Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner.

BACKGROUND: Chemotherapy is included in treatment regimens for many solid cancers, but when administered as a single agent it is rarely curative. The addition of immune checkpoint therapy to standard chemotherapy regimens has improved response rates and increased survival in some cancers. However, most patients do not respond to treatment and immune checkpoint therapy can cause severe side effects. Therefore, there is a need for alternative immunomodulatory drugs that enhance chemotherapy. METHODS: We used gene expression data from cyclophosphamide (CY) responders and non-responders to identify existing clinically approved drugs that could phenocopy a chemosensitive tumor microenvironment (TME), and tested combination treatments in multiple murine cancer models. RESULTS: The vitamin A derivative tretinoin was the top predicted upstream regulator of response to CY. Tretinoin pre-treatment induced an inflammatory, interferon-associated TME, with increased infiltration of CD8 + T cells, sensitizing the tumor to subsequent chemotherapy. However, while combination treatment significantly improved survival and cure rate in a CD4+ and CD8+ T cell dependent manner in AB1-HA murine mesothelioma, this effect was model-selective, and could not be replicated using other cell lines. CONCLUSIONS: Despite the promising data in one model, the inability to validate the efficacy of combination treatment in multiple cancer models deprioritizes tretinoin/cyclophosphamide combination therapy for clinical translation.

A systematic review and meta-analysis of human population studies on the association between exposure to toxic environmental chemicals and left ventricular dysfunction (LVD).

BACKGROUND: Exposure to environmental chemicals has been associated with an elevated risk of heart failure (HF). However, the impact on early markers of HF, such as left ventricular dysfunction (LVD), remains limited. OBJECTIVE: To establish a foundation of evidence regarding early HF markers and their association with environmental pollutants, a systematic review and meta-analysis was conducted. METHODS: The search, conducted on October 13th, 2023, encompassed PubMed, Embase, and Web of Science without filters, focusing on observational studies reporting myocardial geometrical, structural, or functional alterations in individuals without a history of heart disease. This included the general adult population, workers, young people, and the elderly. The risk of bias was assessed using the ROBINS-I tool at both study and item levels. RESULTS: The systematic review included 17 studies involving 43.358 individuals exposed to air pollution and 2038 exposed to heavy metals. Approximately 41% of the effect measures of associations reported significant abnormalities in myocardial structure or function. The metanalyses by pollutants categories indicated positive associations between LV systolic and diastolic abnormalities and exposure to PM2.5 [-0.069 (-0.104, -0.033); -0.044 (-0.062, -0.025)] and PM10 [-0.055 (-0.087, -0.022); -0.030 (-0.050, -0.010)] and NO2 [-0.042 (-0.071, -0.013); -0.021 (-0.037, -0.004)], as well as positive associations between lead exposure and LV systolic abnormalities [-0.033 (-0.051, -0.016)]. CONCLUSIONS: Existing evidence shows that specific early markers of HF may be associated with exposure to chemical pollutants. It is recommended to include such endpoints in new longitudinal and case-control studies to confirm further risk associations. These studies should consider co-exposures, account for vulnerable groups, and identify cardiotoxic compounds that may require regulation. When examining the link between myocardial abnormalities and environmental exposure, it is also advisable to explore the supportive use of Adverse Outcome Pathway (AOP) approaches to confirm a causal relationship.

Fertility in seasonal-calving pasture-based lactating dairy cows following timed artificial insemination or timed embryo transfer with fresh or frozen in vitro-produced embryos.

