ABSTRACT
BACKGROUND: Some evidence suggests that heart rate variability (HRV) biofeedback might be an effective way to treat anxiety and stress symptoms. To examine the effect of HRV biofeedback on symptoms of anxiety and stress, we conducted a meta-analysis of studies extracted from PubMed, PsycINFO and the Cochrane Library. METHODS: The search identified 24 studies totaling 484 participants who received HRV biofeedback training for stress and anxiety. We conducted a random-effects meta-analysis. RESULTS: The pre-post within-group effect size (Hedges' g) was 0.81. The between-groups analysis comparing biofeedback to a control condition yielded Hedges' g = 0.83. Moderator analyses revealed that treatment efficacy was not moderated by study year, risk of study bias, percentage of females, number of sessions, or presence of an anxiety disorder. CONCLUSIONS: HRV biofeedback training is associated with a large reduction in self-reported stress and anxiety. Although more well-controlled studies are needed, this intervention offers a promising approach for treating stress and anxiety with wearable devices.
Subject(s)
Anxiety Disorders/therapy , Anxiety/therapy , Biofeedback, Psychology/physiology , Heart Rate/physiology , Stress, Psychological/therapy , Anxiety/physiopathology , Anxiety Disorders/physiopathology , Humans , Stress, Psychological/physiopathologyABSTRACT
OBJECTIVE: Premature infants, especially those born less than 1500 g, often exhibit slow overall growth after birth and lack of early nutritional support may be an important element. We tested the hypothesis that early administration of amino acids (within the first few hours of life) to infants born at less than 1500 g would be associated with fewer infants that were less than the 10th percentile at 36 weeks post-conceptual age than infants that received amino acids after the first 24 h of life. STUDY DESIGN: A prospective intervention of early amino-acid (EAA) supplementation, began before 24 h of life, in preterm infants, <1500 g, was compared to a retrospective cohort of preterm infants receiving late amino-acid (LAA) supplementation, began after 24 h of life. The primary outcome variable was the proportion of infants at less than the 10th percentile at 36 weeks post-conceptual age. RESULT: Fewer infants fell below the 10th percentile (P<0.001) in the EAA group. Furthermore, infants in the EAA groups had significantly greater weight gains than did the LAA group (P<0.003) after adjusting for gestational age and time from birth to discharge. In addition, shorter duration of parenteral nutrition was associated with EAA supplementation (P<0.001). CONCLUSION: A prospective strategy of EAA in preterm infants <1500 g was associated with an improved weight gain, suggesting that nutrition that included amino acids may be critical during the first 24 h of life.
Subject(s)
Amino Acids/administration & dosage , Infant, Low Birth Weight/growth & development , Infant, Premature/growth & development , Parenteral Nutrition/methods , Weight Gain , Drug Administration Schedule , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Prospective StudiesABSTRACT
To test the hypothesis that pharmacological differentiation between D(1) and D(2) dopamine receptors results from interactions of selective ligands with nonconserved residues lining the binding pocket, we mutated amino acid residues in the D(2) receptor to the corresponding aligned residues in the D(1) receptor and vice versa and expressed the receptors in human embryonic kidney 293 cells. Determinations of the affinity of the 14 mutant D(2) receptors and 11 mutant D(1) receptors for D(1)- and D(2)-selective antagonists, and rhodopsin-based homology models of the two receptors, identified two residues whose direct interactions with certain ligands probably contribute to ligand selectivity. The D(1) receptor mutant W99(3.28)F showed dramatically increased affinity for several D(2)-selective antagonists, particularly spiperone (225-fold), whereas the D(2) receptor mutant Y417(7.43)W had greatly decreased affinity for benzamide ligands such as raclopride (200-fold) and sulpiride (125-fold). The binding of the D(1)-selective ligand R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390) was unaffected, indicating that SCH23390 makes little contact with these ancillary pocket residues. Mutation of A/V(5.39) caused modest but consistent and reciprocal changes in affinity of the receptors for D(1) and D(2)-selective ligands, perhaps reflecting altered packing of the interface of helices 5 and 6. We also obtained some evidence that residues in the second extracellular loop contribute to ligand binding. We conclude that additional determinants of D(1)/D(2) receptor-selective binding are located either in that loop or in the transmembrane helices but, like residue 5.39, indirectly influence the interactions of selective ligands with conserved residues by altering the shape of the primary and ancillary binding pockets.
