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1.
BMC Prim Care ; 25(1): 63, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383303

RESUMO

BACKGROUND: Patient-physician relationships in healthcare can influence healthcare provision, patient engagement, and health outcomes. Little is known about youth preferences on types and characteristics of their healthcare providers. The aim of this study was to assess youth perspectives on preferences for and interactions with their healthcare providers. METHODS: We posed 5 open-ended questions to 1,163 MyVoice participants, a nationwide text message cohort of United States youth aged 14-24, on April 10, 2020 related to youth preferences for healthcare providers. Content analysis was used to develop a codebook. Responses were independently coded by two reviewers with discrepancies discussed to reach consensus. Descriptive statistics were calculated for demographics and frequency of codes. RESULTS: 944 (81%) participants responded to at least one question. Respondents had a mean age of 18.9 years (SD: 2.8) and were a majority female (53.6%) and White (56.3%). Youth reported "kindness" or other personality traits (31%) and education (30%) as important in choosing their doctor. Patient-physician concordance was not important to many youths (44%) and among those who reported concordance as important (55%), having the same gender was the most noted (68%). Youth suggested respect, open conversation, and addressing issues directly to help alleviate uncomfortable situations, though some would simply switch providers. CONCLUSION: Personality and empathy are important provider characteristics valued by youth. Female respondents preferred gender concordant providers, particularly for sexual health-related issues, and non-white respondents were more likely to prefer racial concordance. Strengthening professional and interpersonal skills among youth-serving providers may improve healthcare engagement and satisfaction among youth.


Assuntos
Instalações de Saúde , Relações Médico-Paciente , Humanos , Adolescente , Feminino , Estados Unidos , Pesquisa Qualitativa , Pessoal de Saúde
2.
AJOG Glob Rep ; 3(3): 100253, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560009

RESUMO

BACKGROUND: Quarantining and isolation during previous pandemics have been associated with higher levels of depression symptomatology. Studies in other countries found elevated rates of anxiety and/or depression among pregnant people during the COVID-19 pandemic compared with prepandemic rates. New York City was the initial epicenter of the pandemic in the United States, and the effects of the pandemic on perinatal depression in this population are not well known. OBJECTIVE: This study aimed to evaluate the rates of perinatal depression before and during the COVID-19 pandemic. STUDY DESIGN: This is a single-center retrospective cohort study of patients screened for perinatal depression with the Edinburgh Postnatal Depression Scale at 2 private academic practices in New York City. This screen is done in these practices at the time of the glucose challenge test and at the postpartum visit. Patients aged ≥18 years who completed a screen at a postpartum visit and/or glucose challenge test from February 1, 2019 to July 31, 2019 and from February 1, 2020 to July 31, 2020 were identified, and the 2019 and 2020 groups were compared. The primary outcome was a positive screen, defined as ≥13 and ≥15 for postnatal and prenatal screens, respectively. Secondary outcomes included monthly changes in rates of positive screens and factors associated with perinatal depression. Data were analyzed using Mann-Whitney U test, chi-square, or Fisher exact test, and univariate and multivariate analyses with P<.05 defined as significant. RESULTS: A total of 1366 records met the inclusion criteria; 75% of the prepandemic (2019) records were included, as opposed to 65% of pandemic (2020) records due to a lower screen completion rate in the pandemic cohort. The 2020 cohort had a higher proportion of Hispanic patients (P=.003) and higher rates of diabetes mellitus (P=.007), preterm labor (P=.03), and current or former drug use (P<.001). The 2019 cohort had higher rates of hypertension (P=.002) and breastfeeding (P=.03); 4.6% of the 2020 cohort had a suspected or confirmed COVID-19 infection. There was no difference in perinatal depression between the 2019 and 2020 cohorts (2.8% vs 2.6%; P>.99). This finding persisted after adjusting for baseline differences (adjusted odds ratio, 0.89; 95% confidence interval, 0.38-1.86; P=.76). There were no differences in rates of positive Edinburgh Postnatal Depression Scale by month. Several risk factors were associated with a positive screen, including being unmarried (P<.001), pulmonary disease (P=.02), depression (P<.001), anxiety (P=.01), bipolar disorder (P=.009), and use of anxiolytics (P=.04). CONCLUSION: There were no differences in the rates of perinatal depression between the periods before and during the COVID-19 pandemic. The rate of perinatal depression in this cohort was below the reported averages in the literature. Fewer women were screened for perinatal depression in 2020, which likely underestimated the prevalence of depression in our cohort. These findings highlight potential gaps in care in a pandemic setting.