The objective was to compare pregnancy per service event (P/S) in lactating dairy cows following timed artificial insemination (AI) or timed embryo transfer (ET) using either fresh or frozen in vitro-produced embryos. Oocytes were collected once per week for up to 9 wk using transvaginal ovum pick-up from elite dairy donors (ET-DAIRY; n = 40; Holstein-Friesian and Jersey) and elite beef donors (ET-ELITE-BEEF; n = 21; Angus). Both ET-DAIRY and ET-ELITE-BEEF donors consisted of heifers and cows. In addition, oocytes were collected from the ovaries of beef heifers of known pedigree following slaughter at a commercial abattoir (ET-COMM-BEEF; n = 119). Following in vitro maturation and fertilization, presumptive zygotes were cultured in vitro to the blastocyst stage. Grade 1 blastocysts were either transferred fresh or frozen for on-farm thawing and direct transfer. A total of 1,106 recipient cows (all lactating, predominantly Holstein-Friesian) located on 16 herdlets were blocked based on parity, calving date, and Economic Breeding Index, and randomly assigned to receive AI (n = 243) or ET (n = 863) after estrous synchronization with a 10-d Progesterone-synch protocol. Cows assigned to ET were further randomized to receive fresh (n = 187) or frozen (n = 178) ET-ELITE-BEEF embryos, fresh (n = 169) or frozen (n = 162) ET-DAIRY embryos, or fresh (n = 80) or frozen (n = 87) ET-COMM-BEEF embryos. Pregnancy was diagnosed using transrectal ultrasound on d 32 to 35 after synchronized ovulation and confirmed on d 62 to 65, at which time fetal sex was determined. Pregnancy per service event at d 32 was not different between AI (48.8%) and ET (48.9%) and did not differ between dairy and beef embryos (50.3% vs. 48.1%, respectively). However, P/S was less on d 32 following transfer of frozen embryos (41.6%) compared with fresh embryos (56.1%). Pregnancy loss between d 32 and 62 was greater for ET (15.1%) compared with AI (4.7%), with greater losses observed for frozen beef (18.5%), fresh beef (17.3%), and frozen dairy (19.2%) compared with fresh dairy (6.0%) embryos. Serum progesterone (P4) concentration on d 7 was associated with P/S at d 32 and 62. Cows in the quartile with the least serum P4 concentrations (quartile 1) had less probability of being pregnant on d 32 (33.4%) compared with cows in the 3 upper quartiles for serum P4 (45.7%, 55.6%, and 61.2% for quartile 2, quartile 3, and quartile 4, respectively). Sex ratio (male:female) at d 62 was skewed toward more male fetuses following ET (61.1:38.9) compared with AI (43.2:56.8) and was consistent with the sex ratio among in vitro blastocysts (61.2:38.8). In conclusion, P/S was similar for AI and ET, although pregnancy loss between d 32 and 62 was greater for ET than for AI.

Could the aroma of spices produce a cross-modal enhancement of food saltiness and contribute to reducing salt intake?

BACKGROUND: As a result of its correlation with cardiovascular diseases, salt intake must be reduced. According to multi-sensory integration, aroma plays an important role in saltiness enhancement; this could enable a food's salt content to be reduced without losing acceptance. We therefore studied the effect of three spices, Curcuma longa, Laurus nobilis L. and Petroselinum crispum L., on saltiness enhancement through sensory tests on consumers. This was followed by olfactometric analysis with the aim of relating the effect to the spices' aromatic composition. RESULTS: According to the odour-induced salty taste enhancement (OISE) mean values, bay leaf and turmeric had the highest effect on saltiness enhancement, at a similar level to dry-cured ham aroma, wherwas parsley had a significantly lower OISE value. Only one odour-active compound (OAC), eugenol, showed a direct correlation with the spices' OISE values. Turmeric primarily had OACs with sweet aroma, whereas bay leaf had more OACs belonging to the spicy-aroma category. CONCLUSION: The three spices, turmeric, bay leaf and parsley, investigated in the present study appear to enhance the salty taste of mashed potato with a low salt content. The results suggest that an interaction effect among OACs with different aromatic ranges may exist. Therefore, when the global OAC modified frequency value, grouped according to aroma range, was considered, the sweet range appears to counteract the effect of the spicy aroma on saltiness. © 2024 Society of Chemical Industry.

Resistance Training-Induced Acute Hypoalgesia in Women With Persistent Pain After Breast Cancer Treatment.

