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Aim of the present pilot study was to verify, for the first time ever, the effects of collagen injections in patients with chronic supraspinatus tendinopathy. Eighteen patients with chronic supraspinatus tendinopathy were treated with a series of 4 type I porcine collagen ultrasound-guided injections, at weekly intervals. The effects were verified at 2-week, 1-month and 3-month follow-up by means of shoulder scoring systems and sonography. A very strong evidence (p

Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19.

In this work, we developed an innovative gut-liver-on-chip system useful to predict oral drug administration and first pass metabolism. The two main organs involved in the first pass metabolism are the liver and the intestine. First-pass effects consist mainly in the reduction of bioavailability of drugs and xenobiotics. The prediction of this mechanism is important both for the development of new substances, but also for toxicity testing. For this purpose, we designed a microfluidic device which interconnect 3D human intestinal equivalent (3D-HIE) and HepG2-microtissues, recapitulating the intestinal and hepatic firstpass effect mechanism of ethanol. 3D-HIE were obtained by bottom up approach, using intestinal microtissues moulded into a maturation chamber and HepG2-μTPs were obtained by dynamic cell seeding of Hepg2 and gelatin porous microsphere in a spinner flask bioreactor.

A common approach to modelling fluid flow through discrete fracture networks is to represent the fracture network by an equivalent pipe network model. The major advantage of this approach is its simplicity and computational efficiency, which enables it to deal with complex, reservoir-scale problems. However, the derived flow model depends primarily on the pipe network used and the construction of a representative pipe model is still a very challenging issue, particularly for large and complicated fracture networks. An iterative process was proposed recently to derive such a realistic pipe network model and the work reported in this paper is an extension of that approach with an improvement on how pipes are re-connected during the iteration process to better represent the reality of flow patterns. In particular, the source and sink traces on each fracture are re-evaluated using the boundary element method during each iteration step. As a case study, the proposed approach is applied to the flow analysis of the Habanero geothermal field in the Cooper Basin of South Australia.

War zones in Sub Saharan Africa represent a challenge for public health projects like TB control programs because planning and communication have been disrupted, doctors and medical workers flied to secure zones. We present a TB control program carried out by an Italian NGO, Italian Association for Solidarity among People (AISPO) in a referral Hospital of North Uganda (Lacor H).

Osteoarthritis (OA) is the most frequent degenerative progressive joint disease worldwide, with the hand, hip, and knee being the most-affected joints. Actually, no treatment can alter the course of OA, and therapy is directed at reducing pain and improving function. The exogenous administration of collagen has been investigated as a possible symptomatic adjuvant or stand-alone treatment for OA. The aim of this review is to assess if intra-articular collagen administration can be considered as a valid and safe therapeutic option for OA. A search in the main scientific electronic databases to identify the available scientific articles about the effects of intra-articular collagen as an OA treatment was performed. The results of the seven included studies showed that the intra-articular administration of collagen may stimulate chondrocytes to produce hyaline cartilage and hinder the normal inflammatory response leading to fibrous tissue formation, reducing symptoms, and improving functionality. The use of type-I collagen as an intra-articular treatment for knee OA was found not only to be effective, but also safe with negligible side effects. The reported findings are strongly promising, highlighting the need for further high-quality research to confirm the consistency of these findings.

Lateral meningocele syndrome (LMS) is due to specific pathogenic variants in the last exon of NOTCH3 gene. Besides the lateral meningoceles, this condition presents with dysmorphic features, short stature, congenital heart defects, and feeding difficulties. Here, we report a girl with neurosensorial hearing loss, severe gastroesophageal reflux disease, congenital heart defects, multiple renal cysts, kyphosis and left‐convex scoliosis, dysmorphic features, and mild developmental delay. Exome sequencing detected the previously unreported de novo loss‐of‐function variant in exon 33 of NOTCH3 p.(Lys2137fs). Following the identification of the gene defect, MRI of the brain and spine revealed temporal encephaloceles, inner ears anomalies, multiple spinal lateral meningoceles, and intra‐ and extra‐dural arachnoid spinal cysts. This case illustrates the power of reverse phenotyping to establish clinical diagnosis and expands the spectrum of clinical manifestations related to LMS to include inner ear abnormalities and multi‐cystic kidney disease.

