Spectroscopic characterization of dipicolinic acid and its photoproducts as thymine photosensitizers.
Dipicolinic acid (DPA), present in large amount in bacterial spores, has been proposed to act as an endogenous photosensitizer in spore photoproduct formation. The proposed mechanism involves a triplet-triplet energy transfer from DPA to thymine. However, up to now, no spectroscopic studies have been performed to determine the interaction between the endogenous compound and the nucleobase, probably due to its photolability in aqueous solutions. Here, triplet excited state properties of DPA are reported together with its bimolecular quenching rate constant by thymidine, kq of ca. 5.3 × 109 M-1 s-1. To run more reliable studies, a stable methyl ester derivative of DPA, which exhibits the same spectroscopic properties as the parent compound, is also described. Finally, DPA photoproducts are characterized. Studies of their triplet excited state properties have demonstrated that, interestingly, one of them is able to photosensitize thymidine triplet excited state formation.


ATYPICAL MACULOPATHY IN A PATIENT WITH LIGHT CHAIN DEPOSITION DISEASE MIMICKING ADVANCED GEOGRAPHIC ATROPHY.
To report a previously unreported presentation of advanced geographic atrophy of the macula mimicking nonneovascular (dry) age-related macular degeneration in a patient with light chain deposition disease. Ocular examination included dilated fundus examination, fundus autofluorescence, full-field electroretinography, and spectral domain optical coherence tomography. Single-patient case report. Dilated fundus examination demonstrated diffuse loss of the retinal pigment epithelium in a geographic atrophy pattern in the macula and drusenlike deposits localized to the outer retina and retinal pigment epithelium. There were no signs of choroidal neovascularization or retinal pigment epithelium detachments. Fundus autofluorescence demonstrated wide areas of retinal pigment epithelium loss. Full-field electroretinography was normal. Spectral domain optical coherence tomography displayed atrophy of the outer retinal layers. This is the first documented case of drusenlike deposits and maculopathy in a patient with light chain deposition disease that mimics advanced geographic atrophy that is typically observed in nonneovascular age-related macular degeneration. Physicians should be aware of the macular changes that can be associated with light chain deposition disease, and patients with light chain deposition disease should be regularly evaluated for associated macular disease.


Carbon monoxide and flash evoked potentials from rat cortex and superior colliculus.
In view of the conflict between qualitative reports that flash evoked potentials from superior colliculus (SC) and visual cortex (VC) of rats are uniquely sensitive to low levels of carbon monoxide (CO), and a more quantitative report that the visual cortex evoked potential is not sensitive to low levels of CO, the present report documents the effects of different concentrations of CO upon flash evoked potentials from these areas. The amplitude of the P3-N4 component from the SC evoked potential demonstrated the best dose/effect relationship, increasing up to levels of 38% carboxyhemoglobin (COHb). Latencies were affected only when COHb levels reached 55%. The use of the visual system to determine effects of toxic agents upon the central nervous system in discussed.


Distributions of occupied and vacant butterfly habitats in fragmented landscapes.
We found several rare UK butterflies to be restricted to relatively large and non-isolated habitat patches, while small patches and those that are isolated from population sources remain vacant. These patterns of occurrence are generated by the dynamic processes of local extinction and colonization. Habitat patches act as terrestrial archipelagos in which long-term population persistence, and hence effective long-term conservation, rely on networks of suitable habitats, sufficiently close to allow natural dispersal.


[A patient with an unclassifiable form of neuroaxonal dystrophy].
The authors describe the clinical history of a boy with progressive neurological abnormalities from the age of nine months. After death at the age of four years, histopathological examination demonstrated an unknown form of infantile neuro-axonal dystrophy.


Binding of thromboxane A2/prostaglandin H2 agonists to human platelets.
The competition of [125I]-9, 11 dimethylmethano-11, 12 methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza 15 alpha beta-omega-tetranor-thromboxane A2 ([125I]-PTA-OH), a thromboxane A2/prostaglandin H2 receptor antagonist, with a series of thromboxane A2/prostaglandin H2 (TXA2/PGH2) mimetics for binding to the putative TXA2/PGH2 receptor in washed human platelets was studied. The rank order potency for the series of mimetics to compete with [125I]-PTA-OH for binding was compared with their rank order potency for induction of platelet aggregation. The rank order potency for the mimetics to compete with [125I]-PTA-OH for binding was ONO-11113 greater than SQ-26655 greater than U44069 greater than U46619 = 9, 11-azo PGH2 greater than MB28767. This rank order potency was highly correlated with their rank order potency for inducing platelet aggregation (r = 0.992). Changes in the intra or extracellular concentrations of Na+ did not have a significant effect on the competition between U46619 and [125I]-PTA-OH for binding to the putative receptor. In summary, it appears that these TXA2/PGH2 mimetics activate human platelets through the putative TXA2/PGH2 receptor.


Link of dietary patterns with metabolic syndrome: analysis of the National Health and Nutrition Examination Survey.
Population-based interventions aimed at halting the increasing prevalence of metabolic syndrome (MetS) require thorough understanding of dietary interplays. Objective is to identify the independent dietary nutrients associated with MetS and its components using dietary pattern identification and the single-nutrient approaches in The United States. This is a cross-sectional observation. Participants are selected from the National Health and Nutrition Examination Survey (NHANES) with available dietary intake, biochemical and anthropometrical data from 2001 to 2012. Exposure is diet obtained from 24-h dietary recall. Main outcome measure is MetS and its components. Overall, 23 157 eligible individuals including 6561 with MetS were included in the final analysis. Using principle component analysis, we identified three food patterns that explained 50.8% of the variance of the dietary nutrient consumption. The highest quartile of the factor score representative of saturated/monounsaturated fatty acids or the first dietary pattern was associated with 1.27-fold (95% confidence interval (CI): 1.10-1.46, P=0.001) higher odds of association with MetS when compared with the first quartile. The second pattern representative of vitamins and trace elements had an odds ratio of 0.79 (95% CI: 0.70-0.89, P<0.001) for association with MetS, and the third pattern representative of polyunsaturated fatty acids did not have any association with MetS. The nutrient-by-nutrient approach showed that mild alcohol intake and lower consumption of total saturated fatty acids and sodium were associated with lower risk of MetS. Application of multiple complementary analytic approaches reveals more comprehensive dietary determinants of MetS and its components as potential intervening targets.


Enhancing thermostability of Escherichia coli phytase AppA2 by error-prone PCR.
Phytases are used to improve phosphorus nutrition of food animals and reduce their phosphorus excretion to the environment. Due to favorable properties, Escherichia coli AppA2 phytase is of particular interest for biotechnological applications. Directed evolution was applied in the present study to improve AppA2 phytase thermostability for lowering its heat inactivation during feed pelleting (60-80 degrees C). After a mutant library of AppA2 was generated by error-prone polymerase chain reaction, variants were expressed initially in Saccharomyces cerevisiae for screening and then in Pichia pastoris for characterizing thermostability. Compared with the wild-type enzyme, two variants (K46E and K65E/K97M/S209G) showed over 20% improvement in thermostability (80 degrees C for 10 min), and 6-7 degrees C increases in melting temperatures (T (m)). Structural predictions suggest that substitutions of K46E and K65E might introduce additional hydrogen bonds with adjacent residues, improving the enzyme thermostability by stabilizing local interactions. Overall catalytic efficiency (k (cat) / K (m)) of K46E and K65E/K97M/S209G was improved by 56% and 152% than that of wild type at pH 3.5, respectively. Thus, the catalytic efficiency of these enzymes was not inversely related to their thermostability.


A review on the mitochondrial toxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA).
3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a drug of abuse used by millions worldwide. MDMA human abuse and dependence is well described, but addictive properties are not always consistent among studies. This amphetamine is a substrate type releaser, binding to monoamine transporters, leading to a pronounced release of serotonin and noradrenaline and to a minor extent dopamine. The toxicity of MDMA is well studied at the pre-clinical level, with neurotoxicity and hepatotoxicity being particularly described. In this review, we describe the most relevant MDMA effects at the mitochondrial level found in in vitro and in vivo models, these later conducted in mice and rats. Most of these reports focus on the mitochondria of brain or liver. In in vitro models, MDMA causes depletion of ATP levels and inhibition of mitochondrial complex I and III, loss in mitochondrial membrane potential (ΔΨm) and induction of mitochondrial permeability transition. The involvement of mitochondria in the apoptotic cell death evoked by MDMA has also been shown, such as the release of cytochrome c. Additionally, MDMA or its metabolites impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria. In animal studies, MDMA decreased mitochondrial complex I activity and decreased ATP levels. Moreover, MDMA-evoked oxidative stress has been shown to cause deletion on mitochondrial DNA and impairment in mitochondrial protein synthesis. Although the concentrations and doses used in some studies do not always correlate to the human scenario, the mitochondrial abnormalities evoked by MDMA are well described and are in part responsible for its mechanism of toxicity.


Epidermoid inclusion cysts After APTOS thread insertion: case report with clinicopathologic correlates.
The APTOS threading procedure is a relatively new method in antifacial ptosis surgery. The reported cases present a small percentage of minor complications. A 57-year-old woman experienced scarring after APTOS threading. Scar biopsy showed an epidermoid inclusion cyst. Epidermoid inclusion cysts are a potential complication of APTOS threading. Proper surgical technique may reduce their likelihood.


