Phosphocalcic metabolism and its potential association with biomarkers of kidney disease in dogs with spontaneous hyperadrenocorticism.

The pathogenesis of increased serum phosphate concentration and proteinuria in dogs with spontaneous hyperadrenocorticism (HAC) is unclear. A potential link between proteinuria and calcium/phosphate metabolism has never been studied in dogs with HAC. The aims of the study were: (1) To evaluate calcium/phosphate metabolism in dogs with spontaneous HAC and compare to healthy dogs as well as to dogs with non-HAC illness; (2) to look for associations between markers of calcium/phosphate metabolism and biomarkers of kidney disease in dogs with HAC. Fifty-four dogs were included in the study, classified as HAC (n=27), non-HAC disease (n=17), and healthy (n=10). Serum calcium, phosphate, 25(OH)Vitamin D, 1,25(OH)2Vitamin D, plasma intact parathyroid hormone concentration (iPTH), FGF23, and urinary fractional excretion of calcium and phosphate were evaluated in all dogs at diagnosis and compared between each group. The correlation between these variables and urine protein-to-creatinine ratio (UPC) and urinary N-acetylglucosaminidase-to-creatinine ratio (uNAG/C) was evaluated in the HAC group. Medians [range] of serum phosphate concentration, urinary fractional excretion of calcium (FE(Ca)), and iPTH were significantly higher in dogs with HAC than in dogs with non-HAC illness (P<0.01) and healthy dogs (P<0.01). Increased 1,25(OH)2Vitamin D/25(OH)Vitamin D was also observed (P<0.001). In HAC group, UPC was significantly negatively correlated with 25(OH)Vitamin D (r(s): -0.54; P<0.01). Urinary NAG/C was significantly positively correlated with serum phosphate (r(s): 0.46; P=0.019). Increased serum phosphate, urinary excretion of calcium, and hyperparathyroidism were observed in dogs with HAC. Vitamin D metabolism may be shifted towards increased 1-alpha hydroxylation.

Description of serum symmetric dimethylarginine concentration and of urinary SDS-AGE pattern in dogs with ACTH dependent hyperadrenocorticism

Serum symmetric dimethylarginine (SDMA) and patterns of urinary protein separated by sodium dodecyl sulfate agarose gel electrophoresis (SDS-AGE) have not been investigated as biomarkers in dogs with ACTH-dependent hyperadrenocorticism (ADHAC). This exploratory prospective study aimed to evaluate SDMA, serum creatinine (sCR), and SDS-AGE in dogs with ADHAC with and without proteinuria (ADHAC-P and ADHAC-nP, respectively). Thirty-five pet dogs classified as ADHAC-P (n=16), ADHAC-nP (n=6) and healthy (n=13) were included. Renal biomarkers were evaluated in all dogs at diagnosis. Baseline concentration of SDMA was not significantly different between the three groups (P = 0.15) whereas sCr was significantly lower in dogs in ADHAC dogs compared to healthy dogs (88.0 µmol/L [70.4-132.6; 79.2-114.4]) whether they had proteinuria or not (P = 0.014 and 0.002, respectively). However, baseline concentrations of sCr and SDMA were not significantly different between dogs with ADHAC-P dogs (SDMA, 8 µg/dL [5-12; 7-9]; sCr, 57.2 µmol/L [35.2-212.2; 52.8-92.4]) and ADHAC-nP dogs (SDMA, 8.5 µg/dL [7-13; 8-10]; sCr, 70.4 µmol/L [61.6-79.2; 61.6-70.4]) (P = 0.35 and P = 0.41, respectively). Proteinuria in dogs with ADHAC-P was mainly of glomerular origin (SDS-AGE pattern: glomerular in 10/16 dogs; mixed glomerular/tubular in four dogs). In our study, SDMA was neither significantly different in dogs with ADHAC whether they were proteinuric or not, nor between ADHAC and healthy dogs. Urinary electrophoresis provides additional information to the UPC and further investigations are needed to determine whether it may help identify dogs with ADHAC-P requiring specific antiproteinuric treatment.

