Low vision aids provision in an urban setting in Germany between 2014 and 2017: a regional population based study with healthcare claims data.

PURPOSE: Little is known about the utilization of low vision services (LVS) in Germany. To understand which persons and how often these services would be utilized, this study aimed to investigate low vision aids (LVAs) provision in an urban setting and to describe user characteristics and trends in their characteristics. METHODS: A retrospective study based on a population-based healthcare claims database in Cologne (N = ~ 500,000), Germany. The study population comprised individuals, who were continuously insured at four large statutory health insurers and who redeemed a prescription for visual aids or aids for blindness between January 2014 and December 2017. We examined their socio-demographic and clinical characteristics. Trends in characteristics were examined with logistic and linear regression models over time. RESULTS: Out of ~ 500,000 persons, 781 unique individuals (~ 0.2%) redeemed an LVA prescription. They were mainly female (68.7%), 60 years or older (75.3%) and had macular degeneration (50.6%) and/or glaucoma (25.9%). In the working-age subgroup, 33.8% were employed. Visual aids were most often prescribed (74.1%) and of all types of LVAs, individuals most commonly redeemed a prescription for magnifiers (35.8%), screen readers (34.3%) and/or canes (17.1%). Of the entire study population, 75.4% received their prescription from an ophthalmologist, 5.3% from a general practitioner and 7.1% from other medical specialists. Significant trends in characteristics of individuals who redeemed an LVA prescription were not found. CONCLUSIONS: Between 2014 and 2017, 781 individuals in Cologne redeemed an LVA prescription. They had characteristics which mostly can be explained by the epidemiology of VI. Results indicate that individuals that redeemed LVAs have a magnification requirement of ≥ 1.5-fold and ≥ 6-fold. Furthermore, next to ophthalmologists, general practitioners and other medical specialists seem to play a role in LVA provision as well, which should be taken into account by policy makers when planning interventions for increasing LVS provision. Our findings provide a starting point to examine LVS provision in Germany.

The impact of automated, constant incomplete milking on energy balance, udder health, and subsequent performance in early lactation of dairy cows.

Incomplete milking (IM) is one way of mitigating the negative energy balance (NEB) that is characteristic for early lactation and may increase the risk for disease. Our objectives were to test the effects of IM in early lactation on energy balance (EB), metabolic status, udder health, and subsequent performance. To facilitate the practical application, an automated system was used to remove the milking clusters once a predefined amount of milk is withdrawn. Forty-six Holstein cows were equally allocated to either the treatment (TRT, starting on 8 d in milk) or the control group (CON; conventional cluster removal at milk flow rate <0.3 kg/min). Milk removal in the TRT group was limited to the individual cow's milk yield 1 d before IM started and held constant for 14 d. Thereafter, all cows were conventionally milked and records related to EB, performance, and udder health were continued up to 15 wk of lactation. During the 14 d of IM, on average 11.1% less milk was obtained from the TRT cows than from the CON cows. Thereafter, milk yield increased in the TRT group, eliminating the group difference throughout the remaining observation period until wk 15 of lactation. The TRT cows tended to have less dry matter intake and also water intake than the CON cows. The extent of the NEB and the circulating concentrations of fatty acids, ß-hydroxybutyrate, insulin-like growth factor-1, and leptin mostly did not differ between the groups. The IM did not affect body condition. Udder health was maintained over the entire observation period in all cows. Our results demonstrate the applicability of the automated cluster removal for limiting milk withdrawal to a defined amount in early lactation. However, it remains to be determined whether the absent effect on energy metabolism was due to the relatively stable energy status of the cows or to the relatively mild IM setting used herein.

Characteristics Associated With Clinically Important Treatment Responses in Women Undergoing Nonsurgical Therapy for Fecal Incontinence.

