The Impact of Oxidative Stress on Pregnancy. The Neglected Role of Alcohol Misuse.

Abstract: Oxygen is essential for human life. However, it could cause damaging effects on biological systems causing oxidative stress. Oxidative stress defined as "an alteration in the pro-oxidant-antioxidant balance in favor of the former that leads to potential damage" is characterized by the release of Reactive Oxygen Species (ROS). Oxidative stress is now recognized to play a central role in the pathophysiology of many different disorders, including complications of pregnancy such as placental pathology, PreEclampsia (PE), Intrauterine Growth Restriction (IUGR), gestational diabetes, and miscarriage. This narrative review aims to summarize pieces of evidence about the role of oxidative stress in the pathophysiology of the main obstetric complications with par-ticular interest in the neglected role of alcohol abuse.

Sexual Developmental Disorders in Pediatrics.

Abstract: Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.

Acute alcohol intoxication: a clinical overview.

Abstract: Alcohol is a legal and yet detrimental psychoactive substance, capable of establishing addiction and impacting the physical, mental, social, and economic health of people. Alcohol intake causes a large variety of tissue damages severely impacting the nervous system, digestive and cardiovascular systems and causing oral cavity, oropharyngeal, hypopharyngeal, esophageal, colon-rectal, laryngeal, liver and intrahepatic bile duct, and breast cancers. Alcohol can also play a role in the pathogenesis of diabetes mellitus, cardiomyopathy and hemorrhagic strokes. When drunk during pregnancy it is proved to be responsible for serious damage to fetuses causing a wide range of pathological conditions from miscarriage to Fetal Alcoholic Spectrum Disorder (FASD). Acute ethanol intoxication happens when the amount of alcohol consumed is greater than the disposal capacity of the liver, causing an accumulation of its metabolites displayed by initial dysphoria and disinhibition. Nausea, vomiting, memory loss could happen. Although, it can lead to more serious conditions like impaired speaking, impaired coordination, unstable gait, nystagmus, stupor, or coma. Respiratory depression and death could also happen in such cases. Unfortunately, diagnosis of acute alcohol intoxication is difficult because most of the drinkers deny or minimize their assumption. It is dramatically important to assess when the last intake happened to avoid withdrawal syndrome. Alcohol acute intoxication can be considered a serious harm to health and a relevant issue for healthcare provid-ers working in emergency rooms. Differential diagnosis is crucial to avoid serious outcomes. There is no consensus about therapies for acute intoxication, but supportive and symptomatic treatments were proved effective. The repercussions of alcohol misuse over drinkers' social, familiar, economical and working life enhance the importance of a multidisciplinary approach in such cases.

Caesarean Section in Preventing Stillbirths in Pregnancy Complicated with COVID-19: a Narrative Review.

INTRODUCTION: COVID-19 is a complex syndrome caused by SARS-Cov-2. It mainly affects the respiratory system, but it could cause serious harm during pregnancy. An increase in stillbirths and preterm births has been highlighted by many authors. Although WHO and Royal College of Obstetrics and Gynecology don't recommend elective cesarean section in women with confirmed infection, cesarean sections were performed by many clinicians. This short narrative review aims to analyze pieces of evidence found in literature about the effectiveness of cesarean section in preventing stillbirths in COVID-19 positive mothers. METHODS: Studies included in the present review were retrieved searching MEDLINE (last access August 5th, 2021) with the following keywords: "pregnant woman with covid-19", "Caesarean section", "Ab-dominal Delivery" and "Stillbirth". Studies regarding the mode of delive-ry in pregnant women infected with COVID-19 and neonatal outcomes were included. Studies about biology, anesthesiology and necroscopy were excluded. Filters for "human" and "English" were applied. RESULTS: Searching MEDLINE, 24 references were found. Other 103 articles were found searching bibliography. Two references were excluded after duplicate removal, 77 references after the title screen and 27 after the abstract screen. The final number of references included was 23. Most of the included studies were case reports. Most of them were from China. DISCUSSION: Many authors highlighted the increased risk of fetal death in pregnancies complicated with SARS-Cov-2 infection, but it is not clear if Caesarean Section could reduce this risk. Pieces of evidence show that most clinicians choose to perform an elective cesarean section mostly because of maternal conditions or the fear of possible vertical transmission. Data show that mode of delivery doesn't affect the neonatal outcome and Caesarean Section doesn't reduce the positivity rate among neonates. Different opinions were found about the possible infection of amniotic fluid, cord blood and placenta. The risk of vertical transmission is considered moderate or low by most of the authors. Positivity to SARS-Cov-2 isn't an indication of elective cesarean section by itself, but this mode of delivery should be optioned in patients with other obstetrical indications or with severe conditions due to COVID. The recent increase in stillbirths could be related to the overall deterioration of maternal conditions.