The prevalence of emotional abuse in children living in Sub-Saharan Africa - A systematic review.

OBJECTIVES: This study is meant to put a focus on the prevalence of emotional abuse in low-income states like the Sub-Saharan region. METHODOLOGY: Searching PubMed, Google scholar, and web of science during February and April 2021 a total of 2264 articles were identified, 27 met the inclusion criteria. We added the results of 13 VAC (Violence Against Children and Youth) studies, conducted by UNICEF capturing information about experienced sexual, physical, or emotional violence in 13-24-year-olds, as well as 56 MIC (Multiple Indicator Cluster) studies, conducted by the CDC to research the disciplinary methods used with children aged 1-14 years in the past month by older household members. Finally, in a meta-analytic approach, we aimed to calculate a pooled estimate of the prevalence. RESULTS: The included studies depicted a wide range in prevalence rates across countries. For example, while the VAC study in Lesotho in 2018 showed low incidence rates of emotional violence (6.9 % Females, 3.8 % Males), the average prevalence recorded by the MIC study was as high as 57.8 % for females and 59.2 % for males. On average, the MIC studies displayed a higher incidence and the discrepancy of prevalence of emotional abuse between females and males was small. Calculating a pooled estimate of the prevalence was not possible, due to the heterogeneity of the data. CONCLUSIONS: In general countries displayed a high prevalence. A standardized use of a uniform definition of emotional abuse might help to display a more homogenous data set in the future, giving the opportunity for pooled estimates of prevalence.

Urology mythbusters: Radiation and radiophobia.

In this episode of Mythbusters we critically examine the premise that there is strong biological and epidemiologic evidence that radiation exposure at levels associated with modern genitourinary diagnostic imaging increases the risk of subsequent malignancy, especially in children.

Improving handover between the transport team and neonatal intensive care unit staff in neonatal transports using the plan-do-study-act tool.

OBJECTIVES: The aim was to achieve 100% effective handover from the critical care transport team to the neonatal intensive care unit (NICU) medical team. STUDY DESIGN: All patients transferred from referring hospitals by the critical care transport team to the Level IV NICU were included. Data for each infant was collected prospectively. The percentage of transported patients for which medical team and nursing handover occurred was recorded. A quality improvement project was launched using the Plan-Do-Study-Act (PDSA) tool. We implemented several processes including call from the transport team before arrival and the completion of a transfer of care form on arrival to the NICU. The process measures and the outcome measure of completion of handover were monitored. Run charts of process measures and the outcome measure were analyzed. RESULTS: Completion of medical handover increased from 95% (baseline) to 100% after 3 PDSA cycles and this has been maintained for 18 consecutive months. CONCLUSION: Medical handover from the critical care transport team to the NICU medical staff has been achieved and sustained for all neonatal transports.

Comparative analyses of whole genome sequences of Leishmania infantum isolates from humans and dogs in northeastern Brazil.

The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99.95% identity with each other and slightly less identity with a reference L. infantum genome from a Spanish isolate. Despite the high identity, analysis of individual differences among the 32 million base pair genomes showed sufficient variation to allow the isolates to be clustered based on the primary sequence. A major source of variation detected was in chromosome somy, with only four of the 36 chromosomes being predominantly disomic in all 49 isolates examined. In contrast, chromosome 31 was predominantly tetrasomic/pentasomic, consistent with its regions of synteny on two different disomic chromosomes of Trypanosoma brucei. In the Brazilian isolates, evidence for recombination was detected in 27 of the 36 chromosomes. Clustering analyses suggested two populations, in which two of the five older isolates from the 1990s clustered with a majority of recent isolates. Overall the analyses do not suggest individual sequence variants account for differences in clinical outcome or adaptation to different hosts. For the first known time, DNA of isolates from asymptomatic subjects were sequenced. Of interest, these displayed lower diversity than isolates from symptomatic subjects, an observation that deserves further investigation with additional isolates from asymptomatic subjects.

