The immunoglobulin J chain is an evolutionarily co-opted chemokine.

The joining (J) chain regulates polymerization of multimeric Immunoglobulin(Ig)M and IgA, forming a disulfide bond to the C termini of their Ig heavy chains, and it controls IgM/IgA transport across mucosal epithelia. Like Ig itself and human-like adaptive immunity, J chain emerged in jawed vertebrates (gnathostomes), but its origin has remained mysterious since its discovery over 50 y ago. Here, we show unexpectedly that J chain is a member of the CXCL chemokine family. The J chain gene (JCHAIN) is linked to clustered CXCL chemokine loci in all gnathostomes except actinopterygians that lost JCHAIN. JCHAIN and most CXCL genes have four exons with the same intron phases, including the same cleavage site for the signal peptide/mature protein. The second exon of both genes encodes a CXC motif at the same position, and the lengths of exons 1 to 3 are similar. No other gene in the human secretome shares all of these characteristics. In contrast, intrachain disulfide bonds of the two proteins are completely different, likely due to modifications in J chain to direct Ig polymerization and mucosal transport. Crystal structures of CXCL8 and J chain share a conserved beta-strand core but diverge otherwise due to different intrachain disulfide bonds and extension of the J chain C terminus. Identification of this ancestral affiliation between J chain and CXCL chemokines addresses an age-old problem in immunology.

Author Correction: Elephant shark genome provides unique insights into gnathostome evolution.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An Ancient MHC-Linked Gene Encodes a Nonrearranging Shark Antibody, UrIg, Convergent with IgG.

Gnathostome adaptive immunity is defined by the Ag receptors, Igs and TCRs, and the MHC. Cartilaginous fish are the oldest vertebrates with these adaptive hallmarks. We and others have unearthed nonrearranging Ag receptor-like genes in several vertebrates, some of which are encoded in the MHC or in MHC paralogous regions. One of these genes, named UrIg, was detected in the class III region of the shark MHC that encodes a protein with typical V and C domains such as those found in conventional Igs and TCRs. As no transmembrane region was detected in gene models or cDNAs, the protein does not appear to act as a receptor. Unlike some other shark Ig genes, the UrIg V region shows no evidence of RAG-mediated rearrangement, and thus it is likely related to other V genes that predated the invasion of the RAG transposon. The UrIg gene is present in all elasmobranchs and evolves conservatively, unlike Igs and TCRs. Also, unlike Ig/TCR, the gene is not expressed in secondary lymphoid tissues, but mainly in the liver. Recombinant forms of the molecule form disulfide-linked homodimers, which is the form also detected in many shark tissues by Western blotting. mAbs specific for UrIg identify the protein in the extracellular matrix of several shark tissues by immunohistochemistry. We propose that UrIg is related to the V gene invaded by the RAG transposon, consistent with the speculation of emergence of Ig/TCR within the MHC or proto-MHC.

Collagen IV of basement membranes: II. Emergence of collagen IVα345 enabled the assembly of a compact GBM as an ultrafilter in mammalian kidneys.

The collagen IVα345 (Col-IVα345) scaffold, the major constituent of the glomerular basement membrane (GBM), is a critical component of the kidney glomerular filtration barrier. In Alport syndrome, affecting millions of people worldwide, over two thousand genetic variants occur in the COL4A3, COL4A4, and COL4A5 genes that encode the Col-IVα345 scaffold. Variants cause loss of scaffold, a suprastructure that tethers macromolecules, from the GBM or assembly of a defective scaffold, causing hematuria in nearly all cases, proteinuria, and often progressive kidney failure. How these variants cause proteinuria remains an enigma. In a companion paper, we found that the evolutionary emergence of the COL4A3, COL4A4, COL4A5, and COL4A6 genes coincided with kidney emergence in hagfish and shark and that the COL4A3 and COL4A4 were lost in amphibians. These findings opened an experimental window to gain insights into functionality of the Col-IVα345 scaffold. Here, using tissue staining, biochemical analysis and TEM, we characterized the scaffold chain arrangements and the morphology of the GBM of hagfish, shark, frog, and salamander. We found that α4 and α5 chains in shark GBM and α1 and α5 chains in amphibian GBM are spatially separated. Scaffolds are distinct from one another and from the mammalian Col-IVα345 scaffold, and the GBM morphologies are distinct. Our findings revealed that the evolutionary emergence of the Col-IVα345 scaffold enabled the genesis of a compact GBM that functions as an ultrafilter. Findings shed light on the conundrum, defined decades ago, whether the GBM or slit diaphragm is the primary filter.