Visual outcome and prognostic factors in cataract surgery in ocular tuberculosis.
To analyze the outcome of cataract surgery in patients with ocular tuberculosis (OTB). Medical records of patients with OTB who underwent cataract surgery between 2005 and 2018 were retrospectively reviewed. The primary outcome measure was corrected distant visual acuity (CDVA), and a good outcome was defined as CDVA 20/40 or better. There were 35 patients (41 eyes), of whom 13 (37.1%) were males and 22 (62.9%) were females. The mean age was 41.6 ± 13.8 (range 18-65) years. Anterior uveitis was present in 24 (58.5%) eyes, intermediate uveitis in 5 (12.2%) eyes, posterior uveitis in 6 (14.6%) eyes, and panuveitis in 6 (14.6%) eyes. Posterior sub-capsular cataract (51.2%) was the most common type of cataract. Total cataract was present in 9 (22%) eyes. The two most common ocular comorbidities were small pupil (85.4%) and glaucoma (17.1%). Phacoemulsification was performed in 36 (87.8%) eyes and ECCE was performed in 5 (12.2%) eyes. Intraoperatively the pupil was mechanically dilated in 36 (87.8%) eyes. Overall 26 (63.4%) and 23 (56.1%) eyes achieved CDVA 20/40 or better at 1- and 6-month follow-up visit, respectively. The mean preoperative LogMAR CDVA significantly improved from 1.28 ± 0.57 to 0.38 ± 0.36 at 1-month (P < 0.0001). One eye had fibrinous anterior chamber reaction and 24 (58.5%) eyes had 1 or more episodes of reactivation of uveitis in the follow-up period. The three commonest complications were glaucoma (26.8%), posterior capsule opacification (19.5%), and epiretinal membrane (17.1%). Postoperative posterior segment complications like epiretinal membrane formation, vitreous inflammation and cystoid macular edema affected final visual acuity (P < 0.002). The visual outcome after cataract surgery in OTB was satisfactory as significant number of patients achieved a good final visual acuity.


Magnetic biochar/quaternary phosphonium salt reduced antibiotic resistome and pathobiome on pakchoi leaves.
Antibiotic resistance genes (ARGs) and human pathogenic bacteria (HPB) in leafy vegetable is a matter of concern as they can be transferred from soil, atmosphere, and foliar sprays, and poses a potential risk to public health. While traditional disinfection technologies are effective in reducing the presence of ARGs and HPB in soil. A new technology, foliar spraying with magnetic biochar/quaternary ammonium salt (MBQ), was demonstrated and applied to the leaf surface. High-throughput quantitative PCR targeting 96 valid ARGs and 16 S rRNA sequencing were used to assess its efficacy in reducing ARGs and HPB. The results showed that spraying MBQ reduced 97.0 ± 0.81% of "high-risk ARGs", associated with seven classes of antibiotic resistance in pakchoi leaves within two weeks. Water washing could further reduce "high-risk ARGs" from pakchoi leaves by 19.8%- 24.6%. The relative abundance of HPB closely related to numerous ARGs was reduced by 15.2 ± 0.23% with MBQ application. Overall, this study identified the potential risk of ARGs from leafy vegetables and clarified the significant implications of MBQ application for human health as it offers a promising strategy for reducing ARGs and HPB in leafy vegetables.


The Comparison of Iodine-Type and MnO2-Type Oxidation for Measuring the Levels of Urine Neopterin and Biopterin in Patients with Hyperphenylalaninemia: A Descriptive-Analytic Study in Iran.
Fresh urine sample is required for measurement of pterins in patients with hyperphenylalaninemia (HPA) for detection of tetrahydrobiopterin (BH4) coenzyme deficiency. The present study aimed to measure the levels of neopterin and biopterin in the urine of patients with HPA using manganese dioxide (MnO2) and iodine oxidation methods. The levels of neopterin and biopterin in the urine of 124 patients were measured using two methods of oxidation (MnO2 and iodine) and the results were statistically analyzed using correlation test, Roc-Curve and ANOVA in SPSS-20 software. The level of significant was determined to be P > 0.05. Patients age mean ± SD = 4.96 year, neopterin and biopterin mean ± SD in 124 patients were 2.75 mmol/molcr and 2.49 mmol/molcr. Correlation regression between two methods (iodine and MnO2 oxidation) was 0.99. There was no significant difference between the two oxidation methods (P > 0.05). The results of this study showed that MnO2 oxidation can be a suitable alternative method instead of iodine oxidation for measurement of urine neopterin, biopterin and diagnosis of BH4 deficiency.


Incidence, risk factors and outcome of barotrauma in mechanically ventilated patients.
To determine the incidence, risk factors, and outcome of barotrauma in a cohort of mechanically ventilated patients where limited tidal volumes and airway pressures were used. Prospective cohort of 361 intensive care units from 20 countries. A total of 5183 patients mechanically ventilated for more than 12 h. Baseline demographic data, primary indication for mechanical ventilation, daily ventilator settings, multiple-organ failure over the course of mechanical ventilation and outcome were collected. Barotrauma was present in 154 patients (2.9%). The incidence varied according to the reason for mechanical ventilation: 2.9% of patients with chronic obstructive pulmonary disease; 6.3% of patients with asthma; 10.0% of patients with chronic interstitial lung disease (ILD); 6.5% of patients with acute respiratory distress syndrome (ARDS); and 4.2% of patients with pneumonia. Patients with and without barotrauma did not differ in any ventilator parameter. Logistic regression analysis identified as factors independently associated with barotrauma: asthma [RR 2.58 (1.05-6.50)], ILD [RR 4.23 (95%CI 1.78-10.03)]; ARDS as primary reason for mechanical ventilation [RR 2.70 (95%CI 1.55-4.70)]; and ARDS as a complication during the course of mechanical ventilation [RR 2.53 (95%CI 1.40-4.57)]. Case-control analysis showed increased mortality in patients with barotrauma (51.4 vs 39.2%; p=0.04) and prolonged ICU stay. In a cohort of patients in whom airway pressures and tidal volume are limited, barotrauma is more likely in patients ventilated due to underlying lung disease (acute or chronic). Barotrauma was also associated with a significant increase in the ICU length of stay and mortality.


Drug reimbursement policies in Canada--need for improved access to critical therapies.
Public drug programs in Canada are increasingly implementing cost management strategies. A multidisciplinary review of these strategies--specifically, the special authorization (SA) process--found that implementation of the SA practice is costly and causes inequity in access, underutilization, and delays in treatment for urgently required therapies, all potentially leading to negative health outcomes. We present potential solutions and a set of recommendations for decision-makers to base reimbursement decisions on the best clinical evidence, eliminate regional variability in access, ensure timely access to urgently required treatments, and monitor the impact of reimbursement policies on health outcomes.


Clinical, prognostic, and therapeutic aspects of urachal carcinoma-A comprehensive review with meta-analysis of 1,010 cases.
Urachal carcinoma (UrC) is a rare and poorly investigated disease. Our current knowledge is mainly based on single-institutional studies. Despite growing interest in UrC, the included case numbers in recently published studies are still low. Therefore, we aimed to provide a comprehensive meta-analysis on the clinical, prognostic, and therapeutic aspects of UrC. A systematic Medline/PubMed search was performed on UrC using the terms "urachal carcinoma," "urachal cancer," and "urachus." Original articles and reviews in English language with case numbers>10 were selected. The vast majority (91%, 489/532) of UrCs are diagnosed at later stages (Sheldon≥III) when the tumor invades the urinary bladder. About 21% (136/646) of UrC patients have distant metastasis at first presentation. Although for patients with non-metastatic UrC surgical treatment provides an acceptable disease control, the systemic treatment of patients with progressed/metastatic UrC-in lack of prospective clinical trials-are less well established. Comparing cisplatin-based and 5-FU-based therapies in 74 published UrC cases, we found the latter to be superior in terms of radiographic response rates (9% vs. 44%, P = 0.043), but the combination of these 2 therapies provided the lowest progression rate (14%) with a similarly high response rate (43%). Owing to the lack of evidence-based guidelines, the therapy of UrC remains challenging. Given the infrequency of UrC, large prospective studies comparing different systemic therapies can hardly be conducted. Our metadata indicates that 5-FU-containing chemotherapy regimens are more effective than cisplatin-based treatment modalities, whereas their combination seems to provide the strongest antitumor effect. Nevertheless, in the lack of evidences from prospective clinical trials, therapeutic decision-making necessarily remains on an individual basis. In this situation, targeted therapies may provide a reasonable alternative. Therefore, better understanding of the molecular background of UrC is needed to rationalize treatment decisions in UrC.


A computer-aided grading of glioma tumor using deep residual networks fusion.
Among different cancer types, glioma is considered as a potentially fatal brain cancer that arises from glial cells. Early diagnosis of glioma helps the physician in offering effective treatment to the patients. Magnetic Resonance Imaging (MRI)-based Computer-Aided Diagnosis for the brain tumors has attracted a lot of attention in the literature in recent years. In this paper, we propose a novel deep learning-based computer-aided diagnosis for glioma tumors. The proposed method incorporates a two-level classification of gliomas. Firstly, the tumor is classified into low-or high-grade and secondly, the low-grade tumors are classified into two types based on the presence of chromosome arms 1p/19q. The feature representations of four residual networks have been used to solve the problem by utilizing transfer learning approach. Furthermore, we have fused these trained models using a novel Dempster-shafer Theory (DST)-based fusion scheme in order to enhance the classification performance. Extensive data augmentation strategies are also utilized to avoid over-fitting of the discrimination models. Extensive experiments have been performed on an MRI dataset to show the effectiveness of the method. It has been found that our method achieves 95.87% accuracy for glioma classification. The results obtained by our method have also been compared with different existing methods. The comparative study reveals that our method not only outperforms traditional machine learning-based methods, but it also produces better results to state-of-the-art deep learning-based methods. The fusion of different residual networks enhances the tumor classification performance. The experimental findings indicates that Dempster-shafer Theory (DST)-based fusion technique produces superior performance in comparison to other fusion schemes.


Ambiguity in 3-D patterns induced by lighting assumptions.
A bistable pattern is shown with white and black bars with horizontal and vertical orientations which produce an impression of thin slabs stacked up in depth either toward or away from the observer. It is postulated that the ambiguity is induced by the observer's assumption of the direction of the light source.


Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.
Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting. In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area. First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.


Targeting L-type amino acid transporter 1 in urological malignancy: Current status and future perspective.
Amino acid transporters are responsible for the uptake of amino acids, critical for cell proliferation. L-type amino acid transporters play a major role in the uptake of essential amino acids. L-type amino acid transporter 1 (LAT1) exerts its functional properties by forming a dimer with 4F2hc. Utilizing this cancer-specificity, research on diagnostic imaging and therapeutic agents for malignant tumors targeting LAT1 progresses in various fields. In hormone-sensitive prostate cancer, the up-regulation of L-type amino acid transporter 3 (LAT3) through the androgen receptor (AR) has been identified. On the other hand, in castration-resistant prostate cancer, the negative regulation of LAT1 through AR has been determined. Furthermore, 4F2hc: a binding partner of LAT1, was identified as the specific downstream target of Androgen Receptor Splice Variant 7: AR-V7. LAT1 has been suggested to contribute to acquiring castration resistance in prostate cancer, making LAT1 a completely different therapeutic target from anti-androgens and taxanes. Increased expression of LAT1 has also been found in renal and bladder cancers, suggesting a contribution to acquiring malignancy and progression. In Japan, clinical trials of LAT1 inhibitors for solid tumors are in progress, and clinical applications are now underway. This article will summarize the relationship between LAT1 and urological malignancies.