Short-term outcomes of the multi-institutional bladder exstrophy consortium: Successes and complications in the first two years of collaboration.

INTRODUCTION/BACKGROUND: Bladder exstrophy is a rare diagnosis that presents major reconstructive challenges. To increase experience and proficiency in the care of bladder exstrophy (BE), the Multi-Institutional BE Consortium (MIBEC) was formed, with a focus on refining technical aspects of complete primary repair of bladder exstrophy (CPRE) and subsequent care. OBJECTIVE: Outcome measures included successful CPRE (absence of dehiscence), complications, and integrated points of technique and care over the short-term. STUDY DESIGN: Boston Children's Hospital, Children's Hospital of Philadelphia and Children's Hospital of Wisconsin alternately served as the host, with observation, commentary and critique by visiting collaborating surgeons. CPRE with bilateral iliac osteotomy was performed at 1-3 months of age. High-definition video capture of the surgery allowed local and distant broadcast to facilitate real-time observation and teaching, and recording of all procedures. RESULTS: From February 2013 to February 2015, MIBEC participating surgeons performed CPRE on 27 consecutive patients (22 classic BE, five epispadias). There were no dehiscences in 27 patients (0%, 95% CI 0-12.5%). Thirteen girls and 14 boys underwent CPRE at a median age of 2.3 months (range 0.1-51.6). One boy had a hypospadiac urethral meatus at CPRE completion. Hydronephrosis of mild or moderate grade was present postoperatively in eight girls and two boys. Additional results, per gender, are presented in the Summary table below. DISCUSSION: Absence of dehiscence in this cohort was comparable or compared favorably with the literature. However, several girls had significant obstructive complications following CPRE. The rate of bladder outlet obstruction (BOO) in girls was increased compared with published reports. A low complication rate was noted in the boys following CPRE, which was comparable to reports in the literature, and early signs of continence and spontaneous voiding were noted in some boys and girls. Limitations included variation in patient age at presentation, thereby introducing a wide age range at CPRE. Outcome data were limited by short follow-up regarding voiding with continence. CONCLUSION: This collaborative effort proved beneficial regarding significantly increased surgeon exposure to CPRE, refinement of CPRE technique, surgeon learning and expertise. Technical refinement of CPRE is ongoing.

Serial NIHSS scores in patients with acute cerebral infarction.

AIM: To study time course of neurological deficits in patients with acute cerebral infarction admitted shortly after stroke onset. METHODS: Serial NIHSS scores were obtained whenever feasible in patients admitted because of cerebral infarction within 3 h of symptom onset. Patients receiving and not receiving thrombolysis were compared. Short-term outcome was defined as NIHSS score and modified Rankin score 7 days after stroke onset. The hyperacute phase was defined as the time between stroke onset and the 6- to 9-h interval after stroke onset, acute phase as the time between the 6- to 9-h interval and the 21 to 27-h interval, and the subacute phase as the time between the 21- to 27-h interval and 7 days after stroke onset. RESULTS: Serial NIHSS scores were obtained in 552 patients within three hours of stroke onset. There was a significant improvement (P < 0.001) comprising 62% of the total improvement in the hyperacute phase. There was no significant improvement in the acute phase and a small significant improvement in the subacute phase (P < 0.01). CONCLUSION: Our study demonstrates a hyperacute phase with rapid improvement probably due to early recanalization, an acute phase with no significant improvement and slow improvement in the subacute phase. Different pathophysiological mechanisms are likely involved in the different phases.

Prepubertal presentation of varicocele does not affect outcomes.

