Total Intravenous Anesthesia with Propofol Reduces Discharge Times Compared with Inhaled General Anesthesia in Shoulder Arthroscopy: A Randomized Controlled Trial.

BACKGROUND: Shoulder arthroscopy is commonly performed at ambulatory surgical centers (ASCs) with use of an interscalene block and inhaled general anesthesia (IGA). However, an alternative option known as total intravenous anesthesia with propofol (TIVA-P) has shown promising results in reducing recovery time for other surgeries. The objective of this study was to assess whether there is a clinically meaningful difference in post-anesthesia care unit phase-I (PACU-I) time following shoulder arthroscopy between patients receiving an interscalene block with IGA and those receiving an interscalene block with TIVA-P. METHODS: Patients who underwent shoulder arthroscopy performed by a single surgeon at the ASC of our institution between 2020 and 2023 were enrolled. Enrollment was conducted in blocks, with up to 3 planned interim analyses. After 2 blocks, enrollment was halted because the study arms demonstrated a significant difference in the primary outcome measure, PACU-I time. A total of 96 patients were randomized into the TIVA-P and IGA groups; after patient withdrawals, the groups comprised 42 and 40 patients, respectively. Patients underwent shoulder arthroscopy with use of the anesthesia method corresponding to their assigned group. Pain, satisfaction, antiemetic use, perioperative interventions, surgical time, PACU-II time, postoperative care time, and total time until discharge were recorded and were analyzed with use of chi-square and Mann-Whitney U tests with a significance cutoff of 0.0167 to account for the interim analyses. RESULTS: Across groups, 81.7% of patients were non-Hispanic White and 58.5% were male. Significant differences were observed between the TIVA-P and IGA groups with respect to median PACU-I time (0.0 minutes [interquartile range (IQR), 0.0 to 6.0 minutes] versus 25.5 minutes [IQR, 20.5 to 32.5 minutes]; p < 0.001) and median total time until discharge (135.5 minutes [IQR, 118.5 to 156.8 minutes] versus 148.5 minutes [IQR, 133.8 to 168.8 minutes]; p = 0.0104). The TIVA-P group had a 9.1% quicker discharge time, primarily as a result of bypassing PACU-I (66.7% of patients) and spending 25.5 fewer minutes there overall. The TIVA-P group also had a lower rate of antiemetic use than the IGA group (59.5% versus 92.5% of patients; p = 0.0013). No significant differences were detected between the TIVA-P and IGA groups in terms of median pain improvement (1.0 [IQR, 0.0 to 2.0] versus 1.0 [IQR, 0.0 to 2.0]; p = 0.6734), perioperative interventions (78.6% versus 77.5% of patients, p = 1.0000), or median patient satisfaction (4.0 [IQR, 4.0 to 4.0] versus 4.0 [IQR, 3.8 to 4.0]; p = 0.4148). CONCLUSIONS: TIVA-P showed potential to improve both PACU-I time and the total time until discharge while reducing antiemetic use without impacting pain or satisfaction. TIVA-P thus warrants consideration by orthopaedic surgeons for use in shoulder arthroscopy performed at ASCs. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8.

Dedicator of cytokinesis 8 (DOCK8) mutations lead to a primary immunodeficiency associated with recurrent gastrointestinal infections and poor antibody responses but, paradoxically, heightened IgE to food antigens, suggesting that DOCK8 is central to immune homeostasis in the gut. Using Dock8-deficient mice, we found that DOCK8 was necessary for mucosal IgA production to multiple T cell-dependent antigens, including peanut and cholera toxin. Yet DOCK8 was not necessary in T cells for this phenotype. Instead, B cell-intrinsic DOCK8 was required for maintenance of antigen-specific IgA-secreting plasma cells (PCs) in the gut lamina propria. Unexpectedly, DOCK8 was not required for early B cell activation, migration, or IgA class switching. An unbiased interactome screen revealed novel protein partners involved in metabolism and apoptosis. Dock8-deficient IgA+ B cells had impaired cellular respiration and failed to engage glycolysis appropriately. These results demonstrate that maintenance of the IgA+ PC compartment requires DOCK8 and suggest that gut IgA+ PCs have unique metabolic requirements for long-term survival in the lamina propria.

