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Depression and Anxiety Feb 2016To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic...
BACKGROUND
To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage.
METHODS
Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals.
RESULTS
Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006.
CONCLUSIONS
The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Compulsive Personality Disorder; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Young Adult
PubMed: 26594839
DOI: 10.1002/da.22452 -
Shanghai Archives of Psychiatry Feb 2018Geriatric depression is one of the most common and harmful mental illnesses seen in the elderly. However, there are few studies focusing on the relationship between...
BACKGROUND
Geriatric depression is one of the most common and harmful mental illnesses seen in the elderly. However, there are few studies focusing on the relationship between late-onset depression (LOD) and social and psychological factors, as well as brain structure.
AIMS
To explore factors related to late-onset depression (LOD) in elderly patients.
METHODS
24 first onset LOD patients over 60 years old (meeting ICD-10 diagnostic criteria for depression) and 23 non-depressed elders were selected for inclusion into this study. Scale assessments, including Fazelasscale for white matter hyperintensity (WMH) high signal level and the MTA-scale for medial temporal lobe atrophy levels, were combined with general demography and sociology data to find factors related to LOD.
RESULTS
There was no significant difference in age (=0.419, =0.678), gender (=1.705, =0.244), or years of education (=1.478, =0.146) between the two groups. However, statistical differences were shown on scores on the WMH, (=7.817, =0.008), periventricular white matter hyperintensity (PWMH)(Fisher exact test: =0.031), having or not having religious beliefs (Fisher exact test: =0.265) and family harmony (yes or no) (Fisher exact test: =0.253) between the LOD group and control group. The results of linear regression analysis showed that the total score for WMH, religious beliefs (with or without) and family harmony (yes or no) were associated with depressive symptomology.
CONCLUSION
Scores on the WMH, religious beliefs and family harmony are all potentially related to LOD in elderly patients.
PubMed: 29719354
DOI: 10.11919/j.issn.1002-0829.217038 -
Experimental and Therapeutic Medicine Apr 2020Developmental dysplasia of the hip (DDH), previously known as congenital hip dislocation, is a frequently disabling condition characterized by premature arthritis later...
Developmental dysplasia of the hip (DDH), previously known as congenital hip dislocation, is a frequently disabling condition characterized by premature arthritis later in life. Genetic factors play a key role in the aetiology of DDH. In the present study, a genome-wide linkage scan with the Affymetrix 10K GeneChip was performed on a four-generation Chinese family, which included 19 healthy members and 5 patients. Parametric and non-parametric multipoint linkage analyses were carried out with Genespring GT v.2.0 software, and the logarithm of odds (LOD) score and nonparametric linkage (NPL) score were calculated. Parametric linkage analysis was performed, assuming an autosomal recessive trait with full penetrance and Affymetrix 'Asian' allele frequencies. The strongest evidence for linkage was found on chromosome 8q23-24, with a peak LOD score of 2.658 (θ=0), covering 2.377 Mb from single nucleotide polymorphisms (SNPs) rs724717 to rs720132. This interval included nine additional successive SNPs: rs1566071, rs1902121, rs756404, rs702768, rs777813, rs2033995, rs147959, rs2884367 and rs1898287. The same region also yielded the highest NPL score of 2.883 (P=0.0156) from the non-parametric multipoint linkage analysis. Additionally, the second highest NPL score of 2.727 (P=0.0156) and LOD score of 2.528 (θ=0) were obtained on chromosome 12p12 for three consecutive markers (rs1919980, rs763853 and rs725124). This region overlapped a narrow distance of 0.642 Mb. Notably, in addition to these two regions; no significant linkage was identified for other chromosomal regions (with LOD and NPL scores >2.0). For the first time, at least for this pedigree, the evidence in the present study showed that DDH is mapped to two novel regions at 8q23-q24 and 12p12.
PubMed: 32256763
DOI: 10.3892/etm.2020.8513 -
Frontiers in Immunology 2022We identified and genes as putative effectors of the Quantitative Trait locus (QTL) that we mapped at distal chromosome 7 named for Inflammatory response modulator 1,...
