Temporal trends of extended-spectrum cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae isolates in in- and outpatients in Switzerland, 2004 to 2011

Increasing trends for invasive infections with extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae have been described in many countries worldwide. However, data on the rates of ESC-R isolates in non-invasive infections and in the outpatient setting are scarce. We used a laboratory-based nationwide surveillance system to compare temporal trends of ESC-R rates in Escherichia coli and Klebsiella pneumoniae for in- and outpatients in Switzerland. Our data showed a significant increase in ESC-R rates from 1% to 5.8% in E. coli (p<0.001) and from 1.1% to 4.4% in K. pneumoniae (p=0.002) during an eight-year period (2004–2011). For E. coli, the increase was significantly higher in inpatients (from 1.2% to 6.6%), in patients residing in eastern Switzerland (from 1.0% to 6.2%), in patients older than 45 years (from 1.2% to 6.7%), and in male patients (from 1.2% to 8.1%). While the increase in inpatients was linear (p<0.001) for E. coli, the increase of ESC R K. pneumoniae isolates was the result of multiple outbreaks in several institutions. Notably, an increasing proportion of ESC-R E. coli was co-resistant to both trimethoprim-sulfamethoxazole and quinolones (42% in 2004 to 49.1% in 2011, p=0.009), further limiting the available oral therapeutic options.

β-Glucan Antigenemia Anticipates Diagnosis of Blood Culture–Negative Intraabdominal Candidiasis

Rationale: Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established. Objectives: The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC. Methods: Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared. Measurements and Main Results: Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46–9,557) in IAC versus 99 pg/ml (8–440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse. Conclusions: BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture–negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study

Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients.

Early follicular testosterone level predicts preference for masculinity in male faces — But not for women taking hormonal contraception

It has been shown that women’s preference for masculinity in male faces changes across the menstrual cycle. Preference for masculinity is stronger when conception probability is high than when it is low. These findings have been linked to cyclic fluctuations of hormone levels. The purpose of the present study is to further investigate the link between gonadal steroids (i.e. testosterone, estradiol, and progesterone) and masculinity preference in women, while holding the cycle phase constant. Sixty-two female participants were tested in their early follicular cycle phase, when conception probability is low. Participants were shown face pairs and where asked to choose the more attractive face. Face pairs consisted of a masculinized and feminized version of the same face. For naturally cycling women we found a positive relationship between saliva testosterone levels and masculinity preference, but there was no link between any hormones and masculinity preference for women taking hormonal contraception. We conclude that in naturally cycling women early follicular testosterone levels are associated with masculinity preference. However, these hormonal links were not found for women with artificially modified hormonal levels, that is, for women taking hormonal contraception.

Microcystic macular edema: retrograde maculopathy caused by optic neuropathy

PURPOSE To investigate retrograde axonal degeneration for its potential to cause microcystic macular edema (MME), a maculopathy that has been previously described in patients with demyelinating disease. To identify risk factors for MME and to expand the anatomic knowledge on MME. DESIGN Retrospective case series. PARTICIPANTS We included 117 consecutive patients and 180 eyes with confirmed optic neuropathy of variable etiology. Patients with glaucoma were excluded. METHODS We determined age, sex, visual acuity, etiology of optic neuropathy, and the temporal and spatial characteristics of MME. Eyes with MME were compared with eyes with optic neuropathy alone and to healthy fellow eyes. With retinal layer segmentation we quantitatively measured the intraretinal anatomy. MAIN OUTCOME MEASURES Demographic data, distribution of MME in the retina, and thickness of retinal layers were analyzed. RESULTS We found MME in 16 eyes (8.8%) from 9 patients, none of whom had multiple sclerosis or neuromyelitis optica. The MME was restricted to the inner nuclear layer (INL) and had a characteristic perifoveal circular distribution. Compared with healthy controls, MME was associated with significant thinning of the ganglion cell layer and nerve fiber layer, as well as a thickening of the INL and the deeper retinal layers. Youth is a significant risk factor for MME. CONCLUSIONS Microcystic macular edema is not specific for demyelinating disease. It is a sign of optic neuropathy irrespective of its etiology. The distinctive intraretinal anatomy suggests that MME is caused by retrograde degeneration of the inner retinal layers, resulting in impaired fluid resorption in the macula.

Preservation and representation of human bones and it's importance for anthropological Analysis - an introduction

This paper presents problems arising from the lack of standardized methods for recording skeletal remains. Using practical examples it is shown how preservation and representation of bones can distort observations and how this can be reduced by systematic data acquisition.

Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport

2-Aminoethyl diphenylborinate (2-APB) is a known modulator of the IP3 receptor, the calcium ATPase SERCA, the calcium release-activated calcium channel Orai and TRP channels. More recently, it was shown that 2-APB is an efficient inhibitor of the epithelial calcium channel TRPV6 which is overexpressed in prostate cancer. We have conducted a structure-activity relationship study of 2-APB congeners to understand their inhibitory mode of action on TRPV6. Whereas modifying the aminoethyl moiety did not significantly change TRPV6 inhibition, substitution of the phenyl rings of 2-APB did. Our data show that the diaryl borinate moiety is required for biological activity and that the substitution pattern of the aryl rings can influence TRPV6 versus SOCE inhibition. We have also discovered that 2-APB is hydrolyzed and transesterified within minutes in solution.

The SLC1 high-affinity glutamate and neutral amino acid transporter family

Glutamate transporters play important roles in the termination of excitatory neurotransmission and in providing cells throughout the body with glutamate for metabolic purposes. The high-affinity glutamate transporters EAAC1 (SLC1A1), GLT1 (SLC1A2), GLAST (SLC1A3), EAAT4 (SLC1A6), and EAAT5 (SLC1A7) mediate the cellular uptake of glutamate by the co-transport of three sodium ions (Na(+)) and one proton (H(+)), with the counter-transport of one potassium ion (K(+)). Thereby, they protect the CNS from glutamate-induced neurotoxicity. Loss of function of glutamate transporters has been implicated in the pathogenesis of several diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. In addition, glutamate transporters play a role in glutamate excitotoxicity following an ischemic stroke, due to reversed glutamate transport. Besides glutamate transporters, the SLC1 family encompasses two transporters of neutral amino acids, ASCT1 (SLC1A4) and ASCT2 (SLC1A5). Both transporters facilitate electroneutral exchange of amino acids in neurons and/or cells of the peripheral tissues. Some years ago, a high resolution structure of an archaeal homologue of the SLC1 family was determined, followed by the elucidation of its structure in the presence of the substrate aspartate and the inhibitor d,l-threo-benzyloxy aspartate (d,l-TBOA). Historically, the first few known inhibitors of SLC1 transporters were based on constrained glutamate analogs which were active in the high micromolar range but often also showed off-target activity at glutamate receptors. Further development led to the discovery of l-threo-β-hydroxyaspartate derivatives, some of which effectively inhibited SLC1 transporters at nanomolar concentrations. More recently, small molecule inhibitors have been identified whose structures are not based on amino acids. Activators of SLC1 family members have also been discovered but there are only a few examples known.

Investigations on an egyptian coffin and mummified head from Burgdorf Museum, Switzerland - A case of a historical puzzle

In the Burgdorf Museum of Ethnology, a mummy rests in a coffin. According to the inventory book, it was purchased from the Cairo Egyptian museum in 1926. The coffin was now examined by Egyptologists and the mummy was radiocarbon dated and examined by Anthropologists. The aim of the study was to compare the results and to check whether mummy and coffin actually belong together. The skull was examined morphological-anthropologically and by CT as a “blank sample”. Coffin and skull imply that the individual was female. The coffin dates to the Ptolemaic period. Only skull bones are preserved, the ethmoid is damaged. CT images Show resinous substances, bone fragments and brain remnants inside the skull. The ethmoid bone was probably foraminated during the mummification process and thus ended up inside the skull. The individual was mummified between the New Kingdom and the Ptolemaic period. Due to its style, it is most probable that the coffin comes from the Gamhud necropolis. The Burgdorf museum of ethnology inventory book chronicles were largely falsified by the examinations. There is a time gap between coffin and the mummy, there are two possible interpretations: the body was mummified with older linen, or the mummy and the coffin do not belong together. The authors strongly advise further investigations.

Development of an ultrasound-guided technique for pudendal nerve block in cat cadavers.

The objective of this prospective experimental cadaveric study was to develop an ultrasound-guided technique to perform an anaesthetic pudendal nerve block in male cats. Fifteen fresh cadavers were used for this trial. A detailed anatomical dissection was performed on one cat in order to scrutinise the pudendal nerve and its ramifications. In a second step, the cadavers of six cats were used to test three different ultrasonographic approaches to the pudendal nerve: the deep dorso-lateral, the superficial dorso-lateral and the median transperineal. Although none of the approaches allowed direct ultrasonographical identification of the pudendal nerve branches, the deep dorso-lateral was found to be the most advantageous one in terms of practicability and ability to identify useful and reliable landmarks. Based on these findings, the deep dorso-lateral approach was selected as technique of choice for tracer injections (0.1 ml 1% methylene blue injected bilaterally) in six cat cadavers distinct from those used for the ultrasonographical study. Anatomical dissection revealed a homogeneous spread of the tracer around the pudendal nerve sensory branches in all six cadavers. Finally, computed tomography was performed in two additional cadavers after injection of 0.3 ml/kg (0.15 ml/kg per each injection sites, left and right) contrast medium through the deep dorso-lateral approach in order to obtain a model of volume distribution applicable to local anaesthetics. Our findings in cat cadavers indicate that ultrasound-guided pudendal nerve block is feasible and could be proposed to provide peri-operative analgesia in clinical patients undergoing perineal urethrostomy.