Challenges for Midwives' Healthcare Practice in the Next Decade: COVID-19 - Global Climate Changes - Aging and Pregnancy - Gestational Alcohol Abuse.

Midwives are multifaceted healthcare professionals whose competence spectrum includes a large variety of knowledge and skills going from antenatal care to education and research. The aim of this review is to suggest the future challenges midwives are going to face in the upcoming decade of this Century. COVID-19 and other infections will reasonably impact healthcare workers all over the world. Midwives are frontline healthcare professionals who are constantly at risk of contagion as their job implies close contact with women, physical support and hand touch. Also, menstruation waste plays a large role in the pollution of waters, severely impacting hygiene in the developing countries and fueling climate change. Appropriate disposal of used menstrual material is still insufficient in many countries of the world especially because of lack of sanitary education on girls. As educators, midwives will be more involved into preventing inappropriate disposal of menstrual hygiene devices by educating girls around the world about the green alternatives to the commercial ones. Despite the evidences about the fertility decrement that occurs with aging, women keep postponing reproduction and increasing their chance being childless or suffering complications related to the advanced maternal age. Teen pregnancies are as well an important issue for midwives who will be called to face more age-related issues and use a tailored case to case approach, enhancing their family planning skills. Another crucial role of midwifery regards the information about the risk of drinking alcohol during gestation. Alcohol assumption during pregnancy is responsible for serious damage to the fetus causing a wide range of pathological conditions related to Fetal Alcoholic Spectrum Disorder, leading cause of mental retardation in children of western countries. On the whole, midwives have demonstrated their willingness to expand their practice through continuing professional development, and through specialist and advanced roles especially in preventive and educational positions.

Nerve growth factor serum levels in treatment-resistant schizophrenic patients following electroconvulsive therapy.

BACKGROUND: Electroconvulsive Therapy (ECT) has been widely applied to treat schizophrenia (SCZ) in the presence of resistance to pharmacotherapy. The mechanism of action of ECT in schizophrenia has not been fully clarified, though its intrinsic mechanism presents analogies with some neurobiological processes mediated by nerve growth factor (NGF). OBJECTIVES: The aim of this study was to investigate in patients with treatment-resistant schizophrenia (TRS) the effect of ECT on acute and long-term NGF serum levels and the association with the clinical outcomes. METHODS: Twelve male inpatients with TRS underwent eight sessions of ECT. Blood samples were collected during the first and the eighth ECT at the following time points: 5 minutes before the induction of seizure and then at 0, 5, 15 and 30 minutes after seizure. RESULTS: Following ECT treatment, a substantial clinical improvement in symptom severity was indicated by a significant reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscales scores. Even though the baseline NGF levels showed an increase over time, there were no statistical differences in NGF at time 0 at the first and the eighth ECT session. Furthermore, no correlation was observed between the severity of schizophrenic symptoms and NGF levels. CONCLUSIONS: This is the first study addressing peripheral NGF during ECT treatment in TRS, as well as the first study in which NGF has been evaluated in different ECT sessions at various time points. These findings may potentiate the knowledge about the neurotrophic effects of ECT and the role of NGF in synaptic plasticity related to possible mechanisms of schizophrenia treatment.

