Unleashing the potential of dance: a neuroplasticity-based approach bridging from older adults to Parkinson's disease patients.

Parkinson's disease (PD) is a neurodegenerative disorder that affects >1% of individuals worldwide and is manifested by motor symptoms such as tremor, rigidity, and bradykinesia, as well as non-motor symptoms such as cognitive impairment and depression. Non-pharmacological interventions such as dance therapy are becoming increasingly popular as complementary therapies for PD, in addition to pharmacological treatments that are currently widely available. Dance as a sensorimotor activity stimulates multiple layers of the neural system, including those involved in motor planning and execution, sensory integration, and cognitive processing. Dance interventions in healthy older people have been associated with increased activation of the prefrontal cortex, as well as enhanced functional connectivity between the basal ganglia, cerebellum, and prefrontal cortex. Overall, the evidence suggests that dance interventions can induce neuroplastic changes in healthy older participants, leading to improvements in both motor and cognitive functions. Dance interventions involving patients with PD show better quality of life and improved mobility, whereas the literature on dance-induced neuroplasticity in PD is sparse. Nevertheless, this review argues that similar neuroplastic mechanisms may be at work in patients with PD, provides insight into the potential mechanisms underlying dance efficacy, and highlights the potential of dance therapy as a non-pharmacological intervention in PD. Further research is warranted to determine the optimal dance style, intensity, and duration for maximum therapeutic benefit and to determine the long-term effects of dance intervention on PD progression.

The Applicability of Provocative Functional Tests in the Diagnosis of Rotator Cuff Muscle Injuries of the Best University Athletes.

Rotator cuff disease, external and internal impingement syndromes, low shoulder stability, various types of trauma, and overuse injuries are all related to sports activities. In order to check symptoms in patients with disability and shoulder pain, clinicians use different methods and diagnostic imaging assessment. The research is aimed at evaluating whether there is a difference between provocation function tests (PFT) and ultrasonographic (US) testing of muscles within the rotator cuff in elite collegiate athletes. Patients (n = 184) were recruited from university team sports selections and tested with a standardized US examination of the shoulder and five PFTs (Speed's test, Neer's test, Hawkins test, lift-off test, Yergason's test). Based on the VAS pain assessment scale, 60 subjects had some pain, which was taken for further processing in the work (124 subjects did not have the presence of pain and were excluded from further processing). The US examination was conducted using Voluson 730 apparatus, by a linear probe, with the frequency in the range of 6-12 MHz. The chi-square test showed significant differences between PFT and the occurrence of shoulder muscle tendinitis for the following variables: Speed's test and subscapularis tendinitis (p = 0.02) and Speed's test and infraspinatus tendinitis (p = 0.01); Neer test and biceps brachii caput longum tendinitis (p = 0.01), Neer test and supraspinatus tendinitis (p = 0.02) and Neer test and infraspinatus tendinitis (p = 0.01); lift-off test and subscapularis tendinitis (p = 0.05); and Yergason's test and biceps brachii caput longum tendinitis (p = 0.03) and Yergason's test and subscapitis tendinitis (p = 0.01). The greatest effect of differences was observed in Neer's test and biceps brachii caput longum tendinitis (φ = 0.60), while the other effects can be described as medium and small in most cases. It can be concluded that functional tests are good predictors of soft tissue changes in the muscles of the rotator cuff of the shoulder. Further monitoring and analysis are needed on a larger number of athletes.

Comparison of the Field-Based Intermittent Running Fitness Test 30-15 and the Treadmill Multistage Incremental Test for the Assessment of Cardiorespiratory Fitness in Elite Handball Players.

