Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas.
We developed an original in vitro model dedicated to the exploration of molecular pharmacology of the new oral fluoropyrimidine capecitabine (Xeloda). More specifically, in this report, we investigated whether apoptosis induced by capecitabine was mediated by the Fas/FasL system. To achieve this goal, a specific in vitro coculture model mixing hepatoma and human colorectal cell line was used. A bystander effect was observed between HepG2 and LS174T cells treated with capecitabine. Besides this, Xeloda showed a 7-fold higher cytotoxicity and markedly stronger apoptotic potential in thymidine phosphorylase (TP)-transfected LS174T-c2 cells. The striking enhancement of thymidylate synthase inhibition that we observed in cells with high TP activity was most probably at the origin of the potentiation of capecitabine antiproliferative efficacy. In addition, this increase of sensitivity was accompanied by a strong overexpression of the CD95-Fas receptor on the cell surface. Both Fas and FasL mRNA expression were triggered after exposing TP+ cells to the drug. This implication of Fas in Xeloda-induced apoptosis was next confirmed by using antagonistic anti-Fas and anti-FasL antibodies that proved to reverse capecitabine antiproliferative activity, thus highlighting the key role that Fas could play in the optimization of an antitumor response to fluoropyrimidine drugs. Our data, therefore, show that TP plays a key role in the capecitabine activity and that the Fas/FasL system could be considered as a new determinant for Xeloda efficacy.


The influence of local anesthetic solutions storage on tissue inflammatory reaction.
This study aimed to analyze the influence of storage conditions of local anesthetic solutions in the inflammatory reaction after injection in rats. Twenty-four rats received in their oral mucosa the injection of 2% lidocaine with epinephrine 1:100.000 solutions (LA) submitted to the following storage conditions during a twelve-month period: G1--inside the original packaging, in refrigerator (5±1°C); G2--inside the original box, under light shelter, at room temperature; G3--outside the original box at room temperature (exposed to artificial light for 12 hours/day) and G4--brand new solution. For the controls tests, 0.9% sodium chloride solution was injected in the opposite side. After 6 and 24 hours, three animals of each group were sacrificed and their maxilla along with the soft tissue were removed and submitted to histological analysis (HE). The pH of LA was measured before and after the storage period and no statistically differences were observed between G1 and G4, but both were different from G2 and G3. All the scores of the testing solutions were higher than their respective negative controls, except for G1 at 6 hours. The order of the scores of inflammation after 6 hours was G3>G4>G2=G1. After 24 hours the order was G3>G2>G1>G4. The study showed that the method of storage can influence the pH and the level of inflammatory reaction after the injection of 2% lidocaine with epinephrine 1:100.000.


Behavioural factors associated with fear of litigation as a driver for the increased use of caesarean sections: a scoping review.
To explore the behavioural drivers of fear of litigation among healthcare providers influencing caesarean section (CS) rates. Scoping review. We searched MEDLINE, Scopus and WHO Global Index (1 January 2001 to 9 March 2022). Data were extracted using a form specifically designed for this review and we conducted content analysis using textual coding for relevant themes. We used the WHO principles for the adoption of a behavioural science perspective in public health developed by the WHO Technical Advisory Group for Behavioural Sciences and Insights to organise and analyse the findings. We used a narrative approach to summarise the findings. We screened 2968 citations and 56 were included. Reviewed articles did not use a standard measure of influence of fear of litigation on provider's behaviour. None of the studies used a clear theoretical framework to discuss the behavioural drivers of fear of litigation. We identified 12 drivers under the three domains of the WHO principles: (1) cognitive drivers: availability bias, ambiguity aversion, relative risk bias, commission bias and loss aversion bias; (2) social and cultural drivers: patient pressure, social norms and blame culture and (3) environmental drivers: legal, insurance, medical and professional, and media. Cognitive biases were the most discussed drivers of fear of litigation, followed by legal environment and patient pressure. Despite the lack of consensus on a definition or measurement, we found that fear of litigation as a driver for rising CS rates results from a complex interaction between cognitive, social and environmental drivers. Many of our findings were transferable across geographical and practice settings. Behavioural interventions that consider these drivers are crucial to address the fear of litigation as part of strategies to reduce CS.


Does Training Innate Immunity Confer Broad-spectrum Protection Against Bone and Joint Infection in a Mouse Model?
The innate immune system can recall previous immunologic challenges and thus respond more effectively to subsequent unrelated challenges, a phenomenon called trained immunity. Training the innate immune system before surgery might be a potential option to prevent bone and joint infection. (1) Does the training process cause adverse effects such as fever or organ injury? (2) Does training the innate immune system confer broad-spectrum protection against bone and joint infection in a mouse model? (3) Does trained immunity remain effective for up to 8 weeks in this mouse model? After randomization and group information blinding, we trained the innate immune system of C57BL/6 mice (n = 20 for each group) by intravenously injecting them with either 0.1 mg of zymosan (a toll-like receptor 2 agonist), 0.1 mg of lipopolysaccharide (a toll-like receptor 4 agonist), or normal saline (control). For assessing the host response and possible organ injury after training and infection challenge, we monitored rectal temperature, collected blood to determine leukocyte counts, and performed biochemical and proinflammatory cytokine analyses. After 2 weeks, we then assessed whether trained immunity could prevent infections in an intraarticular implant model subjected to a local or systemic challenge with a broad spectrum of bacterial species (Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes, or Pseudomonas aeruginosa) in terms of culture-positive rate and colony counts. The proportion of culture-positive joint samples from trained and control groups were compared after 4 weeks. Finally, we increased the interval between training and bacterial challenge up to 8 weeks to assess the durability of training efficacies. Training with zymosan and lipopolysaccharide caused mild and transient stress in host animals in terms of elevated rectal temperature and higher blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase levels. Trained mice had fewer culture-positive joint samples after local inoculation with S. aureus (control: 100% [20 of 20]; zymosan: 55% [11 of 20], relative risk 0.55 [95% CI 0.37 to 0.82]; p = 0.001; lipopolysaccharide: 60% [12 of 20], RR 0.60 [95% CI 0.42 to 0.86]; p = 0.003) and systemic challenge with S. aureus (control: 70% [14 of 20]; zymosan: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001; lipopolysaccharide: 15% [3 of 20], RR 0.21 [95% CI 0.07 to 0.63]; p = 0.001) than controls. We observed similar patterns of enhanced protection against local and systemic challenge of E. coli, E. faecalis, S. pyogenes, and P. aeruginosa. Zymosan-trained mice were more effectively protected against both local (control: 20 of 20 [100%], zymosan: 14 of 20 [70%], RR 0.70 [95% CI 0.53 to 0.93]; p = 0.02) and systemic (control: 70% [14 of 20]; zymosan: 30% [6 of 20], RR 0.43 [95% CI 0.21 to 0.89]; p = 0.03) challenge with S. aureus for up to 8 weeks than controls. Trained immunity confers mild stress and broad-spectrum protection against bone and joint infection in a mouse model. The protection conferred by immunity training lasted up to 8 weeks in this mouse model. The results of the current research support further study of this presurgical strategy to mitigate bone and joint infection in other large animal models. If large animal models substantiate the efficacy and safety of presurgical immunity training-based strategies, clinical trials would be then warranted to translate this strategy into clinical practice.


Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length.
Amine containing polymers are extensively studied as special carriers for short-chain RNA (13⁻25 nucleotides), which are applied as gene silencing agents in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of the oligonucleotide⁻polymeric amine interaction. The critical length of the interacting chains is an important parameter which allows us to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interactions of (TCAG)n, n = 1⁻6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethylamino)propyl)(methyl)amino)propyl)-N-methylacrylamide). The critical length for oligonucleotides in interaction with polymeric amines is 8⁻12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells and silencing efficiency against vascular endothelial growth factor (VEGF) was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e., for a sample in which all grafted chains are longer than the critical length for polymeric amine⁻oligonucleotide complexation.


Mechanism of fast protein folding.
An explosion of in vitro experimental data on the folding of proteins has revealed many examples of folding in the millisecond or faster timescale, often occurring in the absence of stable intermediate states. We review experimental methods for measuring fast protein folding kinetics, and then discuss various analytical models used to interpret these data. Finally, we classify general mechanisms that have been proposed to explain fast protein folding into two catagories, heterogeneous and homogeneous, reflecting the nature of the transition state. One heterogeneous mechanism, the diffusion-collision mechanism, can be used to interpret experimental data for a number of proteins.


First molecular characterization of Leishmania infantum species in patients infected with visceral leishmaniasis in Misiones province, Argentina
Introduction: Cutaneous leishmaniasis caused by L. braziliensis has been historically endemic in Argentina and several cases of visceral leishmaniasis following initial cutaneous leishmaniasis have been reported. Visceral leishmaniasis started to appear in Argentina in 2006 in the city of Posadas, Misiones province, affecting both humans and dogs. Objective: To identify the etiologic agent to species level in patients with visceral leishmaniasis diagnosis in Misiones province and describe its clinical and epidemiological characteristics. Materials and methods: A cohort of 24 patients from Misiones province was studied from 2009 to 2016, all with a confirmed diagnosis of visceral leishmaniasis. To identify the Leishmania species involved, patient samples were analyzed by microscopy, serologic studies, DNA detection, and sequencing. Variables such as age, sex, place of residence, clinical signs and symptoms consistent with visceral leishmaniasis were also recorded. Results: 75% (18/24) of the patients studied were males and 25% (6/24) were younger than 4 years. The most frequent symptom was a prolonged fever in 87.5% of the patients (21/24), followed by splenomegaly in 70.8% (17/24). Leishmania infantum was the only parasite species identified in all patients. Conclusion: This finding constitutes the first molecular identification of the Leishmania infantum species in autochthonous patients of Misiones province, Argentina. This study highlights the importance of PCR for species identification in epidemiological studies of visceral leishmaniosis in Argentina.


