Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes.

Fruiting bodies (sporocarps, sporophores or basidiomata) of mushroom-forming fungi (Agaricomycetes) are among the most complex structures produced by fungi. Unlike vegetative hyphae, fruiting bodies grow determinately and follow a genetically encoded developmental program that orchestrates their growth, tissue differentiation and sexual sporulation. In spite of more than a century of research, our understanding of the molecular details of fruiting body morphogenesis is still limited and a general synthesis on the genetics of this complex process is lacking. In this paper, we aim at a comprehensive identification of conserved genes related to fruiting body morphogenesis and distil novel functional hypotheses for functionally poorly characterised ones. As a result of this analysis, we report 921 conserved developmentally expressed gene families, only a few dozens of which have previously been reported to be involved in fruiting body development. Based on literature data, conserved expression patterns and functional annotations, we provide hypotheses on the potential role of these gene families in fruiting body development, yielding the most complete description of molecular processes in fruiting body morphogenesis to date. We discuss genes related to the initiation of fruiting, differentiation, growth, cell surface and cell wall, defence, transcriptional regulation as well as signal transduction. Based on these data we derive a general model of fruiting body development, which includes an early, proliferative phase that is mostly concerned with laying out the mushroom body plan (via cell division and differentiation), and a second phase of growth via cell expansion as well as meiotic events and sporulation. Altogether, our discussions cover 1 480 genes of Coprinopsis cinerea, and their orthologs in Agaricus bisporus, Cyclocybe aegerita, Armillaria ostoyae, Auriculariopsis ampla, Laccaria bicolor, Lentinula edodes, Lentinus tigrinus, Mycena kentingensis, Phanerochaete chrysosporium, Pleurotus ostreatus, and Schizophyllum commune, providing functional hypotheses for ~10 % of genes in the genomes of these species. Although experimental evidence for the role of these genes will need to be established in the future, our data provide a roadmap for guiding functional analyses of fruiting related genes in the Agaricomycetes. We anticipate that the gene compendium presented here, combined with developments in functional genomics approaches will contribute to uncovering the genetic bases of one of the most spectacular multicellular developmental processes in fungi. Citation: Nagy LG, Vonk PJ, Künzler M, Földi C, Virágh M, Ohm RA, Hennicke F, Bálint B, Csernetics Á, Hegedüs B, Hou Z, Liu XB, Nan S, M. Pareek M, Sahu N, Szathmári B, Varga T, Wu W, Yang X, Merényi Z (2023). Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes. Studies in Mycology 104: 1-85. doi: 10.3114/sim.2022.104.01.

FiNuTyper: Design and validation of an automated deep learning-based platform for simultaneous fiber and nucleus type analysis in human skeletal muscle.

AIM: While manual quantification is still considered the gold standard for skeletal muscle histological analysis, it is time-consuming and prone to investigator bias. To address this challenge, we assembled an automated image analysis pipeline, FiNuTyper (Fiber and Nucleus Typer). METHODS: We integrated recently developed deep learning-based image segmentation methods, optimized for unbiased evaluation of fresh and postmortem human skeletal muscle, and utilized SERCA1 and SERCA2 as type-specific myonucleus and myofiber markers after validating them against the traditional use of MyHC isoforms. RESULTS: Parameters including cross-sectional area, myonuclei per fiber, myonuclear domain, central myonuclei per fiber, and grouped myofiber ratio were determined in a fiber-type-specific manner, revealing that a large degree of sex- and muscle-related heterogeneity could be detected using the pipeline. Our platform was also tested on pathological muscle tissue (ALS and IBM) and adapted for the detection of other resident cell types (leucocytes, satellite cells, capillary endothelium). CONCLUSION: In summary, we present an automated image analysis tool for the simultaneous quantification of myofiber and myonuclear types, to characterize the composition and structure of healthy and diseased human skeletal muscle.

Mammography-based radiomics analysis and imaging features for predicting the malignant risk of phyllodes tumours of the breast.

