Effects and mechanotransduction pathways of therapeutic ultrasound on healthy and osteoarthritic chondrocytes: a systematic review of in vitro studies.

OBJECTIVE: To investigate the effects and mechanotransduction pathways of therapeutic ultrasound on chondrocytes. METHOD: PubMed, EMBASE and Web of Science databases were searched up to 19th September 2021 to identify in vitro studies exploring ultrasound to stimulate chondrocytes for osteoarthritis (OA) treatment. Study characteristics, ultrasound parameters, in vitro setup, and mechanotransduction pathways were collected. Risk of bias was judged using the Risk of Bias Assessment for Non-randomized Studies (RoBANS) tool. RESULTS: Thirty-one studies were included comprising healthy and OA chondrocytes and explants. Most studies had high risk of performance, detection and pseudoreplication bias due to lack of temperature control, setup calibration, inadequate semi-quantitatively analyzes and independent experiments. Ultrasound was applied to the culture plate via acoustic gel, water bath or culture media. Regardless of the setup used, ultrasound stimulated the cartilage production and suppressed its degradation, although the effect size was nonsignificant. Ultrasound inhibited p38, c-Jun N-terminal kinases (JNK) and factor nuclear kappa B (NFκB) pathways in OA chondrocytes to reduce apoptosis, inflammation and matrix degradation, while triggered phosphoinositide-3-kinase/akt (PI3K/Akt), extracellular signal-regulated kinase (ERK), p38 and JNK pathways in healthy chondrocytes to promote matrix synthesis. CONCLUSION: The included studies suggest that ultrasound application induces therapeutic effects on chondrocytes. However, these results should be interpreted with caution because high risk of performance, detection and pseudoreplication bias were identified. Future studies should explore the application of ultrasound on human OA chondrocytes cultures to potentiate the applicability of ultrasound towards cartilage regeneration of knee with OA.

Sync and Swarm: Solvable Model of Nonidentical Swarmalators.

We study a model of nonidentical swarmalators, generalizations of phase oscillators that both sync in time and swarm in space. The model produces four collective states: asynchrony, sync clusters, vortexlike phase waves, and a mixed state. These states occur in many real-world swarmalator systems such as biological microswimmers, chemical nanomotors, and groups of drones. A generalized Ott-Antonsen ansatz provides the first analytic description of these states and conditions for their existence. We show how this approach may be used in studies of active matter and related disciplines.

A data-driven model for COVID-19 pandemic - Evolution of the attack rate and prognosis for Brazil.

We introduce a compartmental model SEIAHRV (Susceptible, Exposed, Infected, Asymptomatic, Hospitalized, Recovered, Vaccinated) with age structure for the spread of the SARAS-CoV virus. In order to model current different vaccines we use compartments for individuals vaccinated with one and two doses without vaccine failure and a compartment for vaccinated individual with vaccine failure. The model allows to consider any number of different vaccines with different efficacies and delays between doses. Contacts among age groups are modeled by a contact matrix and the contagion matrix is obtained from a probability of contagion p c per contact. The model uses known epidemiological parameters and the time dependent probability p c is obtained by fitting the model output to the series of deaths in each locality, and reflects non-pharmaceutical interventions. As a benchmark the output of the model is compared to two good quality serological surveys, and applied to study the evolution of the COVID-19 pandemic in the main Brazilian cities with a total population of more than one million. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of We also estimate the attack rate, the total proportion of cases (symptomatic and asymptomatic) with respect to the total population, for all Brazilian states since the beginning of the COVID-19 pandemic. We argue that the model present here is relevant to assessing present policies not only in Brazil but also in any place where good serological surveys are not available.

Silicon microparticles as handles for optical tweezers experiments.

We study the behavior of silicon microparticles in a 1064 nm Gaussian-beam optical tweezers, showing that this semiconductor can be used to perform different types of optical manipulation experiments. Depending on the focal position and the laser power used, the particles can present an oscillatory dynamics in the tweezers or can be stably 3D-trapped with a trap stiffness that allows the application of femtoNewton forces with accuracy. A new, to the best of our knowledge, interpretation based on the photoexcitation of electrons in the valence band is proposed to explain the oscillations, and the quantities associated with such dynamics (e.g., amplitude, period, etc.) were characterized as a function of relevant parameters to optical tweezers setups.

