Auditory perception in people with autism spectrum disorders

Uvod: Pojava atipičnih reakcija na auditivne senzorne draži kod osoba sa poremećajima iz spektra autizma (PSA) zapaža se na ranom uzrastu. Cilj: Ovaj pregled literature imao je za cilj analizu bihevioralnih i elektrofizioloških istraživanja auditivne percepcije kod osoba sa PSA. Metode: Nalazi su organizovani u odnosu na primenjenu metodologiju i stimuluse korišćene u ispitivanju auditivne percepcije. Rezultati: Identifikacija i diskriminacija izolovanih akustičkih karakteristika uglavnom je očuvana ili bolja kod osoba sa PSA, kako za čiste, tako i za složene tonove i govorne stimuluse u odnosu na tipičnu populaciju. Vodeće teorije auditivnog funkcionisanja osoba sa PSA ukazuju na to da je periferna (lokalna) obrada detalja zvuka očuvana ili napredna u odnosu na tipičnu populaciju, a da se teškoće kod osoba sa PSA pojavljuju u integraciji lokalno analiziranih informacija u smislenu celinu (globalna obrada). Razlika između ovih teorija je u tome što Teorija slabe centralne koherencije (Weak Central Coherence ‒ WCC) insistira na sigurnom prisustvu nedostataka u globalnoj obradi, dok Teorija perceptivnog funkcionisanja (Perceptual Functioning theory ‒ EPF) nije toliko isključiva i ukazuje na to da poremećaj u globalnoj obradi može da bude prisutan, ali ne obavezno. Zaključak: Može se zaključiti da je auditivna percepcija i obrada visine tona očuvana ili pojačana kod osoba sa PSA bez obzira na vrstu zvučnog stimulusa, što se objašnjava povećanjem auditivnog kapaciteta za obradu informacija. To je u nekim slučajevima korisno, dok u drugim taj dodatni kapIntroduction. The occurrence of atypical reactions to auditory sensory stimuli is observed in people with autism spectrum disorders (ASD) at an early age. Objective. The goal of this review was to analyze behavioural and electrophysiological examinations of auditory perception in people with ASD. Methods. The findings are organized according to the applied methodology and stimuli used in assessing auditory perception. Results. When compared to the typical population, identification and discrimination of isolated acoustic characteristics are mostly preserved or advanced in people with ASD, both for complex tones and spoken stimuli. The leading theories regarding auditory functioning of people with ASD indicate that peripheral (local) processing of sound details is preserved or advanced compared to the typical population and that difficulties arise in integrating locally analyzed information into a meaningful whole (global processing). The difference between these theories is that the Weak Central Coherence theory insists on a definite presence of deficiencies in global processing, whereas the Perceptual Functioning theory is not as exclusionary and indicates that the inconsistency in global processing can be present but is not requisite. Conclusion. It may be concluded that auditory perception and the processing of tone height are preserved or enhanced in people with ADS regardless of the type of the auditory stimulus. This may be explained by the increase of the auditory capacity for information processing, which is useful in some cases. However, in other cases, the same increased capacity resul

Intermittent Theta Burst Stimulation Ameliorates Cognitive Deficit and Attenuates Neuroinflammation via PI3K/Akt/mTOR Signaling Pathway in Alzheimer’s-Like Disease Model

Neurodegeneration implies progressive neuronal loss and neuroinflammation further contributing to pathology progression. It is a feature of many neurological disorders, most common being Alzheimer’s disease (AD). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive stimulation which modulates excitability of stimulated brain areas through magnetic pulses. Numerous studies indicated beneficial effect of rTMS in several neurological diseases, including AD, however, exact mechanism are yet to be elucidated. We aimed to evaluate the effect of intermittent theta burst stimulation (iTBS), an rTMS paradigm, on behavioral, neurochemical and molecular level in trimethyltin (TMT)-induced Alzheimer’s-like disease model. TMT acts as a neurotoxic agent targeting hippocampus causing cognitive impairment and neuroinflammation, replicating behavioral and molecular aspects of AD. Male Wistar rats were divided into four experimental groups–controls, rats subjected to a single dose of TMT (8 mg/kg), TMT rats subjected to iTBS two times per day for 15 days and TMT sham group. After 3 weeks, we examined exploratory behavior and memory, histopathological and changes on molecular level. TMT-treated rats exhibited severe and cognitive deficit. iTBS-treated animals showed improved cognition. iTBS reduced TMT-induced inflammation and increased anti-inflammatory molecules. We examined PI3K/Akt/mTOR signaling pathway which is involved in regulation of apoptosis, cell growth and learning and memory. We found significant downregulation of phosphorylated forms of Akt and mTOR in TMT-intoxicated animals, which were reverted following iTBS stimulation. Application of iTBS produces beneficial effects on cognition in of rats with TMT-induced hippocampal neurodegeneration and that effect could be mediated via PI3K/Akt/mTOR signaling pathway, which could candidate this protocol as a potential therapeutic approach in neurodegenerative diseases such as AD