AIM: To determine whether the mammography (MG)-based radiomics analysis and MG/ultrasound (US) imaging features could predict the malignant risk of phyllodes tumours (PTs) of the breast. MATERIALS AND METHODS: Seventy-five patients with PTs were included retrospectively (39 with benign PTs, 36 with borderline/malignant PTs) and divided into thetraining (n=52) and validation groups (n=23). The clinical information, MG and US imaging characteristics, and histogram features were extracted from craniocaudal (CC) and mediolateral oblique (MLO) images. The lesion region of interest (ROI) and perilesional ROI were delineated. Multivariate logistic regression analysis was performed to determine the malignant factors of PTs. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC), sensitivity, and specificity were calculated. RESULTS: There was no significant difference found in the clinical or MG/US features between benign and borderline/malignant PTs. In the lesion ROI, variance in the CC view and mean and variance in the MLO view were independent predictors. The AUC was 0.942, sensitivity and specificity were 96.3% and 92%, respectively, in the training group. In the validation group, the AUC was 0.879, the sensitivity was 91.7%, and the specificity was 81.8%. In the perilesional ROI, the AUCs were 0.904 and 0.939, sensitivities were 88.9% and 91.7%, and the specificities were 92% and 90.9% in the training and validation groups, respectively. CONCLUSIONS: MG-based radiomic features could predict the risk of malignancy of patients with PTs and may be used as a potential tool to differentiate benign and borderline/malignant PTs.

[Cheng's Juanbi Decoction enhances autophagy in rheumatoid arthritis fibroblast-like syn-oviocytes by suppressing the PI3K/Akt/mTOR signal axis].

OBJECTIVE: To study the regulatory effect of Cheng's Juanbi Decoction (JBT) on autophagy in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and role of PI3K/Akt/mTOR signaling axis in the mechanism mediating this effect. METHODS: CCK8 assay was used to determine the optimal concentration and treatment time of JBT for inhibiting the viability of RA- FLS. The effect of freeze-dried powder of JBT, RAPA, or both on morphology of the autophagosomes in RA-FLS was observed under transmission electron microscope, and the changes in the number of autophagosomes and autolysosomes were observed with autophagy double-labeled adenovirus experiment. RT-qPCR and Western blotting were used to detect the expression levels of the related indicators. RESULTS: The results of CCK8 assay showed that treatment with 0.5 mg/mL JBT for 12 h produced the optimal effect for inhibiting RA-FLS viability. Observation with transmission electron microscope and the results of the autophagy double-labeled adenovirus experiment both showed the presence of a small number of autophagosomes in control RA-FLS group, and treatment with JBT significantly increased the number of autophagosomes and lowered the number of autophagolysosomes in the cells. Compared with the control cells and the cells treated with JBT or RAPA alone, the cells treated with both JBT and RAPA showed significantly decreased mRNA levels of PI3K, Akt and mTOR (P < 0.01) but without significant changes in their protein expressions (P > 0.05); the combined treatment significantly inhibited the protein expressions of p-PI3K, p-Akt, p-mTOR, and P62 (P < 0.05) and upregulated the protein expressions of Beclin-1 and LC3B (P < 0.05) in the cells. CONCLUSION: JBT can inhibit the survival rate of RA-FLS and increase the level of autophagy possibly through a mechanism that down-regulates PI3K/Akt/mTOR signaling pathway.

Video-assisted anal fistula treatment for complex anorectal fistulas in adults: a systematic review and meta-analysis.

BACKGROUND: Video-assisted anal fistula treatment (VAAFT) has gained increasing acceptance as a sphincter-sparing procedure for treating complex anorectal fistulas (CAF), but no unequivocal conclusions can yet be drawn regarding its ultimate effectiveness. We reviewed the literature and performed a meta-analysis to evaluate the efficacy and safety of VAAFT in CAF patients. METHODS: The study protocol was registered with the PROSPERO database (CRD42021279085). A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases up to June 2021 with no restriction on language based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We used the keywords video-assisted surgery, video-assisted anal fistula treatment, and complex anorectal fistula to identify relevant studies. RESULTS: Fourteen trials (7 prospective and 7 retrospective) with a total of 1201 patients (mean age 43.5 years) were included. The median follow-up duration was 16.5(8-48) months. Pooled analysis showed that the rates of success, recurrence and postoperative complication across the studies were 83% (95% CI 81-85%, I2 = 37.9%), 16% (95% CI 14-18%, I2 = 4.8%), 11% (95% CI 7-15%, I2 = 72.1%), respectively. The postoperative Jorge-Wexner score used to assess the level of anal incontinence was 1.09 (95% CI, 0.9-1.27, I2 = 74.6%). The internal opening detection rate was 97.6% (95% CI 96.1-99.6%, I2 = 48.2%). Recurrence rates varied according to the closure method of internal opening from 21.4% after using staplers, 18.7% after suturing, to 23.5% after advancement flap. The hospital stay was 3.15 days (95% CI 2.96-3.35, I2 = 49.7%). Subgroup analysis indicated that the risk of heterogeneity in the urine retention group was higher  compared with that of the overall group and that retrospective studies may be the source of heterogeneity for postoperative anal incontinence. r . Sensitivity analysis confirmed the stability of the pooled results. Begg's and Egger's tests showed no evidence of publication bias. CONCLUSIONS: According to the available evidence, VAAFT may be a valuable alternative to fistulotomy or seton in treating CAF and has the additional long-term benefits of reducing anal incontinence and surgical morbidity, permitting earlier healing and accelerated rehabilitation.

