Morphological and Pigment Responses to Far-Red and Photosynthetically Active Radiation in an Olive Cultivar Suitable for Super-High-Density Orchards.

Plant density is increasing in modern olive orchards to improve yields and facilitate mechanical harvesting. However, greater density can reduce light quantity and modify its quality. The objective was to evaluate plant morphology, biomass, and photosynthetic pigments under different red/far-red ratios and photosynthetically active radiation (PAR) combinations in an olive cultivar common to super-high-density orchards. In a greenhouse, young olive trees (cv. Arbequina) were exposed to low (L) or high (H) PAR with or without lateral FR supplementation (L+FR, L-FR, H+FR, H-FR) using neutral-density shade cloth and FR light-emitting diode (LED) modules. Total plant and individual organ biomass were much lower in plants under low PAR than under high PAR, with no response to +FR supplementation. In contrast, several plant morphological traits, such as main stem elongation, individual leaf area, and leaf angle, did respond to both low PAR and +FR. Total chlorophyll content decreased with +FR when PAR was low, but not when PAR was high (i.e., a significant FR*PAR interaction). When evaluating numerous plant traits together, a greater response to +FR under low PAR than under high PAR appeared to occur. These findings suggest that consideration of light quality in addition to quantity facilitates a fuller understanding of olive tree responses to a light environment. The +FR responses found here could lead to changes in hedgerow architecture and light distribution within the hedgerow.

Extraction, characterization and properties evaluation of pineapple leaf fibers from Azores pineapple.

Pineapple leaves can provide competitive and high-quality fibers for textile purposes. Despite pineapple being cultivated in the Portugues islands there is still a technology gap for the extraction and treatment of Pineapple Leaf Fibers (PALF) in Europe. Since Azorean Pineapple differs significantly from other plants in the bromeliad family, the properties and characterization of its leaf fibers were explored for the first time. Long fibers have been extracted by hand scraping and compared to biological retting at 25 °C for different time periods. It was explored the properties of PALF from plants of different ages (11- and 18-months) and from different zones of the leaves (beginning, middle, and tip). Physical-mechanical properties of Azores PALF were determined, including diameter, linear density, strength, Young's modulus, and elongation at break and characterized by ATR-FTIR, XRD, TGA/DTG, and FESEM to understand their chemical and morphological characteristics. While slight differences were observed between different ages, variations in physical-mechanical properties were notable among fibers extracted from different leaf positions. Extraction of Azores PALF through 25 °C biological retting for 14 days effectively eliminated non-fibrous matter and produced the thinnest and strongest fibers. These fibers ranged between 34.9 and 168.3 µm in diameter, 1.39 and 7.07 tex in linear mass density, 37-993 MPa in tensile strength, 1.0-3.9 % in elongation at break, and 2.4-21.8 GPa in Young's modulus.

Experience of practicing obstetrician-gynecologists in a surgical training program in total laparoscopic hysterectomy.

BACKGROUND: Advanced surgical techniques, such as total laparoscopic hysterectomy, are often challenging to acquire beyond fellowship training programs for practicing obstetrician-gynecologists. A lack of formative data currently exist for continuing medical education programs, limiting our understanding of how improvement in surgical skills and training programs occur. OBJECTIVE: This study aimed to investigate how practicing obstetrician-gynecologists acting as trainees experience a program that aims to teach them total laparoscopic hysterectomy, and to assess whether their surgical skills improve according to data from formative assessment tools and qualitative data from open-ended survey questions and in-depth interviews. STUDY DESIGN: We report a process analysis of formative data collected during a pilot implementation trial of a surgical training program targeting practicing obstetrician-gynecologists. Eleven consultant obstetrician-gynecologists and 4 experienced surgical mentors participated in 4 hospitals in Queensland, Australia. Total laparoscopic hysterectomy was performed in 700 patients over the course of the study. A total laparoscopic hysterectomy surgical mentorship training program of 10 training days with up to 3 total laparoscopic hysterectomy procedures per day was performed. Both the obstetrician-gynecologists and the surgical mentor completed a formative assessment questionnaire analyzing the trainee's performance after each surgical procedure. Mentors were formatively assessed by the Structured Training Trainer Assessment Report (STTAR) and at the completion of the study by the mini-STTAR, a summative assessment of quality of mentorship. Obstetrician-gynecologists, mentors, hospital leaders, and surgical administrative staff participated in qualitative interviews about the training program. RESULTS: Over time, there was a demonstrated improvement in trainee performance reported by both mentors and trainees in all competency assessment tool domains as the case number increased, with mentors consistently rating trainees' performance higher than the trainees themselves. Most trainees were satisfied with their mentor in all 31 areas during formative assessment, and at the end of the training, structure, attributes, and role modeling were all rated high (average score >4.5; range, 3.79-5.00), whereas training behavior was rated slightly lower at 4.1 (range, 3.79-4.45). Qualitative interviews demonstrated that the trainees found the training to be a beneficial, hands-on experience. CONCLUSION: Formative assessment clearly documented improvement in surgical skills during a total laparoscopic hysterectomy training program for consultant obstetrician-gynecologists.

