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Muscle synergy analysis is a useful tool for the evaluation of the motor control strategies and for the quantification of motor performance. Among the parameters that can be extracted, most of the information is included in the rank of the modular control model (i.e. the number of muscle synergies that can be used to describe the overall muscle coordination). Even though different criteria have been proposed in literature, an objective criterion for the model order selection is needed to improve reliability and repeatability of MSA results. In this paper, we propose an Akaike Information Criterion (AIC)-based method for model order selection when extracting muscle synergies via the original Gaussian Non-Negative Matrix Factorization algorithm. The traditional AIC definition has been modified based on a correction of the likelihood term, which includes signal dependent noise on the neural commands, and a Discrete Wavelet decomposition method for the proper estimation of the number of degrees of freedom of the model, reduced on a synergy-by-synergy and event-by-event basis. We tested the performance of our method in comparison with the most widespread ones, proving that our criterion is able to yield good and stable performance in selecting the correct model order in simulated EMG data. We further evaluated the performance of our AIC-based technique on two distinct experimental datasets confirming the results obtained with the synthetic signals, with performances that are stable and independent from the nature of the analysed task, from the signal quality and from the subjective EMG pre-processing steps.

Muscle synergy analysis has been widely adopted in the literature for the analysis of upper limb surface electromyographic signals during reaching tasks and for the prediction of movement direction for myoelectric control purposes. However, previous studies have characterized movements in constrained or semi-constrained scenarios, in which the subjects performing the movement were instructed to reach particular targets or were given some kind of feedback. In this work, the same synergy model has been applied to a completely unconstrained upper limb reaching experiment, with the aim of classifying the height of the target starting from the activity of the synergies. Results show that the synergistic model is able to extract compact features that can identify with good performance three different reaching heights. Moreover, this representation is able to isolate the signals that contain predictive information about the movement direction from the ones that are related to movement timing; this, together with the good performance of the synergy-based classifier supports the proposal of applying this model to the pre-processing of electromyographic signals when dealing with control systems that use signals from multiple muscles to predict movements.

Background: Severe socio-emotional impairments characterize the behavioral variant of frontotemporal dementia (bvFTD). However, literature reports social cognition disorders in other dementias. Objective: In this study, we investigated the accuracy of social cognition performances in the early and differential diagnosis of bvFTD. Methods: We included 131 subjects: 32 bvFTD, 26 Alzheimer’s disease (AD), 16 primary progressive aphasia (PPA), 17 corticobasal syndrome (CBS), and 40 healthy control (HC). Each subject completed the Ekman 60 faces (Ek-60F) test assessing basic emotion recognition and the Story-based Empathy Task (SET) assessing attribution of intentions/emotions. A combined social measure (i.e., Emotion Recognition and Attribution (ERA) index) was calculated. One-way ANOVA has been used to compare performances among groups, while receiver operating characteristic (ROC) curve tested measures ability to distinguish subjects with and without bvFTD. Results: Ek-60F and ERA index scores were significantly lower in bvFTD versus HC, AD, and PPA groups. ROC analyses significantly distinguished bvFTD from HC (AUC 0.82–0.92), with the Ek-60F test showing the highest performance, followed by the ERA index. These two social measures showed the best accuracy in detecting bvFTD from AD (AUC 0.78–0.74) and PPA (AUC 0.80–0.76). Investigated measures failed in detecting bvFTD from CBS. Conclusion: Accuracy analyses support the advantage of using social cognition tests for bvFTD diagnosis. Short social battery may reduce uncertainties and improve disease identification in clinical settings. We recommend a revision of current clinical criteria considering neuropsychological deficits in emotion recognition and processing tasks as key cognitive markers of this neurodegenerative syndrome.

LTFPGSAED (P7) is a multifunctional hypocholesterolemic and hypoglycemic lupin peptide. While assessing its angiotensin-converting enzyme (ACE) inhibitory activity, it was more effective in intestinal Caco-2 cells (IC50 of 13.7 μM) than in renal HK-2 cells (IC50 of 79.6 μM). This discrepancy was explained by the metabolic transformation mediated by intestinal peptidases, which produced two main detected peptides, TFPGSAED and LTFPG. Indeed LTFPG, dynamically generated by intestinal dipeptidyl peptidase IV as well as its parent peptide P7 were linearly absorbed by mature Caco-2 cells. An in silico study demonstrated that the metabolite was a better ligand of the ACE enzyme than P7. These results are in agreement with an in vivo study, previously performed by Aluko et al., which has shown that LTFPG is an effective hypotensive peptide. Our work highlights the dynamic nature of bioactive food peptides that may be modulated by the metabolic activity of intestinal cells.

Progressive supranuclear palsy (PSP) and behavioural variant frontotemporal dementia – (bv-FTD) share common neuropsychological features except for online monitoring awareness. Therefore, the aim of our study is to explore if this assessment could be used in standard clinical practice. We retrospectively analyse 93 subjects (27 FTD, 25 PSP, 42 healthy controls). Neuropsychological and instrumental examinations were performed for each patient. FTD patients made fewer self-corrections than PSP patients despite a similar number of total errors. We also performed ROC curves: the area under the curve (AUC) is 0.79. A model for a logistic regression was also developed: the only significant predictor is the number of self-corrections (p = 0.004 β = 1244). In conclusion, our findings show online awareness is more compromised in FTD patients than in PSP patients. This difference could be useful for making a differential diagnosis between the two diseases: for each extra point in number of self-corrections the probability of suffering from PSP increases by about three and a half times (OR 3.47).

Smartphone texting while walking is a very common activity among people of different ages, with the so-called “digital natives” being the category most used to interacting with an electronic device during daily activities, mostly for texting purposes. Previous studies have shown how the concurrency of a smartphone-related task and walking can result in a worsening of stability and an increased risk of injuries for adults; an investigation of whether this effect can be identified also in people of a younger age can improve our understanding of the risks associated with this common activity. In this study, we recruited 29 young adolescents (12 ± 1 years) to test whether walking with a smartphone increases fall and injuries risk, and to quantify this effect. To do so, participants were asked to walk along a walkway, with and without the concurrent writing task on a smartphone; several different parameters linked to stability and risk of fall measures were then calculated from an inertial measurement unit and compared between conditions. Smartphone use determined a reduction of spatio-temporal parameters, including step length (from 0.64 ± 0.08 to 0.55 ± 0.06 m) and gait speed (1.23 ± 0.16 to 0.90 ± 0.16 m/s), and a general worsening of selected indicators of gait stability. This was found to be mostly independent from experience or frequency of use, suggesting that the presence of smartphone activities while walking may determine an increased risk of injury or falls also for a population that grew up being used to this concurrency.

