Undetectable Levels Research Articles

A large-scale screening of hepatitis C among men who have sex with men in the community using saliva point-of-care testing

AimTo assess the feasibility and acceptability of massive hepatitis C virus (HCV) testing in point of care on the street using quick tests, determine the characteristics of the population included, and the prevalence of HCV infection in this population.MethodsCross-sectional community-based study including adult men who have sex with men (MSM) who attended the three most important LGTB+ events in Sitges (Catalonia, Spain) in 2022. Points of care were set up on tents on the street and attendees were offered voluntary anti-HCV antibody self-testing. Participants were informed of the study, provided consent, completed the test for identification of risk practices (TIRP), and took the test with the OraQuick® HCV test on a saliva sample (sensitivity: 97.8% [95% confidence interval (CI), 93.2–99.4%] and specificity: 100% [95% CI, 98.4–100%]; gold standard: IgG antibody test for HCV by immunoassay [serum]); participants with positive results were offered HCV virus testing with the Xpert HCV Fingerstick® on a blood drop.ResultsA total of 1249 adults participated in the large-scale screening, of which 1197 (95.8%) were identified as MSM. The screening time was 39 participants/h. Four (0.32%) participants had positive anti-HCV results, all with undetectable HCV RNA levels. Participants’ median (IQR) age was 44 (35, 54) years; most were Europeans, and 13% reported being unaware of their serological HCV status. The mean (SD) TIRP score was 1.40 (1.44) (n = 1062), with 67.41% reporting some risk, and the self-perceived sexually transmitted disease score was 3.0 (2.82) (n = 969).ConclusionThe point-of-care strategy on the street using a quick oral self-test at massive MSM events is feasible, well-accepted, and quick, and may be a useful strategy to reach other populations at risk of HCV infection.

Investigation Growth and Survival Of Some Pathogens In Koumiss

The aim of this study was to investigate the growth and survival of Escherichia coli O157:H7, Listeria monocytogenes and Staphylococcus aureus in koumiss produced from raw mare's milk during the fermentation process. E. coli O157:H7 (Group 1), L. monocytogenes (Group 2) and S. aureus (Group 3) were added to the raw mare’s milk that would used to producing koumiss and a combination of all three pathogens (Group 4) was inoculated. These microorganisms were introduced at 106 cfu/ml concentration into the raw mare’s milk, which served as the base for koumiss production. During fermentation, microbiological and chemical analyses were carried out by taking one sample from each group at the 1st, 5th and 24th hours and at the 2nd, 3rd, 4th and 5th days. As a result of analyzes; pH, dry matter, and protein content declined, while titration acidity and alcohol content increased. A positive correlation was found between the bacterial count and the utilized pathogenic microorganisms. Conversely, a negative correlation was observed with the count of yeast molds. Remarkably, the counts of E. coli O157:H7, L. monocytogenes, and S. aureus reduced starting from the fifth hour of fermentation and diminished to undetectable levels by the second day. This decline in pathogenic microorganisms below detectable thresholds during the fermentation process was linked to the rise in titration acidity and alcohol content and the decrease in pH.

Novel variants impairing Sp1 transcription factor binding in the COL7A1 promoter cause mild cases of recessive dystrophic epidermolysis bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genodermatosis characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications. RDEB is caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils which form attachment structures stabilizing the cutaneous basement membrane zone. Most of the previously reported COL7A1 mutations are located in the coding or intronic regions. We describe 6 patients with localized or intermediate RDEB for whom one recessive pathogenic variant in the coding region and a second variant in the COL7A1 promoter were identified. These substitutions, three of which are novel, are localized in two Sp1 binding sites of the promoter region. DNA pull-down assay showed a drastic reduction of Sp1 binding consistent with a dramatic decrease in COL7A1 transcript and almost undetectable C7 protein levels. Our results reveal that mutations in the COL7A1 promoter on the background of a null allele can underlie localized or intermediate RDEB. They further emphasize the functional importance of Sp1 motifs in the proximal COL7A1 promoter which should be carefully investigated for regulatory mutations in the case of RDEB with only one pathogenic variant identified in the coding or intronic regions.

