Activity and Mode of Action for Methacrylate Polymers as Antimicrobial Agents against Staphylococcus aureus.

There is an urgent need for the development of new antimicrobial agents with novel modes of action effective against drug-resistant bacteria. To that end, synthetic polymers with cationic amphiphilic properties have been designed to mimic naturally occurring host-defense antimicrobial peptides. These polymers display hallmark traits of antimicrobial peptides: broad-spectrum activity, rapid bactericidal activity, and a low propensity for resistance development in bacteria. However, while the broad-spectrum activity of these polymers is useful to eradicate all infectious pathogens, it may negatively impact commensal flora during long-term treatment. It would be ideal to develop antimicrobial polymers with cell-selective or cell-specific activity to reduce the risk of potential side effects. This thesis describes the development of cationic synthetic polymers for potent and selective Staphylococcus aureus agents, as well as investigations into their antimicrobial mechanism. Methacrylate homopolymers with primary ammonium groups in the side chains, and molecular weights of 2,000-3,000, were synthesized by reversible addition-fragmentation chain-transfer polymerization. These polymers are more active against S. aureus than E. coli without causing lysis of human red blood cells. In the presence of serum, the polymers showed potent activity against S. aureus while the activity of conventional antibiotics was reduced. Furthermore, the polymers significantly reduced the number of viable S. aureus cells in a cotton rat nasal colonization. Methacrylate homopolymers bearing primary ammonium groups in the side chains were just as active as analogous homopolymers bearing quaternary ammonium groups in the side chains. These polymers showed more potent activity against a S. aureus cell wall mutant having a higher negative charge density than the wild-type strain, indicating that electrostatic binding of the cationic polymers to anionic cell wall is an important factor in the antimicrobial mechanism of polymers. For mechanistic studies, amphiphilic methacrylate copolymers and cationic homopolymers were tested in an osmoprotection assay, with results indicating that these polymers do not exert their antimicrobial effect by osmotic lysis of bacterial cells in this condition. Overall, cationic methacrylate homopolymers without strong hydrophobic moieties can provide a new platform for anti-S. aureus agents effective in physiological conditions and insight into a previously uncharacterized mode of action for antimicrobial polymers.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108975/1/lmthoma_1.pd

Educators Must Be Advocates: Advocating for Muslim Students

As educators interested in supporting linguistically and culturally diverse learners, we have had to view our roles in different ways since the presidential campaign and the election of Trump. In this article, two teacher educators and two inservice ESL teachers in the U.S. reflect on our various experiences working with Muslim students and preparing teachers to support Muslim students in the current socio-political context. We discuss these experiences with the goal of suggesting some priorities in teacher education. Ultimately, to prepare teachers to be effective teachers for Muslim students requires them to go beyond being culturally responsive to becoming advocates and activists. This advocacy and activism necessitates a push against the cultural norms of Whiteness that dominate U.S. teacher education

Neural correlates of subjective arousal and valence in health and panic disorder

Aberrant emotion processing is a core characteristic of panic disorder (PD). Findings concerning the underlying neural pathways remain inconsistent. We applied functional magnetic resonance imaging (fMRI) in the context of a task based on the circumplex model of affect. This model links affective states to two underlying neurophysiological systems: arousal and valence. Twenty-two healthy participants and 20 participants with PD rated arousal and valence in response to affective faces during fMRI. In healthy controls, we found that arousal modulated the hemodynamic response in the parahippocampus, the ventromedial prefrontal cortex and the cuneus during face perception. Valence and extreme ratings of valence modulated the hemodynamic response in temporal, parietal, somatosensory, premotor and cerebellar regions. Comparing healthy controls to participants with PD, we found that healthy controls showed a stronger modulation of the hemodynamic response during face perception associated with extreme ratings of valence in the parahippocampus and the supplementary motor area. This suggests parahippocampal dysfunction in the processing of highly valenced affective faces in PD, which may underlie aberrant contextualization of strong affective stimuli. Our findings need to be interpreted with care as they were adjusted for multiple comparisons using a liberal correction procedure

