Association of interleukin-1 and interleukin-6 levels in lateralized temporal epilepsy patients.

Objectives: To explore the clinical significance of interleukin-1 and interleukin-6 in the development of lateralized temporal epilepsy. METHODS: The prospective study was conducted from January to April of 2022 at the Neurology Department of Training and Research Hospital, Istanbul Medeniyet University, Turkey, and comprised patients with lateralized temporal epilepsy aged 18-86 years who were in the interictal period in group A and healthy controls in group B. The levels of interleukin-1 and interleukin-6 of patients in both groups were compared. Data was analysed using SPSS 25. RESULTS: Of the 92 subjects, 60(65.2%) were in group A; 35(58.3%) were males and 25(41.7%) were females with a median age of 37.5 years (interquartile range: 2.2-42.7 years). There were 32(34.8%) subjects in group B; 19(40.6%) females and 13(40.6%) males with a median age of 40.5 years (interquartile range: 25-50 years) (p>0.05). Within group A, 41(68.3%) patients had left-sided epilepsy and 19(31.7%) had right-sided epilepsy (p<0.001). Both interleukin-1 and interleukin-6 levels were lower in group A than in group B (p<0.001). Both interleukin levels did not significantly differ between right and leftlateralised temporal seizures (p=0.44). In the left-lateralized temporal seizures, interleukin-1 levels correlated with epilepsy duration (p<0.006), lower onset age (p<0.050), and presence of prenatal risk (p<0.028). Interleukin-1 and interleukin-6 levels were positively correlated with each other for lateralized temporal epileptic hemispheres (p<0.001). CONCLUSIONS: Interleukin-1 level was correlated with epilepsy duration, lower onset age, and presence of prenatal risk in the left-lateralized temporal epilepsy.

HPA axis function in patients with right and left focal lateralized epilepsy.

OBJECTIVES: There is a complex, reciprocal link between epilepsy and the hypothalami pituitary-adrenal (HPA) axis. This study aimed to evaluate the role of the HPA axis in individuals with focal epilepsy, including those with right- or left-hemispheric lateralized epilepsy. MATERIAL AND METHODS: The study comprised 60 individuals with focal epilepsy, ages 18 to 85, with seizures coming from a single hemisphere, no destructive lesions on cranial magnetic resonance imaging, and 32 healthy persons. Blood was drawn from the patient and control groups at 8.00 for serum cortisol level and at 23.00 for serum melatonin level. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were administered to both the patient and control groups. RESULTS: Patients showed decreased melatonin levels (p < 0.001) and poorer sleep quality (p = 0.035). The cortisol level of the patients was found to be lower than the cortisol level of healthy individuals, although it was not statistically significant (p = 0.107). Cortisol and melatonin levels did not significantly differ between patients with seizures coming from the right or left hemisphere. The patients with seizures originating from the left hemisphere had a longer duration of epilepsy disease (p = 0.013), higher seizure frequency (p = 0.013), lower age of first seizure onset (p = 0.038), and a higher rate of polytherapy (p = 0.05). CONCLUSION: Low cortisol and melatonin levels in patients with focal epilepsy may be an indicator of disruption in the HPA axis. There is no significant difference in the HPA axis function between patients with focal epilepsy according to the epileptic hemisphere.

Comparing neuropsychological functioning in Turkish patients with right and left temporal lobe epilepsy.