An Ancestral Major Histocompatibility Complex Organization in Cartilaginous Fish: Reconstructing MHC Origin and Evolution.

Cartilaginous fish (sharks, rays, and chimeras) comprise the oldest living jawed vertebrates with a mammalian-like adaptive immune system based on immunoglobulins (Ig), T-cell receptors (TCRs), and the major histocompatibility complex (MHC). Here, we show that the cartilaginous fish "adaptive MHC" is highly regimented and compact, containing (i) a classical MHC class Ia (MHC-Ia) region containing antigen processing (antigen peptide transporters and immunoproteasome) and presenting (MHC-Ia) genes, (ii) an MHC class II (MHC-II) region (with alpha and beta genes) with linkage to beta-2-microglobulin (ß2m) and bromodomain-containing 2, (iii) nonclassical MHC class Ib (MHC-Ib) regions with 450 million-year-old lineages, and (iv) a complement C4 associated with the MHC-Ia region. No MHC-Ib genes were found outside of the elasmobranch MHC. Our data suggest that both MHC-I and MHC-II genes arose after the second round of whole-genome duplication (2R) on a human chromosome (huchr) 6 precursor. Further analysis of MHC paralogous regions across early branching taxa from all jawed vertebrate lineages revealed that Ig/TCR genes likely arose on a precursor of the huchr9/12/14 MHC paralog. The ß2m gene is linked to the Ig/TCR genes in some vertebrates suggesting that it was present at 1R, perhaps as the donor of C1 domain to the primordial MHC gene. In sum, extant cartilaginous fish exhibit a conserved and prototypical MHC genomic organization with features found in various vertebrates, reflecting the ancestral arrangement for the jawed vertebrates.

Genomic view of the origins of cell-mediated immunity.

NKp30 is an activating natural killer cell receptor (NKR) with a single-exon variable (VJ)-type immunoglobulin superfamily (IgSF) domain. Such VJ-IgSF domains predate the emergence of the antigen receptors (immunoglobulin and T cell receptor), which possess the same domain but undergo gene rearrangement. NCR3, the gene encoding NKp30, is present in jawed vertebrates from sharks to mammals; thus, unlike most NKR that are highly divergent among vertebrate taxa, NKp30 is uniquely conserved. We previously hypothesized that an ancestral NCR3 gene was encoded in the proto-major histocompatibility complex (MHC), the region where many immune-related genes have accumulated. Herein, we searched in silico databases to identify NCR3 paralogues and examined their genomic locations. We found a paralogue, NCR3H, in many vertebrates but was lost in mammals. Additionally, we identified a set of voltage-gated sodium channel beta (SCNB) genes as NCR3-distantly-related genes. Like NCR3, both NCR3H and SCNB proteins contain a single VJ-IgSF domain followed by a transmembrane region. These genes map to MHC paralogous regions, originally described in an invertebrate, along with genes encoding cell adhesion molecules involved in NK cell recognition networks. Other genes having no obvious relationship to immunity also map to these paralogous regions. These gene complexes were traced to several invertebrates, suggesting that the foundation of these cellular networks emerged before the genome-wide duplications in early gnathostome history. Here, we propose that this ancestral region was involved in cell-mediated immunity prior to the emergence of adaptive immunity and that NCR3 piggybacked onto this primordial complex, heralding the emergence of vertebrate NK cell/T cells.

A Highly Complex, MHC-Linked, 350 Million-Year-Old Shark Nonclassical Class I Lineage.

