Draft Genome Sequences of Propionibacterium acnes Type Strain ATCC6919 and Antibiotic-Resistant Strain HL411PA1.

Propionibacterium acnes is a major skin commensal and is associated with acne vulgaris, the most common skin disease. Here we report the draft genome sequences of two P. acnes strains, the type strain ATCC6919 and an antibiotic-resistant strain, HL411PA1

The Self-Perception and Usage of Medical Apps amongst Medical Students in the United States: A Cross-Sectional Survey

Background. Mobile medical software applications (apps) are used for clinical decision-making at the point of care. Objectives. To determine (1) the usage, reliability, and popularity of mobile medical apps and (2) medical students’ perceptions of app usage effect on the quality of patient-provider interaction in healthcare settings. Methods. An anonymous web-based survey was distributed to medical students. Frequency of use, type of app used, and perceptions of reliability were assessed via univariate analysis. Results. Seven hundred thirty-one medical students responded, equating to a response rate of 29%. The majority (90%) of participants thought that medical apps enhance clinical knowledge, and 61% said that medical apps are as reliable as textbooks. While students thought that medical apps save time, improve the care of their patients, and improve diagnostic accuracy, 53% of participants believed that mobile device use in front of colleagues and patients makes one appear less competent. Conclusion. While medical students believe in the utility and reliability of medical apps, they were hesitant to use them out of fear of appearing less engaged. Higher levels of training correlated with a greater degree of comfort when using medical apps in front of patients

CRF Receptor Antagonist Astressin-B Reverses and Prevents Alopecia in CRF Over-Expressing Mice

Corticotropin-releasing factor (CRF) signaling pathways are involved in the stress response, and there is growing evidence supporting hair growth inhibition of murine hair follicle in vivo upon stress exposure. We investigated whether the blockade of CRF receptors influences the development of hair loss in CRF over-expressing (OE)-mice that display phenotypes of Cushing's syndrome and chronic stress, including alopecia. The non-selective CRF receptors antagonist, astressin-B (5 µg/mouse) injected peripherally once a day for 5 days in 4–9 months old CRF-OE alopecic mice induced pigmentation and hair re-growth that was largely retained for over 4 months. In young CRF-OE mice, astressin-B prevented the development of alopecia that occurred in saline-treated mice. Histological examination indicated that alopecic CRF-OE mice had hair follicle atrophy and that astressin-B revived the hair follicle from the telogen to anagen phase. However, astressin-B did not show any effect on the elevated plasma corticosterone levels and the increased weights of adrenal glands and visceral fat in CRF-OE mice. The selective CRF2 receptor antagonist, astressin2-B had moderate effect on pigmentation, but not on hair re-growth. The commercial drug for alopecia, minoxidil only showed partial effect on hair re-growth. These data support the existence of a key molecular switching mechanism triggered by blocking peripheral CRF receptors with an antagonist to reset hair growth in a mouse model of alopecia associated with chronic stress

Case Report: Possible Links between Sickle Cell Crisis and Pentavalent Antimony

For over 60 years, pentavalent antimony (Sbv) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sbv revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sbv, and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sbv caused the SCC

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted

Killed but metabolically active Leishmania infantum as a novel whole-cell vaccine for visceral leishmaniasis

There are currently no effective vaccines for visceral leishmaniasis, the second most deadly parasitic infection in the world. Here, we describe a novel whole-cell vaccine approach using Leishmania infantum chagasi promastigotes treated with the psoralen compound amotosalen (S-59) and low doses of UV A radiation. This treatment generates permanent, covalent DNA cross-links within parasites and results in Leishmania organisms termed killed but metabolically active (KBMA). In this report, we characterize the in vitro growth characteristics of both KBMA L. major and KBMA L. infantum chagasi. Concentrations of S-59 that generate optimally attenuated parasites were identified. Like live L. infantum chagasi, KBMA L. infantum chagasi parasites were able to initially enter liver cells in vivo after intravenous infection. However, whereas live L. infantum chagasi infection leads to hepatosplenomegaly in mice after 6 months, KBMA L. infantum chagasi parasites were undetectable in the organs of mice at this time point. In vitro, KBMA L. infantum chagasi retained the ability to enter macrophages and induce nitric oxide production. These characteristics of KBMA L. infantum chagasi correlated with the ability to prophylactically protect mice via subcutaneous vaccination at levels similar to vaccination with live, virulent organisms. Splenocytes from mice vaccinated with either live L. infantum chagasi or KBMA L. infantum chagasi displayed similar cytokine patterns in vitro. These results suggest that KBMA technology is a potentially safe and effective novel vaccine strategy against the intracellular protozoan L. infantum chagasi. This approach may represent a new method for whole-cell vaccination against other complex intracellular pathogens

