[Comparison of the effectiveness of psychiatric day care treatment between Japan and western countries: a review].
Over the last two decades, day care (DC) treatment for mentally ill patients has come into wide use in Japan, following the precedents get in Western countries providing evidence of effectiveness. Several studies to examine the efficacy of DC treatment have already been performed in Japan. However, they were limited to chronic schizophrenic patients as subjects, and therefore the findings showed only improvement of the negative symptoms of schizophrenia. In contrast, Western studies have included heterogeneous mental disorders, and some showed DC was effective not only for treatment of global mental dysfunction but also for that of antisocial or violent behavior, drug dependence, emotional distress, and other characteristic disorders. Several Japanese and Western studies have shown DC treatment to be superior to outpatient treatment for relieving psychiatric symptoms. Regarding reduction of readmission rate, the Western studies were not supportive, but some Japanese studies showed that DC treatment was preventive against readmission as long as the follow up period was brief (within two or two and a half years). These findings suggested that the effectiveness of DC treatment may be limited. However, recently, medication against negative symptoms of schizophrenia has been revolutionary changing, offering the possibility that the combination of DC treatment and appropriate drug therapy may overcome the great obstacle of rehabilitating mentally ill patients in society. It is also very important that an evidence-based, standardized methodology of DC treatment should be immediately established in Japan.


[Transperitoneal percutaneous cholecystolithotomy].
Transperitoneal percutaneous cholecystolithotomy is a surgical technique for gallstone removal in the otherwise healthy gallbladder. It is a one-stage, alternative surgical procedure to extracorporeal lithotripsy. ESWL treatment of gallstones permits preservation of the compromised organ but has not been reported to achieve the potential good results. We describe the principles of the technique--similar to that of percutaneous renal surgery--and highlight specific aspects in this condition.


TLR9 regulates the autophagy-lysosome pathway to promote dendritic cell maturation and activation by activating the TRAF6-cGAS-STING pathway.
Dysregulated maturation and activation of dendritic cells (DCs) play a significant role in the progression of systemic lupus erythematosus (SLE). The autophagy-lysosome pathway has been identified as a potential mechanism to inhibit DC activation and maturation, but its precise workings remain unclear. We investigated the role and regulatory mechanism of TLR9 in modulating the autophagy-lysosome pathway and DCs activation. The mRNA and protein expressions were assessed using qRT-PCR and/or western blot. NZBW/F1 mice was used to construct a lupus nephritis (LN) model in vivo. Cell apoptosis was analyzed by TUNEL staining. Flow cytometry was adopted to analyze DCs surface markers. Lyso-tracker red staining was employed to analyze lysosome acidification. Levels of anti-dsDNA, cytokines, C3, C4, urine protein and urine creatinine were examined by ELISA. The results showed that TLR9 was markedly increased in SLE patients, and its expression was positively correlated with SLEDAI scores and dsDNA level. Conversely, TLR9 expression showed a negative correlation with C3 and C4 levels. Loss-of function experiments demonstrated that TLR9 depletion exerted a substantial inhibition of renal injury, inflammation, and DCs numbers. Additionally, upregulation of TLR9 promoted DCs maturation and activation through activation of autophagy and lysosome acidification. Further investigation revealed that TLR9 targeted TRAF6 to activate the cGAS-STING pathway. Rescue experiments revealed that inactivation of the cGAS/STING signaling pathway could reverse the promoting effects of TLR9 upregulation on DCs maturation, activation, and autophagy-lysosome pathway. Overall, our findings suggested that TLR9 activated the autophagy-lysosome pathway to promote DCs maturation and activation by activating TRAF6-cGAS-STING pathway, thereby promoting SLE progression.


Treadmill training-induced adaptations in muscle phenotype in persons with incomplete spinal cord injury.
Body weight-supported treadmill (BWST) training has been shown to improve ambulatory capacity in persons with a spinal cord injury (SCI); however, the effect that BWST training has on skeletal muscle phenotype is unknown. We aimed to determine whether 6 months (three sessions/week) of BWST training in neurologically stable persons with a traumatic spinal cord injury (ASIA C) alters skeletal muscle phenotype, ambulatory capacity, and blood lipid profile. Externally supported body weight decreased, and walking velocity and duration of the training sessions increased (all P < 0.05) as a result of training. Muscle biopsies revealed increases in the mean muscle-fiber area of type I and IIa fibers. Training induced a reduction in type IIax/IIx fibers, as well as a decrease in IIX myosin heavy chain, and an increase in type IIa fibers. Maximal citrate synthase and 3-hydroxy-acyl-CoA dehydrogenase activity also increased following training. BWST training brought about reductions in plasma total (-11%) and low-density lipoprotein (-13%) cholesterol. We conclude that, in patients with a spinal cord injury, BWST training is able to induce an increase in muscle fiber size and bring about increases in muscle oxidative capacity. In addition, BWST training can bring about improvements in ambulatory capacity and antiatherogenic changes in blood lipid profile.


Anti-inflammatory therapies for cardiovascular disease.
Atherothrombosis is no longer considered solely a disorder of lipoprotein accumulation in the arterial wall. Rather, the initiation and progression of atherosclerotic lesions is currently understood to have major inflammatory influences that encompass components of both the innate and acquired immune systems. Promising clinical data for 'upstream' biomarkers of inflammation such as interleukin-6 (IL-6) as well as 'downstream' biomarkers such as C-reactive protein, observations regarding cholesterol crystals as an activator of the IL-1β generating inflammasome, and recent Mendelian randomization data for the IL-6 receptor support the hypothesis that inflammatory mediators of atherosclerosis may converge on the central IL-1, tumour necrosis factor (TNF-α), IL-6 signalling pathway. On this basis, emerging anti-inflammatory approaches to vascular protection can be categorized into two broad groups, those that target the central IL-6 inflammatory signalling pathway and those that do not. Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). Both approaches have the potential to benefit patients and reduce vascular events. However, care should be taken when interpreting these trials as outcomes for agents that target IL-6 signalling are unlikely to be informative for therapies that target alternative pathways, and vice versa. As the inflammatory system is redundant, compensatory, and crucial for survival, evaluation of risks as well as benefits must drive the development of agents in this class.


Occult radiopaque jaw lesions in familial adenomatous polyposis coli and hereditary nonpolyposis colorectal cancer.
The purposes of this study were to determine the association, in 10 pedigrees, between adenomatous polyposis coli, hereditary nonpolyposis colorectal cancer, and occult radiopaque jaw lesions, and to assess whether these radiodensities are predictors for adenomatous polyposis. In seven kindreds with adenomatous polyposis, all patients with polyps had jaw lesions; in one kindred, no jaw lesions were found. In one of two kindreds with hereditary nonpolyposis colorectal cancer, no affected individuals had jaw lesions. In the other, the 1 affected patient with dental radiographs had generalized jaw lesions. Twelve children less than 16 yr old at risk for adenomatous polyposis were observed. Seven children with jaw lesions developed polyps after a mean interval of 4 yr. Five children without jaw lesions were polyp-free during a 5-10-yr follow-up. Thus, occult jaw lesions are consistently found only in some families with adenomatous polyposis coli, providing support for heterogeneity in polyposis syndromes. Jaw lesions are good predictors for polyp development in kindreds with adenomatous polyposis coli and jaw lesions. Their role as markers in hereditary nonpolyposis colorectal cancer needs exploration.


Polyorchidism: a case report and review of the literature.
Polyorchidism is defined as the presence of two or more testes. It is a rare anomaly with approximately 77 cases reported in the literature. Polyorchidism is frequently associated with additional urological pathologies such as undescended testis, inguinal hernia, testicular torsion, hydrocoele, malignancy and infertility. Differential diagnosis includes spermatocoele, hydrocoele, epididymal cysts or aberrant epididymis. We report on an interesting case of polyorchidism in a 15-year-old man diagnosed on ultrasound and we review the literature and current management of polyorchidism.


Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD.


NPTX1 mutations trigger endoplasmic reticulum stress and cause autosomal dominant cerebellar ataxia.
With more than 40 causative genes identified so far, autosomal dominant cerebellar ataxias exhibit a remarkable genetic heterogeneity. Yet, half the patients are lacking a molecular diagnosis. In a large family with nine sampled affected members, we performed exome sequencing combined with whole-genome linkage analysis. We identified a missense variant in NPTX1, NM_002522.3:c.1165G>A: p.G389R, segregating with the phenotype. Further investigations with whole-exome sequencing and an amplicon-based panel identified four additional unrelated families segregating the same variant, for whom a common founder effect could be excluded. A second missense variant, NM_002522.3:c.980A>G: p.E327G, was identified in a fifth familial case. The NPTX1-associated phenotype consists of a late-onset, slowly progressive, cerebellar ataxia, with downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging. NPTX1 encodes the neuronal pentraxin 1, a secreted protein with various cellular and synaptic functions. Both variants affect conserved amino acid residues and are extremely rare or absent from public databases. In COS7 cells, overexpression of both neuronal pentraxin 1 variants altered endoplasmic reticulum morphology and induced ATF6-mediated endoplasmic reticulum stress, associated with cytotoxicity. In addition, the p.E327G variant abolished neuronal pentraxin 1 secretion, as well as its capacity to form a high molecular weight complex with the wild-type protein. Co-immunoprecipitation experiments coupled with mass spectrometry analysis demonstrated abnormal interactions of this variant with the cytoskeleton. In agreement with these observations, in silico modelling of the neuronal pentraxin 1 complex evidenced a destabilizing effect for the p.E327G substitution, located at the interface between monomers. On the contrary, the p.G389 residue, located at the protein surface, had no predictable effect on the complex stability. Our results establish NPTX1 as a new causative gene in autosomal dominant cerebellar ataxias. We suggest that variants in NPTX1 can lead to cerebellar ataxia due to endoplasmic reticulum stress, mediated by ATF6, and associated to a destabilization of NP1 polymers in a dominant-negative manner for one of the variants.


Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.
Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease.


Deep sequencing analysis of viral infection and evolution allows rapid and detailed characterization of viral mutant spectrum.
The study of RNA virus populations is a challenging task. Each population of RNA virus is composed of a collection of different, yet related genomes often referred to as mutant spectra or quasispecies. Virologists using deep sequencing technologies face major obstacles when studying virus population dynamics, both experimentally and in natural settings due to the relatively high error rates of these technologies and the lack of high performance pipelines. In order to overcome these hurdles we developed a computational pipeline, termed ViVan (Viral Variance Analysis). ViVan is a complete pipeline facilitating the identification, characterization and comparison of sequence variance in deep sequenced virus populations. Applying ViVan on deep sequenced data obtained from samples that were previously characterized by more classical approaches, we uncovered novel and potentially crucial aspects of virus populations. With our experimental work, we illustrate how ViVan can be used for studies ranging from the more practical, detection of resistant mutations and effects of antiviral treatments, to the more theoretical temporal characterization of the population in evolutionary studies. Freely available on the web at http://www.vivanbioinfo.org : firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Extended Asymmetrical Pedicle Subtraction Osteotomy for Adult Spinal Deformity: 2-Dimensional Operative Video.
Pedicle subtraction osteotomy (PSO) is an effective technique to correct fixed sagittal malalignment. A variation of this technique, the "trans-discal" or "extended" PSO (Schwab grade IV osteotomy), involves extending the posterior wedge resection of the index vertebra to include the superior adjacent disc for radical discectomy. The posterior wedge may be resected in asymmetric fashion to correct concurrent global coronal malalignment.This video illustrates the technical nuances of an extended asymmetrical lumbar PSO for adult spinal deformity. A 62-yr-old female with multiple prior lumbar fusions presented with worsening back pain and posture. Preoperative scoliosis X-rays demonstrated severe global sagittal and coronal malalignment (sagittal vertical axis [SVA, C7-plumbline] of 13.5 cm, pelvic incidence [PI] of 60°, lumbar lordosis [LL] of 14° [in kyphosis], pelvic tilt [PT] of 61°, thoracic kyphosis [TK] of 18°, and rightward coronal shift of 9.3 cm). The patient gave informed consent to surgery and for use of her imaging for medical publication. Briefly, surgery first involved transpedicular instrumentation from T10 to S1 with bilateral iliac screw fixation, and then T11-12 and T12-L1 Smith-Petersen osteotomies were performed. Next, an extended asymmetrical L4 PSO was performed and a 12° lordotic cage (9 × 14 × 40 mm) was placed at the PSO defect. Rods were placed from T10 to iliac bilaterally, and accessory supplemental rods spanning the PSO were attached. Postoperative scoliosis X-rays demonstrated improved alignment: SVA 5.5 cm, PI 60°, LL 55°, PT 36°, TK 37°, and 3.7 cm of rightward coronal shift. The patient had uneventful recovery.


Are There Cochlear Dead Regions Involved in Hearing Loss after Cisplatin Ototoxicity?
The most common complaint of patients affected by chemotherapy-induced hearing loss is difficulty understanding speech in noisy environments despite the use of hearing aids. Cochlear dead regions, those areas with damaged or absent inner hair cells and dendrites, may account for this type of hearing loss. However, it is unknown whether this condition is associated with cisplatin agents. The aim of this study was to determine whether cisplatin is associated with hearing loss and cochlear dead regions. This prospective cross-sectional study was conducted in patients participating in routine audiological monitoring during and after chemotherapy treatment. Adults undergoing audiological evaluation who had completed chemotherapy treatment were invited to participate. Patients were divided into 3 groups according to pure tone thresholds. Group 1 patients had thresholds over 70 dB (HL) at 2,000 Hz and higher frequencies. Group 2 patients had thresholds below 70 dB (HL) up to 2,000 Hz. Patients in the control group had normal thresholds at all frequencies. The threshold equalizing noise test (TEN[HL]) was used to identify cochlear dead regions by repeating thresholds in the presence of TEN noise played from a compact disc. The presence of cochlear dead regions was established when the masked threshold was 10 dB or greater above the TEN level and 10 dB or greater above the absolute threshold at any frequency. Twelve patients were included in study group 1, 10 patients in study group 2, and 7 patients in the control group. Cochlear dead regions were present in all patients with hearing loss and in none of the control group. For groups 1 and 2, mean differences between absolute and masked thresholds were 21 and 16 dB at 500 Hz; 22 and 15 dB at 1,000 Hz; 31 and 17 dB at 2,000 Hz; 32 and 20 dB at 3,000 Hz; and 31 and 21 dB at 4,000 Hz, respectively. Nevertheless, analysis of variance testing with Bonferroni analysis showed a difference between groups 1 and 2 only at 2,000, 3,000, and 4,000 Hz. We found unresponsive or dead cochlear regions in patients who had undergone cisplatin chemotherapy even among patients with mild to moderate hearing loss.


A cytotoxicity and comparative antibacterial study on the effect of Zataria multiflora Boiss, Trachyspermum copticum essential oils, and Enrofloxacin on Aeromonas hydrophila.
this study designed to test the antibacterial potency of enrofloxacin (ENR) and essential oils from Zataria multiflora Boiss (ZEO) and Trachyspermum copticum (TEO) on Aeromonas hydrophila. The antibacterial potency of test compounds was determined by several methods including the inhibition zone diameter determination, microbroth dilution method and colorimetric method of MTT. The cytotoxicity of test substances was assessed on Chinook salmon (Oncorhynchus tshawytscha) embryo (CHSE-214) cells. RESULTS showed that ENR and tested essential oils exert antibacterial effect against A. hydrophila. Moreover, ENR exerted the most potent antibacterial effect with MIC values of 62.5 ng/ml. The natural compounds of ZEO and TEO also showed antibacterial effects with rather high MIC values of 0.315 mg/ml, and 1.25 mg/ml, respectively. None of the tested substances showed toxicity on CHSE-24 cells. It is concluded that ZEO and TEO could be applied to prevent from A. hydrophila infection. Moreover, data also suggest that MTT method could be both cost- and time-effective and accurate method of MIC determination.


[Scientific integrity faces plagiarism fabricated with the ChatGPT].
Among the malpractices that undermine research integrity, plagiarism is a major threat given its frequency and evolving presentations. Plagiarism implies the intentional grabbing of texts, ideas, images, or data belonging to others and without crediting them. However, the different and even masked forms of plagiarism often difficult a clear identification. Currently, the many kinds of fraud and plagiarism account for most retractions in traditional and open access journals. Further, the rate of retracted articles is higher in the Latin American databases LILACS and Scielo than in PubMed and Web of Science. This difference has been related to the typical laxity of our culture and the lack of English writing skills of non-Anglophone researchers. These features explain the conflict experienced by Latin American students in USA where they face a stricter culture regarding academic and scientific plagiarism. In the internet era, the ease of accessing scientific literature has increased the temptation to plagiarize but this ethical breach has been countered by antiplagiarism software. Now, the so-called "paraphragiarism" prompted by paraphrasing tools exceeds the infamous "copy-paste". For instance, the innovative ChatGPT can be used for plagiarizing and paraphragiarizing. Moreover, its inclusion as coauthor in scientific papers has been banned by prestigious journals and the International Committee of Medical Journal Editors because such chatbot cannot meet the required public responsibility criterium. To avoid plagiarism, it is enough to always give due credit in the proper way. Lastly, I question the ill-fated and now prevailing conjunction of blind faith in progress and zero skepticism that prevents us from foreseeing the negative consequences of technological advances.


