940 results on '"Marietta, M."'
Search Results
2. Th17/1 and ex-Th17 cells are detected in patients with polyarticular juvenile arthritis and increase following treatment
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Stephanie Wood, Justin Branch, Priscilla Vasquez, Marietta M. DeGuzman, Amanda Brown, Anna Carmela Sagcal-Gironella, Saimun Singla, Andrea Ramirez, and Tiphanie P. Vogel
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IL-6 ,STAT3 ,Th17 ,Treg ,Th17/1 ,Ex-Th17 ,Pediatrics ,RJ1-570 ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background A better understanding of the pathogenesis of polyarticular juvenile idiopathic arthritis (polyJIA) is needed to aide in the development of data-driven approaches to guide selection between therapeutic options. One inflammatory pathway of interest is JAK-STAT signaling. STAT3 is a transcription factor critical to the differentiation of inflammatory T helper 17 cells (Th17s). Previous studies have demonstrated increased STAT3 activation in adult patients with rheumatoid arthritis, but less is known about STAT3 activation in polyJIA. We hypothesized that Th17 cells and STAT3 activation would be increased in treatment-naïve polyJIA patients compared to pediatric controls. Methods Blood from 17 patients with polyJIA was collected at initial diagnosis and again if remission was achieved (post-treatment). Pediatric healthy controls were also collected. Peripheral blood mononuclear cells were isolated and CD4 + T cell subsets and STAT activation (phosphorylation) were evaluated using flow cytometry. Data were analyzed using Mann–Whitney U and Wilcoxon matched-pairs signed rank tests. Results Treatment-naïve polyJIA patients had increased Th17 cells (CD3 + CD4 + interleukin(IL)-17 +) compared to controls (0.15% v 0.44%, p
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- 2024
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3. Hospital energy demand forecasting for prioritisation during periods of constrained supply
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Megashnee Munsamy, Arnesh Telukdarie, Takeru Igusa, and Marietta M Squire
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energy, healthcare, hospital, business ,Industrial engineering. Management engineering ,T55.4-60.8 ,Social Sciences ,Commerce ,HF1-6182 ,Business ,HF5001-6182 - Abstract
Purpose: Sustaining healthcare operations without adequate energy capacity creates significant challenges, especially during periods of constrained energy supply. This research develops a clinical and non-clinical activity-based hospital energy model for electrical load prioritization during periods of constrained energy supply. Design/methodology/approach: Discrete event modelling is adopted for development of the hospital energy model (HEM). The basis of the HEM is business process mapping of the hospitals clinical and non-clinical activities. The model prioritizes the electrical load demand as Priority 1, 2 and 3; with Priority 1 activities essential to the survival of patients, Priority 2 activities are critical activities that are required after one to four hours, and Priority 3 activities can run for several hours without electricity. Findings: The model was applied to a small, medium, and large hospital. The results demonstrate that Priority 2 activities have the highest energy demand, followed by Priority 1 and Priority 3 activities, respectively for all hospital sizes. For the medium and large hospitals, the top three contributors to energy demand are lighting, HVAC, and patient services. For the small hospital, it is patient services, lighting, and HVAC, respectively. Research limitations/implications: The model is specific to hospitals but can be modified for other healthcare facilities. Practical implications: The resolution of the electrical energy demand down to the business activity level, enables hospitals to evaluate current practices for optimization. It facilitates multiple energy supply scenarios, enabling hospital management to conduct feasibility studies based on available power supply options Social implications: Improved planning of capital expenditure and operational budgets and during constrained energy supply. This reduces risk to hospitals and ensures consistent quality of service. Originality/value: Current hospital energy models are limited, especially for operations management under constrained energy supply. A simple to use model is proposed to assist in planning of activities based on available supply.
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- 2023
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4. Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
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Jonas Johannes Papendorf, Frédéric Ebstein, Sara Alehashemi, Daniela Gerent Petry Piotto, Anna Kozlova, Maria Teresa Terreri, Anna Shcherbina, Andre Rastegar, Marta Rodrigues, Renan Pereira, Sophia Park, Bin Lin, Kat Uss, Sophie Möller, Ana Flávia da Silva Pina, Flavio Sztajnbok, Sofia Torreggiani, Julie Niemela, Jennifer Stoddard, Sergio D. Rosenzweig, Andrew J. Oler, Colton McNinch, Marietta M. de Guzman, Adriana Fonseca, Nicole Micheloni, Melissa Mariti Fraga, Sandro Félix Perazzio, Raphaela Goldbach-Mansky, Adriana A. de Jesus, and Elke Krüger
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proteasomopathy ,proteasome associated autoinflammatory syndrome ,type I interferon ,interferonopathy ,PSMB8 ,PSMB10 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.
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- 2023
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5. Regulation of Mitochondrial Homeostasis and Metabolic Programming in Memory B cells by Mitophagy
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Marietta M. Budai, Min Li, Srikanth Kodali, Min Chen, and Jin Wang
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Cytology ,QH573-671 - Abstract
The formation of long-lived immune memory cells specific for pathogens is critical for the establishment of long-term immune protection against future infections. BNIP3L/NIX and BNIP3, two functionally redundant BCL2 family members required for mitophagy, undergo significant upregulation after memory B cells are formed. Deletion of Bnip3l and Bnip3 leads to mitochondrial accumulation, and increases in oxidative phosphorylation and fatty acid synthesis, resulting in the loss of memory B cells. These observations suggest that after the formation of memory B cells, mitophagy is critical for clearing superfluous mitochondria to re-shape the metabolic programs, thereby protecting the metabolic quiescence and longevity of memory B cells .
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- 2022
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6. Targeting HIV-1 reservoirs in T cell subsets
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Min Li, Marietta M. Budai, Min Chen, and Jin Wang
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HIV-1 ,cell death ,anti-apoptotic molecules ,autophagy ,latency reversal agents ,T cell subsets ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found that treatments of HIV-1 infection by suppressive antiretroviral therapy (ART) led to the establishment of latent HIV reservoirs in naïve, central memory and effector memory T cells. Moreover, SECH treatments could clear latent HIV-1 reservoirs in these different T cell subsets of humanized mice. Co-culture studies showed that T cell subsets latently infected by HIV-1, but not uninfected bystander cells, were susceptible to cell death induced by SECH treatments. Our study suggests that the SECH strategy is effective for specific targeting of latent HIV-1 reservoirs in different T cell subsets.
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- 2023
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7. Particle yields from numerical simulations
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Homor, Marietta M. and Jakovác, Antal
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High Energy Physics - Phenomenology ,Condensed Matter - Statistical Mechanics ,High Energy Physics - Lattice - Abstract
In this paper we use numerical simulations to calculate the particle yields. We demonstrate that in the model of local particle creation the deviation from the pure exponential distribution is natural even in equilibrium, and an approximate Tsallis-Pareto-like distribution function can be well fitted to the calculated yields, in accordance with the experimental observations. We present numerical simulations in classical $\Phi^4$ model as well as in the SU(3) quantum Yang-Mills theory to clarify this issue., Comment: 8 pages, 12 figures
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- 2017
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8. Modeling hospital energy and economic costs for COVID-19 infection control interventions
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Squire, Marietta M., Munsamy, Megashnee, Lin, Gary, Telukdarie, Arnesh, and Igusa, Takeru
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- 2021
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9. Results of treatment with myo-Inositol and D-chiro inositol combination in ratio 5:1 in women with polycystic ovary syndrome
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Tatiana A. Oboskalova, Anna V. Vorontsova, Maksim A. Zvychainyi, Karina G. Gushchina, and Marietta M. Maitesian
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polycystic ovary syndrome ,myo-inositol ,d-chiro inositol ,dikirogen ,Gynecology and obstetrics ,RG1-991 - Abstract
We conducted an observational descriptive study evaluating the effectiveness of therapeutic modification of lifestyle with adding of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination (ratio 5:1) for nutritional support in 104 women of reproductive age with polycystic ovary syndrome (classic phenotype and nonclassical phenotypes in the presence of hyperandrogenism) for 6 months. Revealed changes in anthropometric parameters (decrease in body mass index by 0.89 kg/m2; p0.05 and waist circumference by 3.0 cm; p0.05), skin status (decrease in the incidence of acne from 96.2 up to 58.6%; p0.05 and seborrhea from 34.6 to 5.8%; p0.05), hormonal profile (statistically significant change in all studied parameters; p0.05: decrease in total testosterone to 1.27 nmol/L and a free androgen index up to 4.12% under an increase in globulin binding sex hormones), carbohydrate metabolism (normalization of glucose tolerance without the development of hypoglycemia) and restoration of menstrual cycle (MC) parameters (regular MC in 76.9 %; p0.05, MC duration 33.4 days; p0.05) indicate a significant role of stage I therapy in patients with polycystic ovary syndrome and the possible benefits of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination as a nutritional support.