Multiple osteosclerotic lesions in an Iron Age skull from Switzerland (320 - 250 BC) - An unusual case

The single Hochdorf burial was found in 1887 during construction work in the Canton of Lucerne, Switzerland. It dates from between 320 and 250 BC. The calvarium, the left half of the pelvis and the left femur were preserved. The finding shows an unusual bony alteration of the skull. The aim of this study was to obtain a differential diagnosis and to examine the skull using various methods. Sex and age were determined anthropologically. Radiological examinations were performed with plain X-ray imaging and a multislice computed tomography (CT) scanner. For histological analysis, samples of the lesion were taken. The pathological processing included staining after fixation, decalcification, and paraffin embedding. Hard-cut sections were also prepared. The individual was female. The age at death was between 30 and 50 years. There is an intensely calcified bone proliferation at the right side of the os frontalis. Plain X-ray and CT imaging showed a large sclerotic lesion in the area of the right temple with a partly bulging appearance. The inner boundary of the lesion shows multi-edged irregularities. There is a diffuse thickening of the right side. In the left skull vault, there is a mix of sclerotic areas and areas which appear to be normal with a clear differentiation between tabula interna, diploë and tabula externa. Histology showed mature organised bone tissue. Radiological and histological findings favour a benign condition. Differential diagnoses comprise osteomas which may occur, for example, in the setting of hereditary adenomatous polyposis coli related to Gardner syndrome.

Pharmacokinetics of GHB and detection window in Serum and Urine after single uptake of a low dose of GLB - an Experiment with two volunteers

During the last few years γ-hydroxybutyric acid (GHB) and γ-butyrolactone (GBL) have attracted much interest as recreational drugs and knock-out drops in drug-facilitated sexual assaults. This experiment aims at getting an insight into the pharmacokinetics of GHB after intake of GBL. Therefore Two volunteers took a single dose of 1.5 ml GBL, which had been spiked to a soft drink. Assuming that GBL was completely metabolized to GHB, the corresponding amount of GHB was 2.1 g. Blood and urine samples were collected 5 h and 24 h after ingestion, respectively. Additionally, hair samples (head hair and beard hair) were taken within four to five weeks after intake of GBL. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after protein precipitation with acetonitrile. The following observations were made: spiked to a soft drink, GBL, which tastes very bitter, formed a liquid layer at the bottom of the glass, only disappearing when stirring. Both volunteers reported weak central effects after approximately 15 min, which disappeared completely half an hour later. Maximum concentrations of GHB in serum were measured after 20 min (95 µg/ml and 106 µg/ml). Already after 4-5 h the GHB concentrations in serum decreased below 1 µg/ml. In urine maximum GHB concentrations (140 µg/ml and 120 µg/ml) were measured after 1-2 h, and decreased to less than 1 µg/ml within 8-10 h. The Ratio of GHB in serum versus blood was 1.2 and 1.6

Use of a Th1 Stimulator Adjuvant for Vaccination against Neospora caninum Infection in the Pregnant Mouse Model

Vertical transmission from an infected cow to its fetus accounts for the vast majority of new Neospora caninum infections in cattle. A vaccine composed of a chimeric antigen named recNcMIC3-1-R, based on predicted immunogenic domains of the two microneme proteins NcMIC1 and NcMIC3, the rhoptry protein NcROP2, and emulsified in saponin adjuvants, significantly reduced the cerebral infection in non-pregnant BALB/c mice. Protection was associated with a mixed Th1/Th2-type cytokine response. However, the same vaccine formulation elicited a Th2-type immune response in pregnant mice and did not prevent vertical transmission or disease, neither in dams nor in offspring mice. In this study, an alternative vaccine formulation containing recNcMIC3-1-R emulsified in Freund’s incomplete adjuvant, a stimulator of the cellular immunity, was investigated. No protection against vertical transmission and cerebral infection in the pregnant mice and a very limited protective effect in the non-pregnant mice were observed. The vaccine induced a Th1-type immune response characterized by high IgG2a titres and strong IFN-γ expression, which appeared detrimental to pregnancy.