Surface ElectroMyography (sEMG) is widely used as a non-invasive tool for the assessment of motor control strategies. However, the standardization of the methods used for the estimation of sEMG amplitude is a problem yet to be solved; in most cases, sEMG amplitude is estimated through the extraction of the envelope of the signal via different low-pass filtering procedures with fixed cut-off frequencies chosen by the experimenter. In this work, we have shown how it is not possible to find the optimal choice of the cut-off frequency without any a priori knowledge on the signal; considering this, we have proposed an updated version of an iterative adaptive algorithm already present in literature, aiming to completely automatize the sEMG amplitude estimation. We have compared our algorithm to most of the typical solutions (fixed window filters and the previous version of the adaptive algorithm) for the extraction of the sEMG envelope, showing how the proposed adaptive procedure significantly improves the quality of the estimation, with a lower fraction of variance unexplained by the extracted envelope for different simulated modulating waveforms (p < 0.005). The definition of an entropy-based convergence criterion has allowed for a complete automatization of the process. We infer that this algorithm can ensure repeatability of the estimation of the sEMG amplitude, due to its independence from the experimental choices, so allowing for a quantitative interpretation in a clinical environment.

This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (Camellia sinensis) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity. After specific catechin extraction, a chromatographic separation obtained six fractions were carried out. The fractions were assessed in vitro against the PLpro target. Fraction 5 showed the highest inhibitory activity against the SARS-CoV-2 PLpro (IC50 of 0.125 μg mL−1). The untargeted characterization revealed that (−)-epicatechin-3-gallate (ECG) was the most abundant compound in the fraction and the primary molecule absorbed by differentiated Caco-2 cells. Results indicated that fraction 5 was approximately 10 times more active than ECG (IC50 value equal to 11.62 ± 0.47 μg mL−1) to inhibit the PLpro target. Overall, our findings highlight the synergistic effects of the various components of the crude extract compared to isolated ECG.

Osteogenesis imperfecta (OI) is a rare congenital osteodystrophy. Patients with OI present with osteoporosis, extreme bone fragility and severe deformities of the lower limbs, which predispose them to frequent fractures. The aim of our study is to describe the minimally invasive osteotomy technique to correct the tibial deformities in patients with OI type III, using the Fassier-Duval (FD) intramedullary nailing, which is considered the gold standard in this kind of surgery. We analyzed the results obtained from 14 patients with OI type III, treated for tibial deformities with the minimally invasive percutaneous osteotomy technique and osteosynthesis with the FD telescopic nail. The results were compared with that of a control group composed of 18 patients with OI type III, treated for tibial deformities with open technique osteotomies and osteosynthesis with FD telescopic nail. The follow-up was set at 18 months postoperatively. The data concerning the following were collected from the two groups: duration of surgery, number of osteotomies performed, postoperative pain, time required for functional recovery, and for the formation of bone callus. To analyze the variations in the quality of life, all the patients were given the Pediatric Outcomes Data Collection Instrument questionnaire, before surgery and at the end of the follow-up. In patients who underwent corrective surgery with the percutaneous technique, the average duration of surgery was inferior, the postoperative pain was significantly lower, the recovery of 90° range of motion of knee flexion was reached at an average of 37.8 days, and they ambulated bearing full weight on the leg without auxiliary aids on average 45 days after surgery. The Pediatric Outcomes Data Collection Instrument questionnaire values were satisfactory in both groups. The osteosynthesis with the FD telescopic nail, performed with the minimally invasive surgical technique, has improved the management of deformities in OI. The minimally invasive technique, however, requires the maturation of three distinct learning curves: surgery on patients with OI, open technique with the FD nail, and percutaneous technique with the FD nail.

A preceding paper has shown that a hempseed peptic hydrolysate displays a cholesterol-lowering activity with a statin-like mechanism of action in HepG2 cells and a potential hypoglycemic activity by the inhibition of dipeptidyl peptidase-IV in Caco-2 cells. In the framework of a research aimed at fostering the multifunctional behavior of hempseed peptides, we present here the identification and evaluation of some antioxidant peptides from the same hydrolysate. After evaluation of its diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, a trans-epithelial transport experiment was performed using differentiated Caco-2 cells that permitted the identification of five transported peptides that were synthesized and evaluated by measuring the oxygen radical absorbance capacity (ORAC), the ferric reducing antioxidant power (FRAP), and the 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), and diphenyl-2-picrylhydrazyl radical DPPH assays. The most active peptides, i.e. WVSPLAGRT (H2) and IGFLIIWV (H3), were then tested in cell assays. Both peptides were able to reduce the H2O2-induced reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) production levels in HepG2 cells, via the modulation of Nrf-2 and iNOS pathways, respectively.

12 young adults were requested to walk along a circuitous path including turns, slaloms, stair ascending and descending, while wearing an inertial sensor placed on the back at the lumbar level. The path was completed under two conditions: with no additive cognitive task, and while performing a cognitive task and texting on a smartphone. Different temporal global parameters of gait were extracted from the inertial sensor data, to check for differences driven by the presence of the cognitive task. Regularity, durations, and temporal characteristics of gait resulted significantly affected from the presence of the additional task, and this effect was only in part due to a modification coming from the decrease in walking speed.

Background The above-knee amputation of a lower limb is a severe impairment that affects significantly the ability to walk; considering this, a complex adaptation strategy at the neuromuscular level is needed in order to be able to move safely with a prosthetic knee. In literature, it has been demonstrated that muscle activity during walking can be described via the activation of a small set of muscle synergies. The analysis of the composition and the time activation profiles of such synergies have been found to be a valid tool for the description of the motor control schemes in pathological subjects. Methods In this study, we used muscle synergy analysis techniques to characterize the differences in the modular motor control schemes between a population of 14 people with trans-femoral amputation and 12 healthy subjects walking at two different (slow and normal self-selected) speeds. Muscle synergies were extracted from a 12 lower-limb muscles sEMG recording via non-negative matrix factorization. Equivalence of the synergy vectors was quantified by a cross-validation procedure, while differences in terms of time activation coefficients were evaluated through the analysis of the activity in the different gait sub-phases. Results Four synergies were able to reconstruct the muscle activity in all subjects. The spatial component of the synergy vectors did not change in all the analysed populations, while differences were present in the activity during the sound limb’s stance phase. Main features of people with trans-femoral amputation’s muscle synergy recruitment are a prolonged activation of the module composed of calf muscles and an additional activity of the hamstrings’ module before and after the prosthetic heel strike. Conclusions Synergy-based results highlight how, although the complexity and the spatial organization of motor control schemes are the same found in healthy subjects, substantial differences are present in the synergies’ recruitment of people with trans femoral amputation. In particular, the most critical task during the gait cycle is the weight transfer from the sound limb to the prosthetic one. Future studies will integrate these results with the dynamics of movement, aiming to a complete neuro-mechanical characterization of people with trans-femoral amputation’s walking strategies that can be used to improve the rehabilitation therapies.