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- 2020
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10. Contaminated water delivery as a simple and effective method of experimental Salmonella infection
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Donnell, Hope O, Pham, Oanh H, Benoun, Joseph M, Ravesloot-Chvez, Marietta M, and McSorley, Stephen J
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Microbiology ,Biological Sciences ,Emerging Infectious Diseases ,Digestive Diseases ,Foodborne Illness ,Prevention ,Biodefense ,Infectious Diseases ,Vaccine Related ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Animals ,Disease Models ,Animal ,Drinking Water ,Female ,Intestinal Mucosa ,Mice ,Mice ,Inbred C57BL ,Salmonella Infections ,Animal ,Salmonella typhimurium ,Water Microbiology ,Water Pollution ,alternative infection technique ,experimental stress ,gavage ,intragastric ,natural route ,oral infection ,Salmonella ,water contamination ,Medical Microbiology - Abstract
AimIn most infectious disease models, it is assumed that gavage needle infection is the most reliable means of pathogen delivery to the GI tract. However, this methodology can cause esophageal tearing and induces stress in experimental animals, both of which have the potential to impact early infection and the subsequent immune response.Materials & methodsC57BL/6 mice were orally infected with virulent Salmonella Typhimurium SL1344 either by intragastric gavage preceded by sodium bicarbonate, or by contamination of drinking water.ResultsWe demonstrate that water contamination delivery of Salmonella is equivalent to gavage inoculation in providing a consistent model of infection. Furthermore, exposure of mice to contaminated drinking water for as little as 4 h allowed maximal mucosal and systemic infection, suggesting an abbreviated window exists for natural intestinal entry.ConclusionTogether, these data question the need for gavage delivery for infection with oral pathogens.
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- 2015
11. Mitochondrion-Mediated Cell Death through Erk1-Alox5 Independent of Caspase-9 Signaling
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Min Chen, Lei Wang, Min Li, Marietta M. Budai, and Jin Wang
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caspase-9-independent cell death ,Erk1 ,Alox5 ,ROS ,lipid peroxidation ,Cytology ,QH573-671 - Abstract
Mitochondrial disruption leads to the release of cytochrome c to activate caspase-9 and the downstream caspase cascade for the execution of apoptosis. However, cell death can proceed efficiently in the absence of caspase-9 following mitochondrial disruption, suggesting the existence of caspase-9-independent cell death mechanisms. Through a genome-wide siRNA library screening, we identified a network of genes that mediate caspase-9-independent cell death, through ROS production and Alox5-dependent membrane lipid peroxidation. Erk1-dependent phosphorylation of Alox5 is critical for targeting Alox5 to the nuclear membrane to mediate lipid peroxidation, resulting in nuclear translocation of cytolytic molecules to induce DNA damage and cell death. Consistently, double knockouts of caspase-9 and Alox5 in mice, but not deletion of either gene alone, led to significant T cell expansion with inhibited cell death, indicating that caspase-9- and Alox5-dependent pathways function in parallel to regulate T cell death in vivo. This unbiased whole-genome screening reveals an Erk1-Alox5-mediated pathway that promotes membrane lipid peroxidation and nuclear translocation of cytolytic molecules, leading to the execution of cell death in parallel to the caspase-9 signaling cascade.
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- 2022
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12. Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells
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O'Donnell, Hope, Pham, Oanh H, Li, Lin-xi, Atif, Shaikh M, Lee, Seung-Joo, Ravesloot, Marietta M, Stolfi, Jessica L, Nuccio, Sean-Paul, Broz, Petr, Monack, Denise M, Baumler, Andreas J, and McSorley, Stephen J
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Biomedical and Clinical Sciences ,Immunology ,Emerging Infectious Diseases ,Vaccine Related ,Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Infection ,Animals ,Bacterial Load ,CD4 Antigens ,Chlamydia ,Flow Cytometry ,Immunity ,Innate ,Inflammasomes ,Interleukin-18 ,Mice ,Mice ,Inbred C57BL ,Real-Time Polymerase Chain Reaction ,Salmonella ,Signal Transduction ,Th1 Cells ,Toll-Like Receptor 4 ,Toll-Like Receptors - Abstract
T cell effector functions can be elicited by noncognate stimuli, but the mechanism and contribution of this pathway to the resolution of intracellular macrophage infections have not been defined. Here, we show that CD4(+) T helper 1 (Th1) cells could be rapidly stimulated by microbe-associated molecular patterns during active infection with Salmonella or Chlamydia. Further, maximal stimulation of Th1 cells by lipopolysaccharide (LPS) did not require T-cell-intrinsic expression of toll-like receptor 4 (TLR4), interleukin-1 receptor (IL-1R), or interferon-γ receptor (IFN-γR) but instead required IL-18R, IL-33R, and adaptor protein MyD88. Innate stimulation of Th1 cells also required host expression of TLR4 and inflammasome components that together increased serum concentrations of IL-18. Finally, the elimination of noncognate Th1 cell stimulation hindered the resolution of primary Salmonella infection. Thus, the in vivo bactericidal capacity of Th1 cells is regulated by the response to noncognate stimuli elicited by multiple innate immune receptors.
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- 2014
13. Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
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Papendorf, Jonas Johannes, primary, Ebstein, Frédéric, additional, Alehashemi, Sara, additional, Piotto, Daniela Gerent Petry, additional, Kozlova, Anna, additional, Terreri, Maria Teresa, additional, Shcherbina, Anna, additional, Rastegar, Andre, additional, Rodrigues, Marta, additional, Pereira, Renan, additional, Park, Sophia, additional, Lin, Bin, additional, Uss, Kat, additional, Möller, Sophie, additional, da Silva Pina, Ana Flávia, additional, Sztajnbok, Flavio, additional, Torreggiani, Sofia, additional, Niemela, Julie, additional, Stoddard, Jennifer, additional, Rosenzweig, Sergio D., additional, Oler, Andrew J., additional, McNinch, Colton, additional, de Guzman, Marietta M., additional, Fonseca, Adriana, additional, Micheloni, Nicole, additional, Fraga, Melissa Mariti, additional, Perazzio, Sandro Félix, additional, Goldbach-Mansky, Raphaela, additional, de Jesus, Adriana A., additional, and Krüger, Elke, additional
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- 2023
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14. Development of an Internationalized Dietetic Technician Program for the Milwaukee Area Technical College with a Plan for Implementation and Evaluation.
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Advincula-Carpenter, Marietta M.
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An internationalized dietetic technician (DT) program was developed at the Milwaukee Area Technical College through a process that included the design and development of international modules to be used through infusion or an individual unit approach in selected courses. The following procedures were used: a review of the literature on benefits of international education, models to internationalize curriculum, appropriate instructional design, and appropriate tools to evaluate program impact; establishment of formative committees to provide feedback during the developmental process; establishment of a process for the internationalization of the DT program; use of the framework developed by the author to internationalize the selected courses; establishment of a summative committee to provide feedback on program content and face validity; and development of plans for program implementation and evaluation. Of 15 technical courses in the program, 7 were internationalized by infusion and 8 by the addition of a new unit. The process of infusion was accomplished by adding an internationalized competency or competencies in an existing unit. Evaluation was planned for two years after program implementation. (Contains 129 references. Appendixes include: DT curriculum; diagram of the internationalization process; committee reports; guidebook of internationalized DT courses, with a course outcome summary and example lesson plan; and list of 241 academic support resources.) (YLB)
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- 1996
15. Comparison of Responses on the 1994 Biennial Student Survey by the Consumer and Hospitality Services Division and Overall Students of the Milwaukee Area Technical College.
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Advincula-Carpenter, Marietta M.
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To gather curriculum planning information, the Research, Planning and Development Division of Milwaukee Area Technical College (MATC) conducts student surveys biennially. Responses of 579 MATC students enrolled in consumer and hospitality services division (CHSD) programs to the 1994 survey were compared with those of the 5,071 students constituting MATC's overall student population. Special attention was paid to students' reasons for attending MATC, educational background, major objectives for taking courses at MATC, and student status. Compared to the overall student population, the CHSD students were more likely to be female, have a lower average family income, have chosen MATC based on program rather than on schedule and/or cost, already have a vocational diploma/certificate, and be a full-time student. For both groups, the three biggest factors influencing their decision to attend MATC were the following: class schedule; printed mailed materials, and parents, relatives, and current/former MATC students. The following were among the study recommendations: (1) each program in the CHSD should be promoted to the entire MATC service area; (2) brochures/printed materials should reflect diversity of students and successful graduates; and (3) programs should address students' and industry's need for short-term programs providing skills facilitating employment. (The bibliography contains 11 references. Appended are key study findings and recommendations.) (MN)
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- 1995
16. An Evaluation of the Human Relations Workshops and Training Programs.
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Advincula-Carpenter, Marietta M.