The aim of the present study was to investigate whether the physiological parameters indicative of cardiorespiratory fitness obtained during the 30-15 intermittent fitness (30-15IFT) test and the multistage laboratory treadmill endurance (TR) test differ. Nineteen elite handball players were recruited for the current study and assigned in a cross-over manner to one of two tests to be performed 48 h apart at each visit to the testing facility. The results showed that VO2max (percentage difference [PC] = 6.1%; p = 0.004) and maximal running velocity (V) (PC = 19.4%; p < 0.001) were significantly higher for the 30-15IFT test than that obtained during the TR test. Furthermore, the onset of blood lactate accumulation was shown to be significantly higher for all measures considered to predict it during 30-15IFT compared to TR as follows: VO2max (PC = 12.6%; p = 0.001), running speed (PC = 33.9%; p < 0.001), and maximal heart rate (PC = 7.5%; p < 0.001). The current study highlights the importance of sport-specific testing, particularly for measuring individual cardiorespiratory fitness in elite handball players, as TR may underestimate crucial variables used for both diagnostics and training prescription.

The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice.

Before hearing onset (postnatal day 12 in mice), inner hair cells (IHCs) spontaneously fire action potentials, thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISCs) of Kölliker's organ through the activity of the Ca2+-activated Cl--channel TMEM16A (ANO1). Here, we show that conditional deletion of Ano1 (Tmem16a) in mice disrupts Ca2+ waves within Kölliker's organ, reduces the burst-firing activity and the frequency selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the functional refinement of MNTB projections to the lateral superior olive. These results reveal the importance of the activity of Kölliker's organ for the refinement of central auditory connectivity. In addition, our study suggests the involvement of TMEM16A in the propagation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.

Deletion of BDNF in Pax2 Lineage-Derived Interneuron Precursors in the Hindbrain Hampers the Proportion of Excitation/Inhibition, Learning, and Behavior.

Numerous studies indicate that deficits in the proper integration or migration of specific GABAergic precursor cells from the subpallium to the cortex can lead to severe cognitive dysfunctions and neurodevelopmental pathogenesis linked to intellectual disabilities. A different set of GABAergic precursors cells that express Pax2 migrate to hindbrain regions, targeting, for example auditory or somatosensory brainstem regions. We demonstrate that the absence of BDNF in Pax2-lineage descendants of Bdnf Pax2 KOs causes severe cognitive disabilities. In Bdnf Pax2 KOs, a normal number of parvalbumin-positive interneurons (PV-INs) was found in the auditory cortex (AC) and hippocampal regions, which went hand in hand with reduced PV-labeling in neuropil domains and elevated activity-regulated cytoskeleton-associated protein (Arc/Arg3.1; here: Arc) levels in pyramidal neurons in these same regions. This immaturity in the inhibitory/excitatory balance of the AC and hippocampus was accompanied by elevated LTP, reduced (sound-induced) LTP/LTD adjustment, impaired learning, elevated anxiety, and deficits in social behavior, overall representing an autistic-like phenotype. Reduced tonic inhibitory strength and elevated spontaneous firing rates in dorsal cochlear nucleus (DCN) brainstem neurons in otherwise nearly normal hearing Bdnf Pax2 KOs suggests that diminished fine-grained auditory-specific brainstem activity has hampered activity-driven integration of inhibitory networks of the AC in functional (hippocampal) circuits. This leads to an inability to scale hippocampal post-synapses during LTP/LTD plasticity. BDNF in Pax2-lineage descendants in lower brain regions should thus be considered as a novel candidate for contributing to the development of brain disorders, including autism.

Evaluation of rapeseed varieties using novel integrated fuzzy PIPRECIA - Fuzzy MABAC model.

Decision making is constantly present in agriculture. Choosing the wrong variety carries the risk that the investment in terms of sowing does not pay off at all. Therefore, it is necessary to choose the variety that gives the best results. In order to achieve this, it is necessary to apply multi-criteria decision-making of available varieties, which is, in this paper, done on the example of hybrid varieties of rapeseed that were created by selection at the Institute of Field and Vegetable Crops in Novi Sad. By applying fuzzy logic, a novel integrated Multi-Criteria Decision-Making (MCDM) model is developed and rapeseed varieties were evaluated. For determining four main and 20 subcriteria, fuzzy PIPRECIA (PIvot Pairwise RElative Criteria Importance Assessment) method has been applied based on fuzzy Bonferroni operator, while for ranking alternatives fuzzy MABAC (Multi-Attributive Border Approximation area Comparison) method has been used. The results obtained using the novel integrated fuzzy MCDM model showed that the variety A2 - Zorica has the best results, followed by A1 - NS Ras, while the worst results were seen by the variety A5 - Zlatna. These results were confirmed using other five fuzzy MCDM methods. Sensitivity analysis-changing criteria weights showed the worst results in the variety A6 - Jovana, which took last place in the application of 18 scenarios. The presented model and the results of this research will help farmers to solve this decision problem.