Consumer views of melanoma early detection using 3D total-body photography: cross-sectional survey.

BACKGROUND: Three-dimensional (3D) total-body photography is a recent advance in melanoma early detection that can aid in monitoring and identifying new and changing skin lesions over time. METHODS: A cross-sectional survey of adults living in metropolitan and rural areas of Australia was conducted to assess perceptions of 3D total-body photography. Participants completed a survey detailing their previous use of skin cancer photography, personal skin checking history, perceptions of 3D total-body photography, and willingness to pay. Participants were also asked to describe the potential barriers and facilitators of 3D total-body photography in their own words. RESULTS: A total of 1056 participants completed the survey, with 739 (70%) from metropolitan areas of Australia and 317 (30%) from rural areas. Most participants (95%, n = 1004/1056) indicated they would consider using 3D total-body photography if it became commercially available at their regular medical practice. Most participants indicated 3D total-body photography would be effective to identify suspicious skin spots (94%, n = 995/1056), monitor lesion changes (94%, n = 997/1056), and reduce skin cancer related anxiety (90%, n = 950/1055). In open-ended feedback, participants (87%, n = 918/1056) identified perceived benefits, including more comprehensive screenings, earlier detection, and less human error. Participants (84%, n = 889/1056) also identified potential barriers to 3D total-body photography, including cost, accessibility and availability, trust in the technology, and digital security concerns. CONCLUSIONS: Participant feedback indicated a high level of acceptance and confidence in the technology. To facilitate clinical translation, addressing consumer-identified barriers to 3D total-body photography will be vital.

Influence of commercial starter culture on fermentation dynamics and quality characteristics of yogurts obtained with different formulations.

BACKGROUND: Four commercial starter cultures containing Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (S1, S2, S3 and S4; S3 also contained Limosilactobacillus fermentum) were compared for fermentation, volatile flavor compounds, physicochemical parameters and microbiology, in yogurt prepared from three milk base formulations with increased protein (B1, B2 and B3). RESULTS: The fermentation patterns differed among starters, with Yoflex Mild 1.0 (S4) and SLB95 (S2) showing the longest fermentation time, depending on the formulation. At 21 days, S. thermophilus counts were similar among starters and higher than 8.52 log CFU mL-1 , for all yogurts. The highest counts (6.86 log CFU mL-1 ) for L. delbrueckii subsp. bulgaricus was found for S2 yogurts made from whey protein hydrolysate (B3). Minor water-holding capacity was detected for YF-L811 (S1) yogurts. Yoflex Harmony 1.0 (S3) starter containing Lim. fermentum produced a distinctive volatile profile characterized by aldehydes with respect to yogurts prepared with S1, S2 and S4, which were characterized by ketones. CONCLUSION: Results indicate the usefulness of carrying out studies similar to the present one to select the most appropriate process conditions depending on the desired product. © 2022 Society of Chemical Industry.

Factors influencing participants' engagement with an interactive text-message intervention to improve sun protection behaviors: "SunText" randomized controlled trial.

