Troubleshooting the influence of trace chemical impurities on nanoparticle growth kinetics via electrochemical measurements.

Reproducibility issues resulting from particle growth solutions made with cetyltrimethylammonium bromide (CTAB) surfactant from different lots and product lines in a newly developed synthesis of monometallic palladium (Pd) tetrahexahedra (THH) nanoparticles are investigated via a multi-pronged approach. Time-resolved electrochemical measurements of solution potential, variation of chemical parameters in colloidal synthesis, and correlation to electrodeposition syntheses are used together to uncover the effects of the unknown contaminants on the chemical reducing environment during nanoparticle growth. Iodide-a known impurity in commercial CTAB-is identified as one of the required components for equalizing the reducing environment across multiple CTAB sources. However, an additional component-acetone-is critical to establishing the growth kinetics necessary to enable the reproducible synthesis of THH in each of the CTAB formulations. In one CTAB variety, the powdered surfactant contains too much acetone, and drying of the as-received surfactant and re-addition of solvent is necessary for successful Pd THH synthesis. The relevance of solvent impurities to the reducing environment in aqueous nanoparticle synthesis is confirmed via electrochemical measurement approaches and solvent addition experiments. This work highlights the utility of real-time electrochemical potential measurements as a tool for benchmarking of nanoparticle syntheses and troubleshooting of reproducibility issues. The results additionally emphasize the importance of considering organic solvent impurities in powdered commercial reagents as a possible shape-determining factor during shaped nanomaterials synthesis.

RAFT step-growth polymerization via the Z-group approach and deconstruction by RAFT interchange.

Recycling vinyl polymers is essential to mitigate the environmental impact of plastic waste. However, typical polymerization strategies to construct vinyl polymers lack the ability to incorporate degradable linkers throughout the main chain. We report a RAFT step-growth polymerization through the Z-group approach that is directly carried out by using a common class of symmetric trithiocarbonate based RAFT agents and commercially available bismaleimide monomers. Such synthesized RAFT step-growth polymers contain embedded RAFT agents in every structural unit, allowing chain expansion of the step-growth backbone via controlled chain growth to yield linear multiblock (co)polymers. These polymers can undergo deconstruction via the RAFT interchange process with exogeneous RAFT agents, generating smaller uniform species with narrow molecular weight distribution. In addition, the telechelic bifunctional RAFT agent nature after deconstruction allows repolymerization, showing a promising method for recycling common vinyl polymers.

A qualitative exploration of 40 Hz sound and music for older adults with mild cognitive impairment.

Emerging evidence suggests that 40 Hz auditory stimulation may benefit cognition. Nested within a randomized crossover trial, this qualitative study evaluates the acceptability and experience of three auditory interventions-self-selected music, 40 Hz sound, and a novel combination, termed 40 Hz music-in individuals with Mild Cognitive Impairment (MCI). Semi-structured interviews were conducted with individuals with MCI post-intervention exposure. Findings indicated a preference for self-selected music due to its memory-boosting and emotional benefits, while responses to 40 Hz sound were mixed, with several participants reporting discomfort. The composite 40 Hz music intervention showed promise, striking a balance by enhancing user experience and mitigating the 40 Hz sound's negative aspects. Engagement was influenced by personal music interests, listening routines, and support networks. This study highlights the potential of integrating 40 Hz sound with personalized music to offer a more acceptable 40 Hz auditory intervention for cognition in older adults with MCI.

Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy.

BACKGROUND: Nasal epithelial cells are important regulators of barrier function and immune signaling; however, in allergic rhinitis (AR) these functions can be disrupted by inflammatory mediators. We aimed to better discern AR disease mechanisms using transcriptome data from nasal brushing samples from individuals with and without AR. METHODS: Data were drawn from a feasibility study of individuals with and without AR to Timothy grass and from a clinical trial evaluating 16 weeks of treatment with the following: dupilumab, a monoclonal antibody that binds interleukin (IL)-4Rα and inhibits type 2 inflammation by blocking signaling of both IL-4/IL-13; subcutaneous immunotherapy with Timothy grass (SCIT), which inhibits allergic responses through pleiotropic effects; SCIT + dupilumab; or placebo. Using nasal brushing samples from these studies, we defined distinct gene signatures in nasal tissue of AR disease and after nasal allergen challenge (NAC) and assessed how these signatures were modulated by study drug(s). RESULTS: Treatment with dupilumab (normalized enrichment score [NES] = -1.73, p = .002) or SCIT + dupilumab (NES = -2.55, p < .001), but not SCIT alone (NES = +1.16, p = .107), significantly repressed the AR disease signature. Dupilumab (NES = -2.55, p < .001), SCIT (NES = -2.99, p < .001), and SCIT + dupilumab (NES = -3.15, p < .001) all repressed the NAC gene signature. CONCLUSION: These results demonstrate type 2 inflammation is an important contributor to the pathophysiology of AR disease and that inhibition of the type 2 pathway with dupilumab may normalize nasal tissue gene expression.

