Occurrence and formation of disinfection by-products in the swimming pool environment: A critical review.
Disinfection of water for human use is essential to protect against microbial disease; however, disinfection also leads to formation of disinfection by-products (DBPs), some of which are of health concern. From a chemical perspective, swimming pools are a complex matrix, with continual addition of a wide range of natural and anthropogenic chemicals via filling waters, disinfectant addition, pharmaceuticals and personal care products and human body excretions. Natural organic matter, trace amounts of DBPs and chlorine or chloramines may be introduced by the filling water, which is commonly disinfected distributed drinking water. Chlorine and/or bromine is continually introduced via the addition of chemical disinfectants to the pool. Human body excretions (sweat, urine and saliva) and pharmaceuticals and personal care products (sunscreens, cosmetics, hair products and lotions) are introduced by swimmers. High addition of disinfectant leads to a high formation of DBPs from reaction of some of the chemicals with the disinfectant. Swimming pool air is also of concern as volatile DBPs partition into the air above the pool. The presence of bromine leads to the formation of a wide range of bromo- and bromo/chloro-DBPs, and Br-DBPs are more toxic than their chlorinated analogues. This is particularly important for seawater-filled pools or pools using a bromine-based disinfectant. This review summarises chemical contaminants and DBPs in swimming pool waters, as well as in the air above pools. Factors that have been found to affect DBP formation in pools are discussed. The impact of the swimming pool environment on human health is reviewed.


Prognostic significance of the absolute monocyte counts in lung cancer patients with venous thromboembolism.
We investigated the clinical significance of the absolute monocyte count (AMC) as a predictor of the response to anticoagulation and survival in lung cancer patients with venous thromboembolism (VTE). We retrospectively reviewed 1707 patients with pathologically proven lung cancer who visited the hospital between July 2008 and May 2014. Among them, the clinical data of patients newly diagnosed with VTE and treated with anticoagulation were compared between the low and high AMC groups according to the median value of AMC (640/μL) at the time of VTE diagnosis. The incidence of VTE was 7.9 % during the study period. Most of the patients had non-small-cell lung cancer (82.1 %), stage IV (64.2 %), and pulmonary thromboembolism (76.1 %) and were incidentally diagnosed with VTE (76.9 %). The patients' characteristics and laboratory values were not significantly different between the low and high AMC groups. Among patients available for evaluation of the response to anticoagulation, the high AMC group was significantly more refractory to anticoagulation than the low AMC group (no response to anticoagulation, 21.7 vs. 6.8 %, respectively; p = 0.044). Additionally, the high AMC group showed worse overall survival (OS) than the low AMC group (median, 9.6 vs. 5.9 months; p = 0.038). On multivariate analysis, high AMC, low albumin, and advanced stage were independent poor prognostic factors for OS. High AMC is associated with refractoriness to anticoagulation and poor prognosis in lung cancer patients with VTE.


Incidence Trends and Mortality from Childhood Venous Thromboembolism: A Population-Based Cohort Study.
To determine the incidence, incidence trend, and mortality of venous thromboembolism (VTE) in a general pediatric population during an 11-year period. The administrative health care databases of the province of Québec, Canada were used to identify all children (ages 1-17 years inclusive) diagnosed with incident VTE between January 1, 1994 and December 31, 2004. The incidence rate and trend over the 11-year study period were then analyzed. In total, 487 incident cases of pediatric VTE were documented. The age-standardized incidence rate was 0.29 VTE per 10 000 person-years (95% CI 0.26-0.31). Girls had a statistically significant higher incidence rate (per 10 000 person-years) than boys, 0.37 and 0.21 per 10 000 person-years, respectively, with an incidence rate ratio comparing females with males, adjusted for age group of 1.75 (95% CI 1.46-2.10). Trend analysis illustrated no statistically significant change in the age-standardized incidence rates. Overall all-cause mortality was 11.4 per 1000 children-years (95% CI 8.1-16.1). Pediatric VTE is frequent, although its incidence is stable over time and all-cause mortality is lower than previously reported. Future studies that address possible sex and age group differences in the incidence of pediatric VTE are needed to help determine effective primary thromboprophylaxis strategies in children at high risk for VTE.


Predictive Factors Associated with Success and Failure for Radiofrequency Thermocoagulation in Patients with Trigeminal Neuralgia.
Radiofrequency thermocoagulation (RFT) has been widely used to manage trigeminal neuralgia (TN) refractory to oral medication. Careful selection of patients for managing TN with RFT can decrease morbidity and improve treatment efficacy. The goal of this study was to determine clinical variables related to the treatment outcome in patients with TN undergoing RFT. Retrospective analysis. University hospital in Korea. Demographic and clinical data were garnered by billing records for patients with TN who received RFT by one pain physician between January 2005 and August 2014. A successful outcome was pre-defined as at least 50% pain relief on a 0-10 NRS pain score for longer than 6 months after RFT. Variables evaluated for their association with outcome included age, gender, baseline pain score, etiology, type of pain, co-existing psychopathology, and history of previous intervention. Among 90 patients who underwent RFT for managing TN, 75 patients (83.3%) reported a successful outcome (> 50% pain relief at 6 months after RFT procedure). Pain characteristics was the most significant predictor associated with successful outcomes of RFT in both univariate and multivariate logistic analysis; odds ratio of provoked paroxysmal pain was 131.516 and mixed type of pain was 20.602 in multivariate analysis. Prospective studies are recommended to confirm our findings and ascertain which additional variables can be taken into account to improve the likelihood of a successful outcome for RFT in patients with TN. A provoked paroxysmal pain or mixed pain condition was associated with a positive outcome for RFT in patients with TN. In addition, bilateral TN, high baseline NRS pain score, or co-morbid psychiatric condition was related with negative outcomes in univariate analysis. Pain clinicians should consider these findings when selecting patients for managing TN to increase the efficacy of RFT. IRB No. 1403-118-569.


Telemedicine Use in Refugee Primary Care: Implications for Care Beyond the COVID-19 Pandemic.
The expansion of telemedicine during the COVID-19 pandemic offers an opportunity to reach vulnerable refugee communities with limited access to healthcare; however, there are limited data on characteristics of refugee patients that are associated with telemedicine use. We examined primary care encounters between March 2020 and February 2021. We compared telemedicine encounters among refugee and non-refugee patients and examined patient characteristics associated with telemedicine use in refugee patients. Overall, refugees used telemedicine less (aOR = 0.59, p < .001). Among refugee patients, telemedicine encounters were more likely if the patient had hypertension or diabetes, had an activated patient portal, carried private insurance and spoke English as their primary language. Telemedicine may be a useful modality of care management for refugee patients who require many follow-up visits; however, language barriers remain a concern. This is important to consider as telemedicine efforts continue and are expanded.


CT-measurement predicts shortening of stable intertrochanteric hip fractures.
Intertrochanteric (IT) hip fractures can be treated with sliding hip screws (SHS) or cephalomedullary nails (CMN) based on the stability of the fracture. This stability is affected by the initial impaction of the fracture which can be difficult to assess. The aim of this paper is to develop specific pre-operative computed tomography (CT) measurements of IT fractures which are predictive of post-operative shortening. A retrospective review was performed of 141 patients with AO/OTA 31A1 or 31A2 fracture patterns, who had pre-operative radiographs and CT scans, and who were treated with a SHS or a CMN. Pre-operative and post-operative imaging of IT fractures were analyzed for those fractures that shortened ≥15 mm post-fixation. 11 fractures shortened ≥15 mm with CMN being protective of shortening (6/36 SHS versus 5/105 CMN, p = 0.0268). A novel measurement made on the pre-operative CT scan called the cortical thin point (CTP) detected differences between patients with <15 mm and ≥15 mm of post-operative shortening for the SHS group (p = 0.0375). CTP was found to be a reliable predictor for post-operative shortening of ≥15 mm when a cutoff threshold of 9 mm was used in the SHS group (p = 0.0161). Measuring the CTP is predictive of post-operative shortening after fixation of an IT fracture with a SHS. CMN fixation may be protective of shortening. Patients with a CTP of ≤9 mm are at risk for fracture site shortening of more than 15 mm when treated with a SHS.


Electrodiagnosis: How to Read Electromyography Reports for the Nonneurophysiologist.
An electrodiagnostic evaluation is a neurodiagnostic test commonly used to evaluate neuromuscular conditions. A typical electromyography (EMG) report consists of tabular data summarizing findings from nerve conduction studies (NCS) as well as needle EMG (nEMG). A text summary of these findings is also included, followed by a clinical interpretation that evaluates the obtained NCS and nEMG in the context of the clinical presentation. For electrophysiologists and nonelectrophysiologists alike, understanding the elements of EMG report, patterns of findings in common neuromuscular conditions, and potential technical errors that can erroneously influence the clinical interpretation is vital.


Zinc deficiency in sheep: field cases.
Zinc deficiency was diagnosed in a sheep farm in Khartoum Province; the young sheep and lambs were mostly affected. Skin lesions, depression, wool eating, flexed knees and a markedly stiff gait were observed. Histopathology of the skin revealed mainly hyperkeratosis accompanied sometimes by parakeratosis. The animals responded rapidly to oral administration of zinc oxide.


Activity coefficients and thermodynamic parameters for RbCl/CsCl + amide (acetamide, propanamide, and n-butanamide) + water system at 298.15 K.
Electromotive force (emf) of the chemical cell without liquid-junction K-ISE | RbCl/CsCl ( m(E)) | ISE-Cl and K-ISE | RbCl/CsCl (m(E)), amide (m(N)) | ISE-Cl, have been measured at 298.15 K, where m(E)=(0.005 to 0.5) mol kg(-1) and m(N)= (0.05 to 3.0) mol kg(-1). The activity coefficients of RbCl/CsCl in amide (acetamide, propanamide, and n-butanamide) + water mixture can be obtained from these electromotive force data and in the mean time the Gibbs free energy interaction parameters of RbCl/CsCl + amide pair in water, g(EN), as well as the salt constant, k(S), can be evaluated. The results show that both g(EN)>0, k(S)>0 at 298.15 K, and all the activity coefficients of electrolyte in amide + water mixture increase with increasing the m(N), but it is a little complicated for the dependence of activity coefficients on m(E). These thermodynamic parameters were discussed in terms of a model of the structural interaction and electrostatic interaction and the dependence of them on the number of carbon atoms in amide as well as the radius of metal ions were interpreted by the group additivity principle.


