TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy.

Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer's disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2-/- mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.

Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells.

Conventional dendritic cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2, responsible for priming naive CD8+ and CD4+ T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300ciCre-hCD2R26tdTomato reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo. Single-cell analyses and multiparametric flow cytometry demonstrated that pro-cDC2 encompasses myeloid-derived pre-cDC2 and lymphoid-derived plasmacytoid DC (pDC)-like precursors differentiating into a transcriptionally convergent cDC2 phenotype. Cd300c-traced cDC2 had distinct transcriptomic profiles, phenotypes, and tissue distributions compared with Ms4a3CreR26tdTomato lineage-traced DC3, a monocyte-DC progenitor (MDP)-derived subset that bypasses CDP. Mice with reduced Cd300c-traced cDC2 showed impaired humoral responses to T cell-dependent antigens. We conclude that progenitors of distinct lineages shape the diversity of mature cDC2 across tissues. Thus, ontogenesis may impact tissue immune responses.

Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes.

The aryl-hydrocarbon receptor (AHR) is a ligand-activated transcription factor that buoys intestinal immune responses. AHR induces its own negative regulator, the AHR repressor (AHRR). Here, we show that AHRR is vital to sustaining intestinal intraepithelial lymphocytes (IELs). AHRR deficiency reduced IEL representation in a cell-intrinsic fashion. Single-cell RNA sequencing revealed an oxidative stress profile in Ahrr-/- IELs. AHRR deficiency unleashed AHR-induced expression of CYP1A1, a monooxygenase that generates reactive oxygen species, increasing redox imbalance, lipid peroxidation, and ferroptosis in Ahrr-/- IELs. Dietary supplementation with selenium or vitamin E to restore redox homeostasis rescued Ahrr-/- IELs. Loss of IELs in Ahrr-/- mice caused susceptibility to Clostridium difficile infection and dextran sodium-sulfate-induced colitis. Inflamed tissue of inflammatory bowel disease patients showed reduced Ahrr expression that may contribute to disease. We conclude that AHR signaling must be tightly regulated to prevent oxidative stress and ferroptosis of IELs and to preserve intestinal immune responses.

SLC7A8 is a key amino acids supplier for the metabolic programs that sustain homeostasis and activation of type 2 innate lymphoid cells.

Group 2 innate lymphoid cells (ILC2) are innate counterparts of T helper 2 (Th2) cells that maintain tissue homeostasis and respond to injuries through rapid interleukin (IL)-5 and IL-13 secretion. ILC2s depend on availability of arginine and branched-chain amino acids for sustaining cellular fitness, proliferation, and cytokine secretion in both steady state and upon activation. However, the contribution of amino acid transporters to ILC2 functions is not known. Here, we found that ILC2s selectively express Slc7a8, encoding a transporter for arginine and large amino acids. Slc7a8 was expressed in ILC2s in a tissue-specific manner in steady state and was further increased upon activation. Genetic ablation of Slc7a8 in lymphocytes reduced the frequency of ILC2s, suppressed IL-5 and IL-13 production upon stimulation, and impaired type 2 immune responses to helminth infection. Consistent with this, Slc7a8-deficient ILC2s also failed to induce cytokine production and recruit eosinophils in a model of allergic lung inflammation. Mechanistically, reduced amino acid availability due to Slc7a8 deficiency led to compromised mitochondrial oxidative phosphorylation, as well as impaired activation of mammalian target of rapamycin and c-Myc signaling pathways. These findings identify Slc7a8 as a key supplier of amino acids for the metabolic programs underpinning fitness and activation of ILC2s.

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4+ eosinophils unique to the small intestine.

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile. Clec4a4+ eosinophils expressed high levels of aryl hydrocarbon receptor (Ahr), which drove the expression of Clec4a4 as well as other immunomodulatory features, such as PD-L1. The abundance of Clec4a4+ eosinophils was dependent on dietary AHR ligands, increased with aging, and declined in inflammatory conditions. Mice lacking AHR in eosinophils expanded innate lymphoid cells of type 2 and cleared Nippostrongylus brasiliensis infection more effectively than did wild-type mice. These results highlight the heterogeneity of eosinophils in response to tissue cues and identify a unique AHR-dependent subset of eosinophils in the small intestine with an immunomodulatory profile.

Accuracy to detect neonatal hyperglycaemia using real-time continuous glucose monitoring during postoperative period.