[Establishment of a cytokine release syndrome associated with chimeric antigen receptor T cell treatment in SCID/Beige mice model].

Objective: To establish a cytokine release syndrome (CRS) mouse model related to CAR-T cell therapy and provide a research model for the clinical phenomena. Methods: CAR-T cells targeting human CD19 molecule were constructed by molecular cloning and lentiviral transfection. Flow cytometry (FACS) was used to detect the transfection efficiency of CAR-T cells. The tumor-killing efficiency of CAR-T cells was detected by ELISA and flow cytometry. The CAR-T cells were injected into the tumor-bearing SCID/Beige mice through tail vein, and divided into phosphate buffered solution (PBS) group, low-burden group (1×10(5) Raji-Luc2 cells) and high-burden group (5×10(5) Raji-Luc2 cells). The tumor treatment effect was detected by animal in vivo imaging. Serum levels of cytokines including human IFN-γ, human IL-2, mouse IL-6, and mouse GM-CSF were measured by ELISA. The health status of the mice was evaluated by pathological examination. Results: The health scores of T cell group and T cell+ OKT-3 group were (1.15±0.08) and (2.90±0.15), respectively, after the injection of human T cell and T cell + OKT-3 antibody through tail vein, and the difference was statistically significant (P<0.001). The serum levels of human IL-2, human IFN-γ, human IL-15, mouse IL-6 and mouse GM-CSF in T cell+ OKT-3 group were (1 064.00±50.14), (1 285.00±193.90), (202.4±18.76), (1 478.00±289.20) and (350.70±42.27) pg/ml, respectively, higher than (22.67±6.36), (23.67±3.71), (44.33±14.45), (147.30±36.20), (138.00±22.74) pg/ml in T cell group (P<0.05). OKT-3 combined with human T cells caused a rapid increase in serum levels of human IL-2, human IFN-γ, mouse IL-6 and mouse GM-CSF, accompanied by an increase in body temperature and weight loss. CD19-targeting CAR-T cells were successfully constructed, and the positive rate of CAR-T cells was >30% detected by flow cytometry. ELISA results showed that in the presence of CD19 antigen, IL-2 and IFN-γ secreted by CAR-T19 cells co-incubated with Raji and Nalm were (561.00±37.07), (680.30±71.27), (369±25.71) and (523.00±26.31) pg/ml, respectively, higher than (55.00±20.53) and (64.00±7.55) pg/ml in the co-incubated with K562 group (P<0.001). Activated CAR-T19 cells were reinjected through the tail vein on the seventh day after tumor formation. Imaging experiments in mice showed that on the thirteenth day after tumor formation, the fluorescence intensities of tumors in the low-burden and high-burden groups were lower than on the seventh day of tumor inoculation, and the fluorescence intensity of tumors in the high-burden group decreased from 144.00±24.69 to 5.02±2.35 (P=0.005). The fluorescence intensity of low burden group decreased from 58.47±9.36 to 3.48±1.67 (P=0.004). The serum levels of T cell activation related cytokines IL-2, IL-15 and IFN-γ increased rapidly, and the secretion of monocyte related cytokines IL-16 and GM-CSF increased, accompanied by the typical characteristics of CRS such as increased body temperature and weight loss at 72 hours after injection of CAR-T19 cells. Conclusions: CAR-T cells targeting CD19 molecule are successfully constructed, and CRS phenomenon is verified in tumor-bearing mice by CAR-T cell re-infusion, providing an animal model for the mechanism of CAR-T treatment-related CRS and CRS prevention strategies.

