The Involvement of miR-21 in the Molecular Pathogenesis of Richter Transformation

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Next generation sequencing for characterization of mitochondrial genome in pituitary adenomas

Introduction Disrupted mitochondrial functions and genetic variations of mitochondrial DNA (mtDNA) have been observed in different tumors. Regarding pituitary adenomas mtDNA was evaluated only in oncocytic type using PCR based methods and it showed high prevalence of Complex I variants. Next generation sequencing (NGS) allows high throughput sequencing and it is useful for accurate identification of heteroplasmy of mitochondrial genome as well. Aim We aimed to investigate the entire mitochondrial genome in different adenoma types. Material and methods We collected 22 gonadotroph (GO), 11 growth hormone producing (GH) and 11 null-cell (NC) adenoma specimens from samples removed by transsphenoidal surgery. From fresh frozen tissues DNA extraction was performed using QIAamp Fast DNA Tissue Kit. For library preparation VariantPro™ Amplicon Mitochondrion Panel kit was used. The total mtDNA (16569 bp) was sequenced on Illumina MiSeq Instrument. Following complex bioinformatic analysis Revised Cambridge Reference Sequence (rCRS) of the human mitochondrial DNA was used as reference. Heteroplasmy was determined using 3% cutoff. Results. The whole mitochondrial genome were covered by 630±370 (avg±SE) reads per base. 496 variants were identified in adenomas compared to reference sequence. Overall a low (7.22%) heteroplasmy prevalence was found. Based on mitochondrial sequence variants by hierarchical cluster analysis we could not discriminate different adenoma types. No association between Ki-67 index or recurrent-nonrecurrent status of adenomas and mitochondrial variants were detected. Four variants appeared more often in null-cell adenomas compared to gonadotroph adenomas (chrM_188: 18% vs. 0%, chrM_16093: 18% vs. 0%, chrM_185: 27% vs. 0% and chrM_14798: 36% vs. 5%; Padj=0.0246, 0.0246, 0.01542 and 0.01829, respectively). Of these variants chrM_14798, chrM_4216 and chrM_15452 are non-synonymous polymorphisms leading to amino acid change in MT-CYB (mitochondrially encoded cytochrome b) and in MT-ND1 (mitochondrially encoded NADH dehydrogenase 1) genes. We identified chrM_16189 variant (non-protein coding variant) in 40% (6/15) of nonrecurrent adenomas compared to recurrent ones where this variant was not present (0/11) (p=0.0209). Conclusions Next-generation sequencing is a reliable method for investigating mitochondrial genome and heteroplasmy in pituitary adenomas. In pituitary adenomas the prevalence of heteroplasmy of mitochondrial genome is low suggesting that these alterations may not influence mitochondrial function considerably. Of pituitary tumours only null cell adenomas possess alterations of mitochondrial genome with potential functional consequences suggesting that during the development of this subtype of pituitary tumours mitochondrial function-associated mechanisms may have role

Bilateral cystoid macular edema following docetaxel chemotherapy in a patient with retinitis pigmentosa: a case report.

BACKGROUND: Docetaxel is a chemotherapeutic agent of the taxane class of drugs for the treatment of breast cancer. We present a female patient who noted decreased vision after docetaxel treatment. CASE PRESENTATION: A 45-year-old female patient received docetaxel treatment after resection of a breast carcinoma. Funduscopy and optical coherence tomography (OCT) showed cystoid macular edema on both eyes. Dilated funduscopy also showed bone spicule-like pigmented deposits, typical for retinitis pigmentosa. Besides the fundus appearance restricted peripheral vision and scotopic electroretinogram confirmed the diagnosis of retinitis pigmentosa. Chemotherapy was discontinued following a consulation with the oncologist of the patient. After five weeks, visual acuity improved significantly along with decrease of retinal thickness measured by OCT. CONCLUSION: Docetaxel may cause ocular adverse effects such as cystoid macular edema. Ophthalmological examination is warranted for patients with visual complaints during docetaxel chemotherapy

Influence of the postoperative inflammatory response on cognitive decline in elderly patients undergoing on-pump cardiac surgery: a controlled, prospective observational study