Identifying hyperglycaemia during postoperative period is essential for neonates. The objective of the study was to analyse the accuracy and reliability of continuous glucose monitoring (CGM) device for detecting hyperglycaemia during postoperative period in neonates. In this prospective study, hourly glucose recordings by CGM device and six hourly by glucometer glucose (GG-reference test for patient management) were collected in ten surgical neonates during first three postoperative days. Mean absolute relative difference (MARD) and proportion of CGM values within ± 15%/15 mg/dL, ± 20%/20 mg/dL, and ± 30%/30 mg/dL of GG, were analysed from matched pair CGM and GG recordings. The diagnostic performance of CGM for neonatal hyperglycaemia (> 150 mg/dL) was expressed as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV); and the clinical reliability was assessed in Clarke Error Grid Analysis. A total of 720 CGM glucose readings, 120 matched -paired glucose readings by CGM --GG, and 37 episodes were hyperglycaemia by GG. The MARD was 10.76 %; the percentages of glucose readings within 15%/15 mg/dL, 20%/20 mg/dL, and 30%/30 mg/dL were 94.6%, 97.3% and 100% during the hyperglycaemia period. The sensitivity, specificity, PPV and NPV to detect hyperglycaaemia by CGM device were 100%, 93.9%, 88% and 100 % respectively. In Clarke Error Grid Analysis, 97.3 % points were in zone A and B during the hyperglycaemia period. CONCLUSION: CGM device can be a clinically reliable tool for hyperglycaemia management during postoperative period in neonates. WHAT IS KNOWN: • Neonates are vulnerable for hyperglycaemia during post-operative period and bed side glucometers are used for frequent glucose monitoring in them. • Continuous glucose monitor(CGM) devices are used for the glucose monitoring in adult and paediatric diabetes care. WHAT IS NEW: • For the first time, this study analysed the accuracy and clinical reliability of FreeStyle Libre (CGM device) for identifying hyperglycaemia during post-operative period in neonates. • CGM device has very good accuracy for detecting hyperglycaemia in neonates, it may help the clinician for better glucose stability during post-operative period.

Comparison between Phenobarbitone and Levetiracetam as the initial anticonvulsant in preterm neonatal seizures - a pilot randomized control trial in developing country setup.

This study aimed to compare the efficacy and safety of intravenous Levetiracetam and Phenobarbitone in the treatment of seizures in preterm neonates. It was an open-labeled, parallel randomized controlled trial conducted in a tertiary Neonatal Intensive Care Unit, India. Total 48 preterm neonates (28-36+6 weeks) with clinical seizures were randomized to receive either Levetiracetam (LEV; 40 mg/kg, then 20 mg/kg) or Phenobarbitone (PB; 15 mg/kg, then 10 mg/kg) intravenously as first loading dose in ratio 1:1; second loading was given for persistent seizure. Efficacy was denoted by cessation of clinical seizures with first or second doses of the allotted antiepileptic, and remaining seizure-free for the next 24 h. The demographic characteristics of preterm neonates and seizure types were comparable between both groups. Clinical seizure was controlled in 19 (79%) neonates in LEV group and 17 (70%) neonates in PB group, RR 1.12 (95% CI: 0.80 to 1.55), p = 0.504. There was increased respiratory support in PB group 9 (38%) vs. 3 (13%) in LEV group, RR 3.0 (95% CI: 0.92 to 9.74), p = 0.06.  Conclusion: Levetiracetam and Phenobarbitone were equally efficacious for clinical neonatal seizure control, but increased respiratory support was found with Phenobarbitone use. What is Known: • Preterm neonates are at higher risk of neonatal seizure and Phenobarbitone is commonly used as the first line antiepileptic drugs in treating them. What is New: • Levetiracetam found equally efficacious as Phenobarbitone for cessation of clinical seizures in preterm neonates, with less adverse effect.

Innate lymphoid cells: A potential link between microbiota and immune responses against cancer.

The adaptive immune system plays a crucial role in anti-tumor surveillance. Enhancement of T cell responses through checkpoint blockade has become a major therapeutic avenue of intervention for several tumors. Because it shapes immune responses and regulates their amplitude and duration, the microbiota has a substantial impact on anti-tumor immunity. Innate lymphoid cells (ILCs) comprise a heterogeneous population of lymphocytes devoid of antigen-specific receptors that mirror T helper cells in their ability to secrete cytokines that activate immune responses. Ongoing studies suggest that ILCs contribute to anti-tumor responses. Moreover, since ILCs are present at barrier surfaces, they are stimulated by the microbiota and, reciprocally, influence the composition of the microbiota by regulating the surface barrier microenvironment. Thus, ILC-microbiota cross-talk may in part underpin the effects of the microbiota on anti-tumor responses. In this article, we review current evidence linking ILCs to cancer and discuss the potential impact of ILC-microbiota cross-talk in anti-tumor immune responses.

