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Dieback of dwarf pine scrub (Pinus mugo subsp. mugo) shoots can limit the growth of this species in subalpine areas of the Carpathian Mountains. In July 2023, extensive shoot decline was observed in P. mugo patches in the West Tatra Mountains in southern Poland. Symptomatic shoots showed shoot tip dieback and red‐brown needle discoloration. Internal symptoms included dark discoloration of the pith parenchyma and necrotic lesions in shoot periderms. In this study, we described the symptoms of P. mugo shoot dieback and surveyed the culturable fungi from asymptomatic and symptomatic P. mugo shoots, as well as the bases of needles growing from shoots. In addition, we conducted phylogenetic analyses to distinguish between potential cryptic species of Sydowia polyspora. The dwarf pine scrub shoots and needles were sampled from four patches in the Polish Tatra Mountains. In total, 128 distinct taxa were identified. Ascomycota was dominant, representing 96.6% of the isolates. Among the taxa identified, Sydowia polyspora crypt. sp. I, Lachnellula calyciformis, Mollisia sp. 8, Tympanis sp., Epicoccum mezzettii, E. nigrum, Infundichalara sp., Lophium mytilinum, Cytospora sp., Soosiella sp., Cladosporium westerdijkiae and Hendersonia pinicola were most frequently isolated. In most cases, tissue type and sample site significantly affected the abundance and composition of colonizing fungi. Only S. polyspora was found consistently in all sample types, suggesting that this fungus may be responsible for the shoot dieback of P. mugo. Phylogenetic analyses demonstrated that S. polyspora should be treated as a species complex containing at least four cryptic species (referred to as groups I–IV), that are highly host‐specific to different conifer species. We also found several other well‐known pathogens, namely Allantophomopsis pseudotsugae, Botrytis cinerea, Cytospora sp., Fusarium sp., Sirococcus conigenus and Tympanis sp., which may cause considerable damage to Pinus spp. shoots. Among them, only Cytospora sp., and Tympanis sp. were found often. This is the first comprehensive survey of the fungi associated with extensive shoot dieback of P. mugo in the Carpathian Mountains, and this research led to the discovery of numerous new fungal species associated with P. mugo. [ABSTRACT FROM AUTHOR]

Purpose: Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [13C]bicarbonate in the brain from hyperpolarized [1‐13C]pyruvate using carbon‐13 (13C) MRI provides a unique opportunity for assessing PDH flux in vivo. This study is to assess changes in cerebral PDH flux in response to visual stimuli using in vivo 13C MRS with hyperpolarized [1‐13C]pyruvate. Methods: From seven sedentary adults in good general health, time‐resolved [13C]bicarbonate production was measured in the brain using 90° flip angles with minimal perturbation of its precursors, [1‐13C]pyruvate and [1‐13C]lactate, to test the hypothesis that the appearance of [13C]bicarbonate signals in the brain reflects the metabolic changes associated with neuronal activation. With a separate group of healthy participants (n = 3), the likelihood of the bolus‐injected [1‐13C]pyruvate being converted to [1‐13C]lactate prior to decarboxylation was investigated by measuring [13C]bicarbonate production with and without [1‐13C]lactate saturation. Results: In the course of visual stimulation, the measured [13C]bicarbonate signal normalized to the total 13C signal in the visual cortex increased by 17.1% ± 15.9% (p = 0.017), whereas no significant change was detected in [1‐13C]lactate. Proton BOLD fMRI confirmed the regional activation in the visual cortex with the stimuli. Lactate saturation decreased bicarbonate‐to‐pyruvate ratio by 44.4% ± 9.3% (p < 0.01). Conclusion: We demonstrated the utility of 13C MRS with hyperpolarized [1‐13C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13C]bicarbonate production. [ABSTRACT FROM AUTHOR]

Purpose: [13C]Bicarbonate formation from hyperpolarized [1‐13C]pyruvate via pyruvate dehydrogenase, a key regulatory enzyme, represents the cerebral oxidation of pyruvate and the integrity of mitochondrial function. The present study is to characterize the chronology of cerebral mitochondrial metabolism during secondary injury associated with acute traumatic brain injury (TBI) by longitudinally monitoring [13C]bicarbonate production from hyperpolarized [1‐13C]pyruvate in rodents. Methods: Male Wistar rats were randomly assigned to undergo a controlled‐cortical impact (CCI, n = 31) or sham surgery (n = 22). Seventeen of the CCI and 9 of the sham rats longitudinally underwent a 1H/13C‐integrated MR protocol that includes a bolus injection of hyperpolarized [1‐13C]pyruvate at 0 (2 h), 1, 2, 5, and 10 days post‐surgery. Separate CCI and sham rats were used for histological validation and enzyme assays. Results: In addition to elevated lactate, we observed significantly reduced bicarbonate production in the injured site. Unlike the immediate appearance of hyperintensity on T2‐weighted MRI, the contrast of bicarbonate signals between the injured region and the contralateral brain peaked at 24 h post‐injury, then fully recovered to the normal level at day 10. A subset of TBI rats demonstrated markedly increased bicarbonate in normal‐appearing contralateral brain regions post‐injury. Conclusion: This study demonstrates that aberrant mitochondrial metabolism occurring in acute TBI can be monitored by detecting [13C]bicarbonate production from hyperpolarized [1‐13C]pyruvate, suggesting that [13C]bicarbonate is a sensitive in‐vivo biomarker of the secondary injury processes. [ABSTRACT FROM AUTHOR]

Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post-PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA--89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6-minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)-quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: △PVR (-27.9 ± 20.2% vs. -13.9± 23.9%, p < 0.05) and △mPAP (-17.1 ± 14.4% vs. -8.5 ± 18.0%, p < 0.05). There was a negative correlation between pre-BPA PVR and TTTL (r=-0.47, p < 0.05) which persisted post-BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post-BPA in PP patients. BPA response was not related to TTTL terciles or CTPA-quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of disability worldwide, but the heterogeneous nature of TBI with respect to injury severity and health comorbidities make patient outcome difficult to predict. Injury severity accounts for only some of this variance, and a wide range of preinjury, injury‐related, and postinjury factors may influence outcome, such as sex, socioeconomic status, injury mechanism, and social support. Neuroimaging research in this area has generally been limited by insufficient sample sizes. Additionally, development of reliable biomarkers of mild TBI or repeated subconcussive impacts has been slow, likely due, in part, to subtle effects of injury and the aforementioned variability. The ENIGMA Consortium has established a framework for global collaboration that has resulted in the largest‐ever neuroimaging studies of multiple psychiatric and neurological disorders. Here we describe the organization, recent progress, and future goals of the Brain Injury working group. [ABSTRACT FROM AUTHOR]

Aim: The aim was to compare the quality of sexual life before pregnancy and after delivery and to find out whether and how selected factors affect women's sexuality during this period. Methods: The study group consisted of 433 women who completed the survey containing basic demographic questions and two Female Sexual Function Index (FSFI) questionnaires: a retrospective one, regarding time before pregnancy and the current period. The inclusion criteria: time between 10 weeks and 1 year after delivery, vaginal intercourses before pregnancy and the resumption of vaginal intercourses after delivery. Results: We observed the negative impact of labor on the total FSFI score, regardless of the time that had passed since birth and the delivery mode. The decrease by at least 10% of the initial FSFI score was noticed in 44.3% of the participants. FSD (Female Sexual Dysfunction) occurred statistically more commonly after delivery than before pregnancy (45.3% vs 17.1%; P < 0.001). The following factors had an impact on the risk of post‐partum FSD: pre‐pregnancy FSD (adjusted odds ratio [aOR] = 4.17 [95% confidence interval [CI] 2.38–7.31]) and nulliparity (aOR = 1.67 [95% CI 1.09–2.53]). Conclusion: Childbirth has an undeniable impact on women's sexuality. The prevention and treatment of sexual dysfunctions is very important, especially in this crucial period of life. [ABSTRACT FROM AUTHOR]

Quantification of total phenolic compounds in the heartwood of Picea abies using the Folin–Ciocalteu methods showed that concentrations of phenolic compounds in the heart‐ and sapwood of Picea abies varied, depending on the decay class to which boles were allocated. In the heartwood, mean phenolic concentration was 3.28 mg/g, compared with 2.44 mg/g in sapwood. Experiments using different concentrations of phenolic compounds showed that Heterobasidion parviporum is more sensitive to the effects of phenolic compounds found in sapwood, and less sensitive to phenolic compounds found in heartwood. The high concentration of phenolic compounds extracted from spruce stimulated the decomposition of wood by Armillaria ostoyae. This demonstrates the great ability of A. ostoyae to metabolize phenolic compounds. This is confirmed by natural conditions, where A. ostoyae attacks mainly sapwood and H. parviporum attacks heartwood of P. abies. In heartwood, the average antioxidant activity was approximately 10% higher than in the sapwood. The extraction process and presence of amino acids and reducing sugars might influence on the results. The results suggest that timber quality monitoring in spruce stands could be partly based on measurements of phenol compound concentrations in sapwood, as the technique enables prediction of the potential impact of decay fungi early in succession. [ABSTRACT FROM AUTHOR]

Background: Hodgkin (HL) and non‐Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%‐30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second‐line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. Objective: The aim of this population‐based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. Patients and methods: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second‐line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. Results: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P =.151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram‐positives were predominant. The rate of multidrug‐resistant bacteria was high, especially for Gram‐negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection‐related mortality was comparable for each group. Conclusions: The incidence of IC was comparable during first‐ and second‐line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Efficacy of restorative cognitive rehabilitation can be predicted from baseline patient factors. In addition, patient profiles of functional connectivity are associated with cognitive reserve and moderate the structure-cognition relationship in people with multiple sclerosis (PwMS). Such interactions may help predict which PwMS will benefit most from cognitive rehabilitation. Our objective was to determine whether patient response to restorative cognitive rehabilitation is predictable from baseline structural network disruption and whether this relationship is moderated by functional connectivity.Methods: For this single-arm repeated measures study, we recruited 25 PwMS for a 12-week program. Following magnetic resonance imaging, participants were tested using the Symbol Digit Modalities Test (SDMT) pre- and postrehabilitation. Baseline patterns of structural and functional connectivity were characterized relative to healthy controls.Results: Lower white matter tract disruption in a network of region-pairs centered on the precuneus and posterior cingulate (default-mode network regions) predicted greater postrehabilitation SDMT improvement (P = .048). This relationship was moderated by profiles of functional connectivity within the network (R2 = .385, P = .017, Interaction β = -.415).Conclusion: Patient response to restorative cognitive rehabilitation is predictable from the interaction between structural network disruption and functional connectivity in the default-mode network. This effect may be related to cognitive reserve. [ABSTRACT FROM AUTHOR]