The role of cytokines in head and neck squamous cell carcinoma: A review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, accounting for approximately 6% of all cancer cases and responsible for an estimated 1-2% of all cancer deaths. Much research evidence has accumulated in the recent years on the changes in the expression of pro-inflammatory and, to a lesser extent, anti-inflammatory cytokines, that (i) may have a role in the malignant transformation of HNSCC, (ii) may be used as diagnostic markers in the sera of patients because of their excessive production by the tumor cells and (iii) may act as possible immunotherapeutic targets. Among pro-inflammatory cytokines, interleukin-8 (IL--8) has been reported to have an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL--8 in patients with HNSCC and a positive association with lymph node metastasis and tumor classification, although IL--8 was not significantly associated with shorter overall survival and cancer progression-free survival. Additional evidence on the pathological mechanism of origin, invasion, and metastasis of HNSCC, as well as a better understanding of the implications of cytokines, chemokines and growth factors, are of paramount importance for the advancement of research in head and neck oncology.

Physiological Responses to Induced Stress in Individuals Affected by Alcohol Use Disorder with Dual Diagnosis and Alexithymia.

Alcohol use disorders (AUD) are among the most common and undertreated mental disorders in developed countries. The co-occurrence of psychiatric comorbidity and AUD has already been well documented. Moreover, alexithymia was found associated with heavy drinking and alcohol dependence. A large part of AUD individuals, between 45 and 67%, have been identified as alexithymics. Both psychiatric comorbidity and alexithymia can negatively impact the course of recovery from alcohol. Alcohol consumption has also been shown to significantly influence autonomic responses. Chronic use of alcohol may induce significant changes in heart rate variability, respiratory frequency, electrodermal activity and skin temperature. To date, only a few studies have comprehensively investigated the comorbidity of alexithymia in AUD individuals with dual diagnosis. Thus, the aim and also the novelty of the present investigation were to disclose in individuals with AUD the emotional and cognitive stress responses to selected physiological parameters measured by ProComp5 Infiniti™ encoder in AUD patients suffering alexithymia with or without concomitant dual diagnosis. Quite interestingly, in AUD subjects with concomitant dual diagnosis we found that the alexithymia elevated skin temperature, heart rate variability and decreased respiratory frequency. Alexithymia, if associated with the dual diagnosis condition in AUD individuals, can be considered as a further vulnerability factor to stressing factors, impacting psychosomatic processing and inducing alterations in physiological parameters. In this paper, we discuss the implications of these findings in the early treatment of alexithymic AUD individuals.

A case of motor neuron involvement in Gaucher disease.

Gaucher disease (GD) is a genetic disorder characterized by an accumulation of glucosylceramide in cells in the monocyte-macrophage system. We describe a case of a 33-year-old man with a previous diagnosis of type 3 GD who displayed a progressive weakening of the limbs followed by upper motor neuron involvement. A diagnosis of definite Amyotrophic Lateral Sclerosis was made. This is the first reported case of concurrent Gaucher disease and the ALS phenotype in the same patient.

Modulation of human corticospinal excitability by paired associative stimulation in patients with amyotrophic lateral sclerosis and effects of Riluzole.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes an impairment in both the upper and lower motor neurons. The recent description of numerous non-motor signs points to an involvement of the neocortex networks that is more complex than was previously believed. Paired associative stimulation (PAS), a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation, can enhance motor output in the contralateral hand through an NMDA-mediated sensorimotor mechanism. OBJECTIVE: To describe the effects of PAS on ALS patients before and after Riluzole intake compared with healthy subjects. METHODS: PAS was used to detect differences between 24 newly-diagnosed ALS patients and 25 age-matched healthy controls. MEP amplitude from the abductor pollicis brevis was considered before PAS, immediately after (T0) and after 10 (T10), 20 (T20), 30 (T30) and 60 (T60) minutes. Statistical significance was calculated using RM-ANOVA. RESULTS: In healthy controls, PAS significantly increased MEP amplitude at T10, T20 and T30 (p < 0.05). In ALS patients, a significant increase in MEP amplitude was also observed after 60 min (p < 0.05), thus demonstrating NMDA-mediated enhanced facilitatory plasticity. After two weeks of riluzole intake, no MEP amplitude increase was evident after PAS at any time point. In three monomelic-onset ALS patients, a long lasting sensorimotor facilitation was evident only in the hemisphere corresponding to the affected side and appeared in the opposite hemisphere when the patients manifested contralateral symptoms. CONCLUSIONS: PAS may be considered a useful tool when investigating NMDA-mediated neocortical networks in ALS patients and the modulation of such networks after anti-glutamatergic drug intake.