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The human relations task force of Milwaukee Area Technical College (MATC) sponsors a workshop series to improve human relations/productivity at the college. A practicum study evaluated the workshops by using the postworkshop training evaluation forms completed by workshop participants from 1990 to 1994. Data from a literature review were also incorporated into the evaluation. Of the 202 past workshop participants surveyed, 145 (72%) believed that the workshops trained them to discuss and resolve differences with college objectives and 182 (90%) credited the workshops with helping them treat people with more understanding. Although most participants believed that the workshops increased their understanding of coworkers who are ethnically and culturally different from them, only 32%-46% stated that the workshops improved their understanding of coworkers with disabilities, and 22 (11%) stated that they still did not understand their disabled coworkers after having attended the workshops. It was recommended that the workshops be continued but that their curriculum be modified to include modules on dealing with disabled individuals and that future workshops be offered to part-time faculty and staff. (The bibliography contains 34 references. Appended are lists of task force members and recommendations and postworkshop training evaluation forms and responses to it.) (MN)
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- 1994
17. Unique Auditory Language-Learning Needs of Hearing-Impaired Children: Implications for Intervention.
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Johnson, Barbara Ann and Paterson, Marietta M.
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Twenty-seven hearing-impaired young adults with hearing potentially usable for language comprehension and a history of speech language therapy participated in this study of training in using residual hearing for the purpose of learning spoken language. Evaluation of their recalled therapy experiences indicated that listening to spoken language did not emerge as a memorable speech therapy activity for 81 percent of the subjects. This may indicate that essential listening practice was either neglected or minimized during speech language therapy. Subjects demonstrated poor listening skills (70 percent scored at chance or below on the listening task), and two-thirds reported negative feelings toward listening practice and thought that listening training would not be expected in a speech language therapy program. Study recommendations stress the need to identify clients with potentially usable aided audition and maximize their listening capabilities through training. (16 references) (DB)
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- 1991
18. Regulation of type I interferon responses by mitochondria-derived reactive oxygen species in plasmacytoid dendritic cells
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Zsofia Agod, Tünde Fekete, Marietta M. Budai, Aliz Varga, Attila Szabo, Hyelim Moon, Istvan Boldogh, Tamas Biro, Arpad Lanyi, Attila Bacsi, and Kitti Pazmandi
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Plasmacytoid dendritic cell ,Mitochondrial ROS ,Type I interferon ,Endosomal TLR signaling ,RIG-I signaling ,Antiviral response ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation. Therefore, pDCs provide an ideal model to study the impact of elevated mtROS on the antiviral signaling pathways initiated by receptors with distinct subcellular localization. We found that elevated level of mtROS alone did not change the phenotype and the baseline cytokine profile of resting pDCs. Nevertheless increased mtROS levels in pDCs lowered the TLR9-induced secretion of pro-inflammatory mediators slightly, whereas reduced type I IFN production markedly via blocking phosphorylation of interferon regulatory factor 7 (IRF7), the key transcription factor of the TLR9 signaling pathway. The TLR9-induced expression of RIG-I in pDCs was also negatively regulated by enhanced mtROS production. On the contrary, elevated mtROS significantly augmented the RIG-I-stimulated expression of type I IFNs, as well as the expression of mitochondrial antiviral-signaling (MAVS) protein and the phosphorylation of Akt and IRF3 that are essential components of RIG-I signaling. Collectively, our data suggest that increased mtROS exert diverse immunoregulatory functions in pDCs both in the early and late phase of type I IFN responses depending on which type of viral sensing pathway is stimulated.
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- 2017
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19. Hospital energy demand forecasting for prioritisation during periods of constrained supply
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Munsamy, Megashnee, primary, Telukdarie, Arnesh, additional, Igusa, Takeru, additional, and Squire, Marietta M, additional
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- 2023
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20. Targeting HIV-1 reservoirs in T cell subsets
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Li, Min, primary, Budai, Marietta M., additional, Chen, Min, additional, and Wang, Jin, additional
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- 2023
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21. Performance Assessment for the Waste Isolation Pilot Plant: From Regulation to Calculation for 40 CFR 191.13
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Helton, J. C., Anderson, D. R., Marietta, M. G., and Rechard, R. P.
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- 1997
22. Protection of Quiescence and Longevity of IgG Memory B Cells by Mitochondrial Autophagy
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Srikanth Kodali, Min Li, Marietta M. Budai, Min Chen, and Jin Wang
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Mice, Knockout ,Fatty Acids ,Longevity ,Immunology ,Mitophagy ,Membrane Proteins ,Adoptive Transfer ,Article ,Oxidative Phosphorylation ,Mitochondria ,Mice, Inbred C57BL ,Mitochondrial Proteins ,Mice ,Memory B Cells ,Immunoglobulin G ,Receptor-Interacting Protein Serine-Threonine Kinases ,Necroptosis ,Animals ,Homeostasis ,Immunology and Allergy ,RNA Interference ,RNA, Small Interfering ,Immunologic Memory - Abstract
The development of long-lived immune memory cells against pathogens is critical for the success of vaccines to establish protection against future infections. However, the mechanisms governing the long-term survival of immune memory cells remain to be elucidated. In this article, we show that the maintenance mitochondrial homeostasis by autophagy is critical for restricting metabolic functions to protect IgG memory B cell survival. Knockout of mitochondrial autophagy genes, Nix and Bnip3, leads to mitochondrial accumulation and increases in oxidative phosphorylation and fatty acid synthesis, resulting in the loss of IgG+ memory B cells in mice. Inhibiting fatty acid synthesis or silencing necroptosis gene Ripk3 rescued Nix−/−Bnip3−/− IgG memory B cells, indicating that mitochondrial autophagy is important for limiting metabolic functions to prevent cell death. Our results suggest a critical role for mitochondrial autophagy in the maintenance of immunological memory by protecting the metabolic quiescence and longevity of memory B cells.
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- 2022
23. Autoantibodies Recognizing Specificity Protein 4 Co‐occur With Anti–Transcription Intermediary Factor 1 and Are Associated With Distinct Clinical Features and Immunogenetic Risk Factors in Juvenile Myositis.
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Sherman, Matthew A., Pak, Katherine, Pinal‐Fernandez, Iago, Flegel, Willy A., Targoff, Ira N., Miller, Frederick W., Rider, Lisa G., Mammen, Andrew L., Albert, Daniel A., Arabshahi, Bita, Balboni, Imelda M., Ballinger, Susan, Bayat, Nastaran, Bingham, C. April, Bohnsack, John F., Cartwright, Victoria W., Cron, Randy Q., Curiel, Rodolfo, de la Pena, Wendy, and de Guzman, Marietta M.
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AUTOANTIBODIES ,PROTEINS ,RISK assessment ,DISEASE susceptibility ,DESCRIPTIVE statistics ,RESEARCH funding ,MYOSITIS ,TRANSCRIPTION factors ,AMINOTRANSFERASES ,PHENOTYPES ,DISEASE risk factors ,CHILDREN ,ADOLESCENCE - Abstract
Objective: Autoantibodies recognizing specificity protein 4 (Sp4) were recently discovered in adults with idiopathic inflammatory myopathies (IIM). Anti‐Sp4 autoantibodies co‐occurred in patients with anti–transcription intermediary factor 1 (anti‐TIF1) autoantibody‐positive dermatomyositis (DM) and were associated with a reduced risk of cancer. In the present study, the prevalence and clinical features associated with anti‐Sp4 autoantibodies in juvenile‐onset IIM were investigated. Methods: Serum samples from 336 patients with juvenile myositis in a cross‐sectional cohort and 91 healthy controls were screened for anti‐Sp4 autoantibodies using enzyme‐linked immunosorbent assay. Clinical characteristics, outcomes, and HLA alleles of those with and those without anti‐Sp4 autoantibodies were compared. Results: Anti‐Sp4 autoantibodies were present in 23 patients (7%) with juvenile myositis and were not present in any of the controls. Anti‐Sp4 autoantibodies were found among each clinical myositis subgroup. The frequency of TIF1 autoantibody positivity was significantly higher among those with anti‐Sp4 autoantibodies (21 [91%] versus 92 [30%], P < 0.001). In the anti‐TIF1 autoantibody–positive subgroup, Raynaud's phenomenon (8 [38%] versus 2 [2%], P < 0.001) was more common and peak aspartate aminotransferase was significantly lower in those with anti‐Sp4 autoantibodies. None of the patients with anti‐Sp4 autoantibodies required a wheelchair. Among White patients, DQA1*04 and DRB1*08 were associated with anti‐Sp4 autoantibodies. Conclusion: Anti‐Sp4 autoantibodies were found in patients with juvenile‐onset IIM, predominantly those with coexisting anti‐TIF1 autoantibodies. Patients with anti‐Sp4 autoantibodies represent a phenotypic subset of anti‐TIF1 autoantibody–positive myositis characterized by frequent Raynaud's phenomenon and less pronounced muscle involvement, similar to adults with these autoantibodies. Novel immunogenetic risk factors for White patients with IIM were identified among juveniles with anti‐Sp4 autoantibodies. [ABSTRACT FROM AUTHOR]
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- 2023
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24. HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related autoinflammatory disease
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Jordan S. Orange, Riccardo Castagnoli, Elke Krüger, Marita Bosticardo, Robert A. Krance, Marietta M. de Guzman, Luigi D. Notarangelo, Lisa R. Forbes, M. Cecilia Poli, Ottavia M. Delmonte, Caridad Martinez, Frédéric Ebstein, and Sarah K. Nicholas
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0301 basic medicine ,business.industry ,Immunology ,Cell Biology ,Hematology ,Disease ,Immune dysregulation ,medicine.disease ,medicine.disease_cause ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,Proteasome ,Immunity ,Proteasome assembly ,Primary immunodeficiency ,Medicine ,Letter to Blood ,business ,Immunodeficiency ,030215 immunology - Abstract
Inborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and participates in most cellular processes by degrading ubiquitinated proteins. Mutations in proteasome subunits resulting in proteasome deficiency cause a severe auto-inflammatory disease characterized by chronic auto-inflammation neutrophilic dermatosis and fever, collectively referred to as Proteasome Associated Auto-inflammatory Syndromes (PRAAS). POMP is a chaperone for proteasome assembly and AD mutations in POMP cause a form of PRAAS with prominent immunodeficiency referred to as POMP-related auto-inflammation and immune dysregulation (PRAID) manifesting with recurrent, severe and opportunistic infections in addition to inflammatory features that are characteristic for all PRAAS disorders, most importantly early-onset neutrophilic dermatosis. JAK inhibitors partially control the disease in individuals with PRAAS, however life-threatening, recurrent and opportunistic infections in patients with POMP mutations limit immunosuppressive therapies and prompted consideration of hematopoietic stem cell transplant (HSCT). We describe successful HSCT in two patients with POMP deficiency. Despite POMP being ubiquitously expressed, the immunologic and auto-inflammatory phenotype were both ameliorated through HSCT which suggests that the clinical and immunological features of PRAID are predominantly derived from a proteasome defect in hematopoietic cells. To our knowledge, these are the first patients with a form of PRAAS cured by HSCT, opening new therapeutic possibilities for these diseases.
