Undeclared allergen(s) in commercial food products are responsible for many food recalls, as reported by regulatory agencies in various countries, including the United States. Correct allergen ...labeling practices are essential for the safety of food-allergic consumers. However, this practice may be hindered by the introduction of allergens all along the food supply chain, including unintentionally through cross-contact. To understand the pervasiveness of undeclared allergen(s) in commercial food products, the objective of this review is to summarize the prevalence of undeclared milk, egg, hazelnut, peanut, soy, and gluten as detected by ELISA from previously published surveys. The prevalence of undeclared allergen(s) in products with or without an advisory statement was also summarized and compared. As compiled by this review, there are some food categories that may be at higher risk for containing undeclared allergen(s). However, the data on prevalence and amount of allergen present may vary widely within any particular allergen or food category. Factors, such as food survey product selection, geography, awareness of allergen/gluten issues, and/or the choice of ELISA method, may be responsible for such differences.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Most
-positive lung cancers will develop ALK-independent resistance after treatment with next-generation ALK inhibitors.
amplification has been described in patients progressing on ALK inhibitors, ...but frequency of this event has not been comprehensively assessed.
We performed FISH and/or next-generation sequencing on 207 posttreatment tissue (
= 101) or plasma (
= 106) specimens from patients with ALK-positive lung cancer to detect
genetic alterations. We evaluated ALK inhibitor sensitivity in cell lines with
alterations and assessed antitumor activity of ALK/MET blockade in ALK-positive cell lines and 2 patients with MET-driven resistance.
amplification was detected in 15% of tumor biopsies from patients relapsing on next-generation ALK inhibitors, including 12% and 22% of biopsies from patients progressing on second-generation inhibitors or lorlatinib, respectively. Patients treated with a second-generation ALK inhibitor in the first-line setting were more likely to develop
amplification than those who had received next-generation ALK inhibitors after crizotinib (
= 0.019). Two tumor specimens harbored an identical
rearrangement, one of which had concurrent
amplification. Expressing
in the sensitive H3122 ALK-positive cell line induced resistance to ALK inhibitors that was reversed with dual ALK/MET inhibition. MET inhibition resensitized a patient-derived cell line harboring both
and
amplification to ALK inhibitors. Two patients with ALK-positive lung cancer and acquired
alterations achieved rapid responses to ALK/MET combination therapy.
Treatment with next-generation ALK inhibitors, particularly in the first-line setting, may lead to MET-driven resistance. Patients with acquired
alterations may derive clinical benefit from therapies that target both ALK and MET.
•Current digestibility models solely utilize pepsin stability for safety assessment.•We identified allergenic pepsin and pancreatin stable milk proteins.•β-Lactoglobulin and casein were stable and ...allergenic within intestinal conditions.•Improved digestibility models are needed for improved food safety assessment.
Current models of digestibility solely utilize pepsin stability to assess the safety of allergenic food proteins. However, in vivo complete protein digestion requires acid denaturation and pepsin, trypsin, and/or chymotrypsin cleavage. This study aimed to identify the immunoreactivity and allergenicity of stable bovine milk proteins, using an improved digestibility model to simulate physiological gastric and intestinal conditions in vitro. Gel electrophoresis and immunoblot analysis were used to determine protein stability and immunoreactivity, respectively. Immunoreactivity of bovine milk proteins, β-lactoglobulin (β-LG) and casein (CN) was greatly diminished with gastric simulation (0–60min), but some proteins were stable and immunoreactive with simulated intestinal digestive conditions (0–60min). This study demonstrates the need for improved digestibility models for more accurate assessment of the behavior of food allergens in vivo.
Underestimation of egg allergen from processed foods prompted the evaluation of critical Enzyme-Linked Immunosorbent Assay (ELISA) parameters: (1) extraction of egg proteins from a processed matrix; ...(2) use of anti-heat processed egg antibodies (Abs) on detectability of modified proteins, and (3) utilization of incurred material as standards. The relative affinity of two combinations of raw (R), boiled (B) and fried (F) Abs to unprocessed/processed egg proteins with or without matrix was determined from antibody (Ab) binding curves. In ELISAs using RBF-Abs and BF-Abs, denaturing buffer, and incurred standards, the Limit of Detection (LOD) and Limit of Quantitation (LOQ) were 0.47 and 0.25; and 1.58 and 0.85, respectively, and the linear range was 0–24 μg g−1 egg protein. The recoveries of egg protein from cookies, cereal bar, and muffin (incurred levels 4.8–48 μg g−1) with the developed ELISAs were in an acceptable range (50–130%). These ELISAs consistently detected more declared/undeclared egg proteins in market samples compared to assays using PBS for extraction. Overall, better assay performance was observed using BF-Abs. An ELISA combining anti-processed egg Abs, denaturing buffer, and incurred standards promises improved quantitation of egg proteins in processed foods.