Filtering Statistics on Networks.

Compression, filtering, and cryptography, as well as the sampling of complex systems, can be seen as processing information. A large initial configuration or input space is nontrivially mapped to a smaller set of output or final states. We explored the statistics of filtering of simple patterns on a number of deterministic and random graphs as a tractable example of such information processing in complex systems. In this problem, multiple inputs map to the same output, and the statistics of filtering is represented by the distribution of this degeneracy. For a few simple filter patterns on a ring, we obtained an exact solution of the problem and numerically described more difficult filter setups. For each of the filter patterns and networks, we found three key numbers that essentially describe the statistics of filtering and compared them for different networks. Our results for networks with diverse architectures are essentially determined by two factors: whether the graphs structure is deterministic or random and the vertex degree. We find that filtering in random graphs produces much richer statistics than in deterministic graphs, reflecting the greater complexity of such graphs. Increasing the graph's degree reduces this statistical richness, while being at its maximum at the smallest degree not equal to two. A filter pattern with a strong dependence on the neighbourhood of a node is much more sensitive to these effects.

Distinguishing melanocytic nevi from melanomas using static and dynamic infrared thermal imaging.

BACKGROUND: The incidence rates of melanoma have risen to worrying levels over the last decade. Delayed diagnosis, due to faults on the detection stage, indicates the necessity of new aiding diagnosis techniques. Since metabolic activity is highly connected to neoplasia formation, a detection technique that focuses its results on vascular responses, as Infrared thermal (IRT), seems to be a viable option. MATERIALS AND METHODS: Static and dynamic (cooling) thermal images of melanoma and melanocytic nevi lesions were collected and analysed to retrieve thermal parameters characteristic of this skin lesion types. The steady-state and dynamic variables were tested separately with different machine learning classifiers to verify whether the distinction of melanoma and nevi lesions was achievable. RESULTS: The differentiation of both types of skin tumours was doable, achieving an accuracy of 84.2% and a sensitivity of 91.3% with the implementation of a learner based on support vector machines and an input vector composed by static variables. CONCLUSION: The use of IRT for skin tumour classification is achievable, but some improvement is needed to raise the metrics of sensitivity and specificity. For future work, it is recommended the study of dynamic parameters for the classification of other types of skin neoplasia.

Dissolved Carbon Dioxide Sensing Platform for Freshwater and Saline Water Applications: Characterization and Validation in Aquaculture Environments.

A sensing configuration for the real-time monitoring, detection, and quantification of dissolved carbon dioxide (dCO2) was developed for aquaculture and other applications in freshwater and saline water. A chemical sensing membrane, based on a colorimetric indicator, is combined with multimode optical fiber and a dual wavelength light-emitting diode (LED) to measure the dCO2-induced absorbance changes in a self-referenced ratiometric scheme. The detection and processing were achieved with an embeded solution having a mini spectrometer and microcontroller. For optrode calibration, chemical standard solutions using sodium carbonate in acid media were used. Preliminary results in a laboratory environment showed sensitivity for small added amounts of CO2 (0.25 mg·L-1). Accuracy and response time were not affected by the type of solution, while precision was affected by salinity. Calibration in freshwater showed a limit of detection (LOD) and a limit of quantification (LOQ) of 1.23 and 1.87 mg·L-1, respectively. Results in saline water (2.5%) showed a LOD and LOQ of 1.05 and 1.16 mg·L-1, respectively. Generally, performance was improved when moving from fresh to saline water. Studies on the dynamics of dissolved CO2 in a recirculating shallow raceway system (SRS+RAS) prototype showed higher precision than the tested commercial sensor. The new sensor is a compact and robust device, and unlike other sensors used in aquaculture, stirring is not required for correct and fast detection. Tests performed showed that this new sensor has a fast accurate detection as well as a strong potential for assessing dCO2 dynamics in aquaculture applications.