There is growing evidence suggesting that text-message-based interventions are effective to promote sun protection behaviors. However, it is still unclear how engagement and adherence with the intervention messages can be optimized through intervention design. This study evaluated the effect of different combinations of personalized and two-way interactive messages on participant engagement with a theory-based skin cancer prevention intervention. In the SunText study conducted in February-July 2019 in Queensland, Australia participants 18-40 years were randomized to four different text message schedules using a Latin square design. This study analyzed if the order and intensity in which the schedules were received were associated with participants' level of engagement, and if this differed by demographic factors. Out of the 389 participants enrolled in the study, 375 completed the intervention period and remained for analysis. The overall intervention engagement rate was 71% and decreased from the beginning to the end of the study (82.2%-61.4%). The group starting with personalized, but not interactive messaging showed the lowest engagement rate. The intervention involving interactive messages three times a week for 4 weeks achieved the highest engagement rate. The intervention with increasing frequency (personalized and interactive three times a week for 2 weeks; then daily for 2 weeks) had lower engagement than intervention with constant or decreasing frequency. Engagement with two-way interactive messages was high across all intervention groups. Results suggest enhanced engagement with constant or decreasing message frequency compared to increasing frequency.

Ciprofloxacin in Layered Double Hydroxides: Looking for the Best Synthesis Method.

It is important to develop new methods of release to improve pharmacokinetic parameters of drugs, especially antibiotics, whose plasmatic concentration is determinant to ensure an effective treatment. Layered double hydroxides (LDH) are inorganic and biocompatible materials with high drug intercalation capacity and release properties that can be tuned by controlling the pH value. These materials can be an excellent choice to achieve a sustained release and an optimal drug concentration in plasm. In this work, LDH were synthesized with intercalated ciprofloxacin (CIP) by three different methods: coprecipitation, reconstruction and ion exchange. LDH-CIP complexes were characterized by XRD, TG-DSC, TEM, SEM, FTIR, electrophoretic mobilities, and drug release and dissolution kinetics in NaCl solutions and under physiological conditions. The coprecipitation and reconstruction methods lead to the formation of ill-defined products, whereas the ion exchange method rendered the best intercalation results. CIP release was controlled by dissolution at pH<3 and by desorption and ion exchange at intermediate and high pH. In comparison with a commercial formulation, the LDH-CIP complex prepared by ion exchange presented a slower release profile. The fast dissolution at gastric pH raises the need of developing some type of coating for protecting LDH materials.

Review of educational tools for skin self-examination: A qualitative analysis of laypeople's preferences.

ISSUE ADDRESSED: Skin self-examination (SSE) empowers individuals to be aware of their skin and to identify and present to a doctor with any suspicious lesions; however evidence-based, clear guidance for SSE is lacking. METHODS: A new acronym entitled SCAN (Sore, Changing, Abnormal, New) was compiled to help laypeople recognise early signs of skin cancer. This study undertook a qualitative investigation on how well laypeople understand SCAN and other commonly used educational tools (ABCDE, AC, and "ugly duckling"), whether they have a preferred SSE tool, and whether pictorial presentations enhance their understanding. RESULTS: Seven focus groups were conducted with 28 participants (age range 19-78 years), including 6 participants with a previous melanoma diagnosis. Among all the educational tools presented, SCAN was commonly described as the favoured to guide SSE. SCAN was perceived as patient-oriented due to its simplicity and use of easily understood words, while other tools, although perceived as positive in some aspects, were often identified as complex, difficult to understand and aimed towards clinician use. Pictorial presentations were desired as part of an educational tool; however, many also raised their potential disadvantages. CONCLUSION: This was the first study to determine the patient perspective of SCAN and established a diverse range of potential quality indicators for SSE educational tools. SO WHAT?: The findings of this study suggest that current widely used SSE tools may not be the most effective to promote SSE. SCAN may be preferred, as it simplifies SSE by using lay language and is applicable to all skin cancers.

Culture media based on effluent derived from soy protein concentrate production for Lacticaseibacillus paracasei 90 biomass production: statistical optimisation, mineral characterization, and metabolic activities.