INTRODUCTION: Varicoceles in prepubertal boys are uncommon and little is known of the natural history. Historically, a large percentage of these boys have undergone surgical repair with the belief that such early presentation carried a worse prognosis, making assessment of longitudinal outcomes difficult. OBJECTIVE: While there may be concern that varicocele could represent a progressive disease and therefore prepubertal presentation would portend a worse prognosis, we hypothesized that there would be no difference between the prepubertal boys and other adolescents with varicocele. STUDY DESIGN: We retrospectively reviewed a database of boys at a single institution with a documented left-sided varicocele between 1995 and 2011. Inclusion criteria were one or more of the following: 1. Clinician-documented Tanner 1 status, 2. Right testis orchidometric or ultrasound calculated volume of ≤3 cc's. Patients were drawn from a prospectively maintained database of all boys presenting to the outpatient urology clinic receiving a diagnosis of varicocele. A cohort of adolescent boys was assembled by matching as closely as possible with respect to testis volume disparity and grade of varicocele. All matches were within 2% of volume difference. Volume was calculated using the length*width*height*0.71 formula. Testis size disparity was set to a threshold of ≥20% using the Lambert formula: (VolumeRight - VolumeLeft)/VolumeRight*100%. Our primary outcome was defined as hypotrophy or the need for surgery for hypotrophy at the termination of the study. We planned a single subgroup analysis of boys based on presentation with or without hypotrophy. The decision for surgery or observation was made by the individual clinician at the time of patient assessment. RESULTS: On presentation, the prepubertal cohort was younger (10.8 vs 14.1 years), and with smaller left (2.4 vs 11.6 cc) and right (2.4 vs 11.6 cc) testis volume. There were no significant differences with respect to varicocele grade and volume differentials at presentation. At the end of the study, 76% of the prepubertal cohort had neither hypotrophy nor the requirement for operation, compared with 83% of the matched cohort (P = 0.71, Fisher's exact test). Similarly, there were no significant differences in outcome when comparing prepubertal boys with initial symmetry or hypotrophy to their matched cohort of older adolescents. DISCUSSION: The prepubertal varicocele is a rare clinical problem for which little data exists to guide the clinician. In a review of Pubmed indexed English language manuscripts, we were only able to find five papers with information on Tanner stage; only 31 prepubertal boys have longitudinal data reported. This study approximately doubles the number of boys for whom such data is available in the literature. Our chief limitation was sample size. A power analysis indicated that a final-analysis cohort of 90 prepubertal boys would be required to detect a 20% difference in outcome between that group and a matched cohort of pubertal or post-pubertal boys. We propose that given the lack of evidence for worse outcomes in prepubertal boys with varicocele that prepubertal status, in and of itself, not be considered an additional indication for correction of varicocele. CONCLUSION: In our retrospective cohort of prepubertal boys with left testis varicocele and their matched cohort, we did not detect a difference in the rate of good outcomes, defined as the absence of hypotrophy and lack of need for surgical intervention. While we may have suspected, as have others, that prepubertal presentation would have conveyed a more pressing need to intervene, it is likely that these boys represent the very same patients that we see more commonly later in their adolescence, and should thus be managed in a similarly conservative fashion.

Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats.

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect of in vivo activation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4 (LTB4, PPARα ligand) or 15deoxyΔ(12,14)prostaglandin J2 (15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4 and partially restored by 15dPGJ2 in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas.

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects.

Folic acid and safflower oil supplementation interacts and protects embryos from maternal diabetes-induced damage.

Maternal diabetes increases the risk of embryo malformations. Folic acid and safflower oil supplementations have been shown to reduce embryo malformations in experimental models of diabetes. In this study we here tested whether folic acid and safflower oil supplementations interact to prevent embryo malformations in diabetic rats, and analyzed whether they act through the regulation of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and nitric oxide (NO) and reactive oxygen species production. Diabetes was induced by streptozotocin administration prior to mating. From Day 0.5 of pregnancy, rats did or did not receive folic acid (15 mg/kg) and/or a 6% safflower oil-supplemented diet. Embryos and decidua were explanted on Day 10.5 of gestation for further analysis of embryo resorptions and malformations, MMP-2 and MMP-9 activities, TIMP-1 and TIMP-2 levels, NO production and lipid peroxidation. Maternal diabetes induced resorptions and malformations that were prevented by folic acid and safflower oil supplementation. MMP-2 and MMP-9 activities were increased in embryos and decidua from diabetic rats and decreased with safflower oil and folic acid supplementations. In diabetic animals, the embryonic and decidual TIMPs were increased mainly with safflower oil supplementation in decidua and with folic acid in embryos. NO overproduction was decreased in decidua from diabetic rats treated with folic acid alone and in combination with safflower oil. These treatments also prevented increases in embryonic and decidual lipid peroxidation. In conclusion, folic acid and safflower oil supplementations interact and protect the embryos from diabetes-induced damage through several pathways related to a decrease in pro-inflammatory mediators.