Assessment of compatibility of rhIGF-1/rhIGFBP-3 with neonatal intravenous medications.
Recombinant human (rh)IGF-1/IGFBP-3 protein complex, administered as a continuous intravenous infusion in preterm infants, is being studied for the prevention of complications of prematurity. We conducted in vitro studies to evaluate the physical and chemical compatibility of rhIGF-1/IGFBP-3 with medications routinely administered to preterm neonates. In vitro mixing of rhIGF-1/IGFBP-3 drug product with small-molecule test medications plus corresponding controls was performed. Physical compatibility was defined as no color change, precipitation, turbidity, gas evolution, no clinically relevant change in pH/osmolality or loss in medication content. Chemical compatibility of small molecules was assessed using liquid chromatography (e.g., reverse-phase HPLC and ion chromatography), with incompatibility defined as loss of concentration of ≥ 10%. A risk evaluation was conducted for each medication based on in vitro compatibility data and potential for chemical modification. In vitro physical compatibility was established for 11/19 medications: caffeine citrate, fentanyl, fluconazole, gentamicin, insulin, intravenous fat emulsion, midazolam, morphine sulfate, custom-mixed parenteral nutrition solution (with/without electrolytes), parenteral nutrition solution + intravenous fat emulsion, and vancomycin (dosed from a 5 mg/mL solution), but not for 8/19 medications: amikacin, ampicillin, dopamine, dobutamine, furosemide, meropenem, norepinephrine, and penicillin G, largely owing to changes in pH after mixing. Small-molecule compatibility was unaffected post-mixing, with no loss of small-molecule content. For physically compatible medications, risk analyses confirmed low probability and severity of a risk event. Co-administration of rhIGF-1/rhIGFBP-3 drug product with various medications was assessed by in vitro studies using case-by-case risk analyses to determine the suitability of the products for co-administration.


Personal protective equipment and intensive care unit healthcare worker safety in the COVID-19 era (PPE-SAFE): An international survey.
To survey healthcare workers (HCW) on availability and use of personal protective equipment (PPE) caring for COVID-19 patients in the intensive care unit (ICU). A web-based survey distributed worldwide in April 2020. We received 2711 responses from 1797 (67%) physicians, 744 (27%) nurses, and 170 (6%) Allied HCW. For routine care, most (1557, 58%) reportedly used FFP2/N95 masks, waterproof long sleeve gowns (1623; 67%), and face shields/visors (1574; 62%). Powered Air-Purifying Respirators were used routinely and for intubation only by 184 (7%) and 254 (13%) respondents, respectively. Surgical masks were used for routine care by 289 (15%) and 47 (2%) for intubations. At least one piece of standard PPE was unavailable for 1402 (52%), and 817 (30%) reported reusing single-use PPE. PPE was worn for a median of 4 h (IQR 2, 5). Adverse effects of PPE were associated with longer shift durations and included heat (1266, 51%), thirst (1174, 47%), pressure areas (1088, 44%), headaches (696, 28%), Inability to use the bathroom (661, 27%) and extreme exhaustion (492, 20%). HCWs reported widespread shortages, frequent reuse of, and adverse effects related to PPE. Urgent action by healthcare administrators, policymakers, governments and industry is warranted.


Modulation of the pro-inflammatory cytokines and matrix metalloproteinases production in co-cultivated human keratinocytes and melanocytes.
The human epidermis exerts immunoregulatory functions through the variety of cytokines and other molecules elaborated by keratinocytes and melanocytes. Their constitutive production is very low; however, considerably increased upon stimulation. In vivo, keratinocytes and melanocytes have a typical exposure in the skin, referred as melanocyte epidermal unit. In the present study we co-cultivated these cells in vitro proposing to elucidate some communication links in close cell-to-cell association. We assessed the amounts of IL-6, IL-8, and matrix metalloproteinases (MMP-2 and MMP-9) in individually and co-cultured cells, exposed or not to UVB radiation. Normal human epidermal keratinocytes and melanocytes were grown in specific media and supplements. Cells were exposed to UVB radiation (100 mJ/cm(2)) to create comparable stress to the environmental one. Cytokines were determined with ELISA and confirmed with Western blot and metalloproteinases with gel zimography. Pure cultures of keratinocytes and melanocytes released low amounts of cytokines and metalloproteinases, these secretions being enhanced by UVB irradiation. In co-cultures, the cell-to-cell proximity triggered signals which markedly augmented the cytokines' secretions, whereas metalloproteinases were down-regulated. UVB irradiation did not influence either of these secretions in co-cultures. Concurrently with the highest levels of the pro-inflammatory cytokines, MMP-9 was up-regulated creating pro-inflammatory conditions and premises for changes in cellular survival, differentiation and phenotype. A complex network of interactions occurred between keratinocytes and melanocytes in co-cultures, resulting in modulated pro-inflammatory cytokines and metalloproteinases productions. Therefore, any disturbances in the microenvironmental signaling system and its molecular constituents may result in inflammation or even tumorigenesis in the epidermis.


The Genetic and Neural Substrates of Externalizing Behavior.
To gain more insight into the biological factors that mediate vulnerability to display externalizing behaviors, we leveraged genome-wide association study summary statistics on 13 externalizing phenotypes. After data classification based on genetic resemblance, we performed multivariate genome-wide association meta-analyses and conducted extensive bioinformatic analyses, including genetic correlation assessment with other traits, Mendelian randomization, and gene set and gene expression analyses. The genetic data could be categorized into disruptive behavior (DB) and risk-taking behavior (RTB) factors, and subsequent genome-wide association meta-analyses provided association statistics for DB and RTB (N eff = 523,150 and 1,506,537, respectively), yielding 50 and 257 independent genetic signals. The statistics of DB, much more than RTB, signaled genetic predisposition to adverse cognitive, mental health, and personality outcomes. We found evidence for bidirectional causal influences between DB and substance use behaviors. Gene set analyses implicated contributions of neuronal cell development (DB/RTB) and synapse formation and transcription (RTB) mechanisms. Gene-brain mapping confirmed involvement of the amygdala and hypothalamus and highlighted other candidate regions (cerebellar dentate, cuneiform nucleus, claustrum, paracentral cortex). At the cell-type level, we noted enrichment of glutamatergic neurons for DB and RTB. This bottom-up, data-driven study provides new insights into the genetic signals of externalizing behaviors and indicates that commonalities in genetic architecture contribute to the frequent co-occurrence of different DBs and different RTBs, respectively. Bioinformatic analyses supported the DB versus RTB categorization and indicated relevant biological mechanisms. Generally similar gene-brain mappings indicate that neuroanatomical differences, if any, escaped the resolution of our methods.


Profiling post-translational modifications of histones in neural differentiation of embryonic stem cells using liquid chromatography-mass spectrometry.
The neural differentiation of embryonic stem cells (ESCs) is of great significance for understanding of the mechanism of diseases. Histone post-translational modifications (HPTMs) play a key role in the regulation of ESCs differentiation. Here, we combined the stable isotope chemical derivatization with nano-HPLC-mass spectrometry (MS) for comprehensive analysis and quantification of histone post-translational modifications (HPTMs) in mouse embryonic stem cells (mESCs) and neural progenitor cells (mNPCs) that was derived from ESCs. We identified 85 core HPTM sites in ESCs and 78HPTM sites in NPCs including some novel lysine modifications. Our quantitative analysis results further revealed the changes of HPTMs from ESCs to NPCs and suggested effect of combinational HPTMs in the differentiation. This study demonstrates that HPLC-MS-based quantitative proteomics has a considerable advantage on quantification of combinational PTMs and expands our understanding of HPTMs in the differentiation.


There is little evidence that the Industrial Revolution was caused by a preference shift.
The idea, based on Life History Theory, that the Industrial Revolution was a positive feedback process wherein prosperity induced prosperity-promoting preference shifts is just an intriguing speculation. The evidence does not distinguish this explanation from simple alternatives. For example, increased prosperity may have freed up time for individuals to engage in innovative activity and increased the benefits from doing so.


Effect of defoliation intensity on aboveground and belowground relative growth rates.
According to a simple growth model, grazed and ungrazed plants may have equal absolute growth rates provided that the relative growth rate (RGR) of grazed plants increases exponentially with grazing intensity (proportion of biomass removed). This paper reports results from an experiment designed to determine whether plants of two grass species subjected to a gradient of defoliation intensities, from 0 to 100% aboveground biomass removal, showed such a response. The relationship between aboveground RGR and defoliation intensity was exponential and closely matched the theoretical relationship of equal absolute growth rate. Thus, plants showed the same aboveground growth regardless of defoliation intensity thanks to an exponential stimulation of RGR by defoliation. Belowground RGR was depressed by defoliation of more than 20% of the above-ground biomass. In spite of the drastic modification imposed by the treatments on the relative proportions of different plant parts, after a 42-day recovery period basic allometric relationships, such as root:shoot and leafarea: weight ratios, were not affected by defoliation intensity. Exponential aboveground compensatory responses represent a key feedback process resulting in constant aboveground growth regardless of defoliation intensity and appear to be a simple consequence of strong commitments to certain allometric relationships.