This study aims to characterize in vitro D-chiro-inositol intestinal absorption and identify factors able to improve its bioavailability. D-chiro-inositol, one of the natural occurring stereoisomer of myo-inositol, acts as a second messenger in insulin-regulated glucose metabolism in complementary mode with myo-inositol. Because of their insulin-mimetic activities and safety, both myo-inositol and D-chiro-inositol are often employed as supplements in insulin-resistance treatment.Trans-epithelial passage of D-chiro-inositol was evaluated in the human intestinal Caco-2 cell line differentiated on filter, a widely established in vitro model to study intestinal absorption. D-chiro-inositol transport was assayed in a concentration range corresponding to an estimated in vivo concentration following oral supplementation. α-Lactalbumin peptides, obtained by in vitro simulated gastrointestinal digestion, were tested as possible modulators of the intestinal permeability of D-chiro-inositol.The absorption of this stereoisomer was relatively low and presumably due to passive diffusion, while it was greatly enhanced by the presence of α-Lactalbumin digest. α-Lactalbumin peptides induced an increase in paracellular permeability that was completely reversible, indicating lack of cytotoxicity. This effect involved temporary rearrangement of F-actin apical cytoskeleton and of the tight junction protein ZO-1.Although further studies are required to identify and characterize the most effective peptides, the ability of α-Lactalbumin digest to act as absorption enhancers may have very interesting and promising applications in the fields of nutritional supplements and pharmacology.

Since many years it has been acknowledged that some bacterial species, among which H. pylori, P. aeruginosa, P. acnes accumulate endogenous photosensitizers (PS) in the form of porphyrins. This makes antibacterial photodynamic therapy (PDT) easier to perform due to the possible avoidance of external PS. In this study, we focus on gastric infections associated with the presence of Helicobacter pylori (H. pylori), known to accumulate and release both protoporphyrin IX (PPIX) and coproporphyrins. PDT versus H. pylori can be carried out by modified endoscopes or by new ingestible luminous devices under development. In both cases of in vitro and in vivo applications, either for therapy (PDT) or diagnosis, scientific literature lacks studies on the possible side-effects of light treatments on the surrounding tissues. To this aim we evaluated in vitro side-effects due to a possible intrinsic photosensitivity of gastric mucosa or to a photosensitization by the PS released from the bacterium itself. Photo-toxicity studies were conducted on the AGS cell line (ATCC® CRL-1739™), commonly used as a model for the stomach mucosa tissue, considering PPIX as the photosensitizing agent. After first evaluations of PPIX dark toxicity, its uptake and accumulation sites, photo-toxicity tests were conducted using a LED light source peaked at 400 nm, by varying both PPIX concentration (50 nM – 2 μM) and light dose in the range 0.6–13 J/cm2, representing different treatment procedures found in literature. The oxidative stress consequent to irradiation was investigated both in terms of ROS production and assessment of the activity of enzymes involved in ROS-related biological mechanisms. A significant phototoxic effect was found only for PPIX concentration > 100 nM for all tested light doses. This indicates that the evaluated photo-treatments do not cause side effects even with the sensitization due to PPIX released by the bacteria.

In the search for efficacious pharmacotherapies to treat cocaine addiction much attention has been given to agents targeting dopamine D1 or D3 receptors because of the involvement of these receptors in drug-related behaviors. D1-like and D3 receptor partial agonists and antagonists have been shown to reduce drug reward, reinstatement of drug seeking and conditioned place preference in rodents and non-human primates. However, translation of these encouraging results to clinical settings has been limited due to a number of factors including toxicity, poor pharmacokinetic properties and extrapyramidal and sedative side effects. This review highlights the role of D1 and D3 receptors in drug reward and seeking, the discovery of D1-D3 heteromers and their potential as targets in the treatment of addiction.

A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activation, skeletal muscle stem cells (satellite cells) induce local remodeling of the ECM and the deposition of laminin-α1 and laminin-α5 into the basal lamina of the satellite cell niche. Genetic ablation of laminin-α1, disruption of integrin-α6 signaling or blocking matrix metalloproteinase activity impairs satellite cell expansion and self-renewal. Collectively, our findings establish that remodeling of the ECM is an integral process of stem cell activity to support propagation and self-renewal, and may explain the effect laminin-α1-containing supports have on embryonic and adult stem cells, as well as the regenerative activity of exogenous laminin-111 therapy., Extracellular matrix (ECM) remodelling is thought to have effects on muscle stem cells that support muscle homeostasis. Here the authors show ECM remodeling controls satellite cell self-renewal through deposition of laminin-α1 into the satellite cell niche.

Background Famous face and voice recognition is reported to be impaired both in semantic dementia (SD) and in Alzheimer's Disease (AD), although more severely in the former. In AD a coexistence of perceptual impairment in face and voice processing has also been reported and this could contribute to the altered performance in complex semantic tasks. On the other hand, in SD both face and voice recognition disorders could be related to the prevalence of atrophy in the right temporal lobe (RTL). Objective The aim of the present study was twofold: (1) to investigate famous faces and voices recognition in SD and AD to verify if the two diseases show a differential pattern of impairment, resulting from disruption of different cognitive mechanisms; (2) to check if face and voice recognition disorders prevail in patients with atrophy mainly affecting the RTL. Materials To avoid the potential influence of primary perceptual problems in face and voice recognition, a pool of patients suffering from early SD and AD were administered a detailed set of tests exploring face and voice perception. Thirteen SD (8 with prevalence of right and 5 with prevalence of left temporal atrophy) and 25 CE patients, who did not show visual and auditory perceptual impairment, were finally selected and were administered an experimental battery exploring famous face and voice recognition and naming. Twelve SD patients underwent cerebral PET imaging and were classified in right and left SD according to the onset modality and to the prevalent decrease in FDG uptake in right or left temporal lobe respectively. Correlation of PET imaging and famous face and voice recognition was performed. Results Results showed a differential performance profile in the two diseases, because AD patients were significantly impaired in the naming tests, but showed preserved recognition, whereas SD patients were profoundly impaired both in naming and in recognition of famous faces and voices. Furthermore, face and voice recognition disorders prevailed in SD patients with RTL atrophy, who also showed a conceptual impairment on the Pyramids and Palm Trees test more important in the pictorial than in the verbal modality. Finally, in 12SD patients in whom PET was available, a strong correlation between FDG uptake and face-to-name and voice-to-name matching data was found in the right but not in the left temporal lobe. Discussion The data support the hypothesis of a different cognitive basis for impairment of face and voice recognition in the two dementias and suggest that the pattern of impairment in SD may be due to a loss of semantic representations, while a defect of semantic control, with impaired naming and preserved recognition might be hypothesized in AD. Furthermore, the correlation between face and voice recognition disorders and RTL damage are consistent with the hypothesis assuming that in the RTL person-specific knowledge may be mainly based upon non-verbal representations.

