The diagnostic accuracy of the small fiber neuropathy symptoms inventory questionnaire (SFN-SIQ) for identifying pure small fiber neuropathy

A definite diagnosis of pure small fiber neuropathy (SFN) relies on specific diagnostic testing, such as skin biopsy, quantitative sensory testing (QST), and nociceptive evoked potentials, which require considerable resources that may not be widely available. Accordingly, diagnostic tools with easy implementation in non-specialist centers are warranted to identify patients who require second-level diagnostic tests. In this study, we aimed to test the accuracy of the Small Fiber Neuropathy Symptoms Inventory Questionnaire (SFN-SIQ) in diagnosing pure SFN. We enrolled 86 patients with suspected pure SFN. In these patients, we calculated the diagnostic accuracy of the SFN-SIQ using a combination of clinical examination, QST, and skin biopsy as a reference standard. We found that the SFN-SIQ showed an excellent ability to discriminate between patients with and without pure SFN, with 86% sensitivity and 70% specificity in the diagnosis of pure SFN. Our study providing the diagnostic yield of the SFN-SIQ for pure SFN diagnosis suggests that this questionnaire might be used to screen patients with suspected SFN and identify those requiring second-level diagnostic tests such as QST, skin biopsy, or nociceptive evoked potentials

Notch signaling sustains the expression of Mcl-1 and the activity of eIF4E to promote cell survival in CLL

In chronic lymphocytic leukemia (CLL), Notch1 and Notch2 signaling is constitutively activated and contributes to apoptosis resistance. We show that genetic inhibition of either Notch1 or Notch2, through small-interfering RNA, increases apoptosis of CLL cells and is associated with decreased levels of the anti-apoptotic protein Mcl-1. Thus, Notch signaling promotes CLL cell survival at least in part by sustaining Mcl-1 expression. In CLL cells, an enhanced Notch activation also contributes to the increase in Mcl-1 expression and cell survival induced by IL-4.Mcl-1 downregulation by Notch targeting is not due to reduced transcription or degradation by caspases, but in part, to increased degradation by the proteasome. Mcl-1 downregulation by Notch targeting is also accompanied by reduced phosphorylation of eukaryotic translation initiation factor 4E (eIF4E), suggesting that this protein is another target of Notch signaling in CLL cells.Overall, we show that Notch signaling sustains CLL cell survival by promoting Mcl-1 expression and eIF4E activity, and given the oncogenic role of these factors, we underscore the therapeutic potential of Notch inhibition in CLL

Tunneling mediated by conical waves in a 1D lattice

The nonlinear propagation of 3D wave-packets in a 1D Bragg-induced band-gap system, shows that tranverse effects (free space diffraction) affect the interplay of periodicity and nonlinearity, leading to the spontaneous formation of fast and slow conical localized waves. Such excitation corresponds to enhanced nonlinear transmission (tunneling) in the gap, with peculiar features which differ on the two edges of the band-gap, as dictated by the full dispersion relationship of the localized waves.Comment: 5 pages, 6 figure

Pain associated with COVID-19 vaccination is unrelated to skin biopsy abnormalities

Previous clinical observations raised the possibility that COVID-19 vaccination might trigger a small-fibre neuropathy.Objectives:In this uncontrolled observational study, we aimed to identify small fibre damage in patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination.Methods:We collected clinical data, including a questionnaire for assessing autonomic symptoms (Composite Autonomic Symptom Score-31), and investigated quantitative sensory testing (QST) and skin biopsy in 15 prospectively enrolled patients with generalized sensory symptoms and pain after COVID-19 vaccination. Nine patients complaining of orthostatic intolerance also underwent cardiovascular autonomic tests.Results:We found that all patients experienced widespread pain, and most of them (11 of 15) had a fibromyalgia syndrome. All patients had normal skin biopsy findings, and in the 9 patients with orthostatic intolerance, cardiovascular autonomic tests showed normal findings. Nevertheless, 5 patients had cold and warm detection abnormalities at the QST investigation.Conclusions:In our study, most patients complaining of generalized sensory symptoms and pain after COVID-19 vaccination had clinical and diagnostic test findings compatible with a fibromyalgia syndrome. Although the abnormal QST findings we found in 5 patients might be compatible with a small-fibre neuropathy, they should be cautiously interpreted given the psychophysical characteristics of this diagnostic test. Further larger controlled studies are needed to define precisely the association between small fibre damage and COVID-19 vaccination

Predicting value for incomplete recovery in Bell's palsy of facial nerve ultrasound versus nerve conduction study