We compared neuropsychiatric evaluations in temporal lobe epilepsy according to the lateralized hemisphere. Forty-one (68.3%) left-sided temporal lobe epilepsy (LTLE) were compared to 19 right-sided temporal lobe epilepsy (RTLE) (31.7%) (p < 0.001). RTLE mean age was 37 (22-46) years, and LTLE mean age 38 was (30-42). RTLE disease duration was 10 (6-20) years, and LTLE was 22 (10-33) (p < 0.013). Gender (man/woman) for RTLE was 7/12, and for LTLE was 18/23. LTLE scored poorer on the Wechsler Memory Scale (WMS)-III's Mental Control Months-error, WMS-V's "Forward Number Range" and "Backward Number Range" than RTLE (p < 0.017, p < 0.023, p < 0.004). There were differences between hemispheres for "Number of Items Remembered with a Hint" and "Total number of Recalled Items" (WMS-IV) (p < 0.038, p < 0.045). LTLE had lower scores in the Verbal Fluency -K-A-S letters words and WAIS (Wechsler Adult Intelligence Scale) similarity than RTLE (p < 0.019, p < 0.024, p < 0.033, p < 0.026). Oktem and Boston-number of Self-Named Items Tests were poorer in LTLE than RTLE (p < 0.05, p < 0.043). Mental Control Months-error (WMS-III), "Total Number of Recalled Items", "Number of Items Remembered with Hint" (WMS-IV), forward and backward number range (WMS-V), Oktem, Verbal Fluency -K,-A,-S letters words, WAIS similarity, and Boston-number of Self-Named Items tests, can help identify lateralization, particularly in LTLE.

The usability of neopterin in determining disease course in COVID-19.

OBJECTIVES: To investigate the usability of neopterin in demonstrating the progression of COVID-19. As a result of uncontrolled activation of COVID-19 monocytes and macrophages, IFN gamma increases and the resulting inflammatory response causes organ damage. IFN released from T cells causes an increase in gamma neopterin levels. Therefore, measurement of neopterin levels can be used to indicate immune system activation and disease progression. METHODS: The study was carried out prospectively in two different centers. The patients were divided into two groups (mild-moderate and severe) and clinical, laboratory, imaging findings and neopterin levels at hospitalization were compared. RESULTS: 100 patients were included in our study, 41 of these patients were male. Forty-six patients were identified as severe COVID-19. C-reactive protein, lymphocyte count, fibrinogen, D dimers, lactate dehydrogenase, procalcitonin, troponin and neopterin levels were significant in indicating disease severity. (p<0.05). In ROC analysis, 0.642 for neopterin, 0.698 C-reactive protein, 0.331 lymphocyte count, 0.679 procalcitonin, 0.633 fibrinogen, 0.667 D dimers, 0.655 troponin and 0.706 lactate dehydrogenase were detected and these values were significant. CONCLUSION: In our study, neopterin was detected as an important indicator in determining the course of COVID-19.

Total Lesion Glycolysis Obtained by FDG PET/CT in Diagnosing Solitary Pulmonary Nodules.

OBJECTIVE: To evaluate the diagnostic performance of total lesion glycolysis (TLG) obtained by 18F-FDG PET/ CT to differentiate malignant solitary pulmonary nodules (SPNs) from benign ones. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Nuclear Medicine, Istanbul Medeniyet University School of Medicine, Istanbul, Turkey, from January 2018 to April 2022. METHODOLOGY: Eighty patients, who were found to have SPNs and underwent PET/CT imaging, were enrolled in this retrospective study. Parameters of PET-CT such as metabolic, volumetric, and metabolovolumetric were assessed concerning diagnostic value. Moreover, maximum standard uptake value (SUVmax) and TLG were combined and compared to improve diagnostic accuracy. RESULTS: The number of the detected benign and malignant SPNs was 38 and 42, respectively. Compared to the benign lesions, the malignant nodules presented significantly higher values in terms of SUVmax, TLG, and the volumes of metabolic tumour (MTV) and CT. Considering all parameters, the highest area under the curve (AUC) was occupied by TLG and SUVmax. The values for the sensitivity, specificity, and accuracy of SUVmax, TLG, and SUVmax combined with TLG were as follows respectively: 97.6%, 63.2%, and 81.2%; 85.7%, 92.1%, and 88.7%; and 85.7%, 94.7%, and 90%. CONCLUSION: The conventional value of SUVmax does not yield satisfactory results in order to separate the malignant nodules from the benign ones. The SUVmax value could be more valuable if it is used with TLG measurement in diagnosing SPNs. KEY WORDS: 18F-FDG PET/CT, SUVmax, TLG, Pulmonary nodule.

