The diagnostic value of physical examination tests in adhesive capsulitis: a systematic review.

INTRODUCTION: Adhesive capsulitis, a condition marked by pain and stiffness of the shoulder, can have a frustrating clinical course for patients and health care professionals. Despite huge research interest, a universally accepted and used definition of clinical criteria for the diagnosis of adhesive capsulitis is currently still lacking. This systematic review aimed to identify diagnostic values for clinical examinations tests used in the diagnosis of adhesive capsulitis. EVIDENCE ACQUISITION: A total of 5 electronic databases (PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials [CENTRAL] and PEDro) were searched for relevant studies from 2002 until October 2022 using the terms: "adhesive capsulitis AND diagnosis" and "frozen shoulder AND diagnosis." The Downs and Black Checklist (modified) was used to assess the risk of bias. The study protocol was prospectively registered at the International prospective register of systematic reviews (PROSPERO, CRD42022365993). EVIDENCE SYNTHESIS: The initial database search identified 1799 studies, of which 9 (0.50%) were eventually included in the systematic review. Non-intrusive shoulder range of motion measurements in patients with adhesive capsulitis using the Kinect for Windows (Microsoft, Redmond, WA, USA) showed high correlation with clinical range of motion measurement. Two specific clinical tests, the affected-unaffected shoulder approach of the Coracoid Pain Test and the Distension Test in Passive External Rotation, were identified and presented excellent sensibility and specificity in the diagnosis of adhesive capsulitis, in their original study. Comparison between clinical tests was not possible due to the heterogeneity in clinical tools. CONCLUSIONS: This systematic review identified several physical examination tests developed for the diagnosis of adhesive capsulitis but could not compare them nor advance a set of clinical diagnostic tests that are scientifically validated. Further research is warranted to obtain validation of clinical diagnosis tools for adhesive capsulitis.

Functional performance recovery after individualized nutrition therapy combined with a patient-tailored physical rehabilitation program versus standard physiotherapy in patients with long COVID: a pilot study.

BACKGROUND: Long COVID is suggested to be present in 14 to 43% of COVID 19-survivors. Literature on this new condition states a need for a multidisciplinary approach including physical exercise and nutrition. The aim of the current pilot study is to investigate the feasibility of the proposed protocol to prepare for a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment compared to standard physiotherapy. METHODS: This is a protocol of the UNLOCK (Nutrition and LOComotoric rehabilitation in long COVID) study, a pragmatic, single center, randomized controlled pilot trial with two groups. Patients with persisting symptoms related to a SARS-CoV-2 infection will receive either standard physiotherapy or a personalized multimodal treatment for a period of 12 weeks, consisting of individualized physical exercise program combined with individualized nutritional therapy. They will be followed-up at 6, 12, and 18 weeks after randomization. DISCUSSION: A multidisciplinary approach for dealing with long COVID is needed. Because of the lack of clear data and the fact that this is a very heterogenic group, we aim to prepare and optimize a randomized controlled study that addresses the effectiveness of a personalized multimodal treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05254301 (since February 24, 2022).

Association between Experimental Pain Measurements and the Central Sensitization Inventory in Patients at Least 3 Months after COVID-19 Infection: A Cross-Sectional Pilot Study.

Fatigue, pain, headache, brain fog, anosmia, ageusia, mood symptoms, and sleep disorders are symptoms commonly experienced by people with post-COVID-19 condition. These symptoms could be considered as manifestations of central sensitization. The aim of this study is to evaluate whether there are indicators of central sensitization by using experimental pain measurements and to determine their association with patient-reported outcome measures (PROMs). A cross-sectional study including 42 patients after COVID-19 infection was conducted. The central sensitization inventory (CSI) was administered as a PROM to evaluate central-sensitization-associated symptoms. Pressure pain thresholds (PPT), temporal summation, and descending nociceptive pain inhibition (CPM) were assessed as experimental pain measurements. The median score on the CSI was 46.5 (Q1-Q3: 33-54). The presence of central-sensitization-associated symptoms was seen in 64.3% of patients based on the CSI (≥40/100 points). A deficient CPM was seen in 12% and 14% of patients when measured at the trapezius and rectus femoris, respectively. A negative correlation between pressure sensitivity on the rectus femoris and the CSI score (r = -0.36, 95%CI -0.13 to -0.65, p = 0.007) was observed. Central-sensitization-associated symptoms were present in up to 64.3% of patients post-COVID-19 infection, based on a PROM, i.e., the CSI. A more objective evaluation of nociceptive processing through experimental pain measurements was less suggestive of indicators of central sensitization. Only a small negative correlation between pressure sensitivity and the CSI was observed, thereby pointing towards the discrepancy between the CSI and experimental pain measurements and presumably the complementary need for both to evaluate potential indicators of central sensitization in this population.