Objective This longitudinal study aims at assessing the predictive value of facial nerve high-resolution ultrasound (HRUS) for incomplete clinical recovery in patients with Bell’s palsy, the most common facial nerve disease. Methods We prospectively enrolled 34 consecutive patients with Bell’s palsy. All patients underwent neurophysiological testing (including facial nerve conduction study) and HRUS evaluations 10-15 days (T1), one month (T2), and three months (T3) after the onset of Bell’s palsy. Patients who did not experience complete recovery within three months were also evaluated after six months (T4). We have then compared the accuracy of HRUS with that of the facial nerve conduction study in predicting incomplete clinical recovery at three and six months. Results At T1, the facial nerve diameter, as assessed with HRUS, was larger on the affected side than on the normal side, particularly in patients with incomplete recovery at T2, T3 and T4. ROC curve analysis, however, showed that the facial nerve diameter at T1 had a lower predictive value than the facial nerve conduction study for an incomplete clinical recovery at three (T3) and six (T4) months. Still, the facial nerve diameter asymmetry, as assessed with HRUS, had a relatively high negative predictive value (thus indicating a strong association between normal HRUS examination and a good prognosis). Conclusions Although HRUS shows abnormally increased facial nerve diameter in patients in the acute phase of Bell’s palsy, the predictive value of this technique for incomplete clinical recovery at three and six months is lower than that of the nerve conduction study. Significance: Nerve ultrasound has a low predictive value for incomplete clinical recovery in patients with Bell’s Palsy

How different experimental models of secondary hyperalgesia change the nociceptive flexion reflex

In this neurophysiological study in healthy humans, we assessed how central sensitization induced by either high-frequency stimulation (HFS) or topical capsaicin application modulates features of the RIII reflex response. The ability of these stimuli to engage the endogenous pain modulatory system was also tested. In 26 healthy participants we elicited an RIII reflex using suprathreshold stimulation of the sural nerve. Subsequently HFS or capsaicin were applied to the foot and the RIII reflex repeated after 15 minutes. Contact heating of the volar forearm served as the heterotopic test stimulus to probe activation of the endogenous pain modulatory system. HFS significantly reduced the pain threshold by 29% and the RIII reflex threshold by 20%. Capsaicin significantly reduced the pain threshold by 17% and the RIII reflex threshold by 18%. Both HFS and capsaicin left RIII reflex size unaffected. Numerical Rating Scale (NRS) pain scores elicited by the heterotopic noxious heat stimulus were unaffected by capsaicin and slightly increased by HFS. HFS and capsaicin similarly modulated the pain threshold and RIII reflex threshold, without a concomitant inhibitory effect of the endogenous pain modulatory system. Our neurophysiological study supports the use of the RIII reflex in investigating central sensitization in humans

Wind Direction Data from a Coastal HF Radar System in the Gulf of Naples (Central Mediterranean Sea)

Results on the accuracy of SeaSonde High Frequency (HF) radar wind direction measurements in the Gulf of Naples (Southern Tyrrhenian Sea, Central Mediterranean Sea) are here presented. The investigation was carried out for a winter period (2 February–6 March) and for one summer month (August) of the reference year 2009. HF radar measurements were compared with in situ recordings from a weather station and with model data, with the aim of resolving both small scale and large scale dynamics. The analysis of the overall performance of the HF radar system in the Gulf of Naples shows that the data are reliable when the wind speed exceeds a 5 m/s threshold. Despite such a limitation, this study confirms the potentialities of these systems as monitoring platforms in coastal areas and suggests further efforts towards their improvement

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

Phase 1 clinical trials represent a critical phase of drug development because new candidate therapeutic agents are tested for the first time on humans. Therefore, international guidelines and local laws have been released to mitigate and control possible risks for human health in agreement with the declaration of Helsinki and the international Good Clinical Practice principles. Despite numerous scientific works characterizing the registered clinical trials on ClinicalTrials.gov, the main features and trends of registered phase 1 clinical trials in Europe have not been investigated. This study is aimed at assessing the features and the temporal trend of distribution of phase 1 clinical studies, carried out in the five largest European countries over a ten-year period (2012-2021), and to evaluate the impact of the Italian regulatory framework on the activation of such studies

Prenatal expression of d-aspartate oxidase causes early cerebral d-aspartate depletion and influences brain morphology and cognitive functions at adulthood

The free d-amino acid, d-aspartate, is abundant in the embryonic brain but significantly decreases after birth. Besides its intracellular occurrence, d-aspartate is also present at extracellular level and acts as an endogenous agonist for NMDA and mGlu5 receptors. These findings suggest that d-aspartate is a candidate signaling molecule involved in neural development, influencing brain morphology and behaviors at adulthood. To address this issue, we generated a knockin mouse model in which the enzyme regulating d-aspartate catabolism, d-aspartate oxidase (DDO), is expressed starting from the zygotic stage, to enable the removal of d-aspartate in prenatal and postnatal life. In line with our strategy, we found a severe depletion of cerebral d-aspartate levels (up to 95%), since the early stages of mouse prenatal life. Despite the loss of d-aspartate content, Ddo knockin mice are viable, fertile, and show normal gross brain morphology at adulthood. Interestingly, early d-aspartate depletion is associated with a selective increase in the number of parvalbumin-positive interneurons in the prefrontal cortex and also with improved memory performance in Ddo knockin mice. In conclusion, the present data indicate for the first time a biological significance of precocious d-aspartate in regulating mouse brain formation and function at adulthood