Shifting gears: An inpatient medical record audit and post-discharge survey of return-to-driving following stroke/transient ischaemic attack.
In Australia, all stroke survivors should not drive for four weeks and transient ischaemic attack (TIA) survivors should not drive for two weeks. This study investigates the provision of return-to-driving education in the acute hospital setting and the use of this education by a cohort of Australian patients who have experienced a mild stroke or TIA and who are discharged directly home from their acute hospital admission. A medical record audit was conducted of stroke patients discharged home from a regional hospital in Australia. All audited patients were sent a post-discharge anonymous survey of their post-stroke driving behaviours. A total of 78 medical records were audited (32 women, 46 men; 15 TIA, 63 strokes). Mean age was 67.4 years (SD = 13.7, range 20-89 years). Only 27 (34.6%) patients had documented evidence that return-to-driving was discussed with them by a health professional, with only 10 (12.8%) having a restriction period documented. A total of 31 surveys were analysed (10 females, 21 males) and 20 participants had returned to driving. From 31 survivors of mild stroke/TIA, 21 recalled receiving advice on return-to-driving and seven resumed driving during the non-driving period of one month. Inconsistencies exist in the documentation of return-to-driving management after acute stroke or TIA and it is unknown whether patients who lack documentation in their medical records were provided with education or not.


Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina.
Apoptosis, a physiologically critical process, is characterized by a destruction of the cell after sequential degradation of key cellular components. Here, we set out to explore the fate of the physiologically indispensable nuclear envelope (NE) in this process. The NE mediates the critical nucleocytoplasmic transport through nuclear pore complexes (NPCs). In addition, the NE is involved in gene expression and contributes significantly to the overall structure and mechanical stability of the cell nucleus through the nuclear lamina, which underlies the entire nucleoplasmic face of the NE and thereby interconnects the NPCs, the NE, and the genomic material. Using the nano-imaging and mechanical probing approach atomic force microscopy (AFM) and biochemical methods, we unveiled the fate of the NE during apoptosis. The doomed NE sustains a degradation of both the mediators of the critical selective nucleocytoplasmic transport, namely NPC cytoplasmic filaments and basket, and the nuclear lamina. These observations are paralleled by marked softening and destabilization of the NE and the detection of vesicle-like nuclear fragments. We conclude that destruction of the cell nucleus during apoptosis proceeds in a strategic fashion. Degradation of NPC cytoplasmic filaments and basket shuts down the critical selective nucleocytoplasmic cross-talk. Degradation of the nuclear lamina disrupts the pivotal connection between the NE and the chromatin, breaks up the overall nuclear architecture, and softens the NE, thereby enabling the formation of nuclear fragments at later stages of apoptosis.


Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes.
The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors. The four variants were genotyped in a combined study sample comprising a total of 18,014 subject ascertained from, the population-based Inter99 cohort (n = 6,514), the ADDITION screening cohort (n = 8,662), a population-based study sample (n = 680) and a type 2 diabetic patient group (n = 2,158) from Steno Diabetes Center. No association with overweight, obesity or obesity-related measures was shown for either the INSIG2 rs7566605 or the PFKP rs6602024 variants. However, an interaction between the INSIG2 rs7566605 variant and the level of self-reported physical activity (p(Int) = 0.004) was observed. A BMI difference of 0.53 (SE 0.42) kg/m(2) was found when comparing physically passive homozygous C-allele carriers with physically passive G-allele carriers. No interactions between the two variants and FTO rs9939609 and MC4R rs17782313 were observed. The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. However, if replicated, the INSIG2 rs7566605 may influence the level of BMI in combination with the level of physical activity.


[FISH diagnostics].
For over two decades banding has remained the "gold standard" of cytogenetic analysis, providing the first genome-wide screen for abnormalities. However, conventional cytogenetic banding techniques are limited to the detection of rearrangements involving more than 2 Mb of DNA. In addition,the identification of de novo unbalanced chromosome rearrangements provides a particular challenge for chromosome banding to decipher. In recent years a number of techniques based on FISH have evolved, all of which complement the conventional banding approaches and which have steadily increased the accuracy of cytogenetic diagnosis. FISH is now the method of choice because of the increased sensitivity, and speed with which it can be applied to a variety of cellular targets. In this article we try to highlight the technical aspects of FISH and the practical application of this technique on different tumors (soft tissue tumors, breast carcinomas, renal cell carcinomas, bladder tumors and germ cell tumors).


Protective Role of a Novel Curcuminoid on Alcohol and PUFA-Induced Hyperlipidemia.
Alcohol use is contributing to an unprecedented decline in life expectancy. It induces hyperlipidemia when taken at higher concentrations. Alcoholics usually after a heavy binge of alcohols take fried food items normally made up of polyunsaturated fatty acids (PUFAs). The combined ingestion of alcohol and PUFAs is considered to be dangerous and known to result in hyperlipidemic conditions. Previous studies have shown that curcumin, an active principle of turmeric (Curcuma longa), has antihyperlipidemic properties. So in the present work we have synthesized an analog of curcumin and tested the protective role of that synthetic curcuminoid on alcohol and thermally oxidized sunflower oil-induced hyperlipidemia. Male Albino rats of Wistar strain were used for the experimental study. Antihyperlipidemic activity of the synthetic curcuminoid was evaluated by analyzing the levels of lipids (cholesterol, triglycerides [TGs], phospholipids [PLs], and free fatty acids [FFAs]) in different tissues and histopathological changes in the liver. The results showed that the levels of cholesterol, TGs, and FFAs were increased significantly in alcohol, thermally oxidized sunflower oil (Delta PUFA), and alcohol + Delta PUFAs treated groups. Administration of synthetic curcuminoid effectively reduced these levels. The phospholipid (PL) levels, which were decreased in the liver and kidney and increased in the heart in the alcohol, Delta PUFA, and alcohol + Delta PUFA groups, were positively modulated by treatment with synthetic curcuminoid (CA). Our histopathological observations were also in correlation with the biochemical parameters. From the results obtained, we could conclude that the synthetic curcuminoid effectively protects the system against alcohol and Delta PUFA-induced hyperlipidemia and may become an effective therapeutic agent for the treatment of hyperlipidemia.


Bi-Arrhenius Diffusion and Surface Trapping of ^{8}Li^{+} in Rutile TiO_{2}.
We report measurements of the diffusion rate of isolated ion-implanted ^{8}Li^{+} within ∼120 nm of the surface of oriented single-crystal rutile TiO_{2} using a radiotracer technique. The α particles from the ^{8}Li decay provide a sensitive monitor of the distance from the surface and how the depth profile of ^{8}Li evolves with time. The main findings are that the implanted Li^{+} diffuses and traps at the (001) surface. The T dependence of the diffusivity is described by a bi-Arrhenius expression with activation energies of 0.3341(21) eV above 200 K, whereas at lower temperatures it has a much smaller barrier of 0.0313(15) eV. We consider possible origins for the surface trapping, as well the nature of the low-T barrier.


Serum-free suspension cultivation of PER.C6(R) cells and recombinant adenovirus production under different pH conditions.
PER.C6(R) cell growth, metabolism, and adenovirus production were studied in head-to-head comparisons in stirred bioreactors under different pH conditions. Cell growth rate was found to be similar in the pH range of 7.1-7.6, while a long lag phase and a slower growth rate were observed at pH 6.8. The specific consumption rates of glucose and glutamine decreased rapidly over time during batch cell growth, as did the specific lactate and ammonium production rates. Cell metabolism in both infected and uninfected cultures was very sensitive to culture pH, resulting in dramatic differences in glucose/glutamine consumption and lactate/ammonium production under different pH conditions. It appeared that glucose metabolism was suppressed at low pH but the efficiency of energy production from glucose was enhanced. Adenovirus infection resulted in profound changes in cell growth and metabolism. Cell growth was largely arrested under all pH conditions, while glucose consumption and lactate production were elevated post virus infection. Virus infection induced a reduction in glutamine consumption at low pH but an increase at high pH. The optimal pH for adenovirus production was found to be 7.3 under the experimental conditions used in the study. Deviations from this optimum resulted in significant reductions of virus productivity. The results indicate that culture pH is a very critical process parameter in PER.C6(R) cell culture and adenovirus production.


Multilevel modeling of gingival bleeding on probing in young adult carriers of non-JP2-like strains of Aggregatibacter actinomycetemcomitans.
The influence of Aggregatibacter actinomycetemcomitans on inflammation in subjects with gingivitis has not been studied in great detail. Seventeen healthy young adults with plaque-induced gingivitis or localized mild chronic periodontitis harboring cultivable numbers of A. actinomycetemcomitans were thoroughly examined. Samples of subgingival plaque were obtained from mesial surfaces of all teeth present. In addition, 12 oral mucosal surfaces and unstimulated saliva were sampled. Species identity, presence of the leukotoxin gene, and absence of a specific 530 b deletion in the leukotoxin promoter region indicating non-JP2-like strains were assessed by polymerase chain reaction. Based on a multilevel random intercept model adjusted for probing depth, age, and smoking status, the odds of bleeding on probing was increased by a factor of 1.89 (1.09-3.29, p = 0.024) if, in addition to plaque, A. actinomycetemcomitans could be recovered from the site. At a site without visible supragingival plaque but with cultivable numbers of subgingival A. actinomycetemcomitans the odds ratio of bleeding on probing was 3.37 (0.86-13.2, p = 0.081). Simulating variance partition coefficients revealed that between 1-2% (a clean, shallow site without A. actinomycetemcomitans; a deep site covered by plaque containing A. actinomycetemcomitans) and 6-7% (a moderately deep site with neither visible plaque nor cultivable A. actinomycetemcomitans) of the residual variance was attributable to differences between subjects. The present cross-sectional study indicates that non-JP2-like strains of A. actinomycetemcomitans may enhance gingival bleeding tendency even in the absence of clinically visible supragingival plaque.