ABSTRACT: Fogh Rasmussen, GH, Madeleine, P, Arroyo-Morales, M, Voigt, M, and Kristiansen, M. Resistance training-induced acute hypoalgesia in women with persistent pain after breast cancer treatment. J Strength Cond Res 37(3): e16-e24, 2023-The aim of this study was to determine whether a single bout of resistance training (RT) produces acute exercise-induced hypoalgesia (EIH) in breast cancer survivors (BCS) suffering from persistent pain ≥1.5 years after treatment. Twenty individuals with self-reported pain ≥3 on a 0-10 Numerical Rating Scale after treatment for breast cancer completed 3 experimental sessions, (a) familiarization; (b) 1 repetition maximum (1RM) normalization, and (c) training, consisting of 3 sets of 10 repetitions at 60% of 1 repetition maximum. Pressure pain thresholds (PPTs) were measured before and after training for the dorsal and ventral shoulder regions of the affected side. Movement-evoked pain (MEP) and rating of perceived exertion (RPE) were collected immediately after each set. A p -value less than 0.05 was considered statistically significant. The results demonstrated a significant increase in PPTs of the ventral shoulder region after a single bout of RT ( p ≤ 0.05), indicating a localized analgesic response for this area. By contrast, no change was detected in PPTs on the dorsal shoulder region. No significant differences were found in MEP between sessions despite a significant increase in load and RPE during 1RM assessment ( p ≤ 0.05), indicating that MEP was not affected by increase in absolute and relative intensity. In conclusion, a single bout of submaximal RT reduced PPTs for the ventral shoulder region of BCS with persistent pain after treatment and was well tolerated. Hence, RT may be a useful therapeutic tool for managing persistent pain after breast cancer treatment in clinical practice.

Different coatings on magnetic nanoparticles dictate their degradation kinetics in vivo for 15 months after intravenous administration in mice.

BACKGROUND: The surface coating of iron oxide magnetic nanoparticle (MNPs) drives their intracellular trafficking and degradation in endolysosomes, as well as dictating other cellular outcomes. As such, we assessed whether MNP coatings might influence their biodistribution, their accumulation in certain organs and their turnover therein, processes that must be understood in vivo to optimize the design of nanoformulations for specific therapeutic/diagnostic needs. RESULTS: In this study, three different MNP coatings were analyzed, each conferring the identical 12 nm iron oxide cores with different physicochemical characteristics: 3-aminopropyl-triethoxysilane (APS), dextran (DEX), and dimercaptosuccinic acid (DMSA). When the biodistribution of these MNPs was analyzed in C57BL/6 mice, they all mainly accumulated in the spleen and liver one week after administration. The coating influenced the proportion of the MNPs in each organ, with more APS-MNPs accumulating in the spleen and more DMSA-MNPs accumulating in the liver, remaining there until they were fully degraded. The changes in the physicochemical properties of the MNPs (core size and magnetic properties) was also assessed during their intracellular degradation when internalized by two murine macrophage cell lines. The decrease in the size of the MNPs iron core was influenced by their coating and the organ in which they accumulated. Finally, MNP degradation was analyzed in the liver and spleen of C57BL/6 mice from 7 days to 15 months after the last intravenous MNP administration. CONCLUSIONS: The MNPs degraded at different rates depending on the organ and their coating, the former representing the feature that was fundamental in determining the time they persisted. In the liver, the rate of degradation was similar for all three coatings, and it was faster than in the spleen. This information regarding the influence of coatings on the in vivo degradation of MNPs will help to choose the best coating for each biomedical application depending on the specific clinical requirements.

Iron oxide and iron oxyhydroxide nanoparticles impair SARS-CoV-2 infection of cultured cells.

BACKGROUND: Coronaviruses usually cause mild respiratory disease in humans but as seen recently, some human coronaviruses can cause more severe diseases, such as the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the global spread of which has resulted in the ongoing coronavirus pandemic. RESULTS: In this study we analyzed the potential of using iron oxide nanoparticles (IONPs) coated with biocompatible molecules like dimercaptosuccinic acid (DMSA), 3-aminopropyl triethoxysilane (APS) or carboxydextran (FeraSpin™ R), as well as iron oxyhydroxide nanoparticles (IOHNPs) coated with sucrose (Venofer®), or iron salts (ferric ammonium citrate -FAC), to treat and/or prevent SARS-CoV-2 infection. At non-cytotoxic doses, IONPs and IOHNPs impaired virus replication and transcription, and the production of infectious viruses in vitro, either when the cells were treated prior to or after infection, although with different efficiencies. Moreover, our data suggest that SARS-CoV-2 infection affects the expression of genes involved in cellular iron metabolism. Furthermore, the treatment of cells with IONPs and IOHNPs affects oxidative stress and iron metabolism to different extents, likely influencing virus replication and production. Interestingly, some of the nanoparticles used in this work have already been approved for their use in humans as anti-anemic treatments, such as the IOHNP Venofer®, and as contrast agents for magnetic resonance imaging in small animals like mice, such as the FeraSpin™ R IONP. CONCLUSIONS: Therefore, our results suggest that IONPs and IOHNPs may be repurposed to be used as prophylactic or therapeutic treatments in order to combat SARS-CoV-2 infection.

Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers.

The prevalence of allergic disorders has increased drastically over the last 50 years to the extent that they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy that targets the underlying cause of allergic disorders, and evidence of its superiority is based on data accumulated from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unresolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and the establishment of international reference standards for many allergens. This article discusses issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products from different manufacturers is an appropriate basis for selecting a specific AIT product. Allergen standardization in immunotherapy products is critical for ensuring quality and, thereby, safety and efficacy. However, lack of harmonization in manufacturing processes, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products based solely on major allergen amounts is not rational and, in fact, impossible. Moreover, when rating the information given for a specific product, it is necessary to take into account further inherent characteristics of products and their application in clinical practice, such as the state of extract modification, addition of adjuvant or adjuvant system, route of administration (sublingual/ subcutaneous), and cumulative dose as per posology (including the volume per administration). Finally, only convincing clinical data can serve as the basis for product-specific evaluation and cross-product comparability of individual products.

Nematicidal activity of leaf extract of Moringa oleifera Lam. against Haemonchus contortus and Nacobbus aberrans.

In the present study, the nematicidal activity of a Moringa oleifera ethyl acetate leaf extract against the eggs and larvae of Haemonchus contortus and Nacobbus aberrans, nematodes of agricultural importance, was evaluated. The experimental design for the evaluation of the effects against both nematodes consisted of eight treatments (n = 4). Distilled water, Tween (4%) and a commercial anthelmintic agent (ivermectin, 5 mg/mL) were used as controls, and for treatments 4-8, the concentrations of the extract were 20, 10, 5, 2.5 and 1.25 mg/mL, respectively. Readings were taken at 12 h and 24 h for N. aberrans and 48 h and 72 h for H. contortus post-treatment under an optical microscope (10× and 40×). The data obtained were analysed by analysis of variance through a completely randomized factorial design using the SAS V9 program. The results show that, for H. contortus egg hatching, 85.88% inhibition was obtained at a concentration of 20 mg/mL at 48 h, while for third-stage larva (L3) mortality, the highest percentage was 68.19% at 1.25 mg/mL at 72 h. In the case of N. aberrans, the greatest inhibition of egg hatching was 90.69% at 5 mg/mL at 12 h post-treatment, and for larval mortality, it was 100% at 10 mg/mL at 24 h post-treatment. The main major compounds identified by qualitative analysis and by gas chromatography coupled to mass spectrometry were 9,12,15-octadecatrienoic acid, (Z,Z,Z)-, n-hexadecanoic acid and 2,4-di-tert-butylphenol, and the minor compounds included phytol, γ-sitosterol and α-tocopheryl acetate. It was demonstrated that the ethyl acetate leaf extract of M. oleifera Lam. shows great potential for combating agricultural nematodes.

Real-life cost-effectiveness of benralizumab in patients with severe asthma.

BACKGROUND: Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. METHODS: This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). RESULTS: After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. CONCLUSIONS: All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Conyza bonariensis as an alternative host for Colletotrichum species in Argentina.