OBJECTIVE: To identify baseline clinical and demographic characteristics associated with clinically important treatment responses in a randomized trial of nonsurgical therapies for fecal incontinence (FI). METHODS: Women (N = 296) with FI were randomized to loperamide or placebo- and manometry-assisted biofeedback exercises or educational pamphlet in a 2 × 2 factorial design. Treatment response was defined in 3 ways from baseline to 24 weeks: minimal clinically important difference (MID) of -5 points in St. Mark's score, ≥50% reduction in FI episodes, and combined St. Mark's MID and ≥50% reduction FI episodes. Multivariable logistic regression models included baseline characteristics and treatment groups with and without controlling for drug and exercise adherence. RESULTS: Treatment response defined by St. Mark's MID was associated with higher symptom severity (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.11-1.28) and being overweight vs normal/underweight (aOR 2.15, 95% CI 1.07-4.34); these predictors remained controlling for adherence. Fifty percent reduction in FI episodes was associated with the combined loperamide/biofeedback group compared with placebo/pamphlet (aOR 4.04, 95% CI 1.36-11.98), St. Mark's score in the placebo/pamphlet group (aOR 1.29, 95% CI 1.01-1.65), FI subtype of urge vs urge plus passive FI (aOR 2.39, 95% CI 1.09-5.25), and passive vs urge plus passive FI (aOR 3.26, 95% CI 1.48-7.17). Controlling for adherence, associations remained, except St. Mark's score. DISCUSSION: Higher severity of FI symptoms, being overweight, drug adherence, FI subtype, and combined biofeedback and medication treatment were associated with clinically important treatment responses. This information may assist in counseling patients, regarding efficacy and expectations of nonsurgical treatments of FI.

Branched-chain amino acids: Abundance of their transporters and metabolizing enzymes in adipose tissue, skeletal muscle, and liver of dairy cows at high or normal body condition.

Branched-chain amino acids (BCAA) are major components of milk protein and important precursors for nonessential AA. Thus, the BCAA transport and break-down play a key role in the metabolic adaptation to the high nutrient demands in lactation. However, in monogastrics, increased BCAA levels have been linked with obesity and certain metabolic disorders such as impaired insulin sensitivity. Our objective was to study the effect of over-conditioning at calving on plasma BCAA levels as well as the tissue abundance of the most relevant BCAA transporters and degrading enzymes in dairy cows during late pregnancy and early lactation. Thirty-eight Holstein cows were allocated 15 wk antepartum to either a normal- (NBCS) or over-conditioned (HBCS) group, receiving 6.8 or 7.2 MJ of NEL/kg of DM, respectively, during late lactation to reach the targeted differences in body condition score (BCS) and back fat thickness (BFT; NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until dry-off. During the dry period and next lactation, cows were fed the same diets, whereby differences in BCS and BFT were maintained: prepartum means were 3.16 ± 0.06 and 1.03 ± 0.07 cm (NBCS) vs. 3.77 ± 0.08 and 1.89 ± 0.11 cm (HBCS), postpartum means were 2.89 ± 0.06 and 0.81 ± 0.05 cm (NBCS) vs. 3.30 ± 0.06 and 1.38 ± 0.08 cm (HBCS). Blood and biopsies from liver, semitendinosus muscle, and subcutaneous adipose tissue (scAT) were sampled at d 49 antepartum, 3, 21, and 84 postpartum. Free BCAA were analyzed and the mRNA abundance of solute carrier family 1 member 5 (SLC1A5), SLC7A5, and SLC38A2 as well as branched-chain aminotransferase 2 (BCAT2), branched-chain α-keto acid dehydrogenase E1α (BCKDHA), and branched-chain α-keto acid dehydrogenase E1ß (BCKDHB) as well as the protein abundance of BCKDHA were assessed. Concentrations of all BCAA changed with time, most markedly in HBCS cows, with a nadir around calving. Apart from Ile, neither individual nor total BCAA differed between groups. The HBCS group had greater BCKDHA mRNA as well as higher prepartum BCKDHA protein abundance in scAT than NBCS cows, pointing to a greater oxidative capacity for the irreversible degradation of BCAA transamination products in scAT of over-conditioned cows. Prepartum hepatic BCKDHA protein abundance was lower in HBCS than in NBCS cows. In both groups, SLC1A5, SLC7A5, and BCAT2 mRNA were most abundant in scAT, whereas SLC38A2 was higher in scAT and muscle compared with liver, and BCKDHA and BCKDHB mRNA were greatest in liver and muscle, respectively. Our results indicate that scAT may be a major site of BCAA uptake and initial catabolism, with the former, however, being independent of BCS and time relative to calving in dairy cows.