The synergistic effect between Positivity, socio-demographic factors and smoking cessation: results of a cohort study.

OBJECTIVE: To examine the extent to which a effect does exist between Positivity (POS), smoking and socio-demographic factors in determining quitting smoking in subjects participating in a Group Counselling Program (GCP) for smoking cessation. METHODS: 481 subjects were contacted through a telephone call. A logistic regression analysis was carried out. Possible interaction between sociodemographic variables and POS level was tested using the Synergism Index (SI). RESULTS: For individuals with a POS level over or equal to 3.4 the odds of being smoker was significantly higher among females (OR = 1.55), who smoked at home (OR = 2.16) and lower if there had children at home (OR = 0.53). For individuals with a POS level under 3.4, the only significant variable associated with smoking was beinga female (OR = 2.58). As far concerns the synergistic effect between the variables considered does exist between POS levels and having children at home (SI=1.13) and female gender (SI = 2.8). CONCLUSIONS: The synergistic effect between POS and sociodemographic factors adds evidence on the use of POS as possible determinants of individual happiness.

Novel strategies to treat alcohol dependence with sodium oxybate according to clinical practice.

OBJECTIVE: The treatment of alcohol dependence (AD) with sodium oxybate (SMO) was introduced in Italy and Austria more than 20 years and 15 years ago respectively, and it is now widely employed. In addition to the data obtained from clinical trials, little information is available on specific clinical practices. Thus, the aim of this study was to present and discuss the results of a consensus meeting held after twenty years of using SMO in clinical practice in Italy. MATERIALS AND METHODS: A validated questionnaire study was conducted to investigate the modalities of treatment of AD with SMO currently used in Italy. A group of four referees first drew up the questionnaire which was distributed to fifty experts in the field of alcohol use disorders. The questionnaire consisted of 125 items with five different modalities of response and two or three answer possibilities. RESULTS: The results of this survey showed a broad consensus on some issues regarding, for example, the duration of treatment, and the dose regimen of the drug; however, some aspects of the treatment of AD with SMO still remain controversial. CONCLUSIONS: This is the first consensus study investigating the use of SMO for the treatment of AD through the opinions gained in over twenty years of clinical practice provided by fifty Italian expert clinicians. A consensus on good practice for the correct administration of SMO has clearly emerged; these opinions, along with those derived from previous clinical investigations, will help physicians to use SMO in a better way. However, some issues remain controversial, and others remain unresolved.

Small-fibre neuropathy related to bulbar and spinal-onset in patients with ALS.

We aimed at seeking more precise diagnostic information on the sensory nervous system involvement described in patients with amyotrophic lateral sclerosis (ALS). We investigated large myelinated nerve fibres with nerve conduction study and small-nerve fibres with Quantitative Sensory Testing (QST) (assessing thermal-pain perceptive thresholds) and skin biopsy (assessing intraepidermal nerve fibre density) in 24 consecutive patients with ALS, 11 with bulbar-onset and 13 with spinal-onset. In 23 of the 24 patients, regardless of ALS onset, nerve conduction study invariably showed large myelinated fibre sparing. In patients with bulbar-onset ALS, QST found normal thermal-pain perceptive thresholds and skin biopsy disclosed normal intraepidermal nerve fibre density. Conversely, in patients with spinal-onset, thermal-pain thresholds were abnormal and distal intraepidermal nerve fibre density was reduced. Sensory nervous system involvement in ALS differs according to disease onset. Patients with spinal-onset but not those with bulbar-onset ALS have concomitant distal small-fibre neuropathy. Neurologists should therefore seek this ALS-related non-motor feature to improve its diagnosis and treatment.

H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy.