Foods and food groups associated with the incidence of colorectal polyps: the Adventist Health Study.
Colorectal cancer (CRC) is a leading cause of cancer death in the United States. The majority of CRC arise in adenomatous polyps and 25-35% of colon adenoma risk could be avoidable by modifying diet and lifestyle habits. We assessed the association between diet and the risk of self-reported physician-diagnosed colorectal polyps among 2,818 subjects who had undergone colonoscopy. Subjects participated in 2 cohort studies: the AHS-1 in 1976 and the AHS-2 from 2002-2005. Multivariate logistic regression analysis was used to estimate the period risk of incident cases of polyps; 441 cases of colorectal polyps were identified. Multivariate analysis adjusted by age, sex, body mass index, and education showed a protective association with higher frequency of consumption of cooked green vegetables (OR 1 time/d vs. <5/wk = 0.76, 95% CI = 0.59-0.97) and dried fruit (OR 3+ times/wk vs. <1 time/wk = 0.76, 95%CI = 0.58-0.99). Consumption of legumes at least 3 times/wk reduced the risk by 33% after adjusting for meat intake. Consumption of brown rice at least 1 time/wk reduced the risk by 40%. These associations showed a dose-response effect. High frequency of consumption of cooked green vegetables, dried fruit, legumes, and brown rice was associated with a decreased risk of colorectal polyps.


Biochemical evidence for multiple independent emetine resistance genes in Chinese hamster cells.
Hybridization-complementation studies indicated that mutations in multiple genes can render Chinese hamster cells resistant to the alkaloid translation inhibitor emetine. Two of the genes, emtA and emtB, recognized in Chinese hamster lung and ovary cell lines, respectively, are known to affect the ribosomes of the cells directly. Although mutations in a third gene, emtC, affect the translation apparatus of Chinese hamster peritoneal cells in vitro (Wasmuth et al., Mol. Cell. Biol. 1:58-65, 1981), the molecular product of the emtC locus remains to be determined. To study the molecular basis for genetic complementation among emetine-resistant Chinese hamster cell mutants, we analyzed ribosomal proteins elaborated by complementing, emetine-sensitive hybrid clones (EmtB X EmtA and EmtB X EmtC) and by emetine-resistant clones that segregated from the hybrids. The electrophoretic forms of ribosomal protein S14 (the emtB gene product) elaborated by these clones indicated that the EmtA and EmtC phenotypes are independent of the emtB locus and that the emtA and emtC loci are not chromosomally linked to emtB.


Transport in ferrocene single molecules for terahertz applications.
The transport properties of single ferrocene molecules connected to nanoscopic gold electrodes are investigated in the framework of density functional theory (DFT) calculations using the non-equilibrium Green's function formalism. Our setup describes a molecular rotor, where one cyclopentadienyl (Cp) ring of the ferrocene molecule is fixed by the two electrodes, while the second ring is able to rotate. For small enough rotation energies the barrier between the eclipsed and staggered conformations of the ferrocene molecule ensures the functionality of a molecular oscillator. The changes in the transmission function introduced by the relative rotation angle between the two Cp rings are analyzed in both linear and non-linear bias regimes. For larger rotation energies, the device works in the spinning mode. The real time behavior of the nanomechanical device is investigated using DFT-based molecular dynamics, which shows its feasibility for applications in the terahertz regime. In the oscillating mode the natural frequencies are determined, while the spinning mode shows a remarkably reliable behavior with increasing rotation energy.


Play brick therapy to aid the social skills of children and young people with autism spectrum disorder: the I-SOCIALISE cluster RCT.
Social skills interventions are commonly recommended to help children and young people with autism spectrum disorder develop social skills, but some struggle to engage in these interventions. LEGO® (LEGO System A/S, Billund, Denmark) based therapy, a group social skills intervention, aims to be more interesting and engaging. To evaluate the clinical effectiveness of LEGO® based therapy on the social and emotional skills of children and young people with autism spectrum disorder in school settings compared with usual support. Secondary objectives included evaluations of cost-effectiveness, acceptability and treatment fidelity. A cluster randomised controlled trial randomly allocating participating schools to either LEGO® based therapy and usual support or usual support only. Mainstream schools in the north of England. Children and young people (aged 7-15 years) with autism spectrum disorder, their parent/guardian, an associated teacher/teaching assistant and a facilitator teacher/teaching assistant (intervention schools only). Schools randomised to the intervention arm delivered 12 weekly sessions of LEGO® based therapy, which promotes collaborative play and encourages social problem-solving in groups of three children and young people with a facilitator (trained teacher or teaching assistant). Participants received usual support from school and community services. Participants in the control arm received usual support only. Research assistants and statisticians were blind to treatment allocation. The social skills subscale of the Social Skills Improvement System (SSIS), completed by the children and young people's unblinded teacher pre randomisation and 20 weeks post randomisation. The SSIS social skills subscale measures social skills including social communication, co-operation, empathy, assertion, responsibility and self-control. Participants completed a number of other pre- and post-randomisation measures of emotional health, quality of life, loneliness, problem behaviours, academic competence, service resource utilisation and adverse events. A total of 250 children and young people from 98 schools were randomised: 127 to the intervention arm and 123 to the control arm. Intention-to-treat analysis of the main outcome measure showed a modest positive difference of 3.74 points (95% confidence interval -0.16 to 7.63 points, standardised effect size 0.18; p = 0.06) in favour of the intervention arm. Statistical significance increased in per-protocol analysis, with a modest positive difference (standardised effect size 0.21; p = 0.036). Cost-effectiveness of the intervention was found in reduced service use costs and a small increase in quality-adjusted life-years. Intervention fidelity and acceptability were positive. No intervention-related adverse events or effects were reported. The primary and pre-planned sensitivity analysis of the primary outcome consistently showed a positive clinical difference, with modest standardised effect sizes of between 0.15 and 0.21. There were positive health economics and qualitative findings, corroborated by the difference between arms for the majority of secondary outcomes, which were not statistically significant but favoured the intervention arm. Post hoc additional analysis was exploratory and was not used in drawing this conclusion. Given the small positive change, LEGO® based therapy for children and young people with autism spectrum disorder in schools should be considered. The primary outcome measure was completed by an unblinded teacher (rather than by the facilitator). The study team recommends future research into LEGO® based therapy, particularly in school environments. This trial is registered as ISRCTN64852382. This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: 15/49/32) and is published in full in Public Health Research; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.


TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma.
A metastasizing mouse cell line (TS/A), originated from a mammary adenocarcinoma which arose spontaneously in a BALB/c female retired breeder, has been established in vitro. It displayed a remarkable morphologic heterogeneity, which is evident in plastic adherent cultures (cell types ranging from epithelial-like to fibroblast-like) as well as in semi-solid agar cultures. The TS/A line exhibited the presence of specific cytoplasmic estradiol receptor, with a binding activity of 16 fmoles/mg cytosol protein. The in vivo growth pattern was as follows: a s.c. inoculum of 105 cells caused a 100 per cent tumor take and kill in syngeneic animals; mean survival time was 54 +/- 1 days; it did not show significant transplant immunogenicity in syngeneic animals; it was able to give rise to both spontaneous lung metastases and artificial lung colonies; it had a high capacity to grow in H-2 matched, minor histocompatibility antigen incompatible hosts (10(6) cells killed 100 per cent DBA/2 mice in 58 +/- 2 days). This line of spontaneous mammary tumor cells is proposed as a useful model for studies on the heterogeneity of the neoplastic population in relation to metastatic spread, on tumor immunogenicity, and on therapy of mammary neoplasia.


Monounsaturated Fatty Acid Levels May Not Affect Cardiovascular Events: Results From a Mendelian Randomization Analysis.
Background/Aim: Several observational studies evaluated the links between serum monounsaturated fatty acids (MUFAs) and cardiovascular events with controversial results. In the present study, Mendelian randomization (MR) analysis was applied to obtain unconfounded estimates of the causal associations of genetically determined serum MUFAs with coronary heart disease (CHD), myocardial infarction (MI), cardioembolic stroke (CS), and ischemic stroke (IS). Methods: Four MUFAs were studied (i.e., 10-heptadecenoate, myristoleic, oleic, and palmitoleic acid). Data from the largest genome-wide association studies on MUFAs, CHD, MI, and stroke were analyzed. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, as well as MR-pleiotropy residual sum and outlier were applied. To rule out the impact of single-nucleotide polymorphism (SNP), the leave-one-out method was also performed. Results: Genetically higher-serum 10-heptadecenoate levels did not affect the risk of CHD (IVW = Beta: -0.304, p = 0.185), MI (IVW = Beta: -0.505, p = 0.066), CS (IVW = Beta: -0.056, p = 0.945), and IS (IVW = Beta: -0.121, p = 0.767). Similarly, no significant associations were observed for myristoleic acid (CHD: IVW = Beta: 0.008; MI: IVW = Beta: 0.041; CS: IVW = Beta: 0.881; IS: IVW = Beta: 0.162), oleic acid (CHD: IVW = Beta: -0.2417; MI: IVW = Beta: -0.119; CS: IVW = Beta: 1.059; IS: IVW = Beta: 0.008491), and palmitoleic acid (CHD: IVW = Beta: -0.06957; MI: IVW = Beta: -0.01255; CS: IVW = Beta: 1.042; IS: IVW = Beta: -0.1862). A low likelihood of heterogeneity and pleiotropy was reported, and the observed associations were not driven by single SNPs. Conclusions: In the present MR analysis, serum MUFA levels were not associated with the risk of CHD, MI, CS, and IS. Further research, evaluating more MUFAs, is required to elucidate the links between MUFAs and CVD to contribute to health policy decisions in reducing CVD risk.