AIMS: This study investigated the diversity of Colletotrichum isolates recovered from Conyza bonariensis leaves through the use of morphological characteristics, growth rate, carbon sources utilization and phylogenetic analysis. METHODS AND RESULTS: In all, 30 Colletotrichum isolates recovered from C. bonariensis leaves showing symptoms of disease were included in the present study. Based on the analysis of morphology and sequences, the isolates were distributed into six Colletotrichum species complexes. The concatenated alignment of GAPDH and ITS sequences showed that 20 out of 30 isolates were included in four species complexes which comprise the most important pathogens causing anthracnose in soybean or anthracnose and stalk rot in maize: C. truncatum, C. orchidearum, C. gloeosporioides and C. graminicola. The remaining 10 isolates were included in the C. boninense and C. destructivum species complexes or could not be assigned to any complex with the available information. CONCLUSION: Weeds belonging to genus Conyza are host to soybean and maize potential pathogenic species of Colletotrichum and could have a role as inoculum reservoir for cross contamination in the agroecosystem. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined use of morphological, kinetics and physiological parameters of growth and phylogenetic analysis in Colletotrichum isolates from Conyza leaves allowed the detection of species complexes previously not identified in Argentina.

The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

Inheritance of the SLICK1 allele of PRLR in cattle.

The slick-hair phenotype in cattle is due to one of a series of mutations in the prolactin receptor (PRLR) that cause truncation of the C-terminal region of the protein involved in JAK2/STAT5 activation during prolactin signaling. Here we evaluated whether the inheritance of the SLICK1 allele, the first slick mutation discovered, is inherited in a fashion consistent with Hardy-Weinberg equilibrium. It was hypothesized that any deleterious effect of inheriting the allele on embryonic or fetal function would result in reduced frequency of the allele in offspring. A total of 525 Holstein and Senepol cattle produced from matings involving one or both parents with the SLICK1 allele were genotyped. The observed frequency of the SLICK1 allele (0.247) was not significantly different than the expected frequency of 0.269. These results support the idea that inheritance of the SLICK1 allele does not act in the embryo or fetus to modify its competence to complete development to term.

Relating starter cultures to volatile profile and potential markers in green Spanish-style table olives by compositional data analysis.

This work relates native lactic acid bacteria (LAB) (Lactobacillus pentosus LPG1, L. pentosus Lp13, and Lactobacillus plantarum Lpl15) and yeast (Wickerhamomyces anomalus Y12) starters to the volatile components (VOCs) produced in green Spanish-style table olives. For this aim, the VOC profile was considered as compositional data (CoDa). The CoDa analysis generated new information on the relationship among inocula and VOCs through the tetrahedral plot, CoDa-biplot, variation array matrix, and CoDa dendrogram. The ilr (which includes pivot) coordinates (Euclidean space) from VOCs produced more reliable starters' clustering than the original data. The potential VOC markers, identified by a test based on the pairwise comparison of the logratio variation arrays from the whole data set and the individual groups, were (starters in the parenthesis): 2-phenylethyl acetate (LPG1, Y12, Y12 + LAB), methanol (Lpl15), cis-2-penten-1-ol (LPG1, Y12, Y12 + LAB), 2-methyl-3-hexanol (LPG1, Y12), U (non-identified) C (m/z 83-112-97) (Y12) and UF (m/z 95-154-110) (LPG1, Y12 + LAB). Besides, some VOCs were partial/totally inhibited by specific starters: 2-methyl-1-propanol (Lp13, Y12 + LAB), 2-phenyl ethanol (Lp13), furfuryl methyl ether (Y12 + LAB), purpurocatechol (Y12, Y12 + LAB), 4-ethyl guaiacol (Lp13, Lpl15), 4-ethyl phenol (Lpl15), 5-tert-butylpyrogallol (Lp13, Lpl15), and UE (m/z 111-198) (Lp13). A better understanding of the relationship between starters and their VOC may facilitate modelling the flavour and quality of Spanish-style green table olive fermentations.

Evaluation of Polysaccharide Typhim Vi Antibody Response as a predictor of Humoral Immunodeficiency in Haematological Malignancies.

An increasing healthcare challenge in the management of haematological malignancy (HM) is secondary immunodeficiency. From January 2019, the EMA included the evaluation of specific antibody (Ab) responses to better select patients for immunoglobulin replacement therapy (IgRT). We evaluated Ab responses to pneumococcal and Salmonella typhi pure polysaccharide immunization in a cohort of 42 HM patients and 24 healthy-controls. Pre-post specific Ab concentrations were measured by ELISA at 4 weeks. Globally, significantly lower Typhim Vi (TV) seroprevalence (9%) compared to 23-valent pneumococcal polysaccharide vaccine (PPV) (76%) (p <0.001) was observed. TV non responders (88%) were higher than PPV non responders (62%) (p <0.0001) and correlated better to infectious history. By ROC analysis, pre-post 5-fold TV increase was the best cut-off to discriminate HM with recurrent infections and controls (sensitivity 91%, specificity 100%). Despite the small sample cohort, our results suggest that specific anti-S typhi Ab response is a useful complementary assay in the diagnosis and management decision of SID to HM.

