralazine and hydrochlorothiazide in presence of their degradation products. Finally, the degradation products were characterized through LC-DAD and LC-MS methods. Dihydralazine was sensitive to high temperature and humidity, UV/Vis light and pH ≥ 7. At the same time, it was resistant to acidic conditions. Hydrochlorothiazide was sensitive to high temperature and humidity, UV/Vis light and changes in pH. Its highest level of degradation was observed in 1 M HCl. Degradation of the drugs was higher when they were stressed in the mixture. In the case of dihydralazine, the percentage degradation was 5-15 times higher. What is more, dihydralazine became sensitive to acidic conditions. Hydrochlorothiazide was shown to be more sensitive to UV/Vis light and pH > 4. Degradation of dihydralazine and hydrochlorothiazide followed first-order kinetics. The quickest degradation of dihydralazine was found to be in 1 M NaOH while of hydrochlorothiazide was in 1 M HCl (individual hydrochlorothiazide) or at pH 7-10 (hydrochlorothiazide in the mixture). A number of new degradation products were detected and some of them were identified by our LC-DAD and LC-MS methods. In the stressed individual samples, (phenylmethyl)hydrazine and 1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide were observed for the first time. Interactions between dihydralazine and hydrochlorothiazide in the mixture were confirmed by additional degradation products, e.g., 2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1,4-trioxide.


Clinical perineural invasion of cutaneous head and neck cancer: Impact of radiotherapy, imaging, and nerve growth factor receptors on symptom control and prognosis.
Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes. We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM). Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046). Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.


Robotic Lobectomy Is Cost-effective and Provides Comparable Health Utility Scores to Video-assisted Lobectomy: Early Results of the RAVAL Trial.
The aim of this study was to determine if robotic-assisted lobectomy (RPL-4) is cost-effective and offers improved patient-reported health utility for patients with early-stage non-small cell lung cancer when compared with video-assisted thoracic surgery lobectomy (VATS-lobectomy). Barriers against the adoption of RPL-4 in publicly funded health care include the paucity of high-quality prospective trials and the perceived high cost of robotic surgery. Patients were enrolled in a blinded, multicentered, randomized controlled trial in Canada, the United States, and France, and were randomized 1:1 to either RPL-4 or VATS-lobectomy. EuroQol 5 Dimension 5 Level (EQ-5D-5L) was administered at baseline and postoperative day 1; weeks 3, 7, 12; and months 6 and 12. Direct and indirect costs were tracked using standard methods. Seemingly Unrelated Regression was applied to estimate the cost effect, adjusting for baseline health utility. The incremental cost-effectiveness ratio was generated by 10,000 bootstrap samples with multivariate imputation by chained equations. Of 406 patients screened, 186 were randomized, and 164 analyzed after the final eligibility review (RPL-4: n=81; VATS-lobectomy: n=83). Twelve-month follow-up was completed by 94.51% (155/164) of participants. The median age was 68 (60-74). There were no significant differences in body mass index, comorbidity, pulmonary function, smoking status, baseline health utility, or tumor characteristics between arms. The mean 12-week health utility score was 0.85 (0.10) for RPL-4 and 0.80 (0.19) for VATS-lobectomy ( P =0.02). Significantly more lymph nodes were sampled [10 (8-13) vs 8 (5-10); P =0.003] in the RPL-4 arm. The incremental cost/quality-adjusted life year of RPL-4 was $14,925.62 (95% CI: $6843.69, $23,007.56) at 12 months. Early results of the RAVAL trial suggest that RPL-4 is cost-effective and associated with comparable short-term patient-reported health utility scores when compared with VATS-lobectomy.


Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead.
Immune suppression in the tumor microenvironment (TME) is an intractable issue in anti-cancer immunotherapy. The chemokine receptors CXCR1 and CXCR2 recruit immune suppressive cells such as the myeloid derived suppressor cells (MDSCs) to the TME. Therefore, CXCR1/2 antagonists have aroused pharmaceutical interest in recent years. In this review, the medicinal chemistry of CXCR1/2 antagonists and their relevance in cancer immunotherapy have been summarized. The development of the drug candidates, along with their design rationale, clinical status and current challenges have also been discussed.


