Ineffectiveness of cephalexin in treatment of cephalexin-resistant bacteriuria in patients with chronic indwelling urethral catheters.
Catheterized patients not only are subject to risks of bacteriuria but the catheter also may act as reservoirs for nosocomial infections. Antibiotics that are concentrated in the urine, even those to which the organisms are nominally resistant, have been advocated as a means of treatment and infection control. During a randomized study of repetitive 10-day courses of cephalexin in chronically catheterized patients we observed the impact of such treatment upon susceptible, moderately resistant and highly resistant strains of bacteria. Cephalexin diminished the persistence of cephalexin-susceptible strains. However, its effect upon moderately resistant (inhibited by 200 micrograms per ml.) was not different than its effect upon highly resistant (not inhibited by 200 micrograms per ml.) strains. Indeed, the persistence of strains of moderately and highly resistant organisms during cephalexin courses was similar to that of such organisms during comparable periods in patients not receiving cephalexin. The administration of cephalexin to chronically catheterized patients with moderately or highly resistant organisms causing bacteriuria does not clear these organisms from the urine.


Predicting the solubility of recombinant proteins in Escherichia coli.
We describe a statistical model that uses binomial logistic regression for predicting the solubility of heterologous proteins expressed in E. coli. The model is based on a set of proteins reported to have been expressed in E. coli in either soluble or insoluble form. The 22 parameters used in the final model based on proteins' amino acid composition are discussed. The overall accuracy of the model developed is 94%. The way to use this model on the website http://www.ou.edu/ for the prediction of protein solubility is explained.


Isolation and functional characterization of the Ca-DREBLP1 gene encoding a dehydration-responsive element binding-factor-like protein 1 in hot pepper (Capsicum annuum L. cv. Pukang).
Through the use of subtractive hybridization analysis, we have identified 14 partial cDNA clones (pCa-DSRs) that are rapidly induced by dehydration in hot pepper (Capsicum annuum L.) roots. The predicted proteins encoded by Ca-DSRs are putatively involved in processes as diverse as primary and secondary metabolism, protein degradation, and stress responses, indicating the complexity of cellular responses to water deficit in hot pepper roots. Particularly, we investigated the detailed structural properties and expression profiles of Ca-DSR2 (Ca-DREBLP1: dehydration-responsive element binding-factor-like protein 1) encoding a protein that contains a single ERF/AP2 DNA-binding domain. Based on the conserved 14th valine and 19th glutamic acid residues in the ERF/AP2 domain, a basic amino acid stretch (PKKPAGRKKFR) near its N-terminal region, and DSAW signature sequence at the end of its ERF/AP2 domain, Ca-DREBLP1 was classified as a member of a DREB1-type subfamily. Gel retardation assays revealed that Ca-DREBLP1 was able to form a specific complex with the DRE/CRT motif, but not with the GCC box. When fused to the GAL4 DNA-binding domain, the Ca-DREBLP1(190-215) mutant could effectively function as a trans-activator in yeast. This suggests that the extreme C-terminal region plays an essential role in transcription activation. In hot pepper plants, Ca-DREBLP1 was rapidly induced by dehydration, high salinity and, to a lesser extent, mechanical wounding, but not by cold stress. Thus, although the structural features of Ca-DREBLP1 resemble those of the DREB1-type proteins of Arabidopsis thaliana and rice plants, its induction patterns are reminiscent of the DREB2-type proteins, indicating that Ca-DREBLP1 is a novel class DREB subfamily in hot pepper.


Effects of α-Fe2O3 nanoparticles and biochar on plant growth and fruit quality of muskmelon under cadmium stress.
Cadmium pollution in farmland has become a global environmental problem, threatening ecological security and human health. Biochar is effective in remediation of soil pollution. However, high concentrations of biochar can inhibit plant growth, and low concentrations of biochar have limited mitigation effect on cadmium toxicity. Therefore, the combination of low-concentration biochar and other amendments is a promising approach to alleviate cadmium toxicity in plants and improve the safety of edible parts. In this study, muskmelon was selected as the research object, and different concentrations of α-Fe2O3 nanoparticles were used alone or combined with biochar to explore the effects of different treatments on muskmelon plants in cadmium-contaminated soil. The results showed that the combined application of 250 mg/kg α-Fe2O3 nanoparticles and biochar had a good effect on the repair of cadmium toxicity in muskmelon plants. Compared with cadmium treatment, its application increased plant height by 32.53%, cadmium transport factor from root to stem decreased by 32.95%, chlorophyll content of muskmelon plants increased by 14.27%, and cadmium content in muskmelon flesh decreased by 18.83%. Moreover, after plant harvest, soil available cadmium content in 250 mg/kg α-Fe2O3 nanoparticles and biochar combined treatment decreased by 31.18% compared with cadmium treatment. The results of this study provide an effective reference for the composite application of different exogenous amendments and a feasible idea for soil heavy metal remediation and mitigation of cadmium pollution in farmland.


Evaluation of cost-effectiveness among open, laparoscopic and robotic distal pancreatectomy: A systematic review and meta-analysis.
The cost-effectiveness of minimally invasive distal pancreatectomy (MIDP) is still a matter of debate. This study compares the cost-effectiveness of open (ODP), laparoscopic (LDP) and robotic distal pancreatectomy (RDP). Pubmed, Web of Science and Cochrane Library databases were searched. Studies comparing cost-effectiveness of ODP and MIDP were included. A total of 1052 titles were screened and 16 articles were included in the study, 2431 patients in total. LDP resulted the most cost-efficient procedure, with a mean total cost of 14,682 ± 5665 € and the lowest readmission rates. ODP had lower surgical procedure costs, 3867 ± 768 €. RDP was the safest approach regarding hospital stay costs (5239 ± 1741 €), length of hospital stay, morbidity, clinically relevant pancreatic fistula and reoperations. In this meta-analysis MIDP resulted as the most cost-effective approach. LDP seems to be protective against high costs, but RDP seems to be safer.


Investigation of TGFBI (transforming growth factor beta-induced) Gene Mutations in Families with Granular Corneal Dystrophy Type 1 in the Konya Region.
Granular corneal dystrophies (GCD) are characterized by small, discrete, sharp-edged, grayish-white opacities in the corneal stroma. Among the genes responsible for the development of GCD, the most strongly related gene is transforming growth factor beta-induced (TGFBI), located in the 5q31.1 locus. Studies show that R124H in exon 4 and R555W in exon 12 are hot-spot mutations in the TGFBI gene that lead to GCD development. In this study, we aimed to investigate these two hot-spot mutations in exons 4 and 12 of the TGFBI gene and other possible mutations in the same regions, which code important functional regions of the protein, in Turkish families with GCD and to determine the relationship between the mutations and disease and related phenotypes. The study included 16 individuals diagnosed with GCD type 1 (GCD1), 11 of these patients' healthy relatives, and 28 unrelated healthy individuals. DNA was obtained from peripheral blood samples taken from each individual and polymerase chain reaction was used to amplify target gene regions. Genotyping studies were done by sequence analysis. The R124S mutation in exon 4 of TGFBI was not detected in the patients or healthy individuals in our study. However, all individuals diagnosed as having GCD1 were found to be heterozygous carriers of the R555W mutation in exon 12 of TGFBI. This mutation was not detected in healthy family members or control individuals unrelated to these families. In addition, we detected the silent mutation F540F in exon 12 and c.32924 G>A substitution in an intronic region of the gene in a few patients and healthy individuals. Our study strongly supports the association of GCD1 with R555W mutation in exon 12 region of the TGFBI gene, as reported in the literature.


New Frontiers in Child, Adolescent and Young Adult Psycho-Oncology Survivorship Care.
The landscape of cancer survivorship has changed considerably from Fitzhugh Mullan's conceptualization of the three sequential phases or 'seasons of survival' that an individual might expect to pass through, from the acute (cancer diagnosis and treatment), extended (the period following treatment), and permanent (survivorship, aligned with cure) survivorship phases [...].


Development and validation of an indirect enzyme immunoassay for detection of ovine antibody to Brucella ovis.
An indirect enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Brucella ovis infection was developed. The assay uses a mouse monoclonal antibody to bovine IgG1 horseradish peroxidase (HRPO) conjugate that cross-reacts with immunoglobulin from sheep and a purified antigen from Brucella ovis. The ELISA data were read and analyzed according to a targeting procedure. The ELISA results were compared with a cold complement fixation test (CFT). Sera from 675 rams from three uninfected flocks were used to determine the ELISA cut-off value (O.D. 405 nm: 0.095) and the diagnostic specificity of the ELISA (100%) and the CFT (99.69% +/- 0.42). The ELISA cut-off value was corroborated by receiver operating characteristic (ROC) analysis. Six hundred and forty semen and serum samples from 419 rams from two naturally infected flocks were collected before and after mating-time during two consecutive years. All semen samples were cultured and Brucella ovis was isolated from 28 samples. Sera from the 28 rams with positive semen were used to determine the diagnostic sensitivity of the ELISA (96.43% +/- 6.8) and of the CFT (including suspected positive samples with titers of 1:5; 88.89% +/- 11.85). Considering the CFT suspicious and the anti-complementary reactions as positive resulted in a diagnostic sensitivity value of 89.28% +/- 11.46. Six hundred and ten serum samples from the 640 sera were used to determine relative sensitivity (excluding sera with 1:5) at: ELISA/CFT 97.26% +/- 3.74 and CFT/ELISA was 71.72% +/- 8.87. The percent agreement, beyond chance measured by the Kappa index was 79.7. Relative sensitivity ELISA/CFT (including 1:5 titers in the CFT as positive) was 94.9% +/- 4.83 and CFT/ELISA was 72.84% +/- 8.59. The Kappa index was 79.4.


