Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.

PURPOSE: There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils. METHODS: SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aß)42, K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies. RESULTS: We optimized the protocol for the immobilization of Aß42, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aß in arcAß mice, and AT-8/AT-100-positivity in pR5 mice. CONCLUSION: SPR measurements of small molecules binding to Aß42, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies.

Predictive risk model of recurrence of acute diverticulitis after the first episode.

INTRODUCTION: The recurrence of acute diverticulitis (AD) of the colon is frequent and leads to hospital readmissions and the need for elective surgery in selected cases. It is important to individualize risk factors and develop predictive tools for their identification. MATERIALS AND METHODS: This prospective observational study included 368 patients who were diagnosed with AD between 2016 and 2021 in a tertiary general university hospital during their first episode and who had a good response to antibiotic, percutaneous, or peritoneal lavage treatment. Univariate and multivariate Cox regression analyses of the variables associated with recurrence were performed. Subsequently, a predictive risk score was developed and validated through survival studies. RESULTS: After a median follow-up of 50 months, there were 71 (19.3%) cases of recurrence out of a total of 368 patients. The mean time of recurrence was 15 months, and 73.3% of cases of recurrence occurred before 2 years of follow-up. Recurrence was independently associated with presentation with colonic perforation in the antimesenteric location (HR 3.67 95% CI [1.59-8.4]) and a CRP level greater than 100 mg/dl (HR 1.69 95% CI [1.04-2.77). A score with 5 variables was created that differentiated two risk groups: intermediate risk (0-3 points), with 19% recurrence and high risk (more than 3 points), with 42% recurrence. CONCLUSIONS: The risk of recurrence after the first episode of diverticulitis can be estimated using predictive scores. The detection of high-risk patients facilitates the individualization of follow-up and treatment.

Cell-to-cell transmitted alpha-synuclein recapitulates experimental Parkinson's disease.

Parkinson's disease is characterized by a progressive accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies in the nervous system. Lewy bodies can arise from the cell-to-cell propagation of αSyn, which can occur via sequential steps of secretion and uptake. Here, by fusing a removable short signal peptide to the N-terminus of αSyn, we developed a novel mouse model with enhanced αSyn secretion and cell-to-cell transmission. Expression of the secreted αSyn in the mouse brain was under the control of a novel hybrid promoter in combination with adeno-associated virus serotype 9 (AAV9). This combination of promoter and viral vector induced a robust expression in neurons but not in the glia of injected mice. Biochemical characterization of the secreted αSyn revealed that, in cultured cells, this protein is released to the extracellular milieu via conventional secretion. The released αSyn is then internalized and processed by acceptor cells via the endosome-lysosome pathway indicating that the secreted αSyn is cell-to-cell transmitted. The secreted αSyn is aggregation-prone and amyloidogenic, and when expressed in the brain of wild-type non-transgenic mice, it induces a Parkinson's disease-like phenotype that includes a robust αSyn pathology in the substantia nigra, neuronal loss, neuroinflammation, and motor deficits, all the key features of experimental animal models of Parkinson's disease. In summary, a novel animal model of Parkinson's disease based on enhanced cell-to-cell transmission of αSyn was developed. The neuron-produced cell-to-cell transmitted αSyn triggers all phenotypic features of experimental Parkinson's disease in mice.

Vitamin D Hydroxylation-deficient Rickets Type 1A Misdiagnosed as Normocalcemic Primary Hyperparathyroidism.

Vitamin D hydroxylation-deficient rickets type 1A is an autosomal recessive disorder caused by pathogenic variants in CYP27B1 gene, which encodes for 1α-hydroxylase, the enzyme responsible for the conversion of 25-OH vitamin D into its active form 1,25(OH)2 vitamin D. We report the case of a 3-year-old female Mexican patient with growth retardation and progressive bone deformity, whose laboratory studies showed 25-OH vitamin D deficiency, a normal serum calcium and an elevated intact parathyroid hormone level that remained high despite calcitriol, cholecalciferol, and calcium supplementation. 99mTc sestamibi gammagram showed findings suggestive of parathyroid hyperplasia. Bone histomorphometry showed an image consistent with hyperparathyroidism without findings of osteomalacia, so normocalcemic primary hyperparathyroidism was suspected and a subtotal parathyroidectomy was performed, with the patient developing postoperative hypoparathyroidism. When she arrived at our clinic at age 18 years, she showed calcium- and calcitriol-dependent hypocalcemia, with secondary hyperparathyroidism and low levels of 1,25(OH)2 vitamin D in the absence of a 25-OH vitamin D deficiency, reflecting a defect in 1α-hydroxylation. Molecular testing revealed compound heterozygous variants in CYP27B1 gene. This is the first reported case of an inherited disorder of vitamin D metabolism that was diagnosed and surgically treated as primary hyperparathyroidism.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Background: Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. Methods: Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. Results: THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. Conclusion: We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

A 14-Day Therapeutic Exercise Telerehabilitation Protocol of Physiotherapy Is Effective in Non-Hospitalized Post-COVID-19 Conditions: A Randomized Controlled Trial.

The emergence of COVID-19 has led to serious public health problems. Now that the acute phase of the pandemic has passed, new challenges have arisen in relation to this disease. The post-COVID-19 conditions are a priority for intervention, as months after the onset of the disease, they continue to present symptoms, especially physical and respiratory symptoms. Our aim is to test the efficacy of a fourteen-day telerehabilitation program of respiratory and strength exercises in people with post-COVID-19 conditions. For this purpose, a randomized controlled trial was generated in which data from 48 patients were analyzed using the BS, 30STSTST, MD12, VAFS, and 6MWT tests. The obtained results showed the benefit of the intervention in generating great results with respect to the control group.

Multi-Dimensional Structure and Dynamics Landscape of Proteins in Mammalian Cells Revealed by In-Cell NMR.

Governing function, half-life and subcellular localization, the 3D structure and dynamics of proteins are in nature constantly changing in a tightly regulated manner to fulfill the physiological and adaptive requirements of the cells. To find evidence for this hypothesis, we applied in-cell NMR to three folded model proteins and propose that the splitting of cross peaks constitutes an atomic fingerprint of distinct structural states that arise from multiple target binding co-existing inside mammalian cells. These structural states change upon protein loss of function or subcellular localisation into distinct cell compartments. In addition to peak splitting, we observed NMR signal intensity attenuations indicative of transient interactions with other molecules and dynamics on the microsecond to millisecond time scale.

Protein structure determination in human cells by in-cell NMR and a reporter system to optimize protein delivery or transexpression.

Most experimental methods for structural biology proceed in vitro and therefore the contribution of the intracellular environment on protein structure and dynamics is absent. Studying proteins at atomic resolution in living mammalian cells has been elusive due to the lack of methodologies. In-cell nuclear magnetic resonance spectroscopy (in-cell NMR) is an emerging technique with the power to do so. Here, we improved current methods of in-cell NMR by the development of a reporter system that allows monitoring the delivery of exogenous proteins into mammalian cells, a process that we called here "transexpression". The reporter system was used to develop an efficient protocol for in-cell NMR which enables spectral acquisition with higher quality for both disordered and folded proteins. With this method, the 3D atomic resolution structure of the model protein GB1 in human cells was determined with a backbone root-mean-square deviation (RMSD) of 1.1 Å.

Therapeutic Exercise Interventions through Telerehabilitation in Patients with Post COVID-19 Symptoms: A Systematic Review.

The worldwide incidence of COVID-19 has generated a pandemic of sequelae. These sequelae require multidisciplinary rehabilitative work to address the multisystemic symptoms that patients will present with now and in the future. The aim of the present systematic review is to analyze the current situation of telerehabilitation in patients with COVID-19 sequelae and its effectiveness. Searches were conducted on the following databases: PubMed, Scopus, PEDro, and Web of Science (WOS). There was no complete homogeneity among the five selected articles, so we differentiated two clinical subgroups for the clustering of outcome measures: (group one) patients with post-discharge symptoms and (group two) patients with permanent symptoms or "long COVID-19" defined as persistent symptoms > 2 months. For group one, post-discharge sequelae, improvements were obtained in cardiovascular parameters, and physical test studies in group two presented very favorable results in all the cardiorespiratory measures and physical tests evaluated. Telerehabilitation through therapeutic exercise based on mixed protocols of aerobic, respiratory, and low-load strength exercises appear to be an effective and safe strategy for the recovery of short- and long-term post-COVID-19 sequelae.

Spanish Validation of the PALMS (Physical Activity and Leisure Motivation Scale).

