Synaptic Mechanisms underlying Temporally Precise Information Processing in the VNLL, an auditory brainstem nucleus.

Large glutamatergic, somatic synapses mediate temporally precise information transfer. In the ventral nucleus of the lateral lemniscus (VNLL), an auditory brainstem nucleus, the signal of an excitatory large somatic synapse is sign inverted to generate rapid feed forward inhibition with high temporal acuity at sound onsets, a mechanism involved in the suppression of spurious frequency information. The mechanisms of the synaptically driven input-output functions in the VNLL are not fully resolved. Here, we show in Mongolian gerbils of both sexes that for stimulation frequencies up to 200 Hz the EPSC kinetics together with short-term plasticity allow for faithful transmission with only a small increase in latency. Glutamatergic currents are exclusively mediated by AMPARs and NMDARs. Short-term plasticity is frequency dependent and composed of an initial facilitation followed by depression. Physiologically relevant output generation is limited by the decrease in synaptic conductance through short-term plasticity (STP). At this endbulb synapse, STP acts as a low pass filter and increases the dynamic range of the conductance dependent input-output relation, while NMDAR signaling slightly increases the sensitivity of the input-output function. Our computational model shows that STP-mediated filtering limits the intensity dependence of the spike output, thus maintaining selectivity to sound transients. Our results highlight the interaction of cellular features that together give rise to the computations in the circuit.Significant statementAuditory information processing in the brainstem is a prerequisite for generating our auditory representation of the environment. Thereby, many processing steps rely on temporally precise filtering. Precise feed forward inhibition is a key motif in auditory brainstem processing and produced through sign inversion at several large somatic excitatory synapses. A particular feature of the ventral nucleus of the lateral lemniscus is to produce temporally precise onset inhibition with little temporal variance independent of sound intensity. Our cell-physiology and modeling data explain how the synaptic characteristics of different current components and their short-term plasticity are tuned to establish sound intensity-invariant onset inhibition that is crucial for filtering out spurious frequency information.

The Employers' perspective on barriers and facilitators to employment of people with intellectual disability: A differential mixed-method approach.

BACKGROUND: Obtaining employment is among the most important ambitions of people with intellectual disability. Progress towards comprehensive inclusive employment is hampered by numerous barriers. Limited research is available on these barriers and strategies to overcome them. METHOD: A mixed method approach in a sample of 30 HR-managers was used to assess (i) differences in perceived barriers for employment of people with specific disabilities and mental disorders; (ii) barriers specific to employing people with intellectual disability; (iii) strategies to overcome these barriers. RESULTS: Employers perceive more barriers for hiring people with intellectual disability and mental disorders than for physical disabilities. Employment for this population is hampered by a perceived lack of skills and legal issues. Strategies perceived as beneficial are supplying information, changes in organizational strategies and legal changes. CONCLUSIONS: Employers' differentiated expectations and reservations towards hiring individuals with specific disabilities need to be taken into account to increase employment for people with intellectual disability.

Integrating Spiritual Care into Palliative Consultation: A Case Study in Expanded Practice.

Recognizing and addressing spiritual needs has long been identified as a key component of palliative care (PC). More often than not, the provision of spiritual care involves referral to a hospital chaplain. In this study, we aim to describe the role of a PC chaplain embedded within the interdisciplinary PC team and demonstrate how this palliative chaplain role differs from that of a traditional hospital chaplain. We postulate that integrating spiritual care provision into a PC team may offer a broader spiritual care experience for patients receiving PC and begin to delineate expanded clinical roles for the palliative chaplain.

The association between physical activity, low-grade inflammation, and labour market attachment among people with multimorbidity: A cross-sectional study from the Lolland-Falster Health Study, Denmark.

