Ethnic differences in drinking outcomes following a brief alcohol intervention in the trauma care setting

Background Evidence suggests that brief interventions in the trauma care setting reduce drinking, subsequent injury and driving under the influence (DUI) arrest. However, evidence on the effectiveness of these interventions in ethnic minority groups is lacking. The current study evaluates the efficacy of brief intervention among whites, blacks and Hispanics in the United States. Methods We conducted a two‐group parallel randomized trial comparing brief motivational intervention (BMI) and treatment as usual with assessment (TAU+) to evaluate treatment differences in drinking patterns by ethnicity. Patients were recruited from a level 1 urban trauma center over a 2‐year period. The study included 1493 trauma patients, including 668 whites, 288 blacks and 537 Hispanics. Hierarchical linear modeling was used to evaluate ethnic differences in drinking outcomes including volume per week, maximum amount consumed in 1 day, percentage days abstinent and percentage days heavy drinking at 6‐ and 12‐month follow‐up. Analyses controlled for age, gender, employment status, marital status, prior alcohol treatment, type of injury and injury severity. Special emphasis was given to potential ethnic differences by testing the interaction between ethnicity and BMI. Results At 6‐ and 12‐month follow‐up, BMI significantly reduced maximum amount consumed in 1 day (P < 0.001; P < 0.001, respectively) and percentage days heavy drinking (P < 0.05; P < 0.05, respectively) among Hispanics. Hispanics in the BMI group also reduced average volume per week at 12‐month follow‐up (χ² = 6.8, df = 1, P < 0.01). In addition, Hispanics in TAU+ reduced maximum amount consumed at 6‐ and 12‐month follow‐up (P < 0.001; P < 0.001) and volume per week at 12‐month follow‐up (P < 0.001). Whites and blacks in both BMI and TAU+ reduced volume per week and percentage days heavy drinking at 12‐month follow‐up (P < 0.001; P < 0.01, respectively) and decreased maximum amount at 6‐ (P < 0.001) and 12‐month follow‐up (P < 0.001). All three ethnic groups In both BMI and TAU+ reduced volume per week at 6‐month follow‐up (P < 0.001) and percentage days abstinent at 6‐ (P < 0.001) and 12‐month follow‐up (P < 0.001). Conclusions All three ethnic groups evidenced reductions in drinking at 6‐ and 12‐month follow‐up independent of treatment assignment. Among Hispanics, BMI reduced alcohol intake significantly as measured by average volume per week, percentage days heavy drinking and maximum amount consumed in 1 day.     

The Mixed Evidence for Brief Intervention in Emergency Departments,Trauma Care Centers,and Inpatient Hospital Settings: What Should We Do?

Background: This qualitative review is based on a symposia presented at the 2009 annual conference of the Research Society on Alcoholism (Baird et al., 2009; Field et al., 2009; Monti et al., 2009; Saitz et al., 2009a). The purpose is to describe the mixed evidence supporting brief interventions in the emergency department, trauma care, and in‐patient medical care settings; examine potential moderators of treatment outcome in light of the mixed evidence; and identify methods to move the research and practice of brief interventions beyond their current state. Methods: By drawing upon existing reviews and selected individual studies, we provide examples that reflect the current complexity of research in this area and propose steps for advancing the field. Results: Emergency departments, inpatient hospital settings, and trauma care settings represent three unique contexts within which brief interventions have been tested. While the general efficacy of brief alcohol interventions in these settings has been recognized, the evidence is increasingly mixed. Recent studies investigating potential moderators of treatment outcomes suggest that a more sophisticated approach to evaluating the effectiveness of brief interventions across varying patient populations is needed to further understand its effectiveness. Conclusions: Current dissemination efforts represent a significant advance in broadening the base of treatment for alcohol problems by providing an evidence‐based intervention in health care settings and should not be curtailed. However, additional research is required to enhance treatment outcomes, refine current practice guidelines, and continue to bridge the gap between science and practice. Given the current state of research, a multisetting clinical trial is recommended to account for potential contextual differences while controlling for study design.     

Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins

Epidemiological data associate coffee consumption with a lower prevalence of chronic liver disease and a reduced risk of elevated liver enzyme levels (γ glutamyl transpeptidase and alanine aminotransferase), advanced liver disease and its complications, and hepatocellular carcinoma. Knowledge of the mechanisms underlying these effects and the coffee components responsible for these properties is still lacking. In this study, 1.5 mL/day of decaffeinated coffee or its polyphenols or melanoidins (corresponding to approximately 2 cups of filtered coffee or 6 cups of espresso coffee for a 70-kg person) were added for 8 weeks to the drinking water of rats who were being fed a high-fat, high-calorie solid diet (HFD) for the previous 4 weeks. At week 12, HFD + water rats showed a clinical picture typical of advanced nonalcoholic steatohepatitis compared with control rats (normal diet + water). In comparison, HFD + coffee rats showed: (1) reduced hepatic fat and collagen, as well as reduced serum alanine aminotransferase and triglycerides; (2) a two-fold reduced/oxidized glutathione ratio in both serum and liver; (3) reduced serum malondialdehyde (lipid peroxidation) and increased ferric reducing antioxidant power (reducing activity); (4) reduced expression of tumor necrosis factor α (TNF-α), tissue transglutaminase, and transforming growth factor β and increased expression of adiponectin receptor and peroxisome proliferator-activated receptor α in liver tissue; and (5) reduced hepatic concentrations of proinflammatory TNF-α and interferon-γ and increased anti-inflammatory interleukin-4 and interleukin-10. CONCLUSION: Our data demonstrate that coffee consumption protects the liver from damage caused by a high-fat diet. This effect was mediated by a reduction in hepatic fat accumulation (through increased fatty acid β-oxidation); systemic and liver oxidative stress (through the glutathione system); liver inflammation (through modulation of genes); and expression and concentrations of proteins and cytokines related to inflammation.     

Pregnancy and ��-thalassemia: an Italian multicenter experience

Background

Recent advances in the management of thalassemia have significantly improved life expectancy and quality of life of patients with this hemoglobinopathy, with a consequent increase in their reproductive potential and desire to have children.

Design and Methods

We describe the methods of conception and delivery, as well as the course and outcome of pregnancy including transfusions, iron overload and chelation in 46 women with thalassemia major (58 pregnancies) and in 11 women with thalassemia intermedia (17 pregnancies). Conception was achieved after gonadotrophin-induced ovulation in 33 of the women with thalassemia major and spontaneously in all of those with thalassemia intermedia.

Results

Among the women with thalassemia major, 91% of the pregnancies resulted in successful delivery of 45 singleton live-born neonates, five sets of twins and one set of triplets. No secondary complications of iron overload developed or worsened during pregnancy. When considering only the singleton pregnancies, the proportion of babies with intrauterine growth retardation did not differ from that reported in the general Italian population. The high prevalence of pre-term births (32.7%) was mostly related to multiple pregnancies and precautionary reasons. Pregnancy was safe in most women with thalassemia major or intermedia. However, women with thalassemia intermedia who had never previously been transfused or who had received only minimal transfusion therapy were at risk of severe alloimmune anemia if blood transfusions were required during pregnancy.

Conclusions

Provided that a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia. In women with hypogonadotropic hypogonadism, gonadal function is usually intact and fertility is usually retrievable.     

4H-1,4-benzothiazine, dihydro-1,4-benzothiazinones and 2-amino-5-fluorobenzenethiol derivatives: design, synthesis and in vitro antimicrobial screening

As part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7‐fluoro‐3,4‐dihydro‐2H‐1,4‐benzothiazine derivatives ( 4a–4f , 4h ) and 7‐fluoro‐2H‐1,4‐benzothiazin‐3(4H)‐one analogues ( 4j–4o ) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram‐positive and Gram‐negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro‐substituted‐2‐amino‐5‐fluorobenzenethiol 6a–6c . The biological screening identified in compounds 4a , 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermediates 6a–6c . Surprisingly, 6a–6c emerged as the compounds exhibiting the highest antimicrobial activity by possessing a remarkable antibacterial effect against the Gram‐positive strains with MIC (minimal inhibitory concentration) values between 2 and 8 µg/mL and the fungi panel with MIC values between 2 and 8 µg/mL. These results may prove useful in the design of a novel pool of antimicrobial agents.     

Chromosomal evolution in Rattini (Muridae, Rodentia)

The Rattini (Muridae, Murinae) includes the biologically important model species Rattus norvegicus (RNO) and represents a group of rodents that are of clinical, agricultural and epidemiological importance. We present a comparative molecular cytogenetic investigation of ten Rattini species representative of the genera Maxomys, Leopoldamys, Niviventer, Berylmys, Bandicota and Rattus using chromosome banding, cross-species painting (Zoo-fluorescent in situ hybridization or FISH) and BAC-FISH mapping. Our results show that these taxa are characterised by slow to moderate rates of chromosome evolution that contrasts with the extensive chromosome restructuring identified in most other murid rodents, particularly the mouse lineage. This extends to genomic features such as NOR location (for example, NORs on RNO 3 are present on the corresponding chromosomes in all species except Bandicota savilei and Niviventer fulvescens, and the NORs on RNO 10 are conserved in all Rattini with the exception of Rattus). The satellite I DNA family detected and characterised herein appears to be taxon (Rattus) specific, and of recent origin (consistent with a feedback model of satellite evolution). BAC-mapping using clones that span regions responsible for the morphological variability exhibited by RNO 1, 12 and 13 (acrocentric/submetacentric) and their orthologues in Rattus species, demonstrated that the differences are most likely due to pericentric inversions as exemplified by data on Rattus tanezumi. Chromosomal characters detected using R. norvegicus and Maxomys surifer whole chromosome painting probes were mapped to a consensus sequence-based phylogenetic tree thus allowing an objective assessment of ancestral states for the reconstruction of the putative Rattini ancestral karyotype. This is thought to have comprised 46 chromosomes that, with the exception of a single pair of metacentric autosomes, were acrocentric in morphology.     