Identifying defects in electrical power systems during field inspections is a difficult task, since faults are generally not visible and may be intermittent. To find possible adverse conditions, specific inspection equipment is used. The ultrasound detector is the equipment normally used to inspect outdoor insulating systems; however, using it demands operator experience. To improve the defect condition classification, artificial intelligence techniques are applied to assist the operator in the decision task and thereby facilitate the identification of faulty insulating devices in the grid. The training of artificial neural network (ANN) models is an important step in solving the classification problem. This study aims to evaluate the training capacity in terms of the performance of different optimisation methods for the calculation of the mean square error after convergence. Traditional methods such as Gradient Descent and its variations will be presented, as well as methods that employ high computational effort such as quasi-Newton and Levenberg-Marquardt. In order to base these concepts, a review will be presented on the use of these algorithms and on the problem of classification of insulators in distribution networks. The results show that there is a considerable performance difference between the calculation methods. [ABSTRACT FROM AUTHOR]

Identifying defects in electrical power systems during field inspections is a difficult task, since faults are generally not visible and may be intermittent. To find possible adverse conditions, specific inspection equipment is used. The ultrasound detector is the equipment normally used to inspect outdoor insulating systems; however, using it demands operator experience. To improve the defect condition classification, artificial intelligence techniques are applied to assist the operator in the decision task and thereby facilitate the identification of faulty insulating devices in the grid. The training of artificial neural network (ANN) models is an important step in solving the classification problem. This study aims to evaluate the training capacity in terms of the performance of different optimisation methods for the calculation of the mean square error after convergence. Traditional methods such as Gradient Descent and its variations will be presented, as well as methods that employ high computational effort such as quasi‐Newton and Levenberg–Marquardt. In order to base these concepts, a review will be presented on the use of these algorithms and on the problem of classification of insulators in distribution networks. The results show that there is a considerable performance difference between the calculation methods. [ABSTRACT FROM AUTHOR]

Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bispecific antibodies and multi‐specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from autoimmune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. The identification of biomarkers, the assessment of target organ pharmacokinetic and pharmacodynamics interactions and a wide range of in vitro, ex vivo and in vivo models should contribute to an appropriate prediction of a biological effect in the clinical setting. As human biology may not be perfectly reflected by approaches such as skin equivalents or animal models, novel approaches such as the use of human skin and dermal microperfusion assays in healthy volunteers and patients appear both reasonable and mandatory. These models may indeed generate highly translationally relevant data that have the potential to reduce the failure rate of drugs currently undergoing clinical development. [ABSTRACT FROM AUTHOR]

Cognitive reserve is one's mental resilience or resistance to the effects of structural brain damage. Reserve effects are well established in people with multiple sclerosis (PwMS) and Alzheimer's disease, but the neural basis of this phenomenon is unclear. We aimed to investigate whether preservation of functional connectivity explains cognitive reserve. Seventy‐four PwMS and 29 HCs underwent neuropsychological assessment and 3 T MRI. Structural damage measures included gray matter (GM) atrophy and network white matter (WM) tract disruption between pairs of GM regions. Resting‐state functional connectivity was also assessed. PwMS exhibited significantly impaired cognitive processing speed (t = 2.14, p =.037) and visual/spatial memory (t = 2.72, p =.008), and had significantly greater variance in functional connectivity relative to HCs within relevant networks (p < .001, p < .001, p =.016). Higher premorbid verbal intelligence, a proxy for cognitive reserve, predicted relative preservation of functional connectivity despite accumulation of GM atrophy (standardized‐β =.301, p =.021). Furthermore, preservation of functional connectivity attenuated the impact of structural network WM tract disruption on cognition (β = −.513, p =.001, for cognitive processing speed; β = −.209, p =.066, for visual/spatial memory). The data suggests that preserved functional connectivity explains cognitive reserve in PwMS, helping to maintain cognitive capacity despite structural damage. [ABSTRACT FROM AUTHOR]

