Performance of new crystal cathode pressure gauges for long-pulse operation in the Wendelstein 7-X stellarator.

To improve the reliability of the ASDEX pressure gauges in the plasma vessel of the Wendelstein 7-X stellarator, nine of them were equipped with a LaB6 crystal electron emitter for the first time. These crystal cathode pressure gauges were operated during the last campaign in 2018 (operation phase 1.2b) with only 2 A heating current for over 40 h in a magnetic field of about 2.1 T without failure. Owing to this excellent performance, we have decided to equip all pressure gauges with crystal cathodes for the next campaign of Wendelstein 7-X (operation phase 2). We report on a pretest in a superconducting magnet, show a measurement of the neutral pressure in Wendelstein 7-X, and demonstrate the long-term stability of the crystal cathode pressure gauges.

The ReceptIVFity cohort study protocol to validate the urogenital microbiome as predictor for IVF or IVF/ICSI outcome.

BACKGROUND: During the last decade, research has shown that besides the known predictive factors, such as duration of subfertility, a women's age, the body mass index, also the microbiome might affect fertility. Micro-organisms together with their genetic information and the milieu in which they interact are called the microbiome. Studies have shown that the presence of certain microbiota during assisted reproductive technology (ART) has a positive impact on the outcome. However, the potential role of using the microbiome as a predictor for outcome of ART has not yet been investigated. METHODS: In a prospective study, 300 women of reproductive age and with an indication for in-vitro Fertilization (IVF) with or without Intra Cytoplasmic Sperm Injection (ICSI) treatment will be included. Prior to the IVF or IVF-ICSI treatment, these women provided a midstream urine sample and a vaginal swab. The composition of the urinary and vaginal microbiome will be analysed with both Next Generation Sequencing and the IS-pro technique. The endpoints of the study are pregnancy achieved after fresh embryo transfer (ET) and within the subsequent year after inclusion. External validation of the findings will take place in an additional cohort of 50 women with an IVF or IVF-ICSI indication. DISCUSSION: In the proposed study, the predictive accuracy of the composition of the urinary and vaginal microbiome for IVF or IVF-ICSI outcome will be only validated for fresh ET. Follow-up has to show whether the predictive accuracy will be similar during the consecutive frozen ET's as part of the IVF or IVF-ICSI treatment or for subsequent stimulated or natural cycles. In addition, external validation will take place in another cohort and hospital. Predictive knowledge of the microbiome profile may enable couples to make a more substantiated decision on whether to continue treatment or not. Hence, the unnecessary physical and emotional burden of a failed IVF or IVF-ICSI treatment can be avoided. TRIAL REGISTRATION: ISRCTN ISRCTN83157250 . Registered 17 August 2018. Retrospectively registered.

Host Polymorphisms in TLR9 and IL10 Are Associated With the Outcomes of Experimental Haemophilus ducreyi Infection in Human Volunteers.

BACKGROUND: In humans inoculated with Haemophilus ducreyi, there are host effects on the possible clinical outcomes-pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection. METHODS: DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ(2) tests for trend and logistic regression analyses were performed on the data. RESULTS: In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 -2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype. CONCLUSIONS: Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.

Effect of cytokine level variations in individuals on the progression and outcome of bacterial urogenital infections--a meta-analysis.

Bacterial urogenital infections such as chlamydia, gonorrhoea and syphilis are widespread inflammatory diseases, which may be accompanied by severe complications. These complications can range from basic inflammation to tubal pathology, infertility and neurological dysfunction, though infections go unnoticed in the majority of cases. Cytokines in the host play a vital role in both the initial and long-term immune response and inflammation. However, levels of cytokine expression vary between individuals. A meta-analysis was performed to evaluate the effect of cytokine expression differences on severity of infections with these pathogens. Studies comparing expression of cytokines in humans with inflammation or inflammation-based complications were identified using NCBI, Google Scholar and Cochrane databases. Only studies into human cytokine expressions were included, and three articles per subject were required to be suitably analysed during meta-analysis. A total of 52 articles were included for meta-analysis. It was shown that differences in IL-1, IL-6, IL-8, IL-10, TNFα and IFNγ affect the clinical outcome of Chlamydia trachomatis infection significantly. Similarly, IL-1 and IL-8 expression during Neisseria gonorrhoeae infection significantly affects the outcome of the disease. For Treponema pallidum infection, it was shown that IFNγ variation in hosts could be linked to severity of disease. However, a lack of studies to use in the meta-analysis and fluctuation in the resulting data depending on the adjustments makes adequate evaluation difficult.