[Source control of Pudilan Xiaoyan Oral Liquid--research on quality of Taraxaci Herba based on ultra high performance liquid chromatography fingerprint].

Pudilan Xiaoyan Oral Liquid has been widely used in the clinical treatment of inflammatory diseases such as upper respiratory tract infections. Taraxaci Herba, as the monarch medicine in Pudilan Xiaoyan Oral Liquid, due to its multi-source, multi-origin characteristics, and the difference in the content of active ingredients in different medicinal parts, has become a potential factor for the unstable quality among different batches of Pudilan Xiaoyan Oral Liquid. In this paper, Thermo Scientific Vanquish ultra-high-performance liquid chromatography(UPLC) system was used, and the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2012 Edition) issued by National Pharmacopoeia Commission was used for processing and analysis. The main common peaks were identified and contents were determined by comparison with reference substances. Fingerprints of Taraxaci Herba medicinal materials from different origins were established. 13 common peaks were identified, and 29 batches of samples from five origins had similarities above 0.90. At the same time, an ultra-high performance liquid chromatography method was developed for the determination of monocaffeoyl tartaric acid, chlorogenic acid, caffeic acid, chicoic acid, and luteolin in Taraxaci Herba. The quantitative analysis conditions were verified by methodology, and the average sample recovery was 97.30%-101.8%. The results showed that the content of the same ingredient in Taraxaci Herba from different origins and different medicinal parts was obviously different, and the fluctua-tion range was also different for different ingredients. The establishment of UPLC fingerprints for Taraxaci Herba from different regions combined with multi-component content determination methods provides a reference for improving the quality control of Taraxaci Herba medicinal materials, and also provides a source guarantee for the quality improvement of Pudilan Xiaoyan Oral Liquid.

Costs and Benefits of Initial Certification for Emergency Medicine Residency Graduates.

BACKGROUND: Graduates of emergency medicine residency programs can seek certification from the American Board of Emergency Medicine (ABEM), yet the costs and perceived value by residents is not clear. OBJECTIVE: This report sought to better define the value of board certification by asking physicians taking the ABEM Oral Certification Examination (OCE) to describe its costs (eg, time, money) and perceived benefits. METHODS: A descriptive, cross-sectional, voluntary, anonymous survey was administered to physicians taking the 2018 spring and fall ABEM OCEs. Response frequencies were used to report response rates. RESULTS: There were 2016 physicians who participated in the 2018 OCEs, of whom 1565 (78%) completed a survey. With respect to preparation, 38% (599 of 1565 responses) spent more than 30 hours preparing for the examination. Regarding the expense of preparing for the examination, 21% (328) spent nothing, 50% (776) spent less than $1,000, and 2% (38) spent more than $3,000. Most physicians (80%, 1254) reported a learning benefit to preparing for and taking the OCE. There were 49% (765) of respondents who reported that preparing for the examination reinforced their knowledge of emergency medicine; 20% (311) reported no learning benefit. Most physicians (92%, 1442) reported that ABEM certification provided a career benefit, the most common of which was more career opportunities (69%, 1076). CONCLUSIONS: Initial certification requires a considerable investment of time and money. Physicians seeking initial ABEM certification found both learning and professional benefits, with the most frequently reported being reinforcement of medical knowledge and more career opportunities.

Promoting the One Health concept: Thai Coordinating Unit for One Health.

Within the last decade, One Health has gained momentum in government agencies, academic institutions, intergovernmental organisations and civil society organisations within Thailand. One Health is an approach of multisectoral and multidisciplinary collaboration that connects human, animal and environmental health sectors to improve the health of all. In 2014, the Coordinating Unit for One Health (CUOH), based within the Thai Ministry of Public Health, was officially established to serve as a focal point within Thailand for One Health collaboration both domestically and internationally. The unit's main functions are to share data, information and resources, and to support One Health activities within the country. The CUOH Steering Committee meets regularly to provide technical and administrative guidance on the functions and directions of the CUOH. A memorandum of understanding on One Health, signed in 2016 by seven Ministries and the Thai Red Cross Society, has strengthened One Health collaboration and provides a formalised channel through which the CUOH can facilitate activities across Ministries and with non-governmental agencies in Thailand.