Coronavirus disease 2019 (COVID-19) is the respiratory disease caused by the novel severe acute respiratory syndrome-coronavirus-2 and is characterized by clinical manifestations ranging from mild, flu-like symptoms to severe respiratory insufficiency and multi-organ failure. Patients with more severe symptoms may require intensive care treatments and face a high mortality risk. Also, thrombotic complications such as pulmonary embolisms and disseminated intravascular coagulation are frequent in these patients. Indeed, COVID-19 is characterized by an abnormal inflammatory response resembling a cytokine storm, which is associated to endothelial dysfunction and microvascular complications. To date, no specific treatments are available for COVID-19 and its life-threatening complication. Immunomodulatory drugs, such as hydroxychloroquine and interleukin-6 inhibitors, as well as antithrombotic drugs such as heparin and low molecular weight heparin, are currently being administered with some benefit. Ozone therapy consists in the administration of a mixture of ozone and oxygen, called medical ozone, which has been used for over a century as an unconventional medicine practice for several diseases. Medical ozone rationale in COVID-19 is the possibility of contrasting endothelial dysfunction, modulating the immune response and acting as a virustatic agent. Thus, medical ozone could help to decrease lung inflammation, slow down viral growth, regulate lung circulation and oxygenation and prevent microvascular thrombosis. Ozone-therapy could be considered a feasible, cost-effective and easy to administer adjuvant therapy while waiting for the synthesis of a therapy or the development of the vaccine.

Addiction to drug and alcohol is regarded as a major health problem worldwide for which available treatments show limited effectiveness. The biggest challenge remains to enhance the capacities of interventions to reduce craving, prevent relapse and promote long-term recovery. New strategies to meet these challenges are being explored. Findings from preclinical work suggest that environmental enrichment (EE) holds therapeutic potential for the treatment of substance use disorders, as demonstrated in a number of animal models of drug abuse. The EE intervention introduced after drug exposure leads to attenuation of compulsive drug taking, attenuation of the rewarding (and reinforcing) effects of drugs, reductions in control of behavior by drug cues, and, very importantly, relapse prevention. Clinical work also suggests that multidimensional EE interventions (involving physical activity, social interaction, vocational training, recreational and community involvement) might produce similar therapeutic effects, if implemented continuously and rigorously. In this review we survey preclinical and clinical studies assessing the efficacy of EE as a behavioral intervention for substance use disorders and address related challenges. We also review work providing empirical evidence for EE-induced neuroplasticity within the mesocorticolimbic system that is believed to contribute to the seemingly therapeutic effects of EE on drug and alcohol-related behaviors.

Objectives The aim of the present study is to explore inter-rater reliability of primitive signs in a group of patients assessed for dementia. Patients and methods 97 patients admitted to our University Hospital for cognitive impairment were enrolled in the study. The mean age was 73.04 ± 8.68 (53 females and 44 males). All patients were examined by two cognitive neurologists in a blind fashion. The grasp reflex, the snout reflex, the glabella tap reflex and the palmomental reflex were elicited according to the current literature. Moreover, we add a stretch reflexes (the masseter reflex) to our battery. Results The most frequent primitive reflex was the palmomental reflex followed by the glabella tap, snout, and grasp. The inter-rater reliability was measured for each primitive reflex: grasp reflex (0.884) have a strong correspondence; the glabella tap (0.556), the palmomental (0.516) and the snout reflex (0.445) have otherwise a weak correspondence. The masseter reflex reaches a moderate agreement (0.662). All the measurements reached statistical significance (p Conclusion The results of the study show weak to substantial agreement for primitive signs and the masseter reflex as expressed by the low-to-high kappa values.

Introduction Patients with Osteogenesis Imperfecta (OI) Type 3 may exhibit both primitive deformities and secondary fracture malunions on a femoral level. The orthopaedic surgeon’s objective is to cure the deformities in order to prevent fractures and to treat the fractures in order to prevent deformities, by using telescopic nails as the gold standard method of fixation. However, the titanium elastic nail (TEN) is indicated as a possible alternative in certain selected cases. Materials and methods The Centre for Congenital Osteodystrophy of the Sapienza University of Rome follows 485 patients with osteogenesis imperfecta. For the purpose of this study, we selected 36 patients with OI type 3 (15 females and 21 males), aged between 2 and 10 years old, who were surgically treated for femur fractures with Titanium Elastic Nail (TEN) from January 2007 to December 2009. In 12 cases a single TEN was implanted, while 24 of the cases were treated by implanting 2 TENs with the Sliding Nail (SN) technique. A retrospective evaluation was carried out by analysing the data from the medical charts and dossiers related to pain symptoms, knee and hip Range of Motion (ROM), any possible complications that could cause implant revisions (infections, nail slide failure, nail migration, traumatic events following surgery, delayed consolidation, epiphysiodesis). Results At the 60th post-surgical month, the revision rate was 75%, mostly due to migration, osteolysis, nail slide failure and nail fracture. The Kaplan-Meier's survival curve analysis showed a coefficient of 0.25–60 months (confidence interval −0.31 and 0.81). Discussion The percentage of complications and the high rate of revisions recorded in our sample confirm that telescopic nail is the gold standard in the treatment of femoral fractures in patients with OI type 3. Conclusions In patients under the age of 4, with narrow medullary canals, low life expectancy, few to nil rehabilitative prospectives or severe comorbidities, the use of TEN may be considered as a less invasive approach compared to telescopic nail surgery, however only temporarily, as it will still most probably require a surgical revision a few years down the line.

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.

The purpose of this study is to compare the results obtained using three different systems of osteosynthesis, developed for the surgical treatment of fractures of the trochanteric region of the femur, based on the principle intramedullary nailing: the Gamma nail, the Affixus nail and the ZNN nail. This is a retrospective study: 72 trochanteric fractures treated with the Gamma nail, 68 treated with the Affixus nail and 69 treated with the ZNN nail, between the years 2012 and 2014, with the prerequisite of a minimum follow-up of 18 months. The fractures were classified according to the AO system; the most commonly reported subtype was the A2 fracture. Clinical and radiographic examinations were performed, both at hospital admission and post-operatively, at 1, 3, 6, 12 and 18 months. Of the 209 patients, 171 were women and 38 were men. The average age was 83.12 years old. All three systems guaranteed an early mobilization and ambulation in most of the patients. There were no significant differences in the use of the three nails in terms of recovery of previous functional capacity, or in terms of the time required for the fracture to heal. There were no advantages encountered with the use of one intramedullary nail over another and, in particular, when observing the complications and patient outcome, there were no statistically significant differences detected.