2022 White Paper on Recent Issues in Bioanalysis: FDA Draft Guidance on Immunogenicity Information in Prescription Drug Labeling, LNP & Viral Vectors Therapeutics/Vaccines Immunogenicity, Prolongation Effect, ADA Affinity, Risk-based Approaches, NGS, qPCR, ddPCR Assays (Part 3 - Recommendations on Gene Therapy, Cell Therapy, Vaccines Immunogenicity & Technologies; Immunogenicity & Risk Assessment of Biotherapeutics and Novel Modalities; NAb Assays Integrated Approach).

The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1 (Mass Spectrometry and ICH M10) and Part 2 (LBA, Biomarkers/CDx and Cytometry) are published in volume 15 of Bioanalysis, issues 16 and 15 (2023), respectively.

Retroviral b-Zip protein (HBZ) contributes to the release of soluble and exosomal immune checkpoint molecules in the context of neuroinflammation.

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neuroinflammatory demyelinating condition of the spinal cord. We have previously shown that aberrant expression and activity of immune checkpoint (ICP) molecules such as PD-1 and PD-L1/PD-L2, negatively associates with the cytolytic potential of T cells in individuals with HAM/TSP. Interestingly, ICPs can exist in a soluble cell-free form and can be carried on extracellular vesicles (EVs) and exosomes (small EVs, <300nm) while maintaining their immunomodulatory activity. Therefore, we investigated the role of soluble and exosomal ICPs in HTLV-1 associated neuroinflammation. For the very first time, we demonstrate a unique elevated presence of several stimulatory (CD27, CD28, 4-1BB) and inhibitory (BTLA, CTLA-4, LAG-3, PD-1, PD-L2) ICP receptors in HAM/TSP sera, and in purified exosomes from a HAM/TSP-derived HTLV-1-producing (OSP2) cells. These ICPs were found to be co-localized with the endosomal sorting complex required for transport (ESCRT) pathway proteins and exhibited functional binding with their respective ligands. Viral proteins and cytokines (primarily IFNγ) were found to be present in purified exosomes. IFNγ exposure enhanced the release of ICP molecules while antiretroviral drugs (Azidothymidine and Lopinavir) significantly inhibited this process. HTLV-1 b-Zip protein (HBZ) has been linked to factors that enhance EV release and concurrent knockdown here led to the reduced expression of ESCRT associated genes (eg. Hrs, Vsp4, Alix, Tsg101) as well as abrogated the release of ICP molecules, suggesting HBZ involvement in this process. Moreso, exosomes from OSP2 cells adversely affected CD8 T-cell functions by dimishing levels of cytokines and cytotoxic factors. Collectively, these findings highlight exosome-mediated immunmodulation of T-cell functions with HBZ and ESCRT pathways as an underlying mechanism in the context of HTLV-1-induced neuroinflammation.

2022 White Paper on Recent Issues in Bioanalysis: Enzyme Assay Validation, BAV for Primary End Points, Vaccine Functional Assays, Cytometry in Tissue, LBA in Rare Matrices, Complex NAb Assays, Spectral Cytometry, Endogenous Analytes, Extracellular Vesicles Part 2 - Recommendations on Biomarkers/CDx, Flow Cytometry, Ligand-Binding Assays Development & Validation; Emerging Technologies; Critical Reagents Deep Characterization.

The 16th Workshop on Recent Issues in Bioanalysis (16th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on LBA, Biomarkers/CDx and Cytometry. Part 1 (Mass Spectrometry and ICH M10) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 16 and 14 (2023), respectively.

Association between first trimester platelet to lymphocyte ratio and stillbirth.

