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New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.
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Hipocampo/citología , Neurogénesis , Neuronas/citología , Adolescente , Adulto , Anciano , Animales , Animales Recién Nacidos , Recuento de Células , Proliferación Celular , Niño , Preescolar , Giro Dentado/citología , Giro Dentado/embriología , Epilepsia/patología , Femenino , Desarrollo Fetal , Voluntarios Sanos , Hipocampo/anatomía & histología , Hipocampo/embriología , Humanos , Lactante , Macaca mulatta , Masculino , Persona de Mediana Edad , Células-Madre Neurales/citología , Adulto JovenRESUMEN
Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENT Astrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.
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Astrocitos , Transcriptoma , Envejecimiento/patología , Animales , Astrocitos/fisiología , Femenino , Humanos , Masculino , Ratones , Sinapsis/fisiología , Microambiente TumoralRESUMEN
Women with hypopituitarism have lower fertility rates and worse pregnancy outcomes than women with normal pituitary function. These disparities exist despite the use of assisted reproductive technologies and hormone replacement. In women with hypogonadotropic hypogonadism, administration of exogenous gonadotropins can be used to successfully induce ovulation. Growth hormone replacement in the setting of growth hormone deficiency has been suggested to potentiate reproductive function, but its routine use in hypopituitary women remains unclear and warrants further study. In this review, we will discuss the clinical approach to fertility in a woman with hypopituitarism.
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OBJECTIVE: This study was undertaken to identify molecular mechanisms in brain tissue of Rasmussen encephalitis (RE) when compared to people with non-RE epilepsy (PWE) and control cases using whole exome sequencing (WES), RNAseq, and proteomics. METHODS: Frozen brain tissue (ages = 2-19 years) was obtained from control autopsy (n = 14), surgical PWE (n = 10), and surgical RE cases (n = 27). We evaluated WES variants in RE associated with epilepsy, seizures, RE, and human leukocyte antigens (HLAs). Differential expression was evaluated by RNAseq (adjusted p < .05) and label-free quantitative mass spectrometry (false discovery rate < 5%) in the three groups. RESULTS: WES revealed no common pathogenic variants in RE, but several rare and likely deleterious variants of unknown significance (VUS; ANGPTL7/MTOR, SCN1A, FCGR3B, MTOR) and more common HLA VUS in >25% of RE cases (HLA-DRB1, HLA-DQA2), all with allele frequency < 5% in the general population. RNAseq in RE versus PWE (1516 altered transcripts) revealed significant activation of crosstalk between dendritic and natural killer cells (p = 7.94 × 10-6 , z = 2.65), in RE versus control (7466 transcripts) neuroinflammation signaling activation (p = 6.31 × 10-13 , z = 5.07), and in PWE versus control (945 transcripts) phagosome formation activation (p = 2.00 × 10-13 , z = 5.61). Proteomics detected fewer altered targets. SIGNIFICANCE: In RE, we identified activated immune signaling pathways and immune cell type annotation enrichment that suggest roles of the innate and adaptive immune responses, as well as HLA variants that may increase vulnerability to RE. Follow-up studies could evaluate cell type density and subregional localization associated with top targets, clinical history (neuropathology, disease duration), and whether modulating crosstalk between dendritic and natural killer cells may limit disease progression.
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Encefalitis , Epilepsia , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Encefalitis/patología , Encéfalo/patología , Epilepsia/patología , Serina-Treonina Quinasas TOR , Proteínas Similares a la Angiopoyetina , Proteína 7 Similar a la AngiopoyetinaRESUMEN
BACKGROUND: There are still some controversies about the results of anti-BRAF V600E-specific antibody immunohistochemistry in ameloblastomas. This study aimed to examine the accuracy of V600E-specific antibody immunohistochemistry in detection of BRAF V600E mutation in ameloblastoma tissue sections of different ages. METHODS: The BRAF V600E status of 64 ameloblastoma specimens was assessed using both Sanger sequencing and V600E-specific antibody immunohistochemistry, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The difference in V600E-specific antibody immunohistochemistry staining intensity among the three groups of ameloblastoma tissue blocks of different ages was evaluated by chi-square test. The consistency between V600E-specific antibody immunohistochemistry and DNA sequencing results and the V600E-specific antibody immunohistochemistry staining intensity of 15 paired newly-cut and 3-month storage sections of the same 15 ameloblastomas were also compared. RESULTS: For detection of BRAF V600E mutation, the V600E-specific antibody immunohistochemistry had high sensitivity (98.21% 55/56), specificity (87.5% 7/8), positive predictive value (98.21% 55/56), and negative predictive value (87.5% 7/8). Heterogeneity of the staining intensity was observed in the same tissue section, but all or none expression pattern was noticed in the solid tumor nests. The storage time of paraffin tissue blocks ranging from 2 to 14 years did not affect the V600E-specific antibody-positive staining intensity. However, the three-month storage sections showed a significant diminishment of V600E-specific antibody-positive staining signals. CONCLUSIONS: The BRAF V600E-specific antibody immunohistochemistry is suitable for routine detection of BRAF V600E mutation in ameloblastomas. The all or none expression pattern suggests the BRAF V600E mutation may be an early event in the pathogenesis of ameloblastoma.
