[Rheumatology centers according to the regulations of the Federal Joint Committee]. / Rheumatologische Zentren entsprechend den Regelungen des Gemeinsamen Bundesausschusses.

With the Nursing Staff Strengthening Act (Pflegepersonal-Stärkungs-Gesetz), the legislator delegated the specification of the special tasks of centers and focal points to the Federal Joint Committee (G-BA). Due to extensive preliminary work it was already possible to agree on quality requirements and special tasks for rheumatology centers and centers for pediatric and adolescent rheumatology in the first version of the G­BA regulations. Since publication in the Federal Gazette (Bundesanzeiger) on 12 March 2020, rheumatology centers have been able to negotiate surcharges for their special tasks if they have been designated accordingly by the state authorities responsible for hospital planning. So far, 14 rheumatological centers have been designated. Many patients continue to be treated in healthcare structures that are not specialized in acute inpatient rheumatological care. In addition to the additional remuneration, the designation as a rheumatology center can also contribute to patients becoming even more aware of the healthcare structures that are specialized for them. Acute inpatient rheumatology has several specializations. Some clinics have specialized in the multimodal treatment of chronic rheumatism patients and have gained a high level of expertise in this field. Many of these highly specialized clinics have so far been denied recognition as a center because the regulations of the G­BA require the provision of further specialist departments at the same location. While for a large number of medical specializations the establishment at a maximum care hospital is likely to make sense, the specialist clinics focusing on the multimodal treatment of chronic rheumatism patients offer the possibility of strengthening rural areas.

Impact of volatility reduction agents on dicamba and glyphosate spray solution pH, droplet dynamics, and weed control.

BACKGROUND: Regulations in 2021 required the addition of a volatility reduction agent (VRA) to dicamba spray mixtures for postemergence weed control. Understanding the impact of VRAs on weed control, droplet dynamics, and spray pH is essential. RESULTS: Adding glyphosate to dicamba decreased the solution pH by 0.63 to 1.85 units. Across locations, potassium carbonate increased the tank-mixture pH by 0.85 to 1.65 units while potassium acetate raised the pH by 0.46 to 0.53 units. Glyphosate and dicamba in tank-mixture reduced Palmer amaranth control by 14 percentage points compared to dicamba alone and decreased barnyardgrass control by 12 percentage points compared to glyphosate alone 4 weeks after application (WAA). VRAs resulted in a 5-percentage point reduction in barnyardgrass control 4 WAA. Common ragweed, common lambsquarters, and giant ragweed control were unaffected by herbicide solution 4 WAA. Dicamba alone produced a larger average droplet size and had the fewest driftable fines (% volume < 200 µm). Potassium acetate produced a larger droplet size than potassium carbonate for Dv0.1 and Dv0.5 . The addition of glyphosate to dicamba decreased droplet size from the entire spray droplet spectrum (Dv0.1 , Dv0.5 , Dv0.9 ). CONCLUSION: A reduction in spray pH, droplet size, and weed control was observed from mixing dicamba and glyphosate. It may be advisable to avoid tank-mixtures of these herbicides and instead, apply them sequentially to maximize effectiveness. VRAs differed in their impacts on spray solution pH and droplet dynamics, but resulted in a minimal negative to no impact on weed control. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Transcranial Doppler microemboli and acute brain injury in extracorporeal membrane oxygenation: A prospective observational study.

