Multimodal assessment of painful peripheral neuropathy induced by chronic oxaliplatin-based chemotherapy in mice

<p>Abstract</p> <p>Background</p> <p>A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by <it>in vivo </it>electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice</p> <p>Results</p> <p>We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH.</p> <p>Conclusions</p> <p>Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.</p

Using the Oxford Cognitive Screen to detect cognitive impairment in stroke patients: a comparison with the Mini-Mental State Examination

Background: The Oxford Cognitive Screen (OCS) was recently developed with the aim of describing the cognitive deficits after stroke. The scale consists of 10 tasks encompassing five cognitive domains: attention and executive function, language, memory, number processing, and praxis. OCS was devised to be inclusive and un-confounded by aphasia and neglect. As such, it may have a greater potential to be informative on stroke cognitive deficits of widely used instruments, such as the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment, which were originally devised for demented patients. Objective: The present study compared the OCS with the MMSE with regards to their ability to detect cognitive impairments post-stroke. We further aimed to examine performance on the OCS as a function of subtypes of cerebral infarction and clinical severity. Methods: 325 first stroke patients were consecutively enrolled in the study over a 9-month period. The OCS and MMSE, as well as the Bamford classification and NIHSS, were given according to standard procedures. Results: About a third of patients (35.3%) had a performance lower than the cutoff (<22) on the MMSE, whereas 91.6% were impaired in at least one OCS domain, indicating higher incidences of impairment for the OCS. More than 80% of patients showed an impairment in two or more cognitive domains of the OCS. Using the MMSE as a standard of clinical practice, the comparative sensitivity of OCS was 100%. Out of the 208 patients with normal MMSE performance 180 showed impaired performance in at least one domain of the OCS. The discrepancy between OCS and MMSE was particularly strong for patients with milder strokes. As for subtypes of cerebral infarction, fewer patients demonstrated widespread impairments in the OCS in the Posterior Circulation Infarcts category than in the other categories. Conclusion: Overall, the results showed a much higher incidence of cognitive impairment with the OCS than with the MMSE and demonstrated no false negatives for OCS vs MMSE. It is concluded that OCS is a sensitive screen tool for cognitive deficits after stroke. In particular, the OCS detects high incidences of stroke-specific cognitive impairments, not detected by the MMSE, demonstrating the importance of cognitive profiling

How face perception and visual orienting interact: a comparison between infants and adults

