Rehabilitation after musculoskeletal injury: European perspective.

Trauma is one of the main causes of death in younger people and ongoing disability worldwide. In Europe, while there is generally good organization of trauma reception and acute treatment, rehabilitation from major musculoskeletal injuries is less well defined and provided. This article documents the diverse approaches to rehabilitation after major injury in 6 European nations. The recognition of need is universal, but achieving a robust rehabilitation strategy is more elusive across the varying health care systems. Switzerland has the most robust service in the insured population. In the other countries, particularly where there is a reliance on public institutes, this provision is at best patchy. In the Netherlands, innovative patient-empowering strategies have gained traction with notable success, and in the United Kingdom, a recent randomized trial also showed this approach to be reproducible and robust. Overall, there is a clear need for learning across the national systems and implementation of a minimum set of standards.

In vitro pharmacological characterization of growth hormone secretagogue receptor ligands using the dynamic mass redistribution and calcium mobilization assays.

Ghrelin modulates several biological functions via selective activation of the growth hormone secretagogue receptor (GHSR). GHSR agonists may be useful for the treatment of anorexia and cachexia, while antagonists and inverse agonists may represent new drugs for the treatment of metabolic and substance use disorders. Thus, the identification and pharmacodynamic characterization of new GHSR ligands is of high interest. In the present work the label-free dynamic mass redistribution (DMR) assay has been used to evaluate the pharmacological activity of a panel of GHSR ligands. This includes the endogenous peptides ghrelin, desacyl-ghrelin and LEAP2(1-14). Among synthetic compounds, the agonists anamorelin and HM01, the antagonists HM04 and YIL-781, and the inverse agonist PF-05190457 have been tested, together with HM03, R011, and H1498 from patent literature. The DMR results have been compared to those obtained in parallel experiments with the calcium mobilization assay. Ghrelin, anamorelin, HM01, and HM03 behaved as potent full GHSR agonists. YIL-781 behaved as a partial GHSR agonist and R011 as antagonist in both the assays. LEAP2(1-14) resulted a GHSR inverse agonist in DMR but not in calcium mobilization assay. PF-05190457, HM04, and H1498 behaved as GHSR inverse agonists in DMR experiments, while they acted as antagonists in calcium mobilization studies. In conclusion, this study provided a systematic pharmacodynamic characterization of several GHSR ligands in two different pharmacological assays. It demonstrated that the DMR assay can be successfully used particularly to discriminate between antagonists and inverse agonists. This study may be useful for the selection of the most appropriate compounds to be used in future studies.

Whey-based sports supplements: Heat damage and protein breakdown after in vitro gastrointestinal digestion.

This study was aimed to evaluate the effect of heat damage on the release of total amino acids (AA), essential AA (EAA), branched-chain AA (BCAA) and bioactive peptides following in vitro static simulated gastrointestinal digestion (SGID) of four commercial whey-protein based sports supplements. The extent of protein glycation and denaturation was evaluated through the determination of the content of furosine and soluble whey proteins. The strongest protein breakdown (41.3 %) and the highest release of AA, EAA and BCAA (36.20, 27.78, and 11.30 g/100 g protein, respectively) was observed in the sports supplement characterised by the lowest (52.5 %) level of soluble whey proteins; whereas the protein glycation had a negligible impact on the studied parameters. The SGID also led to the release of several peptides with various reported bioactivities that may be beneficial to sports activity.

Point-of-Care Fluorescence Biosensing System for Rapid Multi-Allergen Screening.

With the steady increase in allergy prevalence worldwide, there is a strong need for novel diagnostic tools for precise, fast, and less invasive testing methods. Herein, a miniatured fluorescence-based biosensing system is developed for the rapid and quantitative detection of allergen-specific immunoglobulin-E. An antibody-based fluorescence assay in a microfluidic-patterned slide, combined with a custom-made portable fluorescence reader for image acquisition and user-friendly software for the data analysis, enables obtaining results for multiple allergens in just ~1 h with only 80 µL of blood serum. The multiplexed detection of common birch, timothy grass, cat epithelia, house dust mite, and dog epithelia shows quantitative IgE-mediated allergic responses to specific allergens in control serum samples with known total IgE concentration. The responses are verified with different control tests and measurements with a commercial fluorescence reader. These results open the door to point-of-care allergy screening for early diagnosis and broader access and for large-scale research in allergies.