Finding the Optimal Nets for Self-Folding Kirigami.

Three-dimensional shells can be synthesized from the spontaneous self-folding of two-dimensional templates of interconnected panels, called nets. However, some nets are more likely to self-fold into the desired shell under random movements. The optimal nets are the ones that maximize the number of vertex connections, i.e., vertices that have only two of its faces cut away from each other in the net. Previous methods for finding such nets are based on random search, and thus, they do not guarantee the optimal solution. Here, we propose a deterministic procedure. We map the connectivity of the shell into a shell graph, where the nodes and links of the graph represent the vertices and edges of the shell, respectively. Identifying the nets that maximize the number of vertex connections corresponds to finding the set of maximum leaf spanning trees of the shell graph. This method allows us not only to design the self-assembly of much larger shell structures but also to apply additional design criteria, as a complete catalog of the maximum leaf spanning trees is obtained.

Recent use of medical infrared thermography in skin neoplasms.

BACKGROUND: Infrared thermal imaging captures the infrared radiation emitted by the skin surface. The thermograms contain valuable information, since the temperature distribution can be used to characterize physiological anomalies. Thus, the use of infrared thermal imaging (IRT) has been studied as a possible medical tool to aid in the diagnosis of skin oncological lesions. The aim of this review is to assess the current state of the applications of IRT in skin neoplasm identification and characterization. METHODS: A literature survey was conducted using the reference bibliographic databases: Scopus, PubMed and ISI Web of Science. Keywords (thermography, infrared imaging, thermal imaging and skin cancer) were combined and its presence was verified at the title and abstract of the article or as a main topic. Only articles published after 2013 were considered during this search. RESULTS: In total, 55 articles were encountered, resulting in 14 publications for revision after applying the exclusion criteria. It was denoted that IRT have been used to characterize and distinguish between malignant and benign neoplasms and different skin cancer types. IRT has also been successfully applied in the treatment evaluation of these types of lesions. CONCLUSION: Trends and future challenges have been established to improve the application of IRT in this field, disclosing that dynamic thermography is a promising tool for early identification of oncological skin conditions.

Hyaluronic Acid.

In recent times, the field of tissue engineering and regenerative medicine (TERM) has considerably increased the extent of therapeutic strategies for clinical application in orthopedics. However, TERM approaches have its rules and requirements, in the respect of the biologic response of each tissue and bioactive agents which need to be considered, respected, and subject of ongoing studies. Different medical devices/products have been prematurely available on the market and used in clinics with limited success. However, other therapeutics, when used in a serious and evidence-based approach, have achieved considerable success, considering the respect for solid expectations from doctors and patients (when properly informed).Orthobiologics has appeared as a recent technological trend in orthopedics. This includes the improvement or regeneration of different musculoskeletal tissues by means of using biomaterials (e.g., hyaluronic acid), stem cells, and growth factors (e.g., platelet-rich plasma). The potential symbiotic relationship between biologic therapies and surgery makes these strategies suitable to be used in one single intervention.However, herein, the recent clinical studies using hyaluronic acid (HA) in the treatment of orthopedic conditions will mainly be overviewed (e.g., osteochondral lesions, tendinopathies). The possibilities to combine different orthobiologic agents as TERM clinical strategies for treatment of orthopedic problems will also be briefly discussed.

Mapping the Structure of Directed Networks: Beyond the Bow-Tie Diagram.

We reveal a hierarchical, multilayer organization of finite components-i.e., tendrils and tubes-around the giant connected components in directed networks and propose efficient algorithms allowing one to uncover the entire organization of key real-world directed networks, such as the World Wide Web, the neural network of Caenorhabditis elegans, and others. With increasing damage, the giant components decrease in size while the number and size of tendril layers increase, enhancing the susceptibility of the networks to damage.

Heparin Resistance During Surgical Resection of Inferior Vena Cava and Right Atrial Tumor Thrombus: A Case Report.