3.
Environ Monit Assess ; 195(7): 852, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37326797

RESUMO

Increasing reports of cyanobacteria or cyanotoxins around the world expose a major threat for the environment, animal, and human health. Current water treatment processes are ineffective at eliminating cyanotoxins; hence, risk management relies mostly on early detection and on the development of specific regulatory frameworks. In developed countries, well-documented monitoring activities offer a good assessment of the cyanobacterial and/or cyanotoxin status and are used to prevent intoxications. In developing countries such as Peru, despite their potential threat to the environment and public health, cyanobacteria and cyanotoxins are still poorly studied. We found that the regulatory measures regarding cyanobacteria and/or cyanotoxin are almost non-existent. We also present and discuss some examples of recent monitoring efforts underwent by isolated local authorities and scientific reports that, whereas limited, may provide some important insights to be considered nationally. A revision of the available information of planktonic cyanobacteria or cyanotoxins in Peruvian freshwater lentic water bodies revealed a total of 50 documented reports of 15 different genera across 19 water bodies, including the reported highly toxic Dolichospermum and Microcystis. A unique case of microcystin-LR has been documented. We propose some recommendations to be implemented to improve potential toxic cyanobacteria risk management that include incorporating a widespread monitoring of cyanobacterial communities in lakes and reservoirs used for human consumption via specific guidelines. Aligning Peruvian regulations on cyanobacteria and cyanotoxins to international standards may also support law enforcement and ensure compliance.


Assuntos
Cianobactérias , Plâncton , Humanos , Animais , Peru , Prevalência , Monitoramento Ambiental , Microcistinas/análise , Toxinas de Cianobactérias , Lagos , Formulação de Políticas
4.
Cureus ; 15(12): e50586, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38222203

RESUMO

In the last couple of decades, much progress has been made in studying bacteria living in humans. However, there is much more to learn about bacteria immune cell interactions. Here, we show that anaerobic bacteria do not grow when cultured overnight with human cells under atmospheric air. Air contains about 18% oxygen, which inhibits the growth of these bacteria while supporting the cultivation of human cells. The bacteria cultured with human peripheral blood mononuclear cells (PBMCs) inflamed with phytohemagglutinin (PHA) greatly increased the production of proinflammatory cytokines like tumor necrosis factor-alpha (TNFα) while inhibiting the production of monocyte chemoattractant protein-1 (MCP-1), an important chemokine.