The waste and by-products of the soybean industry could be an economic source of nutrients to satisfy the high nutritional demands for the cultivation of lactic acid bacteria. The aims of this work were to maximize the biomass production of Lacticaseibacillus paracasei 90 (L90) in three culture media formulated from an effluent derived from soy protein concentrate production and to assess the effects these media have on the enzymatic activity of L90, together with their influence on its fermentation profile in milk. The presence of essential minerals and fermentable carbohydrates (sucrose, raffinose, and stachyose) in the effluent was verified. L90 reached high levels of microbiological counts (∼ 9 log cfu mL-1) and dry weight (> 1 g L-1) on the three optimized media. Enzymatic activities (lactate dehydrogenase and ß-galactosidase) of L90, and its metabolism of lactose and citric acid, as well as lactic acid and pyruvic acid production in milk, were modified depending on the growth media. The ability of the L90 to produce the key flavour compounds (diacetyl and acetoin) was maintained or improved by growing in the optimized media in comparison with MRS.

Protective action of N-acetyl-L-cysteine associated with a polyvalent antivenom on the envenomation induced by Lachesis muta muta (South American bushmaster) in rats.

In this study, we examined the potential use of N-acetyl-L-cysteine (NAC) in association with a polyvalent antivenom and as stand-alone therapy to reduce the acute local and systemic effects induced by Lachesis muta muta venom in rats. Male Wistar rats (300-350 g) were exposed to L. m. muta venom (1.5 mg/kg - i.m.) and subsequently treated with anti-Bothrops/Lachesis serum (antivenom:venom ratio 1:3 'v/w' - i.p.) and NAC (150 mg/kg - i.p.) separately or in association; the animals were monitored for 120 min to assess changes in temperature, locomotor activity, local oedema formation and the prevalence of haemorrhaging. After this time, animals were anesthetized in order to collect blood samples through intracardiac puncture and then euthanized for collecting tissue samples; the hematological-biochemical and histopathological analyses were performed through conventional methods. L. m. muta venom produced pronounced local oedema, subcutaneous haemorrhage and myonecrosis, with both antivenom and NAC successfully reducing the extent of the myonecrotic lesion when individually administered; their association also prevented the occurrence of subcutaneous haemorrhage. Venom-induced creatine kinase (CK) release was significantly prevented by NAC alone or in combination with antivenom; NAC alone failed to reduce the release of hepatotoxic (alanine aminotransferase) and nephrotoxic (creatinine) serum biomarkers induced by L. m. muta venom. Venom induced significant increase of leucocytes which was also associated with an increase of neutrophils, eosinophils and monocytes; antivenom and NAC partially reduced these alterations, with NAC alone significantly preventing the increase of eosinophils whereas neither NAC or antivenom prevented the increase in monocytes. Venom did not induce changes in the erythrogram parameters. In the absence of a suitable antivenom, NAC has the potential to reduce a number of local and systemic effects caused by L. m. muta venom.

Grapevine morphological shade acclimation is mediated by light quality whereas hydraulic shade acclimation is mediated by light intensity.

Plants acclimate to shade by sensing light signals such as low photosynthetic active radiation (PAR), low blue light (BL) levels and low red-to-far red ratios (R:FR) trough plant photoreceptors cross talk. We previously demonstrated that grapevine is irresponsive to variations in R:FR and that BL-attenuation mediates morphological and architectural responses to shade increasing light interception and absorption efficiencies. However, we wondered if grapevine respond to low R:FR when BL is attenuated at the same time. Our objective was to evaluate if morphological, architectural and hydraulic acclimation to shade is mediated by low R:FR ratios and BL attenuation. To test this, we carried out experiments under natural radiation, manipulating light quality by selective sunlight exclusion and light supplementation. We grew grapevines under low PAR (LP) and four high PAR (HP) treatments: HP, HP plus FR supplementation (HP + FR), HP with BL attenuation (HP-B) and HP with BL attenuation plus FR supplementation (HP-B + FR). We found that plants grown under HP-B and HP-B + FR had similar morphological (stem and petiole length, leaf thickness and area), architectural (laminae' angles) and anatomical (stomatal density) traits than plants grown under LP. However, only LP plants presented lower stomata differentiation, lower δ13C and hence lower water use efficiency. Therefore, even under a BL and R:FR attenuated environment, morphological and architectural responses were modulated by BL but not by variation in R:FR. Meanwhile water relations were affected by PAR intensity but not by changes in light quality. Knowing grapevine responses to light quantity and quality are indispensable to adopt tools or design new cultural management practices that manipulate irradiance in the field intending to improve crop performance.