Draft Genome Sequence of a Strictly Anaerobic Dichloromethane-Degrading Bacterium.
An anaerobic, dichloromethane-degrading bacterium affiliated with novel Peptococcaceae was maintained in a microbial consortium. The organism originated from pristine freshwater sediment collected from Rio Mameyes in Luquillo, Puerto Rico, in October 2009 (latitude 18°21'43.9″, longitude -65°46'8.4″). The draft genome sequence is 2.1 Mb and has a G+C content of 43.5%.


The effect of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture with osteoporotic fracture classification after vertebroplasty.
To analyze the clinical and radiological effects of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture after percutaneous vertebroplasty, and explore the prognostic value of osteoporotic fracture classification. Osteoporotic vertebral compression fracture patients who received vertebroplasty from January 1, 2016 to June 30, 2021 were divided into type 2 diabetes mellitus group and control group in this retrospective cohort study. Visual analogue scale, Oswestry Disability Index, bone cement leakage, new compression fracture, anterior, middle, and posterior portion heights of vertebral body and local Cobb angle on X-ray before surgery, 2 days after surgery, 6 months, and 12 months after surgery were recorded, and the osteoporotic fracture classification was performed. P < 0.05 was set as statistical significance. A total of 261 vertebral bodies were included, containing 68 in the type 2 diabetes mellitus group and 193 in the control group. There were no differences in baseline characteristics between the two groups. At 6 months after vertebroplasty, the local Cobb angle of the type 2 diabetes mellitus group was 8.29 ± 4.90° greater than that of the control group 6.05 ± 5.18° (P = 0.002). At 12 months, compared with pre-operation, the anterior portion height recovered 8.13 ± 12.90%, which was less than 12.51 ± 14.92% of the control group (P = 0.032), and 19.07 ± 16.47% of the middle portion height recovery was less than the control group's 24.63 ± 17.67% (P = 0.024). Compared with the control group, osteoporotic fracture 2 vertebral bodies of the type 2 diabetes mellitus group at 12 months postoperatively in middle portion height (14.82 ± 14.71% vs 24.78 ± 18.16%, P = 0.023) and local Cobb angle (5.65 ± 4.06° vs 3.26 ± 4.86°, P = 0.043) restored significantly worse. Besides, osteoporotic fracture 3 with type 2 diabetes mellitus restored worse in anterior portion height (5.40 ± 11.02% vs 13.57 ± 12.79%, P = 0.008), middle portion height (11.22 ± 15.53% vs 17.84 ± 12.36%, P = 0.041) and local Cobb angle (10.85 ± 3.79 vs 7.97 ± 3.83°, P = 0.002) at 12 months postoperatively. There was no difference in radiological outcomes of osteoporotic fracture 4 between the two groups. The degree of fractured vertebral compression, the recovery of the height and angle obtained immediately after surgery and the clinical symptoms in type 2 diabetes mellitus patients were not different from those in the control. However, vertebral body morphology of type 2 diabetes mellitus patients was worse since the sixth month after surgery. Osteoporotic fracture classification has a good prognostic reference value for both the control and the type 2 diabetes mellitus population.


Paraoxonase 1 polymorphisms and ischemic stroke risk: A systematic review and meta-analysis.
Paraoxonase 1 (PON1) polymorphisms have been implicated as risk factors for coronary artery disease, but the results of genetic association studies on the related phenotype of ischemic stroke are inconclusive. We performed a meta-analysis of published studies investigating the association between ischemic stroke and two nonsynonymous PON1 polymorphisms, rs662 (p.Q192R) and rs854560 (p.L55M) in humans. We searched multiple electronic databases through June 30, 2009 for eligible studies. In main analyses, we calculated allele-based odds ratios with random effects models. In secondary analyses, we examined dominant and recessive genetic models as well, and performed subgroup and sensitivity analyses. Regarding rs662, we identified 22 eligible studies (total of 7384 cases/11,074 controls), yielding a summary odds ratio of 1.10 per G allele (95% confidence interval, 1.04-1.17) with no evidence of between-study heterogeneity. For rs854560, 16 eligible studies (total of 5518 cases/8951 controls) yielded a summary odds ratio of 0.97 per T allele (95% confidence interval, 0.90-1.04), again with no evidence of between-study heterogeneity. For both polymorphisms, analyses with dominant and recessive genetic models yielded the same inferences as allele-based comparisons. Subgroup and sensitivity analyses showed similar results. In agreement with observations in coronary artery disease, PON1 rs662 appears to be associated with a small increase in the risk of ischemic stroke.


