Virtual Reality combined with Robotic facilitated movements for pain management and sensory stimulation of the upper limb following a Brachial Plexus injury: A case study

Brachial Plexus injuries are complex in nature caused in large by high impact traffic accidents which can lead to additional complications such as Complex Regional Pain Syndrome and even lead to amputation or the need for further surgical intervention. Treatment options to help repair the brachial plexus initially involve surgical intervention and post-surgery rehabilitation with medication to help with ongoing pain. Pain treatments used for these types of injuries are limited and differ in effectiveness. Paradigms utilising multimodal systems such as the one described in this paper based on virtual reality and robotics could yield results that are non-invasive and provide better rehabilitation outcomes for the sufferers. In this paper we present a single case study exploring whether Virtual Reality plus Haptic feedback have any practical potential for reducing upper limb pain and improving function in patients with brachial plexus injuries. The case study is presented with long standing complex combination of phantom limb and neuropathic pain. A decrease in perceived levels of pain was reported which amounts to a 50% reduction in pain from baseline and an improved range of motion. An examination of the sensory phantom map on the stump seems to indicate an early establishment of the thumb representation on the stump close to the area being stimulated with potential implications for prosthesis use

Tracing groundwater salinization processes in coastal aquifers: a hydrogeochemical and isotopic approach in Na-Cl brackish waters of north-western Sardinia, Italy

Abstract. Throughout the Mediterranean, salinization threatens water quality, especially in coastal areas. This salinization is the result of concomitant processes related to both seawater intrusion and water–rock interaction, which in some cases are virtually indistinguishable. In the Nurra region of northwestern Sardinia, recent salinization related to marine water intrusion has been caused by aquifer exploitation. However, the geology of this region records a long history from the Palaeozoic to the Quaternary, and is structurally complex and comprises a wide variety of lithologies, including Triassic evaporites. Determining the origin of the saline component of the Jurassic and Triassic aquifers in the Nurra region may provide a useful and more general model for salinization processes in the Mediterranean area, where the occurrence of evaporitic rocks in coastal aquifers is a common feature. In addition, due to intensive human activity and recent climatic change, the Nurra has become vulnerable to desertification and, in common with other Mediterranean islands, surface water resources periodically suffer from severe shortages. With this in mind, we report new data regarding brackish and surface waters (outcrop and lake samples) of the Na-Cl type from the Nurra region, including major ions and selected trace elements (B, Br, I, and Sr), in addition to isotopic data including δ18O, δD in water, and δ34S and δ18O in dissolved SO4. To identify the origin of the salinity more precisely, we also analysed the mineralogical and isotopic composition of Triassic evaporites. The brackish waters have Cl contents of up to 2025 mg L−1 , and the ratios between dissolved ions and Cl, with the exception of the Br / Cl ratio, are not those expected on the basis of simple mixing between rainwater and seawater. The δ18O and δD data indicate that most of the waters fall between the regional meteoric water line and the global meteoric water line, supporting the conclusion that they are meteoric in origin. A significant consequence of the meteoric origin of the Na-Cl-type water studied here is that the Br / Cl ratio, extensively used to assess the origin of salinity in fresh water, should be used with care in carbonate aquifers that are near the coast. Overall, δ34S and δ18O levels in dissolved SO4 suggest that water–rock interaction is responsible for the Na-Cl brackish composition of the water hosted by the Jurassic and Triassic aquifers of the Nurra, and this is consistent with the geology and lithological features of the study area. Evaporite dissolution may also explain the high Cl content, as halite was detected within the gypsum deposits. Finally, these Na-Cl brackish waters are undersaturated with respect to the more soluble salts, implying that in a climate evolving toward semi-arid conditions, the salinization process could intensify dramatically in the near future