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- 2021
25. Mitochondrion-Mediated Cell Death through Erk1-Alox5 Independent of Caspase-9 Signaling
- Author
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Chen, Min, primary, Wang, Lei, additional, Li, Min, additional, Budai, Marietta M., additional, and Wang, Jin, additional
- Published
- 2022
- Full Text
- View/download PDF
26. The University of Hartford and CREC Soundbridge: A New Master's of Education in Aural Habilitation and Education of Hearing Impaired Children
- Author
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Paterson, Marietta M. and Cole, Elizabeth
- Abstract
This profile describes the University of Hartford's new Master of Education degree program in Aural Habilitation and Education of Hearing-Impaired Children. The Aural Habilitation and Education graduate program was conceptualized as a model partnership between Capitol Region Education Council (CREC) Soundbridge, the largest public provider of services to children who are deaf or hard of hearing and their families in Connecticut, and the University of Hartford, "a private university with a public purpose." The program was specifically created to address the nationally recognized need to increase the quality and quantity of professionals in auditory-based deaf education who are prepared to work with advanced hearing technology to promote the listening and spoken language development of children who are deaf or hard of hearing. As a result of 9 years of sustained effort, planning, and approvals, the program was launched in July 2007. (Contains 1 table.)
- Published
- 2010
27. Results of treatment with myo-Inositol and D-chiro inositol combination in ratio 5:1 in women with polycystic ovary syndrome
- Author
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Maksim A. Zvychainyi, Tatiana A. Oboskalova, Anna V. Vorontsova, Karina G. Gushchina, and Marietta M. Maitesian
- Subjects
medicine.medical_specialty ,myo-inositol ,media_common.quotation_subject ,Hypoglycemia ,lcsh:Gynecology and obstetrics ,chemistry.chemical_compound ,Internal medicine ,medicine ,Inositol ,lcsh:RG1-991 ,Menstrual cycle ,media_common ,D-chiro-Inositol ,business.industry ,Free androgen index ,Hyperandrogenism ,Obstetrics and Gynecology ,dikirogen ,medicine.disease ,Polycystic ovary ,Endocrinology ,chemistry ,polycystic ovary syndrome ,d-chiro inositol ,business ,Body mass index - Abstract
We conducted an observational descriptive study evaluating the effectiveness of therapeutic modification of lifestyle with adding of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination (ratio 5:1) for nutritional support in 104 women of reproductive age with polycystic ovary syndrome (classic phenotype and nonclassical phenotypes in the presence of hyperandrogenism) for 6 months. Revealed changes in anthropometric parameters (decrease in body mass index by 0.89 kg/m 2 ; p
- Published
- 2020
28. Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis: Hepatic disease in a child with a novel pathogenic variant of FAM111B
- Author
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Kalyani R. Patel, Thuy L. Phung, Paula M. Hertel, Yelena Dokic, Marietta M. de Guzman, Raegan D. Hunt, and Yasser Albahrani
- Subjects
Systemic disease ,medicine.medical_specialty ,Poikiloderma ,Case Report ,Dermatology ,systemic disease ,hereditary fibrosing poikiloderma ,hepatomegaly ,Pulmonary fibrosis ,medicine ,lcsh:Dermatology ,transaminitis ,genetics ,Myopathy ,hypohidrosis ,liver biopsy ,Muscle contracture ,Hypopigmentation ,FAM111B ,medicine.diagnostic_test ,pulmonary fibrosis ,business.industry ,poikiloderma ,cutaneous manifestation of systemic disease ,pancreatic insufficiency ,tendon contractures ,lcsh:RL1-803 ,medicine.disease ,POIKTMP, hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis ,Tendon ,medicine.anatomical_structure ,nonscarring alopecia ,Liver biopsy ,POIKTMP ,muscle contractures ,medicine.symptom ,business ,hypopigmentation ,FAM111B gene ,myopathy - Published
- 2020
29. Clearance of HIV-1 or SIV reservoirs by promotion of apoptosis and inhibition of autophagy: Targeting intracellular molecules in cure-directed strategies
- Author
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Min Chen, Min Li, Marietta M Budai, Andrew P Rice, Jason T Kimata, Mahesh Mohan, and Jin Wang
- Subjects
CD4-Positive T-Lymphocytes ,Immunology ,NF-kappa B ,HIV Infections ,Apoptosis ,Cell Biology ,Macaca mulatta ,Virus Latency ,Transcription Factor AP-1 ,Mice ,HIV-1 ,Autophagy ,Immunology and Allergy ,Animals ,Myeloid Cell Leukemia Sequence 1 Protein ,Virus Activation - Abstract
The reservoirs of the HIV display cellular properties resembling long-lived immune memory cells that could be exploited for viral clearance. Our interest in developing a cure for HIV stems from the studies of immunologic memory against infections. We and others have found that long-lived immune memory cells employ prosurvival autophagy and antiapoptotic mechanisms to protect their longevity. Here, we describe the rationale for the development of an approach to clear HIV-1 by selective elimination of host cells harboring replication-competent HIV (SECH). While reactivation of HIV-1 in the host cells with latency reversing agents (LRAs) induces viral gene expression leading to cell death, LRAs also simultaneously up-regulate prosurvival antiapoptotic molecules and autophagy. Mechanistically, transcription factors that promote HIV-1 LTR-directed gene expression, such as NF-κB, AP-1, and Hif-1α, can also enhance the expression of cellular genes essential for cell survival and metabolic regulation, including Bcl-xL, Mcl-1, and autophagy genes. In the SECH approach, we inhibit the prosurvival antiapoptotic molecules and autophagy induced by LRAs, thereby allowing maximum killing of host cells by the induced HIV-1 proteins. SECH treatments cleared HIV-1 infections in humanized mice in vivo and in HIV-1 patient PBMCs ex vivo. SECH also cleared infections by the SIV in rhesus macaque PBMCs ex vivo. Research efforts are underway to improve the efficacy and safety of SECH and to facilitate the development of SECH as a therapeutic approach for treating people with HIV.
