Barriers and Facilitators Affecting Long-Term Antibiotic Prescriptions for Acne Treatment.

Importance: Dermatologists prescribe more oral antibiotics per clinician than clinicians in any other specialty. Despite clinical guidelines that recommend limitation of long-term oral antibiotic treatments for acne to less than 3 months, there is little evidence to guide the design and implementation of an antibiotic stewardship program in clinical practice. Objective: To identify salient barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Design, Setting, and Participants: This qualitative study assessed data collected from stakeholders (including dermatologists, infectious disease physicians, dermatology resident physicians, and nonphysician clinicians) via an online survey and semistructured video interviews between March and August 2021. Data analyses were performed from August 12, 2021, to January 20, 2024. Main Outcomes and Measures: Online survey and qualitative video interviews developed with the Theoretical Domains Framework. Thematic analyses were used to identify salient themes on barriers and facilitators to long-term antibiotic prescriptions for acne treatment. Results: Among 30 participants (14 [47%] males and 16 [53%] females) who completed the study requirements and were included in the analysis, knowledge of antibiotic guideline recommendations was high and antibiotic stewardship was believed to be a professional responsibility. Five salient themes were to be affecting long-term antibiotic prescriptions: perceived lack of evidence to justify change in dermatologic practice, difficulty navigating patient demands and satisfaction, discomfort with discussing contraception, iPLEDGE-related barriers, and the absence of an effective system to measure progress on antibiotic stewardship. Conclusions and Relevance: The findings of this qualitative study indicate that multiple salient factors affect long-term antibiotic prescribing practices for acne treatment. These factors should be considered in the design and implementation of any future outpatient antibiotic stewardship program for clinical dermatology.

Influence of Iron Substitution and Solution Composition on Brucite Carbonation.

Carbon neutral or negative mining can potentially be achieved by integrating carbon mineralization processes into the mine design, operations, and closure plans. Brucite [Mg(OH)2] is a highly reactive mineral present in some ultramafic mine tailings with the potential to be rapidly carbonated and can contain significant amounts of ferrous iron [Fe(II)] substituted for Mg; however, the influence of this substitution on carbon mineralization reaction products and efficiency has not been thoroughly constrained. To better assess the efficiency of carbon storage in brucite-bearing tailings, we performed carbonation experiments using synthetic Fe(II)-substituted brucite (0, 6, 23, and 44 mol % Fe) slurries in oxic and anoxic conditions with 10% CO2. Additionally, the carbonation process was evaluated using different background electrolytes (NaCl, Na2SO4, and Na4SiO4). Our results indicate that carbonation efficiency decreases with increasing Fe(II) substitution. In oxic conditions, precipitation of ferrihydrite [Fe10IIIO14(OH)2] and layered double hydroxides {e.g., pyroaurite [Mg6Fe2III(OH)16CO3·4H2O]} limited carbonation efficiency. Carbonation in anoxic environments led to the formation of Fe(II)-substituted nesquehonite (MgCO3·3H2O) and dypingite [Mg5(CO3)4(OH)2·âˆ¼5H2O], as well as chukanovite [Fe2IICO3(OH)2] in the case of 23 and 44 mol % Fe(II)-brucite carbonation. Carbonation efficiencies were consistent between chloride- and sulfate-rich solutions but declined in the presence of dissolved Si due to the formation of amorphous SiO2·nH2O and Fe-Mg silicates. Overall, our results indicate that carbonation efficiency and the long-term fate of stored CO2 may depend on the amount of substituted Fe(II) in both feedstock minerals and carbonate products.

Metabolomic Analysis of Diverse Mice Reveals Hepatic Arginase-1 as Source of Plasma Arginase in Plasmodium chabaudi Infection.

Infections disrupt host metabolism, but the factors that dictate the nature and magnitude of metabolic change are incompletely characterized. To determine how host metabolism changes in relation to disease severity in murine malaria, we performed plasma metabolomics on eight Plasmodium chabaudi-infected mouse strains with diverse disease phenotypes. We identified plasma metabolic biomarkers for both the nature and severity of different malarial pathologies. A subset of metabolic changes, including plasma arginine depletion, match the plasma metabolomes of human malaria patients, suggesting new connections between pathology and metabolism in human malaria. In our malarial mice, liver damage, which releases hepatic arginase-1 (Arg1) into circulation, correlated with plasma arginine depletion. We confirmed that hepatic Arg1 was the primary source of increased plasma arginase activity in our model, which motivates further investigation of liver damage in human malaria patients. More broadly, our approach shows how leveraging phenotypic diversity can identify and validate relationships between metabolism and the pathophysiology of infectious disease. IMPORTANCE Malaria is a severe and sometimes fatal infectious disease endemic to tropical and subtropical regions. Effective vaccines against malaria-causing Plasmodium parasites remain elusive, and malaria treatments often fail to prevent severe disease. Small molecules that target host metabolism have recently emerged as candidates for therapeutics in malaria and other diseases. However, our limited understanding of how metabolites affect pathophysiology limits our ability to develop new metabolite therapies. By providing a rich data set of metabolite-pathology correlations and by validating one of those correlations, our work is an important step toward harnessing metabolism to mitigate disease. Specifically, we showed that liver damage in P. chabaudi-infected mice releases hepatic arginase-1 into circulation, where it may deplete plasma arginine, a candidate malaria therapeutic that mitigates vascular stress. Our data suggest that liver damage may confound efforts to increase levels of arginine in human malaria patients.