Cartilaginous fish, or Chondrichthyes, are the oldest extant vertebrates to possess the MHC and the Ig superfamily-based Ag receptors, the defining genes of the gnathostome adaptive immune system. In this work, we have identified a novel MHC lineage, UEA, a complex multigene nonclassical class I family found in sharks (division Selachii) but not detected in chimaeras (subclass Holocephali) or rays (division Batoidea). This new lineage is distantly related to the previously reported nonclassical class I lineage UCA, which appears to be present only in dogfish sharks (order Squaliformes). UEA lacks conservation of the nine invariant residues in the peptide (ligand)-binding regions (PBR) that bind to the N and C termini of bound peptide in most vertebrate classical class I proteins, which are replaced by relatively hydrophobic residues compared with the classical UAA. In fact, UEA and UCA proteins have the most hydrophobic-predicted PBR of all identified chondrichthyan class I molecules. UEA genes detected in the whale shark and bamboo shark genome projects are MHC linked. Consistent with UEA comprising a very large gene family, we detected weak expression in different tissues of the nurse shark via Northern blotting and RNA sequencing. UEA genes fall into three sublineages with unique characteristics in the PBR. UEA shares structural and genetic features with certain nonclassical class I genes in other vertebrates, such as the highly complex XNC nonclassical class I genes in Xenopus, and we anticipate that each shark gene, or at least each sublineage, will have a unique function, perhaps in bacterial defense.

Effectiveness of BNT162b2 vaccine against symptomatic SARS-CoV-2 infection in children aged 5-11 years in Japan during Omicron variant predominate periods.

BACKGROUND: Although the effectiveness of BNT162b2 messenger RNA vaccines against the Omicron variant has been reported in several countries, data are limited in children living in Asian countries. Therefore, this study aimed to estimate the effectiveness of the pediatric primary two-dose monovalent mRNA vaccine series in preventing symptomatic coronavirus disease 2019 (COVID-19) in Japan. METHODS: We conducted a test-negative case-control study (262 test-positive cases and 259 test-negative controls) in patients aged 5-11 years who presented with COVID-19-like symptoms during the Omicron BA.2- and BA.5-predominant periods. Vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, living environment, and PCR test results were obtained using parent-administered questionnaires and clinical records. Vaccine effectiveness (VE) against symptomatic COVID-19 was calculated using a multivariate logistic regression analysis. RESULTS: Of the test-positive cases and test-negative controls, 9.2% (n=24) and 12.7% (n=33) received two vaccine doses, respectively. Having siblings and a BA.5-dominant period were significantly associated with symptomatic COVID-19. After adjusting for age, siblings, study period, and duration after the last vaccination, the overall VE of two-dose vaccination was 50.0% (95% confidence interval [CI], 5%-74%). VE was 72% (95%CI: 24%-89%) within 3 months after the two-dose vaccination, while it decreased to 24% (95%CI: -80% to 68%) after 3 months. CONCLUSION: Two BNT162b messenger RNA vaccine doses provided moderate protection against symptomatic COVID-19 during the Omicron variant period. A time-dependent decrease in VE was noted after the second dose; thus, a booster dose 3 months after the second dose is warranted.

Influence of blood pressure variations during hemodialysis on the prognosis of dialysis patients.

The prognosis of dialysis patients is poorer than that of the general population. The relationship between dialysis patients' blood pressure (BP) and mortality is controversial. We investigated the relationships between mortality and (i) pre-dialysis BP and (ii) BP variation during hemodialysis in maintenance dialysis patients.We retroactively analyzed the cases of the 284 patients on hemodialysis (mean age 68 ± 13 years old) who had been regularly followed at Kokura Daiichi Hospital, Japan in 2018. We assessed the relationship between the patients' BP components and risk of mortality over a 40-month follow-up.The patients' average systolic/diastolic BP values before dialysis in 2018 were 145 ± 18/77 ± 11, and those after dialysis were 129 ± 17/71 ± 10 mmHg. The prevalence of intradialytic hypotension was 46.8%. During an average follow-up of 35 months, 72 patients died, including from infectious diseases (n = 41), cardiovascular diseases (n = 9), malignancies (n = 5), and others (n = 17). The mortality rate was 32.7% in the pre-dialysis SBP < 140 mmHg group, 20.6% in the 140-159 mmHg group, and 22.2% in ≥ 160 mmHg group. In a multivariable-adjusted analysis, the hazard ratio for mortality in the pre-dialysis SBP < 140 mmHg group with intradialytic hypotension was significantly higher than that in the 140-159 mmHg group.In dialysis patients, pre-dialysis SBP < 140 mmHg and intradialytic hypotension posed a significantly higher risk for mortality. Our findings suggest that not only lower pre-dialysis BP, but also intradialytic hypotension is associated with poor prognosis in dialysis patients.