Background and Objectives: Many consider volunteer blood donors as ideal candidates for unrelated haematopoietic progenitor cell (HPC) donation. However, frequent blood donations could influence the results of HPC mobilization. To our best knowledge, there are no data on the possible impact of repeated blood donation on efficiency of subsequent HPC mobilization by granulocyte colony‐stimulating factor (G‐CSF). Materials and Methods: We compared outcomes of HPC mobilization in unrelated donors with and without a history of blood donation. We conducted a prospective study on 287 consecutive donors admitted to the Department of Hematology since January 2016. The final analysis included 153 donors who agreed to take part in the study and had undergone stem cell mobilization with G‐CSF. Results: History of blood donations prior to haematopoietic stem cell mobilization with G‐CSF does not have a significant impact on the number of collected CD34+ cells in the first leucocytapheresis (516.2 x 106 (170–1148) in blood donors vs 490.5 x 106 (101–1154) in non‐donors) (P = 0.32). In all donors, in this study mobilization of HPC was successful: 87.5% of blood donors and 85.6% of non‐donors collected the required cell number in a single apheresis. In blood donors, a higher number of blood donations within 2 and 5 years prior to HPC mobilization correlated significantly with successful donation within one leucocytapheresis (P = 0.014 and P = 0.024, respectively). Conclusion: Multiple blood donations do not significantly influence the outcome of HPC collection in unrelated donors. Blood donors and non‐donors have similar results of HPC collection, so there is no reason to favour either group. [ABSTRACT FROM AUTHOR]

Summary: Objective: Copy number variations (CNVs) represent a significant genetic risk for several neurodevelopmental disorders including epilepsy. As knowledge increases, reanalysis of existing data is essential. Reliable estimates of the contribution of CNVs to epilepsies from sizeable populations are not available. Methods: We assembled a cohort of 1255 patients with preexisting array comparative genomic hybridization or single nucleotide polymorphism array based CNV data. All patients had "epilepsy plus," defined as epilepsy with comorbid features, including intellectual disability, psychiatric symptoms, and other neurological and nonneurological features. CNV classification was conducted using a systematic filtering workflow adapted to epilepsy. Results: Of 1097 patients remaining after genetic data quality control, 120 individuals (10.9%) carried at least one autosomal CNV classified as pathogenic; 19 individuals (1.7%) carried at least one autosomal CNV classified as possibly pathogenic. Eleven patients (1%) carried more than one (possibly) pathogenic CNV. We identified CNVs covering recently reported (HNRNPU) or emerging (RORB) epilepsy genes, and further delineated the phenotype associated with mutations of these genes. Additional novel epilepsy candidate genes emerge from our study. Comparing phenotypic features of pathogenic CNV carriers to those of noncarriers of pathogenic CNVs, we show that patients with nonneurological comorbidities, especially dysmorphism, were more likely to carry pathogenic CNVs (odds ratio = 4.09, confidence interval = 2.51‐6.68; P = 2.34 × 10−9). Meta‐analysis including data from published control groups showed that the presence or absence of epilepsy did not affect the detected frequency of CNVs. Significance: The use of a specifically adapted workflow enabled identification of pathogenic autosomal CNVs in 10.9% of patients with epilepsy plus, which rose to 12.7% when we also considered possibly pathogenic CNVs. Our data indicate that epilepsy with comorbid features should be considered an indication for patients to be selected for a diagnostic algorithm including CNV detection. Collaborative large‐scale CNV reanalysis leads to novel declaration of pathogenicity in unexplained cases and can promote discovery of promising candidate epilepsy genes. [ABSTRACT FROM AUTHOR]

Background: Implementation of precision oncology interventions poses several challenges to informed consent and patient education. This study assessed cancer patients' understanding, expectations, and outcomes regarding participation in research examining the impact of matched tumor and germline sequencing on their clinical care. Methods: A total of 297 patients (mean age: 59 years; 50% female; 96% white) with refractory, metastatic cancer were surveyed, including 217 who completed surveys both before and after undergoing integrated whole exome and transcriptome sequencing as part of a larger clinical research study. Results: At baseline, the vast majority of patients expected to receive several potential direct benefits from study participation, including written reports of sequencing findings (88%), greater understanding of the causes of their cancer (74%), and participation in clinical trials for which sequencing results would make them eligible (84%). In most cases, these benefits were not realized by study completion. Despite explanations from study personnel to the contrary, most participants (67%‐76%) presumed that incidental germline sequencing findings relevant to noncancerous health conditions (eg, diabetes) would automatically be disclosed to them. Patients reported low levels of concern about study risks at baseline and low levels of regret about study participation at follow‐up. Conclusions: Findings suggest that cancer patients participating in precision oncology intervention research have largely unfulfilled expectations of direct benefits related to their study participation. Increased focus on patient education to supplement the informed consent process may help manage patients' expectations regarding the extent and likelihood of benefits received as a result of undergoing genomic sequencing. This study assessed cancer patients' understanding and expectations regarding participation in research examining the impact of matched tumor and germline sequencing on their clinical care. Findings suggest that cancer patients participating in precision oncology intervention research have largely unfulfilled expectations of direct benefits related to their study participation. Increased focus on patient education to supplement the informed consent process may help manage patients' expectations regarding the extent and likelihood of benefits received as a result of undergoing genomic sequencing. [ABSTRACT FROM AUTHOR]

