Integration of Strain Sensors on Additively Manufactured Implantable Devices

The development of personalized healthcare is rapidly growing thanks to the support of low-power electronics, advanced fabrication processes and secured data transmission protocols. Long-acting drug delivery systems able to sustain the release of therapeutics in a controllable manner can provide several advantages in the treatment of chronic diseases. Various systems under development control drug release from an implantable reservoir via concentration driven diffusion through nanofluidic membranes. Given the high drug concentration in the reservoir, an inward osmotic fluid transport occurs across the membrane, which counters the outward diffusion of drugs. The resulting osmotic pressure buildup may be sufficient to cause the failure of implants with associated risks to patients. Confidently assessing the osmotic pressure buildup requires testing in vivo. Here, using metal and polymer AM (additive manufacturing) processes, we designed and developed implantable drug reservoirs with embedded strain sensors to directly measure the osmotic pressure in drug delivery implants in vitro and in vivo

Microcirculatory changes and skeletal muscle oxygenation measured at rest by non-infrared spectroscopy in patients with and without diabetes undergoing haemodialysis

Introduction: Haemodialysis has direct and indirect effects on skin and muscle microcirculatory regulation that are severe enough to worsen tolerance to physical exercise and muscle asthenia in patients undergoing dialysis, thus compromising patients' quality of life and increasing the risk of mortality. In diabetes these circumstances are further complicated, leading to an approximately sixfold increase in the incidence of critical limb ischaemia and amputation. Our aim in this study was to investigate in vivo whether haemodialysis induces major changes in skeletal muscle oxygenation and blood flow, microvascular compliance and tissue metabolic rate in patients with and without diabetes. Methods: The study included 20 consecutive patients with and without diabetes undergoing haemodialysis at Sant Andrea University Hospital, Rome from March to April 2007. Near-infrared spectroscopy (NIRS) quantitative measurements of tissue haemoglobin concentrations in oxygenated [HbO(2)] and deoxygenated forms [HHb] were obtained in the calf once hourly for 4 hours during dialysis. Consecutive venous occlusions allowed one to obtain muscular blood flow (mBF), microvascular compliance and muscle oxygen consumption (mVO(2)). The tissue oxygen saturation (StO(2)) and content (CtO(2)) as well as the microvascular bed volume were derived from the haemoglobin concentration. Nonparametric tests were used to compare data within each group and among the groups and with a group of 22 matched healthy controls. Results: The total haemoglobin concentration and [HHb] increased significantly during dialysis in patients without and with diabetes. Only in patients with diabetes, dialysis involved a [HbO(2)], CtO(2) and mVO(2) increase but left StO(2) unchanged. Multiple regression analysis disclosed a significant direct correlation of StO(2) with HbO(2) and an inverse correlation with mVO(2). Dialysis increased mBF only in diabetic patients. Microvascular compliance decreased rapidly and significantly during the first hour of dialysis in both groups. Conclusions: Our NIRS findings suggest that haemodialysis in subjects at rest brings about major changes in skeletal muscle oxygenation, blood flow, microvascular compliance and tissue metabolic rate. These changes differ in patients with and without diabetes. In all patients haemodialysis induces changes in tissue haemoglobin concentrations and microvascular compliance, whereas in patients with diabetes it alters tissue blood flow, tissue oxygenation (CtO(2), [HbO(2)]) and the metabolic rate (mVO(2)). In these patients the mVO(2) is correlated to the blood supply. The effects of haemodialysis on cell damage remain to be clarified. The absence of StO(2) changes is probably linked to an opposite [HbO(2)] and mVO(2) pattern

Ictal but Not Interictal Epileptic Discharges Activate Astrocyte Endfeet and Elicit Cerebral Arteriole Responses

Activation of astrocytes by neuronal signals plays a central role in the control of neuronal activity-dependent blood flow changes in the normal brain. The cellular pathways that mediate neurovascular coupling in the epileptic brain remain, however, poorly defined. In a cortical slice model of epilepsy, we found that the ictal, seizure-like discharge, and only to a minor extent the interictal discharge, evokes both a Ca2+ increase in astrocyte endfeet and a vasomotor response. We also observed that rapid ictal discharge-induced arteriole responses were regularly preceded by Ca2+ elevations in endfeet and were abolished by pharmacological inhibition of Ca2+ signals in these astrocyte processes. Under these latter conditions, arterioles exhibited after the ictal discharge only slowly developing vasodilations. The poor efficacy of interictal discharges, compared with ictal discharges, to activate endfeet was confirmed also in the intact in vitro isolated guinea pig brain. Although the possibility of a direct contribution of neurons, in particular in the late response of cerebral blood vessels to epileptic discharges, should be taken into account, our study supports the view that astrocytes are central for neurovascular coupling also in the epileptic brain. The massive endfeet Ca2+ elevations evoked by ictal discharges and the poor response to interictal events represent new information potentially relevant to interpret data from diagnostic brain imaging techniques, such as functional magnetic resonance, utilized in the clinic to localize neural activity and to optimize neurosurgery of untreatable epilepsies

