The All4Children project to assess the initial implementation of the Integrated Model of Family Foster Care in Portugal: A description of the study protocol.

BACKGROUND: The All4Children project addresses the urgent need to transition from institutionalization to family-based care for out-of-home children in Portugal. Despite evidence highlighting the detrimental effects of institutionalization, only a small percentage of children (less than 4%) are currently placed in family foster care in the country. In response to European directives for deinstitutionalization, Portuguese legislation now prioritizes non-kinship family foster care as the preferred alternative for young children in need of care. To facilitate this transition, the Integrated Model of Family Foster Care (MIAF) was developed, offering a comprehensive framework covering the entire spectrum of family foster care. OBJECTIVE: This research aims to investigate the initial implementation stage of the MIAF to promote high-quality family foster care in Portugal. METHOD: The study will conduct a mixed-method and longitudinal research project in family foster care agencies across different regions of Portugal, focusing on evaluating the implementation and outcomes of the MIAF model using a multi-informant and multi-method approach. The participants will include caseworkers, children aged 0-9 years entering foster care, and their respective foster families enrolled in the MIAF program. Process evaluation will assess fidelity, feasibility, appropriateness, and acceptability of MIAF modules, while outcome evaluation will examine child safety, stability, well-being, as well as foster family well-being and quality of relational care. OUTCOMES: The insights gained from this research initiative will serve as a foundation for the ongoing enhancement of MIAF. Consequently, this project has the capacity to advance evidence-based child welfare practices by refining processes and strategies to better serve vulnerable children and youth. CONCLUSION: Facilitated by a multidisciplinary team, this project will contribute to advancing research in the field, enhancing practice, and informing policy during a pivotal stage of deinstitutionalization in Portugal.

[Monkeypox: description of two cases under follow-up in Buenos Aires]. / Viruela símica: descripción de dos casos en seguimiento en Buenos Aires.

Monkeypox is an endemic disease in several African countries. In May 2022, an outbreak was reported in dozens of non-endemic countries. On July 23, 2022, the WHO Director-General declared this multinational outbreak a public health emergency of international concern. We report two cases of patients under follow-up in Buenos Aires, Argentina, between June and July 2022. Both were men who have sex with men, with the appearance of lesions in the genital area without a prodromal period. In both cases, treatment was carried out in the first instance with suspicion of sexually transmitted infections. We highlight the importance of considering this pathology as a differential diagnosis, taking into account the current epidemiological context.

La viruela símica es una enfermedad endémica en varios países de áfrica. En mayo de 2022 varios países donde la viruela símica no es endémica notificaron casos, incluyendo algunos países de las Américas. El 23 de julio de 2022, el Director General de la OMS declaró que este brote multinacional constituye una emergencia de salud pública de importancia internacional. Comunicamos dos casos de pacientes en seguimiento en la Ciudad de Buenos Aires, Argentina, entre junio y julio de 2022. Ambos eran hombres que tienen sexo con hombres, con aparición de lesiones en zona genital sin período prodrómico. En los dos casos se realizó tratamiento en primera instancia con sospecha de infecciones de transmisión sexual. Señalamos la importancia de considerar esta enfermedad como diagnóstico diferencial teniendo en cuenta el contexto epidemiológico actual.

Viruela símica: descripción de dos casos en seguimiento en Buenos Aires / Monkeypox: description of two cases under follow-up in Buenos Aires

Resumen La viruela símica es una enfermedad endémica en varios países de África. En mayo de 2022 varios países donde la viruela símica no es endémica notificaron casos, incluyendo algunos países de las Américas. El 23 de julio de 2022, el Director General de la OMS declaró que este brote multinacional constituye una emergencia de salud pública de importancia internacional. Comunicamos dos casos de pacientes en segui miento en la Ciudad de Buenos Aires, Argentina, entre junio y julio de 2022. Ambos eran hombres que tienen sexo con hombres, con aparición de lesiones en zona genital sin período prodrómico. En los dos casos se realizó tratamiento en primera instancia con sospecha de infecciones de transmisión sexual. Señalamos la importancia de considerar esta enfermedad como diagnóstico diferencial teniendo en cuenta el contexto epidemiológico actual.

