Family, lifestyles and new and old type of smoking in young adults: insights from an italian multiple-center study.

BACKGROUND: Tobacco smoke is the epidemic of modern times due to its tremendous burden of diseases and deaths, greater than that produced by alcohol, AIDS, drugs, road accidents, murders and suicides combined. In Italy, 26% of the population smokes and the high prevalence of smoking even among young people is crucial for the Tobacco Industry, because young people are the reservoir which replaces smokers who quit or die. The aim of this study is to investigate smoking habits and determinants of smoking among young adults. METHODS: This cross-sectional study enrolled young people from three Italian regions: Latium (central Italy) Calabria (southern Italy) and Sicily (the largest Italian island). An anonymous, multiple-choice online questionnaire was distributed through social networks. Questions investigated individual habits and lifestyles (smoking, alcohol and coffee consumption, physical activity), the presence of smokers in the family and the use of electronic cigarettes. Descriptive and multivariate analyses were used to describe the characteristics of the sample and to evaluate factors associated with smoking status. All statistical analyses were conducted in SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). All hypothesis tests were 2-tailed and p values <0.05 were considered statistically significant. RESULTS: In a sample of 382 subjects between 18 and 34 years, the prevalence of smoking was 25%. A statistically significant higher percentage of smokers is observed among those who drink coffee and those who drink alcohol. Only 48% of smokers usually smoke classic cigarettes, while 45% roll their own cigarettes and 7% use electronic cigarettes. More than half of the smokers, smoke 1 to 5 cigarettes a day, while 17% smoke over 10 cigarettes a day. In families where there was at least 1 smoker, the percentage of smokers was 34% versus only 15% in families where nobody else smokes. The presence of at least 1 smoker in the family was strongly associated with young adults' smoking behavior: subjects with family members who smoke were more than three times as likely to be current smokers, compared to those with no family smokers (Odds Ratio [OR] = 3.14, 95% confidence interval [CI] 1.8-5.5, p=0.0001). Alcohol, coffee consumption, unemployment and being a student were also found to be independently and significantly associated with smoking of young adults (alcohol OR=2.96, 95%CI 1.64-5.34; coffee OR= 4.33, 95%CI 1.81-10.39; unemployment OR = 4.76, 95%CI 1.26-17.96; being a student OR = 3.21, 95%CI 1.25-8.27). CONCLUSION: Preventing young people from smoking is crucial in order to stop the Tobacco Epidemic. The Tobacco Industry is selling new products and is using new marketing tactics (i.e. the "influencers" in social media) which are hooking young people to addictive products and behaviors, thus threatening to wipe out decades of progress in curbing tobacco use. Effective action to drastically reduce new and old types of smoking or to pursue the "Tobacco Endgame" requires an increasing commitment not only towards young people, but also towards families, that play an important role in influencing young people.

A micro-LED implant and technique for optogenetic stimulation of the rat spinal cord.

To date, relatively few studies have used optogenetic stimulation to address basic science and therapeutic questions within the spinal cord. Even less have reported optogenetic stimulation in the rat spinal cord. This is likely due to a lack of accessible optogenetic implants. The development of a device that can be fabricated and operated by most laboratories, requiring no special equipment, would allow investigators to begin dissecting the functions of specific neuronal cell-types and circuitry within the spinal cord, as well as investigate therapies for spinal ailments like spinal cord injury. Here, we describe a long-term implantable µLED device designed for optogenetic stimulation of the spinal cord in awake, freely moving rats that is simple enough to be fabricated, implanted and operated by most laboratories. This device, which sits above the dorsal cord, can induce robust movements for at least 6 weeks without causing physical or thermal damage to the underlying spinal cord. In this regard, the presented µLED device could help tease apart the complexities of the spinal cord and uncover potential future therapeutics.

Optogenetic surface stimulation of the rat cervical spinal cord.

Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. Here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats, adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.

