Skeletal Muscle Evaluation in Patients With Acromegaly.

Context: Patients with acromegaly are characterized by chronic exposure to high growth hormone (GH) and insulin-like growth factor-1 levels, known for their anabolic effect on skeletal muscle. Therefore, an increased skeletal muscle mass could be hypothesized in these individuals. Herein, we have performed a systematic revision of published evidence regarding skeletal muscle mass, quality, and performance in patients with acromegaly. Evidence Acquisition: A systematic review of the literature in the PubMed database up to September 1, 2023, was conducted with the following query: acromegaly AND ("muscle mass" OR "skeletal muscle"). We excluded studies that did not compare different disease states or used nonradiological methods for the skeletal muscle analyses, except for bioelectrical impedance analysis. Evidence Synthesis: Fifteen studies met the inclusion criteria. A total of 360 patients were evaluated for skeletal muscle mass, 122 for muscle fatty atrophy, and 192 for muscle performance. No clear evidence of increased skeletal muscle mass in patients with active disease compared to control or healthy individuals emerged. As for skeletal muscle quality, we observed a trend toward higher fatty infiltration among patients with acromegaly compared to healthy participants. Likewise, patients with active disease showed consistently worse physical performance compared to control or healthy individuals. Conclusion: Skeletal muscle in acromegaly has lower quality and performance compared to that of healthy individuals. The small number of published studies and multiple confounding factors (eg, use of different radiological techniques) contributed to mixed results, especially regarding skeletal muscle mass. Well-designed prospective studies are needed to investigate skeletal muscle mass in patients with acromegaly.

A retrospective Italian Society of Veterinary Oncology (SIONCOV) study of 56 cats with appendicular osteosarcoma.

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.

CT features of cutaneous and subcutaneous canine mast cell tumors and utility of conventional and indirect lymphography to detect clinically unknown mast cell tumors and to map the sentinel lymph nodes.

Computed tomography is frequently used to stage canine mast cell tumors (MCTs). The aims of this prospective, observational study were to describe the CT features of MCTs, to evaluate the performance of CT in detecting additional or incidental MCTs, to distinguish between cutaneous (cMCT) or subcutaneous (scMCT) MCTs, and to identify one or multiple sentinel lymph nodes (SLNs) by indirect CT lymphography (ICTL). Seventy-two dogs affected by 111 MCTs were included. The recorded parameters were: shape, size, attenuation (Hounsfield units [HU]), location (cutaneous or subcutaneous), and presence of fat stranding. The SLNs were compared with the regional lymph nodes and supplementary MCTs were registered. Mast cell tumors mostly appeared with well-defined margins (89%), round/oval shape (71%), homogeneous enhancement (90%) with a mean postcontrast density of 62.0 ± 23.4 HU and associated with fat stranding (43%). Cutaneous mast cell tumors were more frequently round (P = .003), whereas scMCTs were oval (P = .011) with a larger mean maximal diameter (2.91 ± 1.57 cm vs 1.46 ± 1.28 cm, P = .002) and more feeding vessels (77% vs 39% P = .044). Compared with histopathology, CT accuracy in differentiating cMCTs and sMCTs was 57%, with an interobserver agreement of 88% (three reviewers). Indirect CT lymphography showed the SLN in 82 of 85 (97%) cases, 32% of them not corresponding to the regional node. CT showed additional or incidental MCTs in 23 of 72 (32%) dogs. In conclusion, the common CT appearance of canine cMCTs and scMCTs is reported with some statistical differences between the two categories. CT is useful in identifying clinically undetected MCTs and SLNs, although it shows low accuracy in distinguishing between cMCT and scMCT.

Weaning, food allergens and potential risk factors for delayed introduction: a cross-sectional study.

Much evidence supports that the early introduction of allergenic foods in weaning is useful to prevent food allergies later in life. Real life is often different, with factors related to mothers and infants. Our study aimed to deepen the timing of introducing the foods responsible for most allergic reactions during the weaning and why parents delay their introduction. 110 mothers participated in the study, compiling a questionnaire. Exclusive breastfeeding was associated with a delayed introduction of allergenic foods at 4 months (r = 0.433, p < 0.01) and 1 year (r = 0.486, p < 0.01). Large-for-gestational age at birth was inversely associated with a delayed introduction of allergenic foods (r=-0.204, p < 0.05). This study demonstrates that introducing many allergens is delayed during the weaning. Parents with infants fed with exclusive breastfeeding could need more information about the correct time of introduction of potential allergens in the weaning.