Abstract Monkeypox is an endemic disease in several African countries. In May 2022, an outbreak was repor ted in dozens of non-endemic countries. On July 23, 2022, the WHO Director-General declared this multinational outbreak a public health emergency of international concern. We report two cases of patients under follow-up in Buenos Aires, Argentina, between June and July 2022. Both were men who have sex with men, with the appea rance of lesions in the genital area without a prodromal period. In both cases, treatment was carried out in the first instance with suspicion of sexually transmitted infections. We highlight the importance of considering this pathology as a differential diagnosis, taking into account the current epidemiological context.

Post-Adoption Help-Seeking in Portugal: A Comprehensive Study on Parental Difficulties and Help-Seeking Behaviors and Perceptions.

Effective psychological parenting interventions delivered to adoptive parents may prevent serious adjustment difficulties and promote a healthy functioning; however, less is known about adoptive parents' specific parental difficulties and help-seeking behaviors and perceptions, the understanding of which is deemed necessary to design well-informed interventions. This study aimed to describe parental difficulties, help-seeking behaviors, satisfaction with, and perceived barriers to seek, professional help, and acceptability of psychological parenting interventions among Portuguese adoptive parents. Comparisons with biological parents (Study 1) and between adoptive parents that requested adoption-specialized and non-specialized support (i.e., adoption-specialized vs. non-specialized help-seekers) (Study 2) were explored. A cross-sectional online survey was conducted. Participants were 471 adoptive and 552 biological parents of children aged under 18 years who were recruited through schools, adoption agencies, and social networks. They completed measures assessing parental difficulties, help-seeking behaviors, satisfaction with, and perceived barriers to seek, professional help, and acceptability of psychological parenting interventions. Comparison tests between the study groups, Pearson's correlations, analyses of covariance (ANCOVA) and multivariate logistic regressions (MLR) were performed. Parents' well-being and normative parenting challenges were the most frequent difficulties in both groups, but only associated with adoptive parents' help-seeking. Although difficulties related to a child's problems/parent-child relationship were more frequent among adoptive parents, adoption-related difficulties were rarely reported. Adoptive parents sought professional help more frequently, regardless of parental difficulties. Knowledge-related barriers to seeking help were the most frequent among adoptive parents. Adoption non-specialized help was less satisfactory. Acceptability of psychological parenting interventions was high, but dependent on parental difficulties. Implications for post-adoption services' development are discussed.

Folding Free Energy Determination of an RNA Three-Way Junction Using Fluctuation Theorems.

Nonequilibrium work relations and fluctuation theorems permit us to extract equilibrium information from nonequilibrium measurements. They find application in single-molecule pulling experiments where molecular free energies can be determined from irreversible work measurements by using unidirectional (e.g., Jarzynski's equality) and bidirectional (e.g., Crooks fluctuation theorem and Bennet's acceptance ratio (BAR)) methods. However, irreversibility and the finite number of pulls limit their applicability: the higher the dissipation, the larger the number of pulls necessary to estimate ΔG within a few kBT. Here, we revisit pulling experiments on an RNA three-way junction (3WJ) that exhibits significant dissipation and work-distribution long tails upon mechanical unfolding. While bidirectional methods are more predictive, unidirectional methods are strongly biased. We also consider a cyclic protocol that combines the forward and reverse work values to increase the statistics of the measurements. For a fixed total experimental time, faster pulling rates permit us to efficiently sample rare events and reduce the bias, compensating for the increased dissipation. This analysis provides a more stringent test of the fluctuation theorem in the large irreversibility regime.

Measurement of the specific and non-specific binding energies of Mg2+ to RNA.