Reachability Deficits in Quantum Approximate Optimization.

The quantum approximate optimization algorithm (QAOA) has rapidly become a cornerstone of contemporary quantum algorithm development. Despite a growing range of applications, only a few results have been developed towards understanding the algorithm's ultimate limitations. Here we report that QAOA exhibits a strong dependence on a problem instances constraint to variable ratio-this problem density places a limiting restriction on the algorithms capacity to minimize a corresponding objective function (and hence solve optimization problem instances). Such reachability deficits persist even in the absence of barren plateaus and are outside of the recently reported level-1 QAOA limitations. These findings are among the first to determine strong limitations on variational quantum approximate optimization.

Improved magnetic lateral flow assays with optimized nanotags for point-of-use inductive biosensing.

Lateral flow assays may be used by minimally trained personnel for fast and inexpensive bioanalyses in decentralized non-exigent environments. Their extension to a broader catalog of applications depends on improvements in their quantification and their sensitivity. We report a strategy that combines nanomagnetic tagging of the analyte of interest with radiofrequency inductive sensing, easy to achieve in friendly and portable format. To optimize nanotag performance, we investigated the influences of their magnetic core size and agglomeration. Iron oxide nanoparticles, with sizes from 5 to 23 nm, were synthesized by thermal decomposition and then coated with dimercaptosuccinic acid and functionalized with neutravidin protein. We tested the system by immobilizing biotin in lateral flow membrane strips. When a sample containing the particles flows along the membrane, the biotin captures the neutravidin together with the magnetic nanotags, which are detected by the inductive sensor. The optimal nanotag core size is the critical threshold for superparamagnetic behavior, which maximizes both the initial magnetic permeability and the saturation magnetization. Controlled agglomeration of the nanotags increases the magnetic mass captured in the test line and further amplifies the signal.

Myofascial pain, widespread pressure hypersensitivity, and hyperalgesia in the face, neck, and shoulder regions, in survivors of head and neck cancer.

PURPOSE: Medical treatment for head and neck cancer may induce the presence of inflammation, pain, and dysfunction. The purpose of the current study was to assess the presence of myofascial trigger points (TrPs) and their relationship with widespread pressure hypersensitivity and hyperalgesia in survivors of head and neck cancer (sHNC). METHODS: TrPs and pressure-pain thresholds (PPTs) were quantified in different muscles/joints in the head and neck of 30 sHNC (59.45 ± 13.13 years) and 28 age- and sex-matched controls (58.11 ± 12.67 years). RESULTS: The sHNC had more TrPs in all muscles on the affected side (p < 0.05) than did the healthy controls, and in the temporalis, masseter, and suboccipitalis muscles on the unaffected side (p < 0.05). They also had lower PPTs in all places (p < 0.05) except for the temporalis muscle (p = 0.114) and C5-C6 joint (p = 0.977). The intensity of cervical pain correlated positively with the presence of upper trapezius TrPs. CONCLUSIONS: sHNC suffering cervical and/or temporomandibular joint pain have multiple active TrPs and experience widespread pressure hypersensitivity and hyperalgesia, suggestive of peripheral and central sensitization.

Invariant correlated optical fields driven by multiplicative noise.

We describe the evolution of a linear transmittance when it is perturbed with multiplicative noise; the evolution is approximated through an ensemble of random transmittances that are used to generate diffraction fields. The randomness induces a competition mechanism between noise and transmittance, and it is identified through the self-correlation function. We show that the geometry of the self-correlation function is a single peak preserved in the diffraction field that can be matched with localization-like effects. To corroborate the theoretical predictions, we perform an experiment using a linear grating where the noise is approximated by a stochastic Markov chain. Experimental results are shown.