Objective: Extracorporeal membrane oxygenation (ECMO) carries a high morbidity of acute brain injury (ABI) with resultant mortality increase. Transcranial Doppler (TCD) allows real-time characterization of regional cerebral hemodynamics, but limited data exist on the interpretation of microembolic signals (MES) in ECMO. Methods: This prospective cohort study was conducted at a single tertiary care center, November 2017 through February 2022, and included all adult patients receiving venoarterial (VA) and venovenous (VV) ECMO undergoing TCD examinations, which all included MES monitoring. Results: Of 145 patients on ECMO who underwent at least 1 TCD examination, 100 (68.9%) patients on VA-ECMO received 187 examinations whereas 45 (31.1%) patients on VV-ECMO received 65 examinations (P = .81). MES were observed in 35 (35.0%) patients on VA-ECMO and 2 (4.7%) patients on VV-ECMO (P < .001), corresponding to 46 (24.6%) and 2 (3.1%) TCD examinations, respectively. MES were present in 29.4% of patients on VA-ECMO without additional cardiac support, compared with 38.1% with intra-aortic balloon pump and 57.1% with left ventricular assist device, but these differences were not statistically significant (P = .39; P = .20, respectively). Presence or number of MES was not associated with VA-ECMO cannulation mode (23.4% MES presence in peripheral cannulation vs 25.8% in central cannulation, P = .80). In both VA- and VV-ECMO, MES presence or number was not associated with presence of clot or fibrin in the ECMO circuit or with any studied hemodynamic, laboratory, or ECMO parameters at the time of TCD. ABI occurred in 38% and 31.1% of patients on VA- and VV-ECMO, respectively. In multivariable logistic regression analyses, neither ABI nor a composite outcome of arterial thromboembolic events was associated with presence or number of MES in VA- ECMO. Conclusions: TCD analysis in a large cohort of patients on ECMO demonstrates a significant number of MES, especially in patients on VA-ECMO with intra-aortic balloon pump, and/or left ventricular assist device. However, clinical associations and significance of TCD MES remain unresolved and warrant further correlation with systematic imaging and long-term neurologic follow-up.

Serum Raman spectroscopy combined with Deep Neural Network for analysis and rapid screening of hyperthyroidism and hypothyroidism.

Hyperthyroidism and hypothyroidism may cause a series of clinical complications have a high incidence, and early diagnosis is beneficial to treatment. Based on Raman spectroscopy and deep learning algorithms, we propose a rapid screening method to distinguish serum samples of hyperthyroidism patients, hypothyroidism patients and control subjects. We collected 99 serum samples, including 38 cases from hyperthyroidism patients, 32 cases from hypothyroidism patients and 29 cases from control subjects. By comparing and analyzing the Raman spectra of the three, we found differences in the peak intensity of the spectra, indicating that Raman spectra can be used for the subsequent identification of diseases. After collecting the spectral data, Vancouver Raman algorithm (VRA) was used to remove the fluorescence background of the data, and kernel principal component analysis (KPCA) was used to extract the spectral data features with a cumulative explained variance ratio of 0.9999. Then, five neural network models, the adjusted AlexNet, LSTM-CNN, IndRNNCNN, the adjusted GoogLeNet and the adjusted ResNet, were constructed for classifications. The total accuracy was 91%, 84%, 82%, 75% and 71% respectively. The results of our study show that it is feasible to use Raman spectroscopy combined with deep learning to distinguish hyperthyroidism, hypothyroidism and control subjects. After comparing the models, we found that as the neural network deepens and the complexity of the model increases, the classification effect of Raman spectroscopy gradually deteriorates, and we put forward three conjectures for this.

Peer review of the pesticide risk assessment of the active substance Phlebiopsis gigantea strains VRA 1835, VRA 1984 and FOC PG 410.3.

The conclusions of the EFSA following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State Estonia and co-rapporteur Member State, France, for the pesticide active substance Phlebiopsis gigantea strains VRA 1835, VRA 1984 and FOC PG 410.3 are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012, as amended by Commission Implementing Regulation (EU) No 2018/1659. The conclusions were reached on the basis of the evaluation of the representative use of Phlebiopsis gigantea strains VRA 1835, VRA 1984 and FOC PG 410.3 as a fungicide (field use) on conifer forests: pine, spruce, larch. The reliable end points, appropriate for use in regulatory risk assessment, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.

Diffusion tensor tractography of the lumbar nerves before a direct lateral transpsoas approach to treat degenerative lumbar scoliosis.