Toxoplasma gondii rhomboid protein 1 (TgROM1) is a potential vaccine candidate against toxoplasmosis.
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The rhomboid proteins which are responsible for adhesion and invasion of host cells have been suggested as vaccine candidates against toxoplasmosis. A DNA vaccine (pVAX-ROM1) encoding T. gondii rhomboid protein 1 (TgROM1) gene was constructed and the immune response and protective efficacy of this vaccine against lethal challenge in BALB/c mice were evaluated. The results indicated that specific antibody and lymphocyte proliferative responses were elicited in mice receiving pVAX-ROM1. The production levels of IFN-γ, IL-2, IL-4, and IL-10, as well as the percentage of CD4(+) cells in mice vaccinated with pVAX-ROM1 were significantly increased respectively, compared to controls receiving either pVAX1 alone or PBS. After lethal challenge, the mice immunized with pVAX-ROM1 showed an increased survival time compared with the mice in the controls. Our data suggested that a DNA vaccine pVAX-ROM1 encoding T. gondii rhomboid protein 1 triggered strong humoral and cellular responses, and prolonged survival time against T. gondii infection in BALB/c mice.


A distributable LC-MS/MS method for the measurement of serum thyroglobulin.
Despite its clear advantages over immunoassay-based testing, the measurement of serum thyroglobulin by mass spectrometry remains limited to a handful of institutions. Slow adoption by clinical laboratories could reflect limited accessibility to existing methods that have sensitivity comparable to modern immunoassays, as well as a lack of tools for calibration and assay harmonization. We developed and validated a liquid chromatography-tandem mass spectrometry-based assay for the quantification of serum thyroglobulin. The protocol combined peptide immunoaffinity purification using a commercially available, well-characterized monoclonal antibody and mobile phase modification with dimethylsulfoxide (DMSO) for enhanced sensitivity. To facilitate harmonization with other laboratories, we developed a novel, serum-based 5-point distributable reference material (Husky Ref). The assay demonstrated a lower limit of quantification of 0.15 ng/mL (<20 %CV). Mobile phase DMSO increased signal intensity of the target peptide at least 3-fold, improving quantification at low concentrations. Calibration traceable to Husky Ref enabled harmonization between laboratories in an interlaboratory study. Sensitive mass spectrometry-based thyroglobulin measurement can be achieved using a monoclonal antibody during peptide immunoaffinity purification and the addition of mobile phase DMSO. Laboratories interested in deploying this assay can utilize the provided standard operating procedure and freely-available Husky Ref reference material.


[Histological evaluation of the biocompatibility of PDLLA membranes].
To evaluate the histological response and biocompatibility of implanted domestic bio-degradable PDLLA membranes in vivo. The domestic biodegradable PDLLA membranes and non-degradable ePTFE membranes were in pairs placed subcutaneously in surgical incision made in the dorsum of rats. The tissue responses to these materials were observed histologically at 1, 2, 4, 8 and 12 weeks after placement. The tissue responses of the two kinds of materials were similar to the non-specific reaction mainly infiltrated with lymphocytes, plasmocytes, macrophages, and foreign body giant cells. The polymorphonuclears and foreign body giant cells infiltrated round the ePTFE membranes existed for a relatively long period, in contrast to that of PDLLA membranes. Domestic PDLLA membranes with good biocompatibility will be adapted to making GTR into a single step procedure.


Carbetocin versus rectal misoprostol for management of third stage of labor among women with low risk of postpartum hemorrhage.
To compare effectiveness and safety of carbetocin and misoprostol for prevention of postpartum hemorrhage (PPH) among low-risk women. Randomized controlled trial among 150 pregnant women with low risk of PPH admitted for vaginal delivery at Kasr Al Ainy Hospital, Cairo, Egypt, between July 2018 and May 2019. Participants were assigned to two groups by a web-based randomization system ensuring allocation concealment. After neonatal delivery, the carbetocin group received one ampoule of carbetocin (100 μg/mL) intravenously and the misoprostol group received two rectal tablets of misoprostol (800 μg) for active management of the third stage. Blood pressure, blood loss, and hemoglobin levels were monitored. The primary outcome measure was need for additional uterotonic drugs. The carbetocin group had significantly less blood loss (P<0.001), shorter third stage (P<0.001), and less need for additional uterotonics (P=0.013) or uterine massage (P=0.007). The two drugs were hemodynamically safe. Hemoglobin levels after delivery were comparable in the two groups (P=0.475). Adverse effects were more common in the misoprostol group (P<0.001). Among low-risk women, carbetocin seems to be a better alternative to misoprostol for active management of the third stage of labor; it reduced blood loss and use of additional uterotonic drugs. CLINICALTRIALS.GOV: NCT03556852.


Automatically exposing OpenLifeData via SADI semantic Web Services.
Two distinct trends are emerging with respect to how data is shared, collected, and analyzed within the bioinformatics community. First, Linked Data, exposed as SPARQL endpoints, promises to make data easier to collect and integrate by moving towards the harmonization of data syntax, descriptive vocabularies, and identifiers, as well as providing a standardized mechanism for data access. Second, Web Services, often linked together into workflows, normalize data access and create transparent, reproducible scientific methodologies that can, in principle, be re-used and customized to suit new scientific questions. Constructing queries that traverse semantically-rich Linked Data requires substantial expertise, yet traditional RESTful or SOAP Web Services cannot adequately describe the content of a SPARQL endpoint. We propose that content-driven Semantic Web Services can enable facile discovery of Linked Data, independent of their location. We use a well-curated Linked Dataset - OpenLifeData - and utilize its descriptive metadata to automatically configure a series of more than 22,000 Semantic Web Services that expose all of its content via the SADI set of design principles. The OpenLifeData SADI services are discoverable via queries to the SHARE registry and easy to integrate into new or existing bioinformatics workflows and analytical pipelines. We demonstrate the utility of this system through comparison of Web Service-mediated data access with traditional SPARQL, and note that this approach not only simplifies data retrieval, but simultaneously provides protection against resource-intensive queries. We show, through a variety of different clients and examples of varying complexity, that data from the myriad OpenLifeData can be recovered without any need for prior-knowledge of the content or structure of the SPARQL endpoints. We also demonstrate that, via clients such as SHARE, the complexity of federated SPARQL queries is dramatically reduced.


[Impact of electronic devices used at an early age on language].
The acquisition of language in infants is largely the result of the process of brain maturation, as well as environmental stimulation. Currently, society is in an era of technology and use of electronic devices from an early age. The aim of this study was to demonstrate if the amount of time of use of electronic devices in children under 5 years of age affects language development. An observational, comparative, survey-type study was carried out in 269 infants of both sexes, with an age range of 6 to <60 months. The language development section of the Child Development Scale (EDI) was used. A logistic regression was performed to determine the strength of association between the factors to be studied. 269 participants were included, of which 224 (83.2%) presented their level of neurological maturation, 44 infants (16.4%) presented laged development and one (0.4%) was classified as having developmental delay. It was found that the number of daily hours that an electronic device is used behaved as a risk factor by increasing the risk of delayed language development by 1.37 times for each hour of exposure (OR: 1.37, CI95%: 1.15-1.62). It was shown that a greater number of hours of use of electronic devices is a risk factor for delayed language development in children under 5 years of age. Therefore, it is vital to limit its use in this population.


The role of pH on instability and aggregation of sickle hemoglobin solutions.
Understanding the physical basis of protein aggregation covers strong physical and biomedical interests. Sickle hemoglobin (HbS) is a point-mutant form of normal human adult hemoglobin (HbA). It is responsible for the first identified "molecular disease," as its propensity to aggregation is responsible for sickle cell disease. At moderately higher than physiological pH value, this propensity is inhibited: The rate of aggregate nucleation becomes exceedingly small and solubility after polymerization increases. These order-of-magnitude effects on polymer nucleation rates and concurrent relatively modest changes of solubility after polymerization are here shown to be related to both pH-induced changes of location and shape of the liquid-liquid demixing (LLD) region. This allows establishment of a self-consistent contact between the thermodynamics of the solution as such (i.e., the LLD region), the kinetics of fiber nucleation, the theory of percolation, and the thermodynamics of gelation. The observed pH-induced changes are largely attributable to strong perturbations of hydrophobic hydration configurations and related free energy by electric charges. Similar mechanisms of effective control of aggregate nucleation rates by means of agents such as cosolutes, pH, salts, and additives, shifting the LLD and associated regions of anomalous fluctuations, promise to be relevant to the whole field of protein aggregation pathologies.


The modifications of a fructan from Anemarrhena asphodeloides Bunge and their antioxidant activities.
Polysaccharide modification exerts important significance for enhancing biological activity. In the present study, a fructan (AAP70-1) extracted from Anemarrhena asphodeloides Bunge was modified by carboxymethylation and sulfation modifications to obtain carboxymethylated derivatives (CM-AAP70-1s) and a sulfated derivative (S-AAP70-1), which were prepared by the chloroacetic acid-isopropanol and the chlorosulfonic acid-pyridine methods, respectively. Physicochemical characteristics and antioxidant activities in vitro of modified derivatives were determined. The results of degree of substitution (DS) and FT-IR analysis indicated that the carboxymethylated and sulfated groups were introduced successfully. After modifications, the DS of CM-AAP70-1s varied from 0.18 to 0.52 and the molecular weights (Mw) were between 4.50 × 103 and 8.65 × 103 g/mol. The DS and Mw of S-AAP70-1 were calculated to be 0.61 and 9.76 × 103 g/mol, respectively. The assays of the antioxidant properties demonstrated that the modified derivatives exhibited stronger scavenging effects toward DPPH and hydroxyl radicals compared with AAP70-1. These results revealed that the chemical modifications could effectively improve the potential of polysaccharides as oxidation inhibitor.