Synthesis of Layered Double Hydroxides Intercalated With Drugs for Controlled Release: Successful Intercalation of Ibuprofen and Failed Intercalation of Paracetamol.

This work examines the effect of drug structure and ionization degree on the formation and properties of biocompatible layered double hydroxides (LDH) intercalated with ibuprofen and paracetamol. Ibuprofen (pKa = 5.3) is in its anionic form, whereas paracetamol (pKa 9.4) is only partially ionized at the synthesis pH (9.0), and thus intercalation is expected to be different in the two cases. Chemical analyses, X-ray diffraction, electron microscopy, infrared spectroscopy and thermal analyses were applied to characterize the materials. Dissolution kinetics and drug release kinetics were also investigated, in an ample range of pH (3.0-9.0) in NaCl solutions, and in physiological buffers (1.2, 4.5 and 6.8). All characterization techniques showed that an efficient intercalation of ibuprofen took place, resulting in a material with 30% of its weight corresponding to the drug. On the contrary, all techniques revealed a very poor intercalation of paracetamol (1.2%). The dissolution kinetics of LDHs was highly pH-dependent, being higher as pH decreased. The drug release kinetics, conversely, increased as pH increased. In physiological buffers the release rate depended not only on the pH but also on the type of buffer. This last behavior is useful to control the release in different parts of the digestive system.

Effect of leaf-to-fruit ratios on phenolic and sensory profiles of Malbec wines from single high-wire-trellised vineyards.

BACKGROUND: The single high-wire system is a free canopy trellis system suitable for warm to hot climates. In a global warming scenario, it arouses as a technological solution since it prevents berry overheating and sunburn. Canopy management practices manipulate leaf-to-fruit ratios, affecting berry and wine composition. We aimed to evaluate the phenolic and sensory profiles of Malbec wines from single high-wire trellised vineyards in a hot region in Mendoza (Argentina) and to assess the effect of varying leaf-to-fruit ratios on these attributes. We manipulated leaf-to-fruit ratios by varying shoot trimming (experiment 1: 0.45 m, 0.80 m, and untrimmed) and winter pruning severity (experiment 2: 16, 24, 32, and >32 countable buds per meter). We characterized wine attributes by a descriptive analysis, color by the CIELAB space, and global phenolics compounds and anthocyanins by high-performance liquid chromatography with diode array detection. RESULTS: We found that wines where shoots were trimmed to 0.80 m or left untrimmed had similar and greater intensity of color, violet hue, astringency, and alcohol and a richer aroma profile than wines where shoots were trimmed to 0.45 m. Meanwhile, wines from 16 and >32 buds/m treatments (the latter simulating a box pruning) were similar to each other and had higher color intensity, violet hue, acidity, alcohol, and astringency and a more complex aroma profile than the other pruning treatments. CONCLUSIONS: The best quality wines were achieved by leaving 16 or >32 buds/m and by trimming shoots to 0.80 m or leaving them untrimmed. The modulation of cultural practices in sprawling canopies offers the potential to produce wines with different styles in hot regions. © 2020 Society of Chemical Industry.

Effect of the incorporation of ß-galactosidase in the GOS production during manufacture of soft cheese.

Galactooligosaccharides (GOS) are non-digestible oligosaccharides with recognized prebiotic role. The present study aims to evaluate a ß-galactosidase from K. lactis during soft cheese making and to analyse the impact on carbohydrates metabolism, proteolysis, and volatile compounds production, physicochemical and microbiological characteristics of the product. The enzyme was added to cheese milk (fluid milk plus whey powder) before (40 min.) or simultaneously of the starter addition (Ep and E treatments, respectively); cheese without enzyme addition was also made (C treatment). Also, we characterized fresh and soft commercial cheeses from the point of view of carbohydrate fraction, highlighting GOS, and organic acid profiles. The inclusion of the enzyme in soft cheese making produced a delay in reaching the target pH (~5.2). Carbohydrate fermentation profiles differed among treatments during cheese making and ripening. GOS were only detected in Ep and E cheeses (0.88 and 0.51 g/100 g, respectively). Lactose content was lower, and glucose and galactose levels were higher in E and Ep than C. No differences in physicochemical and microbial composition and organic acids profiles among samples were observed. Bioformation of volatile compounds belonging to the chemical families of aldehydes, ketones, alcohols, esters and acids, was not substantially affected by the modification in the carbohydrate profile. GOS were not detected in any of the commercial cheeses; great variations in the carbohydrate contents and organic acids were found. The results obtained demonstrate the feasibility of obtaining cheeses with GOS. Although the GOS values achieved are not adequate enough for the desired effect, the proposed technological approach turned out to be satisfying and original. Cheeses with prebiotic fiber are not still widespread in the market.