Analysis of surgical complications of thyroid diseases: results of a single institution.
The purpose of this study is to compare the complications of different types of thyroidectomy for benign and malignant thyroidal diseases. Between January 2001 and March 2006, 982 patients underwent thyroidectomy in single institute. A retrospective analysis was performed on demographic characteristics and pathology reports of patients, complications of surgery as well as the follow-up of patients. Sixty patients could not be fully followed up and were excluded. The types of the surgical procedures were as follows; 451 (48.9%) total, 137 (14.9%) subtotal, 60 (6.5%) near-total thyroidectomy and 274 (29.8%) lobectomy with isthmectomy. In the benign group, temporary recurrent laryngeal nerve injury (RLNI) was the most common complication in patients with toxic diffuse goiter (TDG 2%) while this complication occurred in patients with differentiated thyroid cancer (DTC 1.5%) in the malign group. Permanent RLNI in benign thyroidal diseases was seen more commonly in patients with toxic multinodular goiter (1.3%). In benign thyroidal diseases, temporary hypoparathyroidism (THPT) was mostly found in patients with TDG (8%), whereas in malignant thyroidal diseases this was found more in patients with DTC (2%). Permanent HPT (PHPT) in benign thyroidal diseases was observed more commonly in patients with multinodular goiter (0.9%). In malignant thyroidal diseases, it was more frequently observed in patients with DTC (0.5%). Infective complications after thyroid surgery are rarely observed and have a low incidence (0.4%). RLNI and HPT are the most common complications of after thyroid surgery but they may be avoided with an accurate technique (Tab. 3, Ref. 15). Full Text (Free, PDF) www.bmj.sk.


Improving early and intermediate results of truncus arteriosus repair: a new technique of truncal valve repair.
Despite improved surgical results for truncus arteriosus, overall mortality rates, remain higher than those reported for other complex congenital heart diseases, especially with truncal valve regurgitation or an interrupted aortic arch. Seventeen patients had complete repair of the truncus arteriosus at the Cleveland Clinic Foundation between August 1993 and June 1997. The age at operation ranged from 2 days to 4.5 years. Associated abnormalities included interrupted aortic arch in 3 patients and abnormal coronary artery anatomy in 3. Four patients had more than moderate truncal valve insufficiency requiring concomitant truncal valve repair. There were no early deaths and only one late death at a mean follow-up of 24 months. The death occurred 3 months postoperatively and resulted from refractory pulmonary vascular obstructive disease in a patient who was referred at 1 year of age. Reoperation was required in 4 patients. Even in the presence of associated anomalies complete repair was performed with a low mortality rate. Truncal valve repair can be performed safely in the neonate with good results.


Studies of substituent effect on asymmetric epoxidation of chromenes by chiral dioxirane.
A series of 6- and 8-substituted chromenes has been investigated for asymmetric epoxidation using chiral ketone catalysts. Up to 93% ee was achieved. Higher ee's are obtained when substrates are substituted at the 6-position. The enhanced enantioselectivity is likely due to the beneficial interaction between the 6-substituent of the substrate and the N-aryl or alkyl group of the ketone catalyst.


Intraperitoneal vancomycin for peritoneal dialysis-associated peritonitis in children: Evaluation of loading dose guidelines.
Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal (IP) recommended pediatric loading dosage is 1000 mg/L of dialysate. This is based on adult pharmacokinetic (PK) studies and roughly translates to the adult recommendation where 30 mg/kg in 2 L is approximately 1000 mg/L. However, since the dialysate volume in pediatric patients is normalized to body surface area and not weight, the current recommended dosing can result in high vancomycin exposure in children. Vancomycin can potentially cause adverse effects. We aimed to determine if the IP vancomycin dosing of 1000 mg/L was causing elevated vancomycin levels and to offer possible dosing recommendations based on PK modeling and simulation. Retrospective review of pediatric patients who had been treated with IP vancomycin for PD-associated peritonitis. Vancomycin levels obtained for clinical monitoring were analyzed using NONMEM to generate population and individual (empiric Bayesian) estimates of vancomycin PK parameters and estimated peak levels. Predicted vancomycin peaks were also simulated from virtual pediatrics patients 3-70 kg following various dosing strategies. Six episodes of peritonitis in three patients were analyzed. In the two episodes treated with 1000 mg/L, the first vancomycin levels (h post) were 95.6 ug/mL (3) and 49 (33) and following 500 mg/L were 33.2 (11), 30.2 (11), 23.6 (24), and 22.1 (11). All patients were cured of their peritonitis without the need for catheter removal. Based on our population PK model, a 1000 mg/L IP vancomycin loading dose will typically result in peak > 50 mg/L in patients weighing <35 kg and >60 mg/L in patients <15 kg. Vancomycin levels will remain above 20 mg/L for over 2 days without additional vancomycin dosing. The data suggest that a loading dose of vancomycin 1000 mg/L leads to higher than desired vancomycin levels and should be lowered. A 500 mg/L loading dosing appears more appropriate and needs further study.


Risk of venous thromboembolism in patients with inflammatory bowel disease.
There is ample evidence of an increased risk of venous thromboembolism (VTE) in inflammatory bowel disease (IBD). Recent large studies have quantified this risk showing that IBD patients run a 1.5 to 3.6 higher risk of developing VTE than healthy controls. The development of VTE in IBD seems to be multifactorial, resulting from multiple interactions between acquired and inherited risk factors. The most important independent acquired risk factors include disease activity, hospitalization, colonic localization, and recent surgery. The main genetic defects that have been established as risk factors for VTE in the general population are rather uncommon in IBD, but when present, they increase the risk of VTE. IBD has been demonstrated to represent an independent risk factor for the recurrence of VTE. An increased risk of VTE-related mortality when compared with non-IBD patients has been reported. The guidelines for diagnosis and treatment of IBD patients with VTE are similar to that of thrombotic non-IBD patients. There is a consensus on the use of thromboprophylaxis mainly in hospitalized IBD patients with acute flares, but the prevention strategies need further evaluation in future studies.


Spectral convergence in tapping and physiological fluctuations: coupling and independence of 1/f noise in the central and autonomic nervous systems.
When humans perform a response task or timing task repeatedly, fluctuations in measures of timing from one action to the next exhibit long-range correlations known as 1/f noise. The origins of 1/f noise in timing have been debated for over 20 years, with one common explanation serving as a default: humans are composed of physiological processes throughout the brain and body that operate over a wide range of timescales, and these processes combine to be expressed as a general source of 1/f noise. To test this explanation, the present study investigated the coupling vs. independence of 1/f noise in timing deviations, key-press durations, pupil dilations, and heartbeat intervals while tapping to an audiovisual metronome. All four dependent measures exhibited clear 1/f noise, regardless of whether tapping was synchronized or syncopated. 1/f spectra for timing deviations were found to match those for key-press durations on an individual basis, and 1/f spectra for pupil dilations matched those in heartbeat intervals. Results indicate a complex, multiscale relationship among 1/f noises arising from common sources, such as those arising from timing functions vs. those arising from autonomic nervous system (ANS) functions. Results also provide further evidence against the default hypothesis that 1/f noise in human timing is just the additive combination of processes throughout the brain and body. Our findings are better accommodated by theories of complexity matching that begin to formalize multiscale coordination as a foundation of human behavior.


The effect of electrical stimulation of the corticospinal tract on motor units of the human biceps brachii.
In healthy human subjects, descending motor pathways including the corticospinal tract were stimulated electrically at the level of the cervicomedullary junction to determine the effects on the discharge of motoneurones innervating the biceps brachii. Post-stimulus time histograms (PSTHs) were constructed for 15 single motor units following electrical stimulation of the corticospinal tract and for 11 units following electrical stimulation of large diameter afferents at the brachial plexus. Responses were assessed during weak voluntary contraction. Both types of stimulation produced a single peak at short latency in the PSTH (mean 8.5 and 8.7 ms, respectively) and of short duration (< 1.4 ms). In separate studies, we compared the latency of the responses to electrical stimulation of the corticospinal tract in the relaxed muscle with that in the contracting muscle. The latency was the same in the two conditions when the intensity of the stimulation was adjusted so that responses of the same size could be compared. Estimates of the descending conduction velocity and measurements of presumed peripheral conduction time suggest that there is less than 0.5 ms for spinal events (including synaptic delays). We propose that in response to electrical stimulation of the descending tract fibres, biceps motoneurones receive a large excitatory input with minimal dispersion and it presumably contains a dominant monosynaptic component.


One new species of Fannia (Diptera, Fanniidae) from Yunnan, China with a key to the Fanniafuscinata-group in China.
The Fannidae includes over 400 described species, mainly known from the Holarctic Region. The number of species in the Oriental Region are underestimated. The Fanniafuscinata-group was established by Wang et al. in 2011, consisting of nine species at present. A new species of the genus Fannia (Diptera, Fanniidae) is described from Yunnan, part of the Oriental Region in China, namely Fanniamenglaensis sp. nov. The detailed description, photographs and drawings of adults and male terminalia of F.menglaensis sp. nov. are provided. All specimens are preserved in the Museum of Beijing Forestry University.