The environmental Kuznets curve and CO2 emissions in the USA : Is the relationship between GDP and CO2 emissions time varying? Evidence across economic sectors.
In this paper, we analyze the existence of the environmental Kuznets curve as reported by Kuznets (Am Econ Rev 5:1-28, 1955) by using the methodology proposed by Kejriwal and Perron (J Econ 146:59-73, 2008, J Bus Econ Stat 28:503-522, 2010) and applying Jaunky's (Energy Policy 39(3):1228-1240, 2011) specification using quarterly data from 1973:1 to 2015:2. We also allow different behaviors across time and identify it by economic sectors. Our results show the existence of the environmental Kuznets curve (EKC) in the USA only when we allow for structural breaks. Interestingly, the industrial sector shows a different pattern than do other economic sectors; with the beginning of the economic crisis, it appears to have abandoned the objective of the environmental stabilization found until then.


Regulation of receptor by homologous hormone enhances sensitivity and broadens scope of radioreceptor assay for human growth hormone.
In standard competitive binding assays (including radioreceptor assays) unlabeled ligand (hormone) competes with labeled ligand (hormone) for binding to a fixed number of binding (receptor) sites. Detection of the unlabeled ligand occurs when the occupancy of binding sites by the unlabeled ligand is sufficient to reduce the binding of labeled ligand. A common feature of the hormone-receptor interaction is the ability of the hormone to regulate the affinity and/or the concentration of its homologous receptor. In the present study, by exploiting the ability of human GH to regulate by negative feedback the concentration of its own receptors, we have enhanced the sensitivity of the human GH radioreceptor assay 5-fold. The ability of hormone to regulate receptor concentration and affinity affords wide opportunities to broaden the scope as well as to enhance the sensitivity of radioreceptor assays.


Semen characteristics and refrigeration in free-ranging giant anteaters (Myrmecophaga tridactyla).
The giant anteater (Myrmecophaga tridactyla) is considered vulnerable to extinction. Scientific data on the reproductive parameters of this species are scarce. Semen from eight free-ranging giant anteaters was collected to establish its characteristics and the effects of cooling and storage at 5 °C after dilution with the BotuCrio extender without cryoprotectant. The ejaculate presented two distinct sequential fractions, including a whitish fraction, which was milky and rich in sperm cells, and a gel fraction, which was colorless, viscous, and azoospermic. The mean ± standard error of the mean values of the seminal characteristics were as follows: volume of the first fraction, 0.75 ± 0.1 mL; motility, 75 ± 2.9%; vigor, 3.2 ± 0.3; sperm motility index, 68.8 ± 4.3; concentration, 108.5 ± 13.4 × 10(6)/mL; plasma membrane integrity index, 71 ± 4.0%; spermatic defects detected using modified Karras staining, 35.5 ± 3.3%; and spermatic alterations identified by differential interference contrast microscopy, 48.3 ± 6.8%. During refrigeration, the semen presented decreasing motility from 0 to 18 hours, sperm motility index decreased from 0 to 24 hours, and vigor did not change in the first 6 hours and then decreased to 18 hours.


The molecular basis of the antigenic variation of foot-and-mouth disease virus.
We have cloned and sequenced the viral protein (VP1)-coding regions of two foot-and-mouth disease virus (FMDV) serotypes (C1 and A5). Comparison of the derived amino acid sequences with the known VP1 sequence of FMDV O1K and the two FMDV A subtypes A10 and A12 shows two highly variable regions in the protein, at positions 40-60 and 130-160, as possible antigenic sites. In both variable regions, several sites could be detected where all three sequences of the A subtypes are identical but the three types A, C and O differ from each other. The second variable region overlaps with a major immunogenic determinant of the virus.


Evidence for coordinated phosphorylation of keratins and vimentin during mitosis in transformed human amnion cells. Phosphate turnover of modified proteins.
Two-dimensional gel electrophoresis (IEF) analysis of short-term [32P]orthophosphate-labelled intermediate-sized filament proteins (keratins and vimentin) from transformed mitotic amnion cells (AMA), have shown that these proteins are modified coordinately and that the half life of the phosphate is about 13 min for the keratins and 11 min for vimentin. These results support the notion that the preferential modification of intermediate-sized filament proteins during mitosis may play a role in modulating filament associations with organelles and other cellular structures.


Setting Up an Ultra-Fast Next-Generation Sequencing Approach as Reflex Testing at Diagnosis of Non-Squamous Non-Small Cell Lung Cancer; Experience of a Single Center (LPCE, Nice, France).
The number of genomic alterations required for targeted therapy of non-squamous non-small cell lung cancer (NS-NSCLC) patients has increased and become more complex these last few years. These molecular abnormalities lead to treatment that provides improvement in overall survival for certain patients. However, these treated tumors inexorably develop mechanisms of resistance, some of which can be targeted with new therapies. The characterization of the genomic alterations needs to be performed in a short turnaround time (TAT), as indicated by the international guidelines. The origin of the tissue biopsies used for the analyses is diverse, but their size is progressively decreasing due to the development of less invasive methods. In this respect, the pathologists are facing a number of different challenges requiring them to set up efficient molecular technologies while maintaining a strategy that allows rapid diagnosis. We report here our experience concerning the development of an optimal workflow for genomic alteration assessment as reflex testing in routine clinical practice at diagnosis for NS-NSCLC patients by using an ultra-fast-next generation sequencing approach (Ion Torrent Genexus Sequencer, Thermo Fisher Scientific). We show that the molecular targets currently available to personalized medicine in thoracic oncology can be identified using this system in an appropriate TAT, notably when only a small amount of nucleic acids is available. We discuss the new challenges and the perspectives of using such an ultra-fast NGS in daily practice.


Transition to Virtual Microscopy in Medical Undergraduate Pathology Education: First Experience of Turkey in Dokuz Eylül University Hospital.
Pathology education includes an important visual part supporting a wide range of theoretical knowledge. However, the use of traditional microscopes in pathology education has declined over the last decade and there is a lack of interest for microscopy. Virtual microscopy, which was first described in 1985 and has experienced a revolution since 2000, is an alternative technique to conventional microscopy, in which microscopic slides are scanned to form digital images and stored in the web. The aim of this study was to evaluate the use of virtual microscopy in practical pathology sessions and its effects on our students and undergraduate education at our faculty. Second and third year medical students who were used to conventional microscopes were included in the study. The practical sessions were carried out via virtual slides and the effect of the new technique was investigated by a scale at the end of each session. Academic staff from the pathology department joined sessions to promote discussion and respond to questions. Student ratings were analysed statistically. The evaluation of the ratings showed that the students were easily adapted to the use of virtual microscopy. They found it user-friendly and thought that the opportunity of viewing slides at home was advantageous. Collaboration between students and interactive discussions was also improved with this technique. It was concluded that the use of virtual microscopy could contribute to the pathology education of our students.


Skin tests and blood leukocyte histamine release of patients with allergies to laboratory animals.
Skin tests and in vitro histamine-release reactions were used to evaluate 130 patients observed in an employee allergy clinic at a biomedical research facility. The allergens used included extracts from pollens (ragweed, grasses, trees, weeds), molds, mixed feathers, house dust, cat, dog, mouse, rat, rabbit, guinea pig, and hamster. Of all patients, 66% complained of allergic symptoms on laboratory animal exposure, although only 52% worked directly with animals. Among patients with symptoms, 91% were positive by skin test to at least one laboratory animal, and 46% had asthma. The median length of exposure to laboratory animals before onset of symptoms was 2.8 yr with 60% of the patients developing their symptoms within 3 yr. Among patients who had allergic symptoms before exposure to laboratory animals, 79% were skin test positive to laboratory animals when they were evaluated in this study. There was a close association found between the skin test and histamine-release results with the laboratory animal allergens: 91% of the 4+ skin reactors had leukocytes positive for histamine release versus 5% of the leukocyte donors with less than 1+ skin reactions. A close relationship in positive reactions to different laboratory animal allergens was also found. For example, individuals positive to mouse were positive also to rat (95%), rabbit (79%), guinea pig (83%), and hamster (88%). Patients who reacted to laboratory animals also reacted to some extent to house dust and cat and dog allergens, and about one half of the animal-allergic individuals reacted to pollens. Although nonpollen-allergic individuals can develop sensitivity to laboratory animals, the group at higher risk are allergic individuals, especially those sensitive to house dust, cats, or dogs.


[Inhaled corticosteroids for COPD].
Over 60% of patients with COPD are treated with inhaled corticosteroids (ICS), even though their use is still subject to debate. The inflammatory process in the lungs of patients with COPD is dominated by macrophages, CD8+ T-lymphocytes, neutrophilic granulocytes and mast cells, as well as an increased production and/or concentration of IL-8, TNF-alpha and leucotrine B4. This inflammatory process is less sensitive to the effect of corticosteroids than that in asthma. Placebo-controlled clinical studies show a beneficial effect of ICS on the number and severity of exacerbations, symptoms and quality of life, but not on the accelerated decline in lung function. Exacerbations occurred in a subgroup of patients in whom ICS were discontinued. A trial treatment with ICS should be considered in all COPD patients who have previously exhibited signs of asthma or allergy, or who have marked bronchial hyperresponsiveness, considerable reversibility, and recurrent exacerbations. In patients with moderate and severe COPD, a one-year trial with ICS should be considered, with exacerbations and symptoms as primary efficacy parameters and lung function decline as a secondary parameter. The combined use of ICS and long-acting beta-2 agonists may be considered in view of an additional effect on these parameters compared to administering the individual components.


Interactions of liposomes with the reticuloendothelial system. Effects of reticuloendothelial blockade on the clearance of large unilamellar vesicles.
Large unilamellar liposomes (also called reversed phase vesicles or REVs) composed of DPPC and cholesterol are cleared from the circulation of the rat by a process which closely resembles the clearance of colloidal particles by the reticuloendothelial system. Thus, increasing the total amount of REVs administered by giving a loading dose of unlabelled REVs slows the clearance of a test dose of radioactively labelled REVs. This resembles the reticuloendothelial 'blockade' induced by large doses of colloids. Administration of other types of particles known to induce reticuloendothelial blockade, such as latex beads and xenogeneic red cells, also slows the clearance of radioactively labelled REVs. Administration of small unilamellar liposomes (SUVs) can also cause blockade of REV clearance, but the onset of blockade is delayed until a substantial fraction of the SUVs have been removed from the circulation. Blockade caused by the administration of large doses of REVs seems to result from a direct action on reticuloendothelial cells rather than from depletion of opsonic factors in the blood. Partial blockade of REV clearance produces a modest alteration of the tissue distribution of REVs, with enhanced uptake in the lungs. These results suggest that both REVs and SUVs are taken up by the reticuloendothelial system via a process which closely resembles the clearance of other types of colloids.