We identified and genes as putative effectors of the Quantitative Trait locus (QTL) that we mapped at distal chromosome 7 named for Inflammatory response modulator 1, controlling acute inflammatory response (AIR) and the production of IL-1β, dependent on the activation of the NLRP3 inflammasome. We obtained the mapping through genome-wide linkage analysis of Single Nucleotide Polymorphisms (SNPs) in a cross between High (AIRmax) and Low (AIRmin) responder mouse lines that we produced by several generations of bidirectional selection for Acute Inflammatory Response. A highly significant linkage signal (LOD score peak of 72) for IL-1β production limited a 4 Mbp interval to chromosome 7. Sequencing of the locus region revealed 14 SNPs between "High" and "Low" responders that narrowed the locus to a 420 Kb interval. Variants were detected in non-coding regions of , and genes and at the first exon of gene, resulting in an E19K substitution in the protein ASC (apoptosis associated speck-like protein containing a CARD) an adaptor molecule in the inflammasome complex. Silencing of inhibited IL1-β production by stimulated macrophages and the E19K ASC mutation carried by AIRmin mice impaired the IL-1β response and the formation of ASC specks in stimulated cells. IL-1β and ASC specks play major roles in inflammatory reactions and in inflammation-related diseases. Our results delineate a novel genetic factor and a molecular mechanism affecting the acute inflammatory response.
Topics: Animals; CARD Signaling Adaptor Proteins; Genetic Linkage; Inflammasomes; Inflammation; Mice; Quantitative Trait Loci
PubMed: 35799794
DOI: 10.3389/fimmu.2022.899569 -
Analytical Sciences : the International... Sep 2023The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP)...
The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP) and 1-napthyl amine (NA) in their mixtures without prior separation via optimization of different experimental conditions (Δλ 70.0 nm, Δν 4000.0 cm, scan rate 240.0 nm/min, 25.0 °C, methanol). Amplitude-concentration plots have been linear for 1-amino pyrene, AP (0.01-0.1 mg/L) and 1-napthyl amine, NA (0.1-1.0 mg/L). In aqueous methanolic binary mixtures, the mean recoveries (RSD, LOD and LOQ) of AP were found to be 100.09% (0.053, 0.008 mg/L and 0.034 mg/L) for emission, 100.11% (0.141, 0.008 mg/L, 0.034 mg/L) for CWSFS, 100.05% (0.109, 0.007 mg/L and 0.032 mg/L) for first derivative CWSFS, 100.00% (0.148, 0.007 mg/L and 0.031 mg/L) for CESFS, 99.99% (0.109, 0.008 mg/L and 0.035 mg/L) for first derivative CESFS modes respectively. Additionally, for NA the mean recoveries (RSD, LOD and LOQ) were 100.29% (0.360, 0.046 mg/L and 0.204 mg/L) for emission, 100.06% (0.089, 0.098 mg/L, 0.436 mg/L) for CWSFS, 100.09% (0.144, 0.065 mg/L and 0.288 mg/L) for first derivative CWSFS, 100.05% (0.178, 0.077 mg/L and 0.339 mg/L) for CESFS, 100.03% (0.181, 0.082 mg/L and 0.364 mg/L) for first derivative CESFS modes respectively. Considering their safety and greenness, these methods might be considered as green tools using analytical eco-scale approaches (eco-scale score 88.0).
PubMed: 37244980
DOI: 10.1007/s44211-023-00368-8 -
International Journal of Molecular... Dec 2022In the current study, the reversed-phased high-pressure liquid chromatography (RP-HPLC) method was proposed for the estimation of lignocaine hydrochloride (LIG),...
In the current study, the reversed-phased high-pressure liquid chromatography (RP-HPLC) method was proposed for the estimation of lignocaine hydrochloride (LIG), hydrocortisone (HYD) and Ketoprofen (KET) according to International Conference for Harmonization (ICH) Q2 R1 guidelines, in a gel formulation. The chromatographic evaluation was executed using Shimadzu RP-HPLC, equipped with a C8 column and detected using UV at 254 nm wavelength, using acetonitrile and buffer (50:50) as a mobile phase and diluent, at flow rate 1 mL/min and n injection volume of 20 μL. The retention time for LIG, HYD, and KET were 1.54, 2.57, and 5.78 min, correspondingly. The resultant values of analytical recovery demonstrate accuracy and precision of the method and was found specific in identification of the drugs from dosage form and marketed products. The limit of detection (LOD) for LIG, HYD, and KET were calculated to be 0.563, 0.611, and 0.669 ppm, while the limit of quantification (LOQ) was estimated almost at 1.690, 1.833, and 0.223 ppm, respectively. The AGREE software was utilized to evaluate the greenness score of the proposed method, and it was found greener in score (0.76). This study concluded that the proposed method was simple, accurate, precise, robust, economical, reproducible, and suitable for the estimation of drugs in transdermal gels.
