New Evidence of Significant Association between EBV Presence and Lymphoproliferative Disorders Susceptibility in Patients with Rheumatoid Arthritis: A Systematic Review with Meta-Analysis

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD.     

Detecting sarcasm from paralinguistic cues: Anatomic and cognitive correlates in neurodegenerative disease

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimer's disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference — Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes–no questions about the speaker's intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE < 0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speaker's paradoxical intentions.     

Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines

Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.     

Using the global functioning social and role scales in a first-episode sample

Aims: Dysfunction in social and role functioning is a hallmark of schizophrenia, which is present in both the prodromal phase and at the first episode of the illness. Two new measures, Global Functioning: Social and Global Functioning: Role, were developed to address functioning in the prodromal phase of the illness. The purpose of this study was to determine if these measures would be useful in a first episode population. Methods: Forty‐eight stable outpatients were assessed using the new social and role scales. A subsample of 33 subjects was assessed at 6 and 12 months. All subjects were additionally assessed using standardized measures of psychotic symptoms, social functioning, self‐esteem and beliefs about illness. Results: Average ratings on the Global Functioning: Social and Role scales were 6 (standard deviation (SD) = 1.60) and 5.5 (SD = 2.2), respectively. Both social and role scales were significantly correlated with relevant subscales on the Social Functioning Scale. Good social but not role functioning was related to low levels of both positive and negative symptoms and to high self‐esteem. Role but not social functioning was related to personal beliefs about the illness, such as having control over illness and feeling less stigmatized. Repeated measures analyses demonstrated no change over time for either social or role functioning. Conclusion: The Global Functioning: Social and Role scales appear to be useful and valid measures of functioning in first‐episode patients. These ratings are similar to those reported in prodromal studies supporting the idea that poor functioning may be a stable long‐standing deficit.     

Genetic parameters of five new European Standard Set STR loci (D10S1248, D22S1045, D2S441, D1S1656, D12S391) in the population of eastern Croatia

Aim

To establish allele frequencies and genetic parameters in eastern Croatia population and to compare them with those in other populations. The second aim was to compare the genetic profiles obtained with different forensic kits amplifying the same genetic markers.

Methods

Blood samples of 217 unrelated individuals from eastern Croatia were genotyped using AmpFlSTR NGM kit. Allele distribution and other genetic parameters were determined for 15 short tandem repeat (STR) loci, including the 5 loci recently added to the European Standard Set (ESS) of STR loci (D10S1248, D22S1045, D2S441, D1S1656, and D12S391). Ninety-six samples underwent duplicate analysis using AmpFlSTR Identifiler kit.

Results

Power of discrimination was highest for the two new ESS loci, D1S1656 (0.97254) and D12S391 (0.97339). Comparison of allele frequencies for 5 new ESS loci in our sample with previously published population data showed a significant difference from Maghreb population on D2S441 and from American Caucasian population on D1S1656. Comparison of allele frequencies for standard 10 STR loci with all the neighboring populations’ data showed a significant difference only from Albanian population (on D2S1338, D18S51, and TH01). Discordant genotypes were observed in 5 (5.2%) samples at a single locus when amplified with both AmpFlSTR NGM and AmpFlSTR Identifiler kit.

