Sequential ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment—a prospective observational study

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using ¹⁸F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three ¹⁸F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. ¹⁸F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5–5.0 MBq/kg of ¹⁸F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current ⁸F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational ¹⁸F-FDG imaging study across six countries

BACKGROUND: A large proportion of the huge global burden of Extrapulmonary tuberculosis (EPTB) are treated empirically without accurate definition of disease sites, and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 18F-FDG in TB could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across 8 centres located in 6 countries: India, Pakistan, Thailand, South Africa, Serbia, and Bangladesh to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/CT scans were performed within 2 weeks of presentation. FINDINGS: A total of 358 patients with EPTB (189 females; 169 males) were recruited over 45 months. Age range 18-83 years (females: median 30 years; males: median 38 years). 350/358 (98%) patients (183 female, 167 male) had positive scan. 118/350 (33.7%) had a single extrapulmonary site and 232/350 (66.3%) had more than one site (organ) affected. Lymph nodes, skeletal, pleura and brain were common sites. 100/358 (28%) of EPTB patients had 18F-FDG PET/CT positive sites in the lung. 110 patients were 18F-FDG PET/CT positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB, and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies

AMPK Modulation Ameliorates Dominant Disease Phenotypes of CTRP5 Variant in Retinal Degeneration

Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic defects result in accumulation of sub-RPE deposits and leave L-ORD-iRPE susceptible to dedifferentiation. Gene augmentation of L-ORD-iRPE with WT CTRP5 or modulation of AMPK, by metformin, re-sensitize L-ORD-iRPE to changes in cellular energy status alleviating the disease cellular phenotypes. Our data suggests a mechanism for the dominant behavior of CTRP5 mutation and provides potential treatment strategies for L-ORD patients. © 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

Water resources investigation in Pakistan with the help of ERTS imagery, snow surveys, 1975-1976

There are no author-identified significant results in this report

Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution.

Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful (“boar taint”). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene

Olfactory Stimulus Processing by Human Brain-A Functional Study

開始ページ、終了ページ: 冊子体のページ付

Olfactory Stimulus Processing by Human Brain-A Functional Study

開始ページ、終了ページ: 冊子体のページ付

Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the use of a transcervical Foley catheter plus oxytocin infusion compared with oxytocin infusion alone for labor induction and cervical ripening in women 34 weeks of gestation or greater with prelabor rupture of membranes. METHODS: This is a randomized, multicenter trial of women with a live, singleton gestation at 34 weeks of gestation or greater with prelabor rupture of membranes, an unfavorable cervical examination (less than 2 cm or 80% effaced), and no contraindication to labor. Participants were randomly allocated to a transcervical Foley catheter inflated to 30 cc with concurrent oxytocin infusion or oxytocin infusion alone. Oxytocin administration was standardized across sites. The primary study outcome was interval from induction to delivery. To detect a 2.5-hour difference in the interval from induction to delivery, we required outcome data on 194 women, assuming 80% power and a two-tailed α of 5%. Analysis was by intent to treat. RESULTS: We enrolled 201 women: 93 were allocated to Foley and 108 to oxytocin. Demographics were similar between the groups. Time to delivery was not significantly different between groups: in the Foley group, it was 13.9 hours (±6.9 SD) compared with 14.4 hours (±7.9 SD) in the oxytocin group (P=.69). There were more cases of clinical chorioamnionitis (8% compared with 0%, P CONCLUSION: In patients with prelabor rupture of membranes, the use of a transcervical Foley catheter in addition to oxytocin does not shorten the time to delivery compared with oxytocin alone, but may increase the incidence of intraamniotic infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01973036