Quantitative analysis of Cryptosporidium growth in in vitro culture--the impact of parasite density on the success of infection.

Cryptosporidium is an important waterborne pathogen for which no treatment or vaccination is available. This study set out to quantify DNA replication of Cryptosporidium parvum in vitro. Cryptosporidium DNA could be detected at up to 60 % of input level in both host-cell-free and host cell containing cultures 6 days after infection with living sporozoites, but was lost within 2 days in cultures inoculated with UV-inactivated sporozoites. Total DNA increased between days 2 and 6, evidence of successful DNA replication in both cell-free and host-cell-containing cultures. Overall however, only a small fraction (up to 5 %) of parasite DNA could be found associated with host cells or bound to plastic of the cell-free cultures, and the majority of parasite DNA was present in the cell culture medium, separable by simple decantation. After 2 days, in host-cell-containing cultures, the parasite DNA could be concentrated by slow centrifugation, suggesting that it was associated with intact parasite cells, but at 6 days, the majority could not be centrifuged and is therefore thought to have represented copies associated with dead and degraded parasites. In cell-free cultures and in larger plates, the majority of DNA was in this form. Performance of the parasite was best in small culture plates, and least in the largest plate sizes. We interpret these results as suggesting that Cryptosporidium sporozoites first bind to the host cell monolayer or to the plasticware, but then by 2 days, there has been a substantial release of parasites back into the medium. Host-cell-free cultures also supported modest replication and may have represented DNA synthesis in cells beginning merogony. The role of the host cells is unclear, as so much of the parasite DNA is released into the medium. Host cells may provide a feeder role, conditioning the medium for Cryptosporidium development.

CpG DNA analysis of bacterial STDs.

BACKGROUND: Bacterial infections in the genital tract frequently result in morbidity through a variety of inflammation based symptoms. One component of the bacteria that may trigger host inflammatory response is their DNA. CpG motifs in this DNA are known targets for Toll-like receptor 9 (TLR9), which is a pathogen-recognition receptors focusing on CpG DNA. The activation of TLR9 induces the NF-κB inflammatory pathway. This study aims to provide a broad view of the inflammatory potential of CpG DNA motifs in bacteria related to genital diseases: C. trachomatis, E. coli, N. gonorrhoeae, G. vaginalis, H. ducreyi, L. crispatus, L. gasseri, M. hominis, M. genitalium, T. pallidum, and U. urealyticum. METHODS: Publicly available genomic sequences of the bacterial species and strains have been analyzed in silico to produce a CpG index number. This CpG index number shows the relative inflammatory potential of the genome and has previously been used in a study by Lundberg et al. (2003). Higher CpG index values suggest a strong CpG induced inflammation potential during infection and vice versa. RESULTS: The highest observed CpG index belongs to G. vaginalis with a value of 26,2, suggesting a strong pro-inflammatory potential when in contact with TLR9. The lowest index belongs to N. gonorrhoeae with a value of -79,5, suggesting a strong immunoinhibitory effect on TLR9 contact. Interestingly, Lactobacilli showed a mean CpG index value of 4,2, suggesting a weak inflammatory potential. DISCUSSION: Our results show varying CpG index values between bacterial species. Comparison of CpG indices with the clinical course of several pathogens shows the CpG index helps clarify the clinical course of infection. However, we found no links between CpG index values and either obligate pathogenicity or facultative pathogenicity through bacterial vaginosis. Lactobacilli showed relatively low CpG indices which do suggest a lower inflammatory potential from these bacteria. CONCLUSIONS: Our results show varying CpG index values between bacterial species, which may help clarify the clinical course of infection, and may help diagnosis.