Late Prevalence of Typical and Atypical Symptoms of Frey's Syndrome after Parotidectomy for Benign Tumor.

BACKGROUND: The treatment of choice for tumors located in the parotid gland is surgery. Nevertheless, postoperative complications are not infrequent. Regardless of the type of surgical procedure, the most common complication is Frey's syndrome (FS). Traditionally, FS includes unilateral gustatory sweating and flushing of the facial skin lining the parotid compartment. Recent research describes atypical discomfort associated with FS. The aim of this study was to assess the late prevalence and severity of both usual and atypical symptoms after parotidectomy for benign tumors. METHODS: We conducted a cross-sectional study involving 86 subjects who underwent superficial parotidectomy at least one year before the study. The questionnaire included the sweating-flushing-itch-paresthesia-pain (SFIPP) Frey scale supplemented by specific questions about symptoms. RESULTS: Sixty-seven out of eighty-six (77.9%) cases reported almost one symptom. The most frequent symptom was itch (36/67-53.7%), followed by pain (35/67-52.2%), while 28/67 (41.8%) subjects complained of atypical symptoms without flushing or sweating. A desire to treat the discomfort was reported by 50/67 (74.6%) subjects. CONCLUSIONS: Late postparotidectomy local discomfort is not infrequent and includes both usual and "unusual" symptoms almost equally. Our results suggest the importance of informing patients about the occurrence of the syndrome and the available treatment options during pre- and postoperative counseling.

Human Dental Pulp Mesenchymal Stem Cell-Derived Soluble Factors Combined with a Nanostructured Scaffold Support the Generation of a Vascular Network In Vivo.

Among all strategies directed at developing new tools to support re-vascularization of damaged tissues, the use of pro-angiogenic soluble factors, derived from mesenchymal stem cells (MSCs), appears a promising approach for regenerative medicine. Here, we compared the feasibility of two devices, generated by coupling soluble factors of human dental pulp mesenchymal stem cells (DPSCs), with a nanostructured scaffold, to support angiogenesis once transplanted in mice. DPSCs were obtained from impacted wisdom tooth removal, usually considered surgical waste material. After 28 days, we verified the presence of active blood vessels inside the scaffold through optical and scansion electron microscopy. The mRNA expression of surface antigens related to macrophage polarization (CD68, CD80, CD86, CD163, CD206), as well as pro-angiogenic markers (CD31, CD34, CD105, Angpt1, Angpt2, CDH5) was evaluated by real-time PCR. Our results demonstrate the capability of DPSC-scaffold and DPSC soluble factors-scaffold to support angiogenesis, similarly to adipose stem cells, whereas the absence of blood vessels was found in the scaffold grafted alone. Our results provide evidence that DPSC-conditioned medium can be proposed as a cell-free preparation able to support angiogenesis, thus, providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

Can Traditional Food Product Communication Convey Safety to the Younger Generations? The Role of Sustainable Packaging.

Traditional food products (TFPs) represent a defining part of one's culture, identity, and heritage with crucial economic, cultural, and environmental benefits in society. Younger generations have a positive idea of TFPs, even if this does not lead to actual purchase, possibly due to the fact that they are often perceived to not meet safety criteria. This study focuses on product communication (CP) and packaging referring to the territory (PT) and to sustainability (SP) in order to verify if these have a direct or mediated impact on perceived product safety (PPS). A structural equation model was conducted on a sample of 1079 young Italian cheese consumers. The results allowed us to confirm the hypothesized impact of CP on PPS through the mediation of PT and, particularly, SP. SP has a crucial communicative role in the model, demonstrating the ability to enhance the perception of the safety of TFPs. This research adds to the knowledge in the field of TFPs, focusing on communication and sustainable packaging as crucial factors conveying healthiness, nutritiousness, and perceived safety, consequently leading to a greater diffusion of the products themselves in the market.

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis.

Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was used to characterize the scaffold- and sponge-infiltrating cells. Real-time PCR was used to evaluate the expression of pro-angiogenic factors by stimulating Human Umbilical-Vein Endothelial Cells with ASC-conditioned media, obtained in hypoxic and normoxic conditions. We found that, in vivo, ACS-conditioned media can support angiogenesis similar to ASCs and ASC protein extract. Also, we observed that hypoxia increases the pro-angiogenic activities of ASC-conditioned media, compared to normoxia, by generating a secretome enriched in pro-angiogenic soluble factors, with bFGF, Adiponectine, ENA78, GRO, GRO-a, and ICAM1-3, as most regulated factors. Finally, ASC-conditioned media, produced in hypoxic condition, induce the expression of pro-angiogenic molecules in HUVECs. Our results provide evidence that ASC-conditioned-medium can be proposed as a cell-free preparation able to support angiogenesis, thus providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

Zwitterionic or Not? Fast and Reliable Structure Determination by Combining Crystal Structure Prediction and Solid-State NMR.