13-year follow-up of a randomized controlled study on zirconia and titanium abutments

OBJECTIVES: To assess survival rates and compare technical, biological, and esthetic outcomes of customized zirconia and titanium abutments at 13 years post loading. MATERIALS AND METHODS: Initially, 22 patients with 40 implants in posterior regions were included. The sites were randomly assigned to 20 customized zirconia abutments with cemented all ceramic crowns (ACC) and 20 customized titanium abutments with cemented metal ceramic crowns (MCC). At a mean follow-up of 13.4 years, patients were examined and implants/restorations assessed for survival and technical complications, as well as biological and esthetic outcomes (pocket probing depth [PPD], bleeding on probing [BOP], plaque control record [PCR], bone level [BL], papilla index [PAP], mucosal thickness, and recession (distance of the margo mucosae [MM]/margo gingivae MG)). Descriptive analyses were performed for all outcome measures. RESULTS: Fifteen patients with 21 abutments (13 zirconia, 8 titanium) were examined at 13 years. The drop-out rate was 25% (patient level). The technical survival rate of the abutments was 100%. The survival rate on the restorative level (crowns) was 100%. The assessed biological outcomes (PPD, PCR, BOP, BL) and esthetic outcomes (MG, PAP) were similar. CONCLUSIONS: Zirconia and titanium abutments supporting single implant-borne restorations rendered a high survival rate and minimal differences in terms of technical, biological, and esthetic outcomes at 13 years of follow-up

Paving the way for systemic phenomenological psychiatry - the forgotten heritage of Wolfgang Blankenburg

Phenomenological psychopathology focuses on the first-person experience of mental disorders. Although it is in principle descriptive, it also entails an explanatory dimension: single psychological symptoms are conceived as genetically arising from a holistic structure of personal experience, i.e., the patient's being-in-the-world – and of its dynamic unfolding over time. Yet both classical and current phenomenological approaches tend to identify the essential disorder or “trouble générateur” (Minkowski) of mental illness within the individual, thereby neglecting the relevance of the social context not only for the emergence of symptoms but also for their treatment. The work of Wolfgang Blankenburg on schizophrenia represents a noteworthy approach to overcome this individualistic tendency. He introduced the concept of “loss of common sense” as the structural core of schizophrenic experience and being-in-the-world and he considered the social and most importantly familial context for the emergence of schizophrenic experience. By accounting not only for personal experience but also for interactional structures of families and social milieus in which experience is embedded, Blankenburg thereby offered ways to combine phenomenological and systemic explanations of mental disorders. Beside his most renowned work on “the loss of common sense,” in this paper we also present his family studies of young persons with schizophrenia, which have so far received little if no attention. We thus discuss the different ways in which Blankenburg expanded the phenomenological approach into a more systemic and social direction. We then link Blankenburg's work with current systemic explanatory models of schizophrenia and explore the clinical and scientific implications of this link. Finally, we call for further research on the synergy effects between the two

Physical biomarkers for human hematopoietic stem and progenitor cells

Adhesion of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow niche plays critical roles in the maintenance of the most primitive HSPCs. The interactions of HSPC−niche interactions are clinically relevant in acute myeloid leukemia (AML), because (i) leukemia-initiating cells adhered to the marrow niche are protected from the cytotoxic effect by chemotherapy and (ii) mobilization of HSPCs from healthy donors' bone marrow is crucial for the effective stem cell transplantation. However, although many clinical agents have been developed for the HSPC mobilization, the effects caused by the extrinsic molecular cues were traditionally evaluated based on phenomenological observations. This review highlights the recent interdisciplinary challenges of hematologists, biophysicists and cell biologists towards the design of defined in vitro niche models and the development of physical biomarkers for quantitative indexing of differential effects of clinical agents on human HSPCs

Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy – Study design and characteristics of participants