OBJECTIVEThe purpose of this study was to determine the relationship between vertebral bodies, psoas major morphology, and the course of lumbar nerve tracts using diffusion tensor imaging (DTI) before lateral interbody fusion (LIF) to treat spinal deformities.METHODSDTI findings in a group of 12 patients (all women, mean age 74.3 years) with degenerative lumbar scoliosis (DLS) were compared with those obtained in a matched control group of 10 patients (all women, mean age 69.8 years) with low-back pain but without scoliosis. A T2-weighted sagittal view was fused to tractography from L3 to L5 and separated into 6 zones (zone A, zones 1-4, and zone P) comprising equal quarters of the anteroposterior diameters, and anterior and posterior to the vertebral body, to determine the distribution of nerves at various intervertebral levels (L3-4, L4-5, and L5-S1). To determine psoas morphology, the authors examined images for a rising psoas sign at the level of L4-5, and the ratio of the anteroposterior diameter (AP) to the lateral diameter (lat), or AP/lat ratio, was calculated. They assessed the relationship between apical vertebrae, psoas major morphology, and the course of nerve tracts.RESULTSAlthough only 30% of patients in the control group showed a rising psoas sign, it was present in 100% of those in the DLS group. The psoas major was significantly extended on the concave side (AP/lat ratio: 2.1 concave side, 1.2 convex side). In 75% of patients in the DLS group, the apex of the curve was at L2 or higher (upper apex) and the psoas major was extended on the concave side. In the remaining 25%, the apex was at L3 or lower (lower apex) and the psoas major was extended on the convex side. Significant anterior shifts of lumbar nerves compared with controls were noted at each intervertebral level in patients with DLS. Nerves on the extended side of the psoas major were significantly shifted anteriorly. Nerve pathways on the convex side of the scoliotic curve were shifted posteriorly.CONCLUSIONSA significant anterior shift of lumbar nerves was noted at all intervertebral levels in patients with DLS in comparison with findings in controls. On the convex side, the nerves showed a posterior shift. In LIF, a convex approach is relatively safer than an approach from the concave side. Lumbar nerve course tracking with DTI is useful for assessing patients with DLS before LIF.

Glutathione S-Transferase Alpha 4 Prevents Dopamine Neurodegeneration in a Rat Alpha-Synuclein Model of Parkinson's Disease.

Parkinson's disease (PD) is a common, progressive neurodegenerative disease, which typically presents itself with a range of motor symptoms, like resting tremor, bradykinesia, and rigidity, but also non-motor symptoms such as fatigue, constipation, and sleep disturbance. Neuropathologically, PD is characterized by loss of dopaminergic cells in the substantia nigra pars compacta (SNpc) and Lewy bodies, neuronal inclusions containing α-synuclein (α-syn). Mutations and copy number variations of SNCA, the gene encoding α-syn, are linked to familial PD and common SNCA gene variants are associated to idiopathic PD. Large-scale genome-wide association studies have identified risk variants across another 40 loci associated to idiopathic PD. These risk variants do not, however, explain all the genetic contribution to idiopathic PD. The rat Vra1 locus has been linked to neuroprotection after nerve- and brain injury in rats. Vra1 includes the glutathione S-transferase alpha 4 (Gsta4) gene, which encodes a protein involved in clearing lipid peroxidation by-products. The DA.VRA1 congenic rat strain, carrying PVG alleles in Vra1 on a DA strain background, was recently reported to express higher levels of Gsta4 transcripts and to display partial neuroprotection of SNpc dopaminergic neurons in a 6-hydroxydopamine (6-OHDA) induced model for PD. Since α-syn expression increases the risk for PD in a dose-dependent manner, we assessed the neuroprotective effects of Vra1 in an α-syn-induced PD model. Human wild-type α-syn was overexpressed by unilateral injections of the rAAV6-α-syn vector in the SNpc of DA and DA.VRA1 congenic rats. Gsta4 gene expression levels were significantly higher in the striatum and midbrain of DA.VRA1 compared to DA rats at 3 weeks post surgery, in both the ipsilateral and contralateral sides. At 8 weeks post surgery, DA.VRA1 rats suffered significantly lower fiber loss in the striatum and lower loss of dopaminergic neurons in the SNpc compared to DA. Immunofluorescent stainings showed co-expression of Gsta4 with Gfap at 8 weeks suggesting that astrocytic expression of Gsta4 underlies Vra1-mediated neuroprotection to α-syn induced pathology. This is the second PD model in which Vra1 is linked to protection of the nigrostriatal pathway, solidifying Gsta4 as a potential therapeutic target in PD.

A Morphological and Molecular Characterization of the Spinal Cord after Ventral Root Avulsion or Distal Peripheral Nerve Axotomy Injuries in Adult Rats.