Interleukin-37 gene polymorphism and susceptibility to coronavirus disease 19 among Iraqi patients.
Coronavirus disease 19 (COVID-19) is a highly contagious respiratory viral infection. Dysregulated immune response is an important feature of disease, and cytokines are among the most important mediators of dysregulated immunity. Interleukin-37 (IL-37) is one such cytokine and studies have indicated its role in pathogenesis of COVID-19. However, IL37 gene polymorphisms have not been identified in patients with COVID-19. Therefore, this case-control study (100 patients and 100 controls) was performed to understand the role six single nucleotide polymorphisms of IL37 gene (SNPs: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in susceptibility to COVID-19 among cases with severe disease. These polymorphisms were identified by Sanger DNA sequencing. Results revealed that TG genotype of rs3811046 showed a significantly increased frequency in patients compared to controls (61.0 vs. 38.0%; odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.45-4.50; probability [p] = 0.002; corrected p [pc] = 0.01). GA genotype of rs3811047 also showed an increased frequency in patients but the pc-value was not significant (39.0 vs. 24.0%; OR = 2.02; 95% CI = 1.10-3.71; p = 0.033; pc = 0.165). Haplotype analysis revealed a significantly increased frequency of the haplotype G-C-A-T-T-A (in the order: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in COVID-19 patients compared to controls (0.055 vs. 0.006; OR = 10.23; 95% CI = 1.53-68.14; p = 0.003; pc = 0.03). In conclusion, the study indicated that two variants of IL37 gene (rs3811046 and rs3811047) may be associated with susceptibility to COVID-19 among Iraqi population.


Kinking of pedicle vessels and its effect on blood flow and patency in free flaps: an experimental study in rats.
Head rotation may significantly alter the initial position of the vascular pedicle of free flaps in reconstructive surgery of the oral cavity. This may lead to kinking of venous and/or arterial vessels. In spite of some precautions as rotating the head contralaterally for the first few days postoperatively or shortening the pedicle, the problem is still not well understood and remains unsolved. In order to understand the matter better, an experimental study was devised to create intentional kinking of the pedicle of a free-flap. Twenty CD-outbred rats were subdivided into two groups. All rats were operated on by harvesting a muscular free flap from the right-hind limb. Microvascular anastomoses were performed on the femoral artery and vein. In group A (kinking group), the free flap was twisted and placed within the abdomen just under the spleen; by this way the pedicle was rotated by 180 degrees creating a kink. In group B (no kinking, the control-group), the same microvascular flap was performed leaving the limb in the normal anatomical position. Rats were sacrificed 48 h postoperatively and patency of the vessels was established both clinically (Acland test) and microscopically. Only one vein of a rat of group B had preanastomotic thrombosis, so no statistically significant difference was found among the two groups. From this experimental protocol a 180 degrees narrow kinking with a curvature rather than acute angulation of the pedicle does not influence the survival rate of the free flap negatively. This, however, does not refute the possibility that a more acute angular kinking may reduce survival rates of microvascular flaps.


Reconstruction of severe atherosclerotic and obstructive diabetic feet using thoracodorsal artery perforator flaps with long vascular pedicles.
Foot ulcers in diabetic patients often require free flaps. A long vascular pedicle is mandatory so that more proximal vessels can be used as recipient vessels, especially when the flap is used to reconstruct distal foot defects. We evaluated the outcome of diabetic foot defect that were reconstructed using thoracodorsal artery perforator (TDAP) flaps with long vascular pedicles. We reconstructed the foot defects of 22 diabetic patients. Nineteen patients were male, and the mean age was 56.4 years. The defects were located in big toe in 11 patients; fourth and/or fifth toe, including lateral aspect of the foot, in 8 patients; and dorsum of the foot, medial plantar, and first metatarsal medial head in 1 patient each. CT angiography showed that the two main vessels of the lower leg remained intact in 7 patients, only one vessel was intact in the lower leg of 11, and no vessels were visible in 4. The flap size ranged between 5 × 4 cm2 and 18 × 11cm2 , with a mean pedicle length of 16.5 cm. The anterior tibial artery was used as the recipient vessel in 15 patients, while the posterior tibial artery was used in 7. All the flaps survived. Three wound disruptions and two partial flap losses healed conservatively, without further surgery. Ulcer due to diabetes recurred in three cases. The mean follow-up period was 46.1 months. All wounds healed completely. TDAP flaps with long vascular pedicles may be a viable choice for reconstructing defects in the feet of diabetic patients.


Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial.
Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above - 3.0 and no diet differences completed 12 weeks of RT. The participants' diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion. After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p < 0.001 and p = 0.030, respectively). No changes in the BMD were observed after 3 months of the intervention. Twelve weeks of LC supplementation during RT program increased plasma TMAO levels and appeared to affect signaling molecules, as indicated by the increase in the resting SPARC and decorin levels, with no significant modification in the BMD. Retrospectively registered at the ClinicalTrials.gov (NCT05120011).


Characteristics of COVID-19 Infection in Patients without a History of Travel to Infected Areas or Direct Contact with a Case-Patient.
Little is known about COVID-19 patients who have not traveled to infected areas or had direct contact with infected persons. This report describes the clinical features of 28 such patients with confirmed COVID-19 infection. Data on clinical characteristics during hospitalization were collected. Epidemiological exposures were investigated among patients reporting no travel to infected areas or direct contact with a case-patient. Patients presented with various symptoms, increased levels of inflammatory markers, and consolidation or ground-glass opacification on computed tomography scans. The present report contributes critical information on the clinical presentation of COVID-19 patients without typical epidemiological exposures.


Various responses of male pituitary-gonadal axis to different intensities of long-term exercise: Role of expression of KNDYrelated genes.
The essential role of regular physical activity has been emphasized for maintaining a healthy life. However, unfortunately, during the last few decades, the lifestyle of people has led to a decrease in physical activity. Research studies have shown that exercise of different intensities is applied on reproductive performance indices, luteinizing hormone (LH) and testosterone (T), with different effects. Nevertheless, the molecular and cellular mechanisms underlying its function are not completely understood. Therefore, this study aimed to evaluate the role of kisspeptin, neurokinin-B and pro-dynorphin (KNDY) gene-expression changes located in the upstream of GnRH neurons in transferring the effects of different long-term exercise intensities on male reproductive axis. Twenty-one adult Wistar rats were randomly divided into control, 6-month regular moderate exercise (RME-6) and 6-month regular intensive exercise (RIE-6). In moderate and intensive exercise groups, rats were treated 5 days a week for 60 min, at 22 and 35 m/min, respectively. Finally, the hypothalamic arcuate nucleus was isolated and the relative gene expression of kisspeptin (Kiss1), neurokinin-B (Nkb), pro-dynorphin (Pdyn) and gonadotropin-releasing hormone (Gnrh) genes were measured by realtime polymerase chain reaction method. The results showed that RIE-6 treatment decreased Gnrh and increased Pdyn mRNA levels in the arcuate nucleus. Furthermore, although RME-6 treatment decreased Nkb and increased Pdyn mRNA levels, the Gnrh mRNAwas not affected. Regarding the Gnrh mRNA levels and serum concentrations of reproductive indices (LH and T), moderate exercise did not impose harmful effects on the hypothalamic-pituitary-gonadal axis than intensive exercise. The different impacts of diverse long-term exercise intensities on the male pituitary-gonadal axis maybe relay by the various changes in hypothalamic Nkb and Pdyn gene expressions.


18F-FDG PET Radiomics as Predictor of Treatment Response in Oesophageal Cancer: A Systematic Review and Meta-Analysis.
The best treatment strategy for oesophageal cancer patients achieving a complete clinical response after neoadjuvant chemoradiation is a burning topic. The available diagnostic tools, such as 18F-FDG PET/CT performed routinely, cannot accurately evaluate the presence or absence of the residual tumour. The emerging field of radiomics may encounter the critical challenge of personalised treatment. Radiomics is based on medical image analysis, executed by extracting information from many image features; it has been shown to provide valuable information for predicting treatment responses in oesophageal cancer. This systematic review with a meta-analysis aims to provide current evidence of 18F-FDG PET-based radiomics in predicting response treatments following neoadjuvant chemoradiotherapy in oesophageal cancer. A comprehensive literature review identified 1160 studies, of which five were finally included in the study. Our findings provided that pooled Area Under the Curve (AUC) of the five selected studies was relatively high at 0.821 (95% CI: 0.737-0.904) and not influenced by the sample size of the studies. Radiomics models exhibited a good performance in predicting pathological complete responses (pCRs). This review further strengthens the great potential of 18F-FDG PET-based radiomics to predict pCRs in oesophageal cancer patients who underwent neoadjuvant chemoradiotherapy. Additionally, our review imparts additional support to prospective studies on 18F-FDG PET radiomics for a tailored treatment strategy of oesophageal cancer patients. https://www.crd.york.ac.uk/prospero/, identifier CRD42021274636.


The ecology and bioactivity of some Greco-Roman medicinal minerals: the case of Melos earth pigments.
Mineral compounds, as pigments and therapeutics, appeared regularly in the technical and medical texts of the Greco-Roman (G-R) world. We have referred to them as 'G-R medicinal minerals' and we suggest that despite their seeming familiarity, there are actually many unknowns regarding their precise nature and/or purported pharmacological attributes. Earth pigments are part of that group. This paper presents a brief overview of our work over the past twenty years relating to: a. the attempt to locate a select number of them in the places of their origin; b. their chemical/mineralogical characterization; c. the study of their ecology via the identification of the microorganisms surrounding them; d. their testing as antibacterials against known pathogens. In the process, and to fulfil the above, we have developed a novel methodological approach which includes a range of analytical techniques used across many disciplines (mineralogy, geochemistry, DNA extraction and microbiology). This paper focuses on a select number of earth pigments deriving from the island of Melos in the SW Aegean, celebrated in antiquity for its Melian Earth, a white pigment, and asks whether they might display antibacterial activity. We demonstrate that some (but not all) yellow, green and black earth pigments do. We also show that the manner in which they were dispensed (as powders or leachates) was equally important. The results, although preliminary, are informative. Given their use since deep time, earth pigments have never lost their relevance. We suggest that the study of their ecology/mineralogy and potential bioactivity allows for a better understanding of how our perception of them, as both pigments and therapeutics, may have evolved.