5.
J Cannabis Res ; 4(1): 57, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324130

RESUMO

BACKGROUND: Cannabis sativa is a primarily dioecious angiosperm that exhibits sexual developmental plasticity. Developmental genes for staminate male flowers have yet to be elucidated; however, there are regions of male-associated DNA from Cannabis (MADC) that correlate with the formation of pollen producing staminate flowers. MADC2 is an example of a PCR-based genetic marker that has been shown to produce a 390-bp amplicon that correlates with the expression of male phenotypes. We demonstrate applications of a cost-effective high-throughput male genotyping assay and other genotyping applications of male identification in Cannabis sativa. METHODS: In this study, we assessed data from 8200 leaf samples analyzed for real-time quantitative polymerase chain reaction (qPCR) detection of MADC2 in a commercial testing application offered through Steep Hill Laboratories. Through validation, collaborative research projects, and follow-up retest analysis, we observed a > 98.5% accuracy of detection of MADC2 by qPCR. We also carried out assay development for high-resolution melting analysis (HRM), loop-mediated isothermal amplification (LAMP), and TwistDx recombinase amplification (RPA) assays using MADC2 for male identification. RESULTS: We demonstrate a robust high-throughput duplex TaqMan qPCR assay for identification of male-specific genomic signatures using a novel MADC2 qPCR probe. The qPCR cycle quotient (Cq) value representative of MADC2 detection in 3156 males and the detection of tissue control cannabinoid synthesis for 8200 samples and the absence of MADC2 detection in 5047 non-males demonstrate a robust high-throughput real-time genotyping assay for Cannabis. Furthermore, we also demonstrated the viability of using nearby regions to MADC2 with novel primers as alternative assays. Finally, we also show proof of concept of several additional commercially viable sex determination methodologies for Cannabis sativa. DISCUSSION: In industrial applications, males are desirable for their more rapid growth and higher quality fiber quality, as well as their ability to pollinate female plants and produce grain. In medicinal applications, female cultivars are more desirable for their ability to produce large amounts of secondary metabolites, specifically the cannabinoids, terpenes, and flavonoids that have various medicinal and recreational properties. In previous studies, traditional PCR and non-high-throughput methods have been reported for the detection of male cannabis, and in our study, we present multiple methodologies that can be carried out in high-throughput commercial cannabis testing. CONCLUSION: With these markers developed for high-throughput testing assays, the Cannabis industry will be able to easily screen and select for the desired sex of a given cultivar depending on the application.

6.
Rev. peru. biol. (Impr.) ; 29(4)oct. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1424297

RESUMO

La presente comunicación proporciona información de la presencia en Perú de dos especies invasoras del género Ceratium: C. hirundinella (O.F. Müller) Dujardin y C. furcoides (Levander) Langhans. Se brinda información sobre la distribución de ambas especies en cuerpos de agua peruanos, así como datos de sus abundancias.


This works provides information on the presence in Peru of two invasive species of the genus Ceratium: C. hirundinella (O.F. Müller) Dujardin and C. furcoides (Levander) Langhans. Information is provided on the distribution of both species in Peruvian water bodies, as well as data on their abundance.

7.
J Perinat Med ; 50(5): 630-633, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35166090

RESUMO

OBJECTIVES: To examine the relationship between postpartum depression (PPD), mode of delivery (MOD), and indication for unscheduled cesarean delivery (uCD). METHODS: Patients with antenatal and postpartum Edinburgh Postnatal Depression Scale (EPDS) scores were compared by MOD and indication for uCD if applicable. Patients with an antenatal EPDS>12 were excluded to ascertain the incidence of new depression. The primary outcome was EPDS≥13 by MOD. The secondary outcome was EPDS≥13 by indication for uCD. RESULTS: Seven hundred and thirty eight patients met inclusion criteria. There were statistically significant differences in MOD by age, race, BMI, and multi-gestation pregnancy. Patients delivered via uCD had a higher rate of peripartum complications and NICU admission. There were no differences in medical comorbidities or use of psychiatric medications by MOD. There was no difference in EPDS by MOD. The rate of PPD was higher in patients with uCD for non-reassuring fetal heart tones (NRFHT) compared to other indications for uCD (p=0.02). CONCLUSIONS: While there was no difference in the incidence of PPD by MOD, the incidence of PPD was higher among patients delivered via uCD for NRFHT. These findings may have implications for patient counseling, post-operative mental health surveillance, and support of postpartum patients.