Irrational beliefs about COVID-19: A scoping review

Since the emergence of the recent Coronavirus Disease of 2019 (COVID-19) and its spread as a pandemic, there has been a parallel spread of false and misleading information, known as an infodemic. The COVID-19 infodemic has induced distrust in scientific communities, governments, institutions and the population, and a confidence crisis that has led to harmful health behaviours, also impacting on mental health. The aim of this study is to provide a scoping review of the scientific literature about COVID-19-related misinformation and conspiracy theories, focusing on the construction of a conceptual framework which is useful for the interpretation of the conspiracy theory phenomenon surrounding COVID-19, and its consequences. Particular socio-environmental conditions (i.e., low educational level, younger age), psychological processes and attitudes (such as low levels of epistemic trust, the avoidance of uncertainty, extraversion, collective narcissism, and a conspiracy-prone mindset), and contextual factors (e.g., high levels of self-perceived risk and anxiety) seem to underpin the adherence to beliefs that are not solely the domain of paranoids and extremists but a widespread phenomenon that has caused important health, social and political consequences

Going Conservative or Conventional? Investigating Farm Management Strategies in between Economic and Environmental Sustainability in Southern Italy

The European “Green Deal” strategy is aimed at making Europe the first climate-neutral continent by 2050 through integrated actions relying on healthier agricultural systems grounded in (environmental and economic) sustainable practices, including soil carbon management and biodiversity enhancement. In this vein, the present study contrasts the economic-environmental performances of conventional (deep tillage) and conservative (no-tillage and soil ripping) practices for two varieties of durum wheat (Triticum turgidum spp. durum), namely a modern (Anco Marzio) and an ancient landrace (Saragolla Lucana) variety in the Basilicata region (Southern Italy). Field and laboratory analysis (granulometry, mineralogy, and geochemistry) as well as satellite data (RapidEye) were used to characterize the soil and vegetation patterns. The empirical results indicate a higher biomass production and vegetative potential together with higher grain yields in soils managed with conventional deep tillage compared with soil managed with conservative practices. Similarly, the modern wheat variety exhibited better performance with respect to the old landrace. The soils managed with conventional practices had a distribution of exchangeable macro-nutrients characterized by a reduction in Ca+ and an increase in Mg2+ and K+ between pre-sowing and post-harvesting. Such a distribution was also genotype-dependent, with a higher variability for Saragolla Lucana than Anco Marzio, showing a diverging adsorption of macro-elements between the modern and ancient landrace varieties

Mechanisms underlying clinical efficacy of Angiotensin II type 2 receptor (AT(2)R) antagonist EMA401 in neuropathic pain: clinical tissue and in vitro studies

BACKGROUND: The clinical efficacy of the Angiotensin II (AngII) receptor AT(2)R antagonist EMA401, a novel peripherally-restricted analgesic, was reported recently in post-herpetic neuralgia. While previous studies have shown that AT(2)R is expressed by nociceptors in human DRG (hDRG), and that EMA401 inhibits capsaicin responses in cultured hDRG neurons, the expression and levels of its endogenous ligands AngII and AngIII in clinical neuropathic pain tissues, and their signalling pathways, require investigation. We have immunostained AngII, AT(2)R and the capsaicin receptor TRPV1 in control post-mortem and avulsion injured hDRG, control and injured human nerves, and in cultured hDRG neurons. AngII, AngIII, and Ang-(1-7) levels were quantified by ELISA. The in vitro effects of AngII, AT(2)R agonist C21, and Nerve growth factor (NGF) were measured on neurite lengths; AngII, NGF and EMA401 effects on expression of p38 and p42/44 MAPK were measured using quantitative immunofluorescence, and on capsaicin responses using calcium imaging. RESULTS: AngII immunostaining was observed in approximately 75% of small/medium diameter neurons in control (n = 5) and avulsion injured (n = 8) hDRG, but not large neurons i.e. similar to TRPV1. AngII was co-localised with AT(2)R and TRPV1 in hDRG and in vitro. AngII staining by image analysis showed no significant difference between control (n = 12) and injured (n = 13) human nerves. AngII levels by ELISA were also similar in control human nerves (4.09 ± 0.36 pmol/g, n = 31), injured nerves (3.99 ± 0.79 pmol/g, n = 7), and painful neuromas (3.43 ± 0.73 pmol/g, n = 12); AngIII and Ang-(1-7) levels were undetectable (<0.03 and 0.05 pmol/g respectively). Neurite lengths were significantly increased in the presence of NGF, AngII and C21 in cultured DRG neurons. AngII and, as expected, NGF significantly increased signal intensity of p38 and p42/44 MAPK, which was reversed by EMA401. AngII mediated sensitization of capsaicin responses was not observed in the presence of MAP kinase inhibitor PD98059, and the kinase inhibitor staurosporine. CONCLUSION: The major AT(2)R ligand in human peripheral nerves is AngII, and its levels are maintained in injured nerves. EMA401 may act on paracrine/autocrine mechanisms at peripheral nerve terminals, or intracrine mechanisms, to reduce neuropathic pain signalling in AngII/NGF/TRPV1-convergent pathways