Dermatological moulage collections in the Nordic countries.

BACKGROUND: The art of producing and acquiring dermatological wax models, moulages, flourished all over Europe in the beginning of the twentieth century, whereas very little is known about the existence of moulage collections in the Nordic countries. OBJECTIVE: The aim of this study was to elucidate the presence, the origin, the production place, the use and the condition of dermatological moulage collections in the Nordic countries. METHODS: In each Nordic country, an extensive survey was undertaken during spring 2016. Dermatological departments, museums with medical collections, persons assumed to have specific information about wax moulages as well as secondary sources were contacted and interviewed. RESULTS: Several hitherto undescribed collections have survived in each country, most, however, damaged and in disrepair. One Danish and part of a Finnish collection have been restored. Only few moulages are exhibited and some have been photographed and digitalized. Denmark and Sweden have had a local moulage production. Responses to the survey indicate that the result covers all collections of dermatological moulages in the Nordic countries, though some moulages may remain in private collections unknown to the authors, or uncatalogued in museums. CONCLUSION: Moulages are medical gems from bygone days before modern technology facilitated new means of communication. Restoration and appropriate storing should be considered for at least selected items from the Nordic collections.

Candida inconspicua and Candida norvegensis: new insights into identification in relation to sexual reproduction and genome organization.

Candida inconspicua and Candida (Pichia) norvegensis are two emerging pathogenic species that exhibit reduced susceptibility to azole derivatives. Conventional (biochemical) approaches do not readily differentiate between the two species. The first aim of this work was to analyze the performance of biochemical, proteomic (matrix-assisted laser desorption ionization-time of flight [MALDI-TOF]), and molecular approaches in the precise identification of these species. These results then led us to sequence 3 genomic loci, i.e., the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA), the D1/D2 domain of the 28S rDNA, and the elongation factor 1α (EF-1α) gene, either directly or following cloning, of 13 clinical isolates and 9 reference strains belonging to the 5 species included in the Pichia cactophila clade, namely, Pichia cactophila, Pichia insulana, C. inconspicua, C. norvegensis, and P. pseudocactophila. Finally, isolates of C. inconspicua were challenged for sexual reproduction on the appropriate medium. Our results show that EF-1α sequencing and proteic profiling by MALDI-TOF are the two most efficient approaches to distinguish between C. norvegensis and C. inconspicua. As a characteristic of the P. cactophila clade, we found multiple alleles of the rDNA regions in certain strains belonging to the tested species, making ITS or D1/D2 sequencing not appropriate for identification. Whatever the method of identification, including MALDI-TOF and EF-1α sequencing, none could differentiate C. inconspicua from P. cactophila. The results of phylogenetic analysis and the generation of asci from pure cultures of all C. inconspicua strains both support the identification of P. cactophila as the teleomorph of C. inconspicua.

In vitro combination of voriconazole and miltefosine against clinically relevant molds.

Invasive infections caused by filamentous fungi are a major threat for immunocompromised patients. Innate/acquired resistance to antifungal drugs might necessitate combination therapies. We assessed the potential combination of voriconazole with miltefosine, an original drug with antifungal activity against 33 clinically relevant mold isolates, including both azole-susceptible and -resistant Aspergillus. Using complete inhibition as an endpoint, interactions were indifferent for 32/33 isolates. An alternative 50% inhibition endpoint showed synergistic interactions for 14/33 isolates. Antagonism was absent.

Aspergillus fumigatus harbouring the sole Y121F mutation shows decreased susceptibility to voriconazole but maintained susceptibility to itraconazole and posaconazole.