Screening for complications and associated conditions in children, adolescents and young adults with Type 1 diabetes mellitus in the Netherlands: Big differences in a small country.
Children, adolescents and young adults with Type 1 diabetes mellitus need to be screened for chronic complications and associated (autoimmune) diseases. There are no Dutch national guidelines for screening available but the International Society for Pediatric and Adolescent Diabetes (ISPAD) gives recommendations in its guidelines. The ISPAD guidelines from 2014 were updated in 2018. The adherence of the Dutch pediatric diabetes clinics to the international guidelines as stated by the ISPAD. A questionnaire about screening method and frequency was send to all members of the Dutch national committee for pediatric diabetes. The screening policies of the pediatric diabetes clinics were compared to the ISPAD guidelines of 2014 and 2018. Sixty-two percent of all diabetes clinics filled out the questionnaire. None of the diabetes clinics followed all recommendations of the ISPAD. The majority of the clinics had a higher frequency of screening, performed extra blood tests and did not personalize their policy to the individual patient. Approximately one third of the diabetes clinics still commenced screening for chronic complications at the age of 10 years, as recommended in the previous version of the ISPAD guideline. Dutch pediatric diabetes clinics screen their patients on chronic complications and associated conditions very differently and not according to the international (and most recent) guidelines. A more individualized approach with respect to the newest ISPAD guidelines will diminish the burden for the patient and medical costs as well.


Exploring the functional consequences of genomic variation: the 2010 Human Genome Variation Society Scientific Meeting.
The 2010 annual scientific meeting of the Human Genome Variation Society (HGVS) was held on November 2 in Washington, DC. The theme of this year's meeting was "Exploring the Functional Consequences of Genomic Variation." Next generation sequencing technologies now allow investigators to sequence entire genomes of multiple individuals. Each genome contains over 3 million variants in which the functional (or causative) variants need to be identified. Limiting sequencing analysis to only the exome (approximately 1% of the genome) can still result in over 30,000 possible variants per individual that need to be analyzed for their effect on function. Analysis of this massive amount of data will require a combination of computer assisted algorithms and biological studies to identify the causative variants. The 2010 annual meeting of the HGVS focused on methods being designed for this purpose.


Light-induced modulation of Porphyromonas gingivalis growth.
The bacterium Porphyromonas gingivalis is a clinically significant agent in periodontitis, a disease for which there is no definitive cure. Several groups have attempted to kill this bacterium using low levels of light in the absence of a photosensitizer, with conflicting results. We hypothesize that it is not possible to kill P. gingivalis by targeting endogenous porphyrins for a photochemical reaction. We demonstrated that irradiation of P. gingivalis with 455 or 625 nm light emitting diodes did not induce a photochemical killing of the cultures. Controlled temperature experiments indicate that irradiation at either wavelength did not significantly impact the growth of P. gingivalis cultures, as compared to non-irradiated controls. Rather, the irradiation caused a temperature increase in the growth medium, which altered the growth of the cultures. These results indicate that heat-induced killing of P. gingivalis could be the mechanism behind successful irradiation experiments with this bacterium.


A case of laparoscopic resection of leiomyosarcoma arising in the mesentery of descending colon: a case report and review of the literature.
Leiomyosarcoma of mesenteric origin is rare and may be managed by laparoscopic surgery as a less invasive procedure, on the condition that the tumor can be resected with a safe margin.


Histochemical demonstration of nerve cell bodies in the retractor penis muscle and the penile artery of the bull.
The presence of single nerve cell bodies and small ganglia in the retractor penis muscle and the penile artery of the bull was demonstrated by using antisera to neurofilament protein and neuron specific enolase. In the retractor penis muscle the findings were confirmed by staining for acetylcholinesterase. It was also shown that relaxation of strips of the retractor penis muscle induced by 70 microM acetylcholine was totally blocked by a 2.0 microM concentration of the ganglionic blocking drug chlorisondamine. The hypothesis is presented that the relaxation of the bovine retractor penis muscle and the bovine penile artery induced by nicotinic ganglionic stimulating drugs is at least in part mediated via receptors located on the nerve cell bodies described in this study.


Clinical economics education in the International Clinical Epidemiology Network. INCLEN Economics Faculty.
The application of rigorous epidemiologic methods to clinical questions has broadened the scope of research in epidemiology and enhanced the quality of clinical research. The International Clinical Epidemiology Network (INCLEN) has enabled physicians from developing countries to obtain training in epidemiologic methods and to provide leadership in clinical epidemiology in their home schools of medicine. The INCLEN program has recently incorporated another major theme of research training, clinical economics, which introduces research related to the effective use of limited resources. This article describes the rationale for the development of the INCLEN Clinical Economics program, outlines its organization and curriculum, and explores the challenges to its successful implementation.


Self-efficacy as a predictor of treatment outcome in adolescent substance use disorders.
Youth substance abuse relapse prevention was examined as a function of patients' situational self-efficacy (SE), their confidence to abstain from substance use in high-risk situations. An increase in SE has been shown to be enhanced by cognitive behavioral therapy (CBT) in adults. Eighty-eight adolescent substance abusers were randomly assigned to either CBT or psycho-education (PET) group therapy. Substance use and SE were assessed at end of treatment, 3- and 9-months after the end of planned treatment. Increased SE predicted subsequent abstinence independently from drug urinalysis and treatment condition only during treatment, while previous substance use predicted subsequent self-efficacy. CBT was not differentially effective than PET in promoting SE. It is recommended that potential mediators and moderators of SE in the treatment of adolescent substance abuse should be further explored.


Functional characterization of a binding protein for Type-II sex pheromones in the tea geometrid moth Ectropis obliqua Prout.
The tea geometrid moth Ectropis obliqua Prout is one of the most serious moth pests in tea plants, and its sex pheromones have been identified as typical Type-II polyunsaturated hydrocarbons and epoxide derivatives. Therefore, the E. obliqua male olfactory system provides a good model to study the molecular basis of Type-II sex pheromone recognition as well as functional gene evolution towards structurally different types of moth sex pheromones. In this study, we identified the full-length sequence of a pheromone-binding protein, EoblPBP2 and revealed that it clustered together with the lepidopteran PBP2 subfamily, which binds Type I acetate pheromones. These findings suggest that the EoblPBP2 sequence and physiological function are conserved, although E. obliqua evolved Type II hydrocarbon and epoxide sex pheromones structurally different from Type I acetates. To examine this hypothesis, we studied the expression patterns and in vitro functions of EoblPBP2 in detail. Quantitative real-time PCR experiments showed that EoblPBP2 was predominantly expressed in male E. obliqua antennae. Fluorescence in situ hybridization further demonstrated that the EoblPBP2 gene was abundantly expressed in the pheromone-sensitive sensilla trichodea Str-I in male E. obliqua. The physiological function of recombinant EoblPBP2 was then examined using a competitive binding assay. The results showed that EoblPBP2 had high affinities for three E. obliqua Type II sex pheromone components and Type I acetate pheromones in comparison to some plant volatiles. These results indicate that PBP2 is involved in the detection of Type II pheromones in E. obliqua and it still retains high binding affinities to acetate pheromones and some green leaf ester volatiles.


Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature.
The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. A total of 18 studies -8 on type 1 DM and 10 on type 2 DM patients-meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base.


[Myofasciitis under nivolumab treatment].
We report the case of a 73-year-old female patient with malignant melanoma who developed rapidly progressive dermatosclerosis of the arms and legs as well as myalgia and flexion contractures during treatment with the immune checkpoint inhibitor nivolumab. The diagnosis of a myofasciitis was confirmed by imaging and biopsy. Following consultation with the treating dermato-oncologists nivolumab treatment was paused and treatment with methotrexate and prednisolone was initiated. Immune checkpoint inhibitors can induce a variety of immune-mediated side effects and can also imitate symptoms of rheumatological diseases. The occurrence of myofasciitis under immune checkpoint inhibition has been reported in the literature only in a few cases. Further oncological and rheumatological treatment management should be carried out in close interdisciplinary coordination.


Toxicity response of silkworm intestine to Bacillus cereus SW7-1 pathogen.
Bacillus cereus is a foodborne pathogen that causes gastrointestinal disease in hosts. The interactions between pathogenic bacteria and silkworms (Bombyx mori L.) involve complex processes. This study aimed to investigate the potential genetic traits of B. cereus SW7-1 and profile the toxicity response of silkworm intestine upon infection by the SW7-1 pathogen. Bacterial genome sequencing and polymerase chain reaction (PCR) detection indicated that B. cereus SW7-1 possesses multiple antibiotic-resistant genes and nine virulence factor genes. Then, silkworm larvae were infected with SW7-1. Comparative transcriptomic analysis revealed that 273 differentially expressed genes (DEGs) with known functions were successfully annotated to the silkworm reference genome. Specifically, 18 DEGs were up-regulated, and 255 DEGs were down-regulated. Compared with the control group, the treated group revealed down-regulated DEGs that are related to stress reactions, immunity, autophagy and apoptosis, DNA replication, ribosomal stress, and carbohydrate metabolism. Quantitative real time PCR analysis showed that many key genes in the Toll pathway, immune deficiency pathway, Janus kinase/signal transducers and activators of transcription pathway, and melanization reaction were up-regulated. Thus, B. cereus SW7-1 pathogen could damage the silkworm intestine, as confirmed by the histological section assay. In addition, SW7-1 can affect the normal physiological functions of intestinal cells. This study contributes toward an improved understanding of the toxicity response of silkworm to the B. cereus pathogen and provides new insights into the molecular mechanisms of the complex interactions between pathogenic microbes and silkworms.