The Relationship Between Widespread Pollution Exposure and Oxidized Products of Nucleic Acids in Seminal Plasma and Urine in Males Attending a Fertility Center

BACKGROUND: In recent decades, there has been an increase in male infertility, and in many cases, the etiology remains unclear. Several studies relate male hypo-fertility to xenobiotic exposure, even if no data exist about multiple exposure at the environmental level. METHODS: The study involved 86 males with diagnosis of idiopathic male infertility (IMI), and 46 controls with no alteration in sperm characteristics. Seminal plasma (SP) and urine samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify biomarkers of exposure (the main metabolites of benzene, toluene, 1,3-butadiene, 3-monochloropropanediol, styrene, and naphthol) and effect (oxidized products of nucleic acids). RESULTS: Biomarker concentrations were similar in subjects with IMI and controls even if a stronger correlation between biomarkers of exposure and effects were observed in SP. Data show that, both in SP and urine, most metabolites were inter-correlated, indicating a simultaneous co-exposure to the selected substances at the environmental level. Principal component analysis showed in SP the clustering of mercapturic acids indicating a preferential metabolic pathway with Glutathione (GSH) depletion and, consequently, an increase of oxidative stress. This result was also confirmed by multivariable analysis through the development of explanatory models for oxidized products of nucleic acids. CONCLUSIONS: This study highlights how oxidative stress on the male reproductive tract can be associated with a different representation of metabolic pathways making the reproductive tract itself a target organ for different environmental pollutants. Our results demonstrate that SP is a suitable matrix to assess the exposure and evaluate the effects of reproductive toxicants in environmental/occupational medicine. The statistical approach proposed in this work represents a model appropriate to study the relationship between multiple exposure and effect, applicable even to a wider variety of chemicals

Higher circulating levels of proneurotensin are associated with increased risk of incident NAFLD

BackgroundNeurotensin (NT), an intestinal peptide able to promote fat absorption, is implicated in the pathogenesis of obesity. Increased levels of proneurotensin (pro-NT), a stable NT precursor fragment, have been found in subjects with nonalcoholic fatty liver disease (NAFLD); however, whether higher pro-NT levels are associated with an increased NAFLD risk independently of other metabolic risk factors is unsettled. MethodsUltrasound-defined presence of NAFLD was assessed on 303 subjects stratified into tertiles according to fasting pro-NT levels. The longitudinal association between pro-NT levels and NAFLD was explored on the study participants without NAFLD at baseline reexamined after 5 years of follow-up (n = 124). ResultsIndividuals with higher pro-NT levels exhibited increased adiposity, a worse lipid profile, and insulin sensitivity as compared to the lowest tertile of pro-NT. Prevalence of NAFLD was progressively increased in the intermediate and highest pro-NT tertile as compared to the lowest tertile. In a logistic regression analysis adjusted for several confounders, individuals with higher pro-NT levels displayed a raised risk of having NAFLD (OR = 3.43, 95%CI = 1.48-7.97, p = 0.004) than those in the lowest pro-NT tertile. Within the study cohort without NAFLD at baseline, subjects with newly diagnosed NAFLD at follow-up exhibited higher baseline pro-NT levels than those without incident NAFLD. In a cox hazard regression analysis model adjusted for anthropometric and metabolic parameters collected at baseline and follow-up visit, higher baseline pro-NT levels were associated with an increased risk of incident NAFLD (HR = 1.52, 95%CI = 1.017-2.282, p = 0.04). ConclusionHigher pro-NT levels are a predictor of NAFLD independent of other metabolic risk factors

Pectoralis Muscle Transposition in Association with the Ravitch Procedure in the Management of Severe Pectus Excavatum.

Background: Pectus excavatum (PE) is the most common congenital chest wall deformity. PE is sometimes associated with cardiorespiratory impairment, but is often associated with psychological distress, especially for patients in their teenage years. Surgical repair of pectus deformities has been shown to improve both physical limitations and psychosocial well-being in children. The most common surgical approaches for PE treatment are the modified Ravitch technique and the minimally invasive Nuss technique. A technical modification of the Ravitch procedure, which includes bilateral mobilization and midline transposition of the pectoralis muscle flap, is presented here. Methods: From 2010 to 2016, 12 patients were treated by a modified Ravitch procedure with bilateral mobilization and midline transposition of the pectoralis muscle flap for severe PE. Outcomes, morphological results, and complications were analyzed with respect to this new combined surgical approach. Results: There was a statistically significant difference between pre- and postoperative values (P = 0.0025) of the Haller index at the 18-month follow-up, showing a significant morphological improvement for all treated patients. After surgery, no morbidity and mortality were noted. The mean hospital stay was 7 days, and all patients were discharged without major complications. Conclusion: This technique significantly improved patients’ postoperative morphological outcomes and significantly reduced long-term complications, such as wound dehiscence, skin thinning, and hardware exposure