Antimicrobial effects of XF drugs against Candida albicans and its biofilms.

Compared with antibiotics for treating bacterial infections, there are a limited number of antifungal agents. This is due to several factors, including the difficulties of identifying suitable antifungals that target the fungal cell without damaging host cells, and the reduced rates of diagnosis of fungal infections compared with those caused by bacteria. The problem of treating fungal infections is exacerbated by an increasing incidence of antifungal resistance among human fungal pathogens. Three XF drugs (XF-73, XF-70, and DPD-207) have previously displayed innate bactericidal effects and a low propensity for microbial resistance, with XF-73 and XF-70 having a second, light-activated mechanism of action [known as photodynamic therapy (PDT)]. In an effort to expand the repertoire of antifungal agents, this research assessed the in vitro activity of XF drugs via both mechanisms of action against six strains of the fungal pathogen Candida albicans in both planktonic and biofilm cultures. In addition, this research examined the effects of XF drug treatment on biofilms of C. albicans in a reconstituted human oral epithelium model. All C. albicans strains tested were susceptible to XF-73 and XF-70, with minimum inhibitory concentrations (MICs) between 0.25 µg/mL and 2 µg/mL; DPD-207 was less potent, with MICs between 4 µg/mL and 16 µg/mL, and light activation did not enhance these MICs. Complete biofilm eradication was not reported at the tested XF drug concentrations. However, live and dead staining of C. albicans cells in biofilms after XF drug treatment demonstrated that XF-73 and XF-70 were active against most Candida biofilms tested from 64 µg/mL; again, light activation did not enhance anti-biofilm activity. Candida biofilms were more resistant to DPD-207, with fungicidal effects occurring from 256 µg/mL. XF-73 and XF-70 reduced penetration of C. albicans biofilm into reconstituted human oral epithelium (RHOE) and resulted in less damage (as determined by reduced lactate dehydrogenase release) than untreated biofilms. Overall, the results highlight the potential of XF drugs as new drugs for the management of topical infections caused by C. albicans. Further studies are warranted on the development of XF drugs as antifungals, particularly for XF-73 and XF-70.

A novel risk assessment tool for bovine respiratory disease in preweaned dairy calves.

Due to the increased morbidity and mortality of bovine respiratory disease (BRD) in dairy calves, as well as an increasing urgency for the judicious use of antimicrobials in farm animals, a comprehensive risk assessment tool for BRD in preweaned dairy calves has been designed based on a longitudinal and a cross-sectional study. As a multifactorial disease complex in which immune function stressors increase susceptibility to respiratory pathology, risk management programs for environmental and husbandry practices may be an effective approach for BRD control. Practices of known or suspected effect on BRD in preweaned calves have been explored in 2 large studies correlating management factors to BRD prevalence (BRD 100 study) and incidence (BRD 10K study) and forming the scores presented here. Priority was given to results from multivariable over univariable model estimates. However, when used, univariable model estimates were adjusted for confounders or stratified by effect modifiers if necessary. Regression coefficients were translated into scores, which are presented in a field-ready tool consisting of (1) a risk assessment questionnaire, which identifies the herd-specific risk factors and the risk scores associated with each; (2) the California BRD scoring system to estimate the BRD prevalence at the time of risk assessment for future comparison with the prevalence after interventions; and (3) the BRD control and prevention herd management plan, which can be used to plan and track the interventions identified. Scores for 100 dairies across California were used to benchmark a dairy's risk on a spectrum. With the help of the risk assessment tool, dairy producers, calf managers, and veterinarians may be able to adjust management factors that affect BRD risk on a farm and objectively monitor BRD prevalence before and after management interventions. As a result, the BRD risk assessment tool described here is the first comprehensive effort for herd-specific BRD control and prevention.

Management factors associated with bovine respiratory disease in preweaned calves on California dairies: The BRD 100 study.