En l'espace d'une décennie, le recours aux méthodes Une seule santé en Thaïlande s'est intensifié au sein des agences gouvernementales, des institutions académiques, des organisations intergouvernementales et des organisations de la société civile. La collaboration multisectorielle et pluridisciplinaire mise en place selon les principes Une seule santé vise à connecter les secteurs de la santé publique, la santé animale et la santé environnementale afin d'améliorer la santé pour tous. En 2014, l'Unité de coordination Une seule santé (CUOH) a été officiellement créée au sein du ministère thaïlandais de la santé publique dans le but de servir de point focal national pour la collaboration Une seule santé aussi bien dans le pays qu'au niveau international. L'Unité a pour principales fonctions le partage de données, d'informations et de ressources et le soutien aux activités Une seule santé dans le pays. Le comité directeur de la CUOH se réunit régulièrement pour fixer les orientations techniques et administratives des tâches et des objectifs de l'Unité. Un protocole d'accord sur le thème Une seule santé signé en 2016 par sept ministères et la Société thaïlandaise de la Croix rouge renforce cette collaboration Une seule santé et fournit un canal officiel grâce auquel la CUOH peut déployer des activités transversales faisant intervenir plusieurs ministères et organisations non gouvernementales en Thaïlande.

En el curso del último decenio, la noción de Una sola salud ha ido ganando presencia y peso en el seno de organismos públicos, instituciones universitarias, organizaciones intergubernamentales y entidades de la sociedad civil de Tailandia. La filosofía de Una sola salud se traduce en un trabajo de colaboración multisectorial y pluridisciplinar que conecta entre sí los sectores de la salud humana, animal y ambiental con el objetivo último de hacer realidad un mejor estado de salud para todos. En 2014 se estableció oficialmente dentro del Ministerio de Salud Pública de Tailandia la Unidad de Coordinación en pro de Una sola salud, que tiene por cometido ejercer de enlace dentro del país de todas las actividades de colaboración en clave de Una sola salud, ya sean nacionales o internacionales. Sus principales funciones son el intercambio de datos, información y recursos y la prestación de apoyo a dichas actividades dentro del país. Su Comité de Dirección se reúne periódicamente para marcar pautas técnicas y administrativas sobre las funciones y las líneas de trabajo de la Unidad. En 2016, siete ministerios y la Sociedad Tailandesa de la Cruz Roja suscribieron un memorando de entendimiento en torno a la noción de Una sola salud que, además de reforzar la colaboración encuadrada en esta filosofía, abre un cauce oficial a través del cual la Unidad puede facilitar el trabajo interministerial o la colaboración con entidades no gubernamentales en Tailandia.

Cognitive and Functional Status of Persons Newly Enrolled at Dementia-Specific Adult Day Centers and Burden of Their Caregivers.

BACKGROUND AND OBJECTIVES: Recognizing the important role that dementia-specific adult day centers have in maintaining persons with a neurocognitive disorder in their home, this article examines three critical indicators at the time when people first enroll in such a center: cognitive and functional impairment of the enrollee, and burden reported by their family caregivers. We also considered variations in these 3 indicators by race/ethnicity and by the relationship of caregiver to the new enrollee. RESEARCH DESIGN AND METHODS: We conducted a secondary analysis of data collected by a nonprofit organization operating 11 dementia-specific adult day centers located on the east coast of Florida. Nursing staff conducted intake interviews with enrollees and their caregivers, and assessed functional status within one month of admission. Instruments included the Zarit Burden Scale and components of the Minimum Data Set: the Brief Interview for Mental Status (BIMS) and 4 measures of functional status. RESULTS: On average the cognitive scores of newly enrollees were well-within the range indicated for severe impairment, and these levels did not differ by race/ethnicity. Burden reported by caregivers however differed significantly, with Latinx caregivers reporting the greatest burden and African American/Black caregivers reporting the least. Further, while daughters generally reported higher levels of burden than other family caregivers, Black daughters reported the least. DISCUSSION AND IMPLICATIONS: Results suggest a need for greater dissemination efforts about adult day programs to the Latinx community, as well as attention to the disparate burden placed upon differing family relationships of caregivers to enrollees.

