472 research outputs found

    Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

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    The pathogen Mycobacterium tuberculosis (Mtb), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in Mtb-specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host-pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it. The synthesis of many of these constituents has been achieved and aided the elucidation of their function by utilizing the synthetic material to study Mtb immunology. This review summarizes the synthetic efforts of a quarter century of total synthesis and highlights how the synthesis layed the foundation for immunological studies as well as drove the field of organic synthesis and catalysis to efficiently access these complex natural products

    Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

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    Virgin females of the parasitoid wasp Trichogramma turkestanica produce minute amounts of a sex pheromone, the identity of which has not been fully established. The enantioselective synthesis of a putative component of this pheromone, (6S,8S,10S)-4,6,8,10-tetramethyltrideca-2E,4E-dien-1-ol (2), is reported as a contribution to this identification. Catalytic asymmetric conjugate addition of methylmagnesium bromide and stereoselective Horner–Wadsworth–Emmons olefinations are used as the key steps, and 2 was obtained in 16 steps with an overall yield of 4.4%

    Novel compositions and methods for trehalose phospholipids

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    Provided herein are compositions of trehalose phospholipids and uses thereof, e.g., compounds and compositions comprising 6,6'-diphosphatidyltrehalose (diPT) and analogs thereof with modifications of the diPT chemical scaffold, that bind and agonize Mincle, and the use thereof as adjuvants

    Understanding torquetenovirus (TTV) as an immune marker

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    Torquetenovirus (TTV), a small, single stranded anellovirus, is currently being explored as a marker of immunocompetence in patients with immunological impairment and inflammatory disorders. TTV has an extremely high prevalence and is regarded as a part of the human virome, the replication of which is controlled by a functioning immune system. The viral load of TTV in plasma of individuals is thought to reflect the degree of immunosuppression. Measuring and quantifying this viral load is especially promising in organ transplantation, as many studies have shown a strong correlation between high TTV loads and increased risk of infection on one side, and low TTV loads and an increased risk of rejection on the other side. As clinical studies are underway, investigating if TTV viral load measurement is superior for gauging antirejection therapy compared to medication-levels, some aspects nevertheless have to be considered. In contrast with medication levels, TTV loads have to be interpreted bearing in mind that viruses have properties including transmission, tropism, genotypes and mutations. This narrative review describes the potential pitfalls of TTV measurement in the follow-up of solid organ transplant recipients and addresses the questions which remain to be answered.</p

    Long-term health-related quality of life, healthcare utilisation and back-to-work activities in intensive care unit survivors:Prospective confirmatory study from the Frisian aftercare cohort

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    PURPOSE: More substantial information on recovery after Intensive Care Unit (ICU) admission is urgently needed. In a previous retrospective study, the proportion of non-recovery patients was 44%. The aim of this prospective follow-up study was to evaluate changes in Health-Related Quality of Life (HRQoL) in the first year after ICU-admission. METHODS: Long-stay adult ICU-patients (≥ 48 hours) were included. HRQoL was evaluated with the Dutch translation of the RAND-36 item Health Survey (RAND-36) at baseline via proxy measurement, and at three, six, and twelve months after ICU admission. Subsequently, the relation between physical functioning, healthcare utilisation, and work activities was explored. RESULTS: A total of 81 patients were included in this study. Fifty-five percent of patients did not meet criteria for full recovery and were allocated to the Non Recovery (NR)-group (Physical Functioning domain-score: 35 [15-55]). Baseline physical HRQoL differed significantly between the Recovery (R) and NR-group. Patients in the NR-group received home care more often and had higher healthcare utilisation (44 versus 17% in the first three months post-ICU, p = 0.013). Only fourteen percent of NR-patients were able to participate in work activities. Moreover, NR-patients persistently showed impaired overall HRQoL throughout the year after critical illness. CONCLUSIONS: Limited recovery in ICU survivors is reflected in overall impaired HRQoL, as well as in far-reaching consequences for patients' healthcare needs and their ability to reintegrate into society. In our study, baseline HRQoL appeared to be an important predictor of long-term outcomes, but not Clinical Frailty Scale (CFS) score. And, (proxy-derived) HRQoL may help to identify patients at risk of long-term non-recovery

    Cognitive functioning in glioblastoma patients during radiotherapy and temozolomide treatment: initial findings

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    The aim of this study was to evaluate cognitive functioning in newly-diagnosed glioblastoma multiforme (GBM) patients during treatment with radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ). Cognitive assessment took place following surgery, but prior to the start of RT (baseline), after 6 weeks of RT and concomitant TMZ (1st follow-up), and after three cycles of adjuvant TMZ (2nd follow-up). Standardized cognitive summary measures and delta scores for six cognitive domains were calculated at the individual level. Cognitive functioning of progression-free GBM patients was compared to that of matched healthy controls. Analyses were performed on a group of 13 GBM patients that were progression-free during follow-up. The results showed that the majority of patients had deficits in multiple cognitive domains at baseline. Between baseline and 1st follow-up, four patients improved in one cognitive domain, four patients deteriorated in one domain, one patient improved in one domain and deteriorated in another, and four patients remained stable in all six domains. Between 1st and 2nd follow-up, the majority of patients (11) remained stable in all six cognitive domains, whereas one patient declined in one domain, and one patient showed a deterioration in two domains. Overall, between baseline and 2nd follow-up, three patients improved in one cognitive domain, two patients deteriorated in two domains, one patient improved in one domain and deteriorated in another, and seven patients remained stable in all six cognitive domains. In conclusion, preceding treatment, the majority of GBM patients show clear-cut deficits in cognitive functioning. In the course of the first 6 months of their disease, however, progression-free GBM patients undergoing radiotherapy plus concomitant and adjuvant temozolomide treatment do not deteriorate in cognitive functioning
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