Purinergic Modulation of Activity in the Developing Auditory Pathway.

Purinergic P2 receptors, activated by endogenous ATP, are prominently expressed on neuronal and non-neuronal cells during development of the auditory periphery and central auditory neurons. In the mature cochlea, extracellular ATP contributes to ion homeostasis, and has a protective function against noise exposure. Here, we focus on the modulation of activity by extracellular ATP during early postnatal development of the lower auditory pathway. In mammals, spontaneous patterned activity is conveyed along afferent auditory pathways before the onset of acoustically evoked signal processing. During this critical developmental period, inner hair cells fire bursts of action potentials that are believed to provide a developmental code for synaptic maturation and refinement of auditory circuits, thereby establishing a precise tonotopic organization. Endogenous ATP-release triggers such patterned activity by raising the extracellular K+ concentration and contributes to firing by increasing the excitability of auditory nerve fibers, spiral ganglion neurons, and specific neuron types within the auditory brainstem, through the activation of diverse P2 receptors. We review recent studies that provide new models on the contribution of purinergic signaling to early development of the afferent auditory pathway. Further, we discuss potential future directions of purinergic research in the auditory system.

Functional Development of Principal Neurons in the Anteroventral Cochlear Nucleus Extends Beyond Hearing Onset.

Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience.

Tonotopic action potential tuning of maturing auditory neurons through endogenous ATP.

KEY POINTS: Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map. In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell-specific and tonotopically-determined manner. Developmental down-regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, suggesting a high-to-low frequency maturation pattern. Facilitated action potential (AP) generation, measured as higher firing rate, shorter EPSP-AP delay in vivo and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. The long lasting change in intrinsic neuronal excitability is mediated by the heteromeric P2X2/3 receptors. ABSTRACT: Synaptic refinement and strengthening are activity-dependent processes that establish orderly arranged cochleotopic maps throughout the central auditory system. The maturation of auditory brainstem circuits is guided by action potentials (APs) arising from the inner hair cells in the developing cochlea. The AP firing of developing central auditory neurons can be modulated by paracrine ATP signalling, as shown for the cochlear nucleus bushy cells and principal neurons in the medial nucleus of the trapezoid body. However, it is not clear whether neuronal activity may be specifically regulated with respect to the nuclear tonotopic position (i.e. sound frequency selectivity). Using slice recordings before hearing onset and in vivo recordings with iontophoretic drug applications after hearing onset, we show that cell-specific purinergic modulation follows a precise tonotopic pattern in the ventral cochlear nucleus of developing gerbils. In high-frequency regions, ATP responsiveness diminished before hearing onset. In low-to-mid frequency regions, ATP modulation persisted after hearing onset in a subset of low-frequency bushy cells (characteristic frequency< 10 kHz). Down-regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, thus suggesting a high-to-low frequency maturation pattern. Facilitated AP generation, measured as higher firing frequency, shorter EPSP-AP delay in vivo, and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. Finally, by combining recordings and pharmacology in vivo, in slices, and in human embryonic kidney 293 cells, it was shown that the long lasting change in intrinsic neuronal excitability is mediated by the P2X2/3R.

Calculating the costs of waste collection: A methodological proposal.