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Ameloblastoma , Humanos , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/patología , Biomarcadores de Tumor/genética , Distribución de Chi-Cuadrado , Inmunohistoquímica , Mutación , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
PURPOSE: Fatigue is a common symptom of multiple sclerosis (MS) and can adversely affect all aspect of quality of life. The etiology of fatigue remains unclear, and its treatments are suboptimal. Characterizing the phenotypes of fatigued persons with MS may help advance research on fatigue's etiology and identify ways to personalize fatigue interventions to improve quality of life. The purpose of this study was to identify fatigue phenotypes; examine phenotype stability overtime; and characterize phenotypes by health and function, social and environmental determinants, psychosocial factors, and engagement in healthy behaviors. METHODS: We conducted a longitudinal study over a 3-month period with 289 fatigued participants with MS. To identify fatigue phenotypes and determine transition probabilities, we used latent profile and transition analyses with valid self-report measures of mental and physical fatigue severity, the mental and physical impact of fatigue, depression, anxiety, and sleep quality. We used ANOVAs and effect sizes to characterize differences among phenotypes. RESULTS: The best fitting model included six subgroups of participants: Mild Phenotype, Mild-to-Moderate Phenotype, Moderate-to-Severe Phenotype, Severe Phenotype, Fatigue-dominant Phenotype, and Mental Health-dominant Phenotype. The transition analysis indicated that phenotypic membership was highly stable. Variables with a large eta squared effect size included environmental barriers, self-efficacy, and fatigue catastrophizing. CONCLUSION: These results indicate that the magnitude of fatigue experienced may be more important to consider than the type of fatigue when characterizing fatigue phenotypes. Future research should explore whether tailoring interventions to environmental barriers, self-efficacy, and fatigue catastrophizing reduce the likelihood of transitioning to a more severe phenotype.
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Esclerosis Múltiple , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Calidad de Vida/psicología , Estudios Longitudinales , Ansiedad/etiología , Fatiga/psicologíaRESUMEN
Hyaline protoplasmic astrocytopathy (HPA) describes a rare histologic finding of eosinophilic, hyaline cytoplasmic inclusions in astrocytes, predominantly in the cerebral cortex. It has mainly been observed in children and adults with a history of developmental delay and epilepsy, frequently with focal cortical dysplasia (FCD), but the nature and significance of these inclusions are unclear. In this study, we review the clinical and pathologic features of HPA and characterize the inclusions and brain tissue in which they are seen in surgical resection specimens from five patients with intractable epilepsy and HPA compared to five patients with intractable epilepsy without HPA using immunohistochemistry for filamin A, previously shown to label these inclusions, and a variety of astrocytic markers including aldehyde dehydrogenase 1 family member L1 (ALDH1L1), SRY-Box Transcription Factor 9 (SOX9), and glutamate transporter 1/excitatory amino acid transporter 2 (GLT-1/EAAT2) proteins. The inclusions were positive for ALDH1L1 with increased ALDH1L1 expression in areas of gliosis. SOX9 was also positive in the inclusions, although to a lesser intensity than the astrocyte nuclei. Filamin A labeled the inclusions but also labeled reactive astrocytes in a subset of patients. The immunoreactivity of the inclusions for various astrocytic markers and filamin A as well as the positivity of filamin A in reactive astrocytes raise the possibility that these astrocytic inclusions may be the result of an uncommon reactive or degenerative phenomenon.