Impermeable flexible liquid barrier film for encapsulation of DSSC metal electrodes.
Encapsulation of electronic devices such as dye-sensitized solar cells (DSSCs) is prone to degradation under normal atmospheric conditions, even with hermetic barriers on the metal electrodes. Overcoming this problem is crucial to increasing DSSC lifetimes and making them commercially viable. Herein, we report a new impermeable flexible liquid barrier film using polyvinyl alcohol (PVA) and partially reduced graphene oxide (PrGO), which dramatically enhances the lifetime of Ag metal electrodes (typically used in DSSCs) immersed in a highly acidic iodolyte solution. The Ag metal electrode encapsulated by the PVA/PrGO film survived for over 500 hrs, superior to existing barriers of glass frits, epoxy resins and polymers. The PVA/PrGO film strongly adheres to the Ag metal surface, and the resulting PVA/PrGO/Ag electrode is stable even on a curved substrate, with a sheet resistance nearly independent of curvature. These results give new insight for the design of high-performance and solution-processable flexible liquid barrier films for a wide range of applications, in particular for the encapsulation of electronic devices with liquid electrolytes.


Recovery of overground locomotion following partial spinal lesions of different extent in the rat.
In six rats with incomplete low thoracic spinal cord lesions of different extent, basic gait indices such as locomotor speed, step cycle duration, soleus (Sol) muscle activity duration, the interval between the onsets of Sol and tibialis anterior (TA) muscle activities and interlimb coordination were investigated by EMG analysis of the Sol and TA muscles recorded using chronic electrodes. The operated animals were divided into two subgroups: (1) those with a smaller lesion involving the dorsal quadrants of the spinal cord and, to a variable extent, the ventrolateral funiculi, and (2) those with an extensive lesion sparing only parts of the ventral funiculi. The locomotion of all rats was tested once a week for the first 5 weeks postsurgery and then once or twice a month, up to 3.5 months. The surgical lesions affected all analyzed gait indices: the locomotor speed decreased, while all other indices increased compared to recordings made preoperatively. In both subgroups the major improvement in locomotion occurred within the first 5 weeks following surgery and the rats reached a plateau in their recovery at around 2 months postoperatively. The late effects of injury depended on the severity of the spinal lesion: in the subgroup of rats with a smaller lesion, the postoperative changes in the different indices amounted to approximately 20%, while in the subgroup with extensive lesions this was increased by 20-50%, with changes in various indices being strongly correlated with the extent of the injury in individual animals. These postoperative changes were partly due to alterations in the relationships between the analyzed variables.


The main advantages of community based participatory health programs: an experience from the islamic republic of iran.
Community based participatory program is an approach that emphasize on community empowerment as an important tool in health promotion especially in low and middle income countries. This article presents findings from a study of assessing performed participatory community based health programs in the Islamic Republic of Iran. This study was a qualitative study using focus group discussions. Thirteen community based programs related to health that were active for last five years were selected and assessed. Data analysis was based on deductive-inductive content analysis approach considering the predetermined structure according to study questions. In this study, strengths points of community participatory health programs based on the locality of the implementation of the programs; governmental organization and nongovernmental organizations (NGO's) were evaluated. The main strengths of these programs were the presence of the spirit of empathy and high motivation in working for community, absorbing the community assistance, community empowerment, presence of female volunteers, using local volunteers, creation of social prestige and evidence based decision making for community problem solving. Capacity building of the community, NGOs and policymakers plays key role in participation mechanisms, partnership, team working and mobilizing of necessary resources in the promotion of participatory community based health programs.


The Utility of Noninvasive PET/CT Myocardial Perfusion Imaging in Adult Liver Transplant Candidates.
The optimal cardiovascular (CV) risk stratification in liver transplant (LT) candidates remains unclear. The aim of this study was to evaluate concordance of findings between dobutamine stress echocardiography (DSE), positron emission tomography/computed tomography myocardial perfusion imaging (PET/CT MPI), and left heart catheterization in adult LT candidates. Data on 234 consecutive adult LT candidates from February 2015 to June 2018 with PET/CT MPI were reviewed. Adverse CV outcomes were adjudicated via chart review by a board-certified cardiologist. Median age was 60.8, body mass index 30.2 kg/m2, and model of end-stage liver disease-sodium 14; 61% were male, and 54% had diabetes. Thirty-seven percent had nonalcoholic steatohepatitis and 29% alcohol-related liver disease. Sixty-five percent of patients had a DSE, of which 41% were nondiagnostic. No factors were independently associated with having a nondiagnostic DSE. The median global myocardial flow reserve correlated positively with hemoglobin and negatively with model of end-stage liver disease-sodium, age, ejection fraction, and body mass index. Moderate/high-risk MPIs were associated with older age and known CV disease. In patients with 2 cardiac testing modalities, findings were concordant in 87%. Eleven of 53 LT recipients experienced an adverse CV outcome, but no independent predictors were identified for this outcome. Results of different cardiac risk-stratification modalities were concordant across modalities the majority of the time in LT candidates, although these findings were not independently correlated with risk of post-LT CV outcomes. Given the high rates of nondiagnostic DSEs in this population, PET/CT MPI may be the preferred CV risk-stratification modality in older patients and those with known CV disease.


MR and ultrasound in screening of patients with suspected biliary tract disease.
The diagnostic value and cost-efficiency of MR imaging were compared with US before endoscopic retrograde cholangiopancreatography (ERCP) in patients with clinically suspected biliary tract disease. In a prospective study of 219 patients, 85 were examined with both MR and US before ERCP. To find the correct diagnosis in the jaundiced patients the sensitivity of US, MR and ERCP was 53%, 93%, and 89%, respectively. In the patients with abdominal upper quadrant pain and normal serum bilirubin, the sensitivity of US, MR and ERCP was 50%, 100% and 70%, respectively. Examination with MR costs four times more than US. Screening with US and supplemental MR in non-diagnostic cases would cost 80% of the total amount compared to screening with MR only. MR had a higher sensitivity than US for diagnosing biliary tract disease and MR was superior to US in visualising stones in the common bile duct and in diagnosing the cause of cholestasis. However, screening with US and supplemental MR in non-diagnostic cases is at present most cost-effective. With increased accessibility and slightly lower costs, MR will probably replace US as screening method in patients with suspected biliary tract disease.


Multiple Boluses of Intravenous Tranexamic Acid to Reduce Hidden Blood Loss After Primary Total Knee Arthroplasty Without Tourniquet: A Randomized Clinical Trial.
The optimal dosage and timing of tranexamic acid (TXA) in total knee arthroplasty (TKA) are undetermined. The purpose of this study was to explore the effect of multiple boluses of intravenous TXA on hidden blood loss (HBL), inflammatory response, and knee function after primary TKA without tourniquet. A total of 151 patients were randomly divided into 3 groups to receive single bolus of 20 mg/kg IV-TXA before skin incision (group A), or another bolus of 10 mg/kg IV-TXA 3 hours later (group B), or another 2 boluses of 10 mg/kg IV-TXA 3 hours and 6 hours later (group C). TKAs without tourniquet were operated by 1 single surgeon. The primary outcomes were HBL and maximum hemoglobin drop. Other outcome measurements such as total blood loss, transfusion rate, inflammation markers (C-reactive protein, interleukin 6), visual analog scale pain score, limb swelling ratio, Hospital for Surgery Score, range of motion, length of hospital stay (LOH), and deep venous thrombosis were also compared. The mean HBL and maximum Hb drop in group C (467.6 ± 305.9 and 20.9 ± 9.3) was lower than those in group A (763.0 ± 373.3, P < .001; 28.7 ± 12.2, P < .001) and group B (637.5 ± 303.5, P = .010; 25.2 ± 8.4, P = .036). However, such differences were not detected between groups A and B (P = .058 and P = .080, respectively). The mean value of total blood loss in the groups A, B, and C were 967.2 ± 380.1, 803.7 ± 321.8, and 677.6 ± 326.0 mL, respectively, with a significant intergroup difference (P < .001). The mean serum level of C-reactive protein and interleukin 6 in group C were lower than those in group A and group B on postoperative days 1 and 2. The visual analog scale pain score and swelling ratio were also lower in group C than in the other 2 groups with statistical significance on POD 1-3. Moreover, the Hospital for Surgery Score, range of motion, and LOH were better in group C. No episodes of transfusion or deep venous thrombosis had occurred. Multiple boluses of IV-TXA can effectively reduce HBL after primary TKA without tourniquet. What is the most important is that, by adding another bolus of IV-TXA, patients can gain a smaller decline of Hb, less postoperative inflammatory response, less pain, less knee swelling, better knee function, and shorter LOH.


Shoulder Manipulation After Distention Arthrography: Does Audible Cracking Affect Improvement in Adhesive Capsulitis? A Preliminary Study.
To investigate whether an audible cracking sound during shoulder manipulation following distention arthrography is clinically significant in patients with adhesive capsulitis of the shoulder. A total of 48 patients (31 women, 17 men) with primary adhesive capsulitis of the shoulder completed the study. All participants underwent C-arm-guided arthrographic distention of the glenohumeral joint with injections of a corticosteroid and normal saline. After distention, we performed flexion and abduction manipulation of the shoulder. The patients were grouped into sound and non-sound groups based on the presence or absence, respectively, of an audible cracking sound during manipulation. We assessed shoulder pain and disability based on a Numeric Rating Scale (NRS), the Shoulder Pain and Disability Index (SPADI), and passive range of motion (ROM) measurements (flexion, abduction, internal and external rotation) before the procedure and again at 3 weeks and at 6 weeks after the intervention. The patients were divided into two groups: 21 were included in the sound group and 27 in the non-sound group. In both groups, the results of the NRS, SPADI, and ROM assessments showed statistically significant improvements at both 3 and 6 weeks after the procedure. However, there were no significant differences between the two groups except with respect to external rotation at 6 weeks, at which time the sound group showed a significant improvement in external rotation when compared with the non-sound group (p<0.05). These findings showed that manipulation following distention arthrography was effective in decreasing pain and increasing shoulder range of motion. In addition, the presence of an audible cracking sound during manipulation, especially on external rotation, was associated with better shoulder range of motion.