PURPOSE: The aim of this case-control study was to compare implant position and revision rate for UKA, performed with either a robotic-assisted system or with conventional technique. METHODS: Eighty UKA (57 medial, 23 lateral) were performed with robotic assistance (BlueBelt Navio system) between 2013 and 2017. These patients were matched with 80 patients undergoing UKA using the same prosthesis, implanted using conventional technique. The sagittal and coronal component position was assessed on postoperative radiographs. The revision rate was reported at last follow-up. RESULTS: The mean follow-up was 19.7 months ±?9 for the robotic-assisted group, and 24.2 months ±?16 for the control group. The rate of postoperative limb alignment outliers (±?2°) was significantly higher in the control group than in the robotic-assisted group for both lateral UKA (26% in robotic group versus 61% in control group; p?=?0.018) and medial UKA (16% versus 32%, resp.; p?=?0.038). The coronal and sagittal tibial baseplate position had significantly less outliers (±?3°) in the robotic-assisted group, than in the control group. Revision rates were: 5% (n?=?4/80) for robotic assisted UKA and 9% (n?=?7/80) for conventional UKA (n.s.). The reasons for revision were different between groups, with 86% of revisions in the control group occurring in association with component malposition or limb malalignment, compared with none in the robotic-assisted group. CONCLUSION: Robotic-assisted UKA has a lower rate of postoperative limb alignment outliers, as well as a lower revision rate, compared to conventional technique. The accuracy of implant positioning is improved by this robotic-assisted system. LEVEL OF EVIDENCE: Level of evidence III. Retrospective case-control study CLINICAL RELEVANCE: This is the first paper comparing implant position, clinical outcome, and revision rate for UKA performed using the Navio robotic system with a control group.

Recent investigations have focused on food-derived peptides as novel natural inhibitors of dipeptidyl peptidase IV (DPP-IV), a new target for diabetes. This study aimed to optimize fast, sensitive, and cost-effective DPP-IV assays in situ on human intestinal Caco-2 cells and ex vivo on human serum. Both assays were applied to investigate the inhibitory activity of soy and lupin peptides. The best conditions for in situ DPP-IV activity in Caco-2 cells were obtained using 2-day cells and 50 &micro, M Gly-Pro-AMC. Sitagliptin, used as reference inhibitor, showed a dose-dependent response with a 50% inhibition concentration (IC50) of 0.6 &micro, M. A lower IC50 (0.2 &micro, M) was obtained for sitagliptin on human serum incubated with the substrate for 24 h. Both assays were applied to assess the activity of Lup1 (LTFPGSAED) and Soy1 (IAVPTGVA) on DPP-IV. Lup1 and Soy1 inhibited DPP-IV in situ, with IC50 values of of 207.5 and 223.2 &micro, M, respectively, and maintained their inhibitory activity ex vivo on circulating DPP-IV with a slightly lower potency. These assays can be used to characterize the DPP-IV inhibitory activity of food-derived molecules more accurately than in vitro biochemical tests. This combined approach also considers their effects on the circulating form of DPP-IV, correlated to metabolic diseases.

A non-menopausal women underwent gynecological evaluation for spotting and menstrual irregularities. After first line gynecological assessments, the patient underwent office hysteroscopy. By using an in-office technique, two isthmic endometrial polyps and one cervical polyp were removed. One endometFial polyp was found to harbor a B-cell high-grade lymphoma just on the apex (found to be necrotic). The following staging examinatioIns and the pathological assessment of the endometrium, the uterus, the adnexa, and the lymphatic regional nodes did not find any localization of the lymphoma. No additional treatments were done. The patient is alive and disease-free at 18 months follow-up.

Fibroblasts are the most abundant cells in connective tissue and, with fibrillar extracellular matrix, form the structural scaffolding of organs. In solid tumors, interaction with cancer cells induces fibroblasts transdifferentiation into an activated form, which become a fundamental part of the tumor stroma. Within tumor microenvironment stromal and cancer cells engage a crosstalk that is mediated by soluble factors, cellcell contacts and extracellular vesicles trafficlking. Here we report that fibroblasts have the ability to transfer a remarkable amount of proteins and lipids to neighboring cells, in an ectosome-dependent fashion, identifying a novel and native property of these cells. Cancer-associated fibroblasts show an enhanced production and delivering of ectc:Jsomes to cancer cells compared to normal fibroblasts. As a consequence of this phenomenon, tumor cells increase their proliferation rate, indicating that ectosome-mediated trafficking could be a relevant mechanism mediating the trophic function of activated connective tissue on tumor cells.

The purpose of this study is to retrospectively evaluate a group of children affected by cerebral palsy with a recent femoral fracture, and to analyse the results and complications in relation to the treatment used.The analysis was performed on 36 children (21 M, 15 F, 8-14 years old) with cerebral palsy (7 diplegia, 28 tetraparesis, 1 hemiplegia) with a metaphyseal or a diaphyseal femoral fracture. The patients were subdivided into two groups according to their Gross Motor Function Classification System (GMFCS) level: level 2-3 (9 patients) and level 4-5 (27 patients), evaluating the presence of complications and malunions for each group at the end of each follow up.The fractures were displaced in 24 patients and nondisplaced in 12 patients. In 26 cases the treatment involved a closed reduction and immobilisation in a long leg hip spica cast for 7 weeks, while in 10 cases the treatment involved an open reduction-internal fixation (ORIF) followed by a 3-week period in a plaster coated fracture bandage.Taking into consideration the maximum possible recovery of function, an ORIF is preferable to prevent malunion, particularly in distal metaphysis and distal shaft fractures. In the GMFCS level 2-3 patients, surgery has allowed to recover, or at least maintain, the pre-fracture functional level, while in patients with GMFCS level 4-5, it has allowed to reduce the immobilisation times and prevent the development of decubitus lesions.