INTRODUCTION: Heparin resistance is the failure of unusually high doses of heparin to achieve a target activated clotting time (ACT). We present the case of a 47-year-old female patient, ASA 2, who was diagnosed with a neuroendocrine retroperitoneal tumor with thrombus in the left renal vein, inferior vena cava and right atrium. General and cardiothoracic surgeons collaborated to remove the tumor under cardiopulmonary bypass. Heparin resistance was considered and treated with 1000 UI of antithrombin III concentrate. The authors review the mechanisms and management of this entity.

Tears of popliteomeniscal fascicles, diagnostic and clinical implications. A review of the evidence.

Postero-lateral corner of the knee is composed of several structures including the popliteo-meniscal fascicles (PMFs). These fibrous structures form a stable ligamentous complex around the popliteus tendon, which stabilize the lateral meniscus, increasing the strength of postero-lateral corner. Studies were retrieved through an electronic search of CINAHL, EMBASE, and Pub-Med, until May 2016. Studies in English, Italian, French, and Spanish were considered for inclusion. Randomized controlled trials, prospective and retrospective comparative studies, case series, and case reports were included. Studies eligible for inclusion concerned PMFs anatomy, biomechanics, diagnostic assessment of PMFs tears and clinical options for tears management. Thirteen studies were included in this review. There were: 7 case series, 4 case reports and 3 anatomical studies. Through anatomic dissection, two or three PMFs (antero-inferior fascicle, aiPMF; postero-superior fascicle, psPMF; postero-inferior fascicle, piPMF) can be indentified and isolated. Evaluation through MRI can be a useful diagnostic tool in detecting PMFs tears, especially using proton density (PD) sequences. The biomechanical analysis assessed that lateral meniscus (LM) motion is directly related with PMFs integrity and increased with section of one or both the fascicles. The clinical studies clearly state that a snapping syndrome, associated with lateral knee pain, can develop when one or both PMFs are torn. The three PMFs described are considered as relevant components of the popliteal hiatus, in the posterolateral aspect of the knee. MRI evaluation can detect these fibrous fascicles with good sensitivity. More studies with larger samples would be needed for a clear comprehension of PMFs function and clinical management of PMFs tears, especially with large case series and modern biomechanical testing.

Pain reduction and improvement of function following ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid in hip osteoarthritis.

The scientific literature has shown positive results regarding intra-articular injections of hyaluronic acid in osteoarthritic joints. When injecting in the hip joint, the guidance of ultrasound can provide higher injection accuracy and repeatability. However, due to the methodological limitations in the current available literature, its recommendation in the current practice is still controversial. This study shows that ultrasound-guided intra-articular injections of triamcinolone hexacetonide and hyaluronic acid can improve pain, function and quality of life in patients with symptomatic and radiographic hip osteoarthritis. In addition, the administration of triamcinolone hexacetonide and hyaluronic acid to the hip joint in these patients can delay the need for interventional surgery.

Sport and early osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis.

Sports activities are considered favourable for general health; nevertheless, a possible influence of sports practice on the development of early osteoarthritis (OA) is a cause for concern. A higher incidence of OA in knees and ankles of former high-impact sports players than in those of the normal population has been shown and it is still debatable whether the cause is either to be recognized generically in the higher number of injuries or in a joint overload. The possibility to address knee OA in its early phases may be strictly connected to the modification of specific extrinsic or intrinsic factors, related to the patient in order to save the joint from further disease progression; these include sport practice, equipment and load. Non-surgical therapies such as continuative muscles reinforce and training play a strong role in the care of athletes with early OA, particularly if professional. There is an overall agreement on the need of an early restoring of a proper meniscal, ligament and cartilage integrity in order to protect the knee and resume sports safely, whereas alignment is a point still strongly debatable especially for professional athletes. Remaining questions still to be answered are the risks of different sports in relation to one another, although an actual protective effect of low-impact sports, such as walking, swimming or cycling, has been recognized on the appearance or worsening of OA, the effect of continuing or ceasing to practice a sport on the natural history of early OA, and even following appropriate treatment is still unknown.