Randomized controlled trial of suprascapular nerve blocks for subacute adhesive capsulitis.

BACKGROUND: Shoulder pain and loss of function remain a therapeutic challenge in adhesive capsulitis. Suprascapular nerve blocks, a common treatment in adhesive capsulitis, are considered a safe and effective method for the resolution of pain and restoration of shoulder range of motion (ROM). To our knowledge, no data are available on the use of suprascapular nerve blocks in adhesive capsulitis in the subacute phase. AIM: The aim of this study was to compare the efficacy of ultrasound-guided suprascapular nerve blocks versus saline injections for treating adhesive capsulitis in the subacute phase. DESIGN: Randomized double-blinded controlled trial; level of evidence 2. SETTING: Out-patient consultation of Physical and Rehabilitation Medicine in a general hospital. POPULATION: Thirty-five patients with subacute adhesive capsulitis. METHODS: Patients were randomly allocated to receive either 3 successive (1-week interval) ultrasound-guided suprascapular nerve blocks with ropivacaine 5 mL 2 mg/mL (intervention group) or ultrasound-guided injections of 5 mL sterile saline solution (NaCl 0.9%) (control group), at the floor of the suprascapular fossa. Primary outcome was shoulder function assessed by the Constant-Murley Score. Secondary outcomes were shoulder ROM and shoulder pain intensity. Assessments were performed before each injection and 4 weeks after the last injection. RESULTS: A significant increase of Constant-Murley Score (P<0.001), increase of shoulder ROM (all directions: P<0.011) and decrease of pain (P<0.001), were observed over time in both study groups. However, no significant differences were observed between the intervention and the control group. CONCLUSIONS: Three successive suprascapular nerve blocks did not provide a better outcome than saline injections on shoulder function, ROM, and pain in subacute adhesive capsulitis. These negative findings warrant some considerations on the natural history of adhesive capsulitis, as well as timing, type, and placebo effects of injections. CLINICAL REHABILITATION IMPACT: The current place of suprascapular nerve blocks in the treatment strategy of adhesive capsulitis needs to be rediscussed.

The Effect of physical therapy on impairments in COVID-19 patients from intensive care to home rehabilitation: A rapid review.

OBJECTIVE: Guidelines regarding physical therapy for COVID-19 patients are often based on expert opinion. Recent clinical trials have reported effects on several rehabilitation outcomes in COVID-19 patients. This review summarizes the effects of physical therapy in COVID-19 patients. DATA SOURCES: PubMed, Web of Science and Scopus databases were systematically searched for studies investigating the effect of any physical therapy modality on impairments in adult COVID-19 patients. Included studies were (non)-randomized controlled trials, pre-experimental studies, and cohort studies in which a pre-post analysis was performed. DATA EXTRACTION: After the screening process, data of interest were extracted from eligible studies and their risk of bias was assessed. Included outcome measures were divided into 3 groups: pulmonary function, physical function, and psychosocial function. DATA SYNTHESIS: A total of 15 studies were included in this review. Physical therapy seems to have positive effects on pulmonary function, physical function, and psychosocial function. However, these effects differ between clinical settings (e.g. home care, intensive care unit, inpatient units). Due to the low-to-moderate quality of the included studies, no robust conclusions can be drawn. CONCLUSION: Further high-quality research is required, taking into account the different clinical settings, in order to draw conclusions about the effectiveness of physical therapy on impairments in COVID-19 patients.