Background: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. Methods: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. Results: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and 90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. Conclusions: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.We acknowledge funding for HBM4EU from the European Union’s Horizon 2020 research and innovation program under grant agreement #733032 and the national governments of the participating countries. This publication reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the in formation it contains.info:eu-repo/semantics/publishedVersio

HBM4EU-MOM: Prenatal methylmercury-exposure control in five countries through suitable dietary advice for pregnancy - Study design and characteristics of participants

Background: Seafood is a major source of vital nutrients for optimal fetal growth, but at the same time is the main source of exposure to methylmercury (MeHg), an established neurodevelopmental toxicant. Pregnant women must be provided with dietary advice so as to include safely fish in their diet for nutrition and mercury control. The aim of this work is to present the design of a multicentre randomized control trial (RCT), which combines human biomonitoring (HBM) with dietary interventions using seafood consumption advice to pregnant women for MeHg control, and to collect information about other possible sources of exposure to mercury. It also presents the materials developed for the implementation of the study and the characteristics of the study participants, which were self-reported in the first trimester of pregnancy. Methods: The "HBM4EU-MOM" RCT was performed in the frame of the European Human Biomonitoring Initiative (HBM4EU) in five coastal, high fish-consuming European countries (Cyprus, Greece, Spain, Portugal and Iceland). According to the study design, pregnant women (≥120/country, ≤20 weeks gestational age) provided a hair sample for total mercury assessment (THg) and personal information relevant to the study (e.g., lifestyle, pregnancy status, diet before and during the pregnancy, information on seafood and factors related to possible non-dietary exposures to mercury) during the first trimester of pregnancy. After sampling, participants were randomly assigned to "control" (habitual practices) or "intervention" (received the harmonized HBM4EU-MOM dietary advice for fish consumption during the pregnancy and were encouraged to follow it). Around child delivery, participants provided a second hair sample and completed another tailored questionnaire. Results: A total of 654 women aged 18-45 years were recruited in 2021 in the five countries, primarily through their health-care providers. The pre-pregnancy BMI of the participants ranged from underweight to obese, but was on average within the healthy range. For 73% of the women, the pregnancy was planned. 26% of the women were active smokers before the pregnancy and 8% continued to smoke during the pregnancy, while 33% were passive smokers before pregnancy and 23% remained passively exposed during the pregnancy. 53% of the women self-reported making dietary changes for their pregnancy, with 74% of these women reporting making the changes upon learning of their pregnancy. Of the 43% who did not change their diet for the pregnancy, 74% reported that their diet was already balanced, 6% found it difficult to make changes and 2% were unsure of what changes to make. Seafood consumption did not change significantly before and during the first trimester of pregnancy (overall average ∼8 times per month), with the highest frequency reported in Portugal (≥15 times per month), followed by Spain (≥7 times per month). During the first-trimester of pregnancy, 89% of the Portuguese women, 85% of the Spanish women and 90%) were unaware of safe procedures for handling spillage from broken thermometers and energy-saving lamps, though >22% experienced such an incident (>1 year ago). 26% of the women had dental amalgams. ∼1% had amalgams placed and ∼2% had amalgams removed during peri-pregnancy. 28% had their hair dyed in the past 3 months and 40% had body tattoos. 8% engaged with gardening involving fertilizers/pesticides and 19% with hobbies involving paints/pigments/dyes. Conclusions: The study design materials were fit for the purposes of harmonization and quality-assurance. The harmonized information collected from pregnant women suggests that it is important to raise the awareness of women of reproductive age and pregnant women about how to safely include fish in their diet and to empower them to make proper decisions for nutrition and control of MeHg, as well as other chemical exposures.We acknowledge funding for HBM4EU from the European Union’s Horizon 2020 research and innovation program under grant agreement #733032 and the national governments of the participating countries. This publication reflects only the authors’ views, and the European Commission is not responsible for any use that may be made of the information it contains.S

HIV Tropism and Decreased Risk of Breast Cancer

During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk