Whole-genome sequencing reveals two prolonged simultaneous outbreaks involving Pseudomonas aeruginosa high-risk strains ST111 and ST235 with resistance to quaternary ammonium compounds.

OBJECTIVE: Water-bearing systems are known as frequent Pseudomonas aeruginosa (PA) outbreak sources. However, many older buildings continue to have sanitary facilities in high-risk departments such as the ICU. We present two simultaneous prolonged multi-drug-resistant (MDR) PA outbreaks detected at the ICU of a pulmonology hospital, which were resolved by whole-genome sequencing (WGS). METHODS: Outbreak management and investigations were initiated in August 2019 after detecting two patients with nosocomial VIM-2-positive MDR PA. The investigations involved weekly patient screenings for four months and extensive environmental sampling for 15 months. All patient and environmental isolates were collected and analysed by WGS. RESULTS: From April to September 2019, we identified 10 patients with nosocomial MDR PA, including five VIM-2-positive strains. VIM-2-positive strains were also detected in nine sink drains, two toilets, and a cleaning bucket. WGS revealed that of 16 VIM-2-positive isolates, 14 were ST111 that carried qacE, or qacEΔ1 genes, whereas 13 isolates clustered (difference of ≤11 alleles by cgMLST). OXA-2 (two toilets), and OXA-2, OXA-74, PER-1 (two patients, three toilets) qacEΔ1-positive ST235 isolates dominated among VIM-2-negative isolates. The remaining seven PA strains were ST17, ST233, ST273, ST309 and ST446. Outbreak containment was achieved by replacing U-bends, and cleaning buckets, and switching from quaternary ammonium compounds (QUATs) to oxygen-releasing disinfectant products. CONCLUSION: Comprehension and management of two simultaneous MDR PA outbreaks involving the high-risk strains ST111 and ST235 were facilitated by precise control due to identification of different outbreak sources per strain, and by the in-silico detection of high-level QUATs resistance in all isolates.

Comparison of autochthonous and imported cases of hepatitis A or hepatitis E.

BACKGROUND: Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. AIMS: The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. METHODS: Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). RESULTS: Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). CONCLUSIONS: (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases.

Influence of intracervical and intravaginal seminal plasma on the endometrium in assisted reproduction: a double-blind, placebo-controlled, randomized study.

OBJECTIVE: To investigate the effect of intracervical and intravaginal application of seminal plasma on the endometrium, as assessed by endometrial/subendometrial vascularization and endometrial volume between the day of oocyte retrieval and the day of embryo transfer in an in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle. METHODS: This was a double-blind, placebo-controlled, randomized study including patients undergoing a first or second IVF/ICSI cycle. Homologous seminal plasma or placebo (sodium chloride) was injected into the cervix and posterior vaginal fornix just after follicle aspiration. Three-dimensional power Doppler examination was performed 30 min before oocyte retrieval and 30 min before embryo transfer. Main outcome measures were changes in vascularization flow index (VFI), flow index (FI) and vascularization index (VI) of the endometrium/subendometrium using VOCAL™ (Virtual Organ Computer-aided AnaLysis) and endometrial volume. RESULTS: One hundred patients agreed to participate in the study. Twenty-three patients were excluded, mainly as a result of canceled embryo transfer. Data were analyzed from 40 patients receiving seminal plasma and 37 receiving placebo. No significant differences between the two groups were seen in VFI, FI or VI of the endometrium or subendometrium or in endometrial volume on the day of oocyte pick-up and on the day of embryo transfer. CONCLUSION: Neither endometrial/subendometrial vascularization parameters nor endometrial volume seem to be affected by the application of seminal plasma in patients undergoing their first or second IVF/ICSI cycle.

Giant cell hepatitis: an unusual cause of fulminant liver failure.

Giant cell hepatitis is a very rare disease of unknown origin. It has been hypothesized that drugs, viral infections, or autoimmune reactions may play a pathogenetic role. Here, we describe a 33 year old patient with bacterial bronchitis who was treated with doxycycline (100 mg/d) for one week. Furthermore the patient complained of malaise and a distinct jaundice. Liver parameters increased dramatically (AST 4670 U/l, ALT 5350 U/l, bilirubin 226 µmol/l) and liver function was impaired (INR = 1,45). The ultrasound scan showed a hepatomegaly with no signs of cirrhosis, normal spleen size and normal bile ducts; liver perfusion was normal. No evidence of Wilson's disease, hemochromatosis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis, hepatitis A, B, C and E, HIV, CMV, VZV, adenoviral infections, or paracetamol intoxication was found. Subsequently, the patient developed acute liver failure (AST 2134 U/l, ALT 2820 U/l, bilirubin 380 µmol/l, INR 3.0) and a beginning renal failure. Therefore, he was transferred to our transplant center. Due to increasing confusion and somnolence due to cerebral edema mechanical ventilation was needed. Because of an acute renal failure and severe hepatic encephalopathia MARS-hemodialysis was performed. Three weeks after the appearance of the jaundice he underwent liver transplantation (MELD 40). Surprisingly, in the explanted liver the diagnosis of giant cell hepatitis was made. Today--2 years after successful liver transplantation--the patient is in very good condition with normal liver function. In conclusion, giant cell hepatitis is a rare cause of acute liver failure that is often recognized only histologically.