Combination of metabolomics and network pharmacology analysis to decipher the mechanisms of total flavonoids of Litchi seed against prostate cancer.
To explore the underlying mechanism of total flavonoids of Litchi seed (TFLS) in treating prostate cancer (PCa). Cell Counting Kit-8 (CCK-8), EdU incorporation assay, trypan blue dye assay and colony formation assay were employed to evaluate the effect of TFLS on PCa in vitro. The xenograft mouse model was established to explore the anti-tumour effect of TFLS in vivo. Alterations in the metabolic profiles of the PC3 cells and mouse serum were obtained by untargeted metabolomics. Combination with metabolomics analysis and network pharmacology strategies, the potential targets were predicted and further validated by RT-qPCR. TFLS attenuated PCa progression both in vitro and in vivo. Metabolomics results yielded from cells and serum indicated that the anti-cancer effect of TFLS was correlated with synergistic modulation of five common metabolic pathways including glycerophospholipid metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and steroid biosynthesis. Using in silico prediction and RT-qPCR analysis, we further revealed that TFLS exerted anti-PCa activities via regulating the expressions of nine genes, including MAOA, ACHE, ALDH2, AMD1, ARG1, PLA2G10, PLA2G1B, FDFT1 and SQLE. TFLS suppressed tumour proliferation in PCa, which may be associated with regulating lipid and amino acid metabolisms.


Long-term outcomes in elderly patients with resectable large hepatocellular carcinoma undergoing hepatectomy.
In contrast to the feasibility of hepatectomy for resectable large hepatocellular carcinoma (HCC, >5 cm) in the younger patients, the concerns of benefits for the elderly patients remain in practice. This study aimed to evaluate the long-term outcomes and safety after hepatectomy in elderly patients with resectable large HCC compared with younger patients. Between 2003 and 2014, a total of 2211 HCC patients were reviewed using a prospective database and 257 patients with resectable large HCC undergoing hepatectomy were included: 79 elderly patients with age ≥70 years and 178 younger patients with age <70 years. The last follow-up was assessed in December 2017. The complications, long-term outcomes and risk factors of disease-free and overall survival were analysed. The 1-, 3-, 5- and 7-year overall survival rates in the elderly and younger groups were 76%, 55%, 48%, and 42% and 79%, 57%, 51%, and 49%, respectively (P = 0.319). The 1-, 3-, 5-, and 7-year disease-free survival rates in the elderly and younger groups were 60%, 40%, 38%, and 27% and 54%, 36%, 32%, and 32%, respectively (P = 0.633). The analysis of post-operative outcomes of interest, including hospital stay and hospital death and hepatectomy-related complications in both groups revealed no significant difference. Serum albumin and AJCC TNM stage were independent risk factors for survival. Serum alpha-fetoprotein, tumour number and AJCC TNM stage predicted HCC recurrence. Our results suggested that hepatectomy can achieve comparable long-term outcomes in the selected younger and elderly patients with resectable large HCC.


An Atom-Pair Design Strategy for Optimizing the Synergistic Electron Effects of Catalytic Sites in NO Selective Reduction.
Effective adsorption and speedy surface reactions are vital requirements for efficient active sites in catalysis, but it remains challenging to maximize these two functions simultaneously. We present a solution to this issue by designing a series of atom-pair catalytic sites with tunable electronic interactions. As a case study, NO selective reduction occurring on V1 -W1 /TiO2 is chosen. Experimental and theoretical results reveal that the synergistic electron effect present between the paired atoms enriches high-energy spin charge around the Fermi level, simultaneously rendering reactant (NH3 or O2 ) adsorption more effective and subsequent surface reactions speedier as compared with single V or W atom alone, and hence higher reaction rates. This strategy enables us to rationally design a high-performance V1 -Mo1 /TiO2 catalyst with optimized vanadium(IV)-molybdenum(V) electronic interactions, which has exceptional activity significantly higher than the commercial or reported catalysts.


Power computations in time series analyses for traffic safety interventions.
The evaluation of traffic safety interventions or other policies that can affect road safety often requires the collection of administrative time series data, such as monthly motor vehicle collision data that may be difficult and/or expensive to collect. Furthermore, since policy decisions may be based on the results found from the intervention analysis of the policy, it is important to ensure that the statistical tests have enough power, that is, that we have collected enough time series data both before and after the intervention so that a meaningful change in the series will likely be detected. In this short paper, we present a simple methodology for doing this. It is expected that the methodology presented will be useful for sample size determination in a wide variety of traffic safety intervention analysis applications. Our method is illustrated with a proposed traffic safety study that was funded by NIH.


Multiple mechanisms of transmitter release evoked by "pathologically" elevated extracellular [K+]: involvement of transporter reversal and mitochondrial calcium.
The release of [3H]GABA evoked by depolarization with various concentrations of KCl was studied using superfused rat cerebrocortex synaptosomes. Elevating [K+] produced release of [3H]GABA over basal which was increasingly less dependent on external Ca2+ but more sensitive to the GABA transporter blocker SKF 100330 A. Accordingly, the sensitivity to clostridial toxins of the depolarization-evoked amino acid release was inversely correlated to the concentration of KCl used. However, at 50 mM K+, one-third of the stimulated release remained which was external Ca2+-independent but insensitive to SKF 100330 A. This release was prevented by BAPTA, thapsigargin or dantrolene; it also was inhibited by blocking in mitochondria the ATP production with oligomycin, the H+-dependent Ca2+ uniporter with RU 360, the Na+/Ca2+ exchanger with CGP 37157 or by lowering extraterminal [Na+]. In fluorescence experiments with fura-2/AM, 50 mM K+ (in Ca2+ free medium) caused elevation of cytosolic [Ca2+] that was sensitive to thapsigargin or CGP 37157; these compounds produced partially additive effects. When exocytosis was monitored with the fluorescent dye acridine orange, the fluorescence elicited by 50 mM K+ was sensitive to thapsigargin or CGP 37157, which produced additive effects, and to low-Na+ media. To conclude, extracellular K+ concentrations occurring in the CNS in certain pathological conditions provoke GABA release by mechanisms different from classical exocytosis. These include carrier-mediated release and internal Ca2+-dependent exocytosis; in the latter, mitochondrial Ca2+ seems to play a primary role.


Protein migration from transplanted nuclei in Amoeba proteus. I. The relation to the cell cycle and RNA migration, as studied by autoradiography.
Autoradiography has been used to examine the migration of proteins from a radioactively labelled amoeba nucleus following transplantation into an unlabelled homophasic amoeba. Nuclei were transferred at three times in the cell cycle coinciding with DNA synthesis (4 h post-division); a peak of RNA synthesis (25 h); and a relative lull in synthetic activity (43 h). Six amino acids were added individually to the culture medium to label the nuclear proteins. Migration of the proteins from the donor nucleus was found to be greatest following the transfer of [3H]aspartic acid-labelled nuclei and least with protein labelled with the basic amino acids. All amino acids exhibited the greatest extent of migration following the 25-h transfers, i.e., coinciding with a peak of RNA synthesis at 26-27.5 h. Actinomycin D (actD) inhibition of RNA synthesis reduced, but did not eliminate the extent of protein migration from the transplanted nucleus, thus indicating the existence of two classes of migratory proteins. Firstly, proteins, associated with RNA transport, which migrated mainly into the host cytoplasm. The second class migrated into the host nucleus from the transplanted nucleus, irrespective of RNa synthesis. The shuttling character of the latter class of proteins is consistent with a role of regulation of nuclear activity.


Screening services for alcohol misuse and abuse at four-year colleges in the U.S.
We examine the prevalence of screening for student alcohol misuse/abuse among 333 U.S. colleges via a survey of campus leaders. We also use latent class modeling to identify classes of colleges based on screening practices. We found that most colleges conduct screening after a student is involved in an alcohol-related incident, and about 50% of colleges screen students at regular health care visits. Legal, health care, and housing staff are trained in screening at nearly all colleges; other key personnel were trained at about one third of colleges. We identified four classes of colleges: 62% of colleges fit in a class that had many screening components in place, 9% in a class with very limited services, and the remainder (29%) fit in 2 middle classes. Although most colleges had many alcohol misuse/abuse screening components in place, more than one third show need for improvement in how, where, and when screening is conducted.


Analysis of bromodeoxyuridine incorporation into DNA: comparison of gas chromatographic/mass spectrometric, CsCl gradient sedimentation, and specific radioactivity methods.
A sensitive new method for the quantitation of 5-bromodeoxyuridine (BrdUrd) incorporated into DNA by GC/MS analysis of enzymatically released Thy and bromouracil (BrUra) is presented. The hydrolysis procedure was characterized and found to give uniform results when sample size was 1-10 micrograms DNA and incubation time for DNA digestion was between 40 min and 16 h. Samples of DNA containing 3H-labeled BrdUrd were analyzed in parallel by the GC/MS technique and by specific radioactivity and buoyant density measurements, in order to compare the three methods. The GC/MS procedure gave values for percentage replacement of Thy by BrUra which were higher than those obtained by specific activity and lower than those obtained by buoyant density. This GC/MS method can detect 1% replacement in a 1-microgram DNA sample, equivalent to approximately 10(5) cells or 0.1 mg tissue, and will permit sensitive and quantitative analysis of the presence of this chemotherapeutic agent/radiosensitizer in cellular DNA from biopsy samples of normal or tumor tissue.