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•Underestimation of egg from processed foods requires evaluation of critical Enzyme-Linked Immunosorbent Assay parameters.•The advantage of incurred calibrators and anti-processed proteins antibodies for egg detection is demonstrated.•These strategies will help to enhance labeling accuracy by increasing performance of egg detection methods.
Disruption of the growth hormone (GH) signaling pathway promotes insulin sensitivity and is associated with both delayed aging and extended longevity. Two kinds of long-lived mice-Ames dwarfs (df/df) ...and GH receptor gene-disrupted knockouts (GHRKO) are characterized by a suppressed GH axis with a significant reduction of body size and decreased plasma insulin-like growth factor-1 (IGF-1) and insulin levels. Ames dwarf mice are deficient in GH, prolactin, and thyrotropin, whereas GHRKOs are GH resistant and are dwarf with decreased circulating IGF-1 and increased GH. Crossing Ames dwarfs and GHRKOs produced a new mouse line (df/KO), lacking both GH and GH receptor. These mice are characterized by improved glucose tolerance and increased adiponectin level, which could imply that these mice should be also characterized by additional life-span extension when comparing with GHRKOs and Ames dwarfs. Importantly, our longevity experiments showed that df/KO mice maintain extended longevity when comparing with N control mice; however, they do not live longer than GHRKO and Ames df/df mice. These important findings indicate that silencing GH signal is important to extend the life span; however, further decrease of body size in mice with already inhibited GH signal does not extend the life span regardless of improved some health-span markers.
Shellfish allergy affects 2% of the adult population in the United States. Identification of allergenic shrimp proteins is needed for improved management and assessment of shrimp allergy. We ...determined the temporal pepsin and pancreatin stability of total shrimp proteins using simulated physiological digestive conditions in vitro. Gel electrophoresis was used to determine protein stability, whereas immunoreactivity of protease stable proteins was determined using rabbit antigen‐specific antibodies. Potential allergenicity of protease stable proteins was determined utilizing human sera from shrimp allergic patients. Total shrimp myofibrillar proteins were pepsin‐ and pancreatin‐stable for up to 1 h after initiating digestion, whereas only pancreatin‐stable total shrimp proteins were Immunoglobulin G (IgG) immunoreactive. However, shrimp proteins of 32 and 25 kDa were pepsin and/or pancreatin stable and Immunoglobulin E (IgE) reactive, denoting the stability and potential allergenicity. These findings suggest that this in vitro digestibility model may be useful for the identification of shrimp allergenic proteins that are more resistant to physiologic digestive conditions and may elicit an immunologic response in vivo.
Practical Application
Unlike other food allergies, shellfish allergy is typically life‐long and predominantly affects the adult population. A major difficulty in managing shellfish allergy is the lack of reliable diagnostic assays due to limited knowledge of clinically relevant shellfish allergens. Therefore, the identification and characterization of digestive‐stable and immunoreactive food proteins is fundamental to the development of new polyclonal antibodies for improved food allergen detection methods within the food industry.
Rearranged during transfection proto-oncogene (
) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of ...advanced
fusion-positive (
+) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in
+,
+ and
+ NSCLC. Patients with
+,
+, or
+ NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring
,
, or
gene fusion (
= 32;
= 116;
= 67). Patients with
+ NSCLC were older at presentation compared to
+ and
+ patients (median age:
= 64 years;
= 51 years,
< 0.001; ROS = 54 years,
= 0.042) and had a higher frequency of neuroendocrine histology (
= 12%;
= 2%,
= 0.025;
= 0%,
= 0.010). Primary tumors in
+ patients were more likely to be peripheral (
= 69%;
= 47%,
= 0.029;
= 36%,
= 0.003), whereas lobar location, size, and density were comparable across the three groups.
+ NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to
+ NSCLC (
= 32%,
= 10%;
= 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases.
+ NSCLC shares several distinct radiologic features and metastatic spread with
+ and
NSCLC. These features may suggest the presence of
fusions and help identify patients who may benefit from further molecular genotyping.