OBJECTIVES: Voriconazole, itraconazole and posaconazole are members of the azole family and widely used for the treatment of aspergillosis. They act by inhibiting the activity of the fungal Cyp51A enzyme. The emergence of environmental azole-resistant Aspergillus fumigatus strains raises major concerns for human health. METHODS: Recently, a new cyp51A-mediated resistance mechanism (namely TR46/Y121F/T289A) was described in clinical samples and patient-frequented environmental sites. In an azole-naive patient, we isolated an A. fumigatus strain that was not susceptible to voriconazole but was susceptible to itraconazole and posaconazole. RESULTS: A molecular analysis indicated a single Y121F substitution without the TR46 or T289A alterations, which to our knowledge has never been reported. Structure modelling and molecular dynamics offered an explanation for the resistance profile consistent with the structural differences between the three azoles. CONCLUSIONS: Taken together, these observations suggest an original mechanism conferring resistance to azoles mediated by cyp51A of environmental origin. This uncommon susceptibility pattern might represent a 'missing link' between the wild-type A. fumigatus and the fully azole-resistant strain harbouring the TR46/Y121F/T289A mutations.

Emergence of echinocandin-resistant Candida spp. in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?

Since their introduction in the 2000s, echinocandin drugs have become widely used for the treatment and prophylaxis of invasive fungal infections and, notably, invasive candidiasis. Although cases of breakthrough candidiasis in patients receiving echinocandins have been reported, clinical failure during echinocandin treatment due to the acquisition of resistance by a normally susceptible Candida spp. isolate is considered rare. To date, no publications have been published correlating the use of echinocandins and the emergence of echinocandin resistance among Candida species. So, our goal is to report an initial analysis of echinocandin use in relation to the emergence of resistant Candida isolates. We report here a single-centre experience of the emergence of eight resistant isolates belonging to normally susceptible Candida species in six patients receiving echinocandins. We describe the context and analyse the use of echinocandins over the previous decade. For seven of these isolates, we identified FKS gene mutations involved in decreased susceptibility. Seven isolates were obtained in 2011, on the heels of a ten-fold increase in caspofungin use over the preceding decade. In contrast, in 2012, the use of echinocandins decreased in our institution by 19.5 % and, in that year, only one Candida-resistant isolate was detected, despite the stable global epidemiology of invasive candidaemia. This work underlines the necessity of improving the prescription of antifungal drugs. Improvement in the monitoring of strain susceptibility should also be considered in order to better detect the emergence of resistant or non-susceptible yeast strains.

The genome of the simian and human malaria parasite Plasmodium knowlesi.

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.

Rapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin.

Echinocandin drugs are widely used for the treatment of candidemia. Resistance is considered rare, and only a few cases of breakthrough candidiasis in patients receiving echinocandin have been reported worldwide. We report here for the first time a Candida kefyr isolate that acquired echinocandin resistance very rapidly after the initiation of caspofungin treatment for candidemia. We characterized the FKS gene mutation responsible for the resistance via the comparison of isolates sampled before and during treatment.

Low levels of alitretinoin in seminal fluids after repeated oral doses in healthy men.

BACKGROUND: Alitretinoin, like all retinoids, is teratogenic, and can only be given to women of childbearing potential if pregnancy is excluded and a strict contraceptive programme is followed. AIM: This study was designed to determine whether alitretinoin in the semen of men treated with alitretinoin poses a teratogenic risk to their female partners. METHODS: In total, 24 healthy men aged 18-45 years received alitretinoin 20 mg (n = 12) or 40 mg (n = 12), once daily for 14 days. Subjects in the 40 mg dose group provided ejaculate at baseline, on day 1, before and approximately 4 h after dosing on day 2, and at follow-up on study day 21 (± 2). RESULTS: Alitretinoin and 4-oxo-alitretinoin were detected in 11 of the 12 semen samples. The highest level of alitretinoin in semen was 7.92 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be about 80 ng, 1/375,000 of a single 30 mg capsule. Complete absorption of 80 ng of alitretinoin from semen, presuming a volume of distribution confined to 5 L of circulating blood in the partner, would lead to an increase in plasma alitretinoin concentration of 0.016 ng/mL, which appears to be negligible compared with measured endogenous plasma levels. Increases in plasma levels of related retinoids are also negligible. CONCLUSIONS: Alitretinoin in the semen of men receiving up to 40 mg of oral alitretinoin per day is unlikely to be associated with teratogenic risk in their female partners. Barrier contraception is therefore not required for men taking alitretinoin.