The objective of this cross-sectional study was to determine how management practices on California dairies may be associated with bovine respiratory disease (BRD) in preweaned calves. A convenience sample of 100 dairies throughout California, providing a study population of 4,636 calves, were visited between May 2014 and April 2016. During each farm visit, in-person interviews with the herd manager or calf caretaker were conducted to collect information about herd demographics, maternity pen, colostrum and calf management, herd vaccinations, and dust abatement. A random sample of preweaned calves was identified and evaluated for the presence of BRD using a standardized tool. A survey-adjusted generalized linear mixed model with a logit link function was fitted with calf as the unit of analysis and dairy as the random effect. Mean study herd size (±SE) was 1,718 (±189.9) cows. Survey-adjusted estimates of breed types in the sample were 81.6% (±0.6) Holstein, 13.1% (±0.4) Jersey, and 5.3% (±0.5) crossbred or other purebred breeds, and calf sex proportions were 73.8% (±1.0) female and 26.2% (±1.0) male. Overall survey-adjusted BRD prevalence in the study herds was 6.91% (±0.69). Housing factors positively associated with BRD were metal hutches compared with wood hutches [odds ratio (OR) = 11.19; 95% confidence interval (CI) = 2.80-44.78], calf-to-calf contact in calves >75 d of age (OR = 9.95, 95% CI = 1.50-65.86), feeding Holstein calves <2.84 L of milk or replacer per day (OR = 7.16, 95% CI = 1.23-41.68), and lagoon water used for flushing manure under hutches compared with no flush (OR = 12.06, 95% CI = 1.93-75.47). Providing extra shade over hutches (OR = 0.08; 95% CI = 0.02-0.37), feeding calves at least 90% saleable milk (OR = 0.27, 95% CI = 0.13-0.54) or pasteurized milk (OR = 0.10; 95% CI = 0.03-0.36), and feeding >5.68 L of milk or replacer per day to Jersey calves (OR = 0.04; 95% CI = 0.01-0.28) were negatively associated with BRD. Our study identified management practices on California dairies with variability and that may contribute to differences in BRD prevalence, which will be incorporated into a risk-assessment tool to control and prevent BRD in preweaned dairy calves.

Regional management practices and prevalence of bovine respiratory disease in California's preweaned dairy calves.

The objective of this cross-sectional study was to estimate the prevalence of bovine respiratory disease (BRD) in California preweaned dairy calves and identify management practices that are associated with BRD. A convenience sample of 100 dairies in the 3 distinct dairy regions of California was surveyed. Regions evaluated were Northern California (NCA), northern San Joaquin Valley (NSJV), and greater Southern California (GSCA). A questionnaire on calf management practices and demographic information was administered via in-person interviews at each dairy and a random sample of preweaned calves was evaluated using the California BRD scoring system on the same day. Prevalence of BRD varied between the 3 dairy regions: 9.30% in NCA, 4.51% in NSJV, and 7.35% in GSCA. Breed was not associated with BRD prevalence at the statewide level, but differences in prevalence were observed between breeds across the regions with a higher prevalence in NCA for Jerseys and in GSCA for Holsteins, compared with NSJV. Prevalence of BRD was not different between organic and conventional dairies. Colostrum management practices, including heat treatment and feeding colostrum from multiparous cows, varied by region and were associated with lower BRD prevalence. Calves housed in group pens, a practice observed primarily in NCA, had a higher BRD prevalence than those in individual housing. Feeding salable milk was also more common in NCA and was associated with lower BRD prevalence. Ground and road surfaces adjacent to the calf raising area were also variable by region, and paved surfaces were associated with lower BRD prevalence. Management practices associated with BRD varied across the state and may be addressed to inform the adoption and implementation of potentially protective management decisions on California dairies and other regions with similar dairy systems.

Effect of the environment on the risk of respiratory disease in preweaning dairy calves during summer months.

Heat stress has the potential to adversely affect the physiology, passive immunity, and growth of preweaning dairy calves, increasing their risk of respiratory disease. The effect of heat stress on the risk for bovine respiratory disease (BRD) may be mediated in part through housing, ventilation, and management factors. As a result, differences may exist in meteorological measures recorded in the calf-rearing area (macroenvironment) and within a calf's enclosure (microenvironment). The objective of this prospective cohort study was to evaluate and compare the association between exposure to temperature and humidity measured at the macro- and microenvironment, and BRD in preweaning dairy calves; a secondary objective was to evaluate the correlation between the macro- and microenvironment. A cohort of 252 calves from 4 premises in central San Joaquin Valley, California (CA), was followed and evaluated for development of respiratory disease using the CA BRD scoring system for preweaning dairy calves, a standardized and validated scoring system. During this time, the meteorological conditions of the calf-rearing area and the within-hutch environment were measured and showed a significant correlation with regard to temperature and humidity. Mixed effects logistic regression and survival analysis were used to analyze the association between the exposures daily environmental measures of temperature, humidity, and temperature-humidity index (THI) and the outcome BRD, adjusted for dairy premises, calf age, sex, and breed. Results showed a significant positive association between daily maximum temperature and BRD in both the calf's macroenvironment [odds ratio = 1.121 (95% confidence interval (CI) = 1.029-1.222)] and microenvironment [odds ratio = 1.203 (95% CI = 1.020-1.418)]. Estimated hazard rates also showed a significant positive association between BRD and daily maximum temperature in both the macroenvironment [hazard ratio = 1.127 (95% CI = 1.053-1.206)] and microenvironment [hazard ratio = 1.119 (95% CI = 1.047-1.197)]. In contrast, we found no association between daily maximum humidity in a calf's microenvironment and BRD. Daily maximum THI within the hutch was significantly associated with only the rate of BRD cases [hazard ratio = 1.070 (95% CI = 1.003-1,141)] but not the odds of occurrence of BRD. Maximum THI is estimated using temperature and humidity, which in California's hot and dry summers may limit variability in THI, explaining its weaker significant association with risk of BRD (or lack of association with odds of BRD) compared with models for maximum temperature in this study. Calves exposed to high day temperatures and relatively low humidity may be experiencing heat stress that predisposes to BRD. Results of the current study suggest that heat abatement efforts should address heat stress at the microenvironment level to mitigate BRD in calves. Further research should investigate strategies to improve calf hutch systems, including hutch materials and design that may optimize ventilation, provide ample shade, spacing, cleanliness, and protection from heat.

Phenotypical resistance correlation networks for 10 non-typhoidal Salmonella subpopulations in an active antimicrobial surveillance programme.

Antimicrobials play a critical role in treating cases of invasive non-typhoidal salmonellosis (iNTS) and other diseases, but efficacy is hindered by resistant pathogens. Selection for phenotypical resistance may occur via several mechanisms. The current study aims to identify correlations that would allow indirect selection of increased resistance to ceftriaxone, ciprofloxacin and azithromycin to improve antimicrobial stewardship. These are medically important antibiotics for treating iNTS, but these resistances persist in non-Typhi Salmonella serotypes even though they are not licensed for use in US food animals. A set of 2875 Salmonella enterica isolates collected from animal sources by the National Antimicrobial Resistance Monitoring System were stratified in to 10 subpopulations based on serotype and host species. Collateral resistances in each subpopulation were estimated as network models of minimum inhibitory concentration partial correlations. Ceftriaxone sensitivity was correlated with other ß-lactam resistances, and less commonly resistances to tetracycline, trimethoprim-sulfamethoxazole or kanamycin. Azithromycin resistance was frequently correlated with chloramphenicol resistance. Indirect selection for ciprofloxacin resistance via collateral selection appears unlikely. Density of the ACSSuT subgraph resistance aligned well with the phenotypical frequency. The current study identifies several important resistances in iNTS serotypes and further research is needed to identify the causative genetic correlations.

Assessing the outcomes, risks, and costs of local versus general anesthesia: A review with implications for cutaneous surgery.

BACKGROUND: There is a paucity of data providing direct comparison of outcomes, complications, and costs between general and local anesthesia in cutaneous surgery. OBJECTIVE: Analyze the literature from dermatologic and other specialties to compare outcomes, risks, and costs of general and local anesthesia. METHODS: A retrospective analysis of case comparison studies from other specialties comparing outcomes, risks, and/or costs in local versus general anesthesia was performed. A review of the literature from dermatology and other specialties was included. RESULTS: A total of 51 studies were selected; 41 of them directly examined outcomes in procedures performed under local and general anesthesia, and none found a significant difference in outcomes. A total of 41 studies measured adverse effects. Of these, 15 studies (36.6%) report significantly better outcomes between the 2 techniques. Only 2 studies (4.9%) report significantly improved outcomes with use of general anesthesia; 15 of 36 studies (41.7%) report fewer adverse events in local anesthesia. Of the 13 studies that examined costs, all (100%) found significantly decreased costs with use of local anesthesia. LIMITATIONS: These data cannot be seamlessly applied to all cases of cutaneous surgery. CONCLUSION: Local anesthesia techniques provide outcomes equal to or better than general anesthesia and with significantly lower costs.

Survey of management practices related to bovine respiratory disease in preweaned calves on California dairies.

In the spring of 2013, a survey of California (CA) dairies was performed to characterize management practices related to bovine respiratory disease in preweaned calves, compare these practices across geographic regions of the state, and determine the principal components that explain the variability in management between herds. The questionnaire consisted of 53 questions divided into 6 sections to assess management practices affecting dairy calves from precalving to weaning. The questionnaire was mailed to 1,523 grade A licensed dairies in CA and 224 responses (14.7%) were collected. Survey response rates were similar over the 3 defined regions of CA: northern CA, northern San Joaquin Valley, and the greater southern CA region. The mean size of respondent herds was 1,423 milking cows. Most dairies reported raising preweaned calves on-site (59.7%). In 93.3% of dairies, preweaned calves were raised in some form of individual housing. Nonsaleable milk was the most frequent liquid diet fed to preweaned heifers (75.2%). Several important differences were identified between calf-raising practices in CA and practices reported in recent nationwide studies, including herd sizes, housing practices, and sources of milk fed to heifers. The differences between the CA and nationwide studies may be explained by differences in herd size. Regional differences within CA were also identified. Compared with the 2 other regions, northern CA dairies were found to have smaller herds, less Holstein cattle, calves remained with dams for longer periods of time after calving, were more likely to be certified organic dairies, and raised their own calves more often. Principal component analysis was performed and identified 11 components composed of 28 variables (questions) that explained 66.5% of the variability in the data. The identified components and questions will contribute to developing a risk assessment tool for bovine respiratory disease in preweaned dairy calves.

2015 Arte Poster Competition First Place Winner: Assessing the Correlation Between Patient Anxiety and Satisfaction for Mohs Surgery.

Skin cancer and the surgical treatment thereof have the potential to be sources of great anxiety for patients. Examination of patient satisfaction, anxiety, and contributing factors has the potential to provide information surgeons can use to implement practices that have an impact on patient anxiety and satisfaction regarding dermatologic surgery. This study used a prospective interview to catalog patients' anxiety and experiences before and during the surgical process. Our results indicate that several pre- and perioperative factors have the potential to decrease a patient's overall anxiety. Notably, 33% of surgical patients reported a decrease in anxiety from the time of diagnosis until the day of surgery. Factors that contributed to this included a call discussing the diagnosis and what to expect on the day of surgery as well as reading written material or searching the internet for more information regarding the procedure. Furthermore, a call from the physician compared to a call from a nurse or other team member showed a greater effect on decreasing anxiety. During the surgical procedure, our results highlight several factors that can decrease a patient's anxiety. Most notably, eating, watching TV, bringing a guest, and engaging in small talk with surgeon and staff during the procedure subjectively decreased patients' anxiety. In summary, our results suggest that patients respond to a variety of factors to reduce anxiety and that each patient derives relief from anxiety in different manners. Therefore, offering a spectrum of comforting or distracting activities during the Mohs procedure is ideal and may reduce the need for pharmacologic anxiolytics.