The study of novel drug delivery systems represents one of the frontiers of the biomedical research area. Multi-disciplinary scientific approaches combining traditional or engineered technologies are used to provide major advances in improving drug bioavailability, rate of release, cell/tissue specificity and therapeutic index. Biodegradable and bio-absorbable polymers are usually the building blocks of these systems, and their copolymers are employed to create delivery components. For example, poly (lactic acid) or poly (glycolic acid) are often used as bricks for the production drug-based delivery systems as polymeric microparticles (MPs) or micron-scale needles. To avoid time-consuming empirical approaches for the optimization of these formulations, in silico-supported models have been developed. These methods can predict and tune the release of different drugs starting from designed combinations. Starting from these considerations, this review has the aim of investigating recent approaches to the production of polymeric carriers and the combination of in silico and experimental methods as promising platforms in the biomedical field.

Bacterial cellulose (BC) is a highly pure form of cellulose produced by bacteria, which possesses numerous advantages such as good mechanical properties, high chemical flexibility, and the ability to assemble in nanostructures. Thanks to these features, it achieved a key role in the biomedical field and in drug delivery applications. BC showed its ability to modulate the release of several drugs and biomolecules to the skin, thus improving their clinical outcomes. This work displays the loading of a 3D BC nanonetwork with an innovative drug delivery nanoemulsion system. BC was optimized by static culture of SCOBY (symbiotic colony of bacteria and yeast) and characterized by morphological and ultrastructural analyses, which indicate a cellulose fiber diameter range of 30–50 nm. BC layers were then incubated at different time points with a nanocarrier based on a secondary nanoemulsion (SNE) previously loaded with a well-known antioxidant and anti-inflammatory agent, namely, coenzyme-Q10 (Co-Q10). Incubation of Co-Q10–SNE in the BC nanonetwork and its release were analyzed by fluorescence spectroscopy.

Background Pain of musculoskeletal origin is very common in young patients affected by Mucopolysaccharidoses. This scoping review evaluates the evidence for assessment, pharmacological treatment and rehabilitation management for musculoskeletal pain of the latter. Methods A Medline search through PubMed has been performed for studies published in English at least for the past twenty years. Two investigators independently reviewed all search results and extracted those that met the inclusion criteria. Results 29 studies have been selected and analysed in depth, of which 10 related to pain assessment, 11 concerned pharmacological approach, and 8 reported rehabilitation approaches. Conclusion Few data are available in literature concerning the classification and management of pain in children with Mucopolysaccharidoses. Notwithstanding, pain evaluation methods are effectively used to classify pain intensity, according to the age group and communication abilities of young Mucopolysaccharidoses patients. The review emphasizes that drug therapies have a palliative purpose, while rehabilitation reduces musculoskeletal pain and can provide a therapeutic effect on disabilities.

An intestine-on-chip has been developed to study intestinal physiology and pathophysiology as well as intestinal transport absorption and toxicity studies in a controlled and human similar environment. Here, we report that dynamic culture of an intestine-on-chip enhances extracellular matrix (ECM) remodeling of the stroma, basement membrane production and speeds up epithelial differentiation. We developed a three-dimensional human intestinal stromal equivalent composed of human intestinal subepithelial myofibroblasts embedded in their own ECM. Then, we cultured human colon carcinoma-derived cells in both static and dynamic conditions in the opportunely designed microfluidic system until the formation of a well-oriented epithelium. This low cost and handy microfluidic device allows to qualitatively and quantitatively detect epithelial polarization and mucus production as well as monitor barrier function and ECM remodeling after nutraceutical treatment.

SUMMARY Background. COVID-19 outbreak had a massive worldwide impact and several countermeasures to contain its spread have been adopted, such as the interruption of non-urgent outpatient clinics. We wanted to describe the effects of the national lock-down on the well-being of a cohort of Italian patients with musculoskeletal disorders receiving infiltrative treatment. Methods. 40 patients who received intra-or peri-articular treatment were surveyed using a structuralised questionnaire that assessed their well-being during the first national lockdown. Results. 24 out of 40 patients (60%) did not come back after the re-opening of the Clinic because they were afraid of the pandemic. Of these 24 patients, the 83.3% noticed increased pain and stiffness in the joint. Due to the lockdown, the patient’s quality of life was reduced by 61.66 ± 15.72%. After the lockdown, for the 92% of patients, the infiltrative treatment was perceived as more important than before, the 83% of patients perceived long-term security of infiltrative therapy availability as very important, and the 72% of the patients perceived the lockdown as inadequate. Conclusions. The infiltrative outpatient clinic’s interruption was seen to significant-ly worsen the physical condition of subjects with musculoskeletal disorders, with an important increase in both articular pain and stiffness. Therefore, any kind of infiltra-tive treatment suspension or delay should be avoided.