BACKGROUND: Painful neuropathy is associated with plasticity changes in the nervous system. Standard repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used to study changes in cortical excitability and to inhibit pain perception. Deep rTMS is a newer development that allows direct activation of deeper neuronal populations, by a unique coil design termed the H-coil. This study was designed to assess whether deep rTMS applied over the motor cortical lower-limb representation relieves pain in patients with diabetic neuropathy. METHODS: Patients were randomly assigned to receive daily real or sham H-coil rTMS for 5 consecutive days. After a 5-week washout period, they crossed over to the alternative treatment for additional 5 days (according to a crossover study design). Outcome measures were changes in the visual analogue scale (VAS) for pain and in area and threshold of RIII nociceptive flexion reflex (RIII reflex). RESULTS: Of the 25 patients randomized, 23 completed the study. After real rTMS, the VAS scores decreased significantly (p=0.01), and so did RIII reflex area (p<0.01), while no significant effects in these variables were induced by the sham rTMS treatment. The rTMS-induced changes in the outcome measures disappeared about 3 weeks after stimulation. All patients tolerated stimulation well. CONCLUSIONS: Deep H-coil rTMS provides pain relief in patients with diabetic neuropathy. This innovative technique can induce a therapeutic effect on brain areas that otherwise remain difficult to target. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems.

Chronic treatment with rivastigmine in patients with Alzheimer's disease: a study on primary motor cortex excitability tested by 5 Hz-repetitive transcranial magnetic stimulation.

OBJECTIVE: To investigate changes in cortical excitability and short-term synaptic plasticity we delivered 5 Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in 11 patients with mild-to-moderate Alzheimer's disease (AD) before and after chronic therapy with rivastigmine. METHODS: Resting motor threshold (RMT), motor evoked potential (MEP), cortical silent period (CSP) after single stimulus and MEP facilitation during rTMS trains were tested three times during treatment. All patients underwent neuropsychological tests before and after receiving rivastigmine. rTMS data in patients were compared with those from age-matched healthy controls. RESULTS: At baseline, RMT was significantly lower in patients than in controls whereas CSP duration and single MEP amplitude were similar in both groups. In patients, rTMS failed to induce the normal MEP facilitation during the trains. Chronic rivastigmine intake significantly increased MEP amplitude after a single stimulus, whereas it left the other neurophysiological variables studied unchanged. No significant correlation was found between patients' neuropsychological test scores and TMS measures. CONCLUSIONS: Chronic treatment with rivastigmine has no influence on altered cortical excitability and short-term synaptic plasticity as tested by 5 Hz-rTMS. SIGNIFICANCE: The limited clinical benefits related to cholinesterase inhibitor therapy in patients with AD depend on factors other than improved plasticity within the cortical glutamatergic circuits.

Fermi observations of high-energy gamma-ray emission from GRB 080916C.

Gamma-ray bursts (GRBs) are highly energetic explosions signaling the death of massive stars in distant galaxies. The Gamma-ray Burst Monitor and Large Area Telescope onboard the Fermi Observatory together record GRBs over a broad energy range spanning about 7 decades of gammaray energy. In September 2008, Fermi observed the exceptionally luminous GRB 080916C, with the largest apparent energy release yet measured. The high-energy gamma rays are observed to start later and persist longer than the lower energy photons. A simple spectral form fits the entire GRB spectrum, providing strong constraints on emission models. The known distance of the burst enables placing lower limits on the bulk Lorentz factor of the outflow and on the quantum gravity mass.

Skeletal turnover, bone mineral density, and fractures in male chronic abusers of alcohol.

