HLA-DR, DQ genotypes of celiac disease patients and healthy subjects from the West of Ireland

Celiac disease (CD) has one of the strongest class II HLA associations of any human illness. We used DNA-RFLP typing to study the class II HLA genotypes of celiac disease patients from the West of Ireland, the geographic area with the highest rate of celiac disease in the world. We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7. This was done by clearly distinguishing DR7, DQ2 haplotypes from DR7, DQ9 haplotypes, and by "subtraction analysis" of haplotype frequencies. As reported in other populations, most of the patients without DR3 were heterozygous for DR7 and DR11 or 12 (DR5), or had DR4. We used PCR-RFLP and direct sequencing of amplified DNA to examine HLA-DR4 subtypes. The frequency of HLA-DR4 was markedly decreased in patients compared with controls (p=0.000001) and there was a significant alteration of DR4 subtypes of the patients compared with controls (p=0.0227). Moreover, all of the CD patients (5 of 5) with DR4 had a haplotype associated with the DQB1*0302 allele compared with only 11 of 23 control subjects with DR4. Our results in this population with exceptionally high risk of CD strongly support the DQ heterodimer hypothesis and suggest that the recently described sequence difference between the DQB1*02 alleles of DR3 and DR7 may contribute to a synergistic increased risk when these haplotypes are inherited together. In addition, our findings suggest a role for HLA-DQ in DR4-associated CD.     

Fibrolamellar hepatocellular carcinoma coexistent with a hepatocellular carcinoma of common type: Report of a case

A case of small fibrolamellar hepatocellular carcinoma (HCC) coexistent with a HCC of common type is herein reported. A 56-year-old man was diagnosed as having multi-nodular type HCC with liver cirrhosis. The serum alpha-fetoprotein (AFP) level was slightly increased. The patient underwent a partial caudate lobectomy and lateral segmentectomy. Histologically, both resected tumors were small HCCs measuring less than 2 cm in diameter. One was a fibrolamellar type located in the caudate lobe, while the other was the common type in the lateral segment of the liver. Positive immunohistochemical staining for AFP was observed in the tumor cells of the HCC of common type but was not observed in the fibrolamellar HCC. We also reviewed previously reported cases of fibrolamellar HCC in Japan, and discussed the clinicopathologic implications of this disease.     

Composite indicators of dental health: functioning teeth and the number of sound-equivalent teeth (T-Health)

Abstract –This study investigated whether two new composite dental indicators -"the number of functioning teeth" and "the number of sound-equivalent teeth" are more efficient than the conventional DM FT index in revealing the social and behavioural factors which are significantly related to oral health status. The arbitrary set of weights given to the T-Health indicator was also evaluated. The number of functioning teeth was defined as the aggregate of filled (otherwise sound) and sound teeth. The T-Health was defined as a weighted average of sound teeth, filled (otherwise sound) teeth and teeth with some decay, the weights intended in principle to represent the relative amounts of sound tissue in these three categories of teeth. An arbitrary set of weights was used: 4, 2, and 1 for sound, filled, and decayed teeth, respectively. 164 families (father, mother and at least one 13-yr-old child) from Belo Horizonte, Brazil, were randomly selected from 13-yr-old children from private and state schools. The parents'ages ranged from 35 to 44 yr. Socio-economic status, area of residence, level of education, family income, sugar consumption, toothbrushing frequency and type of dental attendance were the social and behavioural oral health risk-factors considered in this study. The results indicated that the two new dental indicators are more sensitive to the influence of social and behavioural factors, such as those investigated here, than is the traditional DM FT index. A different set of weights (4, I, and I for sound, filled, and decayed) was suggested for the construction of the T-Health.     