Subject(s)
Receptors, Dopamine D1/drug effects , Receptors, Dopamine D2/drug effects , Alternative Splicing , Animals , Benzazepines/pharmacology , Cell Line , Dopamine Antagonists/pharmacology , Models, Molecular , Mutation , Protein Conformation , Raclopride/pharmacology , Radioligand Assay , Rats , Receptors, Dopamine D1/chemistry , Receptors, Dopamine D1/genetics , Receptors, Dopamine D2/chemistry , Receptors, Dopamine D2/genetics , Solvents , Spiperone/pharmacology , Sulpiride/pharmacologyABSTRACT
Zinc (II) modulates the function of many integral membrane proteins. To identify the Zn(2+)-binding site responsible for allosteric modulation of the D(2) dopamine receptor, we first demonstrated that the binding site is likely located in extracellular loops or in transmembrane regions that are accessible from the extracellular milieu. We mutated every histidine in these regions to alanine; two mutants, H394A and H399A, exhibited a reduced response to Zn(2+). Combined mutation of H394 and H399 caused a larger effect of zinc than did either single mutation. Mutation of other potential Zn(2+)-binding residues predicted to be in proximity to H394 or H399 did not substantially alter the potency of Zn(2+). The double mutant H394A/H399A was similar to D(2) in affinity for [(3)H]spiperone and ability to inhibit cyclic AMP accumulation. We conclude that binding of Zn(2+) to H394 and H399 on the dopamine D(2) receptor contributes to allosteric regulation of antagonist binding.
Subject(s)
Kidney/metabolism , Receptors, Dopamine D2/chemistry , Receptors, Dopamine D2/metabolism , Zinc/chemistry , Zinc/metabolism , Amino Acid Substitution , Binding Sites , Cell Line , Humans , Mutagenesis, Site-Directed , Protein Binding , Protein Interaction Mapping , Receptors, Dopamine D2/genetics , Structure-Activity RelationshipABSTRACT
Rather than focus on cutting costs, try charging more for a better experience. You'll improve the bottom line, but you'll also put the health care focus back where it belongs: on the consumer--the health and happiness of your patients.
Subject(s)
Health Facility Environment/economics , Hospital-Patient Relations , Patient Satisfaction/economics , Physician-Patient Relations , Total Quality Management/economics , Fees and Charges , Health Services Accessibility , Humans , Organizational Innovation , Total Quality Management/methods , United StatesABSTRACT
Probiotics are live microbial food supplements that benefit the host animal by improving intestinal microbial balance. When they are fed in yogurts, they can fall into the category of functional foods. Functional foods include these probiotics, prebiotics, and, to a certain extent, dietary fiber. Prebiotics are nondigestible food ingredients or supplements that alter the intestinal flora and stimulate the growth of healthy bacteria. Dietary fibers are part of plant foods that are nonstarch polysaccharides and are poorly digested or not digested by human enzymes. The physiologic process in which probiotics and functional foods affect the intestinal flora is through the balance of the intestinal microecology. This review looks at the four major components of intestinal microecology and describes the probiotics in use today and their clinical relevance. Although probiotics hold great promise and appear to be useful in some settings, more clinical study is needed to firmly establish the relevance of probiotic therapy.
Subject(s)
Dietary Fiber/therapeutic use , Gastrointestinal Diseases/therapy , Probiotics/therapeutic use , Humans , Probiotics/administration & dosage , YogurtABSTRACT
The Drosophila signaling factor decapentaplegic (dpp) mediates the effects of hedgehog (hh) in tissue patterning by regulating the expression of tissue-specific genes. In the eye disc, the transcription factors eyeless (ey), eyes absent (eya), sine oculis (so) and dachshund (dac) participate with these signaling molecules in a complex regulatory network that results in the initiation of eye development. Our analysis of functional relationships in the early eye disc indicates that hh and dpp play no role in regulating ey, but are required for eya, so and dac expression. We show that restoring expression of eya in loss-of-function dpp mutant backgrounds is sufficient to induce so and dac expression and to rescue eye development. Thus, once expressed, eya can carry out its functions in the absence of dpp. These experiments indicate that dpp functions downstream of or in parallel with ey, but upstream of eya, so and dac. Additional control is provided by a feedback loop that maintains expression of eya and so and includes dpp. The fact that exogenous overexpression of ey, eya, so and dac interferes with wild-type eye development demonstrates the importance of such a complicated mechanism for maintaining proper levels of these factors during early eye development. Whereas initiation of eye development fails in either Hh or Dpp signaling mutants, the subsequent progression of the morphogenetic furrow is only slowed down. However, we find that clones that are simultaneously mutant for Hh and Dpp signaling components completely block furrow progression and eye differentiation, suggesting that Hh and Dpp serve partially redundant functions in this process. Interestingly, furrow-associated expression of eya, so and dac is not affected by double mutant tissue, suggesting that some other factor(s) regulates their expression during furrow progression.