Although there is abundant evidence supporting an active lifestyle, it is necessary to promote the practice of physical activity among the population. To understand this phenomenon, several studies have been conducted to describe the reasons why people participate in sports activities. The PALMS (Physical Activity and Leisure Motivation Scale) was created as a comprehensive tool to measure the reasons for practicing sports. This tool consists of 40 items related to sports and is designed for the young and adult population. Each of the subscales is formed of five items (mastery, enjoyment, psychological condition, physical condition, appearance, the expectations of others, affiliation, competition/ego) that reflect the possible reasons for practicing sports. This study sought to validate the PALMS in the cultural context of Spain, for the type of population for which it is designed. In total, 596 voluntary participants completed the study from Spain, aged 18 to 53, who regularly practice sports. The adequacy of the model obtained in the exploratory study was confirmed, since a model composed of eight factors and 40 indicators in total was obtained. The parameters were statistically significant (p < 0.05) and the factor loadings presented values greater than 0.5. Regarding internal consistency, the values of Cronbach's alpha and those of the composite reliability were above 0.8. In conclusion, the validation of the Spanish PALMS proved to be a valid and reliable measurement instrument for the evaluation of the reasons that lead the population to perform sports physical activity.

Effects of Foam Rolling vs. Manual Therapy in Patients with Tension-Type Headache: A Randomized Pilot Study.

BACKGROUND: This study compares the effect of foam rolling (FR) vs. manual therapy (MT) on pain, pressure pain threshold (PPT), headache disability (HDI) and impact of headache (HIT-6) in patients with tension-type headache (TTH). METHODS: A total of 38 participants with TTH were randomly assigned to an FR group (FRG, n = 13), an MT group (MTG, n = 13) or a control group (CG, n = 12). FRG received FR treatment; MTG received MT techniques; CG received a placebo treatment. The treatment lasted one month. Outcome measures were assessed at baseline, post-intervention and follow-up. RESULTS: Both FRG and MTG showed significant improvements in all variables after the treatment, but the intervention effect was maintained only for functional disability (p = 0.002 and p = 0.005, respectively), overall disability (p = 0.007; p = 0.030) and HIT-6 (p = 0.002; p = 0.001) at follow-up. After treatment, FRG and MTG presented a significantly higher PPT in right (p = 0.044; p = 0.009) and left suboccipital (p = 0.004; p = 0.021). MTG showed a significantly lower HIT-6 than CG (p = 0.008). No differences between FRG and MTG were found in any variable. CONCLUSIONS: Both FR and MT are effective treatments for the improvement of clinical symptoms in TTH. Further studies are needed to confirm our findings in a larger population.

Non-invasive imaging of tau-targeted probe uptake by whole brain multi-spectral optoacoustic tomography.

PURPOSE: Abnormal tau accumulation within the brain plays an important role in tauopathies such as Alzheimer's disease and frontotemporal dementia. High-resolution imaging of tau deposits at the whole-brain scale in animal disease models is highly desired. METHODS: We approached this challenge by non-invasively imaging the brains of P301L mice of 4-repeat tau with concurrent volumetric multi-spectral optoacoustic tomography (vMSOT) at ~ 115 µm spatial resolution using the tau-targeted pyridinyl-butadienyl-benzothiazole derivative PBB5 (i.v.). In vitro probe characterization, concurrent vMSOT and epi-fluorescence imaging of in vivo PBB5 targeting (i.v.) was performed in P301L and wild-type mice, followed by ex vivo validation using AT-8 antibody for phosphorylated tau. RESULTS: PBB5 showed specific binding to recombinant K18 tau fibrils by fluorescence assay, to post-mortem Alzheimer's disease brain tissue homogenate by competitive binding against [11C]PBB3 and to tau deposits (AT-8 positive) in post-mortem corticobasal degeneration and progressive supranuclear palsy brains. Dose-dependent optoacoustic and fluorescence signal intensities were observed in the mouse brains following i.v. administration of different concentrations of PBB5. In vivo vMSOT brain imaging of P301L mice showed higher retention of PBB5 in the tau-laden cortex and hippocampus compared to wild-type mice, as confirmed by ex vivo vMSOT, epi-fluorescence, multiphoton microscopy, and immunofluorescence staining. CONCLUSIONS: We demonstrated non-invasive whole-brain imaging of tau in P301L mice with vMSOT system using PBB5 at a previously unachieved ~ 115 µm spatial resolution. This platform provides a new tool to study tau spreading and clearance in a tauopathy mouse model, foreseeable in monitoring tau targeting putative therapeutics.

Breathing exercises versus strength exercises through telerehabilitation in coronavirus disease 2019 patients in the acute phase: A randomized controlled trial.