Posterior glenohumeral instability is a relatively uncommon cause of shoulder instability. Recurrent posterior instability with static posterior humeral head subluxation is often associated with ...critical glenoid bone loss. Unlike anterior instability, the amount of bone loss for posterior instability that requires surgical reconstruction remains a topic of debate. Several techniques have been described to treat critical bony defects in patients with recurrent posterior shoulder instability with the use of both autografts and allografts depending on the amount of bone loss present. Open posterior glenoid bone block procedure is associated with increased risk of complications and morbidity to the patient. As such, all-arthroscopic techniques have emerged with the advantage of allowing for the diagnosis and treatment of concomitant glenohumeral pathology and minimizing soft-tissue dissection through the posterior deltoid and rotator cuff muscles. Reported short-term outcomes of arthroscopic posterior bone block stabilization are promising; however, it remains a technically challenging procedure due to intra-articular graft insertion and subsequent fixation congruent to the posterior glenoid articular margin. We describe an all-arthroscopic technique using a fresh distal tibia allograft fixation using 2 partially threaded screws in conjunction with an arthroscopic Latarjet fixation set for a patient with recurrent posterior shoulder instability and associated glenoid bone loss.
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ROS1 fusions are oncogenic drivers in 1% to 3% of NSCLCs. The activity of immune checkpoint inhibitor (ICI) monotherapy or in combination with chemotherapy (chemotherapy with ICI chemo-ICI) in these ...tumors and their immunophenotype have not been systematically described.
In this multi-institutional retrospective study, tumor programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) were evaluated in patients with ROS1-rearranged NSCLC. Time-to-treatment discontinuation (TTD) and objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors RECIST version 1.1) were calculated for patients treated with ICI or chemo-ICI in the metastatic setting.
A total of 184 patients were identified. Among 146 assessable cases, PD-L1 expression was less than 1% in 60 (41%), 1% to 49% in 35 (24%), and greater than or equal to 50% in 51 tumors (35%). Of 100 (92%) TMB-assessable tumors, 92 had less than 10 mutations per megabase. TMB was significantly lower for ROS1-rearranged tumors (n = 97) compared with tumors with EGFR (n = 1250) or KRAS alterations (n = 1653) and all other NSCLC tumors (n = 2753) evaluated with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (median TMB = 2.6 versus 3.5, 7.0, and 6.1 mutations per megabase, p < 0.001). Among patients treated with ICI, median TTD was 2.1 months (95% confidence interval CI: 1.0–4.2 mo; n = 28) and ORR 13% (2 of 16 RECIST-assessable; 95% CI: 2%–38%). Among patients treated with chemo-ICI, median TTD was 10 months (95% CI: 4.7–14.1 mo; n = 11) and ORR 83% (5 of 6 RECIST-assessable; 95% CI: 36%–100%). There was no difference in PD-L1 expression (p = 0.91) or TMB (p = 0.83) between responders and nonresponders.
Most ROS1-rearranged NSCLCs have low PD-L1 expression and TMB. The activity of ICI in these tumors is modest. In contrast, chemo-ICI can achieve meaningful activity.
A comprehensive study was designed to determine the frequency and levels of soy allergen in packaged bakery and snack food products. A representative sample of products with no soy allergen disclosed ...on the label was analysed using two widely used enzyme-linked immunosorbent assay (ELISA) methods. Samples were chosen that either had no soy identified on the product label or which had a soy precautionary statement. Among 558 bakery and snack products, soy protein was detected in 17% of the products using the Neogen (NE) kit and 11% of the products using the Elisa Systems (ES) kit. The disagreement rates between kits were 8.8% for bakery products and 3.3% for snack products. Overall soy protein was detected at higher frequency in bakery products than in snack foods. Among 284 bakery samples, soy protein was detected in 25% of the samples with no precautionary statement and 19% of the samples which had a precautionary statement. Among 274 snack samples, soy protein was detected in 11% of the samples with no precautionary statement and 9% of the samples which had a precautionary statement. The sample repeatability was at an acceptable level (< 9%) for each method and food commodity. The reproducibility between kits was 23% for bakery foods and 36% for snack foods. None of the bakery (21) and snack (6) products without precautionary labelling (measured level > 5 ppm) had a higher level of soy protein per serving compared with the eliciting dose
10
(ED
10
) of 10.6 mg for soy allergic patients. But the level of soy protein per serving may be clinically relevant to a subpopulation of soy allergic patients if a more stringent eliciting dose is applied. These findings emphasise that suitable detection methodologies and references doses are crucial for labelling accuracy and the safety of soy allergic consumers.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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