Viral Vector-Based Gene Therapy for Epilepsy: What Does the Future Hold?

In recent years, many pre-clinical studies have tested gene therapy approaches as possible treatments for epilepsy, following the idea that they may provide an alternative to conventional pharmacological and surgical options. Multiple gene therapy approaches have been developed, including those based on anti-sense oligonucleotides, RNA interference, and viral vectors. In this opinion article, we focus on translational issues related to viral vector-mediated gene therapy for epilepsy. Research has advanced dramatically in addressing issues like viral vector optimization, target identification, strategies of gene expression, editing or regulation, and safety. Some of these pre-clinically validated potential gene therapies are now being tested in clinical trials, in patients with genetic or focal forms of drug-resistant epilepsy. Here, we discuss the ongoing translational research and the advancements that are needed and expected in the near future. We then describe the clinical trials in the pipeline and the further challenges that will need to be addressed at the clinical and economic levels. Our optimistic view is that all these issues and challenges can be overcome, and that gene therapy approaches for epilepsy will soon become a clinical reality.

Surface layer proteins from Lactobacillus helveticus ATCC® 15009™ affect the gut barrier morphology and function.

Paraprobiotics and postbiotics represent a valid alternative to probiotic strains for ameliorating and preserving a healthy intestinal epithelial barrier (IEB). The present study investigated the effects of surface layer proteins (S-layer) of the dairy strain Lactobacillus helveticus ATCC® 15009™ (Lb ATCC® 15009™), as paraprobiotic, on the morpho-functional modulation of IEB in comparison to live or heat-inactivated Lb ATCC® 15009™ in an in vitro co-culture of Caco-2/HT-29 70/30 cells. Live or heat-inactivated Lb ATCC® 15009™ negatively affected transepithelial electrical resistance (TEER) and paracellular permeability, and impaired the distribution of Claudin-1, a tight junction (TJ) transmembrane protein, as detected by immunofluorescence (IF). Conversely, the addition of the S-layer improved TEER and decreased permeability in physiological conditions in co-cultures with basal TEER lower than 50 ohmcm2, indicative of a more permeable physiological IEB known as leaky gut. Transmission electron microscopy (TEM) and IF analyses suggested that the S-layer induces a structural TJ rearrangement and desmosomes' formation. S-layer also restored TEER and permeability in the presence of LPS, but not of a mixture of pro-inflammatory cytokines (TNF-α plus IFN-γ). IF analyses showed an increase in Claudin-1 staining when LPS and S-layer were co-administered with respect to LPS alone; in addition, the S-layer counteracted the reduction of alkaline phosphatase detoxification activity and the enhancement of pro-inflammatory interleukin-8 release both induced by LPS. Altogether, these data corroborate a paraprobiotic role of S-layer from Lb ATCC® 15009™ as a possible candidate for therapeutic and prophylactic uses in conditions related to gastrointestinal health and correlated with extra-intestinal disorders.

Use of patient-specific guides and 3D model in scapula osteotomy for symptomatic malunion.

BACKGROUND: Scapular osteotomy for malunion can lead to resolution of pain and functional improvement in scapula fracture sequelae. Understanding three-dimensional bone morphology and analysing post-traumatic deformity is the main step of planning and the key to success of the procedure. 3D models and patient-specific guides are a growing technology to enhance accuracy of planning and to assist during surgery. CASE PRESENTATION: We report the case of a 50 years old male, complaining of pain and limited function after a malunited scapular body fracture. Clinical assessment showed a severe impairment of shoulder function with active and passive forward flexion limited to 80°, absent external rotation, and internal rotation limited to the buttock. X-rays and CT scan showed an excessive lateral border offset of 53 mm and complete displacement of the glenoid segment anteriorly and medially to the scapular body, with impingement between the lateral most prominent scapular bone spur and humeral shaft. Glenopolar angle was 19°, scapular body angulation on the sagittal plane was 12°. Corrective osteotomy was planned on a virtual interactive rendering and on 3D printed models. Patient-specific guides were developed to perform a body-spine osteotomy with removal of a bone wedge, and a glenoid-spine osteotomy; a patient-specific wedge spacer was used to hold the reduction during plate fixation. Follow-up up to 12 months after surgery demonstrated improvement in scapula anatomy, shoulder girdle function, and patient-reported outcomes. CONCLUSIONS: For the first time in scapula malunion surgery, patient-specific osteotomy guides were succesfully used during surgery to perform osteotomies and to assist in reduction maneuvers.