Inflammatory markers are associated with the progression of gestational diabetes to metabolic syndrome.

The progression of gestational diabetes mellitus (GDM) to metabolic syndrome (MetS) is associated with systemic inflammation. The aim of this study was to compare the levels of inflammatory markers in former GDM patients with and without MetS. Medical records were screened retrospectively for patients who were diagnosed with GDM 10 (±2) years ago. Former GDM patients were invited to the hospital for an assessment of their current health status. Of 52 women with former GDM, 27 (52%) had MetS. C-reactive protein (CRP), interleukin-6 and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in the MetS group while adiponectin was significantly lower (p < .001, p = .037, p = .002 and p = .013, respectively). There was no significant difference in plasma levels of visfatin and tumour necrosis factor-α. Interleukin-6, CRP, PAI-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions can be implemented. IMPACT STATEMENTWhat is already known on this subject? The progression of 'gestational diabetes mellitus' to 'metabolic syndrome' is associated with systemic inflammation. Up to half of cases with former gestational diabetes mellitus (GDM) eventually progress to metabolic syndrome (MetS).What do the results of this study add? Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase.What are the implications of these findings from clinical practice and/or further research? The progression of GDM to MetS is associated with systemic inflammation. Potential therapies should therefore target this inflammatory state. Interleukin-6, C-reactive protein, plasminogen activator inhibitor-1 and adiponectin may be used as biomarkers to detect MetS in the pre-clinical phase. With timely diagnosis, early interventions and lifestyle changes can be implemented to prevent morbidity and mortality associated with full-blown MetS.

The value of parathyroid scintigraphy on lesion detection in patients with normocalcemic primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases. Most of the patients with PHPT are asymptomatic, and only 20% of them become symptomatic with increasing levels of calcium. It has been reported that normocalcemic primary hyperparathyroidism (NPHPT) may be the incipient period of PHPT where calcium (Ca) levels are in normal range, and it may advance to overt PHPT. Early diagnosis of PHPT is important in order to prevent its complications. In this retrospective study, we aimed to evaluate the role of 99mTc-MIBI parathyroid scintigraphy on lesion detection in patients with NPHPT. MATERIAL AND METHODS: The parathyroid scintigraphy database was reviewed retrospectively in patients with PHPT. 117 patients who underwent 99mTc-MIBI scintigraphy were recruited to the study. Serum calcium level above 10.5mg/dl was considered as hypercalcemia. RESULTS: A total of 117 patients (female/male:98/19) mean serum PTH levels (mean±SD) were 149±97pg/ml in normocalcemic group (Ca:9.6±0.6mg/dl, n:38) and 189±135pg/ml in hypercalcemic group (Ca:11.4±0.6mg/dl, n:79) (p:0.072). The sex and ages were not different between the scintigraphy positive and negative groups, but the lesion detection rates with parathyroid scintigraphy were 42% in normocalcemic group and 81% in hypercalcemic group (p<0.0001). CONCLUSIONS: Several factors including serum Ca, the imaging protocol, existence of multiglandular disease, the size and MIBI biokinetics of the adenoma may influence lesion detectability in parathyroid scintigraphy. Although high serum Ca level is an important parameter in predicting its success, parathyroid scintigraphy remains a valuable diagnostic method even in patients with NPHPT.

Evaluation of treatment efficacy after switching to dolutegravir-lamivudine dual therapy in people living with HIV.

