Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption.

In a previously published double-blind, placebo-controlled study, we showed that probiotics intake exerted a positive effect on sleep quality and a general improvement across time in different aspects of the profile of mood state, like sadness, anger, and fatigue in 33 healthy individuals. The present work investigates the impact of the probiotic product, constituted of Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 (all former members of Lactobacillus genus), and Bifidobacterium longum 04, on the gut microbiota composition of the same cohort through a metabarcoding analysis. Both the placebo and probiotic treatments had a significant impact on the microbiota composition. Statistical analysis showed that the microbiota of the individuals could be clustered into three groups, or bacteriotypes, at the baseline, and, inherently, bacterial compositions were linked to different responses to probiotic and placebo intakes. Interestingly, L. rhamnosus and L. fermentum were retrieved in the probiotic-treated cohort, while a bifidogenic effect of maltodextrin, used as placebo, was observed. The present study shed light on the importance of defining bacteriotypes to assess the impact of interventions on the gut microbiota and allowed to reveal microbial components which could be related to positive effects (i.e. sleep quality improvement) to be verified in further studies.

Daily bathing with 4% chlorhexidine gluconate in intensive care settings: a randomized controlled trial.

OBJECTIVES: To investigate whether daily bathing with a soap-like solution of 4% chlorhexidine (CHG) followed by water rinsing (CHGwr) would decrease the incidence of hospital-acquired infections (HAI) in intensive care settings. METHODS: Randomized, controlled trial; infectious diseases specialists were blinded to the intervention status. All patients admitted to the Intensive Care Unit (ICU) and to the Post-operative Cardiosurgical Intensive Care Unit (PC-ICU) of the University Hospital of Perugia were enrolled and randomized to the intervention arm (daily bathing with 4% CHGwr) or to the control arm (daily bathing with standard soap). The incidence rate of acquisition of HAI was compared between the two arms as primary outcome. We also evaluated the incidence of bloodstream infections (BSI), central-line-associated BSI (CLABSI), ventilator-associated pneumonia (VAP) and catheter-associated urinary tract infections (CAUTI), and 4% CHGwr safety. RESULTS: In all, 449 individuals were enrolled, 226 in treatment arm and 223 in control arm. Thirty-four individuals of the 226 (15%) and 57 (25.6%) suffered from at least an HAI in the intervention and control arms, respectively (p 0.008); 23.2 and 40.9 infections/1000 patient-days were detected in the intervention arm and control arm, respectively (p 0.037). The incidence of all bloodstream infections (BSI plus CABSI) was significantly reduced in the intervention arm (9.2 versus 22.6 infections/1000 patient-days, p 0.027); no differences were observed in the mortality between the two arms. CONCLUSIONS: Daily bathing with 4% CHGwr significantly reduced HAI incidence in intensive care settings. CLINICALTRIAL. GOV REGISTRATION: NCT03639363.

Behavioral and neurophysiological investigation of the influence of verbal suggestion on tactile perception.

Recently we demonstrated that it is possible to influence tactile perception by applying a placebo manipulation consisting of verbal suggestion and conditioning and that this influence is associated to changes in the late components (N140 and P200) of somatosensory-evoked potentials (SEPs) (Fiorio et al., 2012). Due to the powerful effects of words in changing symptoms perception in the clinical domain, aim of this study was to investigate whether even in the tactile modality, perception can be changed by the mere use of persuasive words in a specific context. To this purpose, we adopted the same experimental setting of our previous study, apart from the conditioning procedure. A group of subjects (experimental group) has been verbally suggested about the effect of an inert cream in enhancing tactile perception, while a control group was informed about the inefficacy of the cream. In order to unveil the neurophysiological underpinnings of this effect, we compared the amplitude of late SEPs (P100, N140, P200), before and after treatment. Results showed that the experimental group did not perceive an increase of tactile sensation after the treatment and no modification occurred in the late SEPs. This study proves that verbal suggestion alone is not sufficient to induce enhanced tactile perception (at least with this experimental setting), suggesting that a conditioning procedure may be necessary in the tactile modality. The absence of changes in the late SEP components could reflect the lack of strong expectation following the placebo procedure.

Extragenetic factors and clinical penetrance of DYT1 dystonia: an exploratory study.