Background: Bone marrow harvest (BMH) for haematopoietic stem cell transplantation is a well‐established procedure. The guidelines of World Marrow Donor Association provide information on donor selection. However, some of the guidelines regarding donors with anaemia prior to harvest lack in supporting data from clinical studies. With this study, we aimed to provide such data. Material and Methods: In this retrospective, single‐centre study, we analysed the interplay between haemoglobin levels and BMH and BMH impact on haemoglobin levels in a cohort of 149 unrelated BM donors, including 13 subjects with mild anaemia. Results: The BMH led to significantly lower decrease in haemoglobin levels in donors with anaemia than in control group (1·79 g/dl vs. 2·56 g/dl, P < 0·0001). The following parameters: BMH volume (ml), BMH volume/donor body weight (ml/kg), total nucleated cells (TNC) in product (×108) and TNC/kg recipient body weight in product (×108/kg) did not differ significantly between those two analysed groups (P > 0·05). Median BM volume harvested from anaemic donors was 16·34 ml/kg; none of them required blood transfusion after BMH. Conclusion: Mild anaemia prior to BMH does not significantly impact the collection results. The BMH is safe and feasible in donors with mild anaemia. [ABSTRACT FROM AUTHOR]

Summary: Leptomelanconium allescheri was identified for the first time in Poland in 2016 in the Tatra Mts. on Pinus mugo needles. It produced numerous conidiomata on necrotic lesions on live needles. In our study, we provide detailed characteristics of disease symptoms and describe morphology of the structures of the fungus. The shape and size of macroconidia are proven to be more variable in vitro than in situ. The malt extract agar colonies of the fungus obtained from germinating macroconidia are described for the first time. Our observations prove also that, apart from macroconidia, L. allescheri produces in vitro unicellular, hyaline microconidia, 3.5–10 × 1.8–5.0 μm in size, the previously unknown aspect in the development cycle of this species. The BLAST search with ITS and LSU sequences of L. allescheri resulted in the closest match with Cenangium acuum accessions (94%–95% and 99%, respectively). Two gene based, LSU plus ITS, phylogenetic positioning of L. allescheri proves that it belongs to Pezizomycotina, Helotiales. Further, on family level, placement of L. allescheri, as well as its two closest species C. acuum and Piceomphale bulgarioides, remains undefined. The L. allescheri barcode sequences (accession numbers: ITS— MF573935, LSU— MF573936, IGS— MF573937) and cultures were submitted to NCBI GenBank and CBS Utrecht, The Netherlands culture collection. [ABSTRACT FROM AUTHOR]

Introduction Sexual dysfunction ( SD) is one of the common symptoms of multiple sclerosis ( MS) and is often underdiagnosed, especially in women. Relapsing-remitting multiple sclerosis ( RRMS) is the most widespread form of the disease, but the data on SD occurrence in this particular group of patients is limited. The aim of the study was to analyze the associations between demographic factors, symptoms and signs of MS, psychiatric comorbidities and SD in female patients with RRMS. Material & Methods A subgroup of 86 sexually active women with RRMS out of 218 total MS respondents was analyzed. Exclusion criteria included active relapse, EDSS score equal or higher than 6.5, and current pregnancy. All patients completed questionnaires including demographic data, questions about symptoms and signs of MS, Female Sexual Function Index ( FSFI) for sexual performance, Patient Health Questionnaire 9 ( PHQ-9) for depression, and Fatigue Severity Scale ( FSS) for fatigue evaluation. Results According to FSFI, SD occurred in 21 (27.27%) of the respondents. SD occurrence was associated with depression ( p < .05) and speech disturbances ( p < .04). A negative effect on sexual performance was associated with depression intensity ( p < .003), fatigue intensity ( p < .05), more advanced age at diagnosis ( p < .02), lower education level ( p < .05), and smaller area of residence ( p < .002). Conclusions SD in women with RRMS is mostly associated with psychosocial parameters. Patients who are more depressed, presenting speech problems, less educated, and from smaller towns, should be considered high-risk for sexual dysfunction. [ABSTRACT FROM AUTHOR]