Effect of a Multidimensional Physical Activity Intervention on Body Mass Index, Skinfolds and Fitness in South African Children: Results from a Cluster-Randomised Controlled Trial.

Obesity-related conditions impose a considerable and growing burden on low- and middle-income countries, including South Africa. We aimed to assess the effect of twice a 10-week multidimensional, school-based physical activity intervention on children's health in Port Elizabeth, South Africa. A cluster-randomised controlled trial was implemented from February 2015 to May 2016 in grade 4 classes in eight disadvantaged primary schools. Interventions consisted of physical education lessons, moving-to-music classes, in-class activity breaks and school infrastructure enhancement to promote physical activity. Primary outcomes included cardiorespiratory fitness, body mass index (BMI) and skinfold thickness. Explanatory variables were socioeconomic status, self-reported physical activity, stunting, anaemia and parasite infections. Complete data were available from 746 children. A significantly lower increase in the mean BMI Z-score (estimate of difference in mean change: -0.17; 95% confidence interval (CI): -0.24 to -0.09; p < 0.001) and reduced increase in the mean skinfold thickness (difference in mean change: -1.06; 95% CI: -1.83 to -0.29; p = 0.007) was observed in intervention schools. No significant group difference occurred in the mean change of cardiorespiratory fitness (p > 0.05). These findings show that a multidimensional, school-based physical activity intervention can reduce the increase in specific cardiovascular risk factors. However, a longer and more intensive intervention might be necessary to improve cardiorespiratory fitness.

[Evidential research on the source of term "wine"].

During Shang Dynasty, there appeared the wine(Chinese:, Jiuji), a clarified liquid preparation extracted from crude medicine with distilled liquor.The wine had many alternative names in history.In Yuan Dynasty, the connotation of "wine" was completely same as its modern meaning. It was as a specific term of drug types during the Republic of China. In Chinese Traditional Medicine and Materia Medica Subject Headings, the "wine" became a formal subject term. In Chinese Terms in Traditional Chinese Medicine and Pharmacy, "wine" was issued as a standardized name, which considered to be consistent, scientific and concise under scientific naming rules.

Intelligent dynamic clinical checklists improved checklist compliance in the intensive care unit.

BACKGROUND: Checklists can reduce medical errors. However, the effectiveness of checklists is hampered by lack of acceptance and compliance. Recently, a new type of checklist with dynamic properties has been created to provide more specific checklist items for each individual patient. Our purpose in this simulation-based study was to investigate a newly developed intelligent dynamic clinical checklist (DCC) for the intensive care unit (ICU) ward round. METHODS: Eligible clinicians were invited to participate as volunteers. Highest achievable scores were established for six typical ICU scenarios to determine which items must be checked. The participants compared the DCC with the local standard of care. The primary outcomes were the caregiver satisfaction score and the percentages of checked items overall and of critical items requiring a direct intervention. RESULTS: In total, 20 participants were included, who performed 116 scenarios. The median percentage of checked items was 100.0% with the DCC and 73.6% for the scenarios completed with local standard of care ( P <0.001). Critical items remained unchecked in 23.1% of the scenarios performed with local standard of care and 0.0% of the scenarios where the DCC was available ( P <0.001). The mean satisfaction score of the DCC was 4.13 out of 5. CONCLUSIONS: This simulation study indicates that an intelligent DCC significantly increases compliance with best practice by reducing the percentage of unchecked items during ICU ward rounds, while the user satisfaction rate remains high. Real-life clinical research is required to evaluate this new type of checklist further.

Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Initial Validity Analysis of the American Board of Emergency Medicine Enhanced Oral Examination.