Assessment of volumetric changes with a best-fit method in three-dimensional stereophotograms.
Different three-dimensional stereophotogrammetry systems and analyzing methods exist that often use landmarks for comparison. Measurement errors in landmark or surface comparison are mostly within 1 mm, which seems clinically acceptable. The aim of this study was to validate a three-dimensional stereophotogrammetric best-fit method of assessing volumetric changes and to compare three devices. The validation of the best-fit method was at first done on a life-size dummy head. Scans were made in the ideal position, as well as in four additional positions, and a scan was made in which a soft putty specimen was added to the dummy head. The comparison was executed with a best-fit method using triangulation. Student's t tests were used to detect statistically significant differences. Second, comparisons were made among scans of a white man in the ideal position and with volume changes added. The different positions tested for the dummy head showed no significant volume differences within each system or among systems. The differences found when adding a soft putty specimen fell into the same range as the differences between various positions. The differences within a live situation were 10 times greater compared with the dummy-head situation. In a dummy-head situation, the different systems gave similar results when tested with a best-fit method. However, in live situations the differences may become 10 times greater, possibly due to different facial expressions. These differences may become clinically relevant and, therefore, further research in volumetric changes is needed.


Visual-vestibular interaction in multiple sclerosis.
Visual modulation of the vestibuloocular reflex (VOR) was analyzed in 20 patients with multiple sclerosis who had no vestibular or ocular motor symptoms. Visual suppression of the VOR was impaired in 75% of patients. VOR gains in darkness were elevated in 35% of patients. Elevated VOR gain in darkness is attributed to vestibular adaptation to defective smooth pursuit. This vestibular plasticity achieved retinal image stability by matching eye velocity to head velocity when stationary targets were viewed. The high incidence of impaired visual suppression of the VOR rivals the sensitivity of other physiologic tests used to identify multiple sclerosis.


First occurrence of KPC-2-possessing Klebsiella pneumoniae in a Greek hospital and recommendation for detection with boronic acid disc tests.
To investigate the first KPC carbapenemase-producing Klebsiella pneumoniae isolate from a Greek hospital, including phenotypic methods to aid recognition of this resistance type. A carbapenem-resistant clinical isolate of K. pneumoniae was recovered from a hospitalized Greek patient. Detailed susceptibility testing was carried out by the agar dilution method. The isolate was screened by phenotypic and genotypic assays for the presence of various beta-lactamases. Boronic acid disc tests were performed to show the ability of these tests to detect production of the KPC enzymes. The potential for conjugal transfer of carbapenem resistance was examined by biparental matings, plasmid analysis and PCR studies. The isolate possessed on the same self-transferable plasmid the KPC-2 carbapenemase and the SHV-12 extended-spectrum beta-lactamase. Although the isolate did not produce an AmpC-type enzyme, the production of KPC-2 was associated with positive boronic acid disc tests using cephamycins and cefotaxime as well as cefepime and carbapenems as substrates. KPC-2-possessing K. pneumoniae clinical isolates seem to have been introduced in our region. Boronic acid disc tests using boronic acid in combination with carbapenems or cefepime may help the phenotypic detection of KPC enzymes and their distinction from plasmid-mediated AmpC enzymes.


A late-transition metal oxo complex: K7Na9[O=PtIV(H2O)L2], L = [PW9O34]9-.
Terminal mono-oxo complexes of the late transition metal elements have long been considered too unstable to synthesize because of repulsion between the oxygen electrons and the mostly filled metal d orbitals. A platinum(IV)-oxo compound flanked by two polytungstate ligands, K7Na9[O=Pt(H2O)L2], L = [PW9O34(9-)], has now been prepared and isolated at room temperature as air-stable brown crystals. X-ray and neutron diffraction at 30 kelvin revealed a very short [1.720(18) angstrom] Pt-O bond and no evidence of a hydrogen atom at the terminal oxygen, ruling out a better precedented Pt-OH complex. Density functional theory and spectroscopic data account for the stability of the Pt(IV)-oxo unit by electron withdrawal into delocalized orbitals of the polytungstates.


The effects of heterospecific mating frequency on the strength of cryptic reproductive barriers.
Heterospecific mating frequency is critical to hybrid zone dynamics and can directly impact the strength of reproductive barriers and patterns of introgression. The effectiveness of post-mating prezygotic (PMPZ) reproductive barriers, which include reduced fecundity via heterospecific matings and conspecific sperm precedence, may depend on the number, identity and order of mates. Studies of PMPZ barriers suggest that they may be important in many systems, but whether these barriers are effective at realistic heterospecific mating frequencies has not been tested. Here, we evaluate the strength of cryptic reproductive isolation in two leaf beetles (Chrysochus auratus and C. cobaltinus) in the context of a range of heterospecific mating frequencies observed in natural populations. We found both species benefited from multiple matings, but the benefits were greater in C. cobaltinus and extended to heterospecific matings. We found that PMPZ barriers greatly limited hybrid production by C. auratus females with moderate heterospecific mating frequencies, but that their effectiveness diminished at higher heterospecific mating frequencies. In contrast, there was no evidence for PMPZ barriers in C. cobaltinus females at any heterospecific mating frequency. We show that integrating realistic estimates of cryptic isolation with information on relative abundance and heterospecific mating frequency in the field substantially improves our understanding of the strong directional bias in F1 production previously documented in the Chrysochus hybrid zone. Our results demonstrate that heterospecific mating frequency is critical to understanding the impact of cryptic post-copulatory barriers on hybrid zone structure and dynamics, and that future studies of such barriers should incorporate field-relevant heterospecific mating frequencies.


A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures.
Flaviviruses are a genus within the Flaviviridae family of positive-strand RNA viruses and are transmitted principally through mosquito and tick vectors. These viruses are responsible for hundreds of millions of human infections worldwide per year that result in a range of illnesses from self-limiting febrile syndromes to severe neurotropic and viscerotropic diseases and, in some cases, death. A vaccine against the prototype flavivirus, yellow fever virus, has been deployed for 85 years and is highly effective. While vaccines against some medically important flaviviruses are available, others have proven challenging to develop. The emergence and spread of flaviviruses, including dengue virus and Zika virus, demonstrate their pandemic potential. This review highlights the gaps in knowledge that need to be addressed to allow for the rapid development of vaccines against emerging flaviviruses in the future.


The effects of yellow soybean, black soybean, and sword bean on lipid levels and oxidative stress in ovariectomized rats.
Soy isoflavones have been reported to decrease the risk of atherosclerosis in postmenopausal women. However, the effects of dietary consumption of soybean have not been explored. In this study, we evaluated the effects of consuming yellow soybeans, black soybeans (Glycine max), or sword beans (Canavalia gladiate) on lipid and oxidative stress levels in an ovariectomized rat model. Forty-seven nine-week-old female rats were ovariectomized, randomly divided into four groups, and fed one of the following diets for 10 weeks: a diet supplemented with casein (NC, n = 12), a diet supplemented with yellow soybean (YS, n = 12), a diet supplemented with black soybean (BS, n = 12), or a diet supplemented with sword bean (SB, n = 11). Plasma triglyceride (TG) levels in the BS and SB groups were significantly lower than that in the NC group. Notably, the BS group had significantly lower plasma total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels than the other groups. Hepatic total lipid levels were significantly lower in the YS and SB groups, and cholesterol levels were significantly lower in the SB group than in the NC group. Superoxide dismutase (SOD) and catalase (CAT) activities were significantly higher in the groups fed beans compared to the NC group. Hepatic thiobarbituric acid reactive substances (TBARS) levels were also significantly lower in the BS and SB groups than the NC group. In conclusion, our results suggest that consumption of various types of beans may inhibit oxidative stress in postmenopausal women by increasing antioxidant activity and improving lipid profiles. Notably, intake of black soybean resulted in the greatest improvement in risk factors associated with cardiovascular disease.


Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial.
The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30 months, 208 patients continued in an open label study: 101 continued on GA and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on GA showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. Of patients always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or remained stable compared with 57% if GA treatment was delayed. Of relapse-free patients always on GA over six years, only three of 26 (11%) were worse by > or = 1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P < 0.03). Disability, measured every six months, showed that the group of patients always on GA was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using GA as a first-line treatment early in the course of relapsing-remitting MS.