Factors modifying the clinical penetrance of DYT1 dystonia are incompletely defined. Particularly, the contribution of extragenetic factors has been subject to only limited investigation and remains largely unexplored. A possible effect of childhood infections has been proposed, and the effect of other factors, such as perinatal adversity and trauma, has not been systematically investigated. We performed an exploratory analysis of the exposure to perinatal adversity, childhood infections, general anaesthesia and trauma comparing 39 manifesting carriers of the ∆GAG mutation, 23 non-manifesting carriers and 48 non-carriers from a multi-centre European series of 28 families with DYT1 dystonia, by means of a self-completed questionnaire and clinical interview. Detailed information on perinatal adversities (pre-term birth, complications at natural delivery, urgent caesarean section), previous childhood infections, and prior general anaesthesia or physical trauma was recorded. A positive association between a history of complications of vaginal delivery and manifestation of dystonia was detected, which was not confounded by age, gender, or education level (odds ratio 8.47, 95 % confidence interval 1.45-49.4, p = 0.02). We could not observe any significant association between presence of dystonia and the other investigated variables. Comparing non-manifesting carriers to non-carriers, the presence of the ∆GAG mutation per se was not associated with any of the environmental exposures explored. Perinatal adversities might modulate the clinical penetrance of DYT1 dystonia; their interaction with known genetic factors modifying penetrance of this condition should be investigated in new, larger collaborative studies.

Motor system modulation for movement direction and rotation angle during motor imagery.

Transcranial magnetic stimulation (TMS) studies have shown that the motor system is facilitated when we imagine performing motor actions. However, it is not clear whether the individual's motor system modulates bilaterally and selectively for task parameters, such as movement direction and amplitude. To investigate this issue, we applied single-pulse TMS over the left and right primary motor cortex (M1) of healthy subjects, who had to imagine grasping and rotating a clock hour hand, having a starting position at noon, towards four different times: 2, 5, 7 and 10 o'clock. Rotations could be in clockwise (2 and 5 o'clock) or counter-clockwise (7 and 10 o'clock) directions and could require small (2 and 10 o'clock) or large (5 and 7 o'clock) rotation angle. TMS motor-evoked potentials were recorded for three muscles, and movements were imagined with the right and left hands. Results showed that during motor imagery a mirroring pattern was present between the right and the left motor cortices, showing selective activation of the hand-intrinsic muscles spatially close to the direction of the imagined movement. Overall a higher activation for large and a lower activation for small rotation angle were found, but no selective muscle activity was present within the hand-intrinsic muscles for this parameter. Following these results we propose that during action imagination an internally coded covariance between movement parameters is present with a muscle-specific activation for movement direction.

Enhancing non-noxious perception: behavioural and neurophysiological correlates of a placebo-like manipulation.

Sensory perception can be influenced by cognitive functions like attention and expectation. An emblematic case of this is the placebo effect, where a reduction in pain perception can be obtained by inducing expectation of benefit following a treatment. The current study assessed the behavioural and brain activity correlates of a placebo procedure inducing an enhancement of non-noxious somatic sensation. An experimental group was verbally suggested and surreptitiously conditioned about the effect of an inert cream in enhancing tactile perception, while a control group was informed about the actual inefficacy of the cream. Both groups received non-noxious electric shocks activating A-Beta fibres on the right index finger, before and after application of the cream in the same site. The behavioural and neurophysiological effects of this procedure were measured by a numerical rating scale of subjective perception and by recording cortical and subcortical somatosensory-evoked potentials (SEPs). Although the intensity of stimulation was physically identical in the two sessions, the experimental group reported stronger tactile sensation after cream treatment than before. In parallel, the experimental group showed enhanced somatosensory cortical responses (N140, P200) after treatment, whereas subcortical and early-cortical SEP components did not change. We suggest that these findings reflect top-down modulation on tactile perception probably due to an interplay between expectation and attention and might rely on interactions between prefrontal and parietal brain regions.

Abnormal tactile temporal discrimination in psychogenic dystonia.

OBJECTIVE: Neurophysiologic studies demonstrated that patients with primary torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar abnormalities in the motor system. In this study, we evaluated somatosensory function in Psy-D by testing temporal discrimination threshold (TDT), and compared the results with those obtained in patients with PTD. METHODS: TDT of tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and 16 control subjects. The 2 groups of patients were matched for age, gender, disease duration, and distribution of dystonia. Tactile stimuli consisted of pairs of non-noxious electrical shocks delivered to the right or left hand at interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was defined as the value at which subjects recognized the 2 stimuli as asynchronous. RESULTS: TDT was higher in Psy-D and PTD compared to control subjects, for both the right and the left hand. In a subgroup of patients with unilateral dystonia (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected side in both groups of patients. Disease duration was not correlated to the increased TDT value. CONCLUSIONS: Our study suggests an impaired processing of somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a neurophysiological trait predisposing to develop a dystonic posture triggered by psychiatric and psychological factors.