Effects of short-to-long term enzyme replacement therapy (ERT) on skeletal muscle tissue in late onset Pompe disease (LOPD).

AIMS: Pompe disease is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid α-glucosidase (GAA) enzyme. Histopathological hallmarks in skeletal muscle tissue are fibre vacuolization and autophagy. Since 2006, enzyme replacement therapy (ERT) is the only approved treatment with human recombinant GAA alglucosidase alfa. We designed a study to examine ERT-related skeletal muscle changes in 18 modestly to moderately affected late onset Pompe disease (LOPD) patients along with the relationship between morphological/biochemical changes and clinical outcomes. Treatment duration was short-to-long term. METHODS: We examined muscle biopsies from 18 LOPD patients at both histopathological and biochemical level. All patients underwent two muscle biopsies, before and after ERT administration respectively. The study is partially retrospective because the first biopsies were taken before the study was designed, whereas the second biopsy was always performed after at least 6 months of ERT administration. RESULTS: After ERT, 15 out of 18 patients showed improved 6-min walking test (6MWT; P = 0.0007) and most of them achieved respiratory stabilization. Pretreatment muscle biopsies disclosed marked histopathological variability, ranging from an almost normal pattern to a severe vacuolar myopathy. After treatment, we detected morphological improvement in 15 patients and worsening in three patients. Post-ERT GAA enzymatic activity was mildly increased compared with pretreatment levels in all patients. Protein levels of the mature enzyme increased in 14 of the 18 patients (mean increase = +35%; P < 0.05). Additional studies demonstrated an improved autophagic flux after ERT in some patients. CONCLUSIONS: ERT positively modified skeletal muscle pathology as well as motor and respiratory outcomes in the majority of LOPD patients.

Preterm birth: incidence, risk factors and second trimester cervical length in a single center population. A two-year retrospective study.

OBJECTIVE: To report the incidence and the major risk factors (RFs) associated with preterm birth (PTB), combining both maternal RFs and cervical length (CL), and to understand if cervical length measurement is really useful in all the patients. PATIENTS AND METHODS: The study population consisted of 2048 women admitted to the Department of Obstetrics and Gynecology, University Hospital of Messina, over a 2-year period. Preterm cases represented approximately 8.64% of our total population and, exactly, 65% were late preterm, 32% were preterm, and 3% were extremely preterm. RESULTS: An analysis of PTB sub-categories based on gestational age showed a stronger correlation between gestational age and CL among preterm and extremely preterm, while no correlation was found among late preterm. Between preterm cases and controls, there was a significant difference in pre-pregnancy weight and Body Mass Index (BMI). Moreover, a significant association between PTB and uterine anomalies, poli-oligodramnios and hypertension was found. CONCLUSIONS: We strongly suggest adding a transvaginal ultrasound CL universal screening to all pregnant women at the time of the second trimester ultrasound. We encourage further studies to identify new RFs of PTB and to define the mechanisms by which risk factors are related to PTB.

Enhancing Fluorogold-based neural tract tracing.

BACKGROUND: Fluorogold (FG) is used by many groups to retrogradely trace nervous system pathways. Fluorogold, while a robust tracer, also is neurotoxic and causes tissue damage at the injection site and leads to motor deficits. NEW METHOD: In the current study, we describe a method for enhancing FG-uptake using Triton™ and an overall procedure for reducing FG-related tissue damage while still allowing effective quantification. RESULTS: Triton™ decreases the amount of FG, as well as the time required for long-distance transport from the thoracic spinal cord to the motor cortex by >4 fold when this distance is >10in. Although small FG concentrations and injection volumes are ideal for minimizing associated tissue damage and motor deficits, they result in difficult-to-detect fluorescence. This can be solved using FG antiserum paired with an ABC chromogen reaction. This ABC chromogen reaction product can remain stable for at least 9 years. COMPARISON WITH EXISTING METHOD(S): This study is the first to collectively address FG-induced tissue damage and describe methods for minimizing this damage. CONCLUSIONS: Triton™ enhances the uptake of FG in the nervous system, reduces the FG required, and allows for a substantial decrease in tracing time that limits FG-induced motor deficits. Small FG concentration and volume decreases tissue damage but also decreases FG fluorescent detection. Detection challenges are resolved using FG anti-serum and chromogen reactions.