Prospective hatching of embryos developed from oocytes exhibiting difficult oolemma penetration during ICSI.

BACKGROUND: The hormonal milieu during ovarian stimulation is known to affect oolemma behaviour as well as zona pellucida thickness and structure. This led us to investigate whether a special subgroup of patients with oocytes where penetration of the oolemma is difficult during ICSI may benefit from assisted hatching. METHODS: A total of 77 couples (mean age: 32.9 +/- 4.6 years; range: 22-38) had oocytes that could hardly be penetrated by the ICSI pipette. Nineteen patients underwent two ICSI cycles, giving a total number of 96 cycles, which were randomly split into either the study group (n = 52) or the non-hatching group (n = 44). Hatching was done using a non-contact 1.48 mm wavelength diode laser. Implantation and pregnancy rates were recorded. RESULTS: The pregnancy rate was 36.6% (19/52) in the study group and 13.6% (6/44) in the non-hatching group (P < 0.05). In addition, a higher number (P < 0.05) of embryos implanted in the study group (23/106; 21.7%) than in the non-hatching group (9/92; 9.8%). CONCLUSIONS: Once oolema penetration during ICSI has proven difficult, prospective hatching of embryos considered for transfer may increase their implantation behaviour.

Laser assisted immobilization of spermatozoa prior to intracytoplasmic sperm injection in humans.

BACKGROUND: The conventional method of immobilization of spermatozoa prior to intracytoplasmic sperm injection (ICSI) is mechanical breakage of the tail by pressing it against the bottom of the injection dish. METHODS: This prospective self-controlled study was set up to evaluate the potential of a non-contact 1.48 microm wavelength diode laser in terms of immobilization. In addition, the fertilization rate and further development potential of such zygotes were investigated. The patients included in our study (n = 60) had oestradiol concentrations >2000 pg/ml, and thus a relatively high number of MII oocytes could be expected. Approximately half the oocytes were injected with laser treated spermatozoa (n = 262, study group) and the other half with mechanically immobilized spermatozoa (n = 252, control group). RESULTS: No significant differences between the two groups in terms of fertilization rate, early cleavage or blastocyst formation were observed. However, time required for identification, aspiration and injection of a potential spermatozoa was significantly shorter in the laser immobilized sperm group (P < 0.001). CONCLUSIONS: The application of a non-contact diode laser for sperm immobilization prior to ICSI is a potentially useful alternative to the conventional mechanical approach.

Three-dimensional endometrial volume estimation as a predictor of pituitary down-regulation in an IVF-embryo transfer programme.

To examine the role of three-dimensional (3D) volume estimation in predicting pituitary down-regulation in an IVF-embryo transfer programme, 46 women were treated with buserelin acetate for down-regulation prior to and concomitantly with ovarian stimulation. Receiver operating characteristic (ROC) curve analysis was used for statistics. The area under the curve (AUC) provides a measure to show how good (AUC close to 1) or how poor (AUC close to 0.5) a test is. If down-regulation was defined as oestradiol <40, <60 or <80 pg/ml, the AUC of 3D-ultrasound was 0.57, 0.83 and 0.97 respectively. The highest sensitivity (100%) and specificity (93.2%) of 3D-ultrasound was achieved if down-regulation was defined as oestradiol <80 pg/ml (n = 44), with an endometrial volume of 1.9 ml. If down-regulation was defined as oestradiol <60 pg/ml (n = 42) the best combination of highest sensitivity (95.2%) and specificity (75. 0%) was obtained with an endometrial volume of 1.9 ml. The comparison of 3D volume calculation with endometrial thickness measurement revealed no significant difference in predicting down-regulation. 3D volume estimation provides a new tool for diagnosing relative hypo-oestrogenism or down-regulation, but it was not superior to two-dimensional ultrasound.

Conformational analysis of 2-hydroxy-2',5'-diazachalcones.

Spatial arrangement of 2-hydroxy-2',5'-diazachalcones was studied by means of infrared and NMR spectral data and molecular models calculations. The models were calculated in vacuum using semi-empirical AM1 method (software HyperChem 5.1). The initial geometries of the molecules were built by means of standard parameters and then optimized by Polak-Ribiere geometrical optimization. It was found that (E)-s-cis-conformers with synperiplanar arrangement of C-alpha and C-6 have the lowest heats of formation (standard heat of formation).

Elective transfer of embryos selected on the basis of first polar body morphology is associated with increased rates of implantation and pregnancy.