Clinical Validation of BCI-Controlled Wheelchairs in Subjects With Severe Spinal Cord Injury.
Brain-controlled wheelchairs are one of the most promising applications that can help people gain mobility after their normal interaction pathways have been compromised by neuromuscular diseases. The feasibility of using brain signals to control wheelchairs has been well demonstrated by healthy people in previous studies. However, most potential users of brain-controlled wheelchairs are people suffering from severe physical disabilities or who are in a "locked-in" state. To further validate the clinical practicability of our previously proposed P300-based brain-controlled wheelchair, in this study, 10 subjects with severe spinal cord injuries participated in three experiments and completed ten predefined tasks in each experiment. The average accuracy and information transfer rate (ITR) were 94.8% and 4.2 bits/min, respectively. Moreover, we evaluated the physiological and cognitive burdens experienced by these individuals before and after the experiments. There were no significant changes in vital signs during the experiment, indicating minimal physiological and cognitive burden. The patients' average systolic blood pressure before and after the experiment was 113±13.7 mmHg and 114±11.9 mmHg, respectively (P = 0.122). The patients' average heart rates before and after the experiment were 79±8.4/min and 79±8.2/min, respectively (P = 0.147). The average task load, measured by the National Aeronautics and Space Administration task load index, ranged from 10.0 to 25.5. The results suggest that the proposed P300-based brain-controlled wheelchair is safe and reliable; additionally, it does not significantly increase the patient's physical and mental task burden, demonstrating its potential value in clinical applications. Our study promotes the development of a more practical brain-controlled wheelchair system.


Vitamin C and COVID-19.
In numerous animal studies, vitamin C has prevented and alleviated viral and bacterial infections. In a few dozen placebo-controlled trials with humans, vitamin C has shortened infections caused by respiratory viruses, which indicates that the vitamin can also influence viral infections in humans. In critically ill patients, plasma vitamin C levels are commonly very low. Gram doses of vitamin C are needed to increase the plasma vitamin C levels of critically ill patients to the levels of ordinary healthy people. A meta-analysis of 12 trials with 1,766 patients calculated that vitamin C reduced the length of ICU stay on average by 8%. Another meta-analysis found that vitamin C shortened the duration of mechanical ventilation in ICU patients. Two randomized placebo-controlled trials found statistically significant reduction in the mortality of sepsis patients. The effects of vitamin C on acute respiratory distress syndrome (ARDS) frequently complicating COVID-19 pneumonia should be considered. Vitamin C is a safe and inexpensive essential nutrient.


Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives.
Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well-conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient-deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.


Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.
Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.


5-HT1 and 5-HT2 binding properties of derivatives of the hallucinogen 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA).
The affinities of a series of 1-(2,5-dimethoxyphenyl)-2-aminopropane (2,5-DMA) derivatives, most of which are hallucinogenic in man, and several related agents were determined for rat cortical serotonin (5-HT) binding sites. Competition assays were performed in which these agents were competed for the 5-HT2 binding of [3H]ketanserin, or the 5-HT1 binding of [3H]LSD (in the presence of ketanserin). The R(-)-isomers of DOI, DOM and DON (i.e. the 4-iodo, -methyl and -nitro derivatives of 2,5-DMA) were found to be more potent than their racemates and demonstrated selectivity for 5-HT2 sites. These same agents in competing for [3H]ketanserin binding resulted in Hill coefficients significantly less than unity; computer-assisted analysis indicated a two-state model better fit the data. In the presence of 10(-4) M Gpp(NH)p the competition curve for R(-)-DOI produced a Hill coefficient close to unity. These results are consistent with the hypothesis that certain derivatives of 2,5-DMA, in particular R(-)-DOI, may be potent and selective agonists at 5-HT2 binding sites, sites that may constitute a serotonin receptor that is regulated by a guanine nucleotide regulatory protein. Conversely, the interactions of these agents at 5-HT1 sites was with a lower affinity and a lack of stereoselectivity. Although DOI and DOM are amongst the most potent of these agents as hallucinogens, it is still too premature to draw any conclusions regarding a possible relationship between 5-HT binding and hallucinogenic potency.


Site-specific parameter values for the Nuclear Regulatory Commission's food pathway dose model.
Routine operations at the Savannah River Site (SRS) in Western South Carolina result in radionuclide releases to the atmosphere and to the Savannah River. The resulting radiation doses to the off-site maximum individual and the off-site population within 80 km of the SRS are estimated on a yearly basis. These estimates are currently generated using dose models prescribed for the commercial nuclear power industry by the Nuclear Regulatory Commission (NRC). The NRC provides default values for dose-model parameters for facilities without resources to develop site-specific values. A survey of land- and water-use characteristics for the Savannah River area has been conducted to determine site-specific values for water recreation, consumption, and agricultural parameters used in the NRC Regulatory Guide 1.109 (1977) dosimetric models. These site parameters include local characteristics of meat, milk, and vegetable production; recreational and commercial activities on the Savannah River; and meat, milk, vegetable, and seafood consumption rates. This paper describes how parameter data were obtained at the Savannah River Site and the impacts of such data on off-site dose. Dose estimates using site-specific parameter values are compared to estimates using the NRC default values.


An alternative approach using long elephant trunk for extensive aortic aneurysm: elephant trunk anastomosis at the base of the innominate artery.
Although a staged elephant trunk procedure has been widely used, the early mortality of the first stage operation as well as the interval mortality between operations remains unsatisfactory. We developed an alternative elephant trunk procedure to reduce mortality and morbidity. Ascending aorta and arch vessels were minimally dissected. During systemic cooling, a four-branched arch graft with a sewing "collar" and a long "elephant trunk" was prepared. The ascending aorta was opened under selective brain perfusion with moderate hypothermia (25 degrees C), and the elephant trunk was then pulled down into the descending aorta using the catching catheter introduced via a femoral artery. The elephant trunk anastomosis using the collar was made at the base of the innominate artery. The arch vessels were divided and closed at aortic stump, and grafted separately as a consequence of the very proximal site for the elephant trunk anastomosis. Between October 1998 and September 2001, 17 patients, ranging in age from 25 to 79 years (mean 67 years) with extensive aortic aneurysm underwent this operation. Preoperative cardiac complications included coronary artery disease in 5, aortic regurgitation in 3, and 3 of these 8 patients had poor left ventricular function with an ejection fraction less than 40%. Nine patients underwent a second stage operation, in 1 of them the permanent elephant trunk procedure was initially attempted but the second stage procedure was done because of increasing endo-leakage. The mean interval between operations was 8 days (range 1 to 14 days) in the remaining 8 patients. In 5 of 6 patients who underwent the permanent elephant trunk procedure, a decrease in the size of the aneurysm based on thromboexclusion was observed using serial computed tomography scans. A single stage repair was performed in 1 patient. The 30-day survival rate of all operations was 100%, however, there was 1 in-hospital death (6%) after the second operation. There was no stroke, however, paraplegia occurred after the first operation in 1 patient (6%) of the in-hospital death. No new phrenic or recurrent laryngeal nerve palsy occurred as a result of surgery. The present technique using a modification of the elephant trunk technique for extensive aortic aneurysm provides acceptable mortality and morbidity. The present strategy would be an alternative for the standard elephant trunk procedure in some high-risk patients with advanced age and comorbidities.


In vivo and in vitro maturation of oocytes collected from superstimulated wood bison (Bison bison athabascae) during the anovulatory and ovulatory seasons.
Experiments were done to compare the in vivo and in vitro maturational characteristics of cumulus-oocyte complexes (COC) collected from live wood bison. In Experiment 1 (anovulatory season), follicular ablation was done to synchronize follicle wave emergence among bison on Day -1, and FSH was given on Days 0 and 2. Bison were then assigned to 5 groups (n=5/group) in which COC were collected by transvaginal follicle aspiration on Day 4 and either fixed immediately with no maturation (control), matured in vitro for 24 or 30h, or collected on Day 5 after in vivo maturation for 24 or 30h (i.e., after hCG treatment). In Experiment 2 (ovulatory season), bison were treated as described for Experiment 1, but PGF2α (cloprostenol) was given to control the luteal phase on Days -9 and 3. In both experiments, cumulus cell expansion was more extensive following in vivo than in vitro maturation, and the percentage of fully expanded COC was highest in the in vivo 30h groups. Nuclear maturation occurred more rapidly in vitro; 60-70% of oocytes were at the MII stage 24h after in vitro maturation while only 25-27% of oocytes had reached the MII stage after 24h of in vivo maturation. In conclusion, nuclear maturation occurred more rapidly during in vitro vs. in vivo maturation, but was associated with less cumulus expansion than in vivo maturation. In vivo oocyte maturation was more complete at 30 vs. 24h after hCG treatment. Season had no effect on the maturational capacity of wood bison oocytes.


Quantitative angle-resolved SPR imaging of DNA-DNA and DNA-drug kinetics.
We demonstrate the quantitative characterization of DNA-DNA and DNA-drug interactions by angle-resolved surface plasmon resonance (SPR) imaging. Combining the angle-scanning capabilities of traditional SPR with the spatial definition capabilities of imaging, we directly measure DNA and drug surface coverages and kinetics simultaneously for multiple patterned spots. We find excellent agreement of DNA-DNA hybridization kinetics and thermodynamics measured by both the imaging system and traditional SPR. Instrument response and sensitivity is further demonstrated by successful measurement of association and dissociation kinetics of actinomycin-D binding to a low-density doubled-stranded DNA binding sequence. Without independent calibration, analysis of angle-resolved SPR imaging data yields 2.9 +/- 0.1 drugs per duplex at saturation coverage, consistent with all available duplex binding sites being occupied.