Ethical considerations in CYP2D6 genotype testing for codeine-prescribed breastfeeding mothers.

In this issue, Madadi et al. report on interviews with codeine-prescribed breastfeeding mothers concerning preferences and attitudes toward receiving their CYP2D6 genotype and overall study findings. We address three sets of ethics questions raised by this article. Should genetic information be disclosed to research participants in genetic research? What should clinicians take into account when considering this genetic test in managing infant opioid toxicity risk? What conditions support or hinder the integration of genetic information into patient care?

Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.

Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved in diabetic embryopathy. Previous works have found diminished concentrations of PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of increasing embryonic PGE(2) concentrations through the activation of the nuclear receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils, respectively. The aim of this study was to analyze the capability of dietary supplementation with either 6% olive or 6% safflower oils to regulate PGE(2), PGI(2) and NO concentrations in embryos and deciduas from control and diabetic rats during early organogenesis. Diabetes was induced by a single injection of streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil-supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were measured by EIA and NO through the evaluation of its stable metabolites nitrates-nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower oil-supplemented treatments highly reduced resorption and malformation rates in diabetic animals, and that they were able to prevent maternal diabetes-induced alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover, these dietary treatments prevented NO overproduction in embryos and deciduas from diabetic rats. These data indicate that in maternal diabetes both the embryo and the decidua benefit from the olive and safflower oil supplementation probably through mechanisms that involve the rescue of aberrant prostaglandin and NO generation and that prevent developmental damage during early organogenesis.

Predictors of use of health care services among elderly lung cancer patients: the first year after diagnosis.

In this study, we investigated predictors of utilization of physician, hospital, and emergency room services in a sample of 277 elderly patients during the first year following a diagnosis of lung cancer. Data were obtained by a combination of patient interview and patient self-administered questionnaire at four intervals: baseline (wave 1), 3 months (wave 2), 6 months (wave 3), and 12 months (wave 4). Of the 277 patients, 242 provided data at wave 1, 209 at wave 2, 157 at wave 3, and 115 at wave 4. Symptomatology was assessed with the Symptom Experience Scale (simple count of symptoms present, chosen from a list of 37 cancer-related symptoms), and physical functioning was assessed with the Medical Outcomes Study 36-Item Short Form Health Survey. Analysis of covariance models were implemented separately for the active treatment period (0-6 months) and the continuing care period (6-12 months) to determine how age, gender, comorbidity, length of survival, treatment status, stage of disease, cancer site, physical functioning, and symptom count were related to physician visits, nights in hospital, and emergency room visits. During the active treatment period, patients with worse physical functioning reported more hospital nights (p=0.002) and more emergency room visits (p=0.013), while men reported more frequent emergency room visits (p=0.032) and more nights in hospital (p=0.006) than women. Patients reporting more symptoms also reported more physician visits (p=0.020). During the continuing care period, physical functioning had a similar relation to hospital nights (p=0.005) and emergency room visits (p=0.003), and patients with late-stage disease reported more physician visits than patients with early-stage disease (p=0.003).

Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates.