Background: People living with HIV need to use antiretroviral therapy throughout their lives. Objectives: Studies on the efficacy and safety of dual therapy are limited in Turkey. We sought to evaluate the treatment efficacy and side effects among patients who were given a combination of dolutegravir (DTG) and lamivudine (3TC) as a maintenance therapy. Methods: This retrospective, single-centre study included individuals with viral suppression who were older than 18 years of age, living with HIV, switched from a combination antiretroviral therapy regimen to DTG-3TC dual therapy, and followed up for at least 6 months. Results: The study included 63 patients living with HIV. The median age was 42 years (interquartile range (IQR): 36-51 years). The median follow-up under the DTG-3TC regimen was 10.4 months (7.1-16.0 months). In the course of dual therapy, no patients developed any serious adverse effects that would necessitate a therapy switch, but virological blips were seen in two patients. Two patients lost their lives, with one dying from suicide and one dying from respiratory failure associated with the underlying chronic obstructive pulmonary disease. Conclusion: The DTG-3TC dual-therapy regimen is a promising and effective therapy that can be used as a treatment of choice for eligible patients.

Colorectal cancer in the Linxian China Nutrition Intervention Trial: Risk factors and intervention results.

BACKGROUND: Colorectal cancer (CRC) is among the most common cancers in economically developed countries and developing world. While dietary factors are associated with risk of CRC in the West and urban China, little is known about risk or protective factors in rural China. METHODS: The Linxian General Population Nutrition Intervention Trial (NIT) cohort was established over 30 years ago to test whether daily multivitamin/mineral supplements could reduce the incidence and mortality of esophageal/gastric cardia cancer. The cohort included a total of 29,553 healthy participants 40-69 years old who were randomly assigned to supplements or placebos via a 24 fractional factorial study design. We examined risk factors for the development of CRC as well as the effects of four different nutritional factors (Factor A: retinol, zinc; B: riboflavin, niacin; C: ascorbic acid, molybdenum; D: selenium, alpha-tocopherol, beta-carotene,) on CRC incidence following 5.25 years of supplementation in this randomized, placebo-controlled intervention trial. RESULTS: CRC risk increased with age and height as well as piped water usage, family history of CRC, and consumption of foods cooked in oil, eggs, and fresh fruits. No effect on CRC was seen for any of these four intervention factors tested in both genders, but CRC was reduced 37% in females who received Factor D (selenium/alpha-tocopherol/beta-carotene) (RR = 0.63, 95% CI = 0.43-0.92, P = 0.016) compared to females who did not receive Factor D. CONCLUSIONS: In this undernourished rural Chinese population, CRC risk factors in this Chinese cohort showed both similarities and differences compared to Western and urban Asian Chinese populations. Intervention results suggested a potential benefit for women supplemented with selenium/alpha-tocopherol/beta-carotene.

Is mean platelet volume related to disease activity in systemic lupus erythematosus?

INTRODUCTION: Systemic lupus erythematosus (SLE) is a connective tissue disease that is chronic, recurrent and multisystem with unknown aetiology. There is still no single biomarker that is pathognomonic for the disease. We know that platelets are the main part of haemostasis and thrombosis. We aimed to investigate whether there is a connection between MPV with SLE and inflammatory markers. MATERIAL AND METHODS: We have included 39 female patients with SLE and 45 controls in this study. In both groups, erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) levels and MPV levels were investigated. Clinical findings and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were evaluated in patients. RESULTS: There was no significant difference between the two groups in terms of demographic data. The MPV was 8.1 ± 0.5 (mean ± SD) in the patient's group and 7.6 ± 0.3 in the control group. There was a significant difference between the two groups in terms of MPV (P < .001). The ESR level was 30.7 ± 29 in the patient's group and 16.7 ± 10 in the control group. In the patient's group, the CRP levels were higher compared with that of the control group (8.2 ± 13, 4.5 ± 4, respectively). We found a statistically significant positive correlation between MPV with arthritis (r = .310,P = .004), nephritis (r = .446,P < .001), central nervous system involvement (r = .241,P = .027), vasculitis (r = .228,P = .037) and SLEDAI (r = .329,P = .002). In our study, we found increased levels of MPV in patients with SLE. Also, we observed a positive correlation among MPV with sedimentation, CRP, clinical manifestations and SLEDAI. CONCLUSION: We consider that MPV may be a new activation indicator for the SLE.