BACKGROUND: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been investigated as inflammatory markers of malignancies, cardiovascular and autoimmune diseases. We explored the association between NLR, PRL, measured during pregnancy, and stillbirth (SB). METHODS: We conducted a retrospective case control study at a tertiary hospital center in New York City from May 2015 to July 2018. Cases were defined as SB pregnancies and controls as uncomplicated pregnancies. We calculated NLR and PLR using the complete blood count components routinely collected during prenatal care in the first trimester. The groups were matched by age, parity, body mass index (BMI) and race. We used receiver operating characteristic (ROC) curve analysis to evaluate the association of NLR and PLR to SB. RESULTS: We identified 28 patients with SB pregnancies and matched them with 28 controls. Age, parity, BMI, and race were equally distributed between the groups. The median gestational age of SB was 30 weeks (22-34). In the first trimester PLR was significantly lower in SB cases compared to controls (124.8 vs. 153.4, P=0.044) with an area under the curve (AUC) of 0.65. A PLR value higher than 156.4 accurately excluded SB with a sensitivity of 0.50, specificity of 0.89, positive predictive value of 0.013 and a negative predictive value of 0.998. NLR did not show a significant difference in the first trimester. CONCLUSIONS: A PLR higher than 156.4 in the first trimester appears to reliably exclude the occurrence of SB later during pregnancy. Lower platelet and higher lymphocyte levels may be related to an early inflammatory process. We speculate that pregnancies in which the initial myometrial invasion by the placental cells is dysfunctional and reflected by a high level of inflammation in the peripheral maternal blood, may contribute to fetal demise. Larger studies are needed to confirm our results.

Predictive value of preoperative complete blood count components on the occurrence of surgical site infection after elective cesarean section.

BACKGROUND: To analyze the predictive value of the preoperative complete blood count components on the occurrence of surgical site infection (SSI) after elective cesarean section. METHODS: We conducted a retrospective case control study in a tertiary care hospital located in New York City during the period of November 1, 2018, to October 30, 2020. We included patients who developed SSI after elective cesarean section as cases and patients who did not develop SSI as controls. We tested the ability of neutrophil, lymphocyte, platelet, hemoglobin, hematocrit, total white blood cells, neutrophil to lymphocyte ratio, hemoglobin to platelet ratio, platelet to lymphocyte ratio, platelet to neutrophil ratio, platelet to hemoglobin ratio and neutrophil to hemoglobin ratio to identify the occurrence of SSI after cesarean section. RESULTS: We compared ten cases and 20 controls. The median lymphocyte and lymphocyte to hemoglobin ratio were statistically significantly higher in cases compared to controls (P=0.049 and P=0.04, respectively). A lymphocyte value higher than 1.5 x103/µL was the best cut-off to exclude the occurrence of SSI, with a sensitivity of 95%, a specificity of 50%, a positive predictive value of 5.5% and a negative predictive value of >99%. A lymphocyte to hemoglobin ratio higher than 1.13 was the best cut off to exclude the occurrence of SSI, with a sensitivity of 95%, a specificity of 60%, a positive predictive value of 6.8% and a negative predictive value >99%. CONCLUSIONS: The preoperative lymphocyte and lymphocyte to hemoglobin ratio should be incorporated into patient counseling and preoperative algorithms to identify patients who will develop SSI. The biological mechanisms involved remain to be investigated and our data should be confirmed by further and larger studies.

Antibody and Cell-Based Therapies against Virus-Induced Cancers in the Context of HIV/AIDS.

Infectious agents, notably viruses, can cause or increase the risk of cancer occurrences. These agents often disrupt normal cellular functions, promote uncontrolled proliferation and growth, and trigger chronic inflammation, leading to cancer. Approximately 20% of all cancer cases in humans are associated with an infectious pathogen. The International Agency for Research on Cancer (IARC) recognizes seven viruses as direct oncogenic agents, including Epstein-Barr Virus (EBV), Kaposi's Sarcoma-associated herpesvirus (KSHV), human T-cell leukemia virus type-1 (HTLV-1), human papilloma virus (HPV), hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus type 1 (HIV-1). Most viruses linked to increased cancer risk are typically transmitted through contact with contaminated body fluids and high-risk behaviors. The risk of infection can be reduced through vaccinations and routine testing, as well as recognizing and addressing risky behaviors and staying informed about public health concerns. Numerous strategies are currently in pre-clinical phases or undergoing clinical trials for targeting cancers driven by viral infections. Herein, we provide an overview of risk factors associated with increased cancer incidence in people living with HIV (PLWH) as well as other chronic viral infections, and contributing factors such as aging, toxicity from ART, coinfections, and comorbidities. Furthermore, we highlight both antibody- and cell-based strategies directed against virus-induced cancers while also emphasizing approaches aimed at discovering cures or achieving complete remission for affected individuals.