Aim: Evidence suggests low-grade inflammation (LGI) to be associated with multimorbidity. Furthermore, there are links between inflammation markers, physical activity (PA), and labour market participation. The aims of this study were to examine the association between PA and LGI in people with multimorbidity and if this association was moderated by self-reported labour market attachment. Methods: Cross-sectional data were collected in the Lolland-Falster Health Study (LOFUS) from 2016-2020. We included 1,106 participants with multimorbidity and valid accelerometer data. PA was measured as the average counts per minute (CPM) per day during wake time and split in time spent in moderate to vigorous intensity (MVPA) and light intensity (LPA). Degree of inflammation was determined by high sensitive C-reactive protein (hsCRP) level. Associations were investigated using multiple logistic regression analyses, stratified by labour market attachment. Results: The odds of having LGI was higher with lower amount of daily LPA. The highest odds of LGI was observed for CPM < 200 per day (odds ratio (OR) 2.55; 95% confidence interval (CI) 1.46-4.43), MVPA < 15 minutes per day (OR 2.97; 95 % CI 1.56-5.62), and LPA < 90 (OR 2.89; 95 % CI 1.43-5.81) with the reference groups being CPM ≥ 400 per day, MVPA ≥ 30, and LPA ≥ 180 min per day, respectively. We could not preclude an interaction between LPA and labour market attachment (p = 0.109). Conclusion: PA recommendations should be developed with attention to people with chronic diseases, who may experience barriers to reach PA at high intensities. People with no labour market attachment may benefit from primary and secondary prevention of multimorbidity.

Minimal Number of Required Inputs for Temporally Precise Action Potential Generation in Auditory Brainstem Nuclei.

The auditory system relies on temporal precise information transfer, requiring an interplay of synchronously activated inputs and rapid postsynaptic integration. During late postnatal development synaptic, biophysical, and morphological features change to enable mature auditory neurons to perform their appropriate function. How the number of minimal required input fibers and the relevant EPSC time course integrated for action potential generation changes during late postnatal development is unclear. To answer these questions, we used in vitro electrophysiology in auditory brainstem structures from pre-hearing onset and mature Mongolian gerbils of either sex. Synaptic and biophysical parameters changed distinctively during development in the medial nucleus of the trapezoid body (MNTB), the medial superior olive (MSO), and the ventral and dorsal nucleus of the lateral lemniscus (VNLL and DNLL). Despite a reduction in input resistance in most cell types, all required fewer inputs in the mature stage to drive action potentials. Moreover, the EPSC decay time constant is a good predictor of the EPSC time used for action potential generation in all nuclei but the VNLL. Only in MSO neurons, the full EPSC time course is integrated by the neuron's resistive element, while otherwise, the relevant EPSC time matches only 5-10% of the membrane time constant, indicating membrane charging as a dominant role for output generation. We conclude, that distinct developmental programs lead to a general increase in temporal precision and integration accuracy matched to the information relaying properties of the investigated nuclei.

The impact of age and gender on the ICF-based assessment of chronic low back pain.

PURPOSE: To evaluate the impact of age and gender on the international classification of functioning, disability and health (ICF)-based assessment for chronic low back pain. METHODS: Two hundred forty-four chronic low back pain patients (52% female) with a mean age of 49 years (SD =17.64) were interviewed with the comprehensive ICF core set for activities and participation, and environmental factors. After conducting explorative factor analysis, the impact of age and gender on the different factors was analyzed using analyzes of variances. RESULTS: Results revealed that older patients experienced more limitations within "self-care and mobility" and "walking" but less problems with "transportation" compared to younger patients. Older or middle-aged low back pain patients further perceived more facilitation through "architecture and products for communication", "health services", and "social services and products for mobility" than younger patients. Regarding gender differences, women reported more restriction in "housework" than men. An interaction effect between age and gender was found for "social activities and recreation" with young male patients reporting the highest impairment. CONCLUSIONS: The study demonstrated that the comprehensive ICF core set classification for chronic low back pain is influenced by age and gender. This impact is relevant for ICF-based assessments in clinical practice, and should be considered in intervention planning for rehabilitative programs. Implications for rehabilitation It is important to consider age and gender differences when classifying with the ICF. The intervention planning based on the ICF should focus on improvement of bodily functioning and mobility in older patients, facilitation of household activities in women, consideration of work-life balance and recreation (e.g., through mindfulness based stress reduction), and reduction of dissatisfaction with rehabilitation in younger patients. It is important to offer patients the opportunity to participate in intervention planning based on the ICF. For intervention planning professionals should bear in mind the resource-oriented approach of the ICF (e.g., facilitation through environmental factors), and a collaboration with other professionals.