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Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ∼445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objective To evaluate the extent to which the current designs of clinical trials in knee osteoarthritis (OA) permit detection of a therapeutic effect of disease-modifying OA drugs (DMOADs) on the incidence of knee replacement, and to provide estimates of the required sample sizes. Methods We selected distinct subcohorts of the Osteoarthritis Initiative (OAI), based on available information on eligibility criteria for clinical knee OA trials () and additional subcohorts stratified for age, sex, and the severity of radiographic OA. The observed incidence of knee replacement in these OAI subcohorts was used to estimate the expected incidence of knee replacement in the control group of a clinical trial. Based on this estimate, the sample sizes required to detect hypothetical treatment effects on the incidence of knee replacement were calculated, assuming observation periods of 2, 5, or 7 years. Results The cumulative knee replacement incidence rates in the OAI subcohorts ranged from 0.9% to 12.9%. The corresponding sample sizes required to detect 50% improvement by the DMOAD, with a power of 80% and 95% confidence, were 5,459 and 362, respectively. Including only women with advanced age and radiographic OA increased the incidence of knee replacement and decreased the required sample size. Conclusion The sample sizes that are commonly used in clinical trials do not enable the effects of a DMOAD on incident knee replacement to be detected with sufficient power and confidence. The estimated incidence rates of knee replacement and the corresponding sample sizes are important for informing the design of trials for disease course-modifying effects as well as for socioeconomic evaluation of a DMOAD in terms of preventing knee replacement. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA was found to be highly mutated in colorectal cancer cells. One of the key molecules involved in the maintenance of the mitochondrial genome is the nuclear-encoded polymerase gamma. The aim of our study was to determine if there is a link between polymorphisms within the polymerase gamma gene ( POLG) and somatic mutations within the mitochondrial genome in cancer cells. We investigated POLG sequence variability in 50 colorectal cancer patients whose complete mitochondrial genome sequences were determined. Relative mtDNA copy number was also determined. We identified 251 sequence variants in the POLG gene. Most of them were germline-specific (∼92%). Twenty-one somatic changes in POLG were found in 10 colorectal cancer patients. We have found no association between the occurrence of mtDNA somatic mutations and the somatically occurring variants in POLG. MtDNA content was reduced in patients carrying somatic variants in POLG or germline nucleotide variants located in the region encoding the POLG polymerase domain, but the difference did not reach statistical significance. Our findings suggest that somatic mtDNA mutations occurring in colorectal cancer are not a consequence of somatic mutations in POLG. Nevertheless, POLG nucleotide variants may lead to a decrease in mtDNA content, and consequently result in mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

In the field of cancer research, scientific investigations are based on analysing differences in the secretome, the proteome, the transcriptome, the expression of cell surface molecules, and the deregulation of signal transduction pathways between neoplastic and normal cells. Accumulating evidence indicates a crucial role in carcinogenesis concerning not only stromal cells but also normal cells from target organs and tissue where tumours emerge. The tumour microenvironment ( TME) definitively plays an important role in regulating neighbouring cell behaviour. To date, limited attention has been focused upon interactions between cancer cells and normal cells. This review concentrates on the interactions between stromal and healthy cells from the TME in cancer development. In the article, the authors also describe mutations, genes and proteins expression pattern that are involved in tumour development in target organ. [ABSTRACT FROM AUTHOR]

Polymeric biomaterials are being widely used for the treatment of various traumata, diseases and defects in human beings due to ease in their synthesis. As biomaterials have direct interaction with the extracellular environment in the biological world, biocompatibility is a topic of great significance. The introduction or enhancement of biocompatibility in certain polymers is still a challenge to overcome. Polymer biocompatibility can be controlled by surface modification. Various physical and chemical methods (e.g., chemical and plasma treatment, ion implantation, and ultraviolet irradiation etc.) are in use or being developed for the modification of polymer surfaces. However an important limitation in their employment is the alteration of bulk material. Different surface and bulk properties of biomaterials are often desirable for biomedical applications. Because extreme ultraviolet (EUV) radiation penetration is quite limited even in low density mediums, it could be possible to use it for surface modification without influencing the bulk material. This article reviews the degree of biocompatibility of different polymeric biomaterials being currently employed in various biomedical applications, the surface properties required to be modified for biocompatibility control, plasma and laser ablation based surface modification techniques, and research studies indicating possible use of EUV for enhancing biocompatibility. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3298-3310, 2014. [ABSTRACT FROM AUTHOR]

Bilir B, Yapici Z, Yalcinkaya C, Baris I, Carvalho CMB, Bartnik M, Ozes B, Eraksoy M, Lupski JR, Battaloglu E. High frequency of GJA12/ GJC2 mutations in Turkish patients with Pelizaeus-Merzbacher disease. Pelizaeus-Merzbacher disease is an early onset dysmyelinating leukodystrophy. About 80% of PMD cases have been associated with duplications and mutations of the proteolipid protein 1 ( PLP1) gene. Pelizaeus-Merzbacher-like disease is a genetically heterogeneous autosomal recessive disease and rarely caused by mutations in gap junction protein α12 ( GJA12/ GJC2) gene. The molecular basis of the disease was investigated in a cohort of 19 Turkish families. This study identified novel chromosomal rearrangements proximal and distal to, and exclusive of the PLP1 gene, showed equal frequencies of PLP1 and GJA12/ GJC2 mutations at least in our cohort, and suggested further genetic heterogeneity. [ABSTRACT FROM AUTHOR]