BACKGROUND: The role of non-infective inflammatory response (IR) in the aetiology of postoperative cognitive dysfunction (POCD) is still controversial. The aim of this controlled, prospective observational study was to assess the possible relationship between the grade of IR, defined by procalcitonin (PCT) changes, and development of POCD related to cardiac surgery. METHODS: Forty-two patients, who were >/= 60 years of age and scheduled for elective cardiac surgery, were separated into the low inflammatory (LIR) and high inflammatory (HIR) response groups based on their PCT levels measured on the first postoperative day. A matched normative control group of 32 subjects was recruited from primary care practice. The PCT and C-reactive protein (CRP) levels were monitored daily during the first five postoperative days. The cognitive function and mood state were preoperatively tested with a set of five neurocognitive tests and two mood inventories and at the seventh postoperative day. The Reliable Change Index modified for practice (RCIp) using data from normative controls was applied to determine the significant decline in test performance. RESULTS: The LIR (n = 20) and HIR (n = 22) groups differed significantly in the PCT (p 0.05). Additionally, there was no difference in the mood states, anxiety levels and perioperative parameters known to influence the development of POCD. CONCLUSIONS: In this study, the magnitude of the non-infective inflammatory response generated by on-pump cardiac surgery did not influence the development of POCD in the early postoperative period in elderly patients

Autistic and schizotypal traits exhibit similarities in their impact on mentalization and adult attachment impairments

Deficits in mentalizing and attachment occur in the autism and schizophrenia spectrum, and their extended traits in the general population. Parental attachment and the broader social environment highly influence the development of mentalizing. Given the similarities in the symptomatology and neurodevelopmental correlates of autism spectrum disorder (ASD) and schizophrenia (SCH), it is crucial to identify their overlaps and differences to support screening, differential diagnosis, and intervention. This cross-sectional study utilized questionnaire data from 2203 adults (65.1% female, mean age[SD] = 37.98[9.66]), including participants diagnosed with ASD, SCH, and those exhibiting subclinical traits to investigate the associations between mentalizing, attachment, and perceived social support during adolescence across the autistic and schizotypy spectrum. Results revealed that both autistic and schizotypal traits have comparable effects on insecure adult attachment, primarily through challenges in mentalizing. The impact of mentalizing deficits on adult attachment slightly varies between autistic and schizotypal traits. Conversely, perceived social support during adolescence relates to improved mentalizing and secure adult attachment as a protective factor during development. These outcomes highlight the significance of supportive therapeutic relationships and community care while suggesting directions for further research and collaborative treatments addressing ASD and SCH, considering the differential impact of mentalizing on adult attachment

Intact ultrafast memory consolidation and learning dynamics in children and adults with autism and neurotypicals with autism traits

To comprehend learning processes in autism spectrum disorder (ASD), it is crucial to examine memory consolidation. The discovery of ultrafast memory consolidation has emerged in the last five years. These studies have revealed that learning can take place not only during practice but also during ultrashort (<1 min) rests between practice blocks, termed ultrafast offline learning. To date, no study has investigated this fundamental learning mechanism in autistic individuals. Therefore, we conducted a series of research with three different samples: 1) children, 2) adults, and 3) neurotypical adults with distinct levels of autistic traits. Participants performed a well-established probabilistic learning task, allowing us to measure statistical learning (i.e., probability-based regularities) and general skill learning (i.e., speed-up regardless of probabilities) separately. Individual differences in online (during blocks) and offline (between blocks) changes of statistical learning were observed. Regarding general skill learning, performance improved between blocks and deteriorated during practice. The results of individual studies indicate that neither ASD status nor the extent of autistic traits influenced the ultrafast consolidation or the dynamics of learning. Our results suggest that ultrafast memory consolidation, a fundamental learning mechanism, is intact in autism

Intact predictive processing in autistic adults – evidence from statistical learning

Impairment in predictive processes gained a lot of attention in recent years as an explanation for autistic symptoms. However, empirical evidence does not always underpin this framework. Thus, it is unclear what aspects of predictive processing are affected in Autism Spectrum Disorder (ASD). In this study, we tested autistic adults on a task in which participants acquire probability-based regularities by mere exposure (that is, a statistical learning task). Twenty neurotypical (NTP) and 22 autistic adults learned a probabilistic, temporally distributed regularity for about 40 minutes. We found that autistic adults performed comparably to NTP adults, and the dynamics of learning did not differ either, supported by Bayesian analyses. Thus, our study provides evidence for intact statistical learning in autistic adults. Furthermore, we discuss potential ways this result can extend the scope of the predictive processing framework, noting that atypical processing might not always mean a deficit in performance

Alleviation of Osmotic Stress Effects by Exogenous Application of Salicylic or Abscisic Acid on Wheat Seedlings

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 μM) to solutions containing half-strength Hoagland medium and PEG 6000 (−0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity