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BACKGROUND: Platelet-rich plasma (PRP) has been used in different non-transfusion indications due to its role in tissue regeneration and healing. The aim of this overview of systematic reviews (umbrella review) is to provide a summary of the existing research syntheses related to PRP use for sports-related muscle, tendon and ligament injuries. MATERIALS AND METHODS: Literature searches were performed in MEDLINE, Embase, and Cochrane Library to identify systematic reviews focusing on PRP use for sports-related muscle, tendon and ligament injuries. The methodological quality of included studies was assessed using the checklist for systematic reviews and research syntheses developed by the Joanna Briggs Institute and the GRADE assessment. RESULTS: Twenty-two studies met the inclusion criteria. Five studies evaluated PRP use for acute muscle injury, and 17 evaluated PRP use for tendon and ligament injury. Studies were heterogeneous in terms of the dose and number of PRP injections, and the control groups. Three of the 5 reviews evaluating acute muscle injury concluded that PRP had no effect on the outcomes considered. One review shows superior efficacy of rehabilitation exercise compared to PRP. One review shows that PRP may result in an earlier return to sport for acute grade I-II injury. Eight out of the 17 reviews evaluating PRP for tendon and ligament injuries show a statistically significant (p

BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate the benefit of platelet rich plasma (PRP) in oral surgery. MATERIALS AND METHODS: We performed a systematic search of the literature. The GRADE system was used to assess the certainty of the body of evidence. RESULTS: We found 21 randomised controlled trials that met our inclusion criteria: 12 studies included patients with periodontal defects, five studies focused on healing of extraction sockets, three studies on sinus lift augmentation, and one study on periapical osseous defects. However, for the quantitative synthesis (meta-analysis), we evaluated “periodontal defects” studies only, since for other clinical contexts the number of studies were too low and the procedural heterogeneity was too high to allow pooling of data. PRP-containing regimens were compared to non-PRP-containing regimens. Primary outcomes for the evaluation of periodontal defects were probing depths, clinical attachment level, gingival recession, and radiographic bone defect. It is not usually clear whether or not the use of PRP compared to controls affects “probing depth” at long-term follow up; the between group differences were small and unlikely to be of clinical importance (i.e., very low quality of evidence). For the other outcomes analysed (“clinical attachment levels”, “gingival recession”, “bony defect”), we observed a very slight marginal clinical benefit of PRP compared to controls. The available evidence for these comparisons was rated as low quality as most of the studies selected showed inconsistency, imprecision, and risk of bias. DISCUSSION: Evidence from a comparison between the use in oral surgery of PRP-containing regimens compared to other regimens not-containing PRP was of low quality. The results of the meta-analysis, limited to studies in patients with periodontal defects, document that PRP was slightly more effective compared to controls not-containing PRP.

The aim of this investigation was to study the welfare of 3 captive groups of cotton-top tamarins housed in different zoological parks. Ethological observations were conducted during 1 year. In addition, fecal samples were collected and the concentrations of glucocorticoids, androgens, and progestogens were measured. Within each group, no significant differences in fecal cortisol concentrations were found between subjects. The fecal concentrations of testosterone and progesterone significantly differed depending on the sexes and ages of the tamarins. A significant association was found among hormone concentrations, exhibit dimensions, and group composition. A highly significant correlation was found between all hormones considered and the space available for each subject. Significant differences in behavioral patterns were observed among groups, including social–individual, affiliative–aggressive, and anogenital–suprapubic scent marking. Correlations between hormone measurements and behaviors were detected. In conclusion, this study confirmed the associations between some behaviors exhibited by these nonhuman primates and both cortisol and testosterone; these data also highlight the role played by progesterone in these behaviors.

This study is based on an adult male fossa (Cryptoprocta ferox) that arrived at Garda Zoological Park (Italy) exhibiting stereotyped and self-injuring behaviours and follows its subsequent rehabilitation through a long-term environmental enrichment programme. Data were collected over a period of six months. Continuous focal animal sampling was used to collect behavioural data during 90-minute sessions; 24 sessions took place over the first two months and two sessions took place six months after his arrival. Data were analysed using non-parametric tests. At the beginning of the study period, the predatory behaviour of the fossa was not species-specific since he was not able to find food items when they were hidden in the enclosure. It usually interacted with items for just a few minutes. Rub-bing different scents on enclosure furniture promoted play only for a few minutes. After two months of behavioural observations, its behaviour only improved slightly and stereotyped and self-injuring behaviours were maintained. However, we continued the intense enrichment programme for a longer period. Six months after its arrival rare undesirable behaviours or noticeable side effects were ob-served whilst species-specific behaviours were recorded. Results showed that the environmental enrichment curtailed the aberrant behaviours. In conclusion, this case study provides evidence sup-porting the hypothesis that a suitable enrichment programme could have a therapeutic effect on pathological behaviour in captive animals.