Obstructive sleep apnea in poorly controlled asthmatic children: effect of adenotonsillectomy.
Asthma and obstructive sleep apnea (OSA) in children share multiple epidemiological risk factors and the prevalence of snoring is higher in asthmatic children, suggesting that the latter may be at increased risk for OSA. Since both asthma and OSA are inflammatory disorders, we hypothesized that polysomnographically demonstrated OSA would be more frequent among poorly controlled asthmatics (PCA), and that treatment of OSA, if present, would ameliorate the frequency of acute asthmatic exacerbations (AAE). Children with PCA were referred for an overnight sleep study, and adenotonsillectomy (tonsillectomy and adenoidectomy, T&A) was performed if OSA was present. Frequency of asthma symptoms and exacerbations were compared. Ninety-two PCA children, ages 3-10 years, with a mean frequency of AAE of 3.4 ± 0.4/year were prospectively referred for a sleep study. OSA (i.e., AHI > 5/hrTST) was present in 58 patients (63.0%; OR: 40.9, 12.9-144.1, P < 0.000001 compared to the prevalence of OSA in a non-asthmatic population). Information at 1-year follow-up was available for 35 PCA children after T&A. The annual frequency of AAE, rescue inhaled use, and asthma symptoms in this sub-group decreased compared to no changes in the group without OSA. The prevalence of OSA is markedly increased among PCA children and treatment of OSA appears to be associated with substantial improvements in the severity of the underlying asthmatic condition.


Do common genetic variants in endotoxin signaling pathway contribute to predisposition to alcoholic liver cirrhosis?
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), produced by endotoxin-activated Kupffer cells, play a key role in the pathogenesis of alcoholic liver cirrhosis (ALC). Alleles TNFA -238A, IL1B -31T and variant IL1RN*2 of repeat polymorphism in the gene encoding the IL-1 receptor antagonist increase production of TNF-alpha and IL-1beta, respectively. Alleles CD14 -159T, TLR4 c.896G and TLR4 c.1196T modify activation of Kupffer cells by endotoxin. We confirmed the published associations between these common variants and genetic predisposition to ALC by means of a large case-control association study conducted on two Central European populations. The study population comprised a Czech sample of 198 ALC patients and 370 controls (MONICA project), and a German sample of 173 ALC patients and 331 controls (KORA-Augsburg), and 109 heavy drinkers without liver disease. Single locus analysis revealed no significant difference between patients and controls in all tested loci. Diplotype [IL1RN 2/ 2; IL1B -31T+] was associated with increased risk of ALC in the pilot study, but not in the validation samples. Although cytokine mediated immune reactions play a role in the pathogenesis of ALC, hereditary susceptibility caused by variants in the corresponding genes is low in Central European populations.


Points of regulation for auxin action.
There have been few examples of the application of our growing knowledge of hormone action to crop improvement. In this review we discuss what is known about the critical points regulating auxin action. We examine auxin metabolism, transport, perception and signalling and identify genes and proteins that might be keys to regulation, particularly the rate-limiting steps in various pathways. Certain mutants show that substrate flow in biosynthesis can be limiting. To date there is little information available on the genes and proteins of catabolism. There have been several auxin transport proteins and some elegant transport physiology described recently, and the potential for using transport proteins to manage free indole-3-acetic acid (IAA) concentrations is discussed. Free IAA is very mobile, and so while it may be more practical to control auxin action through managing the receptor and signalling pathways, the candidate genes and proteins through which this can be done remain largely unknown. From the available evidence, it is clear that the reason for so few commercial applications arising from the control of auxin action is that knowledge is still limited.


Detection of phosphodiester resonances in the perfused heart from vertebrate ectotherms with nuclear magnetic resonance.
In vivo 31P NMR has been used to characterize the phosphorylated compounds present in the heart from vertebrate ectotherms. The perfused hearts from all animals experimented showed prominent resonances between the inorganic phosphate and phosphocreatine peaks. The pattern of these compounds was found to be different in the heart of the different species. As shown by 31P and proton NMR of perchloric extracts, the chemical shift of some of the compounds was characteristic of glycerophosphorylcholine, glycerophosphorylinositol, phosphorylcholine, phosphorylserine, phosphorylethanolamine and phosphoenolpyruvate. The non-identified resonances were found to be phosphodiesters, as demonstrated by alkaline phosphatase hydrolysis. The physiological significance of these high levels of phosphodiesters in the heart from vertebrate ectotherms is discussed.


Clinical study of ammonium acid urate urolithiasis.
Ammonium acid urate (AAU) urolithiasis is a rare condition; however, it is endemic in some countries, with an especially high incidence in Asia. This study was conducted to investigate the special presentation of patients with AAU urolithiasis in Taiwan. Reports of 3457 stones were retrospectively reviewed from January 2005 to January 2010 and 25 patients with urinary stones (0.7%) containing AAU crystals were identified. The clinical and biochemical presentation of all stones were compared to evaluate the specific comorbidities of AAU stones. AAU stones were observed in 11 males (44%) and 14 females (56%) with a mean age of 60.60 ± 16.81 years and mean body mass index of 25.55 ± 3.73 kg/m(2). AAU stones were frequently observed in the bladder (44%) and they were significantly larger (mean size 1.90 cm) than the non-AAU stones (mean size 1.22 cm). Other significant comorbidities of AAU stones included chronic kidney disease (CKD) (60%), urinary tract infections (UTIs) (52%), irritable bowel syndrome (IBS) (36%), and gout (28%). In addition, there were also three patients with coexisting urothelial carcinoma (12%) in the AAU-stone group. Patients with AAU urolithiasis were predominantly female, older in age, had increased bladder presentation, larger stones and a high percentage of coexisting CKD, UTIs, IBS, gout, and even urothelial carcinoma. Therefore, it is important for clinicians to evaluate and protect renal function in patients with AAU urolithiasis.


Adsorption of Cr(VI) and As(V) ions by modified magnetic chitosan chelating resin.
Cross-linked magnetic chitosan anthranilic acid glutaraldehyde Schiff's base (CAGS) was prepared for adsorption of both As(V) and Cr(VI) ions and their determination by ICP-OES. Prepared cross-linked magnetic CAGS was investigated by means of SEM, FTIR, wide angle X-ray diffraction (WAXRD) and TGA analysis. The adsorption properties of cross-linked magnetic CAGS resin toward both As(V) and Cr(VI) were evaluated. Various factors affecting the uptake behavior such as pH, temperature, contact time, initial concentration of metal ions, effect of other ions and desorption were studied. The equilibrium was achieved after about 110 min and 120 min for As(V) and Cr(VI), respectively at pH=2. The adsorption kinetics followed the mechanism of the pseudo-second order equation for all systems studied, evidencing chemical sorption as the rate-limiting step of adsorption mechanism and not involving a mass transfer in solution. The equilibrium data were analyzed using the Langmuir, Freundlich, and Tempkin isotherm models. The best interpretation for the equilibrium data was given by Langmuir isotherm, and the maximum adsorption capacities were 58.48 and 62.42 mg/g for both Cr(VI) and As(V), respectively. Cross-linked magnetic CAGS displayed higher adsorption capacity for Cr(VI). The adsorption capacity of the metal ions increased with increasing temperature under optimum conditions in case of Cr(VI), but decreased in case of As(V). The metal ion-loaded cross-linked magnetic CAGS were regenerated with an efficiency of greater than 88% using 0.2M sodium hydroxide (NaOH).


A purified acidic polysaccharide from Sarcandra glabra as vaccine adjuvant to enhance anti-tumor effect of cancer vaccine.
Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that p-SGP has a unique mechanism of enhancing anti-tumor immunity.


Delta-like 1 homolog (DLK1) inhibits proliferation and myotube formation of avian QM7 myoblasts.
Delta-like 1 homolog (DLK1) has been implicated as an important regulator in mammalian muscle development. Our previous studies showed that different alternative splicing isoforms have distinct functions in the regulation of myogenesis in mice. Unlike most mammals, including mice, pigs, cattle, and sheep, DLK1 mRNA for avian species has a single form without alternative splicing. In the current study, we have used QM7 cells, a quail myoblast, to study the role of DLK1 in the regulation of avian myogenesis. Overexpression of DLK1 inhibited myogenesis with a lower fusion rate and thinner myotube compared to the control QM7 cells. Comparison of relative levels of protein and mRNA showed down-regulation of PAX7, MYOG, and MHC, and up-regulation of MYOD by DLK1, suggesting that quail DLK1 inhibits myogenesis at later stages of myogenic differentiation and myotube formation. DLK1 reduced the QM7 cell growth rate which is accompanied by a lower percentage of bromodeoxyuridine positive cells, indicating an inhibitory role of DLK1 in proliferation. During the early post-hatch ages, the relatively slower increase in the amount of total DNA mass in breast muscle of the heavy weight quail line, that has been selected for over 40 generations, could be partially explained by the higher expression of DLK1 compared to the control quail. Taken together, DLK1 inhibits myogenic differentiation and proliferation by regulating the expression levels of myogenic factors in quail. In addition, the regulation of expression level and cleavage of full-length DLK1 may be important factors for regulating myogenesis in quail having no splicing variants of DLK1.


[Postural control related to age in patients with benign positional paroxysmal vertigo].
To study the relationship between age and posturography in patients with benign positional paroxysmal vertigo. Prospective study performed in 65 patients with benign positional paroxysmal vertigo (BPPV) in any variant. Sensory Organization Test outcomes were recorded and compared with their equivalents in a control group by means of scatter-plot diagrams and regression line. For statistical study, Mann-Whitney's U-test was used. Slope for regression lines in composite was -0.0934 in group NORMAL; in group BPPV it was -0.4284. This difference is due to conditions 5 and 6. Results were statistically significative. BPPV patients have a worse postural control than control group. The difference is bigger the older the patient is. It is due to a failure in conditions 5 and 6, so it should be from a vestibular origin.