Focal dystonia in musicians: phenomenology, pathophysiology, triggering factors, and treatment.
Musician's dystonia is a task-specific movement disorder that manifests itself as a loss of voluntary motor control in extensively trained movements. Approximately 1% of all professional musicians develop musician's dystonia, and in many cases, the disorder terminates the careers of affected musicians. The pathophysiology of the disorder is not completely clarified. Findings include 1) reduced inhibition at different levels of the central nervous system, 2) maladaptive plasticity and altered sensory perception, and 3) alterations in sensorimotor integration. Epidemiological data demonstrate a higher risk for those musicians who play instruments requiring maximal fine-motor skills. For instruments where workload differs across hands, focal dystonia appears more often in the more intensely used hand. In psychological studies, musicians with dystonia have more anxiety and perfectionist tendencies than healthy musicians. These findings strengthen the assumption that behavioral factors may be involved in the etiology of musician's dystonia. Preliminary findings also suggest a genetic contribution to focal task-specific dystonia with phenotypic variations including musician's dystonia. Treatment options include pharmacological interventions, such as trihexyphenidyl or botulinum toxin-A, as well as retraining programs and ergonomic changes in the instrument. Patient-tailored treatment strategies may significantly improve the situation of musicians with focal dystonia. Positive results after retraining and unmonitored technical exercises underline the benefit of an active involvement of patients in the treatment process. Only a minority of musicians, however, return to normal motor control using the currently available therapies.


A Tool Preference Choice Method for RNA Secondary Structure Prediction by SVM with Statistical Tests.
The Prediction of RNA secondary structures has drawn much attention from both biologists and computer scientists. Many useful tools have been developed for this purpose. These tools have their individual strengths and weaknesses. As a result, based on support vector machines (SVM), we propose a tool choice method which integrates three prediction tools: pknotsRG, RNAStructure, and NUPACK. Our method first extracts features from the target RNA sequence, and adopts two information-theoretic feature selection methods for feature ranking. We propose a method to combine feature selection and classifier fusion in an incremental manner. Our test data set contains 720 RNA sequences, where 225 pseudoknotted RNA sequences are obtained from PseudoBase, and 495 nested RNA sequences are obtained from RNA SSTRAND. The method serves as a preprocessing way in analyzing RNA sequences before the RNA secondary structure prediction tools are employed. In addition, the performance of various configurations is subject to statistical tests to examine their significance. The best base-pair accuracy achieved is 75.5%, which is obtained by the proposed incremental method, and is significantly higher than 68.8%, which is associated with the best predictor, pknotsRG.


Whole blood: back to the future.
We present data comparing whole blood with blood components and summarize the data that support increased availability of whole blood for patients with life-threatening bleeding. Recent data indicate that whole-blood transfusion is associated with improved or comparable survival compared with resuscitation with blood components. These data complement randomized controlled trials indicating that platelet-containing blood products stored at 4 °C have superior hemostatic function, compared with platelet-containing blood products at 22 °C. Whole blood is rarely available in civilian hospitals and, thus, is rarely transfused into patients with hemorrhagic shock. Misconceptions that whole blood must be ABO specific, that whole blood cannot be leukoreduced and maintain platelets, and that cold storage causes loss of platelet function have limited its availability. Understanding that these barriers are not insurmountable will improve the availability of whole blood and facilitate its use. In addition, there are logistical advantages of whole-blood-based resuscitation, as compared with component therapy, for hemorrhagic shock. Low titer Group O whole blood stored for up to 21 days at 4 °C merits further study to compare its efficacy and safety with current resuscitation approaches for patients with life-threatening bleeding.


Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.
A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.


Electrochemical microsensors for the detection of cadmium(II) and lead(II) ions in plants.
Routine determination of trace metals in complex media is still a difficult task for many analytical instruments. The aim of this work was to compare three electro-chemical instruments [a standard potentiostat (Autolab), a commercially available miniaturized potentiostat (PalmSens) and a homemade micropotentiostat] for easy-to-use and sensitive determination of cadmium(II) and lead(II) ions. The lowest detection limits (hundreds of pM) for both metals was achieved by using of the standard potentiostat, followed by the miniaturized potentiostat (tens of nM) and the homemade instrument (hundreds of nM). Nevertheless, all potentiostats were sensitive enough to evaluate contamination of the environment, because the environmental limits for both metals are higher than detection limits of the instruments. Further, we tested all used potentiostats and working electrodes on analysis of environmental samples (rainwater, flour and plant extract) with artificially added cadmium(II) and lead(II). Based on the similar results obtained for all potentiostats we choose a homemade instrument with a carbon tip working electrode for our subsequent environmental experiments, in which we analyzed maize and sunflower seedlings and rainwater obtained from various sites in the Czech Republic.


Surveillance for Violent Deaths - National Violent Death Reporting System, 39 States, the District of Columbia, and Puerto Rico, 2018.
In 2018, approximately 68,000 persons died of violence-related injuries in the United States. This report summarizes data from CDC's National Violent Death Reporting System (NVDRS) on violent deaths that occurred in 39 states the District of Columbia, and Puerto Rico in 2018. Results are reported by sex, age group, race and ethnicity, method of injury, type of location where the injury occurred, circumstances of injury, and other selected characteristics. 2018. NVDRS collects data regarding violent deaths obtained from death certificates, coroner and medical examiner reports, and law enforcement reports. This report includes data collected for violent deaths that occurred in 2018. Data were collected from 36 states with statewide data (Alabama, Alaska, Arizona, Colorado, Connecticut, Delaware, Georgia, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Rhode Island, South Carolina, Utah, Vermont, Virginia, Washington, West Virginia, and Wisconsin), three states with data from counties representing a subset of their population (21 California counties, 28 Illinois counties, and 39 Pennsylvania counties), the District of Columbia, and Puerto Rico. NVDRS collates information for each death and links deaths that are related (e.g., multiple homicides, homicide followed by suicide, or multiple suicides) into a single incident. For 2018, NVDRS collected information on 52,773 fatal incidents involving 54,170 deaths that occurred in 39 states and the District of Columbia. In addition, information was collected on 880 fatal incidents involving 975 deaths in Puerto Rico. Data for Puerto Rico were analyzed separately. Of the 54,170 deaths, the majority (64.1%) were suicides, followed by homicides (24.8%), deaths of undetermined intent (9.0%), legal intervention deaths (1.4%) (i.e., deaths caused by law enforcement and other persons with legal authority to use deadly force acting in the line of duty, excluding legal executions), and unintentional firearm deaths (<1.0%). (The term "legal intervention" is a classification incorporated into the International Classification of Diseases, Tenth Revision, and does not denote the lawfulness or legality of the circumstances surrounding a death caused by law enforcement.) Demographic patterns and circumstances varied by manner of death. The suicide rate was higher among males than among females and was highest among adults aged 35-64 years and non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic White persons. The most common method of injury for suicide was a firearm among males and hanging, strangulation, or suffocation among females. Suicide was most often preceded by a mental health, intimate partner, or physical health problem, or a recent or impending crisis during the previous or upcoming 2 weeks. The homicide rate was highest among persons aged 20-24 years and was higher among males than females. Non-Hispanic Black males experienced the highest homicide rate of any racial or ethnic group. The most common method of injury for homicide was a firearm. When the relationship between a homicide victim and a suspect was known, the suspect was most frequently an acquaintance or friend for male victims and a current or former intimate partner for female victims. Homicides most often were precipitated by an argument or conflict, occurred in conjunction with another crime, or, for female victims, were related to intimate partner violence. Homicide suspects were primarily male and the highest proportion were aged 25-44 years. When race and ethnicity information was known, non-Hispanic Black persons comprised the largest group of suspects overall and among those aged ≤44 years, and non-Hispanic White persons comprised the largest group of suspects among those aged ≥45 years. Almost all legal intervention deaths were experienced by males, and the legal intervention death rate was highest among males aged 30-34 years. Non-Hispanic AI/AN males had the highest legal intervention death rate, followed by non-Hispanic Black males. A firearm was used in the majority of legal intervention deaths. When a specific type of crime was known to have precipitated a legal intervention death, the type of crime was most frequently assault or homicide. The most frequent circumstances reported for legal intervention deaths were use of a weapon by the victim in the incident and a mental health or perceived substance use problem (other than alcohol use). Law enforcement officers who inflicted fatal injuries in the context of legal intervention deaths were primarily males aged 25-44 years. Unintentional firearm deaths were most frequently experienced by males, non-Hispanic White persons, and persons aged 15-24 years. These deaths most often occurred while the shooter was playing with a firearm and most frequently were precipitated by a person unintentionally pulling the trigger or mistakenly thinking that the firearm was unloaded. The rate of deaths of undetermined intent was highest among males, particularly among non-Hispanic Black and non-Hispanic AI/AN males, and among persons aged 45-54 years. Poisoning was the most common method of injury in deaths of undetermined intent, and opioids were detected in approximately 80% of decedents tested for those substances. This report provides a detailed summary of data from NVDRS on violent deaths that occurred in 2018. The suicide rate was highest among non-Hispanic AI/AN and non-Hispanic White males, and the homicide rate was highest among non-Hispanic Black males. Mental health problems, intimate partner problems, interpersonal conflicts, and acute life stressors were primary circumstances for multiple types of violent death. Circumstances for suspects of homicide varied by age group and included having prior contact with law enforcement and involvement in incidents that were precipitated by another crime, intimate partner violence, and drug dealing or substance use. NVDRS data are used to monitor the occurrence of violence-related fatal injuries and assist public health authorities in developing, implementing, and evaluating programs, policies, and practices to reduce and prevent violent deaths. For example, Arizona and Wisconsin used their state-level VDRS data to support suicide prevention efforts within their respective states. Wisconsin VDRS used multiple years of data (2013-2017) to identify important risk and protective factors and subsequently develop a comprehensive suicide prevention plan. Arizona VDRS partners with the Arizona Be Connected Initiative to provide customized community-level data on veteran suicide deaths in Arizona. Similarly, states participating in NVDRS have used their VDRS data to examine intimate partner violence-related deaths to support prevention efforts. For example, data from the South Carolina VDRS were used to examine intimate partner homicides that occurred in South Carolina during 2017. South Carolina VDRS found that 12% of all homicides that occurred in 2017 were intimate partner violence-related, with females accounting for 52% of intimate partner homicide-related victims. These data were shared with domestic violence prevention collaborators in South Carolina to bolster their efforts in reducing intimate partner violence-related deaths. In 2018, NVDRS data included four additional states compared with 2017, providing more comprehensive and actionable violent death information for public health efforts to reduce violent deaths.