The aim of this dissertation is to investigate the role of face and non-face stimuli in influencing the orienting of visuo-spatial attention, both in infants and adults. Visual orienting of attention and face processing are two theme issues that, separately, have a long research tradition. Less extensive is the literature that has tried to connect the two areas, to verify whether face stimuli, to which we are biased to pay attention even from birth, might bias the allocation of visual attention, when compared with non-face stimuli. Considering that faces in adults are processing by a specific anatomical and functional face system, that becomes increasingly specialized as a consequence of an experience-dependent activity, the purpose of this dissertation is to compare the performance of adult participants and infant participants of different ages. In particular, the hypothesis is that, given a different degree of experience with faces in infancy and adulthood, different will be the degree of influence of this stimuli on orienting of visual attention. With this consideration in mind, my dissertation begins with three theoretical chapters: Chapter 1 describes the mechanisms of visual orienting and the way to study it in adults; Chapter 2 refers to the development of visual orienting in infancy jointly to the maturation of neural substrates that mediate its mechanisms, and to the behavioral performances putatively linked to these substrates; Chapter 3 describes face processing both in adults and infants accordingly to an experience-dependent perspective. Subsequently, in the second part of the dissertation I describe two studies aiming at investigating the role of face and non-face stimuli in biasing orienting of attention, by means of two attentive effects, already documented both in adults and infants. Importantly, adults and infants are administered the same experimental paradigms, and their eye movements are recorded by means of an eye-tracker system (ASL). In particular in Study 1 (Chapter 4) the modulation of the inhibition of return effect by social stimuli to the detriment of non-social stimuli is investigated in adults and 4- and 7-month-old infants. The inhibition of return refers to a bias against attending to visual stimuli at recently attended locations. I hypothesized that an upright face (social stimulus) that compared in the previously attended location, given its biological value, could escape this spatial tagging, when compared with inverted face and house (non-social stimuli). Results seems to confirm a overall modulation of the inhibition of return effect, that is different according to the different ages tested. In Study 2 (Chapter 5) the gap effect is employed, with the aim to verify if the attention disengagement could be modulated by social stimuli to the detriment of non-social stimuli, in adults and 4- and 7-month-old infants. The gap effect consists in a reduction in the disengagement latency toward peripherally appearing targets when the fixation point disappears a short time before target (gap trials), compared to when both the fixation point and the peripheral target stay together on the screen (overlap trials). I hypothesized (Study 2a) that the disengagement latencies would be affected by the presence of an upright face (social stimulus) as fixation point or peripheral target more than an inverted or a noise face (non-social stimuli). Further I hypothesized (Study 2b) that the disengagement latencies would be affected by the presence of emotional expressions (social stimuli) as fixation point or peripheral target more than a noise face (non-social stimulus). Results seems to confirm a overall modulation of disengagement latencies only in the overlap trials by the social stimuli, but this modulation varies according to the different ages tested. Overall the results confirm a modulation of orienting of attention by the nature of the stimuli employed, but, as hypothesized, given a different degree of experience with faces in infancy and adulthood, different is degree of influence of this stimuli on orientingL’obiettivo di questa tesi è quello di indagare il ruolo dei volti e dei non volti nell’orientamento dell’attenzione visuo-spaziale, sia nei bambini che negli adulti. L’orientamento dell’attenzione visiva e il processamento del volto sono due temi che, separatamente, hanno una lunga tradizione di ricerca. Meno estesa è la letteratura che ha provato a collegare le due aree, per verificare se gli stimoli volti, per i quali siamo propensi a prestare attenzione fin dalla nascita, possano influenzare l’orientamento dell’attenzione visiva, quando confrontati con stimoli non volti. Considerando che i volti negli adulti sono processati da un specifico sistema anatomico e funzionale, che diventa progressivamente specializzato in conseguenza di una crescente esperienza, lo scopo della tesi è confrontare la performance di soggetti adulti e di bambini di diverse età. In particolare, l’ipotesi riguarda il fatto che, dato un diverso grado di esperienza con i volti nell’infanzia e nell’età adulta, diverso sia il gradi di influenza di questi stimoli sull’orientamento dell’attenzione visiva. Sulla base di queste considerazioni, la mia tesi inizia con tre capitoli teorici: il Capitolo 1 descrive i meccanismi di orientamento visivo ed i modi per studiarli negli adulti; il Capitolo 2 si riferisce allo sviluppo dell’orientamento visivo nell’infanzia, unitamente alla maturazione dei substrati neurali che sottostanno ai suoi meccanismi, e ai compiti comportamentali che si presume siano connessi a tali substrati; il Capitolo 3 descrive il processamento dei volti sia negli adulti che nei bambini in accordo ad una prospettiva dipendente dall’esperienza. Successivamente, nella seconda parte della tesi descrivo due studi tesi ad indagare il ruolo di stimoli volti e non volti nell’influenzare l’orientamento dell’attenzione, attraverso due effetti attentivi già dimostrati sia negli adulti che nei bambini. Ad adulti e bambini sono stati somministrati gli stessi paradigmi sperimentali ed i loro movimenti oculari sono stati registrati tramite un sistema di inseguimento dei movimenti oculari (ASL). In particolare nello Studio 1 (Capitolo 4) si è indagata la modulazione dell’effetto di inibizione di ritorno da parte di stimoli sociali, a discapito di stimoli non sociali, in adulti e in bambini di 4 e 7 mesi di vita. L’inibizione di ritorno si riferisce ad un bias a riportare l’attenzione verso uno stimolo visivo che compare in una posizione già esplorata. Ho ipotizzato che un volto dritto (stimolo sociale) che compariva in una posizione spaziale già esplorata, dato il suo valore biologico, poteva sottrarsi all’etichettatura spaziale, quando confrontato con un volto invertito e con una casa (stimoli non sociali). I risultati confermano un generale effetto di modulazione dell’effetto di inibizione di ritorno, che varia in base alle diverse età testate. Nello Studio 2 (Capitolo 5) si è utilizzato l’effetto gap, con l’obiettivo di verificare se il disancoraggio dell’attenzione potesse essere modulato dagli stimoli sociali a discapito di quelli non sociali, in adulti e bambini di 4 e 7 mesi di vita. L’effetto gap consiste in una riduzione delle latenze di disancoraggio verso target periferici, quando il punto di fissazione scompare un certo intervallo di tempo prima della comparsa del target (trial gap), rispetto a quando sia il punto di fissazione che il target periferico restano entrambi sul monitor (trial overlap). Ho ipotizzato (Studio 2a) che le latenze di disancoraggio sarebbero state influenzate dalla presenza di un volto dritto (stimolo sociale) come punto di fissazione o target periferico più di un volto invertito o di un non volto (stimoli non sociali). Inoltre, ho ipotizzato (Studio 2b) che le latenze di disancoraggio sarebbero state influenzate dalla presenza di espressioni emotive (stimoli sociali) come punti di fissazione o target periferici più di un non volto (stimolo non sociale). I risultati sembrano confermare un generale modulazione del disancoraggio dell’attenzione solo nei trial overlap da parte degli stimoli sociali, ma questa modulazione varia in base alle diverse età testate. Globalmente i dati confermano una modulazione dell’orientamento dell’attenzione da parte della natura degli stimoli utilizzati, ma, come ipotizzato, dato un diverso grado di esperienza con i volti nell’infanzia e nell’età adulta, diverso è il gradi di influenza di questi stimoli sull’orientament