Analogues of chloramphenicol as mechanism-based inactivators of rat liver cytochrome P-450: modifications of the propanediol side chain, the p-nitro group, and the dichloromethyl moiety.
The importance of the p-nitro group, the propanediol side chain, and the dichloromethyl moiety of chloramphenicol in regulating its effectiveness and selectivity as a mechanism-based inactivator of rat liver cytochromes P-450 has been examined. 1-p-Nitrophenyl-2-dichloroacetamidoethane, 1-p-nitrophenyl-2-dibromoacetamidoethane, and 1-phenyl-2-dichloroacetamidoethane were as effective as chloramphenicol at inactivating the major phenobarbital-inducible isozyme of rat liver cytochrome P-450, whereas 1-p-nitrophenyl-2-difluoroacetamidoethane caused no enzyme inactivation. Unlike chloramphenicol, 1-p-nitrophenyl-2-dichloroacetamidoethane and 1-phenyl-2-dichloroacetamidoethane also inactivated the major beta-naphthoflavone-inducible isozyme of rat liver cytochrome P-450. Alkaline hydrolysis of the adducts formed upon in vitro incubation of liver microsomes from phenobarbital- and beta-naphthoflavone-induced rats with [14C]-1-p-nitrophenyl-2-dichloroacetamidoethane resulted in the release of 4-nitro-1-phenethyl-1,2-dicarboxylic acid amide and oxalic acid. Enzymatic digests of the radio-labeled protein produced by incubation of a reconstituted system containing the major isozymes induced by beta-naphthoflavone or phenobarbital with [14C]-1-p-nitrophenyl-2-dichloroacetamidoethane led to the release of 4-nitro-1-phenethyl-1,2-dicarboxylic acid amide and 4-nitro-1-phenethyl oxamyl lysine. These results suggest that a single oxamyl chloride intermediate is responsible for the covalent modification and, hence, inactivation of both isozymes by 1-p-nitrophenyl-2-dichloroacetamidoethane.


Auditory Oddball Responses Across the Schizophrenia-Bipolar Spectrum and Their Relationship to Cognitive and Clinical Features.
Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.


Virtual screening of curcumin and its analogs against the spike surface glycoprotein of SARS-CoV-2 and SARS-CoV.
COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74% identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.Communicated by Ramaswamy H. Sarma.


The DSM-5 Limited Prosocial Emotions subtype of Conduct Disorder in incarcerated male and female juvenile delinquents.
The aim of the present study was to analyze the relevance of the DSM-5's Conduct Disorder new Limited Prosocial Emotions (CD LPE) specifier in incarcerated juvenile delinquents. A sample of 201 males and 98 females from the Juvenile Detention Centers managed by the Portuguese Ministry of Justice diagnosed with Conduct Disorder (CD) was used. Results showed that male juvenile delinquents with the CD LPE specifier scored higher on callous-unemotional traits (CU), general psychopathic traits, psychopathy taxon membership, self-reported delinquency, and crime seriousness, and lower on prosocial behavior and social desirability, while female juvenile delinquents with the CD LPE specifier scored higher on callous-unemotional traits (CU) and general psychopathic traits, and lower on prosocial behavior. Significant associations for both genders were found between the CD LPE specifier and age of crime onset and first problems with the law.


The epidemiology and prevention of drowning in Singapore.
The aim of this study was to derive a profile of drowning victims in Singapore in the 10-year period 1992-2001 and determine if there are any patterns, trends or factors which may affect the risk profile of victims. Another objective was to recommend measures for reducing deaths from drowning through a review of some of the current literature and studies on drowning prevention. Data for epidemiological analysis were studied and analysed. Data was primarily obtained from the annual drowning statistics reported in the annual reports of the Singapore Life Saving Society, which were in turn obtained from the Registry of Births and Deaths, and the Coroner's Court. The review of current literature and studies on drowning was concentrated on the publications of leading drowning experts and agencies and on the papers presented at two important international conferences, the International Drowning Symposium in May 1996 and the first World Congress on Drowning in June 2002. The review was done with a view to identify successful drowning prevention measures that may be adopted or enhanced in Singapore. The study revealed a few important findings. Firstly, Singapore had a drowning rate per 100,000 population that varied from a low of 0.88 in one year to a high of 1.72 in another in the period 1992-2001. Secondly, the male drowning mortality rate in Singapore was much higher than the female drowning mortality rate. Thirdly, persons in the age group of 20-29 years were at the highest risk. Fourthly, the sea, rivers and swimming pools were the locations with the highest number of drowning victims. The study also showed that the main measures of drowning prevention may be broadly divided into supervision, environmental design changes, legislation, swimming lessons and aquatic safety education. The situation in Singapore is generally comparable to that in high income or developed countries although there are some differences. Further studies and research need to be done to provide a better understanding of the epidemiology and prevention of drowning in Singapore. In the meantime, the main measures of drowning prevention should, as far as possible, be followed or enhanced.


Acute flaccid rhombencephalomyelitis with radiculitis in a child with an enterovirus A71 infection seen for the first time in Denmark: a case report.
Acute flaccid myelitis is a serious condition of the spinal cord. More than 80% of patients experience a mild respiratory illness or fever consistent with a viral infection prior to acute flaccid myelitis development. Enterovirus A71 is known to circulate in Denmark, and has previously been associated with severe neurological symptoms. In this case report we describe acute flaccid rhombencephalomyelitis with radiculitis in an infant with an enterovirus infection. The 8-month-old male of Asian origin presented with fever and gastrointestinal symptoms, followed by severe neurological deficits such as flaccid paralysis of the neck and upper extremities. An initial magnetic resonance imaging scan of the brain was normal, and the boy was treated for encephalitis. A follow-up magnetic resonance imaging scan of the brain and spinal cord 1 week later showed the development of pathological symmetrical gray matter hyperintensity lesions on T2-weighted images in the brainstem and upper medulla spinalis, and nerve enhancement in the terminal thread of the spinal cord and the cervical roots; findings consistent with rhombencephalomyelitis with radiculitis causing flaccid paralysis. Enterovirus A71 was detected in both nasopharyngeal and fecal specimens. Other differential diagnostic etiologies of viral and bacterial encephalitis, including poliovirus, were excluded. This is the first case in Denmark of a patient diagnosed with acute flaccid rhombencephalomyelitis strongly linked to an enterovirus A71 infection. This case emphasizes the diagnostic importance of combining a history of respiratory and/or gastrointestinal illness, fever, and delayed onset of varying degrees of paralysis with progressive characteristic spinal and brain lesions. Analysis of respiratory, fecal, and cerebrospinal samples for the presence of enterovirus, and eliminating other differential pathogens, is essential to confirm the diagnosis.


AlphaSimR: an R package for breeding program simulations.
This paper introduces AlphaSimR, an R package for stochastic simulations of plant and animal breeding programs. AlphaSimR is a highly flexible software package able to simulate a wide range of plant and animal breeding programs for diploid and autopolyploid species. AlphaSimR is ideal for testing the overall strategy and detailed design of breeding programs. AlphaSimR utilizes a scripting approach to building simulations that is particularly well suited for modeling highly complex breeding programs, such as commercial breeding programs. The primary benefit of this scripting approach is that it frees users from preset breeding program designs and allows them to model nearly any breeding program design. This paper lists the main features of AlphaSimR and provides a brief example simulation to show how to use the software.


Stress fracture of the scapula in two horses.
Stress fracture of the scapula in two horses is described. Both horses had a history of acute lameness after strenuous exercise. Using elective nuclear scintigraphy focal increased radiopharmaceutical uptake in the affected scapula consistent with a fracture was identified. Standing radiography was nondiagnostic in both horses. Ultrasonographic findings in one horse were consistent with a minimally displaced incomplete fracture. Both horses were treated conservatively and returned to train and race successfully postinjury. Veterinary


Sex as a moderator of body composition following a randomized controlled lifestyle intervention among Latino youth with obesity.
Body composition differences between males and females emerge during adolescence and continue throughout adulthood; however, whether sex moderates body composition changes in adolescents with obesity after an intervention is unknown. To examine sex as a moderator of changes in adiposity following lifestyle intervention. A total of 136 Latino youth with obesity (BMI% 98.2 ± 1.3) aged 14 to 16 years old were randomized to either a 12-week lifestyle intervention (27 males/40 females) or control (35 males/34 females) group. The intervention included nutrition education (1 h/wk) and moderate-to-vigorous physical activity (3 h/wk). Anthropometric data (body mass index [BMI], BMI%, waist circumference, total body fat, and fat-free mass) were obtained pre- and post-intervention. Sex differences were examined by general linear models with significance determined at P < .05 for the F-statistic. Sex did not moderate changes in BMI (F1,115 = 0.01, P = .9), BMI% (F1,115 = 0.14, P = .7), or waist circumference (F1,117 = 1.1, P = .3). Sex significantly moderated changes in body fat percent (F1,117 = 5.3, P = .02), fat mass (F1,116 = 4.5, P = .04), and fat-free mass (F1,116 = 4.3, P = .04). Intervention males compared with females had greater relative reductions in fat percent (-4.1 ± 0.8% vs -1.2 ± 0.7%, P = .02) and fat mass (-5.0 ± 1.1 kg vs -1.5 ± 0.9 kg, P = .02) and gained more fat free mass (3.6 ± 0.9 kg vs 0.5 ± 0.8 kg, P = .02) when compared with same sex controls. Males and females exhibited a differential response to lifestyle intervention for percent fat, fat mass, and fat-free mass indicating that sex-specific improvements in body composition favours males over females.