Oral histories: lessons we can learn from the past.

The COVID-19 pandemic has brought to light the importance of hindsight in response to global health crises. Although globalization has amplified worldwide perspectives, many lessons learned from past outbreaks in Indigenous communities have been overlooked. Oral histories are deeply rooted traditions that have played a significant role in the health practices of Indigenous communities across Canada. These practices can provide valuable insights into past epidemics or casualty events and their short- to long-term impacts. They have shaped responses to COVID-19, with Indigenous communities implementing self-determination efforts, such as community closures, contact tracing, and isolation measures. These traditions have heavily influenced population health practices in other contexts, such as the 1700 Cascadia earthquake, smallpox, and tuberculosis outbreaks. However, challenges remain in facilitating disease data transparency and Indigenous sovereignty. Efforts should be made to promote recognizing and respecting Indigenous knowledge and practices within the broader health system.

Evaluation of Illumina® COVIDSeq™ as a tool for Omicron SARS-CoV-2 characterisation.

The continued emergence and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants requires ongoing genetic surveillance to support public health responses. The expansion of reliable next generation sequence (NGS) platforms has enabled the rapid characterisation of the constant emergence of new SARS-CoV-2 variants using nasopharyngeal swab specimens. Several studies have assessed the ability of COVIDSeq to type earlier SARS-CoV-2 strains (pre-Delta) rapidly and successfully, however, there is limited data showing suitability against Omicron variants. In the present study, we evaluated the performance of the Illumina COVIDSeq Assay as a streamlined amplicon-based NGS platform for detection and typing of Omicron variants. Our results demonstrate the high performance of SARS-CoV-2 sequencing using the COVIDSeq approach, with good repeatability, reproducibility and sensitivity for samples approaching CT 31. The COVIDSeq approach was 100% concordant with samples previously characterized by sequencing methods. The quick library preparation process and high throughput kit made it ideal for reflex testing, with a total time required for sequencing and analysis of approximately two days. This study demonstrates the effectiveness and versatility of the amplicon-based NGS characterisation method for SARS-CoV-2, providing a foundation for further research and development of custom-designed amplicon panels targeting different microorganisms.

Rapid inactivation and sample preparation for SARS-CoV-2 PCR-based diagnostics using TNA-Cifer Reagent E.

RT-qPCR remains a key diagnostic methodology for COVID-19/SARS-CoV-2. Typically, nasal or saliva swabs from patients are placed in virus transport media (VTM), RNA is extracted at the pathology laboratory, and viral RNA is measured using RT-qPCR. In this study, we describe the use of TNA-Cifer Reagent E in a pre-clinical evaluation study to inactivate SARS-CoV-2 as well as prepare samples for RT-qPCR. Adding 1 part TNA-Cifer Reagent E to 5 parts medium containing SARS-CoV-2 for 10 min at room temperature inactivated the virus and permitted RT-qPCR detection. TNA-Cifer Reagent E was compared with established column-based RNA extraction and purification methodology using a panel of human clinical nasal swab samples (n = 61), with TNA-Cifer Reagent E showing high specificity (100%) and sensitivity (97.37%). Mixtures of SARS-CoV-2 virus and TNA-Cifer Reagent E could be stored for 3 days at room temperature or for 2 weeks at 4°C without the loss of RT-qPCR detection sensitivity. The detection sensitivity was preserved when TNA-Cifer Reagent E was used in conjunction with a range of VTM for saliva samples but only PBS (Gibco) and Amies Orange for nasal samples. Thus, TNA-Cifer Reagent E improves safety by rapidly inactivating the virus during sample processing, potentially providing a safe means for molecular SARS-CoV-2 testing outside traditional laboratory settings. The reagent also eliminates the need for column-based and/or automated viral RNA extraction/purification processes, thereby providing cost savings for equipment and reagents, as well as reducing processing and handling times.