Identification of the Fc-alpha/mu receptor in Xenopus provides insight into the emergence of the poly-Ig receptor (pIgR) and mucosal Ig transport.

The polyimmunoglobulin receptor (pIgR) transcytoses J chain-containing antibodies through mucosal epithelia. In mammals, two cis-duplicates of PIGR, FCMR, and FCAMR, flank the PIGR gene. A PIGR duplication is first found in amphibians, previously annotated as PIGR2 (herein xlFCAMR), and is expressed by APCs. We demonstrate that xlFcamR is the equivalent of mammalian FcamR. It has been assumed that pIgR is the oldest member of this family, yet our data could not distinguish whether PIGR or FCAMR emerged first; however, FCMR was the last family member to emerge. Interestingly, bony fish "pIgR" is not an orthologue of tetrapod pIgR, and possibly acquired its function via convergent evolution. PIGR/FCAMR/FCMR are members of a larger superfamily, including TREM, CD300, and NKp44, which we name the "double-disulfide Ig superfamily" (ddIgSF). Domains related to each ddIgSF family were identified in cartilaginous fish (sharks, chimeras) and encoded in a single gene cluster syntenic to the human pIgR locus. Thus, the ddIgSF families date back to the earliest antibody-based adaptive immunity, but apparently not before. Finally, our data strongly suggest that the J chain arose in evolution only for Ig multimerization. This study provides a framework for further studies of pIgR and the ddIgSF in vertebrates.

An Ancient, MHC-Linked, Nonclassical Class I Lineage in Cartilaginous Fish.

Cartilaginous fishes, or chondrichthyans, are the oldest jawed vertebrates that have an adaptive immune system based on the MHC and Ig superfamily-based AgR. In this basal group of jawed vertebrates, we identified a third nonclassical MHC class I lineage (UDA), which is present in all species analyzed within the two major cartilaginous subclasses, Holocephali (chimaeras) and Elasmobranchii (sharks, skates, and rays). The deduced amino acid sequences of UDA have eight out of nine typically invariant residues that bind to the N and C termini of bound peptide found in most vertebrae classical class I (UAA); additionally, the other predicted 28 peptide-binding residues are perfectly conserved in all elasmobranch UDA sequences. UDA is distinct from UAA in its differential tissue distribution and its lower expression levels and is mono- or oligomorphic unlike the highly polymorphic UAA UDA has a low copy number in elasmobranchs but is multicopy in the holocephalan spotted ratfish (Hydrolagus colliei). Using a nurse shark (Ginglymostoma cirratum) family, we found that UDA is MHC linked but separable by recombination from the tightly linked cluster of UAA, TAP, and LMP genes, the so-called class I region found in most nonmammalian vertebrates. UDA has predicted structural features that are similar to certain nonclassical class I genes in other vertebrates, and, unlike polymorpic classical class I, we anticipate that it may bind to a conserved set of specialized peptides.

Genome evolution in the allotetraploid frog Xenopus laevis.

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

Swallowing dysfunction and the onset of fever in older residents with special care needs: a thirteen-month longitudinal prospective study.