Topics: Ketoprofen; Chromatography, High Pressure Liquid; Hydrocortisone; Limit of Detection; Reproducibility of Results
PubMed: 36613881
DOI: 10.3390/ijms24010440 -
BMC Nephrology Feb 2017Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Optimising filter life and performance efficiency in continuous renal replacement therapy has been a focus of considerable recent research. Larger high quality studies have predominantly focussed on optimal anticoagulation however CRRT is complex and filter life is also affected by vascular access, circuit and management factors. We performed a systematic search of the literature to identify and quantify the effect of vascular access, circuit and patient factors that affect filter life and presented the results as a meta-analysis.
METHODS
A systematic review and meta-analysis was performed by searching Pubmed (MEDLINE) and Ovid EMBASE libraries from inception to 29 February 2016 for all studies with a comparator or independent variable relating to CRRT circuits and reporting filter life. Included studies documented filter life in hours with a comparator other than anti-coagulation intervention. All studies comparing anticoagulation interventions were searched for regression or hazard models pertaining to other sources of variation in filter life.
RESULTS
Eight hundred nineteen abstracts were identified of which 364 were selected for full text analysis. 24 presented data on patient modifiers of circuit life, 14 on vascular access modifiers and 34 on circuit related factors. Risk of bias was high and findings are hypothesis generating. Ranking of vascular access site by filter longevity favours: tunnelled semi-permanent catheters, femoral, internal jugular and subclavian last. There is inconsistency in the difference reported between femoral and jugular catheters. Amongst published literature, modality of CRRT consistently favoured continuous veno-venous haemodiafiltration (CVVHD-F) with an associated 44% lower failure rate compared to CVVH. There was a trend favouring higher blood flow rates. There is insufficient data to determine advantages of haemofilter membranes. Patient factors associated with a statistically significant worsening of filter life included mechanical ventilation, elevated SOFA or LOD score, elevations in ionized calcium, elevated platelet count, red cell transfusion, platelet factor 4 (PF-4) antibodies, and elevated fibrinogen. Majority of studies are observational or report circuit factors in sub-analysis. Risk of bias is high and findings require targeted investigations to confirm.
CONCLUSION
The interaction of patient, pathology, anticoagulation, vascular access, circuit and staff factors contribute to CRRT filter life. There remains an ambiguity from published data as to which site and side should be the first choice for vascular access placement and what interaction this has with patient factors and timing. Early consideration of tunnelled semi-permanent access may provide optimal filter life if longer periods of CRRT are anticipated. There remains an absence of robust evidence outside of anti-coagulation strategies despite over 20 years of therapy delivery however trends favour CVVHD-F over CVVH.
Topics: Autoantibodies; Calcium; Erythrocyte Transfusion; Fibrinogen; Hemodiafiltration; Humans; Kidney Failure, Chronic; Organ Dysfunction Scores; Platelet Factor 4; Renal Dialysis; Renal Replacement Therapy; Respiration, Artificial; Thrombocytosis; Time Factors
PubMed: 28219324
DOI: 10.1186/s12882-017-0445-5 -
Neurogenetics Dec 2017Amyotrophic lateral sclerosis (ALS) is a motor neuron disease eventually leading to death from respiratory failure. Recessive inheritance is very rare. Here, we describe...
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease eventually leading to death from respiratory failure. Recessive inheritance is very rare. Here, we describe the clinical findings in a consanguineous family with five men afflicted with recessive ALS and the identification of the homozygous mutation responsible for the disorder. The onset of the disease ranged from 12 to 35 years of age, with variable disease progressions. We performed clinical investigations including metabolic and paraneoplastic screening, cranial and cervical imaging, and electrophysiology. We mapped the disease gene to 9p21.1-p12 with a LOD score of 5.2 via linkage mapping using genotype data for single-nucleotide polymorphism markers and performed exome sequence analysis to identify the disease-causing gene variant. We also Sanger sequenced all coding sequences of SIGMAR1, a gene reported as responsible for juvenile ALS in a family. We did not find any mutation in SIGMAR1. Instead, we identified a novel homozygous missense mutation p.(His705Arg) in GNE which was predicted as damaging by online tools. GNE has been associated with inclusion body myopathy and is expressed in many tissues. We propose that the GNE mutation underlies the pathology in the family.