Consensus for management of sacral fractures: from the diagnosis to the treatment, with a focus on the role of decompression in sacral fractures.

BACKGROUND: There is no evidence in the current literature about the best treatment option in sacral fracture with or without neurological impairment. MATERIALS AND METHODS: The Italian Pelvic Trauma Association (A.I.P.) decided to organize a consensus to define the best treatment for traumatic and insufficiency fractures according to neurological impairment. RESULTS: Consensus has been reached for the following statements: When complete neurological examination cannot be performed, pelvic X-rays, CT scan, hip and pelvis MRI, lumbosacral MRI, and lower extremities evoked potentials are useful. Lower extremities EMG should not be used in an acute setting; a patient with cauda equina syndrome associated with a sacral fracture represents an absolute indication for sacral reduction and the correct timing for reduction is "as early as possible". An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an indication for laminectomy after reduction in the case of a displaced sacral fracture in a high-energy trauma, while a worsening and progressive radicular neurological deficit represents an indication. In the case of a displaced sacral fracture and neurological deficit with imaging showing no evidence of nerve root compression, a laminectomy after reduction is not indicated. In a patient who was not initially investigated from a neurological point of view, if a clinical investigation conducted after 72 h identifies a neurological deficit in the presence of a displaced sacral fracture with nerve compression on MRI, a laminectomy after reduction may be indicated. In the case of an indication to perform a sacral decompression, a first attempt with closed reduction through external manoeuvres is not mandatory. Transcondylar traction does not represent a valid method for performing a closed decompression. Following a sacral decompression, a sacral fixation (e.g. sacroiliac screw, triangular osteosynthesis, lumbopelvic fixation) should be performed. An isolated and complete radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. An isolated and incomplete radicular neurological deficit of the lower limbs does not represent an absolute indication. A worsening and progressive radicular neurological deficit of the lower limbs represents an indication for laminectomy after reduction in the case of a displaced sacral fracture in a low-energy trauma associated with imaging suggestive of root compression. In the case of a displaced sacral fracture and neurological deficit in a low-energy trauma, sacral decompression followed by surgical fixation is indicated. CONCLUSIONS: This consensus collects expert opinion about this topic and may guide the surgeon in choosing the best treatment for these patients. LEVEL OF EVIDENCE: IV. TRIAL REGISTRATION: not applicable (consensus paper).

Combined Arthroscopic-Assisted Lower Trapezius Tendon Transfer and Superior Capsule Reconstruction for Massive Irreparable Posterior-Superior Rotator Cuff Tears: Surgical Technique.

Primary or revision irreparable rotator cuff tears remain a challenge. Clear algorithms do not exist. Several joint-preserving options are available, but no technique has been definitely proven to be better than another. Although superior capsule reconstruction has been shown to be effective in restoring motion, lower trapezius transfer can provide strong external rotation and abduction moment. The aim of the present article was to describe an easy and reliable technique to combine both options in 1 surgery, aiming to maximize the functional outcome by getting motion and strength back.

Use of the iliac-outlet and iliac-inlet combined views in percutaneous posterior column retrograde screw fixation.