An association between reduced susceptibility to echinocandins and changes in the 1,3-beta-d-glucan synthase (GS) subunit Fks1p was investigated. Specific mutations in fks1 genes from Saccharomyces cerevisiae and Candida albicans mutants are described that are necessary and sufficient for reduced susceptibility to the echinocandin drug caspofungin. One group of amino acid changes in ScFks1p, ScFks2p, and CaFks1p defines a conserved region (Phe 641 to Asp 648 of CaFks1p) in the Fks1 family of proteins. The relationship between several of these fks1 mutations and the phenotype of reduced caspofungin susceptibility was confirmed using site-directed mutagenesis or integrative transformation. Glucan synthase activity from these mutants was less susceptible to caspofungin inhibition, and heterozygous and homozygous Cafks1 C. albicans mutants could be distinguished based on the shape of inhibition curves. The C. albicans mutants were less susceptible to caspofungin than wild-type strains in a murine model of disseminated candidiasis. Five Candida isolates with reduced susceptibility to caspofungin were recovered from three patients enrolled in a clinical trial. Four C. albicans strains showed amino acid changes at Ser 645 of CaFks1p, while a single Candida krusei isolate had a deduced R1361G substitution. The clinical C. albicans mutants were less susceptible to caspofungin in the disseminated candidiasis model, and GS inhibition profiles and DNA sequence analyses were consistent with a homozygous fks1 mutation. Our results indicate that substitutions in the Fks1p subunit of GS are sufficient to confer reduced susceptibility to echinocandins in S. cerevisiae and the pathogens C. albicans and C. krusei.

Predictors of depressive symptomatology of geriatric patients with colorectal cancer: a longitudinal view.

Colorectal cancer constitutes a major health problem for elderly patients. The disease and its stage, treatment, and attendant symptoms can have significant negative impact on the mental functioning of these patients. As part of a larger longitudinal study, 158 patients 65 years of age or older with an incident diagnosis of colorectal cancer were recruited from 23 sites within a Midwestern state. Random effects regression analysis techniques were used to analyze how age, gender, race, presence of a family caregiver, co-morbid conditions, stage of disease at diagnosis, and the time-dependent variables marital status, employment status, symptoms, physical functioning, social functioning, and treatment predict depressive symptomatology at four assessments over the 1st year following diagnosis. Gender, race, co-morbid conditions, physical functioning, social functioning, and symptoms were significant predictors of depressive symptomatology over the four waves of the study. Female patients, African Americans, and patients with two or more co-morbid conditions exhibited more depressive symptomatology. Both more symptoms and more restricted physical and social functioning corresponded to higher levels of depressive symptomatology. At a clinical level of patient care, these findings mandate early identification of psychosocial difficulties experienced, an individualized symptom management plan and the application of other interventions, such as information giving, reassurance and referral to other resources, with particular attention to African American and female patients.

The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro.

Caspofungin acetate is an antifungal antibiotic that inhibits synthesis of 1,3-beta-D-glucan, an essential component of the fungal cell wall. While caspofungin causes cell death in yeasts and dimorphic fungi such as Candida albicans, its effect on Aspergillus fumigatus is less well understood. We used the fluorescent dyes 5,(6)-carboxyfluorescein diacetate (CFDA) and bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC), which stain live and dead cells, respectively, to further characterize the antifungal activity of caspofungin. For comparison, compounds whose mode of action was either fungistatic (fluconazole, itraconazole) or fungicidal (amphotericin B) were also evaluated. A correlation between caspofungin-induced loss of viability, decreased CFDA staining, and increased DiBAC staining was established first with C. albicans. For A. fumigatus, caspofungin caused similar dye-staining changes, which were quantified by fluorimetric analysis of stained hyphae grown in a medium that promoted dispersed growth. The minimum concentration of caspofungin required to produce these changes also decreased the level of growth-dependent reduction of the indicator dye Alamar Blue. We observed a differential effect of caspofungin as a function of cell position: 88% of apical cells and 61% of subapical branching cells failed to stain with the viable dye CFDA, but only 24% of subapical cells were unstained. Complementary results were seen with germlings from DiBAC-stained, caspofungin-treated cultures. Extended incubation of A. fumigatus with a single dose of caspofungin affected the same proportion of apical and subapical branching cells for up to 72 h. The dye-staining patterns illustrate that the cells at the active centers for new cell wall synthesis within A. fumigatus hyphae are killed when they are exposed to caspofungin.