Subject(s)
Drosophila Proteins , Drosophila/growth & development , Eye Proteins/physiology , Eye/growth & development , Insect Proteins/physiology , Animals , Animals, Genetically Modified , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Drosophila/genetics , Drosophila/physiology , Eye Proteins/genetics , Feedback , Gene Expression Regulation, Developmental , Genes, Insect , Hedgehog Proteins , Homeodomain Proteins/genetics , Homeodomain Proteins/physiology , In Situ Hybridization , Insect Proteins/genetics , Microscopy, Confocal , Morphogenesis , Mutation , Nuclear Proteins/genetics , Nuclear Proteins/physiology , Phenotype , Signal TransductionABSTRACT
A widely applicable, positive cDNA selection method was developed to identify RNAs synthesized by Mycobacterium tuberculosis in response to phagocytosis by cultured human primary macrophages. cDNAs for sigE and sigH (alternative sigma factors), aceA (isocitrate lyase), ponA (class I penicillin-binding protein), pks2 (polyketide synthase), uvrA (UvrABC endonuclease), and ctpV (putative cation transporter) were obtained from macrophage-grown bacteria. cDNAs for ORFs Rv3070, Rv3483c, Rv0903c (encoding a putative bacterial two-component transcriptional activator), and Rv0170 of the mce1 virulence operon also were obtained from phagocytized bacilli. cDNAs for these genomic regions were not obtained from approximately 1, 000-fold more bacteria grown in laboratory broth. Methods described here, which have identified M. tuberculosis genes expressed in response to host interaction, will allow the study of gene expression in a variety of microorganisms, including expression resulting from interaction with human tissues in natural disease states.
Subject(s)
Macrophages/immunology , Mycobacterium tuberculosis/genetics , Phagocytosis , RNA, Bacterial/biosynthesis , RNA, Messenger/biosynthesis , Trans-Activators , Bacterial Proteins/genetics , Cells, Cultured , DNA, Complementary/analysis , Humans , Mycobacterium tuberculosis/immunology , Sigma Factor/geneticsABSTRACT
The vertebrate Six genes are homologues of the Drosophila homeobox gene sine oculis (so), which is essential for development of the entire visual system. Here we describe two new Six genes in Drosophila, D-Six3 and D-Six4, which encode proteins with strongest similarity to vertebrate Six3 and Six4, respectively. In addition, we report the partial sequences of 12 Six gene homologues from several lower vertebrates and show that the class of Six proteins can be subdivided into three major families, each including one Drosophila member. Similar to so, both D-Six3 and D-Six4 are initially expressed at the blastoderm stage in narrow regions of the prospective head and during later stages in specific groups of head midline neurectodermal cells. D-Six3 may also be essential for development of the clypeolabrum and several head sensory organs. Thus, the major function of the ancestral Six gene probably involved specification of neural structures in the cephalic region.
Subject(s)
Drosophila Proteins , Drosophila/embryology , Drosophila/genetics , Genes, Homeobox , Head/embryology , Trans-Activators , Zebrafish Proteins , Amino Acid Sequence , Animals , Embryo, Mammalian/anatomy & histology , Embryo, Nonmammalian/anatomy & histology , Eye Proteins/analysis , Eye Proteins/genetics , Homeodomain Proteins/analysis , Homeodomain Proteins/genetics , Mice , Molecular Sequence Data , Morphogenesis , Multigene Family , Nerve Tissue Proteins/analysis , Nerve Tissue Proteins/genetics , Phylogeny , Sequence Homology, Amino Acid , Tissue Distribution , Zebrafish/genetics , Homeobox Protein SIX3ABSTRACT
LIM-homeodomain transcription factors (LIM-HD) regulate expression of genes that pattern the body and generate cell specificity during development in invertebrates and vertebrates. It is especially interesting that most are expressed in and participate in the development of the nervous system. LIM-HD proteins are themselves regulated by both intramolecular and intermolecular interactions mediated by the LIM domains. LIM domains positively regulate LIM-HD activity by promoting protein-protein interactions that allow cooperative binding to regulatory regions of tissue-specific promoters. They also negatively regulate LIM-HD activity, possibly by preventing HD association with DNA. Interaction of LIM domains with other proteins relieves this interference, permitting DNA binding and providing a mechanism for refining LIM-HD activity. The recurrence of LIM-HD proteins in fundamental developmental processes emphasizes the importance of their function and regulation and provides an opportunity to identify mechanisms and molecules underlying patterning and cell specification.