- Published
- 2022
30. The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages
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Czimmerer, Zsolt, Daniel, Bence, Horvath, Attila, Rückerl, Dominik, Nagy, Gergely, Kiss, Mate, Peloquin, Matthew, Budai, Marietta M., Cuaranta-Monroy, Ixchelt, Simandi, Zoltan, Steiner, Laszlo, Nagy, Bela, Jr., Poliska, Szilard, Banko, Csaba, Bacso, Zsolt, Schulman, Ira G., Sauer, Sascha, Deleuze, Jean-Francois, Allen, Judith E., Benko, Szilvia, and Nagy, Laszlo
- Published
- 2018
- Full Text
- View/download PDF
31. Clearance of HIV-1 or SIV reservoirs by promotion of apoptosis and inhibition of autophagy: Targeting intracellular molecules in cure-directed strategies
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Chen, Min, primary, Li, Min, additional, Budai, Marietta M, additional, Rice, Andrew P, additional, Kimata, Jason T, additional, Mohan, Mahesh, additional, and Wang, Jin, additional
- Published
- 2022
- Full Text
- View/download PDF
32. Position paper on the safety/efficacy profile of direct oral anticoagulants in patients with chronic kidney disease. Consensus document from the SIN, FCSA and SISET
- Author
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Grandone, E, Aucella, F, Barcellona, D, Brunori, G, Forneris, G, Gresele, P, Marietta, M, Poli, D, Testa, S, Tripodi, A, Genovesi, Sc., Grandone, E, Aucella, F, Barcellona, D, Brunori, G, Forneris, G, Gresele, P, Marietta, M, Poli, D, Testa, S, Tripodi, A, and Genovesi, S
- Subjects
Metabolic Clearance Rate ,Pyridines ,Pyridones ,Direct anticoagulants, chronic kidney disease, stroke, bleeding ,Antidotes ,Administration, Oral ,Hemorrhage ,urologic and male genital diseases ,Kidney ,Antithrombins ,Haemostasis and Thrombosis ,Cohort Studies ,Rivaroxaban ,Atrial Fibrillation ,Humans ,Drug Interactions ,Renal Insufficiency, Chronic ,Randomized Controlled Trials as Topic ,Dabigatran ,Stroke ,Observational Studies as Topic ,Thiazoles ,Practice Guidelines as Topic ,Polypharmacy ,Pyrazoles ,Drug Monitoring ,Glomerular Filtration Rate - Abstract
Direct oral anticoagulants (DOAC) are mostly prescribed to prevent cardioembolic stroke in patients with non-valvular atrial fibrillation (AF). An increasing number of guidelines recommend DOAC in AF patients with preserved renal function for the prevention of thromboembolism, and an increased use of DOAC in daily practice has been recorded also in elderly patients. Ageing is associated with a reduction in glomerular filtration rate, and impaired renal function, regardless of the cause, increases the risk of bleeding. Multiple medication use (polypharmacy) for treating superimposed co-morbidities is common in both elderly and chronic kidney disease (CKD) patients and drug-drug interaction may cause accumulation of DOAC, thereby increasing the risk of bleeding. The safety profile of DOAC in patients with CKD has not been defined with any certainty, particularly in those with severely impaired renal function or end stage renal disease. This has been due to the heterogeneity of studies and the relative paucity of data. This document reports the position of three Italian scientific societies engaged in the management of patients with atrial fibrillation who are treated with DOAC and present with CKD.
- Published
- 2020
33. Physical activity improved by adherence to prophylaxis in an Italian population of children, adolescents and adults with severe haemophilia A: The SHAPE Study
- Author
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Zanon, E., Tagliaferri, A., Pasca, S., Ettorre, C. P., Notarangelo, L. D., Biasioli, C., Aru, A. B., Milan, M., Linari, S., Rocino, A., Gagliano, F., Di Minno, G., Gamba, G., Santoro, R. C., Schinco, P., Marietta, M., Seuser, A., Von MacKensen, S., Zanon, E., Tagliaferri, A., Pasca, S., Ettorre, C. P., Notarangelo, L. D., Biasioli, C., Aru, A. B., Milan, M., Linari, S., Rocino, A., Gagliano, F., Di Minno, G., Gamba, G., Santoro, R. C., Schinco, P., Marietta, M., Seuser, A., and Von MacKensen, S.
- Subjects
Adult ,Male ,Factor VIII ,Severe haemophilia ,Adolescent ,Adherence to treatment ,FVIII replacement therapy ,Orthopaedic haemophilia scores ,Physical activity ,Child ,Exercise ,Female ,Hemophilia A ,Humans ,Italy ,Patient Compliance ,Prospective Studies ,Young Adult ,Orthopaedic haemophilia score ,Haemostasis - Abstract
Background - Physical activity in people with haemophilia (PWH) reduces the development of severe arthropathy, but it must be performed after regular, proper prophylaxis. Strict adherence to treatment is crucial to achieving effectiveness and established outcomes. The primary aim of this study was to collect prospective data on adherence to prophylaxis for over 36 months. A secondary aim was to verify whether adherence correlates with physical activity. Materials and methods - Italian patients with severe haemophilia A treated on prophylaxis with octocog alfa were included in the study. Physical findings were assessed by the Haemophilia and Exercise Project (HEP)-Test-Q and the Early Prophylaxis Immunologic Challenge (EPIC)-Norfolk Physical Activity Questionnaire; orthopaedic status was assessed by the Hemophilia Joint Health Score (HJHS). Adherence was measured as percentage of empty vials returned with respect to the prescribed amount. Results - Forty-two PWH were enrolled: 31% children, 21.4% adolescents, and 47.6% adults. Type, frequency and impact of physical activities differed among the three groups. The HEP-Test-Q showed the highest impairments in the domains "endurance" and "strength/co-ordination". Eight percent of patients were classified as adherent to prophylaxis. Among them, 50% had at least one bleeding episode in the year before enrolment; this percentage dropped during the three years of the study. While remaining stable in the "non-adherent" group, the HJHS score decreased in the "adherent" patients. The mean number of school/work days lost was lower in adherent patients (from 3.4±6.8 to 0.2±0.9) than in non-adherent ones. Discussion - PWH with better orthopaedic scores reported better physical performance. Adherence to long-term prophylaxis proved to be high and correlated with a reduction in bleeds, target joints, school/work days lost, and with a performance improvement in endurance sports activities over time.
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- 2020
34. Variability in Kawasaki Disease Practice Patterns: A Survey of Hospitalists at Pediatric Hospital Medicine 2017
- Author
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Shelley Kumar, Mary E M Rocha, Marietta M. de Guzman, John B. Darby, Nisha Tamaskar, Kristen Sexson, and Stanford T. Shulman
- Subjects
medicine.medical_specialty ,Cross-sectional study ,MEDLINE ,Survey question ,Mucocutaneous Lymph Node Syndrome ,Pediatrics ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,030225 pediatrics ,Pediatric hospital ,medicine ,Humans ,Initial treatment ,030212 general & internal medicine ,Practice Patterns, Physicians' ,Child ,Practice patterns ,business.industry ,Immunoglobulins, Intravenous ,General Medicine ,Hospitals, Pediatric ,Plenary session ,medicine.disease ,Cross-Sectional Studies ,Hospitalists ,Pediatrics, Perinatology and Child Health ,Emergency medicine ,Kawasaki disease ,business - Abstract
OBJECTIVE: To explore practice variations in the care of patients with Kawasaki disease (KD) among pediatric hospitalist physicians (PHPs). METHODS: A 13-item questionnaire was developed by a multi-institutional group of KD experts. The survey was administered via live-audience polling by using smartphone technology during a KD plenary session at the 2017 Pediatric Hospital Medicine National Meeting, and simple descriptive statistics were calculated. RESULTS: Of the 297 session attendees, 90% responded to at least 1 survey question. Approximately three-quarters of respondents identified as PHPs practicing in the United States. The reported length of inpatient monitoring after initial intravenous immunoglobulin (IVIG) therapy demonstrated a wide time distribution (30% 24 hours, 36% 36 hours, and 31% 48 hours). Similarly, PHP identification of the treatment failure interval, indicated by recrudescent fever after IVIG, demonstrated a broad distribution (56% 24 hours, 27% 36 hours, and 16% 48 hours). Furthermore, there was variation in routine consultation with non-PHP subspecialists. In contrast, PHPs reported little variation in their choice of initial and refractory treatment of patients with KD. CONCLUSIONS: In a convenience sample at a national hospitalist meeting, there was variation in reported KD practice patterns, including observation time after initial treatment, time when the recurrence of fever after initial therapy was indicative of nonresponse to IVIG, and routine consultation of non-PHP subspecialists. These results may guide future study of KD practice patterns and inform efforts to improve evidence-based practices in the care of patients with KD.
