Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD.

Background and Objectives: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. Materials and Methods: One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. Results: Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. Conclusions: ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with "sunny" cyclothymic features might escape the attention of clinicians unless ADHD is present.

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.

Toxoplasmosis in a Cohort of Italian Patients With Bipolar and Psychotic Disorders: How Infection May Affect Clinical Features?

This study investigated the seroprevalence of Toxoplasma gondii in a cohort of 101 Italian inpatients affected by mood or schizophrenia-spectrum disorders and compared clinical features between seronegative and seropositive subjects. Patients diagnosed according to DSM-5 criteria underwent clinical assessments and blood collection to test parasite-specific IgG/IgM serum levels. Twenty-eight patients (27.7%) had IgG anti-T. gondii, and none had IgM antibodies. We found higher prevalence rate in patients aged 40 years or older, as compared with younger. No significant association was detected between T. gondii and a specific diagnostic category; however, bipolar disorder (BD)-II showed the highest positivity rate (40.9%). The seropositive status was significantly associated with a lower presence of psychotic symptoms, higher number of total episodes of predominant excitatory polarity, longer illness duration, and lower severity of current episode, particularly anxiety, depressive, and withdrawal/retardation symptoms. These preliminary results seem to point out an association between chronic toxoplasmosis and a specific subtype of BD.

High levels of butyrate and propionate in early life are associated with protection against atopy.

BACKGROUND: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. METHODS: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. RESULTS: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. CONCLUSION: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite?

Recent evidence suggests the involvement of Toxoplasma gondii infection in the emergence of psychotic and affective disorders. In this report, we describe the case of a young Brazilian woman affected by recurrent ocular toxoplasmosis and presenting with a manic episode with psychotic features in the context of a diagnosis of Bipolar Disorder (BD), type I. We observed a relationship between ocular manifestations and the clinical course of bipolar illness, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG. This case report is the first showing the presence of circulating parasite DNA at the time of occurrence of psychiatric symptoms, thus providing further support for a possible role of the parasite in the pathogenesis of some cases of BD.

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses.

The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.

Intestinal dendritic cells.

PURPOSE OF REVIEW: The intestinal immune system is constantly exposed to foreign antigens, which for the most part should be tolerated, but the immune system retains the ability to react rapidly and effectively to eliminate pathogens. Dendritic cells are at the front line in maintaining intestinal integrity as they are widely distributed within the intestinal lamina propria, Peyer's patches and mesenteric lymph nodes. RECENT FINDINGS: The identification of dendritic cell subsets and phenotypic markers within the healthy and diseased intestine has progressed significantly, including improved identification of dendritic cell subsets within the human intestine. Recently, the role for dietary factors and the microbiome in modulating the intestinal dendritic cell functions has begun to be better investigated, resulting in a number of new findings relating to retinoic acid metabolism, pattern recognition receptor triggering and G-protein-coupled receptor activation. In addition, the interactions between goblet cells and mucin with intestinal dendritic cells are being better defined. SUMMARY: In this review, we discuss the recent findings relating to intestinal dendritic cells, in particular the importance of dendritic cells in sensing the intestinal microenvironment and the consequences for health and disease.

Beneficial effects of CHF6467, a modified human nerve growth factor, in experimental neonatal hypoxic-ischaemic encephalopathy.