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Epilepsia Refractaria , Epilepsia , Niño , Adulto , Humanos , Filaminas/metabolismo , Hialina , Encéfalo/patología , Astrocitos/patologíaRESUMEN
The identification of precision blood biomarkers which can accurately indicate damage to brain tissue could yield molecular diagnostics with the potential to improve how we detect and treat neurological pathologies. However, a majority of candidate blood biomarkers for neurological damage that are studied today are proteins which were arbitrarily proposed several decades before the advent of high-throughput omic techniques, and it is unclear whether they represent the best possible targets relative to the remainder of the human proteome. Here, we leveraged mRNA expression data generated from nearly 12,000 human specimens to algorithmically evaluate over 17,000 protein-coding genes in terms of their potential to produce blood biomarkers for neurological damage based on their expression profiles both across the body and within the brain. The circulating levels of proteins associated with the top-ranked genes were then measured in blood sampled from a diverse cohort of patients diagnosed with a variety of acute and chronic neurological disorders, including ischemic stroke, hemorrhagic stroke, traumatic brain injury, Alzheimer's disease, and multiple sclerosis, and evaluated for their diagnostic performance. Our analysis identifies several previously unexplored candidate blood biomarkers of neurological damage with possible clinical utility, many of which whose presence in blood is likely linked to specific cell-level pathologic processes. Furthermore, our findings also suggest that many frequently cited previously proposed blood biomarkers exhibit expression profiles which could limit their diagnostic efficacy.
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Biomarcadores/metabolismo , Lesiones Encefálicas/diagnóstico , Enfermedades del Sistema Nervioso/metabolismo , Adulto , Anciano , Enfermedad de Alzheimer/metabolismo , Biomarcadores/sangre , Encéfalo/metabolismo , Lesiones Encefálicas/sangre , Biología Computacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/metabolismo , Enfermedades del Sistema Nervioso/sangre , Neuropatología/métodos , Proteoma/metabolismo , Accidente Cerebrovascular/metabolismoRESUMEN
Combustion is often difficult to spatially direct or tune associated kinetics-hence a run-away reaction. Coupling pyrolytic chemical transformation to mass transport and reaction rates (Damköhler number), however, we spatially directed ignition with concomitant switch from combustion to pyrolysis (low oxidant). A 'surface-then-core' order in ignition, with concomitant change in burning rate,is therefore established. Herein, alkysilanes grafted onto cellulose fibers are pyrolyzed into non-flammable SiO2 terminating surface ignition propagation, hence stalling flame propagating. Sustaining high temperatures, however, triggers ignition in the bulk of the fibers but under restricted gas flow (oxidant and/or waste) hence significantly low rate of ignition propagation and pyrolysis compared to open flame (Liñán's equation). This leads to inside-out thermal degradation and, with felicitous choice of conditions, formation of graphitic tubes. Given the temperature dependence, imbibing fibers with an exothermically oxidizing synthon (MnCl2 ) or a heat sink (KCl) abets or inhibits pyrolysis leading to tuneable wall thickness. We apply this approach to create magnetic, paramagnetic, or oxide containing carbon fibers. Given the surface sensitivity, we illustrate fabrication of nm- and µm-diameter tubes from appropriately sized fibers.
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BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants that may cause long-term lung dysfunction. Accumulating evidence supports the vascular hypothesis of BPD, in which lung endothelial cell dysfunction drives this disease. We recently reported that endothelial carnitine palmitoyltransferase 1a (Cpt1a) is reduced by hyperoxia, and that endothelial cell-specific Cpt1a knockout mice are more susceptible to developing hyperoxia-induced injury than wild type mice. Whether Cpt1a upregulation attenuates hyperoxia-induced endothelial cell dysfunction and lung injury remains unknown. We hypothesized that upregulation of Cpt1a by baicalin or L-carnitine ameliorates hyperoxia-induced endothelial cell dysfunction and persistent lung injury. METHODS: Lung endothelial cells or newborn mice (< 12 h old) were treated with baicalin or L-carnitine after hyperoxia (50% and 95% O2) followed by air recovery. RESULTS: We found that incubation with L-carnitine (40 and 80 mg/L) and baicalin (22.5 and 45 mg/L) reduced hyperoxia-induced apoptosis, impaired cell migration and angiogenesis in cultured lung endothelial cells. This was associated with increased Cpt1a gene expression. In mice, neonatal hyperoxia caused persistent alveolar and vascular simplification in a concentration-dependent manner. Treatment with L-carnitine (150 and 300 mg/kg) and baicalin (50 and 100 mg/kg) attenuated neonatal hyperoxia-induced alveolar and vascular simplification in adult mice. These effects were diminished in endothelial cell-specific Cpt1a knockout mice. CONCLUSIONS: Upregulating Cpt1a by baicalin or L-carnitine ameliorates hyperoxia-induced lung endothelial cell dysfunction, and persistent alveolar and vascular simplification. These findings provide potential therapeutic avenues for using L-carnitine and baicalin as Cpt1a upregulators to prevent persistent lung injury in premature infants with BPD.