COVID-19 morbidity in an ethnic minority: changes during the first year of the pandemic.

OBJECTIVES: During the COVID-19 pandemic, ethnic minorities have been more susceptible to infection and demonstrated poorer outcomes. This study describes COVID-19 morbidity and mortality by ethnic group, represented by Arab and Jewish localities in Israel, during the different waves of the outbreak and addresses sociocultural aspects of the pandemic. STUDY DESIGN: A retrospective national archive study was conducted in Israel. METHODS: Data were obtained from the Ministry of Health's database, including daily information on Arab, Jewish or mixed localities, from February 2020 to February 2021. RESULTS: During the first wave of the pandemic, the incidence of COVID-19 in Arab compared with Jewish localities was 67% lower and mortality was 85% lower, in addition to lower rates of severe disease requiring hospitalisation. During the second and third waves, these trends reversed, with the proportion of positive tests, incidence and mortality in Arab localities reaching and then surpassing rates in Jewish localities. By September 2020, COVID-19 mortality was twice as high in Arab compared with Jewish localities. CONCLUSIONS: After low morbidity during the first wave of the COVID-19 pandemic, a surge in infections occurred in the Arab population during subsequent waves, to match and surpass the high incidence seen in the Jewish population. This unique pattern highlights the changing experiences of a minority group as the pandemic progressed and demonstrates how COVID-19 exacerbates existing disparities.

Host Energy Source Is Important for Disease Tolerance to Malaria.

Pathologic infections are accompanied by a collection of short-term behavioral perturbations collectively termed sickness behaviors [1, 2]. These include changes in body temperature, reduced eating and drinking, and lethargy and mimic behaviors of animals in torpor and hibernation [1, 3-6]. Sickness behaviors are important, pathogen-specific components of the host response to infection [1, 3, 7-9]. In particular, host anorexia has been shown to be beneficial or detrimental depending on the infection [7, 8]. While these studies have illuminated the effects of anorexia on infection, they consider this behavior in isolation from other behaviors and from its effects on host metabolism and energy. Here, we explored the temporal dynamics of multiple sickness behaviors and their effect on host energy and metabolism throughout infection. We used the Plasmodium chabaudi AJ murine model of malaria as it causes severe pathology from which most animals recover. We found that infected animals did become anorexic, skewing their metabolism toward fatty acid oxidation and ketosis. Metabolism of fats requires oxygen for the production of ATP. In this model, animals also suffer severe anemia, limiting their ability to carry oxygen concurrent with their switch toward fatty acid metabolism. We reasoned that the combination of anorexia and anemia would increase pressure on glycolysis as a critical energy pathway because it does not require oxygen. Treating infected mice when anorexic with the glycolytic inhibitor 2-deoxyglucose (2DG) reduced survival; treating animals with glucose improved survival. Peak parasite loads were unchanged, demonstrating changes in disease tolerance. Parasite clearance was reduced with 2DG treatment, suggesting altered resistance.

Attenuating the rate of total body fat accumulation and alleviating liver damage by oral administration of vitamin D-enriched edible mushrooms in a diet-induced obesity murine model is mediated by an anti-inflammatory paradigm shift.

BACKGROUND: Hypovitaminosis D is associated with many features of the metabolic syndrome, including non-alcoholic fatty liver disease. Vitamin D-enriched mushrooms extracts exert a synergistic anti-inflammatory effect. The aim of the present study is to determine the immunomodulatory effect of oral administration of vitamin D-enriched mushrooms extracts on high-fat diet (HFD) animal model of non-alcoholic steatohepatitis (NASH). METHODS: C57BL/6 mice on HFD were orally administered with vitamin D supplement, Lentinula edodes (LE) mushrooms extract, or vitamin D-enriched mushrooms extract for 25 weeks. Mice were studied for the effect of the treatment on the immune system, liver functions and histology, insulin resistance and lipid profile. RESULTS: Treatment with vitamin D-enriched LE extracts was associated with significant attenuation of the rate of total body fat accumulation, along with a decrease in hepatic fat content as measured by an EchoMRI. Significant alleviation of liver damage manifested by a marked decrease in ALT, and AST serum levels (from 900 and 1021 U/L in the control group to 313 and 340; 294 and 292; and 366 and 321 U/L for ALT and AST, in Vit D, LE and LE + Vit D treated groups, respectively). A corresponding effect on hepatocyte ballooning were also noted. A significant decrease in serum triglycerides (from 103 to 75, 69 and 72 mg/dL), total cholesterol (from 267 to 160, 157 and 184 mg/dL), and LDL cholesterol (from 193 mg/dL to 133, 115 and 124 mg/dL) along with an increase in the HDL/LDL ratio, and improved glucose levels were documented. These beneficial effects were associated with a systemic immunomodulatory effect associated with an increased CD4/CD8 lymphocyte ratio (from 1.38 in the control group to 1.69, 1.71 and 1.63), and a pro- to an anti-inflammatory cytokine shift. CONCLUSIONS: Oral administration of vitamin-D enriched mushrooms extracts exerts an immune modulatory hepato-protective effect in NASH model.