Evaluation of autochthonous cultures to improve the cheese flavor: A case study in hard cheese model.

The characterization of autochthonous cultures based on their contribution to cheese flavor is an additional selection criterion for their use in cheese making. The objective of the present work was to assess the ability of three strains of mesophilic lactobacilli: Lactobacillus casei 72 (Lc72), L. paracasei 90 (Lp90), and L. plantarum 91 (Lp91), one strain of thermophilic lactobacillus: L. helveticus 209 (Lh209), and the thermophilic-mesophilic combinations, to grow and produce aroma compounds in a hard cheese model. Microbiological counts, pH, and the profiles of carbohydrates, organic acids, and volatile compounds were analyzed during incubation for 14 days at 37 ℃. The population of mesophilic lactobacilli reached levels around 8.0 log CFU ml-1 at three days, but then decreased until ∼7.0 log CFU ml-1 toward 14 days. Thermophilic lactobacillus population reached and maintained levels around 7.7 log CFU ml-1 during incubation. Carbohydrates were absent in the hard cheese model, and so no change in the pH values and in the levels of lactic acid was detected. Mesophilic lactobacilli, inoculated individually or in association with Lh209, metabolized the citric acid and produced ethanoic acid. The profiles of volatile compounds of mesophilic lactobacilli (characterized mainly by butan-2-one, 3-hydroxybutan-2-one, 3-methylbutan-1-ol, hexan-1-ol, 2-phenylethanol, and ethanoic acid) were different from the profile of thermophilic lactobacillus Lh209 (characterized mainly by heptan-2-one, ethyl acetate, isoamyl hexanoate, pentan-1-ol, decanoic acid, and 2- and 3-methylbutanal). Cooperative effects in the production of compounds related to cheese flavor, such as 3-hydroxybutan-2-one, ethyl butanoate, ethanol, pentan-2-ol, hexan-1-ol, benzeneacetaldehyde, 2-phenylethanol, and heptanoic acid, were largely evidenced between Lh209 and Lp91; in a lesser extent, cooperative effects were also found for Lh209+Lp90 for the following compounds: 3-hydroxybutan-2-one, isoamyl acetate, and ethanoic acid. Of the mesophilic lactobacilli strains evaluated, Lp91 and Lp90 would be interesting candidates for its use as adjunct cultures in hard cheeses to improve and diversify the flavor.

Fire damage to cambium affects localized xylem anatomy and hydraulics: the case of Nothofagus pumilio in Patagonia.

PREMISE: Fire scars on trees are created by excessive heat from a fire that kills the vascular cambium. Although, fires are one of the most important forest disturbances in Patagonia, the effects of fire on tree physiology and wood anatomy are still unknown. In this study, we hypothesized that abnormal functioning of the cambium after a fire will induce anatomical changes in the wood. We also assumed that these anatomical changes would affect xylem safety transport. METHODS: We quantified wood anatomical traits in Nothofagus pumilio, the dominant subalpine tree species of Patagonia, using two approaches: time and distance. In the first, anatomical changes in tree rings were compared before, during, and after fire occurrence. In the second, the spatial extent of these changes was evaluated with respect to the wound by measuring anatomical traits in sampling bands in two directions (0° and 45°) with respect to the onset of healing. RESULTS: Reductions in lumen diameter and vessel number were the most conspicuous changes associated with fire damage and observed in the fire ring and subsequent post-fire rings. In addition, the fire ring had more rays than in control rings. In terms of distance, anatomical changes were only restricted to short distances from the wound. CONCLUSIONS: Post-fire changes in wood anatomical traits were confined close to the wound margins. These changes might be associated with a defense strategy related to the compartmentalization of the wound and safety of water transport.

Deregulated miRNAs in osteoporosis: effects in bone metastasis.