Interleukin-6 blockade with tocilizumab increases Tregs and reduces T effector cytokines in renal graft inflammation: A randomized controlled trial.
Interleukin-6 (IL-6) is a proinflammatory cytokine and key regulator of Treg: T effector cell (Teff) balance. We hypothesized that IL-6 blockade with tocilizumab, a monoclonal antibody to IL-6R, would increase Tregs, dampen Teff function, and control graft inflammation. We conducted a randomized controlled clinical trial (2014-2018) of clinically stable kidney transplant recipients on calcineurin inhibitor, mycophenolate mofetil, and prednisone, with subclinical graft inflammation noted on surveillance biopsies during the first year posttransplant. Subjects received tocilizumab (8 mg/kg IV every 4 weeks; 6 doses; n = 16) or no treatment (controls; n = 14) on top of usual maintenance immunosuppression. Kidney biopsies pre- and post-treatment were analyzed using Banff criteria. Blood was analyzed for serum cytokines, Treg frequencies, and T cell effector molecule expression (IFN-γ, IL-17, granzyme B) post-stimulation ex vivo. Tocilizumab-treated subjects were more likely to show improved Banff ti-score (62.5% vs. 21.4%, p = .03), increased Treg frequency (7.1% ± 5.55% vs. 3.6% ± 1.7%, p = .0168), and a blunted Teff cytokine response compared to controls. Changes in Banff i- and t-scores were not significantly different. The treatment was relatively well tolerated with no patient deaths or graft loss. Blockade of IL-6 is a novel and promising treatment option to regulate the T cell alloimmune response in kidney transplant recipients. NCT02108600.


[Cerebral cystercosis. 3. cases observed in the Paris area in immigrant workers].
The three cases described involve two Portugese patients and a Spaniard working in the Paris are who had presented with epilepsy, being focal in two. Diagnosis was made in two cases as a result of the existence of muscular and sub-cutaneous calcifications; in one case because of eosinophilia of the cerebro-spinal fluid. The clinical and therapeutic features of cerebral cysticercosis are recalled briefly in connection with these cases.


Deterministic small-scale undulations of image-based risk predictions from the deep learning of lung tumors in motion.
Deep learning (DL) models that use medical images to predict clinical outcomes are poised for clinical translation. For tumors that reside in organs that move, however, the impact of motion (i.e., degenerated object appearance or blur) on DL model accuracy remains unclear. We examine the impact of tumor motion on an image-based DL framework that predicts local failure risk after lung stereotactic body radiotherapy (SBRT). We input pre-therapy free breathing (FB) computed tomography (CT) images from 849 patients treated with lung SBRT into a multitask deep neural network to generate an image fingerprint signature (or DL score) that predicts time-to-event local failure outcomes. The network includes a convolutional neural network encoder for extracting imaging features and building a task-specific fingerprint, a decoder for estimating handcrafted radiomic features, and a task-specific network for generating image signature for radiotherapy outcome prediction. The impact of tumor motion on the DL scores was then examined for a holdout set of 468 images from 39 patients comprising: (1) FB CT, (2) four-dimensional (4D) CT, and (3) maximum-intensity projection (MIP) images. Tumor motion was estimated using a 3D vector of the maximum distance traveled, and its association with DL score variance was assessed by linear regression. The variance and amplitude in 4D CT image-derived DL scores were associated with tumor motion (R2 = 0.48 and 0.46, respectively). Specifically, DL score variance was deterministic and represented by sinusoidal undulations in phase with the respiratory cycle. DL scores, but not tumor volumes, peaked near end-exhalation. The mean of the scores derived from 4D CT images and the score obtained from FB CT images were highly associated (Pearson r = 0.99). MIP-derived DL scores were significantly higher than 4D- or FB-derived risk scores (p < 0.0001). An image-based DL risk score derived from a series of 4D CT images varies in a deterministic, sinusoidal trajectory in a phase with the respiratory cycle. These results indicate that DL models of tumors in motion can be robust to fluctuations in object appearance due to movement and can guide standardization processes in the clinical translation of DL models for patients with lung cancer.


Traditional Chinese medicine as a therapeutic option for cardiac fibrosis: Pharmacology and mechanisms.
Cardiovascular diseases are one of the leading causes of death worldwide and cardiac fibrosis is a common pathological process for cardiac remodeling in cardiovascular diseases. Cardiac fibrosis not only accelerates the deterioration progress of diseases but also becomes a pivotal contributor for futile treatment in clinical cardiovascular trials. Although cardiac fibrosis is common and prevalent, effective medicines to provide sufficient clinical intervention for cardiac fibrosis are still unavailable. Traditional Chinese medicine (TCM) is the natural essence experienced boiling, fry, and other processing methods, including active ingredients, extracts, and herbal formulas, which have been applied to treat human diseases for a long history. Recently, research has increasingly focused on the great potential of TCM for the prevention and treatment of cardiac fibrosis. Here, we aim to clarify the identified pro-fibrotic mechanisms and intensively summarize the application of TCM in improving cardiac fibrosis by working on these mechanisms. Through comprehensively analyzing, TCM mainly regulates the following pathways during ameliorating cardiac fibrosis: attenuation of inflammation and oxidative stress, inhibition of cardiac fibroblasts activation, reduction of extracellular matrix accumulation, modulation of the renin-angiotensin-aldosterone system, modulation of autophagy, regulation of metabolic-dependent mechanisms, and targeting microRNAs. We also discussed the deficiencies and the development direction of anti-fibrotic therapies on cardiac fibrosis. The data reviewed here demonstrates that TCM shows a robust effect on alleviating cardiac fibrosis, which provides us a rich source of new drugs or drug candidates. Besides, we also hope this review may give some enlightenment for treating cardiac fibrosis in clinical practice.


Computed tomography in deep-seated peripheral neurofibromas.
Seven peripheral deep-seated neurofibromas in five patients were examined by computed tomography (CT). This proved to be the most helpful investigation for demonstrating the precise size, shape and localisation of the lesion prior to surgery. In some cases CT may suggest the correct diagnosis where this has not previously been considered.


Phorbol diesters promote beta-adrenergic receptor phosphorylation and adenylate cyclase desensitization in duck erythrocytes.
Preincubation of duck erythrocytes with tumor promoting phorbol diesters or catecholamines leads to attenuation of adenylate cyclase activity. 12-0-Tetradecanoyl phorbol-13-acetate (TPA) and phorbol 12,13-dibutyrate treatment induced a 38% and 30% desensitization of isoproterenol-stimulated adenylate cyclase activity, respectively. In contrast, the inactive phorbol diester, 4 alpha-phorbol 12,13-didecanoate, was without effect in promoting adenylate cyclase desensitization. The catecholamine isoproterenol induced a 51% desensitization. Incubation of 32Pi labeled erythrocytes with TPA promoted a 3- to 4-fold increase in phosphorylation of the beta-adrenergic receptor as did incubation with isoproterenol. Treatment of the cells with both TPA and isoproterenol together resulted in desensitization and receptor phosphorylation which were no greater than those observed with either agent alone. These data suggest a potential role for protein kinase C in regulating beta-adrenergic receptor function.


Polar transport of auxin: carrier-mediated flux across the plasma membrane or neurotransmitter-like secretion?
Auxin (indole-3-acetic acid) has its name derived from the Greek word auxein, meaning 'to increase', and it drives plant growth and development. Auxin is a small molecule derived from the amino acid tryptophan and has both hormone- and morphogen-like properties. Although there is much still to be learned, recent progress has started to unveil how auxin is transported from cell-to-cell in a polar manner. Two recent breakthrough papers from Gerd Jürgens' group indicate that auxin transport is mediated by regulated vesicle trafficking, thus encompassing neurotransmitter-like features.


Phosphofructokinases Axis Controls Glucose-Dependent mTORC1 Activation Driven by E2F1.
Cancer cells rely on mTORC1 activity to coordinate mitogenic signaling with nutrients availability for growth. Based on the metabolic function of E2F1, we hypothesize that glucose catabolism driven by E2F1 could participate on mTORC1 activation. Here, we demonstrate that glucose potentiates E2F1-induced mTORC1 activation by promoting mTORC1 translocation to lysosomes, a process that occurs independently of AMPK activation. We showed that E2F1 regulates glucose metabolism by increasing aerobic glycolysis and identified the PFKFB3 regulatory enzyme as an E2F1-regulated gene important for mTORC1 activation. Furthermore, PFKFB3 and PFK1 were found associated to lysosomes and we demonstrated that modulation of PFKFB3 activity, either by substrate accessibility or expression, regulates the translocation of mTORC1 to lysosomes by direct interaction with Rag B and subsequent mTORC1 activity. Our results support a model whereby a glycolytic metabolon containing phosphofructokinases transiently interacts with the lysosome acting as a sensor platform for glucose catabolism toward mTORC1 activity.


Unveiling beauty: Insight into being tattooed postmastectomy.
It could be argued that mastectomy tattoos are being considered by some women in contemporary society as an alternative to breast reconstruction. To gain insight into the experience of "being" tattooed where breast(s) once occupied space, six women with mastectomy tattoos were interviewed. The teachings of Gadamer's philosophical hermeneutics were engaged to better understand what it means "to be" tattooed postmastectomy. Discoveries include feeling sad and damaged postmastectomy, embodying the tattoo as a novel representation of self for women living without breast(s), and reclaiming power, control, and confidence in a way that is symbolically meaningful. Health care providers working with women diagnosed with breast cancer are invited to learn from women with mastectomy tattoos and to consider expanding discourse about care to include options beyond breast reconstruction.