[Preoperative chemoradiotherapy with S-1 for advanced low rectal cancer].
We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.


On the Factors Which Determine Massive beta-Carotene Accumulation in the Halotolerant Alga Dunaliella bardawil.
Dunaliella bardawil, a beta-carotene-accumulating halotolerant alga, has been analyzed for the effect of various growth conditions on its pigment content, and compared with Dunaliella salina, a beta-carotene nonaccumulating species. In D. bardawil, increasing light intensity and light period or inhibiting growth by various stress conditions such as nutrient deficiency or high salt concentration caused a decrease in the content of chlorophyll per cell and an increase in the amount of beta-carotene per cell. As a result, the beta-carotene-to-chlorophyll ratio increased from about 0.4 to 13 grams per gram and the alga changed its visual appearance from green to deep orange. D. salina grown similarly decreased in content of both chlorophyll and beta-carotene per cell and the culture turned from green to yellowish. Low chlorophyll-containing cells of D. bardawil or D. salina exhibit very high photosynthetic rates when expressed on a chlorophyll basis ( approximately 600 micromoles O(2) evolved per milligram chlorophyll per hour).Variation of pigment content in D. bardawil by a large variety of environmental agents has been correlated with the integral irradiance received by the algal culture during a division cycle. The higher the integral irradiance per division cycle, the lower the chlorophyll content per cell; the higher the beta-carotene content per cell, and therefore the higher the beta-carotene-to-chlorophyll ratio. The results are interpreted as indicating a protecting effect of beta-carotene against injury by high irradiance under conditions of impairment in chlorophyll content per cell.


Desire to die in terminally ill people: a framework for assessment and intervention.
"Desire-to-die" statements made by people with terminal illness may be expressions of depression, suicidal intent, or coping. Careful evaluation can help the social worker understand the meaning of a particular patient's statement. The framework presented in this article suggests that all patients expressing a wish for death be assessed for both depression and suicide risk. This assessment can identify those patients who are depressed or suicidal, as well as those using these statements as a way of coping or as an indication of a rational choice for suicide. Differentiating among patients' meanings in this way leads to appropriate interventions.


Validity and Reliability of the Korean Version of the Health Information Technology Usability Evaluation Scale: Psychometric Evaluation.
Rigorous development of mobile technologies requires the use of validated instruments to evaluate the usability of these tools, which has become more relevant with the expansion of these technologies. Although various usability evaluation tools have been developed, there are relatively few simple evaluation instruments that have been validated across diseases and languages in mobile health (mHealth) information technology for use in multiple diseases. The purpose of this study is to validate the Korean version of the Health Information Technology Usability Evaluation Scale (Korean Health-ITUES) and assess its applicability for different health conditions. To develop the Korean Health-ITUES, we used a validation process involving the following 3 steps: (1) customization of the Health-ITUES for menstrual symptoms, (2) translation of the Health-ITUES from English into Korean, and (3) examination of the reliability and validity of the instrument. The translation process adhered to the World Health Organization (WHO) guidelines for translation and back-translation, expert review, and reconciliation. The Korean Health-ITUES showed reliable internal consistency with Cronbach α=.951; meanwhile, factor loadings of the 20 items in the 4 subscales ranged from 0.416 to 0.892. The Health-ITUES demonstrated reliability and validity for its use in assessing mHealth apps' usability in young Korean women with menstrual discomfort. Given the strong psychometric properties of this tool in Korean and English and across 2 different health conditions, the Health-ITUES is a valid and reliable instrument for assessing the usability of mHealth apps. The Health-ITUES is also a valid instrument for evaluating mHealth technologies, which are widely used by patients to self-manage their health and by providers to improve health care delivery.


Progesterone Induced Blocking Factor Reduces Hypertension and Placental Mitochondrial Dysfunction in Response to sFlt-1 during Pregnancy.
Preeclampsia (PE) is characterized by new onset hypertension in association with placental ischemia, reduced fetal weight, elevated soluble fms-like tyrosine kinase-1 (sFlt-1), and placental mitochondrial (mt) dysfunction and oxidative stress (ROS). Progesterone induced blocking factor (PIBF) is a product of progesterone signaling that blocks inflammatory processes and we have previously shown PIBF to lower mean arterial blood pressure (MAP) and sFlt-1 in a rat model of PE. Infusion of sFlt-1 causes hypertension and many characteristics of PE in pregnant rodents, however, its role in causing mt dysfunction is unknown. Therefore, we hypothesize that PIBF will improve mt function and MAP in response to elevated sFlt-1 during pregnancy. We tested our hypothesis by infusing sFlt-1 via miniosmotic pumps in normal pregnant (NP) Sprague-Dawley rats (3.7 μg·kg-1·day-1) on gestation days (GD) 13-19 in the presence or absence of PIBF (2.0 µg/mL) injected intraperitoneally on GD 15 and examined mean arterial blood pressure (MAP) and placental mt ROS on GD 19. sFlt-1 increased MAP to 112 + 2 (n = 11) compared to NP rats (98 + 2 mmHg, n = 15, p < 0.05), which was lowered in the presence of sFlt-1 (100 + 1 mmHg, n = 5, p < 0.05). Placental mtATP was reduced in sFlt-1 infused rats versus NP controls, but was improved with PIBF. Placental mtROS was elevated with sFlt-1 compared to NP controls, but was reduced with PIBF. Sera from NP + sFlt-1 increased endothelial cell mtROS, which was attenuated with PIBF. These data demonstrate sFlt-1 induced HTN during pregnancy reduces placental mt function. Importantly, PIBF improved placental mt function and HTN, indicating the efficacy of improved progesterone signaling as potential therapeutics for PE.


Catalytic role of gold in gold-based catalysts: a density functional theory study on the CO oxidation on gold.
Gold-based catalysts have been of intense interests in recent years, being regarded as a new generation of catalysts due to their unusually high catalytic performance. For example, CO oxidation on Au/TiO(2) has been found to occur at a temperature as low as 200 K. Despite extensive studies in the field, the microscopic mechanism of CO oxidation on Au-based catalysts remains controversial. Aiming to provide insight into the catalytic roles of Au, we have performed extensive density functional theory calculations for the elementary steps in CO oxidation on Au surfaces. O atom adsorption, CO adsorption, O(2) dissociation, and CO oxidation on a series of Au surfaces, including flat surfaces, defects and small clusters, have been investigated in detail. Many transition states involved are located, and the lowest energy pathways are determined. We find the following: (i) the most stable site for O atom on Au is the bridge site of step edge, not a kink site; (ii) O(2) dissociation on Au (O(2)-->2O(ad)) is hindered by high barriers with the lowest barrier being 0.93 eV on a step edge; (iii) CO can react with atomic O with a substantially lower barrier, 0.25 eV, on Au steps where CO can adsorb; (iv) CO can react with molecular O(2) on Au steps with a low barrier of 0.46 eV, which features an unsymmetrical four-center intermediate state (O-O-CO); and (v) O(2) can adsorb on the interface of Au/TiO(2) with a reasonable chemisorption energy. On the basis of our calculations, we suggest that (i) O(2) dissociation on Au surfaces including particles cannot occur at low temperatures; (ii) CO oxidation on Au/inactive-materials occurs on Au steps via a two-step mechanism: CO+O(2)-->CO(2)+O, and CO+O-->CO(2); and (iii) CO oxidation on Au/active-materials also follows the two-step mechanism with reactions occurring at the interface.


Catheter-directed therapy for acute renal vein thrombosis in systemic lupus erythematosus: A case report.
We report our experience using catheter-directed thrombectomy/thrombolysis (CDT) to treat a patient with acute renal vein thrombosis (RVT) associated with systemic lupus erythematosus (SLE). A 34-year-old woman presented with persistent left flank pain, and a renal ultrasonography examination revealed an enlarged left kidney. Contrast-enhanced computed tomography confirmed the presence of acute left RVT. Because medical treatment failed to relieve her pain and the renal function was deteriorating, we attempted to salvage the occluded left renal vein using an endovascular approach. The pain was completely relieved after a CDT and an overnight urokinase infusion. A follow-up computed tomography examination revealed the complete resolution of the thrombus. The creatinine level returned to normal (1.7-0.4 mg/dL), along with contrast enhancement in the left kidney, and this suggested the preservation of renal function. To our knowledge, this is the first report utilizing CDT to treat SLE-associated RVT. When the renal function is deteriorating, CDT is worth considering for RVT if conventional medical treatment has failed. © 2016 Wiley Periodicals, Inc.