A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE). Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL) IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE) followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX) (375 mg/m2 weekly for 4 weeks). Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

Non melanoma skin cancer (NMSC), including basal cell (BCC, 80% of NMSC) and squamous cell carcinoma (SCC, 20%) is the most frequent cancer in Caucasians. Its incidence has dramatically increased in the last years due to sun exposure and immunosuppression: i.e. transplant recipient have a 100-fold and a 10-fold risk increase of developing SCC and BCC, respectively. Sensitive diagnostic techniques have detected a few Human Papillomavirus (HPV) species in lesions of patients affected by these tumours, particularly belonging to the Beta-papillomavirus Genus. This Genus includes viruses with a cutaneous tropism, while high risk HPVs , responsible of almost all cervical cancers in woman, have a mucosal tropism. A few Beta HPVs, such as HPV8 and HPV5, are found associated with skin cancer lesions and are thus considered etiologically related to these pathologies. For preventing mucosal HPV infection, prophylactic vaccines based on the viral L1 major capsid protein, assembled into empty virion like particles are already available. Preventive vaccines targeting non structural viral proteins, such as the oncogenic proteins E6 or E7 are also under study. Instead, for cutaneous HPVs, no vaccine strategies have yet been described. Plants have been proposed as alternative platforms for producing foreign antigens for vaccine production and immunisation purposes. Antigens expressed in plants can be administered in different ways, including direct oral ingestion of plant tissue (edible vaccine). We have recently undertaken a project aimed at obtaining vaccines against cutaneous HPVs, based on the expression in plants of the major L1 capsid and of the E7 protein of HPV 8. To evaluate protein expression in plants tissue, polyclonal antibodies were raised in rabbits against purified GST-L1 and GST-E7 fusion proteins, produced in E. coli. For the expression in plants, 35S-based cassettes for (1) the full length L1 protein, (2) an L1 protein deprived of a putative nuclear localisation signal, (3) the E7 protein and (4) an L1-E7 fusion construct were thus generated and used for both transient and stable expression experiments. For transient expression, infiltration of N. benthamiana leaves with A. tumefaciens carrying the different constructs (agroinfiltration) was carried out. Transgene expression was followed both at the RNA and protein level. Simultaneous infiltration of agrobacteria carrying genes for silencing suppressors, such as p19 from Cymbidium ringspot virus, and/or HC-Pro from Potato virus Y enhanced transgene expression of all constructs. Data concerning the molecular characterisation of N. benthamiana lines transgenic for the L1 and E7 antigens and their derivatives will be presented.

The overall use of allogeneic blood transfusions in clinical practice remains relatively high and still varies widely among centres and practitioners. Moreover, allogeneic blood transfusions have historically been linked with risks and complications: some of them (e.g. transfusion reactions and transmission of pathogens) have been largely mitigated through advancements in blood banking whereas some others (e.g. immunomodulation and transfusion-related acute lung injury) appear to have more subtle etiologies and are more difficult to tackle. Furthermore, blood transfusions are costly and the supply of blood is limited. Finally, evidence indicates that a great number of the critically ill patients who are being transfused today may not be having tangible benefits from the transfusion. Patient blood management is an evidence-based, multidisciplinary, multimodal, and patient-tailored approach aimed at reducing or eliminating the need for allogeneic transfusion by managing anaemia, perioperative blood conservation, surgical haemostasis, and blood as well as plasma-derivative drug use. From this point of view, the reduction of allogeneic blood usage is not an end in itself but a tool to achieve better patient clinical outcome. This article focuses on the three-pillar matrix of patient blood management where the understanding of basic physiology and pathophysiology is at the core of evidence-based approaches to optimizing erythropoiesis, minimising bleeding and tolerating anemia. Anesthesiologists and critical care physicians clearly have a key role in patient blood management programmes are and should incorporate its principles into clinical practice-based initiatives that improve patient safety and clinical outcomes.