分级诊疗背景下多病共存患者就医机构选择行为及其影响因素研究

背景 近年来,国内针对多病共存患者在分级诊疗背景下就医机构选择行为的研究较少,研究多病共存患者的就医机构选择行为有重要的现实意义。目的 以分级诊疗为视角,分析多病共存患者就医机构选择行为及其影响因素,为进一步落实分级诊疗制度和合理配置医疗资源提供研究参考。方法 采用随机抽样法,选取2019-06-01至2020-01-01在上海市杨浦区中心医院医疗联合体（上海市杨浦区中心医院和上海市杨浦区定海、延吉、长白社区卫生服务中心）就诊的多病共存患者为研究对象。采用自设问卷对其进行调查,收集多病共存患者的一般资料,了解其对分级诊疗政策的认知情况及实际遵守情况、在不同疾病控制状况下至社区卫生服务中心首诊的意愿,以及其选择就诊医疗机构时考虑的因素等。采用二分类Logistic回归分析多病共存患者此次因病就医是否选择至社区卫生服务中心首诊的影响因素。结果 共发放1 100份问卷,回收有效问卷1 072份,有效问卷回收率为97.45%。1 072例多病共存患者中,老年（≥60岁）多病共存患者占85.07%(912/1 072)。624例（58.21%）患者表示知晓分级诊疗制度;940例（87.69%）患...     

妊娠早期女性非稳态负荷水平与抑郁的相关性研究

背景 已知慢性应激与抑郁发生相关,非稳态负荷（AL）作为评估机体慢性应激反应的综合生理指标可能在抑郁的发生过程中起着重要作用。目的 探讨妊娠早期女性AL水平与抑郁的关系。方法 采用便利抽样法,选取2021年11月—2022年6月于中国人民解放军联勤保障部队第901医院、六安市金安区妇幼保健院产检的630例妊娠早期女性为研究对象,根据有无抑郁分为抑郁组（n=162）和非抑郁组（n=468）。采用一般资料调查表、妊娠相关焦虑量表、爱丁堡产后抑郁量表进行问卷调查,通过体格检查和实验室检查收集AL相关数据。采用多因素Logistic回归模型分析妊娠早期女性AL与抑郁的相关性。结果 630例妊娠早期女性抑郁发生率为25.7%(162/630)。低水平AL(AL<3分)孕妇427例（67.8%）,高水平AL(AL≥3分)孕妇203例（32.2%）。多因素Logistic回归分析显示,高水平AL是妊娠早期女性抑郁的危险因素[OR=1.651,95%CI(1.096,2.489),P<0.05]。结论 妊娠早期女性AL与抑郁存在正向关联,高水平AL会增加抑郁的发生风险。     

Elongated peptides,not the predicted nonapeptide stimulate a major histocompatibility complex class I-restricted cytotoxic T lymphocyte clone with specificity for a bacterial heat shock protein

The peptides recognized by an H-2D^b-restricted CD8 cytotoxic T lymphocyte (CTL) clone which is specific for the 60-kDa mycobacterial heat shock protein (hsp) and cross-reacts with stressed host cells were characterized. None of the nonapeptides from hsp60 conforming to the H-2D^b binding motif were able to sensitize target cells for lysis by this CTL clone. Sequence analysis of the stimulatory fraction from a trypsin digest of hsp60, together with synthetic peptide studies, defined a cluster of overlapping epitopes. Carboxy-terminal extension by at least one amino acid of the nonamer predicted to bind best to H-2D^b was essential for CTL recognition. Two such elongated peptides, a 10-mer and a 12-mer stimulated the clone at similarly low concentrations in the 100 pM range. We assume that these two peptides comply best with the natural epitope. In contrast, the 11-mer was inactive. The stimulatory 10-mer bound to H-2D^b with an efficacy similar to that of the nonapeptide corresponding to the H-2D^b motif, as revealed by peptide induced major histocompatibility complex (MHC) surface expression on RMA-S cells and competitive blocking of epitope recognition by the nonamer. Binding of these carboxy-terminally extended peptides to the MHC groove can be explained by anchoring through the amino acid residue Asn in position 5 of the peptide and by intrusion of the hydrophobic carboxy-terminal Ala (10-mer) or Leu (12-mer), but not Gly (11-mer), into the hydrophobic pocket of the H-2D^b cleft. Because the carboxy-terminal part is thus larger than predicted this region of the peptide may arch up from the binding groove. We assume that recognition of steric components of the MHC/peptide complex broaden the range of epitope specificity for a single T cell receptor. This flexibility not only promotes recognition of several overlapping peptides from a single antigen, but may also increase the chance of cross-reaction with similar peptides from unrelated proteins, including autoantigens. Consistent with this latter assumption, the T cell clone cross-recognizes mycobacterial hsp60 and stressed host cells.     