A decline in swallowing function is frequently observed among older residents in nursing homes. We investigated whether swallowing dysfunction was related to the onset of fever in such individuals. Older residents aged ≥ 65 years from three nursing homes were included in this prospective study conducted from July 2017 to May 2019. The follow-up period was 13 months. The outcome was fever incidence in relation to the swallowing dysfunction. Baseline data on the activities of daily living, cognitive function, swallowing function, respiratory function, tongue pressure, and comorbidity conditions were collected. Dates on which the axillary temperature measured ay of participants was > 37.5 °C during the follow-up period were also recorded. For the statistical analyses, swallowing function assessed by the modified water swallow test (MWST) score was used to divide the participants into three groups: scores ≤ 3, 4, and 5. A total of 52 participants [median age, 89.5 years (67-104)] were enrolled. Kaplan-Meier analysis showed that the average periods until onset of fever in participants with MWST scores of ≤ 3, 4, and 5 were 8.0 (6.0-11.0), 10.0 (7.0-12.0), and 12.0 (10.0-13.0) months, respectively. Cox's proportional hazards regression model revealed that participants with an MWST score ≤ 3 were at a higher risk of fever than those with an MWST score of 5 (hazard ratio 11.5, 95% confidence interval 1.5-63.4, adjusted for possible confounders. The swallowing dysfunction correlated with the risk of fever in older residents of nursing homes.

Lost structural and functional inter-relationships between Ig and TCR loci in mammals revealed in sharks.

Immunoglobulins and T cell receptors (TCR) have obvious structural similarities as well as similar immunogenetic diversification and selection mechanisms. Nevertheless, the two receptor systems and the loci that encode them are distinct in humans and classical murine models, and the gene segments comprising each repertoire are mutually exclusive. Additionally, while both B and T cells employ recombination-activating genes (RAG) for primary diversification, immunoglobulins are afforded a supplementary set of activation-induced cytidine deaminase (AID)-mediated diversification tools. As the oldest-emerging vertebrates sharing the same adaptive B and T cell receptor systems as humans, extant cartilaginous fishes allow a potential view of the ancestral immune system. In this review, we discuss breakthroughs we have made in studies of nurse shark (Ginglymostoma cirratum) T cell receptors demonstrating substantial integration of loci and diversification mechanisms in primordial B and T cell repertoires. We survey these findings in this shark model where they were first described, while noting corroborating examples in other vertebrate groups. We also consider other examples where the gnathostome common ancestry of the B and T cell receptor systems have allowed dovetailing of genomic elements and AID-based diversification approaches for the TCR. The cartilaginous fish seem to have retained this T/B cell plasticity to a greater extent than more derived vertebrate groups, but representatives in all vertebrate taxa except bony fish and placental mammals show such plasticity.

Analysis of shark NCR3 family genes reveals primordial features of vertebrate NKp30.

Natural killer (NK) cells play major roles in innate immunity against viruses and cancer. Natural killer receptors (NKR) expressed by NK cells recognize foreign- or self-ligands on infected and transformed cells as well as healthy cells. NKR genes are the most rapidly evolving loci in vertebrates, and it is generally difficult to detect orthologues in different taxa. The unique exception is NKp30, an activating NKR in mammals that binds to the self-ligand B7H6. The NKp30-encoding gene, NCR3, has been found in most vertebrates including sharks, the oldest vertebrates with human-type adaptive immunity. NCR3 has a special, non-rearranging VJ-type immunoglobulin superfamily (IgSF) domain that predates the emergence of the rearranging antigen receptors. Herein we show that NCR3 loci are linked to the shark major histocompatibility complex (MHC), proving NCR3's primordial association with the MHC. We identified eight subtypes of differentially expressed highly divergent shark NCR3 family genes. Using in situ hybridization, we detected one subtype, NS344823, to be expressed by predominantly single cells outside of splenic B cell zones. The expression by non-B cells was also confirmed by PCR in peripheral blood lymphocytes. Surprisingly, high expression of NS344823 was detected in the thymic cortex, demonstrating NS344823 expression in developing T cells. Finally, we show for the first time that shark T cells are found as single cells or in small clusters in the splenic red pulp, also unassociated with the large B cell follicles we previously identified.

Inferring the "Primordial Immune Complex": Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics.