- Published
- 2019
35. Engineered Cardiac Tissues Generated in the Biowire II: A Platform for Human-Based Drug Discovery
- Author
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Marietta M Gustilo, Roozbeh Aschar-Sobbi, Xiaoping Xu, Tim P. Chendrimada, Rishabh Singh, Isabella Pallotta, Khuram W. Chaudhary, Robert N. Willette, Nicole Feric, Danielle R. Bogdanowicz, and Michael P. Graziano
- Subjects
0301 basic medicine ,Inotrope ,drug safety ,cardiomyocytes ,Emerging Technologies, Methods and Models ,030204 cardiovascular system & hematology ,Toxicology ,contractility ,drug discovery ,Contractility ,03 medical and health sciences ,0302 clinical medicine ,medicine ,in vitro models ,Chemistry ,Drug discovery ,Calcium channel ,Levosimendan ,In vitro ,Featured ,Cell biology ,Omecamtiv mecarbil ,030104 developmental biology ,Milrinone ,engineered cardiac tissue ,medicine.drug - Abstract
Recent advances in techniques to differentiate human induced pluripotent stem cells (hiPSCs) hold the promise of an unlimited supply of human derived cardiac cells from both healthy and disease populations. That promise has been tempered by the observation that hiPSC-derived cardiomyocytes (hiPSC-CMs) typically retain a fetal-like phenotype, raising concern about the translatability of the in vitro data obtained to drug safety, discovery, and development studies. The Biowire II platform was used to generate 3D engineered cardiac tissues (ECTs) from hiPSC-CMs and cardiac fibroblasts. Long term electrical stimulation was employed to obtain ECTs that possess a phenotype like that of adult human myocardium including a lack of spontaneous beating, the presence of a positive force-frequency response from 1 to 4 Hz and prominent postrest potentiation. Pharmacology studies were performed in the ECTs to confirm the presence and functionality of pathways that modulate cardiac contractility in humans. Canonical responses were observed for compounds that act via the β-adrenergic/cAMP-mediated pathway, eg, isoproterenol and milrinone; the L-type calcium channel, eg, FPL64176 and nifedipine; and indirectly effect intracellular Ca2+ concentrations, eg, digoxin. Expected positive inotropic responses were observed for compounds that modulate proteins of the cardiac sarcomere, eg, omecamtiv mecarbil and levosimendan. ECTs generated in the Biowire II platform display adult-like properties and have canonical responses to cardiotherapeutic and cardiotoxic agents that affect contractility in humans via a variety of mechanisms. These data demonstrate that this human-based model can be used to assess the effects of novel compounds on contractility early in the drug discovery and development process.
- Published
- 2019
36. Exchange of Guanine Nucleotide between GTP-Binding Proteins That Regulate Neuronal Adenylate Cyclase
- Author
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Hatta, Shinichi, Marcus, Marietta M., and Rasenick, Mark M.
- Published
- 1986
37. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1
- Author
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Keestra, A. Marijke, Winter, Maria G., Auburger, Josef J., Frassle, Simon P., Xavier, Mariana N., Winter, Sebastian E., Kim, Anita, Poon, Victor, Ravesloot, Marietta M., Waldenmaier, Julian F.T., Tsolis, Renee M., Eigenheer, Richard A., and Baumler, Andreas J.
- Subjects
Transfection ,Immunopathology -- Research ,Nucleotides -- Properties ,Guanosine triphosphatase -- Physiological aspects ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns (1). However, these are produced by all microbes, regardless of their pathogenic potential. To distinguish virulent [...]
- Published
- 2013
38. Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells
- Author
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O’Donnell, Hope, Pham, Oanh H., Li, Lin-xi, Atif, Shaikh M., Lee, Seung-Joo, Ravesloot, Marietta M., Stolfi, Jessica L., Nuccio, Sean-Paul, Broz, Petr, Monack, Denise M., Baumler, Andreas J., and McSorley, Stephen J.
- Published
- 2014
- Full Text
- View/download PDF
39. Consensus statements on vaccination in patients with haemophilia—Results from the Italian haemophilia and vaccinations (HEVA) project
- Author
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Santagostino E., Riva A., Cesaro S., Esposito S., Matino D., Mazzucchelli R. I., Molinari, Angelo Claudio, Mura R., Notarangelo L. D., Tagliaferri A., Di Minno G., Clerici M., Ambaglio C., Brigida Aru A., Baldacci E., Barillari G., Basso M., Bernasconi S., Bertamino M., Bertoni E., Biasoli C., Federica Biguzzi E., Bonetti E., Borchiellini A., Bulgarelli S., Cabibbo S., Cantori I., Castaman G., Castiglia P., Coluccia A., Coppetelli U., Coppola A., Cultrera D., De Candia E., Delios G., Di Gennaro L., Di Gregorio P., Di Minno M., Dragani A., Pietro Ettorre C., Franchini M., Galli M., Gallo G., Giordano P., Giuffrida G., Iannaccaro P., Lassandro G., Lazzareschi I., Linari S., Luciani M., Macchi S., Malcangi G., Malizia R., Marietta M., Marino R., Massoud M., Gabriella Mazzucconi M., Milan M., Morfini M., Napolitano M., Pasca S., Pedrazzi P., Peyvandi F. A., Piscitelli L., Pollio B., Preti P., Quintavalle G., Radossi P., Raso S., Ricca I., Rocino A., Santoro C., Carlotta Santoro R., Sarolo L., Schiavoni M., Schiavulli M., Sciancalepore P., Luisa Serino M., Mario Siragusa S., Sottilotta G., Svahn J., Valdre L., Cristina Vedovati M., Zanon E., Santagostino, E., Riva, A., Cesaro, S., Esposito, S., Matino, D., Mazzucchelli, R. I., Molinari, Angelo Claudio, Mura, R., Notarangelo, L. D., Tagliaferri, A., Di Minno, G., Clerici, M., Ambaglio, C., Brigida Aru, A., Baldacci, E., Barillari, G., Basso, M., Bernasconi, S., Bertamino, M., Bertoni, E., Biasoli, C., Federica Biguzzi, E., Bonetti, E., Borchiellini, A., Bulgarelli, S., Cabibbo, S., Cantori, I., Castaman, G., Castiglia, P., Coluccia, A., Coppetelli, U., Coppola, A., Cultrera, D., De Candia, E., Delios, G., Di Gennaro, L., Di Gregorio, P., Di Minno, M., Dragani, A., Pietro Ettorre, C., Franchini, M., Galli, M., Gallo, G., Giordano, P., Giuffrida, G., Iannaccaro, P., Lassandro, G., Lazzareschi, I., Linari, S., Luciani, M., Macchi, S., Malcangi, G., Malizia, R., Marietta, M., Marino, R., Massoud, M., Gabriella Mazzucconi, M., Milan, M., Morfini, M., Napolitano, M., Pasca, S., Pedrazzi, P., Peyvandi, F. A., Piscitelli, L., Pollio, B., Preti, P., Quintavalle, G., Radossi, P., Raso, S., Ricca, I., Rocino, A., Santoro, C., Carlotta Santoro, R., Sarolo, L., Schiavoni, M., Schiavulli, M., Sciancalepore, P., Luisa Serino, M., Mario Siragusa, S., Sottilotta, G., Svahn, J., Valdre, L., Cristina Vedovati, M., and Zanon, E.
- Subjects
Adult ,medicine.medical_specialty ,Consensus ,Delphi Technique ,Vaccination schedule ,Delphi method ,haemophilia ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,immunization ,Hemophilia B ,bleeding disorder ,factor VIII inhibitor ,vaccination ,Child ,Evidence-Based Medicine ,Humans ,Italy ,Vaccination ,03 medical and health sciences ,0302 clinical medicine ,Vaccine administration ,Medicine ,In patient ,Clinical Haemophilia ,Genetics (clinical) ,business.industry ,Original Articles ,Hematology ,General Medicine ,Evidence-based medicine ,medicine.disease ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Immunization ,Family medicine ,Original Article ,business ,030215 immunology - Abstract
Vaccination against communicable diseases is crucial for disease prevention, but this practice poses challenges to healthcare professionals in patients with haemophilia. Poor knowledge of the vaccination requirements for these patients and safety concerns often result in vaccination delay or avoidance. In order to address this issue, a panel of 11 Italian haemophilia and immunization experts conducted a Delphi consensus process to identify the main concerns regarding the safe use of vaccines in patients with haemophilia. The consensus was based on a literature search of the available evidence, which was used by the experts to design 27 consensus statements. A group of clinicians then rated these statements using the 5‐point Likert‐type scale (1 = strongly disagree; 5 = strongly agree). The main issues identified by the expert panel included vaccination schedule for haemophilic patients; protocol and optimal route of vaccine administration; vaccination of haemophilic patients with antibodies inhibiting coagulation factor VIII (inhibitors); and vaccination and risk of inhibitor development. This manuscript discusses these controversial areas in detail supported by the available literature evidence and provides evidence‐ and consensus‐based recommendations. Overall, participants agreed on most statements, except those addressing the potential role of vaccination in inhibitor formation. Participants agreed that patients with haemophilia should receive vaccinations according to the institutional schedule for individuals without bleeding disorders; however, vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk. Data also suggest vaccination timing does not need to take into consideration when the patient received factor VIII replacement.