BACKGROUND AND PURPOSE: Therapeutic hypothermia (TH) has become the standard care to reduce morbidity and mortality in neonates affected by moderate-to-severe hypoxic-ischaemic encephalopathy (HIE). Despite the use of TH for HIE, the incidence of mortality and disabilities remains high. EXPERIMENTAL APPROACH: Nerve growth factor (NGF) is a potent neurotrophin, but clinical use is limited by its pain eliciting effects. CHF6467 is a recombinant modified form of human NGF devoid of algogenic activity (painless NGF). KEY RESULTS: In rodent hippocampal slices exposed to oxygen and glucose deprivation, CHF6467 protected neurons from death and reverted neurotransmission impairment when combined with hypothermia. In a model of rat neonatal HIE, intranasal CHF6467 (20 µg kg-1) significantly reduced brain infarct volume versus vehicle when delivered 10 min or 3 h after the insult. CHF6467 (20 and 40 µg kg-1, i.n.), significantly decreased brain infarct volume to a similar extent to TH and when combined, showed a synergistic neuroprotective effect. CHF6467 (20 µg kg-1, i.n.) per se and in combination with hypothermia reversed locomotor coordination impairment (Rotarod test) and memory deficits (Y-maze and novel object recognition test) in the neonatal HIE rat model. Intranasal administration of CHF6467 resulted in meaningful concentrations in the brain, blunted HIE-induced mRNA elevation of brain neuroinflammatory markers and, when combined to TH, significantly counteracted the increase in plasma levels of neurofilament light chain, a peripheral marker of neuroaxonal damage. CONCLUSION AND IMPLICATIONS: CHF6467 administered intranasally is a promising therapy, in combination with TH, for the treatment of HIE.

Development of a self-report screening instrument for emotional dysregulation: the Reactivity, Intensity, Polarity and Stability questionnaire, screening version (RIPoSt-SV).

BACKGROUND: Emotional dysregulation (ED) refers to the inability to manage emotional experiences or expressions hindering goal-oriented behavior. Moderate impairment on at least two domains among temper control, affective lability, and emotional over-reactivity has been proposed to identify ED in adults with attention-deficit/hyperactivity disorder (ADHD). No screening measure designed for use in diverse psychiatric samples exists. We aimed to develop a self-report screening tool for ED based on the 40-item version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40). METHODS: 150 adult outpatients with non-psychotic conditions were enrolled between February and July 2023 at the Second Psychiatry Unit of Pisa University Hospital. Clinically significant ED (CSED) was defined based on the previously suggested approach for ADHD. Differences between patients with and without CSED were tested. To develop our screening instrument, a decision tree algorithm was trained by hyperparameter tuning through 5-fold cross-validation in 120 subjects and tested on the remaining 30. RESULTS: 75 subjects met criteria for CSED (50 %). CSED was associated with lower age and higher prevalence of psychiatric conditions, including minor mood disorders, ADHD, cannabis use disorders, and eating disorders. We identified a decision tree consisting of six items from RIPoSt-40 that effectively detected CSED, with accuracy, sensitivity, specificity, positive and negative predictive values of 80 % or higher in both the training and testing sets. LIMITATIONS: Tertiary-level; no consensus on criteria; sample size. CONCLUSION: The screening version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-SV) demonstrates promise as a valuable tool for ED screening in clinical settings.

Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse.

Negative symptoms, conceptualized as clinical manifestations of schizophrenia, and subsequently described in other psychiatric disorders, include the loss of normal arousal, drive and affective reactivity. In the field of substance abuse, an interesting analogy can be detected between negative symptoms, in their classical meaning, and the amotivational syndrome (AS), which has been described as a form of chronic cannabis intoxication. AS also shows a close resemblance to the reward deficiency syndrome (RDS) of alcoholics and stimulant abusers, and to the post-withdrawal syndrome (PWS) of detoxified heroin addicts. A variety of substances share a common tropism for the dopaminergic system, leading to a state of hypophoria, which seems to represent a common pathway for chronic substance abusers. In the light of these convergences, a common treatment principle for addictive disorders can be enunciated. This consists in resorting to pro-dopaminergic drugs, that are supposed to replace damaged functions and control craving, and in avoiding anti-dopaminergic drugs, that are expected to exacerbate craving and impede the reversal of the reward deficiency.

History of Childhood/Adolescence Referral to Speciality Care or Treatment in Adult Patients with Attention-Deficit/Hyperactivity Disorder: Mutual Relations with Clinical Presentation, Psychiatric Comorbidity and Emotional Dysregulation.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that only rarely remits in adulthood. While several studies underlined differences between child and adult ADHD, the relationship between adult clinical presentation and early referral/treatment has been rarely investigated. In our study, 100 adults with ADHD were recruited and subdivided according to a history of referral to speciality care or treatment with methylphenidate (MPH) during childhood/adolescence. The early referral was associated with a history of disruptive behaviors during childhood/adolescence. Current ADHD symptoms were more pronounced in patients first referred during childhood/adolescence but never treated with MPH. Early MPH treatment was associated with lower rates of mood disorders and lower severity of emotional dysregulation at the time of assessment. Negative emotionality mediated the relationship between MPH treatment and mood disorders comorbidity. ADHD patients first referred during childhood/adolescence are characterized by more externalizing features than those first referred in adulthood. MPH treatment during the developmental age may have a role in preventing mood disorders in patients with ADHD, possibly by reducing emotional dysregulation.

Long-term treatment of adult ADHD in a naturalistic setting: Clinical predictors of attrition, medication choice, improvement, and response.

OBJECTIVES: The aim of this study was to identify clinical predictors of treatment attrition, medication choice, improvement and response to pharmacotherapy in adult attention-deficit/hyperactivity disorder (ADHD). METHODS: 150 ADHD patients were enrolled and naturalistically followed-up for at least 4 months. Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) were used to measure ADHD severity. RESULTS: 58 subjects (38.7%) were lost at follow-up, while 75 (50%) completed follow-up assessment, on average after 26.05 ± 11.99 weeks; 35 were treated with atomoxetine (ATX) and 40 with methylphenidate (MPH). Treatments were moderately effective (d = 0.72) and 37 patients (49.3%) were responders (≥30% CAARS-O:SV decrease). Patients lost at follow-up had lower inattentive symptoms, less generalised anxiety and family history of bipolar disorder, more amphetamine use disorder than follow-up completers. Compared to ATX-treated subjects, MPH-treated patients had greater severity of hyperactivity/impulsivity and were more frequently diagnosed with alcohol use disorder. While MPH and ATX showed similar efficacy, more pronounced improvements were observed in patients with combined ADHD, anxiety and substance use disorders. ADHD severity and comorbid substance use positively predicted response. CONCLUSIONS: Consensus-based hierarchical treatment of ADHD comorbidity is not consistently supported. Comorbid anxiety, mood and substance use disorders should not discourage the treatment of adult ADHD.

Plasma fluvoxamine levels and OCD symptoms/response in adult patients.

OBJECTIVE: In this study, we explored the possible relationships between plasma fluvoxamine levels and clinical features and/or response in adult obsessive-compulsive disorder (OCD) patients treated with this drug for 6 months. METHODS: Twenty OCD outpatients of both sexes who were already taking fluvoxamine (mean dose ± SD: 216.7 ± 86.2) for at least 4 weeks were included in the study. The severity of OCD was assessed by means of the Yale-Brown obsessive-compulsive scale (Y-BOCS). The fluvoxamine plasma levels were measured by high-performance liquid chromatography analysis. All evaluations were performed after 4 weeks (t1) and 6 months (t2) of fluvoxamine intake. RESULTS: The plasma levels of fluvoxamine remained stable at the two assessment times, with no sex-related differences. Sixteen (80%) patients responded to treatment as shown by the significant (>35%) decrease of the Y-BOCS total score. Men's compulsions improved more than those of women. Significant and positive correlations were detected between fluvoxamine plasma levels at t1 and t2 and the difference (delta) of the Y-BOCS total and compulsion subscale scores between t1 and t2. Another significant, albeit negative, correlation was measured between the difference of the compulsion subscale score and the difference of fluvoxamine levels at t1 and t2. CONCLUSIONS: These findings underline the potential importance of evaluating fluvoxamine plasma levels in OCD and their relationships with the clinical response that may be gender-related on specific symptoms.

Depressive symptoms in Parkinson's disease.

