Trial of Endovascular Thrombectomy for Large Ischemic Strokes.

BACKGROUND: Trials of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes have been carried out in limited populations. METHODS: We performed a prospective, randomized, open-label, adaptive, international trial involving patients with stroke due to occlusion of the internal carotid artery or the first segment of the middle cerebral artery to assess endovascular thrombectomy within 24 hours after onset. Patients had a large ischemic-core volume, defined as an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower scores indicating larger infarction) or a core volume of at least 50 ml on computed tomography perfusion or diffusion-weighted magnetic resonance imaging. Patients were assigned in a 1:1 ratio to endovascular thrombectomy plus medical care or to medical care alone. The primary outcome was the modified Rankin scale score at 90 days (range, 0 to 6, with higher scores indicating greater disability). Functional independence was a secondary outcome. RESULTS: The trial was stopped early for efficacy; 178 patients had been assigned to the thrombectomy group and 174 to the medical-care group. The generalized odds ratio for a shift in the distribution of modified Rankin scale scores toward better outcomes in favor of thrombectomy was 1.51 (95% confidence interval [CI], 1.20 to 1.89; P<0.001). A total of 20% of the patients in the thrombectomy group and 7% in the medical-care group had functional independence (relative risk, 2.97; 95% CI, 1.60 to 5.51). Mortality was similar in the two groups. In the thrombectomy group, arterial access-site complications occurred in 5 patients, dissection in 10, cerebral-vessel perforation in 7, and transient vasospasm in 11. Symptomatic intracranial hemorrhage occurred in 1 patient in the thrombectomy group and in 2 in the medical-care group. CONCLUSIONS: Among patients with large ischemic strokes, endovascular thrombectomy resulted in better functional outcomes than medical care but was associated with vascular complications. Cerebral hemorrhages were infrequent in both groups. (Funded by Stryker Neurovascular; SELECT2 ClinicalTrials.gov number, NCT03876457.).

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

Endovascular Thrombectomy for Large Ischemic Stroke Across Ischemic Injury and Penumbra Profiles.

Importance: Whether endovascular thrombectomy (EVT) efficacy for patients with acute ischemic stroke and large cores varies depending on the extent of ischemic injury is uncertain. Objective: To describe the relationship between imaging estimates of irreversibly injured brain (core) and at-risk regions (mismatch) and clinical outcomes and EVT treatment effect. Design, Setting, and Participants: An exploratory analysis of the SELECT2 trial, which randomized 352 adults (18-85 years) with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) and large ischemic core to EVT vs medical management (MM), across 31 global centers between October 2019 and September 2022. Intervention: EVT vs MM. Main Outcomes and Measures: Primary outcome was functional outcome-90-day mRS score (0, no symptoms, to 6, death) assessed by adjusted generalized OR (aGenOR; values >1 represent more favorable outcomes). Benefit of EVT vs MM was assessed across levels of ischemic injury defined by noncontrast CT using ASPECTS score and by the volume of brain with severely reduced blood flow on CT perfusion or restricted diffusion on MRI. Results: Among 352 patients randomized, 336 were analyzed (median age, 67 years; 139 [41.4%] female); of these, 168 (50%) were randomized to EVT, and 2 additional crossover MM patients received EVT. In an ordinal analysis of mRS at 90 days, EVT improved functional outcomes compared with MM within ASPECTS categories of 3 (aGenOR, 1.71 [95% CI, 1.04-2.81]), 4 (aGenOR, 2.01 [95% CI, 1.19-3.40]), and 5 (aGenOR, 1.85 [95% CI, 1.22-2.79]). Across strata for CT perfusion/MRI ischemic core volumes, aGenOR for EVT vs MM was 1.63 (95% CI, 1.23-2.16) for volumes ≥70 mL, 1.41 (95% CI, 0.99-2.02) for ≥100 mL, and 1.47 (95% CI, 0.84-2.56) for ≥150 mL. In the EVT group, outcomes worsened as ASPECTS decreased (aGenOR, 0.91 [95% CI, 0.82-1.00] per 1-point decrease) and as CT perfusion/MRI ischemic core volume increased (aGenOR, 0.92 [95% CI, 0.89-0.95] per 10-mL increase). No heterogeneity of EVT treatment effect was observed with or without mismatch, although few patients without mismatch were enrolled. Conclusion and Relevance: In this exploratory analysis of a randomized clinical trial of patients with extensive ischemic stroke, EVT improved clinical outcomes across a wide spectrum of infarct volumes, although enrollment of patients with minimal penumbra volume was low. In EVT-treated patients, clinical outcomes worsened as presenting ischemic injury estimates increased. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

A worldwide review of illness outbreaks involving mixed salads/dressings and factors influencing product safety and shelf life.