Comparative analyses suggest that the MHC was derived from a prevertebrate "primordial immune complex" (PIC). PIC duplicated twice in the well-studied two rounds of genome-wide duplications (2R) early in vertebrate evolution, generating four MHC paralogous regions (predominantly on human chromosomes [chr] 1, 6, 9, 19). Examining chiefly the amphibian Xenopus laevis, but also other vertebrates, we identified their MHC paralogues and mapped MHC class I, AgR, and "framework" genes. Most class I genes mapped to MHC paralogues, but a cluster of Xenopus MHC class Ib genes (xnc), which previously was mapped outside of the MHC paralogues, was surrounded by genes syntenic to mammalian CD1 genes, a region previously proposed as an MHC paralogue on human chr 1. Thus, this gene block is instead the result of a translocation that we call the translocated part of the MHC paralogous region (MHCtrans) Analyses of Xenopus class I genes, as well as MHCtrans, suggest that class I arose at 1R on the chr 6/19 ancestor. Of great interest are nonrearranging AgR-like genes mapping to three MHC paralogues; thus, PIC clearly contained several AgR precursor loci, predating MHC class I/II. However, all rearranging AgR genes were found on paralogues derived from the chr 19 precursor, suggesting that invasion of a variable (V) exon by the RAG transposon occurred after 2R. We propose models for the evolutionary history of MHC/TCR/Ig and speculate on the dichotomy between the jawless (lamprey and hagfish) and jawed vertebrate adaptive immune systems, as we found genes related to variable lymphocyte receptors also map to MHC paralogues.

Ancient Use of Ig Variable Domains Contributes Significantly to the TCRδ Repertoire.

The loci encoding B and T cell Ag receptors are generally distinct in commonly studied mammals, with each receptor's gene segments limited to intralocus, cis chromosomal rearrangements. The nurse shark (Ginglymostoma cirratum) represents the oldest vertebrate class, the cartilaginous fish, with adaptive immunity provided via Ig and TCR lineages, and is one species among a growing number of taxa employing Ig-TCRδ rearrangements that blend these distinct lineages. Analysis of the nurse shark Ig-TCRδ repertoire found that these rearrangements possess CDR3 characteristics highly similar to canonical TCRδ rearrangements. Furthermore, the Ig-TCRδ rearrangements are expressed with TCRγ, canonically found in the TCRδ heterodimer. We also quantified BCR and TCR transcripts in the thymus for BCR (IgHV-IgHC), chimeric (IgHV-TCRδC), and canonical (TCRδV-TCRδC) transcripts, finding equivalent expression levels in both thymus and spleen. We also characterized the nurse shark TCRαδ locus with a targeted bacterial artifical chromosome sequencing approach and found that the TCRδ locus houses a complex of V segments from multiple lineages. An IgH-like V segment, nestled within the nurse shark TCRδ translocus, grouped with IgHV-like rearrangements we found expressed with TCRδ (but not IgH) rearrangements in our phylogenetic analysis. This distinct lineage of TCRδ-associated IgH-like V segments was termed "TAILVs." Our data illustrate a dynamic TCRδ repertoire employing TCRδVs, NARTCRVs, bona fide trans-rearrangements from shark IgH clusters, and a novel lineage in the TCRδ-associated Ig-like V segments.

Relationship between salt intake and sleep disordered breathing in dialysis patients.

BACKGROUND: The prevalence of sleep disordered breathing is high in patients with end-stage renal disease. Salt intake is related to the severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. We investigated the relationship between salt intake and sleep disordered breathing in patients on maintenance hemodialysis. PATIENTS AND METHODS: We studied 128 dialysis outpatients (mean age 63 ± 11 years) who were followed at Kokura Daiichi Hospital. We estimated each patient's salt intake using an InBody S10 body composition analyzer and measured the 3% oxygen desaturation index (ODI) during sleep using a Pulsewatch: PMP-200 GplusX. RESULTS: The average estimated salt intake was 8.0 ± 2.6 g/day, and the median value of that was 7.5 g/day. Blood pressure (BP) before and after dialysis were 140 ± 18/78 ± 11 and 127 ± 13/72 ± 8 mmHg, respectively. The geometric average number of 3% ODI was 7.1, and sleep disordered breathing was detected in 30% of all subjects. The patients with ≥ 7.5 g/day salt intake were younger and more frequently male and had higher body mass index (BMI) and BP before dialysis compared to those with salt intakes < 7.5 g/day. Patients with ≥ 7.5 g/day salt intake had a significantly higher geometric average number of 3% ODI; however, this relationship became weaker after adjusting for BMI. The same relationship was obtained for the prevalence of sleep disordered breathing. CONCLUSION: The prevalence of sleep disordered breathing in patients on maintenance hemodialysis was high, and the sleep disordered breathing was associated with salt intake and BMI.