Determining the non-specific and specific electrostatic contributions of magnesium binding to RNA is a challenging problem. We introduce a single-molecule method based on measuring the folding energy of a native RNA in magnesium and at its equivalent sodium concentration. The latter is defined so that the folding energy in sodium equals the non-specific electrostatic contribution in magnesium. The sodium equivalent can be estimated according to the empirical 100/1 rule (1 M NaCl is equivalent to 10 mM MgCl2), which is a good approximation for most RNAs. The method is applied to an RNA three-way junction (3WJ) that contains specific Mg2+ binding sites and misfolds into a double hairpin structure without binding sites. We mechanically pull the RNA with optical tweezers and use fluctuation theorems to determine the folding energies of the native and misfolded structures in magnesium (10 mM MgCl2) and at the equivalent sodium condition (1 M NaCl). While the free energies of the misfolded structure are equal in magnesium and sodium, they are not for the native structure, the difference being due to the specific binding energy of magnesium to the 3WJ, which equals ΔG≃ 10 kcal/mol. Besides stabilizing the 3WJ, Mg2+ also kinetically rescues it from the misfolded structure over timescales of tens of seconds in a force-dependent manner. The method should generally be applicable to determine the specific binding energies of divalent cations to other tertiary RNAs.

Genetic susceptibility to telomere shortening through the rs2293607 polymorphism is associated with a greater risk of alcohol use disorder.

Telomere shortening is usually considered a biomarker of ageing. Harmful alcohol use promotes accelerated biological ageing and alcohol use disorders (AUDs) are associated with short telomere length (TL). This study was conducted to examine the relationship of TL to AUD and determine whether single nucleotide polymorphisms (SNPs) in TERC and TERT modulate this association. For this purpose, we genotyped TERC SNPs rs2293607, rs12696304, and rs16847897 and TERT SNPs rs2735940, rs2736100, and rs2736098 in 308 male patients with AUD and 255 sex-matched healthy controls and measured TL in a subset of 99 patients and 99 controls paired by age and smoking status. Our results showed that the mean TL was shorter in patients with AUD than in controls. The area under the ROC curve was 0.70 (P < 0.001). The GG genotype of TERC rs2293607 was more common among patients with AUD than among controls (9.8% vs. 5.1%; P = 0.038). No difference was found for the other SNPs. Carriers of the GG genotype of rs2293607 had shorter telomeres than did allele A carriers. In conclusion, patients with AUD had shorter telomeres. Genetic susceptibility to telomere shortening through the rs2293607 SNP is associated with a greater risk of AUD.

Supplementation with Resveratrol, Piperine and Alpha-Tocopherol Decreases Chronic Inflammation in a Cluster of Older Adults with Metabolic Syndrome.

Metabolic Syndrome (MetS) is increasing worldwide regardless of culture, genetic, gender, and geographic differences. While multiple individual risk factors, such as obesity, hypertension, diabetes, and hyperlipidemia, can cause cardiovascular disease (CVD), it is the intercurrence of these risk factors that defines MetS as a cluster that creates an environment for atherosclerosis and other manifestations of CVD. Despite the advances in the knowledge and management of each of the components of MetS, there are two molecular biology processes, chronic inflammation and oxidative stress, which are still underdiagnosed and undertreated. In order to assess the effect of a dietary supplement on chronic inflammation in MetS, we conducted a clinical trial with volunteers receiving a formula composed of resveratrol, piperine and alpha tocopherol (FRAMINTROL®), together with their habitual treatment, for three months. The inflammatory state was evaluated by ultrasensitive C reactive protein (US CRP) and ferritin in plasma, and oxygen consumption and chemiluminescence in neutrophils. The results showed that ferritin decreased by 10% (p < 0.05), US-CRP by 33% (p < 0.0001), oxygen consumption by 55% (p < 0.0001), and spontaneous chemiluminiscence was by 25% (p < 0.005) after treatment. As far as we know, this is the first study showing a chronic inflammation decrease in MetS patients due to the administration of a biopower Resveratrol-piperine and alpha tocopherol dietary supplement together with conventional therapy.

Study of non-covalent interactions on dendriplex formation: Influence of hydrophobic, electrostatic and hydrogen bonds interactions.

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe2R]+, R=Me, (CH2)2OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G1O3(NMe2(CH2)2OH))6]6+; the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation.

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men.

BACKGROUND: Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). METHODS: We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. RESULTS: The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32-4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50-6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. CONCLUSIONS: To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD.

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects.