The trends toward healthy living, vegetarianism, and busy schedules have increased salad popularity. Salads are usually consumed raw without any thermal treatment, and therefore, without proper care they can become major vehicles for foodborne illness outbreaks. This review examines the microbial quality of 'dressed' salads which contain two or more vegetables/fruits and salad dressings. The possible sources of ingredient contamination, recorded illnesses/outbreaks, and overall microbial quality observed worldwide, besides the antimicrobial treatments available are discussed in detail. Noroviruses were most frequently implicated in outbreaks. Salad dressings usually play a positive role in influencing microbial quality. However, this depends on several factors like the type of contaminating microorganism, storage temperature, dressing pH and ingredients, plus the type of salad vegetable. Very limited literature exists on antimicrobial treatments that can be used successfully with salad dressings and 'dressed' salads. The challenge with antimicrobial treatments is to find ones sufficiently broad in spectrum, compatible with produce flavour which can be applied at competitive cost. It is evident that renewed emphasis on prevention of produce contamination at the producer, processor, wholesale and retail levels plus enhanced hygiene vigilance at foodservice will have a major impact on reducing the risk of foodborne illnesses from salads.

Detection of Salmonella Enteritidis in Milk Using Conductometric Immunosensor Coated on Polyaniline/Zinc Oxide Nanocomposite.

The demand for rapid and accurate detection methods for Salmonella Enteritidis necessitates the development of highly sensitive and specific biosensors to ensure proper monitoring of food safety and quality requirements in the food sector and to secure human health. This study focused on development of a polyaniline/zinc oxide (PANI/ZnO) nanocomposite film on a gold electrode conductometric immunosensor for detection of Salmonella Enteritidis. The sensor was modified with monoclonal anti-Salmonella Enteritidis antibodies as biorecognition elements. The fabricated sensor was able to detect and quantify the target pathogen within 30 min and showed a good detection range from 101 to 105 colony-forming units (CFU)/mL for Salmonella Enteritidis and a minimum detection limit of 6.44 CFU/mL in 0.1% peptone water. Additionally, the fabricated sensor showed good selectivity and detection limit toward the target bacterium and successfully determined Salmonella Enteritidis content in ultrahigh heat-treated skim milk samples without pretreatment of the food sample.

The relationship of sinus opacification, olfaction and dupilumab efficacy in patients with CRSwNP.

BACKGROUND: Loss of sense of smell is one of the most burdensome symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP) but its relationship to sinus disease on imaging is unclear. Dupilumab improves sense of smell and radiographic severity of sinus disease in patients with CRSwNP. We investigated the relationship of sinus opacification severity and loci to olfactory impairment and dupilumab efficacy in patients with CRSwNP from the SINUS-24/SINUS-52 (NCT02912468/NCT02898454) studies. METHODS: Sinus opacification was evaluated using the Lund-Mackay computed tomography (LMK-CT) score and sense of smell using patient-reported loss of smell (LoS) score, University of Pennsylvania Smell Identification Test (UPSIT) score and the 22-item Sino-Nasal Outcome Test (SNOT-22) smell/taste item. RESULTS: At baseline, 95% of patients (688/724) had impaired sense of smell and opacification was extensive across all sinuses. Greater olfactory impairment was associated with greater opacification, especially in the ethmoid, sphenoid and frontal sinuses. At Week 24, reductions in LMK-CT total score and ethmoid and sphenoid sinus scores with dupilumab were weakly correlated with improvements in sense of smell assessed by LoS, UPSIT and SNOT-22 smell/taste item. More dupilumab than placebo patients achieved clinically meaningful improvement in LMK-CT total score at Week 24 and Week 52. CONCLUSION: Radiographic disease severity on imaging was associated with smell outcomes in this cohort. Opacification of the ethmoid, sphenoid and frontal sinuses was associated with severe smell loss. These data suggest that dupilumab effects on smell may be partly mediated through reduced sinus inflammation.

Convalescent plasma transfusion in severe COVID-19 patients: Clinical and laboratory outcomes.