OBJECTIVES: The American Board of Emergency Medicine (ABEM) has introduced a new testing format for the oral certification examination (OCE): the enhanced oral or "eOral" format. The purpose of this study was to perform initial validity analyses of the eOral format. The two hypotheses were: 1) the case content in the eOral format was sufficiently similar to clinical practice and 2) the eOral case materials were sufficiently similar to clinical practice. The eOral and traditional formats were compared for these characteristics. METHODS: This was a prospective survey study. The survey was administered as a voluntary postexamination activity at the end of the 2015 spring (April 25-27) and fall (October 10-13) ABEM OCEs. The survey is a routine part of the ABEM oral examination experience. For 2015, two additional questions were added to gauge the similarity of the eOral format to clinical practice. Validity was defined by content and substantive elements within Messick's model of construct validity as well as portions of Kane's validity model. RESULTS: Of the 1,746 physicians who took the oral examination, 1,380 physicians (79.0%) completed all or part of the study survey questions. The majority of respondents agreed the patient presentations in the cases were similar (strongly agreed or agreed) to cases seen in clinical practice, in both the traditional cases (95.1%) and the eOral cases (90.1%). Likewise, the majority of respondents answered that the case materials (e.g., laboratory, radiographs) were similar (strongly agreed or agreed) to what they encounter in clinical practice, both in the traditional format (85.8%) and in the eOral cases (93.7%). CONCLUSIONS: Most emergency physicians reported that the types of cases tested in the traditional and eOral formats were similar to cases encountered in clinical practice. In addition, most physicians found the case materials to be similar to what is seen in clinical practice. This study provides early validity evidence for the eOral format.

Intestinal parasites, growth and physical fitness of schoolchildren in poor neighbourhoods of Port Elizabeth, South Africa: a cross-sectional survey.

BACKGROUND: As traditional lifestyle and diets change with social and economic development, disadvantaged communities in low- and middle-income countries increasingly face a double burden of communicable and non-communicable diseases. We studied the relationship between physical fitness and infections with soil-transmitted helminths (STHs), intestinal protozoa and Helicobacter pylori among schoolchildren in Port Elizabeth, South Africa. METHODS: We conducted a cross-sectional survey among 1009 children, aged 9 to 12 years, from eight primary schools in socioeconomically disadvantaged neighbourhoods of Port Elizabeth. Physical fitness was determined using field-deployable tests of the Eurofit fitness test battery. Stool samples were analysed with the Kato-Katz thick smear technique to diagnose STHs and with rapid diagnostic tests (RDTs) to detect intestinal protozoa and H. pylori infections. Haemoglobin (Hb) levels were assessed and anthropometric indicators determined. RESULTS: Complete data were available for 934 children (92 %). In two schools, high STH prevalences were found (Ascaris lumbricoides 60 and 72 %; Trichuris trichiura 65 % each). For boys and girls co-infected with A. lumbricoides and T. trichiura (n = 155) the maximal oxygen uptake (VO2 max) was estimated to be 50.1 and 47.2 ml kg(-1) min(-1), compared to 51.5 and 47.4 ml kg(-1) min(-1) for their non-infected peers (n = 278), respectively. On average, children without helminth infections had greater body mass (P = 0.011), height (P = 0.009) and a higher body mass index (P = 0.024) and were less often stunted (P = 0.006), but not significantly less wasted compared to their peers with a single or dual species infection. Among 9-year-old boys, a negative correlation between helminth infections and VO2 max, grip strength and standing broad jump distance was observed (P = 0.038). The overall mean Hb level was 122.2 g l(-1). In the two schools with the highest prevalence of STHs the Hb means were 119.7 and 120.5 g l(-1), respectively. CONCLUSIONS: Intestinal parasite infections appear to have a small but significant negative effect on the physical fitness of infected children, as expressed by their maximal oxygen uptake. We observed a clear impact on anthropometric indicators.

Disease, activity and schoolchildren's health (DASH) in Port Elizabeth, South Africa: a study protocol.