Prevalence of measurable residual disease in patients with refractory/relapsed multiple myeloma who reached complete response: a cross-sectional multicentric study

BackgroundMultiple myeloma (MM) is an incurable hematologic malignancy, and even though the complete response (CR) rate has been growing, a high percentage of patients continues to relapse. Recent research showed that most relapses may be related to the persistence of measurable residual disease (MRD). In this study, we intended to evaluate the MRD status in MM patients who reached CR in their second or third lines of treatment.MethodsThis was a cross-sectional, multicentre, non-interventional study to describe the MRD status in patients with relapsed or refractory MM (rrMM), with documented CR; adult male and female patients, from 11 Portuguese sites, in their second or third line of treatment were included. Bone marrow MRD was assessed through next-generation flow cytometry (NGF) technology.ResultsAmong the 68 subjects who gave informed consent, 48 were considered eligible for the study. Of the 48 subjects with confirmed CR, 31 (64.6%) had undetectable MRD levels. The incidence of undetectable MRD was lower in International Staging System (ISS) III patients compared with ISS I/II patients (60% vs. 70.8%; p = 0.45), and lower in patients treated without daratumumab-containing regimens compared with those treated with daratumumab-containing regimens (57.1% vs. 75.0%; p = 0.30). Notably, despite the small sample size, the incidence of undetectable MRD was significantly lower in patients with high-risk cytogenetics compared to those with standard risk (33.3% vs. 76.0%; p = 0.04).DiscussionOur results highlight the possibility of achieving undetectable MRD in the rrMM setting, especially in earlier stages and with highly effective protocols. We expect that this work leverages the implementation of larger real-world evidence studies in rrMM patients, in which MRD may also be defined as a primary endpoint.

True and false positive HIV point of care test results in a prospective multinational study of at-risk African women: implications for large-scale repeat HIV testing in HIV prevention programs.

Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, though false (both negative and positive) results are expected to occur. We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using three contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. HIV serologic testing was conducted quarterly using two parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and ribonucleic acid (RNA). 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (i.e., one negative and one positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing but six (9.7%) had dually-positive rapid results and four (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. Although the majority of rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.

Bisphenol A in Indian Take-Out Soups: Compliance, Implications and Sustainable Solutions

This research investigates the migration of Bisphenol A (BPA) from packaging containers into take-out vegetable soups and premixed tomato soups through three replicate studies. The samples underwent extraction using solid-phase extraction (SPE) cartridges, followed by separation on a C18 column. BPA concentrations in the soups were assessed at 15, 30, and 45-minute intervals, consistently revealing undetectable levels (<LOQ). Plastic packaging samples, known for BPA utilization in production, remained below the Specific Migration Limit (SML) set at 0.5 mg.kg-1, irrespective of material type or contact conditions. These results, conforming to EC regulations, suggest that food-contact materials (FCMs) in the Indian market pose no apparent health hazards during initial use. The absence of detectable BPA levels is attributed to the limited time-temperature relationship during the study. However, caution is warranted as BPA migration can occur with repeated use, emphasizing the importance of considering material quality and intended use of FCMs. The study underscores the significance of understanding BPA leaching under varied conditions, necessitating further research to explore long-term implications. Overall, the findings provide valuable insights for regulators, manufacturers, and consumers, contributing to the ongoing discourse on food safety and using plastic materials in food packaging.

Control of Bacillus cereus in rice cake and food contact surfaces with novel Becedseptimavirus genus phage BCC348 and its partial SPOR domain-containing endolysin LysBCC348

Here, we investigated the novel bacteriophage BCC348 and its endolysin LysBCC348 as alternative antimicrobials against the major foodborne pathogen Bacillus cereus. The Becedseptimavirus genus phage BCC348 effectively inhibited the growth of B. cereus ATCC 27348 with a remarkable burst size of ∼600 PFU/infected cell. The cation-dependent amidase endolysin LysBCC348 lysed the host B. cereus and Listeria monocytogenes and EDTA-treated Gram-negative pathogens. In a cold storage model of Korean rice cake, Garaetteok, BCC348 significantly reduced artificially contaminated B. cereus counts to undetectable levels within 3 days. Treatment with LysBCC348 also achieved a ∼1.3-log reduction of B. cereus and ∼60% biofilm removal from food contact surfaces. Genes related to DNA modification and sporulation prevention in BCC348, as well as a partial sporulation-related repeat (SPOR) domain in LysBCC348, are thought to enhance the efficacy of BCC348 in controlling B. cereus. These results suggest that BCC348 and LysBCC348 are promising alternative candidates to mitigate B. cereus contamination in the food industry.