INTRODUCTION: The objective of this study was to investigate the effect of convalescent plasma (CP) transfusion on clinical and serial laboratory parameters in severe COVID-19 patients. The Coronavirus Disease 2019 (COVID-19) pandemic presents a challenge to the healthcare system worldwide due to the limited treatment options available. The body of evidence reported that CP containing anti- COVID-19 antibodies could be effective against the infection. MATERIALS AND METHODS: This was a cross-sectional study that involved retrospective data collection of severe COVID-19 adult patients who received CP transfusion along with the best-of-care (CP group, n: 53) and best-of-care only (control group, n: 53). An age, gender, and comorbidity were manually matched approximately at a 1:1 ratio. RESULTS: The prevalence of adverse transfusion reactions was 5.7%. A shorter duration of oxygen support (median: 12 days vs 14 days, P=0.030) and a shorter duration of mechanical ventilation (median: 6 days vs 10 days, P=0.048) were found in the CP group. The laboratory parameters were also improved. However, there was no significant difference in the mechanical ventilation rate, length of hospital stay, length of intensive care unit (ICU) stay, and mortality rate across both groups (P = 0.492, 0.614, 0.793, 0.374). CONCLUSION: CP transfusion is safe and effective in the treatment of severe COVID-19 patients. However, a revision of our approaches such as early CP transfusion and use of a high-titre anti-COVID-19 neutralising antibody (nAb) unit is necessary to unlock the full potential benefits of CP transfusion among COVID-19 patients.

Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation.

Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.

We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75-55·97; P < 0·001) and had ≥ 3-point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26-55·34; P < 0·001) and ≥ 4-point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69-45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment-emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. CONCLUSIONS: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile.

Pharmacist assessment of drug-gene interactions and drug-induced phenoconversion in major depressive disorder: a case report.

BACKGROUND: Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity. CASE PRESENTATION: A patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization. CONCLUSION: This case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.

Autoimmunity in Human CE: Correlative with The Fertility Status of The CE Cyst.

Cystic echinococcosis is speculated to exert several immune-evasion strategies involving autoimmune-phenomena. We evaluated the hypothesizes that the prevalence of autoantibodies increases in the sera of CE patients that may evidence the association between the parasite and autoimmune diseases. Sera from 63 subjects at distinct types of CE cyst fertility were investigated for antinuclear antibodies (ANA), and anti-CCP antibodies. Plasma levels and cellular production of IL-17A cytokine were specifically defined as being assumed to prime for autoimmunity. Healthy-controls were age and gender-matched to test sera. ANA expressions inside the surgically removed metacestode and adventitial layer were also assayed. Out of 63 patients, 35 % had fertile highly viable cysts (group-1), 41 % had fertile low viable cysts (group-2) and 24 % had non-fertile cysts (group-3). A four-fold increase in ANA sera-levels was detected in group-1 compared with their controls (p-value 0.001) while anti-CCP levels were of insignificant differences. In group-2 and group-3, no significant differences were detected between ANA and anti-CCP sera-levels in CE patients and their controls. IL-17A sera-levels in group-1 and group- 2 were significantly higher than their healthy-controls while being of insignificant differences in group-3, p-value= 0.300. No association was detected between sera-levels of IL-17A and ANA as well as anti-CCP antibodies. Interestingly, relative IL-17A cellular expression associated positive ANA deposition in the parasite cells and adventitial layer. Collectively, based on the parasite fertility, IL-17A and ANA seemed to be involved in the host immune defenses against CE. There is no association between CE and anti-CCP antibodies.

Antagonistic effects of Lactobacillus reuteri against Escherichia coli O157:H7 in white-brined cheese under different storage conditions.

This study aimed to investigate the survival of the foodborne pathogen Escherichia coli O157:H7 in white-brined cheeses as influenced by the presence of Lactobacillus reuteri. The white cheeses were made from pasteurized bovine milk inoculated with E. coli O157:H7 (cocktail of 3 strains) to achieve ∼5 log10 cfu/g with absence or presence of Lb. reuteri (∼6 log10 cfu/g). Cheese samples were brined in 10% or 15% NaCl solution and stored at 10°C and 25°C for 28 d. The white-brined cheeses were assessed for salt content, pH, water activity (Aw), and numbers of E. coli O157:H7, Lb. reuteri, nonstarter lactic acid bacteria (NSLAB), yeasts, and molds. Results showed that E. coli O157:H7 survived in cheese stored in both brine solutions at 10°C and 25°C regardless of the presence of Lb. reuteri. A substantial reduction was observed in cheese stored in 10% NaCl brine at 25°C, followed by cheese stored in 15% NaCl brine at 10°C by 2.64 and 2.16 log10 cfu/g, respectively, in the presence of Lb. reuteri and by 1.02 and 1.87 log10 cfu/g, respectively, in the absence of Lb. reuteri under the same conditions. The pathogen in brine solutions survived but at a lower rate. Furthermore, the growth of Lb. reuteri and NSLAB were enhanced or slightly decreased in cheese and brine by 28 d, respectively. The salt concentrations of cheese ranged from 4 to 6% and 5 to 7% (wt/wt), during 28-d ripening in 10 and 15% brine, respectively. Values of pH and Aw slightly increased at d 1 after exposure to brine and reached 4.69 to 6.08 and 0.91 to 0.95, respectively, in all treatments. Therefore, the addition of Lb. reuteri can be used as a biopreservation method to inhibit the survival of E. coli O157:H7 in white-brined cheese when combined with the appropriate temperature, NaCl level, and storage time.