Assuntos
Depressão Pós-Parto , Cesárea/efeitos adversos , Cesárea/psicologia , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/etiologia , Depressão Pós-Parto/psicologia , Feminino , Humanos , Período Pós-Parto , Gravidez , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos
8.
J Clin Med Res ; 12(9): 543-559, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32849943

RESUMO

BACKGROUND: The use of ventricular assist devices (VADs) has become predominant in this era of medicine. It is commonly used as a bridge to transplant, recovery and as a destination therapy for patients with severe heart failure, who are not responsive to maximum optimal management or ineligible for transplant. However, several complications are known to occur with the use of these devices. In this research, we will compare gastrointestinal bleeding in patients who used centrifugal flow versus axial flow VADs. We hope that the result of this meta-analysis and the review presented provide adequate information to future researchers, physicians and other healthcare professionals who are interested in this topic. METHODS: Published articles evaluated for inclusion were obtained from MEDLINE (PubMed), Cochrane, EBSCO, clinicaltrials.gov, and international clinical trials registry. This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Procured articles were reviewed by two independent reviewers. Only randomized control trials and observational studies were used. Quality assessment was done with Cochrane Collaboration's tool (RoB.2 with visualization through robviz) and Newcastle-Ottawa Scale (NOS). Data analysis was carried out with the use of R data analysis tool (version 4.0.0; release date: April 24th, 2020). RESULTS: At the end of this meta-analysis, the occurrence of gastrointestinal bleeding was not significantly different between both groups; with odds ratio (OR): 0.81; 95% confidence interval (CI): 0.65 - 1.00; P value = 0.05. Between-study variance (Tau-squared) was zero (0), standard error (SE) = 0.06. The degree of heterogeneity measured with I-squared statistic was 0% (minimal). Egger's regression test was not statistically significant, P = 0.93. Symmetry of distribution was observed on the funnel plot. Trim and fill analysis showed no missing studies on the left; SE = 1.68. CONCLUSIONS: The result obtained from this research indicates that the occurrence of gastrointestinal bleeding is not significantly different in both groups of patients, irrespective of the type of continuous flow VAD used. Although, the study sample used in this meta-analysis was limited.

10.
PLoS One ; 14(9): e0222363, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31513654

RESUMO

Terpenes are responsible for most or all of the odor and flavor properties of Cannabis sativa, and may also impact effects users experience either directly or indirectly. We report the diversity of terpene profiles across samples bound for the Washington dispensary market. The remarkable degree of variation in terpene profiles ultimately results from action of a family of terpene synthase genes, only some of which have been described. Using a recently available genome assembly we describe 55 terpene synthases with genomic context, and tissue specific expression. The family is quite diverse from a protein similarity perspective, and subsets of the family are expressed in all tissues in the plant, including a set of root specific monoterpene synthases that could well have agronomic importance. Ultimately understanding and breeding for specific terpene profiles will require a good understanding of the gene family that underlies it. We intend for this work to serve as a foundation for that.


Assuntos
Alquil e Aril Transferases/genética , Cannabis/genética , Terpenos/metabolismo , Alquil e Aril Transferases/metabolismo , Cannabis/química , Clonagem Molecular/métodos , Evolução Molecular , Flores/genética , Genes de Plantas , Genoma de Planta/genética , Genômica , Filogenia , Terpenos/química
11.
AoB Plants ; 11(6): plz074, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32010439

RESUMO

Gene copy number (CN) variation is known to be important in nearly every species where it has been examined. Alterations in gene CN may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many of which have medicinal utility. Two major cannabinoids-THCA (delta-9-tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid)-are products of a three-step biochemical pathway. Using whole-genome shotgun sequence data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in CN. Transcriptome sequence data show that the cannabinoid paralogs are differentially expressed among lineages within the species. We also found that CN partially explains variation in cannabinoid content levels among Cannabis plants. Our results demonstrate that biosynthetic genes found at multiple points in the pathway could be useful for breeding purposes, and suggest that natural and artificial selection have shaped CN variation. Truncations in specific paralogs are associated with lack of production of particular cannabinoids, showing how phytochemical diversity can evolve through a complex combination of processes.