3D-printed model for resection of positive surgical margins in robot-assisted prostatectomy.

To improve precision of secondary resection (SR) after positive surgical margin (PSM) detection by frozen section (FS) during nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) by employing a personalised three-dimensional (3D)-printed prostate model derived from pelvic magnetic resonance imaging (MRI). This model was used to mark positive surgical margins (PSM) and guide intraoperative SR during NS-RARP. Prospective multicentre cohort study with 100 patients undergoing NS-RARP between September 2018 and August 2021. Primary and secondary endpoints were the conversion rate of FS-identified PSM to a tumour-free margin and functional/oncological parameters within a 12-month follow-up, respectively. A PSM was identified in 23% of cases during FS, with a conversion to negative surgical margins (NSM) in 83% (19/23 cases) by model-guided SR. The tumour detection rate in SR specimens was 39% (nine of 23 cases). Among the 19 patients with converted margins, 18 (95%) achieved undetectable prostate-specific antigen levels 2 months postoperatively, with six (32%) having subsequent biochemical recurrence within 12 months. prostate-specific-membrane-antigen positron emission tomography computed tomography found one local recurrence, and five cases of metastatic disease. In converted patients, the baseline median five-item version of the International Index of Erectile Function score decreased by 16% after 1 year, with no significant difference compared to patients with primarily NSM. Limitations include the absence of a control group, the potential for false-negative FS results and limited accuracy of MRI. The integration of 3D-printed prostate models into NS-RARP has the potential to positively impact surgical outcomes by improving the precision of SR and optimising pathosurgical communication.

A pan-genotypic hepatitis E virus replication inhibitor with high potency in a rat infection model

BACKGROUND & AIMSHepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs. METHODSHEV subgenomic replicon systems were used to screen a small library of pre-selected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems; the efficacy of the compound was assessed in the athymic nude rat HEV infection model. RESULTSCompound JNJ-9117 exerts pan-genotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between three crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5’-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was in infected rats highly effective in lowering viral RNA load in liver and feces to (almost) undetectable levels. CONCLUSIONSJNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase 1 studies with JNJ-9117 have been initiated in healthy human volunteers.

Development of active films with thymol-based hydrophobic eutectic solvents

Thymol, known for its antimicrobial properties, was combined with acetic acid, betaine, and caprylic acid to form hydrophobic natural eutectic solvents (NAES), whose influence on the properties of bovine gelatin films was investigated. Films showed enhanced mechanical performance and a clear plasticizing effect provided by the natural eutectic solvents. At 300 wt% concentration, tensile strength and elongation at break reached 871 ± 78 kPa and 141 ± 10 % for acetic acid, 391 ± 41 kPa and 159 ± 10 % for betaine, and 1209 ± 52 kPa and 198 ± 15 % for caprylic acid. Water vapor permeability and total soluble matter were reduced, and swelling decreased to ~250 %, ~150 %, and ~ 200 % for films with 300 wt% of acetic acid, betaine, and caprylic acid, respectively. Pure thymol exhibited significant volatility, with 17.10 ± 1.50 % weight loss over one week, while the NADES demonstrated dramatically reduced losses (up to 1.15 ± 0.04 %). The films displayed exceptional antibacterial activity, achieving inhibition diameters of 34 mm against Gram-positive and Gram-negative bacteria, and films with caprylic or acetic NAES achieved undetectable CFU levels for major pathogens on chicken breast. These results highlight the antimicrobial potency and enhanced stability of NAES-based gelatin films for active packaging applications.

A Therapeutic Proposal for Mini-Puberty in Male Infants with Hypogonadotropic Hypogonadism: A Retrospective Case Series.

Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic-pituitary-gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5-500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5-75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH.