Self-reactive IgG4 antibodies are associated with blocking of pathology in human lymphatic filariasis.

Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases.

Utilization of plant-derived recombinant human ß-defensins (hBD-1 and hBD-2) for averting salmonellosis.

We describe the use of plant-made ß-defensins as effective antimicrobial substances for controlling salmonellosis, a deadly infection caused by Salmonella typhimurium (referred to further as S. typhi). Human ß-defensin-1 (hBD-1) and -2 (hBD-2) were expressed under the control of strong constitutive promoters in tobacco plants, and bio-active ß-defensins were successfully extracted. In the in vitro studies, enriched recombinant plant-derived human ß-defensin-1 (phBD-1) and -2 (phBD-2) obtained from both T1 and T2 transgenic plants showed significant antimicrobial activity against Escherichia coli and S. typhi when used individually and in various combinations. The 2:1 peptide combination of phBD-1:phBD-2 with peptides isolated from T1-and T2-generation plants reduced the growth of S. typhi by 96 and 85 %, respectively. In vivo studies employing the mouse model (Balb/c) of Salmonella infection clearly demonstrated that the administration of plant-derived defensins individually and in different combinations enhanced the mean survival time of Salmonella-infected animals. When treatment consisted of the 2:1 phBD-1:phBD-2 combination, approximately 50 % of the infected mice were still alive at 206 h post-inoculation; the lowest number of viable S. typhi was observed in the liver and spleen of infected animals. We conclude that plant-made recombinant ß-defensins (phBD-1 and phBD-2) are promising antimicrobial substances and have the potential to become additional tools against salmonellosis, particularly when used in combination.

Filarial antigens mediate apoptosis of human monocytes through Toll-like receptor 4.

BACKGROUND: Apoptosis of several host cells induced by parasites/parasite products has been investigated in human filariasis to understand immune hyporesponsiveness. However, apoptosis of monocytes-one of the major antigen presenting cells in peripheral circulation, which are chronically exposed to filarial antigens in infected subjects-is yet to be understood. METHODS: Apoptosis of human monocytes with Brugia pahangi antigen (BpA) was demonstrated by scoring several apoptotic markers using flow cytometry. Ability of BpA and plasma of infected subjects to suppress lymphocyte proliferation was demonstrated by (3)H thymidine incorporation assay and carboxyfluorescein succinimidyl ester dilution assay. RESULTS: BpA induced significant apoptosis of normal human monocytes, primarily through Toll-like receptor 4 (TLR4), and suppressed phytohemagglutinin (PHA)-mediated proliferation of normal human T lymphocytes. However, monocytes of Wuchereria bancrofti-infected subjects were resistant to BpA-induced apoptosis. Plasma of infected subjects also mediated apoptosis of normal monocytes, presumably due to circulating filarial antigens, and resulted in inhibition of PHA-induced proliferation. CONCLUSION: Normal human monocytes were found to be qualitatively different from those of filariasis-infected subjects; whereas filarial antigens mediate apoptosis of normal human monocytes through TLR4, those of infected subjects were found to be resistant.

Chitohexaose activates macrophages by alternate pathway through TLR4 and blocks endotoxemia.