Evaluation of screening and treatment of cryptococcal antigenaemia among HIV-infected persons in Soweto, South Africa.

OBJECTIVES: We retrospectively evaluated clinic-based screening to determine the prevalence of cryptococcal antigenaemia and management and outcome of patients with antigenaemia. METHODS: Cryptococcal antigen (CrAg) screening of HIV-infected adults who attended the HIV clinic at Chris Hani Baragwanath Hospital was conducted over 19 months. Data collected from CrAg-positive patients included CD4 T-lymphocyte count at screening, prior or subsequent cryptococcal meningitis (CM), antifungal and antiretroviral treatment and outcome after at least 8 months. RESULTS: Of 1460 patients with no prior CM, 30 (2.1%) had a positive CrAg test. The prevalence of antigenaemia among patients with a CD4 count < 100 cells/µl and no prior CM was 2.8% (20 of 708). Of 29 evaluable CrAg-positive patients with no prior CM, 14 (48%) did not return for post-screening follow-up. Of these 14, five developed CM and one (7%) was known to be alive at follow-up. Of 15 patients who returned for follow-up, two already had evidence of nonmeningeal cryptococcosis. Overall, 11 received fluconazole, one did not and fluconazole treatment was unknown for three. Among these 15, one developed CM and 10 (67%) were known to be alive at follow-up. Overall, 18 (62%) of 29 CrAg-positive patients died or were lost to follow-up. Seven (0.5%) of 1430 CrAg-negative patients developed CM a median of 83 days post-screening (range 34 to 219 days). CONCLUSIONS: Loss to follow-up is the major operational issue relevant to scale-up of screen-and-treat. Patient outcomes may be improved by rapid access to CrAg results and focus on linkage to and retention in HIV care.

Spin-Current to Charge-Current Conversion and Magnetoresistance in a Hybrid Structure of Graphene and Yttrium Iron Garnet.

The use of graphene in spintronic devices depends, among other things, on its ability to convert a spin excitation into an electric charge signal, a phenomenon that requires a spin-orbit coupling (SOC). Here we report the observation of two effects that show the existence of SOC in large-area CVD grown single-layer graphene deposited on a single crystal film of the ferrimagnetic insulator yttrium iron garnet (YIG). The first is a magnetoresistance of graphene induced by the magnetic proximity effect with YIG. The second is the detection of a dc voltage along the graphene layer resulting from the conversion of the spin current generated by spin pumping from microwave driven ferromagnetic resonance into a charge current, which is attributed to the inverse Rashba-Edelstein effect.

Animal model for chronic massive rotator cuff tear: behavioural and histologic analysis.

PURPOSE: Massive rotator cuff tears (MRCT) are usually chronic lesions that present associated degenerative changes of the myotendinous unit that have been implicated in limitations for surgical repair. In order to develop effective therapies, it is important to establish animal models that mimic the hallmarks of the injury itself. Therefore, in the present work, we aimed to (1) optimize a rodent animal model of MRCT that closely reproduces the fatty infiltration of the cuff muscles seen in humans and (2) describe the effects of unilateral or bilateral lesion in terms of histology and behaviour. METHODS: Massive tear was defined as two rotator cuff tendons-supraspinatus and infraspinatus-section. Twenty-one Wistar rats were randomly assigned to four groups: bilateral lesion (five animals), right-sided unilateral lesion (five animals), left-sided unilateral lesion (five animals) and control (six animals). Behaviour was analyzed with open field and staircase test, 16 weeks after lesion. After that, animals were killed, and the supraspinatus and infraspinatus muscles were processed. RESULTS: Histologic analysis revealed adipocytes, fatty infiltration and atrophy in the injured side with a greater consistency of these degenerative changes in the bilateral lesion group. Behaviour analysis revealed a significant functional impairment of the fine motor control of the forepaw analyzed in staircase test where the number of eaten pellets was significantly higher in sham animals (sham = 7 ± 5.0; left unilateral = 2.6 ± 3.0; right unilateral = 0 ± 0; and bilateral = 0 ± 0, p < 0.05). A trend to reach a lower level of steps, in more injured animals, was also observed (sham animals = 3 ± 1.6 > left unilateral = 2 ± 2.1 > right unilateral = 0.8 ± 1.3 > bilateral = 0.8 ± 1.1). CONCLUSIONS: The present study has been able to establish an animal model that disclosed the hallmarks of MRCT. This can now be used as a valuable, cost-effective, pre-clinical instrument to assist in the development of advanced tissue engineered strategies. Moreover, this animal model overcomes some of the limitations of those that have been reported so far and thus represents a more reliable source for the assessment of future therapeutic strategies with potential clinical relevance.