The ER stress sensor inositol-requiring enzyme 1α in Kupffer cells promotes hepatic ischemia-reperfusion injury.
Hepatic ischemia/reperfusion (I/R) injury is an inflammation-mediated process arising from ischemia/reperfusion-elicited stress in multiple cell types, causing liver damage during surgical procedures and often resulting in liver failure. Endoplasmic reticulum (ER) stress triggers the activation of the unfolded protein response (UPR) and is implicated in tissue injuries, including hepatic I/R injury. However, the cellular mechanism that links the UPR signaling to local inflammatory responses during hepatic I/R injury remains largely obscure. Here, we report that IRE1α, a critical ER-resident transmembrane signal transducer of the UPR, plays an important role in promoting Kupffer-cell-mediated liver inflammation and hepatic I/R injury. Utilizing a mouse model in which IRE1α is specifically ablated in myeloid cells, we found that abrogation of IRE1α markedly attenuated necrosis and cell death in the liver, accompanied by reduced neutrophil infiltration and liver inflammation following hepatic I/R injury. Mechanistic investigations in mice as well as in primary Kupffer cells revealed that loss of IRE1α in Kupffer cells not only blunted the activation of the NLRP3 inflammasome and IL-1β production, but also suppressed the expression of the inducible nitric oxide synthase (iNos) and proinflammatory cytokines. Moreover, pharmacological inhibition of IRE1α's RNase activity was able to attenuate inflammasome activation and iNos expression in Kupffer cells, leading to alleviation of hepatic I/R injury. Collectively, these results demonstrate that Kupffer cell IRE1α mediates local inflammatory damage during hepatic I/R injury. Our findings suggest that IRE1α RNase activity may serve as a promising target for therapeutic treatment of ischemia/reperfusion-associated liver inflammation and dysfunction.


The efficacy of blood flow restricted exercise: A systematic review & meta-analysis.
To systematically search and assess studies that have combined blood flow restriction (BFR) with exercise, and to perform meta-analysis of the reported results to quantify the effectiveness of BFR exercise on muscle strength and hypertrophy. A systematic review. A computer assisted database search was conducted for articles investigating the effect of exercise combined with BFR on muscle hypertrophy and strength. A total of 916 hits were screened in order based on title, abstract, and full article, resulting in 47 articles that fit the review criteria. A total of 400 participants were included from 19 different studies measuring muscle strength increases when exercise is combined with BFR. Exercise was separated into aerobic and resistance exercise. Resulting from BFR aerobic exercise, there was a mean strength improvement of 0.4Nm between the experimental group and control group, while BFR resistance exercise resulted in a mean improvement of 0.3kg. A total of 377 participants were included in 19 studies measuring muscle size increase (cross sectional area) when exercise was combined with BFR. The mean difference in muscle size between the experimental group and control group was 0.4cm(2). Current evidence suggests that the addition of BFR to dynamic exercise training is effective for augmenting changes in both muscle strength and size. This effect was consistent for both resistance training and aerobically-based exercise, although the effect sizes varied. The magnitude of observed changes are noteworthy, particularly considering the relatively short duration of the average intervention.


Epidemiology of hospitalization for acute bronchiolitis in children: differences between RSV and non-RSV bronchiolitis.
We study the clinical, management and outcome differences between respiratory syncytial virus (RSV) positive and negative bronchiolitis. A retrospective review of the medical records of children ≤ 2 years of age with acute bronchiolitis between January 1995 and December 2006 was done. There were 2,384 patients hospitalized for acute bronchiolitis, and 1,495 (62.7%) were RSV infections. Overall, hospitalization rate was 55/1,000 admissions. Mortality occurred in 0.08% of cases. Bronchiolitis due to RSV was more frequent from November to March (97%). RSV bronchiolitis had longer hospital stays (6 vs. 5 days, P<0.0001), higher risk of intensive care unit (ICU) admission (OR 2.7; 95%CI 1.87-3.9) and more oxygen use (OR 2.2; 95%CI 1.8-2.6). Infants < 2 months had longer median hospital stay (6 vs. 5 days, P <0.0001) and higher risk of ICU admission (OR 3.4; 95%CI 2.5-4.6). Prematures of < 32 gestational weeks, congenital heart disease, and atelectasis/condensation were the main risk factors for ICU admission in both RSV and non-RSV bronchiolitis. The introduction of palivizumab in prematures diminished hospitalization for RSV bronchiolitis, oxygen need, length of hospital stay and mechanical ventilation. In conclusion, this study supports that RSV bronchiolitis seems to be a more severe disease than that caused by other viruses.


Postoperative changes over time in size of anterior capsulorrhexis in phacoemulsification/aspiration.
In the present study, we attempted to determine the extent to which an anterior capsulorrhexis carried out during cataract surgery contracts postoperatively. The size of the continuous curvilinear capsulorrhexis (CCC) was measured at the end of surgery and at the final follow-up examination in 52 eyes of 40 patients who underwent phacoemulsification/aspiration and implantation of an intraocular lens (IOL) with 6-mm optics. Images obtained by video during surgery and by slit-lamp microscopy were used to determine the CCC size with reference to the optics of the IOL. The average CCC size was 5.0 mm at the end of surgery; it contracted to 4.4 mm by the final postoperative examination. The contraction of the anterior capsule progressed rapidly in the first 50 days following surgery and then gradually thereafter. The extent of contraction was greater in older patients. The smaller the CCC size immediately after surgery, the more rapidly it contracted. The size of the capsulorrhexis contracted an average of 22% following cataract surgery. The contraction rate tended to be higher in older patients. The results suggest that the capsulorrhexis carried out in cataract surgery for elderly patients should be sufficiently large, but not larger than the optics size of the IOL.


Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in Zearalenone-treated mouse endometrial stromal cells.
Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin found in several food commodities worldwide. Although the toxicity of ZEA have been widely studied in a number of cell types, the mechanistic role of ZEA on apoptosis of endometrial stromal cells (ESCs) remains poorly understood. The objective of this study was to determine the effects of ZEA on apoptosis of mouse ESCs and explore the signaling pathway underlying the cytotoxicity of ZEA. The results showed that ZEA treatment caused obvious apoptosis in ESCs as determined by the flow cytometry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. Immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR) revealed that ZEA treatment increased the ratio of Bax/Bcl-2. The enzymatic activity assays revealed that caspases-3 and caspase-9 were activated by ZEA treatment in a dose-dependent manner. In addition, flow cytometry show that the apoptotic percentages of cells pretreated with Z-VAD-FMK and Z-LEHD-FMK were markedly reduced compared to the ZEA-treated cells. Overall, the results suggested that ZEA induced obvious apoptosis in ESCs via a Bcl-2 family and caspases-dependent signaling pathway.


Histological acoustic tumor involvement of the VIIth nerve and multicentric origin in the VIIIth nerve.
The surgical plane between the VIIth nerve and acoustic tumor is often elusive. This histological relationship was reviewed in three patients who underwent VII-VII neuroanastomosis at tumor removal disclosing an inseparable surgical plane in two. In the third patient, tissue sections did not accurately show the relationship. In all three, surgical planes were not apparent at tumor removal. Another patient had a second, isolated tumor in the same VIIIth nerve proximally at the brain stem root entry zone. This was seen only on permanent section. In considering "total" tumor removal by microsurgical standards, these histological findings should be kept in mind. We advocate removal of the entire VIIIth nerve to the brain stem root entry zone along with smaller tumors.


Antegrade Wire Escalation Case Selection and Strategies: Four Wires for Success.
The North American Hybrid Algorithm has become the standard method for percutaneous intervention for coronary chronic total occlusions. In this article, the authors discuss antegrade wire escalation as it applies to the North American Hybrid Algorithm for chronic total occlusion percutaneous coronary intervention. There is a multitude of guidewires available to operators on the market, which can quickly prove overwhelming in terms of selection, cost, and practicality. The authors simplify wires into four overall groups or families. Operators should be able to pare their toolbox down to four wires only to achieve success at antegrade wire escalation.


Painful and multiple anogenital lesions are common in men with Treponema pallidum PCR-positive primary syphilis without herpes simplex virus coinfection: a cross-sectional clinic-based study.
Chancres, the hallmark of primary syphilis, are classically described as single, painless ulcers at the site of Treponema pallidum inoculation. We aimed to determine the frequency of painful or multiple anogenital lesions of primary syphilis among men, whether there was concurrent herpes simplex virus (HSV) infection and whether HIV status altered clinical presentations. This study was conducted among men with T. pallidum PCR-positive lesions, attending a clinic in Melbourne, Australia, between 2009 and 2014. Lesions were also tested with HSV PCR, and syphilis serology undertaken. 183 men with T. pallidum PCR-positive primary anogenital lesions were included. 89% were men who have sex with men, and 10.9% were heterosexual. 38 men (20.8%) were HIV positive. Anal lesions were more common in HIV-positive men (34.2%) than in HIV-negative men (11.6%). Primary lesions were frequently painful (49.2%) or multiple (37.7%), and infrequently associated with HSV (2.7%). Of 37 men with both painful and multiple primary lesions, only 8% had concurrent HSV. Presentation was not significantly altered by HIV status. Primary syphilis lesions are often painful and/or multiple in the absence of herpes coinfection, and may be clinically misdiagnosed.


Perioperative Blood Transfusions and Anastomotic Leak After Colorectal Surgery for Cancer in an Australian Hospital.
Peri-operative blood transfusion has been identified as a risk factor for anastomotic leak in recent studies, but little is known about which patients are at risk for blood transfusion. This study aims to assess the relationship between blood transfusion and anastomotic leak and factors predisposing to leak in patients undergoing colorectal cancer surgery. This retrospective cohort study was conducted in a tertiary hospital in Brisbane, Australia, between 2010 and 2019. A total of 522 patients underwent resection of colorectal cancer with primary anastomosis with no covering stoma and the prevalence of anastomotic leak was compared between those who had had perioperative blood transfusion(s) and those who had not. A total of 19 of 522 patients undergoing surgery for colorectal cancer had developed an anastomotic leak (3.64%). 11.3% of patients who had had a perioperative blood transfusion developed an anastomotic leak whereas 2.2% of patients who had not had a blood transfusion developed an anastomotic leak (p = 0.0002). Patients undergoing procedure on their right colon had proportionally more blood transfusions and this approached statistical significance (p = 0.06). Patients who received a greater quantity of units of blood transfusion prior to their diagnosis of anastomotic leak were more likely to develop an anastomotic leak (p = 0.001). Perioperative blood transfusions are associated with a significantly increased risk of an anastomotic leak following bowel resection with primary anastomosis for colorectal cancer.