BACKGROUND Myo-inositol is a natural molecule with important therapeutic applications and an impaired oral absorption may result in a reduced clinical effect. Aim of this study was to determine if the combined oral administration of α-lactalbumin and myo-inositol in healthy subjects, could increase the plasma level of myo-inositol administered alone. In vitro studies on human differentiated intestinal Caco-2 cells were also conducted to identify the mechanisms involved in myo-inositol absorption. OBJECTIVE The in vivo study was conducted on healthy volunteers in two phases. Subjects received a single oral myo-inositol dose. After 7 days washout, the same subjects were administered a single dose of myo-inositol and α-lactalbumin. Cmax, Tmax and AUC for myo-inositol in plasma were calculated from samples collected at different times. Transepithelial myo-inositol passage, with or without addition of digested α-lactalbumin, was measured in vitro in differentiated Caco-2 cells and compared to transepithelial electrical resistance and phenol red passage. RESULTS The bioavailability of myo-inositol was modified by the concomitant administration of α- lactalbumin. Although peak concentration of myo-inositol at 180 min (Tmax) was similar for both treatments, administration of α-lactalbumin with myo-inositol in a single dose, significantly increased the plasma concentrations of myo-inositol compared to when administered alone. In vitro, myo-inositol absorption in Caco-2 cells was improved in the presence of digested α-lactalbumin, and this change was associated with an increase in tight junction permeability. CONCLUSION Better myo-inositol absorption when orally administered with α-lactalbumin can be beneficial in non-responder patients. Preliminary in vitro findings suggest that peptides deriving from α- lactalbumin digestion may modulate tight junction permeability allowing increased absorption of myoinositol.

The β-amyloid precursor protein undergoes cleavages by β- and γ-secretasses yielding amyloid-β peptides (Aβ) that accumulate in Alzheimer's disease. Subsequently, Aβ peptides are targets of additional truncations or endoproteolytic cleavages explaining the diversity of Aβ-related fragments recovered in cell media or pathologic human fluids. Here, we focused on Aβ1-34 (Aβ34) that has been detected both in vitro and in vivo and that derives from the hydrolysis of Aβ by β-secretase. We have obtained and fully characterized by immunologic and biochemical approaches, a polyclonal antibody that specifically recognizes the C-terminus of Aβx-34. We present immunohistochemical evidence for the presence of Aβx-34 in the brain of 3xTg mice and Alzheimer's disease-affected human brains. Finally, we demonstrate a neprilysin-mediated degradation process of Aβ34 and the ability of synthetic Aβ34 to protect HEK cells overexpressing either wild type or Swedish-mutated β-amyloid precursor protein from apoptosis.

Background and rationale An enormous amount of resources has been devoted to the development of pharmacotherapies for drug addiction, with relatively little or no long-term successreported. Thecurrent reviewarguesthatasuccessfuldrug addiction treatment program will likely be one that focuses on both theneuralmechanismsand the environmental contingencies that mediate drug use. Further, because the neural mechanisms and environmental factors that support abstinence in humans are similar in laboratory animals, several animal models of abstinence and relapse have been developed. Thus, this review also compares the similarities in the mechanisms that lead to abstinence between animals and humans. Objective We evaluate the construct and face validities of the behavioralstrategiesthathelpsupporthumandrugabstinence. Further, we crucially evaluate animal models by assessing their validity and utility in addressing human behavior that leads to long-term abstinence. Conclusions We found that the behavioral strategies with the greatest likelihood of supporting long-term abstinence are those that are carried out in drug addicts’ natural setting(s) and while drug is readily available. Further, the behavioral strategies that may be most successful in supporting abstinence in humans are those that employ both positive consequences for abstinent related behavior and negative consequences for continued drug seeking or taking. Moreover, the animal models of abstinence and relapse that more closely represent the factors that support long-term abstinence in humans are those that limit their use of extinction or forced abstinence and present negative consequences for drug seeking and taking.

The essential micronutrient zinc has long been known to be a functional component of diverse structural proteins and enzymes. More recently, important roles for free or loosely bound intracellular zinc as a signaling factor have been reported. Insufficient zinc intake was shown to exacerbate symptoms in mouse models of inflammation such as experimental colitis, while zinc supplementation was found to improve intestinal barrier function. Herein, we provide evidence that intracellular zinc is essential for maintaining intestinal epithelial integrity when cells are exposed to the inflammatory cytokine Tumor Necrosis Factor (TNF)α. Using the human intestinal Caco-2/TC7 cell line as an in vitro model, we demonstrate that depletion of intracellular zinc affects TNFα-triggered signaling by shifting intestinal cell fate from survival to death. The mechanism underlying this effect was investigated. We show that TNFα promotes a zinc-dependent survival pathway that includes modulation of gene expression of transcription factors and signaling proteins. We have identified multiple regulatory steps regulated by zinc availability which include the induction of cellular Inhibitor of APoptosis (cIAP2) mRNA, possibly through activation of Nuclear Factor-Kappa B (NF-κB), as both nuclear translocation of the p65 subunit of NF-κB and up-regulation of cIAP2 mRNA were impaired following zinc depletion. Moreover, X-linked inhibitor of apoptosis protein level was profoundly reduced by zinc depletion. Our results provide a possible molecular explanation for the clinical observation that zinc supplements ameliorate Crohn's disease symptoms and decrease intestinal permeability in experimental colitis.

Osteoarticular infections are found frequently in drug addicted individuals, representing one of the main reasons for their hospitalization. Through inoculation, the pathogenic agents can enter the individual's system directly through the skin or parenterally, transmitted, that is, through syringes and other objects used during such practice. In these particular conditions, or when the medical history is vague, a warranted suspicion and the execution of targeted research can help in the diagnosis of high-risk patients such as addicts.With this paper, the Authors are presenting a case of septic arthritis in the hip joint, in a drug addicted patient with the habit of injecting narcotics into the femoral vein, in correspondence of the anatomical region known as the triangle of Scarpa. Following an examination of the bacterial culture samples taken by arthrocentesis, the S. Aureus infection was identified and a targeted antibiotic therapy (coxacillin and aminoglycosides) was prescribed. After one year, with clinical examination and medical scans resulting negative for infection, there was a remaining deformity of the femoral head and, therefore, a total hip arthroplasty (THA) was performed. The 14 year post-operative clinical examination and medical scan check-up showed a complete articular functionality and recovery of normal daily and work related activities.

The purpose of this study is to compare the results of 2 techniques, tension band wiring (TBW) and fixation with screws, in olecranon fractures in children affected with osteogenesis imperfecta (OI) type I. Between 2010 and 2014, 21 olecranon fractures in 18 children with OI (average age: 12 years old) were treated surgically. Ten patients were treated with the screw fixation and 11 with TBW. A total of 65% of olecranon fractures occurred as a result of a spontaneous avulsion of the olecranon during the contraction of the triceps muscle. The average follow-up was 36 months. Among the children treated with 1 screw, 5 patients needed a surgical revision with TBW due to a mobilization of the screw. In this group, the satisfactory results were 50%. In patients treated with TBW, the satisfactory results were 100% of the cases. The average Z-score, the last one recorded in the patients before the trauma, was −2.53 in patients treated with screw fixation and −2.04 in those treated with TBW. TBW represents the safest surgical treatment for patients suffering from OI type I, as it helps to prevent the rigidity of the elbow through an earlier recovery of the range of motion, and there was no loosening of the implant. In analyzing the average Z-score before any fracture, the fixation with screws has an increased risk of failure in combination with low bone mineral density.