A review of traditional and novel oral anticoagulant and antiplatelet therapy for dermatologists and dermatologic surgeons.

BACKGROUND: Dermatologic surgeons will increasingly encounter patients on novel oral antiplatelet and anticoagulant medications. OBJECTIVES: We conducted a complete overview of the pharmacokinetics, pharmacodynamics, and side effects of traditional and novel oral anticoagulant and antiplatelet therapies along with dietary supplements with anticoagulant or antiplatelet properties. METHODS: A PubMed search was completed for "aspirin," "warfarin," "clopidogrel," "dabigatran," "rivaroxaban," "apixaban," "prasugrel," and "ticagrelor." Review articles and publications emphasizing perioperative management of oral anticoagulant or antiplatelet medications were selected. An additional PubMed search was completed for "hemorrhage," "bleeding," and "thrombosis" in conjunction with "dermatology," "dermatologic surgery," and "cutaneous surgery." RESULTS: Aspirin, clopidogrel, and warfarin have shortfalls in dosing, monitoring, and efficacy. Several trials show superior efficacy with dabigatran, rivaroxaban, and apixaban, with equal or reduced risk of bleeding compared with warfarin. Prasugrel and ticagrelor may be associated with an increased bleeding risk. Many over-the-counter medications also have anticoagulant properties with associated bleeding risks that cannot be overlooked. LIMITATIONS: There are few publications evaluating the novel oral anticoagulants' effects on outpatient surgical procedures. CONCLUSION: Novel anticoagulant and antiplatelet drugs are revolutionizing therapy for cardiovascular diseases. As these medications become more prevalent, dermatologists and dermatologic surgeons must be mindful of the bleeding risk that will apply in our everyday practices.

Management of unusual cutaneous malignancies: atypical fibroxanthoma, malignant fibrous histiocytoma, sebaceous carcinoma, extramammary Paget disease.

Atypical fibroxanthoma, malignant fibrous histiocytoma, sebaceous carcinoma, and extramammary Paget disease are rare cutaneous tumors. Their recognition and diagnosis are critical in decreasing long-term morbidity and mortality. Surgical excision is the treatment of choice for these tumors, and Mohs micrographic surgery has been shown to be as favorable or better than wide local excision in providing long-term clearance rates.

Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma: a systematic review.

OBJECTIVES: To conduct a systematic review to determine clearance rates and adverse effects of topical imiquimod or fluorouracil therapy in the treatment of nonmelanoma skin cancers such as basal (BCC) and squamous cell carcinoma (SCC), and to develop recommendations for the use of topical imiquimod or fluorouracil to treat BCC and SCC. DATA SOURCES: MEDLINE, CANCERLIT, and Cochrane databases. STUDY SELECTION: Prospective, retrospective, and case studies in English containing a minimum of 4 subjects and a 6-month follow-up or posttreatment histologic evaluation. DATA EXTRACTION: We calculated the rate of clearance and adverse effects for BCC subtypes and invasive and in situ SCC treated with topical imiquimod or fluorouracil. DATA SYNTHESIS: Clearance rates varied by drug regimen, and most of the studies lacked long-term follow-up. Imiquimod use produced the following clearance rates: 43% to 100% for superficial BCC, 42% to 100% for nodular BCC, 56% to 63% for infiltrative BCC, 73% to 88% for SCC in situ, and 71% for invasive SCC. Fluorouracil use produced the following clearance rates: 90% for superficial BCC and 27% to 85% for SCC in situ. Up to 100% and 97% of patients applying imiquimod and fluorouracil, respectively, experienced at least 1 adverse event. Adverse event intensity ranged from mild to severe; erythema, pruritus, and pain were common. CONCLUSIONS: Evidence supports the use of topical imiquimod as monotherapy for superficial BCC and topical fluorouracil as monotherapy for superficial BCC and SCC in situ. Based on the available evidence, the strength of any recommendations for the use of these 2 agents in the primary treatment of these tumors is weak. We recommend that their use be limited to patients with small tumors in low-risk locations who will not or cannot undergo treatment with better-established therapies for which long-term clearance rates have been determined. Long-term clinical follow-up is essential for patients treated with topical imiquimod or fluorouracil. Limitations of therapy include high rates of adverse effects, lower clearance rates than other treatment modalities, dependence on patient adherence to treatment, and higher costs than other therapies.