Posterior column fractures are common acetabular injuries. Although displaced fractures require open reduction and fixation, undisplaced patterns may benefit from percutaneous screw fixation. The combination of iliac oblique with inlet and outlet views offers an intuitive and panoramic rendering of the bony corridor into the posterior column; lateral cross table view completes the sequence of fluoroscopic projections. Herein we describe the use of outlet/inlet iliac views and a detailed procedure for percutaneous retrograde posterior column screw fixation.

A multi-centre peptidomics investigation of food digesta: current state of the art in mass spectrometry analysis and data visualisation.

Mass spectrometry has become the technique of choice for the assessment of a high variety of molecules in complex food matrices. It is best suited for monitoring the evolution of digestive processes in vivo and in vitro. However, considering the variety of equipment available in different laboratories and the diversity of sample preparation methods, instrumental settings for data acquisition, statistical evaluations, and interpretations of results, it is difficult to predict a priori the ideal parameters for optimal results. The present work addressed this uncertainty by executing an inter-laboratory study with samples collected during in vitro digestion and presenting an overview of the state-of-the-art mass spectrometry applications and analytical capabilities available for studying food digestion. Three representative high-protein foods - skim milk powder (SMP), cooked chicken breast and tofu - were digested according to the static INFOGEST protocol with sample collection at five different time points during gastric and intestinal digestion. Ten laboratories analysed all digesta with their in-house equipment and applying theirconventional workflow. The compiled results demonstrate in general, that soy proteins had a slower gastric digestion and the presence of longer peptide sequences in the intestinal phase compared to SMP or chicken proteins, suggesting a higher resistance to the digestion of soy proteins. Differences in results among the various laboratories were attributed more to the peptide selection criteria than to the individual analytical platforms. Overall, the combination of mass spectrometry techniques with suitable methodological and statistical approaches is adequate for contributing to the characterisation of the recently defined digestome.

Management of distal femoral fractures with metaphyseal and articular comminution (AO/OTA 33C) using nail and plate fixation: a technical note and case series of 14 patients.

PURPOSE: To describe the surgical technique and the outcome of a case series of comminuted intra-articular distal femur fractures (AO/OTA 33C) treated with a nail-plate combination (NPC) implant. METHODS: We retrospectively analyzed a case series of 14 patients with comminuted intra-articular distal femur fractures (DFF) treated with an intramedullary retrograde nail in combination with a lateral low-contact condylar locking plate, in a period between June 2020 and January 2023 at a Level 1 trauma center. Baseline demographic and clinical data were recorded. Time to bone healing, function using Schatzker Lambert Score, and complications were documented. RESULTS: Fourteen patients, 8 males and 6 females, with a total of 15 NPC implants, were included in this study. Eight out of 14 patients had open fractures, all with a Gustilo Anderson type IIIA exposure. The mean age was 48.5 ± 18.05 years. The median follow-up was 392 days, with only one patient lost to follow-up. 11 out of 15 implants achieved complete radiographic consolidation during follow-up, at a mean of 5.40 ± 1.07 months. At the 12-month follow-up, all patients could fully bear weight painlessly or with mild pain. Schatzker Lambert Score was excellent for 4 patients, good for 2 patients, fair for 5 patients, and failure for 2 patients. The main postoperative complications were rigidity (3 cases), limb shortening (2 cases), and septic non-union (1 case). CONCLUSION: This study suggests that the nail-plate combination (NPC) may provide a more effective surgical technique for addressing the challenges associated with comminuted intra-articular distal femur fractures (AO/OTA 33C).

Implant retention with serial debridement and use of antibiotic-loaded calcium sulfate beads in acute fracture-related infection (FRI) after pelvic ring or acetabular fractures: A retrospective case series of 7 cases.

BACKGROUND: The development of a pelvic wound infection in the presence of hardware after open reduction and internal fixation presents a clinical dilemma and there is little literature to aid in decision-making. The purpose of this study was to describe the possibility of debridement, antibiotic pearls and retention of the implant (DAPRI) procedure to eradicate the infection. METHODS: Tumor-like debridement, antibiotic pearls and retention of the implant (DAPRI) aimed to remove the biofilm allowing a higher and prolonged local antibiotic concentration by using calcium sulfate antibiotic-added beads. Wound status, radiological signs of bone healing, gait and functional activity of the patient were evaluated. RESULTS: Seven patients underwent this technique. The mean follow up time was nine months (range: 6 -16 months). Complete wound healing was achieved in all the patients with no major complications. Average time of bony union was 4.3 months (range: 3-6 months) with no need for implant removal. CONCLUSION: The DAPRI technique might represent a safe and more conservative treatment for management of early fracture-related infections (FRI) of the pelvis and acetabulum.