Chronic intestinal inflammatory disorders, such as Inflammatory Bowel Diseases (IBDs), are characterized by excessive release of proinflammatory mediators, intestinal barrier dysfunction and excessive activation of NF-kB cascade. Previous studies shown that TNF-α plays a central role in intestinal inflammation of IBDs and supported beneficial effects of flavonoids against chronic inflammatory diseases. In this study, we employed an in vitro model of acute intestinal inflammation using intestinal Caco-2 cells exposed to TNF-α. The protective effects of cyanidin-3-glucoside (C3G), an anthocyanin widely distributed in mediterranean diet, were then evaluated. Caco-2 cells exposure to TNF-α activated NF-kB proinflammatory pathway and induced IL6 and COX-2 expression. Cells pretreatment for 24h with C3G (20-40μM) prevented TNF-α-induced changes, and improved intracellular redox status. Our results demonstrated that C3G, also without any kind of stimulus, increased the translocation of the transcription factor Nrf2 into the nucleus so activating antioxidant and detoxifying genes. In conclusion, C3G exhibited protective effects through the inhibition of NF-kB signalling in Caco-2 cells and these beneficial effects appear to be due to its ability to activate cellular protective responses modulated by Nrf2. These data suggest that anthocyanins could contribute, as complementary or preventive approaches, to the management of chronic inflammatory diseases.

Background: Osteogenesis imperfecta (OI) is a rare congenital genetic osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in the synthesis of procollagen-α type 1. Seven different forms of diverse clinical entity have been classified by Sillence and Glorieux, although, recently, up to 11 forms characterized by different genetic mutations have been recognized. Patients with OI suffer from extreme bone fragility and osteoporosis, which often predisposes them to frequent fractures. This paper presents the case of a child with OI type IV who, at birth, was also diagnosed with a severe clubfoot (congenital talipes equinovarus) grade III. Patient's mother also suffers from OI type IV. Methods: The treatment was started by placing femoro-podalic corrective casts, according to the Ponseti method, but some unexpected problems occurred during this treatment. When the patient was 3 months of age, we decided to correct the clubfoot before the time limit planned, performing a bilateral posteromedial surgical release. Results: Three weeks after surgery the casts were removed and replaced with bilateral Spica cast-like braces. On the 6th postoperative week, the patient began wearing Bebax corrective shoes, after 1 year ambidextrous orthopedic shoes. Now, he is 2 years old and has started to walk properly without any orthesis. Conclusion: In the presence of an orthopedic pathology associated with OI, it is recommended to manage the patient according to the underlying pathology, always considering the bone fragility associated with OI. The final surgical treatment to correct the clubfoot can be done earlier, if necessary. In our opinion, this uncommon association between OI and clubfoot is non-syndromic. This means that the two congenital diseases are not necessarily included in a singular uncommon genetic syndrome, but the clubfoot was caused by multifactorial causes, especially by both the mother's bisphosphonate drug therapy and the amniocentesis performed during her pregnancy to drain polyhydramnios. In our analysis, those environmental factors could have interacted with an already altered genetic substratum, contributing to develop this rare combination of congenital disorders.

Purpose Increasing cellular phone service and nonresponse are causing random digit dial (RDD) users to search for alternative ways of sampling geographically large populations. This study evaluated the feasibility and utility in using a modified version of respondent-driven sampling (RDS) as an alternative method. Methods Using RDS, 469 residents of Albany County, New York were enrolled into a telephone-based health survey. Participants answered health and RDS feasibility questions. Results were compared to a previously collected RDD sample and census data. Results Participation was high (81.4%) and participants referred at least one peer 65.9% of the time. The RDS method produced a more ethnically diverse sample, otherwise respondent demographics were similar to the RDD sample. The most common reason for participating (51.9%) was because a peer told them about the study; 44.9% would not have participated in an RDD study. Persons not willing to participate in a RDD study reported being less healthy and less likely to participate in healthy activities (e.g., have a physical exam in the past 24 months). Conclusions Although more research is needed, RDS methods may be developed into a viable alternative for collecting health data from large general populations.

ObjectivesThe Heart Manual (HM) is the UK’s leading facilitated home-based cardiac rehabilitation (CR) programme for individuals recovering from myocardial infarction and revascularisation. This audit explored patient-reported outcomes of home-based CR in relation to current Scottish, UK and European guidelines.SettingPatients across the UK returned their questionnaire after completing the HM programme to the HM Department (NHS Lothian).ParticipantsQualitative data from 457 questionnaires returned between 2011 and 2018 were included for thematic analysis. Seven themes were identified from the guidelines. This guided initial deductive coding and provided the basis for inductive subthemes to emerge.ResultsThemes included: (1) health behaviour change and modifiable risk reduction, (2) psychosocial support, (3) education, (4) social support, (5) medical risk management, (6) vocational rehabilitation and (7) long-term strategies and maintenance. Both (1) and (2) were reported as having the greatest impact on patients' daily lives. Subthemes for (1) included: guidance, engagement, awareness, consequences, attitude, no change and motivation. Psychosocial support comprised: stress management, pacing, relaxation, increased self-efficacy, validation, mental health and self-perception. This was followed by (3) and (4). Patients less frequently referred to (5), (6) and (7). Additional themes highlighted the impact of the HM programme and that patients attributed the greatest impact to a combination of all the above themes.ConclusionsThis audit highlighted the HM as comprehensive and inclusive of key elements proposed by Scottish, UK and EU guidelines. Patients reported this had a profound impact on their daily lives and proved advantageous for CR.