Starting from their role exerted on osteoblast and osteoclast differentiation and activity pathways, microRNAs (miRNAs) have been recently identified as regulators of different processes in bone homeostasis. For this purpose, in a recent review, we highlighted, as deregulated miRNAs could be involved in different bone diseases such as osteoporosis. In addition, recent studies supported the concept that osteoporosis-induced bone alterations might offer a receptive site for cancer cells to form bone metastases, However, to date, no data on specific-shared miRNAs between osteoporosis and bone metastases have been considered and described to clarify the evidence of this link. The main goal of this review is to underline as deregulated miRNAs in osteoporosis may have specific roles in the development of bone metastases. The review showed that several circulating osteoporotic miRNAs could facilitate tumor progression and bone-metastasis formation in several tumor types, i.e., breast cancer, prostate cancer, non-small-cell lung cancer, esophageal squamous cell carcinoma, and multiple myeloma. In detail, serum up-regulation of pro-osteoporotic miRNAs, as well as serum down-regulation of anti-osteoporotic miRNAs are common features of all these tumors and are able to promote bone metastasis. These results are of key importance and could help researcher and clinicians to establish new therapeutic strategies connected with deregulation of circulating miRNAs and able to interfere with pathogenic processes of osteoporosis, tumor progressions, and bone-metastasis formation.

Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis.

MicroRNA (miRNA) has shown to enhance or inhibit cell proliferation, differentiation and activity of different cell types in bone tissue. The discovery of miRNA actions and their targets has helped to identify them as novel regulations actors in bone. Various studies have shown that miRNA deregulation mediates the progression of bone-related pathologies, such as osteoporosis. The present review intends to give an exhaustive overview of miRNAs with experimentally validated targets involved in bone homeostasis and highlight their possible role in osteoporosis development. Moreover, the review analyzes miRNAs identified in clinical trials and involved in osteoporosis.

Engineered exosomes: A new promise for the management of musculoskeletal diseases.

BACKGROUND: Exosomes are nanovesicles actively secreted by potentially all cell types, including tumour cells, with the primary role of extracellular systemic communication mediators, both at autocrine and paracrine levels, at short and long distances. Recently, different studies have used exosomes as a delivery system for a plethora of different molecules, such as drugs, microRNAs and proteins. This has been made possible thanks to the simplicity in exosomes engineering, their great stability and versatility for applications in oncology as well as in regenerative medicine. SCOPE OF REVIEW: The aim of this review is to provide information on the state-of-the-art and possible applications of engineered exosomes, both for cargo and specific cell-targeting, in different pathologies related to the musculoskeletal system. MAJOR CONCLUSIONS: The use of exosomes as therapeutic agents is rapidly evolving, different studies explore drug delivery with exosomes using different molecules, showing an enormous potential in various research fields such as oncology and regenerative medicine. GENERAL SIGNIFICANCE: However, despite the significant progress made by the different studies carried out, currently, the use of exosomes is not a therapeutic reality for the considerable difficulties to overcome.

Gene therapy for chondral and osteochondral regeneration: is the future now?

Gene therapy might represent a promising strategy for chondral and osteochondral defects repair by balancing the management of temporary joint mechanical incompetence with altered metabolic and inflammatory homeostasis. This review analysed preclinical and clinical studies on gene therapy for the repair of articular cartilage defects performed over the last 10 years, focussing on expression vectors (non-viral and viral), type of genes delivered and gene therapy procedures (direct or indirect). Plasmids (non-viral expression vectors) and adenovirus (viral vectors) were the most employed vectors in preclinical studies. Genes delivered encoded mainly for growth factors, followed by transcription factors, anti-inflammatory cytokines and, less frequently, by cell signalling proteins, matrix proteins and receptors. Direct injection of the expression vector was used less than indirect injection of cells, with or without scaffolds, transduced with genes of interest and then implanted into the lesion site. Clinical trials (phases I, II or III) on safety, biological activity, efficacy, toxicity or bio-distribution employed adenovirus viral vectors to deliver growth factors or anti-inflammatory cytokines, for the treatment of osteoarthritis or degenerative arthritis, and tumour necrosis factor receptor or interferon for the treatment of inflammatory arthritis.