Pesticide residues in table-ready foods in Tanzania.
This study investigated the presence of pesticide residues in table-ready foods in Tanzania. One-hundred-and-eighty nine samples of 11 widely used foods at table ready stage were analysed using US FDA multi-residue methods. Pesticide residues were detected in 29% of all samples analysed. The spread of contamination in individual foods was: spinach 72.7%, rice 50%, beef meat 42.1%, stiff porridge 8.6%, and beans 6.7%. After allocating Non-detects levels a half value of Method Detection Limit i.e., (MDL)/2, the mean concentrations of the pesticide residues in the foods were; In spinach: g-HCH 0.08 microg/kg; DDT 2.89 microg/kg; Chlorpyrifos 0.02 microg/kg. In rice: g-HCH 0.08 microg/kg; DDT 1.70 microg/kg; and Chlorpyrifos 0.02 microg/kg. In beef meat: g-HCH 0.14 microg/kg; DDT 0.76 microg/kg. In stiff porridge: g-HCH 0.06 microg/kg; and DDT 0.30 microg/kg. In beans: g-HCH 0.04 microg/kg; and DDT 0.13 microg/kg. In fish variety: g-HCH 0.05 microg/kg. Converted into consumer Average Daily Doses, these concentrations were within ADI/ PTDI levels set by CODEX and, therefore, posed no significant health risk. However, the presence of pp-DDT in many samples indicates a possible recent contamination of food raw materials with DDT. A more effective pesticides control system should be put in place before lifting the ban on DDT for restricted uses in vector control programs in Tanzania.


Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging.
Non-invasive imaging deep into organs at microscopic scales remains an open quest in biomedical imaging. Although optical microscopy is still limited to surface imaging owing to optical wave diffusion and fast decorrelation in tissue, revolutionary approaches such as fluorescence photo-activated localization microscopy led to a striking increase in resolution by more than an order of magnitude in the last decade. In contrast with optics, ultrasonic waves propagate deep into organs without losing their coherence and are much less affected by in vivo decorrelation processes. However, their resolution is impeded by the fundamental limits of diffraction, which impose a long-standing trade-off between resolution and penetration. This limits clinical and preclinical ultrasound imaging to a sub-millimetre scale. Here we demonstrate in vivo that ultrasound imaging at ultrafast frame rates (more than 500 frames per second) provides an analogue to optical localization microscopy by capturing the transient signal decorrelation of contrast agents--inert gas microbubbles. Ultrafast ultrasound localization microscopy allowed both non-invasive sub-wavelength structural imaging and haemodynamic quantification of rodent cerebral microvessels (less than ten micrometres in diameter) more than ten millimetres below the tissue surface, leading to transcranial whole-brain imaging within short acquisition times (tens of seconds). After intravenous injection, single echoes from individual microbubbles were detected through ultrafast imaging. Their localization, not limited by diffraction, was accumulated over 75,000 images, yielding 1,000,000 events per coronal plane and statistically independent pixels of ten micrometres in size. Precise temporal tracking of microbubble positions allowed us to extract accurately in-plane velocities of the blood flow with a large dynamic range (from one millimetre per second to several centimetres per second). These results pave the way for deep non-invasive microscopy in animals and humans using ultrasound. We anticipate that ultrafast ultrasound localization microscopy may become an invaluable tool for the fundamental understanding and diagnostics of various disease processes that modify the microvascular blood flow, such as cancer, stroke and arteriosclerosis.