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Displasia Broncopulmonar , Hiperoxia , Lesión Pulmonar , Enfermedades Vasculares , Animales , Ratones , Animales Recién Nacidos , Displasia Broncopulmonar/tratamiento farmacológico , Displasia Broncopulmonar/prevención & control , Carnitina/farmacología , Carnitina O-Palmitoiltransferasa/genética , Células Endoteliales/metabolismo , Hiperoxia/complicaciones , Hiperoxia/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/etiología , Lesión Pulmonar/prevención & control , Ratones NoqueadosRESUMEN
The HIV-1 envelope protein (Env) of early-replicating viruses encodes several distinct transmission signatures. One such signature involves a reduced number of potential N-linked glycosylation sites (PNGs). This transmission signature underscores the importance of posttranslational modifications in the fitness of early-replicating isolates. An additional signature in Env involves the overrepresentation of basic amino acid residues at a specific position in the Env signal peptide (SP). In this report, we investigated the potential impact of this SP signature on gp120 glycosylation and antigenicity. Two recombinant gp120s were constructed, one derived from an isolate that lacks this signature and a second from an early-replicating isolate that includes this signature. Chimeric gp120s were also constructed in which the two SPs were swapped between the isolates. All four gp120s were probed with glycan-, structure- and receptor- specific probes in a surface plasmon resonance binding assay. We found that the SP of Env influences qualitative aspects of Env glycosylation that in turn affect the antigenicity of Env in a major way. The SP impacts the affinity of Env for DC-SIGN, a lectin receptor expressed on dendritic cells that is believed to play a role in mucosal transmission. Additionally, affinity for the monoclonal antibodies 17b and A32, which recognize a CD4-induced, open conformation of Env is also altered. These results demonstrate that natural variation in the SP of HIV Env can significantly impact the antigenicity of mature gp120. Thus, the SP is likely subject to antibody-mediated immune pressure.
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Proteína gp120 de Envoltorio del VIH , Señales de Clasificación de Proteína/genética , Proteínas Recombinantes de Fusión , Anticuerpos Monoclonales/metabolismo , Células Dendríticas , Glicosilación , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/metabolismo , VIH-1/inmunología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
BACKGROUND/PURPOSE: Our previous study found the serum gastric parietal cell antibody (GPCA) positivity in 12.3% of burning mouth syndrome (BMS) patients. This study assessed whether GPCA-positive BMS (GPCA+BMS) patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-negative BMS (GPCA-BMS) patients. METHODS: The mean corpuscular volume, blood hemoglobin (Hb), and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels were measured and compared between any two of three groups of 109 GPCA+BMS patients, 775 GPCA-BMS patients, and 442 healthy control subjects. RESULTS: We found that 109 GPCA+BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than 775 GPCA-BMS patients (all P-values < 0.01). Moreover, 775 GPCA-BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.005). Pernicious anemia (45.5%) and normocytic anemia (24.2%) were the two most common types of anemia in 33 anemic GPCA+BMS patients. Moreover, normocytic anemia (61.3%), thalassemia trait-induced anemia (15.5%), and iron deficiency anemia (14.1%) were the three most common types of anemia in 142 anemic GPCA-BMS patients. CONCLUSION: GPCA+BMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-BMS patients.