Nociceptin/Orphanin FQ receptor expression in clinical pain disorders and functional effects in cultured neurons

The Nociceptin/Orphanin FQ peptide receptor (NOP), activated by its endogenous peptide ligand Nociceptin/Orphanin FQ (N/OFQ), exerts several effects including modulation of pain signalling. We have examined, for the first time, the tissue distribution of the NOP receptor in clinical visceral and somatic pain disorders by immunohistochemistry, and assessed functional effects of NOP and [micro] opioid receptor activation in cultured human and rat dorsal root ganglion (DRG) neurons. Quantification of NOP-positive nerve fibres within the bladder sub-urothelium revealed a remarkable several-fold increase in Detrusor Overactivity (p<0.0001) and Painful Bladder Syndrome patient specimens (p=0.0014), compared to controls. In post-mortem control human DRGs, 75-80% of small/medium neurons (<=50 [micro]m diameter) in the lumbar (somatic) and sacral (visceral) DRG were positive for NOP, and fewer large neurons; avulsion-injured cervical human DRG neurons showed similar numbers. NOP-immunoreactivity was significantly decreased in injured peripheral nerves (p=0.0004), and also in painful neuromas (p=0.025). Calcium imaging studies in cultured rat DRG neurons demonstrated dose-dependent inhibition of capsaicin responses in the presence of N/OFQ, with an IC50 of 8.6 pM. In cultured human DRG neurons, 32% inhibition of capsaicin responses was observed in the presence of 1 pM N/OFQ (p<0.001). The maximum inhibition of capsaicin responses was greater with N/OFQ than [mu]-opioid receptor agonist DAMGO. Our findings highlight the potential of NOP agonists, particularly in urinary bladder overactivity and pain syndromes. The regulation of NOP expression in visceral and somatic sensory neurons by target-derived neurotrophic factors deserves further study, and the efficacy of NOP selective agonists in clinical trials

Loss-Based Estimation with Cross-Validation: Applications to Microarray Data Analysis and Motif Finding

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable loss function and candidate estimators are generated using this (or possibly another) loss function. Cross-validation is applied to select an optimal estimator among the candidates and to assess the overall performance of the resulting estimator. This general estimation framework encompasses a number of problems which have traditionally been treated separately in the statistical literature, including multivariate outcome prediction and density estimation based on either uncensored or censored data. This article provides an overview of the methodology and describes its application to two problems in genomic data analysis: the prediction of biological and clinical outcomes (possibly censored) using microarray gene expression measures and the identification of regulatory motifs (i.e., transcription factor binding sites) in DNA sequences

Robotic Therapy for Phantom Limb Pain in Upper Limb Amputees

The system described in this paper combines virtual reality with haptic feedback to increase the level of immersion and invoke the sense of agency in patients with phantom limb pain with the aim of reducing perceived pain. This paper presents three case studies of an on-going clinical study. The initial results suggest an increased sense of embodiment of the virtual limb promotes a decrease in perceived levels of pain. The results strengthen the view that the cortical map does not fully “disappear” yet lays dormant

Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS

Acid-sensing ion channels (ASICs) are a family of ion channels permeable to cations and largely responsible for the onset of acid-evoked ion currents both in neurons and in different types of cancer cells, thus representing a potential target for drug discovery. Owing to the limited attention ASIC2 has received so far, an exploratory program was initiated to identify ASIC2 inhibitors using diminazene, a known pan-ASIC inhibitor, as a chemical starting point for structural elaboration. The performed exploration enabled the identification of a novel series of ASIC2 inhibitors. In particular, compound 2u is a brain penetrant ASIC2 inhibitor endowed with an optimal pharmacokinetic profile. This compound may represent a useful tool to validate in animal models in vivo the role of ASIC2 in different neurodegenerative central nervous system pathologies