How face perception and visual orienting interact: a comparison between infants and adults

The aim of this dissertation is to investigate the role of face and non-face stimuli in influencing the orienting of visuo-spatial attention, both in infants and adults. Visual orienting of attention and face processing are two theme issues that, separately, have a long research tradition. Less extensive is the literature that has tried to connect the two areas, to verify whether face stimuli, to which we are biased to pay attention even from birth, might bias the allocation of visual attention, when compared with non-face stimuli. Considering that faces in adults are processing by a specific anatomical and functional face system, that becomes increasingly specialized as a consequence of an experience-dependent activity, the purpose of this dissertation is to compare the performance of adult participants and infant participants of different ages. In particular, the hypothesis is that, given a different degree of experience with faces in infancy and adulthood, different will be the degree of influence of this stimuli on orienting of visual attention. With this consideration in mind, my dissertation begins with three theoretical chapters: Chapter 1 describes the mechanisms of visual orienting and the way to study it in adults; Chapter 2 refers to the development of visual orienting in infancy jointly to the maturation of neural substrates that mediate its mechanisms, and to the behavioral performances putatively linked to these substrates; Chapter 3 describes face processing both in adults and infants accordingly to an experience-dependent perspective. Subsequently, in the second part of the dissertation I describe two studies aiming at investigating the role of face and non-face stimuli in biasing orienting of attention, by means of two attentive effects, already documented both in adults and infants. Importantly, adults and infants are administered the same experimental paradigms, and their eye movements are recorded by means of an eye-tracker system (ASL). In particular in Study 1 (Chapter 4) the modulation of the inhibition of return effect by social stimuli to the detriment of non-social stimuli is investigated in adults and 4- and 7-month-old infants. The inhibition of return refers to a bias against attending to visual stimuli at recently attended locations. I hypothesized that an upright face (social stimulus) that compared in the previously attended location, given its biological value, could escape this spatial tagging, when compared with inverted face and house (non-social stimuli). Results seems to confirm a overall modulation of the inhibition of return effect, that is different according to the different ages tested. In Study 2 (Chapter 5) the gap effect is employed, with the aim to verify if the attention disengagement could be modulated by social stimuli to the detriment of non-social stimuli, in adults and 4- and 7-month-old infants. The gap effect consists in a reduction in the disengagement latency toward peripherally appearing targets when the fixation point disappears a short time before target (gap trials), compared to when both the fixation point and the peripheral target stay together on the screen (overlap trials). I hypothesized (Study 2a) that the disengagement latencies would be affected by the presence of an upright face (social stimulus) as fixation point or peripheral target more than an inverted or a noise face (non-social stimuli). Further I hypothesized (Study 2b) that the disengagement latencies would be affected by the presence of emotional expressions (social stimuli) as fixation point or peripheral target more than a noise face (non-social stimulus). Results seems to confirm a overall modulation of disengagement latencies only in the overlap trials by the social stimuli, but this modulation varies according to the different ages tested. Overall the results confirm a modulation of orienting of attention by the nature of the stimuli employed, but, as hypothesized, given a different degree of experience with faces in infancy and adulthood, different is degree of influence of this stimuli on orientingL’obiettivo di questa tesi è quello di indagare il ruolo dei volti e dei non volti nell’orientamento dell’attenzione visuo-spaziale, sia nei bambini che negli adulti. L’orientamento dell’attenzione visiva e il processamento del volto sono due temi che, separatamente, hanno una lunga tradizione di ricerca. Meno estesa è la letteratura che ha provato a collegare le due aree, per verificare se gli stimoli volti, per i quali siamo propensi a prestare attenzione fin dalla nascita, possano influenzare l’orientamento dell’attenzione visiva, quando confrontati con stimoli non volti. Considerando che i volti negli adulti sono processati da un specifico sistema anatomico e funzionale, che diventa progressivamente specializzato in conseguenza di una crescente esperienza, lo scopo della tesi è confrontare la performance di soggetti adulti e di bambini di diverse età. In particolare, l’ipotesi riguarda il fatto che, dato un diverso grado di esperienza con i volti nell’infanzia e nell’età adulta, diverso sia il gradi di influenza di questi stimoli sull’orientamento dell’attenzione visiva. Sulla base di queste considerazioni, la mia tesi inizia con tre capitoli teorici: il Capitolo 1 descrive i meccanismi di orientamento visivo ed i modi per studiarli negli adulti; il Capitolo 2 si riferisce allo sviluppo dell’orientamento visivo nell’infanzia, unitamente alla maturazione dei substrati neurali che sottostanno ai suoi meccanismi, e ai compiti comportamentali che si presume siano connessi a tali substrati; il Capitolo 3 descrive il processamento dei volti sia negli adulti che nei bambini in accordo ad una prospettiva dipendente dall’esperienza. Successivamente, nella seconda parte della tesi descrivo due studi tesi ad indagare il ruolo di stimoli volti e non volti nell’influenzare l’orientamento dell’attenzione, attraverso due effetti attentivi già dimostrati sia negli adulti che nei bambini. Ad adulti e bambini sono stati somministrati gli stessi paradigmi sperimentali ed i loro movimenti oculari sono stati registrati tramite un sistema di inseguimento dei movimenti oculari (ASL). In particolare nello Studio 1 (Capitolo 4) si è indagata la modulazione dell’effetto di inibizione di ritorno da parte di stimoli sociali, a discapito di stimoli non sociali, in adulti e in bambini di 4 e 7 mesi di vita. L’inibizione di ritorno si riferisce ad un bias a riportare l’attenzione verso uno stimolo visivo che compare in una posizione già esplorata. Ho ipotizzato che un volto dritto (stimolo sociale) che compariva in una posizione spaziale già esplorata, dato il suo valore biologico, poteva sottrarsi all’etichettatura spaziale, quando confrontato con un volto invertito e con una casa (stimoli non sociali). I risultati confermano un generale effetto di modulazione dell’effetto di inibizione di ritorno, che varia in base alle diverse età testate. Nello Studio 2 (Capitolo 5) si è utilizzato l’effetto gap, con l’obiettivo di verificare se il disancoraggio dell’attenzione potesse essere modulato dagli stimoli sociali a discapito di quelli non sociali, in adulti e bambini di 4 e 7 mesi di vita. L’effetto gap consiste in una riduzione delle latenze di disancoraggio verso target periferici, quando il punto di fissazione scompare un certo intervallo di tempo prima della comparsa del target (trial gap), rispetto a quando sia il punto di fissazione che il target periferico restano entrambi sul monitor (trial overlap). Ho ipotizzato (Studio 2a) che le latenze di disancoraggio sarebbero state influenzate dalla presenza di un volto dritto (stimolo sociale) come punto di fissazione o target periferico più di un volto invertito o di un non volto (stimoli non sociali). Inoltre, ho ipotizzato (Studio 2b) che le latenze di disancoraggio sarebbero state influenzate dalla presenza di espressioni emotive (stimoli sociali) come punti di fissazione o target periferici più di un non volto (stimolo non sociale). I risultati sembrano confermare un generale modulazione del disancoraggio dell’attenzione solo nei trial overlap da parte degli stimoli sociali, ma questa modulazione varia in base alle diverse età testate. Globalmente i dati confermano una modulazione dell’orientamento dell’attenzione da parte della natura degli stimoli utilizzati, ma, come ipotizzato, dato un diverso grado di esperienza con i volti nell’infanzia e nell’età adulta, diverso è il gradi di influenza di questi stimoli sull’orientament

Facial expressions as a model to test the role of the sensorimotor system in the visual perception of the actions