- Published
- 2019
40. Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus
- Author
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Napolitano, M, Saccullo, G, Marietta, M, Carpenedo, M, Castaman, G, Cerchiara, E, Chistolini, A, Contino, L, De Stefano, V, Falanga, A, Federici, AB, Rossi, E, Santoro, R, Siragusa, S, Napolitano, Mariasanta, Saccullo, Giorgia, Marietta, Marco, Carpenedo, Monica, Castaman, Giancarlo, Cerchiara, Elisabetta, Chistolini, Antonio, Contino, Laura, De Stefano, Valerio, Falanga, Anna, Federici, Augusto B, Rossi, Elena, Santoro, Rita, Siragusa, Sergio, Napolitano, M, Saccullo, G, Marietta, M, Carpenedo, M, Castaman, G, Cerchiara, E, Chistolini, A, Contino, L, De Stefano, V, Falanga, A, Federici, A, Rossi, E, Santoro, R, and Siragusa, S
- Subjects
venous thrombosis, thrombocytopenia, blood cancer, anticoagulant treatment, consensus ,anticoagulants ,blood cancer ,blood platelets ,venous thromboembolism ,thrombocytopenia ,Heparin, Low-Molecular-Weight ,heparin ,platelet count ,anticoagulant treatment ,Settore MED/15 - MALATTIE DEL SANGUE ,Venous thromboembolism, haematological malignancy,thrombocytopenia ,consensus ,low-molecular-weight ,Original Article ,hematologic neoplasms ,cardiovascular diseases ,venous thrombosis ,humans ,heparin, low-molecular-weight ,Anticoagulant treatment ,Blood cancer ,Consensus ,Thrombocytopenia ,Venous thrombosis - Abstract
Background. Management of venous thromboembolism (VTE) in patients with haematologic malignancies and thrombocytopenia is clinically challenging due to the related risks. No prospective studies or clinical trials have been carried out and, therefore, no solid evidence on this compelling issue is available. Methods. Given this, an expert panel endorsed by the Gruppo Italiano Malattie Ematologiche dell'Adulto Working Party on Thrombosis and Haemostasis was set up to produce a formal consensus, according to the RAND method, in order to issue clinical recommendations about the platelet (PLT) cut-off for safe administration of low molecular weight heparin (LMWH) in thrombocytopenic (PLT
- Published
- 2019
41. Severe Covid-19 infection in a child receiving immunotherapy for cancer
- Author
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Sarah B. Whittle, Ryan D. Coleman, Flor M. Munoz, Jennifer Foster, Marietta M. de Guzman, Shoba A. Navai, and Valeria Smith
- Subjects
Oncology ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Extramural ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,MEDLINE ,Cancer ,Hematology ,Immunotherapy ,medicine.disease ,Article ,Internal medicine ,Pediatrics, Perinatology and Child Health ,medicine ,Pediatrics, Perinatology, and Child Health ,business - Published
- 2020
42. Modeling Hospital Energy and Economic Costs for COVID-19 Infection Control Interventions
- Author
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Arnesh Telukdarie, Gary Lin, Megashnee Munsamy, Takeru Igusa, and Marietta M. Squire
- Subjects
medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,020209 energy ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Secondary infection ,0211 other engineering and technologies ,Psychological intervention ,02 engineering and technology ,Article ,Economic cost ,021105 building & construction ,0202 electrical engineering, electronic engineering, information engineering ,Medicine ,Infection control ,Operations management ,Electrical and Electronic Engineering ,health care economics and organizations ,Civil and Structural Engineering ,Energy demand ,business.industry ,Mechanical Engineering ,Building and Construction ,Cost savings ,Initial cost ,Emergency medicine ,business - Abstract
The objective of this study was to assess the energy demand and economic cost of two hospital-based COVID-19 infection control interventions. The intervention control measures evaluated include use of negative pressure (NP) treatment rooms and xenon pulsed ultraviolet (XP-UV) infection control equipment. After projecting COVID-19 hospitalizations, a Hospital Energy Model and Infection De-escalation Models are applied to quantify increases in energy demand and reductions in secondary infections. The scope of the interventions consisted of implementing NP in 11, 22, and 44 rooms (at small, medium, and large hospitals) while the XP-UV equipment was used eight, nine, and ten hours a day, respectively. The annum kilowatt-hours (kWh) for NP (and costs were at $0.1015 per kWh) were 116,700 ($11,845), 332,530 ($33,752), 795,675 ($80,761) for small, medium, and large hospitals ($1,077, $1,534 $1,836 added annum energy cost per NP room). For XP-UV, the annum kilowatt-hours and costs were 438 ($45), 493 ($50), 548 ($56) for small, medium, and large hospitals. There are other initial costs associated with the purchase and installation of the equipment, with XP-UV having a higher initial cost. XP-UV had a greater reduction in secondary COVID-19 infections in large and medium hospitals. NP rooms had a greater reduction in secondary SARS-CoV-2 transmission in small hospitals. Early implementation of interventions can result in realized cost savings through reduced hospital-acquired infections.
- Published
- 2020
- Full Text
- View/download PDF
43. Heparin induced thrombocytopenia: position paper from the Italian Society on Thrombosis and Haemostasis (SISET)
- Author
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Marcucci, R., Berteotti, M., Gori, A. M., Giusti, B., Rogolino, A. A., Sticchi, E., Liotta, A. A., Ageno, W., De Candia, E., Gresele, P., Marchetti, M., Marietta, M., and Tripodi, A.
- Subjects
Platelets ,platelets ,thrombocytopenia ,heparin ,argatroban ,danaparoid ,fondaparinux ,Heparin ,Settore MED/09 - MEDICINA INTERNA ,Anticoagulants ,Disease Management ,Thrombocytopenia ,Argatroban ,Haemostasis and Thrombosis ,Fondaparinux ,Italy ,Danaparoid ,Humans ,Societies, Medical - Abstract
Heparin induced thrombocytopenia (HIT) is a rare immune mediated adverse drug reaction occurring after exposure to heparin. It is a serious and potentially fatal condition, which may be associated with the development of arterial or venous thrombotic events. Although known for many years, HIT is still often misdiagnosed. Pre- test clinical probability, screening for anti-PF4/heparin antibodies and documentation of their platelet activating capacity are the cornerstones of diagnosis. However, both clinical algorithms and test modalities have limited predictive values and limited diffusion so that the diagnosis and management is challenging in the clinical practice. For this reason, there is an unmet need for novel rational non-anticoagulant therapies based on the pathogenesis of HIT. The present paper reports the position of the Italian Society on Haemostasis and Thrombosis (SISET) in order to increase awareness of HIT among clinicians and other health care professionals and to provide information on the most appropriate management.
- Published
- 2020
44. Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol
- Author
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Marietta, M, Vandelli, P, Mighali, P, Vicini, R, Coluccio, V, D'Amico, R, Aschieri, D, Brugioni, L, Clini, E, Codeluppi, M, Imberti, D, Magnacavallo, A, Meschiari, M, Mussini, C, Orlando, S, Pinelli, G, Pietrangelo, A, Sarti, L, and Silva, M.