The design of 3D culture studies remains challenging due to the limited understanding of extracellular matrix (ECM)-dependent hindered diffusion and the lack of simple diffusivity assays. To address these limitations, we set up a cost-effective diffusivity assay based on a Transwell plate and the spectrophotometer of a Microplate Reader, which are readily accessible to cell biology groups. The spectrophotometer-based assay was used to assess the apparent diffusivity D of FITC-dextrans with molecular weight (4-70kDa) spanning the physiological range of signaling factors in a panel of acellular ECM gels including Matrigel, fibrin and type I collagen. Despite their technical differences, D data exhibited ∼15% relative difference with respect to FRAP measurements. Our results revealed that diffusion hindrance of small particles is controlled by the enhanced viscosity of the ECM gel in conformance with the Stokes-Einstein equation rather than by geometrical factors. Moreover, we provided a strong rationale that the enhanced ECM viscosity is largely contributed to by unassembled ECM macromolecules. We also reported that gels with the lowest D exhibited diffusion hindrance closest to the large physiologic hindrance of brain tissue, which has a typical pore size much smaller than ECM gels. Conversely, sparse gels (≤1mg/ml), which are extensively used in 3D cultures, failed to reproduce the hindered diffusion of tissues, thereby supporting that dense (but not sparse) ECM gels are suitable tissue surrogates in terms of macromolecular transport. Finally, the consequences of reduced diffusivity in terms of optimizing the design of 3D culture experiments were addressed in detail.

Monte Carlo simulations of enzymatic reactions in crowded media. Effect of the enzyme-obstacle relative size.

We perform Monte Carlo simulations in three-dimensional (3D) lattice in order to study diffusion-controlled and mixed activation-diffusion reactions following an irreversible Michaelis-Menten scheme in crowded media. The simulation data reveal the rate coefficient dependence on time for diffusion-controlled bimolecular reactions developing in three-dimensional media with obstacles, as predicted by fractal kinetics approach. For the cases of mixed activation-diffusion reactions, the fractality of the reaction decreases as the activation control increases. We propose a modified form of the Zipf-Mandelbrot equation to describe the time dependence of the rate coefficient, k(t)=k0(1+t/τ)(-)(h). This equation provides a good description of the fractal regime and it may be split into two terms: one that corresponds to the initial rate constant (k0) and the other one correlated with the kinetics fractality. Additionally, the proposed equation contains and links two limit expressions corresponding to short and large periods of time: k1=k0 (for t≪τ) that relates to classical kinetics and the well-known Kopelman's equation k∼t(-)(h) (for t≫τ) associated to fractal kinetics. The τ parameter has the meaning of a crossover time between these two limiting behaviours. The value of k0 is mainly dependent on the excluded volume and the enzyme-obstacle relative size. This dependence can be explained in terms of the radius of an average confined volume that every enzyme molecule feels, and correlates very well with the crossover length obtained in previous studies of enzyme diffusion in crowding media.

Macromolecular crowding effect upon in vitro enzyme kinetics: mixed activation-diffusion control of the oxidation of NADH by pyruvate catalyzed by lactate dehydrogenase.

Enzyme kinetics studies have been usually designed as dilute solution experiments, which differ substantially from in vivo conditions. However, cell cytosol is crowded with a high concentration of molecules having different shapes and sizes. The consequences of such crowding in enzymatic reactions remain unclear. The aim of the present study is to understand the effect of macromolecular crowding produced by dextran of different sizes and at diverse concentrations in the well-known reaction of oxidation of NADH by pyruvate catalyzed by L-lactate dehydrogenase (LDH). Our results indicate that the reaction rate is determined by both the occupied volume and the relative size of dextran obstacles with respect to the enzyme present in the reaction. Moreover, we analyzed the influence of macromolecular crowding on the Michaelis-Menten constants, vmax and Km. The obtained results show that only high concentrations and large sizes of dextran reduce both constants suggesting a mixed activation-diffusion control of this enzymatic reaction due to the dextran crowding action. From our knowledge, this is the first experimental study that depicts mixed activation-diffusion control in an enzymatic reaction due to the effect of crowding.

Effect of crowding by Dextrans in enzymatic reactions.