Subject(s)
Homeodomain Proteins/physiology , Transcription Factors/physiology , Amino Acid Sequence , Animals , Embryonic and Fetal Development , Gene Expression Regulation, Developmental , Homeodomain Proteins/chemistry , Homeodomain Proteins/genetics , Humans , Molecular Sequence Data , Nervous System/growth & development , Sequence Homology, Amino Acid , Transcription Factors/chemistry , Transcription Factors/geneticsABSTRACT
Mycobacterium avium is an intracellular pathogen that has evolved to be a frequent cause of disseminated infection in immunocompromised patients. Although these bacilli are readily phagocytized, they are able to survive and even multiply within human macrophages. The process whereby mycobacteria circumvent the lytic functions of the macrophages is currently not well understood, but this is a key aspect in the pathogenicity of all pathogenic mycobacteria. Previously, we identified a gene in M. avium, designated mig (for macrophage-induced gene), the expression of which is induced when the bacilli grow in human macrophages (G. Plum and J. E. Clark-Curtiss, Infect. Immun. 62:476-483, 1994). In the present study we show that (i) the nucleotide sequence of the mig gene has an open reading frame of 295 amino acids with a strong bias for mycobacterial codon usage, (ii) the mig gene also codes for a putative signal peptide of 19 amino acid residues, (iii) mig is induced by acidity to be expressed as an early-secreted 30-kDa protein, and (iv) the Mig protein exhibits an AMP-binding domain signature. However, beyond this motif which is common to enzymes that activate a large variety of substrates, no homologies to known sequences are found. We also show that (v) Mycobacterium smegmatis strains expressing the Mig protein have a limited advantage for survival in macrophages. These findings may be concordant with a role of the mig gene in the virulence of M. avium.
Subject(s)
Bacterial Proteins/biosynthesis , Genes, Bacterial , Macrophages/immunology , Mycobacterium avium/genetics , Amino Acid Sequence , Bacterial Proteins/analysis , Bacterial Proteins/genetics , Base Sequence , Blotting, Southern , Cells, Cultured , Cloning, Molecular , Codon , Escherichia coli/genetics , Female , Humans , Molecular Sequence DataABSTRACT
The Arrowhead gene encodes a LIM-homeodomain transcription factor required for establishment of a subset of imaginal tissues: the abdominal histoblasts and the salivary gland imaginal rings. Consistent with its role in development, during embryogenesis Arrowhead is expressed in each abdominal segment and in the labial segment. Late in embryonic development, expression is refined to the abdominal histoblasts and salivary gland imaginal ring cells themselves. When ectopically expressed in imaginal disc cells, Arrowhead causes programmed cell death and loss of corresponding adult structures. Therefore, Arrowhead expression is required for development of one set of imaginal cells and is incompatible with development of another, emphasizing the specificity of Arrowhead and the sensitivity of different target cells to its expression. Loss-of-function mutations in Arrowhead affect conserved or invariant amino acids in the LIM- and homeo-domains demonstrating the importance of these residues in LIM homeodomain protein activity.
Subject(s)
Drosophila Proteins , Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental/physiology , Homeodomain Proteins/genetics , Transcription Factors/genetics , Abdomen/embryology , Amino Acid Sequence , Animals , Apoptosis , Cloning, Molecular , Drosophila melanogaster/embryology , Drosophila melanogaster/growth & development , Genes, Insect/genetics , Homeodomain Proteins/physiology , LIM-Homeodomain Proteins , Larva , Molecular Sequence Data , RNA, Messenger/analysis , Salivary Glands/embryology , Sequence Alignment , Sequence Analysis, DNA , Transcription Factors/physiologyABSTRACT
A major focus of leprosy research in the last 10 years has been the identification and characterization of antigens of Mycobacterium leprae that interact with antibodies and T cells of the host's immune response. Through the combined efforts of many different laboratories, a substantial number of protein antigens have been identified and characterized. In this MicroReview we present an updated list of M. leprae protein antigens, and, with emphasis on recent developments, summarize what is known regarding their functional and immunological features.