Impact of in vitro static digestion method on the release of ß-casomorphin-7 from bovine milk and cheeses with A1 or A2 ß-casein phenotypes.

Beta-casomorphin-7 (BCM7) represents the fragment Val60-Ile66 of bovine ß-casein (ß-CN), and there is evidence that it is more easily released during gastrointestinal digestion (GID) of A1 ß-CN variant, in comparison to the A2 variant. This study aimed at investigating the effect of type of enzymes and the protease/protein (P/S) ratio on BCM7 release during the intestinal step of in vitro static GID of bovine milk and cheeses with A1 or A2 ß-CN phenotypes. BCM7 occurred in digests of both A1 and A2 samples, being the release more marked for A1 counterparts. Nonetheless, the BCM7 release depended on both the type of GID enzymes and the P/S ratio. These findings highlight the importance of GID conditions which may affect the outcomes for possible differences between A1 and A2 milk based on BCM7 release during in vitro GID.

Endosteal plating for the treatment of malunions and nonunions of distal femur fractures.

PURPOSE: To describe the surgical technique and the outcome of a case series of nonunion and malunion of distal femur fractures treated with an endosteal medial plate combined with a lateral locking plate and with autogenous bone grafting. METHODS: We retrospectively analyzed a series of patients with malunion or nonunion of the distal femur treated with a medial endosteal plate in combination with a lateral locking plate, in a period between January 2011 and December 2019, Database from chart review was obtained including all the clinical relevant available baseline data (demographics, type of fracture, mechanism of injury, time from injury to surgery, number of previous surgical procedures, type of bone graft, and type of lateral plate). Time to bone healing, limb alignment at follow-up and complications were documented. RESULTS: Ten patients were included into the study: 7 male and 3 female with mean age of 48.3 years (range 21-67). The mechanism of trauma was in 8 cases a road traffic accident and in 2 cases a fall from height. According to AO/OTA classification 5 fractures were 33 A3, 3 were 33 C1, 1 was 33 C2 and 1 was 33 C3. The average follow up was 13.5 months. In all cases but one bony union was achieved. Bone healing was observed in average 3.3 months after surgery. No intraoperative or postoperative complications were reported. CONCLUSION: A medial endosteal plate is a useful augmentation for lateral plate fixation in nonunion or malunion following distal femur fractures, particularly in cases of medial bone loss, severe comminution, or poor bone quality. LEVEL OF EVIDENCE: Level IV (retrospective case series).

Sulcus Angle, Trochlear Depth, and Dejour's Classification Can Be Reliably Applied To Evaluate Trochlear Dysplasia: A Systematic Review of Radiological Measurements.

PURPOSE: To summarize data on the reliability of available imaging criteria for the assessment of trochlear dysplasia and to assess the methodological quality of the included studies. METHODS: This systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Search was performed using major electronic databases from their inception to September 2021. All studies enrolling patients of any age who underwent a radiological exam to rule out features related to trochlear dysplasia were included. After the identification of available imaging criteria, reliability studies were analyzed. Descriptive statistics were used to summarize findings. Methodological quality was assessed using the Quality Appraisal of Reliability studies checklist. RESULTS: A total of 2391 articles were identified, and 33 articles comprising 3036 patients with a mean age of 28.6 years were included. Thirty different measurements were extracted. Magnetic resonance imaging (MRI) was the most used imaging modalities (21 studies), followed by computed tomography (10 studies), conventional radiology (8 studies) and ultrasonography (US) (1 study). Sulcus angle, trochlear depth, and Dejour's classification were the most explored measurements. Overall, sulcus angle can be reliably assessed on radiography, CT and MRI, whereas trochlear depth can be reliably measured only with CT and MRI. Reliability of Dejour's classification ranged from poor or fair to very good for all imaging modalities. Methodological quality of included studies varied from 2 to 9 positive items out of 11 possible. Twenty-four studies (72.7%) were considered at high risk of bias. CONCLUSION: Trochlear dysplasia can be reliably evaluated at least with 3 measurements: sulcus angle, trochlear depth and Dejour's classification. Methodological quality assessment showed high risk of bias in most included studies. LEVEL OF EVIDENCE: Level III, systematic review of Level II-III studies.