- Subjects
medicine.medical_specialty ,Letter ,Randomization ,Blinding ,Dose ,medicine.drug_class ,Low-molecular weight heparin ,medicine.medical_treatment ,Medicine (miscellaneous) ,Low molecular weight heparin ,law.invention ,03 medical and health sciences ,COVID-19, Randomised controlled trial, Protocol, Low-molecular weight heparin, Enoxaparin, Pneumonia, Coagulopathy ,0302 clinical medicine ,Randomized controlled trial ,Coagulopathy ,law ,Internal medicine ,Protocol ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Enoxaparin ,COVID-19 ,Randomised controlled trial ,Pneumonia ,Mechanical ventilation ,lcsh:R5-920 ,business.industry ,medicine.disease ,Sample size determination ,lcsh:Medicine (General) ,business ,030217 neurology & neurosurgery - Abstract
Objectives To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are: more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were receiving standard oxygen therapyIMV in patients who at randomisation were receiving non-invasive mechanical ventilationSimilar in terms of major bleeding risk Trial design Multicentre, randomised controlled, superiority, open label, parallel group, two arms (1:1 ratio), in-hospital study. Participants Inpatients will be recruited from 7 Italian Academic and non-Academic Internal Medicine Units, 2 Infectious Disease Units and 1 Respiratory Disease Unit. Inclusion Criteria (all required) Age > 18 and < 80 years Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material) Severe pneumonia defined by the presence of at least one of the following criteria: Respiratory Rate ≥25 breaths /minArterial oxygen saturation≤93% at rest on ambient airPaO2/FiO2 ≤300 mmHg Coagulopathy, defined by the presence of at least one of the following criteria: D-dimer >4 times the upper level of normal reference rangeSepsis-Induced Coagulopathy (SIC) score >4 No need of IMV Exclusion Criteria Age 80 years IMV Thrombocytopenia (platelet count < 80.000 mm3) Coagulopathy: INR >1.5, aPTT ratio > 1.4 Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation < 30 ml/min) Known hypersensitivity to enoxaparin History of heparin induced thrombocytopenia Presence of an active bleeding or a pathology susceptible of bleeding in presence of anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular aneurysms, arteriovenous malformations) Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation, venous thromboembolism, prosthetic heart valves) Concomitant double antiplatelet therapy Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization; prophylactic doses are allowed Pregnancy or breastfeeding or positive pregnancy test Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing medical condition) Lack or withdrawal of informed consent Intervention and comparator Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at standard prophylactic dose (i.e., 4000 UI subcutaneously once day). Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table. This dose is commonly used in Italy when a bridging strategy is required for the management of surgery or invasive procedures in patients taking anti-vitamin K oral anticoagulants Body Weight (kg)Enoxaparin dose every 12 hours (IU)200050-69400070-89600090-1108000>11010000 The treatment with Enoxaparin will be initiated soon after randomization (maximum allowed starting time 12h after randomization). The treatment will be administered every 12 hours in the intervention group and every 24 hours in the control group. Treatments will be administered in the two arms until hospital discharge or the primary outcomes detailed below occur. Main outcomes Primary Efficacy Endpoint: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first: DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV, in patients who at randomisation were in Cpap or NIV Time to the occurrence of each of these events will be recorded. Clinical worsening will be analysed as a binary outcome as well as a time-to-event one. Secondary Efficacy Endpoints: Any of the following events occurring within the hospital stay DeathAcute Myocardial Infarction [AMI]Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]Need of either: Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orIMV in patients who at randomisation were in standard oxygen therapy by delivery interfacesNeed for IMV in patients who at randomisation were in Cpap or NIVImprovement of laboratory parameters of disease severity, including: o D-dimer levelo Plasma fibrinogen levelso Mean Platelet Volumeo Lymphocyte/Neutrophil ratioo IL-6 plasma levels Mortality at 30 days Information about patients’ status will be sought in those who are discharged before 30 days on Day 30 from randomisation. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Primary safety endpoint: Major bleeding, defined as an acute clinically overt bleeding associated with one or more of the following: Decrease in haemoglobin of 2 g/dl or more;Transfusion of 2 or more units of packed red blood cells;Bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal];Bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death);Bleeding that necessitates surgical intervention Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Secondary safety endpoint: Clinically Relevant non-major bleeding, defined as an acute clinically overt bleeding that does not meet the criteria for major and consists of: Any bleeding compromising hemodynamicSpontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic causeIntramuscular hematoma documented by ultrasonographyEpistaxis or gingival bleeding requiring tamponade or other medical interventionBleeding from venipuncture for >5 minutesHaematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive proceduresHaemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical interventionAny other bleeding requiring temporary cessation of a study drug. Time to the occurrence of each of these events will be recorded. Each of these events will be analysed as a binary outcome and as a time-to-event one. Randomisation Randomisation (with a 1:1 randomisation ratio) will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment. Blinding (masking) The study is conceived as open-label: patients and all health-care personnel involved in the study will be aware of the assigned group. Numbers to be randomised (sample size) The target sample size is based on the hypothesis that LMWH administered at high doses versus low doses will significantly reduce the risk of clinical worsening. The overall sample size in this study is expected to be 300 with 150 in the Low-Dose LMWH control group and 150 in the High-Dose LMWH intervention group, recruited over 10-11 months. Assuming an alpha of 5% (two tailed) and a percentage of patients who experience clinical worsening in the control group being between 25% and 30%, the study will have 80% power to detect at least 50% relative reduction in the risk of death between low and high doses of heparin. Trial Status Protocol version 1.2 of 11/05/2020. Recruitment start (expected): 08/06/2020 Recruitment finish (expected): 30/04/2021 Trial registration EudraCT 2020-001972-13, registered on April 17th, 2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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- 2020
45. Social Distancing is Effective at Mitigating COVID-19 Transmission in the United States
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Max Marshall, Lauren Gardner, Hamada S. Badr, Hongru Du, Ensheng Dong, and Marietta M. Squire
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Government ,Coronavirus disease 2019 (COVID-19) ,Social distance ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,media_common.quotation_subject ,law.invention ,Transmission (mechanics) ,State (polity) ,law ,Mobile phone ,Development economics ,Business ,Variable intensity ,media_common - Abstract
COVID-19 is present in every state and over 90 percent of all counties in the United States. Decentralized government efforts to reduce spread, combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the U.S.a challenge. We generate a novel metric to represent social distancing behavior derived from mobile phone data and examine its relationship with COVID-19 case reports at the county level. Our analysis reveals that social distancing is strongly correlated with decreased COVID-19 case growth rates for the 25 most affected counties in the United States, with a lag period consistent with the incubation time of SARS-CoV-2. We also demonstrate evidence that social distancing was already under way in many U.S. counties before state or local-level policies were implemented. This study strongly supports social distancing as an effective way to mitigate COVID-19 transmission in the United States.
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- 2020
46. Association between mobility patterns and COVID-19 transmission in the USA: a mathematical modelling study
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Hongru Du, Maximilian Marshall, Lauren Gardner, Ensheng Dong, Hamada S. Badr, and Marietta M. Squire
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medicine.medical_specialty ,Pneumonia, Viral ,Disease ,Article ,law.invention ,03 medical and health sciences ,Betacoronavirus ,0302 clinical medicine ,Phone ,law ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,Enforcement ,Pandemics ,030304 developmental biology ,0303 health sciences ,Models, Statistical ,SARS-CoV-2 ,Public health ,Social distance ,COVID-19 ,Timeline ,United States ,Infectious Diseases ,Geography ,Transmission (mechanics) ,Quarantine ,Government Regulation ,Public Health ,Coronavirus Infections ,Demography - Abstract
Summary Background Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge. Methods We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Zurich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county. Findings Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0·7 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35–63% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9–12 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message. Interpretation This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future. Funding None.
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- 2020
47. Diagnosis and management of 365 ureteric injuries following obstetric and gynecologic surgery in resource-limited settings
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Marietta M. Mahendeka, Carrie J. Ngongo, and Thomas J. I. P. Raassen
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medicine.medical_specialty ,Fistula ,Urology ,Iatrogenic Disease ,030232 urology & nephrology ,Urogenital System ,Injury ,Vesicovaginal fistula ,03 medical and health sciences ,Gynecologic Surgical Procedures ,0302 clinical medicine ,Ureter ,Pregnancy ,medicine ,Humans ,Ureteral Diseases ,Ureteric ,Retrospective Studies ,Reimplantation ,030219 obstetrics & reproductive medicine ,Genitourinary system ,business.industry ,General surgery ,Incidence (epidemiology) ,Obstetrics and Gynecology ,Retrospective cohort study ,Delivery, Obstetric ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Iatrogenic ,Cohort ,Female ,Original Article ,business - Abstract
Introduction Ureteric injuries are among the most serious complications of pelvic surgery. The incidence in low-resource settings is not well documented. Methods This retrospective review analyzes a cohort of 365 ureteric injuries with ureterovaginal fistulas in 353 women following obstetric and gynecologic operations in 11 countries in Africa and Asia, all low-resource settings. The patients with ureteric injury were stratified into three groups according to the initial surgery: (a) obstetric operations, (b) gynecologic operations, and (c) vesicovaginal fistula (VVF) repairs. Results The 365 ureteric injuries in this series comprise 246 (67.4%) after obstetric procedures, 65 (17.8%) after gynecologic procedures, and 54 (14.8%) after repair of obstetric fistulas. Demographic characteristics show clear differences between women with iatrogenic injuries and women with obstetric fistulas. The study describes abdominal ureter reimplantation and other treatment procedures. Overall surgical results were good: 92.9% of women were cured (326/351), 5.4% were healed with some residual incontinence (19/351), and six failed (1.7%). Conclusions Ureteric injuries after obstetric and gynecologic operations are not uncommon. Unlike in high-resource contexts, in low-resource settings obstetric procedures are most often associated with urogenital fistula. Despite resource limitations, diagnosis and treatment of ureteric injuries is possible, with good success rates. Training must emphasize optimal surgical techniques and different approaches to assisted vaginal delivery.
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- 2017
48. Results of treatment with myo-Inositol and D-chiro inositol combination in ratio 5:1 in women with polycystic ovary syndrome
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Oboskalova, Tatiana A., primary, Vorontsova, Anna V., additional, Zvychainyi, Maksim A., additional, Gushchina, Karina G., additional, and Maitesian, Marietta M., additional
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- 2020
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49. Ragweed pollen extract intensifies lipopolysaccharide-induced priming of NLRP3 inflammasome in human macrophages
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Varga, Aliz, Budai, Marietta M., Milesz, Sándor, Bácsi, Attila, Tözsér, József, and Benkö, Szilvia
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- 2013
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50. More on: platelet count and the Use of Recombinant Factor VIIa for the treatment of Bleeding Complications after Hematopoietic Stem Cell Transplantation
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MARIETTA, M., FACCHINI, L., GIRARDIS, M., LUPPI, M., and TORELLI, G.
- Published
- 2006
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