Conservative treatment of fractures of the proximal phalanx: an option even for unstable fracture patterns.

PURPOSE: The purpose of the study was to assess the efficacy of the conservative management of proximal phalangeal fractures in a dorsal plaster slab. METHODS: Twenty-three consecutive patients with extra-articular proximal phalangeal fractures were included in this prospective study. Fourteen patients (62%) presented with fractures considered unstable. The fractures were reduced and the position was held with a dorsal plaster slab for three weeks. The patients were followed up for an average of seven weeks (range 2 to 45) after the injury. Range of motion of the finger and radiological evidence of union, non-union or malunion was documented after removal of the plaster. RESULTS: Ninety-one percent of fractures maintained an acceptable reduction. All cases measured less than 15° of angulation. On average 1,1 mm of shortening was measured. In two (9%) cases the reduction was not accepted on follow up assessment and the fractures were managed surgically. CONCLUSION: Most extra-articular proximal phalanx fractures can be managed conservatively with acceptable results.

Neck injuries caused by automatic two-point seat belts: an analysis of four cases.

Although seat belts significantly reduce the extent and severity of injuries sustained by motor vehicle occupants, seat belts are known to be associated with chest and abdominal trauma. Less commonly understood are severe neck injuries caused by the use of two-point automatic shoulder harnesses without concurrent use of a manual lap belt. Such injuries may include cervical spine fractures, craniocervical dislocations and rarely decapitation. Recognizing patterned injuries caused by seat belts and the ability to correlate autopsy findings with the circumstances surrounding the death will allow for correct interpretation of seat-belt related trauma. The four cases described detail fatal neck injuries as a result of improper seat belt use in which an automatic two-point shoulder harness was used without a manual lap restraint. In two of the cases, the victims were decapitated.

A prospective study to assess the outcome of steroid injections and wrist splinting for the treatment of carpal tunnel syndrome.

Surgery is the definitive treatment for carpal tunnel syndrome. Conservative treatments, such as wrist splinting and steroid injections, are also effective for the relief of carpal tunnel symptoms, but their use remains controversial because they only offer long-term relief in a minority of patients. A prospective study was performed to assess the role of steroid injections combined with wrist splinting for the management of carpal tunnel syndrome. A total of 73 patients with 99 affected hands were studied. Patients presenting with known medical causes or muscle wasting were excluded. Diagnosis was made clinically and electrodiagnostic studies were performed only when equivocal clinical signs were present. Each patient received up to three betamethasone injections into the carpal tunnel and wore a neutral-position wrist splint continuously for 9 weeks. After that period, symptomatic patients received an open carpal tunnel release, and those who remained asymptomatic were followed up regularly for at least 1 year. Patients who relapsed were scheduled for surgery. At a minimum follow-up of 1 year, seven patients (9.6 percent) with 10 affected hands (10.1 percent) remained asymptomatic. This group had a significantly shorter duration of symptoms (2.9 months versus 8.35 months; p = 0.039, Mann-Whitney test) and significantly less sensory change (40 percent versus 72 percent; p = 0.048, Fisher's exact test) at presentation when compared with the group who had surgery. It is concluded that steroid injections and wrist splinting are effective for relief of carpal tunnel syndrome symptoms but have a long-term effect in only 10 percent of patients. Symptom duration of less than 3 months and absence of sensory impairment at presentation were predictive of a lasting response to conservative treatment. It is suggested that selected patients (i.e., with no thenar wasting or obvious underlying cause) presenting with mild to moderate carpal tunnel syndrome receive either a single steroid injection or wear a wrist splint for 3 weeks. This will allow identification of the 10 percent of patients who respond well to conservative therapy and do not need surgery.