Aspergillus fumigatus and aspergillosis: From basics to clinics.

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP 51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP 51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.

Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.

Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB coinfected patients in India.

SETTING: Y R Gaitonde Centre for AIDS Research and Education, Chennai, India. OBJECTIVE: To compare anti-tuberculosis treatment outcomes in individuals with human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin (RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg. DESIGN: A retrospective study was conducted of two HIV-TB co-infected cohorts between 2003 and 2014. Basic demographic and TB outcome data were obtained from an electronic database and patient records. The χ(2) and Fisher's exact test were used to compare daily and intermittent RBT treatment groups. RESULTS: Of 292 individuals on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar in sex, age, previous history of TB, site of TB and acid-fast bacilli smear status. More individuals in the daily vs. the intermittent RBT group achieved clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in relapse/recurrence or all-cause mortality between groups. CONCLUSION: There were higher rates of clinical TB cure in individuals on a boosted protease inhibitor-based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal RBT dosing in this setting requires further investigation.

A diagenetic control on the Early Triassic Smithian-Spathian carbon isotopic excursions recorded in the marine settings of the Thaynes Group (Utah, USA).

In the aftermath of the end-Permian mass extinction, Early Triassic sediments record some of the largest Phanerozoic carbon isotopic excursions. Among them, a global Smithian-negative carbonate carbon isotope excursion has been identified, followed by an abrupt increase across the Smithian-Spathian boundary (SSB; ~250.8 Myr ago). This chemostratigraphic evolution is associated with palaeontological evidence that indicate a major collapse of terrestrial and marine ecosystems during the Late Smithian. It is commonly assumed that Smithian and Spathian isotopic variations are intimately linked to major perturbations in the exogenic carbon reservoir. We present paired carbon isotopes measurements from the Thaynes Group (Utah, USA) to evaluate the extent to which the Early Triassic isotopic perturbations reflect changes in the exogenic carbon cycle. The δ(13) Ccarb variations obtained here reproduce the known Smithian δ(13) Ccarb -negative excursion. However, the δ(13) C signal of the bulk organic matter is invariant across the SSB and variations in the δ(34) S signal of sedimentary sulphides are interpreted here to reflect the intensity of sediment remobilization. We argue that Middle to Late Smithian δ(13) Ccarb signal in the shallow marine environments of the Thaynes Group does not reflect secular evolution of the exogenic carbon cycle but rather physicochemical conditions at the sediment-water interface leading to authigenic carbonate formation during early diagenetic processes.

Failure to detect infection by oral polio vaccine virus following natural exposure among inactivated polio vaccine recipients.

While oral polio vaccine (OPV) has been shown to be safe and effective, it has been observed that it can circulate within a susceptible population and revert to a virulent form. Inactivated polio vaccine (IPV) confers protection from paralytic disease, but provides limited protection against infection. It is possible, then, that an IPV-immunized population, when exposed to OPV, could sustain undetected circulation of vaccine-derived poliovirus. This study examines the possibility of polio vaccine virus circulating within the United States (highly IPV-immunized) population that borders Mexico (OPV-immunized). A total of 653 stool and 20 sewage samples collected on the US side of the border were tested for the presence of poliovirus. All samples were found to be negative. These results suggest that the risk of circulating vaccine-derived poliovirus is low in fully immunized IPV-using populations in developed countries that border OPV-using populations.

Identification of drinking water contaminants in the course of a childhood cancer investigation in Toms River, New Jersey.

Using a combination of gas chromatography/mass spectrometry (GC/MS) and gas chromatography/infrared spectroscopy (GC/IR) spectroscopic techniques, chemical contaminants and their hydrolysis products were identified in well water sampled in connection with a suspected childhood cancer cluster located in Dover Township, Ocean County, New Jersey. The drinking water contamination resulted from the leaching of industrial waste chemicals from drums that were disposed of at the site known as Reich Farm. Contaminants identified include dinitrile-tetralin compounds, known as 'trimers,' that are by-products of a polymerization process widely used by several polymer manufactures during the 1970s and 1980s (and still used today). Also identified were 'trimer' hydrolysis products, formed by the hydrolysis of their nitrile groups to amides. These industrial contaminants were not present in any of the mass or IR spectral library databases, and their identification required unconventional spectroscopic methods (including high resolution mass spectrometry, chemical ionization mass spectrometry, and IR spectroscopy), along with scientific reasoning and interpretation. It is currently not known whether these chemical contaminants are responsible for the childhood cancers observed in this area.

The influence of ostomy surgery on body image in patients with cancer.

A one group repeated measures design was used to describe changes in body image in 45 patients treated with ostomy for bowel or bladder cancer. Body image was measured preoperatively and at two postoperative points: 1 month and in 6 months or postclosure. The Body Cathexis Scale, Draw-a-Person, and subjective responses to open-ended questions were used. There was a significant difference in Body Cathexis scores between the immediate 1 month postoperative period and 6 months later (F(2, 88) = 3.13, p = .049). Body image scores did not change significantly between the preostomy and first postostomy measures. Qualitative data suggested that cancer diagnosis and its associated concerns were paramount on subjects' minds preoperatively and thus negatively influenced body image before the creation of the ostomy. Although altered body image is an appropriate nursing diagnosis for patients with ostomy in both the preoperative and postoperative periods, other issues may be dominant especially in the preoperative period.

Immobilization of Rocky Mountain elk with Telazol and xylazine hydrochloride, and antagonism by yohimbine hydrochloride.