OBJECTIVE: To compare the effectiveness of two different exercise-based programs through telerehabilitation in patients with coronavirus disease 2019. DESIGN: Randomized, controlled, parallel, double-blinded, three-arm clinical trial. SETTING: Patients' homes through telerehabilitation devices. SUBJECTS: Subjects with coronavirus disease 2019 in the acute phase. INTERVENTIONS: Subjects were divided into three groups: breathing exercises group, strength exercises group or no treatment/control group. MAIN MEASURES: We analysed visual analogue scale for fatigue, 6-minute walking test, 30-seconds sit-to-stand test, multidimensional dyspnoea-12 questionnaire and Borg scale at baseline and 14 days later. RESULTS: From 93 subjects recruited, 88 were enrolled, and 77 patients (mean [SD] age 39.40 [11.71]) completed the 14-days intervention and were included in the analysis: 26 in strength exercises group, 29 in breathing exercises group and 22 in control group. The intergroup analysis shows significant differences between the study groups and control group in all variables (p < 0.05); Borg scale, multidimensional dyspnoea-12 questionnaire (pre-post intervention score: strength exercises group: 7.85 [6.82] - 4.54[4.82], breathing exercises group: 11.04 [6.49] - 5.32 [3.63], control group: 10.27 [6.49] - 10.59[6.58]), visual analogue scale for fatigue, 6-minute walking test and 30-seconds sit-to-stand test (pre-post intervention score: strength exercises group: 12.19 [4.42] - 13.58 [5.37], breathing exercises group: 11.18 [3.42] - 12.79 [4.00], control group: 10.45 [2.15] - 9.86[1.88]). The greatest effect sizes were found in the variables Borg Scale (R2 = 0.548) and multidimensional dyspnoea-12 questionnaire (R2 = 0.475). CONCLUSIONS: Strength exercises group and breathing exercises group obtained significant improvements in fatigue, dyspnoea, perceived effort, and physical state, compared to control group, although the greatest benefits were found for dyspnoea and aerobic capacity in breathing exercises group.

Slow-wave sleep affects synucleinopathy and regulates proteostatic processes in mouse models of Parkinson's disease.

Slow-wave sleep (SWS) modulation in rodent models of Alzheimer's disease alters extracellular amyloid burden. In Parkinson's disease (PD), SWS appears to be closely linked with disease symptoms and progression. PD is characterized by damaging intracellular α-synuclein (αSyn) deposition that propagates extracellularly, contributing to disease spread. Intracellular αSyn is sensitive to degradation, whereas extracellular αSyn may be eliminated by glymphatic clearance, a process increased during SWS. Here, we explored whether long-term slow-wave modulation in murine models of PD presenting αSyn aggregation alters pathological protein burden and, thus, might constitute a valuable therapeutic target. Sleep-modulating treatments showed that enhancing slow waves in both VMAT2-deficient and A53T mouse models of PD reduced pathological αSyn accumulation compared to control animals. Nonpharmacological sleep deprivation had the opposite effect in VMAT2-deficient mice, severely increasing the pathological burden. We also found that SWS enhancement was associated with increased recruitment of aquaporin-4 to perivascular sites, suggesting a possible increase of glymphatic function. Furthermore, mass spectrometry data revealed differential and specific up-regulation of functional protein clusters linked to proteostasis upon slow wave­enhancing interventions. Overall, the beneficial effect of SWS enhancement on neuropathological outcome in murine synucleinopathy models mirrors findings in models of Alzheimer. Modulating SWS might constitute an effective strategy for modulating PD pathology in patients.

Vojta Therapy in Neuromotor Development of Pediatrics Patients with Periventricular Leukomalacia: Case Series.

Background and Objectives: Vojta therapy is used by physiotherapists and is based on stimulation through peripheral pressure that leads to the activation of involuntary motor response patterns, thus triggering patterns of reflex locomotion, hence also called reflex locomotion therapy. Objective: To analyze the changes produced by Vojta therapy in the evolution of infant motor development in patients with maturational delay due to periventricular leukomalacia. Materials and methods: One session of Vojta Therapy per week for eleven months, patients' neuromotor development was evaluated through the Denver II Test and the Baleys Scale. Results: A clinically significant increase in the development of the patients is observed. Conclusions: Neuromotor development seems to generate an adequate progression in the motor area.

Short-Term Effects of a Conditioning Telerehabilitation Program in Confined Patients Affected by COVID-19 in the Acute Phase. A Pilot Randomized Controlled Trial.