Sepsis is a consequence of systemic bacterial infections leading to hyper activation of immune cells by bacterial products resulting in enhanced release of mediators of inflammation. Endotoxin (LPS) is a major component of the outer membrane of Gram negative bacteria and a critical factor in pathogenesis of sepsis. Development of antagonists that inhibit the storm of inflammatory molecules by blocking Toll like receptors (TLR) has been the main stay of research efforts. We report here that a filarial glycoprotein binds to murine macrophages and human monocytes through TLR4 and activates them through alternate pathway and in the process inhibits LPS mediated classical activation which leads to inflammation associated with endotoxemia. The active component of the nematode glycoprotein mediating alternate activation of macrophages was found to be a carbohydrate residue, Chitohexaose. Murine macrophages and human monocytes up regulated Arginase-1 and released high levels of IL-10 when incubated with chitohexaose. Macrophages of C3H/HeJ mice (non-responsive to LPS) failed to get activated by chitohexaose suggesting that a functional TLR4 is critical for alternate activation of macrophages also. Chitohexaose inhibited LPS induced production of inflammatory molecules TNF-α, IL-1ß and IL-6 by macropahges in vitro and in vivo in mice. Intraperitoneal injection of chitohexaose completely protected mice against endotoxemia when challenged with a lethal dose of LPS. Furthermore, Chitohexaose was found to reverse LPS induced endotoxemia in mice even 6/24/48 hrs after its onset. Monocytes of subjects with active filarial infection displayed characteristic alternate activation markers and were refractory to LPS mediated inflammatory activation suggesting an interesting possibility of subjects with filarial infections being less prone to develop of endotoxemia. These observations that innate activation of alternate pathway of macrophages by chtx through TLR4 has offered novel opportunities to cell biologists to study two mutually exclusive activation pathways of macrophages being mediated through a single receptor.

The diagnostic performance of mean neutrophil volume in neonatal sepsis: A systematic review and meta-analysis.

BACKGROUND: There is a need for reliable diagnostic tests for early identification of sepsis to prevent neonatal mortality and antibiotic misuse. During sepsis, many immature neutrophils came into the bloodstream, altering the mean neutrophil volume (MNV) shown in the previous studies. OBJECTIVES: To summarize the diagnostic performance of mean neutrophil volume (MNV) in neonatal sepsis from the published literature. METHOD: Databases such as PubMed, Scopus, and Web of Science were searched from January 1990 to April 2023 for studies reporting MNV as a diagnostic test in neonatal sepsis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve of MNV were estimated with reference blood culture-positive sepsis and clinical sepsis for meta-analysis. RESULT: The diagnostic performance of MNV was analyzed in 1685 neonates, including 829 septic and 856 non-septic neonates, from six prospective studies. The pooled sensitivity and specificity of MNV were 0.87 and 0.75, respectively, for neonatal sepsis; the DOR was 20.01 (95% CI: 5.90-67.82); and the AUC of the SROC for MNV was 0.81 (95% CI: 0.69-0.88). Higgins I2 was 92.1% (95% CI: 85.5%-95.7%). The diagnostic performance of MNV was better during sub-group analysis of studies reporting culture-positive sepsis (DOR 85.61). CONCLUSION: The diagnostic performance of MNV is moderate for neonatal sepsis. As the evidence originated from a small number of studies with marked heterogeneity, further large-scale diagnostic accuracy studies are recommended to resolve heterogeneity in the future.

Lower Hemoglobin Levels as a Risk Factor for the Development of Retinopathy of Prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is an important cause of visual morbidity among preterm infants. The objective of the study was to assess the relationship between the initial hematological parameters of the complete blood count (CBC) and ROP development in preterm neonates. METHOD: This retrospective cohort study was conducted in a neonatal intensive care unit in Odisha. The hematological parameters of the CBC conducted within the first 48 hours of age, demographic characteristics, neonatal morbidities, and ROP screening findings of preterm neonates (gestational age <34 weeks) were analyzed. Independent risk factors associated with ROP development were identified in a multivariate logistic regression model. RESULT: A total of 43 (29.1%) out of 148 neonates had any of the ROP stages (stage 1-26, 2-08, and 3-09). Birth weight (aOR 0.003; 95% CI 0.00, 0.11);hemoglobin (Hb) level (aOR 0.70; 95% CI 0.54, 0.90); presence of respiratory distress syndrome (RDS) (aOR 7.61; 95% CI 1.5, 36.39); and need for packed red blood cell (PRBC) transfusion (aOR 4.26; 95% CI 1.1, 16.44) were independently associated with ROP development. The odds of ROP were higher among the neonates with initial Hb 10.5-15.4 g/dL (OR (95% CI) 3.7(1.5, 8.9), p=0.003) and for neonates with Hb 15.4-17.3 g/dL (OR (95% CI) 2.5(1.01, 6.16), p=0.047) in comparison to neonates with initial Hb >17.3 g/dL. CONCLUSION: Preterm neonates with a lower level of Hb during the early postnatal days are at higher risk for ROP development and need to be prioritized for screening.

Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases.

Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.

Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway.

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity.

Assessment, analysis and appraisal of road traffic noise pollution in Rourkela city, India.