Robust prototypical anti-icing coatings with a self-lubricating liquid water layer between ice and substrate.
A robust prototypical anti-icing coating with a self-lubricating liquid water layer (SLWL) is fabricated via grafting cross-linked hygroscopic polymers inside the micropores of silicon wafer surfaces. The ice adhesion on the surface with SLWL is 1 order of magnitude lower than that on the superhydrophobic surfaces and the ice formed atop of it can be blown off by an action of strong breeze. The surface with self-lubricating liquid water layer exhibits excellent capability of self-healing and abrasion resistance. The SLWL surface should also find applications in antifogging and self-cleaning by rainfall, in addition to anti-icing and antifrosting.


Immunogenicity and Protective Activity of Pigeon Circovirus Recombinant Capsid Protein Virus-Like Particles (PiCV rCap-VLPs) in Pigeons (Columba livia) Experimentally Infected with PiCV.
Pigeon circovirus (PiCV) is the most recurrent virus diagnosed in pigeons and is among the major causative agents of young pigeon disease syndrome (YPDS). Due to the lack of an established laboratory protocol for PiCV cultivation, development of prophylaxis is hampered. Alternatively, virus-like particles (VLPs), which closely resemble native viruses but lack the viral genetic material, can be generated using a wide range of expression systems and are shown to have strong immunogenicity. Therefore, the use of VLPs provides a promising prospect for vaccine development. In this study, transfected human embryonic kidney (HEK-293) cells, a mammalian expression system, were used to express the PiCV capsid protein (Cap), which is a major component of PiCV and believed to contain antibody epitopes, to obtain self-assembled VLPs. The VLPs were observed to have a spherical morphology with diameters ranging from 12 to 26 nm. Subcutaneous immunization of pigeons with 100 µg PiCV rCap-VLPs supplemented with water-in-oil-in-water (W/O/W) adjuvant induced specific antibodies against PiCV. Observations of the cytokine expression and T-cell proliferation levels in spleen samples showed significantly higher T-cell proliferation and IFN- γ expression in pigeons immunized with VLPs compared to the controls (p < 0.05). Experimentally infected pigeons that were vaccinated with VLPs also showed no detectable viral titer. The results of the current study demonstrated the potential use of PiCV rCap-VLPs as an effective vaccine candidate against PiCV.


Anatomical localization revealed by MEG recordings of the human somatosensory system.
A 14-channel cryogenic magnetometer system (BTi) was used to record the magnetic fields over the left hemisphere of 3 human subjects in order to locate the sources of responses to tactile stimulation of the index, the thumb and the little finger of the right hand. The locations of the active dipole sources determined using the spherical model were then projected onto the magnetic resonance image (MRI) of the individual subjects providing an anatomical localization. The MRI slices were also used to construct a 3-dimensional image to enhance visualization of the area of the calculated sources. The locations of the dipole sources from the 3 fingers were distinct from one another in all subjects. An analysis of variance ('ANOVA') showed the most significant (P less than 0.05) difference in source location between the little finger and the thumb with the former being superior to the sources of the other 2 fingers in all of the subjects. In all cases, the sources were found to be located on the postcentral gyrus. The strength of the equivalent dipole sources and the amplitudes of the responses to stimulation for all 3 fingers showed a consistent trend among all of the 3 subjects, with the thumb having the largest response. In general, no signs of habituation were found.


Stereoselective interaction between DNA and chiral surfaces.
ssDNA exhibits much different adsorption behaviors on enantiomer modified surfaces, which can be explained by the stereoselective H-bond interaction between DNA and the chiral surfaces. This effect not only may help to understand the stereospecific cell/substrate interaction and the origin of the chiral preference in nature but also brings novel insights to the study of DNA properties and the application in biochemical devices.


Childhood obesity: rapid weight gain in early childhood and subsequent cardiometabolic risk.
Dynamic changes in body weight have long been recognized as important indicators of risk for human health. Many population-based observational studies have shown that rapid weight gain during infancy, including a catch-up growth phenomenon or adiposity rebound in early childhood, predisposes a person to the development of obesity, type 2 diabetes, and cardiovascular diseases later in life. However, a consensus has not been established regarding which period of weight gain contributes to future risks. This review evaluates recent evidence on the relationship between early rapid growth and future obesity and cardiometabolic risk, with a focus on the differential significance of rapid weight gain in infancy and early childhood. Although there is a need for attention to childhood growth during early infancy before 1 yr of age as it may be related to future obesity, emerging evidence strongly suggests that toddlers showing an increase in body mass index (BMI) before 3 yr of age, a period normally characterized by decreased BMI, are prone to developing later cardiometabolic risk.


Thiol-Ene Photo-Click Collagen-PEG Hydrogels: Impact of Water-Soluble Photoinitiators on Cell Viability, Gelation Kinetics and Rheological Properties.
Thiol-ene photo-click hydrogels were prepared via step-growth polymerisation using thiol-functionalised type-I collagen and 8-arm poly(ethylene glycol) norbornene-terminated (PEG-NB), as a potential injectable regenerative device. Type-I collagen was thiol-functionalised by a ring opening reaction with 2-iminothiolane (2IT), whereby up to 80 Abs.% functionalisation and 90 RPN% triple helical preservation were recorded via 2,4,6-Trinitrobenzenesulfonic acid (TNBS) colorimetric assay and circular dichroism (CD). Type, i.e., either 2-Hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone (I2959) or lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP), and concentration of photoinitiator were varied to ensure minimal photoinitiator-induced cytotoxicity and to enable thiol-ene network formation of collagen-PEG mixtures. The viability of G292 cells following 24 h culture in photoinitiator-supplemented media was largely affected by the photoinitiator concentration, with I2959-supplemented media observed to induce higher toxic response (0.1 → 0.5% (w/v) I2959, cell survival: 62 → 2 Abs.%) compared to LAP-supplemented media (cell survival: 86 → 8 Abs.%). In line with the in vitro study, selected photoinitiator concentrations were used to prepare thiol-ene photo-click hydrogels. Gelation kinetics proved to be largely affected by the specific photoinitiator, with LAP-containing thiol-ene mixtures leading to significantly reduced complete gelation time (τ: 187 s) with respect to I2959-containing mixtures (τ: 1683 s). Other than the specific photoinitiator, the photoinitiator concentration was key to adjusting the hydrogel storage modulus (G'), whereby 15-fold G' increase (232 → 3360 Pa) was observed in samples prepared with 0.5% (w/v) compared to 0.1% (w/v) LAP. Further thiol-ene formulations with 0.5% (w/v) LAP and varied content of PEG-NB were tested to prepare photo-click hydrogels with porous architecture, as well as tunable storage modulus (G': 540⁻4810 Pa), gelation time (τ: 73⁻300 s) and swelling ratio (SR: 1530⁻2840 wt %). The photoinitiator-gelation-cytotoxicity relationships established in this study will be instrumental to the design of orthogonal collagen-based niches for regenerative medicine.


Granulocyte-macrophage colony-stimulating factor (GM-CSF) ameliorates chemotherapy-induced neutropenia in children with solid tumors.
Neutropenia is one of the risk factors for severe therapy-related morbidity in childhood malignancies. We have studied the potential of GM-CSF to shorten the neutropenic period after normal-dose chemotherapy in children who were treated for solid tumors. Patients with osteosarcomas, with Ewing sarcomas, or with rhabdomyosarcomas received 10 daily subcutaneous doses GM-CSF (Leucomax, 5 micrograms/kg) after a course of normal-dose chemotherapy in an open-label study. Because these patients were treated with different combinations of chemotherapeutic agents, they were randomized before each pair of identical courses of chemotherapy to receive GM-CSF after the first or after the second course. Fourteen such combinations could be evaluated in eight patients. The results show that GM-CSF significantly reduced the mean duration of the chemotherapy-induced neutropenia (mean reduction +/- SEM in days: 2.2 +/- 0.6, P = .003). There was no significant difference between the mean number of days with fever in either group. GM-CSF was well tolerated by all patients. We conclude that GM-CSF reduced the mean neutropenic period in children with solid tumors who were treated with standard-dose chemotherapy.


Evidence for a Relationship between H Excretion and Auxin in Shoot Gravitropism.
The role of auxin and protons in the gravitropic response of the sunflower (Helianthus annuus L. cv Sungold) hypocotyl has been investigated. No physiological asymmetry in acid-growth capacity could be detected between the upper and lower surfaces of gravistimulated hypocotyls. These data imply that neutral buffers inhibit shoot gravitropism by preventing the establishment of a lateral proton gradient along gravitropically stimulated hypocotyls. Indirect evidence that auxin is involved in the establishment and/or maintenance of such a gradient derives from the quantitative assessment of the effects of exogenous auxin, anti-auxins, and vanadate on gravicurvature. At low concentrations, exogenous auxin accelerated curvature; at high concentrations, curvature was prevented. Vanadate, an inhibitor of auxin-enhanced H(+) secretion, alpha-(p-chlorophenoxy)isobutyric acid (PCIB), an anti-auxin, and 2,3,5-triiodobenzoic acid (TIBA), an auxin-transport inhibitor, prevented observable asymmetric proton excretion using a brom cresol purple agar technique and also inhibited gravicurvature. Vanadate, PCIB, and TIBA inhibition of gravicurvature could be reversed with acid treatment to the lower surface of a gravistimulated hypocotyl. Auxin treatment to the lower surface of a gravistimulated hypocotyl did not reverse vanadate-induced inhibition, but it did partially reverse PCIB- and TIBA-induced inhibition. These results indicate a close relationship between the acid-growth theory and the differential growth responses of the sunflower hypocotyl during gravitropism.