Regulation of human T-cell leukemia virus type 1 antisense promoter by myocyte enhancer factor-2C in the context of adult T-cell leukemia and lymphoma.

Adult T-cell leukemia and lymphoma (ATLL) is an intractable T-cell neoplasia caused by a retrovirus, namely human T-cell leukemia virus type 1 (HTLV-1). Patients suffering from ATLL present a poor prognosis and have a dearth of treatment options. In contrast to the sporadic expression of viral transactivator protein Tax present at the 5' promoter region long terminal repeats (LTR), HTLV-1 bZIP gene (HBZ) is encoded by 3'LTR (the antisense promoter) and maintains its constant expression in ATLL cells and patients. The antisense promoter is associated with selective retroviral gene expression and has been an understudied phenomenon. Herein, we delineate the activity of transcription factor MEF (myocyte enhancer factor)-2 family members, which were found to be enriched at the 3'LTR and play an important role in the pathogenesis of ATLL. Of the four MEF isoforms (A to D), MEF-2A and 2C were highly overexpressed in a wide array of ATLL cell lines and in acute ATLL patients. The activity of MEF-2 isoforms were determined by knockdown experiments that led to decreased cell proliferation and regulated cell cycle progression. High enrichment of MEF-2C was observed at the 3'LTR along with cofactors Menin and JunD resulting in binding of MEF-2C to HBZ at this region. Chemical inhibition of MEF-2 proteins resulted in the cytotoxicity of ATLL cells in vitro and reduction of proviral load in a humanized mouse model. Taken together, this study provides a novel mechanism of 3'LTR regulation and establishes MEF-2 signaling a potential target for therapeutic intervention for ATLL.

ZFTA (Zinc Finger Translocation Associated) Fusion in Supratentorial Ependymomas: Low Prevalence in South Asians and No Correlation with Survival.

BACKGROUND: Supratentorial ependymomas (STEs) are an aggressive group of ependymomas, topographically distinct from their posterior fossa and spinal counterparts. Zinc finger translocation associated (ZFTA) fusion-positive cases have been reported to account for the majority of STEs, although data on its association with poorer outcomes are inconsistent. MATERIALS AND METHODS: We assessed the prevalence of the ZFTA fusion by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization in a cohort of 61 patients (68 samples) with STE. Our primary outcome was to determine the role of the ZFTA fusion on progression-free and overall survival of patients with STE. Our secondary objectives were to assess the impact of ZFTA fusion on nuclear factor (NF)-kB pathway signaling via surrogate markers of this pathway, namely COX-2, CCND1, and L1 cell adhesion molecule. RESULTS: ZFTA fusion was noted in 21.3% of STEs in our cohort. The presence of this rearrangement did not significantly impact the progression-free or overall survival of patients with STEs and was not associated with upregulation of markers of the NF-kB pathway. Only gross total resection was significantly associated with better progression-free survival. CONCLUSIONS: In contradiction to previous reports from across the world, the ZFTA fusion is far less prevalent among our population. It does not appear to drive NF-kB signaling or significantly affect outcomes. Gross total resection must be attempted in all cases of STE and adjuvant radiation and/or chemotherapy employed when gross total resection is not achieved.

Hispanic race is a risk factor for COVID-19 during pregnancy: data from an urban New York City hospital.