Resonance Properties in Auditory Brainstem Neurons.

Auditory signals carry relevant information on a large range of time scales from below milliseconds to several seconds. Different stages in the auditory brainstem are specialized to extract information in specific frequency domains. One biophysical mechanism to facilitate frequency specific processing are membrane potential resonances. Here, we provide data from three different brainstem nuclei that all exhibit high-frequency subthreshold membrane resonances that are all most likely based on low-threshold potassium currents. Fitting a linear model, we argue that, as long as neurons possess active subthreshold channels, the main determinant for their resonance behavior is the steady state membrane time constant. Tuning this leak conductance can shift membrane resonance frequencies over more than a magnitude and therefore provide a flexible mechanism to tune frequency-specific auditory processing.

Intrinsic frequency response patterns in mechano-sensory neurons of the leech.

Animals employ mechano-sensory systems to detect and explore their environment. Mechano-sensation encompasses stimuli such as constant pressure, surface movement or vibrations at various intensities that need to be segregated in the central nervous system. Besides different receptor structures, sensory filtering via intrinsic response properties could provide a convenient way to solve this problem. In leech, three major mechano-sensory cell types can be distinguished, according to their stimulus sensitivity, as nociceptive, pressure and touch cells. Using intracellular recordings, we show that the different mechano-sensory neuron classes in Hirudo medicinalis differentially respond supra-threshold to distinct frequencies of sinusoidal current injections between 0.2 and 20 Hz. Nociceptive cells responded with a low-pass filter characteristic, pressure cells as high-pass filters and touch cells as an intermediate band-pass filter. Each class of mechano-sensory neurons is thus intrinsically tuned to a specific frequency range of voltage oscillation that could help segregate mechano-sensory information centrally.

Comparisons in Muscle Function and Training Rehabilitation Outcomes Between Avoidance-Endurance Model Subgroups.

OBJECTIVES: Evidence suggests that chronic low back pain patients with fear-avoidance (FAR) or endurance behavior are at risk of treatment failure and pain maintenance, with bodily overuse or underuse being assumed as mediating mechanisms for pain chronification. This study sought to examine whether or not the avoidance-endurance model subgroups, FAR, distress-endurers (DER), eustress-endurers (EER), and adaptive responders (AR), differed in physical measures and outcomes after training therapy. MATERIALS AND METHODS: A total of 137 chronic low back pain patients were assessed before, at the end of, and 6 months after a 6-month rehabilitation training. Patients performed maximum back extension strength and trunk range-of-motion measures, flexion-relaxation tests, and completed the following questionnaires: Avoidance-Endurance Questionnaire, Roland-Morris Disability Questionnaire, Pain Disability Index, 36-Item Short-Form Health Survey, International Physical Activity Questionnaire, and visual analog scale. Statistical analysis included cluster analysis, analysis of covariances, and mixed-effects models. RESULTS: At baseline, avoidance-endurance model subgroups did not differ in physical measures and activity levels. At the end of training, patients' back-related health was significantly improved in all subgroups. However, the DER and the FAR were found to be more impaired before and after the intervention compared with EER and AR, as indicated by a higher pain intensity, higher disability levels, lower quality of life, and inferior working capacity. DISCUSSION: Although FAR and DER did not differ in physical measures or activity levels from EER and AR, they demonstrated poor lower back-related health at baseline and after intervention. Thus, future research should elucidate as to which additional interventions could optimize their health.