Thyroid hormone autoantibodies: are they a better marker to detect early thyroid damage in patients with hematologic cancers receiving tyrosine kinase inhibitor or immunoregulatory drug treatments?

BACKGROUND: Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage that leads to dysfunction of the gland. To find a more reliable thyroid marker, we assessed the presence of antibodies binding thyroid hormones (thAbs) in a cancer population undergoing potentially thyrotoxic treatment. METHODS: From April 2010 to September 2013, 82 patients with hematologic malignancies treated with tyrosine kinase inhibitors or immunoregulatory drugs were recruited. Healthy volunteers (n = 104) served as control subjects. Thyroid function, autoimmunity tests, thAbs, and thyroid sonography were assessed once during treatment. RESULTS: Overall, thAb positivity was recorded in 13% of the entire cohort. In most cases, the thAbs were of a single type, with a predominance of T3 immunoglobulin G. More specifically, thAbs were detected in 11 cancer patients; and abnormal levels of thyroid-stimulating hormone, thyroglobulin antibody, and thyroperoxidase antibody were detected in 6 (p = 0.05), 0 (p = 0.0006), and 2 cancer patients (p = 0.001) respectively. Ultrasonographic alterations of the thyroid were observed in 12 cancer patients. In contrast, of the 104 healthy control subjects, only 1 was positive for thAbs (1%). CONCLUSIONS: We have demonstrated for the first time that thAbs are a reliable marker of early thyroid dysfunction when compared with the widely used standard thyroid tests. A confirmatory prospective trial aiming at evaluating thAbs at various time points during treatment could clarify the incidence and timing of antibody appearance.

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer: Preliminary Results in 26 Patients.

BACKGROUND: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. PATIENTS AND METHODS: Patients with LpC having prostate volume ≤90 cm(3) were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. RESULTS: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. CONCLUSIONS: Our preliminary results of SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Impact of treatment duration and lesion size on effectiveness of chondroitinase treatment post-SCI.

The effects of 2weeks of intralesional chondroitinase abc (ch'abc) treatment on anatomical plasticity and behavioral recovery are examined in adult cats and compared to results achieved with 4weeks of treatment following tightly controlled lateral hemisection injuries. Analyses also were completed using 35 cats with a range of hemisection magnitudes to assess relationships between treatment duration, lesion size and functional recovery. Results indicate that both 2 and 4weeks of treatment significantly increased the number of rubrospinal tract (RuST) neurons with axons below the lesion, but neither affected the number of corticospinal tract neurons. Similarly, both treatment periods also accelerated recovery of select motor tasks, which carries considerable importance with respect to human health care and rehabilitation. Four weeks of treatment promoted recovery beyond that seen with 2weeks in its significant impact on accuracy of movement critical for placement of the ipsilateral hindlimb onto small support surfaces during the most challenging locomotor tasks. Analyses, which extended to a larger group of cats with a range of lesion magnitudes, indicate that 4weeks of ch'abc treatment promoted earlier recovery as well as significantly greater targeting accuracy even in cats with larger lesions. Together, these results support the potential for ch'abc to promote anatomical and behavioral recovery and suggest that intraspinal treatment with ch'abc continues to enhance motor recovery and performance beyond the subacute injury period and diminishes the impact of lesion size.

Clinical and molecular aspects of 30 patients with late-onset Pompe disease (LOPD): unusual features and response to treatment.