Infection-related declines in chill coma recovery and negative geotaxis in Drosophila melanogaster.

Studies of infection in Drosophila melanogaster provide insight into both mechanisms of host resistance and tolerance of pathogens. However, research into the pathways involved in these processes has been limited by the relatively few metrics that can be used to measure sickness and health throughout the course of infection. Here we report measurements of infection-related declines in flies' performance on two different behavioral assays. D. melanogaster are slower to recover from a chill-induced coma during infection with either Listeria monocytogenes or Streptococcus pneumoniae. L. monocytogenes infection also impacts flies' performance during a negative geotaxis assay, revealing a decline in their rate of climbing as part of their innate escape response after startle. In addition to providing new measures for assessing health, these assays also suggest pathological consequences of and metabolic shifts that may occur over the course of an infection.

A young male with coexisting astrocytoma and renal cell carcinoma.

Familial cancer syndrome is a genetic condition that causes an individual to be at increased risk for specific types of cancers. There are different familial cancer syndromes, each of which is associated with a specific set of characteristic cancers. Atypical presentations such as the combination of two types of cancers involving the same primary site with a slightly different pathology are not uncommon. The reason for such a high degree of phenotypic variation could be due to somatic mosaicisms which, although rare, have been reported in association with some of the familial cancer syndromes. We report a case of a 44-year-old Caucasian male with coexisting astrocytoma and Renal Cell Carcinoma (RCC), in whom the diagnosis of Von Hippel-Lindau (VHL) syndrome was considered. Although the patient tested negative for the classic VHL gene, the possibility of somatic mosaicism could not be ruled out. This case reflects the importance of having a high index of suspicion to screen the patients with more than one type of malignancies for familial cancer syndrome, as it may present with atypical features and the diagnosis of familial cancer syndrome has important implications in genetic counseling.

Catastrophic antiphospholipid antibody syndrome in a young woman in the postpartum period.

A 27-year-old Hispanic female was admitted to hospital with fever, a sudden marked decrease in vision, and multi-organ failure shortly after preterm delivery by cesarean section for eclampsia. Her past history was significant for a spontaneous first trimester abortion and one live birth complicated by intrauterine growth retardation. She was found to have several focal brain infarcts, exudative retinal detachment, bilateral adrenal hemorrhage, renal insufficiency, hypertension and subsequently hypotension. Positive anticardiolipin antibodies, lupus anticoagulant, and anti-B2 glycoprotein-I, as well as deranged coagulation profile and PTT mixing studies aided in the diagnosis of catastrophic antiphospholipid antibody syndrome. Anticoagulation and high-dose intravenous steroids led to significant improvement in the patient's condition, including her vision.

Hypertension increases the probability of Alzheimer's disease and of mild cognitive impairment in an Arab community in northern Israel.

BACKGROUND: We aimed to determine whether vascular risk factors are associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) in an elderly Arab population. METHODS: An Arabic-speaking team performed a door-to-door survey of consecutive residents aged > or =65 years. We estimated the odds of AD or MCI versus normal controls as a function of age, gender, education and presence of vascular factors by multinomial logistic regression with interactions. RESULTS: Out of 767 subjects (54% men), 444 were cognitively normal, 234 had MCI and 89 had AD. AD was significantly associated with hypertension (p = 0.01; OR = 2.08; 95% CI: 1.18-3.65), age (p < 0.0001; OR = 1.19; 95% CI: 1.14-1.24), female gender (p = 0.0016; OR = 3.06; 95% CI: 1.53-6.15) and education (p = 0.0002; OR = 0.75; 95% CI: 0.65-0.88). MCI was significantly associated with hypertension (p = 0.0042; OR = 1.69; 95% CI: 1.25-2.44), age (p < 0.0001; OR = 1.06; 95% CI: 1.03-1.09) and education (p < 0.0001; OR = 0.76; 95% CI: 0.71-0.83), but not with gender. CONCLUSIONS: Hypertension, older age and low education significantly increase the probability of AD and MCI. The effect of hypertension on the odds of AD versus controls is over and above the effects of age, gender and education. For MCI versus controls there is no gender effect, and the effect of hypertension is over and above the effects of age and education.