12.
J Autism Dev Disord ; 49(1): 410-414, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30047098

RESUMO

Previous research indicates that infection, especially from viruses in the family Herpesviridae, may play a role in the etiology of some cases of autism spectrum disorder (ASD). Using a case-control design and the polymerase chain reaction with site-specific primers, we screened newborn and childhood blood samples for the presence of eight human herpesviruses. Herpesvirus DNA was detected in 4 of 225 ASD individuals and 2 of 235 controls, with the most frequently detected virus being HHV-6B. Although this study does not detect a significant ASD-Herpesviridae association, it is limited by the use of site-specific primers. We suggest that new techniques using bioinformatics to search next-generation sequencing databases will be more revealing of possible ASD-virus associations.


Assuntos
Transtorno do Espectro Autista/virologia , Infecções por Herpesviridae/epidemiologia , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Infecções por Herpesviridae/sangue , Humanos
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1061-1062: 438-444, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28820982

RESUMO

Pre-analytical treatment of blood plasma is a time consuming and often rate limiting step in the workflow of LC/MS analysis. We present in this pilot study a new approach for quantitative LC/MS based on weak affinity chromatography (WAC) of crude plasma. The steroid hormone cortisol was selected as a clinically relevant biomarker, as it currently requires extensive pre-analytical preparation. A WAC unit with saturating, immobilized albumin as a prototypic weak binder was used in combination with an ion-funnel MS/MS detector to perform zonal affinity chromatography of cortisol directly from a plasma sample, followed by quantitative multiple reaction monitoring (MRM). This procedure also allowed us to determine the amount of bioavailable cortisol in the clinical plasma sample which is of significant therapeutic interest. This WAC-MS approach showed an excellent correlation (R2=0.86 (P<0.0001 (highly significant); n=60) with a state-of-the-art, clinical competitive immunoassay procedure for plasma cortisol analysis. With integration of WAC into LC/MS workflow, it may be possible to both accelerate and improve assay performance by eliminating the sample extraction step. Preliminary data with other steroid hormones indicate that WAC-MS can be applied to various biomolecules using a plasma transport protein such as albumin.


Assuntos
Cromatografia de Afinidade/métodos , Cromatografia Líquida/métodos , Hidrocortisona/sangue , Espectrometria de Massas em Tandem/métodos , Disponibilidade Biológica , Humanos , Hidrocortisona/metabolismo , Modelos Lineares , Projetos Piloto , Sensibilidade e Especificidade
15.
Sci Rep ; 7: 46528, 2017 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-28422145

RESUMO

As the most widely used illicit drug worldwide, and as a source of numerous under-studied pharmacologically-active compounds, a precise understanding of variability in psychological and physiological effects of Cannabis varieties is essential. The National Institute on Drug Abuse (NIDA) is designated as the sole legal producer of Cannabis for use in US research studies. We sought to compare the chemical profiles of Cannabis varieties that are available to consumers in states that have state-legalized use versus what is available to researchers interested in studying the plant and its effects. Our results demonstrate that the federally-produced Cannabis has significantly less variety and lower concentrations of cannabinoids than are observed in state-legal U.S. dispensaries. Most dramatically, NIDA's varieties contain only 27% of the THC levels and as much as 11-23 times the Cannabinol (CBN) content compared to what is available in the state-legal markets. Research restricted to using the current range of federally-produced Cannabis thus may yield limited insights into the chemical, biological and pharmacological properties, and medical potential of material that is available in the state markets. Investigation is urgently needed on the full diversity of Cannabis chemotypes known to be available to the public.