Child Advocacy Center intervention with sibling sexual abuse cases: Cross-cultural comparison of professionals' perspectives and experiences.
Despite being a complex phenomenon with potentially significant short- and long-term consequences for all involved including siblings, parents and the family as a whole, sibling sexual abuse (SSA) has not received sufficient empirical and clinical attention. Practitioners are often left to cope without appropriate guidance. This study aimed to compare staff perspectives and experiences of working with sibling sexual abuse cases across two Child Advocacy Centers (CACs) within different countries and different cultural and legal contexts. Participants were staff members from two Child Advocacy Centers: one in Jerusalem, Israel, and the other in Montgomery County, Pennsylvania, United States of America. This qualitative cross-cultural comparative study analyzes staff experiences of sibling sexual abuse cases based upon 14 focus groups, in Jerusalem (N = 7) and Montgomery County (N = 7). Findings reveal that both CACs focused on parents, the parents' negative emotional responses to SSA, and the impossible nature of their predicament. The Montgomery County CAC tended to emphasize the needs of the victim while being attuned to the legal proceedings, whereas the Jerusalem CAC emphasized supportive therapeutic responses for the whole family. The differences across the two Child Advocacy Centers are related to the different legal and cultural contexts of the two CACs and underscore the need to review what may be the most appropriate policy and practice response to SSA that does not itself cause further harm.


Treatment of hypertonicity in muscles of lip retraction.
An EMG biofeedback program was developed for a 56-year-old Parkinsonism patient who exhibited pathological lip hypertonia and retraction. The program was designed to achieve the following goals: (1) to demonstrate a reduction in postural lip hypertonicity and (2) to demonstrate a reduction in lip hypertonicity during a series of increasingly complex speech activities. To achieve the first goal, contrastive tasks of full contraction and relaxation were utilized. Each posture was sustained while voltage measurements were made at specific intervals. Procedures to modify lip retraction during speech included five tasks in which the patient was to monitor the audio feedback signal. The tasks involved: prolongation of a neutral vowel, consonant-vowel combinations, monosyllabic words, sentences, and a paragraph-reading task. Data collected over six biofeedback sessions are presented. Trend analyses showed consistent muscular reduction within each task. The following explanations for the decrease in the patient's hypertonicity were discussed: (1) reduction of anisometric contraction, (2) reduction of isometric contraction, (3) relearning of agonistic-antagonistic muscle balance.


Progressive neurodegenerative disease in presumed spinal cord injury: case report of a patient with prion disease.
Prion diseases or transmissible spongiform encephalopathies (TSEs) are neurodegenerative syndromes caused by proteinaceous infectious particles (or "prions"), are fatally progressive, and affect humans and animals. Human prion disease may be familial, sporadic, or due to iatrogenic causes. The signs and symptoms include dementia, ataxia, myoclonus, dysautonomia, pyramidal and extrapyramidal tract signs, and akinesia. The incubation period of iatrogenic TSE ranges from 15 months to 30 years, and clinical presentations may be atypical. Case report. This article presents the case study of a 39-year-old man who fell at work and subsequently complained of subjective lower extremity weakness, followed by onset of ataxia, bowel and bladder incontinence, and progressive decline in ambulation over 6 months. In the absence of a unifying diagnosis, the patient was presumed to have had a spinal cord injury (SCI). Because neuro-axis imaging studies failed to explain his symptoms, the patient's complaints were thought to have a large psychologic component. The patient then developed neurologic abnormalities proximal to the presumed SCI. Somatosensory evoked potentials were suggestive of a thoracic or lumbar cord myelopathy and cerebrospinal fluid analysis was suggestive of prion disease. Family members eventually revealed that the patient had had injections of growth hormones derived from cadaveric human pituitary glands as a child. Postmortem brain examination later revealed definitive Creutzfeldt-Jakob disease.


Fourteen years follow up after Lisfranc fracture-dislocation: functional and radiological results.
Injuries to the Lisfranc joint have a high potential for chronic disability. Posttraumatic arthritis remains the most common complication but not all patients who develop degenerative radiographic changes are symptomatic. A cohort of 32 patients with a Lisfranc fracture dislocation was reviewed. Initial reduction and secondary displacement were measured by the Myerson scale. Radiographic evidence of osteoarthritis (OA) was also investigated. Long-term radiographical data were classified as good, fair or poor results. Functional outcome was measured using several different scales. Mean follow up was 14 years. Seventeen patients with anatomic close reduction but instability were treated with closed reduction and K-wire fixation followed by cast immobilisation. Eight patients with stable anatomic close reduction were treated with closed reduction and cast. Seven patients with unacceptable closed reduction were treated with open reduction and K-wire stabilisation. The analysis of radiological long-term data showed 15 patients with good results, 8 with fair results and 9 with poor results. Final mean AOFAS score was 91.7/100. There was no statistically significant difference between overall PFS scores and different type of treatment, Hardcastle long-term radiological scores or Hardcastle type of fracture (p >0.05). Overall, there was a poor association between the extent of radiological arthritis and clinical scores. We advocate that for the evaluation of long-term outcome of these injuries functional parameters should be the focus of assessment, instead of radiological changes.


Transcriptome analysis in the spleen of Northern Snakehead (Channa argus) challenged with Nocardia seriolae.
Northern snakehead (Channa argus) is an indigenous fish species and is one of popularly cultured snakeheads in China and other Asian countries. Unfortunately, Nocardia seriolae infections have caused considerable losses in the snakehead aquaculture industry. However, the infectivity and the immune response induced by N. seriolae in snakehead are unclear. In order to better understand the immune response of Northern snakehead in a series of time points after N. seriolae challenge, we conducted the transcriptomic comparison in snakehead spleen at 48, 96, and 144 h after the challenge of N. seriola against their control counterparts. Gene annotation and pathway analysis of differentially expressed genes (DEGs) were carried out to understand the functions of the DEGs. Additionally, protein-protein interaction networks were conducted to obtain the interaction relationships of immune-related DEGs. These results revealed the expression changes of multiple DEGs and signaling pathways involved in immunity during N. seriolae infection, which will facilitate our comprehensive understanding of the mechanisms involved in the immune response to bacterial infection in the northern snakehead.


Analysis of optical side-effects of fs-laser therapy in human presbyopic lens simulated with modified contact lenses.
In a single-blinded study, optical side-effects of a potential femtosecond (fs)-laser therapy in presbyopic human lenses were tested. Simulation of this therapy was carried out by applying fs-laser patterns into standard contact lenses (CL). In the first part of the study, the influence of the numerical aperture on optical side-effects was investigated by comparing a typical fs-LASIK configuration to a fs-presbyopia treatment (n = 11). The second part focused on a possible improvement of visual performance by comparing a regular grid pattern to a randomly chosen spacing of the laser spots (n = 16). Visual acuity was measured with ETDRS charts, contrast sensitivity with F.A.C.T. charts and mesopic vision with Mesotest II. Forward scattered light was measured with the C-Quant (both instruments: Oculus Optikgeräte GmbH, Germany). A questionnaire detected subjective quality of vision. Differences between laser-treated and untreated CL and among the modifications were analyzed. The laser-treated and standard CL indicated no significant difference in visual acuity, contrast sensitivity and mesopic vision without glare. While wearing modified lenses with a regular grid, quality of vision decreased significantly by means of mesopic vision with glare and subjective straylight. These modifications also caused an impairment of subjective quality of vision. In contrast, there was no significant difference between the random pattern and standard CL. The increase of optical side-effects was reproducibly dependent on the geometry of the laser-structure. A randomized grid induced the least limitation. The study results are useful for planning possible laser-patterns in fs-laser therapy of the presbyopic lens.


Ochratoxin A production in aniseed-based media by selected fungal strains and in anise fruits (Pimpinella anisum L.).
The growth conditions and ochratoxin A (OTA) production of Aspergillus strains were studied in aniseed (Pimpinella anisum L.)-based media. The results showed that methanol/NaHCO3 (50:50, v/v) mixture for extraction and competitive direct ELISA analytical method are capable of detecting low OTA concentrations in this raw material, which were confirmed by HPLC with fluorescence detection (R (2) = 0.994). In aniseed meal extract agar artificially contaminated with selected fungi, the higher OTA values obtained were 283.8 ± 28.1 μg L(-1) for A. carbonarius and between 1.7 ± 0.1 μg L(-1) and 16.5 ± 12.8 μg L(-1) for A. steynii strains. While the optimal conditions of growth for A. carbonarius and A. steynii are 28°C and 0.98 a w, the optimal production of OTA was observed at 0.99 a w for both A. carbonarius and A. steynii but at 22°C and 28°C, respectively. Except in one sample, all the aniseed samples analysed were negative for OTA natural contamination. This study demonstrates that aniseed can be a matrix capable to contamination with OTA, at least produced by A. carbonarius and A. steynii strains, regardless of the antimicrobial properties of aniseed essential oil.


Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails in Manx cats.
Most mammals possess a tail, humans and the Great Apes being notable exceptions. One approach to understanding the mechanisms and evolutionary forces influencing development of a tail is to identify the genetic factors that influence extreme tail length variation within a species. In mice, the Tailless locus has proven to be complex, with evidence of multiple different genes and mutations with pleiotropic effects on tail length, fertility, embryogenesis, male transmission ratio, and meiotic recombination. Five cat breeds have abnormal tail length phenotypes: the American Bobtail, the Manx, the Pixie-Bob, the Kurilian Bobtail, and the Japanese Bobtail. We sequenced the T gene in several independent lineages of Manx cats from both the US and the Isle of Man and identified three 1-bp deletions and one duplication/deletion, each predicted to cause a frameshift that leads to premature termination and truncation of the carboxy terminal end of the Brachyury protein. Ninety-five percent of Manx cats with short-tail phenotypes were heterozygous for T mutations, mutant alleles appeared to be largely lineage-specific, and a maximum LOD score of 6.21 with T was obtained at a recombination fraction (Θ) of 0.00. One mutant T allele was shared with American Bobtails and Pixie-Bobs; both breeds developed more recently in the US. The ability of mutant Brachyury protein to activate transcription of a downstream target was substantially lower than wild-type protein. Collectively, these results suggest that haploinsufficiency of Brachyury is one mechanism underlying variable tail length in domesticated cats.