Aortofemoral graft occlusion: strategy and timing of reoperation.
The authors' experience with 46 patients treated over 8.5 years was reviewed to determine the optimal secondary revascularization procedure after occlusion of a unilateral aortobifemoral graft limb. A total of 64 procedures was performed on these patients to restore and maintain graft patency. Repetitive operations for reocclusion were needed in 14 patients (30%). Transcatheter thrombolytic therapy was used in 14 patients, four as sole therapy and 10 in conjunction with operation. The mean time from aortofemoral grafting to presentation with graft limb occlusion was 59.4 months. Rest pain or severe ischemia was present in 85%, and severe claudication in the remainder. Some 78% had urgent operation after diagnostic angiography and catheter-directed thrombolytic therapy was attempted in 22%. The etiology of graft thrombosis was outflow obstruction in 78.2% of cases. Inflow was obtained by surgical thrombectomy in 35 and by lytic therapy in 13. Extra-anatomic inflow was used in 11 and intra-abdominal thrombectomy or redo aortofemoral grafting in five. Outflow procedures, mainly profundaplasty, were performed in all but five cases (four urokinase and one surgical). Infrainguinal bypass was needed in 10 cases in addition to the groin reconstruction. Catheter-directed thrombolysis was successful in 13 of 14 instances; however, in nine of these residual stenosis was disclosed in the outflow requiring surgical repair. Ultimately, 12 of 14 cases treated with thrombolysis required surgical intervention. Cumulative patency for all procedures was 68%. Complications were seen in 14% of cases. Operative mortality was 5%, and limb salvage was obtained in 85%.(ABSTRACT TRUNCATED AT 250 WORDS)


Can a Shockable Initial Rhythm Identify Out-of-Hospital Cardiac Arrest Patients with a Short No-flow Time?
Initial shockable rhythms may be a marker of shorter duration between collapse and initiation of cardiopulmonary resuscitation, known as no-flow time (NFT), for patients suffering an out-of-hospital cardiac arrest (OHCA). Eligibility for extracorporeal resuscitation is conditional on a short NFT. Patients with an unwitnessed OHCA could be candidate for extracorporeal resuscitation despite uncertain NFT if an initial shockable rhythm is a reliable stand-in. Herein, we sought to describe the sensitivity and specificity of an initial shockable rhythm for predicting a NFT of five minutes or less. Using a registry of OHCA in Montreal, Canada, adult patients who experienced a witnessed non-traumatic OHCA, but who did not receive bystander cardiopulmonary resuscitation, were included. The sensitivity and specificity of an initial shockable rhythm for predicting a NFT of five minute or less were calculated. The association between the NFT and the presence of a shockable rhythm was evaluated using a multivariable logistic regression. A total of 2450 patients were included, of whom 863 (35%) had an initial shockable rhythm and 1085 (44%) a NFT of five minutes or less. The sensitivity of an initial shockable rhythm to predict a NFT of five minutes or less was 36% (95% confidence interval [95%CI] 33-39), specificity was 66% (95%CI 63-68), the positive likelihood ratio was 1.05 (95%CI 0.94-1.17) and the negative likelihood ratio of 0.97 (95%CI 0.92-1.03). The probabilities of observing a shockable rhythm stayed stable up to 15 minutes, while the probabilities of observing a PEA lowered rapidly initially. Longer NFT were associated with lower odds of observing an initial shockable rhythm (adjusted odds ratio = 0.97 [95%CI 0.94-0.99], p = 0.012). An initial shockable rhythm is a poor predictor of a short NFT, despite there being an association between the NFT and the presence of a shockable rhythm.


Prevention of stricture with intraluminal stenting through laparotomy after corrosive esophageal burns.
We sought to present our experience in preventing esophageal stricture formation using modified intraluminal stenting in patients with caustic burns. Between April 1976 and June 2005, 33 of 162 patients with corrosive esophageal burns were included in this study. Endoscopy was performed to define the degree of injury in all the patients but one. Among the 33 patients, 31 underwent modified esophageal intraluminal stenting through laparotomy 2-3 weeks after ingestion of corrosive agent and the remaining 2 patients underwent immediately after experiencing esophageal perforation. There was no death in this series. A 1-year-old child had aspiratory pneumonia because of poor compliance. The stent was removed without requiring anesthesia after it had been in situ for 4-6 months in the 33 patients. All the patients had a normal intake of food after removal of the stents, and stricture was not found on barium swallow. However, five patients had esophageal stenosis from 2 to 3 months during follow-up. One of them responded to esophageal bougienage, the remaining four patients required esophageal reconstruction and had a normal diet postoperatively. Twenty-four-hour pH monitoring in five patients showed that there was no gastroesophageal reflux. The modified esophageal intraluminal stent is able to prevent the formation of caustic esophageal stricture.


A benzil and isoflavone from Iris tenuifolia.
Two compounds, tenuifodione (1) and tenuifone (2), and 12 known compounds, izalpinin (3), alpinone (4), arborinone (5), irilin B (6), irisone A (7), irisone B (8), betavulgarin (9), beta-sitosterol (10), 5,7-dihydroxy-2',6-dimethoxyisoflavone (11), 2',5-dihdroxy-6,7-methylenedioxy flavanone (12), irisoid A (13) and ethyl-beta-d-glucopyranoside (14) were isolated from the whole plant of Iris tenuifolia Pall. All compounds, except 12, were isolated for the first time from this plant. Compounds 2, 3 and 11 have shown a considerable DPPH radical scavenging activity. Structures of these compounds were identified on the basis of spectroscopic techniques, including 2D NMR. Compounds 3, 5 and 7 were also subjected to single-crystal X-ray diffraction analysis and their structures were unambiguously deduced.


Structure-toxicity relationships, toxicity mechanisms and health risk assessment of food-borne modified deoxynivalenol and zearalenone: A comprehensive review.
Mycotoxin, as one of the most common pollutants in foodstuffs, poses great threat to food security and human health. Specifically, deoxynivalenol (DON) and zearalenone (ZEN)-two mycotoxin contaminants with considerable toxicity widely existing in food products-have aroused broad public concerns. Adding to this picture, modified forms of DON and ZEN, have emerged as another potential environmental and health threat, owing to their higher re-transformation rate into parent mycotoxins inducing accumulation of mycotoxin in humans and animals. Given this, a better understanding of the toxicity of modified mycotoxins is urgently needed. Moreover, the lack of toxicity data means a proper risk assessment of modified mycotoxins remains challenging. To better evaluate the toxicity of modified DON and ZEN, we have reviewed the relationship between their structures and toxicities. The toxicity mechanisms behind modified DON and ZEN have also been discussed; briefly, these involve acute, subacute, chronic, and combined toxicities. In addition, this review also addresses the global occurrence of modified DON and ZEN, and summarizes novel methods-including in silico analysis and implementation of relative potency factors-for risk assessment of modified DON and ZEN. Finally, the health risk assessment of modified DON and ZEN has also been discussed comprehensively.


Aldosterone metabolites and possible aldosterone precursors in hypertension.
The value of the urine tests: free aldosterone, aldosterone-18-glucuronide, tetrahydroaldosterone 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone in distinguishing primary aldosteronism from essential hypertension was studied in patients with typical and atypical primary aldosteronism and in patients with essential hypertension. The discriminating function of the tetrahydroaldosterone determination was the best, followed by 18-hydroxycorticosterone, free aldosterone and aldosterone-18-glucuronide. The measurement of 18-hydroxydeoxycorticosterone was without distinguishing value. Three cases with hypertension, adrenal adenoma, elevated 18-hydroxycorticosterone but normal aldosterone values were observed. In longitudinal studies the excretions of aldosterone, aldosterone metabolites and possible precursors periodically varied independently of each other. Determinations of urine aldosterone, aldosterone metabolites, 18-hydroxycorticosterone and 18-hydroxydeoxycorticosterone were not applicable for differential diagnosis of the adenoma and hyperplasia forms of primary aldosteronism.


Facile Synthesis of 2-Methylnicotinonitrile through Degenerate Ring Transformation of Pyridinium Salts.
Nucleophilic recyclization of pyridinium salts involving a CCN interchange ring transformation for the synthesis of 2-methylnicotinonitrile derivatives was herein developed. 3-Aminocrotononitrile (3-ACN) produced in situ from CH3CN acted as a C-nucleophile, as well as the source of CH3 and CN groups, which was supported by isotope-labeling and control experiments.


Cilia Train Spotting.
Cilium formation depends on intraflagellar transport trains that move bidirectionally along ciliary microtubules. Reporting in Science, Stepanek and Pigino (2016) employ correlative light and electron microscopy in algae to determine the ultrastructure of anterograde and retrograde trains and discover that these trains avoid collision by running on B- and A-tubules, respectively.


Effectiveness and predictability of titanium-prepared platelet-rich fibrin for the management of multiple gingival recessions.
Titanium-prepared platelet-rich fibrin (T-PRF) is activated with titanium, which results in a more mature and aggregated form than PRF. In our previous studies, we established that the fibrin carpet formed with titanium had a firmer network structure, and longer resorption time in the tissue than the fibrin carpet formed with glass. The purpose of this randomized controlled clinical trial is to compare the effects of autogenous T-PRF and connective tissue graft (CTG). A total of 114 Miller Class I/II gingival recessions with abrasion defects were treated either T-PRF (63 teeth) or CTG (51 teeth) using a modified tunnel technique. Clinical periodontal indexes, keratinized tissue (KTW), gingival thickness, and recession depth were recorded before surgery and at 6- and 12-month follow-up examinations. The visual analog scale and healing index scores were assessed. The mean root coverages were 93.29 and 93.22% in the T-PRF and CTG groups, respectively, at 12 months post-operatively. CTG resulted in greater gingival thickness than T-PRF at 6 and 12 months post-surgery compared to baseline. Furthermore, the mean amounts of KTW increased by 1.97 and 0.75 mm in the T-PRF and CTG groups, respectively. Within the limits of this study, the results demonstrated that T-PRF is safe and effective for treatment of multiple Miller Class I/II gingival recession defects. T-PRF can serve as a good autogenous alternative to CTG, which is the gold standard for root coverage.


The role of IL-8 in the SDF-1α/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma.
Stromal cell-derived factor-1 (SDF-1) (CXCL12) has been observed to promote laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) invasion through cooperation with its receptor CXCR4. Here, we further explore the angiogenesis mechanism induced by SDF-1/CXCR4 interaction in LHSCCs. Immunohistochemistry (IHC) reveals the significant correlation between CXCR4 and angiogenesis in tumors. After blocking the function of CXCR4 by specific inhibitor AMD3100 and neutralized antibody 12G5 or inhibiting the expression by siRNA, we were able to disrupt the HUVECs tube formation, demonstrating that SDF-1/CXCR4 indeed regulated the angiogenesis mechanism. The angiogenesis profiling from angiogenesis array and reverse transcription polymerase chain reaction indicates that IL-8 can be significantly triggered by SDF-1/CXCR4 interaction in LHSCCs. We also demonstrate that IL-8 secretion mechanism is regulated by Akt phosphorylation after SDF-1 stimulation. These results point out the importance of SDF-1/CXCR4 interaction in LHSCCs angiogenesis. The angiogenic factor IL-8 would be triggered by the cooperation of SDF-1 and CXCR4 through an Akt-dependent pathway. This provides a new targeting therapy utility, disrupting SDF-1/CXCR4 interaction combined with downstream-induced angiogenic factors in LHSCCs would be beneficial to improve clinical outcome.