BACKGROUND: Chronic alcohol abuse is a risk factor for osteoporosis and fractures, whose pathogenesis is still unclear. We investigated the influence of alcoholism and other risk factors on calcium and skeletal metabolism, bone mineral density (BMD), and fractures. MATERIALS AND METHODS: In 51 chronic male alcoholics without liver failure and 31 healthy controls, serum total and ionised calcium, phosphate, creatinine, 25-hydroxy vitamin D (25OHD), PTH, total (ALP) and bone-specific (BALP) alkaline phosphatase, osteocalcin (BGP), carboxy-terminal telopeptide of type I collagen (beta-CTx), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were assessed. In patients only, we also measured serum testosterone, 17-beta estradiol, LH, and IGF-I. BMD was measured by dual energy x-ray absorptiometry at lumbar spine (LS-) and femur [neck (FN-) and total hip (TF-)]. Vertebral fractures were identified by a semiquantitative method on thoraco-lumbar spine x-ray, non-vertebral fractures (as life-style factors) by history. RESULTS: Alcoholics were leaner, had significantly higher ALP and BALP, and lower BGP and 25OHD levels than controls. No significant difference in other calcium and bone metabolism parameters was found. OPG/RANKL ratio was significantly higher in alcoholics. Beta-CTx negatively correlated with abuse duration. OPG positively correlated with daily alcohol assumption and with indexes of liver cytolysis. Though LS-, FN- and TF-BMD of alcoholics and controls did not significantly differ, patients had a much higher prevalence of vertebral fractures. The same was found considering both vertebral and non-vertebral fractures. CONCLUSIONS: Ethanol-induced skeletal damage seems mainly dependent on negative effects on bone formation. Lifestyle factors and traumas likely contribute to the high fracture incidence of alcohol abusers, independently of BMD.

Acute and chronic effects of ethanol on cortical excitability.

OBJECTIVE: We designed this study to find out whether 5Hz repetitive transcranial magnetic stimulation (rTMS) would disclose changes in cortical plasticity after acute intake of ethanol and in patients with chronic alcohol consumption. METHODS: Ten stimuli-5Hz-rTMS trains were applied over the primary motor cortex in 10 healthy subjects before and after acute ethanol intake and in 13 patients with chronic ethanol abuse, but negative blood ethanol levels when studied. The motor evoked potential (MEP) amplitude and the cortical silent period (CSP) duration during the course of rTMS trains were measured. Short-interval intracortical inhibition (3ms) and intracortical facilitation (10ms) were studied by paired-pulse TMS in 4 healthy subjects and 4 patients. RESULTS: In healthy subjects before and after acute ethanol intake, 5Hz-rTMS produced a significant increase in the MEP size and CSP duration during rTMS. The first CSP in the train was significantly longer after than before ethanol intake. In patients 5Hz-rTMS failed to produce the normal MEP facilitation but left the CSP increase unchanged. CONCLUSIONS: Acute and chronic ethanol intake alters cortical excitability and short-term plasticity of the primary motor cortex as tested by the MEP size facilitation and CSP lengthening after 5Hz-rTMS. SIGNIFICANCE: This finding suggests that rTMS is a valid tool for investigating the effects of ethanol on cortical plasticity in humans.

Chronic and acute alcohol exposure prevents monocyte-derived dendritic cells from differentiating and maturing.

Increasing evidence suggests that alcohol abuse may be linked to adverse immunomodulatory effects on immune responses. Our study was undertaken to clarify the immunological consequences of chronic and acute alcohol exposure on differentiation and maturation of human dendritic cells (DCs). Using immunochemical and cytofluorimetric analysis we determined the phenotype and functions of monocyte-derived DCs from alcoholics and healthy subjects and analyzed their ability to respond to lipopolysaccharide (LPS) in the presence or absence of ethanol (EtOH) exposure. Our results showed that alcoholics inverted exclamation mark| monocytes differentiated to immature DCs with altered phenotype and functions (alc-iDCs). Alc-iDCs showed fewer CD1a+ cells, weaker CD86 expression and higher HLA-DR expression associated with lower endocytosis and allostimulatory functions than iDCs from healthy subjects (control-iDCs). Despite these impairments, alc-iDCs produced TNF-alpha and IL-6 in large amounts. LPS stimulation failed to induce full phenotypical and functional alc-iDC maturation. In vitro acute EtOH exposure also prevented alc-iDCs and control-iDCs from maturing in response to LPS. T-cell priming experiments showed that EtOH treatment prevented LPS-stimulated control-iDCs from priming and polarizing naïve allogeneic T cells into Th1 cells, thus favouring a predominant Th2 environment. Collectively, our results provide evidence that chronic and acute alcohol exposure prevents DCs from differentiating and maturing in response to a microbial stimulus.