Analysis of a family with hypouricemia due to type Ⅰ xanthinuria

This article reports a patient presenting with"extremely low uric acid levels in blood and urine"clinically along with reviewing relevant literature to consider a diagnosis of xanthinuria. Peripheral blood samples of the patient and her family were further collected for xanthine dehydrogenase(XDH) gene sequencing, showing that the patient had compound heterozygous mutations in exon 19:c.1995_2006del12(p.His666_Gly669del) and exon 10:c.871G>T(p.Glu291*), however no mutations were found in the gene encoding MOCOS on chromosome 18, confirming the diagnosis of hereditary xanthinuria type Ⅰ.The patient's father, son and daughter carried heterozygous mutations in exon 19:c.1995_2006del12(p.His666_Gly669del), and the mother carried heterozygous mutations in exon 10:c.871G>T(p.Glu291*).Mutations in the XDH gene cause a lack of xanthine oxidoreductase function, which hinders the production of uric acid, leading to very low or undetectable levels in blood and urine. Patients present clinically with hematuria, renal colic, urolithiasis, and even acute renal failure. Through the diagnosis and treatment of this patient and literature review, the article aims to deepen the understanding of purine metabolism and uric acid production process, and improve the clinicians' diagnosis and treatment ability of hypouricemia.

Safety and Efficacy of Teclistamab in Patients With Relapsed or Refractory AL Amyloidosis

ABSTRACTIntroductionTeclistamab has demonstrated deep responses in patients with multiple myeloma in the MajesTEC‐1 study. However, the safety and efficacy of teclistamab in patients with AL amyloidosis are unknown.MethodsWe retrospectively analyzed patients with biopsy‐proven relapsed/refractory AL amyloidosis who were treated with teclistamab from December 2022 to February 2024 at the University of Pennsylvania. The data cutoff was 2/29/24. Adverse events (AE) were extracted from the electronic medical record. Patients were assessed for hematologic and organ response per consensus guidelines.ResultsEight patients were included in this case series: median age 63 (range 59–67), 75% female, 88% White. All eight patients achieved at least very good partial response (VGPR) and had normalization of free light chains (FLC), and six (75%) patients achieved undetectable FLC levels. Of the six patients with immunofixation completed, all six (100%) achieved hematologic complete response (hCR). The median time to hematologic VGPR and hCR was 13 days (range 12–18 days) and 88 days (range 32–150 days), respectively. The median duration of follow‐up was 8.5 months (range 1–14 months). Of the five patients with cardiac involvement, four (80%) achieved a cardiac response. Of the seven patients with renal involvement, two patients already achieved renal response prior to teclistamab, and of the remaining five, three (60%) achieved renal response. Six patients (75%) developed low‐grade cytokine release syndrome (CRS). No patients developed ICANS. Neutropenia and AKI both occurred in 25% of patients, respectively.ConclusionsIn this series of patients, teclistamab showed outstanding depth of response and was well‐tolerated. Teclistamab shows promise in treating patients with relapsed AL amyloidosis.

Ocular Mucous Membrane Pemphigoid Demonstrates a Distinct Autoantibody Profile from Those of Other Autoimmune Blistering Diseases: A Preliminary Study.

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.

Iron-Catalyzed Cross-Electrophile Coupling

AbstractMetal-catalyzed cross-coupling reactions have transformed molecular synthesis. Although metal-catalyzed reactions have been used for cross-electrophile coupling reactions, they remain challenging due to homodimer formation. Recently, our group developed an iron-catalyzed cross-electrophile coupling of benzyl halides and disulfides to produce thioethers without the use of an exogenous reductant or photoredox conditions, and with undetectable levels of elimination. This Synpacts article highlights both our design strategy to obviate detrimental homodimer formation and the generality of the method.1 Introduction2 Conceptualization and Development3 Mechanistic Studies and Hypothesis4 Conclusion and Future Directions

Understanding how CD19 expression levels impact the response to loncastuximab tesirine: a plain language summary.