Management of 2nd-degree facial burns using the Versajet(®) hydrosurgery system and xenograft: a prospective evaluation of 20 cases.
There is no single therapeutic scheme for the management of intermediary 2nd-degree facial burns, which can cause problems because of their uncertain course. It is preferable to obtain optimal healing of the face in order to avoid functional or cosmetic sequelae. Some practitioners recommend early excision (first week) of these burns, whereas others prefer to wait and perform surgery later (after 2 weeks). The practice in our burns unit is early surgery (from the first week) associated with hydrosurgical excision and application of a biosynthetic dressing (xenograft). A prospective follow-up of 20 cases was carried out to evaluate the efficacy of our protocol. The prospective evaluation was performed with follow-up at 2 weeks and 3, 6 and 12 months. The patients included had intermediary 2nd-degree burns on at least 15% of the face and no life-threatening prognosis. The mean age in our series was 40.5 years (16-72), the mean percentage of burn surface area was 27.75% and the mean percentage of facial burn was 60.75%. Early excision was performed (day 5-10) using the Versajet(®) system, which allows tangential water-dissection. Porcine xenograft (E-Z Derm(®)) was applied immediately afterwards. Patients whose healing process was not complete at 2 weeks were then scheduled to receive a thin autograft. Patients were followed up 2 weeks, 3, 6 and 12 months after discharge. Excision was performed at a mean 7.6 days, and mean initial healing time was 13.4 days. In three cases, a full-thickness skin graft was used, whereas healing occurred in the other patients without further grafts. Two patients had functional sequelae (ectropion) corrected later by repair surgery. The course of healing for the other patients proceeded normally. There is no consensus about the management of intermediate depth 2nd-degree facial burns. We chose to perform early surgery using the Versajet(®) system, which allows fine, precise excision, leaving nearly all of the healthy tissue in place. The Versajet(®) is particularly adapted to facial contours and is clearly more efficacious than the customary dermatomes. The use of a xenograft may augment facial healing while reducing the number of dressings and lessening patient discomfort. Our protocol provides the advantages of early management (limitation of functional sequelae, reduced hospitalization time), while avoiding too extensive or deep an excision through use of the Versajet(®).


Radiofrequency vapor ablation for Barrett's esophagus: feasibility, safety and proof of concept in a stepwise study with in vitro, animal, and the first in-human application.
The Radiofrequency Vapor Ablation (RFVA) System (AquaMedical, Inc., Santa Ana, CA) is a novel ablation system for eradication of Barrett's esophagus, that generates vapor at 100 °C using an RF electrode located in the catheter tip. We performed in-vitro dosimetry studies and the first in-human feasibility study. The system includes an RFVA generator with syringe pump and a through-the-scope-catheter. The RFVA system was tested in-vitro (lean-beef and porcine study) and ablation depth was compared to focal RFA. Two doses were selected for further in-vivo testing in dysplatic BE patients. Repeat endoscopy with histology was performed after 8 weeks to assess squamous conversion. In porcine, RFVA 3-seconds was comparable to RFA, whereas RFVA 5-seconds produced slightly deeper ablation. We selected a conservative 1-second and 3-seconds for human study. Fifty-three ablations were successfully applied in 15 patients with no adverse events. Follow-up endoscopy showed a median squamous conversion of 55 % (IQR 33 - 74) and 98 % (56 - 99) for 1 and 3-seconds, respectively. In this 3-phase study with lean-beef, porcine and the first in-human application, the RFVA system was feasible for esophageal ablation and successfully and safely converted targeted BE areas into squamous epithelium.


Comparison of Urologic Transfers to Academic Medical Centers: A Multi-institutional Perspective.
To examine urologic transfers and rate of tertiary center interventions from 4 geographically distinct academic medical centers. Four academic medical centers were selected for this study including Baylor College of Medicine, University of Alabama at Birmingham, University of Kentucky, and University of Pennsylvania Hospital (Penn). Baylor College of Medicine and Penn primarily service large metropolitan city centers and University of Kentucky and University of Alabama at Birmingham primarily service large rural populations. Transfer logs were pulled for each institution over a 2-year period, and a retrospective chart review was performed to evaluate transfer diagnosis and need for procedural management upon admission. Date of transfer, transfer diagnosis, and interventions performed during tertiary center admission were extracted from the transfer log data sets. The transfer diagnosis was categorized into 1 of 11 mutually exclusive categories. Overall, 984 urologic transfers were included. Sixty-nine percent (682/984) of patients were transferred to the 2 rural centers, and 30.7% (302/984) were transferred to the 2 metropolitan centers. The most common reason for transfer was nephrolithiasis at 26% (256 of 984 transfers). The overall surgical intervention rate for all urologic transfers in this study was 44.4% (437 of 984 total transfers). Rural center transfers had a lower rate of surgical intervention than metropolitan centers (42.7% vs 48.3%) as well as a markedly higher number of total transfers during the study period (682 vs 302). Given that a majority of patients did not require surgical intervention, methods for avoiding unnecessary urologic transfers are warranted.


Evaluation of automated nucleic acid extraction methods for virus detection in a multicenter comparative trial.
Five European veterinary laboratories participated in an exercise to compare the performance of nucleic acid extraction robots. Identical sets of coded samples were prepared using serial dilutions of bovine viral diarrhoea virus (BVDV) from serum and cell culture propagated material. Each laboratory extracted nucleic acid from this panel using available robotic equipment (12 separate instruments, comprising 8 different models), after which the processed samples were frozen and sent to a single laboratory for subsequent testing by real-time RT-PCR. In general, there was good concordance between the results obtained for the different automated extraction platforms. In particular, the limit of detection was identical for 9/12 and 8/12 best performing robots (using dilutions of BVDV infected-serum and cell culture material, respectively), which was similar to a manual extraction method used for comparison. The remaining equipment and protocols used were less sensitive, in an extreme case for serum, by a factor of 1000. There was no evidence for cross-contamination of RNA template in any of the negative samples included in these panels. These results are not intended to replace local optimisation and validation, but provide reassurance to laboratories to indicate that the best performing optimised nucleic acid extraction systems can have similar performance.


Mortality risk prediction in burn injury: Comparison of logistic regression with machine learning approaches.
Predicting mortality from burn injury has traditionally employed logistic regression models. Alternative machine learning methods have been introduced in some areas of clinical prediction as the necessary software and computational facilities have become accessible. Here we compare logistic regression and machine learning predictions of mortality from burn. An established logistic mortality model was compared to machine learning methods (artificial neural network, support vector machine, random forests and naïve Bayes) using a population-based (England & Wales) case-cohort registry. Predictive evaluation used: area under the receiver operating characteristic curve; sensitivity; specificity; positive predictive value and Youden's index. All methods had comparable discriminatory abilities, similar sensitivities, specificities and positive predictive values. Although some machine learning methods performed marginally better than logistic regression the differences were seldom statistically significant and clinically insubstantial. Random forests were marginally better for high positive predictive value and reasonable sensitivity. Neural networks yielded slightly better prediction overall. Logistic regression gives an optimal mix of performance and interpretability. The established logistic regression model of burn mortality performs well against more complex alternatives. Clinical prediction with a small set of strong, stable, independent predictors is unlikely to gain much from machine learning outside specialist research contexts.


Eosinophilic lingual tonsillitis induced by sublingual immunotherapy: A case series.
The new observation of eosinophilic lingual tonsillitis as a possible adverse reaction to sublingual immunotherapy is likely to stimulate new investigations aimed at improving the understanding of the mechanisms of biodistribution of extracts placed at the sublingual level.


Magnitude and predictors of anemia among preschool children (36-59 months) in Atingo town, Jimma, Ethiopia.
Anemia is a serious public health concern that affects more than 25% of the world's population. It is still widespread and at its most severe in Ethiopia. This study pointed to identify the magnitude and predictors of anemia in preschool children in Atinago. A structured interview and anthropometric metrics had been used in a cross-sectional study to collect data from 309 preschool children using a systematic sampling strategy from May 10 to June 25, 2022. Frequencies, percentages, means, and a bar chart were created as descriptive statistics. Factors that were significant at the 25% level in univariate analysis were run through multiple logistic models. Odds ratios with respective 95% confidence intervals were developed to determine the relevant predictors. The majority (51.7%) of preschool children in Atinago town had anemia. The finding reveals that poor dietary diversity (adjusted odds ratio [AOR] = 1.77, 95% confidence interval [CI] = 1.02-3.07), children from families with food insecurity (AOR = 2.28, 95% CI = 1.31-3.9), child-mothers used iron folate for less than 3 months during pregnancy (AOR = 1.93, 95% CI = 1.07-3.48), households with more than five children (AOR = 1.880, 95% CI = 1.12-3.18), and stunted children (AOR = 1.78, 95% CI = 1.05-3.01) were highly susceptible to anemia. The findings indicate that anemia was a serious issue among preschool children in Atinago. Therefore, stakeholders should provide community-based nutrition training on consuming diverse diets, dietary improvements in the home, consuming iron-rich meals, and the like; encourage mothers to participate in early ANC follow-up; and strengthen activities aimed at identifying households with food insecurity status.


Heparin-induced skin necrosis associated with thrombocytopenia and acquired protein C and protein S deficiency.
We have described a patient with colon cancer and liver metastases who developed heparin-induced thrombocytopenia and skin necrosis. We believe that the skin necrosis caused by the heparin/platelet factor 4 antibody was exacerbated by the acquired protein C and protein S deficiency. After the heparin was discontinued and infection treated, the skin necrosis and thrombocytopenia resolved. This case illustrates the fact that, in patients with heparin-induced skin necrosis, a search must be undertaken for an underlying pro-thrombotic state, which may precipitate the microthrombosis responsible for skin necrosis. We could not find any previous case reports of heparin-induced skin necrosis associated with isolated protein C deficiency, or combined protein C and protein S deficiency.