Intra-operative central vein angioplasty during arteriovenous access creation.
Central vein stenosis or occlusion due to prior use of central vein hemodialysis catheters may lead to disabling extremity edema or cause early failure after arteriovenous access construction. Our integrated program for arteriovenous access management enables us to identify these stenoses pre-operatively. We carried out intra-operative angiography and angioplasty during arteriovenous access creation in 3 patients with good immediate and long-term results. Intra-operative endovascular therapy is a new application of peripheral vascular surgery techniques for patients with significant central vein stenosis undergoing access surgery, which exploits the high postoperative flow state to maintain patency after angioplasty. It may also be applicable in situations such as proximal arterial stenosis with anticipated steal syndrome and other conditions that may compromise access patency.


Skin microbiome: genomics-based insights into the diversity and role of skin microbes.
Recent advances in DNA sequencing methodology have facilitated studies of human skin microbes that circumvent difficulties in isolating and characterizing fastidious microbes. Sequence-based approaches have identified a greater diversity of cutaneous bacteria than studies using traditional cultivation techniques. However, improved sequencing technologies and analytical methods are needed to study all skin microbes, including bacteria, archaea, fungi, viruses and mites, and how they interact with each other and their human hosts. This review discusses current skin microbiome research, with a primary focus on bacteria, and the challenges facing investigators striving to understand how skin microorganisms contribute to health and disease.


Maternal clinical findings in malaria in pregnancy in a region of northwestern Colombia.
In malaria-endemic regions of Latin America, little is known about malaria in pregnancy. To characterize the clinical and laboratory findings of maternal infection, we evaluated 166 cases of pregnant women infected with Plasmodium spp. in a prospective study conducted in northwestern Colombia during 2005-2006. A total of 89.8% (149 of 166) had fever or a history of fever in the past 48 hours, 9.0% (15 of 166) had severe malaria, of which 66.7% was caused by Plasmodium vivax and 33.3% by P. falciparum. Hepatic dysfunction was the main complication (9 of 15) observed. The proportion of severe cases was similar for both species (P = 0.41). In malaria-endemic areas of Colombia, malaria in pregnancy has a broad clinical spectrum. In pregnant women, P. vivax infection frequently leads to organ-specific complications.


Pontine spongy degeneration of white matter associated with hepatic encephalopathy.
Spongy degeneration of white matter localized to basis pontis was found in a 47-year-old woman with hepatic encephalopathy. In this clinical setting, the lesion resembled those changes described by Victor et al and found primarily in cerebral cortex, subcortical white matter, and putamen. Isolated involvement of the basis pontis and ventral midline tegmentum of pons has not, to our knowledge, been previously reported. The morphologic appearance and distribution distinguish this lesion from central pontine myelinolysis. The possible vascular cause of this localized interstitial edema is discussed.


The association of HLA-DR15 and intermediate uveitis.
To evaluate the association between human leukocyte antigen (HLA-DR15) specificity and intermediate uveitis. Eighteen patients diagnosed with intermediate uveitis underwent HLA-DR15 serotyping. Additionally, DNA-based phenotyping for a specific HLA-DR15 allele was performed in four patients. The clinical features of HLA-DR15-positive intermediate uveitis were compared with those of HLA-DR15-negative intermediate uveitis. Thirteen of 18 patients (72%) were positive for HLA-DR15. The frequency of the HLA-DR15 specificity in intermediate uveitis patients was significantly higher than in the control subjects (relative risk, 6.36; P < .001). Each of four patients tested carried the specific allele, DR beta 1*1501, which has been associated with multiple sclerosis. In the HLA-DR15-positive group were four patients (31%) with coexisting multiple sclerosis or optic neuritis, one patient with coexisting narcolepsy, and three patients (23%) with a family history of multiple sclerosis. Retinal periphlebitis, especially if bilateral, was a frequent ophthalmoscopic finding in HLA-DR15-positive intermediate uveitis. This study identifies a significant association between intermediate uveitis and the HLA-DR15 specificity. Patients who are HLA-DR15-positive and have intermediate uveitis may have systemic findings of another HLA-DR15-related disorder. Intermediate uveitis may belong to a constellation of HLA-DR15-related disorders, which includes multiple sclerosis, optic neuritis, and narcolepsy.


Diagnosis of Enterocytozoon bieneusi (microsporidia) infections by polymerase chain reaction in stool samples using primers based on the region coding for small-subunit ribosomal RNA.
Enterocytozoon bieneusi is the most prevalent microsporidian causing chronic diarrhea in patients with acquired immunodeficiency syndrome. The current methods used for routine diagnosis of infections caused by microsporidia are based on microscopic detection of the microorganism spores in stained smears. We evaluated the usefulness of the polymerase chain reaction (PCR) technique as a tool to diagnose Enterocytozoon bieneusi infections, using the species-specific diagnostic primer pair EBIEF1/EBIER1 on stool samples that were also analyzed by optical microscopy. To perform PCR in such samples, we developed a novel protocol to obtain DNA free of PCR inhibitors. This protocol was based on disruption of spores using glass beads and overnight digestion with proteinase K; final purification was accomplished with the RapidPrep Micro Genomic DNA isolation Kit for Cells and Tissues (Pharmacia Biotech Inc, Piscataway, NJ). We also evaluated this approach on aliquots of a sample fixed in formalin from 1 to 10 days. PATIENTS AND SAMPLES: We evaluated the PCR technique on 64 stool samples obtained from patients with acquired immunodeficiency syndrome who had persistent chronic diarrhea. Patients were from Spain, Brazil, Germany, and the United States. Using this approach, we could confirm the presence of E bieneusi in all 17 positive samples; no false-positive results were observed. We could also amplify E bieneusi DNA in 10 aliquots of one sample fixed up to 10 days in 10% formalin. We conclude that PCR technology is very suitable for species identification of microsporidia in stool samples and may have a potential application in prospective studies in formalin-fixed samples.


Multidisciplinary Versus One-on-One Setting: A Qualitative Study of Clinicians' Perceptions of Their Relationship With Patients With Prostate Cancer.
Previous studies indicate that a multidisciplinary approach could be suitable for dealing with the complex issues faced by physicians in the management of prostate cancer; however, few studies have investigated clinicians' perceptions of multidisciplinary care. Our aim was to evaluate clinicians' perceptions of the patient-clinician relationship in a multidisciplinary context, and to compare this with physicians' perceptions of providing care independently. A qualitative observational study was performed in 2009. Three radiation oncologists, three urologists, three medical oncologists and one psychologist from the multidisciplinary clinic (MDC) team at the Prostate Program of Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, were interviewed to assess their perceptions of their relationship with the patient. Clinicians reported that the MDC has advantages regarding providing patients with more accurate information and acquiring information from patients, but a clear preference for a multidisciplinary setting did not emerge. Clinicians reported that in one-on-one examinations (1) they feel more comfortable listening to the patient and more able to manage communication, and that (2) the process of building trust is easier. Clinicians appear to recognize the value of the MDC in terms of effective communication with patients but feel that other aspects of relationship building are hindered in a multidisciplinary setting. Organizational and teamwork issues need to be addressed to optimize the implementation of a multidisciplinary approach.


Relationships between Strength and Step Frequency with Fatigue Index in Repeated Sprint Ability.
Force-velocity profile (FVP) and repeated-sprint ability (RSA) tests are indicators of physical capacities in most team sport players. The purpose of this study was to examine the stride kinematics during a repeated-sprint ability (RSA) test and to analyze the relationship between Bosco's force-velocity profile (FVP) and RSA performance in elite female field hockey players. Thirteen elite-female players performed both RSA (six 30 m maximal sprints) and jumping (CMJ weighted and body weight) tests. Sprinting time fatigue indexes during a 30 m RSA test were correlated with step frequency fatigue indexes (r > 0.7; p < 0.01). CMJ50 showed a large relationship with sprint time fatigue indexes. FV50 showed a very large relationship with sprint time fatigue indexes (r > 0.7; p < 0.01), and a large relationship with the step frequency fatigue indexes (r > 0.5; p < 0.05). This study highlighted two possible ways to improve fatigue indexes in RSA, with the aim of maximizing the distances covered at high-intensities during the matches: (a) strength training and (b) focusing on step frequency during speed training.


Development and validation of a curriculum for laparoscopic supracervical hysterectomy.
To develop and validate a three-step curriculum for laparoscopic supracervical hysterectomy (LSH) designed for a busy clinical setting. Single-centre, prospective, cohort study. Twelve eligible gynaecological trainees were included (group 1). The theoretical part (step 1) was a validated multiple-choice test. The practical part (step 2) consisted of five tasks on a virtual reality simulator. The participants had to reach a pre-defined proficiency level before advancing to performing a LSH (step 3). The validation of the curriculum was based on the surgical performance. The surgical procedure was recorded and assessed by two experts using Global Operative Assessment of Laparoscopic Skills (GOALS) and Competence Assessment Tool - Laparoscopic Supracervical Hysterectomy (CAT-LSH). The scores were compared with scores from gynaecological trainees who performed their first LSH without virtual reality simulator training (group 2). Ten trainees completed the curriculum and performed a LSH that was recorded and evaluated. Mean duration of the training period (step 1 and 2) was 57 days (SD 26.0), and mean training time spent on the simulator to reach the pre-set proficiency level was 173 min (SD 49). The mean GOALS score was 18.5 (SD 5.8) in group 1 and 13.6 (SD 3.3) in group 2, p=0.027. The mean CAT-LSH score of the performance of the hysterectomy was 42.1 (SD 6.9) in group 1 and 34.8 (SD 4.3) in group 2, p= 0.009. Trainees who completed the curriculum appeared to have a higher performance score compared with trainees who did not perform structured training.