Differences between unipolar and bipolar I depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil.
Alterations in GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme in GABA synthesis. This study aimed to differentiate between unipolar and bipolar I depression using quantitative evaluation of GAD-immunoreactive (GAD-ir) neuropil in several brain regions known to be involved in the pathophysiology of mood disorders. Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLPFC), the entorhinal cortex, the hippocampal formation and the medial dorsal and lateral dorsal (LD) thalamic nuclei, with a quantitative densitometric analysis of GAD-ir neuropil. The study was performed on paraffin-embedded brains from 9 unipolar and 12 bipolar I depressed patients (8 and 6 suicidal patients, respectively) and 18 matched controls. In unipolar patients, compared with controls, only the increased relative density of GAD-ir neuropil in the right LD was different from the previous results in depressed suicides from the same cohort (Gos et al. in J Affect Disord 113:45-55, 2009). On the other hand, the left DLPFC was the only area where a significant decrease was observed, specific for bipolar I depression. Significant differences between both diagnostic groups were found in these regions. By revealing abnormalities in the relative density of GAD-ir neuropil in brain structures, our study suggests a diathesis of the GABAergic system in mood disorders, which may differentiate the pathophysiology of unipolar from that of bipolar I depression.


Case report: Transvaginal single-port extraperitoneal laparoscopic sacrospinous ligament fixation for apical prolapse: A single-center case series.
Sacrospinous ligament fixation (SSLF) is a minimally invasive and effective procedure for the treatment of apical prolapse. Because intraoperative exposure of the sacrospinous ligament is difficult, SSLF is difficult. The aim of our article is to determine the safety and feasibility of single-port extraperitoneal laparoscopic SSLF for apical prolapse. This single-center, single-surgeon case series study included 9 patients with pelvic organ prolapse quantification (POP-Q) III or IV apical prolapse who underwent single-port laparoscopic SSLF. Additionally, transobturator tension-free vaginal tap (TVT-O) was performed in 2 patients, and anterior pelvic mesh reconstruction was performed in 1 patient. The operative time ranged from 75 to 105 (mean, 88.9 ± 10.2) min, and blood loss ranged from 25 to 100 (mean, 43.3 ± 22.6) ml. No serious operative complications, blood transfusions, visceral injuries, or postoperative gluteal pain were reported for these patients. After 2-4 months of follow-up, no recurrence of POP, gluteal pain, urinary retention/incontinence, or other complications was observed. Transvaginal single-port SSLF is a safe, effective, and easy-to-master operation for apical prolapse.


Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation.
The present paradigm of atherogenesis proposes that low density lipoproteins (LDL) are trapped in subendothelial space of the vascular wall where they are oxidized. Myeloperoxidase (MPO) plays a key role in oxidative damage. We propose that LDL oxidation by myeloperoxidase (Mox-LDL) could occur at the surface of the endothelial cells and not restricted to the subendothelial space. The triad constituted by endothelial cells, circulating LDL and MPO in close interaction, constitutes a synergic mechanism for the genesis of Mox-LDL.


Routes to psychiatric inpatient care in an Inner London Borough.
A study is reported in which pathways to psychiatric inpatient care were investigated in an Inner London Borough. Data were collected on a series of 52 consecutive admissions of adults to the psychiatric wards serving the area. The most striking feature of the results was the variety of routes taken to inpatient care, combined with a high level of police involvement (23.1% of admissions) and low level of referral from General Practitioners (15.4% of admissions). Significant age differences in routes to care were found: those under 30 years were usually brought to hospital by the police or presented directly to psychiatric emergency services; those over 30 typically came via medical/surgical hospital services, domiciliary psychiatric services or psychiatric outpatients. There were no differences in the routes taken by Afro-Caribbean and white people or by men and women. Higher proportions of Afro-Caribbeans received a diagnosis of schizophrenia, considered themselves to have nothing wrong with them and were compulsorily detained. Higher proportions of whites were diagnosed as depressed and considered themselves to have physical problems rather than psychiatric ones. However, results clearly indicated that it was ethnic status rather than diagnostic category that accounted for the higher rates of compulsory detention of Afro-Caribbean people. The implications of the findings for service development and delivery are considered.


Health professional's job satisfaction and its determinants in Ethiopia: a systematic review and meta-analysis.
Health professional's job satisfaction is directly related to patient satisfaction and quality of care. Without satisfied health professionals the health system is not functional, and the national and global health related plans are not achieved. However, little is known on the level of health professional's job satisfaction in sub Saharan African countries including Ethiopia. In addition, in Ethiopia there is no summarized evidence helped us an input to design strategies. Therefore, we aimed to assess the pooled prevalence of health professional's job satisfaction and its determinants in Ethiopia. Articles were searched from PubMed, PsycINFO, Hinari, Science Direct, web of science and African journal of online (AJOL) databases, Google and Google scholar. A standardized Microsoft excel spread sheet and STATA software version 16 were used for data extraction and analysis respectively. We followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis to write this report. A random effect meta-analysis model was used to determine the pooled prevalence of job satisfaction. I2 was done to check heterogeneity. Egger's test and funnel plot were conducted to detect publication bias. Subgroup analysis was also conducted. Association was expressed through pooled odd ratio with a 95% CI. In this review and meta-analysis, a total of 29 studies were included. The pooled prevalence of health professional's job satisfaction was 46.17% [95% CI (43.08, 49.26)]. The heterogeneity and publication bias test results were I2 = 87.3%, P < 0.001 and Eggers', P = 0.16. Female sex; OR: 2.20 [95% CI (1.63, 2.97)], working environment; OR: 9.50 [95% CI (6.25, 14.44)], opportunity for professional growth and development; OR: 5.53 [95% CI (1.56, 19.56)], staff relationship; OR: 3.89 [95% CI (1.65, 9.17)] and supportive supervision; OR: 5.32 [95% CI (1.77, 15.92)] were associated with health professional's job satisfaction. More than half of professionals were dissatisfied with their jobs. Therefore, the ministry of health and stakeholders better to design strategies to increase the level of satisfaction. Furthermore, it is better to strengthen staff relationship and making the working environment more attractive and equipped.


Suicide among foreign residents of Japan.
The suicide rate of Koreans living in Japan is twice as high as that of Koreans in South Korea. Reasons for this high suicide rate are discussed, including effects of economic crises and discrimination.


Cochlear dead regions constrain the benefit of combining acoustic stimulation with electric stimulation.
The aims of this study were to (1) detect the presence and edge frequency (fe) of a cochlear dead region in the ear with residual acoustic hearing for bimodal cochlear implant users, and (2) determine whether amplification based on the presence or absence of a dead region would improve speech understanding and sound quality. Twenty-two listeners with a cochlear implant in one ear and residual acoustic hearing in the nonimplanted ear were tested. Eleven listeners had a cochlear dead region in the acoustic-hearing ear and 11 did not. Dead regions were assessed with the threshold-equalizing noise (TEN) and the sweeping noise, psychophysical tuning curve tests. Speech understanding was assessed with monosyllabic words and the AzBio sentences at +10 dB signal-to-noise ratio. Speech- and music-quality judgments were obtained with the Judgment of Sound Quality questionnaire. Using shifted tips of the psychophysical tuning curve as a basis for diagnosis, the TEN had high sensitivity (0.91) and poor specificity (0.55) for this population. The value of fe was lower when estimated with the sweeping noise, psychophysical tuning curve test than with the TEN test. For the listeners with cochlear dead regions, speech understanding, speech quality and music quality were best when no amplification was applied for frequencies within the dead region. For listeners without dead regions, speech understanding was best with full-bandwidth amplification and was reduced when amplification was not applied when the audiometric threshold exceeded 80 dB HL. The data from this study suggest that, to improve bimodal benefit for listeners who combine electric and acoustic stimulation, audiologists should routinely test for the presence of cochlear dead regions and determine amplification bandwidth accordingly.


Cardiac radioablation for ventricular tachycardia: Which approach for incorporating cardiorespiratory motions into the planning target volume?
To evaluate different approaches for generating a cardiorespiratory ITV for cardiac radioablation. Four patients with ventricular tachycardia were included in this study. For each patient, cardiac-gated and respiration-correlated 4D-CT scans were acquired. The cardiorespiratory ITV was defined using registrations of the cardiac and respiratory 4D-CT images. Five different approaches, which differed in the number of incorporated cardiac phases (1, 2, 10, or 1 with a fixed 3 mm margin (FM) expansion) and respiratory phases (2 or 10), were evaluated. For each approach, a VMAT treatment plan was simulated. Target coverage (TC) and spill were evaluated geometrically and dosimetrically for each approach. When employing one cardiac phase, the TC did not exceed 85%. Using the two extreme phases of the cardiac and respiratory cycles resulted in a geometric TC < 88% for two patients, with a dosimetric TC of 83% for one patient. An acceptable TC for all patients (geometric TC > 89%, dosimetric TC > 92%) was only achieved when combining 10 respiratory phases with either 2 or 10 cardiac phases or a single cardiac phase with FM. The use of a single cardiac phase with FM combined with 10 respiratory phases lead to a mean geometric and dosimetric spill of 43% and 35%, respectively. For cardiac radioablation, the use of two extreme cardiac phases combined with 10 respiratory phases is a robust approach to generate a cardiorespiratory ITV. The use of a single cardiac phase with or without fixed margin expansion is not recommended based on this study.


Nail Psoriasis in Older Adults: Epidemiology, Diagnosis, and Topical Therapy.
Nail involvement is common in patients with cutaneous psoriasis, which is prevalent among older adults. Nail psoriasis greatly impacts patients' quality of life and self-esteem. Concomitant psoriatic arthritis is common. Treating nail psoriasis in the geriatric population may be challenging. General nail care measures may prevent exacerbations. Topical therapy is relatively effective, with a low rate of adverse events and little to no risk of systemic toxicity or drug interactions. However, application under occlusion may be cumbersome. There is a need for randomized controlled clinical trials in the elderly population to make more evidence-based treatment guidelines.