Carvalho CMB, Bartnik M, Pehlivan D, Fang P, Shen J, Lupski JR. Evidence for disease penetrance relating to CNV size: Pelizaeus-Merzbacher disease and manifesting carriers with a familial 11 Mb duplication at Xq22. The potential causes for the incomplete penetrance of Pelizaeus-Merzbacher disease (PMD) in female carriers of PLP1 mutations are not well understood. We present a family with a boy having PMD in association with PLP1 duplication and three females who are apparent manifesting carriers. Custom high-resolution oligonucleotide array comparative genomic hybridization (aCGH) and breakpoint junction sequencing were performed and revealed a familial complex duplication consisting of a small duplicated genomic interval (∼56 kb) and a large segmental duplication (∼11 Mb) that resulted in a PLP1 copy number variation gain. Breakpoint junction analysis implicates a replication-based mechanism underlying the rearrangement formation. X-inactivation studies (XCI) showed a random to moderate advantageous skewing pattern in peripheral blood cells but a moderate to extremely skewed (≥90%) pattern in buccal cells. In conclusion, our data show that complex duplications involving PLP1 are not uncommon, can be detected at the level of genome resolution afforded by clinical aCGH and duplication and inversion can be produced in the same event. Furthermore, the observation of three manifesting carriers with a large genomic rearrangement supports the contention that duplication size along with genomic content can be an important factor for penetrance of the PMD phenotype in females. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia in elderly people, and age is the major nongenetic risk factor for sporadic AD. A hallmark of AD is the accumulation of amyloid in the brain, which is composed mainly of the amyloid beta-peptide (Aβ) in the form of oligomers and fibrils. However, how aging induces Aβ aggregation is not yet fully determined. Some residues in the Aβ sequence seem to promote Aβ-induced toxicity in association with age-dependent risk factors for AD, such as (i) increased GM1 brain membrane content, (ii) altered lipid domain in brain membrane, (iii) oxidative stress. However, the role of Aβ sequence in promoting aggregation following interaction with the plasma membrane is not yet demonstrated. As Tyr10 is implicated in the induction of oxidative stress and stabilization of Aβ aggregation, we substituted Tyr 10 with a synthetic amino acid that abolishes Aβ-induced oxidative stress and shows an accelerated interaction with GM1. This variant peptide shows impaired aggregation properties and increased affinity for GM1. It has a dominant negative effect on amyloidogenesis in vitro, in cellulo, and in isolated synaptosomes. The present study shed new light in the understanding of Aβ-membrane interactions in Aβ-induced neurotoxicity. It demonstrates the relevance of Aβ sequence in (i) Aβ-membrane interaction, underlining the role of age-dependent enhanced GM1 content in promoting Aβ aggregation, (ii) Aβ aggregation, and (iii) Aβ-induced oxidative stress. Our results open the way for the design of peptides aimed to inhibit Aβ aggregation and neurotoxicity. [ABSTRACT FROM AUTHOR]

Mutations in genes encoding voltage-gated sodium channels are significant factors in the etiology of neurological diseases and psychiatric disorders, including various types of idiopathic epilepsy. Using a clinical exon-targeted oligonucleotide array comparative genomic hybridization (aCGH), we have identified a de novo ∼110-kb deletion involving exons 1-2 of SCN2A and non-coding exon 1a of SCN3A in a 25-year-old female with mental retardation, neurobehavioral and psychiatric abnormalities, and a history of infantile seizures with abnormal EEG. We propose that haploinsufficiency of SCN2A may play an important role in the genetic basis of neurodevelopmental and neurobehavioral disorders and emphasize the efficacy of detecting exonic copy-number variation (CNV) by exon-targeted oligo aCGH. [ABSTRACT FROM AUTHOR]

Coronary artery disease and type 2 diabetes are chronic diseases of substantial and growing prevalence. Their coincidence is common, markedly enhancing mortality and morbidity. The risk for cardiovascular disease increases along a spectrum of blood glucose concentrations already apparent at levels regarded as normal. Accordingly, strategies for the early detection of glucometabolic disturbances are needed to find ways to prevent the occurrence of cardiovascular complications or to treat them already at an early stage. More specifically, abnormal glucose tolerance is almost twice as common amongst patients with a myocardial infarction as in population-based controls and a normal glucose regulation is indeed less common than abnormal glucose metabolism also amongst patients with stable coronary artery disease. Already an abnormal glucose tolerance is a strong risk factor for future cardiovascular events after an acute myocardial infarction. An oral glucose tolerance test should, therefore, be a part of the evaluation of total risk in all patients with coronary artery disease. As glucose disturbances are common and easy to detect, they may be suitable targets for novel secondary preventive efforts. [ABSTRACT FROM AUTHOR]

Background information. The nuclear gene hSUV3 (human SUV3) encodes an ATP-dependent DNA/RNA helicase. In the yeast Saccharomyces cerevisiae the orthologous Suv3 protein is localized in mitochondria, and is a subunit of the degradosome complex which regulates RNA surveillance and turnover. In contrast, the functions of human SUV3 are not known to date.Results. In the present study, we show that a fraction of human SUV3 helicase is localized in the nucleus. Using small interfering RNA gene silencing in HeLa cells, we demonstrate that down-regulation of hSUV3 results in cell cycle perturbations and in apoptosis, which is both AIF- and caspase-dependent, and proceeds with the induction of p53.Conclusions. In addition to its mitochondrial localization, human SUV3 plays an important role in the nucleus and is probably involved in chromatin maintenance. [ABSTRACT FROM AUTHOR]