Occult Adrenal Insufficiency in Renal Amyloidosis Patients.

OBJECTIVE: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. METHODS: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 µg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. RESULTS: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients' stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). CONCLUSION: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.

A Five-Year Retrospective Analysis of Basal Cell Carcinoma: A Monocentric Study.

OBJECTIVE: Our aim in this study is to define the histopathological subtypes, body site distribution, and incidence rates of single or multiple of BCCs. The study is conducted on patients from a single institution in Istanbul which has a migrant-receiving population reflecting that of the country overall. METHOD: We retrospectively analyzed data concerning 896 cases of BCC seen between 2014 and 2018. Data about patient demographics (age and sex), tumor diameter,its anatomic localization, histological type, presence of ulceration, lymphovascular/perineural invasion, and single or multiple tumor formations were retrieved from both the hospital's automated system and archived records of the pathology clinic. RESULTS: Our univariate analysis showed that the patients' age, tumor size, and tumor multicentricity were all significantly related to their gender (p=0.011, p=0.001, and p=0.021, respectively). Further, age, male gender, and tumor size were all significantly related to tumor multicentricity (p=0.003, p=0.021, and p=0.001, respectively). BCC was most commonly found in male, and the diameters of the BCC tumors were also larger in male patients. Multiple BCC was more frequently seen in older and male patients, and the tumors had larger diameters in these groups. The nodular type of BCC was the most frequently seen type in all age groups. CONCLUSION: As our study is the first BCC study that has the greatest number of cases in Turkey and as Istanbul reflects the population of Turkey, it is important for the data of BCC cases in Turkey.

Genetic Characterization of Three Distinct Mechanisms Supporting RNA-Driven DNA Repair and Modification Reveals Major Role of DNA Polymerase ζ.

DNA double-stranded breaks (DSBs) are dangerous lesions threatening genomic stability. Fidelity of DSB repair is best achieved by recombination with a homologous template sequence. In yeast, transcript RNA was shown to template DSB repair of DNA. However, molecular pathways of RNA-driven repair processes remain obscure. Utilizing assays of RNA-DNA recombination with and without an induced DSB in yeast DNA, we characterize three forms of RNA-mediated genomic modifications: RNA- and cDNA-templated DSB repair (R-TDR and c-TDR) using an RNA transcript or a DNA copy of the RNA transcript for DSB repair, respectively, and a new mechanism of RNA-templated DNA modification (R-TDM) induced by spontaneous or mutagen-induced breaks. While c-TDR requires reverse transcriptase, translesion DNA polymerase ζ (Pol ζ) plays a major role in R-TDR, and it is essential for R-TDM. This study characterizes mechanisms of RNA-DNA recombination, uncovering a role of Pol ζ in transferring genetic information from transcript RNA to DNA.

Ribonucleotide incorporation in yeast genomic DNA shows preference for cytosine and guanosine preceded by deoxyadenosine.

Despite the abundance of ribonucleoside monophosphates (rNMPs) in DNA, sites of rNMP incorporation remain poorly characterized. Here, by using ribose-seq and Ribose-Map techniques, we built and analyzed high-throughput sequencing libraries of rNMPs derived from mitochondrial and nuclear DNA of budding and fission yeast. We reveal both common and unique features of rNMP sites among yeast species and strains, and between wild type and different ribonuclease H-mutant genotypes. We demonstrate that the rNMPs are not randomly incorporated in DNA. We highlight signatures and patterns of rNMPs, including sites within trinucleotide-repeat tracts. Our results uncover that the deoxyribonucleotide immediately upstream of the rNMPs has a strong influence on rNMP distribution, suggesting a mechanism of rNMP accommodation by DNA polymerases as a driving force of rNMP incorporation. Consistently, we find deoxyadenosine upstream from the most abundant genomic rCMPs and rGMPs. This study establishes a framework to better understand mechanisms of rNMP incorporation in DNA.

Following Chemotherapy: Serum Cytokine (Tumor Necrosis Factor, Interleukin-2, Interleukin-11), Immunoglobulin, Complement, Vascular Endothelial Growth Factor Levels, and the Systemic Symptoms like Capillary Leak Syndrome.

Several problems such as myalgia, arthralgia, fever, dyspnea, generalized edema, and pleural effusion can occur in cancer patients following the chemotherapy, especially at the first cycle of the first chemotherapy treatment. Although it is assumed that some cytokines are associated with the development of these symptoms and signs, their pathophysiology has not been discovered completely yet. They are usually mild, but they may rarely progress to the severe stage of "Systemic Capillary Leak Syndrome" with a high mortality rate. The objective of this study was to investigate the association between the serum levels of interleukin-2 (IL-2), interleukin-11 (IL-11), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and these symptoms and signs. A total of 44 cancer patients who had neither heart, lung, liver, renal, or thyroid disease were recruited into this study. Their symptoms and signs were examined and questioned before the first cycle of the first chemotherapy treatment and the 24 h after this chemotherapy. All participant's serum samples were taken, and the VEGF, TNF, IL-2, and IL-11 levels were studied. There was no association between the chemotherapeutic drugs, and the symptoms and signs such as edema, dyspnea, coughing, and flu-like symptoms. There was a significant decrease in IL-11 levels in the other treatment group compared with the group receiving paclitaxel, docetaxel, gemcitabine, and vinorelbine in the first day following chemotherapy (P = .006). However, no relation was observed between the symptoms and signs, the response to the chemotherapy, and the serum levels of VEGF, TNF, IL-2, and IL-11. These symptoms and life-threatening syndrome have been a current topic between the clinicians. Although some drugs and mediators are accused, its pathophysiology has not been discovered completely yet. In this study, we could not detect any association between the symptoms, signs, and the cytokine levels following the chemotherapy.

Modulating native GABAA receptors in medulloblastoma with positive allosteric benzodiazepine-derivatives induces cell death.

PURPOSE: Pediatric brain cancer medulloblastoma (MB) standard-of-care results in numerous comorbidities. MB is comprised of distinct molecular subgroups. Group 3 molecular subgroup patients have the highest relapse rates and after standard-of-care have a 20% survival. Group 3 tumors have high expression of GABRA5, which codes for the α5 subunit of the γ-aminobutyric acid type A receptor (GABAAR). We are advancing a therapeutic approach for group 3 based on GABAAR modulation using benzodiazepine-derivatives. METHODS: We performed analysis of GABR and MYC expression in MB tumors and used molecular, cell biological, and whole-cell electrophysiology approaches to establish presence of a functional 'druggable' GABAAR in group 3 cells. RESULTS: Analysis of expression of 763 MB tumors reveals that group 3 tumors share high subgroup-specific and correlative expression of GABR genes, which code for GABAAR subunits α5, ß3 and γ2 and 3. There are ~ 1000 functional α5-GABAARs per group 3 patient-derived cell that mediate a basal chloride-anion efflux of 2 × 109 ions/s. Benzodiazepines, designed to prefer α5-GABAAR, impair group 3 cell viability by enhancing chloride-anion efflux with subtle changes in their structure having significant impact on potency. A potent, non-toxic benzodiazepine ('KRM-II-08') binds to the α5-GABAAR (0.8 µM EC50) enhancing a chloride-anion efflux that induces mitochondrial membrane depolarization and in response, TP53 upregulation and p53, constitutively phosphorylated at S392, cytoplasmic localization. This correlates with pro-apoptotic Bcl-2-associated death promoter protein localization. CONCLUSION: GABRA5 expression can serve as a diagnostic biomarker for group 3 tumors, while α5-GABAAR is a therapeutic target for benzodiazepine binding, enhancing an ion imbalance that induces apoptosis.

An Approach to Detect and Study DNA Double-Strand Break Repair by Transcript RNA Using a Spliced-Antisense RNA Template.

A double-strand break (DSB) is one of the most dangerous DNA lesion, and its repair is crucial for genome stability. Homologous recombination is considered the safest way to repair a DNA DSB and requires an identical or nearly identical DNA template, such as a sister chromatid or a homologous chromosome for accurate repair. Can transcript RNA serve as donor template for DSB repair? Here, we describe an approach that we developed to detect and study DNA repair by transcript RNA. Key features of the method are: (i) use of antisense (noncoding) RNA as template for DSB repair by RNA, (ii) use of intron splicing to distinguish the sequence of the RNA template from that of the DNA that generates the RNA template, and (iii) use of a trans and cis system to study how RNA repairs a DSB in homologous but distant DNA or in its own DNA, respectively. This chapter provides details on how to use a spliced-antisense RNA template to detect and study DSB repair by RNA in trans or cis in yeast cells. Our approach for detection of DSB repair by RNA in cells can be applied to cell types other than yeast, such as bacteria, mammalian cells, or other eukaryotic cells.

Comparison of composite indices with global synovitis score on ultrasound for detecting remission.

We aimed to compare composite indices with Ultrasound Global Synovitis Score (GLOESS) for remission in rheumatoid arthritis (RA). RA patients in remission according to the clinician were investigated with Disease Activity Score28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and RAPID-3 (Routine Assessment of Patient Index Data 3). Ultrasonography was performed using the GLOESS scores. Patients in CDAI-remission had lower GLOESS (median (IQR), 5(3-9.75) vs 7(4-11.75), p = 0.048) with a similar trend in SDAI (5(3-9.25) vs 7(4-11.25), p = 0.064). This was not observed with DAS28-CRP and RAPID3. Our results show that CDAI is superior to other indices to assess remission in RA.

Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair.

RNA can serve as a template for DNA double-strand break repair in yeast cells, and Rad52, a member of the homologous recombination pathway, emerged as an important player in this process. However, the exact mechanism of how Rad52 contributes to RNA-dependent DSB repair remained unknown. Here, we report an unanticipated activity of yeast and human Rad52: inverse strand exchange, in which Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA. We show that in eukaryotes, inverse strand exchange between homologous dsDNA and RNA is a distinctive activity of Rad52; neither Rad51 recombinase nor the yeast Rad52 paralog Rad59 has this activity. In accord with our in vitro results, our experiments in budding yeast provide evidence that Rad52 inverse strand exchange plays an important role in RNA-templated DSB repair in vivo.

Six-joint ultrasound in rheumatoid arthritis: a feasible approach for implementing ultrasound in remission.

OBJECTIVES: Subclinical disease activity in rheumatoid arthritis (RA) detected by imaging methods is predictive for flares and damage. Lack of time is the major limitation for not screening for subclinical disease in routine practice. We aimed to determine the most feasible protocol to screen patients with no clinical disease activity by ultrasound (US). METHODS: A hundred consecutive RA patients with no clinical activity according to the physician had an US scan for 38 joints. The prevalence of power Doppler (PD) signal in each joint was determined and different combinations of joints were assessed for their ability to capture this information. The most practical combination with a good sensitivity was tested in another group of 50 RA patients. RESULTS: Having any PD signal was not linked to the disease activity parameters whereas presence of PD of ≥2 was associated with higher DAS28CRP. Sixty patients had at least one joint with PD of grade ≥2 (60%). A combination of the wrists and 2nd-3rd MCP joints bilaterally (PD-6 joints) was able to detect 45/60 (75%) cases with PD signals and 45% of the whole patient population. The correlation between PD-38 and PD-6 joints was excellent (r=0.820, p<0.0001). PD-6 joints in the 2nd cohort was also able to detect 22/50 (44%) of the whole group. CONCLUSIONS: Subclinical disease activity could be detected in 60% of RA patients when 38 joints screened by US. Limiting the screening to wrists, 2nd-3rd MCPs bilaterally was acceptable as it detected 75% of cases with subclinical disease and increased the feasibility.