Dupilumab reduces systemic corticosteroid use and sinonasal surgery rate in CRSwNP.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease with a high symptom burden and poor quality of life. Treatment options include recurrent surgeries and/or frequent systemic corticosteroids (SCS). Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key drivers of type 2-mediated inflammation. We report results of pooled analyses from 2 randomised, double-blind, placebo-controlled phase 3 studies (SINUS 24 [NCT02912468]; SINUS-52 [NCT02898454]) to evaluate dupilumab effect versus placebo in adults with CRSwNP with/without SCS use and sinonasal surgery. METHODOLOGY: SINUS-24 patients were randomised 1:1 to subcutaneous dupilumab 300 mg (n=143) or placebo (n=133) every 2 weeks (q2w) for 24 weeks. SINUS-52 patients were randomised 1:1:1 to 52 weeks of subcutaneous dupilumab 300 mg q2w (n=150), 24 weeks q2w followed by 28 weeks of dupilumab 300 mg every 4 weeks (n=145) or 52 weeks of placebo q2w (n=153). RESULTS: Dupilumab reduced the number of patients undergoing sinonasal surgery (82.6%), the need for in-study SCS use (73.9%), and SCS courses (75.3%). Significant improvements were observed with dupilumab vs placebo regardless of prior sinonasal surgery or SCS use in nasal polyp, nasal congestion, Lund-MacKay, and Sinonasal Outcome Test (22-items) scores, and the University of Pennsylvania Smell Identification Test. CONCLUSIONS: Dupilumab demonstrated significant improvements in disease signs and symptoms and reduced the need for sino-nasal surgery and SCS use versus placebo in patients with severe CRSwNP, regardless of SCS use in the previous 2 years, or prior sinonasal surgery.

Formation of furan in baby food products: Identification and technical challenges.

Furan is generally produced during thermal processing of various foods including baked, fried, and roasted food items such as cereal products, coffee, canned, and jarred prepared foods as well as in baby foods. Furan is a toxic and carcinogenic compound to humans and may be a vital hazard to infants and babies. Furan could be formed in foods through thermal degradation of carbohydrates, dissociation of amino acids, and oxidation of polyunsaturated fatty acids. The detection of furan in food products is difficult due to its high volatility and low molecular weight. Headspace solid-phase microextraction coupled with gas chromatography/mass spectrometer (GC/MS) is generally used for analysis of furan in food samples. The risk assessment of furan can be characterized using margin of exposure approach (MOE). Conventional strategies including cooking in open vessels, reheating of commercially processed foods with stirring, and physical removal using vacuum treatment have remained unsuccessful for the removal of furan due to the complex production mechanisms and possible precursors of furan. The innovative food-processing technologies such as high-pressure processing (HPP), high-pressure thermal sterilization (HPTS), and Ohmic heating have been adapted for the reduction of furan levels in baby foods. But in recent years, only HPP has gained interest due to successful reduction of furan because of its nonthermal mechanism. HPP-treated baby food products are commercially available from different food companies. This review summarizes the mechanism involved in the formation of furan in foods, its toxicity, and identification in infant foods and presents a solution for limiting its formation, occurrence, and retention using novel strategies.

eV-Scale Sterile Neutrino Search Using Eight Years of Atmospheric Muon Neutrino Data from the IceCube Neutrino Observatory.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV^{2}. The best-fit point is found to be at sin^{2}(2θ_{24})=0.10 and Δm_{41}^{2}=4.5 eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Microbial safety of oily, low water activity food products: A review.

Oily, low water activity (OL aw) products including tahini (sesame seed paste), halva (tahini halva), peanut butter, and chocolate, have been recently linked to numerous foodborne illness outbreaks and recalls. This review discusses the ingredients used and processing of OL aw products with a view to provide greater understanding of the routes of their contamination with foodborne pathogens and factors influencing pathogen persistence in these foods. Adequate heat treatment during processing may eliminate bacterial pathogens from OL aw foods; however, post-processing contamination commonly occurs. Once these products are contaminated, their high fat and sugar content can enhance pathogen survival for long periods. The physiological basis and survival mechanisms used by pathogens in these products are comprehensively discussed here. Foodborne outbreaks and recalls linked to OL aw foods are summarized and it was observed that serotypes of Salmonella enterica were the predominant pathogens causing illnesses. Further, intervention strategies available to control foodborne pathogens such as thermal inactivation, use of natural antimicrobials, irradiation and hydrostatic pressure are assessed for their usefulness to achieve pathogen control and enhance the safety of OL aw foods. Sanitation, hygienic design of manufacturing facilities, good hygienic practices, and environmental monitoring of OL aw food industries were also discussed.