Waste collection and transport can generate up to 70% of the total costs of the system. Separated collection of recyclables implies additional costs for which the sale of recycled waste often does not compensate, but there is increased pressure to reach the long-term recycling objectives set by law. The proper estimation and monitoring of waste collection costs are essential to define the most cost-effective waste collection system. The aim of this study is to propose and implement a management tool to determine waste collection costs for different waste collection schemes. Based on input data, such as waste quantity and composition, the number of waste bins, the location of collection points, the type of collection vehicle, crew, collection route, etc., the developed tool can calculate the time and costs of waste collection (per vehicle, collection point or tonne of collected waste). This tool uses Excel spreadsheets and it was tested on a district in the central area of the city of Kragujevac to calculate the costs of waste collection for two scenarios: Collecting all waste as mixed waste, and collecting separately recyclables and residual waste. The developed tool can be useful for municipal solid waste management companies, since it allows benchmarking and variance analysis.

Using multi-criteria decision making for selection of the optimal strategy for municipal solid waste management.

Multi-criteria decision making (MCDM) is a relatively new tool for decision makers who deal with numerous and often contradictory factors during their decision making process. This paper presents a procedure to choose the optimal municipal solid waste (MSW) management system for the area of the city of Kragujevac (Republic of Serbia) based on the MCDM method. Two methods of multiple attribute decision making, i.e. SAW (simple additive weighting method) and TOPSIS (technique for order preference by similarity to ideal solution), respectively, were used to compare the proposed waste management strategies (WMS). Each of the created strategies was simulated using the software package IWM2. Total values for eight chosen parameters were calculated for all the strategies. Contribution of each of the six waste treatment options was valorized. The SAW analysis was used to obtain the sum characteristics for all the waste management treatment strategies and they were ranked accordingly. The TOPSIS method was used to calculate the relative closeness factors to the ideal solution for all the alternatives. Then, the proposed strategies were ranked in form of tables and diagrams obtained based on both MCDM methods. As shown in this paper, the results were in good agreement, which additionally confirmed and facilitated the choice of the optimal MSW management strategy.

Purinergic modulation of neuronal activity in developing auditory brainstem.

In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca(2+) signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

Therapeutic effects of combined treatment with ribavirin and tiazofurin on experimental autoimmune encephalomyelitis development: clinical and histopathological evaluation.

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and the helpful tool in preclinical testing of various substances considered for treatment of this human CNS disease. Ribavirin (R) and tiazofurin (T) are purine nucleoside analogues, with the broad spectrum of anti-viral, anti-tumoral and anti-inflammatory properties. We proposed that combined treatment with RT, administrated during the effector phase of EAE, would attenuate disease severity, both clinically and pathologically. Ribavirin was given daily at a dosage of 30 mg/kg and tiazofurin was given at a dosage of 10 mg/kg every other day for 15 days. We detected amelioration of clinical signs and faster recovery in the RT group compared to the control group. Immunohistochemical analyses revealed that RT treatment decrease the number of T cells, macrophages and microglia. In the controls, we detected reactive type of microglia, while in the RT group we noticed ramified/resting form. Demyelination areas and axonal damage were not recorded in the RT group, in contrast to the control group where multiple areas of demyelination zones and axonal loss were found. RT combination treatment suppresses ongoing EAE, prevents demyelination and axonal loss, and therefore may well be the potential therapy for the treatment of MS.

Contingency awareness and fear inhibition in a human fear-potentiated startle paradigm.

Fear-potentiated startle is defined as an increase in the magnitude of the startle reflex in the presence of a stimulus that was previously paired with an aversive event. It has been proposed that a subject's awareness of the contingencies in the experiment may affect fear-potentiated startle. The authors adapted a conditional discrimination procedure (AX+/BX-), previously validated in animals, to a human fear-potentiated startle paradigm in 50 healthy volunteers. This paradigm allows for an assessment of fear-potentiated startle during threat conditions as well as inhibition of fear-potentiated startle during safety conditions. A response keypad was used to assess contingency awareness on a trial-by-trial basis. Both aware and unaware subjects showed fear-potentiated startle. However, awareness was related to stimulus discrimination and fear inhibition.