Visualizing the global trends of peptides in wound healing through an in-depth bibliometric analysis.
Wound healing is a complicated and multistage biological process for the repair of damaged/injured tissues, which requires intelligent designs to provide comprehensive and convenient treatment. Peptide-based wound dressings have received extensive attention for further development and application due to their excellent biocompatibility and multifunctionality. However, the current lack of intuitive analysis of the development trend and research hotspots of peptides applied in wound healing, as well as detailed elaboration of possible research hotspots, restricted obtaining a comprehensive understanding and development in this field. The present study analysed publications from the Web of Science (WOS) Core Collection database and visualized the hotspots and current trends of peptide research in wound healing. Data between January 1st, 2003, and December 31st, 2022, were collected and subjected to a bibliometric analysis. The countries, institutions, co-authorship, co-citation reference, and co-occurrence of keywords in this subject were examined using VOSviewer and CiteSpace. We provided an intuitive, timely, and logical overview of the development prospects and challenges of peptide application in wound healing and some solutions to the major obstacles, which will help researchers gain insights into the investigation of this promising field.


Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence.
Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation.


Effectiveness of the manual diaphragmatic stretching technique on respiratory function in cerebral palsy: A randomised controlled trial.
Respiratory failure resulting from diaphragmatic muscle weakness is a major cause of long-term hospitalization in children with cerebral palsy (CP). Manual diaphragmatic stretching technique (MDST) can be directly applied to stretch diaphragmatic muscle and has been reported to improve respiratory function in patients with asthma and COPD. However, there have been no studies among CP. This study aimed to examine the effects of a six-week MDST course on respiratory function among CP. Fifty-three children with spastic CP were randomly assigned to experimental (n = 27) and control (n = 26) groups. The experimental group received MDST on non-consecutive days, three days per week for six weeks alongside standard physiotherapy (SDPT), while the control group received only SDPT. The outcome variables were diaphragmatic mobility, pulmonary function and chest wall expansion. MDST significantly improved diaphragmatic mobility on both sides of the body, with a between-group difference of 0.97 cm (95% CI 0.55-1.39 cm, p < 0.001) for the right side and 0.82 cm (95% CI 0.35-1.29 cm, p = 0.001) for the left side. MDST significantly improved chest wall expansion at the xiphoid process and umbilical levels, with between-group differences of 0.57 cm (95% CI 0.12-1.20 cm, p = 0.013) and 0.87 cm (95% CI 0.31-1.43 cm, p = 0.003), respectively. There was no significant difference in pulmonary function testing between the groups. MDST could significantly improve diaphragmatic mobility, and lower and abdominal chest wall expansion, among children with CP. Therefore, MDST could be considered as an additional technique for physiotherapy programmes, to improve diaphragmatic function in spastic CP.


Effect of sea ice retreat on marine aerosol emissions in the Southern Ocean, Antarctica.
Sea ice retreat in the polar region is expected to increase the emissions of sea salt aerosols and biogenic gases, which may significantly impact the climate by increasing cloud condensation nuclei (CCN) population and changing solar radiation. In this study, aerosol compositions were measured at high-time-resolution (1 h) with an in-situ gas and aerosol composition monitoring system in polynya regions of the Southern Ocean (SO) to access the effects of sea ice concentrations on the sea salt aerosol (SSA) and secondary biogenic aerosol (SBA) in the SO. SSA emissions increased by more than 30% as sea ice concentration decreased from 85% to 29%. However, SSA emissions did not increase monotonically as the sea ice concentration decreased. The highest SSA concentration occurred in drifting sea ice region. Sea ice melting increased SBA concentrations by enhancing the air-sea exchanges of SBA precursor gases and the release of algae from sea ice. Positive correlations between SSA and wind speed were present in different sea ice regions, while SBA didn't reveal an obvious correlation with wind speed in the SO. The impact of wind speed on the SSA emissions were very different, Higher slope value of 41.83 and 35.81 were present in the DSI and SIF region, while the value was only about 16.74 in the SIC region. The results extended the knowledge of the effect of future sea ice retreat on marine aerosol emissions and potential climate changes in the polar region.


Increased dopamine transporter density in Parkinson's disease patients with Social Anxiety Disorder.
Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.


Mental Well-Being and Self-Efficacy of Healthcare Workers in Saudi Arabia During the COVID-19 Pandemic.
To assess mental well-being (MW), self-efficacy (SE), and their predictors among healthcare workers (HCWs) in Saudi Arabia during the COVID-19 pandemic. Analytical cross-sectional study recruited 1046 HCWs by cluster random sampling technique. Socio-demographic, health, and occupational characteristics were collected for all participants. The WHO five Well-Being Index (WHO-5) and General Self-Efficacy Scale (GSES) were used to assess MW and SE of the participants, respectively. The binary logistic regression model was fit to the dependent (outcomes), namely mental well-being and self-efficacy, and independent other variables (predictors). Out of all participants (n=1046), 27.2% had negative MW scores, and 36.6% had low SE scores. The mean scores of both MW and SE were in the normal levels (16.7±5.90 and 31.5±6.63 out of 25 and 40, respectively). Younger and older ages, irregular exercise, nursing professions, history of anxiety and/or depression, lesser years of experience, and longer daily working hours were found to be the main predictors of negative MW and low SE, among study participants. Mental well-being (MW) and self-efficacy (SE) of the HCWs in Saudi Arabia are satisfactory but attention should be paid towards supporting the vulnerable groups for promoting the resilience of HCWs during the battle against the current pandemic.


Endometrial cells on Pap tests: ideal reporting is more complex than just finding the right age.
The age for reporting normal endometrial cells (EMCs) on Pap tests was changed to ≥ 45 years in the latest Bethesda update (2014). This recommendation is solely based on age with no consensus on optimal reporting guidelines. Pap tests with EMCs for women ≥40 years were retrieved from our Laboratory Information System (LIS). Patient age, last menstrual period (LMP) and available follow-up histology were recorded. Follow-up diagnoses were categorized as: no significant pathology, benign, hyperplasia ± atypia, or malignant. The Fisher's exact test was used to assess the association between categorical variables, p < .05 (two-sided test) was considered significant. Of the 352 cases with EMCs, 155 had surgical follow-up. They showed no malignancy in the 89 women between 40-49 years, compared with five malignancies in the 66 women 50+ years (p = .016). The number of cases with significant pathology (hyperplasia and malignant) was 4 (40-49 years) vs. 11 (50+ years) (p = 0.029). The LMP was inconsistently provided (57%) and women identified as postmenopausal on requisition comprised all the malignancies and half the hyperplasias. Combined effort by pathologists and clinicians necessitates determining the best standardized clinicopathologic guidelines to report EMCs and appropriate follow-up. Increasing the required age to ≥50 years would provide more optimal patient management; however, there are other considerations beyond age. Reporting EMCs in postmenopausal women is a reasonable alternative requiring consistent and accurate recording of LMP. Improving provided information for pathologists, determining reporting requirements for EMCs and standardizing clinical follow-up should be a multidisciplinary effort. Diagn. Cytopathol. 2017;45:587-591. © 2017 Wiley Periodicals, Inc.


Contribution of road dust from Low Impact Development (LID) construction sites to atmospheric pollution from heavy metals.
The re-suspension of road dust due to intense Low Impact Development (LID) construction activities may be a major contributor to atmospheric metal pollution. However, the distribution characteristics, mobility potential, and pollutant load of atmospheric particles at LID construction sites are not clear. Consequently, management practices to mitigate air pollution from LID construction are lacking. We investigated the atmospheric metal pollution from road dust produced during different construction stages of rain gardens and porous pavements and estimated the ecological risks posed by the heavy metals. Although concentrations of heavy metals in road dust at LID construction sites were lower than at sites without LID construction, the ecological risks posed by the atmospheric heavy metals at LID construction sites were generally higher due to the greater mass of road dust produced during LID construction. Hence, LID management practices should focus on the removal of road dust, especially finer particles (<44 μm) produced during early construction stages. In roads, the zones influenced by LID construction is related to road types based on traffic volume; these road types in descending order of zone influenced by LID construction are: arterial road (400-600 m) > collector road (100-150 m) > access road (50-100 m) > laneway (30-50 m). Based on the study sites, we estimate LID construction in China will contribute 2.31 and 6.23 times as much as the current load of atmospheric particles by 2020 and 2030; and we project atmospheric heavy metals will be 1.45-2.18 and 2.82-4.73 times greater than the current load by 2020 and 2030 from the intense LID construction. Based on our results, several regulatory recommendations are presented to mitigate air pollution at LID construction sites.


Novel therapy using a fish scale collagen scaffold for rotator cuff healing in rat models.
Large and massive rotator cuff tears are challenging for surgeons because of postoperative complications such as repaired site retears. Recently, collagen extracted from fish scales has gained more attention because fish byproducts are considered a safer collagen source than other animal-derived scaffolds. This study aimed to evaluate the biological efficacy of tilapia scale-derived collagen scaffolds for rotator cuff repair in rat models. The infraspinatus tendon was resected from the greater tuberosity of Sprague-Dawley rats. In the control group, the tendon edge was sutured directly to the humeral head. In the augmentation group, the repaired site was augmented with a tilapia scale-derived collagen scaffold. Histologic examinations were performed at 2 and 4 weeks postoperatively via safranin O and immunofluorescence staining (isolectin B4 and type II collagen) in the bone-tendon junction. For mechanical analysis, the ultimate failure load of the tendon-humeral head complex was evaluated at 6 weeks postoperatively. During safranin O staining, the repaired enthesis demonstrated greater proteoglycan staining in the augmentation group than in the control group at 4 weeks postoperatively. Compared to controls, the augmentation group had significantly higher vascular staining with isolectin B4 at 2 and 4 weeks postoperatively, type II collagen expression at 4 weeks postoperatively, and ultimate failure load at 6 weeks postoperatively. Augmentation therapy using tilapia scale-derived type I collagen scaffolds promoted angiogenesis and fibrocartilage regeneration at the enthesis and provided higher mechanical strength than controls.