In this article, we summarize results from a clinical study called LOTIS-2, in which researchers looked at patients with a type of blood cancer called diffuse large B-cell lymphoma, or DLBCL for short. Patients received the drug loncastuximab tesirine, or Lonca for short, which targets a marker on the surface of tumor cells called CD19.Patient information from the LOTIS-2 study, other studies of Lonca, and information from scientific publications was used to develop a quantitative systems pharmacology (QSP) model, which can predict how Lonca works in the body. The goal was to use the QSP model to see if CD19 levels can predict tumor size changes after Lonca treatment and if Lonca can still work to treat DLBCL when CD19 levels are very low. The prior LOTIS-1 and LOTIS-2 trials demonstrated an acceptable safety profile for Lonca, and therefore the current study did not evaluate safety data. Researchers used immunohistochemistry, a common technique to evaluate CD19 expression. They found that there was no association between patients who responded to Lonca treatment and levels of CD19 on their tumor cells. Some patients with low or even undetectable levels of CD19 on their tumor cells had observable decreases in tumor size after Lonca treatment. While Lonca uses the CD19 target to find and destroy cancer cells, Lonca does not require a large amount of CD19 to kill tumor cells. These results mean that Lonca may be an effective treatment for patients with DLBCL, even if CD19 expression in tumors is undetectable by immunohistochemistry.

JAK1/2 inhibitor ruxolitinib for the treatment of systemic chronic active Epstein-Barr virus disease: a phase 2 study

AbstractSystemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare intractable EBV-positive T-cell or natural killer (NK)-cell lymphoid neoplasm with systemic inflammation. The only curative treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Disease activity defined by multiple inflammatory symptoms is associated with poor survival. In sCAEBV, signal transducer and activator of transcription 3 (STAT3) is constitutively activated in EBV-infected T and NK cells and promotes their activation and survival. Ruxolitinib, a Janus kinase 1/2 inhibitor, suppresses the STAT3 activation in vitro, suggesting its clinical potential. We conducted a phase 2, multicenter, open-label study to investigate the effects of ruxolitinib on disease activity of sCAEBV. Complete response (CR) and partial response were defined as complete and partial resolution of disease activity, respectively. Nine patients received ruxolitinib, and 7 patients completed the study. The primary end point, CR rate (%) 56 days after the administration or at early termination as defined in the protocol, was 22.2% (2/9). No patient showed hematopoietic toxicity nor disease progression. Notably, 71.4% (5/7) of patients who completed the study were treated at our outpatient clinic. One patient developed a severe adverse event of oral bleeding due to lesion shrinkage during the treatment, and ruxolitinib was discontinued. EBV-DNA levels in whole blood did not change significantly whether the treatment was effective or not. After ruxolitinib treatment, 7 patients received allo-HSCT, and 5 of them achieved CR with undetectable EBV-DNA levels in whole blood. Ruxolitinib is a potent treatment drug that may improve allo-HSCT outcomes by suppressing disease activity of sCAEBV. The trial was registered at UMIN, numbered UMIN000035121.

Association of baseline cytokines with antibody concentrations after diphtheria-tetanus-acellular pertussis booster vaccination in Finnish children

BackgroundDespite extensive vaccinations, pertussis remains endemic and epidemic in multiple countries. The persistence of cases can be partly attributed to the significant individual variation in vaccine responses. This study evaluated the association of baseline cytokines (before booster vaccination) on antibody concentrations to Tdap-vaccine antigens. MethodsHealthy Finnish children (7–10y, n = 36), adolescents (11–15y, n = 37), young adults (20–34y, n = 25), and older adults (60–70y, n = 23) received a Tdap3-IPV booster. Serum antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), fimbriae 2/3, diphtheria toxoid (DT), and tetanus toxoid (TT), as well as PT neutralizing antibodies were measured before, one month, and one year after the booster. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17 A and IL-17F were determined. ResultsThe proportion of detectable and undetectable baseline cytokines varied between age groups 58.3 % of children had a higher proportion of detectable IL-5, IL-10, IL-13, and IL-17F compared to adolescents (IL-5, 37.8 %; IL-10, 48.6 %; IL-13, 48.6 %; IL-17F, 37.7 %), young adults (IL-5, 36.0 %; IL-10, 28.0 %; IL-13, 36.0 %; IL-17F, 44.0 %), and older adults (IL-5, 26.1 %; IL-10, 21.7 %; IL-13, 39.1 %; IL-17F, 30.4 %). IFN-γ had a lower detectability in children (44.4 %) and young (40.0 %) and older adults (39.1 %) in contrast to adolescents (62.2 %). IL-2 was undetectable in all age groups while the proportion of detectable IL-17 A decreased with age. A mixed model showed that undetectable baseline levels of IFN-γ, IL-2, IL-10, and IL-17 A were associated with higher antibody concentrations in children before and after vaccination, particularly against PT. Positive associations were observed in adolescents for anti-TT concentrations and young adults for anti-FHA IgA concentrations. ConclusionThese findings indicate a possible role of existing cytokines in pertussis booster antibody concentrations in children and warrant further studies in different populations. However, the results should be interpreted with caution as the number of subjects is limited.