Topics: Adult; Amyotrophic Lateral Sclerosis; Asian People; Chromosome Mapping; Exons; Genotype; Humans; Male; Middle Aged; Mutation; Mutation, Missense; Phenotype; Phosphotransferases (Alcohol Group Acceptor); Polymorphism, Single Nucleotide
PubMed: 29086072
DOI: 10.1007/s10048-017-0527-3 -
Plants (Basel, Switzerland) Sep 2022Soil salinity is a major abiotic stress that causes disastrous losses in crop yields. To identify favorable alleles that enhance the salinity resistance of rice ( L.)...
Soil salinity is a major abiotic stress that causes disastrous losses in crop yields. To identify favorable alleles that enhance the salinity resistance of rice ( L.) crops, a set of 120 Cheongcheong Nagdong double haploid (CNDH) lines derived from a cross between the variety Cheongcheong and the variety Nagdong were used. A total of 23 QTLs for 8 different traits related to salinity resistance on chromosomes 1-3 and 5-12 were identified at the seedling stage. A QTL related to the salt injury score (SIS), qSIS-3b, had an LOD score of six within the interval RM3525-RM15904 on chromosome 3, and a phenotypic variation of 31% was further examined for the candidate genes. Among all the CNDH populations, five resistant lines (CNDH 27, CNDH 34-1, CNDH 64, CNDH 78, and CNDH 112), five susceptible lines (CNDH 52-1, CNDH 67, CNDH 69, CNDH 109, and CNDH 110), and the parent lines Cheongcheong and Nagdong were selected for relative gene expression analysis. Among all the genes, two candidate genes were highly upregulated in resistant lines, including the auxin-responsive protein IAA13 (Os03g0742900) and the calmodulin-like protein 4 (Os03g0743500-1). The calmodulin-like protein 4 (Os03g0743500-1) showed a higher expression in all the resistant lines than in the susceptible lines and a high similarity with other species in sequence alignment and phylogenetic tree, and it also showed a protein-protein interaction with other important proteins. The genes identified in our study will provide new genetic resources for improving salt resistance in rice using molecular breeding strategies in the future.
PubMed: 36235331
DOI: 10.3390/plants11192467 -
Kidney International Feb 2022Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys...
Amyloid A amyloidosis is a serious clinical condition resulting from the systemic deposition of amyloid A originating from serum amyloid A proteins with the kidneys being the most commonly and earliest affected organ. Previously described amyloid A amyloidosis is linked to increased production and deposition of serum amyloid A proteins secondary to inflammatory conditions arising from infectious, metabolic, or genetic causes. Here we describe a family with primary amyloid A amyloidosis due to a chr11:18287683 T>C (human genome version19) mutation in the SAA1 promoter linked to the amyloidogenic SAA1.1 haplotype. This condition leads to a doubling of the basal SAA1 promoter activity and sustained elevation of serum amyloid A levels that segregated in an autosomal dominant pattern in 12 genetically affected and in none of six genetically unaffected relatives, yielding a statistically significant logarithm of odds (LOD) score over 5. Affected individuals developed proteinuria, chronic kidney disease and systemic deposition of amyloid composed specifically of the SAA1.1 isoform. Tocilizumab (a monoclonal antibody against the interleukin-6 receptor) had a beneficial effect when prescribed early in the disease course. Idiopathic forms represent a significant and increasing proportion (15-20%) of all diagnosed cases of amyloid A amyloidosis. Thus, genetic screening of the SAA1 promoter should be pursued in individuals with amyloid A amyloidosis and no systemic inflammation, especially if there is a positive family history.
Topics: Amyloidosis; Humans; Mutation; Promoter Regions, Genetic; Serum Amyloid A Protein
PubMed: 34560138
DOI: 10.1016/j.kint.2021.09.007