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Anemia , Síndrome de Boca Ardiente , Hematínicos , Hiperhomocisteinemia , Síndrome de Boca Ardiente/epidemiología , Ácido Fólico , Deficiencia de Ácido Fólico/complicaciones , Deficiencia de Ácido Fólico/epidemiología , Glositis , Hemoglobinas/análisis , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/epidemiología , Hierro , Células Parietales Gástricas , Vitamina B 12 , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/epidemiologíaRESUMEN
Fabrication of tunable fine textures on solid metal surfaces often demands sophisticated reaction/processing systems. By exploiting inâ situ polymerization and self-assembly of inorganic adducts derived from liquid metals (the so-called HetMet reaction) with concomitant solidification, solid metal films with tunable texture are readily fabricated. Serving as a natural dimensional confinement, interparticle pores and capillary-adhered thin liquid films in a pre-packed bed of undercooled liquid metal particles lead to the expeditious surface accumulation of organometallic synthons, which readily oligomerize and self-assemble into concentration-dictated morphologies/patterns. Tuning particle size, particle packing (flat or textured), and reactant concentration generates diverse, autonomously organized organometallic structures on a metal particle bed. Concomitant solidification and sintering of the underlying undercooled particle bed led to a multiscale patterned solid metal surface. The process is illustrated by creating tunable features on pre-organized metal particle beds with concomitant tunable wettability as illustrated through the so-called petal and lotus effects.
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OBJECTIVE: Obesity is a well-known risk factor for infertility. However, the use of weight loss medications prior to conception is underutilized. The objectives of our study are to describe weight loss, pregnancy rates, and live birth rates after short-term phentermine use in women with obesity and infertility. METHODS: This was a retrospective analysis of 55 women (18 to 45 years old) who were overweight or obese, diagnosed with infertility, and prescribed phentermine for weight loss in an ambulatory endocrinology clinic at a single, tertiary level academic medical center. Main outcome measures were mean percent weight change at 3 months after starting phentermine, and pregnancy, and live birth rates from start of phentermine to June 30, 2017. RESULTS: Median duration of phentermine use was 70 days (Q1, Q3 [33, 129]). Mean ± SD percent weight change at 3 months after starting phentermine was -5.3 ± 4.1% (P<.001). The pregnancy rate was 60% and the live birth rate was 49%. There was no significant difference in pregnancy rates (52% versus 68%; P = .23) or live birth rates (44% versus 54%; P = .50) in women who lost ≥5% versus <5% of their baseline weight. The number of metabolic comorbidities was negatively associated with the pregnancy rate. Phentermine was generally well-tolerated with no serious adverse events. CONCLUSION: Phentermine can produce clinically significant weight loss in women with obesity during the preconception period. Higher pregnancy or live birth rates were not observed with a greater degree of weight loss with phentermine.
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Fármacos Antiobesidad , Pérdida de Peso , Adolescente , Adulto , Femenino , Humanos , Persona de Mediana Edad , Fentermina/efectos adversos , Embarazo , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: Burning mouth syndrome (BMS) is characterized by burning sensation of the oral mucosa in the absence of clinically apparent oral mucosal alterations. This study evaluated the anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity in 884 BMS patients. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, GPCA levels in 884 BMS patients were measured and compared with the corresponding levels in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 175 (19.8%), 143 (16.2%), 42 (4.8%), 20 (2.3%), 170 (19.2%), and 109 (12.3%) BMS patients had blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 884 BMS patients had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 442 healthy control subjects (all P-values < 0.005). Of 175 anemic BMS patients, 95 had normocytic anemia, 27 had thalassemia trait-induced anemia, 21 had iron deficiency anemia, 15 had pernicious anemia, 15 had macrocytic anemia other than pernicious anemia, and 2 had microcytic anemia other than iron deficiency anemia and thalassemia trait-induced anemia. Burning sensation of oral mucosa (100.0%), dry mouth (48.1%), numbness of oral mucosa (30.7%), and dysfunction of taste (16.7%) were the four common symptoms in 884 BMS patients. CONCLUSION: BMS patients have significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects.