The interior of the living cell is highly concentrated and structured with molecules that have different shapes and sizes. Almost all experimental biochemical data have been obtained working in dilute solutions, situations which do not reflect the in vivo conditions. The consequences of such crowding upon enzymatic reactions remain unclear. In this paper, we have studied and compared the initial velocity of the hydrolysis of N-succinyl-L-phenyl-Ala-p-nitroanilide catalyzed by alpha-chymotrypsin, the oxidation of ABTS by H2O2 catalyzed by HRP and the oxidation of NADH in presence of pyruvate catalyzed by LDH. These reactions were chosen as model enzymatic processes occurring in different in vitro crowded media. The systems crowding has been built by introducing Dextran of several concentrations and sizes. Our results indicate that the volume occupied by the crowding agent, but not its size, plays an important role on the initial velocity of reactions involving tiny enzymes. However, the enzyme size is another important factor influencing the velocity of the reactions of large enzymes occurring in Dextran crowded media. In this situation, the reaction initial velocity depends on both occupied volume and dimension of the crowding agent that is present in the reaction media.

Prevalence of hepatitis C virus infection in alcoholic patients: cohort study and systematic review.

AIMS: Prevalence of chronic hepatitis C virus (HCV) infection among alcoholics is thought to be higher than in the general population, although prevalence rates reported are quite variable. Our study is aimed to analyze HCV prevalence in a cohort of alcoholics and to perform a systematic review on this topic. PATIENTS AND METHODS: A total of 396 alcoholic patients consecutively referred to our Alcoholism Unit were included. HCV infection status and other clinical variables were recorded for each patient. Variables associated with HCV infection were analyzed by means of logistic regression. Additionally, we performed a systematic review focused on previous studies on this topic. RESULTS: Among our alcoholic patients, 14 of them (3.53%) had chronic HCV infection. Variables independently associated with HCV infection were female gender, injection drug use (IDU) and the presence of alcoholic liver disease (ALD). Twenty-four studies analyzing HCV prevalence in alcoholic patients were included in our systematic review, showing prevalence rates of HCV infection ranging from 2.1 to 51% and an average weighted prevalence of 16.32%. CONCLUSION: In our series, the prevalence rate of chronic HCV infection among alcoholic patients is lower than previously reported, which is probably explained by the relatively low number of patients with ALD or IDU in our sample. Prevalence rates previously published are quite different and the presence of ALD and/or IDU can act as confounding factors for HCV prevalence among alcoholics.

Decreased peripheral blood CD4+/CD25+ regulatory T cells in patients with alcoholic hepatitis.

BACKGROUND: Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs). METHODS: PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4⁺CD25hiCD127-/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro-stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level. RESULTS: Patients with AH showed decreased (p < 0.05) numbers of PB CD4⁺CD25hiCD127-/lo Tregs at the expense of all maturation-associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4⁺CD25hiCD127-/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte-derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups. CONCLUSIONS: PB CD4⁺CD25hiCD127-/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.

Molecular dynamics simulation of the spherical electrical double layer of a soft nanoparticle: effect of the surface charge and counterion valence.

Molecular dynamics simulations were performed to study the ion and water distribution around a spherical charged nanoparticle. A soft nanoparticle model was designed using a set of hydrophobic interaction sites distributed in six concentric spherical layers. In order to simulate the effect of charged functionalyzed groups on the nanoparticle surface, a set of charged sites were distributed in the outer layer. Four charged nanoparticle models, from a surface charge value of -0.035 C m(-2) to -0.28 C m(-2), were studied in NaCl and CaCl(2) salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the surface charge, counterion valence, and concentration of added salt. We obtain that Na(+) and Ca(2+) ions enter inside the soft nanoparticle. Monovalent ions are more accumulated inside the nanoparticle surface, whereas divalent ions are more accumulated just in the plane of the nanoparticle surface sites. The increasing of the the salt concentration has little effect on the internalization of counterions, but significantly reduces the number of water molecules that enter inside the nanoparticle. The manner of distributing the surface charge in the nanoparticle (uniformly over all surface sites or discretely over a limited set of randomly selected sites) considerably affects the distribution of counterions in the proximities of the nanoparticle surface.