Corticospinal excitability during action observation in task-specific dystonia: a transcranial magnetic stimulation study.

Observation of actions performed by other individuals activates the onlooker's motor system in a way similar to real movement execution. The functioning of this mechanism in the pathological domain is not clear yet. The aim of this study was to explore whether action observation activates the motor system of patients affected by a task-specific form of dystonia, such as writer's cramp. Transcranial magnetic stimulation was applied over the primary motor cortex and motor evoked potentials were recorded from hand (FDI and ADM) and forearm (FCR) muscles at baseline and during observation of actions (grasping and writing) or images. Writing actions could be performed with healthy or dystonic movement patterns. Results showed a highly specific and reversed pattern of activation in the FDI muscle of the two groups. Differences between the two writing conditions were significantly opposite in the two groups: control subjects had higher activation during observation of the dystonic compared to the healthy action, whereas in patients observation of the healthy writing led to higher activation than the dystonic writing. This opposite corticospinal modulation might be explained by a different self-attribution of the observed actions in the two groups.

Expertise with pathological actions modulates a viewer's motor system.

Brain mechanisms for action understanding rely on matching the observed actions into the viewer's motor system. Health professionals, who treat patients affected by movement disorders as dystonia, frequently see hyperkinetic action patterns characterized by an overflow of muscle co-contractions. To avert an overload of the motor system during observation of those actions, they might need to look at dystonic motor symptoms in a cool, detached way. To investigate whether visual expertise about atypical movement kinematics influences the viewer's motor system, we applied transcranial magnetic stimulation to clinicians and to naive subjects, while they observed handwriting actions performed with two different kinematics: fluent and non-fluent. Crucially, the latter movement pattern was easily recognized by the clinicians as a typical expression of writer's cramp, whereas it was unknown to the naive subjects. Results showed that clinicians had similar corticospinal activation during observation of dystonic and healthy writings, whereas naive subjects were hyper-activated during observation of dystonic movements. Hyper-activation was selective for the muscles directly involved in the dystonic co-contractions and inversely correlated with subjective movement fluency scores, hinting at a fine-tuned association between the breakdown of observed movement fluency and corticospinal activation. These findings suggest that observation of unusual pathological actions differently modulates the viewer's motor system, depending on knowledge, visual expertise, and ability in recognizing suboptimal movement kinematics.

Somatosensory temporal discrimination in patients with primary focal dystonia.

PURPOSES: To determine whether somatosensory temporal discrimination will reliably detect subclinical sensory impairment in patients with various forms of primary focal dystonia. METHODS: The somatosensory temporal discrimination threshold (STDT) was tested in 82 outpatients affected by cranial, cervical, laryngeal and hand dystonia. Results were compared with those for 61 healthy subjects and 26 patients with hemifacial spasm, a non-dystonic disorder. STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms followed by a progressively increasing interstimulus interval. RESULTS: STDT was abnormal in all the different forms of primary focal dystonias in all three body regions (eye, hand and neck), regardless of the distribution and severity of motor symptoms. Receiver operating characteristic curve analysis calculated in the three body regions yielded high diagnostic sensitivity and specificity for STDT abnormalities. CONCLUSIONS: These results provide definitive evidence that STDT abnormalities are a generalised feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities.

Genotype-phenotype interactions in primary dystonias revealed by differential changes in brain structure.

Our understanding of how genotype determines phenotype in primary dystonia is limited. Familial young-onset primary dystonia is commonly due to the DYT1 gene mutation. A critical question, given the 30% penetrance of clinical symptoms in DYT1 mutation carriers, is why the same genotype leads to differential clinical expression and whether non-DYT1 adult-onset primary dystonia, with and without family history share pathophysiological mechanisms with DYT1 dystonia. This study examines the relationship between dystonic phenotype and the DYT1 gene mutation by monitoring whole-brain structure using voxel-based morphometry. We acquired magnetic resonance imaging data of symptomatic and asymptomatic DYT1 mutation carriers, of non-DYT1 primary dystonia patients, with and without family history and control subjects with normal DYT1 alleles. By crossing the factors genotype and phenotype we demonstrate a significant interaction in terms of brain anatomy confined to the basal ganglia bilaterally. The explanation for this effect differs according to both gene and dystonia status: non-DYT1 adult-onset dystonia patients and asymptomatic DYT1 carriers have significantly larger basal ganglia compared to healthy subjects and symptomatic DYT1 mutation carriers. There is a significant negative correlation between severity of dystonia and basal ganglia size in DYT1 mutation carriers. We propose that differential pathophysiological and compensatory mechanisms lead to brain structure changes in non-DYT1 primary adult-onset dystonias and DYT1 gene carriers. Given the range of age of onset, there may be differential genetic modulation of brain development that in turn determines clinical expression. Alternatively, a DYT1 gene dependent primary defect of motor circuit development may lead to stress-induced remodelling of the basal ganglia and hence dystonia.