Terpenoids as Human Neutrophil Elastase (HNE) Inhibitors: A Comprehensive Review of Natural Anti-inflammatory Isoprenoids.
Human neutrophil elastase (HNE) is an enzyme that plays a key role in the body's inflammatory response. It has been linked to several diseases such as chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. As potential treatments for these diseases, HNE inhibitors are of great interest. Metabolites derived from plants, particularly terpenoids such as β-caryophyllene found in black pepper and other plants, and geraniol present in several essential oils, are recognized as significant sources of inhibitors for HNE. Because of their ability to inhibit HNE, terpenoids are considered promising candidates for developing novel therapies to treat inflammatory conditions such as COPD and emphysema. Furthermore, nature can serve as an excellent designer, and it may offer a safer drug candidate for inhibiting HNE production and activity in the future. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were searched to get relevant and up-to-date literature on terpenoids as human neutrophil elastase inhibitors. This review focuses on the isolation, chemical diversity, and inhibition of human neutrophil elastase (HNE) of various terpenoids reported from natural sources up to 2022. A total of 251 compounds from various terpenoids classes have been reported. Further, it also provides a summary of HNE inhibitors and includes a thorough discussion on the structure-activity relationship.


Decomposition characteristics of indigenous organic fertilisers and introduced quick compost and their short-term nitrogen availability in the semi-arid Ethiopian Rift Valley.
Case studies on the assessment of local organic fertilisers (OFs) in their quality (decomposition characteristics and nutrient availability for crops) are few in sub-Saharan Africa (SSA). This study assessed the quality of local OFs from the Ethiopian Rift Valley. The decomposition characteristics were assessed by acid detergent fibre analysis methods, while the short-term nitrogen availability was assessed by a combination of laboratory incubations and inorganic nitrogen and acid detergent soluble nitrogen determinations. A commercial hand-held reflectometer (RQFlex) was used for determining nitrogen components. The mean acid detergent soluble organic matter contents exceeded 250 mg g-1, indicating the OF feedstock contained much of the readily decomposable organic matter. Some of the indigenous compost (kosi) samples showed net nitrogen immobilisation during the initial period of incubation, followed by net nitrogen mineralisation in one month of incubation with 4% of the nitrogen mineralisation rate. Kosi should be applied to a field one month before seeding. Short-term nitrogen availability from kosi was too low to substitute for inorganic fertilisers. The combination of the simple analysis methods shown in this study is a quick, cost-saving, and accurate quality assessment approach for OFs, which can be useful in the field and at experimental stations in SSA.


Are all stem cells equal? Systematic review, evidence map, and meta-analyses of preclinical stem cell-based therapies for bronchopulmonary dysplasia.
Regenerative stem cell-based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta-analysis (NMA) of preclinical studies testing cell-based therapies in experimental neonatal lung injury. Fifty-three studies assessing 15 different cell-based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell-based therapies has been assessed, few head-to-head comparisons and unclear risk of bias exists. Successful clinical translation of cell-based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting.


Trochanteric osteotomy: analysis of pattern of wire fixation failure and complications.
Problems and complications following trochanteric osteotomy in 277 total hip replacements demonstrated that while the value of trochanteric osteotomy is obvious, the incidence of problems and complications in 277 total hip replacements was about 15%. Analysis was made of the location and sequence of wire failure following different techniques of trochanteric wiring. The usual method of wire failure was by fatigue fracture, although early fracture in the post-operative phase may be secondary to tensile failure, The incidence of wire tensile failure can be increased by inadvertent kinking or scoring of the wire during trochanteric fixation. An ununited trochanter should be protected against wire failure and its sequelae.


Influence of Escherichia coli infection on intestinal mucosal barrier integrity of germ-free piglets.
We focused on investigating the influence of Escherichia coli (E. coli) on the intestinal barrier. We studied changes in the distribution and secretory activities of goblet cells and enteroendocrine cells (EECs), as well as changes in the population of mast cells (MCs) in the jejunal and colonic mucosa of germ-free (GF) piglets as a healthy control group and GF piglets whose intestines were colonised with E. coli bacteria on day 5. The results suggest that the colon of GF piglets is more resistant and less prone to coliform bacterial infection compared to the jejunum. This can be confirmed by a lower degree of histopathological injury index as well as an improvement of the morphometric parameters of the colonic mucosa, together with a significantly increased (p < 0.05) expression of MUC1/EMA, and ZO-3. We also observed a significant decrease in the population of activated MCs (p < 0.001) and EECs (p < 0.001). These findings may indicate a rapid response and better preparation of the intestinal barrier for possible pathological attacks and the subsequent development of mucosal lesions during the development and progression of the intestinal diseases. To date, gut-targeted therapeutic approaches that can modulate bacterial translocation and chronic inflammation are still in their infancy but represent one of the most promising areas of research for the development of new effective treatments or clinical strategies in the future. Therefore, a better understanding of these processes can significantly contribute to the development of these targeted strategies for disease prevention and treatment.


Self-aggregates of 3,6-O,O'-dimyristoylchitosan derivative are effective in enhancing the solubility and intestinal permeability of camptothecin.
The aim of this work was to investigate the potential of a new 3,6-O,O'-dimyristoyl derivative amphiphilic chitosan (DMCh), in improving the solubility of camptothecin (CPT), a hydrophobic anticancer drug, and its potential oral delivery. FTIR, 1H NMR and solid-state 13C NMR spectroscopy were used to characterize DMCh and to determine its average degree of substitution (DS¯=6.8%). DMCh/CPT micelles size ranged from (281-357nm), zeta potential (+32-50mV) of encapsulation efficiency of 42-100%. The in vitro cell viability showed that DMCh/CPT micelles were able to reduce the toxicity of CPT. The in vitro permeability of CPT through Caco-2 and Caco-2/HT29-MTX intestinal models was increased up to ten fold when formulated into DMCh micelles, underlining the mucoadhesive properties of the nanocarrier. DMCh/CPT micelles are able to enhance CPT solubility and bioavailability while reduce its cytotoxicity, showing the great potential for intestinal delivery of hydrophobic drugs.


Release of human neurophysin I during insulin-induced hypoglycemia in depressed patients is abolished after recovery with clomipramine treatment.
Release of human neurophysin I (hNp I) and neurophysin II (hNp II) during insulin-induced hypoglycemia was studied in 10 unipolar depressed women before and after 4-5 weeks of standard antidepressant drug treatment with daily intravenous infusions of clomipramine. Before treatment, a significant increase of hNp I but not of hNp II serum levels in response to hypoglycemia was observed. At retest during clomipramine administration, a marked clinical amelioration occurred in all patients as determined with the Hamilton Rating Scale for Depression; the hNp I response to insulin was abolished, but no effect on hNp II concentration could be demonstrated. No correlation was found between the degree of the depression score decrease and the amplitude of the inhibition of hNp I release or serum levels of clomipramine or its metabolite, desmethylclomipramine. The meaning of this difference in reactivity of the neurohypophyseal system in the course of depressive illness, based on the pharmacological and biochemical profiles of clomipramine action, is discussed.


Renal function in infants with hyperbilirubinemia.
A total of 45 infants were studied on the fourth or fifth day of life: 13 term and 10 pre-term infants with serum bilirubin levels ranging between 257 and 390 mumol/l were compared with 12 term and 10 pre-term infants with serum bilirubin levels below 195 mumol/l. The groups did not differ with regard to mean gestational age or mean post-natal age. GFR and CPAH were determined with the single injection clearance method and ability to excrete Na+ was determined following an oral loading of sodium chloride. GFR was lower in infants with hyperbilirubinemia and correlated negatively to the highest recorded serum bilirubin value. CPAH was similar in hyperbilirubinemic infants and controls. The urinary sodium excretion was significantly higher in infants with hyperbilirubinemia.


Understanding Vietnam's drug policy for amphetamine-type stimulants misuse.
The emergence of widespread amphetamine-type stimulants (ATSs) usage has created significant challenges for drug control and treatment policies in Southeast Asian countries. This study analyses the development of drug policies and examines current treatment program constraints in Vietnam to deal with ATS misuse. The aim was to gain insights that may be useful for national and international drug-related policy development and revision. A desk review of national policy documents and 22 in-depth key informant interviews were conducted from 2019 to 2021. Thematic content analysis was employed to identify key themes and their connections. Analysis identified Vietnam's 30-year history of developing policies and formulating strategies to reduce supply, demand, and harm from illicit drugs. With the increasing number of people who use ATS (PWUA), Vietnam has recently promoted harsh policy and law enforcement to deter drug use and supply. This policy trend prevails in many Asian countries. The three main constraints in dealing with ATS misuse emerged from punitive and restrictive drug policies. First, the general public believed that Centre-based compulsory treatment (CCT) is the only appropriate treatment for all types of illicit drug addiction despite its low-quality service provision. The rigid drug policy has led to social persuasion with impractical expectations for CCT effectiveness. Second, the emphasis on punishment and detention has hampered new drug treatment service development in Vietnam. CCT has become monopolistic in the context of impoverished services. Third, people who use drugs tend to hide their needs and avoid formal treatment and support services, resulting in declined social coherence. While new drugs are constantly evolving, the current law enforcement approach potentially constrains expertise to adopt effective treatment services. This study suggests that the top-down policing mechanism presently hinders the development of an appropriate intervention strategy for ATS misuse and diminishes social support to service providers.