When it comes to crystal structure determination, computational approaches such as Crystal Structure Prediction (CSP) have gained more and more attention since they offer some insight on how atoms and molecules are packed in the solid state, starting from only very basic information without diffraction data. Furthermore, it is well known that the coupling of CSP with solid-state NMR (SSNMR) greatly enhances the performance and the accuracy of the predictive method, leading to the so-called CSP-NMR crystallography (CSP-NMRX). In this paper, we present the successful application of CSP-NMRX to determine the crystal structure of three structural isomers of pyridine dicarboxylic acid, namely quinolinic, dipicolinic and dinicotinic acids, which can be in a zwitterionic form, or not, in the solid state. In a first step, mono- and bidimensional SSNMR spectra, i.e., 1H Magic-Angle Spinning (MAS), 13C and 15N Cross Polarisation Magic-Angle Spinning (CPMAS), 1H Double Quantum (DQ) MAS, 1H-13C HETeronuclear CORrelation (HETCOR), were used to determine the correct molecular structure (i.e., zwitterionic or not) and the local molecular arrangement; at the end, the RMSEs between experimental and computed 1H and 13C chemical shifts allowed the selection of the correct predicted structure for each system. Interestingly, while quinolinic and dipicolinic acids are zwitterionic and non-zwitterionic, respectively, in the solid state, dinicotinic acid exhibits in its crystal structure a "zwitterionic-non-zwitterionic continuum state" in which the proton is shared between the carboxylic moiety and the pyridinic nitrogen. Very refined SSNMR experiments were carried out, i.e., 14N-1H Phase-Modulated (PM) pulse and Rotational-Echo Saturation-Pulse Double-Resonance (RESPDOR), to provide an accurate N-H distance value confirming the hybrid nature of the molecule. The CSP-NMRX method showed a remarkable match between the selected structures and the experimental ones. The correct molecular input provided by SSNMR reduced the number of CSP calculations to be performed, leading to different predicted structures, while RMSEs provided an independent parameter with respect to the computed energy for the selection of the best candidate.

Using Wearable Inertial Sensors to Monitor Effectiveness of Different Types of Customized Orthoses during CrossFit® Training.

BACKGROUND: Dynamic balance plays a key role in high-impact sports, such as CrossFit, where athletes are required to maintain balance in various weightlifting exercises. The loss of balance in these sport-specific movements may not only affect athlete performance, but also increase the risk of injuries. OBJECTIVES: The aim of the study is to achieve greater insight into the balance and athlete position during the CrossFit training by means of inertial sensors, with a particular focus on the role of different custom foot orthoses (CFOs) in order to detect correlations with the role of the cavus foot. METHODS: A total of 42 CrossFit® athletes, aged 25 to 42 years, were enrolled in this study. One-way ANOVA tests with post-hoc analysis of variance were used to compare foot posture groups and effects of different types of customized foot orthoses. RESULTS: When comparing the effects of CFOs with the respective balance basal level during the pistol squat exercise, we observed a significant (p = 0.0001) decrease in the sway area, antero-posterior displacement (APD) and medio-lateral displacement (MLD) compared to the basal using both types of CFOs. CONCLUSION: No significant positive effects of CFOs were observed in some static tests. On the contrary, positive effects of CFOs and, in particular, postural insoles, are relevant to dynamic balance.

CT features of divisional bile ducts in healthy Labrador Retrievers.

Computed tomography (CT) is increasingly being used for the study of gallbladder and bile duct diseases. The first step in interpreting CT findings is understanding the cross-sectional anatomy of the structures involved, but there are no published studies describing the CT features of the divisional bile ducts. In dogs, anatomic studies report two common patterns including three or four divisional bile ducts. The aim of this retrospective, descriptive, anatomical study was to describe the size and pattern of the visible divisional bile ducts, based on their location and extension, using contrast-enhanced CT in a group of Labrador Retrievers without evidence of hepatobiliary diseases. The correlation between the biliary duct number and dimensions, and the visceral fat area percentage (VFA%) was also evaluated. The right lateral divisional duct (RLD) was visualized in four of 40 dogs, the left lateral divisional duct (LLD) in nine of 40 dogs, and in 17 of 40 dogs, both were simultaneously visualized. In 10 of 40 dogs, the RLD and LLD were not highlighted. When visible, the RLD has a median diameter of 0.23 cm and a median length of 0.82 cm. The LLD has a median diameter of 0.23 cm and a median length of 2.72 cm. The median diameter of the common bile duct before and after the insertion of divisional bile ducts was 0.23 and 0.25 cm, respectively. No correlation with the VFA% was found. At least one of the divisional bile ducts could be visualized using contrast-enhanced CT in the majority of sampled dogs (75%) .