Pharmacokinetic interactions between alitretinoin and ketoconazole or simvastatin or ciclosporin A.

BACKGROUND: Based on in vitro data with isolated cytochrome P450 (CYP) isoenzymes, alitretinoin interacts only with CYP3A4, and the potential for drug-drug interactions is considered negligible. AIM: To confirm in humans the lack of potential interactions between CYP3A4 and alitretinoin in vivo. METHODS: This was a multiple-dose, open-label, parallel-group, single-centre study, which enrolled 54 healthy male volunteers aged 18-45 years. Subjects were divided into three groups, with 18 in each group: group 1 received either alitretinoin 30 mg and ketoconazole 200 mg, group 2 alitretinoin 30 mg and simvastatin 40 mg, and group 3 alitretinoin 30 mg and ciclosporin A 300-mg. RESULTS: At the highest therapeutic dose of 30 mg, alitretinoin had no significant effect on the pharmacokinetics (PK) of ketoconazole and ciclosporin A. There was a significant but not clinically relevant effect of simvastatin on the area under the curve (AUC) of plasma concentration vs. time and on maximum plasma concentration (C(max)) after repeated administration of alitretinoin. Exposure to simvastatin concomitantly with alitretinoin was decreased by 16% for AUC and 23% for C(max). The CYP3A4 ± PgP substrates of simvastatin and ciclosporin A did not affect the single or repeated dose PK of alitretinoin. The strong CYP3A4/PgP inhibitor ketoconazole led to significant increases in both AUC and C(max) values for alitretinoin. CONCLUSIONS: Single and repeated doses of alitretinoin do not alter the PK of ciclosporin A and ketoconazole. Simvastatin levels were slightly but significantly reduced by co-administration of alitretinoin. Substrates of CYP3A4 did not affect the PK of alitretinoin. However, ketoconazole significantly increased the plasma levels of alitretinoin, therefore, co-administration with CYP3A4 inhibitors such as ketoconazole may require a dose reduction of alitretinoin.

Ischemic stroke on hormonal contraceptives: Characteristics, mechanisms and outcome.

INTRODUCTION: Systemic contraceptives increase the risk of ischemic stroke but little is known about the characteristics, mechanisms and long-term outcome post stroke of patients on hormonal contraception. We sought to To assess characteristics and outcome of acute ischemic stroke (AIS) in young women using systemic hormonal contraceptives (SHC) and compare them to strokes in non-contraceptive users. PATIENTS AND METHODS: Using the Acute STroke Registry and Analysis of Lausanne (ASTRAL), we analyzed demographics, risk factors, clinical, radiological and treatment data of consecutive female patients of <50 years between 2003 to 2015. We compared groups with and without SHC in a logistic regression analysis. RESULTS: Of the 179 female patients of <50 years during the observation period, 57 (39.6%) used SHC, 71.9% of whom, a combined oral contraceptive pill. On logistic regression contraceptive users were significantly younger but had comparable stroke severity. They had less migraine with aura and tobacco use, and more hyperlipidaemia. Also, contraceptive users had significantly less intra and extracranial stenosis and occlusion on arterial imaging, but more focal hypoperfusion on CT-perfusion. Undetermined mechanism of stroke was more frequent with SHC users, whereas rare mechanisms were more frequent in non-users. The contraceptive user group had a more favourable adjusted 12-month outcome with significantly fewer ischemic recurrences after stopping systemic contraception in all. CONCLUSION: Contraceptive users with ischemic strokes are younger and have lesser tobacco use and migraine with aura and more hyperlipidemia. Their stroke mechanism is more often undetermined using a standardised work-up, and their adjusted long-term outcome is more favourable with less stroke recurrence.