A long-term debate concerns whether the sensorimotor coding carried out during transitive actions observation reflects the low-level movement implementation details or the movement goals. On the contrary, phonemes and emotional facial expressions are intransitive actions that do not fall into this debate. The investigation of phonemes discrimination has proven to be a good model to demonstrate that the sensorimotor system plays a role in understanding actions acoustically presented. In the present study, we adapted the experimental paradigms already used in phonemes discrimination during face posture manipulation, to the discrimination of emotional facial expressions. We submitted participants to a lower or to an upper face posture manipulation during the execution of a four alternative labelling task of pictures randomly taken from four morphed continua between two emotional facial expressions. The results showed that the implementation of low-level movement details influence the discrimination of ambiguous facial expressions differing for a specific involvement of those movement details. These findings indicate that facial expressions discrimination is a good model to test the role of the sensorimotor system in the perception of actions visually presented

Detecting Fakers of the autobiographical IAT

Autobiographical memories might be identified using a variant of the implicit association test (IAT), or the autobiographical IAT (aIAT). The IAT provides a measure of association between true sentences and sentences describing an autobiographical event. This tool might be used to evaluate whether specific autobiographical information is encoded within the respondent’s mind/brain. This paper examines possible problems arising when the aIAT is used as a lie-detector technique. The results indicate that, when given previous instruction or training with an aIAT, examinees can alter their results and beat the ‘memory-detector’. However, we have been able to detect successful fakers of aIATon the basis of their specific response patterns. Our algorithm has the ability to spot the faker in a satisfactory manner. If, as demonstrated here, faking can be detected, then the real autobiographical event might also be identified when the examinee attempts to alter their results

Newborns’ attention is driven by the translational movement

The present study investigated whether 2-day-old newborns are able to discriminate two translating meaningless Point-Light Displays (PLD) videos, in which the shape of one of them changes compared to that of the other along the trajectory, independently from movement kinematics, and if this ability is present both when stimuli differed at the end or at the beginning of the movement. To manipulate the instant in which along the movement the difference between stimuli was evident, and to maintain every unspecific dissimilarity possibly determining the preference, videos were played in a loop either forward or backwards. In Experiment 1, PLD stimuli moved with natural accelerated-decelerated kinematics; in Experiment 2 they moved at constant velocity. Four groups of newborns were submitted to the preferential looking technique experiments. Results showed that newborns looked longer at natural kinematics and that, irrespective of the type of kinematics, they discriminated the two stimuli only when videos were played forward, that is, only when stimuli differed at the end of the movement. These data suggest that, independently from kinematics, movement translational components induce newborns to allocate attention at the end of the observed movement. Given the strict link between attention and eye movements, we suggest that this effect may bootstrap the system and give rise to proactive gaze, the typical gaze behaviour present during executed and observed goal-directed actions

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study

Abstract Objective To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. Study design Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n = 23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n = 20), letrozole (2.5 mg/day; group L; n = 11) or ulipristal acetate (5 mg/day; group U; n = 7). Patients underwent hysteroscopic resection of the myomas. Results All medical treatments caused a significant decrease in the volume of myomas (group T, p <.001; group L, p <.001; group U, p =.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p =.001) and in group L (p =.010). The hysteroscopy time was higher in group S than in group T (p <.001) and in group L (p =.001); there was no significant difference in the hysteroscopy time between group S and group U (p =.206). Fluid absorption was lower in group T than in group S (p =.002) and in group L than in group S (p =.048); fluid absorption was similar in group S and group U (p =.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p <.005). Conclusions Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas

Combining implicit and explicit techniques to reveal social desirability bias in electricity conservation self-reports

none6While questionnaires are still the most common way to survey consumers’ behaviors, it is known that respondents’ answers can be affected by the social desirability attributed to the behavior under investigation. To check whether a social desirability bias also affects electricity consumption self-reports, a study was carried out adopting an explicit (questionnaire) and implicit measurement technique (the autobiographical Implicit Association Test). Three behaviors were probed in this way, with a sample of 180 participants (60 for each behavior). The analysis of the congruence between explicit and implicit answers confirms that desirability bias is at stake in self-reported measures of electricity conservation; it also shows that different behaviors—in this same domain—can be subject to this bias to a different extent and that a considerable amount of participants need to be considered as ambivalent. The methodological and conceptual implications of these findings and of the method are discussed with respect to pro-environmental studies and interventions.noneGamberini; L.; Spagnolli; A.; Corradi; N.; Sartori; G.; Ghirardi; V.; Jacucci; G.Gamberini, Luciano; Spagnolli, Anna; Corradi, N.; Sartori, Giuseppe; Ghirardi, Valentina; Jacucci, G