Selective Arsenic Removal from Groundwaters Using Redox-Active Polyvinylferrocene-Functionalized Electrodes: Role of Oxygen.
In this work, we investigate selective sorption of arsenic from simulated groundwaters at pH 8 by a redox-active polyvinylferrocene (PVF)-functionalized electrode using a modified double potential step chronoamperometry (DPSC) method. Our results show that effective and sustainable As(III) removal can be achieved at 0 V once the electrode is activated via anodic polarization. During activation, ferrocene (Fc) in PVF is oxidized to the ferrocenium ion (Fc+) with the latter facilitating As(III) sorption and subsequent oxidation as well as As(V) sorption. The high affinity of Fc+ to As and weak attraction to competing anions at 0 V ensure high selectivity of As over Cl-, SO42-, and NO3- at concentrations typical of groundwaters. Following the removal process, efficient regeneration of the electrode is achieved at -1.2 V wherein Fc+ is reduced to Fc thereby facilitating As desorption from the electrode surface. Our results further show that O2 and associated generation of hydrogen peroxide during the regeneration step drive the oxidation of Fc to Fc+, thereby maintaining the constant generation of Fc+ required to achieve As(III) removal in subsequent cycles. Our results show that 91.8 ± 0.6% of As(III) could be selectively removed from simulated groundwater over 10 cycles at an ultralow energy consumption of 0.12 kWh m-3.


Characterization and functional analysis of fibrinogen-related protein (FreP) in the black tiger shrimp, Penaeus monodon.
Ficolin is classified as an immune related protein containing collagen-like and fibrinogen-related domain (FreD). In invertebrates, the functions of fibrinogen-related proteins (FrePs) are of importance to innate immunity. In this study, a FreP in the black tiger shrimp Penaeus monodon was identified and characterized. The PmFreP cDNA is 1,007 bp long with a 921 bp-open reading frame that encodes for 306 amino acids. The deduced PmFreP sequence consists of a signal peptide, an unknown region and the FreD. Phylogenetic analysis showed that PmFreP was clustered with fibrinogen-like proteins in crustaceans which was separated from vertebrate ficolin-like proteins. The deduced fibrinogen-like domain contains four conserved cysteine residues (Cys96, Cys127, Cys249, and Cys262) that are responsible for the formation of disulfide bridges. Gene expression analysis shows that Pmfrep is mainly expressed in the intestine and the expression is significantly upregulated after Vibrio harveyi and white spot syndrome virus (WSSV) challenge. Recombinant PmFreP (rPmFreP) were successfully expressed and purified, and forms a trimeric structure as judged by native-PAGE. Bacterial binding assay showed that the rPmFreD can bind and agglutinate Gram-negative and Gram-positive bacteria in the presence of calcium (Ca2+) ions. Moreover, the rPmFreP facilitates the clearance of V. harveyi in vivo. Overall, our results suggested that the PmFreP may serve as pattern recognition receptors implicated in shrimp innate immunity.


Material and biofilm load of K wires in toe surgery: titanium versus stainless steel.
Recurrence rates for toe deformity correction are high and primarily are attributable to scar contractures. These contractures may result from subclinical infection. We hypothesized that (1) recurrence of toe deformities and residual pain are related to low-grade infections from biofilm formation on percutaneous K wires, (2) biofilm formation is lower on titanium (Ti) K wires compared with stainless steel (SS) K wires, and (3) clinical outcome is superior with the use of Ti K wires compared with SS K wires. In this prospective nonrandomized, comparative study, we investigated 135 lesser toe deformities (61 patients; 49 women; mean ± SD age, 60 ± 15 years) temporarily fixed with K wires between August 2010 and March 2011 (81 SS, 54 Ti). K wires were removed after 6 weeks. The presence of biofilm-related infections was analyzed by sonication. High bacterial loads (> 500 colony-forming units [CFU]/mL) were detected on all six toes requiring revision before 6 months. Increased bacterial load was associated with pain and swelling but not recurrence of the deformity. More SS K wires had greater than 100 CFU/mL bacteria than Ti K wires. For K wires with a bacterial count greater than 100 CFU/mL, toes with Ti K wires had a lower recurrence rate, less pain, and less swelling than toes with SS K wires. Ti K wires showed superior clinical outcomes to SS K wires. This appears to be attributable to reduced infection rates. Although additional study is needed, we currently recommend the use of Ti K wires for the transfixation of toe deformities. Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Specific production of eosinophil colony stimulating factor from sensitized T cells from a patient with allergic eosinophilia.
To explore the possibility that an eosinophil colony stimulating factor (EO-CSF) is elaborated independently of neutrophil CSF (N-CSF), we compared the effect on the production of EO-CSF and N-CSF of adding a specific antigen, an aspergillus extract, to peripheral blood leucocytes of an eosinophilic patient with allergic bronchopulmonary aspergillosis. Conditioned media prepared from the patient's mononuclear (MN) and T cells were assayed for EO-CSF and N-CSF activities by agar culture technique, using normal human nonphagocytic MN bone marrow cells as target cells. The addition of the specific antigen to the cultures of the patient's MN or T cells significantly stimulated the production of EO-CSF, but not that of N-CSF, while the patient's non-T cells and normal MN or T cells were not stimulated by the antigen challenge to produce either CSF. These results suggest that EO-CSF is a factor distinct from N-CSF, that its production is dependent on the presence of sensitized T cells with antigen-specific stimulation, and that it might be one of the causes of blood eosinophilia in this patient.


Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters.
To investigate the correlation between estrogen receptor-positive basal cells of the meibomian glands of the lower lid with age, gender, and subjective and objective dry-eye parameters. Sixteen lower lid specimens were collected from 7 female and 9 male patients (age range 22-88 years) during tumor surgery requiring whole-thickness excision. Prior to surgery the patients were asked about any dry-eye symptoms (score 0-4, where 0=no dry-eye symptoms). Tear break-up time was measured, and Schirmer I and II tests were performed. We obtained histological sections from the outer margins of the formalin-fixed and paraffin-embedded specimens and performed immunohistochemical staining for estrogen, progesterone and androgen receptors. At least 500 cells were counted per specimen, and the proportion of positively stained cells was calculated and correlated to the age and dry-eye parameters. All meibomian glands had positive nuclear staining with antibodies for estrogen receptors in their outer cell layers, i.e., the basal cell layer. The proportion of cells expressing estrogen receptors increased with age independent of gender (correlation coefficient=0.67, P<0.005). No correlation was found between estrogen receptor positivity and subjective dry-eye symptoms, tear break-up time, or Schirmer I and II test results. There was no difference in the proportion of cells expressing estrogen receptors between female and male patients (P=0.5). The amount of meibomian gland cells expressing estrogen receptors in the lower lid seems to increase with age independent of gender and seems not to affect the fat layer and stability of the tear film.


Prediction of shape diameter undergoing coil embolization of saccular intracranial aneurysm treatment using a hybrid decision support system.
The purpose of the study was to design a hybrid decision support system (HDSS) that could simulate the embolized coil selection pattern of the radiologists in aneurysms treatment. As the longest available length of the coils should be used in most cases, therefore only the shape diameter (SD) selection was modeled and varied. Ninety-eight aneurysms successfully treated by a radiologist with coil embolization were divided into two groups (86 for training and 12 randomly selected for validating). Eight aneurysms treated by another radiologist were also used to cross validate the proposed HDSS. The HDSS was developed using the classification and the linear regression methods (LRM). The dome and the width of an aneurysm were used as the system inputs. The system outputs were the SDs of the first three coils indexed according to the insertion order. The HDSS that consisted of Bagging classification and LRM achieved the highest accuracy for all cases. The errors were within 1 mm for the SD selection of the first two coils. For the third coil, the SD selection within 1 mm bound had 80 % accuracy. The experimental results indicated the feasibility of using the HDSS as the guidance for selecting the SDs of the first two coils. The selection of the third coil required more training data for the rarely used SD. Moreover, the cross validation with another radiologist showed the feasibility of using the proposed HDSS as the guidance, however further validation with more data is recommended.


Apoptotic and survival signaling mediated through death receptor members during metamorphosis in the African clawed frog Xenopus laevis.
The tumor necrosis factor (TNF) superfamily includes death receptor (DR) ligands, such as TNF-α, FasL, and TRAIL. Death receptors (DRs) induce intracellular signaling upon engagement of their cognate DR ligands, either leading to apoptosis, survival, or proinflammatory responses. The DR signaling is mediated by the recruitment of several death domain (DD)-containing molecules such as Fas-associated death domain (FADD) and receptor-interacting protein (RIP) 1. In this review, we describe DR signaling in mammals, and describe recent findings of DR signaling during metamorphosis in the African clawed frog Xenopus laevis. Specifically, we focus on the cell fate (apoptosis or survival) mediated through a DR ligand, TNF-α or TRAIL in endothelial cells or red blood cells (RBCs). In addition, we discuss relationships between thyroid hormone-induced metamorphosis and DR signaling.


Induction of protein catabolism in myotubes by 15(S)-hydroxyeicosatetraenoic acid through increased expression of the ubiquitin-proteasome pathway.
The potential role of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) as an intracellular signal for increased protein catabolism and induction of the expression of key components of the ubiquitin-proteasome proteolytic pathway induced by a tumour cachectic factor, proteolysis-inducing factor has been studied in murine C(2)C(12) myotubes. 15(S)-HETE induced protein degradation in these cells with a maximal effect at concentrations between 78 and 312 nM. The effect was attenuated by the polyunsaturated fatty acid, eicosapentaenoic acid (EPA). There was an increase in 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the proteasome, in the same concentration range as that inducing total protein degradation, and this effect was also attenuated by EPA. 15(S)-hydroxyeicosatetraenoic acid also increased maximal expression of mRNA for proteasome subunits C2 and C5, as well as the ubiquitin-conjugating enzyme, E2(14k), after 4 h incubation, as determined by quantitative competitive RT-PCR. The concentrations of 15-HETE affecting gene expression were the same as those inducing protein degradation. Western blotting of cellular supernatants of myotubes treated with 15(S)-HETE for 24 h showed increased expression of p42, an ATPase subunit of the regulatory complex at similar concentrations, as well as a decrease in expression of myosin in the same concentration range. 15(S)-hydroxyeicosatetraenoic acid activated binding of nuclear factor-kappaB (NF-kappaB) in the myotube nucleus and stimulated degradation of I-kappaBalpha. The effect on the NF-kappaB/I-kappaBalpha system was attenuated by EPA. In addition, the NF-kappaB inhibitor peptide SN50 attenuated the increased chymotrypsin-like enzyme activity in the presence of 15(S)-HETE. These results suggest that 15(S)-HETE induces degradation of myofibrillar proteins in differentiated myotubes through an induction of an increased expression of the regulatory components of the ubiquitin-proteasome proteolytic pathway possibly through the intervention of the nuclear transcription factor NF-kappaB, and that this process is inhibited by EPA.