Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated gastrointestinal allergic disorder. Large population-based FPIES studies are lacking. Objective We sought to ...determine the incidence and clinical characteristics of FPIES in Australian infants. Methods An Australia-wide survey (2012-2014) was undertaken through the Australian Paediatric Surveillance Unit, with monthly notification of new cases of acute FPIES in infants aged less than 24 months by 1400 participating pediatricians. Results Two hundred thirty infants with FPIES were identified. The incidence of FPIES in Australian infants (<24 months) was 15.4/100,000/y. Median age of first episode, diagnosis, and notification were 5, 7, and 10 months, respectively. There was no sex predilection. Seven percent of infants had siblings with a history of FPIES, and 5% reacted during exclusive breast-feeding. Sixty-eight had a single food trigger (20% had 2 and 12% had ≥3 food triggers). The most common FPIES triggers were rice (45%), cow's milk (33%), and egg (12%). Fifty-one percent of infants reacted on their first known exposure. Infants with FPIES to multiple versus single food groups were younger at the initial episode (4.6 vs 5.8 months mean, P = .001) and more frequently had FPIES to fruits, vegetables, or both (66% vs 21%, P < .0001). Infants exclusively breast-fed for more than 4 months had a trend toward lower rates of FPIES to multiple food groups (23% vs 36%, P = .06). Sixty-four percent of infants with FPIES to multiple foods, which included cow's milk, had coassociated FPIES to solid foods. Forty-two percent of infants with FPIES to fish reacted to other food groups. Conclusions FPIES is not rare, with an estimated incidence of 15.4/100,000/y. Rice is the most common food trigger in Australia. Factors associated with FPIES to multiple foods included early-onset disease and FPIES to fruits, vegetables, or both.
We report an Indian farmer who had fluctuating trypanosome parasitemia associated with febrile episodes for five months. Morphologic examination of the parasites indicated the presence of large ...numbers of trypanosomes belonging to the species Trypanosoma evansi, which is normally a causative agent of animal trypanosomiasis known as surra. Basic clinical and biologic examinations are described, using several assays, including parasitologic, serologic, and molecular biologic tests, all of which confirmed the infecting species as T. evansi. Analysis of cerebrospinal fluid indicated no invasion of the central nervous system (CNS) by trypanosomes. Suramin, a drug used exclusively for treatment of early-stage human African trypanosomiasis with no CNS involvement, effected apparent cure in the patient. This is the first case reported of human infection due to Trypanosoma evansi, which was probably caused by transmission of blood from an infected animal.
Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality ...with risk and severity of COVID-19 and its interaction with socioeconomic deprivation.
We used data from 592 571 participants of the smartphone-based COVID-19 Symptom Study. Diet information was collected for the prepandemic period using a short food frequency questionnaire, and diet quality was assessed using a healthful Plant-Based Diet Score, which emphasises healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate HRs and 95% CIs for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalisation with oxygen support, respectively.
Over 3 886 274 person-months of follow-up, 31 815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR 0.91; 95% CI 0.88 to 0.94) and severe COVID-19 (HR 0.59; 95% CI 0.47 to 0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (P
=0.005). The corresponding absolute excess rate per 10 000 person/months for lowest vs highest quartile of diet score was 22.5 (95% CI 18.8 to 26.3) among persons living in areas with low deprivation and 40.8 (95% CI 31.7 to 49.8) among persons living in areas with high deprivation.
A diet characterised by healthy plant-based foods was associated with lower risk and severity of COVID-19. This association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.
Thrombosis, or blood clot formation, and its sequelae remain a leading cause of morbidity and mortality, and recurrent thrombosis is common despite current optimal therapy. Protein disulfide ...isomerase (PDI) is an oxidoreductase that has recently been shown to participate in thrombus formation. While currently available antithrombotic agents inhibit either platelet aggregation or fibrin generation, inhibition of secreted PDI blocks the earliest stages of thrombus formation, suppressing both pathways. Here, we explored extracellular PDI as an alternative target of antithrombotic therapy. A high-throughput screen identified quercetin-3-rutinoside as an inhibitor of PDI reductase activity in vitro. Inhibition of PDI was selective, as quercetin-3-rutinoside failed to inhibit the reductase activity of several other thiol isomerases found in the vasculature. Cellular assays showed that quercetin-3-rutinoside inhibited aggregation of human and mouse platelets and endothelial cell-mediated fibrin generation in human endothelial cells. Using intravital microscopy in mice, we demonstrated that quercetin-3-rutinoside blocks thrombus formation in vivo by inhibiting PDI. Infusion of recombinant PDI reversed the antithrombotic effect of quercetin-3-rutinoside. Thus, PDI is a viable target for small molecule inhibition of thrombus formation, and its inhibition may prove to be a useful adjunct in refractory thrombotic diseases that are not controlled with conventional antithrombotic agents.
Susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outcome of coronavirus disease 2019 (COVID-19) have been linked to underlying health conditions and the age of ...affected individuals. Here, we assessed the effect of age on SARS-CoV-2 infection using a ferret model. For this, young (6-month-old) and aged (18- to 39-month-old) ferrets were inoculated intranasally with various doses of SARS-CoV-2. By using infectious virus shedding in respiratory secretions and seroconversion, we estimated that the infectious dose of SARS-CoV-2 in aged animals is ∼32 PFU per animal, while in young animals it was estimated to be ∼100 PFU. We showed that viral replication in the upper respiratory tract and shedding in respiratory secretions is enhanced in aged ferrets compared to young animals. Similar to observations in humans, this was associated with higher transcription levels of two key viral entry factors, ACE2 and TMPRSS2, in the upper respiratory tract of aged ferrets.
In humans, ACE2 and TMPRSS2 are expressed in various cells and tissues, and differential expression has been described in young and old people, with a higher level of expressing cells being detected in the nasal brushing of older people than young individuals. We described the same pattern occurring in ferrets, and we demonstrated that age affects susceptibility of ferrets to SARS-CoV-2. Aged animals were more likely to get infected when exposed to lower infectious dose of the virus than young animals, and the viral replication in the upper respiratory tract and shedding are enhanced in aged ferrets. Together, these results suggest that the higher infectivity and enhanced ability of SARS-CoV-2 to replicate in aged individuals is associated, at least in part, with transcription levels of ACE2 and TMPRSS2 at the sites of virus entry. The young and aged ferret model developed here may represent a great platform to assess age-related differences in SARS-CoV-2 infection dynamics and replication.
The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization ...(MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.
We prospectively quantified the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of integrated parallel acquisition technique (PAT) and simultaneous multislice (SMS) acceleration and ...various combinations thereof, and we further compared two 4-fold-accelerated (PAT2-SMS2) high-resolution turbo spin echo (TSE) magnetic resonance imaging (MRI) protocols of the knee against a clinical 2-fold-accelerated (PAT2-SMS1) TSE standard.
Institutional review board approval was obtained, and all subjects gave informed consent. Fourteen knee MRI examinations were obtained (8 men, 6 women; mean age, 46 years; age range, 28-62 years) using a 3 T MRI system and a TSE pulse sequence prototype that allowed for the combination of PAT and SMS acceleration. Predicted whole-body specific absorption rates were recorded for all pulse sequences. For quantitative analysis, the difference method was used to calculate SNR and CNR analysis of 6 different TSE acceleration schemes (PAT2-SMS1, PAT3-SMS1, PAT1-SMS2, PAT1-SMS3, PAT2-SMS2, and PAT2-SMS3). For qualitative analysis, sagittal intermediate-weighted and axial fat-suppressed T2-weighted MR images were obtained with PAT2-SMS1 and PAT2-SMS2 acceleration schemes using similar parameters. One faster PAT2-SMS2 acceleration scheme with decreased repetition time and longer echo train was labeled with the addition SPEED for the purpose of this report. Two readers rated the data sets for image quality, structural visibility, and overall observer satisfaction using equidistant 5-point Likert scales. Readers additionally noted the presence of cartilage defects, meniscal tears, tendons and ligament tears, and bone marrow edema pattern. Friedman and Kruskal-Wallis tests were used. P values of less than 0.01 were considered significant.
All pulse sequences were successfully executed and reconstructed inline. Whole-body specific absorption rates ranged between 1.4 and 3.9 W/kg for all acquisitions and remained within mandated limits. Quantitatively, mean SNR and CNR were significantly higher for SMS than those for PAT and similar for PAT2-SMS2 and PAT2-SMS1. Fluid was brightest on PAT2-SMS1, whereas noise, edge sharpness, contrast resolution, and fat suppression were similar on PAT2-SMS1 and SMS2-PAT2 and mildly inferior on PAT2-SMS2 SPEED. Articular cartilage received mildly higher ratings on PAT2-SMS1, whereas visibility of menisci was mildly inferior on PAT2-SMS2 SPEED. Observer preferences were similarly high for PAT2-SMS1 and PAT2-SMS2 and mildly inferior for the faster PAT2-SMS2 SPEED images. Four cartilage defects and 2 meniscal tears were seen by both readers on all sequences.
We demonstrate the signal preservation capabilities of SMS over PAT acceleration, which allow for similar SNR and CNR of 4-fold PAT2-SMS2 and 2-fold PAT2-SMS1 acceleration. Four-fold-accelerated TSE through the combination of PAT2 and SMS2 enables approximately 50% shorter acquisition times compared with regular PAT2 acceleration, similar quantitative and qualitative image quality, and holds promise for a meaningful increase of the efficiency of clinical 2-dimensional MRI of the knee.
Advanced shape analysis studies such as regression and classification need to be performed on curved manifolds, where often, there is a lack of standard statistical formulations. To overcome these ...limitations, we introduce a novel machine-learning method on the shape space of curves that avoids direct inference on infinite-dimensional spaces and instead performs Bayesian inference with spherical Gaussian processes decomposition. As an application, we study the shape of the cochlear spiral-shaped cavity within the petrous part of the temporal bone. This problem is particularly challenging due to the relationship between shape and gender, especially in children. Experimental results for both synthetic and real data show improved performance compared to state-of-the-art methods.
With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility ...is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.
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