Impaired olfactory performance and anxiety-like behavior in a rat model of multiple sclerosis are associated with enhanced adenosine signaling in the olfactory bulb via A1R, A2BR, and A3R

The present study shows that animals with experimental autoimmune encephalomyelitis (EAE) exhibit olfactory dysfunction and impaired general cognitive abilities, as well as anxiety-like behavior. Olfactory dysfunction occurs on average at 2 dpi, well before the onset of the first motor signs of EAE (8–10 dpi). After the initial olfactory dysfunction, the EAE animals show a fluctuation in olfactory performance that resembles the relapsing–remitting course of human MS. The study also shows severe neuroinflammation in the olfactory bulb (OB), with numerous infiltrated CD4+ T cells and peripheral macrophages in the superficial OB layers, marked microgliosis, and massive induction of TNF-α, IL-1β, and IL-6. Reduced tyrosine hydroxylase activity in the glomerular layer, pronounced granule cell atrophy, and reduced numbers of type B neuroblasts in the rostral migratory stream also indicate altered plasticity of the neuronal network in the OB. Considering the exceptionally high purinome expression in the OB, the possible involvement of purinergic signaling was also investigated. The study shows that macrophages infiltrating the OB overexpress A3R, while highly reactive microglia overexpress the adenosine-producing enzyme eN/ CD73 as well as A2BR, A3R, and P2X4R. Given the simultaneous induction of complement component C3, the results suggest that the microglial cells develop a functional phenotype of phagocytizing microglia. The study also demonstrates transcriptional and translational upregulation of A1R in mitral and tufted cells, which likely influence resting network activity in OB and likely contribute to olfactory dysfunction in EAE. Overall, our study shows that olfactory dysfunction and altered social and cognitive behavior in EAE are associated with increased adenosine signaling via A1R, A2BR, and A3R

Significance of LDL and HDL subclasses characterization in the assessment of risk for colorectal cancer development

Introduction: Dyslipidaemia contributes to the occurrence of colorectal cancer (CRC). We hypothesized that qualitative changes of lipoproteins are associated with the risk for CRC development. This study analyses low-density lipoprotein (LDL) and high-density lipoprotein (HDL) diameters, as well as distribution of LDL and HDL subclasses in patients with CRC, with an aim to determine whether advanced lipid testing might be useful in predicting the risk for the onset of this malignancy. Materials and methods: This case-control study included 84 patients with newly diagnosed CRC and 92 controls. Gradient gel electrophoresis was applied for separation of lipoprotein subclasses and for LDL and HDL diameters determination. Lipid parameters were measured using routine enzymatic methods. Results: Total cholesterol, HDL and LDL-cholesterol were significantly lower in CRC patients compared to controls (4.47 mmol/L vs. 5.63 mmol/L; 0.99 mmol/L vs. 1.27 mmol/L; 2.90 mmol/L vs. 3.66 mmol/L; P lt 0.001, respectively). Patients had significantly smaller LDL (25.14 nm vs. 26.92 nm; P lt 0.001) and HDL diameters (8.76 nm vs. 10.17 nm; P lt 0.001) and greater proportion of small, dense LDL particles (54.0% vs. 52.9%; P = 0.044) than controls. Decreased LDL and HDL diameters were independent predictors of CRC (OR = 0.5, P = 0.001 and OR = 0.5, P = 0.008, respectively), and alongside with age and HDL-cholesterol concentrations formed the optimal cost-effective model, providing adequate discriminative abilities for CRC (AUC = 0.89) and correct patients classification (81%). Conclusions: Patients with CRC have decreased LDL and HDL diameters and increased proportion of smaller particles. LDL and HDL diameters determination could be useful in assessing the risk for CRC development

UTJECAJ SREDSTVA ZA UKORJENJAVANJE NA RAZMNOŽAVANJE KADULJE (SALVIA OFFICINALIS L.) I RUŽMARINA (ROSMARINUS OFFICINALIS L.) ZELENIM REZNICAMA

Vegetative propagation of medicinal and aromatic herbs with green cuttings is mainly used because of seed low germination percentage and duration of such reproduction. The aim of this investigation was to determine the effect of commercial rooting powder Rhizopon I on the sage rooting (Salvia officinalis L.) and rosemary (Rosmarinus officinalis L.) green cutting. The investigation was conducted in the greenhouse of the Faculty of Agriculture, University of Banja Luka during April till July of 2012. The experiment consisted of two variants. Cuttings of sage and rosemary were treated with rooting powder or planted directly into the substrate without being previously treated. Morphological properties such as plant height, number of leaves, root length, fresh weight and dry weight of plants were recorded. The treatment with rooting powder resulted in significantly higher values of all morphological parameters tested. Therefore, it is highly recommendable to use it in transplants production thus ensuring the proper rooting of cuttings for earlier transplanting.Vegetativno razmnožavanje ljekovitoga i aromatičnoga bilja provodi se onda kada je postotak klijavosti sjemena nizak te zbog skraćivanja postupka dobivanja presadnica. Cilj je ovog istraživanja utvrditi utjecaj komercijalnoga sredstva za ukorjenjivanje Rhizopon I na ukorjenjivanje zelenih reznica kadulje (Salvia officinalis L.) i ružmarina (Rosmarinus officinalis L.). Istraživanje je provedeno u periodu od travanja do srpanja 2012. na Agronomskome fakultetu Sveučilišta u Banja Luci. Pokus se sastajao od dvije varijante. Reznice kadulje i ružmarina tretirane su sredstvom za ukorjenjivanje ili direktno posađene u supstrat bez prethodnoga tretiranja. Tijekom istraživanja zabilježeni su sljedeći parametri: visina biljke, broj listova, dužina korijena, svježa masa biljaka i suha masa biljaka. Statističkom analizom podataka utvrđeno je da su biljke tretirane hormonom Rhizopon I imale statistički značajno veće vrijednosti svih istraživanih parametara. Stoga, preporučljivo ga je koristiti prilikom vegetativnoga razmnožavanja reznicama te tako osigurati pravilno ukorjenjivanje reznica za ranije presađivanje