Despite many research efforts in recent decades, the major pathogenetic mechanisms of osteoarthritis (OA), including gene alterations occurring during OA cartilage degeneration, are poorly understood, and there is no disease‐modifying treatment approach. The present study was therefore initiated in order to identify differentially expressed disease‐related genes and potential therapeutic targets.This investigation consisted of a large gene expression profiling study performed based on 78 normal and disease samples, using a custom‐made complementary DNA array covering >4,000 genes.Many differentially expressed genes were identified, including the expected up‐regulation of anabolic and catabolic matrix genes. In particular, the down‐regulation of important oxidative defense genes, i.e., the genes for superoxide dismutases 2 and 3 and glutathione peroxidase 3, was prominent. This indicates that continuous oxidative stress to the cells and the matrix is one major underlying pathogenetic mechanism in OA. Also, genes that are involved in the phenotypic stability of cells, a feature that is greatly reduced in OA cartilage, appeared to be suppressed.Our findings provide a reference data set on gene alterations in OA cartilage and, importantly, indicate major mechanisms underlying central cell biologic alterations that occur during the OA disease process. These results identify molecular targets that can be further investigated in the search for therapeutic interventions. [ABSTRACT FROM AUTHOR]

A new method for mounting protein crystals and other environmentally sensitive samples for room-temperature diffraction measurements is described. A crystal is retrieved using a microfabricated sample mount as recently reported, and the mount is inserted into a modified goniometer-compatible base. A transparent thin-wall polyester tube sealed at one end and filled with stabilizing liquid is then drawn over the crystal and sealed to the goniometer base. Compared with mounting using glass capillaries, this method can provide lower-background X-ray scattering, especially at higher resolutions; dramatically improved ease of crystal mounting with minimal chance of damage; accurate and reproducible crystal positioning relative to the goniometer base; improved crystal visibility and ease of alignment, especially for very small crystals; and compatibility with high-throughput approaches. Crystals can be rapidly screened and eliminated earlier in the data collection pipeline, and the cause of poor low-temperature diffraction can be diagnosed. [ABSTRACT FROM AUTHOR]

BACKGROUND: A high prevalence of newly detected diabetes and impaired glucose tolerance (abnormal glucose tolerance) was recently reported in patients with acute myocardial infarction. It is important to verify whether this finding is specific for the patients or attributable to the population, from which they were recruited. OBJECTIVE: To verify whether abnormal glucose tolerance is more prevalent in patients than in controls chosen from the same population and to compare metabolic characteristics between the two groups. DESIGN AND SUBJECTS: The metabolic state was assessed in patients (n = 181) admitted with acute myocardial infarction and no history of diabetes before discharge and after 3 months. Sex- and age-matched controls (n = 185) without previously known diabetes or cardiovascular disease except hypertension were recruited from the general population. MAIN OUTCOME MEASURES: Oral glucose tolerance test, glucosylated haemoglobin A1c (HbA1c), insulin, proinsulin, lipid profile, fibrinolytic function and inflammatory markers. RESULTS: Abnormal glucose tolerance was more common (number/all classified) in patients at discharge 113/168 (67%) and after 3 months 95/145 (66%) than in controls 65/185 (35%) (P < 0.001). Dyslipidaemia (70% vs. 29%; P < 0.001) and previously treated hypertension (32% vs. 18%; P = 0.028) were more frequent amongst patients whilst obesity (18% vs. 24%) did not differ significantly. Blood glucose, HbA1c, proinsulin, proinsulin/insulin ratio, triglycerides, insulin resistance (by HOMA) and fibrinogen were consistently higher in patients than controls (P < 0.01). CONCLUSIONS: Abnormal glucose tolerance was almost twice as common amongst patients with acute myocardial infarction as in matched controls. Impaired glycaemic control accompanied by insulin resistance, dyslipidaemia, hypertension, together with increased plasma fibrinogen and proinsulin levels were main features characterizing patients. [ABSTRACT FROM AUTHOR]

In rat liver some highly unsaturated fatty acids are partially degraded. In contrast to ‘normal’ β-oxidation some intermediates accumulate in this catabolic pathway. When a docosapolyenoic acid with the first double bond in position 4 is metabolized, two degradation products are to be found. The sequence of reactions has been elucidated. As a first step the docosapolyenoic acid loses its double bond in position 4 while the carbon chain remains unchanged. The enzyme involved has tentatively been called 4-enoyl-CoA reductase. Subsequently chain shortening occurs. Using polyenoic acids with different chain lengths and different double bond positions, it has been possible to demonstrate that the double bond positions rather than the chain length determine whether or not an unsaturated fatty acid is partially degraded. The four double bonds in the positions 4, 7, 10 and 13 seem to be the minimal structural requirement for docosapolyenoic acids in order to function as substrates for the 4-enoyl-CoA reductase. 4, 7,10-docosatrienoic, 4, 7-docosadienoic, and 4-docosenoic acid, which have not been detected in nature so far, are not metabolized when incubated with rat liver mitochondria. [ABSTRACT FROM AUTHOR]