There are limited studies on predisposing factors for COVID-19 positivity in asymptomatic pregnant women. The literature published to date on asymptomatic COVID-19 pregnant carriers does not focus on pregnancy or pre-pregnancy comorbidities. We wanted to identify risk factors for COVID-19 in asymptomatic pregnant women. We performed a retrospective chart review of 263 asymptomatic pregnant women admitted to labour and delivery at New York City Health + Hospitals/Lincoln.We analysed the association between race, body mass index (BMI), smoking, indication for admission, gravidity, parity, pre-pregnancy comorbidity, pregnancy comorbidity via uni- and multivariate statistical tests. Only Hispanic race was significant in the univariate analysis (p = .049). At the post-hoc analysis, Hispanics had a higher proportion of COVID-19 cases compared to non-Hispanic Blacks (p = .019). No variables were significantly associated with COVID-19 positivity in the multivariate analysis.Hispanic race appears to be a risk factor for asymptomatic COVID-19 infection during pregnancy. We speculate that the cultural and socioeconomic reality of Hispanic women living in our community leads to more exposure opportunities and therefore, a higher infection rate.Impact statementWhat is already known on this subject? Little is known on the role of comorbidities and risk factors that can favour COVID-19 infection during pregnancy.What do the results of this study add? We found that Hispanic pregnant asymptomatic women had a higher rate of COVID-19 in comparison to non-Hispanic Black women. Pre-pregnancy comorbidities such as pregestational diabetes, hypertension and asthma were not associated with COVID-19 positivity.What are the implications of these findings for clinical practice and/or further research? The reasons why the Hispanic race is more affected by COVID-19 during pregnancy is unclear. The social environment of Hispanic women living in our community, such as their tendency to live in multigenerational and multi-family households, might contribute to a higher infection rate. More resources might be dedicated in the future to Hispanic-dense neighbourhoods.

Can Soluble Immune Checkpoint Molecules on Exosomes Mediate Inflammation?

Immune checkpoints (ICPs) are major co-signaling pathways that trigger effector functions in immune cells, with isoforms that are either membrane bound, engaging in direct cell to cell activation locally, or soluble, acting at distant sites by circulating freely or potentially via extracellular vesicles (EVs). Exosomes are small EVs secreted by a variety of cells carrying various proteins and nucleic acids. They are distributed extensively through biological fluids and have major impacts on infectious diseases, cancer, and neuroinflammation. Similarly, ICPs play key roles in a variety of disease conditions and have been extensively utilized as a prognostic tool for various cancers. Herein, we explored if the association between exosomes and ICPs could be a significant contributor of inflammation, particularly in the setting of cancer, neuroinflammation and viral infections, wherein the up regulation in both exosomal proteins and ICPs correlate with immunosuppressive effects. The detailed literature review of existing data highlights the significance and complexity of these two important pathways in mediating cancer and potentiating neuroinflammation via modulating overall immune response. Cells increasingly secret exosomes in response to intracellular signals from invading pathogens or cancerous transformations. These exosomes can carry a variety of cargo including proteins, nucleic acids, cytokines, and receptors/ligands that have functional consequences on recipient cells. Illustration generated using BioRender software.

Foxo3a tempers excessive glutaminolysis in activated T cells to prevent fatal gut inflammation in the murine IL-10-/- model of colitis.

Mutations in susceptibility alleles correlate with gut-inflammatory diseases, such as Crohn's disease; however, this does not often impact the disease progression indicating the existence of compensatory genes. We show that a reduction in Foxo3a expression in IL-10-deficient mice results in a spontaneous and aggressive Crohn's- like disease with 100% penetrance, which is rescued by deletion of myeloid cells, T cells and inhibition of mTORC1. In Foxo3a-/- IL-10-/- mice, there is poor cell death of myeloid cells in the gut, leading to increased accumulation of myeloid and T cells in the gut. Myeloid cells express high levels of inflammatory cytokines, and regulatory T cells are dysfunctional despite increased abundance. Foxo3a signaling represses the transcription of glutaminase (GLS/GLS2) to prevent over-consumption of glutamine by activated T cells and its conversion to glutamate that contributes to the TCA cycle and mTORC1 activation. Finally, we show that Foxo3a restricts the abundance of colitogenic microbiota in IL-10-deficient mice. Thus, by suppressing glutaminolysis in activated T cells Foxo3a mediates a critical checkpoint that prevents the development of fulminant gut inflammatory disease.

A collaborative approach intended to reduce the duration of short term urinary catheters in adult patients at a tertiary care medical center also significantly reduced the duration of hospitalization.