Conclusion

New ESS STR loci are highly polymorphic and short, and therefore very useful for the analysis of challenging forensic samples. DNA samples purposed for establishing databases should be routinely amplified in duplicate.To facilitate DNA profiles comparison between databases of different European countries, The European Network of Forensic Science Institutes (ENFSI) and European DNA Profiling Group (EDNAP) have recently added five new loci (D10S1248, D22S1045, D2S441, D1S1656, and D12S391) to the European Standard Set of short tandem repeat (STR) loci (1,2). These new loci were included into the AmpFlSTR NGM PCR amplification kit (NGM kit; Life Technologies, Foster City, CA, USA).The Laboratory for DNA Analysis in Osijek was established to participate in the identification of missing persons after the war in Croatia (1991-1995). In collaboration with the laboratories in Zagreb and Split, a database of genotypes of missing persons’ relatives was created including approximately 5000 persons. The greatest part of the included genetic information is based on the 15 loci incorporated in AmpFlSTR Identifiler PCR amplification kit (Identifiler kit; Life Technologies, Foster City, CA, USA). Skeletal remains are identified by comparing the genotype of each piece of skeletal remains with the genotypes in the missing persons’ relatives database. Such non-targeted matching in a database containing several thousands genotypes considerably decreases the reliability of the established match. Still, the majority of identified skeletal remains were matched in such a way, as genotypes of the missing persons from the father-mother-child trio. Even within so large a database, hundreds of genotypes of skeletal remains still do not have a match, due to a lack of adequate relatives. Matching a profile created from a piece of skeletal remains across the whole database returns many adventitious matches, partly because some genotyped loci have low discrimination power (2). An especially large number of adventitious matches is present if the genetic profile from skeletal remains is partial.In a targeted approach to DNA typing, loci on the Y-chromosome and mtDNA can be amplified, but at a database level more useful are the loci on somatic chromosomes. Evidential value of a genetic match based on STR typing relies on high polymorphism and a large number of STR loci. In order to obtain as much as possible genetic information, we used the NGM kit. Our aim was to increase the number of genetic markers in order to achieve higher evidential value of STR typing and to amplify short STR loci, often better preserved in degraded samples. Especially valuable are three new “mini” STR loci (D10S1248, D22S1045, and D2S441), engineered to produce short amplicons (up to 150 bp) that are more successfully obtained from the most degraded samples. The remaining two new loci (D1S1656 and D12S391) are also relatively short and highly polymorphic (3-7). Besides obtaining information on the 5 new loci, the NGM kit includes improved chemistry that maximizes performance on challenging samples.In the new European Standard Set (ESS) of STR loci, allele distribution and genetic parameters still have to be determined. A population study on the new loci has been performed for several countries (including Belgium, Germany, Hungary, Maghreb countries, Poland, and USA) (7-12). However, there has been no such study either for Croatian or its neighboring populations. Therefore, we carried out a population study on a sample from eastern Croatia, which might be the most appropriate regional sample, because this part of the country sustained the greatest human losses during the war. Since the greatest part of our relatives’ database is based on the Identifiler kit, which shares 10 loci with NGM kit (D3S1358, vWA, D16S539, D2S1338, D8S1179, D21S11, D18S51, D19S433, TH01, and FGA), we compared the genetic profiles obtained with both of these kits amplifying the same genetic markers. We also compared the obtained genetic parameters for 15 STR loci with the available population data from the neighboring countries.     

Clinical implications from drug–drug and drug–disease interactions in older people

相似文献   

The WHO diagnostic criteria for polycythemia vera—role of red cell mass versus hemoglobin/hematocrit level and morphology

Regarding diagnosis of polycythemia vera (PV), discussion persists about hemoglobin (Hb) and/or hematocrit (Hct) threshold values as surrogate markers for red cell mass (RCM) and the diagnostic impact of bone marrow (BM) morphology. We performed a retrospective study on 290 patients with PV (151 males, 139 females; median age 65 years) presenting with characteristic BM features (initial biopsies, centralized evaluation) and endogenous erythroid colony (EEC) formations. This cohort included (1) a group of 229 patients when following the 2008 versus 256 patients diagnosed according to the 2016 World Health Organization (WHO) guidelines, all presented with increased RCM; (2) masked PV patients with low Hb (n?=?143)/Hct (n?=?45) recruited from the 2008 WHO cohort; (3) a cohort of 17 PV patients with elevated diagnostic Hb/Hct levels but low RCM; and (4) nine PV patients with increased RCM, opposing low Hb/Hct values. All patients were treated according to current PV guidelines (phlebotomies 87%, hydroxyurea 79%, and acetylsalicylic acid 87%). Applying the 2016 WHO criteria significantly increased concordance between RCM and Hb values compared with the 2008 WHO criteria (90 vs. 43% in males and 83 vs. 64% in females). Further analysis of the WHO 2016 PV cohort revealed that increased RCM is associated with increased Hb/Hct (93.8/94.6%). Our study supports and extends the diagnostic impact of the 2016 revised WHO classification for PV by highlighting the importance of characteristic BM findings and implies that Hb/Hct threshold values may be used as surrogate markers for RCM measurements.