A novel coded excitation scheme to improve spatial and contrast resolution of quantitative ultrasound imaging.
Quantitative ultrasound (QUS) imaging techniques based on ultrasonic backscatter have been used successfully to diagnose and monitor disease. A method for improving the contrast and axial resolution of QUS parametric images by using the resolution enhancement compression (REC) technique is proposed. Resolution enhancement compression is a coded excitation and pulse compression technique that enhances the -6-dB bandwidth of an ultrasonic imaging system. The objective of this study was to combine REC with QUS (REC-QUS) and evaluate and compare improvements in scatterer diameter estimates obtained using the REC technique to conventional pulsing methods. Simulations and experimental measurements were conducted with a single-element transducer (f/4) having a center frequency of 10 MHz and a -6-dB bandwidth of 80%. Using REC, the -6-dB bandwidth was enhanced to 155%. Images for both simulation and experimental measurements contained a signal-to-noise ratio of 28 dB. In simulations, to monitor the improvements in contrast a software phantom with a cylindrical lesion was evaluated. In experimental measurements, tissue-mimicking phantoms that contained glass spheres with different scatterer diameters were evaluated. Estimates of average scatterer diameter in the simulations and experiments were obtained by comparing the normalized backscattered power spectra to theory over the -6-dB bandwidth for both conventional pulsing and REC. Improvements in REC-QUS over conventional QUS were quantified through estimate bias and standard deviation, contrast-to-noise ratio, and histogram analysis of QUS parametric images. Overall, a 51% increase in contrast and a 60% decrease in the standard deviation of average scatterer diameter estimates were obtained during simulations, while a reduction of 34% to 71% was obtained in the standard deviation of average scatterer diameter for the experimental results.


Radioiodine Biogeochemistry and Prevalence in Groundwater.
129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these knowledge gaps will not alter the observation that 129I is primarily mobile, but it will likely permit demonstration that the entire 129I pool in the source term is not moving at the same rate and some may be tightly bound to the sediment, thereby smearing the modeled 129I peak and reducing maximum calculated risk.


Elevated skull fractures in pediatric age group: report of two cases.
Elevated fractures of the skull, which are rarely reported in the literature, are always compound, have maximal neurological deficits at presentation and have been reported only in adults. We report two cases of elevated skull fractures in the pediatric age group, one of which was a simple elevated fracture and presented with delayed neurological deterioration. The etiologies were a fall in first case and an animal attack (bear maul) in the second case as reported for the first time. One of the cases presented with delayed onset of left focal hemispheric signs. The first case underwent debridement, duraplasty and reduction of fracture whereas in the second case the bone flap was not replaced immediately because of gross contamination. Both patients had an excellent outcome. Elevated skull fractures are not uncommon in the pediatric age group. Compound elevated skull fractures should be managed early as open depressed fractures. Reduction of a simple elevated fracture presenting with neurological deficits not explained by any other lesion can result in a good outcome.


[Toxoplasmic and chagasic meningoencephalitis in patients with human immunodeficiency virus infection: anatomopathologic and tomographic differential diagnosis].
Twenty-two HIV+ patients with encephalitis were studied. Of these, 7 had meningoencephalitis due to Toxoplasma gondii (MT) and 15 due to Trypanosoma cruzi (MC). Pathologic and computerized axial tomography (CAT) changes were compared. We found that focal necrotizing encephalitis due to Toxoplasma involved the cerebral cortex and the basal ganglia, whereas lesions due to Trypanosoma cruzi were centered in the white matter, sometimes extending into the cortex. Hemorrhages, myelin lesions and organisms were more pronounced in chagasic than in toxoplasmic encephalitis. These findings are consistent with the literature reviewed.


Fear of COVID-19 when experiencing pregnancy or childbirth in the pandemic: what are the associated factors?
to identify factors associated with fear of COVID-19 among women who experienced pregnancy or childbirth during the pandemic. a cross-sectional study, nested within a prospective cohort, using an online survey, from August 2021 to February 2022, based on descriptive data analysis. of the 431 participants, 52.8% were postpartum women and 20.1% were pregnant women. With regard to fear of COVID-19, a mean score of 20.46 was obtained (moderate fear). The highest fear scores were present in women whose newborns were admitted to hospital in neonatal critical units (p=0.032), and the lowest among those covered by supplementary health (insurance) (p=0.016). among pregnant and postpartum women, high fear of COVID-19 translated into the possibility of having newborns admitted to hospital in a critical unit. The importance of supporting actions to support pregnant/postpartum women's mental health in relation to COVID-19 or other threats that may influence the neonatal outcome stands out.


Laparoscopic live donor nephrectomy: outcomes equivalent to open surgery.
A shortage of kidney donors has contributed to the interest in laparoscopic live-donor nephrectomy. Three transperitoneal ports are used, as is an AESOP robot. To maintain urine flow, the donor is kept volume expanded during the procedure, and the pneumoperitoneum pressure is minimized. The most critical and hazardous part of the surgery is dissection of the renal artery and vein. Abundant periureteral tissue should be left to protect the blood supply. Harvest of the right kidney is more difficult. Placing the extraction incision in the right upper quadrant and using a Satinsky clamp instead of a stapling device at the origin of the renal vein will provide maximum venous length and help prevent postoperative thrombosis of the allograft. In the first 175 laparoscopic renal harvest procedures at Johns Hopkins, the complication rate was 14%, the rate of open conversion was 2%, and 3% of the patients required transfusions. These rates improved with experience. There was no significant difference in the performance of the allografts or the recovery of the recipients from what is seen after open kidney harvest. Wider acceptance of laparoscopic renal harvest will increase the number of donors and will be helped by development of methods and devices that shorten the learning curve.


Loss of Fc gamma receptor and impaired phagocytosis of polymorphonuclear leukocytes in gingival crevicular fluid.
Immunoglobulin G type II and III receptors (Fc gamma RII and Fc gamma RIII) are essential for polymorphonuclear leukocytic (PMNs) phagocytosis. Our previous study demonstrated a downregulation of Fc gamma RIII on PMNs in gingival crevicular fluid (GCF). To determine whether this receptor downregulation may contribute to the periodontal host defence borne by PMNs, we examined the correlation between Fc gamma RII and Fc gamma RIII expressions and the phagocytic capacity of GCF-PMNs. In order to verify at which level of cellular events the loss of Fc gamma R occurs, we quantified mRNA levels to assess a de novo synthesis of these receptors. GCF was collected from 21 patients with adult periodontitis by gingival crevicular washing. Autologous peripheral blood (PB) PMNs served as control. Surface expressions of Fc gamma Rs and phagocytic capacity via Fc gamma Rs were analysed by flow cytometry. The difference in Fc gamma R mRNA levels between GCF- and PB-PMNs was assessed by reverse transcription polymerase chain reaction (RT-PCR). The amplified products were visualized by agarose gel electrophoresis and the endproduct yields were quantified by computerized image-analysis. Both Fc gamma RII and Fc gamma RIII expressions and phagocytic capacity on GCF-PMNs were significantly lower than those on PB-PMNs (p < 0.001). The downregulation of Fc gamma Rs on GCF-PMNs significantly correlated with the phagocytic capacity (r = 0.66 for Fc gamma RIII, p < 0.01; r = 0.50 for Fc gamma RII, p < 0.05). The mRNA level of Fc gamma RIII of GCF-PMNs was significantly lower than that of PB-PMNs (p < 0.05). Thus, GCF-PMNs are characterized by the decreased surface expressions and mRNA levels of Fc gamma Rs, and the impaired phagocytosis.


Application of xCELLigence real-time cell analysis to the microplate assay for pertussis toxin induced clustering in CHO cells.
The microplate assay with Chinese Hamster Ovary (CHO) cells is currently used as a safety test to monitor the residual pertussis toxin (PT) amount in acellular pertussis antigens prior to vaccine formulation. The assay is based on the findings that the exposure of CHO cells to PT results in a concentration-dependent clustering response which can be used to estimate the amount of PT in a sample preparation. A major challenge with the current CHO cell assay methodology is that scoring of PT-induced clustering is dependent on subjective operator visual assessment using light microscopy. In this work, we have explored the feasibility of replacing the microscopy readout for the CHO cell assay with the xCELLigence Real-Time Cell Analysis system (ACEA BioSciences, a part of Agilent). The xCELLigence equipment is designed to monitor cell adhesion and growth. The electrical impedance generated from cell attachment and proliferation is quantified via gold electrodes at the bottom of the cell culture plate wells, which is then translated into a unitless readout called cell index. Results showed significant decrease in the cell index readouts of CHO cells exposed to PT compared to the cell index of unexposed CHO cells. Similar endpoint concentrations were obtained when the PT reference standard was titrated with either xCELLigence or microscopy. Testing genetically detoxified pertussis samples unspiked or spiked with PT further supported the sensitivity and reproducibility of the xCELLigence assay in comparison with the conventional microscopy assay. In conclusion, the xCELLigence RTCA system offers an alternative automated and higher throughput method for evaluating PT-induced clustering in CHO cells.