OBJECTIVE: To determine the relationship between first polar body morphology and implantation rate and pregnancy rate (PR), to facilitate decision making concerning elective ET. DESIGN: Prospective, randomized study. SETTING: Fertility center. PATIENT(S): One hundred fifty-eight consecutive patients (173 intracytoplasmic sperm injection cycles) resulting in embryo transfers. INTERVENTION(S): In our study group, priority in ET was given to embryos derived from well-shaped first polar bodies, whereas selection of embryos for transfer in the control group was based exclusively on the degree of embryo fragmentation. MAIN OUTCOME MEASURE(S): Total numbers of implantations and pregnancies, PR and implantation rate, and rates of multiple pregnancy and miscarriage. RESULT(S): In the study cohort, 212 embryos were transferred. In the control group, 313 embryos were transferred. The implantation rate and PR were significantly lower in the control group than in the study cohort. In addition, the rate of multiple pregnancy was significantly higher in the study group. CONCLUSION(S): Elective transfer of embryos selected on the basis of first polar body morphology results in higher implantation and pregnancy rates. Multiple pregnancy can be avoided by transferring a reduced number of embryos selected on the basis of first polar body morphology.

Different transfers of N-acetyl-p-aminobenzoic acid and p-aminobenzoic acid across the placenta and the small intestine in rats.

The aim of the present study was to evaluate the transfer of N-acetyl-p-aminobenzoic acid (AcPABA) across the rat term placenta and the rat small intestine and to compare it with that of its parent drug p-aminobenzoic acid (PABA). Umbilical perfusion of the rat term placenta was used to determine the materno-fetal transfer. AcPABA appeared in the fetal compartment significantly more slowly than PABA (k transfer = 0.023 and 0.064 min(-1), respectively). The rate of equilibration between the maternal and fetal compartments was slightly lower for AcPABA than for the parent drug (k eqilibration = 0.0082 and 0.011 min(-1), respectively). Similarly, AcPABA was shown to be absorbed from the small intestine significantly more slowly than PABA (ka = 0.052 and 0.82 min(-); tmax = 37 and 3.1 min, respectively). Our results showed that both investigated compounds which are structurally related and very similar in their physical-chemical characteristics crossed both the placental and small intestinal barrier with a different kinetics. AcPABA was transported across both barriers significantly more slowly than its parent compound, which might indicate a possible equipment of the placenta with a carrier for PABA, a similar one to that previously found in the rat small intestine.

[Substances affecting the synthesis and activity of leukotrienes]. / Slouceniny ovlivnujicí tvorbu a pusobení leukotrienu.

Leukotrienes play an important role in inflammation and asthma. This paper briefly deals with compounds influencing leukotriene biosynthesis and activity. 5-Lipoxygenase inhibitors (e.g., zileuton) and FLAP inhibitors (e.g., quiflapon) hinder biosynthesis of all leukotrienes. LTB4 production may be limited by LTA4-hydrolase inhibitors. Attention is also paid to leukotriene receptor antagonists. LTB4 antagonists (e.g., SC-51146) should be useful in the treatment of diseases in which a prominent neutrophil infiltrate is present, especially psoriasis and inflammatory bowel disease. Peptidoleukotriene (LTC4, LTD4, LTE4) antagonists, such as zafirlukast and pranlukast, are currently being developed as antiasthmatics.

Development of a dual function sensor system for measuring pressure and temperature at the tip of a single optical fiber.

A dual function sensor system has been developed for measuring pressure and temperature at the tip of a single optical fiber. The sensor contains three parts: a filter band-edge shift temperature based spectral modulation pressure sensor. The sensor system uses a separate and distinct LED for interrogating each sensor, three 100/140 microns step-index fused couplers for managing light, and separate paired photodiode assemblies for analyzing the return light signal from each sensor. In bench tests, each sensor performed to specification and, importantly, there was no crosstalk between sensors. This dual function sensor design has potential catheter applications where catheter size must be kept to an absolute minimum.

Development of a medical fiber-optic pH sensor based on optical absorption.

A new fiber-optic pH sensor system has been developed. The sensor uses an absorbtive indicator compound with a long wave-length absorption peak near 625 nm; change in absorption over the pH range 6.8 to 7.8 is reasonably linear. The sensor is interrogated by a pulsed, red LED. Return light signal is split into short and long wave-length components with a dichroic mirror; the respective signals are detected by photodiodes, and their photocurrents are used to form a ratiometric output signal. In laboratory tests, the sensor system provided resolution of 0.01 pH, accuracy of +/- 0.01 pH, and response time of 30-40 s. Following gamma sterilization, laboratory sensor testing with heparinized human blood yielded excellent agreement (e.g., r = 0.992 for n = 42) with a clinical blood gas analyzer. Excellent sensor performance and low cost, solid-state instrumentation are hallmarks of this sensor-system design.