Background and objectives: The COVID-19 pandemic has become a challenge for health systems and, specifically, to physical therapists obligated to adapt their job and stop face-to-face consultations. In this situation, therapeutic exercise has been implemented in different COVID-19 patients. This study evaluated the feasibility and effectiveness of a novel therapeutic exercise program through telerehabilitation tools in COVID-19 patients with mild to moderate symptomatology in the acute stage. Materials and Methods: A total of 40 subjects were randomized an experimental group, based on muscle conditioning, and in a control group, who did not perform physical activity. Thirty-six subjects, 18 in each group, completed the one-week intervention. We measured the six-minute walking test, multidimensional dyspnoea-12, thirty seconds sit-to-stand test, and Borg Scale. Results: Both groups were comparable at baseline. Statistically significant improvement between groups (p < 0.05) in favor of the experimental group was obtained. No differences between gender were found (p > 0.05). Ninety percent adherence was found in our program. Conclusion: A one-week telerehabilitation program based on muscle toning exercise is effective, safe, and feasible in COVID-19 patients with mild to moderate symptomatology in the acute stage.

Perspectives and Attitudes of Patients with COVID-19 toward a Telerehabilitation Programme: A Qualitative Study.

The total isolation of patients with coronavirus disease 2019 (COVID-19) requires non-face-to-face medical assistance. There is evidence of the efficacy of home treatments with exercises in patients with respiratory disorders which could become the therapeutic method of choice for the treatment and supervision of patients isolated due to infection during home confinement. This study's objective was to analyse the experience and opinions of isolated patients with COVID-19 included in a programme of telerehabilitation exercises for 14 days and it is intended to reflect, from a qualitative point of view, the viability and usefulness of telerehabilitation tools in the management of these patients. Twenty-five participants of a telerehabilitation programme were interviewed by telephone through semi-structured interviews, following a positivist and objective model. The data were categorised and analysed through NVIVO qualitative analysis software. The information obtained was classified into four main topics (telerehabilitation programme, perception of clinical benefit, psychological aspects and level of health care) and six subtopics (technical aspects, communication, improvement aspects, exercise plan, motivation and applicability to public health systems). The telerehabilitation programme established in patients confined by COVID-19 is very well received, without considerable technical difficulties and generates physical and psychological improvements. Patients highlight the importance of applying this type of programme in public health systems.

Short-Term Effects of a Respiratory Telerehabilitation Program in Confined COVID-19 Patients in the Acute Phase: A Pilot Study.

The COVID-19 pandemic has caused distress for healthcare providers due to the respiratory problems it causes, among others. In this situation, rehabilitation of the respiratory system has been suggested and implemented in different COVID-19 patients. This study evaluated the feasibility and effectiveness of a novel program based on breathing exercises through telerehabilitation tools in COVID-19 patients with mild to moderate symptomatology in the acute stage. Forty subjects were randomized in an experimental group, based on pulmonary rehabilitation, and in a control group, of which the subjects did not perform physical activity. Thirty-eight subjects, with nineteen in each group, completed the one-week intervention. We performed measurements using the Six-Minute Walk Test, Multidimensional Dyspnoea-12, Thirty-Second Sit-To-Stand Test, and Borg Scale. Both groups were comparable at baseline. Significant differences were found for all of the outcome measures in favour of the experimental group. Ninety percent adherence was found in our program. A one-week telerehabilitation program based on respiratory exercises is effective, safe, and feasible in COVID-19 patients with mild to moderate symptomatology in the acute stage.

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications.

The highly infectious disease COVID-19 caused by the Betacoronavirus SARS-CoV-2 poses a severe threat to humanity and demands the redirection of scientific efforts and criteria to organized research projects. The international COVID19-NMR consortium seeks to provide such new approaches by gathering scientific expertise worldwide. In particular, making available viral proteins and RNAs will pave the way to understanding the SARS-CoV-2 molecular components in detail. The research in COVID19-NMR and the resources provided through the consortium are fully disclosed to accelerate access and exploitation. NMR investigations of the viral molecular components are designated to provide the essential basis for further work, including macromolecular interaction studies and high-throughput drug screening. Here, we present the extensive catalog of a holistic SARS-CoV-2 protein preparation approach based on the consortium's collective efforts. We provide protocols for the large-scale production of more than 80% of all SARS-CoV-2 proteins or essential parts of them. Several of the proteins were produced in more than one laboratory, demonstrating the high interoperability between NMR groups worldwide. For the majority of proteins, we can produce isotope-labeled samples of HSQC-grade. Together with several NMR chemical shift assignments made publicly available on covid19-nmr.com, we here provide highly valuable resources for the production of SARS-CoV-2 proteins in isotope-labeled form.