Background: The prevention or early treatment of pathological scars is the most appropriate therapeutic approach. Gels and patches containing onion extract and allantoin are safe and effective in patients with scars of various origins and severity. However, no controlled studies have evaluated the effects of the patch formulation in women after Cesarean delivery. This study aimed to investigate the effects of a patch containing Allium cepa and allantoin on Cesarean section (C-section) scars. Methods: This is an observational study. Women were consecutively recruited at the University Hospital of Salerno and subdivided into two groups considering the number of C-section. Group A included subjects without and group B with a history of C-section. Scars assessment was made using digital photographs and the Patient and Observer Scar Assessment Scale (POSAS). After 4 weeks, the C-section of the women who had applied a patch containing Allium cepa and allantoin and those of women who had not used any products (controls) were re-evaluated as at baseline. The Observers independently performed the scars assessment at baseline and after 4 weeks. Data are expressed as the difference of the POSAS scores after 4 weeks minus the POSAS scores at baseline. The statistical significance was established at a p value

National and international healthcare organizations propose guidelines for physical activity worldwide, defining its characteristics. These guidelines&rsquo, practical applications are difficult to estimate, since they are not fully followed. The aim of the present cross-sectional observational study was to assess awareness about guidelines for physical activity and to evaluate their practical applications in a sample of the Italian population. In total, 310 participants completed an online survey (mean age 29.10 &plusmn, 4.44), assessing the habits, beliefs and health effects of physical activity. In total, 39.35% of respondents were inactive. In total, 6.91% of active respondents did not perform a warm-up phase at the beginning of each training session and 77.14% did not check their own heart rate during the training session. Approximately half of respondents reported erroneous beliefs about the type, frequency and volume of physical activity, compared to data proposed by the guidelines. The preventive effect of physical activity was clearly perceived for cardiovascular diseases, diabetes, metabolic syndrome and depression. Several subjects misinterpreted the preventive role of physical activity in colon and breast cancers, and in femur and vertebral fractures. Habits and beliefs about physical activity in the general population are far from the guidelines and recommendations. Therefore, it is necessary to strengthen the conscious practice of physical activity further.

The brachial plexus represents a complex anatomical structure in the upper limb. This “network” of peripheral nerves permits the rearrangement of motor efferent fibers, coming from different spinal nerves, in several terminal branches directed to upper limb muscles. Moreover, afferent information coming from different cutaneous regions in upper limb are sorted in different spinal nerves through the brachial plexus. Severe brachial plexus injuries are a rare clinical condition in the general population and in sport medicine, but with dramatic consequences on the motor and sensory functions of the upper limb. In some sports, like martial arts, milder injuries of the brachial plexus can occur, with transient symptoms and with a full recovery. Clinical evaluation represents the cornerstone in the assessment of the athletes with brachial plexus injuries. Electrodiagnostic studies and imaging techniques, like magnetic resonance and high-frequency ultrasound, could be useful to localize the lesion and to define an appropriate treatment and a functional prognosis. Several conservative and surgical techniques could be applied, and multidisciplinary rehabilitative programs could be performed to guide the athlete toward the recovery of the highest functional level, according to the type of injury.

Objective: To assess the prevalence of temporomandibular disorders (TMD) in a sample of tinnitus patients and to determine the association between tinnitus, TMD, neck disability, and oral parafunctions. Methods: Seventy-nine tinnitus patients were enrolled and underwent standardized clinical examination for TMD. The tinnitus severity was measured with the Tinnitus Handicap Inventory (THI). The oral parafunctions were self-reported with the Oral Behavior Checklist (OBC). The neck disability was recorded with the Neck Disability Index (NDI). Results: More than half of the sample presented TMD, and the most frequent diagnosis was TMD pain. Higher THI was observed in TMD-pain individuals, compared to TMD-free (β 18.4; 95%CI 6.7, 30.1; p = 0.002). The OBC showed a significant low-to-moderate positive correlation with the THI (rho= 0.368, p = 0.001), while the NDI did not. Discussion: Standardized assessment of TMD and oral behaviors should be integrated into the routine diagnostic evaluations of tinnitus patients.