Mutations in activation-induced cytidine deaminase in patients with hyper IgM syndrome

Recent studies have shown that mutations in a newly described RNA editing enzyme, activation-induced cytidine deaminase (AID), can cause an autosomal recessive form of hyper IgM syndrome. To determine the relative frequency of mutations in AID, we evaluated a group of 27 patients with hyper IgM syndrome who did not have defects in CD40 ligand and 23 patients with common variable immunodeficiency. Three different mutations in AID were identified in 18 patients with hyper IgM syndrome, including 14 French Canadians, 2 Lumbee Indians, and a brother and sister from Okinawa. No mutations were found in the remaining 32 patients. In the group of patients with hyper IgM syndrome, the patients with mutations in AID were older at the age of diagnosis, were more likely to have positive isohemagglutinins, and were less likely to have anemia, neutropenia, or thrombocytopenia. Lymphoid hyperplasia was seen in patients with hyper IgM syndrome and normal AID as well as the patients with hyper IgM syndrome and defects in AID.     

Copy number variation burden does not predict severity of neurodevelopmental phenotype in children with a sex chromosome trisomy

Sex chromosome trisomies (SCTs) (XXX, XXY, and XYY karyotypes) are associated with an elevated risk of neurodevelopmental disorders. The range of severity of the phenotype is substantial. We considered whether this variable outcome was related to the presence of copy number variants (CNVs)—stretches of duplicated or deleted DNA. A sample of 125 children with an SCT were compared with 181 children of normal karyotype who had been given the same assessments. First, we compared the groups on measures of overall CNV burden: number of CNVs, total span of CNVs, and likely functional impact (probability of loss‐of‐function intolerance, pLI, summed over CNVs). Differences between groups were small relative to within‐group variance and not statistically significant on overall test. Next, we considered whether a measure of general neurodevelopmental impairment was predicted by pLI summed score, SCT versus comparison group, or the interaction between them. There was a substantial effect of SCT/comparison status but the pLI score was not predictive of outcomes in either group. We conclude that variable presence of CNVs is not a likely explanation for the wide phenotypic variation in children with SCTs. We discuss methodological challenges of testing whether CNVs are implicated in causing neurodevelopmental problems.     

<Emphasis Type="Italic">Helicobacter pylori</Emphasis> and <Emphasis Type="Italic">cagA</Emphasis> and <Emphasis Type="Italic">vacA</Emphasis> gene status in children from Brazil with chronic gastritis

Helicobacter pylori has been shown to be strongly associated with chronic gastritis, gastric and duodenal ulceration, and is a risk factor for gastric carcinoma. Histology, urease, culture, and polymerase chain reaction have been employed as for H. pylori diagnostic methods, pre and post treatment or during follow-up of dyspeptic adult individuals referred for endoscopy. In order to obtain a more-sensitive and specific method for H. pylori detection, we evaluated gastric body and antrum biopsies of 134 consecutive Brazilian consecutive dyspeptic children aged 1-16 years by rapid urease test, histology and polymerase chain reaction using two pairs of oligonucleotides. Our results indicated that polymerase chain reaction with Southern blotting and hybridization with specific chemiluminescent probes increased the number of positive H. pylori patients by 35%. The genotyping of H. pylori strains directly from gastric biopsy using the same nucleic acid methodology revealed that there is no association of chronic gastritis in our infant patients with vacA s1 and the presence of the cagA gene. These data suggest an initial infection of children with normal mucosa and probably others factors than vacA s1 genotype or the presence of the cagA gene are associated with the onset of gastric disease. Altogether, our results reinforce the need for using more sensitive diagnostic methods in order to understand the role of H. pylori in the genesis of gastric disease in children and its progression in adults.