Tongue cleaning maintains respiratory function in older individuals: A 1-year randomised controlled trial.

OBJECTIVE: The aim of this 1-year longitudinal randomised controlled trial was to evaluate the effectiveness of tongue cleaning on the maintenance of respiratory function in older adults requiring care. METHODS: The participants included 24 residents of two nursing homes in Kitakyushu, Japan. The participants were randomised to receive tongue cleaning with routine oral care (intervention group, n = 12), or routine oral care alone (control group, n = 12). Among the participants, three in the intervention group and four in the control group had cerebrovascular disease history, four in the intervention group and four in the control group had a history of cardiac disease, and five in the intervention group and four in the control group were without medical history. Respiratory function was assessed on the basis of the peak expiratory flow rate (PEFR). Tongue pressure, swallowing function, oral health status, activities of daily living and nutritional status were also measured at baseline and at the end of the 1-year follow-up period. RESULTS: The number of analysed participants in each group was 12. In the control group, the PEFR (1.6 [0.4-4.2] L s-1 vs 1.4 [0.4-3.2] L s-1 , P = .034) and tongue pressure (16.4 [1.7-35.2] kPa vs 8.0 [1.4-38.6] kPa, P = .032) significantly declined after 1-year. However, the PEFR (1.5 [0.8-2.9] L s-1 vs 1.6 [0.7-4.2] L s-1 , P = .366) and tongue pressure (18.1 [4.2-37.1] kPa vs 16.1 [5.2-41] kPa, P = .307) were maintained in the intervention group. The change in the PEFR was significantly greater in the intervention group compared with the control group (0.130 [-0.45-1.70] L s-1 vs -1.70 [-10.00-10.00] L s-1 , P = .028). CONCLUSION: Our findings suggest that tongue cleaning may help maintain tongue and respiratory function in older adults requiring care.

Haptoglobin Is a Divergent MASP Family Member That Neofunctionalized To Recycle Hemoglobin via CD163 in Mammals.

In mammals, haptoglobin (Hp) is an acute-phase plasma protein that binds with high affinity to hemoglobin (Hb) released by intravascular hemolysis. The resultant Hp-Hb complexes are bound and cleared by the scavenger receptor CD163, limiting Hb-induced oxidative damage. In this study, we show that Hp is a divergent member of the complement-initiating MASP family of proteins, which emerged in the ancestor of jawed vertebrates. We demonstrate that Hp has been independently lost from multiple vertebrate lineages, that characterized Hb-interacting residues of mammals are poorly conserved in nonmammalian species maintaining Hp, and that the extended loop 3 region of Hp, which mediates CD163 binding, is present only in mammals. We show that the Hb-binding ability of cartilaginous fish (nurse shark, Ginglymostoma cirratum; small-spotted catshark, Scyliorhinus canicula; and thornback ray, Raja clavata) and teleost fish (rainbow trout, Oncorhynchus mykiss) Hp is species specific, and where binding does occur it is likely mediated through a different structural mechanism to mammalian Hp. The continued, high-level expression of Hp in cartilaginous fishes in which Hb binding is not evident signals that Hp has (an)other, yet unstudied, role(s) in these species. Previous work indicates that mammalian Hp also has secondary, immunomodulatory functions that are independent of Hb binding; our work suggests these may be remnants of evolutionary more ancient functions, retained after Hb removal became the primary role of Hp in mammals.