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Anemia/etiología , Síndrome de Boca Ardiente/sangre , Deficiencia de Ácido Fólico/sangre , Hiperhomocisteinemia/sangre , Deficiencia de Vitamina B 12/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Estudios de Casos y Controles , Índices de Eritrocitos , Femenino , Ácido Fólico/sangre , Hemoglobinas/análisis , Humanos , Hierro/sangre , Masculino , Persona de Mediana Edad , Células Parietales Gástricas/inmunología , Vitamina B 12/sangre , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are organ-specific autoantibodies. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in burning mouth syndrome (BMS) patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 884 BMS patients and in 442 age- and sex-matched healthy control subjects. RESULTS: We found that 12.3%, 21.6%, and 22.7% of 884 BMS patients and 1.8%, 2.3%, and 2.9% of 442 healthy control subjects had the serum GPCA, TGA, and TMA positivities, respectively. BMS patients had significantly higher frequencies of GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). We also found that 20 (2.3%), 130 (14.7%), and 181 (20.5%) BMS patients and 3 (0.7%), 8 (1.8%), and 6 (1.4%) healthy control subjects had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) organ-specific autoantibody in their sera, respectively. Of 255 TGA/TMA-positive BMS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.8%, 5.1%, and 7.1% of these TGA/TMA-positive BMS patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 37.5% of 884 BMS patients have serum GPCA/TGA/TMA positivity. Moreover, 12.3%, 21.6%, and 22.7% of 884 BMS patients have the serum GPCA, TGA, and TMA positivities, respectively. Only 5.1% and 7.1% of TGA/TMA-positive BMS patients have hyperthyroidism and hypothyroidism, respectively. It needs further studies to know whether GPCA-positive BMS patients may finally become as having autoimmune atrophic gastritis.
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Síndrome de Boca Ardiente , Autoanticuerpos , Estudios de Casos y Controles , Humanos , Hipertiroidismo , Células Parietales GástricasRESUMEN
BACKGROUND/PURPOSE: Emergency air medical transport (EAMT) of patients in remote areas with neurological emergencies to higher-level facilities is an integral part of the regionalized healthcare system. EAMT is safe and feasible for head injuries. Debates persist on the high cost, safety, and risk of EAMT, thereby calling for alternatives. METHODS: We conducted a retrospective cohort study by including all patients with intracranial hemorrhage (ICH) who visited the Kinmen Hospital from January 2006 to December 2016. Routine neurosurgical dispatch (RNSD) implemented since 2009, dispatches neurosurgeons to Kinmen. EAMT and 90-day mortality were assessed. RESULTS: We enrolled 560 patients: 173 pre-stage and 387 post-stage. RNSD resulted in less EAMT deployment ([adjusted odds ratio AOR] = 0·23, p < 0·001) and lower 90-day mortality ([adjusted hazard ratio AHR] 0·66, p = 0·043). RNSD resulted in decreased EAMT among all subgroups, especially in age ≥81 years (AOR 0.03, p < 0.001), age 41-60 years (AOR 0.10, p < 0.001), traumatic intracranial hemorrhage (TICH) (AOR 0·11, p < 0·001), and Glasgow Coma Scale (GCS) 9-12 (AOR 0.14, p 0.001). The risk of 90-day mortality was higher in male (AHR 1.81, p = 0·006), GCS 3-8 (AHR 35.52, p < 0·001) and GCS 9-12 (AHR 7.46, p < 0·01) and lower in age 21-40 years (AHR 0.46, p = 0.034). CONCLUSION: Incorporating RNSD with EAMT is a plausible alternative to EAMT with a significant decrease in EAMT and decreased 90-day mortality in patients with ICH compared with non-neurosurgical care with EAMT. Despite a 34% decrease in 90-day mortality after RNSD, patient characteristics such as disease severity, age, and sex still dictated patient outcomes.
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Ambulancias Aéreas , Enfermedad Crítica/mortalidad , Servicios Médicos de Urgencia/estadística & datos numéricos , Hemorragias Intracraneales/mortalidad , Transporte de Pacientes/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Causas de Muerte , Niño , Preescolar , Enfermedad Crítica/terapia , Servicios Médicos de Urgencia/métodos , Femenino , Escala de Coma de Glasgow , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Taiwán/epidemiología , Factores de Tiempo , Transporte de Pacientes/métodos , Adulto JovenRESUMEN
BACKGROUND/PURPOSE: Normocytosis is defined as having the mean corpuscular volume (MCV) between 80 fL and 99.9 fL. This study evaluated whether 944 atrophic glossitis (AG) patients with normocytosis had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects or 1064 AG patients. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 944 AG patients with normocytosis, 1064 AG patients, and 532 healthy control subjects were measured and compared. RESULTS: We found that 12.4%, 14.5%, 2.3%, 2.0%, 9.0%, and 25.7% of 944 AG patients with normocytosis had blood hemoglobin (Hb), iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Furthermore, 944 AG patients with normocytosis had significantly higher frequencies of blood Hb, iron, vitamin B12, folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). On the contrary, 944 AG patients with normocytosis had significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall 1064 AG patients (all P-values < 0.05). CONCLUSION: We conclude that there are significantly higher frequencies of anemia and serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with normocytosis than in healthy control subjects. On the contrary, AG patients with normocytosis have significantly lower frequencies of blood Hb and vitamin B12 deficiencies and hyperhomocysteinemia than overall AG patients.