VGF: an inducible gene product, precursor of a diverse array of neuro-endocrine peptides and tissue-specific disease biomarkers

The vgf gene (non-acronymic) is induced in vivo by neurotrophins including Nerve Growth Factor (NGF), Brain Derived Growth Factor (BDNF) and Glial Derived Growth Factor (GDNF), by synaptic activity and by homeostatic and other stimuli. Post-translational processing of a single VGF precursor gives raise to a varied multiplicity of neuro-endocrine peptides, some of which are secreted upon stimulation both in vitro and in vivo. Several VGF peptides, accounting for ～20% of the VGF precursor sequence, have shown biological roles including regulation of food intake, energy balance, reproductive and homeostatic mechanisms, synaptic strengthening, long-term potentiation (LTP) and anti-depressant activity. From a further ～50% of VGF derive multiple "fragments", largely identified in the human cerebro-spinal fluid by proteomic studies searching for disease biomarkers. These represent an important starting point for discovery of further VGF products relevant to neuronal brain functions, as well as to neurodegenerative and psychiatric disease conditions. A distinct feature of VGF peptides is their cell type specific diversity in all neuroendocrine organs studied so far. Selective differential profiles are found across the cell populations of pituitary, adrenal medulla and pancreatic islets, and in gastric neuroendocrine as well as some further mucosal cells, and are yet to be investigated in neuronal systems. At the same time, specific VGF peptide/s undergo selective modulation in response to organ or cell population relevant stimuli. Such pattern argues for a multiplicity of roles for VGF peptides, including endocrine functions, local intercellular communication, as well as the possible mediation of intracellular mechanisms.     

CLEC-2 signaling via Syk in myeloid cells can regulate inflammatory responses

Myeloid cells express a plethora of C-type lectin receptors (CLRs) that can regulate immune responses. CLEC-2 belongs to the Dectin-1 sub-family of CLRs that possess an extracellular C-type lectin-like domain and a single intracellular hemITAM motif. CLEC-2 is highly expressed on mouse and human platelets where it signals via Syk to promote aggregation. We generated a monoclonal antibody (mAb) against mouse CLEC-2 and found that CLEC-2 is additionally widely expressed on leukocytes and that its expression is upregulated during inflammation. MAb-mediated crosslinking of CLEC-2 leads to hemITAM-dependent signaling via Syk, Ca(2+) and NFAT and, in myeloid cells, modulates the effect of toll-like receptor (TLR) agonists to selectively potentiate production of IL-10. A macrophage/dendritic cell-dependent increase in IL-10 is also observed in mice given anti-CLEC-2 mAb together with LPS. Collectively, these data indicate that CLEC-2 is expressed in myeloid cells and acts as a Syk-coupled CLR able to modulate TLR signaling and inflammatory responses.     

Intrinsic expression of Nod2 in CD4+ T lymphocytes is not necessary for the development of cell-mediated immunity and host resistance to Toxoplasma gondii

Nod2 belongs to the nucleotide-binding domain leucine-rich repeat family of proteins and senses bacterial cell wall components to initiate innate immune responses against various pathogens. Recently, it has been reported that T-cell-intrinsic expression of Nod2 promotes host defense against Toxoplasma gondii infection by inducing type 1 immunity. Here, we present results that demonstrate that Nod2 does not play a role in the defense against T. gondii infection. Nod2-deficient mice were fully capable of inducing Th1 immune responses and did not show enhanced susceptibility to infection. Upon TCR stimulation in vitro, Nod2-deficient CD4(+) T cells showed normal activation, IL-2 production, proliferation, and Th1/2 differentiation. Nod2 mRNA and protein were expressed in CD4(+) T and CD8(+) T cells at substantial levels. Therefore, Nod2, although expressed in CD4(+) T cells, does not have an intrinsic function in T-cell activation and differentiation.