Assuntos
Canabinoides/análise , Cannabis/química , Maconha Medicinal/química , Canabinoides/química , Cannabis/crescimento & desenvolvimento , Estados Unidos
16.
G3 (Bethesda) ; 7(4): 1287-1299, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-28235828

RESUMO

Maternal exposure to environmental pollutants could affect fetal brain development and increase autism spectrum disorder (ASD) risk in conjunction with differential genetic susceptibility. Organohalogen congeners measured in maternal midpregnancy blood samples have recently shown significant, but negative associations with offspring ASD outcome. We report the first large-scale maternal and fetal genetic study of the midpregnancy serum levels of a set of 21 organohalogens in a subset of 790 genotyped women and 764 children collected in California by the Early Markers for Autism (EMA) Project. Levels of PCB (polychlorinated biphenyl) and PBDE (polybrominated diphenyl ether) congeners showed high maternal and fetal estimated SNP-based heritability (h2g ) accounting for 39-99% of the total variance. Genome-wide association analyses identified significant maternal loci for p,p'-DDE (P = 7.8 × 10-11) in the CYP2B6 gene and for BDE-28 (P = 3.2 × 10-8) near the SH3GL2 gene, both involved in xenobiotic and lipid metabolism. Fetal genetic loci contributed to the levels of BDE-100 (P = 4.6 × 10-8) and PCB187 (P = 2.8 × 10-8), near the potential metabolic genes LOXHD1 and PTPRD, previously implicated in neurodevelopment. Negative associations were observed for BDE-100, BDE153, and the sum of PBDEs with ASD, partly explained by genome-wide additive genetic effects that predicted PBDE levels. Our results support genetic control of midgestational biomarkers for environmental exposures by nonoverlapping maternal and fetal genetic determinants, suggesting that future studies of environmental risk factors should take genetic variation into consideration. The independent influence of fetal genetics supports previous hypotheses that fetal genotypes expressed in placenta can influence maternal physiology and the transplacental transfer of organohalogens.


Assuntos
Poluentes Ambientais/sangue , Feto/metabolismo , Exposição Materna , Transtorno do Espectro Autista/sangue , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Padrões de Herança/genética , Modelos Lineares , Desequilíbrio de Ligação/genética , Polimorfismo de Nucleotídeo Único/genética , Gravidez
17.
Autism Open Access ; 6(2)2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27853655

RESUMO

The killing activity of natural killer cells is largely regulated by the binding of class I human leukocyte antigen cognate ligands to killer cell immunoglobulin - like receptor proteins. The killer cell immunoglobulin - like receptor gene - complex contains genes that activate and others that inhibit the killing state of natural killer cells depending on the binding of specific human leukocyte antigen cognate ligands. It has been suggested in previous publications that activating human leukocyte antigen/killer - cell immunoglobulin - like receptor complexes are increased in people with autism. We present data, which suggests that an activating cB01/tA01 killer cell immunoglobulin - like receptor gene - content haplotype and the cognate ligand human leukocyte antigen - C1k that activates this haplotype is significantly increased in autism. This is an important observation suggesting that the interaction between two proteins encoded on different chromosomes increases natural killer cell killing in autism.

18.
Front Neurosci ; 10: 463, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27812316

RESUMO

The "common variant-common disease" hypothesis was proposed to explain diseases with strong inheritance. This model suggests that a genetic disease is the result of the combination of several common genetic variants. Common genetic variants are described as a 5% frequency differential between diseased vs. matched control populations. This theory was recently supported by an epidemiology paper stating that about 50% of genetic risk for autism resides in common variants. However, rare variants, rather than common variants, have been found in numerous genome wide genetic studies and many have concluded that the "common variant-common disease" hypothesis is incorrect. One interpretation is that rare variants are major contributors to genetic diseases and autism involves the interaction of many rare variants, especially in the brain. It is obvious there is much yet to be learned about autism genetics. Evidence has been mounting over the years indicating immune involvement in autism, particularly the HLA genes on chromosome 6 and KIR genes on chromosome 19. These two large multigene complexes have important immune functions and have been shown to interact to eliminate unwanted virally infected and malignant cells. HLA proteins have important functions in antigen presentation in adaptive immunity and specific epitopes on HLA class I proteins act as cognate ligands for KIR receptors in innate immunity. Data suggests that HLA alleles and KIR activating genes/haplotypes are common variants in different autism populations. For example, class I allele (HLA-A2 and HLA-G 14 bp-indel) frequencies are significantly increased by more than 5% over control populations (Table 2). The HLA-DR4 Class II and shared epitope frequencies are significantly above the control populations (Table 2). Three activating KIR genes: 3DS1, 2DS1, and 2DS2 have increased frequencies of 15, 22, and 14% in autism populations, respectively. There is a 6% increase in total activating KIR genes in autism over control subjects. And, more importantly there is a 12% increase in activating KIR genes and their cognate HLA alleles over control populations (Torres et al., 2012a). These data suggest the interaction of HLA ligand/KIR receptor pairs encoded on two different chromosomes is more significant as a ligand/receptor complex than separately in autism.