The problem of road traffic noise pollution has become a concern for both the public and the policy makers. Noise level was assessed in 12 different squares of Rourkela city during different specified times (7-10 a.m., 11 a.m.-2 p.m., 3-6 p.m., 7-10 p.m., 10 p.m.-12 midnight and 4-6 a.m.). Noise descriptors such as L,eq, traffic noise index, noise pollution level, noise climate, Lday, Levening, Lnight and Lden were assessed to reveal the extent of noise pollution due to heavy traffic in this city. The equivalent noise levels of all the 12 squares were found to be much beyond the permissible limit (70dB during day time and 55dB during night time). Appallingly, even the minimum L eq and NPL values were more than 82 dB and 96 dB during day time and 69 dB and 91 dB during night time respectively. Lden values of investigated squares ranged from 83.4 to 86.1 dB and were even more than the day time permissible limit of traffic noise. The prediction model was used in the present study to predict noise pollution level instead of Leq. Comparison of predicted with that of the actual measured data demonstrated that the model used for the prediction has the ability to calibrate the multicomponent traffic noise and yield reliable results close to that by direct measurement. Lastly, it is inferred that the dimension of the traffic generated noise pollution in Rourkela is critical.

Pregnancy-induced differential expression of SARS-CoV-2 and influenza a viral entry factors in the lower respiratory tract.

Despite differences in the clinical presentation of coronavirus disease-19 and pandemic influenza in pregnancy, fundamental mechanistic insights are currently lacking because of the difficulty in recruiting critically ill pregnant subjects for research studies. Therefore, to better understand host-pathogen interaction during pregnancy, we performed a series of foundational experiments in pregnant rats at term gestation to assess the expression of host entry factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) and genes associated with innate immune response in the lower respiratory tract. We report that pregnancy is characterized by a decrease in host factors mediating SARS-CoV-2 entry and an increase in host factors mediating IAV entry. Furthermore, using flow cytometric assessment of immune cell populations and immune provocation studies, we show an increased prevalence of plasmacytoid dendritic cells and a Type I interferon-biased environment in the lower respiratory tract of pregnancy, contrary to the expected immunological indolence. Our findings, therefore, suggest that the dissimilar clinical presentation of COVID-19 and pandemic influenza A in pregnancy could partly be due to differences in the extent of innate immune activation from altered viral tropism and indicate the need for comparative mechanistic investigations with live virus studies.

Screening and Management of Congenital Hypothyroidism - Guidelines by American Academy of Pediatrics, 2023.

Guidelines for screening and management of congenital hypothyroidism in neonates have been recently updated by the American Academy of Pediatrics (AAP). This article compares new AAP guideline with the Indian Society for Pediatric and Adolescent Endocrinology (ISPAE) Guidelines, 2018 and lists the changes in screening, diagnosis, and management of congenital hypothyroidism suggested in the new guidelines, along with clinical utilization in the Indian scenario.

Agreement between Noninvasive Hemoglobin and Laboratory Hemoglobin Measurements in Neonates: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: The noninvasive hemoglobin (NHb) devices are recently evaluated as an alternative to laboratory hemoglobin (LHb) in neonates. This systematic review explores the diagnostic accuracy of NHb devices for neonatal hemoglobin measurement. METHODS: Literature related to the comparison of NHb device with LHb in neonates was searched from Medline, PubMed Central, PubMed, Web of Science, Google Scholar, and Scopus databases after PROSPERO registration. The quality of included publications was assessed by QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The pooled correlation coefficient and bias (precision) in Bland-Altman difference plots were used for summary statistics using MetaXL 5.0 software. RESULTS: A total of 1,477 paired NHb-LHb observations were analyzed from 1,047 neonates in 10 studies. Massimo radical-pulse co-oximetry (8 studies) and Mediscan-2000 (2 studies) were used for NHb estimation. The pooled correlation coefficient between NHb and LHb was r = 0.94 (95% CI: 0.83-0.98, p < 0.001), and the pooled bias (precision) was -0.013 (1.4) gm/dL between NHb and LHb measurements in Bland-Altman analysis. NHb device had better precision in stable neonates (0.91gm/dL) over sick neonates (1.66 gm/dL). CONCLUSIONS: Hemoglobin measurement by NHb is excellently correlated with LHb measurement with a minimal average difference. It may be used as a screening tool for hemoglobin measurement in neonates to avoid frequent phlebotomy.