Brain-derived neurotrophic factor as a biomarker in cancer-related cognitive impairment among adolescent and young adult cancer patients.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment.

LncRNA H19 mediates BMP9-induced angiogenesis in mesenchymal stem cells by promoting the p53-Notch1 angiogenic signaling axis.

BMP9 mediated osteogenic differentiation mechanisms of MSCs were widely explored, however, mechanisms of BMP9-induced angiogenesis still need to be clarified. We previously characterized that Notch1 promoted BMP9-induced osteogenesis-angiogenesis coupling process in mesenchymal stem cells (MSCs). Here, we explored the underlying mechanisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through activating Notch1 signaling. We demonstrated that basal expression level of H19 was high in MSCs, and silencing H19 attenuates BMP9-induced osteogenesis and angiogenesis of MSCs both in vitro and in vivo. Meanwhile, we identified that BMP9-induced production of CD31+ cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9-induced production of CD31+ cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mechanistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phosphorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings suggested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.

A protocol for a wait list control trial of an intervention to improve pain and depressive symptoms among middle-aged and older African American women.

BACKGROUND: Pain and depression frequently co-occur among older adults with comorbidities and can exacerbate one another. The intersection of race, gender and age puts older African American women at high risk of experiencing comorbid pain and depression. The purpose of this study is to test the feasibility and acceptability of a 12-week behavioral activation intervention called DAPPER (Depression and Pain Perseverance through Empowerment and Recovery) that uses non-pharmacological, tailored strategies to target pain and mood symptoms. We will measure pain intensity and depressive symptoms as outcomes, although we are not powered to test differences. METHODS: We describe the protocol for this study that uses a randomized waitlist control design to examine acceptability and feasibility of an intervention. The study population is comprised of self-identified African American women, 50 years of age or older with chronic pain and who self-report of depressive symptoms. Participants must also be pre-frail or frail and have an ADL or IADL limitation. The intervention consists of eight 1-2-h visits with a nurse interventionist via in-person or virtual telecommunication methods and two visits for non-invasive specimen collection. The primary outcomes include goal attainment, pain and depressive symptoms. Secondary outcomes include stress, frailty, and communication with providers. Follow-up qualitative interviews are conducted with participants to assess intervention acceptability. DISCUSSION: Findings from this pilot study will provide further evidence supporting the use of non-pharmacological techniques to intervene in the cycle of pain and depression among an at-risk sub-population.

Assessment of clinical outcomes in patients with fibromyalgia: Analysis from the UK Medical Cannabis Registry.

INTRODUCTION: There are limited therapeutic options for individuals with fibromyalgia. The aim of this study is to analyze changes in health-related quality of life and incidence of adverse events of those prescribed cannabis-based medicinal products (CBMPs) for fibromyalgia. METHODS: Patients treated with CBMPs for a minimum of 1 month were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in validated patient-reported outcome measures (PROMs). A p-value of <.050 was deemed statistically significant. RESULTS: In total, 306 patients with fibromyalgia were included for analysis. There were improvements in global health-related quality of life at 1, 3, 6, and 12 months (p < .0001). The most frequent adverse events were fatigue (n = 75; 24.51%), dry mouth (n = 69; 22.55%), concentration impairment (n = 66; 21.57%), and lethargy (n = 65; 21.24%). CONCLUSION: CBMP treatment was associated with improvements in fibromyalgia-specific symptoms, in addition to sleep, anxiety, and health-related quality of life. Those who reported prior cannabis use appeared to have a greater response. CBMPs were generally well-tolerated. These results must be interpreted within the limitations of study design.

Rapid molecular detection of CMY-2, and CTX-M group 1 and 9 variants via recombinase polymerase amplification.

Background: Due to their prevalence worldwide, the ß-lactamases CTX-M and plasmid-mediated CMY-2 are important antimicrobial resistance enzymes in a clinical setting. While culture- and PCR-based detection methods exist for these targets, they are time consuming and require specialist equipment and trained personnel to carry out. Methods: In this study, three rapid diagnostic single-plex and a prototype triplex assay were developed, using recombinase polymerase amplification with lateral flow detection (RPA-LF), and tested for their sensitivity and specificity using two isolate DNA panels (n = 90 and n = 120 isolates). In addition, the RPA-LF assays were also tested with a small number of faecal extract samples (n = 18). Results: The RPA-LF assays were able to detect bla CXT-M-group-1, bla CTX-M-group-9 and bla CMY-2-type variants with high sensitivity (82.1%-100%) and specificity (100%) within a short turnaround time (15-20 min for amplification and detection). Conclusions: RPA-LF assays developed in this study have the potential to be used at or close to the point of care, as well as in low-resource settings, producing rapid results to support healthcare professionals in their treatment decisions.

Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study.

BACKGROUND: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. METHODS: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]). RESULTS: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function. CONCLUSION: With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070).

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story.

BACKGROUND: A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS: HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS: Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS: HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.

Circular Upcycling of Bottlebrush Thermosets.

The inability to re-process thermosets hinders their utility and sustainability. An ideal material should combine closed-loop recycling and upcycling capabilities. This trait is realized in polydimethylsiloxane bottlebrush networks using thermoreversible Diels-Alder cycloadditions to enable both reversible disassembly into a polymer melt and on-demand reconfiguration to an elastomer of either lower or higher stiffness. The crosslink density was tuned by loading the functionalized networks with a controlled fraction of dormant crosslinkers and crosslinker scavengers, such as furan-capped bis-maleimide and anthracene, respectively. The resulting modulus variations precisely followed the stoichiometry of activated furan and maleimide moieties, demonstrating the lack of side reactions during reprocessing. The presented circularity concept is independent from the backbone or side chain chemistry, making it potentially applicable to a wide range of brush-like polymers.

Comparison of the Inflammatory Circuits in Psoriasis Vulgaris, Non‒Pustular Palmoplantar Psoriasis, and Palmoplantar Pustular Psoriasis.

Palmoplantar pustular psoriasis (PPPP) and non‒pustular palmoplantar psoriasis (NPPP) are localized, debilitating forms of psoriasis. The inflammatory circuits involved in PPPP and NPPP are not well-understood. To compare the cellular and immunological features that differentiate PPPP and NPPP, skin biopsies were collected from a total of 30 participants with PPPP, NPPP, and psoriasis vulgaris (PV) and from 10 healthy participants. A subset consented to a second biopsy after 3 additional weeks off medication. Histologic staining of lesional and nonlesional skin showed higher neutrophil counts in PPPP than in NPPP and PV and higher CD8+ T-cell counts in NPPP. RNA sequencing and transcriptional analysis of skin biopsies showed enhanced IFN-γ pathway activation in NPPP lesions but stronger signatures of IL-17 pathway and neutrophil-related genes (e.g., IL36A) in PPPP lesional skin. Serum analysis on the Olink platform detected higher concentrations of T helper type 1, IFN-γ‒inducible chemokines in NPPP, and higher neutrophil-associated cytokines in PPPP. Taken together, this evidence suggests more pronounced T helper 1‒mediated inflammation in NPPP than in PV and PPPP and stronger neutrophil-associated activity in PPPP than in NPPP and PV. These data support targeting inflammatory pathways associated with neutrophilic inflammation (e.g., IL-36 signaling) for therapeutic development in PPPP.

SARS-CoV-2 RT-PCR to Screen for B.1.617.2 (Delta) Variant of Concern.

The continuous transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has required that diagnostic capabilities be constantly monitored and updated as new variants emerge and prior variants disappear. Although whole genome sequencing provides full characterisation of SARS-CoV-2 directly from patient samples, this has limited throughput and requires sufficient resources. To enhance screening for circulating variants, we designed a rapid in-house RT-PCR assay to target a spike mutation (D950N) in Delta variants, which is not detected in the remaining variants of concern (VOCs). Assay sensitivity for detecting Delta variants was 93% and specificity was 100% using a sequenced sample bank of several lineages. As the D950N mutation is prevalent in >95% of the global Delta variant sequences deposited in GISAID, this assay has the potential to provide rapid results to determine if the samples are presumptively Delta variants and can support clinicians in timely clinical decision-making for effective treatments and surveillance.

REGN1908/1909 prevented cat allergen-induced early asthmatic responses in an environmental exposure unit.