Surgical management of congenital dermatofibrosarcoma protuberans.

Congenital dermatofibrosarcoma protuberans (DFSP) is a rare tumor with varying clinical presentations that is commonly misdiagnosed. Treatment of congenital DFSP is complicated by delays in diagnosis and its propensity for subclinical spread. Of 61 reported cases, 11 (18%) were treated with Mohs micrographic surgery (MMS) and 46 (75%) were treated with wide local excision (WLE). One case was treated with imatinib, and the remaining 3 did not differentiate between receiving MMS or WLE. In the cases of congenital DFSP treated with MMS the clearance rate was 100% with an average follow-up of 4.3 years. The clearance rate seen with WLE was 89% with an average follow-up period of 1.9 years. The average margins taken during MMS (1.7 cm) were smaller than those taken with WLE (2.8 cm). Fifty percent of cases with available follow-up undergoing WLE required multiple surgeries. Based on superior cure rates with long-term follow-up, smaller surgical margins, and fewer surgical sessions, MMS should be considered as first-line treatment for congenital DFSP.

J/psi and psi(2S) Radiative Transitions to eta_{c}.

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

Observation of D+ --> etae + nue.

Using a 281 pb-1 data sample collected at the psi(3770) resonance with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of D+ --> etae + nue. We also set upper limits for D+ --> eta'e + nue and D + --> varphie + nue that are about 2 orders of magnitude more restrictive than those obtained by previous experiments.

Fabric preferences of atopic dermatitis patients.

BACKGROUND: Atopic dermatitis (AD) patients have sensitive skin with impaired barrier function. Lyocell is a cellulosic fiber that offers unique characteristics and may be suitable for use by AD patients. OBJECTIVE: To compare preferences of subjects with atopic dermatitis and normal skin for 100% lyocell clothing and bedding versus 100% cotton fabrics. METHODS: Thirty subjects were enrolled and randomly selected to use cotton or lyocell shirts, pajamas, and bedding for 1 week. Following a 1-week washout period, participants wore the other fabric for 1 week. At the end of each week, participants completed a preference questionnaire, and AD subjects also rated daily itching on a visual analog scale. A random subset of AD and normal participants underwent measurement of transepidermal water loss (TEWL). RESULTS: Overall, there was a significant preference for lyocell (vs cotton) for its softness, temperature control, moisture control, and wrinkle resistance. AD subjects did not have stronger fabric preferences than did normal subjects. Although not significant, lower average itching and decreased TEWL were seen in participants while they wore lyocell. CONCLUSION: Lyocell is superior to cotton in many performance characteristics and equivalent to cotton for itch reduction. Lyocell is currently available as a beneficial fabric to improve patient comfort.

Search for lepton flavor violation in upsilon decays.

In this Letter, we describe a search for lepton flavor violation (LFV) in the bottomonium system. We search for leptonic decays Upsilon(nS)-->mutau (n=1, 2, and 3) using the data collected with the CLEO III detector. We identify the tau lepton using its leptonic decay nu_{tau}nu[over ]_{e}e and utilize multidimensional likelihood fitting with probability density function shapes measured from independent data samples. We report our estimates of 95% C.L. upper limits on LFV branching fractions of Upsilon mesons. We interpret our results in terms of the exclusion plot for the energy scale of a hypothetical new interaction versus its effective LFV coupling in the framework of effective field theory.