Ten trapped Rocky Mountain elk (Cervus elaphus nelsoni) were successfully immobilized with a combination of 500 mg Telazol and 60 mg xylazine hydrochloride (HCl) from 9 July to 25 August 1993 in Custer State Park, South Dakota (USA). Mean (SD) dosages of 2.5 (0.6) mg/kg Telazol and 0.3 (0.1) mg/kg xylazine HCl, respectively, were administered, resulting in a mean (SD) induction time of 4.6 (0.8) min. Induction time varied with weight and dosage. Respiratory rate (breaths/min) increased following injection of Telazol and xylazine HCl and remained elevated or continued to increase through 10 min post-injection and then declined. There were no mortalities in this study. Forty mg of yohimbine HCl was used as an antagonist in eight elk, resulting in a mean (SD) recovery time of 14.0 (9.9) min when administered intravenously (n = 6), and 124.7 (9.5) min when given intramuscularly (n = 2). Recovery time varied with weight and dosage of yohimbine. Elk given 2.1 to 2.6 mg/kg Telazol and 0.1 to 0.3 mg/kg xylazine HCl responded to yohimbine HCl when administered intravenously.

The pattern of personal knowing in nurse clinical decision making.

The struggle to teach clinical decision making effectively continues despite recent efforts aimed at improvement. In recognizing that a complex activity like clinical decision making entails multiple patterns of knowing, qualitative research methodology was used to gain a practice-based understanding of clinical decision making. The result is a description of the pattern of personal knowledge in nurse clinical decision making. Nurse informants label the pattern of personal knowledge as knowing, and describe their success in making clinical decisions as highly dependent upon the quality of interpersonal relationships with patients, peer nursing staff, and physicians. The dynamic of interpersonal relationships and the difficulties in establishing them are identified as important influencing factors in nurses' clinical decision making.

Glycosylated hemoglobin as a stable alternative to serum glucose in white-tailed deer.

We compared serum glucose concentration and percent glycosylated hemoglobin (GH) in captive and wild white-tailed deer (Odocoileus virginianus) to determine stability of glucose relative to GH. Temporal changes in levels of serum glucose and GH were ascertained from serial blood samples collected from three captive deer over a 2-week period. State of glycemia also was determined for 17 wild deer that were collected from three populations in southeastern Oklahoma and southwestern Arkansas (USA). Concentration of serum glucose of captive deer decreased (P = 0.04) from 190.4 to 155.8 mg/dl over the 2 weeks; percent GH did not differ temporally (P = 0.30). Percent GH of wild deer did not differ (P = 0.23) when deer were separated into 2 groups (high and low state of glycemia) based on the median serum glucose concentration. We found a significant difference (P = 0.04) in percent GH among wild deer populations; serum glucose concentration did not differ (P = 0.72) among populations. Our results indicate that percent GH is more stable than serum glucose concentration and may be useful in population comparisons of nutritional condition.

Success in NCLEX-RN: identifying predictors and optimal timing for intervention.

This ex post facto study was designed to identify predictors of success in the NCLEX-RN and determine the optimal point in time for identifying students at risk. The convenience sample consisted of 407 graduates of an integrated, upper division, baccalaureate nursing program, 1984-1987. Prematriculation (total lower division GPA, science GPA, type of lower division College, age, and sex), junior year (three Nursing theory course grades) and pre graduation variables (three senior year nursing theory course grades and Mosby ASSESSTEST) were analyzed for predictive value. Nursing theory courses at the junior and senior year and the Mosby ASSESSTEST strongly correlated (p less than .0001) with NCLEX performance. Discriminant analysis enabled successful classification of 62% of the sample at prematriculation, 81% at the end of the junior year, and 86% at the end of the senior year. The study indicates that students at high risk can be identified at the end of the junior year so that enrichment and support programs can be introduced at that time.

Digiscan activity: automated measurement of thigmotactic and stereotypic behavior in rats.

Visual measures of stereotypy, margin time (thigmotaxis or wall-hugging), and center time were correlated with automated measures using a revised 16 beam version of the Digiscan Animal Activity Monitor System. Rats were injected with d-amphetamine (1.25, 2.5, 5.0 and 10.0 mg/kg), scopolamine (1.25 and 2.5 mg/kg) or saline and drugs were found to increase center time and decrease margin time in a dose-dependent manner, with the maximum effect occurring with 1.25 and 2.5 mg/kg, respectively. At higher doses, an opposite effect was observed. Extremely high correlations between visual and automated recordings of both margin time and center time were found. Since thigmotaxic or wall-hugging behavior has been used as an indicator of emotionality in rats, the results of the present study suggest that these two locomotor variables may be useful additions to the Digiscan multivariate analysis of locomotor behavior. It was also found that a redefinition of stereotypic behavior improved its correlation with visual measurements compared to earlier studies.

Endometriosis with ascites.

Endometriosis associated with massive ascites is an unusual combination unknown to most practicing gynecologists. Only 11 cases have been reported since this entity was first described by Brews in 1954. The authors report an additional case recently encountered at the Bethesda Naval Hospital. A review of the literature and tabular comparison of similarities among patients are presented. The possible etiologic mechanisms of the ascites are explored and recommendations for diagnosis and appropriate management are provided.

Benign hepatic adenoma associated with oral contraceptive use mimicking pelvic inflammatory disease. A case report.

An increased incidence of benign hepatic adenoma among users of oral contraceptives has been reported by several investigators during the past ten years. The majority of patients present with right-upper-quadrant pain, often associated with an upper abdominal mass. Our patient had an unusual clinical presentation simulating pelvic inflammatory disease. The appropriate diagnosis was reached with the aid of pelvic and abdominal sonography, liver-spleen scan and culdocentesis. The definitive management is partial hepatectomy, although there are reports of complete regression without surgery in minimally symptomatic patients following cessation of oral contraceptives.