Retrograde cell death in sensory dorsal root ganglion cells following peripheral nerve injury is well established. However, available data regarding the underlying mechanism behind injury induced motoneuron death are conflicting. By comparing morphological and molecular changes in spinal motoneurons after L4-L5 ventral root avulsion (VRA) and distal peripheral nerve axotomy (PNA) 7 and 14 days postoperatively, we aimed to gain more insight about the mechanism behind injury-induced motoneuron degeneration. Morphological changes in spinal cord were assessed by using quantitative immunohistochemistry. Neuronal degeneration was revealed by decreased immunostaining for microtubule-associated protein-2 in dendrites and synaptophysin in presynaptic boutons after both VRA and PNA. Significant motoneuron atrophy was already observed at 7 days post-injury, independently of injury type. Immunostaining for ED1 reactive microglia was significantly elevated in all experimental groups, as well as the astroglial marker glial fibrillary acidic protein (GFAP). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of the ventral horn from L4-L5 spinal cord segments revealed a significant upregulation of genes involved in programmed cell death including caspase-3, caspase-8, and related death receptors TRAIL-R, tumor necrosis factor (TNF)-R, and Fas following VRA. In contrast, following PNA, caspase-3 and the death receptor gene expression levels did not differ from the control, and there was only a modest increased expression of caspase-8. Moreover, the altered gene expression correlated with protein changes. These results show that the spinal motoneurons reacted in a similar fashion with respect to morphological changes after both proximal and distal injury. However, the increased expression of caspase-3, caspase-8, and related death receptors after VRA suggest that injury- induced motoneuron degeneration is mediated through an apoptotic mechanism, which might involve both the intrinsic and the extrinsic pathways.

Astrocytic Expression of GSTA4 Is Associated to Dopaminergic Neuroprotection in a Rat 6-OHDA Model of Parkinson's Disease.

Idiopathic Parkinson's disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD. We therefore investigated whether PVG alleles in Vra1 are neuroprotective in a toxin-induced model of PD and if this effect is coupled to Gsta4. We performed unilateral 6-hydroxydopamine (6-OHDA) partial lesions in the striatum and compared the extent of neurodegeration in parental (DA) and congenic (DA.VRA1) rats. At 8 weeks after 6-OHDA lesion, DA.VRA1 rats displayed a higher density of remaining dopaminergic fibers in the dorsolateral striatum compared to DA rats (44% vs. 23%, p < 0.01), indicating that Vra1 alleles derived from the PVG strain protect dopaminergic neurons from 6-OHDA toxicity. Gsta4 gene expression levels in the striatum and midbrain were higher in DA.VRA1 congenic rats compared to DA at 2 days post-lesion (p < 0.05). The GSTA4 protein co-localized with astrocytic marker GFAP, but not with neuronal marker NeuN or microglial marker IBA1, suggesting astrocyte-specific expression. This is the first report on Vra1 protective effects on dopaminergic neurodegeneration and encourages further studies on Gsta4 in relation to PD susceptibility.

Prediction of frequency-specific hearing threshold using chirp auditory brainstem response in infants with hearing losses.

OBJECTIVES: To investigate the clinical usefulness of the LS-chirp auditory brainstem response for estimation of behavioral thresholds in young children with mild to severe hearing losses. METHODS: 68 infants (136 ears) aged 6-12 months (mean age=9.2 months) with bilateral mild to severe hearing losses were studied at Children's Hospital of Fudan University. In all cases, the children were referred for LS-chirp ABR and visual reinforcement audiometric (VRA) measurements. The low-frequency band chirp (LF-chirp) thresholds (frequency band=0.1-0.85kHz) were compared to the average VRA thresholds (frequency band=0.25-0.5kHz), whereas the high-frequency band chirp (HF-chirp) thresholds (frequency band=1-10kHz) were compared to the average VRA thresholds (frequency band=1-4kHz) using statistical correlation coefficient values. RESULTS: The LS-chirp ABR thresholds are very close to behavioral hearing levels. The mean differences between chirp-ABR and VRA thresholds were within 5dBHL for all measurements. The smallest mean threshold difference (<3dBHL) was obtained for the severe hearing loss group. The correlation coefficient values (r) were 0.97 at low-frequency and high-frequency bands. For each carrier frequency, the best correlations between chirp-ABR thresholds and VRA thresholds were obtained at VRA frequency of 0.25kHz/LF-chirp (r=0.98) and VRA frequency of 1kHz/HF-chirp (r=0.98). CONCLUSIONS: This study demonstrates the effectiveness using chirp-ABR predicted frequency-specific thresholds, especially of low and middle frequencies. LS-chirp ABR thresholds determined behavioral thresholds in patients with severe hearing losses were better than for mild hearing losses. The use of a chirp-ABR testing ensures higher sensitivity and accuracy than that of auditory stead-state evoked response (ASSR) for measuring frequency-specific thresholds in young children.