Blood transfusions have become indispensable to treat the anemia associated with a variety of medical conditions ranging from genetic disorders and cancer to extensive surgical procedures. In developed countries, the blood supply is generally adequate. However, the projected decline in blood donor availability due to population ageing and the difficulty in finding rare blood types for alloimmunized patients indicate a need for alternative red blood cell (RBC) transfusion products. Increasing knowledge of processes that govern erythropoiesis has been translated into efficient procedures to produce RBC ex vivo using primary hematopoietic stem cells, embryonic stem cells, or induced pluripotent stem cells. Although in vitro-generated RBCs have recently entered clinical evaluation, several issues related to ex vivo RBC production are still under intense scrutiny: among those are the identification of stem cell sources more suitable for ex vivo RBC generation, the translation of RBC culture methods into clinical grade production processes, and the development of protocols to achieve maximal RBC quality, quantity, and maturation. Data on size, hemoglobin, and blood group antigen expression and phosphoproteomic profiling obtained on erythroid cells expanded ex vivo from a limited number of donors are presented as examples of the type of measurements that should be performed as part of the quality control to assess the suitability of these cells for transfusion. New technologies for ex vivo erythroid cell generation will hopefully provide alternative transfusion products to meet present and future clinical requirements.

Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications.The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined.In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data.The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.

Erythropoiesis is a tightly regulated process which becomes decoupled from its normal differentiation program in patients with polycythemia vera (PV). Somatic mutations in JAK2 are commonly associated with this myeloid proliferative disorder. To gain insight into the molecular events that are required for abnormally developing erythroid cells to escape dependence on normal growth signals, we performed in vitro expansion of mature erythroblasts (ERY) from seven normal healthy donors and from seven polycythemic patients in the presence of IL3, EPO, SCF for 10, 11, or 13 days. Normal ERYs required exposure to the glucocorticoid dexamethasone (Dex) for expansion, while PV-derived ERYs expanded in the absence of dexamethasone. RNA expression profiling revealed enrichment of two known oncogenes, GPR56 and RAB4a, in PV-derived ERYs along with reduced expression levels of transcription factor TAL1 (ANOVA FDR < 0.05). While both normal and polycythemic-derived ERYs integrated signaling cascades for growth, they did so via different signaling pathways which are represented by their differential phospho-profiles. Our results show that normal ERYs displayed greater levels of phosphorylation of EGFR, PDGFRβ, TGFβ, and cKit, while PV-derived ERYs were characterized by increased phosphorylation of cytoplasmic kinases in the JAK/STAT, PI3K, and GATA1 pathways. Together these data suggest that PV erythroblast expansion and maturation may be maintained and enriched in the absence of dexamethasone through reduced TAL1 expression and by accessing additional signaling cascades. Members of this acquired repertoire may provide important insight into the pathogenesis of aberrant erythropoiesis in myeloproliferative neoplasms such as polycythemia vera.

Captive breeding is vital for primate conservation, with modern zoos serving a crucial role in breeding populations of threatened species and educating the general public. However, captive populations can experience welfare issues that may also undermine their reproductive success. To enhance the wellbeing of endangered zoo primates, we conducted a study to assess the effects of a new scent enrichment program on captive red-ruffed lemurs (Varecia rubra), black howler monkeys (Alouatta caraya), siamangs (Symphalangus syndactylus), lar gibbons (Hylobates lar) and orangutans (Pongo pygmaeus pygmaeus). We combined behavioral observations and fecal endocrinology analyses to evaluate the effects of a series of essential oils (benzoin, lavender, lemongrass) on five captive troops (N = 19) housed at Dudley Zoo & Castle and Twycross Zoo (UK). We recorded observations of natural species-specific and abnormal stress-related behaviors for 480 h using instantaneous scan sampling. We collected 189 fecal samples and measured the fecal cortisol concentrations using radioimmunoassay. We found a significant effect of the scent enrichment on behaviors, with red-ruffed lemurs and black howler monkeys reducing their social interactions, as well as red-ruffed lemurs and lar gibbons decreasing their stress-related behaviors after they were exposed to the series of essential oils. We also found that red-ruffed lemurs displayed a significant increase in fecal glucocorticoids following exposure to essential oils. Our contradictory findings suggest that the effects of this series of essential oils may change depending on the species-specific social lives and olfactory repertoires of primates. In conclusion, we cannot recommend using these essential oils widely with zoo primates without additional evaluation.