Comparison of sonographic and CT findings for the identification of renal nodules in dogs and cats.

Ultrasonography (US) and computed tomography (CT) are used to diagnose neoplastic and non-neoplastic focal renal lesions in dogs and cats; however, comparative studies between these two diagnostic tools are lacking. The aim of this retrospective, methods comparison study was to evaluate and compare the performance of US compared to CT in identifying at least one renal nodule in animals with confirmed focal renal lesions. Imaging studies of animals with uni- or bilateral renal nodules smaller than 3 cm that underwent both US and CT and that had a pathologically confirmed diagnosis were reviewed. Animals with renal cysts and infarcts were excluded. Recorded features for both modalities included the following: shape, size, number, localization, margins, renal profile. For CT only, recorded features also included attenuation (HU) and pattern of enhancement.  For US only, recorded features also included echogenicity, echostructure, and rate of visibility. Final diagnosis was obtained by cytology or histopathology. Using CT, lesions were identified in all 39 (100%) kidneys of 18 dogs and seven cats. Most lesions were multiple, cortical, well-defined, iso-attenuating (precontrast), hypo-attenuating, and moderately enhancing (postcontrast). Using US, lesions were identified in 29 of 39 (74%) kidneys. Overall, nine (31%) lesions were poorly visible; 10 (26%) kidneys appeared normal; in 17 (59%) organs, lesions' number was underestimated. Isoechoic, non-protruding lesions were difficult to identify by US. Ultrasonography underestimated renal lesions compared to CT in 59% of the kidneys (P = 0.001). Final diagnoses included metastatic disease (n = 16), infiltration by feline lymphoma (n = 4), primary neoplasia (n = 3), and non-neoplastic benign lesions (n = 2).

Comparison of the Conventional and Mechanochemical Syntheses of Cyclodextrin Derivatives.

Many scientists are working hard to find green alternatives to classical synthetic methods. Today, state-of-the-art ultrasonic and grinding techniques already drive the production of organic compounds on an industrial scale. The physicochemical and chemical behavior of cyclodextrins often differs from the typical properties of classic organic compounds and carbohydrates. The usually poor solubility and complexing properties of cyclodextrins can require special techniques. By eliminating or reducing the amount of solvent needed, green alternatives can reform classical synthetic methods, making them attractive for environmentally friendly production and the circular economy. The lack of energy-intensive synthetic and purification steps could transform currently inefficient processes into feasible methods. Mechanochemical reaction mechanisms are generally different from normal solution-chemistry mechanisms. The absence of a solvent and the presence of very high local temperatures for microseconds facilitate the synthesis of cyclodextrin derivatives that are impossible or difficult to produce under classical solution-chemistry conditions. Although mechanochemistry does not provide a general solution to all problems, several good examples show that this new technology can open up efficient synthetic pathways.

Muscle mass loss in breast cancer patients of reproductive age (≤ 45 years) undergoing neoadjuvant chemotherapy.