Current insights into non-thermal preservation technologies alternative to conventional high-temperature short-time pasteurization of drinking milk.

Milk is an important nutritional food source characterized by a perishable nature and conventionally thermally treated to guarantee its safety. In recent years, an increasing focus on competing non-thermal food processing technologies has been driven mainly by consumers' expectations for minimally processed products. Due to the heat sensitivity of milk, much research interest has been addressed to mild non-thermal pasteurization processing to keep safety, 'fresh-like' taste and to maintain the organoleptic qualities of raw milk. This review provides an overview of the current literature on non-thermal treatments as standalone alternative technologies to high-temperature short-time (HTST) pasteurization of drinking milk. Results of lab-scale experimentations suggest the feasibility of most emerging non-thermal processing technologies, including high hydrostatic pressure, pulsed electric field, cold plasma, cavitation and light-based technologies, as alternative to thermal treatment of drinking milk with premium in shelf life duration. Nevertheless, a series of regulatory, technological and economical hurdles hinder the industrial scaling-up for most of these substitutes. To date, only high hydrostatic pressure treatments are applied as alone alternative to HTSH pasteurization for processing of "cold pasteurized" drinking milk. Milk submitted to HTST treatment combined to ultraviolet light is currently accepted in EU countries as novel food.

Neural precursor cells tune striatal connectivity through the release of IGFBPL1.

The adult brain retains over life endogenous neural stem/precursor cells (eNPCs) within the subventricular zone (SVZ). Whether or not these cells exert physiological functions is still unclear. In the present work, we provide evidence that SVZ-eNPCs tune structural, electrophysiological, and behavioural aspects of striatal function via secretion of insulin-like growth factor binding protein-like 1 (IGFBPL1). In mice, selective ablation of SVZ-eNPCs or selective abrogation of IGFBPL1 determined an impairment of striatal medium spiny neuron morphology, a higher failure rate in GABAergic transmission mediated by fast-spiking interneurons, and striatum-related behavioural dysfunctions. We also found IGFBPL1 expression in the human SVZ, foetal and induced-pluripotent stem cell-derived NPCs. Finally, we found a significant correlation between SVZ damage, reduction of striatum volume, and impairment of information processing speed in neurological patients. Our results highlight the physiological role of adult SVZ-eNPCs in supporting cognitive functions by regulating striatal neuronal activity.

FRAGILITY FRACTURES OF THE SACRUM: A SILENT EPIDEMIC.

Fragility fractures of the sacrum (FFS) are caused by low-energy trauma in the elderly population. Due to the nuanced symptomatology, many FFS remains unrecognized and the prevalence is underestimated. The clinical presentation varies, typically presenting with weightbearing low back pain without even remembering of a previous trauma. Radiographs are usually insufficient for the diagnosis and second level imaging modalities are required. In particular, magnetic resonance demonstrated the highest diagnostic accuracy. Treatment should aim to guarantee early mobilization and weightbearing, efficient pain relief and early discharge from the hospital to a proper facility for rehabilitation. Conservative treatment is reserved to non-displaced fractures with an adequate pain relief within one week allowing early mobilization. Otherwise, surgical treatment must be preferred. Nowadays, minimally invasive techniques, such as ileo-sacral screws or trans-sacral bar osteosynthesis, are safe and effective procedures and have overcome open procedures. In more complex patterns, with complete dissociation between the pelvic ring and the ilio-lumbar spine, spino-pelvic fixation is the procedure of choice.