Asunto(s)
Deficiencia de Ácido Fólico , Glositis , Hematínicos , Hiperhomocisteinemia , Deficiencia de Vitamina B 12 , Estudios de Casos y Controles , Índices de Eritrocitos , Ácido Fólico , Deficiencia de Ácido Fólico/complicaciones , Glositis/complicaciones , Hemoglobinas/análisis , Humanos , Células Parietales Gástricas , Vitamina B 12 , Deficiencia de Vitamina B 12/complicacionesRESUMEN
BACKGROUND/PURPOSE: Our previous study found that 127 of 1064 atrophic glossitis (AG) patients have hyperhomocysteinemia. This study assessed whether the AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, hematinic deficiencies, and serum gastric parietal cell antibody (GPCA) positivity than AG patients without hyperhomocysteinemia or healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 127 AG patients with hyperhomocysteinemia, 937 AG patients without hyperhomocysteinemia, and 532 healthy control subjects were measured and compared. RESULTS: We found that 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of blood Hb and serum iron, vitamin B12, and folic acid deficiencies and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of blood Hb and serum vitamin B12 and folic acid deficiencies and serum GPCA positivity than 937 AG patients without hyperhomocysteinemia (all P-values < 0.001). Moreover, 127 AG patients with hyperhomocysteinemia had significantly higher frequencies of macrocytic anemia and significantly lower frequencies of normocytic anemia than 937 AG patients without hyperhomocysteinemia (both P-values < 0.001). Pernicious anemia (22 cases) was found only in AG patients with hyperhomocysteinemia but not in AG patients without hyperhomocysteinemia. CONCLUSION: AG patients with hyperhomocysteinemia had significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, and serum GPCA positivity than healthy control subjects and significantly higher frequencies of anemia, serum vitamin B12 and folic acid deficiencies, and serum GPCA positivity than AG patients without hyperhomocysteinemia.
Asunto(s)
Anemia/etiología , Autoanticuerpos/sangre , Ácido Fólico/sangre , Glositis/sangre , Hiperhomocisteinemia/sangre , Células Parietales Gástricas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Atrofia , Estudios de Casos y Controles , Recuento de Eritrocitos , Índices de Eritrocitos , Femenino , Hemoglobinas/análisis , Humanos , Hierro/sangre , Masculino , Persona de Mediana Edad , Taiwán , Vitamina B 12/sangre , Adulto JovenRESUMEN
Atrophic glossitis (AG) is characterized by the partial or complete absence of filiform papillae on the dorsal surface of the tongue. AG may reflect the significant deficiencies of some major nutrients including riboflavin, niacin, pyridoxine, vitamin B12, folic acid, iron, zinc, and vitamin E. Moreover, protein-calorie malnutrition, candidiasis, Helicobacter pylori colonization, xerostomia, and diabetes mellitus are also the etiologies of AG. Our previous study found the serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 26.7%, 28.4%, and 29.8% of 1064 AG patients, respectively. We also found anemia, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 19.0%, 16.9%, 5.3%, 2.3%, and 11.9% of 1064 AG patients, respectively. Moreover, GPCA-positive AG patients tended to have relatively higher frequencies of hemoglobin, iron, and vitamin B12 deficiencies and hyperhomocysteinemia than GPCA-negative AG patients. Supplementations with vitamin BC capsules plus corresponding deficient hematinics for those AG patients with hematinic deficiencies can achieve complete remission of oral symptoms and AG in some AG patients. Therefore, it is very important to examine the complete blood count, serum hematinic, homocysteine, and autoantibody levels in AG patients before we start to offer treatments for AG patients.