Subject(s)
Antigens, Bacterial/immunology , Mycobacterium leprae/immunology , Antigens, Bacterial/classification , Humans , Leprosy/diagnosis , Leprosy/immunology , Serologic Tests , T-Lymphocytes/immunologyABSTRACT
Metamorphosis in Drosophila melanogaster requires synchronization of numerous developmental events that occur in isolated imaginal precursor tissues. The imaginal primordia are established during embryonic stages and are quiescent for much of larval life. The Arrowhead gene is necessary for establishment of proper numbers of cells within a subset of imaginal precursor tissues. Loss-of-function mutations in Arrowhead reduce the number of abdominal histoblasts and salivary gland imaginal ring cells before the proliferative stages of their development. The number of abdominal histoblasts in mutant animals is approximately half that of wild-type, as might result from failure of a single early division of these cells. A neomorphic Arrowhead allele results in the specific loss of the retinal precursors by the early third instar, before they have begun to differentiate. Since Arrowhead mutations affect only subsets of imaginal tissue, there must be distinctions in the developmental regulation of different imaginal precursors. Arrowhead may be part of a regulatory pathway responsible for establishing the proper number of abdominal histoblasts and salivary gland imaginal ring cells. The neomorphic Arrowhead allele, which may cause misexpression of the Arrowhead gene in the eye-antenna imaginal disc, interferes with the establishment or proliferation of retinal precursor cells.
Subject(s)
Drosophila melanogaster/embryology , Genes, Insect , Metamorphosis, Biological , Proteins/genetics , Stem Cells/physiology , Abdomen/embryology , Animals , Cell Division , Drosophila melanogaster/genetics , Eye/embryology , Eye/ultrastructure , Gene Deletion , Gene Expression , Immunohistochemistry , Microscopy, Electron, Scanning , Salivary Glands/embryology , Salivary Glands/ultrastructureABSTRACT
Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen. M. leprae can infect a variety of cells in vivo, including epithelial cells, muscle cells, and Schwann cells, in addition to macrophages. The ligand-receptor interactions important in the attachment and ingestion of M. leprae by these nonmacrophage cells remains unknown. Fibronectin (FN) significantly enhances both attachment and ingestion of M. leprae by epithelial and Schwann cell lines. We cloned an M. leprae FN binding protein (FN attachment protein [FAP]) distinct from the 85ABC complex which has been shown previously to bind FN. The FAP open reading frame predicts a protein of 29.5 kDa with a 39-amino-acid signal peptide and was previously described as an antigen in leprosy patients. M. leprae FAP has homologies in M. vaccae, M. avium, and M. tuberculosis, as determined by Southern blotting and direct peptide analysis. Both anti-FAP antibodies and an Escherichia coli-expressed recombinant protein significantly blocked M. leprae attachment and internalization by T-24, an epithelial cell line, and JS1, a Schwann cell line. These data suggest that FN can be a bridging opsonic ligand for attachment of mycobacteria to nonphagocytes and that FAP plays an important role in this process. This may be an important step in the initiation of M. leprae infection in vivo.
Subject(s)
Adhesins, Bacterial/genetics , Antigens, Bacterial/genetics , Bacterial Adhesion , Bacterial Proteins/genetics , Fibronectins/metabolism , Genes, Bacterial , Mycobacterium leprae/pathogenicity , Adhesins, Bacterial/metabolism , Amino Acid Sequence , Base Sequence , Cloning, Molecular , Epithelium/microbiology , Gene Expression , Molecular Sequence Data , Mycobacterium leprae/genetics , Oligonucleotide Probes/chemistry , RNA, Messenger/genetics , Schwann Cells/microbiology , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
Little is known about the bacterial factors that enable pathogenic mycobacteria to survive and multiply within the macrophages of the infected host. By preparing cDNA from Mycobacterium avium bacilli grown in human-derived macrophages and in broth culture and using subtractive hybridization to remove commonly expressed genes, a procedure was developed to identify genes of M. avium that are specifically expressed when the bacilli are growing within macrophages. Total RNA was isolated from M. avium recovered 5 days after infection of human macrophages and from bacilli grown in vitro in broth. Mycobacterial mRNAs were converted to cDNA by reverse transcription. Biotin-modified cDNAs prepared from M. avium grown in broth culture were used to subtract the housekeeping genes from the cDNAs of the macrophage-derived M. avium. After each round of subtraction, a sample of the unsubtracted cDNA was amplified, labeled, and hybridized to cosmid clones of M. avium DNA. After three rounds of subtraction, the amplified DNA hybridized to approximately 1% of the cosmid clones under stringent conditions. Although the majority of the genes that are induced in phagocytized M. avium cells are expressed in the broth-grown bacilli, one DNA fragment that was identified coded for an mRNA that is highly specific for M. avium in phagosomes. This procedure will be especially useful for identifying genes that are expressed in response to growth in specific environments from organisms with genetic systems that are not well characterized.