Modulation of beta oscillations in the subthalamic area during action observation in Parkinson's disease.

Mapping observed actions into the onlooker's motor system seems to provide the neurofunctional mechanisms for action understanding. Subthalamic nucleus (STN) local field potential (LFP) recordings in patients with movement disorders disclosed that network oscillations in the beta range are involved in conveying motor and non-motor information across the cortico-basal ganglia-thalamo-cortical loop. This evidence, together with the existence of connections between the STN and cortical areas active during observation of actions performed by other people, suggests that the STN oscillatory activity in specific frequency bands could encode not only motor information, but also information related to action observation. To test this hypothesis we directly recorded STN oscillations through electrodes for deep brain stimulation in patients with Parkinson's disease during observation of actions and of static objects. We found selective action-related oscillatory modulations in two functionally distinct beta bands: whereas low-beta oscillations (10-18 Hz) selectively desynchronized only during action-observation, high-beta oscillations (20-30 Hz) synchronized both during the observation of action and action-related objects. Low-beta modulations are therefore specific to action observation and high-beta modulations are related to the action scene. Our findings show that in the basal ganglia there are functional changes spreading to the action environment, probably presetting the motor system in relation to the motor context and suggesting that the dynamics of beta oscillations can contribute to action understanding mechanisms.

Impaired body movement representation in DYT1 mutation carriers.

OBJECTIVE: The only known genetic cause of early-onset primary torsion dystonia is the GAG deletion in the DYT1 gene. Due to the reduced penetrance, many mutation carriers remain clinically asymptomatic, despite the presence of subclinical abnormalities, mainly in the motor control circuitry. Our aim was to investigate whether the DYT1 mutation impairs the inner simulation of movements, a fundamental function for motor planning and execution, which relies upon cortical and subcortical systems, dysfunctional in dystonia. METHODS: DYT1 manifesting patients, DYT1 non-manifesting carriers and control subjects were asked to fixate body (hand, foot, face) or non-body (car) stimuli on a computer screen. Stimuli were presented at different degrees of orientations and subjects had to mentally rotate them, in order to give a laterality judgement. Reaction times and accuracy were collected. RESULTS: DYT1 carriers, manifesting and non-manifesting dystonic symptoms, were slower in mentally rotating body parts (but not cars) than control subjects. CONCLUSIONS: The DYT1 gene mutation is associated with a slowness in mental simulation of movements, independently from the presence of motor symptoms. SIGNIFICANCE: These findings suggest that the cognitive representation of body movements may be altered subclinically in dystonia, thus contributing to the endophenotypic trait of disease.

Tactile temporal discrimination in patients with blepharospasm.

BACKGROUND: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and eyelid spasms. Studies have shown the presence of sensory deficits associated with dystonia. AIM: To rule out any confounding effect of muscle spasms on sensory performance in affected and unaffected body regions of patients with blepharospasm and with hemifacial spasm. METHODS: Participants (19 patients with blepharospasm, 19 patients with hemifacial spasm and 19 control subjects) were asked to discriminate between two stimuli that were either simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 ms (in 10-ms steps) to the hands or on the skin over the orbicularis oculi muscle. RESULTS: Tactile stimuli elicited similar TDTs in control subjects and patients with hemifacial spasm, but significantly higher TDTs in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. CONCLUSIONS: As TDT was abnormal in unaffected body regions of patients with blepharospasm, and patients with hemifacial spasm processed tactile stimuli normally, TDT deficits in blepharospasm depend on central rather than peripheral factors. This study further supports the link between focal dystonia and impaired temporal processing of somatosensory inputs.

Incidence of surgical site infections in general surgery in Italy.