BACKGROUND: An in-depth epidemiological investigation on intestinal parasite infections in an impoverished area of Port Elizabeth, South Africa provides a unique opportunity for research on its impact on children's physical fitness, cognitive performance and psychosocial health. Additionally, we will screen risk factors for the development of diabetes and hypertension in adulthood. METHODS/DESIGN: A 2-year longitudinal cohort study will be conducted, consisting of three cross-sectional surveys (baseline and two follow-ups), in eight historically black and coloured (mixed race) primary schools located in different townships in Port Elizabeth, South Africa. Approximately 1000 Grade 4 primary schoolchildren, aged 8 to 12 years, will be enrolled and followed. At each survey, disease status, anthropometry and levels of physical fitness, cognitive performance and psychosocial health will be assessed. After each survey, individuals diagnosed with parasitic worm infections will be treated with anthelminthic drugs, while children with other infections will be referred to local clinics. Based on baseline results, interventions will be tailored to the local settings, embedded within the study and implemented in half of the schools, while the remaining schools will serve as controls. Implementation of the interventions will take place over two 8-week periods. The effect of interventions will be determined with predefined health parameters. DISCUSSION: This study will shed new light on the health burden incurred by children in deprived urban settings of South Africa and provide guidance for specific health interventions. Challenges foreseen in the conduct of this study include: (i) difficulty in obtaining written informed consent from parents/guardians; (ii) administration of questionnaires in schools where three languages are spoken (Afrikaans, Xhosa and English); (iii) challenges in grasping concepts of psychosocial health among schoolchildren using a questionnaire; and (iv) loss to follow-up due to the study setting where illiteracy, mobility and violence are common. Finally, designing the health interventions together with local principals and teachers will allow all concerned with the research to bolster a sense of community ownership and sustained use of the interventions after the study has ceased. TRIAL REGISTRATION: Controlled-trials.com; identifier: ISRCTN68411960 (date assigned: 14 February 2014).

A clustering method to identify who benefits most from the treatment group in clinical trials.

In randomized controlled trials (RCTs), the most compelling need is to determine whether the treatment condition was more effective than control. However, it is generally recognized that not all participants in the treatment group of most clinical trials benefit equally. While subgroup analyses are often used to compare treatment effectiveness across pre-determined subgroups categorized by patient characteristics, methods to empirically identify naturally occurring clusters of persons who benefit most from the treatment group have rarely been implemented. This article provides a modeling framework to accomplish this important task. Utilizing information about individuals from the treatment group who had poor outcomes, the present study proposes an a priori clustering strategy that classifies the individuals with initially good outcomes in the treatment group into: (a) group GE (good outcome, effective), the latent subgroup of individuals for whom the treatment is likely to be effective and (b) group GI (good outcome, ineffective), the latent subgroup of individuals for whom the treatment is not likely to be effective. The method is illustrated through a re-analysis of a publically available data set from the National Institute on Drug Abuse. The RCT examines the effectiveness of motivational enhancement therapy from 461 outpatients with substance abuse problems. The proposed method identified latent subgroups GE and GI, and the comparison between the two groups revealed several significantly different and informative characteristics even though both subgroups had good outcomes during the immediate post-therapy period. As a diagnostic means utilizing out-of-sample forecasting performance, the present study compared the relapse rates during the long-term follow-up period for the two subgroups. As expected, group GI, composed of individuals for whom the treatment was hypothesized to be ineffective, had a significantly higher relapse rate than group GE (63% vs. 27%; χ2 = 9.99, p-value = .002).

The role of race and ethnicity in predicting length of hospice care among older adults.

BACKGROUND: The purpose of the study was to examine both direct and interactive roles of race/ethnicity with patients' characteristics (age, gender, relationship with caregiver, diagnosis, referral source, and payment type) in predicting length of hospice care. METHOD: This study included a total of 16,323 patients 65 years of age and older (M(age)=81.4, SD=8.3) who were served by a hospice in central Florida during a four-year period, 2002-2006. Survival analyses were conducted using the Cox proportional hazards model to predict the length of hospice care and test the interaction effects of race/ethnicity. RESULTS: The majority of subjects (83.5%) were white, 7.6% were African-American, and 8.9% were Hispanic. During the study period, 58.5% died. All patient characteristics were significantly associated with the length of hospice care (p < .05). Overall, Hispanics had the longest hospice stay (M=98.84 days), followed by African-Americans (M=90.29) and whites (M=88.20). With the exception of African-American women who were no more likely to stay longer under hospice care than African-American men, the women in this study stayed longer under hospice care than men did. Patients referred from long-term care (LTC) settings had shorter stays in hospice care compared to those referred by physicians in other settings. Additionally, African-Americans and Hispanics referred from LTC had significantly shorter hospice stays than those referred by primary physicians. CONCLUSION: In this limited sample of hospice patients, length of stay was longer for minority patients than white patients.