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

Regulatory T Cells in the Pathogenesis and Healing of Chronic Human Dermal Leishmaniasis Caused by Leishmania (Viannia) Species

The immune inflammatory response is a double edged sword. During infectious diseases, regulatory T cells can prevent eradication of the pathogen but can also limit inflammation and tissue damage. We investigated the role of regulatory T cells in chronic dermal leishmaniasis caused by species of the parasite Leishmania that are endemic in South and Central America. We found that although individuals with chronic lesions have increased regulatory T cells in their blood and at skin sites where immune responses to Leishmania were taking place compared to infected individuals who do not develop disease, their capacity to control the inflammatory response to Leishmania was inferior. However, healing of chronic lesions at the end of treatment was accompanied by an increase in the number and capacity of regulatory T cells to inhibit the function of effector T cells that mediate the inflammatory response. Different subsets of regulatory T cells, defined by the expression of molecular markers, were identified during chronic disease and healing, supporting the participation of distinct regulatory T cells in the development of disease and the control of inflammation during the healing response. Immunotherapeutic strategies may allow these regulatory T cell subsets to be mobilized or mitigated to achieve healing

Seasonal variations in pore water and sediment geochemistry of littoral lake sediments (Asylum Lake, MI, USA)

BACKGROUND: Seasonal changes in pore water and sediment redox geochemistry have been observed in many near-surface sediments. Such changes have the potential to strongly influence trace metal distribution and thus create seasonal fluctuations in metal mobility and bioavailability. RESULTS: Seasonal trends in pore water and sediment geochemistry are assessed in the upper 50 cm of littoral kettle lake sediments. Pore waters are always redox stratified, with the least compressed redox stratification observed during fall and the most compressed redox stratification observed during summer. A 2-step sequential sediment extraction yields much more Fe in the first step, targeted at amorphous Fe(III) (hydr)oxides (AEF), then in the second step, which targets Fe(II) monosulfides. Fe extracted in the second step is relatively invariant with depth or season. In contrast, AEF decreases with sediment depth, and is seasonally variable, in agreement with changes in redox stratification inferred from pore water profiles. A 5-step Tessier extraction scheme was used to assess metal association with operationally-defined exchangeable, carbonate, iron and manganese oxide (FMO), organic/sulfide and microwave-digestible residual fractions in cores collected during winter and spring. Distribution of metals in these two seasons is similar. Co, As, Cd, and U concentrations approach detection limits. Fe, Cu and Pb are mostly associated with the organics/sulfides fraction. Cr and Zn are mostly associated with FMO. Mn is primarily associated with carbonates, and Co is nearly equally distributed between the FMO and organics/sulfide fractions. CONCLUSION: This study clearly demonstrates that near-surface lake sediment pore water redox stratification and associated solid phase geochemistry vary significantly with season. This has important ramifications for seasonal changes in the bioavailability and mobility of trace elements. Without rate measurements, it is not possible to quantify the contribution of various processes to natural organic matter degradation. However, the pore water and solid phase data suggest that iron reduction and sulfate reduction are the dominant pathways in the upper 50 cm of these sediments

Process Improvement in Construction Management

The objective of this project is to determine the most efficient ways to mitigate problematic disruptions in construction management. The rationale for this project is the devastation of the Covid-19 pandemic on all businesses. When the workforce is depleted, it causes economic distress on individuals and the country as a whole. The state of the art is similar studies done by the US Bureau of Labor Statistics, the American Bar Association, White House reports on supply chains, and business reports done by MIT and WPI. The methods used for this project are research analysis, interview tactics, and hands on experience. The major results from this project are remote working from home, “no damages for delay” insurance policy, increased rate of follow-up calls with subcontractors and manufacturers, and heightened awareness. The conclusions of this project are to not be hesitant to change routine tactics when they cease to provide positive results, adjust the supply and demand of workforce, and strive for strong relationships with subcontractors and manufacturers