BACKGROUND: Epidemiological study to determine surgical site infection (SSI) rates in surgical patients in Italy using the National Nosocomial Infections Surveillance system (NNIS), to monitor current surgical antimicrobial prophylaxis, and to identify possible modifiable risk factors for SSI. MATERIALS AND METHODS: Thirty-two general surgeries participated in the study. Main criteria for site inclusion were: > 20 operations per week and amoxycillin/clavulanate among prophylactic options. Each patient operated from April 1st to May 30th 2002 was surveyed until 30 days after the operation. SSI cumulative incidence rates and 95% confidence intervals (95%CI) were calculated. RESULTS: During the study period, 3,066 surgical procedures were performed in 2,972 patients. A total of 158 SSI were diagnosed in 154 patients: 96 (62.3%) were at superficial incision, 23 (14.9%) were at deep incision and 35 (22.7%) were at organ-space site. Incidence of SSI every 100 operations was 5.2% (95% CI 4.4-6.0). Of the 2,437 operated patients with clean or elective clean/contaminated or contaminated surgical procedure, 2,105 (86.4%) received antimicrobial prophylaxis, mainly amoxicillin/clavulanate (28.3%) and ceftizoxime (11.4%). Pre-operative hospital stay > or = 48 h, diabetes, obesity, and HIV/AIDS infection were statistically significantly associated with increased risk of SSI. CONCLUSIONS: The SSI rates found are comparable with European studies and can be a benchmark for national incidence data and for inter- and intra-hospital SSI rate comparisons.

Clonal spread of Acinetobacter baumannii in a general intensive care unit.

The epidemiological characterization of multiply resistant Acinetobacter baumannii isolates from a six-bed Intensive Care Unit (ICU) is described. Investigations for A. baumannii were performed in three subsequent surveillance studies. In the first study, surveillance cultures were taken from patients, health care personnel and the environment; in the second study surveillance cultures were taken at 0, 4, and 7 days from all patients admitted consecutively to the ward; and in the third study surveillance cultures were taken from patients, health care personnel and the environment. During the first study all four hospitalized patients were found to harbour A. baumannii. Hand cultures did not grow any A. baumannii when staff entered the ward from home, but 7 positive health care workers were identified out of 25 samples taken during work, and two cultures of environmental specimens grew A. baumannii. During the second study, 4 of 86 (4.6%) patients resulted colonized with A. baumannii. In the third epidemiological study, no A. baumannii was cultured from either patients, health care personnel or the environment. All isolates recovered from various patients or sources produced conserved macrorestriction Pulsed-Field Gel Electrophoresis (PFGE) patterns and showed the same antibiotic resistance; therefore, they can be considered indistinguishable. The same antibiotic resistance and macrorestriction patterns were observed in previously isolated A. baumannii strains in the ward during May 1997, suggesting the persistence of a single A. baumannii in the ICU. The present study confirms that molecular typing is an essential tool in the epidemiology and control of nosocomial infections, showing here the persistence of a single A. baumannii clone in the ICU. The origin of this strain remains unknown but, when basic infection control measures were reinforced, emphasizing the importance of hand antisepsis and judicious use of gloves, control of A. baumannii spread in the ward was achieved.

Prospective, randomized, double-blind trial comparing teicoplanin and cefazolin as antibiotic prophylaxis in prosthetic vascular surgery.

To compare efficacy, tolerability, and cost of antibiotic prophylaxis with teicoplanin and cefazolin in clean prosthetic vascular surgery, a randomized, prospective, double-blind study was performed at the Vascular Surgery Unit of a tertiary-care university hospital. Two-hundred thirty-eight consecutive patients undergoing elective, clean, abdominal or lower-limb prosthetic vascular surgery were allocated to receive a single intravenous dose of teicoplanin (400 mg) or cefazolin (2 g) at the induction of anesthesia. Surgical-site infections occurred in 5.9% of teicoplanin recipients (4.2% wound infection, 1.7% graft infection) and 1.7% of cefazolin recipients (1.7% wound infection, 0% graft infection) (P=0.195). Other postoperative infections occurred in 10% of teicoplanin recipients (pneumonia 7%, urinary tract infection 3%) and 12% of cefazolin recipients (pneumonia 7%, urinary tract infection 2.5%, bloodstream infections 2.5%). Overall mortality rate was 3.4% in teicoplanin recipients (4 patients) and 2.5% in cefazolin recipients (3 patients). Infective deaths occurred in one patient for each group. The two prophylactic regimens were well tolerated. Cost savings of US $52,510 favoring cefazolin were related to the lower acquisition cost (US $1034 vs US $4740) and to the shorter duration of the hospital stay (1762 days vs 1928 days). Cefazolin can still be regarded as the drug of choice for prophylaxis in clean vascular surgery.