Pompe disease is a rare metabolic disorder, due to mutations in the gene encoding acid alpha-glucosidase (GAA), of which infantile and late-onset forms may occur. Aim of the work was to analyze clinical and laboratory data of a cohort of late-onset Pompe disease (LOPD) patients, collected during the last 15 years and to point out unusual phenotypic/genotypic features as well as enzyme replacement therapy (ERT) responses. We diagnosed 30 LOPD patients; at follow-up, they underwent motor, respiratory, cardiac and muscle MRI evaluations. Motor performances were tested by Walton Gardner-Medwin, GSGC and 6MWT tests. Respiratory function was assessed as FVC% in upright/supine position. LOPD presentations were represented by presymptomatic hyperCKemia (37%), proximal/axial muscle weakness (53%) and respiratory impairment (10%). Median diagnostic delay was 8.6 years (± 8.8). Atypical features were observed in 4 patients: marked distal muscle weakness and severe hearing loss at onset, as well as leukoencephalopathy and mesial temporal sclerosis during the disease course. By GAA sequence analysis, two causing mutations were detected in 22/30 patients, only one in the remaining 8 subjects. Overall, 29/30 patients harbored the common c.-32-13T>G mutation (2 were homozygous). Two new DNA variations were discovered (c.2395C>G, c.1771C>T). 14 patients received ERT for up to 60 months. Our study confirms LOPD clinical and genetic heterogeneity: atypical features may contribute to expand the clinical phenotype highlighting its multi-systemic nature. A timely diagnosis could allow early ERT start. An accurate follow-up is recommended to evaluate treatment responses.

Autoantibodies in traumatic brain injury and central nervous system trauma.

Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. Of interest, is the occurrence of autoantibodies which are produced following CNS trauma-induced disruption of the blood-brain barrier (BBB) and released into peripheral circulation mounted against self-brain-specific proteins acting as autoantigens. Recently, autoantibodies have been proposed as the new generation class of biomarkers due to their long-term presence in serum compared to their counterpart antigens. The diagnostic and prognostic value of several existing autoantibodies is currently being actively studied. Furthermore, the degree of direct and latent contribution of autoantibodies to CNS insult is still not fully characterized. It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.

An updated overview of animal models in neuropsychiatry.

Animal models are vital tools to study the genetic, molecular, cellular, and environmental parameters involved in several neuropsychiatric disorders. Over the years, these models have expanded our understanding of the pathogenesis of many neuropsychiatric disorders and neurodegenerative diseases. Although animal models have been widely used in psychiatry, and despite several years of extensive research with these models, their validity is still being investigated and presents a challenge to both investigators and clinicians as well. In this concise review, we will describe the most common animal models utilized in neuropsychiatry, including animal models of depression, anxiety, and psychosis. In addition, we will also discuss the validity and reliability of these models and current challenges in this domain. Furthermore, this work will discuss the role of gene-environment interaction as an additional contributing factor that modulates neuropsychological outcome and its implication on animal models. This overview will give a succinct summary of animal models in psychiatry which will be useful both to the seasoned researcher, as well as novices in the field.

Genotoxic effects of anesthetic agents.

BACKGROUND: Preliminary research results indicate that exposure to anesthetics affects health. OBJECTIVE: To provide, with evidence-based knowledge, the answer to the question: What are the genotoxic effects threatening people exposed to anesthetics? METHOD: A systematic review of scientific literature. A systematic search of The Cochrane Library, MedLine, and CINAHL resulted in a screening of 212 abstracts of which 54 articles were assessed for quality. The 54 articles assessed covered areas on general health effects (neurobehavioral effects, immunology) and, in particular, genotoxic effects. RESULTS/CONCLUSION: In the scientific literature reviewed, there is evidence of exposure to anesthetics, especially nitrous oxide and halogenated gases, being associated with general health and genotoxic risks, but conflicting results have been obtained. The result of this review further stresses the need for scientific knowledge in this area and enhances the studies, above all, on people exposed for long periods.