Toxicity evaluation of perfluorooctane sulfonate (PFOS) in the liver of common carp (Cyprinus carpio).

Perfluorooctane sulfonate (PFOS) has been manufactured for over 50 years in increasing quantities and has been used for several industrial and commercial aims. Due to persistence and bioaccumulation of this pollutant, it can be found worldwide in wildlife and humans. Biochemical effects of PFOS exposure are mainly studied in mammalian model species and information about effects on fish species remain largely scarce. This lack of toxicity data points out that there is an urgent need for the mechanistic molecular understanding of the mode of action of this pollutant. In the present study, common carp (Cyprinus carpio) was exposed through water for 14 days at concentrations of 0.1, 0.5 and 1 mg/l PFOS. Liver was selected as target tissue. Custom microarrays were constructed from cDNA libraries obtained with Suppression Subtractive Hybridization-Polymerase Chain Reaction (SSH-PCR) experiments. Microarray data revealed that the expression of several genes in the liver was influenced by PFOS exposure and real-time PCR was used to confirm these gene expression changes. The affected genes were mainly involved in energy metabolism, reproduction and stress response. Furthermore, the relative condition factor, the hepatosomatic index, and the available glycogen reserves of the exposed fish were significantly lower after 14 days of exposure than in the control fish. At all levels of biological organization, indications of a trade-off between the metabolic cost of toxicant exposure on one hand and processes vital to the survival of the organism on the other hand were seen. Our results support the prediction that increases in energy expenditure negatively affects processes vital to the survival of an organism, such as growth.

[What is needed for rTMS to become a treatment?]. / Que manque-t-il à la rTMS pour devenir une thérapie?

Repetitive trans-cranial magnetic stimulation (rTMS) can modulate cortical excitability. Consequently, it appears appealing for the treatment of some affections such as depression or hallucinations. There is already some proof that the concept is valid, but rTMS is slow in progressing in the therapeutic field as a true armamentum. Indeed its effects are of short duration and even inconstant from one patient to the next. These drawbacks depend on certain factors that we will discuss. Until now, there has been inadequate control of the stimulation site. It is possible that this site could vary on an individual basis. It seems logical to propose the use of functional imaging for such a purpose, but its use should be adapted to the symptom. Even after localizing the site, the coil has to be placed accurately. This could be facilitated by a neuronavigator. Stimulation protocols are currently defined by three parameters: the frequency modulating the cortical action either as a stimulation (>5 Hz) or an inhibition (<1 Hz), the intensity and the number of stimuli influencing, notably, the amplitude and duration of the effect. Unfortunately, the effect is inconstant in a given patient and paradoxical reactions have been observed in more than 15% of normal individuals. Improved reliability and amplification of the effect rely on the better control of other parameters: pattern of stimulation, pre and post-conditioning, state of the cortex during stimulation, associated medications, endogenous idiosyncratic factors and related pathology. We will review the current physiological literature to discuss the possible options that would constitute a rational basis for setting up more efficient protocols.

Performance of Aspergillus PCR in cerebrospinal fluid for the diagnosis of cerebral aspergillosis.