Science Without Publication Paywalls: cOAlition S for the Realisation of Full and Immediate Open Access.

In this Perspective, a group of national funders, joined by the European Commission and the European Research Council, announce plans to make Open Access publishing mandatory for recipients of their agencies' research funding.

Science without publication paywalls: cOAlition S for the realisation of full and immediate Open Access.

In this Perspective, a group of national funders, joined by the European Commission and the European Research Council, announce plans to make Open Access publishing mandatory for recipients of their agencies' research funding.

Directed evolution of the suicide protein O6-alkylguanine-DNA alkyltransferase for increased reactivity results in an alkylated protein with exceptional stability.

Here we present a biophysical, structural, and computational analysis of the directed evolution of the human DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (hAGT) into SNAP-tag, a self-labeling protein tag. Evolution of hAGT led not only to increased protein activity but also to higher stability, especially of the alkylated protein, suggesting that the reactivity of the suicide enzyme can be influenced by stabilizing the product of the irreversible reaction. Whereas wild-type hAGT is rapidly degraded in cells after alkyl transfer, the high stability of benzylated SNAP-tag prevents proteolytic degradation. Our data indicate that the intrinstic stability of a key α helix is an important factor in triggering the unfolding and degradation of wild-type hAGT upon alkyl transfer, providing new insights into the structure-function relationship of the DNA repair protein.

Dual chaperone role of the C-terminal propeptide in folding and oligomerization of the pore-forming toxin aerolysin.

Throughout evolution, one of the most ancient forms of aggression between cells or organisms has been the production of proteins or peptides affecting the permeability of the target cell membrane. This class of virulence factors includes the largest family of bacterial toxins, the pore-forming toxins (PFTs). PFTs are bistable structures that can exist in a soluble and a transmembrane state. It is unclear what drives biosynthetic folding towards the soluble state, a requirement that is essential to protect the PFT-producing cell. Here we have investigated the folding of aerolysin, produced by the human pathogen Aeromonas hydrophila, and more specifically the role of the C-terminal propeptide (CTP). By combining the predictive power of computational techniques with experimental validation using both structural and functional approaches, we show that the CTP prevents aggregation during biosynthetic folding. We identified specific residues that mediate binding of the CTP to the toxin. We show that the CTP is crucial for the control of the aerolysin activity, since it protects individual subunits from aggregation within the bacterium and later controls assembly of the quaternary pore-forming complex at the surface of the target host cell. The CTP is the first example of a C-terminal chain-linked chaperone with dual function.

Preliminary crystallographic analysis of two oligomerization-deficient mutants of the aerolysin toxin, H132D and H132N, in their proteolyzed forms.

Aerolysin is a major virulence factor produced by the Gram-negative bacterium Aeromonas hydrophila and is a member of the ß-pore-forming toxin family. Two oligomerization-deficient aerolysin mutants, H132D and H132N, have been overproduced, proteolyzed by trypsin digestion and purified. Crystals were grown from the proteolyzed forms and diffraction data were collected for the two mutants to 2.1 and 2.3 Šresolution, respectively. The prism-shaped crystals belonged to space group C2. The crystal structure of the mutants in the mature, but not heptameric, aerolysin form will provide insight into the intermediate states in the oligomerization process of a pore-forming toxin.

Features of the secondary structure of a protein molecule from powder diffraction data.

Protein powder diffraction is shown to be suitable for obtaining de novo solutions to the phase problem at low resolution via phasing methods such as the isomorphous replacement method. Two heavy-atom derivatives (a gadolinium derivative and a holmium derivative) of the tetragonal form of hen egg-white lysozyme were crystallized at room temperature. Using synchrotron radiation, high-quality powder patterns were collected in which pH-induced anisotropic lattice-parameter changes were exploited in order to reduce the challenging and powder-specific problem of overlapping reflections. The phasing power of two heavy-atom derivatives in a multiple isomorphous replacement analysis enabled molecular structural information to be obtained up to approximately 5.3 A resolution. At such a resolution, features of the secondary structure of the lysozyme molecule can be accurately located using programs dedicated to that effect. In addition, the quoted resolution is sufficient to determine the correct hand of the heavy-atom substructure which leads to an electron-density map representing the protein molecule of proper chirality.