BACKGROUND: Urinary tract infections are the leading cause of nosocomial infections in the United States. The major contributing factor is the placement of indwelling urinary catheters. METHODS: Following a chart review of adult patients hospitalized at a tertiary care medical center who required the use of a short-term (≤ 2 weeks) indwelling urinary catheter, a collaborative effort was initiated by an Infectious Diseases physician to develop protocols focused on the clinical service involved for the expeditious removal of short-term indwelling urinary catheters. The protocols relied in part on the standards of practice by pertinent medical/surgical subspecialty societies. Usage of urinary catheters and duration of hospitalization following implementation of the protocols was assessed. RESULTS: Based on a multivariate analysis controlling for demographic variables, comorbidities, medical vs surgical service, and indication for the urinary catheterization, the median duration of catheterization was significantly reduced from 6.7 days to 3.6 days after the protocols were initiated (P < .001), and the median duration of hospitalization was significantly reduced from 9.5 days to 5.9 days (P < .001). No patient had to have the urinary catheter reinserted. CONCLUSIONS: Development of collaborative protocols for the removal of short-term indwelling urinary catheters significantly reduced both the duration of catheterization and the duration of hospitalization.

Intrauterine transmission of COVID-19 in Pregnancy: case report and review of literature.

We report the first case of SARS-CoV-2 pregnancy in the U.S. Our literature review highlights the rarity of COVID-19 intrauterine transmission and the need for clinicians to promptly test neonates born to SARS-CoV-2 positive mothers at delivery for COVID-19. It is imperative to establish the real risk of intrauterine transmission and to develop appropriate preventive and treatment strategies.

Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization.

Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and CD40L, it was T follicular helper (TFH) cell, germinal center, and T follicular regulatory (TFR) cell-independent. In contrast, IgG1 and IgE production to peanut required TFH cells. These data suggest an alternative paradigm in which the cellular mechanism of IgA production to food antigens is distinct from IgE and IgG1. We developed an equivalent assay to study this process in stool samples from healthy, nonallergic humans, which revealed substantial levels of peanut-specific IgA that were stable over time. Similar to mice, patients with loss of CD40L function had impaired titers of gut peanut-specific IgA. This work challenges two widely believed but untested paradigms about antibody production to dietary antigens: (i) the steady state/tolerogenic response to food antigens includes IgA production and (ii) TFH cells drive food-specific gut IgA.

Influence of p-n junction mechanism and alumina overlayer on the photocatalytic performance of TiO2 nanotubes.

Modified hybrid structures of TiO2 nanotubes (TONT), p-Al doped TONT/n-TONT with an additional overlayer of alumina, are constructed to achieve 99.57% photodegradation of the stable organic pollutant methylene blue (MB) within 180 min, a degradation rate 17 times higher than pure TONTs. The anodization at three different temperatures 2, 28 and 40 °C followed by impregnation of Al is used for their preparation. The analyses of structure, chemical composition and morphology are completed using x-ray diffraction, x-ray photoelectron spectroscopy (XPS) and high resolution transmission microscopy, respectively, Rutherford back scattering and field emission scanning electron microscopy confirm the formation of the hybrid structure. This structure exhibits the highest photodegradation rate with TONT based catalysts to date for MB blue, by enhancing the electron-hole separation, the absorption of visible photons and the adsorption sites for the pollutant. The optical data coupled with valence band XPS is used for elucidating the energy band structure of the p-n junctions and to gain insight into the effect of the junction mechanism on photoactivity. The rectification ratios of the impregnated p-n junctions, determined by current-voltage measurements, are found to vary from 102 to 106.

Increasing incidence and changing epidemiology of babesiosis in the Hudson Valley region of New York State: 2009-2016.

Babesiosis is an emerging infection in parts of New York State. From 2009 through 2016, there was a significant increase in the incidence rate of babesiosis in the Hudson Valley region of New York State (P = 0.002), an inland geographic location in which babesiosis only first emerged in 2001. A significant increase in cases was found for both the Upper Hudson Valley (UHV) region (P < 0.001) as well as for the Lower Hudson Valley region (P = 0.03). The greatest increase in the incidence rate was found for the UHV, with a 16.8-fold increase in incidence over the 8-year time period. In conclusion, babesiosis is a rapidly emerging infection in the Hudson Valley region of New York State, the geographic region now accounting for more cases than any other single geographic area in the state.

Identification of a T follicular helper cell subset that drives anaphylactic IgE.

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (TFH) cells direct the affinity and isotype of antibodies produced by B cells. Although TFH cell-derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13-producing TFH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These "TFH13" cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and coexpress the transcription factors BCL6 and GATA3. TFH13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking TFH13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.