PURPOSE: Loss of muscle mass is associated with negative clinical outcome in breast cancer (BC) patients. Therefore, the aim of the study is to evaluate if there is pectoralis muscle area (PMA) depletion, reflecting loss of muscle mass, in breast cancer patients of reproductive age (≤ 45 years) undergoing neoadjuvant chemotherapy (NAC) and to correlate PMA with clinical and histopathological data. MATERIAL AND METHODS: This monocentric study, approved by our institutional review board, enrolled a total of 52 consecutive patients (mean age 37 ± 4.96 years) with histologically proven primary breast cancer between January 2019 and September 2021, treated with NAC and in whom tumor response and PMA were assessed with breast MRI. Two radiologists calculated PMA before and after NAC independently and blindly on axial 3D FLASH pre-contrast T1-weighted images. Wilcoxon-Mann-Whitney U test compared median values and percentage changes of pectoralis muscle area at the beginning and at the end of NAC (158 ± 25.5 days). Multivariate regression analysis on ΔPMA (difference between PMA pre-NAC and PMA post-NAC) was done according to clinical and histopathological data. Inter-reader and intra-reader agreement was estimated with K statistics. RESULTS: Pre-NAC PMA mean value was larger than post-NAC PMA mean value (9.6 ± 2.6 cm2 vs. 8.7 ± 2.2 cm2, p < 0.001, delta value 1.41). According to the RECIST criteria, no significant differences between complete and partial response were found. Multivariate regression analysis did not show any significant relationships between ΔPMA and age, time between MRI examinations, estrogen and progesterone receptor status, human epidermal growth factor receptor 2 status, Ki-67 expression, lymph node involvement, RECIST criteria, histological type, and different regimes of NAC. Inter-reader (k = 0.74) and intra-reader agreement (0.67 and 0.73) in PMA assessment was good. CONCLUSIONS: PMA variation in BC young patients, directly estimated on breast MRI, could be a potential tool to monitor body composition during NAC with potential implications in improving outcome.

Trends of Phase I Clinical Trials in the Latest Ten Years across Five European Countries.

BACKGROUND: Phase 1 clinical trials represent a critical phase of drug development because new candidate therapeutic agents are tested for the first time on humans. Therefore, international guidelines and local laws have been released to mitigate and control possible risks for human health in agreement with the declaration of Helsinki and the international Good Clinical Practice principles. Despite numerous scientific works characterizing the registered clinical trials on ClinicalTrials.gov, the main features and trends of registered phase 1 clinical trials in Europe have not been investigated. This study is aimed at assessing the features and the temporal trend of distribution of phase 1 clinical studies, carried out in the five largest European countries over a ten-year period (2012-2021), and to evaluate the impact of the Italian regulatory framework on the activation of such studies. METHODS: The main data and characteristics of phase 1 clinical studies registered on the ClinicalTrials.gov database for France, Germany, Italy, Spain and the United Kingdom have been investigated and subsequently compared. The above-mentioned countries were selected based on similarities in terms of demographic and Gross Domestic Product (GDP) data available on official government websites. (3) Results: A total number of 6878 phase 1 clinical trials were registered for the five selected countries in the ClinicalTrials.gov database during the ten years analyzed; the studies were predominantly randomized (39.33%) and for-profit (76.64%). The most represented area of investigations was oncology (52.15%), followed by hematology (24.99%) and immunology (12.04%). The variability observed between the analyzed countries showed that the UK, Germany and France presented the highest reduction in the number of phase 1 clinical trials, while for Spain and Italy, a stable/increased trend was observed, although with a lower number of trials registered on the ClinicalTrials.gov database. (4) Conclusions: Italy displayed the lowest number of registered phase 1 clinical trials, even though it showed a stable trend over the years. In this regard, the Italian regulatory framework must urgently be adapted to that of other European countries (Spain has been the first country to implement the new Regulation (EU) No 536/2014) and streamline the process of clinical trial application to increase the attractiveness of the country. Moreover, nonprofit phase 1 clinical trials (which represent 19.81% of the total number of phase 1 clinical trials registered in Italy vs. 80.19% of profit phase 1 clinical studies) should be promoted and supported by the institutions, even from a financial point of view, to allow independent researchers to develop new therapeutic drugs.

Myeloma Spine and Bone Damage Score (MSBDS) on Whole-Body Computed Tomography (WBCT): Multiple Reader Agreement in a Multicenter Reliability Study.

Objective: To assess the reliability of the myeloma spine and bone damage score (MSBDS) across multiple readers with different levels of expertise and from different institutions. Methods: A reliability exercise, including 104 data sets of static images and complete CT examinations of patients affected by multiple myeloma (MM), was performed. A complementary imaging atlas provided detailed examples of the MSBDS scores, including low-risk and high-risk lesions. A total of 15 readers testing the MSBDS were evaluated. ICC estimates and their 95% confidence intervals were calculated based on mean rating (k = 15), absolute agreement, a two-way random-effects model and Cronbach's alpha. Results: Overall, the ICC correlation coefficient was 0.87 (95% confidence interval: 0.79-0.92), and the Cronbach's alpha was 0.93 (95% confidence interval: 0.94-0.97). Global inter- and intra-observer agreement among the 15 readers with scores below or equal to 6 points and scores above 6 points were 0.81 (95% C.I.: 0.72-0.86) and 0.94 (95% C.I.:0.91-0.98), respectively. Conclusion: We present a consensus-based semiquantitative scoring systems for CT in MM with a complementary CT imaging atlas including detailed examples of relevant scoring techniques. We found substantial agreement among readers with different levels of experience, thereby supporting the role of the MSBDS for possible large-scale applications. Significance and Innovations • Based on previous work and definitions of the MSBDS, we present real-life reliability data for quantitative bone damage assessment in multiple myeloma (MM) patients on CT. • In this study, reliability for the MSBDS, which was tested on 15 readers with different levels of expertise and from different institutions, was shown to be moderate to excellent. • The complementary CT imaging atlas is expected to enhance unified interpretations of the MSBDS between different professionals dealing with MM patients in their routine clinical practice.