19.
Front Neurosci ; 10: 218, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242422

RESUMO

BACKGROUND: An etiological role for immune factors operating during early brain development in children with autism spectrum disorders (ASD) has not yet been established. A major obstacle has been the lack of early biologic specimens that can be linked to later diagnosis. In a prior study, we found lower risk of ASD associated with higher levels of maternally-derived total IgG and Toxoplasmosis gondii (Toxo) IgG in newborn blood spot specimens from children later diagnosed with ASD compared to population controls. METHODS: We obtained maternal mid-gestational serum specimens and newborn screening blood spots from the California Genetics Disease Screening Program (GDSP) for linked mother-baby pairs for 84 children with ASD and 49 children with developmental delay but not ASD (DD) identified from California Department of Developmental Services records and for 159 population controls sampled from birth certificates.Immunoglobulin levels in maternal and newborn specimens were measured by solid phase immunoassays and analyzed in logistic regression models for total IgG, total IgM, and Toxo IgG, and, for maternal specimens only, Toxo IgM. Correlations between maternal and newborn ranked values were evaluated. RESULTS: In both maternal and newborn specimens, we found significantly lower risk of ASD associated with higher levels of Toxo IgG. In addition, point estimates for all comparisons were < 1.0 suggesting an overall pattern of lower immunoglobulin levels associated with higher ASD risk but most did not reach statistical significance. We did not find differences in maternal or newborn specimens comparing children with DD to controls. DISCUSSION: These results are consistent with evidence from our prior study and other published reports indicating that immune factors during early neurodevelopment may be etiologically relevant to ASD. Lowered immunoglobulin levels may represent suboptimal function of the maternal immune system or reduced maternal exposure to common infectious agents. CONCLUSION: Patterns seen in these selected immunoglobulins may provide clues to mechanisms of early abnormalities in neurodevelopment contributing to ASD. We recommend further study of immunoglobulin profiles in larger samples of linked mother-baby pairs to evaluate possible etiologic relevance.

20.
PLoS One ; 8(10): e76978, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24204716

RESUMO

Effects of parental genotype or parent-offspring genetic interaction are well established in model organisms for a variety of traits. However, these transgenerational genetic models are rarely studied in humans. We have utilized an autism case-control study with 735 mother-child pairs to perform genome-wide screening for maternal genetic effects and maternal-offspring genetic interaction. We used simple models of single locus parent-child interaction and identified suggestive results (P<10(-4)) that cannot be explained by main effects, but no genome-wide significant signals. Some of these maternal and maternal-child associations were in or adjacent to autism candidate genes including: PCDH9, FOXP1, GABRB3, NRXN1, RELN, MACROD2, FHIT, RORA, CNTN4, CNTNAP2, FAM135B, LAMA1, NFIA, NLGN4X, RAPGEF4, and SDK1. We attempted validation of potential autism association under maternal-specific models using maternal-paternal comparison in family-based GWAS datasets. Our results suggest that further study of parental genetic effects and parent-child interaction in autism is warranted.


Assuntos
Transtorno Autístico/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Criança , Bases de Dados Genéticas , Feminino , Genótipo , Humanos , Modelos Genéticos , Relações Mãe-Filho , Fenótipo , Proteína Reelina
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