N-terminal pro-B-type natriuretic peptide (Nt-proBNP) is a peptide released from myocardium in response to ventricular wall stress and dysfunction. Nt-proBNP plasma levels are elevated in a variety of cardiovascular disorders and are largely used for diagnosis and treatment of cardiac diseases. The cardiac cycle efficiency (CCE) is a haemodynamic variable that represents the left ventricle wall stress and the heart's effort to maintain an adequate blood flow to tissues. We investigated the relationship between Nt-proBNP and CCE values in patients undergoing cardiac surgery. Twenty-five patients undergoing aortic valve replacement were studied. Plasma Nt-proBNP concentrations were performed by electroluminescence immunoassay before starting surgery (t0), at the end of extracorporeal circulation (t1) and 3 hours after surgery (t2). CCE measurements were acquired at the same intervals and correlations with Nt-proBNP levels were calculated. Nt-proBNP plasma concentration was 1430 ± 341 pg/ml at t0, peaked significantly at t1 (2129 ± 561 pg/ml, p

Objective Patients are seeking greater choice and flexibility in how they engage with self-management programmes. While digital innovations offer opportunities to deliver supportive interventions to patients undergoing cardiac rehabilitation little is known about how accessible, useful and acceptable they are for this group. This project developed a digital version of a leading evidenced cardiac rehabilitation programme, the Heart Manual (HM). The prototype was developed and evaluated iteratively in collaboration with end users. Methods Using a mixed methods design 28 participants provided feedback using semi-structured questionnaires and telephone interviews. Results Rich data revealed the perceived user-friendliness of the HM digital format and its effectiveness at communicating the programme’s key messages. It flagged areas requiring development, such as more flexible and intuitive navigation pathways. These suggestions informed the refinement of the resource. Conclusion This evaluation offers support for the new Digital Heart Manual and confirms the value of employing a user-centred approach when developing and improving online interventions. The system is now in use and recommendations from the evaluation are being translated into quality improvements. Practice implications The Digital Heart Manual is user friendly and accessible to patients and health professionals, regardless of age, presenting a suitable alternative to the paper version.

We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.

This randomized, controlled study aims to evaluate the tolerability and the efficacy of curcumin in overweight subjects affected from metabolic syndrome, with a focus on impaired glucose intolerance and android-type fat accumulation.Forty-four subjects, selected among those who after 30 days of diet and intervention lifestyle have shown a weight loss2%, have been treated for further 30 days either with curcumin complexed with phosphatidylserine in phytosome form or with pure phosphatidylserine. Outcomes concerning anthropometric measurements and body composition were analyzed at enrollment and after 30 and 60 days.Curcumin administration increased weight loss from 1.88 to 4.91%, enhanced percentage reduction of body fat (from 0.70 to 8.43%), increased waistline reduction (from 2.36 to 4.14%), improved hip circumference reduction from 0.74 to 2.51% and enhanced reduction of BMI (from 2.10 to 6.43%) (p0.01 for all comparisons). Phosphatidylserine did not show any statistical significant effect. Tolerability was very good for both treatments, and no drop-out was reported.Although preliminary, our findings suggest that a bioavailable form of curcumin is well-tolerated and can positively influence weight management in overweight people.

We describe a simple protocol to inactivate the biosafety level 3 (BSL3) pathogens Brucella prior to their analysis by matrix-assisted laser desorption ionization–time of flight mass spectrometry. This method is also effective for several other bacterial pathogens and allows storage, and eventually shipping, of inactivated samples; therefore, it might be routinely applied to unidentified bacteria, for the safety of laboratory workers.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS.

Epidemiological studies suggest that moderate and prolonged consumption of coffee is associated with a reduced risk of developing type 2 diabetes but the molecular mechanisms underlying this effect are not known. In this study, we report the effects of physiological concentrations of caffeic acid, easily achievable by normal dietary habits, in endothelial cells cultured in 25 mM of glucose (high glucose, HG). In HG, the presence of 10 nM caffeic acid was associated with a decrease of glucose uptake but not to changes of GLUT-1 membrane localization or mRNA levels. Moreover, caffeic acid countered HG-induced loss of barrier integrity, reducing actin rearrangement and FITC-dextran passage. The decreased flux of glucose associated to caffeic acid affected HG induced apoptosis by down-regulating the expression of initiator (caspase 8 and 9) and effector caspases (caspase 7 and 3) and by increasing the levels of phosphorylated Bcl-2. We also observed that caffeic acid in HG condition was associated to a reduction of p65 subunit nuclear levels with respect to HG alone. NF-κB activation has been shown to lead to apoptosis in HG treated cells and the analysis of the expression of a panel of about 90 genes related to NF-κB signaling pathway revealed that caffeic acid significantly influenced gene expression changes induced by HG. In conclusion, our results suggest that caffeic acid, decreasing the metabolic stress induced by HG, allows the activation of survival mechanisms mediated by a different modulation of NF-κB-related signaling pathways and to the activation of anti-apoptotic proteins.

Introduction Hemorrhage is the principal cause of death in the first few hours following severe injury. Coagulopathy is a frequent complication of critical bleeding. A network of Italian trauma centers recently developed a protocol to prevent and treat trauma-induced coagulopathy. A pre-post cohort multicenter study was conducted to assess the impact of the early coagulation support (ECS) protocol on blood products consumption, mortality and treatment costs. Methods We prospectively collected data from all severely injured patients (Injury Severity Score (ISS) >15) admitted to two trauma centers in 2013 and compared these findings with the data for 2011. Patients transfused with at least 3 units of packed red blood cells (PRBCs) within 24 hours of an accident were included in the study. In 2011, patients with significant hemorrhaging were treated with early administration of plasma with the aim of achieving a high (≥1:2) plasma-to-PRBC ratio. In 2013, the ECS protocol was the treatment strategy. Outcome data, blood product consumption and treatment costs were compared between the two periods. Results The two groups were well matched for demographics, injury severity (ISS: 32.9 in 2011 versus 33.6 in 2013) and clinical and laboratory data on admission. In 2013, a 40% overall reduction in PRBCs was observed, together with a 65% reduction in plasma and a 52% reduction in platelets. Patients in the ECS group received fewer blood products: 6.51 units of PRBCs versus 8.14 units. Plasma transfusions decreased from 8.98 units to 4.21 units (P P Conclusions The introduction of the ECS protocol in two Italian trauma centers was associated with a marked reduction in blood product consumption, reaching statistical significance for plasma and platelets, and with a non-significant trend toward a reduction in early and 28-day mortality. The overall costs for transfusion and coagulation support (including point-of-care tests) decreased by 23% between 2011 and 2013.

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology - follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL) - was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

The aim of this study was to define the permeability characteristics of the parental Caco-2/ATCC cell line and of three clonal lines (Caco-2/TC7, Caco-2/AQ, Caco-2/15) differentiated in serum-supplemented or in serum-free defined medium. The Caco-2 cells were grown in DMEM supplemented with either 10% foetal calf serum or insulin-transferrin-selenium and lipids (cholesterol, palmitic acid, oleic acid) for up to 24 days after seeding on polyethylene terephthalate filter inserts (1 microm pore diameter). The permeability of the cell monolayer was assessed by measuring trans-epithelial electrical resistance (TEER) and the apparent permeability (Papp) of the extracellular marker mannitol during differentiation from day 6 until day 24. In all lines TEER values increased during differentiation reaching a plateau value around day 15 after seeding, while the Papp for mannitol decreased sharply around day 8 and levelled off thereafter. Substantial differences were observed in the maximal TEER values achieved during differentiation in the four lines examined (Caco-2/TC7