Decreased dosage of acidified sodium chlorite reduces microbial contamination and maintains organoleptic qualities of ground beef products.
Acidified sodium chlorite (ASC) spray was evaluated at decreased dosages and application rates to determine its efficacy for reducing bacterial contamination on boneless beef trimmings used for production of raw ground beef products while maintaining desirable consumer qualities in the finished ground beef products. Two different applications of ASC (600 ppm applied at a rate of 1.3 oz/lb and 300 ppm applied at a rate of 1 oz/lb) were used to treat boneless beef trimmings before grinding. The effect of ASC treatment on 50/50 lean beef trimmings was greater than on 90/10 trimmings. ASC at 600 ppm reduced both the aerobic plate counts (APC) and Enterobacteriaceae counts (EBC) by 2.3 log CFU/g on 50/50 trimmings, whereas treatment with 300 ppm ASC reduced APC and EBC of 50/50 trimmings by 1.1 and 0.7 log CFU/g, respectively. Ground beef formulations of 90/10 and 73/27 were produced from the treated boneless beef trim and packaged in chubs and in modified atmosphere packaging. The efficacy of ASC spray treatment to inhibit APC and EBC over the shelf life of each ground beef product was monitored. The APC and EBC in ground beef chubs were reduced by 1.0 to 1.5 log CFU/g until day 20. The APC and EBC for products in modified atmosphere packaging were reduced 1.5 to 3.0 log CFU/g throughout their shelf life. Both decreased dosages of ASC were equally effective on 90/10 lean ground beef, but the 300 ppm ASC treatment was slightly better at reducing the EBC of 73/27 ground beef. The organoleptic qualities (color, odor, and taste) of the ground beef products treated with 300 ppm ASC were found to be superior to those treated with 600 ppm ASC. Our results indicated that decreased dosages of ASC reduce contamination and lengthen the shelf life of ground beef. Furthermore, the 300 ppm ASC treatment reduced bacterial counts while maintaining desirable organoleptic ground beef qualities.


Comparison of the effects of racemic ketamine and S-ketamine for anesthesia in Rheem gazelles (Gazella subgutturosa marica) and Subgutturosa gazelles (Gazella subgutturosa subgutturosa).
To evaluate effects of racemic ketamine and S-ketamine in gazelles. 21 male gazelles (10 Rheem gazelles [Gazella subgutturosa marica] and 11 Subgutturosa gazelles [Gazella subgutturosa subgutturosa]), 6 to 67 months old and weighing (mean±SD) 19 ± 3 kg. In a randomized, blinded crossover study, a combination of medetomidine (80 μg/kg) with racemic ketamine (5 mg/kg) or S-ketamine (3 mg/kg) was administered i.m.. Heart rate, blood pressure, respiratory rate, rectal temperature, and oxygen saturation (determined by means of pulse oximetry) were measured. An evaluator timed and scored induction of, maintenance of, and recovery from anesthesia. Medetomidine was reversed with atipamezole. The alternate combination was used after a 4-day interval. Comparisons between groups were performed with Wilcoxon signed rank and paired t tests. Anesthesia induction was poor in 2 gazelles receiving S-ketamine, but other phases of anesthesia were uneventful. A dominant male required an additional dose of S-ketamine (0.75 mg/kg, i.m.). After administration of atipamezole, gazelles were uncoordinated for a significantly shorter period with S-ketamine than with racemic ketamine. Recovery quality was poor in 3 gazelles with racemic ketamine. No significant differences between treatments were found for any other variables. Time from drug administration to antagonism was similar between racemic ketamine (44.5 to 53.0 minutes) and S-ketamine (44.0 to 50.0 minutes). Administration of S-ketamine at a dose 60% that of racemic ketamine resulted in poorer induction of anesthesia, an analogous degree of sedation, and better recovery from anesthesia in gazelles with unremarkable alterations in physiologic variables, compared with racemic ketamine.


Different outcomes for transplant-eligible newly diagnosed multiple myeloma patients in Latin America according to the public versus private management: a GELAMM study.
The aim of this study was to describe clinical and survival characteristics of transplant-eligible multiple myeloma (MM) patients in Latin America (LA), with a special focus on differences between public and private healthcare facilities. We included 1293 patients diagnosed between 2010 and 2018. A great disparity in outcomes and survival between both groups was observed. Late diagnosis and low access to adequate frontline therapy and ASCT in public institutions probably explain these differences. Patients treated with novel drug induction protocols, followed by autologous stem cell transplantation (ASCT) and maintenance, have similar overall survival compared to that published internationally.


[Blue nevus of the uterine cervix].
Seven cases of blue nevus of the endocervix were examined macroscopically and histologically. The endocervical blue nevus is a rare lesion which can be incidentally found in surgical pieces after hysterectomy in middle-aged women. It looks like a blue-blackish little lesion, located superficially in the submucosa of the endocervix. The immunohistochemical results are positive for Protein S100 of the nevus cells. Due of its localization in the cervical duct the lesion can be hardly identified through colposcopy. Histogenetical hypotheses are finally discussed.


Benzothiazole derivatives as novel inhibitors of human 11beta-hydroxysteroid dehydrogenase type 1.
Selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) have considerable potential as treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. Here, we report the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11beta-HSD1 from human hepatic microsomes measured using a radioimmunoassay (RIA) method. The benzothiazole derivatives 1 and 2 showed greater than 80% inhibition for 11beta-HSD1 at 10 microM and exhibited IC50 values in the low micromolar range. The preliminary SAR study suggested the introduction of a chlorine substituent at the 4 position of the benzothiazole ring greatly enhanced the inhibitory activities. Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11beta-HSD1 revealed how the molecule may interact with the enzyme and cofactor.


Thymoquinone content in marketed black seed oil in Malaysia.
Thymoquinone (TQ) is the major active compound in black seed oil (BSO). Many pharmacological effects of TQ, such as anti-inflammatory, hypoglycemic, antioxidant, immune stimulator, and anticancer, have been reported. TQ can be considered as a biomarker for BSO, but its content in the commercial products is rarely reported. TQ content varies based on the oil source and extraction method. This study aimed to quantify the TQ content in the commercial BSO products in Malaysia and to evaluate whether the products can be used as a source of TQ for therapeutic benefits. TQ was quantified using an established high-performance liquid chromatography (HPLC) method. TQ human equivalent dose (HED) was calculated based on reported animal studies from literature, and theoretical BSO amount containing the TQ dose was calculated based on the HPLC analysis. TQ content in the commercial BSO products ranged from 0.07% wt/wt to 1.88% wt/wt. The product with the highest TQ concentration is approximately 27-fold higher than the product with the lowest TQ concentration. Consequently, theoretical BSO amounts needed for specific diseases varied and some products cannot provide practical amount of TQ. This study recommends the regulation of TQ content in BSO and suggests that the BSO might be fortified with extra TQ to be effectively used in some diseases.


Major league baseball career length in the twentieth century.
Although baseball is considered "the" American pastime, little is known about the career prospects of the individuals who play the game. This study fills that void by examining the careers of baseball players over the last century. Between 1902 and 1993, 5,989 position players started their careers and played 33,272 person years of major league baseball. A rookie position player can expect to play 5.6 years; one in five position players will have only a single-year career, and at every point of a player's career, the chance of exiting is at least 11%. Position players who start younger and begin their career in more recent decades all have longer and more stable careers; nevertheless, baseball careers are not compressed versions of normal careers, but are substantially skewed toward early exit.


Adductor Muscle Injuries in UEFA Soccer Athletes: A Matched-Cohort Analysis of Injury Rate, Return to Play, and Player Performance From 2000 to 2015.
The effects of adductor muscle injury on performance in soccer athletes are unknown. To (1) determine the rate and time to return to play (RTP) after adductor muscle injury, (2) investigate the rate of reinjury after RTP, and (3) investigate any long-term effects of injury on elite soccer player performance. Cohort study; Level of evidence, 3. Using publicly available records, athletes sustaining adductor muscle injury were identified across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2015. Injured athletes were matched to controls by demographic characteristics and performance metrics from 1 season before the index timepoint. Investigations included the rate of RTP, reinjuries, player characteristics associated with RTP within 2 seasons, player availability, field time, and performance metrics during the 4 seasons after injury. A total of 671 players with adductor muscle injury were included. Based on time to RTP, 86% of injuries were mild to moderate (4-28 days missed), and 4% required surgical intervention. Players with adductor muscle injury were absent for a median of 22 days (range, 1-700 days) and 4 games (range, 1-76 games). A total of 521 (78%) players returned at the same level, with no demographic or clinical characteristics associated with RTP on the multivariable regression. Of those returning to play, 143 (21%) experienced adductor reinjury. After RTP, defenders demonstrated decreased field time compared with controls (P < .05). As compared with controls, defenders and midfielders scored more points and goals per game during the season of the injury (P < .01), while attackers recorded more goals and assists per game the season after injury (P < .05). Only 3 in 4 players (78%) returned to participate in an official match, and the reinjury rate was high (21%). After RTP, defenders demonstrated decreased field time versus controls. On the other hand, defenders and midfielders recorded more points and goals per game, while attackers recorded more goals and assists per game versus controls. Although the multivariable analysis results did not identify player characteristics associated with RTP, there was a position-dependent association on player performance after RTP.