Sympathetic activation and heart rate thresholds for cardiovascular risk in chronic kidney disease.

AIM: The current study was designed at assessing whether the sympathetic cardiovascular drive (SNS) is differently activated in chronic kidney disease (CKD) patients displaying less or more elevated resting heart rate (HR) values. It was also designed at determining at which HR cutoff value the SNS displays a greater activation. METHODS: In 95 CKD middle-age patients we evaluated muscle sympathetic nerve activity (MSNA, microneurography) and venous plasma norepinephrine (HPLC assay), subdividing the patients in different groups according to their resting clinic and 24-h HR. RESULTS: In CKD progressively greater values of clinic or 24-h HR were associated with a progressive increase in both MSNA and norepinephrine. HR cutoff values indicated by large-scale clinical trials for determining cardiorenal risk, that is more than 80 bpm, were associated with MSNA values significantly greater than the ones detected in patients with lower HR, this being the case also for norepinephrine. Both MSNA and norepinephrine were significantly related to clinic ( r  = 0.47, P  < 0.0001 and r  = 0.26, P  < 0.0001, respectively) and 24-h ( r  = 0.42, P  < 0.0001 and r  = 0.27, P  < 0.0001, respectively) HR. MSNA, norepinephrine, but not HR, were significantly and inversely related to estimated glomerular filtration rate (eGFR) values ( r  = -0.47, r  = -0.23, P  < 0.0001 and P  < 0.02, respectively). CONCLUSION: In CKD both clinic and 24-h HR values greater than 80 bpm are associated with an enhanced sympathetic activation, which parallelles for magnitude the HR elevations. The sensitivity of HR as sympathetic marker is limited; however, no significant relationship being detected between HR and eGFR or left ventricular mass index.

Human Adipose-Derived Stem Cell-Conditioned Medium Promotes Vascularization of Nanostructured Scaffold Transplanted into Nude Mice.

Several studies have been conducted on the interaction between three-dimensional scaffolds and mesenchymal stem cells for the regeneration of damaged tissues. Considering that stem cells do not survive for sufficient time to directly sustain tissue regeneration, it is essential to develop cell-free systems to be applied in regenerative medicine. In this work, by in vivo experiments, we established that a collagen-nanostructured scaffold, loaded with a culture medium conditioned with mesenchymal stem cells derived from adipose tissue (hASC-CM), exerts a synergic positive effect on angiogenesis, fundamental in tissue regeneration. To this aim, we engrafted athymic BALB-C nude mice with four different combinations: scaffold alone; scaffold with hASCs; scaffold with hASC crude protein extract; scaffold with hASC-CM. After their removal, we verified the presence of blood vessels by optical microscopy and confirmed the vascularization evaluating, by real-time PCR, several vascular growth factors: CD31, CD34, CD105, ANGPT1, ANGPT2, and CDH5. Our results showed that blood vessels were absent in the scaffold grafted alone, while all the other systems appeared vascularized, a finding supported by the over-expression of CD31 and CDH5 mRNA. In conclusion, our data sustain the capability of hASC-CM to be used as a therapeutic cell-free approach for damaged tissue regeneration.

Crowdsourcing and COVID-19: How Public Administrations Mobilize Crowds to Find Solutions to Problems Posed by the Pandemic.

We discuss how public administrations have used crowdsourcing to find solutions to specific problems posed by the COVID-19 pandemic, and to what extent crowdsourcing has been instrumental in promoting open innovation and service co-creation. We propose a conceptual typology of crowdsourcing challenges based on the degree of their openness and collaboration with the crowd that they establish. Using empirical evidence collected in 2020 and 2021, we examine the extent to which these types have been used in practice. We discuss each type of crowdsourcing challenge identified and draw implications for public policy.