BACKGROUND: The dominant allergen in cat dander, Felis domesticus allergen 1 (Fel d 1), is a persistent trigger for allergic rhinitis and asthma symptoms. OBJECTIVE: We evaluated the efficacy of Fel d 1 monoclonal antibodies (REGN1908/1909) in preventing cat allergen-induced early asthmatic responses (EARs) in cat-allergic patients with mild asthma. METHODS: Patients were randomized to single-dose REGN1908/1909 600 mg (n = 29) or placebo (n = 27). The FEV1 was measured for up to 4 hours in a cat allergen environmental exposure unit up to 85 days after dosing. Assessments included between-group differences in change from baseline in FEV1 area under the curve (AUC; 0-2 hours) and incidence of EAR (FEV1 reduction ≥20%). TRIAL REGISTRATION: NCT03838731. RESULTS: Single-dose REGN1908/1909 significantly prevented reductions in FEV1 on days 8, 29, 57, and 85. Most REGN1908/1909 patients did not have an EAR by 4 hours (the last time point tested). In contrast, placebo-treated patients experienced a ≥20% mean FEV1 reduction on days 8, 29, 57, and 85 after dosing, with most experiencing an EAR within 1 hour. REGN1908/1909-treated patients tolerated 3-fold higher allergen quantities (P < .05 at all time points) versus placebo. REGN1908/1909 substantially reduced skin test reactivity to cat allergen versus placebo at all time points tested (nominal P < .001). REGN1908/1909 was generally well tolerated; no serious adverse events or deaths were reported. CONCLUSION: Single-dose REGN1908/1909 significantly prevented reductions in FEV1 in cat-allergic patients with mild asthma on cat allergen environmental exposure unit exposure at 8 days and up to 85 days after dose.

Histo-blood group antigens and rotavirus vaccine virus shedding in Australian infants.

Rotavirus vaccine performance varies between high and low income countries. One possible explanation is inherited histo-blood group antigens (HBGAs) the expression of which differs between populations. HBGAs are polymorphic glycans on mucosal surfaces. Their presence indicates the secretor phenotype, while their absence identifies a non-secretor status. HBGAs can act as rotavirus receptors and might influence live-attenuated rotavirus vaccine virus replication and shedding. Studies in low and middle income countries of the human rotavirus vaccine Rotarix (RV1), suggest HBGA secretor phenotype is important for vaccine immunogenicity. We investigated in a high income country the association between HBGA phenotype (secretor and Lewis) and the bovine-human reassortment vaccine RotaTeq (RV5) vaccine shedding in the stools of infants following each vaccine dose. Eighty-two infants from an Australian birth cohort provided saliva and weekly stool samples after RV5 vaccination doses. Lewis and secretor HBGA phenotyping was identified from saliva samples and confirmed by genotyping. Vaccine virus strains were detected by real-time polymerase chain reaction assays. No significant association between secretor status and vaccine virus shedding was identified. The proportion of infants who shed rotavirus following the first RV5 dose for secretor and non-secretor infants was 57/64 (89%) and 17/18 (94%), respectively, decreasing to 24/64 (33%) and 9/18 (50%) after the second dose and 26/64 (42%) and 8/18 (44%) following the third vaccine dose, respectively. Similarly, no significant differences were observed in vaccine virus shedding by Lewis, or combined Lewis and secretor status, after each vaccine dose. We found HBGAs were not associated with RV5 vaccine virus shedding in Australian infants.

Concurrent presentation of IgG4-related tubulointerstitial nephritis and ANCA MPO crescentic glomerulonephritis.

Concurrent IgG4-related tubulointerstitial nephritis and anti-neutrophil cytoplasmic antibodies (ANCA) myeloperoxidase (MPO) crescentic glomerulonephritis is an uncommon scenario, and the link between the two conditions, if any, is incompletely understood. We report the case of a 58-year-old woman who presented with a 2-month history of malaise and joint pain and was found to have acute kidney injury and hemato-proteinuria. Initial immunological tests revealed positive anti-neutrophil cytoplasmic antibodies with a peri-nuclear pattern (pANCA). An enzyme-linked immunoassay (ELISA) for anti-MPO antibodies was also positive, leading to a tentative diagnosis of ANCA-associated small vessel vasculitis with renal involvement. Steroid treatment was commenced, and an urgent kidney biopsy was performed. This showed crescentic glomerulonephritis, but also demonstrated concurrent tubulointerstitial nephritis with a dominance of IgG4-producing plasma cells. Serum IgG4 levels were also elevated. The patient was initially treated with intravenous cyclophosphamide and steroids and then switched to rituximab. When last seen, she was well after 1 dose of rituximab, with kidney function, inflammatory parameters, and serum IgG4 levels returning to normal levels. The concurrent presentation of ANCA-associated vasculitis and IgG4 renal disease is rare with only few cases reported in the literature. More work is needed to understand pathophysiology, outcomes, and management options for this complex scenario.