OBJECTIVES: Cerebral aspergillosis is a rare but often fatal form of invasive aspergillosis that remains difficult to diagnose. The literature has shown the value of Aspergillus PCR in blood-derived samples for the diagnosis of invasive aspergillosis but provides far less information for cerebrospinal fluid (CSF) in cerebral aspergillosis. Here, we evaluated the usefulness of an Aspergillus PCR assay performed on CSF for the diagnosis of cerebral aspergillosis. METHODS: This retrospective study involved 72 patients with suspected cerebral aspergillosis for a total of 88 CSF samples in whom CSF Aspergillus PCR was performed. RESULTS: Seventeen patients had proven/probable invasive aspergillosis according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, including 12 cases of proven/probable cerebral aspergillosis. Aspergillus PCR in CSF was positive in nine of the twelve patients with cerebral aspergillosis, i.e. 75% sensitivity. In contrast, CSF culture was positive for Aspergillus in only two patients. In the non-cerebral aspergillosis group (60 patients), PCR was positive in one patient, i.e. 98.3% specificity. In this particular population of high-risk patients with suspicion of cerebral aspergillosis, the disease incidence was 16.7%. Therefore, the positive and negative predictive values of PCR were 90% and 95.2%, respectively. CONCLUSION: The results of this study indicate that Aspergillus PCR in CSF is an interesting tool that may eliminate the need for cerebral biopsy in patients with suspected cerebral aspergillosis.

Why do people buy dogs with potential welfare problems related to extreme conformation and inherited disease? A representative study of Danish owners of four small dog breeds.

A number of dog breeds suffer from welfare problems due to extreme phenotypes and high levels of inherited diseases but the popularity of such breeds is not declining. Using a survey of owners of two popular breeds with extreme physical features (French Bulldog and Chihuahua), one with a high load of inherited diseases not directly related to conformation (Cavalier King Charles Spaniel), and one representing the same size range but without extreme conformation and with the same level of disease as the overall dog population (Cairn Terrier), we investigated this seeming paradox. We examined planning and motivational factors behind acquisition of the dogs, and whether levels of experienced health and behavior problems were associated with the quality of the owner-dog relationship and the intention to re-procure a dog of the same breed. Owners of each of the four breeds (750/breed) were randomly drawn from a nationwide Danish dog registry and invited to participate. Of these, 911 responded, giving a final sample of 846. There were clear differences between owners of the four breeds with respect to degree of planning prior to purchase, with owners of Chihuahuas exhibiting less. Motivations behind choice of dog were also different. Health and other breed attributes were more important to owners of Cairn Terriers, whereas the dog's personality was reported to be more important for owners of French Bulldogs and Cavalier King Charles Spaniels but less important for Chihuahua owners. Higher levels of health and behavior problems were positively associated with a closer owner-dog relationship for owners of Cavalier King Charles Spaniels and Chihuahuas but, for owners of French Bulldogs, high levels of problems were negatively associated with an intention to procure the same breed again. In light of these findings, it appears less paradoxical that people continue to buy dogs with welfare problems.

Discontinuation of echinocandin and azole treatments led to the disappearance of an FKS alteration but not azole resistance during clonal Candida glabrata persistent candidaemia.

To give an indication of a fitness cost conferred by FKS mutation-associated echinocandin resistance in Candida glabrata during human infection. Six C. glabrata clinical strains sequentially isolated from blood and a hepatic abscess in a solid organ transplant recipient were analysed. The patient had received long-term azole and echinocandin therapy for invasive aspergillosis and persistent candidaemia. Minimal inhibitory concentrations were determined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. Molecular mechanisms of antifungal resistance were determined by sequencing hot spots of the FKS. Strain relatedness was determined using a microsatellite-based typing method. Typing analysis revealed an identical microsatellite pattern for all isolates, supporting a close relation. The first C. glabrata isolate showed wild-type phenotype (i.e. susceptibility to echinocandins and low level of azole resistance). After voriconazole therapy, the C. glabrata quickly acquired pan-azole resistance. Later, echinocandin treatment led to the emergence of a FKS2 S663P alteration and echinocandin resistance. After disruption of both azole and echinocandin therapy in favour of liposomal amphotericin B, C. glabrata isolates regained full susceptibility to echinocandin and lost the FKS2 S663P alteration while nonetheless maintaining their pan-azole resistance. Our clinical report supports the potential existence of a fitness cost conferred by FKS mutation in C. glabrata, as disruption of treatment led to a rapid disappearance of the resistant clone. This suggests that a more restricted use and/or a discontinuous administration of echinocandins may limit the spread of clinical resistance to this class.