Small-angle X-ray scattering and in silico modeling approaches for the accurate functional annotation of an LysR-type transcriptional regulator.

Xylella fastidiosa is a xylem-limited, Gram-negative phytopathogen responsible for economically relevant crop diseases. Its genome was thus sequenced in an effort to characterize and understand its metabolism and pathogenic mechanisms. However, the assignment of the proper functions to the identified open reading frames (ORFs) of this pathogen was impaired due to a lack of sequence similarity in the databases. In the present work, we used small-angle X-ray scattering and in silico modeling approaches to characterize and assign a function to a predicted LysR-type transcriptional regulator in the X. fastidiosa (XfLysRL) genome. XfLysRL was predicted to be a homologue of BenM, which is a transcriptional regulator involved in the degradation pathway of aromatic compounds. Further functional assays confirmed the structural prediction because we observed that XfLysRL interacts with benzoate and cis,cis-muconic acid (also known as 2E,4E-hexa-2,4-dienedioic acid; hereafter named muconate), both of which are co-factors of BenM. In addition, we showed that the XfLysRL protein is differentially expressed during the different stages of X. fastidiosa biofilm formation and planktonic cell growth, which indicates that its expression responds to a cellular signal that is likely related to the aromatic compound degradation pathway. The assignment of the proper function to a protein is a key step toward understanding the cellular metabolic pathways and pathogenic mechanisms. In the context of X. fastidiosa, the characterization of the predicted ORFs may lead to a better understanding of the cellular pathways that are linked to its bacterial pathogenicity.

Biomechanical and cellular segmental characterization of human meniscus: building the basis for Tissue Engineering therapies.

OBJECTIVE: To overcome current limitations of Tissue Engineering (TE) strategies, deeper comprehension on meniscus biology is required. This study aims to combine biomechanical segmental analysis of fresh human meniscus tissues and its correlation with architectural and cellular characterization. METHOD: Morphologically intact menisci, from 44 live donors were studied after division into three radial segments. Dynamic mechanical analysis (DMA) was performed at physiological-like conditions. Micro-computed tomography (CT) analysis of freeze-dried samples assessed micro-structure. Flow cytometry, histology and histomorphometry were used for cellular study and quantification. RESULTS: Anterior segments present significantly higher damping properties. Mid body fresh medial meniscus presents higher values of E' compared to lateral. Cyclic loads influence the viscoelastic behavior of menisci. By increasing the frequency leads to an increase in stiffness. Conversely, with increasing frequencies, the capacity to dissipate energy and damping properties initially decrease and then rise again. Age and gender directly correlate with higher E' and tan δ. Micro-CT analysis revealed that mean porosity was 55.5 (21.2-89.8)% and 64.7 (47.7-81.8)% for freeze-dried lateral and medial meniscus, respectively. Predominant cells are positive for CD44, CD73, CD90 and CD105, and lack CD31, CD34 and CD45 (present in smaller populations). Histomorphometry revealed that cellularity decreases from vascular zone 1 to zone 3. Anterior segments of lateral and medial meniscus have inferior cellularity as compared to mid body and posterior ones. CONCLUSION: Menisci are not uniform structures. Anterior segments have lower cellularity and higher damping. Cyclic loads influence viscoelastic characteristics. Future TE therapies should consider segmental architecture, cellularity and biomechanics of fresh tissue.