'Broken symmetries' in macromolecular crystallography: phasing from unmerged data.

The space-group symmetry of a crystal structure imposes a point-group symmetry on its diffraction pattern, giving rise to so-called symmetry-equivalent reflections. Instances in macromolecular crystallography are discussed in which the symmetry in reciprocal space is broken, i.e. where symmetry-related reflections are no longer equivalent. Such a situation occurs when the sample suffers from site-specific radiation damage during the X-ray measurements. Another example of broken symmetry arises from the polarization anisotropy of anomalous scattering. In these cases, the genuine intensity differences between symmetry-related reflections can be exploited to yield phase information in the structure-solution process. In this approach, the usual separation of the data merging and phasing steps is abandoned. The data are kept unmerged down to the Harker construction, where the symmetry-breaking effects are explicitly modelled and refined and become a source of supplementary phase information.

Explosive strength imbalances in professional basketball players.

CONTEXT: Despite the high rate of lower limb injuries in basketball players, studies of the dominant-limb effect in elite athletes often neglect injury history. OBJECTIVE: To determine lower limb explosive-strength asymmetries in professional basketball players compared with junior basketball players and control participants. DESIGN: Cohort study. SETTING: Academic medical institution. PATIENTS OR OTHER PARTICIPANTS: 15 professional basketball players, 10 junior basketball players, and 20 healthy men. MAIN OUTCOME MEASURE(S): We performed an isokinetic examination to evaluate the knee extensor (Ext) and flexor (Fl) concentric peak torque at 60 degrees .s(-1) and 240 degrees .s(-1) and (Fl only) eccentric peak torque at 30 degrees .s(-1) and 120 degrees .s(-1). Functional evaluation included countermovement jump, countermovement jump with arms, 10-m sprint, single-leg drop jump, and single-leg, 10-second continuous jumping. Variables were compared among groups using analysis of variance or a generalized linear mixed model for bilateral variables. RESULTS: The 2 groups of basketball players demonstrated better isokinetic and functional performances than the control group did. No differences in functional or relative isokinetic variables were noted between professional and junior basketball players. Professional players with a history of knee injury failed to reach normal knee extensor strength at 60 degrees .s(-1). Knee Ext (60 degrees .s(-1)) and Fl (eccentric 120 degrees .s(-1)) torque values as well as 10-second continuous jumping scores were higher in those professional players without a history of knee injury than those with such a history. Compared with the group without a history of knee injury, the group with a history of knee injury maintained leg asymmetry ratios greater than 10% for almost all isokinetic variables and more than 15% for unilateral functional variables. CONCLUSIONS: The relative isokinetic and functional performances of professional basketball players were similar to those of junior players, with no dominant-side effect. A history of knee injury in the professional athlete, however, was reflected in bilateral isokinetic and functional asymmetries and should be considered in future studies of explosive strength.

Exploiting the anisotropy of anomalous scattering boosts the phasing power of SAD and MAD experiments.

The X-ray polarization anisotropy of anomalous scattering in crystals of brominated nucleic acids and selenated proteins is shown to have significant effects on the diffraction data collected at an absorption edge. For conventionally collected single- or multi-wavelength anomalous diffraction data, the main manifestation of the anisotropy of anomalous scattering is the breakage of the equivalence between symmetry-related reflections, inducing intensity differences between them that can be exploited to yield extra phase information in the structure-solution process. A new formalism for describing the anisotropy of anomalous scattering which allows these effects to be incorporated into the general scheme of experimental phasing methods using an extended Harker construction is introduced. This requires a paradigm shift in the data-processing strategy, since the usual separation of the data-merging and phasing steps is abandoned. The data are kept unmerged down to the Harker construction, where the symmetry-breaking is explicitly modelled and refined and becomes a source of supplementary phase information. These ideas have been implemented in the phasing program SHARP. Refinements using actual data show that exploitation of the anisotropy of anomalous scattering can deliver substantial extra phasing power compared with conventional approaches using the same raw data. Examples are given that show improvements in the phases which are typically of the same order of magnitude as those obtained in a conventional approach by adding a second-wavelength data set to a SAD experiment. It is argued that such gains, which come essentially for free, i.e. without the collection of new data, are highly significant, since radiation damage can frequently preclude the collection of a second-wavelength data set. Finally, further developments in synchrotron instrumentation and in the design of data-collection strategies that could help to maximize these gains are outlined.