Association of µ-opioid receptor (OPRM1) gene polymorphism with response to naltrexone in alcohol dependence: a systematic review and meta-analysis.

Previous studies have suggested that the effect of naltrexone in patients with alcohol dependence may be moderated by genetic factors. In particular, the possession of the G allele of the A118G polymorphism of the µ-opioid receptor gene (OPRM1) has been associated with a better response to naltrexone, although controversial results have been reported. The aim of this paper is to combine previous findings by means of a systematic review and a meta-analysis. We retrieved studies on the relationship between A118G polymorphism in OPRM1 gene and response to treatment with naltrexone in patients with alcohol dependence by means of electronic database search. A meta-analysis was conducted using a random-effects model. Calculations of odds ratio (OR) and their confidence intervals (CI) and tests for heterogeneity of the results have been performed. Six previous studies have analyzed the role of A118G polymorphism in response to naltrexone for alcohol dependence. After meta-analysis, we found that naltrexone-treated patients carrying the G allele had lower relapse rates than those who were homozygous for the A allele (OR: 2.02, 95% CI 1.26-3.22; P = 0.003). There were no differences in abstinence rates. Our results support the fact that the G allele of A118G polymorphism of OPRM1 moderates the effect of naltrexone in patients with alcohol dependence. This genetic marker may therefore identify a subgroup of individuals more likely to respond to this treatment.

Cannabinoid receptor 1 gene is associated with alcohol dependence.

BACKGROUND: Alcohol dependence (AD) vulnerability is determined by a complex array of genetic factors. Given the potential role of endocannabinoid system in AD, polymorphisms within cannabinoid receptor 1 gene (CNR1) have been potentially associated with susceptibility to this disease. We thus aimed to examine the relationship between 3 allelic variants of CNR1 (rs6454674, rs1049353, and rs806368) and AD. METHODS: Genotyping of the aforementioned polymorphisms was carried out by PCR in 298 male alcoholics (187 of them with AD) and 155 healthy controls. Single-marker, haplotype, and interaction analysis were performed to analyze the influence of CNR1 gene on AD susceptibility. RESULTS: We found an association between CNR1 gene and AD after haplotype analysis. Alcoholic patients with TGT haplotype (corresponding to rs6454674-rs1049353-rs806368 polymorphisms in this order) were less prone to have AD (p = 0.017). Besides, alcoholics with a G/T substitution of the first marker (GGT haplotype) or a C/T substitution of the third marker (TGC haplotype) were more likely to develop AD (p = 0.006 and 0.004, respectively) and an interaction was found between the G allele of rs6454674 single nucleotide polymorphism (SNP) and the C allele of rs806368 SNP (p = 0.009). CONCLUSIONS: Our findings support previously reported associations of CNR1 with dependence to alcohol and other substances and emphasizes the relevance of endocannabinoid system in AD.

A semi-grand canonical Monte Carlo simulation model for ion binding to ionizable surfaces: proton binding of carboxylated latex particles as a case study.

In this paper, we present a computer simulation study of the ion binding process at an ionizable surface using a semi-grand canonical Monte Carlo method that models the surface as a discrete distribution of charged and neutral functional groups in equilibrium with explicit ions modelled in the context of the primitive model. The parameters of the simulation model were tuned and checked by comparison with experimental titrations of carboxylated latex particles in the presence of different ionic strengths of monovalent ions. The titration of these particles was analysed by calculating the degree of dissociation of the latex functional groups vs. pH curves at different background salt concentrations. As the charge of the titrated surface changes during the simulation, a procedure to keep the electroneutrality of the system is required. Here, two approaches are used with the choice depending on the ion selected to maintain electroneutrality: counterion or coion procedures. We compare and discuss the difference between the procedures. The simulations also provided a microscopic description of the electrostatic double layer (EDL) structure as a function of pH and ionic strength. The results allow us to quantify the effect of the size of the background salt ions and of the surface functional groups on the degree of dissociation. The non-homogeneous structure of the EDL was revealed by plotting the counterion density profiles around charged and neutral surface functional groups.