Increased Odds of Metabolic Dysfunction-Associated Steatotic Liver Disease Are Linked to Reduced n-6, but Not n-3 Polyunsaturated Fatty Acids in Plasma

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611–0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD

Association among resistin, adenylate cyclase-associated protein 1 and high-density lipoprotein cholesterol in patients with colorectal cancer: a multi-marker approach, as a hallmark of innovative predictive, preventive, and personalized medicine

Background: Elevated concentrations of resistin have been reported in colorectal cancer (CRC), but its interactions with adenylate cyclase-associated protein 1 (CAP-1) are largely unexplored. We investigated resistin plasma concentration, peripheral blood mononuclear cells (PBMCs) resistin messenger ribonucleic acid (mRNA), and CAP-1 mRNA levels in CRC patients, as well as the impact of resistin gene polymorphism rs1862513 on the examined markers. We also explored associations of resistin with high-density lipoprotein cholesterol (HDL-C) and predictive potential of our parameters for CRC. Methods: Eighty-six patients with CRC and 75 healthy adults were included. Commercial ELISA kit was used for obtaining resistin’s concentrations, while polymerase chain reaction (PCR) method was applied for evaluation of resistin and CAP-1 mRNA levels and rs1862513 polymorphism. Results: Plasma resistin and CAP-1 mRNA levels were higher in CRC patients (p < 0.001 and p < 0.05, respectively), while resistin mRNA levels were lower (p < 0.001). Negative association existed among plasma resistin and HDL-C concentrations (ρ = − 0.280; p < 0.05). A model including age, body-mass index, HDL-C, low-density lipoprotein cholesterol (LDL-C), and plasma resistin concentrations as independent predictors of CRC showed very good diagnostic accuracy (AUC = 0.898). We found no associations of rs1862513 with the examined markers. Conclusions: Our study demonstrated increased plasma resistin and CAP-1 mRNA levels, implying their possible interaction in CRC. The association among plasma resistin and HDL-C might indicate that HDL-C is involved in alterations of resistin’s secretion process. As a hallmark of personalized medicine, multi-marker approach in determination of resistin-related parameters might be useful for prediction and prevention of CRC development

Downregulation of CD73/A2AR-Mediated Adenosine Signaling as a Potential Mechanism of Neuroprotective Effects of Theta-Burst Transcranial Magnetic Stimulation in Acute Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by autoimmune-mediated inflammation in the central nervous system. Purinergic signaling is critically involved in MS-associated neuroinflammation and its most widely applied animal model—experimental autoimmune encephalomyelitis (EAE). A promising but poorly understood approach in the treatment of MS is repetitive transcranial magnetic stimulation. In the present study, we aimed to investigate the effect of continuous theta-burst stimulation (CTBS), applied over frontal cranial bone, on the adenosine-mediated signaling system in EAE, particularly on CD73/A2AR/A1R in the context of neuroinflammatory activation of glial cells. EAE was induced in two-month-old female DA rats and in the disease peak treated with CTBS protocol for ten consecutive days. Lumbosacral spinal cord was analyzed immunohistochemically for adenosine-mediated signaling components and pro- and anti-inflammatory factors. We found downregulated IL-1β and NF- κB-ir and upregulated IL-10 pointing towards a reduction in the neuroinflammatory process in EAE animals after CTBS treatment. Furthermore, CTBS attenuated EAE-induced glial eN/CD73 expression and activity, while inducing a shift in A2AR expression from glia to neurons, contrary to EAE, where tight coupling of eN/CD73 and A2AR on glial cells is observed. Finally, increased glial A1R expression following CTBS supports anti-inflammatory adenosine actions and potentially contributes to the overall neuroprotective effect observed in EAE animals after CTBS treatment

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. Results: We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average similar to 62 million reads (53.4% of similar to 116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR lt 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR lt 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter (R) we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Conclusions: Our results demonstrate that RNA sequencing of RNA obtained from archived FFPE lung tissues is feasible. The results obtained from FFPE tissue are highly comparable to FF tissues. The ability to perform RNA-Seq on archived FFPE IPF tissues should greatly enhance the availability of tissue biopsies for research in IPF