Combination of Rituximab, Low-Dose Cyclophosphamide, and Prednisone for Primary Membranous Nephropathy: A Case Series With Extended Follow Up.
B-cell depletion with rituximab has emerged as a first-line therapy for primary membranous nephropathy (MN). However, most patients do not achieve complete remission with rituximab monotherapy. In this case series, we report longer-term remission and relapse rates, anti-phospholipase A2 receptor (PLA2R) antibody levels, B-cell levels, and serious adverse events in patients with primary MN who received rituximab combined with an initial short course of low-dose oral cyclophosphamide and a course of rapidly tapered prednisone. Single-center retrospective case series. 60 consecutive patients with primary MN treated with the combination of rituximab, low-dose cyclophosphamide, and prednisone at the Vasculitis and Glomerulonephritis Center at the Massachusetts General Hospital. After treatment initiation, median follow-up was 38 (interquartile range [IQR], 25-62) months; 100% of patients achieved partial remission, defined as a urinary protein-creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline, at a median of 3.4 months. By 2 years after treatment initiation, 83% achieved complete remission, defined as a UPCR < 0.3 g/g. The median time to complete remission was 12.4 months. Immunologic remission (defined by an anti-PLA2R titer < 14 RU/mL) was achieved by 86% and 100% of anti-PLA2R seropositive patients (n = 29) at 3 and 6 months, respectively, after treatment initiation. After 1 year, the median UPCR fell from 8.4 (IQR, 5.0-10.7) to 0.3 (IQR, 0.2-0.8) g/g (P < 0.001). No patient relapsed throughout the duration of B-cell depletion. Relapse occurred in 10% of patients at 2 years after the onset of B-cell reconstitution following the last rituximab dose. Over a combined follow-up time of 228 patient-years, 18 serious adverse events occurred. One death occurred unrelated to treatment or primary MN, and 1 patient progressed to kidney failure requiring kidney replacement therapy. Absence of a comparison group. All patients with primary MN treated with combination therapy achieved partial remission and most achieved a durable complete remission with an acceptable safety profile.


Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.
Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high-performance less-oxygen-dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type-I PSs with aggregation-induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type-I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet-triplet energy gap, respectively. With the aid of a lysosomal acid-activated TAT-peptide-modified amphiphilic polymer poly(lactic acid)12k-poly(ethylene glycol)5k-succinic anhydride-modified TAT, the corresponding TTFMN-loaded nanoparticles accompanied with acid-triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type-I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate "Good Steel Used in the Blade" tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine.


Biometric measurements in fetuses of different race and gender.
Sonographic fetal biometric measurements on 6082 low-risk patients were compared in the second and third trimesters of pregnancy with respect to fetal race and gender. Ultrasonic measurements were obtained from fetuses of women participating in the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS), who underwent both an early sonographic evaluation between 15 and 22 weeks' gestation and a later scan between 31 and 35 weeks' gestation. In the 16-21-week scans, male fetuses had significantly larger biparietal diameter measurements compared to female fetuses (estimated difference 0.852 mm, 95% CI 0.737-0.967). There was only minimal difference in biparietal diameter between Black and White fetuses. Femur length was similar in both female and male fetuses, but longer in Black compared to White fetuses (estimated difference 0.808 mm, 95% CI 0.539-1.078). During the 31-35-week scans, male fetuses continued to have larger biparietal diameter measurements compared to female fetuses (estimated difference 1.22 mm, 95% CI 1.04-1.40), and femur lengths were persistently longer in Black compared to White fetuses (estimated difference 0.563 mm, 95% CI 0.234-0.893). Further investigation is necessary to evaluate the effect of these slight differences in morphometric fetal measurements between races and genders, so that we can determine how best to use them for optimizing prenatal care.


Nurse mentoring study demonstrates a magnetic work environment: predictors of mentoring benefits among pediatric nurses.
This descriptive, correlational research study applied a business mentoring model, the Mutual Benefits Model (M. G. Zey, 1991), to explore relationships among mentoring quality, mentoring quantity, mentoring type, length of employment, and mentoring benefits among pediatric staff nurse protégés in a single Midwestern, Magnet-designated, freestanding children's hospital. Results support the hypothesis that the linear combination of quality of mentoring and length of employment explained 40% of the variance in mentoring benefits, more than any one factor alone (R=.63, p=.01). Nurse mentoring, conceptually and experientially, demonstrates the Magnet model components and provides implications for the Magnet Journey.


Birth control pills and risk of hypothyroidism: a cross-sectional study of the National Health and Nutrition Examination Survey, 2007-2012.
The association between use of birth control pills and thyroid function in women has not ever been well studied, but potential risk has been implicated by small sample-sized studies. We aimed to determine this association using a large epidemiological survey. Cross-sectional study. National Health and Nutrition Examination Survey conducted in the USA from 2007 to 2012. Female respondents aged 18+ who had data on history of taking birth control pills and thyroid function were included. History of taking birth control pills was based on responses on the reproductive health questionnaire. Participants not on antithyroid medication with thyroid-stimulating hormone (TSH) >5.6 mIU/L and those on thyroid hormone replacement regardless of TSH were categorised as hypothyroid. Participants not on thyroid hormone replacement or antithyroid medication who had TSH between 0.34 mIU/L and 5.6 mIU/L were classified as euthyroid. Association between use of birth control pills and hypothyroidism based on multivariate logistic regression analysis. A total of 5116 female adults with history of taking birth control pills (n=3034) and without (n=2082) were included. A higher prevalence of hypothyroidism was found in those who have ever taken birth control pills (17.7% vs 14.1%; p=0.003). Multivariate logistic regression adjusted for confounding covariables, including age, race, education, body mass index, smoking status, alcohol use, history of thyroid disease, current thyroid disease, first menstrual age, pregnancy history, menopause status and history of hormone replacement use, demonstrated a significant association between history of taking birth control pills for more than 10 years and hypothyroidism (OR, 3.837; 95% CI 1.402 to 10.500; p=0.009). Longer history of using birth control pills was strongly associated with hypothyroidism, especially for more than 10 years.


WITHDRAWN: Polymyositis of bilateral upper legs seen on FDG-PET/CT in a patient with rheumatoid arthritis.
This article has been withdrawn at the request of the author and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Creating aesthetic success through proper clinician and laboratory technical communication.
High-quality aesthetic restorations that look great, function ideally, and last can only be predictably produced through implementation of excellent communication techniques and systems between the doctor and ceramist. With the availability of technology and the Internet, it is now easy to involve the laboratory via digital photographs. This article challenges one to begin including the laboratory early in the process and routinely use reliable techniques to transfer clinically significant information to the laboratory bench.


Induction of cellular differentiation and apoptosis by signal transduction inhibitors.
We have isolated signal transduction inhibitors of low molecular weight from microorganisms and plants. Since inducers of differentiation and apoptosis may be developed as new anticancer agents, we have studied induction of differentiation and apoptosis in neoplastic cells by our signal transduction inhibitors. Aristeromycin isolated as an Abl function inhibitor induced erythroid differentiation in human CML K562 cells. Aristeromycin may induce differentiation by inhibition of methylating reactions in the cell. We isolated dephostatin from Streptomyces as a tyrosine phosphatase inhibitor, and synthesized its stable analogue, 3,4-dephostatin. The stable analogue, 3,4-dephostatin, potentiated NGF-induced morphological differentiation in rat pheochromocytoma PC12h cells, possibly by inhibition of tyrosine dephosphorylation of MAPK. Erbstatin, a tyrosine kinase inhibitor, induced morphological apoptosis and internucleosomal DNA fragmentation in mouse leukemia L1210 and human SCLC cells. Erbstatin was shown to induce apoptosis by hydrogen peroxide formation. Thus, these signal transduction inhibitors appear to be useful tools for the mechanistic study of cellular differentiation and apoptosis.


Association of appropriateness for ICU admission with resource use, organ support and long-term survival in critically ill cancer patients.
We aimed to evaluate the characteristics, resource use and outcomes of critically ill patients with cancer according to appropriateness of ICU admission. This was a retrospective cohort study of patients with cancer admitted to ICU from January 2017 to December 2018. Patients were classified as appropriate, potentially inappropriate, or inappropriate for ICU admission according to the Society of Critical Care Medicine guidelines. The primary outcome was ICU length of stay (LOS). Secondary outcomes were one-year, ICU, and hospital mortality, hospital LOS and utilization of ICU organ support. We used logistic regression and competing risk models accounting for relevant confounders in primary outcome analyses. From 6700 admitted patients, 5803 (86.6%) were classified as appropriate, 683 (10.2%) as potentially inappropriate and 214 (3.2%) as inappropriate for ICU admission. Potentially inappropriate and inappropriate ICU admissions had lower likelihood of being discharged from the ICU than patients with appropriate ICU admission (sHR 0.55, 95% CI 0.49-0.61 and sHR 0.65, 95% CI 0.53-0.81, respectively), and were associated with higher 1-year mortality (OR 6.39, 95% CI 5.60-7.29 and OR 11.12, 95% CI 8.33-14.83, respectively). Among patients with appropriate, potentially inappropriate, and inappropriate ICU admissions, ICU mortality was 4.8%, 32.6% and 35.0%, and in-hospital mortality was 12.2%, 71.6% and 81.3%, respectively (p < 0.01). Use of organ support was more common and longer among patients with potentially inappropriate ICU admission. The findings of our study suggest that inappropriateness for ICU admission among patients with cancer was associated with higher resource use in ICU and higher one-year mortality among ICU survivors.


Differences in Healthcare Use Between Patients With Persistent and Paroxysmal Atrial Fibrillation Undergoing Catheter-Based Atrial Fibrillation Ablation: A Population-Based Cohort Study From Ontario, Canada.
Background Patients with persistent atrial fibrillation (AF) undergoing catheter-based AF ablation have lower success rates than those with paroxysmal AF. We compared healthcare use and clinical outcomes between patients according to their AF subtypes. Methods and Results Consecutive patients undergoing AF ablation were prospectively identified from a population-based registry in Ontario, Canada. Via linkage with administrative databases, we performed a retrospective analysis comparing the following outcomes between patients with persistent and paroxysmal AF: healthcare use (defined as AF-related hospitalizations/emergency room visits), periprocedural complications, and mortality. Multivariable Poisson modeling was performed to compare the rates of AF-related and all-cause hospitalizations/emergency room visits in the year before versus after ablation. Between April 2012 and March 2016, there were 3768 consecutive patients who underwent first-time AF ablation, of whom 1040 (27.6%) had persistent AF. The mean follow-up was 1329 days. Patients with persistent AF had higher risk of AF-related hospitalization/emergency room visits (hazard ratio [HR], 1.21; 95% CI, 1.09-1.34), mortality (HR, 1.74; 95% CI, 1.15-2.63), and periprocedural complications (odds ratio, 1.36; 95% CI, 1.02-1.75) than those with paroxysmal AF. In the overall cohort, there was a 48% reduction in the rate of AF-related hospitalization/emergency room visits in the year after versus before ablation (rate ratio [RR], 0.52; 95% CI, 0.48-0.56). This reduction was observed for patients with paroxysmal (RR, 0.45; 95% CI, 0.41-0.50) and persistent (RR, 0.74; 95% CI, 0.63-0.87) AF. Conclusions Although patients with persistent AF had higher risk of adverse outcomes than those with paroxysmal AF, ablation was associated with a favorable reduction in downstream AF-related healthcare use, irrespective of AF type.


Fine resolution air quality dynamics related to socioeconomic and land use factors in the most polluted desert metropolitan in the American Southwest.
Air pollution kills approximately 4.2 million people every year. As air pollution varies significantly in different urban areas, the assessment of urban emissions is key to taking appropriate actions and formulating policies for sustainable built environments and to promote the wellbeing of people. The overarching goal of this study was to generate fine resolution aerosol optical depth (AOD) using Landsat imagery and examine both the socioeconomic inequalities of air pollution exposure and the air quality variation related to different land-use categories. This study has focused on a period of unusual population growth, 2000-2010, in the Phoenix Metropolitan Area. It was found that socioeconomic factors, vegetation indexes, and land use land cover types are all strong predictors of AOD, and the negative coefficients of socioeconomic values reveal insight into the social inequality of air pollution exposure. Results suggest that the government regulation on air pollution during the study period helped to improve air quality. Meanwhile, planting vegetation to mitigate air pollution should be carefully examined in order to find the right vegetation species and spatial configuration of vegetation cover in urban settings.


Fast formation of SnO2 nanoboxes with enhanced lithium storage capability.
SnO(2) nanoboxes with uniform morphology, good structural stability, and tunable interior volume can be facilely synthesized by template-engaged coordinating etching of pregrown Cu(2)O nanocubes at room temperature. When evaluated for their lithium storage properties, these SnO(2) nanoboxes manifest improved capacity retention.


Colonisation of gingival epithelia by subgingival biofilms in vitro: role of "red complex" bacteria.
Biofilm formation on tooth surface results in colonisation and invasion of the juxtaposed gingival tissue, eliciting strong inflammatory responses that lead to periodontal disease. This in vitro study investigated the colonisation of human gingival multi-layered epithelium by multi-species subgingival biofilms, and evaluated the relative effects of the "red complex" species (Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola). The grown biofilm consisted of Fusobacterium nucleatum, Campylobacter rectus, Veillonella dispar, P. gingivalis, Prevotella intermedia, T. forsythia, T. denticola, Actinomyces oris, Streptococcus anginosus and Streptococcus oralis, or its variant lacking the "red complex". After 48h in co-culture with the gingival epithelia, the bacterial species in the biofilm were quantified, whereas their localisation on the cell surface was investigated by combining confocal-laser scanning microscopy (CLSM) and fluorescence in situ hybridisation (FISH), as well as by scanning electron microscopy (SEM). Exclusion of the "red complex" quantitatively affected S. oralis, but not other species. The "red-complex" species were all able to colonise the gingival epithelial cells. A co-localisation trend was observed between P. gingivalis and T. denticola, as determined by FISH. However, in the absence of all three "red complex" bacteria from the biofilm, an immense colonisation of streptococci (potentially S. oralis) was observed on the gingival epithelia, as confirmed by both CLSM and SEM. While the "red complex" species synergise in colonizing gingival epithelia, their absence from the biofilm enhances streptococcal colonisation. This antagonism with streptococci reveals that the "red complex" may regulate biofilm virulence, with potential implications in periodontal pathogenesis.


Position of Cladribine Tablets in the Management of Relapsing-Remitting Multiple Sclerosis: An Expert Narrative Review From the United Arab Emirates.
The use of immune reconstitution therapies (IRT) in patients with relapsing-remitting multiple sclerosis (RRMS) is associated with a prolonged period of freedom from relapses in the absence of continuously applied therapy. Cladribine tablets is a disease-modifying treatment (DMT) indicated for highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features. Treatment with cladribine tablets is effective and well tolerated in patients with active MS disease and have a low burden of monitoring during and following treatment. In this article, an expert group of specialist neurologists involved in the care of patients with MS in the United Arab Emirates provides their consensus recommendations for the practical use of cladribine tablets according to the presenting phenotype of patients with RRMS. The IRT approach may be especially useful for patients with highly active MS insufficiently responsive to treatment with a first-line DMT, those who are likely to adhere poorly to a continuous therapeutic regimen, treatment-naïve patients with high disease activity at first presentation, or patients planning a family who are prepared to wait until at least 6 months after the end of treatment. Information available to date does not suggest an adverse interaction between cladribine tablets and COVID-19 infection. Data are unavailable at this time regarding the efficacy of COVID-19 vaccination in patients treated with cladribine tablets. Robust immunological responses to COVID-19 infection or to other vaccines have been observed in patients receiving this treatment, and treatment with cladribine tablets per se should not represent a barrier to this vaccination.


Fatal disseminated pyogenic infection due to hypermucoviscous hypervirulent Klebsiella pneumoniae: A case report and literature review.
Hypervirulent Klebsiella pneumonia is becoming recognized globally and has been associated with serious sequelae including death. However, ethnicity and metastatic infections are characteristics for hypermucoviscous hypervirulent Klebsiella pneumoniae (hvKp) and should be rolled in/out by PCR and/or string test.


Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: investigation of dose level with clinical correlates.
Incubating hematopoietic stem cells with IL-2 in vitro for 24 h generates cytotoxic T cells. When infused into patients, these cells may stimulate a graft-versus-tumor (GVT) effect. This clinical trial was designed to assess the ability of IL-2 activated peripheral blood stem cells (PBSC) to reconstitute hematopoiesis, to investigate dose levels and dose-limiting toxicities of IL-2, and to evaluate clinical results and preliminary laboratory effects using a combination of IL-2-activated autologous PBSC followed by IL-2 after transplantation. Sixty-one women with stage II-IV breast cancer were treated. After the administration of carboplatin (200 mg/m2/day for 3 days) and cyclophosphamide (2 g/m2/day for 3 days), patients received autologous PBSC that were cultured in IL-2 for 24 h followed by parenteral administration of IL-2 beginning the day of transplantation. Three escalating doses of IL-2 were evaluated with increasing duration up to 4 weeks. Of the 57 patients receiving IL-2 after tranplantation, 19 patients (33.3%) were unable to complete the planned course of IL-2 therapy due to persistent fevers (n = 9), diarrhea (n = 2), pulmonary capillary leak syndrome (n = 3), development of a rash (n = 1), atrial fibrillation (n = 1), or patient's request (n = 3). One death occurred during hospitalization. Engraftment of neutrophils occurred on day 11.5 (mean; range 8-21 days) and platelets on day 11.7 (mean; range 7-33 days). The maximal tolerated dose of IL-2 was 6 x 10(5) IU/m2/day for 4 weeks. Disease-free survival rates for all stages were comparable to current reports in the literature. Preliminary laboratory evaluations include FACScan analysis of the IL-2 activated PBSC demonstrating an increased percentage of CD3+, CD25+, HLA-DR+ T cells. Phenotypically similar cells were present in peripheral blood samples of patients when tested 15 days after transplantation. This study demonstrates successful engraftment with IL-2-activated PBSC after high-dose chemotherapy for women with stage II-IV breast cancer. The regimen is feasible and, although toxicities are common, they are manageable and correlate with increasing dose and duration of IL-2.


Jaundice.
Jaundice is caused by an increase in bilirubin in the blood. This can occur before the bilirubin is conjugated by the liver, or after the bilirubin has been conjugated. If the bilirubin has not yet ben conjugated, it will not be able to pass through lipid membranes and will not be soluble in water. Therefore it will not be present in urine. Increases in conjugated bilirubin by the liver, or problems in the conjugation itself. If the increase is conjugated bilirubin, the disorder lies within the outlet channels of the hepatocyte, or there is some kind of obstruction in the biliary outlet system. Within the liver itself, the most common causes of difficulty are acute and chronic hepatitis, alcoholic cirrhosis and drug-induced liver dysfunction. Extra-hepatic obstructions are usually associated with the gall bladder, but may result from tumors of sclerosing secondary to chronic bowel disease.