Effect of Boiling and Roasting Treatments on the Nutrients, Lipid Quality, and Flavor of Peanuts.

Roasted peanuts (OPs) are more often used in daily life than boiled peanuts (BPs); the main reason may be related to the pleasurable flavor in OPs. This study comparatively investigated the effects of boiling and roasting on nutritional components contents, taste, and aroma to reveal the advantages of roasting in terms of the nutrition and flavor of peanuts. Results showed that boiling increased fat content to 54.47% of peanuts, diluted or reduced sugar content to an undetectable level, noticeably changed the contents of poly/monounsaturated fatty acids, and significantly decreased the content of free amino acid (FAA, 1.05 mg/g peanuts) in peanuts. Roasting simply decreased the contents of sugar and FAA to 2.78 and 1.82 mg/g peanuts, respectively. Compared with roasting, boiling had more discernible effects on fatty acids and FAAs. Both BPs and OPs have good dietary lipid quality. In terms of flavor, OPs had more FAAs (2 types) that contributed remarkably to the taste of peanuts than BPs (0 types), more volatile substances (40 types) than BPs (12 types), and a higher number of key volatile aroma components (8 types) than BPs (3 types). That is, roasting induced a relatively small effect on nutritional components and gave peanuts a richer taste and stronger aroma than boiling; therefore, roasting is an ideal peanut processing method. This study proved the different changes in peanuts caused by boiling and roasting on a material basis and corroborated the irreplaceability of roasting in peanut processing.

Comparative analysis of Lox-1 and CD36 expression in human platelets and on circulating microparticles during ARDS-induced coagulopathy

IntroductionAcute respiratory distress syndrome (ARDS) patients are at risk of thrombosis through mechanisms implicating oxidized low-density lipoprotein (oxLDL). Endothelial cells, immune cells and platelets were reported to express scavenger receptors for oxLDL: Lox-1 and CD36. We hypothesized that platelets shed a soluble Lox-1 ectodomain (sLox-1) and release CD36–bearing procoagulant microparticles (MPs), that both become elevated in subjects with ARDS-induced coagulopathy. MethodsUsing anti-extracellular and anti-intracellular Lox-1 antibodies, we first tested by western blot whether platelets express Lox-1 and shed sLox-1 upon activation. Next, we measured sLox-1 in blood plasma of 23 healthy donors and 48 ARDS Omega patients with and without coagulopathy, and assessed the corresponding MP fraction for Lox-1/sLox-1 and CD36. We evaluated mechanisms of sLox-1-MP association. Recombinant proteins were used as controls. ResultsResting platelets expressed abundant CD36 (7.8 ng/μg protein extract) which was released upon oxLDL stimulation, but undetectable levels of full-length 37 kDa Lox-1 receptor or 24 kDa sLox-1 (below 10 pg/μg). In an RNAseq meta-analysis, platelets expressed negligible OLR1, the mRNA encoding Lox-1, compared to CD36. A subset of ARDS patients showed elevated plasma sLox-1 and MP-associated sLox-1 compared to healthy controls that was positively associated with 90-day survival and low coagulopathy. MP-associated CD36 was reduced in ARDS plasma compared to healthy donors and did not correlate with survival, coagulopathy, or sLox-1. oxLDL promoted sLox-1 binding to CD36-deficient MPs. ConclusionsLox-1 arising from a non-platelet cell source associates with circulating MPs which could serve a protective role in ARDS.