Airway compromise in children with anterior neck burns: Beware the scalded child.
The aim of the study was to describe characteristics of children with anterior neck burns admitted to our Paediatric Intensive Care Unit (PICU) and to highlight potential airway complications associated with these injuries, especially in children with scalds. Retrospective review of children with anterior neck burns requiring admission to PICU January 2004-December 2013. Fifty-two children with anterior neck burns were admitted; average age 6.6 years. Thirty sustained flame/explosion injuries; 22 scalds. Seventy-nine per cent were male. Mean total body surface area (TBSA) burn 21%. Forty-seven were intubated. Some primary reasons for intubation included unconsciousness, inhalational/ingestion/direct airway injury and large TBSA. Majority, however, required intubation for airway complications secondary to subcutaneous/soft tissue anterior neck oedema not associated with airway injury/ingestion/inhalational burns. The scalds subgroup mean age was 2.3 years. Eighty-two per cent were male. Mean TBSA 18%. There were no inhalational/ingestion/airway injuries. Nineteen children were intubated; average 9.3 h post-injury. Majority (63%) were intubated post-arrival in the Burn Unit, compared with flame/explosion group (32%). Primary reasons for intubation included large burns, although majority (74%) required intubation for airway complications secondary to subcutaneous and soft tissue anterior neck oedema. For the flame/explosion group this was the case in only 46%, with other primary reasons such as unconsciousness or inhalational injury being the immediate precedent. These results demonstrate that subcutaneous and soft tissue oedema secondary to anterior neck burns may contribute to airway narrowing and compromise requiring intubation. When assessing children's airways, evolving oedema should be recognised and higher observation or early intubation considered regardless of the mechanism of injury.


Purification of RNA-DNA hybrids by exclusion chromatography.
A simple method for selection of RNA-DNA hybrids has been developed and applied to the purification of adenovirus-specific messenger RNA. Cytoplasmic RNA prepared from adenovirus type 2 (ad2)-infected HeLa cells or from an ad2-transformed rat cell line was hybridized in solution to the complementary strands of ad2 DNA. The hybridization mixture was subsequently fractionated by chromatography on a Sepharose 2B column. The intact probe DNA as well as the RNA-DNA hybrids are excluded from the gel matrix and elute with the void volume. Nonhybridized RNA, in contrast, is included into the gel matrix and elutes as a broad peak well separated from the excluded fractions. Fractions corresponding to the void volume, were collected and the RNA-DNA hybrids were denatured in 90% formamide. The selected RNA was separated from the DNA by affinity chromatography on poly(U)-Sepharose. Restriction endonuclease fragments of DNA with a large enough size to make them excluded from the agarose column were also used for hybridization. In these experiments hybridizations were carried out under conditions which would allow R-loop formation (Thomas, M., White, R.L., and Davis, R.W. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 2294-2298) and the hybridized RNA was separated from unhybridized RNA by Sepharose chromatography. The validity of the method was demonstrated by programming an in vitro protein-synthesizing system with selected RNA.


Cytotoxic Activities of O-Cholesteryl-O-Phenyl-N-Phenylphosphoramidate and Its Organometallic Tin(lV) Derivatives.
O-Cholesteryl-O-phenyl-N-phenylphosphoramidate (1) and four organotin (lV) derivatives of the ambidentate O-cholesteryl-O -phenyl phosphorothioate ligand formulated as Me(3) SnOSPR'R"(2), Ph(3)SnOSPR'R"(3), O(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(4), S(CH(2)CH(2)S)(2)Sn(n-Bu)OSPR'R"(5), (R' = O-phenyl; R"= O-cholesteryl) were subjected to cytotoxicity screening against KB (nasopharingel carcinoma), OVCAR-5 (ovarium carcinoma) and SQC-1 UlSO (squamous cell cervix carcinoma) cell cultures. The results of the bioassay showed that these compounds possess potent antitumor activities against the studied human carcinoma cell lines.


60Co-irradiation as an alternate method for sterilization of penicillin G, neomycin, novobiocin, and dihydrostreptomycin.
The effects of the use of 60Co-irradiation to sterilize antibiotics were evaluated. The antibiotic powders were only occasionally contaminated with microorganisms. The D-values of the products and environmental isolates were 0.028, 0.027, 0.015, 0.046, 0.15, 0.018, and 0.19 Mrads for Aspergillus species (UC 7297, 7298), A. fumigatus (UC 7299), Rhodotorula species (UC 7300), Penicillium oxalicum (UC 7269), Pseudomonas maltophilia (UC 6855), and a biological indicator microorganism, Bacillus pumilus spores (ATCC 27142). An irradiation dose of 1.14 Mrads, therefore, was sufficient to achieve a six-log cycle destruction of B. pumilus spores. Based on the bioburden data, a minimum irradiation dose of 1.05 Mrads was calculated to be sufficient to obtain a 10(-6) probability of sterilizing the most radioresistant isolate, Pen. oxalicum. To determine the radiolytic degradation scheme and the stability of the antibiotics following irradiation, high-performance liquid chromatographic (HPLC) methods were developed. The resulting rates of degradation for the antibiotics were 0.6, 1.2, 2.3, and 0.95%/Mrad for penicillin G, neomycin, novobiocin, and dihydrostreptomycin, respectively. Furthermore, radiolytic degradation pathways for the antibiotics were identified and found to be similar to those commonly encountered when antibiotics are subjected to acidic, basic, hydrolytic, or oxidative treatments. No radiolytic compounds unique to 60Co-irradiation were found.


Isolation, characterization, and expression of fatty acid binding protein in the liver of Gallus domesticus.
1. Fatty acid binding protein (FABP) was isolated from chicken liver cytosol. 2. Apparent molecular weight, pI, functional activity, and hybridization of a rat hFABP cDNA probe with chicken liver mRNA suggest that chicken liver FABP is structurally related to hepatic FABP (hFABP) previously isolated and characterized in the rat. 3. Fatty acids bound to liver FABP affect the electrophoretic nature of FABP. 4. Levels of liver FABP mRNA isolated from chickens at various stages of development parallel developmental alterations in lipid metabolism, being highest in day old chicks and laying hens versus juvenile birds.


Novel nonsense mutation of ABHD5 in Dorfman-Chanarin syndrome with unusual findings: a challenge for genotype-phenotype correlation.
Dorfman-Chanarin syndrome is a rare neutral lipid disorder characterised by icthyosis, hepatic steatosis and multisystemic involvement of varying magnitude. It is an autosomal recessive disease caused by mutations in the ABHD5 gene. We report a consanguineous family of Afgani origin, with four affected siblings who were found to have a novel homozygous nonsense mutation g. [27606 G > T]; [27606 G > T]. The clinical findings were unusual in the form of early cirrhosis and hepatic decompensation in one sibling, presence of corneal opacities in male siblings and tessellated fundus in all affected children. Steatosis was minimal in liver biopsy specimens and all children had low vitamin D levels. Genotype-phenotype correlations have not been possible in Dorfman-Chanarin syndrome and the present report raises further challenges for the same.


Urgent closed reduction of the dislocated cervical spine in New Zealand.
Emergent decompression, either by closed reduction or surgical decompression, of the acutely compressed cervical spinal cord is recognized as important in minimizing the neurological outcomes of these injuries. The aim of this study is to optimize New Zealand's capability to perform closed reductions. Regional hospitals throughout New Zealand were surveyed on their capability to reduce acute cervical spine dislocations using traction. A systematic literature review was performed to investigate aspects of patient selection, reduction technique and the outcomes achieved with closed reduction of such injuries. This information was combined with our local experience to develop an evidence-based guideline. Most (12/14) of the regional centres throughout New Zealand have recent experience, remain willing and have the resources necessary to reduce appropriate cervical spine injuries using traction. Fourteen published studies from nine countries detail a 75% success rate from 363 cases of attempted closed reduction, with the greatest neurological recovery noted in patients with shorter time period from injury to reduction. One patient suffered neurological worsening. The published protocols were compared and coupled with our local practice to create an online, step-by-step, evidence-based reference to help clinicians in regional hospitals perform a safe and successful closed reduction. To optimize the capability of inexperienced personnel to perform closed reductions in a safe and timely manner, we have developed an online, step-by-step, evidence-based reference (www.closedreduction.co.nz). This forms part of New Zealand's strategy to achieve urgent cord decompression for appropriate cervical spinal cord injuries.


The relationship between 67Ga accumulation and ATP metabolism in tumor cells in vitro.
Previously, we reported that the deposition of 67Ga into malignant tumors may be a sensitive index of proliferative activity in tumor cells. For the purpose of elucidation of this hypothesis, we investigated the relationship between the accumulation of 67Ga into malignant tumor cells and the intra cellular ATP metabolism in vitro. The uptake of 67Ga into tumor cells was inhibited by adding NaF which is an inhibitor of ATP production. Furthermore, the uptake of 67Ga into tumor cells was strongly inhibited by adding ouabain which is a specific inhibitor of Na+-K+-ATPase. From these in vitro results, it was concluded that there is a correlation between 67Ga uptake and intra cellular ATP metabolism in tumor cells.


The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes.
To determine the false-negative rate of a surgical sentinel lymph node (SLN) mapping algorithm that incorporates more than just removing SLNs in detecting metastatic endometrial cancer. A prospective database of all patients who underwent lymphatic mapping for endometrial cancer was reviewed. Cervical injection of blue dye was used in all cases. The surgical algorithm is as follows: 1) peritoneal and serosal evaluation and washings; 2) retroperitoneal evaluation including excision of all mapped SLNs and suspicious nodes regardless of mapping; and 3) if there is no mapping on a hemi-pelvis, a side-specific pelvic, common iliac, and interiliac lymph node dissection (LND) is performed. Paraaortic LND is performed at the attendings' discretion. The algorithm was retrospectively applied. From 9/2005 to 4/2011, 498 patients received a blue dye cervical injection for SLN mapping. At least one LN was removed in 95% of cases (474/498); at least one SLN was identified in 81% (401/498). SLN correctly diagnosed 40/47 patients with nodal metastases who had at least one SLN mapped, resulting in a 15% false-negative rate. After applying the algorithm, the false-negative rate dropped to 2%. Only one patient, whose LN spread would not have been caught by the algorithm, had an isolated positive right paraaortic LN with a negative ipsilateral SLN and pelvic LND. Satisfactory SLN mapping in endometrial cancer requires adherence to a surgical SLN algorithm and goes beyond just the removal of blue SLNs. Removal of any suspicious node along with side-specific lymphadenectomy for failed mapping are an integral part of this algorithm. Further validation of the false-negative rate of this algorithm is necessary.