The Achilles tendon is the thickest, strongest and largest tendon in the human body, but despite its size and tensile strength, it frequently gets injured. Achilles tendon ruptures (ATRs) mainly occur during sports activities, and their incidence has increased over the last few decades. Achilles tendon tears necessitate a prolonged recovery time, sometimes leaving long-term functional limitations. Treatment options include conservative treatment and surgical repair. There is no consensus on which is the best treatment for ATRs, and their management is still controversial. Limited scientific evidence is available for optimized rehabilitation regimen and on the course of recovery after ATRs. Furthermore, there are no universally accepted outcomes regarding the return to play (RTP) process. Therefore, the aim of this narrative review is to give an insight into the mechanism of injuries of an ATR, related principles of rehabilitation, and RTP.

Intestine-Liver-on-chip systems can be useful to predict oral drug administration and first-pass metabolism in vitro in order to partly replace the animal model. While organ-on-chip technology can count on sophisticated micro-physiological devices, the engineered organs still remain artificial surrogates of the native counterparts. Here, we used a bottom-up tissue engineering strategy to build-up physiologically functional 3D Human Intestine Model (3D-HIM) as well as 3D Liver-microtissues (HepG2-μTPs) in vitro and designed a microfluidic Intestine-Liver-On-Chip (InLiver-OC) to emulate first-pass mechanism occurring in vivo. Our results highlight the ethanol-induced 3D-HIM hyper-permeability and stromal injury, the intestinal prevention on the liver injury, as well as the synergic contribution of the two 3D tissue models on the release of metabolic enzymes after high amount of ethanol administration.

Background. Lateral epicondylitis, or tennis elbow, is the prevalent cause of elbow pain among adults. Collagen injections are used to treat different musculoskeletal disorders. Type I porcine collagen has proved to enhance tendon repair in vitro. Aims of the present pilot study were to verify the effects of type I porcine collagen injections on pain and disability in patients with tennis elbow and therefore to check if there are grounds for carry out a randomized controlled trial. Methods. Fifty patients, who have been suffering lateral epicondylitis for at least 6 months, were treated with a series of 5 type I porcine collagen injections, at weekly intervals. The Patient-Rated Tennis Elbow Evaluation questionnaire was employed to verify the effects of collagen injections at 1-month and 3-month follow-up. Results. As regards the baseline, the total score showed an average reduction of 57% (55% in terms of pain and 58% in terms of function) at 1-month follow-up and an average reduction of 66.1% (68.9% in terms of pain and 63.2% in terms of function) at 3-month follow-up. The results were statistically significant (p

Tissue-on-chip (TOC) systems aim at replicating complex biological dynamics in vitro with the potential either to improve the understanding of human biology or to develop more accurate therapeutic strategies. To replicate faithfully the intricate interrelationships between cells and their surrounding microenvironment, the three-dimensional (3D) tissue model must possess a responsive extracellular matrix (ECM). ECM remodeling plays a pivotal role in guiding cells and tissues functions and such aspect is somewhat denied during in vitro studies. For this purpose, we fabricated a micro-perfusion bioreactor capable to sustain the viability of 3D engineered tissue models recapitulating the process of the native ECM deposition and assembly. Engineered human dermis micro-tissue precursors (HD-mu TP) were used as building blocks to generate a final tissue. HD-mu TP were loaded in the perfusion space of the micro-perfusion bioreactor and, under the superimposition of different fluid dynamic regimes and biochemical stimulation, they synthesized new collagen proteins that were, then, assembled in the perfusion space forming a continuum of cells embedded in their own ECM. The micro-perfusion bioreactor was fabricated to allow the on-line monitoring of the oxygen consumption and the assembly of the newly formed collagen network via real time acquisition of the second harmonic generation (SHG) signal. The possibility to detect the collagen reorganization due to both fluid dynamic and biochemical stimulation, let us to define the optimal perfusion configuration in order to obtain a TOC system based on an endogenous and responsive ECM.