Long-term effects of a lumbosacral ventral root avulsion injury on axotomized motor neurons and avulsed ventral roots in a non-human primate model of cauda equina injury.

Here, we have translated from the rat to the non-human primate a unilateral lumbosacral injury as a model for cauda equina injury. In this morphological study, we have investigated retrograde effects of a unilateral L6-S2 ventral root avulsion (VRA) injury as well as the long-term effects of Wallerian degeneration on avulsed ventral roots at 6-10 months post-operatively in four adult male rhesus monkeys. Immunohistochemistry for choline acetyl transferase and glial fibrillary acidic protein demonstrated a significant loss of the majority of the axotomized motoneurons in the affected L6-S2 segments and signs of an associated astrocytic glial response within the ventral horn of the L6 and S1 spinal cord segments. Quantitative analysis of the avulsed ventral roots showed that they exhibited normal size and were populated by a normal number of myelinated axons. However, the myelinated axons in the avulsed ventral roots were markedly smaller in caliber compared to the fibers of the intact contralateral ventral roots, which served as controls. Ultrastructural studies confirmed the presence of small myelinated axons and a population of unmyelinated axons within the avulsed roots. In addition, collagen fibers were readily identified within the endoneurium of the avulsed roots. In summary, a lumbosacral VRA injury resulted in retrograde motoneuron loss and astrocytic glial activation in the ventral horn. Surprisingly, the Wallerian degeneration of motor axons in the avulsed ventral roots was followed by a repopulation of the avulsed roots by small myelinated and unmyelinated fibers. We speculate that the small axons may represent sprouting or axonal regeneration by primary afferents or autonomic fibers.

Neuroprotective effects of mesenchymal stem cells on spinal motoneurons following ventral root axotomy: synapse stability and axonal regeneration.

Compression of spinal roots is an important medical problem, which may arise from intervertebral disc herniation, tumor growth or as a result of high energy accidents. Differently from avulsion, root crushing maintains the central/peripheral nervous system (CNS/PNS) connection, although the axons are axotomized and motoneurons degenerate. Such neuronal death may decrease and delay motor function recovery. In the present study we have investigated the neuroprotective effects of mesenchymal stem cell (MSC) therapy following such proximal lesions. Motor recovery and synaptic stabilization were analyzed by the use of morphological and functional approaches. For that, crushing the ventral roots at L4, L5 and L6 was unilaterally performed in Lewis rats. Four weeks after injury, an increased motoneuron survival was observed in the MSC-treated group, coupled with a smaller decrease of inputs at the motoneuron surface and nearby neuropil, seen by synaptophysin and synapsin immunolabeling and decreased astrogliosis, seen by GFAP immunolabeling. In this sense, MSC-treated group displayed a significant preservation of GABAergic terminals, indicating a possible neuroprotection to glutamate excitotoxicity. Motor function recovery was acutely improved in MSC-treated group as compared to Dulbeco's modified eagle medium (DMEM)-treated. Overall, we provide evidence that ventral root crushing (VRC), although milder than avulsion, results in significant loss of motoneurons (~51%) that can be reduced by MSC administration within the spinal cord. Such treatment also improves the number of synapses immunoreactive against molecules present in inhibitory inputs. Also, an increased number of regenerated axons was obtained in the MSC-treated group, in comparison to the DMEM-treated control. Overall, MSC therapy acutely improved limb strength and gait coordination, indicating a possible clinical application of such treatment following proximal lesions at the CNS/PNS interface.