Common sense model of mental illness: Understanding the impact of cognitive and emotional representations of mental illness on recovery through the mediation of self-stigma.
The present study applied the common sense model to understand the underlying mechanism of how cognitive and emotional representations of mental illness among people in recovery of mental illness would impact their endorsement of self-stigma, and how that would, in turn, affect clinical and personal recovery. A cross-sectional survey was administered to 376 people in recovery. Participants were recruited from seven public specialty outpatient clinics and substance abuse assessment clinics across various districts in Hong Kong. They were asked to report their perception towards their mental illness, self-stigma, symptom severity, and personal recovery. The results of structural equation modeling partially supported the hypothesized mediation model indicating that controllability, consequences, and emotional concern of mental illness, but not cause, timeline, and identity, were associated with self-stigma, which was subsequently negatively associated with clinical and personal recovery. The present study demonstrated the mediating role of self-stigma in the relationship between individuals' illness representations towards their mental illness and their recovery. Illness management programs aimed at addressing the maladaptive mental illness-related beliefs and emotions are recommended. Implications on developing self-directed and empowering mental health services are discussed.


AC biosusceptometry in the study of drug delivery.
Conventionally, pharmaceutical substances are administered orally because the gastrointestinal tract possesses the appropriate features for drug absorption. Nevertheless, the gastrointestinal tract physiology is complex and influenced by many factors. These factors must be completely understood for the optimization of oral drug delivery systems. Although in vitro tests provide information about release and drug absorption profiles, in vivo studies are essential, due to the biological variability. Several techniques have been employed in an attempt to conveniently characterize the behavior of solid dosage forms in vivo. The noninvasive biomagnetic technique of alternate current biosusceptometry (ACB) has been used in studies focusing on gastrointestinal motility and, more recently, to evaluate the performance of magnetic dosage forms. This article will discuss the main characteristics of AC biosusceptometry and its applicability for determination of the relationship between the human gastrointestinal tract and orally administered pharmaceutical dosage forms.


Feasibility and Safety of Robotic Excision of Ipsilateral Retroperitoneal Recurrence After Nephrectomy for Renal Cell Carcinoma.
To determine feasibility and safety of robotic excision of local ipsilateral recurrences after nephrectomy for renal cell carcinoma (RCC). Surgical resection is an option for treatment of low burden locally recurrent RCC, potentially delaying the use of systemic therapy. This has historically been performed by open technique, which can impart significant morbidity. We present our experience with robotic excision. We reviewed our institutional experience of patients with surgically excised RCC who underwent robotic excision of ipsilateral retroperitoneal recurrence in 2015-2018. Demographics and clinicopathological variables, including operative and postoperative outcomes, were examined. Twelve robotic excisions of ipsilateral local recurrences were performed in our hospital in 2015-2018. Mean age was 65.48 years (± standard deviation, SD: 9.51), 10 patients were male, and mean BMI 34.75 kg/m2 (± 6.71). Nine patients recurred after radical nephrectomy, and 3 after partial nephrectomy. Mean size of recurrence was 2.97 cm (±1.69). Mean anesthesia time, EBL, and LOS were 213 minutes (± 38.92), 152 mL (± 130.75), and 43 hours (± 12.64), respectively. All surgical margins were negative. No surgical complications were reported. Median follow-up was 19.0 months [interquartile range, IQR 12.7-30.0]. Five patients out of 12 recurred following robotic excision, these were treated with either systemic therapy, radiation, or palliative surgeries. Mean time for subsequent recurrence was 26.5 months. In this small case series, robotic excision of ipsilateral RCC retroperitoneal recurrence appears safe, technically feasible, and oncologically sound in expert hands and carefully selected patients.


Potent antirheumatic activity of a new DNA vaccine targeted to B7-2/CD28 costimulatory signaling pathway in autoimmune arthritis.
Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.


Effect of nutrient deprivation on lipid, carbohydrate, DNA, RNA, and protein levels in Vibrio cholerae.
The response of Vibrio cholerae to low nutrient levels was determined by measuring the concentrations of lipids, carbohydrates, DNA, RNA, and proteins over a 30-day starvation period. Ultrastructural integrity was observed by transmission electron microscopy. Total lipids and carbohydrates declined rapidly within the first 7 days, while DNA and protein exhibited a more constant decline over the 30 days of starvation. In contrast, RNA showed little decrease upon starvation. Although neutral lipids were lost, the percentage of neutral lipids did not decline as rapidly as the phospholipids. Detectable levels of poly-beta-hydroxybutyrate disappeared completely by 7 days. Carbohydrate profiles revealed the relative loss of the five-carbon sugar ribose and N-acetylglucosamine and a relative increase in the total six-carbon sugars, especially glucose. Morphologically, ribosomes appeared to exhibit no structural change, while inclusion bodies and mesosomelike structures disappeared completely, and cell wall and membrane integrity was lost. The data suggest that V. cholerae differs somewhat from other marine vibrios in its response to low nutrients but shares some characteristics in common with them. The data also suggest that certain lipids and carbohydrates may provide the endogenous energy sources needed for dormancy preparation and cell maintenance under nutrient starvation.


Wood Dust Flammability Analysis by Microscale Combustion Calorimetry.
To study the practicability of a micro combustion calorimeter to analyze the calorimetry kinetics of wood, a micro combustion calorimeter with 13 heating rates from 0.1 to 5.5 K/s was used to perform the analysis of 10 kinds of common hardwood and softwood samples. As a microscale combustion measurement method, MCC (microscale combustion calorimetry) can be used to judge the flammability of materials. However, there are two methods for measuring MCC: Method A and Method B. However, there is no uniform standard for the application of combustible MCC methods. In this study, the two MCC standard measurement Methods A and B were employed to check their practicability. With Method A, the maximum specific heat release rate, heat release temperature, and specific heat release of the samples were obtained at different heating rates, while for Method B, the maximum specific combustion rate, combustion temperature and net calorific values of the samples were obtained at different heating rates. The ignition capacity and heat release capacity were then derived and evaluated for all the common hardwood and softwood samples. The results obtained by the two methods have significant differences in the shape of the specific heat release rate curves and the amplitude of the characteristic parameters, which lead to the differences of the derived parameters. A comparison of the specific heat release and the net calorific heat of combustion with the gross caloric values and heating values obtained by bomb calorimetry was also made. The results show that Method B has the potentiality to evaluate the amount of combustion heat release of materials.


Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.
Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.


Mutations in the YRB1 gene encoding yeast ran-binding-protein-1 that impair nucleocytoplasmic transport and suppress yeast mating defects.
We identified two temperature-sensitive (ts) mutations in the essential gene, YRB1, which encodes the yeast homolog of Ran-binding-protein-1 (RanBP1), a known coregulator of the Ran GTPase cycle. Both mutations result in single amino acid substitutions of evolutionarily conserved residues (A91D and R127K, respectively) in the Ran-binding domain of Yrb1. The altered proteins have reduced affinity for Ran (Gsp1) in vivo. After shift to restrictive temperature, both mutants display impaired nuclear protein import and one also reduces poly(A)+ RNA export, suggesting a primary defect in nucleocytoplasmic trafficking. Consistent with this conclusion, both yrb1ts mutations display deleterious genetic interactions with mutations in many other genes involved in nucleocytoplasmic transport, including SRP1 (alpha-importin) and several beta-importin family members. These yrb1ts alleles were isolated by their ability to suppress two different types of mating-defective mutants (respectively, fus1Delta and ste5ts), indicating that reduction in nucleocytoplasmic transport enhances mating proficiency. Indeed, in both yrb1ts mutants, Ste5 (scaffold protein for the pheromone response MAPK cascade) is mislocalized to the cytosol, even in the absence of pheromone. Also, both yrb1ts mutations suppress the mating defect of a null mutation in MSN5, which encodes the receptor for pheromone-stimulated nuclear export of Ste5. Our results suggest that reimport of Ste5 into the nucleus is important in downregulating mating response.


The importance of biological factors affecting trace metal concentration as revealed from accumulation patterns in co-occurring terrestrial invertebrates.
As physicochemical properties of the soil highly influence the bioavailable fraction of a particular trace metal, measured metal body burdens in a particular species are often assumed to be more reliable estimators of the contamination of the biota. To test this we compared the Cd, Cu and Zn content of three spiders (generalist predators) and two amphipods (detritivores), co-occurring in seven tidal marshes along the river Schelde, between each other and with the total metal concentrations and the concentrations of four sequential extractions of the soils. Correlations were significant in only one case and significant site x species interactions for all metals demonstrate that factors affecting metal concentration were species and site specific and not solely determined by site specific characteristics. These results emphasize that site and species specific biological factors might be of the utmost importance in determining the contamination of the biota, at least for higher trophic levels. A hypothetical example clarifies these findings.