A tandem of SH3-like domains participates in RNA binding in KIN17, a human protein activated in response to genotoxics.

The human KIN17 protein is an essential nuclear protein conserved from yeast to human and expressed ubiquitously in mammals. Suppression of Rts2, the yeast equivalent of gene KIN17, renders the cells unviable, and silencing the human KIN17 gene slows cell growth dramatically. Moreover, the human gene KIN17 is up-regulated following exposure to ionizing radiations and UV light, depending on the integrity of the human global genome repair machinery. Its ectopic over-expression blocks S-phase progression by inhibiting DNA synthesis. The C-terminal region of human KIN17 is crucial for this anti-proliferation effect. Its high-resolution structure, presented here, reveals a tandem of SH3-like subdomains. This domain binds to ribonucleotide homopolymers with the same preferences as the whole protein. Analysis of its structure complexed with tungstate shows structural variability within the domain. The interaction with tungstate is mediated by several lysine residues located within a positively charged groove at the interface between the two subdomains. This groove could be the site of interaction with RNA, since mutagenesis of two of these highly conserved lysine residue weakens RNA binding.

Crystal structure of the PP2A phosphatase activator: implications for its PP2A-specific PPIase activity.

PTPA, an essential and specific activator of protein phosphatase 2A (PP2A), functions as a peptidyl prolyl isomerase (PPIase). We present here the crystal structures of human PTPA and of the two yeast orthologs (Ypa1 and Ypa2), revealing an all alpha-helical protein fold that is radically different from other PPIases. The protein is organized into two domains separated by a groove lined by highly conserved residues. To understand the molecular mechanism of PTPA activity, Ypa1 was cocrystallized with a proline-containing PPIase peptide substrate. In the complex, the peptide binds at the interface of a peptide-induced dimer interface. Conserved residues of the interdomain groove contribute to the peptide binding site and dimer interface. Structure-guided mutational studies showed that in vivo PTPA activity is influenced by mutations on the surface of the peptide binding pocket, the same mutations that also influenced the in vitro activation of PP2Ai and PPIase activity.

Crystallization and halide phasing of the C-terminal domain of human KIN17.

Here, the crystallization and initial phasing of the C-terminal domain of human KIN17, a 45 kDa protein mainly expressed in response to ionizing radiation and overexpressed in certain tumour cell lines, are reported. Crystals diffracting to 1.4 A resolution were obtained from 10% ethylene glycol, 27% PEG 6000, 500 mM LiCl and 100 mM sodium acetate pH 6.3 in space group P2(1)2(1)2(1), with unit-cell parameters a = 45.75, b = 46.31, c = 60.80 A and one molecule in the asymmetric unit. Since this domain has a basic pI, heavy-atom derivatives were obtained by soaking the crystals with negatively charged ions such as tungstate and iodine. The replacement of LiCl by KI in the cryosolution allowed the determination of phases from iodide ions to give an interpretable electron-density map.

Crystal structure of yeast YER010Cp, a knotable member of the RraA protein family.

We present here the structure of Yer010c protein of unknown function, solved by Multiple Anomalous Diffraction and revealing a common fold and oligomerization state with proteins of the regulator of ribonuclease activity A (RraA) family. In Escherichia coli, RraA has been shown to regulate the activity of ribonuclease E by direct interaction. The absence of ribonuclease E in yeast suggests a different function for this family member in this organism. Yer010cp has a few supplementary secondary structure elements and a deep pseudo-knot at the heart of the protein core. A tunnel at the interface between two monomers, lined with conserved charged residues, has unassigned residual electron density and may constitute an active site for a yet unknown activity.