OBJECTIVE: We aimed to investigate the relationship between the presence and severity of depression and the degree of motor and functional disability in Parkinson's disease (PD). METHODS: One hundred twenty-two outpatients with PD were enrolled in a neurology department: 65 satisfied the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria for major depression, and 57 did not (PD-C). Depressive symptoms were assessed by means of the Hamilton Rating Scale for Depression (HRSD), and the PD severity was assessed according to the Hoehn and Yahr System. Activities of daily living and motor symptoms were measured by the Unified PD Rating Scale (UPDRS), parts II and III. RESULTS: Twenty-nine patients had a mild depression (HRSD total score ranging between 8 and 17), 30 had a moderate depression (HRSD total score ranging between 18 and 24), and 6 had a severe depression (HRSD total score, ≥25). By comparing the 3 groups of patients, it emerged that those with a severe depression showed significantly higher scores at the UPDRS II, UPDRS III, and HY scales than did PD-C or patients with a mild depression. Moreover, patients with a moderate depression scored significantly higher on the UPDRS II, UPDRS III, and HY scales than did PD-C or those with a mild depression. CONCLUSIONS: Our findings suggest that depression and motor symptoms/well-being are highly intertwined in patients with PD.

Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

BACKGROUND: The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. METHODS: Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. RESULTS: No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. CONCLUSIONS: Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.

Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection.

BACKGROUND: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. METHODS: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated cell wall in controlling viral induced inflammation using a murine model of influenza infection. We monitored mortality and morbidity over a 10-day period and viral load, differential broncho alveolar lavage (BAL) fluid inflammatory cell counts, Lung tissue histology, BAL and serum cytokines, markers of vascular damage and cell death were quantified. FINDINGS: Intranasal administration of Bifidobacterium longum35624® or its isolated cell wall prior to virus inoculation significantly reduced viral load within the lungs and significantly improved survival. Reduced viral load was associated with reduced lung injury as suggested by cell death and vascular leakage markers, a shift from neutrophil to macrophage recruitment, reduced inflammatory cytokine levels (including IL-6), reduced type 1 and 2 interferon levels, but increased levels of interferon-λ and surfactant protein D. These protective effects were maintained when the bifidobacterial cell wall preparation was administered 24 h after viral inoculation. The protective effects were also observed for the Bifidobacterium longumPB-VIR™ strain. INTERPRETATION: Exposure to these bifidobacterial strains protect against the inflammatory sequelae and damage associated with uncontrolled viral replication within the lung. FUNDING: This work has been funded, in part, by a research grant from GlaxoSmithKline, PrecisionBiotics Group Ltd., Swiss National Science Foundation grants (project numbers CRSII3_154488, 310030_144219, 310030_127356 and 310030_144219) and Christine Kühne - Center for Allergy Research and Education (CK-CARE).

Resveratrol plus carboxymethyl-ß-glucan in infants with common cold: A randomized double-blind trial.

OBJECTIVES: To evaluate effectiveness of a nasal resveratrol/carboxymethyl-ß-glucan solution compared to nasal saline solution: a) on common cold symptoms by means of a validated measure scale (CARIFS score), b) on Rhinovirus infection and CCL2, CCL5, IL8, IL6, CXCL10 and TLR2 expression in nasal swabs, c) on frequency of relapses after 30 days of follow-up. METHODS: 89 infants with respiratory infection symptoms were randomly assigned to receive either a nasal resveratrol/carboxymethyl-ß-glucan solution or nasal saline solution.All patients were evaluated with CARIFS score at enrollment, after 48 h, 7 and 30 days by physicians and parents. Nasal swabs were obtained at enrollment, after 48 h and after one week. RESULTS: CARIFS score improved in both groups. Episodes of sneezing and cough were fewer in study group after 7 days of follow-up (p < 0.05). No significant differences were found on nasopharyngeal swabs in Rhinovirus detection and cytokines expression after 48 h, nor in 30 days relapses. TLR2 expression was significantly higher in Rhinovirus infected children of the study group. No adverse effects occurred. CONCLUSIONS: These data suggest that a solution containing resveratrol plus carboxymethyl-ß-glucan might have a positive impact on both clinical and socio-economic burden due to infant common cold.